Javtor/biomedical-topic-categorization-cased

A smartphone-based test for the assessment of attention deficits in delirium: A case-control diagnostic test accuracy study in older hospitalised patients. Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients.

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A happiness magnet? Reviewing the evidence for repetitive transcranial magnetic stimulation in major depressive disorder. First, to conduct a historical review of the evidence for repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder and determine a clinical algorithm. Second, to identify opportunities for research.

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VP2 of Chicken Anaemia Virus Interacts with Apoptin for Down-regulation of Apoptosis through De-phosphorylated Threonine 108 on Apoptin. Chicken anaemia virus (CAV) is an important contagious agent that causes immunosuppressive disease in chickens. CAV Apoptin is a nucleoplasmic shuffling protein that induces apoptosis in chicken lymphoblastoid cells. In the present study, confocal microscopy revealed co-localisation of expressed CAV non-structural protein VP2 with Apoptin in the nucleus of MDCC-MSB1 cells and the nucleoplasmic compartment of CHO-K1 cells. In vitro pull-down and ex vivo biomolecular fluorescent complementation (BiFC) assays further showed that the VP2 protein directly interacts with Apoptin. Transient co-expression of VP2 and Apoptin in MDCC-MSB1 cells significantly decreased the rate of apoptosis compared with that in cells transfected with the Apoptin gene alone. In addition, the phosphorylation status of threonine 108 (Thr108) of Apoptin was found to decrease upon interaction with VP2. Although dephosphorylated Thr108 did not alter the subcellular distribution of Apoptin in the nucleus of MDCC-MSB1 cells, it did suppress apoptosis. These findings provide the first evidence that VP2 directly interacts with Apoptin in the nucleus to down-regulate apoptosis through alterations in the phosphorylation status of the latter. This information will be useful to further elucidate the underlying mechanism of viral replication in the CAV life cycle.

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Immunohistochemical detection of procalcitonin in fibrolamellar hepatocellular carcinoma. A 25-year-old woman with fever and epigastric pain was referred to our hospital. Blood examination showed significant liver dysfunction, markedly high C-reactive protein (CRP 19.1 mg/dL) and procalcitonin (48.3 ng/mL) levels. Dynamic computed tomography showed a tumor approximately 120 mm in size in the right lobe of the liver, but with no abscess formation. The patient was hospitalized and started on antibiotics; her CRP level improved, but the procalcitonin level did not decrease. Histopathological examination of the liver tumor biopsy revealed fibrolamellar hepatocellular carcinoma (FLC). Positive staining of the FLC with an anti-procalcitonin antibody suggested the production of procalcitonin.

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Gambling and the COVID-19 pandemic: A scoping review. The impact of COVID-19 on mental health is tremendous. Since the beginning of the pandemic, several actors have raised concerns about the impact of the pandemic on gambling. Many actors fear a switch to online gambling in the context of the closure of many land-based gambling activities due to the restrictions imposed by public health authorities, such as physical distancing and lockdowns. This switch is worrisome because online gambling is considered a high-risk game. In that context, we need to know more about the impacts of the pandemic on gambling. This scoping review aims to summarize the literature that addresses the impacts of the COVID-19 pandemic on gambling. To our knowledge, this is the first review to focus on this subject.

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Identification of Brassinosteroid Signaling Complexes by Coimmunoprecipitation and Mass Spectrometry. A combination of coimmunoprecipitation (coIP) of tagged proteins followed by protein identification and quantitation using Liquid Chromatography Mass Spectrometry/Mass Spectrometry (LCMS/MS) has proven to be a reliable method to qualitatively characterize membrane-bound receptor complexes from plants. Success depends on a range of parameters, such as abundance and stability of the complex and functionality of the tagged receptors, efficiency of the protein complex isolation procedure, MS equipment, and analysis software in use. In this Chapter, we focus on the use of one of the green fluorescent protein-tagged receptors of the SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) family, of which SERK3, also known as BRASSINOSTEROID INSENSITIVE1 (BRI1) ASSOCIATED KINASE1 (BAK1), is a coreceptor of BRI1. Like BRI1 itself, SERK3 is a leucine-rich repeat receptor kinase (LRR RK) with a single-pass transmembrane domain. The latest updated laboratory protocol is presented as well as examples of data analysis and typical results obtained. Potential drawbacks of the procedure employed for plant membrane proteins will be pointed out.

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Changes in normothermia during surgery. The aim of the study was to monitor changes in normothermia in patients undergoing surgery under general anaesthesia.

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Haptoglobin expression correlates with tumor differentiation and five-year overall survival rate in hepatocellular carcinoma. Elevated serum haptoglobin (Hp) is identified as a prognostic marker in multiple types of solid tumors, which is correlated with poor prognosis. HCC is one of the major causes of cancer deaths in worldwide, which remains poor prognosis and is clinically urgent for discovering early diagnostic markers. However, except for serum Hp, the correlation of tumor Hp expression with hepatocellular carcinoma (HCC) progression is still unclear. In this study, we evaluated and identified the tissue Hp expression as a prognostic marker to predict the survival rate of HCC patients. To evaluate the prognostic value of Hp expression for HCC, two cohorts were enrolled in our study, including total 130 matched pair tissue sections (both adjacent non-tumorous and tumor tissue derived from same patient) of HCC patients from Changhua Christian Hospital (CCH) and total 316 RNA-seq data with clinical information of HCC patients from The Cancer Genome Atlas (TCGA) database. In contrast to other types of cancers, HCC tumor tissues have lower Hp protein expression in CCH cohort and have lower Hp mRNA expression in TCGA cohort as compared with adjacent non-tumorous tissues (p < 0.001). Moreover, lower Hp expression is significantly correlated with different stages of HCC cancer differentiation in CCH cohort (one-way ANOVA, p < 0.001). Most importantly, lower Hp expression is highly correlated with poor five-year overall survival rate in TCGA cohort (p < 0.01). Based on our data, we conclude that tissue Hp expression positively correlates with better HCC tumor differentiation and increased five-year overall survival rate of HCC patients. The results indicated that tissue Hp is potentially a prognostic marker for HCC patients. Our findings may further provide a new insight of effective treatments along with biopsy diagnosis of HCC patients.

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Cell type-specific novel long non-coding RNA and circular RNA in the BLUEPRINT hematopoietic transcriptomes atlas. Transcriptional profiling of hematopoietic cell subpopulations has helped to characterize the developmental stages of the hematopoietic system and the molecular bases of malignant and non-malignant blood diseases. Previously, only the genes targeted by expression microarrays could be profiled genome-wide. High-throughput RNA sequencing, however, encompasses a broader repertoire of RNA molecules, without restriction to previously annotated genes. We analyzed the BLUEPRINT consortium RNA-sequencing data for mature hematopoietic cell types. The data comprised 90 total RNA-sequencing samples, each composed of one of 27 cell types, and 32 small RNA-sequencing samples, each composed of one of 11 cell types. We estimated gene and isoform expression levels for each cell type using existing annotations from Ensembl. We then used guided transcriptome assembly to discover unannotated transcripts. We identified hundreds of novel non-coding RNA genes and showed that the majority have cell type-dependent expression. We also characterized the expression of circular RNA and found that these are also cell type-specific. These analyses refine the active transcriptional landscape of mature hematopoietic cells, highlight abundant genes and transcriptional isoforms for each blood cell type, and provide a valuable resource for researchers of hematologic development and diseases. Finally, we made the data accessible via a web-based interface: https://blueprint.haem.cam.ac.uk/bloodatlas/.

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Experiences of Body Image Changes in Chinese Patients Living with Inflammatory Bowel Disease: A Descriptive Qualitative Study. Body image changes are common among patients living with inflammatory bowel disease (IBD) because of the illness and related treatments. Currently, there is little known about how those patients experience and perceive their altered body image in the literature. The aim of this study was to explore the experiences of body image changes in patients with IBD in China and to describe how those changes influence patients' perception of body and self.

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Keeping the power on to home medical devices. Advances in digital health technologies have revolutionised home medical care. Yet many home medical devices (HMEDs, which includes devices referred to as 'life support equipment') rely upon a stable and resilient electricity supply. For users of HMEDs, interruptions to electricity supply can compromise treatment, well-being or survival. This paper addresses a challenge critical to the continued innovation in digital health technologies: the reliable supply of electricity. We bridge the current gap between electricity networks and digital health technologies through a novel method for the remote detection of the phase (that is, which part of the network that each house is connected to), in order to eliminate avoidable interruptions to supply for HMED users. We present an unsupervised phase identification algorithm capable of remote phase detection at scale, and without transformer data. This method translates data insights into actionable energy provision for HMED users and other vulnerable customers, enables more accurate management and planning, and improves electricity reliability which is critical for HMED users and the continued advances in digital health technologies.

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Morphological Reconstruction-Based Image-Guided Fuzzy Clustering with a Novel Impact Factor. The guided filter is a novel explicit image filtering method, which implements a smoothing filter on "flat patch" regions and ensures edge preserving on "high variance" regions. Recently, the guided filter has been successfully incorporated into the process of fuzzy c-means (FCM) to boost the clustering results of noisy images. However, the adaptability of the existing guided filter-based FCM methods to different images is deteriorated, as the factor ε of the guided filter is fixed to a scalar. To solve this issue, this paper proposes a new guided filter-based FCM method (IFCM_GF), in which the guidance image of the guided filter is adjusted by a newly defined influence factor ρ . By dynamically changing the impact factor ρ , the IFCM_GF acquires excellent segmentation results on various noisy images. Furthermore, to promote the segmentation accuracy of images with heavy noise and simplify the selection of the influence factor ρ , we further propose a morphological reconstruction-based improved FCM clustering algorithm with guided filter (MRIFCM_GF). In this approach, the original noisy image is reconstructed by the morphological reconstruction (MR) before clustering, and the IFCM_GF is performed on the reconstructed image by utilizing the adjusted guidance image. Due to the efficiency of the MR to remove noise, the MRIFCM_GF achieves better segmentation results than the IFCM_GF on images with heavy noise and the selection of the influence factor for the MRIFCM_GF is simple. Experiments demonstrate the effectiveness of the presented methods.

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Chinese Medicine for Alzheimer's Disease: A Meta-Analysis of Randomized Controlled Trials. To evaluate the effificacy of oral Chinese medicine (CM) in comparison with donepezil, a cholinesterase inhibitor (ChEI), for the treatment of Alzheimer's disease (AD).

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Label-free Separation of Circulating Tumor Cells Using a Self-Amplified Inertial Focusing (SAIF) Microfluidic Chip. Circulating tumor cells (CTCs) are rare cells existing in the bloodstream with a relatively low number, which facilitate as a predictor of cancer progress. However, it is difficult to obtain highly purified intact CTCs with desired viability due to the low percentage of CTCs among blood cells. In this work, we demonstrate a novel self-amplified inertial focused (SAIF) microfluidic chip that enables size-based, high-throughput, label-free separation of CTCs from a patient's blood. The SAIF chip introduced in this study demonstrated the feasibility of an extremely narrow zigzag channel (with 40 μm channel width) connected with two expansion regions to effectively separate different-sized cells with amplified separation distance. The chip performance was optimized with different-sized polystyrene (PS) particles and blood cells spiked with three different types of cancer cells. The separation efficiencies for blood cells and spiked cancer cells are higher than 80%. Recovery rates of cancer cells were tested by spiking 1500 lung cancer cells (A549), breast cancer cells (MCF-7), and cervical cancer cells (HeLa) separately to 3 mL 0.09% saline with 3 × 10 6 white blood cells (WBCs). The recovery rates for larger cells (MCF-7 and HeLa) were 79.1 and 85.4%, respectively. Viabilities of the cells harvested from outlets were all higher than 97% after culturing for 24, 48, and 72 h. The SAIF chip performance was further confirmed using the real clinical patient blood samples from four lung cancer patients. Theoretical force balance analysis in physics, computational simulations, and experimental observations indicate that the SAIF chip is simple but effective, and high-throughput separation CTCs can be readily achieved without complex structures.

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Genome-wide identification of heat shock factors and heat shock proteins in response to UV and high intensity light stress in lettuce. Heat shock factors (Hsfs) and Heat shock proteins (Hsps) belong to an essential group of molecular regulators involved in controlling cellular processes under normal and stress conditions. The role of Hsfs and Hsps is well known in model plant species under diverse stress conditions. While plants Hsfs are vital components of the signal transduction response to maintain cellular homeostasis, Hsps function as chaperones helping to maintain folding of damaged and newly formed proteins during stress conditions. In lettuce (Lactuca sativa), a highly consumed vegetable crop grown in the field and in hydroponic systems, the role of these gene families in response to artificial light is not well characterized.

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Apolipoprotein A1 Forms 5/5 and 5/4 Antiparallel Dimers in Human High-density Lipoprotein. Apolipoprotein A1 (APOA1), the major protein of high-density lipoprotein (HDL), contains 10 helical repeats that play key roles in protein-protein and protein-lipid interactions. The current structural model for HDL proposes that APOA1 forms an antiparallel dimer in which helix 5 in monomer 1 associates with helix 5 in monomer 2 along a left-left (LL5/5) interface, forming a protein complex with a 2-fold axis of symmetry centered on helix 5. However, computational studies suggest that other orientations are possible. To test this idea, we used a zero-length chemical cross-linking reagent that forms covalent bonds between closely apposed basic and acidic residues. Using proteolytic digestion and tandem mass spectrometry, we identified amino acids in the central region of the antiparallel APOA1 dimer of HDL that were in close contact. As predicted by the current model, we found six intermolecular cross-links that were consistent with the antiparallel LL5/5 registry. However, we also identified three intermolecular cross-links that were consistent with the antiparallel LL5/4 registry. The LL5/5 is the major structural conformation of the two complexes in both reconstituted discoidal HDL particles and in spherical HDL from human plasma. Molecular dynamic simulations suggest that that LL5/5 and LL5/4 APOA1 dimers possess similar free energies of dimerization, with LL5/5 having the lowest free energy. Our observations indicate that phospholipidated APOA1 in HDL forms different antiparallel dimers that could play distinct roles in enzyme regulation, assembly of specific protein complexes, and the functional properties of HDL in humans.

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Effects of muscle damage on 31 P-MRS indices of energetic status and sarcolemma integrity in young mdx mice. The article of Lopez et al describes the use of a multi-parametric MR approach to study muscle T 2 relaxation times and 31 P-MRS indices of energetics and sarcolemma integrity in a mouse model of DMD, the mdx mouse. Muscular dystrophies have a multi-factorial disease cascade, and there are several MR methods used to assess these. Aspects that reflect disease progression are outlined on the left, while features that are more related to disease activity are outlined on the right.

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Optimisation of a batch thermal combustion method using a tube furnace oxidation system (pyrolyser) and LSC for carbon-14 determination in environmental matrices. Accelerator mass spectrometry and benzene synthesis coupled with liquid scintillation spectrometry are often used for accurate measurements of 14 C activity in the environmental matrices. Thermal oxidation is one of the methods employed for 14 C determination in environmental matrices. In this method, the sample is oxidised at high temperature (600-900 °C) to convert carbon species to CO 2 and trapped in an amine-based absorber for determining the activity in a liquid scintillation counting (LSC) system. In this study, the performance of a commercially available tube furnace system (pyrolyser), for batch combustion of samples, was evaluated for the determination of 14 C specific activity in terrestrial biota samples. Significant improvements over the manufacturer specified method, which is primarily designed for analysis of samples with activity well above the environmental background level, was implemented to achieve accurate determination of 14 C specific activity at ambient background level. In the improved method, the CO 2 produced from the combustion of the sample was isolated from the combustion products through cryogenic trapping and then absorbed in the absorber (Carbo-Sorb E) through a simple off-line transfer process. This allowed (i) optimisation of CO 2 absorption by the absorber (2.2477 g of CO 2 /10 mL), (ii) achieving good accuracy and precision in the measurements, and a minimum detectable activity value of 13 Bq kg -1 C for a counting time of 300 min (7 Bq kg -1 C for 1000 min), (iii) avoiding uncertainty associated with the determination of recovery of 14 C in the combustion and trapping process, and (iv) elimination of the need for an independent determination of carbon content (%) for expressing the results in terms of 14 C specific activity. The method is capable of yielding accurate results with a deviation of <2.4% from the target value for IAEA C3 quality assurance reference material (with a relative standard deviation of 1.40%, and relative error of 0.34%). The combined uncertainty (1σ) associated with the measurements was computed to be 3.4%. Upon optimisation, the suitability of the method for the determination of 14 C specific activity in typical terrestrial biota samples of clean air region (region not affected by local anthropogenic sources) and for the quantification of a small increase in the 14 C activity above ambient levels in the vicinity of a nuclear power plant is demonstrated.

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N-dihydrogalactochitosan-supported tumor control by photothermal therapy and photothermal therapy-generated vaccine. Photothermal therapy (PTT) is recently clinically established cancer therapy that uses near-infrared light for thermal ablation of solid tumors. The biopolymer N-dihydrogalactochitosan (GC) was shown in multiple reports to act as a very effective adjunct to tumor PTT. In the present study, mouse tumor model SCCVII (squamous cell carcinoma) was used with two protocols, in situ tumor PTT and therapeutic PTT vaccine for tumors, for investigating the effects of GC. The results reveal that GC can potentiate tumoricidal action of PTT through both direct and indirect mechanisms. In addition to previously known capacity of GC for activating immune effector cells, the indirect means is shown to include reducing the populations of immunoregulatory T cells (Tregs) in PTT-treated tumors. Testing the effects of GC on PTT-treated SCCVII tumor cells in vitro uncovered the existence of a direct mechanism evident by reduced colony survival of these cells. Fluorescence microscopy demonstrated increased binding of fluorescein-labeled GC to PTT-treated compared to untreated SCCVII cells that can be blocked by pre-exposure to annexin V. The results of additional in vitro testing with specific inhibitors demonstrate that these direct mechanisms do not involve the engagement of death surface receptors that trigger extrinsic apoptosis pathway signaling but may be linked to pro-survival activity of caspase-1. Based on the latter, it can be suggested that GC-promoted killing of PTT-treated cells stems from interference of GC bound to damaged membrane components with the repair of these structures that consequently hinders cell survival.

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Automated recognition of the pericardium contour on processed CT images using genetic algorithms. This work proposes the use of Genetic Algorithms (GA) in tracing and recognizing the pericardium contour of the human heart using Computed Tomography (CT) images. We assume that each slice of the pericardium can be modelled by an ellipse, the parameters of which need to be optimally determined. An optimal ellipse would be one that closely follows the pericardium contour and, consequently, separates appropriately the epicardial and mediastinal fats of the human heart. Tracing and automatically identifying the pericardium contour aids in medical diagnosis. Usually, this process is done manually or not done at all due to the effort required. Besides, detecting the pericardium may improve previously proposed automated methodologies that separate the two types of fat associated to the human heart. Quantification of these fats provides important health risk marker information, as they are associated with the development of certain cardiovascular pathologies. Finally, we conclude that GA offers satisfiable solutions in a feasible amount of processing time.

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Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering. Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

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Determination of the just suspended speed for solid particle in torus reactor. With the considerable use of pipelines and reactors in the engineering industry, determining the deposition velocity enabling hydraulic transport is of utmost importance. This has been investigated throughout the years, scrupulously in several types of reactors used in water treatment and solid transport. The primary focus has been extended to torus reactors, due to their significant advantage in chemical, biochemical and mixing processes. In the present work, we have studied the solid-liquid suspension in a torus reactor. We elaborated an experimental method based on visual assessment SBAM (Steady Bed Angle Method), which enabled us to analytically determine the just suspended speed 'Njs' at which no solid remains stationary at the bed and further parametrically study the effect of several parameters including solid loadings, particle sizes and densities. The just suspended speed values obtained experimentally have been compared to a modified Zwietering's correlation.

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[Preliminary study on effect of Gegen Qinlian Decoction on enzyme activity, gene expression and methylation level of FASN in adipose tissue of rats with insulin resistance]. To investigate the effect of Gegen Qinlian Decoction(GQD) on enzyme activity, gene expression and methylation level of fatty acid synthase(FASN) in adipose tissue from rats with insulin resistance induced by high-fat diet. The 60% fat-powered high-fat diet was continuously given to male SD rats to induce the insulin resistance model. Then, they were divided into five groups randomly and administrated by gavage every day for 16 weeks with following drugs respectively: 10 mL·kg~(-1)water for control group(C) and insulin resistance model control group(IR), 1.65 g·kg~(-1)GQD per day for low-dose group(GQDL), 4.95 g·kg~(-1)GQD per day for medium-dose group(GQDM), 14.85 g·kg~(-1)GQD per day for high-dose group(GQDH), and 5 mg·kg~(-1) rosiglitazone per day for rosiglitazone group(RGN). Epididymal adipose tissue was taken to determine enzyme activity of FASN by colorimetric method, mRNA expression level of Fasn by quantitative Real-time PCR(Q-PCR) and CpGs methylation level between +313 and +582 by bisulfite sequencing PCR(BSP). These results showed that Fasn expression was significantly lowered in IR model rats compared with the control rats(P<0.01). Enzymatic activity and CpGs methylation level of Fasn in IR group showed downward trends. Low and medium-dose GQD can increase enzyme activity of FASN(P<0.05). Moreover, low-dose GQD increased the total CpGs methylation level of Fasn fragment between +313 and +582 in insulin resistance rats(P<0.05). For GQDM group, the methylation frequency of CpGs at positions +506 and +508(P<0.01) as well as the methylation frequency of CpGs on the binding sites of transcription factorzinc finger protein 161(P<0.05) were significantly increased. The methylation frequency of CpG at +442 position was positively correlated with Fasn expression(P<0.01, r=0.735), and methylation frequencies of CpGs at +345 and +366 positions were positively associated to enzyme activity of FASN respectively(P<0.05, r=0.479; P<0.01, r=0.640). In conclusion, GQD can reverse enzyme activity of FASN and methylation level of Fasn in adipose tissue of insulin resistant rats, and CpG sites at positions +506 and +508 may be the targets of GQD. The methylation level of CpGs at + 345 and + 366 sites were possibly related to FASN activity, while methylation of CpG at + 442 site may be closely correlated with mRNA level of Fasn. In addition, GQD did not significantly change mRNA expression level of Fasn, but effectively reversed enzymatic activity, suggesting that GQD may regulate the post transcriptional expression of Fasn.

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A meta-synthesis of qualitative studies of the link between anxiety, depression and perfectionism: implications for treatment. Meta-analyses show an association between perfectionism and depression and anxiety (negative affect), and that therapy for perfectionism impacts positively on negative affect. No systematic reviews have focused on qualitative studies of perfectionism.

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Mucoadhesive Particles: A Novel, Prolonged-Release Nanocarrier of Sitagliptin for the Treatment of Diabetics. Sitagliptin (MK-0431) is a widely and commonly used oral hypoglycemic drug in the treatment of type 2 diabetes mellitus; patients typically take higher doses of this drug (50 mg, twice daily). One drawback is that only 38% of the drug is bound reversibly to plasma proteins and 79% is excreted in urine without being metabolized. To overcome this issue, there is a need for a better drug-delivery method to improve its efficacy in patients. It has been found that in existing formulations, the drug content is 72.5% ± 5% and the percentage yield is 84.9% ± 3%. In this study, sitagliptin nanoparticles (sizes ranging from 210 to 618 nm) were developed. The bioadhesion properties of the nanoparticles, as well as the swelling of the nanoparticles on the mucus membrane aided in sustained drug release. The pattern of drug release was in accordance with the Peppas model. Fourier-transform infrared (FTIR) spectroscopy demonstrated that there were no significant interactions between sitagliptin and chitosan. Differential scanning calorimetry (DSC) results showed an absence of drug peaks due to the fact that the drug was present in an amorphous state. Mucoadhesive nanoparticles were formulated using sitagliptin and were effective for about 12 hours in the gastrointestinal tract. When compared to conventional sitagliptin administration, use of a nanoparticle delivery system demonstrated greater benefits for use in oral delivery applications. This is the first time that a drug-delivery method based on the mucoadhesive properties of nanoparticles could prolong the drug-release time of sitagliptin.

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Major Stress-Related Symptoms During the Lockdown: A Study by the Italian Society of Psychophysiology and Cognitive Neuroscience. The clinical effects of the Covid-19 pandemic are now the subject of numerous studies worldwide. But what are the effects of the quarantine imposed by the states that implemented the measures of lockdown? The present research aims to explore, in a preliminary way, the major stress-related symptoms during the lockdown, due to Covid-19, in the Italian population. Subjects were asked to fill out a survey, that traced a line identifying the most relevant psychophysiological symptoms that took into account factors such as perceived stress, body perception, perceived pain, quality of sleep, perceptive variations (i.e., olfactory, gustatory, visual, acoustic, and haptic perception). A network approach formulating a hypothesis-generating exploratory analysis was adopted. Main results of the network analysis showed that the beliefs of having had the Covid-19 was related to individual variables (i.e., gender, working in presence, sleep quality, anxiety symptoms), while the familiarity of Covid-19 disease was related to contextual factors (e.g., number of recorded cases in the Region, working in presence). The self-perception of olfactory and perceptive alterations highlighted a great sensorial cross-modality, additionally, the olfactory impairment was related to the belief of having had the Covid-19. Compared to general network data, BAI, perceived stress, anxiety and chronic pain were in relation to daily sleep disturbance. Main study's results show how the management of the Covid-19 stressful representation, in its cognitive aspects, can modulate the psychophysiological responses.

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Radial/Ulnar angioplasty in selected patients undergoing elective angiography or PCI using complex forearm approach. Angioplasty on the radial artery have been performed with good success rates in patients with critical hand ischemia. We sought to assess the feasibility and safety of radial angioplasty on complex radial access in patients undergoing coronary angiography.

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False-negative Results of Human Immunodeficiency Virus (HIV) Rapid Testing in HIV Controllers. Serological assays were performed on 85 human immunodeficiency virus-controller samples . 6% presented a negative rapid screening test 7% presented an indeterminate Western blot. The enzyme immunoassay ratio decreased in controllers who had continual negative ultrasensitive HIV RNA results since inclusion.

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Paratesticular rhabdomyosarcoma-Impact of locoregional approach on patient outcome: A report from the European paediatric Soft tissue sarcoma Study Group (EpSSG). Paratesticular rhabdomyosarcoma (PT RMS) is rare compared to benign scrotal pathology. Inappropriate first surgery (InFS) required supplementary treatment to maintain excellent outcomes. Initial staging of regional lymph nodes is important. The aim of this study was to determine to what extent the quality of locoregional approach impacted on patient morbidity and survival.

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Adjuvant Chemotherapy for Gastric Cancer Patients with Mismatch Repair Deficiency or Microsatellite Instability: Systematic Review and Meta-Analysis. Mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) status serves as a predictor of a poor response to adjuvant chemotherapy among stage 2 colon cancer patients. This study aimed to investigate the efficacy of adjuvant chemotherapy in dMMR/MSI-H gastric cancer (GC).

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Targeting Amyloids with [ 18 F]AV-45 for Medullary Thyroid Carcinoma Positron Emission Tomography/Computed Tomography Imaging: A Pilot Clinical Study. Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a β-amyloid-specific radiotracer, [ 18 F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [ 18 F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [ 18 F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [ 18 F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[ 18 F]fluoro-d-glucose ([ 18 F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [ 18 F]AV-45 uptake. Postoperative histopathological analysis confirmed the [ 18 F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [ 18 F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [ 18 F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.

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Deciphering the role of nanostructured materials in the point-of-care diagnostics for COVID-19: a comprehensive review. The infamous COVID-19 outbreak has left a crippling impact on the economy, healthcare infrastructure, and lives of the general working class, with all the scientists determined to find suitable and efficient diagnostic techniques and therapies to contain its ramifications. This article presents the complete outline of the diagnostic platforms developed using nanoparticles in the detection of SARS-CoV-2, delineating the direct and indirect use of nanomaterials in COVID-19 diagnosis. The properties of nanostructured materials and their relevance in the development of novel point-of-care diagnostic approaches for COVID-19 are highlighted. More importantly, the advantages of nanotechnologies over conventional reverse transcriptase-polymerase chain reaction technique and few other methods used in the detection of SARS-CoV-2 along with the viewpoints are discussed. Also, the future perspectives highlighting the commercial aspects of the nanotechnology-based diagnostic tools developed to combat the COVID-19 pandemic are presented.

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Assessment of mask-wearing adherence and social distancing compliance in public places in Hamadan, Iran, during the COVID-19 pandemic. The determination of the rate of social distancing compliance and mask-wearing adherence is essential to address the health aspects of COVID-19. The present study aimed to estimate the adherence to mask-wearing and maintaining the social distancing in public places in Hamadan, western Iran, during the COVID-19 pandemic.

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National report on aggressions to physicians in Spain 2010-2015: violence in the workplace-ecological study. Aggressions against health staff is a phenomenon that is not widely studied worldwide. To date, there is no national study analyzing this situation in Spain. Our objective is to describe and analyze aggressions to physicians of the whole Spanish territory in the period 2010-2015, through an observational analytical study by conglomerates (ecological) with all aggressions to physicians identified by the 52 official medical associations of Spain over 6 years of study.

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Modeling the spread of capripoxvirus among livestock and optimal vaccination strategies. Capripox is an important transboundary animal disease that is endemic across Africa, the Middle East, and some parts of Asia. The disease is highly contagious and considered to be a major obstacle causing significant economic loses in many agricultural areas. In this study, a mathematical model is developed to describe the transmission dynamics of capripoxvirus (CaPV) among livestock. This proposed model incorporates direct and indirect transmission of CaPV, together with two vaccination strategies, to investigate their effects on the severity of outbreaks and the prevalence of CaPV among the livestock population. The results suggest that ratio of potential vectors to livestock, successful probability of infection, vaccination rates, waning rate of vaccine-conferred protection, and virus introduction time play crucial roles in determining the outbreak severity and the prevalence level. The results also show that it is optimal to vaccinate newborns at the maximum effort throughout the control program and moderately increase vaccination rate for a susceptible pool to reach its maximum level after the outbreak.

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Pretreatment optimisation and kinetics of batch anaerobic digestion of liquidised OFMSW treated with NaOH: Models verification with experimental data. The enormous generation of municipal solid waste (MSW) due to increased urbanization is causing threat to the environment. MSW is a mixed waste and it comprises of organic fraction as the key fraction called organic fraction of municipal solid waste (OFMSW) along with other fractions. The pretreatment of OFMSW is necessary step to increase the biogas yield. In the present work, NaOH hydrolysis of mechanically liquidised OFMSW was carried out to reduce its complexity and improve the biogas production. Furthermore, hydrolysis parameters were optimised by RSM model for NaOH pretreatment. Optimised conditions achieved from RSM analysis were 0.46 N NaOH loading, 72 h reaction time and 36.05 °C operating temperature. The RSM predicted values of response sCOD and VFA at optimum condition were in good agreement with experimental data signifying the model adequacy. The kinetic of batch anaerobic digestion of OFMSW treated with NaOH at different concentrations and optimised condition had been studied to see the suitability of first order model and modified Gompartz model. The experimental results obtained were best fitted using normalized root mean square error analysis. Biogas production after pretreatment at 0.1, 0.5, 0.9 N NaOH concentration and RSM optimised condition was 369.24, 435.24, 327.84 and 465.67 NL/kg VS, respectively.

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Automated deep learning design for medical image classification by health-care professionals with no coding experience: a feasibility study. Deep learning has the potential to transform health care; however, substantial expertise is required to train such models. We sought to evaluate the utility of automated deep learning software to develop medical image diagnostic classifiers by health-care professionals with no coding-and no deep learning-expertise.

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Surmising synchrony of sound and sight: Factors explaining variance of audiovisual integration in hurdling, tap dancing and drumming. Auditory and visual percepts are integrated even when they are not perfectly temporally aligned with each other, especially when the visual signal precedes the auditory signal. This window of temporal integration for asynchronous audiovisual stimuli is relatively well examined in the case of speech, while other natural action-induced sounds have been widely neglected. Here, we studied the detection of audiovisual asynchrony in three different whole-body actions with natural action-induced sounds-hurdling, tap dancing and drumming. In Study 1, we examined whether audiovisual asynchrony detection, assessed by a simultaneity judgment task, differs as a function of sound production intentionality. Based on previous findings, we expected that auditory and visual signals should be integrated over a wider temporal window for actions creating sounds intentionally (tap dancing), compared to actions creating sounds incidentally (hurdling). While percentages of perceived synchrony differed in the expected way, we identified two further factors, namely high event density and low rhythmicity, to induce higher synchrony ratings as well. Therefore, we systematically varied event density and rhythmicity in Study 2, this time using drumming stimuli to exert full control over these variables, and the same simultaneity judgment tasks. Results suggest that high event density leads to a bias to integrate rather than segregate auditory and visual signals, even at relatively large asynchronies. Rhythmicity had a similar, albeit weaker effect, when event density was low. Our findings demonstrate that shorter asynchronies and visual-first asynchronies lead to higher synchrony ratings of whole-body action, pointing to clear parallels with audiovisual integration in speech perception. Overconfidence in the naturally expected, that is, synchrony of sound and sight, was stronger for intentional (vs. incidental) sound production and for movements with high (vs. low) rhythmicity, presumably because both encourage predictive processes. In contrast, high event density appears to increase synchronicity judgments simply because it makes the detection of audiovisual asynchrony more difficult. More studies using real-life audiovisual stimuli with varying event densities and rhythmicities are needed to fully uncover the general mechanisms of audiovisual integration.

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Depression in Poststroke Aphasia. Purpose The aim of this tutorial is to provide speech-language pathologists with foundational knowledge of poststroke depression comorbidly occurring with aphasia. Given the negative effect of depression on functional outcomes and mortality, it is crucial that speech-language pathologists possess this knowledge in order to better advocate for and treat their patients. Method and Results Three areas of complementary expertise (speech-language pathology, psychology, and neurology) collaborated on this tutorial to address the following areas: (a) provide terminology associated with depression and related mood disorders, (b) describe the potential underlying pathophysiology of depression in the general population, (c) provide an overview of our existing understanding of comorbid poststroke depression and aphasia, and (d) summarize current assessment methods and interventions for poststroke depression in adults with aphasia. Conclusion Given the compounding impact aphasia and depression have on rehabilitation outcomes, it is imperative that speech-language pathologists understand terminology, assessment, and treatment practices for depression.

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Fertilization accelerates the decomposition of microplastics in mollisols. Agricultural films composed of low-density polyethylene (LDPE) have been widely used in farmland, and LDPE microplastics (LDPE-MPs) produced from LDPE degradation can pollute soils and can exert negative effects on biota. Both nitrogen (N) and phosphorus (P) can alter the activity of soil microorganisms and may alter the LDPE-MP degradation process in soils. In this study, LDPE-MP surface morphology, particle size, abundance and mass in a mollisol were evaluated after the application of a gradient of N and P fertilizer in a laboratory incubation experiment. The results showed the following: (1) LDPE-MP particles became fragmented into smaller debris with a coarse surface after 40 days of incubation, and the effect was more obvious with increased P or N application; (2) high N and P fertilization significantly reduced the abundance of LDPE-MP particles >100 μm by 38.5-50.0% and increased the abundance of LDPE-MP particles <20 μm by 43.2-59.5% after 40 days of incubation; (3) high N and P fertilization significantly increased the mass of LDPE-MP particles <75 μm by 25.5-60.1% and decreased the mass of LDPE-MP particles >150 μm by 32.4-37.5%; (4) the mass of LDPE-MPs decreased with increasing incubation time after N and P fertilization, which could be simulated by exponential models (p < 0.05), LDPE degradation was rapid in the first 20 days after N or P fertilization, and both N and P caused a "priming effect" of LDPE degradation; and (5) N and P fertilization increased both the biodiversity and abundance of several predominant genera of soil microorganisms that degrade LDPE. Therefore, N and P fertilization can accelerate LDPE-MP degradation, and the relatively large amounts of fine debris from degraded LDPE-MPs can be problematic for the environment and soil biota. LDPE-MP pollution should be strictly controlled in mollisols, and the degradation mechanisms of LDPE-MPs warrant further study.

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Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer's disease. Although many therapeutic strategies for Alzheimer's disease (AD) have been explored, these strategies are seldom used in the clinic. Therefore, AD therapeutic research is still urgently needed. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. Herein, we devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau.

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UK audit of target volume and organ at risk delineation and dose optimisation for cervix radiotherapy treatments. Assessment of the extent of variation in delineations and dose optimisation performed at multiple UK centres as a result of interobserver variation and protocol differences.

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Transjugular Portosystemic Shunt Reductions: A Retrospective Single-Center Experience. To report the results of transjugular intrahepatic portosystemic shunt (TIPS) reductions for hepatic encephalopathy (HE), acute liver failure (ALF), and pulmonary hypertension (PH).

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Care of the stoma: complications and treatments. Quality patient education of how to care for their stoma improves patient outcomes and enhances quality of care and efficacy. There is a need for home visits to assist ostomates with rehabilitation of their stoma formation, as they often feel stigmatised and are likely to withdraw from social activities. It has previously been highlighted that community care is often the weakest link in rehabilitation, highlighting the need for effective teamwork and collaboration between stoma nurse specialists and community nurses. This article will focus on some of the more common complications of stomas which will be seen in the community setting, how to treat these conditions and when patients should be referred to the specialist stoma care nurse.

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Fabrication and sensing properties of phenolphthalein based colorimetric and turn-on fluorogenic probe for CO 3 2- detection and its living-cell imaging application. Herein, an easy assembled colorimetric and ''turn-on'' fluorescent sensor (probe P4SC) based on phenolphthalein was developed for carbonate ion (CO 3 2- ) sensing in a mixture of EtOH/H 2 O (v/v, 80/20, pH = 7, Britton-Robinson buffer) media. The probe P4SC demonstrated high sensitive and selective monitoring toward CO 3 2- over other competitive anions. Interaction of CO 3 2- with the probe P4SC resulted in a significant increment in emission intensity at λ em = 498 nm (λ ex = 384 nm) due to the strategy of blocking the photo induced electron transfer (PET) mechanism. 1 H NMR titration and Job's methods, as well as the theoretical study were carried out to support the probable stoichiometry of the reaction (1:2) between P4SC and CO 3 2- . The binding constant of the probe P4SC with CO 3 2- was calculated as 2.56 × 10 10 M -2 . The probe P4SC providing rapid response time (~0.5 min) with a satisfactorily low detection limit (14.7 nM) may be useful as a valuable realistic sensor. The imaging studies on the liver cancer cells (HepG2) shows the great potential of the probe P4SC for the sensation of intracellular CO 3 2- anions. Furthermore, the satisfactory recovery and RSD values obtained for water application confirming that the probe P4SC could be applied to sensing of CO 3 2- ion.

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Enhancement of enzyme activities and VFA conversion by adding Fe/C in two-phase high-solid digestion of food waste: Performance and microbial community structure. Two-phase high-solid digestion is conducive to the degradation of food waste. In this study, Fe/C was added in high-solid digestion in different acidification and/or methanogenic phase. The experimental results indicated that it significantly increased the cumulative yield of biomethane. When Fe/C was added to the acidification phase only and both the acidification and methanogenic phases, the biomethane yield reached 474.07 ± 7.03 and 475.47 ± 4.68 mL·g VS -1 , respectively, and the biodegradation rate reached 87.30% and 87.58%, respectively, indicating that Fe/C had mainly effect on the performance of acidification phase. In a two-phase anaerobic fermentation system, the activity of dehydrogenases and the concentration of coenzyme F 420 were 2.23-2.95 mg·g -1 ·h -1 and 0.0063-0.0294 mol·g -1 volatile solids, respectively. Additionally, the archaeal communities production pathway of methane from using acetic acid to using hydrogen as the reactant.

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Framework for the environmental impact assessment of operational shipping. Shipping is an important source of pollution affecting both atmospheric and aquatic environments. To allow for efficient mitigation of environmental degradation, it is essential to know the extent of the impacts of shipping in relation to other sources of pollution. Here, we give a perspective on a holistic approach to studies of the environmental impacts of operational shipping through presentation of an assessment framework developed and applied on a case of shipping in the Baltic Sea. Through transfer of knowledge and concepts, previously used in assessments of air pollution, now applied to assessments of marine pollution and underwater noise, the horizon of understanding of shipping-related impacts is significantly improved. It identifies the main areas of environmental degradation caused by shipping and potential improvements through legislation and technological development. However, as the vast majority of contaminants discharged into the sea are not routinely monitored and assessed, the links between pressure of contaminants from shipping and environmental state and impacts will not be caught in the current environmental regulatory frameworks.

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Evaluating the quality of remote sensing products for agricultural index insurance. Agricultural index insurance contracts increasingly use remote sensing data to estimate losses and determine indemnity payouts. Index insurance contracts inevitably make errors, failing to detect losses that occur and issuing payments when no losses occur. The quality of these contracts and the indices on which they are based, need to be evaluated to assess their fitness as insurance, and to provide a guide to choosing the index that best protects the insured. In the remote sensing literature, indices are often evaluated with generic model evaluation statistics such as R2 or Root Mean Square Error that do not directly consider the effect of errors on the quality of the insurance contract. Economic analysis suggests using measures that capture the impact of insurance on the expected economic well-being of the insured. To bridge the gap between the remote sensing and economic perspectives, we adopt a standard economic measure of expected well-being and transform it into a Relative Insurance Benefit (RIB) metric. RIB expresses the welfare benefits derived from an index insurance contract relative to a hypothetical contract that perfectly measures losses. RIB takes on its maximal value of one when the index contract offers the same economic benefits as the perfect contract. When it achieves none of the benefits of insurance it takes on a value of zero, and becomes negative if the contract leaves the insured worse off than having no insurance. Part of our contribution is to decompose this economic well-being measure into an asymmetric loss function. We also argue that the expected well-being measure we use has advantages over other economic measures for the normative purpose of insurance quality ascertainment. Finally, we illustrate the use of the RIB measure with a case study of potential livestock insurance contracts in Northern Kenya. We compared 24 indices that were made with 4 different statistical models and 3 remote sensing data sources. RIB for these indices ranged from 0.09 to 0.5, and R2 ranged from 0.2 to 0.51. While RIB and R2 were correlated, the model with the highest RIB did not have the highest R2. Our findings suggest that, when designing and evaluating an index insurance program, it is useful to separately consider the quality of a remote sensing-based index with a metric like the RIB instead of a generic goodness-of-fit metric.

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Comparison of 10-Year Survival Outcomes for Early Single Hepatocellular Carcinoma following Different Treatments. To compare the actual 10-year survival outcomes of early single hepatocellular carcinoma (HCC) patients between 3 first-line treatments: radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT).

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A Critical Review on Transplacental Transfer of Per- and Polyfluoroalkyl Substances: Prenatal Exposure Levels, Characteristics, and Mechanisms. Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has aroused public concerns as it can pose multiple health threats to pregnant women and cause adverse birth outcomes for fetuses. In previous studies, the prenatal exposure levels and transplacental transfer efficiencies (TTE) of PFASs have been reported and discussed. Specifically, the binding affinities between PFASs and some transporters were determined, demonstrating that the TTE values of PFASs are highly dependent on their binding behaviors. To summarize primary findings of previous studies and propose potential guidance for future research, this article provides a systematic overview on levels and characteristics of prenatal exposure to PFASs worldwide, summarizes relationships between TTE values and structures of PFASs, and discusses possible transplacental transfer mechanisms, especially for the combination between PFASs and transporters. Given the critical roles of transporters in the transplacental transfer of PFASs, we conducted molecular docking to further clarify the binding behaviors between PFASs and the selected transporters. We proposed that the machine learning can be a superior method to predict and reveal behaviors and mechanisms of the transplacental transfer of PFASs. In total, this is the first review providing a comprehensive overview on the prenatal exposure levels and transplacental transfer mechanisms of PFASs.

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Predator-Prey Interactions in the Anthropocene: Reconciling Multiple Aspects of Novelty. Ecological novelty, when conditions deviate from a historical baseline, is increasingly common as humans modify habitats and communities across the globe. Our ability to anticipate how novelty changes predator-prey interactions will likely hinge upon the explicit evaluation of multiple forms of novelty, rather than a focus on single forms of novelty (e.g., invasive predators or climate change). We provide a framework to assess how multiple forms of novelty can act, alone or in concert, on components shared by all predator-prey interactions (the predation sequence). Considering how novelty acts throughout the predation sequence could improve our understanding of predator-prey interactions in an increasingly novel world, identify important knowledge gaps, and guide conservation decisions in the Anthropocene.

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Spinal cord infarction caused by extensive aortic intramural hematoma. We report the case of a 62-year-old Caucasian man, an ex-smoker, who presented to the emergency room complaining of intense lower back pain followed by immediate bilateral loss of inferior limbs motor function. Clinical examination showed complete paralysis and paranesthesia in both legs, while pain and temperature sensory examination revealed a sensory level at dermatome T6, with normal touch, vibration, and position senses. His blood pressure was 190∕100 mmHg. Computed tomography demonstrated dilated thoracic aorta (maximum diameter 44 mm) and abdominal aorta (maximum 58 mm), with extended intramural hematoma (IMH), thus establishing the diagnosis of type A aortic IMH complicated with paraplegia through spinal perfusion deficit. Due to the extension of the lesions, surgical intervention for aortic repair was considered at high risk while cerebrospinal fluid drainage was not recommended by the neurologist. The patient remained stable while hospitalized and was released from the hospital with mild improvement of neurological deficiencies.

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Dystonia is a Common Phenotypic Feature of MEGDEL Syndrome. In Response To: Giron C, Roze E, Degos, B, Méneret A, Jardel C, Lannuzel A, et al. Adult-onset generalized dystonia as the main manifestation of MEGDEL syndrome. Tremor Other Hyperkinet Mov. 2018; 8. doi: 10.7916/D8VM5VBQ.

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Hospital Enforcement of Early Cholecystectomy for Acute Cholecystitis. International guidelines state that early laparoscopic cholecystectomy (ELC) is appropriate for all severity grades of acute cholecystitis and leads to reduced hospital stays and costs. A multicenter prospective randomized controlled trial recommends ELC over delayed laparoscopic cholecystectomy (DLC) management because in addition to reduced hospital stays and costs, ELC also leads to reduced patient morbidity. Therefore, ELC is standard of care for acute cholecystitis. We hypothesize that 1) international guidelines are not presently followed and that 2) a quality improvement (QI) project enforcing ELC for acute cholecystitis will increase rates of ELC management. A retrospective chart review of all surgical consults for cholecystitis from January 2016 to December 2018 was undertaken. A total of 307 patients diagnosed with acute cholecystitis were included. ELC was defined as cholecystectomy within hospital admission. Pre-QI ELC versus DLC rates were 77.4 per cent (233/301) versus 22.6 per cent (68/301). Eight DLC patients (11.8%) returned to the ED after discharge secondary to persistent signs and symptoms of cholecystitis and 62.5 per cent (5/8) received an immediate cholecystectomy before their elective surgery date. After QI initiatives, ELC rates rose to 100 per cent (6/6). These data show there was a lack of consistent ELC management of acute cholecystitis.

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Glutathione-glutaredoxin is an efficient electron donor system for mammalian p53R2-R1-dependent ribonucleotide reductase. Deoxyribonucleotides are DNA building blocks and are produced de novo by reduction of ribose to deoxyribose. This reduction is catalyzed by ribonucleotide reductase (RNR), a heterodimeric tetramer enzyme in mammalian cells, having one of two free radical-containing subunits called R2 and p53R2. R2 is S-phase specific and used for DNA replication, whereas p53R2 functions in DNA repair and mitochondrial DNA synthesis. The larger RNR subunit, R1, has catalytically active cysteine thiols in its buried active site and a C-terminal swinging arm, with a Cys-Leu-Met-Cys sequence suggested to act as a shuttle dithiol/disulfide for electron transport. After each catalytic cycle the active site contains a disulfide, which has to be reduced for turnover. Thioredoxin (Trx) and glutaredoxin (Grx) systems have been implicated as electron donors for the RNR disulfide reduction via the swinging arm. Using mouse R1-R2 and R1-p53R2 complexes, we found here that the catalytic efficiency of the GSH-Grx system is 4-6 times higher than that of the Trx1 system. For both complexes, the V max values for Grx are strongly depended on GSH concentrations. The GSH disulfide resulting from the Grx reaction was reduced by NADPH and GSH reductase and this enzyme was essential because reaction with GSH alone yielded only little activity. These results indicate that C-terminal shuttle dithiols of mammalian R1 have a crucial catalytic role and that the GSH-Grx system favors the R1-p53R2 enzyme for DNA replication in hypoxic conditions, mitochondrial DNA synthesis, and in DNA repair outside the S-phase.

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Fañanas cells-the forgotten cerebellar glia cell type: Immunocytochemistry reveals two potassium channel-related polypeptides, Kv2.2 and Calsenilin (KChIP3) as potential marker proteins. For long times astrocytes had been regarded as supporting cells, passively filling the spaces between neuronal cell bodies and their extensions. Now it is known that astrocytes are actively involved in a variety of important biological functions such as regulating cerebral blood flow, supporting neuronal metabolism, controlling the extracellular potassium concentration, and clearing neurotransmitters from the extracellular space. In line with this multitude of tasks astrocytes display conspicuous functional and regional heterogeneity. Using three complementary labeling methods nine classes of astrocytes have been differentiated, which were termed protoplasmic, fibrous, velate, radial, and perivascular astrocytes in addition to Bergmann, marginal, and ependymal glial cells. To complete this list retinal Müller cells and a largely forgotten astrocytic cell type, the "feathered cell" of Fañanas need to be added. So far, Fañanas cells could be only recognized with the tedious gold-sublimate procedure. Consequently, data indicating a potential biological function are completely missing. In a parallel investigation we used a battery of antibodies against potassium channels and related proteins to identify potential marker proteins for the immunocytochemical visualization of distinct cell types in the cerebellar cortex. Here we present novel marker proteins, the Kv2.2 potassium channel and calsenilin, to visualize Fañanas cells in the cerebellar Purkinje cell layer. Such markers will allow to identify Fañanas cell subsequent to patching and electrophysiological characterization. This may pave the path to obtain new functional data, which may be helpful to understand the role of these enigmatic cells in normal biological function and disease.

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Simple laparoscopic repair of perforated peptic ulcer without omental patch. We evaluated the outcomes of laparoscopic repair of perforated peptic ulcers using simple closure only.

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Implementation of a Prevention Program Based on Adapted Physical Activity and Recommendations for Adolescents and Young Adults with Cancer: PREVAPAJA Study. Purpose: In Europe, 20,000 Adolescent and Young Adults (AYAs) aged 15-25 years are diagnosed with cancer annually. Although prognosis is good, AYA cancer survivors are at greater risk of second primary cancers, cardiovascular disease, and various long-term effects. Benefits of physical activity (PA) in AYAs reported in current studies remain difficult to generalize; none has been performed in France. This single-arm intervention study tested the feasibility of combining hospital-based supervised and home-based unsupervised physical activity sessions (PAS) and providing cancer prevention recommendations for AYAs. Methods: The AYAs attended PAS concomitant to treatment and participated in one face-to-face prevention interview. PA (international physical activity questionnaire), 6-min walk distance (6MWD), sedentarity, anthropometrics, quality of life (QoL), and fatigue were assessed at baseline (T1) and end of intervention (T2). PA, satisfaction and cancer prevention behaviors were assessed 1 year after baseline (T3). Results: Fifty-nine AYAs (mean 19 years) participated in the study. Acceptability and attrition were 80% and 12%, respectively. Between T1 and T2, 6MWD and global QoL improved ( p < 0.001), and fatigue decreased ( p = 0.003). Total PA improved and sitting time decreased ( p < 0.001) overall (T1-T3). Assessment at T3 showed interindividual differences in how participants considered risk factors (e.g., more attention to PA, UV exposures, nutrition). Conclusion: Combined supervised and unsupervised home-based PAS in AYAs undergoing cancer treatment is acceptable and feasible. The program contributes to maintaining and improving physical fitness and QoL, while reducing fatigue and other cancer and treatment symptoms. Larger randomized controlled trials are needed to confirm these results.

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Attenuation-based kV pair selection in dual source dual energy computed tomography angiography of the chest: impact on radiation dose and image quality. The purpose of this study was to evaluate the impact of attenuation-based kilovoltage (kV) pair selection in dual source dual energy (DSDE)-pulmonary embolism (PE) protocol examinations on radiation dose savings and image quality.

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Generating retinal flow maps from structural optical coherence tomography with artificial intelligence. Despite advances in artificial intelligence (AI), its application in medical imaging has been burdened and limited by expert-generated labels. We used images from optical coherence tomography angiography (OCTA), a relatively new imaging modality that measures retinal blood flow, to train an AI algorithm to generate flow maps from standard optical coherence tomography (OCT) images, exceeding the ability and bypassing the need for expert labeling. Deep learning was able to infer flow from single structural OCT images with similar fidelity to OCTA and significantly better than expert clinicians (P < 0.00001). Our model allows generating flow maps from large volumes of previously collected OCT data in existing clinical trials and clinical practice. This finding demonstrates a novel application of AI to medical imaging, whereby subtle regularities between different modalities are used to image the same body part and AI is used to generate detailed inferences of tissue function from structure imaging.

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Physical and emotional well-being and support in newly diagnosed head and neck cancer patient-caregiver dyads. The purpose of this study was to examine the physical and emotional well-being and social support in newly diagnosed head and neck cancer (HNC) patients and caregivers and identify sociodemographic, clinical, and behavioral risk factors associated with compromised well-being in patients and caregivers. Newly diagnosed HNC patients and their primary caregivers (N = 72 dyads) completed questionnaires before treatment assessing physical and mental well-being, depression, cancer worry, and open-ended support questions. Patients reported worse physical well-being than caregivers (p < 0.05) but similar levels of mental well-being. Caregivers reported providing emotional and instrumental support most frequently with an emphasis on nutrition and assistance with speech, appearance, and addictions. Both patients and their caregivers reported suboptimal mental well-being and depression. Smoking was associated with compromised well-being in patients, caregivers, and dyads. Compromised well-being in patients and their caregivers was more likely when patients were younger, had worse symptoms, and smoked/consumed alcohol (p < 0.05). While patients face more physical strain than caregivers, both equally confront emotional challenges. Results highlight risk factors for compromised well-being in both patients and their caregivers that should be assessed at diagnosis to guide identification of needed dyadic-focused supportive care resources.

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Predicting Oral Absorption of fenofibrate in Lipid-Based Drug Delivery Systems by Combining In Vitro Lipolysis with the Mucus-PVPA Permeability Model. The aim of this work was to develop a new in vitro lipolysis-permeation model to predict the in vivo absorption of fenofibrate in self-nanoemulsifying drug delivery systems (SNEDDSs). More specifically, the in vitro intestinal lipolysis model was combined with the mucus-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model. Biosimilar mucus (BM) was added to the surface of the PVPA barriers to closer simulate the intestinal mucosa. SNEDDSs for which pharmacokinetic data after oral dosing to rats was available in the literature were prepared, and the ability of the SNEDDSs to maintain fenofibrate solubilized during in vitro lipolysis was determined, followed by the assessment of drug permeation across the mucus-PVPA barriers. The amount of drug solubilized over time during in vitro lipolysis did not correlate with the AUC (area under the curve) of the plasma drug concentration curve. However, the AUC of the drug permeated after in vitro lipolysis displayed a good correlation with the in vivo AUC (R 2 > 0.9). Thus, it was concluded that the in vitro lipolysis-mucus-PVPA permeation model, simulating the physiological digestion and absorption processes, was able to predict in vivo absorption data, exhibiting great potential for further prediction of in vivo performance of SNEDDSs.

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Use of the Menstrual Cycle to Enhance Female Sports Performance and Decrease Sports-Related Injury. The impact of the menstrual cycle on female sports performance is a growing interest area in sports and athletics. In March 2017, the British Journal of Sports Medicine, published the article, "Sport, Exercise and the Menstrual Cycle: Where is the Research?", highlighting the significant under-representation of women included in sport and exercise medicine research studies. Dr. Georgie Bruinvels, a research scientist, is focused primarily on menstruation in female athletes and use of the menstrual cycle to optimize training and performance, while decreasing injury. Bruinvels, states, "There is a body of research emerging that highlights that strength training is more advantageous in the first half of the menstrual cycle because the body adapts and recovers better. Pediatric and Adolescent Gynecology has a place in this emerging interest area, given our level of expertise in menstruation, female physiology and the often-avoided female pubertal physiology.

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Serotonin augmentation therapy by escitalopram has minimal effects on amyloid-β levels in early-stage Alzheimer's-like disease in mice. Dysfunction of the serotonergic (5-HTergic) system has been implicated in the cognitive and behavioural symptoms of Alzheimer's disease (AD). Accumulation of toxic amyloid-β (Aβ) species is a hallmark of AD and an instigator of pathology. Serotonin (5-HT) augmentation therapy by treatment with selective serotonin reuptake inhibitors (SSRIs) in patients with AD has had mixed success in improving cognitive function, whereas SSRI administration to mice with AD-like disease has been shown to reduce Aβ pathology. The objective of this study was to investigate whether an increase in extracellular levels of 5-HT induced by chronic SSRI treatment reduces Aβ pathology and whether 5-HTergic deafferentation of the cerebral cortex could worsen Aβ pathology in the APP swe /PS1 ΔE9 (APP/PS1) mouse model of AD.

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Monitoring and adapting endurance training on the basis of heart rate variability monitored by wearable technologies: A systematic review with meta-analysis. To systematically perform a meta-analysis of the scientific literature to determine whether the outcomes of endurance training based on heart rate variability (HRV) are more favorable than those of predefined training.

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Shared yet dissociable neural codes across eye gaze, valence and expectation. The direction of the eye gaze of others is a prominent social cue in primates and is important for communication 1-11 . Although gaze can signal threat and elicit anxiety 6,12,13 , it remains unclear whether it shares neural circuitry with stimulus value. Notably, gaze not only has valence, but can also serve as a predictor of the outcome of a social encounter, which can be either negative or positive 2,8,12,13 . Here we show that the neural codes for gaze and valence overlap in primates and that they involve two different mechanisms: one for the outcome and another for its expectation. Monkeys participated in the human intruder test 13,14 , in which a human participant had either a direct or averted gaze, interleaved with blocks of aversive and appetitive conditioning. We find that single neurons in the amygdala encode gaze 15 , whereas neurons in the anterior cingulate cortex encode the social context 16 , but not gaze. We identify a shared population in the amygdala for which the neural responses to direct and averted gaze parallel the responses to aversive and appetitive stimulus, respectively. Furthermore, we distinguish between two neural mechanisms-an overall-activity scheme that is used for gaze and the unconditioned stimulus, and a correlated-selectivity scheme that is used for gaze and the conditioned stimulus. These findings provide insights into the origins of the neural mechanisms that underlie the computations of both social interactions and valence, and could help to shed light on mechanisms that underlie social anxiety and the comorbidity between anxiety and impaired social interactions.

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The relationship between intracranial pressure and neurocognitive function before and after the repair of a skull injury. This study examines the relationship between intracranial pressure (ICP) changes after skull injury repair and neurocognitive function before and after the repair.

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MicroRNA31 and MMP-1 contribute to the differentiated pathway of invasion -with enhanced epithelial-to-mesenchymal transition- in squamous cell carcinoma of the skin. Epithelial to mesenchymal transition (EMT) is an important mechanism of invasion in cutaneous squamous cell carcinomas (cSCCs) and has been found to be enhanced in tumors originated from actinic keratosis with transformation limited to the basal epithelial layer -differentiated pathway-, compared to cases with invasion subsequent to complete epidermal transformation -classical pathway-. Several microRNAs and proteins can contribute to EMT modulation in cSCCs. MicroRNA21 and microRNA31 are involved in posttranscriptional regulation of protein expression and could play a relevant role in EMT and cSCC progression. Throughout the EMT process upregulation of matrix metalloproteinases (MMPs) enhances invasiveness and MMP-1 and MMP-3 contribute to local invasion, angiogenesis and metastasis in cSCCs. Additionally, cSCC development is associated with PTEN loss and NF-κB, NOTCH-1 and p63 activation. The aim of this work is to identify differences in the expression of those molecules between both pathways of cSCCs development. Eight tissue microarrays from 80 consecutive cSCCs were analyzed using LNA-based miRNA in situ hybridization for miRNA21 and miRNA31 evaluation, and immunohistochemistry for MMP-1, MMP-3, PTEN, NOTCH-1, NF-κB, p63 and CD31. Significantly higher expression of miRNA31 (p < 0.0001) and MMP-1 (p = 0.0072) and angiogenesis (p = 0.0199) were found in the differentiated pathway, whereas PTEN loss (p = 0.0430) was more marked in the classical pathway. No significant differences were found for the other markers. Our findings support a contribution of miRNA31 and MMP-1 in the differentiated pathway, associated to EMT and increased microvascularization. The greater PTEN loss in the classical pathway indicate that its relevance in cSCC is not EMT-related.

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Animal board invited review: Animal source foods in healthy, sustainable, and ethical diets - An argument against drastic limitation of livestock in the food system. Animal source foods are evolutionarily appropriate foods for humans. It is therefore remarkable that they are now presented by some as unhealthy, unsustainable, and unethical, particularly in the urban West. The benefits of consuming them are nonetheless substantial, as they offer a wide spectrum of nutrients that are needed for cell and tissue development, function, and survival. They play a role in proper physical and cognitive development of infants, children, and adolescents, and help promote maintenance of physical function with ageing. While high-red meat consumption in the West is associated with several forms of chronic disease, these associations remain uncertain in other cultural contexts or when consumption is part of wholesome diets. Besides health concerns, there is also widespread anxiety about the environmental impacts of animal source foods. Although several production methods are detrimental (intensive cropping for feed, overgrazing, deforestation, water pollution, etc.) and require substantial mitigation, damaging impacts are not intrinsic to animal husbandry. When well-managed, livestock farming contributes to ecosystem management and soil health, while delivering high-quality foodstuffs through the upcycling of resources that are otherwise non-suitable for food production, making use of marginal land and inedible materials (forage, by-products, etc.), integrating livestock and crop farming where possible has the potential to benefit plant food production through enhanced nutrient recycling, while minimising external input needs such as fertilisers and pesticides. Moreover, the impacts on land use, water wastage, and greenhouse gas emissions are highly contextual, and their estimation is often erroneous due to a reductionist use of metrics. Similarly, whether animal husbandry is ethical or not depends on practical specificities, not on the fact that animals are involved. Such discussions also need to factor in that animal husbandry plays an important role in culture, societal well-being, food security, and the provision of livelihoods. We seize this opportunity to argue for less preconceived assumptions about alleged effects of animal source foods on the health of the planet and the humans and animals involved, for less top-down planning based on isolated metrics or (Western) technocratic perspectives, and for more holistic and circumstantial approaches to the food system.

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Anemic Women are More at Risk of Injectable Contraceptive Discontinuation due to Side Effects in Ethiopia. This paper investigates the importance of women's physiological condition, alongside sociocultural factors, for predicting the risk of discontinuation of the injectable contraceptive due to side effects in Ethiopia. Contraceptive calendar data from the 2016 Ethiopian Demographic and Health Survey were analyzed. Women aged 15-49 who had initiated the injectable contraceptive in the last two years were included in the analysis (n = 1,513). Physiological factors investigated were body mass, iron status, reproductive depletion, and physical strain. After checking for reverse causality, associations between physiological and sociocultural risk factors and discontinuation due to side effects (DSE) or discontinuation due to other reasons (DOR) were estimated using multivariate Cox proportional regression analyses. Anemia status was associated with DSE, but not DOR. Anemic women were two times more at risk of DSE compared with nonanemic women (adjusted hazard ratios [aHR] = 2.38, confidence interval [CI] = 1.41-4.00). DOR was predicted by religion, wealth, and relationship status. Accounting for diversity in physiological condition is key for understanding contraceptive discontinuation due to side effects. To reduce side effects, family planning programs might benefit from providing hormonal contraception within an integrated package addressing anemia.

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Biosynthesis pathways and strategies for improving 3-hydroxypropionic acid production in bacteria. 3-Hydroxypropionic acid (3-HP) represents an economically important platform compound from which a panel of bulk chemicals can be derived. Compared with petroleum-dependent chemical synthesis, bioproduction of 3-HP has attracted more attention due to utilization of renewable biomass. This review outlines bacterial production of 3-HP, covering aspects of host strains (e.g., Escherichia coli and Klebsiella pneumoniae), metabolic pathways, key enzymes, and hurdles hindering high-level production. Inspired by the state-of-the-art advances in metabolic engineering and synthetic biology, we come up with protocols to overcome the hurdles constraining 3-HP production. The protocols range from rewiring of metabolic networks, alleviation of metabolite toxicity, to dynamic control of cell size and density. Especially, this review highlights the substantial contribution of microbial growth to 3-HP production, as we recognize the synchronization between cell growth and 3-HP formation. Accordingly, we summarize the following growth-promoting strategies: (i) optimization of fermentation conditions; (ii) construction of gene circuits to alleviate feedback inhibition; (iii) recruitment of RNA polymerases to overexpress key enzymes which in turn boost cell growth and 3-HP production. Lastly, we propose metabolic engineering approaches to simplify downstream separation and purification. Overall, this review aims to portray a picture of bacterial production of 3-HP.

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Effects of water stably-enriched with oxygen as a novel method of tissue oxygenation on mitochondrial function, and as adjuvant therapy for type 2 diabetes in a randomized placebo-controlled trial. Diabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans.

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Methodological tools to study species of the genus Burkholderia. Bacteria belonging to the Burkholderia genus are extremely versatile and diverse. They can be environmental isolates, opportunistic pathogens in cystic fibrosis, immunocompromised or chronic granulomatous disease patients, or cause disease in healthy people (e.g., Burkholderia pseudomallei) or animals (as in the case of Burkholderia mallei). Since the genus was separated from the Pseudomonas one in the 1990s, the methodological tools to study and characterize these bacteria are evolving fast. Here we reviewed the techniques used in the last few years to update the taxonomy of the genus, to study gene functions and regulations, to deepen the knowledge on the drug resistance which characterizes these bacteria, and to elucidate their mechanisms to establish infections. The availability of these tools significantly impacts the quality of research on Burkholderia and the choice of the most appropriated is fundamental for a precise characterization of the species of interest.Key points• Updated techniques to study the genus Burkholderia were reviewed.• Taxonomy, genomics, assays, and animal models were described.• A comprehensive overview on recent advances in Burkholderia studies was made.

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The Evolving Role of Public Health in Medical Education. Medical education in the twentieth century was largely influenced by the Flexner Report, with significant proportions of instruction dedicated to the molecular underpinnings of the pathologic pathways and minimal mention of the socio-ecological determinants of health. When examining the predominant diseases of the twenty first century landscape, widening health disparities, and significant changes in the United States healthcare system, it is imperative to view wellness and sickness in a broader public health context rather than a singular focus of the biomedical model. While undergraduate opportunities to study public health are on the rise in the United States, there is a parallel urgency for medical curricula to recognize the importance of the complex interrelated socio-ecological root causes of health, well-being, and illness. In order to reduce the risk of non-communicable diseases and increase health equity, it is necessary for medical education to integrate core public health knowledge and competencies. Contemporary health challenges require a public health approach, in addition to clinical skills, for physicians to provide equitable care. The COVID-19 pandemic further underscores the necessity to mitigate the effects of socio-ecological determinants of health. Seven key recommendations are presented from a training to practice timeline emphasizing the important linkages between medical education, socio-ecological influences on health, and public health. As the health challenges in society and communities shift, so too must training of future physicians. There is a need and an opportunity for medicine and public health to address the shared health challenges of our global society.

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Validation of ICD-10 codes shows intracranial venous thrombosis incidence to be higher than previously reported. Intracranial venous thrombosis (ICVT) accounts for around 0.5% of all stroke cases. There have been no previously published studies of the International Classification of Diseases, Tenth Edition (ICD-10) validation for the identification of ICVT admissions in adults.

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A comprehensive analysis of the Lactuca sativa, L. transcriptome during different stages of the compatible interaction with Rhizoctonia solani. The leafy green vegetable Lactuca sativa, L. is susceptible to the soil-born fungus Rhizoctonia solani AG1-IB. In a previous study, we reported on the transcriptional response of R. solani AG1-IB (isolate 7/3/14) during the interspecies interaction with L. sativa cv. Tizian by means of RNA sequencing. Here we present the L. sativa transcriptome and metabolome from the same experimental approach. Three distinct interaction zones were sampled and compared to a blank (non-inoculated) sample: symptomless zone 1, zone 2 showing light brown discoloration, and a dark brown zone 3 characterized by necrotic lesions. Throughout the interaction, we observed a massive reprogramming of the L. sativa transcriptome, with 9231 unique genes matching the threshold criteria for differential expression. The lettuce transcriptome of the light brown zone 2 presents the most dissimilar profile compared to the uninoculated zone 4, marking the main stage of interaction. Transcripts putatively encoding several essential proteins that are involved in maintaining jasmonic acid and auxin homeostasis were found to be negatively regulated. These and other indicator transcripts mark a potentially inadequate defence response, leading to a compatible interaction. KEGG pathway mapping and GC-MS metabolome data revealed large changes in amino acid, lignin and hemicellulose related pathways and related metabolites.

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COMPLEX CHEST WALL DEFORMITY CAUSING CARDIAC ARREST: A PECULIAR PEDIATRIC CASE. Congenital chest wall deformities are common in children, causing self and parental concern mainly due to cosmesis. These defects rarely cause severe symptoms in patients.

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New answers to the old RIDDLE: RNF168 and the DNA damage response pathway. The chromatin-based DNA damage response pathway is tightly orchestrated by histone post-translational modifications, including histone H2A ubiquitination. Ubiquitination plays an integral role in regulating cellular processes including DNA damage signaling and repair. The ubiquitin E3 ligase RNF168 is essential in assembling a cohort of DNA repair proteins at the damaged chromatin via its enzymatic activity. RNF168 ubiquitinates histone H2A(X) at the N terminus and generates a specific docking scaffold for ubiquitin-binding motif-containing proteins. The regulation of RNF168 at damaged chromatin and the mechanistic implication in the recruitment of DNA repair proteins to the damaged sites remain an area of active investigation. Here, we review the function and regulation of RNF168 in the context of ubiquitin-mediated DNA damage signaling and repair. We will also discuss the unanswered questions that require further investigation and how understanding RNF168 targeting specificity could benefit the therapeutic development for cancer treatment.

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Designing Ecological Security Patterns Based on the Framework of Ecological Quality and Ecological Sensitivity: A Case Study of Jianghan Plain, China. Researchers and managers of natural resource conservation have increasingly emphasized the importance of maintaining a connected network of important ecological patches to mitigate landscape fragmentation, reduce the decline of biodiversity, and sustain ecological services. This research aimed to guide landscape management and decision-making by developing an evaluation framework to construct ecological security patterns. Taking the Jianghan Plain as the study area, we identified key ecological sources by overlaying the spatial patterns of ecological quality (biodiversity, carbon storage, and water yield) and ecological sensitivity (habitat sensitivity, soil erosion sensitivity, and water sensitivity) using the Integrated Valuation of Environmental Services and Tradeoffs (InVEST) model and the Chinese Soil Loss Equation Function. Ecological corridors were obtained by the least-cost path analysis method and circuit theory. A total of 48 ecological sources (3812.95 km 2 ), primarily consisting of water area, forestland, and cropland, were identified. Ninety-one ecological corridors were derived, with a total length of 2036.28 km. Forty barriers and 40 pinch points with the highest improvement coefficient scores or priority scores were selected. There were 11 priority corridors with very high levels of connectivity improvement potential and conservation priority, occupying 16.15% of the total length of corridors. The overall potential for ecological connectivity is high on the Jianghan Plain. Our framework offers a valuable reference for constructing ecological security patterns and identifying sites for ecological restoration at the regional scale.

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The Impact of Sex on Strength Training in Adults With Cardiovascular Disease. Cardiovascular disease (CVD) is the leading killer of American males and females. Outcomes of treatment for CVD have historically been worse in females than in males. The inability to recover, may be, at least in part, due to lower levels of skeletal muscle mass in females; which is made worse with the onset of menopause and especially when a catabolic event like surgery and / or illness occurs. We theorize that while regaining cardiorespiratory fitness (CRF) after treatment for CVD is very important, it is only part of what is required for complete recovery. Regaining strength and muscle mass is just as important for healthy physiologic aging and recovery from illness. We outline a simply strategy for helping males and females train for strength while recovering from CVD.

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Cephalic muscle development in the Australian lungfish, Neoceratodus forsteri. Lungfishes are the extant sister group of tetrapods. As such, they are important for the study of evolutionary processes involved in the water to land transition of vertebrates. The evolution of a true neck, that is, the complete separation of the pectoral girdle from the cranium, is one of the most intriguing morphological transitions known among vertebrates. Other salient changes involve new adaptations for terrestrial feeding, which involves both the cranium and its associated musculature. Historically, the cranium has been extensively investigated, but the development of the cranial muscles much less so. Here, we present a detailed study of cephalic muscle development in the Australian lungfish, Neoceratodus forsteri, which is considered to be the sister taxon to all other extant lungfishes. Neoceratodus shows several developmental patterns previously described in other taxa; the tendency of muscles to develop from anterior to posterior, from their region of origin toward insertion, and from lateral to ventral/medial (outside-in), at least in the branchial arches. The m.protractor pectoralis appears to develop as an extension of the most posterior m.levatores arcuum branchialium, supporting the hypothesis that the m.cucullaris and its derivatives (protractor pectoralis, levatores arcuum branchialium) are branchial muscles. We present a new hypothesis regarding the homology of the ventral branchial arch muscles (subarcualis recti and obliqui, transversi ventrales) in lungfishes and amphibians. Moreover, the morphology and development of the cephalic muscles confirms that extant lungfishes are neotenic and have been strongly influenced via paedomorphosis during their evolutionary history.

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Integrating Genomics Into Management of Fibrotic Interstitial Lung Disease. Fibrotic interstitial lung diseases (ILDs) have a high mortality rate with an unpredictable disease course and clinical features that frequently overlap. Recent data indicate important roles for genomics in the mechanisms underlying susceptibility and progression of pulmonary fibrosis. The impact of these genomic markers on pharmacotherapy and their contribution to outcomes is increasingly recognized. Interstitial lung abnormalities, frequently considered representative of early ILD, have been consistently associated with the MUC5B promoter polymorphism, a common gene variant. Other rare gene variant mutations, including TERT, TERC, SFTPC, and DKC1, may be present in patients with familial interstitial pneumonia and are frequently associated with a usual interstitial pneumonia pattern of fibrosis. The minor allele of the MUC5B rs35705950 genotype is prevalent in several sporadic forms of ILD, including idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. Gene mutations that characterize familial pulmonary fibrosis may be present in patients with connective tissue disease-related ILD, such as rheumatoid arthritis-ILD. Additionally, shorter telomere lengths and mutations in telomere biology-related genes have been demonstrated in both familial and sporadic ILD, with significant implications for disease progression, lung function, and survival. An improved understanding of the impact of genetic and genomic risk factors on disease progression would better guide personalized therapeutic choices in persons with fibrotic ILD.

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COVID-19 Suspected myopericarditis without pulmonary involvement. Myopericarditis is a rare consequence of COVID-19 infection. Although extremely rare, COVID-19 can present without pulmonary involvement, and there have been reports of isolated cardiac involvement in one prior case We report a case of a young African American man presenting with myopericarditis following a recently recovered COVID-19 infection. Complicated by ICU admission requiring vasopressors; with eventual resolution following initiation of aspirin and colchicine for myopericarditis. Life threatening myopericarditis can occur following resolution of COVID-19 disease. The degree of cardiac involvement correlates poorly to the severity of pulmonary involvement.

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Part by Part: Synthetic Biology Parts Used in Solventogenic Clostridia. The solventogenic Clostridia are of interest to the chemical industry because of their natural ability to produce chemicals such as butanol, acetone and ethanol from diverse feedstocks. Their use as whole cell factories presents multiple metabolic engineering targets that could lead to improved sustainability and profitability of Clostridium industrial processes. However, engineering efforts have been held back by the scarcity of genetic and synthetic biology tools. Over the past decade, genetic tools to enable transformation and chromosomal modifications have been developed, but the lack of a broad palette of synthetic biology parts remains one of the last obstacles to the rapid engineered improvement of these species for bioproduction. We have systematically reviewed existing parts that have been used in the modification of solventogenic Clostridia, revealing a narrow range of empirically chosen and nonengineered parts that are in current use. The analysis uncovers elements, such as promoters, transcriptional terminators and ribosome binding sites where increased fundamental knowledge is needed for their reliable use in different applications. Together, the review provides the most comprehensive list of parts used and also presents areas where an improved toolbox is needed for full exploitation of these industrially important bacteria.

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The Pharmaceutical Industry in 2021. An Analysis of FDA Drug Approvals from the Perspective of Molecules. Similar to last year, 2021 will be remembered for the COVID-19 pandemic. Although five vaccines have been approved by the two most important drug regulatory agencies, namely the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the pandemic has still not been brought under control. However, despite the context of a global pandemic, 2021 has been an excellent year with respect to drug approvals by the FDA. In 2021, 50 drugs have been authorized, making it the fourth-best year after 2018 (59 drugs) and 1996 and 2020 (53 each). Regarding biologics, 2021 has been the third-best year to date, with 14 approvals, and it has also witnessed the authorization of 36 small molecules. Of note, nine peptides, eight monoclonal antibodies, two antibody-drug conjugates, and two oligonucleotides have been approved this year. From them, five of the molecules are pegylated and three of them highly pegylated. The presence of nitrogen aromatic heterocycles and/or fluorine atoms are once again predominant among the so-called small molecules. This report analyzes the 50 new drugs approved in 2021 from a chemical perspective, as it did for those authorized in the previous five years. On the basis of chemical structure alone, the drugs that received approval in 2021 are classified as the following: biologics (antibodies, antibody-drug conjugates, enzymes, and pegylated proteins); TIDES (peptide and oligonucleotides); combined drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

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Polyglutamine-Related Aggregates Can Serve as a Potent Antigen Source for Cross-Presentation by Dendritic Cells. Protective MHC class I-dependent immune responses require an overlap between repertoires of proteins directly presented on target cells and cross-presented by professional APC, specifically dendritic cells. How stable proteins that rely on defective ribosomal proteins for direct presentation are captured for cell-to-cell transfer remains enigmatic. In this study, we address this issue using a combination of in vitro (C57BL/6-derived mouse cell lines) and in vivo (C57BL/6 mouse strains) approaches involving stable and unstable versions of OVA model Ags displaying defective ribosomal protein-dependent and -independent Ag presentation, respectively. Apoptosis, but not necrosis, of donor cells was found associated with robust global protein aggregate formation and captured stable proteins permissive for cross-presentation. Potency of aggregates to serve as Ag source was directly demonstrated using polyglutamine-equipped model substrates. Collectively, our data implicate global protein aggregation in apoptotic cells as a mechanism that ensures the overlap between MHC class I epitopes presented directly or cross-presented by APC and demonstrate the unusual ability of dendritic cells to process stable protein aggregates.

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An analysis of the radiological factors associated with respiratory failure in COVID-19 pneumonia and the CT features among different age categories. To investigate CT patterns of COVID-19 pneumonia associated with respiratory failure (RF) focused on the distribution of lesions.

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Prevalence of COVID-19 Mimics in the Emergency Department. Objective Due to the lack of specific clinical manifestations and symptoms, it is difficult to distinguish COVID-19 from mimics. A common pitfall is to rush to make a diagnosis when encountering a patient with COVID-19-like symptoms. The present study describes a series of COVID-19 mimics using an outpatient database collected from a designated COVID-19 healthcare facility in Tokyo, Japan. Methods We established an emergency room (ER) tailored specifically for patients with suspected or confirmed COVID-19 called the "COVID-ER." In this single-center retrospective cohort study, we enrolled patients who visited the COVID-ER from February 1 to September 5, 2020. The outcomes included the prevalence of COVID-19, admission, potentially fatal diseases and final diagnosis. Results We identified 2,555 eligible patients. The median age was 38 (interquartile range, 26-57) years old. During the study period, the prevalence of COVID-19 was 17.9% (457/2,555). Non-COVID-19 diagnoses accounted for 82.1% of all cases. The common cold had the highest prevalence and accounted for 33.0% of all final diagnoses, followed by gastroenteritis (9.4%), urinary tract infections (3.8%), tonsillitis (2.9%), heat stroke (2.6%) and bacterial pneumonia (2.1%). The prevalence of potentially fatal diseases was 14.2% (298/2,098) among non-COVID-19 patients. Conclusion Several potentially fatal diseases remain masked among the wave of COVID-19 mimics. It is imperative that a thorough differential diagnostic panel be considered prior to the rendering of a COVID-19 diagnosis.

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Comparison of appendicular lean mass indices for predicting physical performance in Korean hemodialysis patients: A cross-sectional study. Few studies have examined the optimal adjustment indices for predicting low muscle strength or physical performance in hemodialysis (HD) patients. Thus, the present study aimed to identify optimal adjustment indices for predicting strength and/or physical performance in HD patients.Our study was performed at an HD center (n = 84). Appendicular lean mass (ALM; kg) was calculated using dual-energy X-ray absorptiometry. ALM were adjusted to body weight, height2 (Ht2), body surface area, or body mass index. Physical performance tests (sit-to-stand test performed 5 times test, sit-to-stand for 30 second test, 6-minute walk test, timed up and go test, gait speed, hand grip strength, average steps per day (AST), and short physical performance battery) were also evaluated. Participants with a below median value for each physical performance test were defined as the low group.The mean participant age was 55.6 ± 12.8 years; 44 (52.4%) were men. The univariate analysis revealed a significant difference in ALM/Ht2 values between the low and normal physical performance group in all physical performance tests except short physical performance battery. The multivariate analysis revealed a significant difference in ALM/Ht2 between the low and normal physical performance groups in hand grip strength, 5 times sit-to-stand test, sit-to-stand for 30-second test, and AST. In women on HD, most indices were not associated with physical performance or strength.We demonstrated that, in men on HD, ALM/Ht2 may be the most valuable among various variables adjusted for ALM for predicting physical performance or strength.

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The budget impact of adding pralsetinib to a US health plan formulary for treatment of non-small cell lung cancer and thyroid cancer with RET alterations. BACKGROUND: Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung cancer (NSCLC) accounts for 80% to 85% of all lung cancers. Thyroid cancer, while generally not as lethal as lung cancer, has a large prevalent population and a rapidly increasing incidence in the United States. Pralsetinib is a highly potent, selective rearranged during transfection ( RET ) inhibitor indicated for the treatment of RET -positive NSCLC and thyroid cancer tumors. OBJECTIVE: To estimate the budget impact of adding pralsetinib to a 1 million-member US health plan formulary for the treatment of patients with metastatic RET fusion-positive NSCLC, advanced or metastatic RET -mutant medullary thyroid cancer (MTC), or advanced or metastatic RET fusion-positive thyroid cancer (non-MTC). METHODS: A budget impact model with a 3-year time horizon was developed in Microsoft Excel to estimate the number of eligible RET -positive NSCLC and thyroid cancer patients in a plan and quantify associated treatment costs (2020 USD). Comparators in the analyses included pralsetinib, selpercatinib, and cabozantinib, as well as indication-specific use of pembrolizumab, pemetrexed/carboplatin combination, vandetanib, lenvatinib, and sorafenib. Drug acquisition, molecular testing, treatment monitoring, and adverse event management costs were included to estimate total annual costs and per-member per-month (PMPM) costs in current (without pralsetinib) and potential future market scenarios, where pralsetinib is assumed to split the projected RET inhibitor market share with selpercatinib. The number of treated patients was based on age- and sex-adjusted incidence of disease, the proportion of patients diagnosed with advanced or metastatic disease, and projected RET testing rates. Treatment duration was based on progression-free survival or duration of response data from clinical trials. Medical resources were monetized using standardized sources such as Medicare reimbursement and wholesale acquisition cost (WAC). RESULTS: The model estimated that there would be approximately 6 new treatment-eligible patients in a 1 million-member plan annually. Monthly WAC is $19,243 for pralsetinib and $20,600 for selpercatinib at the recommended starting dose. Adoption of pralsetinib, with corresponding increases in pralsetinib market share, would be slightly cost saving to a payer, decreasing the overall budget impact to the health plan by $49,985 in year 3 (-$0.0042 PMPM; -$0.0030, -$0.0006, and -$0.0005 for NSCLC, MTC, and thyroid cancer [non-MTC], respectively). In year 3, drug costs were the key driver of total costs (~80%-98%) and cost savings. All other medical resource categories were cost-neutral or nominally cost saving or additive in the budget impact analysis. CONCLUSIONS: Quantifying the budget impact associated with the adoption of new targeted precision therapies is an important consideration for payers. For eligible NSCLC and thyroid cancer patients, our analysis suggests that adoption of pralsetinib is expected to result in modest cost savings for US payers. DISCLOSURES: Support for this study was provided by Blueprint Medicines Corporation. This study was conducted by Veritas Health Economics Consulting, Inc., in collaboration with Blueprint Medicines, which was involved in the design of the study; collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the report for publication. Duff is an employee of Veritas Health Economics Consulting, which received research funding from Blueprint Medicines to develop the budget impact model. Norregaard and Sullivan are employees of Blueprint Medicines. Bargiacchi and Brener were employees of Blueprint Medicines at the time of the research study. This study was presented as a poster at the AMCP Virtual Learning Event, April 2021.

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A reliable and easy to transport quality control method for chlamydia and gonorrhoea molecular point of care testing. Quality control (QC) is an essential component of point-of-care testing programs. In the context of a randomised-controlled trial (TTANGO) using GeneXpert (Xpert) Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG) point-of-care testing in remote areas of Australia, we aimed to develop and utilise a stable positive control material. Bacterial cultures of CT and NG were resuspended together to provide cycle threshold (C t ) values of approximately 25 cycles for both CT and NG when tested on the Xpert CT/NG assay. These positive control suspensions were dried in aliquots, heat inactivated, and then provided to 12 participating health services as research-only QC samples in kit form. At each service, a QC sample was resuspended and tested each month on the Xpert. QC results, including Xpert C t values, were analysed from each site over 30 months and we calculated costs per QC sample. Overall, at 12 health services there were 89 QC samples tested (average of 8 tests per site per year). Mean C t values for the 89 controls samples were 25.25 cycles (SD = 1.15) for CT, 24.04 cycles (SD = 1.400) for one NG target and 23.35 cycles (SD = 1.55) for the other NG target. No significant differences in C t value for CT or NG controls were observed over a trial period of 30 months. Positive QC samples for research use in a trial of a molecular point-of-care assay were inexpensive to produce and stable when stored at 2-8°C. For routine use, additional requirements such as meeting National Association of Testing Authority (NATA) regulations and Therapeutic Goods Administration (TGA) approval will need to be achieved.

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Experience with thoracic endovascular aortic repair applied in treating Stanford type B aortic dissection: An analysis of 98 cases. Thoracic endovascular aortic repair (TEVAR) has been frequently applied in Stanford type B aortic dissection since thoracic aortic diseases were first treated with artificial vessels.

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Discovery of BP3 as an efficacious proteolysis targeting chimera (PROTAC) degrader of HSP90 for treating breast cancer. Heat shock protein 90 (HSP90) is involved in the stabilization and activation of oncoproteins, rendering it essential for oncogenic transformation. However, the HSP90 inhibitors evaluated to date have not led to the expected effects in cancer therapy. Herein, we systematically described the design, synthesis, and evaluation of HSP90 degraders based upon the proteolysis-targeting chimera (PROTAC) strategy. The results showed that the candidate compound 16b (BP3) potently degraded HSP90 and effectively inhibited the growth of human breast cancer cells. When used as a single agent, BP3 led to effective tumor suppression in mice. These findings demonstrate that our HSP90-targeting PROTAC strategy has potential novel applications in breast cancer therapy.

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The Contribution of Psychosocial Interventions to Precision Medicine for Heart Health. This paper reviews the value of incorporating psychosocial interventions into precision medicine for heart health. First, we review the empirical literature on prevalence of common mental health comorbidities among individuals with cardiovascular disease (CVD). We then review transdiagnostic approaches for conceptualization and treatment of mental health in individuals with CVD. We highlight recent studies that have used novel methods to individualize psychosocial interventions. Finally, we propose a preliminary framework intended to support Health Care Providers in individualizing treatment, which includes: 1) assessment of patient risk factors, characteristics, and expectations; 2) consideration of transdiagnostic processes underlying several psychiatric symptoms that contribute to CVD risk; 3) patient engagement in shared decision-making for psychosocial treatment; and 4) ongoing outcome monitoring to evaluate treatment responsiveness. We anticipate that the proposed framework will evolve with the emergence of new empirical evidence; as such, future directions and challenges for research are discussed.

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Forces controlling organ growth and size. One of the fundamental questions in developmental biology is what determines the final size and shape of an organ. Recent research strongly emphasizes that besides cell-cell communication, biophysical principals govern organ development. The architecture and mechanics of a tissue guide cellular processes such as movement, growth or differentiation. Furthermore, mechanical cues do not only regulate processes at a cellular level but also provide constant feedback about size and shape on a tissue scale. Here we review several models and experimental systems which are contributing to our understanding of the roles mechanical forces play during organ development. One of the best understood processes is how the remodeling of bones is driven by mechanical load. Culture systems of single cells and of cellular monolayers provide further insights into the growth promoting capacity of mechanical cues. We focus on the Drosophila wing imaginal disc, a well-established model system for growth regulation. We discuss theoretical models that invoke mechanical feedback loops for growth regulation and experimental studies providing empirical support. Future progress in this exciting field will require the development of new tools to precisely measure and modify forces in living tissue systems.

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Targeting Metabolism as a Novel Therapeutic Approach to Autoimmunity, Inflammation, and Transplantation. Immune cell activation and differentiation occurs concurrently with metabolic reprogramming. This ensures that activated cells generate the energy and substrates necessary to perform their specified function. Likewise, the metabolic programs among different cells of the immune system vary. By targeting different metabolic pathways, these differences allow for selective regulation of immune responses. Further, the relative susceptibility of cells to a metabolic inhibitor is dictated by their metabolic demands; cellular selectivity is based on demand. Therefore, where differences exist in metabolic pathways between healthy and pathogenic cells, there is opportunity for selective regulation with agents lacking intrinsic specificity. There are now a host of studies demonstrating how inhibitors of metabolism (e.g., glycolysis, glutamine metabolism, and fatty acid oxidation) can regulate immune responses and treat immune-mediated pathogenesis. In this brief review we detail how inhibitors of metabolism can be employed to regulate immune responses in both autoimmunity and transplantation.

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Tbx18-positive cells differentiated from murine ES cells serve as proepicardial progenitors to give rise to vascular smooth muscle cells and fibroblasts. Proepicardium (PE) cells generate cardiac fibroblasts, smooth muscle cells (SMCs) and endothelial cells that form coronary arteries. T-box18 (Tbx18) is a well-known marker of PE cells and epicardium. We examined whether Tbx18-positive cells differentiated from murine embryonic stem (ES) cells serve as PE progenitors to give rise to vascular SMCs and fibroblasts. To collect Tbx18-positive cells, we established Tbx18-EGFP knock-in mouse ES cells using the CRISPR/Cas9 system. We harvested the Tbx18-EGFP-positive cells on day 8, 10 and 14 after the initiation of differentiation; Tbx18 mRNA was enriched on day 8 to 14 and Snai2 mRNA was enriched on day 8 and 10, indicating successful collection of Tbx18-positive cells. Tbx18-EGFP-positive cells expressed the PE marker WT1 on day 8 and 10. They also expressed the SMC marker Acta2 and fibroblast markers Thy1 and Fsp1 on day 8 to 14, but did not express the endothelial cell marker PECAM or the cardiac cell marker CD166 or Myh7. In conclusion, Tbx18-positive cells represent a part of PE cells in the initial phase of differentiation and subsequently include SMCs as well as fibroblasts. These results indicate that Tbx18-positive cells serve as a PE progenitor to supply a variety of cells that contribute to the formation of coronary arteries.

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Association between type 2 diabetes status and osteoarthritis in adults aged ≥ 50 years. Increasingly, studies have addressed the possible association between type 2 diabetes mellitus (T2DM) and osteoarthritis (OA), although this remains an issue of controversy. Our aim in this study was to investigate the association between T2DM and OA among 7781 adults ≥50 years of age, through a cross-sectional analysis of the National Health and Nutrition Examination Survey from 2011 through 2018.

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Urinary proteomics to diagnose chronic active antibody-mediated rejection in pediatric kidney transplantation - a pilot study. Chronic antibody-mediated rejection (cABMR) is the main cause of long-term renal graft loss. Late-stage diagnosis is made by detecting donor-specific antibodies (DSA) in blood combined with typical histomorphological lesions in renal allografts. There is a need for noninvasive biomarkers for cABMR that might permit screening and earlier diagnosis. In a case control study of 24 pediatric renal transplant recipients, urine samples were analyzed using capillary electrophoresis and mass spectrometry. Patients were matched with 36 pediatric renal transplant patients without cABMR. Statistical analysis used the nonparametric Wilcoxon test to identify 79 significant biomarkers, which were combined to a support vector machine-based classifier. After validation in an independent test cohort of eight pediatric patients with and 12 without cABMR, the area under the receiver operating characteristic (ROC) curve (AUC) for detection of cABMR was 0.92 (95% CI 0.71-0.99) with a sensitivity of 100% (95% CI 63-100%) and a specificity of 75% (95% CI 43-95%). Combining this classifier with the urinary proteomic marker CKD273 improved the detection of patients with cABMR with misclassification in only 2/20 of the patients. These data indicate that a biomarker pattern derived from urinary proteomics allows the detection of cABMR in pediatric renal transplant recipients with high sensitivity and moderate specificity.

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SeedVicious: Analysis of microRNA target and near-target sites. Here I describe seedVicious, a versatile microRNA target site prediction software that can be easily fitted into annotation pipelines and run over custom datasets. SeedVicious finds microRNA canonical sites plus other, less efficient, target sites. Among other novel features, seedVicious can compute evolutionary gains/losses of target sites using maximum parsimony, and also detect near-target sites, which have one nucleotide different from a canonical site. Near-target sites are important to study population variation in microRNA regulation. Some analyses suggest that near-target sites may also be functional sites, although there is no conclusive evidence for that, and they may actually be target alleles segregating in a population. SeedVicious does not aim to outperform but to complement existing microRNA prediction tools. For instance, the precision of TargetScan is almost doubled (from 11% to ~20%) when we filter predictions by the distance between target sites using this program. Interestingly, two adjacent canonical target sites are more likely to be present in bona fide target transcripts than pairs of target sites at slightly longer distances. The software is written in Perl and runs on 64-bit Unix computers (Linux and MacOS X). Users with no computing experience can also run the program in a dedicated web-server by uploading custom data, or browse pre-computed predictions. SeedVicious and its associated web-server and database (SeedBank) are distributed under the GPL/GNU license.

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Title/Abstract stringlengths 12 94.8k	T001 int64 0 1	T007 int64 0 1	T008 int64 0 1	T023 int64 0 1	T026 int64 0 1	T028 int64 0 1	T032 int64 0 1	T033 int64 0 1	T037 int64 0 1	T039 int64 0 1	T040 int64 0 1	T041 int64 0 1	T042 int64 0 1	T043 int64 0 1	T044 int64 0 1	T045 int64 0 1	T046 int64 0 1	T047 int64 0 1	T048 int64 0 1	T049 int64 0 1	T050 int64 0 1	T054 int64 0 1	T055 int64 0 1	T057 int64 0 1	T058 int64 0 1	T059 int64 0 1	T060 int64 0 1	T061 int64 0 1	T062 int64 0 1	T063 int64 0 1	T064 int64 0 1	T065 int64 0 1	T066 int64 0 1	T067 int64 0 1	T069 int64 0 1	T070 int64 0 1	T073 int64 0 1	T074 int64 0 1	T075 int64 0 1	T078 int64 0 1	T079 int64 0 1	T080 int64 0 1	T081 int64 0 1	T082 int64 0 1	T086 int64 0 1	T090 int64 0 1	T091 int64 0 1	T093 int64 0 1	T101 int64 0 1	T109 int64 0 1	T114 int64 0 1	T116 int64 0 1	T121 int64 0 1	T122 int64 0 1	T123 int64 0 1	T126 int64 0 1	T130 int64 0 1	T167 int64 0 1	T168 int64 0 1	T169 int64 0 1	T170 int64 0 1	T184 int64 0 1	T191 int64 0 1	T196 int64 0 1	T201 int64 0 1
A smartphone-based test for the assessment of attention deficits in delirium: A case-control diagnostic test accuracy study in older hospitalised patients. Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
A happiness magnet? Reviewing the evidence for repetitive transcranial magnetic stimulation in major depressive disorder. First, to conduct a historical review of the evidence for repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder and determine a clinical algorithm. Second, to identify opportunities for research.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
VP2 of Chicken Anaemia Virus Interacts with Apoptin for Down-regulation of Apoptosis through De-phosphorylated Threonine 108 on Apoptin. Chicken anaemia virus (CAV) is an important contagious agent that causes immunosuppressive disease in chickens. CAV Apoptin is a nucleoplasmic shuffling protein that induces apoptosis in chicken lymphoblastoid cells. In the present study, confocal microscopy revealed co-localisation of expressed CAV non-structural protein VP2 with Apoptin in the nucleus of MDCC-MSB1 cells and the nucleoplasmic compartment of CHO-K1 cells. In vitro pull-down and ex vivo biomolecular fluorescent complementation (BiFC) assays further showed that the VP2 protein directly interacts with Apoptin. Transient co-expression of VP2 and Apoptin in MDCC-MSB1 cells significantly decreased the rate of apoptosis compared with that in cells transfected with the Apoptin gene alone. In addition, the phosphorylation status of threonine 108 (Thr108) of Apoptin was found to decrease upon interaction with VP2. Although dephosphorylated Thr108 did not alter the subcellular distribution of Apoptin in the nucleus of MDCC-MSB1 cells, it did suppress apoptosis. These findings provide the first evidence that VP2 directly interacts with Apoptin in the nucleus to down-regulate apoptosis through alterations in the phosphorylation status of the latter. This information will be useful to further elucidate the underlying mechanism of viral replication in the CAV life cycle.	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0
Immunohistochemical detection of procalcitonin in fibrolamellar hepatocellular carcinoma. A 25-year-old woman with fever and epigastric pain was referred to our hospital. Blood examination showed significant liver dysfunction, markedly high C-reactive protein (CRP 19.1 mg/dL) and procalcitonin (48.3 ng/mL) levels. Dynamic computed tomography showed a tumor approximately 120 mm in size in the right lobe of the liver, but with no abscess formation. The patient was hospitalized and started on antibiotics; her CRP level improved, but the procalcitonin level did not decrease. Histopathological examination of the liver tumor biopsy revealed fibrolamellar hepatocellular carcinoma (FLC). Positive staining of the FLC with an anti-procalcitonin antibody suggested the production of procalcitonin.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Gambling and the COVID-19 pandemic: A scoping review. The impact of COVID-19 on mental health is tremendous. Since the beginning of the pandemic, several actors have raised concerns about the impact of the pandemic on gambling. Many actors fear a switch to online gambling in the context of the closure of many land-based gambling activities due to the restrictions imposed by public health authorities, such as physical distancing and lockdowns. This switch is worrisome because online gambling is considered a high-risk game. In that context, we need to know more about the impacts of the pandemic on gambling. This scoping review aims to summarize the literature that addresses the impacts of the COVID-19 pandemic on gambling. To our knowledge, this is the first review to focus on this subject.	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Identification of Brassinosteroid Signaling Complexes by Coimmunoprecipitation and Mass Spectrometry. A combination of coimmunoprecipitation (coIP) of tagged proteins followed by protein identification and quantitation using Liquid Chromatography Mass Spectrometry/Mass Spectrometry (LCMS/MS) has proven to be a reliable method to qualitatively characterize membrane-bound receptor complexes from plants. Success depends on a range of parameters, such as abundance and stability of the complex and functionality of the tagged receptors, efficiency of the protein complex isolation procedure, MS equipment, and analysis software in use. In this Chapter, we focus on the use of one of the green fluorescent protein-tagged receptors of the SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) family, of which SERK3, also known as BRASSINOSTEROID INSENSITIVE1 (BRI1) ASSOCIATED KINASE1 (BAK1), is a coreceptor of BRI1. Like BRI1 itself, SERK3 is a leucine-rich repeat receptor kinase (LRR RK) with a single-pass transmembrane domain. The latest updated laboratory protocol is presented as well as examples of data analysis and typical results obtained. Potential drawbacks of the procedure employed for plant membrane proteins will be pointed out.	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Changes in normothermia during surgery. The aim of the study was to monitor changes in normothermia in patients undergoing surgery under general anaesthesia.	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haptoglobin expression correlates with tumor differentiation and five-year overall survival rate in hepatocellular carcinoma. Elevated serum haptoglobin (Hp) is identified as a prognostic marker in multiple types of solid tumors, which is correlated with poor prognosis. HCC is one of the major causes of cancer deaths in worldwide, which remains poor prognosis and is clinically urgent for discovering early diagnostic markers. However, except for serum Hp, the correlation of tumor Hp expression with hepatocellular carcinoma (HCC) progression is still unclear. In this study, we evaluated and identified the tissue Hp expression as a prognostic marker to predict the survival rate of HCC patients. To evaluate the prognostic value of Hp expression for HCC, two cohorts were enrolled in our study, including total 130 matched pair tissue sections (both adjacent non-tumorous and tumor tissue derived from same patient) of HCC patients from Changhua Christian Hospital (CCH) and total 316 RNA-seq data with clinical information of HCC patients from The Cancer Genome Atlas (TCGA) database. In contrast to other types of cancers, HCC tumor tissues have lower Hp protein expression in CCH cohort and have lower Hp mRNA expression in TCGA cohort as compared with adjacent non-tumorous tissues (p < 0.001). Moreover, lower Hp expression is significantly correlated with different stages of HCC cancer differentiation in CCH cohort (one-way ANOVA, p < 0.001). Most importantly, lower Hp expression is highly correlated with poor five-year overall survival rate in TCGA cohort (p < 0.01). Based on our data, we conclude that tissue Hp expression positively correlates with better HCC tumor differentiation and increased five-year overall survival rate of HCC patients. The results indicated that tissue Hp is potentially a prognostic marker for HCC patients. Our findings may further provide a new insight of effective treatments along with biopsy diagnosis of HCC patients.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Cell type-specific novel long non-coding RNA and circular RNA in the BLUEPRINT hematopoietic transcriptomes atlas. Transcriptional profiling of hematopoietic cell subpopulations has helped to characterize the developmental stages of the hematopoietic system and the molecular bases of malignant and non-malignant blood diseases. Previously, only the genes targeted by expression microarrays could be profiled genome-wide. High-throughput RNA sequencing, however, encompasses a broader repertoire of RNA molecules, without restriction to previously annotated genes. We analyzed the BLUEPRINT consortium RNA-sequencing data for mature hematopoietic cell types. The data comprised 90 total RNA-sequencing samples, each composed of one of 27 cell types, and 32 small RNA-sequencing samples, each composed of one of 11 cell types. We estimated gene and isoform expression levels for each cell type using existing annotations from Ensembl. We then used guided transcriptome assembly to discover unannotated transcripts. We identified hundreds of novel non-coding RNA genes and showed that the majority have cell type-dependent expression. We also characterized the expression of circular RNA and found that these are also cell type-specific. These analyses refine the active transcriptional landscape of mature hematopoietic cells, highlight abundant genes and transcriptional isoforms for each blood cell type, and provide a valuable resource for researchers of hematologic development and diseases. Finally, we made the data accessible via a web-based interface: https://blueprint.haem.cam.ac.uk/bloodatlas/.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Experiences of Body Image Changes in Chinese Patients Living with Inflammatory Bowel Disease: A Descriptive Qualitative Study. Body image changes are common among patients living with inflammatory bowel disease (IBD) because of the illness and related treatments. Currently, there is little known about how those patients experience and perceive their altered body image in the literature. The aim of this study was to explore the experiences of body image changes in patients with IBD in China and to describe how those changes influence patients' perception of body and self.	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Keeping the power on to home medical devices. Advances in digital health technologies have revolutionised home medical care. Yet many home medical devices (HMEDs, which includes devices referred to as 'life support equipment') rely upon a stable and resilient electricity supply. For users of HMEDs, interruptions to electricity supply can compromise treatment, well-being or survival. This paper addresses a challenge critical to the continued innovation in digital health technologies: the reliable supply of electricity. We bridge the current gap between electricity networks and digital health technologies through a novel method for the remote detection of the phase (that is, which part of the network that each house is connected to), in order to eliminate avoidable interruptions to supply for HMED users. We present an unsupervised phase identification algorithm capable of remote phase detection at scale, and without transformer data. This method translates data insights into actionable energy provision for HMED users and other vulnerable customers, enables more accurate management and planning, and improves electricity reliability which is critical for HMED users and the continued advances in digital health technologies.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Morphological Reconstruction-Based Image-Guided Fuzzy Clustering with a Novel Impact Factor. The guided filter is a novel explicit image filtering method, which implements a smoothing filter on "flat patch" regions and ensures edge preserving on "high variance" regions. Recently, the guided filter has been successfully incorporated into the process of fuzzy c-means (FCM) to boost the clustering results of noisy images. However, the adaptability of the existing guided filter-based FCM methods to different images is deteriorated, as the factor ε of the guided filter is fixed to a scalar. To solve this issue, this paper proposes a new guided filter-based FCM method (IFCM_GF), in which the guidance image of the guided filter is adjusted by a newly defined influence factor ρ . By dynamically changing the impact factor ρ , the IFCM_GF acquires excellent segmentation results on various noisy images. Furthermore, to promote the segmentation accuracy of images with heavy noise and simplify the selection of the influence factor ρ , we further propose a morphological reconstruction-based improved FCM clustering algorithm with guided filter (MRIFCM_GF). In this approach, the original noisy image is reconstructed by the morphological reconstruction (MR) before clustering, and the IFCM_GF is performed on the reconstructed image by utilizing the adjusted guidance image. Due to the efficiency of the MR to remove noise, the MRIFCM_GF achieves better segmentation results than the IFCM_GF on images with heavy noise and the selection of the influence factor for the MRIFCM_GF is simple. Experiments demonstrate the effectiveness of the presented methods.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Chinese Medicine for Alzheimer's Disease: A Meta-Analysis of Randomized Controlled Trials. To evaluate the effificacy of oral Chinese medicine (CM) in comparison with donepezil, a cholinesterase inhibitor (ChEI), for the treatment of Alzheimer's disease (AD).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Label-free Separation of Circulating Tumor Cells Using a Self-Amplified Inertial Focusing (SAIF) Microfluidic Chip. Circulating tumor cells (CTCs) are rare cells existing in the bloodstream with a relatively low number, which facilitate as a predictor of cancer progress. However, it is difficult to obtain highly purified intact CTCs with desired viability due to the low percentage of CTCs among blood cells. In this work, we demonstrate a novel self-amplified inertial focused (SAIF) microfluidic chip that enables size-based, high-throughput, label-free separation of CTCs from a patient's blood. The SAIF chip introduced in this study demonstrated the feasibility of an extremely narrow zigzag channel (with 40 μm channel width) connected with two expansion regions to effectively separate different-sized cells with amplified separation distance. The chip performance was optimized with different-sized polystyrene (PS) particles and blood cells spiked with three different types of cancer cells. The separation efficiencies for blood cells and spiked cancer cells are higher than 80%. Recovery rates of cancer cells were tested by spiking 1500 lung cancer cells (A549), breast cancer cells (MCF-7), and cervical cancer cells (HeLa) separately to 3 mL 0.09% saline with 3 × 10 6 white blood cells (WBCs). The recovery rates for larger cells (MCF-7 and HeLa) were 79.1 and 85.4%, respectively. Viabilities of the cells harvested from outlets were all higher than 97% after culturing for 24, 48, and 72 h. The SAIF chip performance was further confirmed using the real clinical patient blood samples from four lung cancer patients. Theoretical force balance analysis in physics, computational simulations, and experimental observations indicate that the SAIF chip is simple but effective, and high-throughput separation CTCs can be readily achieved without complex structures.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Genome-wide identification of heat shock factors and heat shock proteins in response to UV and high intensity light stress in lettuce. Heat shock factors (Hsfs) and Heat shock proteins (Hsps) belong to an essential group of molecular regulators involved in controlling cellular processes under normal and stress conditions. The role of Hsfs and Hsps is well known in model plant species under diverse stress conditions. While plants Hsfs are vital components of the signal transduction response to maintain cellular homeostasis, Hsps function as chaperones helping to maintain folding of damaged and newly formed proteins during stress conditions. In lettuce (Lactuca sativa), a highly consumed vegetable crop grown in the field and in hydroponic systems, the role of these gene families in response to artificial light is not well characterized.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Apolipoprotein A1 Forms 5/5 and 5/4 Antiparallel Dimers in Human High-density Lipoprotein. Apolipoprotein A1 (APOA1), the major protein of high-density lipoprotein (HDL), contains 10 helical repeats that play key roles in protein-protein and protein-lipid interactions. The current structural model for HDL proposes that APOA1 forms an antiparallel dimer in which helix 5 in monomer 1 associates with helix 5 in monomer 2 along a left-left (LL5/5) interface, forming a protein complex with a 2-fold axis of symmetry centered on helix 5. However, computational studies suggest that other orientations are possible. To test this idea, we used a zero-length chemical cross-linking reagent that forms covalent bonds between closely apposed basic and acidic residues. Using proteolytic digestion and tandem mass spectrometry, we identified amino acids in the central region of the antiparallel APOA1 dimer of HDL that were in close contact. As predicted by the current model, we found six intermolecular cross-links that were consistent with the antiparallel LL5/5 registry. However, we also identified three intermolecular cross-links that were consistent with the antiparallel LL5/4 registry. The LL5/5 is the major structural conformation of the two complexes in both reconstituted discoidal HDL particles and in spherical HDL from human plasma. Molecular dynamic simulations suggest that that LL5/5 and LL5/4 APOA1 dimers possess similar free energies of dimerization, with LL5/5 having the lowest free energy. Our observations indicate that phospholipidated APOA1 in HDL forms different antiparallel dimers that could play distinct roles in enzyme regulation, assembly of specific protein complexes, and the functional properties of HDL in humans.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Effects of muscle damage on 31 P-MRS indices of energetic status and sarcolemma integrity in young mdx mice. The article of Lopez et al describes the use of a multi-parametric MR approach to study muscle T 2 relaxation times and 31 P-MRS indices of energetics and sarcolemma integrity in a mouse model of DMD, the mdx mouse. Muscular dystrophies have a multi-factorial disease cascade, and there are several MR methods used to assess these. Aspects that reflect disease progression are outlined on the left, while features that are more related to disease activity are outlined on the right.	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Optimisation of a batch thermal combustion method using a tube furnace oxidation system (pyrolyser) and LSC for carbon-14 determination in environmental matrices. Accelerator mass spectrometry and benzene synthesis coupled with liquid scintillation spectrometry are often used for accurate measurements of 14 C activity in the environmental matrices. Thermal oxidation is one of the methods employed for 14 C determination in environmental matrices. In this method, the sample is oxidised at high temperature (600-900 °C) to convert carbon species to CO 2 and trapped in an amine-based absorber for determining the activity in a liquid scintillation counting (LSC) system. In this study, the performance of a commercially available tube furnace system (pyrolyser), for batch combustion of samples, was evaluated for the determination of 14 C specific activity in terrestrial biota samples. Significant improvements over the manufacturer specified method, which is primarily designed for analysis of samples with activity well above the environmental background level, was implemented to achieve accurate determination of 14 C specific activity at ambient background level. In the improved method, the CO 2 produced from the combustion of the sample was isolated from the combustion products through cryogenic trapping and then absorbed in the absorber (Carbo-Sorb E) through a simple off-line transfer process. This allowed (i) optimisation of CO 2 absorption by the absorber (2.2477 g of CO 2 /10 mL), (ii) achieving good accuracy and precision in the measurements, and a minimum detectable activity value of 13 Bq kg -1 C for a counting time of 300 min (7 Bq kg -1 C for 1000 min), (iii) avoiding uncertainty associated with the determination of recovery of 14 C in the combustion and trapping process, and (iv) elimination of the need for an independent determination of carbon content (%) for expressing the results in terms of 14 C specific activity. The method is capable of yielding accurate results with a deviation of <2.4% from the target value for IAEA C3 quality assurance reference material (with a relative standard deviation of 1.40%, and relative error of 0.34%). The combined uncertainty (1σ) associated with the measurements was computed to be 3.4%. Upon optimisation, the suitability of the method for the determination of 14 C specific activity in typical terrestrial biota samples of clean air region (region not affected by local anthropogenic sources) and for the quantification of a small increase in the 14 C activity above ambient levels in the vicinity of a nuclear power plant is demonstrated.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
N-dihydrogalactochitosan-supported tumor control by photothermal therapy and photothermal therapy-generated vaccine. Photothermal therapy (PTT) is recently clinically established cancer therapy that uses near-infrared light for thermal ablation of solid tumors. The biopolymer N-dihydrogalactochitosan (GC) was shown in multiple reports to act as a very effective adjunct to tumor PTT. In the present study, mouse tumor model SCCVII (squamous cell carcinoma) was used with two protocols, in situ tumor PTT and therapeutic PTT vaccine for tumors, for investigating the effects of GC. The results reveal that GC can potentiate tumoricidal action of PTT through both direct and indirect mechanisms. In addition to previously known capacity of GC for activating immune effector cells, the indirect means is shown to include reducing the populations of immunoregulatory T cells (Tregs) in PTT-treated tumors. Testing the effects of GC on PTT-treated SCCVII tumor cells in vitro uncovered the existence of a direct mechanism evident by reduced colony survival of these cells. Fluorescence microscopy demonstrated increased binding of fluorescein-labeled GC to PTT-treated compared to untreated SCCVII cells that can be blocked by pre-exposure to annexin V. The results of additional in vitro testing with specific inhibitors demonstrate that these direct mechanisms do not involve the engagement of death surface receptors that trigger extrinsic apoptosis pathway signaling but may be linked to pro-survival activity of caspase-1. Based on the latter, it can be suggested that GC-promoted killing of PTT-treated cells stems from interference of GC bound to damaged membrane components with the repair of these structures that consequently hinders cell survival.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Automated recognition of the pericardium contour on processed CT images using genetic algorithms. This work proposes the use of Genetic Algorithms (GA) in tracing and recognizing the pericardium contour of the human heart using Computed Tomography (CT) images. We assume that each slice of the pericardium can be modelled by an ellipse, the parameters of which need to be optimally determined. An optimal ellipse would be one that closely follows the pericardium contour and, consequently, separates appropriately the epicardial and mediastinal fats of the human heart. Tracing and automatically identifying the pericardium contour aids in medical diagnosis. Usually, this process is done manually or not done at all due to the effort required. Besides, detecting the pericardium may improve previously proposed automated methodologies that separate the two types of fat associated to the human heart. Quantification of these fats provides important health risk marker information, as they are associated with the development of certain cardiovascular pathologies. Finally, we conclude that GA offers satisfiable solutions in a feasible amount of processing time.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering. Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Determination of the just suspended speed for solid particle in torus reactor. With the considerable use of pipelines and reactors in the engineering industry, determining the deposition velocity enabling hydraulic transport is of utmost importance. This has been investigated throughout the years, scrupulously in several types of reactors used in water treatment and solid transport. The primary focus has been extended to torus reactors, due to their significant advantage in chemical, biochemical and mixing processes. In the present work, we have studied the solid-liquid suspension in a torus reactor. We elaborated an experimental method based on visual assessment SBAM (Steady Bed Angle Method), which enabled us to analytically determine the just suspended speed 'Njs' at which no solid remains stationary at the bed and further parametrically study the effect of several parameters including solid loadings, particle sizes and densities. The just suspended speed values obtained experimentally have been compared to a modified Zwietering's correlation.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[Preliminary study on effect of Gegen Qinlian Decoction on enzyme activity, gene expression and methylation level of FASN in adipose tissue of rats with insulin resistance]. To investigate the effect of Gegen Qinlian Decoction(GQD) on enzyme activity, gene expression and methylation level of fatty acid synthase(FASN) in adipose tissue from rats with insulin resistance induced by high-fat diet. The 60% fat-powered high-fat diet was continuously given to male SD rats to induce the insulin resistance model. Then, they were divided into five groups randomly and administrated by gavage every day for 16 weeks with following drugs respectively: 10 mL·kg~(-1)water for control group(C) and insulin resistance model control group(IR), 1.65 g·kg~(-1)GQD per day for low-dose group(GQDL), 4.95 g·kg~(-1)GQD per day for medium-dose group(GQDM), 14.85 g·kg~(-1)GQD per day for high-dose group(GQDH), and 5 mg·kg~(-1) rosiglitazone per day for rosiglitazone group(RGN). Epididymal adipose tissue was taken to determine enzyme activity of FASN by colorimetric method, mRNA expression level of Fasn by quantitative Real-time PCR(Q-PCR) and CpGs methylation level between +313 and +582 by bisulfite sequencing PCR(BSP). These results showed that Fasn expression was significantly lowered in IR model rats compared with the control rats(P<0.01). Enzymatic activity and CpGs methylation level of Fasn in IR group showed downward trends. Low and medium-dose GQD can increase enzyme activity of FASN(P<0.05). Moreover, low-dose GQD increased the total CpGs methylation level of Fasn fragment between +313 and +582 in insulin resistance rats(P<0.05). For GQDM group, the methylation frequency of CpGs at positions +506 and +508(P<0.01) as well as the methylation frequency of CpGs on the binding sites of transcription factorzinc finger protein 161(P<0.05) were significantly increased. The methylation frequency of CpG at +442 position was positively correlated with Fasn expression(P<0.01, r=0.735), and methylation frequencies of CpGs at +345 and +366 positions were positively associated to enzyme activity of FASN respectively(P<0.05, r=0.479; P<0.01, r=0.640). In conclusion, GQD can reverse enzyme activity of FASN and methylation level of Fasn in adipose tissue of insulin resistant rats, and CpG sites at positions +506 and +508 may be the targets of GQD. The methylation level of CpGs at + 345 and + 366 sites were possibly related to FASN activity, while methylation of CpG at + 442 site may be closely correlated with mRNA level of Fasn. In addition, GQD did not significantly change mRNA expression level of Fasn, but effectively reversed enzymatic activity, suggesting that GQD may regulate the post transcriptional expression of Fasn.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
A meta-synthesis of qualitative studies of the link between anxiety, depression and perfectionism: implications for treatment. Meta-analyses show an association between perfectionism and depression and anxiety (negative affect), and that therapy for perfectionism impacts positively on negative affect. No systematic reviews have focused on qualitative studies of perfectionism.	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Mucoadhesive Particles: A Novel, Prolonged-Release Nanocarrier of Sitagliptin for the Treatment of Diabetics. Sitagliptin (MK-0431) is a widely and commonly used oral hypoglycemic drug in the treatment of type 2 diabetes mellitus; patients typically take higher doses of this drug (50 mg, twice daily). One drawback is that only 38% of the drug is bound reversibly to plasma proteins and 79% is excreted in urine without being metabolized. To overcome this issue, there is a need for a better drug-delivery method to improve its efficacy in patients. It has been found that in existing formulations, the drug content is 72.5% ± 5% and the percentage yield is 84.9% ± 3%. In this study, sitagliptin nanoparticles (sizes ranging from 210 to 618 nm) were developed. The bioadhesion properties of the nanoparticles, as well as the swelling of the nanoparticles on the mucus membrane aided in sustained drug release. The pattern of drug release was in accordance with the Peppas model. Fourier-transform infrared (FTIR) spectroscopy demonstrated that there were no significant interactions between sitagliptin and chitosan. Differential scanning calorimetry (DSC) results showed an absence of drug peaks due to the fact that the drug was present in an amorphous state. Mucoadhesive nanoparticles were formulated using sitagliptin and were effective for about 12 hours in the gastrointestinal tract. When compared to conventional sitagliptin administration, use of a nanoparticle delivery system demonstrated greater benefits for use in oral delivery applications. This is the first time that a drug-delivery method based on the mucoadhesive properties of nanoparticles could prolong the drug-release time of sitagliptin.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Major Stress-Related Symptoms During the Lockdown: A Study by the Italian Society of Psychophysiology and Cognitive Neuroscience. The clinical effects of the Covid-19 pandemic are now the subject of numerous studies worldwide. But what are the effects of the quarantine imposed by the states that implemented the measures of lockdown? The present research aims to explore, in a preliminary way, the major stress-related symptoms during the lockdown, due to Covid-19, in the Italian population. Subjects were asked to fill out a survey, that traced a line identifying the most relevant psychophysiological symptoms that took into account factors such as perceived stress, body perception, perceived pain, quality of sleep, perceptive variations (i.e., olfactory, gustatory, visual, acoustic, and haptic perception). A network approach formulating a hypothesis-generating exploratory analysis was adopted. Main results of the network analysis showed that the beliefs of having had the Covid-19 was related to individual variables (i.e., gender, working in presence, sleep quality, anxiety symptoms), while the familiarity of Covid-19 disease was related to contextual factors (e.g., number of recorded cases in the Region, working in presence). The self-perception of olfactory and perceptive alterations highlighted a great sensorial cross-modality, additionally, the olfactory impairment was related to the belief of having had the Covid-19. Compared to general network data, BAI, perceived stress, anxiety and chronic pain were in relation to daily sleep disturbance. Main study's results show how the management of the Covid-19 stressful representation, in its cognitive aspects, can modulate the psychophysiological responses.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Radial/Ulnar angioplasty in selected patients undergoing elective angiography or PCI using complex forearm approach. Angioplasty on the radial artery have been performed with good success rates in patients with critical hand ischemia. We sought to assess the feasibility and safety of radial angioplasty on complex radial access in patients undergoing coronary angiography.	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
False-negative Results of Human Immunodeficiency Virus (HIV) Rapid Testing in HIV Controllers. Serological assays were performed on 85 human immunodeficiency virus-controller samples . 6% presented a negative rapid screening test 7% presented an indeterminate Western blot. The enzyme immunoassay ratio decreased in controllers who had continual negative ultrasensitive HIV RNA results since inclusion.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Paratesticular rhabdomyosarcoma-Impact of locoregional approach on patient outcome: A report from the European paediatric Soft tissue sarcoma Study Group (EpSSG). Paratesticular rhabdomyosarcoma (PT RMS) is rare compared to benign scrotal pathology. Inappropriate first surgery (InFS) required supplementary treatment to maintain excellent outcomes. Initial staging of regional lymph nodes is important. The aim of this study was to determine to what extent the quality of locoregional approach impacted on patient morbidity and survival.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Adjuvant Chemotherapy for Gastric Cancer Patients with Mismatch Repair Deficiency or Microsatellite Instability: Systematic Review and Meta-Analysis. Mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) status serves as a predictor of a poor response to adjuvant chemotherapy among stage 2 colon cancer patients. This study aimed to investigate the efficacy of adjuvant chemotherapy in dMMR/MSI-H gastric cancer (GC).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Targeting Amyloids with [ 18 F]AV-45 for Medullary Thyroid Carcinoma Positron Emission Tomography/Computed Tomography Imaging: A Pilot Clinical Study. Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a β-amyloid-specific radiotracer, [ 18 F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [ 18 F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [ 18 F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [ 18 F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[ 18 F]fluoro-d-glucose ([ 18 F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [ 18 F]AV-45 uptake. Postoperative histopathological analysis confirmed the [ 18 F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [ 18 F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [ 18 F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Deciphering the role of nanostructured materials in the point-of-care diagnostics for COVID-19: a comprehensive review. The infamous COVID-19 outbreak has left a crippling impact on the economy, healthcare infrastructure, and lives of the general working class, with all the scientists determined to find suitable and efficient diagnostic techniques and therapies to contain its ramifications. This article presents the complete outline of the diagnostic platforms developed using nanoparticles in the detection of SARS-CoV-2, delineating the direct and indirect use of nanomaterials in COVID-19 diagnosis. The properties of nanostructured materials and their relevance in the development of novel point-of-care diagnostic approaches for COVID-19 are highlighted. More importantly, the advantages of nanotechnologies over conventional reverse transcriptase-polymerase chain reaction technique and few other methods used in the detection of SARS-CoV-2 along with the viewpoints are discussed. Also, the future perspectives highlighting the commercial aspects of the nanotechnology-based diagnostic tools developed to combat the COVID-19 pandemic are presented.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Assessment of mask-wearing adherence and social distancing compliance in public places in Hamadan, Iran, during the COVID-19 pandemic. The determination of the rate of social distancing compliance and mask-wearing adherence is essential to address the health aspects of COVID-19. The present study aimed to estimate the adherence to mask-wearing and maintaining the social distancing in public places in Hamadan, western Iran, during the COVID-19 pandemic.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
National report on aggressions to physicians in Spain 2010-2015: violence in the workplace-ecological study. Aggressions against health staff is a phenomenon that is not widely studied worldwide. To date, there is no national study analyzing this situation in Spain. Our objective is to describe and analyze aggressions to physicians of the whole Spanish territory in the period 2010-2015, through an observational analytical study by conglomerates (ecological) with all aggressions to physicians identified by the 52 official medical associations of Spain over 6 years of study.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Modeling the spread of capripoxvirus among livestock and optimal vaccination strategies. Capripox is an important transboundary animal disease that is endemic across Africa, the Middle East, and some parts of Asia. The disease is highly contagious and considered to be a major obstacle causing significant economic loses in many agricultural areas. In this study, a mathematical model is developed to describe the transmission dynamics of capripoxvirus (CaPV) among livestock. This proposed model incorporates direct and indirect transmission of CaPV, together with two vaccination strategies, to investigate their effects on the severity of outbreaks and the prevalence of CaPV among the livestock population. The results suggest that ratio of potential vectors to livestock, successful probability of infection, vaccination rates, waning rate of vaccine-conferred protection, and virus introduction time play crucial roles in determining the outbreak severity and the prevalence level. The results also show that it is optimal to vaccinate newborns at the maximum effort throughout the control program and moderately increase vaccination rate for a susceptible pool to reach its maximum level after the outbreak.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pretreatment optimisation and kinetics of batch anaerobic digestion of liquidised OFMSW treated with NaOH: Models verification with experimental data. The enormous generation of municipal solid waste (MSW) due to increased urbanization is causing threat to the environment. MSW is a mixed waste and it comprises of organic fraction as the key fraction called organic fraction of municipal solid waste (OFMSW) along with other fractions. The pretreatment of OFMSW is necessary step to increase the biogas yield. In the present work, NaOH hydrolysis of mechanically liquidised OFMSW was carried out to reduce its complexity and improve the biogas production. Furthermore, hydrolysis parameters were optimised by RSM model for NaOH pretreatment. Optimised conditions achieved from RSM analysis were 0.46 N NaOH loading, 72 h reaction time and 36.05 °C operating temperature. The RSM predicted values of response sCOD and VFA at optimum condition were in good agreement with experimental data signifying the model adequacy. The kinetic of batch anaerobic digestion of OFMSW treated with NaOH at different concentrations and optimised condition had been studied to see the suitability of first order model and modified Gompartz model. The experimental results obtained were best fitted using normalized root mean square error analysis. Biogas production after pretreatment at 0.1, 0.5, 0.9 N NaOH concentration and RSM optimised condition was 369.24, 435.24, 327.84 and 465.67 NL/kg VS, respectively.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Automated deep learning design for medical image classification by health-care professionals with no coding experience: a feasibility study. Deep learning has the potential to transform health care; however, substantial expertise is required to train such models. We sought to evaluate the utility of automated deep learning software to develop medical image diagnostic classifiers by health-care professionals with no coding-and no deep learning-expertise.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Surmising synchrony of sound and sight: Factors explaining variance of audiovisual integration in hurdling, tap dancing and drumming. Auditory and visual percepts are integrated even when they are not perfectly temporally aligned with each other, especially when the visual signal precedes the auditory signal. This window of temporal integration for asynchronous audiovisual stimuli is relatively well examined in the case of speech, while other natural action-induced sounds have been widely neglected. Here, we studied the detection of audiovisual asynchrony in three different whole-body actions with natural action-induced sounds-hurdling, tap dancing and drumming. In Study 1, we examined whether audiovisual asynchrony detection, assessed by a simultaneity judgment task, differs as a function of sound production intentionality. Based on previous findings, we expected that auditory and visual signals should be integrated over a wider temporal window for actions creating sounds intentionally (tap dancing), compared to actions creating sounds incidentally (hurdling). While percentages of perceived synchrony differed in the expected way, we identified two further factors, namely high event density and low rhythmicity, to induce higher synchrony ratings as well. Therefore, we systematically varied event density and rhythmicity in Study 2, this time using drumming stimuli to exert full control over these variables, and the same simultaneity judgment tasks. Results suggest that high event density leads to a bias to integrate rather than segregate auditory and visual signals, even at relatively large asynchronies. Rhythmicity had a similar, albeit weaker effect, when event density was low. Our findings demonstrate that shorter asynchronies and visual-first asynchronies lead to higher synchrony ratings of whole-body action, pointing to clear parallels with audiovisual integration in speech perception. Overconfidence in the naturally expected, that is, synchrony of sound and sight, was stronger for intentional (vs. incidental) sound production and for movements with high (vs. low) rhythmicity, presumably because both encourage predictive processes. In contrast, high event density appears to increase synchronicity judgments simply because it makes the detection of audiovisual asynchrony more difficult. More studies using real-life audiovisual stimuli with varying event densities and rhythmicities are needed to fully uncover the general mechanisms of audiovisual integration.	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Depression in Poststroke Aphasia. Purpose The aim of this tutorial is to provide speech-language pathologists with foundational knowledge of poststroke depression comorbidly occurring with aphasia. Given the negative effect of depression on functional outcomes and mortality, it is crucial that speech-language pathologists possess this knowledge in order to better advocate for and treat their patients. Method and Results Three areas of complementary expertise (speech-language pathology, psychology, and neurology) collaborated on this tutorial to address the following areas: (a) provide terminology associated with depression and related mood disorders, (b) describe the potential underlying pathophysiology of depression in the general population, (c) provide an overview of our existing understanding of comorbid poststroke depression and aphasia, and (d) summarize current assessment methods and interventions for poststroke depression in adults with aphasia. Conclusion Given the compounding impact aphasia and depression have on rehabilitation outcomes, it is imperative that speech-language pathologists understand terminology, assessment, and treatment practices for depression.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Fertilization accelerates the decomposition of microplastics in mollisols. Agricultural films composed of low-density polyethylene (LDPE) have been widely used in farmland, and LDPE microplastics (LDPE-MPs) produced from LDPE degradation can pollute soils and can exert negative effects on biota. Both nitrogen (N) and phosphorus (P) can alter the activity of soil microorganisms and may alter the LDPE-MP degradation process in soils. In this study, LDPE-MP surface morphology, particle size, abundance and mass in a mollisol were evaluated after the application of a gradient of N and P fertilizer in a laboratory incubation experiment. The results showed the following: (1) LDPE-MP particles became fragmented into smaller debris with a coarse surface after 40 days of incubation, and the effect was more obvious with increased P or N application; (2) high N and P fertilization significantly reduced the abundance of LDPE-MP particles >100 μm by 38.5-50.0% and increased the abundance of LDPE-MP particles <20 μm by 43.2-59.5% after 40 days of incubation; (3) high N and P fertilization significantly increased the mass of LDPE-MP particles <75 μm by 25.5-60.1% and decreased the mass of LDPE-MP particles >150 μm by 32.4-37.5%; (4) the mass of LDPE-MPs decreased with increasing incubation time after N and P fertilization, which could be simulated by exponential models (p < 0.05), LDPE degradation was rapid in the first 20 days after N or P fertilization, and both N and P caused a "priming effect" of LDPE degradation; and (5) N and P fertilization increased both the biodiversity and abundance of several predominant genera of soil microorganisms that degrade LDPE. Therefore, N and P fertilization can accelerate LDPE-MP degradation, and the relatively large amounts of fine debris from degraded LDPE-MPs can be problematic for the environment and soil biota. LDPE-MP pollution should be strictly controlled in mollisols, and the degradation mechanisms of LDPE-MPs warrant further study.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer's disease. Although many therapeutic strategies for Alzheimer's disease (AD) have been explored, these strategies are seldom used in the clinic. Therefore, AD therapeutic research is still urgently needed. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. Herein, we devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	0	0	1	0	0	0	0	0	0	0	0
UK audit of target volume and organ at risk delineation and dose optimisation for cervix radiotherapy treatments. Assessment of the extent of variation in delineations and dose optimisation performed at multiple UK centres as a result of interobserver variation and protocol differences.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Transjugular Portosystemic Shunt Reductions: A Retrospective Single-Center Experience. To report the results of transjugular intrahepatic portosystemic shunt (TIPS) reductions for hepatic encephalopathy (HE), acute liver failure (ALF), and pulmonary hypertension (PH).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Care of the stoma: complications and treatments. Quality patient education of how to care for their stoma improves patient outcomes and enhances quality of care and efficacy. There is a need for home visits to assist ostomates with rehabilitation of their stoma formation, as they often feel stigmatised and are likely to withdraw from social activities. It has previously been highlighted that community care is often the weakest link in rehabilitation, highlighting the need for effective teamwork and collaboration between stoma nurse specialists and community nurses. This article will focus on some of the more common complications of stomas which will be seen in the community setting, how to treat these conditions and when patients should be referred to the specialist stoma care nurse.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Fabrication and sensing properties of phenolphthalein based colorimetric and turn-on fluorogenic probe for CO 3 2- detection and its living-cell imaging application. Herein, an easy assembled colorimetric and ''turn-on'' fluorescent sensor (probe P4SC) based on phenolphthalein was developed for carbonate ion (CO 3 2- ) sensing in a mixture of EtOH/H 2 O (v/v, 80/20, pH = 7, Britton-Robinson buffer) media. The probe P4SC demonstrated high sensitive and selective monitoring toward CO 3 2- over other competitive anions. Interaction of CO 3 2- with the probe P4SC resulted in a significant increment in emission intensity at λ em = 498 nm (λ ex = 384 nm) due to the strategy of blocking the photo induced electron transfer (PET) mechanism. 1 H NMR titration and Job's methods, as well as the theoretical study were carried out to support the probable stoichiometry of the reaction (1:2) between P4SC and CO 3 2- . The binding constant of the probe P4SC with CO 3 2- was calculated as 2.56 × 10 10 M -2 . The probe P4SC providing rapid response time (~0.5 min) with a satisfactorily low detection limit (14.7 nM) may be useful as a valuable realistic sensor. The imaging studies on the liver cancer cells (HepG2) shows the great potential of the probe P4SC for the sensation of intracellular CO 3 2- anions. Furthermore, the satisfactory recovery and RSD values obtained for water application confirming that the probe P4SC could be applied to sensing of CO 3 2- ion.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0
Enhancement of enzyme activities and VFA conversion by adding Fe/C in two-phase high-solid digestion of food waste: Performance and microbial community structure. Two-phase high-solid digestion is conducive to the degradation of food waste. In this study, Fe/C was added in high-solid digestion in different acidification and/or methanogenic phase. The experimental results indicated that it significantly increased the cumulative yield of biomethane. When Fe/C was added to the acidification phase only and both the acidification and methanogenic phases, the biomethane yield reached 474.07 ± 7.03 and 475.47 ± 4.68 mL·g VS -1 , respectively, and the biodegradation rate reached 87.30% and 87.58%, respectively, indicating that Fe/C had mainly effect on the performance of acidification phase. In a two-phase anaerobic fermentation system, the activity of dehydrogenases and the concentration of coenzyme F 420 were 2.23-2.95 mg·g -1 ·h -1 and 0.0063-0.0294 mol·g -1 volatile solids, respectively. Additionally, the archaeal communities production pathway of methane from using acetic acid to using hydrogen as the reactant.	1	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Framework for the environmental impact assessment of operational shipping. Shipping is an important source of pollution affecting both atmospheric and aquatic environments. To allow for efficient mitigation of environmental degradation, it is essential to know the extent of the impacts of shipping in relation to other sources of pollution. Here, we give a perspective on a holistic approach to studies of the environmental impacts of operational shipping through presentation of an assessment framework developed and applied on a case of shipping in the Baltic Sea. Through transfer of knowledge and concepts, previously used in assessments of air pollution, now applied to assessments of marine pollution and underwater noise, the horizon of understanding of shipping-related impacts is significantly improved. It identifies the main areas of environmental degradation caused by shipping and potential improvements through legislation and technological development. However, as the vast majority of contaminants discharged into the sea are not routinely monitored and assessed, the links between pressure of contaminants from shipping and environmental state and impacts will not be caught in the current environmental regulatory frameworks.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Evaluating the quality of remote sensing products for agricultural index insurance. Agricultural index insurance contracts increasingly use remote sensing data to estimate losses and determine indemnity payouts. Index insurance contracts inevitably make errors, failing to detect losses that occur and issuing payments when no losses occur. The quality of these contracts and the indices on which they are based, need to be evaluated to assess their fitness as insurance, and to provide a guide to choosing the index that best protects the insured. In the remote sensing literature, indices are often evaluated with generic model evaluation statistics such as R2 or Root Mean Square Error that do not directly consider the effect of errors on the quality of the insurance contract. Economic analysis suggests using measures that capture the impact of insurance on the expected economic well-being of the insured. To bridge the gap between the remote sensing and economic perspectives, we adopt a standard economic measure of expected well-being and transform it into a Relative Insurance Benefit (RIB) metric. RIB expresses the welfare benefits derived from an index insurance contract relative to a hypothetical contract that perfectly measures losses. RIB takes on its maximal value of one when the index contract offers the same economic benefits as the perfect contract. When it achieves none of the benefits of insurance it takes on a value of zero, and becomes negative if the contract leaves the insured worse off than having no insurance. Part of our contribution is to decompose this economic well-being measure into an asymmetric loss function. We also argue that the expected well-being measure we use has advantages over other economic measures for the normative purpose of insurance quality ascertainment. Finally, we illustrate the use of the RIB measure with a case study of potential livestock insurance contracts in Northern Kenya. We compared 24 indices that were made with 4 different statistical models and 3 remote sensing data sources. RIB for these indices ranged from 0.09 to 0.5, and R2 ranged from 0.2 to 0.51. While RIB and R2 were correlated, the model with the highest RIB did not have the highest R2. Our findings suggest that, when designing and evaluating an index insurance program, it is useful to separately consider the quality of a remote sensing-based index with a metric like the RIB instead of a generic goodness-of-fit metric.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Comparison of 10-Year Survival Outcomes for Early Single Hepatocellular Carcinoma following Different Treatments. To compare the actual 10-year survival outcomes of early single hepatocellular carcinoma (HCC) patients between 3 first-line treatments: radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
A Critical Review on Transplacental Transfer of Per- and Polyfluoroalkyl Substances: Prenatal Exposure Levels, Characteristics, and Mechanisms. Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has aroused public concerns as it can pose multiple health threats to pregnant women and cause adverse birth outcomes for fetuses. In previous studies, the prenatal exposure levels and transplacental transfer efficiencies (TTE) of PFASs have been reported and discussed. Specifically, the binding affinities between PFASs and some transporters were determined, demonstrating that the TTE values of PFASs are highly dependent on their binding behaviors. To summarize primary findings of previous studies and propose potential guidance for future research, this article provides a systematic overview on levels and characteristics of prenatal exposure to PFASs worldwide, summarizes relationships between TTE values and structures of PFASs, and discusses possible transplacental transfer mechanisms, especially for the combination between PFASs and transporters. Given the critical roles of transporters in the transplacental transfer of PFASs, we conducted molecular docking to further clarify the binding behaviors between PFASs and the selected transporters. We proposed that the machine learning can be a superior method to predict and reveal behaviors and mechanisms of the transplacental transfer of PFASs. In total, this is the first review providing a comprehensive overview on the prenatal exposure levels and transplacental transfer mechanisms of PFASs.	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Predator-Prey Interactions in the Anthropocene: Reconciling Multiple Aspects of Novelty. Ecological novelty, when conditions deviate from a historical baseline, is increasingly common as humans modify habitats and communities across the globe. Our ability to anticipate how novelty changes predator-prey interactions will likely hinge upon the explicit evaluation of multiple forms of novelty, rather than a focus on single forms of novelty (e.g., invasive predators or climate change). We provide a framework to assess how multiple forms of novelty can act, alone or in concert, on components shared by all predator-prey interactions (the predation sequence). Considering how novelty acts throughout the predation sequence could improve our understanding of predator-prey interactions in an increasingly novel world, identify important knowledge gaps, and guide conservation decisions in the Anthropocene.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Spinal cord infarction caused by extensive aortic intramural hematoma. We report the case of a 62-year-old Caucasian man, an ex-smoker, who presented to the emergency room complaining of intense lower back pain followed by immediate bilateral loss of inferior limbs motor function. Clinical examination showed complete paralysis and paranesthesia in both legs, while pain and temperature sensory examination revealed a sensory level at dermatome T6, with normal touch, vibration, and position senses. His blood pressure was 190∕100 mmHg. Computed tomography demonstrated dilated thoracic aorta (maximum diameter 44 mm) and abdominal aorta (maximum 58 mm), with extended intramural hematoma (IMH), thus establishing the diagnosis of type A aortic IMH complicated with paraplegia through spinal perfusion deficit. Due to the extension of the lesions, surgical intervention for aortic repair was considered at high risk while cerebrospinal fluid drainage was not recommended by the neurologist. The patient remained stable while hospitalized and was released from the hospital with mild improvement of neurological deficiencies.	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dystonia is a Common Phenotypic Feature of MEGDEL Syndrome. In Response To: Giron C, Roze E, Degos, B, Méneret A, Jardel C, Lannuzel A, et al. Adult-onset generalized dystonia as the main manifestation of MEGDEL syndrome. Tremor Other Hyperkinet Mov. 2018; 8. doi: 10.7916/D8VM5VBQ.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Hospital Enforcement of Early Cholecystectomy for Acute Cholecystitis. International guidelines state that early laparoscopic cholecystectomy (ELC) is appropriate for all severity grades of acute cholecystitis and leads to reduced hospital stays and costs. A multicenter prospective randomized controlled trial recommends ELC over delayed laparoscopic cholecystectomy (DLC) management because in addition to reduced hospital stays and costs, ELC also leads to reduced patient morbidity. Therefore, ELC is standard of care for acute cholecystitis. We hypothesize that 1) international guidelines are not presently followed and that 2) a quality improvement (QI) project enforcing ELC for acute cholecystitis will increase rates of ELC management. A retrospective chart review of all surgical consults for cholecystitis from January 2016 to December 2018 was undertaken. A total of 307 patients diagnosed with acute cholecystitis were included. ELC was defined as cholecystectomy within hospital admission. Pre-QI ELC versus DLC rates were 77.4 per cent (233/301) versus 22.6 per cent (68/301). Eight DLC patients (11.8%) returned to the ED after discharge secondary to persistent signs and symptoms of cholecystitis and 62.5 per cent (5/8) received an immediate cholecystectomy before their elective surgery date. After QI initiatives, ELC rates rose to 100 per cent (6/6). These data show there was a lack of consistent ELC management of acute cholecystitis.	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Glutathione-glutaredoxin is an efficient electron donor system for mammalian p53R2-R1-dependent ribonucleotide reductase. Deoxyribonucleotides are DNA building blocks and are produced de novo by reduction of ribose to deoxyribose. This reduction is catalyzed by ribonucleotide reductase (RNR), a heterodimeric tetramer enzyme in mammalian cells, having one of two free radical-containing subunits called R2 and p53R2. R2 is S-phase specific and used for DNA replication, whereas p53R2 functions in DNA repair and mitochondrial DNA synthesis. The larger RNR subunit, R1, has catalytically active cysteine thiols in its buried active site and a C-terminal swinging arm, with a Cys-Leu-Met-Cys sequence suggested to act as a shuttle dithiol/disulfide for electron transport. After each catalytic cycle the active site contains a disulfide, which has to be reduced for turnover. Thioredoxin (Trx) and glutaredoxin (Grx) systems have been implicated as electron donors for the RNR disulfide reduction via the swinging arm. Using mouse R1-R2 and R1-p53R2 complexes, we found here that the catalytic efficiency of the GSH-Grx system is 4-6 times higher than that of the Trx1 system. For both complexes, the V max values for Grx are strongly depended on GSH concentrations. The GSH disulfide resulting from the Grx reaction was reduced by NADPH and GSH reductase and this enzyme was essential because reaction with GSH alone yielded only little activity. These results indicate that C-terminal shuttle dithiols of mammalian R1 have a crucial catalytic role and that the GSH-Grx system favors the R1-p53R2 enzyme for DNA replication in hypoxic conditions, mitochondrial DNA synthesis, and in DNA repair outside the S-phase.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Fañanas cells-the forgotten cerebellar glia cell type: Immunocytochemistry reveals two potassium channel-related polypeptides, Kv2.2 and Calsenilin (KChIP3) as potential marker proteins. For long times astrocytes had been regarded as supporting cells, passively filling the spaces between neuronal cell bodies and their extensions. Now it is known that astrocytes are actively involved in a variety of important biological functions such as regulating cerebral blood flow, supporting neuronal metabolism, controlling the extracellular potassium concentration, and clearing neurotransmitters from the extracellular space. In line with this multitude of tasks astrocytes display conspicuous functional and regional heterogeneity. Using three complementary labeling methods nine classes of astrocytes have been differentiated, which were termed protoplasmic, fibrous, velate, radial, and perivascular astrocytes in addition to Bergmann, marginal, and ependymal glial cells. To complete this list retinal Müller cells and a largely forgotten astrocytic cell type, the "feathered cell" of Fañanas need to be added. So far, Fañanas cells could be only recognized with the tedious gold-sublimate procedure. Consequently, data indicating a potential biological function are completely missing. In a parallel investigation we used a battery of antibodies against potassium channels and related proteins to identify potential marker proteins for the immunocytochemical visualization of distinct cell types in the cerebellar cortex. Here we present novel marker proteins, the Kv2.2 potassium channel and calsenilin, to visualize Fañanas cells in the cerebellar Purkinje cell layer. Such markers will allow to identify Fañanas cell subsequent to patching and electrophysiological characterization. This may pave the path to obtain new functional data, which may be helpful to understand the role of these enigmatic cells in normal biological function and disease.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Simple laparoscopic repair of perforated peptic ulcer without omental patch. We evaluated the outcomes of laparoscopic repair of perforated peptic ulcers using simple closure only.	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Implementation of a Prevention Program Based on Adapted Physical Activity and Recommendations for Adolescents and Young Adults with Cancer: PREVAPAJA Study. Purpose: In Europe, 20,000 Adolescent and Young Adults (AYAs) aged 15-25 years are diagnosed with cancer annually. Although prognosis is good, AYA cancer survivors are at greater risk of second primary cancers, cardiovascular disease, and various long-term effects. Benefits of physical activity (PA) in AYAs reported in current studies remain difficult to generalize; none has been performed in France. This single-arm intervention study tested the feasibility of combining hospital-based supervised and home-based unsupervised physical activity sessions (PAS) and providing cancer prevention recommendations for AYAs. Methods: The AYAs attended PAS concomitant to treatment and participated in one face-to-face prevention interview. PA (international physical activity questionnaire), 6-min walk distance (6MWD), sedentarity, anthropometrics, quality of life (QoL), and fatigue were assessed at baseline (T1) and end of intervention (T2). PA, satisfaction and cancer prevention behaviors were assessed 1 year after baseline (T3). Results: Fifty-nine AYAs (mean 19 years) participated in the study. Acceptability and attrition were 80% and 12%, respectively. Between T1 and T2, 6MWD and global QoL improved ( p < 0.001), and fatigue decreased ( p = 0.003). Total PA improved and sitting time decreased ( p < 0.001) overall (T1-T3). Assessment at T3 showed interindividual differences in how participants considered risk factors (e.g., more attention to PA, UV exposures, nutrition). Conclusion: Combined supervised and unsupervised home-based PAS in AYAs undergoing cancer treatment is acceptable and feasible. The program contributes to maintaining and improving physical fitness and QoL, while reducing fatigue and other cancer and treatment symptoms. Larger randomized controlled trials are needed to confirm these results.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Attenuation-based kV pair selection in dual source dual energy computed tomography angiography of the chest: impact on radiation dose and image quality. The purpose of this study was to evaluate the impact of attenuation-based kilovoltage (kV) pair selection in dual source dual energy (DSDE)-pulmonary embolism (PE) protocol examinations on radiation dose savings and image quality.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Generating retinal flow maps from structural optical coherence tomography with artificial intelligence. Despite advances in artificial intelligence (AI), its application in medical imaging has been burdened and limited by expert-generated labels. We used images from optical coherence tomography angiography (OCTA), a relatively new imaging modality that measures retinal blood flow, to train an AI algorithm to generate flow maps from standard optical coherence tomography (OCT) images, exceeding the ability and bypassing the need for expert labeling. Deep learning was able to infer flow from single structural OCT images with similar fidelity to OCTA and significantly better than expert clinicians (P < 0.00001). Our model allows generating flow maps from large volumes of previously collected OCT data in existing clinical trials and clinical practice. This finding demonstrates a novel application of AI to medical imaging, whereby subtle regularities between different modalities are used to image the same body part and AI is used to generate detailed inferences of tissue function from structure imaging.	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Physical and emotional well-being and support in newly diagnosed head and neck cancer patient-caregiver dyads. The purpose of this study was to examine the physical and emotional well-being and social support in newly diagnosed head and neck cancer (HNC) patients and caregivers and identify sociodemographic, clinical, and behavioral risk factors associated with compromised well-being in patients and caregivers. Newly diagnosed HNC patients and their primary caregivers (N = 72 dyads) completed questionnaires before treatment assessing physical and mental well-being, depression, cancer worry, and open-ended support questions. Patients reported worse physical well-being than caregivers (p < 0.05) but similar levels of mental well-being. Caregivers reported providing emotional and instrumental support most frequently with an emphasis on nutrition and assistance with speech, appearance, and addictions. Both patients and their caregivers reported suboptimal mental well-being and depression. Smoking was associated with compromised well-being in patients, caregivers, and dyads. Compromised well-being in patients and their caregivers was more likely when patients were younger, had worse symptoms, and smoked/consumed alcohol (p < 0.05). While patients face more physical strain than caregivers, both equally confront emotional challenges. Results highlight risk factors for compromised well-being in both patients and their caregivers that should be assessed at diagnosis to guide identification of needed dyadic-focused supportive care resources.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Predicting Oral Absorption of fenofibrate in Lipid-Based Drug Delivery Systems by Combining In Vitro Lipolysis with the Mucus-PVPA Permeability Model. The aim of this work was to develop a new in vitro lipolysis-permeation model to predict the in vivo absorption of fenofibrate in self-nanoemulsifying drug delivery systems (SNEDDSs). More specifically, the in vitro intestinal lipolysis model was combined with the mucus-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model. Biosimilar mucus (BM) was added to the surface of the PVPA barriers to closer simulate the intestinal mucosa. SNEDDSs for which pharmacokinetic data after oral dosing to rats was available in the literature were prepared, and the ability of the SNEDDSs to maintain fenofibrate solubilized during in vitro lipolysis was determined, followed by the assessment of drug permeation across the mucus-PVPA barriers. The amount of drug solubilized over time during in vitro lipolysis did not correlate with the AUC (area under the curve) of the plasma drug concentration curve. However, the AUC of the drug permeated after in vitro lipolysis displayed a good correlation with the in vivo AUC (R 2 > 0.9). Thus, it was concluded that the in vitro lipolysis-mucus-PVPA permeation model, simulating the physiological digestion and absorption processes, was able to predict in vivo absorption data, exhibiting great potential for further prediction of in vivo performance of SNEDDSs.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Use of the Menstrual Cycle to Enhance Female Sports Performance and Decrease Sports-Related Injury. The impact of the menstrual cycle on female sports performance is a growing interest area in sports and athletics. In March 2017, the British Journal of Sports Medicine, published the article, "Sport, Exercise and the Menstrual Cycle: Where is the Research?", highlighting the significant under-representation of women included in sport and exercise medicine research studies. Dr. Georgie Bruinvels, a research scientist, is focused primarily on menstruation in female athletes and use of the menstrual cycle to optimize training and performance, while decreasing injury. Bruinvels, states, "There is a body of research emerging that highlights that strength training is more advantageous in the first half of the menstrual cycle because the body adapts and recovers better. Pediatric and Adolescent Gynecology has a place in this emerging interest area, given our level of expertise in menstruation, female physiology and the often-avoided female pubertal physiology.	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Serotonin augmentation therapy by escitalopram has minimal effects on amyloid-β levels in early-stage Alzheimer's-like disease in mice. Dysfunction of the serotonergic (5-HTergic) system has been implicated in the cognitive and behavioural symptoms of Alzheimer's disease (AD). Accumulation of toxic amyloid-β (Aβ) species is a hallmark of AD and an instigator of pathology. Serotonin (5-HT) augmentation therapy by treatment with selective serotonin reuptake inhibitors (SSRIs) in patients with AD has had mixed success in improving cognitive function, whereas SSRI administration to mice with AD-like disease has been shown to reduce Aβ pathology. The objective of this study was to investigate whether an increase in extracellular levels of 5-HT induced by chronic SSRI treatment reduces Aβ pathology and whether 5-HTergic deafferentation of the cerebral cortex could worsen Aβ pathology in the APP swe /PS1 ΔE9 (APP/PS1) mouse model of AD.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Monitoring and adapting endurance training on the basis of heart rate variability monitored by wearable technologies: A systematic review with meta-analysis. To systematically perform a meta-analysis of the scientific literature to determine whether the outcomes of endurance training based on heart rate variability (HRV) are more favorable than those of predefined training.	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Shared yet dissociable neural codes across eye gaze, valence and expectation. The direction of the eye gaze of others is a prominent social cue in primates and is important for communication 1-11 . Although gaze can signal threat and elicit anxiety 6,12,13 , it remains unclear whether it shares neural circuitry with stimulus value. Notably, gaze not only has valence, but can also serve as a predictor of the outcome of a social encounter, which can be either negative or positive 2,8,12,13 . Here we show that the neural codes for gaze and valence overlap in primates and that they involve two different mechanisms: one for the outcome and another for its expectation. Monkeys participated in the human intruder test 13,14 , in which a human participant had either a direct or averted gaze, interleaved with blocks of aversive and appetitive conditioning. We find that single neurons in the amygdala encode gaze 15 , whereas neurons in the anterior cingulate cortex encode the social context 16 , but not gaze. We identify a shared population in the amygdala for which the neural responses to direct and averted gaze parallel the responses to aversive and appetitive stimulus, respectively. Furthermore, we distinguish between two neural mechanisms-an overall-activity scheme that is used for gaze and the unconditioned stimulus, and a correlated-selectivity scheme that is used for gaze and the conditioned stimulus. These findings provide insights into the origins of the neural mechanisms that underlie the computations of both social interactions and valence, and could help to shed light on mechanisms that underlie social anxiety and the comorbidity between anxiety and impaired social interactions.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
The relationship between intracranial pressure and neurocognitive function before and after the repair of a skull injury. This study examines the relationship between intracranial pressure (ICP) changes after skull injury repair and neurocognitive function before and after the repair.	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
MicroRNA31 and MMP-1 contribute to the differentiated pathway of invasion -with enhanced epithelial-to-mesenchymal transition- in squamous cell carcinoma of the skin. Epithelial to mesenchymal transition (EMT) is an important mechanism of invasion in cutaneous squamous cell carcinomas (cSCCs) and has been found to be enhanced in tumors originated from actinic keratosis with transformation limited to the basal epithelial layer -differentiated pathway-, compared to cases with invasion subsequent to complete epidermal transformation -classical pathway-. Several microRNAs and proteins can contribute to EMT modulation in cSCCs. MicroRNA21 and microRNA31 are involved in posttranscriptional regulation of protein expression and could play a relevant role in EMT and cSCC progression. Throughout the EMT process upregulation of matrix metalloproteinases (MMPs) enhances invasiveness and MMP-1 and MMP-3 contribute to local invasion, angiogenesis and metastasis in cSCCs. Additionally, cSCC development is associated with PTEN loss and NF-κB, NOTCH-1 and p63 activation. The aim of this work is to identify differences in the expression of those molecules between both pathways of cSCCs development. Eight tissue microarrays from 80 consecutive cSCCs were analyzed using LNA-based miRNA in situ hybridization for miRNA21 and miRNA31 evaluation, and immunohistochemistry for MMP-1, MMP-3, PTEN, NOTCH-1, NF-κB, p63 and CD31. Significantly higher expression of miRNA31 (p < 0.0001) and MMP-1 (p = 0.0072) and angiogenesis (p = 0.0199) were found in the differentiated pathway, whereas PTEN loss (p = 0.0430) was more marked in the classical pathway. No significant differences were found for the other markers. Our findings support a contribution of miRNA31 and MMP-1 in the differentiated pathway, associated to EMT and increased microvascularization. The greater PTEN loss in the classical pathway indicate that its relevance in cSCC is not EMT-related.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	1	0	0
Animal board invited review: Animal source foods in healthy, sustainable, and ethical diets - An argument against drastic limitation of livestock in the food system. Animal source foods are evolutionarily appropriate foods for humans. It is therefore remarkable that they are now presented by some as unhealthy, unsustainable, and unethical, particularly in the urban West. The benefits of consuming them are nonetheless substantial, as they offer a wide spectrum of nutrients that are needed for cell and tissue development, function, and survival. They play a role in proper physical and cognitive development of infants, children, and adolescents, and help promote maintenance of physical function with ageing. While high-red meat consumption in the West is associated with several forms of chronic disease, these associations remain uncertain in other cultural contexts or when consumption is part of wholesome diets. Besides health concerns, there is also widespread anxiety about the environmental impacts of animal source foods. Although several production methods are detrimental (intensive cropping for feed, overgrazing, deforestation, water pollution, etc.) and require substantial mitigation, damaging impacts are not intrinsic to animal husbandry. When well-managed, livestock farming contributes to ecosystem management and soil health, while delivering high-quality foodstuffs through the upcycling of resources that are otherwise non-suitable for food production, making use of marginal land and inedible materials (forage, by-products, etc.), integrating livestock and crop farming where possible has the potential to benefit plant food production through enhanced nutrient recycling, while minimising external input needs such as fertilisers and pesticides. Moreover, the impacts on land use, water wastage, and greenhouse gas emissions are highly contextual, and their estimation is often erroneous due to a reductionist use of metrics. Similarly, whether animal husbandry is ethical or not depends on practical specificities, not on the fact that animals are involved. Such discussions also need to factor in that animal husbandry plays an important role in culture, societal well-being, food security, and the provision of livelihoods. We seize this opportunity to argue for less preconceived assumptions about alleged effects of animal source foods on the health of the planet and the humans and animals involved, for less top-down planning based on isolated metrics or (Western) technocratic perspectives, and for more holistic and circumstantial approaches to the food system.	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Anemic Women are More at Risk of Injectable Contraceptive Discontinuation due to Side Effects in Ethiopia. This paper investigates the importance of women's physiological condition, alongside sociocultural factors, for predicting the risk of discontinuation of the injectable contraceptive due to side effects in Ethiopia. Contraceptive calendar data from the 2016 Ethiopian Demographic and Health Survey were analyzed. Women aged 15-49 who had initiated the injectable contraceptive in the last two years were included in the analysis (n = 1,513). Physiological factors investigated were body mass, iron status, reproductive depletion, and physical strain. After checking for reverse causality, associations between physiological and sociocultural risk factors and discontinuation due to side effects (DSE) or discontinuation due to other reasons (DOR) were estimated using multivariate Cox proportional regression analyses. Anemia status was associated with DSE, but not DOR. Anemic women were two times more at risk of DSE compared with nonanemic women (adjusted hazard ratios [aHR] = 2.38, confidence interval [CI] = 1.41-4.00). DOR was predicted by religion, wealth, and relationship status. Accounting for diversity in physiological condition is key for understanding contraceptive discontinuation due to side effects. To reduce side effects, family planning programs might benefit from providing hormonal contraception within an integrated package addressing anemia.	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Biosynthesis pathways and strategies for improving 3-hydroxypropionic acid production in bacteria. 3-Hydroxypropionic acid (3-HP) represents an economically important platform compound from which a panel of bulk chemicals can be derived. Compared with petroleum-dependent chemical synthesis, bioproduction of 3-HP has attracted more attention due to utilization of renewable biomass. This review outlines bacterial production of 3-HP, covering aspects of host strains (e.g., Escherichia coli and Klebsiella pneumoniae), metabolic pathways, key enzymes, and hurdles hindering high-level production. Inspired by the state-of-the-art advances in metabolic engineering and synthetic biology, we come up with protocols to overcome the hurdles constraining 3-HP production. The protocols range from rewiring of metabolic networks, alleviation of metabolite toxicity, to dynamic control of cell size and density. Especially, this review highlights the substantial contribution of microbial growth to 3-HP production, as we recognize the synchronization between cell growth and 3-HP formation. Accordingly, we summarize the following growth-promoting strategies: (i) optimization of fermentation conditions; (ii) construction of gene circuits to alleviate feedback inhibition; (iii) recruitment of RNA polymerases to overexpress key enzymes which in turn boost cell growth and 3-HP production. Lastly, we propose metabolic engineering approaches to simplify downstream separation and purification. Overall, this review aims to portray a picture of bacterial production of 3-HP.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Effects of water stably-enriched with oxygen as a novel method of tissue oxygenation on mitochondrial function, and as adjuvant therapy for type 2 diabetes in a randomized placebo-controlled trial. Diabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	1	0
Methodological tools to study species of the genus Burkholderia. Bacteria belonging to the Burkholderia genus are extremely versatile and diverse. They can be environmental isolates, opportunistic pathogens in cystic fibrosis, immunocompromised or chronic granulomatous disease patients, or cause disease in healthy people (e.g., Burkholderia pseudomallei) or animals (as in the case of Burkholderia mallei). Since the genus was separated from the Pseudomonas one in the 1990s, the methodological tools to study and characterize these bacteria are evolving fast. Here we reviewed the techniques used in the last few years to update the taxonomy of the genus, to study gene functions and regulations, to deepen the knowledge on the drug resistance which characterizes these bacteria, and to elucidate their mechanisms to establish infections. The availability of these tools significantly impacts the quality of research on Burkholderia and the choice of the most appropriated is fundamental for a precise characterization of the species of interest.Key points• Updated techniques to study the genus Burkholderia were reviewed.• Taxonomy, genomics, assays, and animal models were described.• A comprehensive overview on recent advances in Burkholderia studies was made.	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The Evolving Role of Public Health in Medical Education. Medical education in the twentieth century was largely influenced by the Flexner Report, with significant proportions of instruction dedicated to the molecular underpinnings of the pathologic pathways and minimal mention of the socio-ecological determinants of health. When examining the predominant diseases of the twenty first century landscape, widening health disparities, and significant changes in the United States healthcare system, it is imperative to view wellness and sickness in a broader public health context rather than a singular focus of the biomedical model. While undergraduate opportunities to study public health are on the rise in the United States, there is a parallel urgency for medical curricula to recognize the importance of the complex interrelated socio-ecological root causes of health, well-being, and illness. In order to reduce the risk of non-communicable diseases and increase health equity, it is necessary for medical education to integrate core public health knowledge and competencies. Contemporary health challenges require a public health approach, in addition to clinical skills, for physicians to provide equitable care. The COVID-19 pandemic further underscores the necessity to mitigate the effects of socio-ecological determinants of health. Seven key recommendations are presented from a training to practice timeline emphasizing the important linkages between medical education, socio-ecological influences on health, and public health. As the health challenges in society and communities shift, so too must training of future physicians. There is a need and an opportunity for medicine and public health to address the shared health challenges of our global society.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Validation of ICD-10 codes shows intracranial venous thrombosis incidence to be higher than previously reported. Intracranial venous thrombosis (ICVT) accounts for around 0.5% of all stroke cases. There have been no previously published studies of the International Classification of Diseases, Tenth Edition (ICD-10) validation for the identification of ICVT admissions in adults.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
A comprehensive analysis of the Lactuca sativa, L. transcriptome during different stages of the compatible interaction with Rhizoctonia solani. The leafy green vegetable Lactuca sativa, L. is susceptible to the soil-born fungus Rhizoctonia solani AG1-IB. In a previous study, we reported on the transcriptional response of R. solani AG1-IB (isolate 7/3/14) during the interspecies interaction with L. sativa cv. Tizian by means of RNA sequencing. Here we present the L. sativa transcriptome and metabolome from the same experimental approach. Three distinct interaction zones were sampled and compared to a blank (non-inoculated) sample: symptomless zone 1, zone 2 showing light brown discoloration, and a dark brown zone 3 characterized by necrotic lesions. Throughout the interaction, we observed a massive reprogramming of the L. sativa transcriptome, with 9231 unique genes matching the threshold criteria for differential expression. The lettuce transcriptome of the light brown zone 2 presents the most dissimilar profile compared to the uninoculated zone 4, marking the main stage of interaction. Transcripts putatively encoding several essential proteins that are involved in maintaining jasmonic acid and auxin homeostasis were found to be negatively regulated. These and other indicator transcripts mark a potentially inadequate defence response, leading to a compatible interaction. KEGG pathway mapping and GC-MS metabolome data revealed large changes in amino acid, lignin and hemicellulose related pathways and related metabolites.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
COMPLEX CHEST WALL DEFORMITY CAUSING CARDIAC ARREST: A PECULIAR PEDIATRIC CASE. Congenital chest wall deformities are common in children, causing self and parental concern mainly due to cosmesis. These defects rarely cause severe symptoms in patients.	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
New answers to the old RIDDLE: RNF168 and the DNA damage response pathway. The chromatin-based DNA damage response pathway is tightly orchestrated by histone post-translational modifications, including histone H2A ubiquitination. Ubiquitination plays an integral role in regulating cellular processes including DNA damage signaling and repair. The ubiquitin E3 ligase RNF168 is essential in assembling a cohort of DNA repair proteins at the damaged chromatin via its enzymatic activity. RNF168 ubiquitinates histone H2A(X) at the N terminus and generates a specific docking scaffold for ubiquitin-binding motif-containing proteins. The regulation of RNF168 at damaged chromatin and the mechanistic implication in the recruitment of DNA repair proteins to the damaged sites remain an area of active investigation. Here, we review the function and regulation of RNF168 in the context of ubiquitin-mediated DNA damage signaling and repair. We will also discuss the unanswered questions that require further investigation and how understanding RNF168 targeting specificity could benefit the therapeutic development for cancer treatment.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	0	0	0	0	0	0	0	0	0
Designing Ecological Security Patterns Based on the Framework of Ecological Quality and Ecological Sensitivity: A Case Study of Jianghan Plain, China. Researchers and managers of natural resource conservation have increasingly emphasized the importance of maintaining a connected network of important ecological patches to mitigate landscape fragmentation, reduce the decline of biodiversity, and sustain ecological services. This research aimed to guide landscape management and decision-making by developing an evaluation framework to construct ecological security patterns. Taking the Jianghan Plain as the study area, we identified key ecological sources by overlaying the spatial patterns of ecological quality (biodiversity, carbon storage, and water yield) and ecological sensitivity (habitat sensitivity, soil erosion sensitivity, and water sensitivity) using the Integrated Valuation of Environmental Services and Tradeoffs (InVEST) model and the Chinese Soil Loss Equation Function. Ecological corridors were obtained by the least-cost path analysis method and circuit theory. A total of 48 ecological sources (3812.95 km 2 ), primarily consisting of water area, forestland, and cropland, were identified. Ninety-one ecological corridors were derived, with a total length of 2036.28 km. Forty barriers and 40 pinch points with the highest improvement coefficient scores or priority scores were selected. There were 11 priority corridors with very high levels of connectivity improvement potential and conservation priority, occupying 16.15% of the total length of corridors. The overall potential for ecological connectivity is high on the Jianghan Plain. Our framework offers a valuable reference for constructing ecological security patterns and identifying sites for ecological restoration at the regional scale.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	1	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The Impact of Sex on Strength Training in Adults With Cardiovascular Disease. Cardiovascular disease (CVD) is the leading killer of American males and females. Outcomes of treatment for CVD have historically been worse in females than in males. The inability to recover, may be, at least in part, due to lower levels of skeletal muscle mass in females; which is made worse with the onset of menopause and especially when a catabolic event like surgery and / or illness occurs. We theorize that while regaining cardiorespiratory fitness (CRF) after treatment for CVD is very important, it is only part of what is required for complete recovery. Regaining strength and muscle mass is just as important for healthy physiologic aging and recovery from illness. We outline a simply strategy for helping males and females train for strength while recovering from CVD.	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cephalic muscle development in the Australian lungfish, Neoceratodus forsteri. Lungfishes are the extant sister group of tetrapods. As such, they are important for the study of evolutionary processes involved in the water to land transition of vertebrates. The evolution of a true neck, that is, the complete separation of the pectoral girdle from the cranium, is one of the most intriguing morphological transitions known among vertebrates. Other salient changes involve new adaptations for terrestrial feeding, which involves both the cranium and its associated musculature. Historically, the cranium has been extensively investigated, but the development of the cranial muscles much less so. Here, we present a detailed study of cephalic muscle development in the Australian lungfish, Neoceratodus forsteri, which is considered to be the sister taxon to all other extant lungfishes. Neoceratodus shows several developmental patterns previously described in other taxa; the tendency of muscles to develop from anterior to posterior, from their region of origin toward insertion, and from lateral to ventral/medial (outside-in), at least in the branchial arches. The m.protractor pectoralis appears to develop as an extension of the most posterior m.levatores arcuum branchialium, supporting the hypothesis that the m.cucullaris and its derivatives (protractor pectoralis, levatores arcuum branchialium) are branchial muscles. We present a new hypothesis regarding the homology of the ventral branchial arch muscles (subarcualis recti and obliqui, transversi ventrales) in lungfishes and amphibians. Moreover, the morphology and development of the cephalic muscles confirms that extant lungfishes are neotenic and have been strongly influenced via paedomorphosis during their evolutionary history.	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Integrating Genomics Into Management of Fibrotic Interstitial Lung Disease. Fibrotic interstitial lung diseases (ILDs) have a high mortality rate with an unpredictable disease course and clinical features that frequently overlap. Recent data indicate important roles for genomics in the mechanisms underlying susceptibility and progression of pulmonary fibrosis. The impact of these genomic markers on pharmacotherapy and their contribution to outcomes is increasingly recognized. Interstitial lung abnormalities, frequently considered representative of early ILD, have been consistently associated with the MUC5B promoter polymorphism, a common gene variant. Other rare gene variant mutations, including TERT, TERC, SFTPC, and DKC1, may be present in patients with familial interstitial pneumonia and are frequently associated with a usual interstitial pneumonia pattern of fibrosis. The minor allele of the MUC5B rs35705950 genotype is prevalent in several sporadic forms of ILD, including idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. Gene mutations that characterize familial pulmonary fibrosis may be present in patients with connective tissue disease-related ILD, such as rheumatoid arthritis-ILD. Additionally, shorter telomere lengths and mutations in telomere biology-related genes have been demonstrated in both familial and sporadic ILD, with significant implications for disease progression, lung function, and survival. An improved understanding of the impact of genetic and genomic risk factors on disease progression would better guide personalized therapeutic choices in persons with fibrotic ILD.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
COVID-19 Suspected myopericarditis without pulmonary involvement. Myopericarditis is a rare consequence of COVID-19 infection. Although extremely rare, COVID-19 can present without pulmonary involvement, and there have been reports of isolated cardiac involvement in one prior case We report a case of a young African American man presenting with myopericarditis following a recently recovered COVID-19 infection. Complicated by ICU admission requiring vasopressors; with eventual resolution following initiation of aspirin and colchicine for myopericarditis. Life threatening myopericarditis can occur following resolution of COVID-19 disease. The degree of cardiac involvement correlates poorly to the severity of pulmonary involvement.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Part by Part: Synthetic Biology Parts Used in Solventogenic Clostridia. The solventogenic Clostridia are of interest to the chemical industry because of their natural ability to produce chemicals such as butanol, acetone and ethanol from diverse feedstocks. Their use as whole cell factories presents multiple metabolic engineering targets that could lead to improved sustainability and profitability of Clostridium industrial processes. However, engineering efforts have been held back by the scarcity of genetic and synthetic biology tools. Over the past decade, genetic tools to enable transformation and chromosomal modifications have been developed, but the lack of a broad palette of synthetic biology parts remains one of the last obstacles to the rapid engineered improvement of these species for bioproduction. We have systematically reviewed existing parts that have been used in the modification of solventogenic Clostridia, revealing a narrow range of empirically chosen and nonengineered parts that are in current use. The analysis uncovers elements, such as promoters, transcriptional terminators and ribosome binding sites where increased fundamental knowledge is needed for their reliable use in different applications. Together, the review provides the most comprehensive list of parts used and also presents areas where an improved toolbox is needed for full exploitation of these industrially important bacteria.	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The Pharmaceutical Industry in 2021. An Analysis of FDA Drug Approvals from the Perspective of Molecules. Similar to last year, 2021 will be remembered for the COVID-19 pandemic. Although five vaccines have been approved by the two most important drug regulatory agencies, namely the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the pandemic has still not been brought under control. However, despite the context of a global pandemic, 2021 has been an excellent year with respect to drug approvals by the FDA. In 2021, 50 drugs have been authorized, making it the fourth-best year after 2018 (59 drugs) and 1996 and 2020 (53 each). Regarding biologics, 2021 has been the third-best year to date, with 14 approvals, and it has also witnessed the authorization of 36 small molecules. Of note, nine peptides, eight monoclonal antibodies, two antibody-drug conjugates, and two oligonucleotides have been approved this year. From them, five of the molecules are pegylated and three of them highly pegylated. The presence of nitrogen aromatic heterocycles and/or fluorine atoms are once again predominant among the so-called small molecules. This report analyzes the 50 new drugs approved in 2021 from a chemical perspective, as it did for those authorized in the previous five years. On the basis of chemical structure alone, the drugs that received approval in 2021 are classified as the following: biologics (antibodies, antibody-drug conjugates, enzymes, and pegylated proteins); TIDES (peptide and oligonucleotides); combined drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Polyglutamine-Related Aggregates Can Serve as a Potent Antigen Source for Cross-Presentation by Dendritic Cells. Protective MHC class I-dependent immune responses require an overlap between repertoires of proteins directly presented on target cells and cross-presented by professional APC, specifically dendritic cells. How stable proteins that rely on defective ribosomal proteins for direct presentation are captured for cell-to-cell transfer remains enigmatic. In this study, we address this issue using a combination of in vitro (C57BL/6-derived mouse cell lines) and in vivo (C57BL/6 mouse strains) approaches involving stable and unstable versions of OVA model Ags displaying defective ribosomal protein-dependent and -independent Ag presentation, respectively. Apoptosis, but not necrosis, of donor cells was found associated with robust global protein aggregate formation and captured stable proteins permissive for cross-presentation. Potency of aggregates to serve as Ag source was directly demonstrated using polyglutamine-equipped model substrates. Collectively, our data implicate global protein aggregation in apoptotic cells as a mechanism that ensures the overlap between MHC class I epitopes presented directly or cross-presented by APC and demonstrate the unusual ability of dendritic cells to process stable protein aggregates.	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
An analysis of the radiological factors associated with respiratory failure in COVID-19 pneumonia and the CT features among different age categories. To investigate CT patterns of COVID-19 pneumonia associated with respiratory failure (RF) focused on the distribution of lesions.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Prevalence of COVID-19 Mimics in the Emergency Department. Objective Due to the lack of specific clinical manifestations and symptoms, it is difficult to distinguish COVID-19 from mimics. A common pitfall is to rush to make a diagnosis when encountering a patient with COVID-19-like symptoms. The present study describes a series of COVID-19 mimics using an outpatient database collected from a designated COVID-19 healthcare facility in Tokyo, Japan. Methods We established an emergency room (ER) tailored specifically for patients with suspected or confirmed COVID-19 called the "COVID-ER." In this single-center retrospective cohort study, we enrolled patients who visited the COVID-ER from February 1 to September 5, 2020. The outcomes included the prevalence of COVID-19, admission, potentially fatal diseases and final diagnosis. Results We identified 2,555 eligible patients. The median age was 38 (interquartile range, 26-57) years old. During the study period, the prevalence of COVID-19 was 17.9% (457/2,555). Non-COVID-19 diagnoses accounted for 82.1% of all cases. The common cold had the highest prevalence and accounted for 33.0% of all final diagnoses, followed by gastroenteritis (9.4%), urinary tract infections (3.8%), tonsillitis (2.9%), heat stroke (2.6%) and bacterial pneumonia (2.1%). The prevalence of potentially fatal diseases was 14.2% (298/2,098) among non-COVID-19 patients. Conclusion Several potentially fatal diseases remain masked among the wave of COVID-19 mimics. It is imperative that a thorough differential diagnostic panel be considered prior to the rendering of a COVID-19 diagnosis.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Comparison of appendicular lean mass indices for predicting physical performance in Korean hemodialysis patients: A cross-sectional study. Few studies have examined the optimal adjustment indices for predicting low muscle strength or physical performance in hemodialysis (HD) patients. Thus, the present study aimed to identify optimal adjustment indices for predicting strength and/or physical performance in HD patients.Our study was performed at an HD center (n = 84). Appendicular lean mass (ALM; kg) was calculated using dual-energy X-ray absorptiometry. ALM were adjusted to body weight, height2 (Ht2), body surface area, or body mass index. Physical performance tests (sit-to-stand test performed 5 times test, sit-to-stand for 30 second test, 6-minute walk test, timed up and go test, gait speed, hand grip strength, average steps per day (AST), and short physical performance battery) were also evaluated. Participants with a below median value for each physical performance test were defined as the low group.The mean participant age was 55.6 ± 12.8 years; 44 (52.4%) were men. The univariate analysis revealed a significant difference in ALM/Ht2 values between the low and normal physical performance group in all physical performance tests except short physical performance battery. The multivariate analysis revealed a significant difference in ALM/Ht2 between the low and normal physical performance groups in hand grip strength, 5 times sit-to-stand test, sit-to-stand for 30-second test, and AST. In women on HD, most indices were not associated with physical performance or strength.We demonstrated that, in men on HD, ALM/Ht2 may be the most valuable among various variables adjusted for ALM for predicting physical performance or strength.	0	0	0	0	0	0	1	0	0	0	1	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The budget impact of adding pralsetinib to a US health plan formulary for treatment of non-small cell lung cancer and thyroid cancer with RET alterations. BACKGROUND: Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung cancer (NSCLC) accounts for 80% to 85% of all lung cancers. Thyroid cancer, while generally not as lethal as lung cancer, has a large prevalent population and a rapidly increasing incidence in the United States. Pralsetinib is a highly potent, selective rearranged during transfection ( RET ) inhibitor indicated for the treatment of RET -positive NSCLC and thyroid cancer tumors. OBJECTIVE: To estimate the budget impact of adding pralsetinib to a 1 million-member US health plan formulary for the treatment of patients with metastatic RET fusion-positive NSCLC, advanced or metastatic RET -mutant medullary thyroid cancer (MTC), or advanced or metastatic RET fusion-positive thyroid cancer (non-MTC). METHODS: A budget impact model with a 3-year time horizon was developed in Microsoft Excel to estimate the number of eligible RET -positive NSCLC and thyroid cancer patients in a plan and quantify associated treatment costs (2020 USD). Comparators in the analyses included pralsetinib, selpercatinib, and cabozantinib, as well as indication-specific use of pembrolizumab, pemetrexed/carboplatin combination, vandetanib, lenvatinib, and sorafenib. Drug acquisition, molecular testing, treatment monitoring, and adverse event management costs were included to estimate total annual costs and per-member per-month (PMPM) costs in current (without pralsetinib) and potential future market scenarios, where pralsetinib is assumed to split the projected RET inhibitor market share with selpercatinib. The number of treated patients was based on age- and sex-adjusted incidence of disease, the proportion of patients diagnosed with advanced or metastatic disease, and projected RET testing rates. Treatment duration was based on progression-free survival or duration of response data from clinical trials. Medical resources were monetized using standardized sources such as Medicare reimbursement and wholesale acquisition cost (WAC). RESULTS: The model estimated that there would be approximately 6 new treatment-eligible patients in a 1 million-member plan annually. Monthly WAC is $19,243 for pralsetinib and $20,600 for selpercatinib at the recommended starting dose. Adoption of pralsetinib, with corresponding increases in pralsetinib market share, would be slightly cost saving to a payer, decreasing the overall budget impact to the health plan by $49,985 in year 3 (-$0.0042 PMPM; -$0.0030, -$0.0006, and -$0.0005 for NSCLC, MTC, and thyroid cancer [non-MTC], respectively). In year 3, drug costs were the key driver of total costs (~80%-98%) and cost savings. All other medical resource categories were cost-neutral or nominally cost saving or additive in the budget impact analysis. CONCLUSIONS: Quantifying the budget impact associated with the adoption of new targeted precision therapies is an important consideration for payers. For eligible NSCLC and thyroid cancer patients, our analysis suggests that adoption of pralsetinib is expected to result in modest cost savings for US payers. DISCLOSURES: Support for this study was provided by Blueprint Medicines Corporation. This study was conducted by Veritas Health Economics Consulting, Inc., in collaboration with Blueprint Medicines, which was involved in the design of the study; collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the report for publication. Duff is an employee of Veritas Health Economics Consulting, which received research funding from Blueprint Medicines to develop the budget impact model. Norregaard and Sullivan are employees of Blueprint Medicines. Bargiacchi and Brener were employees of Blueprint Medicines at the time of the research study. This study was presented as a poster at the AMCP Virtual Learning Event, April 2021.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
A reliable and easy to transport quality control method for chlamydia and gonorrhoea molecular point of care testing. Quality control (QC) is an essential component of point-of-care testing programs. In the context of a randomised-controlled trial (TTANGO) using GeneXpert (Xpert) Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG) point-of-care testing in remote areas of Australia, we aimed to develop and utilise a stable positive control material. Bacterial cultures of CT and NG were resuspended together to provide cycle threshold (C t ) values of approximately 25 cycles for both CT and NG when tested on the Xpert CT/NG assay. These positive control suspensions were dried in aliquots, heat inactivated, and then provided to 12 participating health services as research-only QC samples in kit form. At each service, a QC sample was resuspended and tested each month on the Xpert. QC results, including Xpert C t values, were analysed from each site over 30 months and we calculated costs per QC sample. Overall, at 12 health services there were 89 QC samples tested (average of 8 tests per site per year). Mean C t values for the 89 controls samples were 25.25 cycles (SD = 1.15) for CT, 24.04 cycles (SD = 1.400) for one NG target and 23.35 cycles (SD = 1.55) for the other NG target. No significant differences in C t value for CT or NG controls were observed over a trial period of 30 months. Positive QC samples for research use in a trial of a molecular point-of-care assay were inexpensive to produce and stable when stored at 2-8°C. For routine use, additional requirements such as meeting National Association of Testing Authority (NATA) regulations and Therapeutic Goods Administration (TGA) approval will need to be achieved.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Experience with thoracic endovascular aortic repair applied in treating Stanford type B aortic dissection: An analysis of 98 cases. Thoracic endovascular aortic repair (TEVAR) has been frequently applied in Stanford type B aortic dissection since thoracic aortic diseases were first treated with artificial vessels.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Discovery of BP3 as an efficacious proteolysis targeting chimera (PROTAC) degrader of HSP90 for treating breast cancer. Heat shock protein 90 (HSP90) is involved in the stabilization and activation of oncoproteins, rendering it essential for oncogenic transformation. However, the HSP90 inhibitors evaluated to date have not led to the expected effects in cancer therapy. Herein, we systematically described the design, synthesis, and evaluation of HSP90 degraders based upon the proteolysis-targeting chimera (PROTAC) strategy. The results showed that the candidate compound 16b (BP3) potently degraded HSP90 and effectively inhibited the growth of human breast cancer cells. When used as a single agent, BP3 led to effective tumor suppression in mice. These findings demonstrate that our HSP90-targeting PROTAC strategy has potential novel applications in breast cancer therapy.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The Contribution of Psychosocial Interventions to Precision Medicine for Heart Health. This paper reviews the value of incorporating psychosocial interventions into precision medicine for heart health. First, we review the empirical literature on prevalence of common mental health comorbidities among individuals with cardiovascular disease (CVD). We then review transdiagnostic approaches for conceptualization and treatment of mental health in individuals with CVD. We highlight recent studies that have used novel methods to individualize psychosocial interventions. Finally, we propose a preliminary framework intended to support Health Care Providers in individualizing treatment, which includes: 1) assessment of patient risk factors, characteristics, and expectations; 2) consideration of transdiagnostic processes underlying several psychiatric symptoms that contribute to CVD risk; 3) patient engagement in shared decision-making for psychosocial treatment; and 4) ongoing outcome monitoring to evaluate treatment responsiveness. We anticipate that the proposed framework will evolve with the emergence of new empirical evidence; as such, future directions and challenges for research are discussed.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Forces controlling organ growth and size. One of the fundamental questions in developmental biology is what determines the final size and shape of an organ. Recent research strongly emphasizes that besides cell-cell communication, biophysical principals govern organ development. The architecture and mechanics of a tissue guide cellular processes such as movement, growth or differentiation. Furthermore, mechanical cues do not only regulate processes at a cellular level but also provide constant feedback about size and shape on a tissue scale. Here we review several models and experimental systems which are contributing to our understanding of the roles mechanical forces play during organ development. One of the best understood processes is how the remodeling of bones is driven by mechanical load. Culture systems of single cells and of cellular monolayers provide further insights into the growth promoting capacity of mechanical cues. We focus on the Drosophila wing imaginal disc, a well-established model system for growth regulation. We discuss theoretical models that invoke mechanical feedback loops for growth regulation and experimental studies providing empirical support. Future progress in this exciting field will require the development of new tools to precisely measure and modify forces in living tissue systems.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Targeting Metabolism as a Novel Therapeutic Approach to Autoimmunity, Inflammation, and Transplantation. Immune cell activation and differentiation occurs concurrently with metabolic reprogramming. This ensures that activated cells generate the energy and substrates necessary to perform their specified function. Likewise, the metabolic programs among different cells of the immune system vary. By targeting different metabolic pathways, these differences allow for selective regulation of immune responses. Further, the relative susceptibility of cells to a metabolic inhibitor is dictated by their metabolic demands; cellular selectivity is based on demand. Therefore, where differences exist in metabolic pathways between healthy and pathogenic cells, there is opportunity for selective regulation with agents lacking intrinsic specificity. There are now a host of studies demonstrating how inhibitors of metabolism (e.g., glycolysis, glutamine metabolism, and fatty acid oxidation) can regulate immune responses and treat immune-mediated pathogenesis. In this brief review we detail how inhibitors of metabolism can be employed to regulate immune responses in both autoimmunity and transplantation.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tbx18-positive cells differentiated from murine ES cells serve as proepicardial progenitors to give rise to vascular smooth muscle cells and fibroblasts. Proepicardium (PE) cells generate cardiac fibroblasts, smooth muscle cells (SMCs) and endothelial cells that form coronary arteries. T-box18 (Tbx18) is a well-known marker of PE cells and epicardium. We examined whether Tbx18-positive cells differentiated from murine embryonic stem (ES) cells serve as PE progenitors to give rise to vascular SMCs and fibroblasts. To collect Tbx18-positive cells, we established Tbx18-EGFP knock-in mouse ES cells using the CRISPR/Cas9 system. We harvested the Tbx18-EGFP-positive cells on day 8, 10 and 14 after the initiation of differentiation; Tbx18 mRNA was enriched on day 8 to 14 and Snai2 mRNA was enriched on day 8 and 10, indicating successful collection of Tbx18-positive cells. Tbx18-EGFP-positive cells expressed the PE marker WT1 on day 8 and 10. They also expressed the SMC marker Acta2 and fibroblast markers Thy1 and Fsp1 on day 8 to 14, but did not express the endothelial cell marker PECAM or the cardiac cell marker CD166 or Myh7. In conclusion, Tbx18-positive cells represent a part of PE cells in the initial phase of differentiation and subsequently include SMCs as well as fibroblasts. These results indicate that Tbx18-positive cells serve as a PE progenitor to supply a variety of cells that contribute to the formation of coronary arteries.	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Association between type 2 diabetes status and osteoarthritis in adults aged ≥ 50 years. Increasingly, studies have addressed the possible association between type 2 diabetes mellitus (T2DM) and osteoarthritis (OA), although this remains an issue of controversy. Our aim in this study was to investigate the association between T2DM and OA among 7781 adults ≥50 years of age, through a cross-sectional analysis of the National Health and Nutrition Examination Survey from 2011 through 2018.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Urinary proteomics to diagnose chronic active antibody-mediated rejection in pediatric kidney transplantation - a pilot study. Chronic antibody-mediated rejection (cABMR) is the main cause of long-term renal graft loss. Late-stage diagnosis is made by detecting donor-specific antibodies (DSA) in blood combined with typical histomorphological lesions in renal allografts. There is a need for noninvasive biomarkers for cABMR that might permit screening and earlier diagnosis. In a case control study of 24 pediatric renal transplant recipients, urine samples were analyzed using capillary electrophoresis and mass spectrometry. Patients were matched with 36 pediatric renal transplant patients without cABMR. Statistical analysis used the nonparametric Wilcoxon test to identify 79 significant biomarkers, which were combined to a support vector machine-based classifier. After validation in an independent test cohort of eight pediatric patients with and 12 without cABMR, the area under the receiver operating characteristic (ROC) curve (AUC) for detection of cABMR was 0.92 (95% CI 0.71-0.99) with a sensitivity of 100% (95% CI 63-100%) and a specificity of 75% (95% CI 43-95%). Combining this classifier with the urinary proteomic marker CKD273 improved the detection of patients with cABMR with misclassification in only 2/20 of the patients. These data indicate that a biomarker pattern derived from urinary proteomics allows the detection of cABMR in pediatric renal transplant recipients with high sensitivity and moderate specificity.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
SeedVicious: Analysis of microRNA target and near-target sites. Here I describe seedVicious, a versatile microRNA target site prediction software that can be easily fitted into annotation pipelines and run over custom datasets. SeedVicious finds microRNA canonical sites plus other, less efficient, target sites. Among other novel features, seedVicious can compute evolutionary gains/losses of target sites using maximum parsimony, and also detect near-target sites, which have one nucleotide different from a canonical site. Near-target sites are important to study population variation in microRNA regulation. Some analyses suggest that near-target sites may also be functional sites, although there is no conclusive evidence for that, and they may actually be target alleles segregating in a population. SeedVicious does not aim to outperform but to complement existing microRNA prediction tools. For instance, the precision of TargetScan is almost doubled (from 11% to ~20%) when we filter predictions by the distance between target sites using this program. Interestingly, two adjacent canonical target sites are more likely to be present in bona fide target transcripts than pairs of target sites at slightly longer distances. The software is written in Perl and runs on 64-bit Unix computers (Linux and MacOS X). Users with no computing experience can also run the program in a dedicated web-server by uploading custom data, or browse pre-computed predictions. SeedVicious and its associated web-server and database (SeedBank) are distributed under the GPL/GNU license.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0