Javtor/biomedical-topic-categorization-2022only-cased

A call for more clarity around causality in neuroscience. In neuroscience, the term 'causality' is used to refer to different concepts, leading to confusion. Here we illustrate some of those variations, and we suggest names for them. We then introduce four ways to enhance clarity around causality in neuroscience.

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Making rights from wrongs: The crucial role of beliefs and justifications for the expression of aversive personality. Whereas research focusing on stable dispositions has long attributed ethically and socially aversive behavior to an array of aversive (or "dark") traits, other approaches from social-cognitive psychology and behavioral economics have emphasized the crucial role of social norms and situational justifications that allow individuals to uphold a positive self-image despite their harmful actions. We bridge these research traditions by focusing on the common core of aversive traits (the dark factor of personality [D]) and its defining aspect of involving diverse beliefs that serve to construct justifications. In particular, we theoretically specify the processes by which D is expressed in aversive behavior-namely, through diverse beliefs and the justifications they serve. In six studies (total N > 25,000) we demonstrate (a) that D involves higher subjective justifiability of those aversive behaviors that individuals high in D are more likely to engage in, (b) that D uniquely relates to diverse descriptive and injunctive beliefs-related to distrust (e.g., cynicism), hierarchy (e.g., authoritarianism), and relativism (e.g., normlessness)-that serve to justify aversive behavior, and (c) a theoretically derived pattern of moderations and mediations supporting the view that D accounts for aversive behavior because it fosters subjective justifiability thereof-at least in part owing to certain beliefs and the justifications they afford. More generally, our findings highlight the role of (social) cognitions within the conceptual definitions of personality traits and processes through which they are expressed in behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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Ability to Care in Acute Situations-The Influence of Simulation-Based Education on New Graduate Nurses. Simulation-based education is frequently used in transition programs for new graduate nurses. Simulation-based education is implemented as a measure to practice nursing skills, gain experience, and prepare nurses for caring in challenging situations, such as acute situations. However, concerns about the data supporting the use of simulation are obtained from small studies that do not use validated measurement scales.

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Perspectives on using bacteriophages in biogerontology research and interventions. With the development of materials engineering, gerontology-related research on new tools for diagnostic and therapeutic applications, including precision and personalised medicine, has expanded significantly. Using nanotechnology, drugs can be precisely delivered to organs, tissues, cells, and cell organelles, thereby enhancing their therapeutic effects. Here, we discuss the possible use of bacteriophages as nanocarriers that can improve the safety, efficiency, and sensitivity of conventional medical therapies. Phages are a new class of targeted-delivery vectors, which can carry high concentrations of cargo and protect other nontargeted cells from the senescent cell killing effects of senolytics. Bacteriophages can also be subjected to chemical and/or genetic modifications that would acquire novel properties and improve their ability to detect senescent cells and deliver senolytics. Phage research in experimental biogerontology will also develop strategies to efficiently deliver senolytics, target senescent cells, activate extrinsic apoptosis pathways in senescent cells, trigger immune cells to recognise senescent cells, induce autophagy, promote cell and tissue regeneration, inhibit senescence-associated secretory phenotype (SASP) by senomorphic activity, stimulate the properties of mild stress-inducing hormetic agents and hormetins, and modulate the gut microbiome.

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Mapping and understanding of correlated electroencephalogram (EEG) responses to the newsvendor problem. Decision-making is one of the most critical activities of human beings. To better understand the underlying neurocognitive mechanism while making decisions under an economic context, we designed a decision-making paradigm based on the newsvendor problem (NP) with two scenarios: low-profit margins as the more challenging scenario and high-profit margins as the less difficult one. The EEG signals were acquired from healthy humans while subjects were performing the task. We adopted the Correlated Component Analysis (CorrCA) method to identify linear combinations of EEG channels that maximize the correlation across subjects ([Formula: see text]) or trials ([Formula: see text]). The inter-subject or inter-trial correlation values (ISC or ITC) of the first three components were estimated to investigate the modulation of the task difficulty on subjects' EEG signals and respective correlations. We also calculated the alpha- and beta-band power of the projection components obtained by the CorrCA to assess the brain responses across multiple task periods. Finally, the CorrCA forward models, which represent the scalp projections of the brain activities by the maximally correlated components, were further translated into source distributions of underlying cortical activity using the exact Low Resolution Electromagnetic Tomography Algorithm (eLORETA). Our results revealed strong and significant correlations in EEG signals among multiple subjects and trials during the more difficult decision-making task than the easier one. We also observed that the NP decision-making and feedback tasks desynchronized the normalized alpha and beta powers of the CorrCA components, reflecting the engagement state of subjects. Source localization results furthermore suggested several sources of neural activities during the NP decision-making process, including the dorsolateral prefrontal cortex, anterior PFC, orbitofrontal cortex, posterior cingulate cortex, and somatosensory association cortex.

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Seronegative Autoimmune Limbic Encephalitis: A Case Report. Autoimmune encephalitis (AE) is an immune-mediated disorder of the central nervous system (CNS). Its definitive diagnosis relies on the identification of a specific antibody. Autoimmune limbic encephalitis (LE) is a subset of AE characterized by inflammation of the limbic cerebral cortex. Cognitive decline, behavioral disturbance, and seizures are its cardinal manifestations. We present the case of a 70-year-old man with subacute progressive gait imbalance, cognitive impairment, and psychiatric manifestations. Extensive serum and cerebrospinal fluid (CSF) investigations did not reveal any abnormality. Autoimmune and paraneoplastic encephalitis antibody panels were negative. Magnetic resonance imaging (MRI) and positron emission tomography (PET) brain scans suggested LE. He responded well to immunotherapy. This case illustrates that AE must be suspected in the appropriate setting, even in the absence of a specific antibody. These patients should be given the benefit of early immunotherapy.

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Self-sealing MEMS spray-nozzles to prevent bacterial contamination of portable inhalers for aqueous drug delivery. Pulmonary drug delivery by portable inhalers is the gold standard in lung disease therapy. An increasing focus on environmentally friendly inhalation currently spurs the development of propellant-free devices. However, the absence of propellants in the drug creates a need for suitable sealing systems that can ensure the pathogenic safety of devices. Traditionally, liquid drug inhalers incorporate a spray nozzle and a separate check valve. Here we show a fully integrated MEMS-based spray system for aqueous drug solutions and demonstrate its bacterial safety. The device comprises a thin silicon membrane with spray orifices, which self-seal against a compliant parylene valve seat underneath. This sealing system prevents bacterial ingrowth in its default closed state, while actuation lifts the membrane from the valve seat upon pressurization and sprays an inhalable aerosol from the nozzles. To seal against bacterial contamination effectively, we found that a contact force between the valve seat and the membrane (featuring the spray nozzles) is needed. In our testing, both self-sealing and an otherwise identical unvalved version of the spray chip can be bacterially safe in continued use when thoroughly cleaned of excess fluids and subjected to low bacterial loads for brief periods. However, when directly exposed to [Formula: see text] CFU/ml of our test organism Citrobacter rodentium for 24 h, unvalved systems become contaminated in nearly 90% of cases. In contrast, self-sealing spray chips reduced contamination probability by 70%. This development may enable preservative-free drug formulations in portable inhalers that use propellant-free aqueous drug solutions.

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PD-1 is expressed in cytotoxic granules of NK cells and rapidly mobilized to the cell membrane following recognition of tumor cells. The contribution of the T cell-related inhibitory checkpoint PD-1 to the regulation of NK cell activity is still not clear with contradictory results concerning its expression and role in the modulation of NK cell cytotoxicity. We provide novel key findings on the mechanism involved in the regulation of PD-1 expression on NK cell membrane and its functional consequences for the elimination of cancer cells. In contrast to freshly isolated NK cells from cancer patients, those from healthy donors did not express PD-1 on the cell membrane. However, when healthy NK cells were incubated with tumor target cells, membrane PD-1 expression increased, concurrent with the CD107a surface mobilization. This finding suggested that PD-1 was translocated to the cell membrane during NK cell degranulation after contact with target cells. Indeed, cytosolic PD-1 was expressed in freshly-isolated-NK cells and partly co-localized with CD107a and GzmB, confirming that membrane PD-1 corresponded to a pool of preformed PD-1. Moreover, NK cells that had mobilized PD-1 to the cell membrane presented a significantly reduced anti-tumor activity on PD-L1-expressing-tumor cells in vitro and in vivo , which was partly reversed by using anti-PD-1 blocking antibodies. Our results indicate that NK cells from healthy individuals express cytotoxic granule-associated PD-1, which is rapidly mobilized to the cell membrane after interaction with tumor target cells. This novel finding helps to understand how PD-1 expression is regulated on NK cell membrane and the functional consequences of this expression during the elimination of tumor cells, which will help to design more efficient NK cell-based cancer immunotherapies.

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Acts of appetite: neural circuits governing the appetitive, consummatory, and terminating phases of feeding. The overconsumption of highly caloric and palatable foods has caused a surge in obesity rates in the past half century, thereby posing a healthcare challenge due to the array of comorbidities linked to heightened body fat accrual. Developing treatments to manage body weight requires a grasp of the neurobiological basis of appetite. In this Review, we discuss advances in neuroscience that have identified brain regions and neural circuits that coordinate distinct phases of eating: food procurement, food consumption, and meal termination. While pioneering work identified several hypothalamic nuclei to be involved in feeding, more recent studies have explored how neuronal populations beyond the hypothalamus, such as the mesolimbic pathway and nodes in the hindbrain, interconnect to modulate appetite. We also examine how long-term exposure to a calorically dense diet rewires feeding circuits and alters the response of motivational systems to food. Understanding how the nervous system regulates eating behaviour will bolster the development of medical strategies that will help individuals to maintain a healthy body weight.

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Tailoring Cu 2+ -loaded electrospun membranes with antibacterial ability for guided bone regeneration. Copper (Cu)-loaded electrospun membranes were tailored for guided bone regeneration (GBR), targeting the stimulation of innate cells active in bone growth and the prevention of bacterial infections. Functional GBR membranes were produced via an electrospinning set-up using a silk-based solution associated with polyethylene oxide (Silk/PEO - control). Experimental groups were loaded with copper oxide using varying weight percentages (0.05 % to 1 % of CuO). The morphological, structural, chemical, and mechanical properties of membranes were evaluated. Direct and indirect in vitro cytocompatibility experiments were performed with primary human bone mesenchymal stem cells and primary human umbilical vein endothelial cells. The antibacterial potential of membranes was tested with Staphylococcus aureus and Fusobacterium nucleatum biofilm. CuO was successfully incorporated into membranes as clusters without compromising their mechanical properties for clinical applicability. Increased Cu concentrations generated membranes with thinner nanofibers, greater pore areas, and stronger antimicrobial effect (p < 0.01). Cu 2+ ion was released from the nanofiber membranes during 1 week, showing higher release in acidic conditions. CuO 0.1 % and CuO 0.05 % membranes were able to support and stimulate cell adhesion and proliferation (p < 0.05), and favor angiogenic responses of vascular cells. In addition, detailed quantitative and qualitative analysis determined that amount of the attached biofilm was reduced on the tailored functional Cu 2+ -loaded GBR membrane. Importantly, these qualities represent a valuable strategy to improve the bone regeneration process and diminish the risk of bacterial infections.

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Novel GRIA2 variant in a patient with atypical autism spectrum disorder and psychiatric symptoms: a case report. As sequencing technology has advanced in recent years, a series of synapse-related gene variants have been reported to be associated with autism spectrum disorders (ASDs). The α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor is a subtype of the ionotropic glutamate receptor, whose number or composition changes can regulate the strength and plasticity of synapses.

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Nurse preceptors' orientation competence and associated factors-A cross-sectional study. To identify distinct orientation competence profiles amongst nurse preceptors and explain the associated factors.

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[Prevention and management of pegaspargase associated-toxicities (excluding coagulation abnormalities). Recommendations of the French Society of Children and Adolescent Cancers (Leukemia committee)]. Pegaspargase (Oncaspar®), a pegylated form of native Escherichia Coli-derived L-asparaginase is an essential component chemotherapy used in the treatment of acute lymphoblastic leukemia (ALL) in pediatric and adult patients. Its particular toxicity profile requires a specific management to improve safety and tolerability and optimize treatment outcome and therefore survival. Within the framework of workshops of practice harmonization of the French Society of Children and Adolescent Cancers, diagnostic and management of the most commonly occuring toxicities (excluding coagulation abnormalities) during Pegaspargase treatment were reviewed according to the analysis of published studies.

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Is the chemical and mechanical ageing of clear aligners during use the reason why predicted results don't always align with final clinical outcomes? Data sources The online databases of Scopus, Web of Science, ScienceDirect, PubMed, ProQuest and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP), from inception to September 2021, were searched with no restrictions to identify eligible studies measuring the changes in surface morphology, chemical and mechanical properties of clear aligners before and after intraoral usage.Study selection Only studies investigating changes in Smart Track (LD30) material met the inclusion criteria. In vitro studies, studies with a sample size of less than ten, studies not assessing the properties of aligners after usage and those assessing the old material of Invisalign were excluded.Data extraction and synthesis Two reviewers independently assessed the studies, and disagreements were resolved through consultation with a third reviewer. Data was pooled using Review Manager (RevMan) version 5.3. Inconsistency test (I2) was used to examine heterogeneity between studies. Meta-analysis was performed based on a random-effects model. Qualitative synthesis was used to assess outcomes from a single study or where different outcome measures were used between studies.Results Two randomised non-control studies and two cohort studies met the inclusion criteria and were included in this systematic review. All included studies were judged to have a moderate risk of bias when assessed using Cochrane collaboration tools (RoB 2 and ROBINS-I). Qualitative assessment of all studies showed LD30 exhibited changes in surface morphology after clinical usage. Mechanical properties were analysed using the pooled estimate of data from 70 aligners. Significant decreases in both Martens hardness (SMD = -3.37; 95% CI [-6.24, -0.52]; P = 0.02) and indentation modulus (SMD = -2.41; 95% CI [-3.39, -1.43]; P = 0.02) indicate changes in mechanical properties before and after usage.Conclusions Within the limitations of the included studies, the authors concluded that LD30 exhibited changes in surface morphology, chemical and mechanical properties during usage, which may have an impact on the differences between predicted and final clinical results. There is currently insufficient evidence to precisely determine the best material that could serve treatment needs.

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Biofilm with highly heterogeneous interior structure for pollutant removal: Effects of individual extracellular polymeric substance. For the first time, this study reveals the effects of an individual component of extracellular polymeric substances on the substrate consumption rates by the embedded cells based on the highly heterogeneous interior structures of a working biofilm. The flow-across mode in operation established a boundary-layer flow field with high transport resistance, making the uniformly structured model valid. Conversely, the flow field of the flow-through mode is determined by 46% jointly by proteins and β-d-glucopyranose polysaccharides. The substrate consumption rates hindered by β-d-glucopyranose polysaccharide is up to 60% over the 20%-40% biofilm height from the bottom, much lower than expected by the uniformly structured models. The strategies to maximize the biofilm performance have been suggested.

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Using the Multidimensional AIMES to Estimate Connection-to-Nature in an Australian Population: A Latent Class Approach to Segmentation. Individuals can interact and develop multiple connections to nature (CN) which have different meanings and reflect different beliefs, emotions, and values. Human population are not homogenous groups and often generalised approaches are not effective in increasing connectedness to nature. Instead, target-group specific approaches focusing on different segments of the population can offer a promising approach for engaging the public in pro-environmental behaviours. This research employed latent class analysis to identify subgroups of individuals in a large, representative sample ( n = 3090) of an Australian region. Three groups were identified using the AIMES measure of CN with its focus on five types of connection to nature. The high CN group comprised about one-third (35.4%) of participants while the group with the lowest profile of scores contained around a fifth (18.6%) of participants. The majority (46.0%) of participants registered CN levels between the high and low groups. These classes were then regressed on predictor variables to further understand differences between the groups. The largest, consistent predictors of class membership were biocentric and social-altruistic value orientations, stronger intentions to perform pro-environmental behaviours in public (e.g., travel on public transport), the amount of time spent in nature, and the age of participants.

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Analytical and Preformulation Characterization Studies of Human Papillomavirus Virus-Like Particles to Enable Quadrivalent Multi-Dose Vaccine Formulation Development. Introducing multi-dose formulations of Human Papillomavirus (HPV) vaccines will reduce costs and enable improved global vaccine coverage, especially in low- and middle-income countries. This work describes the development of key analytical methods later utilized for HPV vaccine multi-dose formulation development. First, down-selection of physicochemical methods suitable for multi-dose formulation development of four HPV (6, 11, 16, and 18) Virus-Like Particles (VLPs) adsorbed to an aluminum adjuvant (Alhydrogel®, AH) was performed. The four monovalent AH-adsorbed HPV VLPs were then characterized using these down-selected methods. Second, stability-indicating competitive ELISA assays were developed using HPV serotype-specific neutralizing mAbs, to monitor relative antibody binding profiles of the four AH-adsorbed VLPs during storage. Third, concentration-dependent preservative-induced destabilization of HPV16 VLPs was demonstrated by addition of eight preservatives found in parenterally administered pharmaceuticals and vaccines, as measured by ELISA, dynamic light scattering, and differential scanning calorimetry. Finally, preservative stability and effectiveness in the presence of vaccine components were evaluated using a combination of RP-UHPLC, a microbial growth inhibition assay, and a modified version of the European Pharmacopoeia assay (Ph. Eur. 5.1.3). Results are discussed in terms of analytical challenges encountered to identify and develop high-throughput methods that facilitate multi-dose formulation development of aluminum-adjuvanted protein-based vaccine candidates.

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mRNA COVID-19 vaccines were linked to myocarditis at 28 d (0.15 to 10 excess events/100 000 vaccinated persons). Karlstad Ø, Hovi P, Husby A, et al. SARS-CoV-2 vaccination and myocarditis in a Nordic cohort study of 23 million residents. JAMA Cardiol. 2022;7:600-12. 35442390.

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Trpc6 gain-of-function disease mutation enhances phosphatidylserine exposure in murine platelets. Platelets enhance coagulation by exposing phosphatidylserine (PS) on their cell surface in response to strong agonist activation. Transient receptor potential channels, including TRPC6, have been implicated in the calcium influx central to this process. Here, we characterize the effect of a Trpc6 gain-of-function (GOF) disease-associated, and a dominant negative (DN), mutation on murine platelet activation. Platelets from mice harboring Trpc6E896K/E896K (GOF) and Trpc6DN/DN mutations were subject to in vitro analysis. Trpc6E896K/E896K and Trpc6DN/DN mutant platelets show enhanced and absent calcium influx, respectively, upon addition of the TRPC3/6 agonist GSK1702934A (GSK). GSK was sufficient to induce integrin αIIbβ3 activation, P-selection and PS exposure, talin cleavage, and MLC2 phosphorylation in Trpc6E896K/E896K, but not in wild-type, platelets. Thrombin-induced calcium influx and PS exposure were enhanced, and clot retraction delayed, by GOF TRPC6, while no differences were noted between wild-type and Trpc6DN/DN platelets. In contrast, Erk activation upon GSK treatment was absent in Trpc6DN/DN, and enhanced in Trpc6E896K/E896K, platelets, compared to wild-type. The positive allosteric modulator, TRPC6-PAM-C20, and fluoxetine maintained their ability to enhance and inhibit, respectively, GSK-mediated calcium influx in Trpc6E896K/E896K platelets. The data demonstrate that gain-of-function mutant TRPC6 channel can enhance platelet activation, including PS exposure, while confirming that TRPC6 is not necessary for this process. Furthermore, the results suggest that Trpc6 GOF disease mutants do not simply increase wild-type TRPC6 responses, but can affect pathways not usually modulated by TRPC6 channel activity, displaying a true gain-of-function phenotype.

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Recyclable polysaccharide/stimuli-responsive polymer composites and their applications in water remediation. The use of composites of stimuli-responsive polymers with polysaccharides during water remediation has gained impetus in recent years. The applications of composites of polysaccharides (chitosan, cellulose and cyclodextrin) with stimuli-responsive polymers (CO 2 -, thermo-, light-, and pH-responsive polymers) were reviewed in this paper. These smart composites have tuneable physicochemical properties that enable them to form tailor-made adsorbents for the adsorption of pollutants from water. Adsorption and desorption of pollutants can be switched on and off by adjusting appropriate stimuli without the use of toxic organic solvents. The polysaccharide/stimuli-responsive polymer-based adsorbents, therefore, can be easily recovered during water remediation by adjusting the stimuli, and this makes them to be eco-friendly and recyclable. These attributes of the polysaccharide/stimuli-responsive polymer-based composites were explored in detail in this review. In addition, the challenges associated with the use of these smart composites as well as their future prospects were also articulated in this paper.

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A commercial ARHGEF17/TEM4 antibody cross-reacts with Nuclear Mitotic Apparatus protein 1 (NuMA). The Rho family Guanine nucleotide exchange factor (GEF) ARHGEF17 (also known as TEM4) is a large protein with only 3 annotated regions: an N-terminal actin-binding domain, a Rho-specific dbl homology (DH)- pleckstrin homology (PH) type GEF domain and a seven bladed β propeller fold at the C-terminus with unknown function. TEM4 has been implicated in numerous activities that rely on regulation of the cytoskeleton including cell migration, cell-cell junction formation and the spindle assembly checkpoint during mitosis. Here we have assessed the specificity of a TEM4 polyclonal antibody that has been commonly used as a Western blotting and immunocytochemistry probe for TEM4 in mammalian cells. We find that this antibody, in addition to its intended target, cross-reacts with the Nuclear Mitotic Apparatus Protein 1 (NuMA) in Western blotting and immunoprecipitation, and detects NuMA preferentially in immunocytochemistry. This cross-reactivity, with an abundant chromatin- and mitotic spindle-associated factor, is likely to affect the interpretation of experiments that make use of this antibody probe, in particular by immunocytochemistry and immunoprecipitation.

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Diagnostic performance of serum calprotectin in discriminating active from inactive ulcerative colitis in an outpatient setting. There are limited and conflicting data on the value of serum calprotectin (sCp) in discriminating active from inactive disease activity in ulcerative colitis (UC). Faecal calprotectin (fCp), sCp, serum C-reactive protein (sCRP) and platelets were compared in patients with UC who had clinically active (n = 29) and clinically inactive (n = 42) disease. Serum calprotectin was measured with Bühlmann® (BMN sCp) and ImmunodiagnostikTM (IDK sCp) assays. Median (interquartile range) fCp was higher in active than inactive disease [1004 (466-1922) versus 151 (55-280) µg/g; p < 0.0001). BMN sCp [4534 (3387-6416) versus 4031 (2401-5414) ng/mL; p = 0.1825], IDK sCp [4531 (2920-6433) versus 3307 (2104-4789) ng/mL; p = 0.1065], sCRP [ 4 (2-8) versus 2 (1-4) mg/L; p = 0.0638) and platelets [269 (233-331) versus 280 (227-325) ×10-9/L; p = 0.8055] were similar in active and inactive disease respectively. The area under the receiver operator characteristics curves with 95% confidence limits were 0.85 (0.76-0.94) for fCp, 0.61 (0.47-0.74) for BMN sCp, 0.61 (0.48-0.75) for IDK sCp, 0.69 (0.56-0.81) for sCRP and 0.52 (0.38-0.66) for blood platelets. Faecal calprotectin is the optimum biomarker for discriminating between active and inactive UC. The diagnostic performance of sCp, irrespective of assay, and systemic biomarkers was poor; of these sCRP performed best.

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Driven by notifications - exploring the effects of badge notifications on user experience. Notification badges are an unexplored category of visual feedback to which we are continuously exposed. This study aims to deepen knowledge on the topic by measuring the behavioral effects of notification badges on a large sample of smartphone users. More precisely, the goal of the study is to observe if the presence of notification badges increases the frequency of clicks on apps. More than 1000 participants were involved in a remote between-subjects experiment, allocated into fifteen equinumerous groups of comparison. Each participant was presented with a smartphone screen displaying fifteen app icons and just one badge notification. Participants were asked to perform a remote user test called First Impression Click Test: a methodology that indicates where they would click first to accomplish a given task (i.e., Where would you click first on this screen?). Our results show a large increase in the number of clicks on apps with notification badges compared to those without notification badges and suggest the important ability of these small affordances to attract attention and stimulate action. Based on the evidence provided, our findings have practical implications for user experience design.

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Preclinical platforms to study therapeutic efficacy of human γδ T cells. Gamma delta (γδ) T lymphocytes are promising candidate for adoptive T cell therapy, however, their treatment efficacy is not satisfactory. Vδ2 T cells are unique to primates and few suitable models are available to assay their anti-tumour function.

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CCL20/CCR6 axis mediates macrophages to promote proliferation and migration of ESCs by blocking autophagic flux in endometriosis. Endometriosis (EMs) is a common benign gynecological disease that affects approximately 10% of females of reproductive age. Endometriosis ectopic lesions could recruit macrophages, which in turn facilitates endometriosis progression. Several studies have indicated that CCL20 derived from macrophages activates the expression of CCR6 in several cells and induces cell proliferation and migration. However, the function of the CCL20/CCR6 axis in the interactions between macrophages and endometriotic stromal cells (ESCs) in EMs has yet to be elucidated.

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Bacterial membrane vesicles in inflammatory bowel disease. Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation with no cure. The intestine is fundamental in controlling human health. Disruption of the microbial ecosystem in the intestine is considered an important cause of IBD. The interaction between the host and microbiota significantly impacts the intestinal epithelial barrier and immune function. Bacterial membrane vesicles (MVs) are vital participants in bacteria-bacteria and host-microbiota communication. Currently, MVs have been found to exhibit many important regulating effects for intestinal microecology and have excellent application potential in clinical disease therapies. In the present review, we review the current knowledge on MVs, and specifically focus on gut bacterial MVs and their roles in the IBD. In addition, we summarized the potential utility of MVs as a novel therapeutic approach in IBD patients.

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Self-Assembly of Optimally Packed Cylindrical Clusters inside Spherical Shells. Systems with short-range attraction and long-range repulsion can form ordered microphases in bulk and under confinement. Using grand canonical Monte Carlo simulations, we study a colloidal system with competing interactions under confinement in narrow spherical shells at thermodynamic conditions at which the hexagonal phase of cylindrical clusters is stable in bulk. We observe spontaneous formation of different ordered structures. The results of the simulations are in a very good agreement with the predictions of a simple mathematical model based on the geometry and optimal packing of colloidal clusters. The results of the simulations and the explanation provided by a relatively simple geometric model may be helpful in manufacturing copolymer nanocapsules and may indicate possible ways of coiling DNA strands on spherical objects.

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The tribe Cybalomiini (Lepidoptera: Pyraloidea, Crambidae, Glaphyrinae) of sub-Saharan Africa. The Cybalomiini (Crambidae, Glaphyrinae) of Africa south of the Sahara are revised. One new genus Melouia is described, 26 new species: Crambicybolomia similis, Goniophysetis aarviki, G. cuthberti, Trichophysetis collinsi, T. vumbensis, T. foveolatae, T. zariensis, T. samueli, T. ethiopica, T. mossi, T. trilinealis, T. cataracta, Melouia krooni, M. aspidophoralis, Ptychopseustis maesi, P. sharporum, P. baringensis, P. abyssinica, P. catherinae, P. butleri, P. fuscalis, P. beccarii, P. sinualis, P. umbroterminalis, P. brunneoflavalis, and P. suffusalis are described and one new synonymy is declared.

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Future prospect of "Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients". Recently, we read the article "Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients" with interest, and it is preliminary suggested that gut microbiota is closely related to therapeutic effect of nivolumab. Based on the meaningful results of this article, several valuable research directions are proposed to enhance the therapeutic effect of immune checkpoint inhibitors on advanced hepatocellular carcinoma.

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Myopia and BMI: a nationwide study of 1.3 million adolescents. This study analyzed the association between adolescent BMI and myopia severity.

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Three-dimensional echo decorrelation monitoring of radiofrequency ablation in ex vivo bovine liver. Three-dimensional (3D) echo decorrelation imaging was investigated for monitoring radiofrequency ablation (RFA) in ex vivo bovine liver. RFA experiments (N = 14) were imaged by 3D ultrasound using a matrix array, with in-phase and quadrature complex echo volumes acquired about every 11 s. Tissue specimens were then frozen at -80 °C, sectioned, and semi-automatically segmented. Receiver operating characteristic (ROC) curves were constructed for assessing ablation prediction performance of 3D echo decorrelation with three potential normalization approaches, as well as 3D integrated backscatter (IBS). ROC analysis indicated that 3D echo decorrelation imaging is potentially a good predictor of local RFA, with the best prediction performance observed for globally normalized decorrelation. Tissue temperatures, recorded by four thermocouples integrated into the RFA probe, showed good correspondence with spatially averaged decorrelation and statistically significant but weak correlation with measured echo decorrelation at the same spatial locations. In tests predicting ablation zones using a weighted K-means clustering approach, echo decorrelation performed better than IBS, with smaller root mean square volume errors and higher Dice coefficients relative to measured ablation zones. These results suggest that 3D echo decorrelation and IBS imaging are capable of real-time monitoring of thermal ablation, with potential application to clinical treatment of liver tumors.

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Acute pancreatitis in 60 Iranian children: do pediatricians follow the new guidelines in diagnosis and management of acute pancreatitis? The incidence of acute pancreatitis in children is increasing, but causes and diagnostic and therapeutic methods are various in different centers. The aim of this study was to investigate the common causes and routine diagnostic and therapeutic methods of acute pancreatitis in children in a pediatric gastrointestinal referral center and its accordance with existing guidelines.

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In Vitro Assessment of Poly-N-Vinylpyrrolidone/Acrylic Acid Nanoparticles Biocompatibility in a Microvascular Endothelium Model. An amphiphilic copolymer of N-vinyl-2-pyrrolidone and acrylic acid-namely, p(VP-AA)-OD6000 (p(VP-AA))-was synthesized to prepare p(VP-AA) nanoparticles (NPs). Furthermore, the copolymer was linked with CFSE, and the so-prepared nanoparticles were loaded with the DiI dye to form D nanoparticles (DNPs). In this study, as demonstrated by immunofluorescence microscopy, immunofluorescence, and confocal microscopy, DNPs were readily taken up by human microvascular endothelial cells (HMEC-1) cells in a concentration-dependent manner. Upon uptake, both the CFSE dye (green stain) and the DiI dye (red stain) were localized to the cytoplasm of treated cells. Treatment with p(VP-AA) did not affect the viability of normal and challenged with LPS, HMEC-1 cells at 0.010 mg/mL and induced a dose-dependent decrease of these cells' viability at the higher concentrations of 0.033 and 0.066 mg/mL ( p ≤ 0.01; p ≤ 0.001, respectively). Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon p(VP-AA) NPs treatment by assessing the expression of adhesion molecules (E-Selectin, ICAM-1, and V-CAM). NPs treatments at concentrations utilized ( p = NS) did not affect individual adhesion molecules' expression. p(VP-AA) NPs do not activate the endothelium and do not affect its viability at pharmacologically relevant concentrations.

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The anatomy of social dynamics in escape rooms. From sport and science production to everyday life, higher-level pursuits demand collaboration. Despite an increase in the number of data-driven studies on human behavior, the social dynamics of collaborative problem solving are still largely unexplored with network science and other computational and quantitative tools. Here we introduce escape rooms as a non-interventional and minimally biased social laboratory, which allows us to capture at a high resolution real-time communications in small project teams. Our analysis portrays a nuanced picture of different dimensions of social dynamics. We reveal how socio-demographic characteristics impact problem solving and the importance of prior relationships for enhanced interactions. We extract key conversation rules from motif analysis and discuss turn-usurping gendered behavior, a phenomenon particularly strong in male-dominated teams. We investigate the temporal evolution of signed and group interactions, finding that a minimum level of tense communication might be beneficial for collective problem solving, and revealing differences in the behavior of successful and failed teams. Our work unveils the innovative potential of escape rooms to study teams in their complexity, contributing to a deeper understanding of the micro-dynamics of collaborative team processes.

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A systematic review and meta-analysis on the association between ambient air pollution and pulmonary tuberculosis. There is inconclusive evidence on the association between ambient air pollution and pulmonary tuberculosis (PTB) incidence, tuberculosis-related hospital admission and mortality. This review aimed to assess the extent to which selected air pollutants are associated to PTB incidence, hospital admissions and mortality. This was a systematic review of studies published in English from January 1st, 1946, through May 31st, 2022, that quantitatively assessed the association between PM 2.5 , PM 10 , NO 2 , SO 2 , CO, O 3 and the incidence of, hospital admission or death from PTB. Medline, Embase, Scopus and The Cochrane Library were searched. Extracted data from eligible studies were analysed using STATA software. Random-effect meta-analysis was used to derive pooled adjusted risk and odds ratios. A total of 24 studies (10 time-series, 5 ecologic, 5 cohort, 2 case-control, 1 case cross-over, 1 cross-sectional) mainly from Asian countries were eligible and involved a total of 437,255 tuberculosis cases. For every 10 μg/m 3 increment in air pollutant concentration, there was a significant association between exposure to PM 2.5 (pooled aRR = 1.12, 95% CI: 1.06-1.19, p < 0.001, N = 6); PM 10 (pooled aRR = 1.06, 95% CI: 1.01-1.12, p = 0.022, N = 8); SO 2 (pooled aRR = 1.08, 95% CI: 1.04-1.12, p < 0.001, N = 9); and the incidence of PTB. There was no association between exposure to CO (pooled aRR = 1.04, 95% CI: 0.98-1.11, p = 0.211, N = 4); NO 2 (pooled aRR = 1.08, 95% CI: 0.99-1.17, p = 0.057, N = 7); O 3 (pooled aRR = 1.00, 95% CI: 0.99-1.02, p = 0.910, N = 6) and the incidence of PTB. There was no association between the investigated air pollutants and mortality or hospital admissions due to PTB. Overall quality of evidence was graded as low (GRADE approach). Exposure to PM 2.5 , PM 10 and SO 2 air pollutants was found to be associated with an increased incidence of PTB, while exposure to CO, NO 2 and O 3 was not. There was no observed association between exposure to these air pollutants and hospital admission or mortality due to PTB. The quality of the evidence generated, however, remains low. Addressing the tuberculosis epidemic by 2030 as per the 4th Sustainable Development Goal may require a more rigorous exploration of this association.

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Illness perceptions and outcome in multiple sclerosis: A systematic review of the literature. According to Leventhal's self-regulation model, ill people construct personal representations of their disease, namely illness perceptions, which impact their coping strategies and the emotional response to their condition. Since these representations develop in the social environment, the individuals' perceptions may also be related to the opinions of their caregivers. This systematic review aims at synthesising and critically appraising literature pertaining the relationship between illness perceptions and outcome in persons with multiple sclerosis and their caregivers. A literature search was conducted in MEDLINE, PsycINFO, and CINAHL. Only papers with the following characteristics were included: quantitative studies; written in English or Italian; published from 1992; investigating the relationship between illness perceptions and any outcome in persons with multiple sclerosis and/or their caregivers; using validated scales assessing illness perceptions. Twenty papers were included and appraised through the 16-item Quality Assessment Tool for Studies with Diverse Designs. The quality of the papers was acceptable. Eighteen out of 20 papers reported the existence of a moderate effect size when analysing the relationship between illness perceptions and outcome, whereby "positive" perceptions (e.g. stronger beliefs of control) related to better outcomes, while "negative" ones (e.g. attribution of negative consequences to the disease) related to worse outcome.

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Current appetite influences relative differences in the expected satiety of foods for momentary, but not hypothetical, expected satiety assessments. Research has shown that expected satiety is highly associated with portion-size selection and can vary (kcal-for-kcal) significantly between foods. However, research has not adequately investigated whether current appetite influences relative differences in the expected satiety of foods. This is important to explore to better understand how current motivational state influences food choice and portion selection. This study used 'hypothetical' and 'momentary' expected-satiety assessments to understand whether methods requiring a reflection on current motivational state [momentary] versus more hypothetical considerations when assessing expected satiety can influence the interpretation of results. It was hypothesised that current appetite would only influence relative differences in expected satiety between foods for momentary, but not hypothetical, expected satiety assessments. Participants (n = 54) were shown images of twelve foods, once when hungry and once when full. In each case, they selected a portion for each food to 1) match the expected satiety of a fixed-portion 'standard' food [hypothetical], and 2) stave off hunger until their next meal [momentary]. Results showed that the relative between-food comparison of expected satiety was stable for hypothetical (p=.73) but not momentary assessments (p<.001) suggesting that while current motivational state may influence food choice and portion selection in the moment, more generalised comparisons of the satiating abilities of foods (learned over a longer period) remain stable. This is important 1) for methods in future studies, as immediate dietary intake does not appear to influence hypothetical expected satiety, thus dietary control is not necessary before participants undertake these assessments, and 2) as it confirms that difficulties associated with dietary regulation may not be due to inaccurate hypothetical judgements about foods, but instead appear to be influenced by contextual nuances that occur in the moment.

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Prenatal exposure to bisphenol S and bisphenol A differentially affects male reproductive system in the adult offspring. Early exposure to bisphenol may result in adverse reproductive health in later life. The use of bisphenol S (BPS) has increased considerably after bisphenol A (BPA) is regulated worldwide. However, little is known about the fetal exposure to BPS compared with BPA and its effects on the reproductive system in the adult male offspring. Here, we investigated the effects of orally administered BPS and BPA (0.4, 4.0, 40.0 μg/kg bw/d) during gestation (gD4-21) on testicular development by evaluating the sperm DNA damage & methylation and testicular functions in the 90 d Wistar rats. Male offspring prenatally exposed to BPS (0.4 μg/kg) had higher plasma testosterone than BPA and control. The testis histology reveals thickened membrane by producing a wide interstitial gap between seminiferous tubules, increased testicular inflammation, oxidative stress, TIMP-1 expression, and decreased VCAM-1 expression. BPS promotes apoptosis by up-regulating IL-6, cleaved caspases, and a spike in sperm DNA fragmentation. Prenatal BPS exposure reduces sperm motility mediated via impaired PI3K-AKT signaling and increases testicular TEX11 expression in the offspring. Exposure of the fetus to BPS interferes developmental programming of the male reproductive system in the offspring. BPS could be an equally potent endocrine disruptor affecting male reproductive functions.

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Rising abuse of veterinary drugs. There has been a significant increase in veterinary drugs found on toxicology screens and postmortem analyses, especially in the Northeast region of the US. This article details the effects and treatment of two common culprits: xylazine and tiletamine-zolazepam.

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[18 F]FDG brain uptake of C57Bl/6 male mice is affected by locomotor activity after cocaine use: A small animal positron emission tomography study. We verified if cocaine-induced peripheral activation might disrupt [18 F]FDG brain uptake after a cocaine challenge and suggested an optimal protocol to measure cocaine-induced brain metabolic alterations in mice. C57Bl/6 male mice were injected with [18 F]FDG and randomly separated into three groups. Groups 1 and 2 were kept conscious after [18 F]FDG administration and after 5 min received saline or cocaine (20 mg/kg). The animals in group 1 (n = 5) were then evaluated in the open field for 30 min and those from group 2 (n = 6) were kept alone in a home cage for the same period. Forty-five minutes after [18 F]FDG administration, images were acquired for 30 min. Group 3 (n = 6) was kept anesthetized and image acquisition started immediately after tracer injection, for 75 min. Saline (Day 1) or cocaine (Day 2) was injected 5 min after starting acquisition. Another set of animals (n = 5) were treated with cocaine every other day for 10 days or saline (n = 6) and were scanned with the dynamic protocol to verify its efficacy. [18 F]FDG uptake increased after cocaine administration when compared to baseline only in animals kept under anesthesia. No brain effect of cocaine was observed in animals submitted to the open field or kept in the home cage. The use of anesthesia is essential to visualize cocaine-induced changes in brain metabolism by [18 F]FDG PET, providing an interesting preclinical approach to investigate naïve subjects and enabling a bidirectional translational science approach for better understanding of cocaine use disorder.

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Indirect calculation of LDL using thirteen equations in Pakistani population. Owing to the atherogenic properties, low density lipoprotein cholesterol (LDL-C) is the primary target for treatment and diagnosis of cardiovascular diseases (CVDs), hence accurate measurement of LDL-C is critical. Despite the availability of direct measurement assays for LDL-C, it is routinely calculated by Friedewald equation in clinical settings in Pakistan mostly due to financial constraints. However, the validity of this equation is impacted by several factors, therefore several other equations have been developed for the calculation of LDL-C.

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Time Line of Occlusion for Intracranial Aneurysms Treated with the Pipeline Embolization Device. Rates of aneurysm occlusion following treatment with flow-diverting stents have been quantified at predefined time points in clinical trials, but data characterizing the continuous temporal progression of aneurysm occlusion are lacking. This study used real-world variability in timing of angiographic follow-up to characterize the time line of aneurysm occlusion following treatment with the Pipeline embolization device (PED).

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Biological sample donation and informed consent for neurobiobanking: Evidence from a community survey in Ghana and Nigeria. Genomic research and neurobiobanking are expanding globally. Empirical evidence on the level of awareness and willingness to donate/share biological samples towards the expansion of neurobiobanking in sub-Saharan Africa is lacking.

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Sublethal and lethal Cd toxicity in soybean roots specifically affects the metabolome, Cd binding to proteins and cellular distribution of Cd. Soybean (Glycine max (L.) Merr.) plants were exposed to various Cd concentrations from background and low non-toxic (0.5-50 nM) via sublethally toxic (< 550 nM) to highly, ultimately lethally toxic (3 µM) concentrations. Plants were cultivated hydroponically for 10 weeks until pod development stage of the control plants. The threshold and mechanism of sublethal Cd toxicity was investigated by metabolomics and metalloproteomics (HPLC-ICP-MS) measuring metal binding to proteins in the harvested roots. Spatial distribution of Cd was revealed by µXRF-CT. Specific binding of Cd to proteins already at 50 nM Cd revealed the likely high-affinity protein binding targets in roots, identified by protein purification from natural abundance. This revealed allantoinase, aquaporins, peroxidases and protein disulfide isomerase as the most likely high-affinity targets of Cd binding. Cd was deposited in cortex cell vacuoles at sublethal and bound to the cell walls of the outer cortex and the vascular bundle at lethal Cd. Cd binding to proteins likely inhibits them, and possibly induces detoxification mechanisms, as verified by metabolomics: allantoic acid and allantoate increased due to sublethal Cd toxicity. Changes of the Cd binding pattern indicated a detoxification strategy at lower Cd, but saturated binding sites at higher Cd concentrations.

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Genomic insights into the emergence and spread of NDM-1-producing Vibrio spp. isolates in China. Carbapenemase-producing Vibrio spp., which exhibit an XDR phenotype, have become increasingly prevalent and pose a severe threat to public health.

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The Occurrence of Squalene in Human Milk and Infant Formula. (1) Background: The aim of the conducted research was to analyze the squalene content in infants' food. (2) Methods: The experimental material included human milk collected from 100 women from Poland and three different infant formulas. The breast milk fat was extracted according to the Rose-Gottlieb method (AOAC), while the squalene content was determined using the high-performance liquid chromatography (HPLC) method. (3) Results: The highest amount of squalene was identified in the milk of women aged 18-25 ( p < 0.05), and its content in milk decreased with the age of lactating women. Moreover, the greatest amount of squalene was identified in milk from the first lactation period (colostrum), while in mature milk, its content was more than two times lower. There was a correlation between breastfeeding BMI and the squalene content in milk (r = 0.78). (4) Conclusions: The conducted research shows that the level of squalene in human milk depends on physiological factors such as the lactation period and individual factors (age, BMI). The results of the conducted research indicate that breast milk is richer in squalene than modified milk. This study shows the importance of breastfeeding and indicates the superiority of breast milk over infant formulas.

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Search and rescue incidents among persons 65 years and older in the USA: Examination of factors associated with death. Older people are vulnerable to becoming lost from home, especially if alone and in unfamiliar environments. Incidents of older persons becoming lost are frequently reported and often requiring a search and rescue (SAR) response. Becoming lost is distressing to the person concerned, their carer, and family and may result in physical injury and/or death. This study examined what factors are associated with death among older persons reported lost from home.

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The Brain Protein Acylation System Responds to Seizures in the Rat Model of PTZ-Induced Epilepsy. Abnormal energy expenditure during seizures and metabolic regulation through post-translational protein acylation suggest acylation as a therapeutic target in epilepsy. Our goal is to characterize an interplay between the brain acylation system components and their changes after seizures. In a rat model of pentylenetetrazole (PTZ)-induced epilepsy, we quantify 43 acylations in 29 cerebral cortex proteins; levels of NAD + ; expression of NAD + -dependent deacylases (SIRT2, SIRT3, SIRT5); activities of the acyl-CoA-producing/NAD + -utilizing complexes of 2-oxoacid dehydrogenases. Compared to the control group, acylations of 14 sites in 11 proteins are found to differ significantly after seizures, with six of the proteins involved in glycolysis and energy metabolism. Comparing the single and chronic seizures does not reveal significant differences in the acylations, pyruvate dehydrogenase activity, SIRT2 expression or NAD + . On the contrary, expression of SIRT3, SIRT5 and activity of 2-oxoglutarate dehydrogenase (OGDH) decrease in chronic seizures vs. a single seizure. Negative correlations between the protein succinylation/glutarylation and SIRT5 expression, and positive correlations between the protein acetylation and SIRT2 expression are shown. Our findings unravel involvement of SIRT5 and OGDH in metabolic adaptation to seizures through protein acylation, consistent with the known neuroprotective role of SIRT5 and contribution of OGDH to the Glu/GABA balance perturbed in epilepsy.

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Effect of acetone fraction of Ottelia alismoides on the G2/M cell cycle arrest and apoptosis in the human carcinoma cell lines. The North-eastern parts of India have immense therapeutic floras, Ottelia alismoides is an aquatic plant that has been in use for a long time in traditional medicine for treating diseases like cancer, tuberculosis, diabetes, febrifuge, hemorrhoids, and rubefacient. In lung and skin carcinoma cells with a high rate of proliferation and metastasis including drug resistance and non-specific target activity, generates important challenges towards their treatment strategy. Thus, finding novel therapeutic targets to treat lung and skin cancer progression is essential to enhance the patients' survival with treatment.

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Cigarette Smoking Among US Adults With Selected Chronic Diseases Associated With Smoking, 2010-2019. People who smoke cigarettes are at greater risk of developing chronic diseases and related complications. Our study provides recent estimates and trends in cigarette smoking among people with respiratory and cardiovascular diseases, cancers, and diabetes.

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ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies. Alzheimer's disease (AD) is the most common cause of dementia worldwide, and its prevalence is rapidly increasing due to extended lifespans. Among the increasing number of genetic risk factors identified, the apolipoprotein E (APOE) gene remains the strongest and most prevalent, impacting more than half of all AD cases. While the ε4 allele of the APOE gene significantly increases AD risk, the ε2 allele is protective relative to the common ε3 allele. These gene alleles encode three apoE protein isoforms that differ at two amino acid positions. The primary physiological function of apoE is to mediate lipid transport in the brain and periphery; however, additional functions of apoE in diverse biological functions have been recognized. Pathogenically, apoE seeds amyloid-β (Aβ) plaques in the brain with apoE4 driving earlier and more abundant amyloids. ApoE isoforms also have differential effects on multiple Aβ-related or Aβ-independent pathways. The complexity of apoE biology and pathobiology presents challenges to designing effective apoE-targeted therapeutic strategies. This review examines the key pathobiological pathways of apoE and related targeting strategies with a specific focus on the latest technological advances and tools.

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Enhancement of transdermal permeation of cannabinoids and their pharmacodynamic evaluation in rats. The objective of the present study was to enhance the transdermal permeation of cannabinoids: cannabidiol (CBD), cannabigerol (CBG) and tetrahydrocannabivarin (THCV) using chemical permeation enhancer approach and evaluate them for their anti-inflammatory effect in vivo in a paw edema model in rats. Cannabinoids gel formulations were developed using FDA approved inactive ingredients: lactic acid (LA), polyethylene glycol-400 (PEG-400), N-methyl-2 pyrrolidone (NMP), dimethyl sulfoxide (DMSO). In vitro skin permeation testing (IVPT) showed flux of ∼ 13.25 μg/cm 2 /h for CBD, ∼9.38 μg/cm 2 /h for CBG and ∼ 51.74 μg/cm 2 /h for THCV. Additionally, IVPT study showed cumulative drug permeation of 610.96 ± 88.92 μg/cm 2 , 432.09 ± 35.59 μg/cm 2 and 2384.44 ± 42.22 μg/cm 2 from CBD, CBG and THCV gel formulations respectively. Further, effect of excipients on cannabinoid permeation showed that, formulation containing lactic acid, NMP and DMSO showed significantly (p < 0.0001) enhanced flux of cannabinoids as compared to formulation without LA, NMP and DMSO. In vivo studies showed that paw edema was significantly (p < 0.0001) reduced in the groups containing CBD, CBG, THCV as compared to control and placebo formulation. In conclusion, flux of CBD, CBG and THCV was significantly enhanced using chemical permeation enhancers approach which helped in reducing rat paw edema.

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The Purified Siderophore from Streptomyces tricolor HM10 Accelerates Recovery from Iron-Deficiency-Induced Anemia in Rats. Iron-deficiency-induced anemia is associated with poor neurological development, including decreased learning ability, altered motor functions, and numerous pathologies. Siderophores are iron chelators with low molecular weight secreted by microorganisms. The proposed catechol-type pathway was identified based on whole-genome sequences and bioinformatics tools. The intended pathway consists of five genes involved in the biosynthesis process. Therefore, the isolated catechol-type siderophore (Sid) from Streptomyces tricolor HM10 was evaluated through an anemia-induced rat model to study its potential to accelerate recovery from anemia. Rats were subjected to an iron-deficient diet (IDD) for 42 days. Anemic rats (ARs) were then divided into six groups, and normal rats (NRs) fed a standard diet (SD) were used as a positive control group. For the recovery experiment, ARs were treated as a group I; fed an IDD (AR), group II; fed an SD (AR + SD), group III, and IV, fed an SD with an intraperitoneal injection of 1 μg Sid Kg -1 (AR + SD + Sid1) and 5 μg Sid Kg -1 (AR + SD + Sid5) twice per week. Group V and VI were fed an iron-enriched diet (IED) with an intraperitoneal injection of 1 μg Sid Kg -1 (AR + IED + Sid1) and 5 μg Sid Kg -1 (AR + IED + Sid5) twice per week, respectively. Weight gain, food intake, food efficiency ratio, organ weight, liver iron concentration (LIC) and plasma (PIC), and hematological parameters were investigated. The results showed that ~50-60 mg Sid L -1 medium could be producible, providing ~25-30 mg L -1 purified Sid under optimal conditions. Remarkably, the AR group fed an SD with 5 μg Sid Kg -1 showed the highest weight gain. The highest feed efficiency was observed in the AR + SD + Sid5 group, which did not significantly differ from the SD group. Liver, kidneys, and spleen weight indicated that diet and Sid concentration were related to weight recovery in a dose-dependent manner. Liver iron concentration (LIC) in the AR + IED + Sid1 and AR + IED + Sid5 groups was considerably higher than in the AR + SD + Sid1 AR + SD + Sid5 groups or the AR + SD group compared to the AR group. All hematological parameters in the treated groups were significantly closely attenuated to SD groups after 28 days, confirming the efficiency of the anemia recovery treatments. Significant increases were obtained in the AR + SD + Sid5 and AR + IED + Sid5 groups on day 14 and day 28 compared to the values for the AR + SD + Sid1 and AR + IED + Sid1 groups. The transferrin saturation % (TSAT) and ferritin concentration (FC) were significantly increased with time progression in the treated groups associatively with PIC. In comparison, the highest significant increases were noticed in ARs fed IEDs with 5 μg Kg -1 Sid on days 14 and 28. In conclusion, this study indicated that Sid derived from S. tricolor HM10 could be a practical and feasible iron-nutritive fortifier when treating iron-deficiency-induced anemia (IDA). Further investigation focusing on its mechanism and kinetics is needed.

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The Top 100 Most Cited Scientific Papers in the Public, Environmental & Occupational Health Category of Web of Science: A Bibliometric and Visualized Analysis. (1) Background: The main basis for the public recognition of the merits of scientists has always been the system of scientific publications and citations. Our goal is to identify and analyze the most cited articles in the Public, Environmental & Occupational Health category. (2) Methods: We searched the Web of Science for all articles published in the "Public, Environmental & Occupational Health" category up to March 2022 and selected the 100 most cited articles. We recorded the number of citations, the journal, the year of publication, quartile, impact factor, institution, country, authors, topic, type of publication and collaborations. (3) Results: 926,665 documents were analyzed. The top 100 had 401,620 citations. The journal with the most articles was the Journal of Clinical Epidemiology and the one with the highest number of citations was Medical Care. The year with the highest number of articles in the top 100 was 1998. The country with the highest percentage of publications was the USA and the most productive institution was Harvard. The most frequent keywords were bias, quality, and extension. The largest collaboration node was between the USA, Canada, Germany, Spain, Australia, France, and Sweden. (4) Conclusions: This bibliometric study on Public, Environmental & Occupational Health provides valuable information not only to identify topics of interest in the analyzed category, but also to identify the differences in the topics they study.

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Enhanced Robustness of the Mouse Retinal Circadian Clock Upon Inherited Retina Degeneration. Daily biological rhythms are fundamental to retinal physiology and visual function. They are generated by a local circadian clock composed of a network of cell type/layer-specific, coupled oscillators. Animal models of retinal degeneration have been instrumental in characterizing the anatomical organization of the retinal clock. However, it is still unclear, among the multiple cell-types composing the retina, which ones are essential for proper circadian function. In this study, we used a previously well-characterized mouse model for autosomal dominant retinitis pigmentosa to examine the relationship between rod degeneration and the retinal circadian clock. This model carries the P23H mutation in rhodopsin, which induces mild rod degeneration in heterozygous and rapid loss of photoreceptors in homozygous genotypes. By measuring PER2::LUC bioluminescence rhythms, we show that the retinal clock in P23H/+ heterozygous mice displays circadian rhythms with significantly increased robustness and amplitude. By treating retinal explants with L-α aminoadipic acid, we further provide evidence that this enhanced rhythmicity might involve activation of Müller glial cells.

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Analysis of Complications and Recipients' and Graft Survival in Patients 60 Years of Age and Older in the Long-Term Follow-up Period After Kidney Transplant: A Single-Center, Paired Kidney Analysis. Long-term results of kidney transplant (KTx) in older patients may differ from younger recipients owing to increased cardiovascular comorbidities. The study aimed to analyze surgical and nonsurgical complications that develop in the long-term follow-up period after KTx, and factors that influence results of KTx in recipients aged 60 years and older (≥60) compared with younger recipients (<60).

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Toxicological assessment compilation of selected examples of raw materials for homeopathic and anthroposophic medicinal products - Part 2. The present successor article comprises more than 180 substances representing a continuative compilation of toxicologically evaluated starting materials prompted by the wide use and high number of homeopathic and anthroposophic medicinal products (HMP) on the market together with the broad spectrum of active substances of botanical, mineral, chemical or animal origin contained therein, and by the equally important requirement of applying adequate safety principles as with conventional human medicinal products in line with the European regulatory framework. The February 2019 issue of the Regulatory Toxicology and Pharmacology journal includes the antecedent article bearing the same title and entailing safety evaluations of more than 170 raw materials processed in HMP. This part 2 article highlights scientific evaluation following recognized methods used in toxicology with a view to drug-regulatory authority's assessment principles and practice in the context of HMP, and offers useful systematic, scientifically substantiated and simultaneously pragmatic approaches in differentiated HMP risk assessment. As a unique feature, both articles provide the most extensive publicly available systematic compilation of a considerable number of substances processed in HMP as a transparent resource for applicants, pharmaceutical manufacturers, the scientific community and healthcare authorities to actively support regulatory decision making in practice.

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Standardized Methods Using EUS-guided Fine-needle Biopsy and a Minimal Medium Creates Three Pancreatic Cancer Organoids. Recently, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has been conducted for diagnosing pancreatic ductal adenocarcinoma (PDAC), after which obtained samples were used in organoid cultures. However, no standardized method for PDAC organoid cultures exists. Therefore, to standardize or simplify sample collection and culture methods for PDAC organoids, we performed a floating culture using non-minced specimens obtained by EUS-FNB in a minimal medium, lacking growth factors or inhibitors for pancreatic organoids.

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Global transcriptome analyses and regulatory mechanisms in Halothece sp. PCC 7418 exposed to abiotic stresses. Halotolerant species are of interest since they occur naturally in environments with excess toxic ions. The cyanobacterium Halothece sp. PCC 7418 (hereafter referred to as Halothece) exhibits remarkable halotolerance and was used to examine stress-responsive regulatory mechanisms. The effects of five different stimuli on Halothece transcriptomes were examined using RNA sequencing. In response to diverse stresses, there were both common and stress-specific transcriptional responses. A common upregulated gene set under all stresses consisted of nine differentially expressed genes (DEGs). We also found that osmotic stress elicited the largest set of DEGs. Salt- and osmotic-responsive regulatory mechanisms shared common pathways. DEGs that were upregulated under salt stress encoded proteins involved in photosynthesis and related machineries. Furthermore, DEGs encoding two-component system (TCS) factors, transcriptional factors, scaffolds for protein-protein interactions, transporters, protein turnover factors, and lipid biosynthesis enzymes were also identified under salt stress. Notably, one-carbon (1C) metabolism factors, glycine betaine (GB) synthesis enzymes, and GB transporters were upregulated under salt stress. Metabolic analyses revealed that GB accumulated under salt stress, while mycosporine-2-glycine (M2G) accumulated under salt or osmotic stress. None of the nutrient starvations induced GB nor M2G accumulation. These results suggested that GB and M2G are two osmoprotectants that contribute to halotolerance. Based on our results, we proposed regulatory mechanisms that are crucial for halotolerance, which are coordinated with the GB, M2G, 1C, amino acid, and central carbon interlinking metabolic pathways. 1C metabolism directly fulfills the high metabolite requirements for halotolerance together with the ancillary role of several metabolic pathways.Key Points• Global transcriptome surveys together with molecular and metabolite analyses provide insights into regulatory networks that are crucial for halotolerance• Regulatory networks that are crucial for halotolerance coordinated with the two key osmoprotectants, one carbon, amino acid, and central carbon interlinking metabolic pathways• The findings have translational relevance in genomic and transcriptomic mechanisms of halotolerance.

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T cells dominate peripheral inflammation in a cross-sectional analysis of obesity-associated diabetes. Myeloid cells dominate metabolic disease-associated inflammation (metaflammation) in mouse obesity, but the contributions of myeloid cells to the peripheral inflammation that fuels sequelae of human obesity are untested. This study used unbiased approaches to rank contributions of myeloid and T cells to peripheral inflammation in people with obesity across the spectrum of metabolic health.

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COVID-19 increases the risk for the onset of atrial fibrillation in hospitalized patients. COVID-19 is associated with significant extrapulmonary symptoms. Myocardial involvement has been described for infections with SARS-CoV-2 which may lead to an increase in morbidity and mortality. The objective of our study was to investigate the association of COVID-19 and atrial fibrillation (AF) or atrial flutter (AFl) in hospitalized patients. This retrospective study used electronic medical records to detect patients with COVID-19 and their comorbidities within the Mass General Brigham hospital system. All patients ≥ 18 years who were hospitalized and received a PCR test for SARS-CoV-2 were screened for inclusion as well as patients from a pre-pandemic cohort. We matched on common risk factors for AF and then used multivariable logistic regression to estimate the odds for AF or AFl. Of 78,725 patients eligible for analysis, 11,004 COVID-19 negative patients were matched to 3,090 COVID-19 positive patients and 5005 pre-pandemic patients were matched to 2283 COVID-19 positive patients. After adjusting for demographics and comorbidities, COVID-19 positive patients had 1.19 times the odds (95% CI 1.00, 1.41) of developing AF compared to COVID-19 negative patients and 1.57 times the odds (95% CI 1.23, 2.00) of developing AF compared to pre-pandemic patients. Our study demonstrated an increased risk for AF, directing the attention for improved screening and treatment regimens for the sequelae of COVID-19. While COVID-19 continues to affect many people around the world, AF may be a significant cause for morbidity and mortality. Adequate detection and treatment of AF is essential to reduce the burden of disease.

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[Characteristics and influencing factors of soil nitrification potential in coastal salinized farmland]. Understanding the nitrification capacity of coastal saline farmland soils and its main drivers is of great significance to regulate soil nitrification and improve the utilization efficiency of nitrogen fertilization in farmland. Using a combination of field investigations and laboratory analyses, we examined farmland soil nitrification potential and soil physical, chemical, and biological properties in the coastal muddy tidal flat saline soil area (Dongying and Dongtai). We established the correlation between soil properties and soil nitrification potential with multiple stepwise regression analyses and structural equation modeling (SEM). The results showed that soil pH value was relatively stable and other soil properties and soil nitrification potential varied in coastal saline farmland. The soil nitrification potential ranged from 0.04 to 10.42 mg·kg -1 ·d -1 and decreased with the increases of soil salinization level. Soil nitrification potential had the strongest correlation with soil organic matter, cation exchange capacity, and Cl - , with the correlation coefficient being 0.409, 0.397 and -0.337, respectively. The results of multiple stepwise regression analysis showed that Na + , silt, cation exchange capacity, and CO 3 2- +HCO 3 - were the main influencing factors of soil nitrification potential. The results from the SEM analysis suggested that Na + , silt, cation exchange capacity, and CO 3 2- +HCO 3 - directly affected soil nitrification potential, and soil organic matter, clay, Cl - and SO 4 2- had indirect effects. In all, soil Na + and cation exchange capacity were the two main factors affecting nitrification. Adjusting soil NaCl content and cation exchange capacity was an effective means of regulating soil nitrification.

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Hepatitis B core-related antigen: Are we near a treatment endpoint? Different serological and virological markers in chronic hepatitis B patients guide staging of viral infection, and initiation and response to therapy. Due to the persistence of intrahepatic covalently closed circular DNA (cccDNA) in the hepatocyte nucleus, hepatitis B is not curable. Even after undetectable hepatitis B virus DNA levels, the persistence of hepatitis B surface antigen and novel markers such as hepatitis B core-related antigen (HBcrAg) indicate the persistence of intrahepatic cccDNA. In this study, HBcrAg levels at baseline and after 24 and 48 wk of antiviral therapy predicted hepatitis B e antigen seroconversion. Due to the poor sensitivity of assays and detectable levels in HBsAg-negative patients, the long-term utility of HBcrAg needs future research.

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Integrated Transcriptome and Targeted Metabolite Analysis Reveal miRNA-mRNA Networks in Low-Light-Induced Lotus Flower Bud Abortion. Most Nelumbo nucifera (lotus) flower buds were aborted during the growing season, notably in low-light environments. How lotus produces so many aborted flower buds is largely unknown. An integrated transcriptome and targeted metabolite analysis was performed to reveal the genetic regulatory networks underlying lotus flower bud abortion. A total of 233 miRNAs and 25,351 genes were identified in lotus flower buds, including 68 novel miRNAs and 1108 novel genes. Further enrichment analysis indicated that sugar signaling plays a potential central role in regulating lotus flower bud abortion. Targeted metabolite analysis showed that trehalose levels declined the most in the aborting flower buds. A potential regulatory network centered on miR156 governs lotus flower bud abortion, involving multiple miRNA-mRNA pairs related to cell integrity, cell proliferation and expansion, and DNA repair. Genetic analysis showed that miRNA156-5p-overexpressing lotus showed aggravated flower bud abortion phenotypes. Trehalose-6-P synthase 1 (TPS1), which is required for trehalose synthase, had a negative regulatory effect on miR156 expression. TPS1 -overexpression lotus showed significantly decreased flower bud abortion rates both in normal-light and low-light environments. Our study establishes a possible genetic basis for how lotus produces so many aborted flower buds, facilitating genetic improvement of lotus' shade tolerance.

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Multisite phosphorylation and binding alter conformational dynamics of the 4E-BP2 protein. Intrinsically disordered proteins (IDPs) play critical roles in regulatory protein interactions, but detailed structural/dynamic characterization of their ensembles remain challenging, both in isolation and when they form dynamic "fuzzy" complexes. Such is the case for mRNA cap-dependent translation initiation, which is regulated by the interaction of the predominantly folded eukaryotic initiation factor 4E (eIF4E) with the intrinsically disordered eIF4E binding proteins (4E-BPs) in a phosphorylation-dependent manner. Single-molecule Förster resonance energy transfer showed that the conformational changes of 4E-BP2 induced by binding to eIF4E are non-uniform along the sequence; while a central region containing both motifs that bind to eIF4E expands and becomes stiffer, the C-terminal region is less affected. Fluorescence anisotropy decay revealed a non-uniform segmental flexibility around six different labeling sites along the chain. Dynamic quenching of these fluorescent probes by intrinsic aromatic residues measured via fluorescence correlation spectroscopy report on transient intra- and inter-molecular contacts on nanosecond-to-microsecond timescales. Upon hyperphosphorylation, which induces folding of ∼40 residues in 4E-BP2, the quenching rates decreased at most labeling sites. The chain dynamics around sites in the C-terminal region far away from the two binding motifs significantly increased upon binding to eIF4E, suggesting that this region is also involved in the highly dynamic 4E-BP2:eIF4E complex. Our time-resolved fluorescence data paint a sequence-level rigidity map of three states of 4E-BP2 differing in phosphorylation or binding status and distinguish regions that form contacts with eIF4E. This study adds complementary structural and dynamics information to recent studies of 4E-BP2, and it constitutes an important step toward a mechanistic understanding of this important IDP via integrative modeling.

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Prevalence and gender distribution of trichotillomania: A systematic review and meta-analysis. Epidemiological studies have provided varying prevalence estimates of trichotillomania (TTM) and other hair-pulling behaviors. We performed a systematic review and meta-analysis to provide data-driven prevalence estimates of TTM and hair-pulling. PubMed, PsycInfo and Embase were searched on June 2020 (updated in November 2021). Studies reporting the frequency of TTM defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria or hair-pulling behaviors were included. Prevalence data was extracted for both genders, and female-to-male odds ratios (OR) were computed for TTM and any hair-pulling behaviors. Data were pooled through random-effects meta-analyses. Of the 713 records identified through database searches, 30 studies involving 38,526 participants were included. Meta-analyses indicated TTM had a prevalence of 1.14% (95% CI 0.66%, 1.96%), while any hair-pulling behavior had a prevalence of 8.84% (95% CI 6.33%, 12.20%). Meta-analyses demonstrated females were at an increased risk of any hair-pulling when noticeable hair loss was required (OR = 2.23, 95% CI 1.60, 3.10, p < 0.0001), but not of any hair-pulling when noticeable hair loss was not required (OR = 0.90, 95% CI 0.72, 1.64, p = 0.33). Meta-analyses did not indicate female preponderance in TTM (k = 10; N = 22,775; OR = 1.29; 95% CI 0.91, 1.83; I 2 = 28%, p = 0.15), although there was considerable heterogeneity across studies. This study demonstrates that TTM impacts ∼1% of the population, while general hair-pulling behaviors affects ∼8%, highlighting the significant public health impact of this understudied condition. Additional research should clarify the gender distribution of TTM in epidemiological samples.

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Maternity Healthscapes: Conceptualization and Index Development. This article provides a conceptualization and an index of the multidimensional concept of maternity healthscapes (MHS).

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Elucidation of Key Interactions between VirF and the virB Promoter in Shigella flexneri Using E. coli MarA- and GadX-Based Homology Models and In Vitro Analysis of the DNA-Binding Domains of VirF and MarA. Infection with Shigella, the organism responsible for the diarrheal disease shigellosis, leads to approximately 200,000 deaths globally annually. Virulence of this pathogen is primarily controlled by the DNA-binding transcriptional activator VirF. This AraC family protein activates transcription of two major virulence genes, virB and icsA, which lead to the pathogen's ability to invade and spread within colonic epithelial cells. While several AraC proteins have been studied, few studies of VirF's binding to its DNA promoters have been reported, and VirF's three-dimensional structure remains unsolved. Here, we used structures of two E. coli VirF homologs, GadX and MarA-marRAB, to generate homology models of the VirF DNA-binding domain in free and DNA-bound conformations. We conducted alanine scanning mutagenesis on seven residues within MarA that make base-specific interactions with its promoter, marRAB, and the corresponding residues within VirF (identified by sequence and structural homologies). In vitro DNA-binding assays studying both wild-type and mutant MarA and VirF proteins identified residues important for binding to the marRAB and virB promoters, respectively. Comparison of the effects of these DNA-binding domain mutants validated our MarA-based homology model, allowing us to identify crucial interactions between VirF and the virB promoter. Proteins with mutations to helix 3 within both MarA(W42A, R46A) and MalE-VirF(R192A, K193A) exhibited significant reductions in DNA binding, while the effects of mutations in helix 6 varied. This suggests the shared importance of helix 3 in the binding to these promoters, while helix 6 is transcription factor specific. These results can inform further development of virulence-targeting inhibitors as an alternative to traditional antimicrobial drug design. IMPORTANCE Globally, infection with Shigella flexneri is a leading cause of bacterial dysentery, particularly affecting children under the age of 5 years. The virulence of this pathogen makes it highly infectious, allowing it to spread easily within areas lacking proper sanitation or access to clean drinking water. VirF is a DNA-binding transcription factor that activates S. flexneri virulence once the bacteria infect the human colon. Development of drugs that target VirF's DNA-binding activity can be an effective treatment to combat shigellosis as an alternative or addition to traditional antibiotics. Due to the lack of structural data, analysis of VirF's DNA-binding activity is critical to the development of potent VirF inhibitors.

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Microcystic elongated and fragmented (MELF) pattern of invasion: Molecular features and prognostic significance in the PORTEC-1 and -2 trials. Microcystic, elongated fragmented (MELF) pattern of myometrial invasion is a distinct histologic feature occasionally seen in low-grade endometrial carcinomas (EC). The prognostic relevance of MELF invasion was uncertain due to conflicting data, and it had not yet appropriately been studied in the context of the molecular EC classification. We aimed to determine the relation of MELF invasion with clinicopathological and molecular characteristics, and define its prognostic relevance in early-stage low/intermediate risk EC.

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NK cell immunometabolism as target for liver cancer therapy. Natural killer (NK) cells are being used effectively as a potential candidate in tumor immunotherapy. However, the migration and transport of NK cells to solid tumors is inadequate. NK cell dysfunction, tumor invasiveness, and metastasis are associated with altered metabolism of NK cells in the liver cancer microenvironment. However, in liver cancers, metabolic impairment of NK cells is still not understood fully. Evidence from various sources has shown that the interaction of NK cell's immune checkpoints with its metabolic checkpoints is responsible for the regulation of the development and function of these cells. How immune checkpoints contribute to metabolic programming is still not fully understood, and how this can be beneficial needs a better understanding, but they are emerging to be incredibly compelling to rebuilding the function of NK cells in the tumor. It is expected to represent a potential aim that focuses on improving the efficacy of therapies based on NK cells for treating liver cancer. Here, the recent advancements made to understand the NK cell's metabolic reprogramming in liver cancer have been summarized, along with the possible interplay between the immune and the metabolic checkpoints in NK cell function. Finally, an overview of some potential metabolic-related targets that can be used for liver cancer therapy treatment has been presented.

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Cytoophidia coupling adipose architecture and metabolism. Tissue architecture determines its unique physiology and function. How these properties are intertwined has remained unclear. Here we show that the metabolic enzyme CTP synthase (CTPS) form filamentous structures termed cytoophidia along the adipocyte cortex in Drosophila adipose tissue. Loss of cytoophidia, whether due to reduced CTPS expression or a point mutation that specifically abrogates its polymerization ability, causes impaired adipocyte adhesion and defective adipose tissue architecture. Moreover, CTPS influences integrin distribution and dot-like deposition of type IV collagen (Col IV). Col IV-integrin signaling reciprocally regulates the assembly of cytoophidia in adipocytes. Our results demonstrate that a positive feedback signaling loop containing both cytoophidia and integrin adhesion complex couple tissue architecture and metabolism in Drosophila adipose tissue.

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Protocol for the generation of HIV-1 genomic RNA with altered levels of N 6 -methyladenosine. N 6 -methyladenosine (m 6 A) modification of human immunodeficiency virus type 1 (HIV-1) RNA plays a critical role in regulating viral replication and evasion of innate immunity. Here, we describe a protocol for the production of HIV-1 with altered m 6 A levels by manipulating the expression of m 6 A demethylases in HIV-1 producer cells. RNA from purified virions is analyzed by northern blot and dot blot for m 6 A levels prior to use in downstream assays to determine the function of m 6 A modification of viral RNA. For complete details on the use and execution of this protocol, please refer to Chen et al. (2021).

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Gold nanoparticles targeting the autophagy-lysosome system to combat the inflammation-compromised osteogenic potential of periodontal ligament stem cells: From mechanism to therapy. Although substantial data indicate that the osteogenic potential of periodontal ligament stem cells (PDLSCs) is compromised under inflammatory conditions, the underlying mechanism remains largely unexplored. In this study, we found that both the autophagy levels and autophagic flux levels were decreased in PDLSCs incubated under inflammatory conditions (I-PDLSCs). Based on the increased expression of LC3 II (at an autophagy level) and decreased accumulation of LC3 II (at an autophagic flux level) in I-PDLSCs, we speculated that the disruption of I-PDLSC autophagy arose from dysfunction of the cellular autophagy-lysosome system. Subsequently, our hypothesis was demonstrated by inhibited autophagosome-lysosome fusion, damaged lysosomal function, and suppressed activation of transcription factor EB (TFEB, a master regulator of the autophagy-lysosome system) in I-PDLSCs and verified by TFEB overexpression in I-PDLSCs. We found that gold nanoparticle (Au NP) treatment rescued the osteogenic potential of I-PDLSCs by restoring the inflammation-compromised autophagy-lysosome system. In this context, Au NP ceased to be effective when TFEB was knocked down in PDLSCs. Our data demonstrate the crucial role of the autophagy-lysosome system in cellular osteogenesis under inflammatory conditions and suggest a new target for rescuing inflammation-induced cell dysfunction using nanomaterials to aid cell biology and tissue regeneration.

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Implementation of a Night-Float Curriculum: Impact on Intern Confidence over Time. Formal nighttime education is becoming increasingly necessary as more internal medicine (IM) residency programs adopt night-float rotations (NFRs); however, the efficacy of an NFR curriculum throughout an academic year and which topics in an NFR curriculum increase trainee confidence are unknown. We implemented a 12-module, self-paced NFR curriculum for 76 postgraduate year-1 residents at an academic IM residency program. We evaluated the impact of this curriculum on postgraduate year-1 residents' clinical confidence, as well as longitudinal efficacy of the curriculum.

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Title/Abstract stringlengths 45 11.7k	T001 int64 0 1	T002 int64 0 1	T005 int64 0 1	T007 int64 0 1	T023 int64 0 1	T025 int64 0 1	T026 int64 0 1	T028 int64 0 1	T031 int64 0 1	T032 int64 0 1	T033 int64 0 1	T034 int64 0 1	T037 int64 0 1	T038 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	T046 int64 0 1	T047 int64 0 1	T048 int64 0 1	T054 int64 0 1	T055 int64 0 1	T056 int64 0 1	T057 int64 0 1	T058 int64 0 1	T060 int64 0 1	T061 int64 0 1	T062 int64 0 1	T065 int64 0 1	T067 int64 0 1	T068 int64 0 1	T069 int64 0 1	T073 int64 0 1	T074 int64 0 1	T078 int64 0 1	T080 int64 0 1	T081 int64 0 1	T090 int64 0 1	T091 int64 0 1	T093 int64 0 1	T097 int64 0 1	T098 int64 0 1	T099 int64 0 1	T104 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	T129 int64 0 1	T130 int64 0 1	T131 int64 0 1	T167 int64 0 1	T168 int64 0 1	T170 int64 0 1	T190 int64 0 1	T191 int64 0 1	T192 int64 0 1	T195 int64 0 1	T196 int64 0 1	T200 int64 0 1	T204 int64 0 1
A call for more clarity around causality in neuroscience. In neuroscience, the term 'causality' is used to refer to different concepts, leading to confusion. Here we illustrate some of those variations, and we suggest names for them. We then introduce four ways to enhance clarity around causality in neuroscience.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Making rights from wrongs: The crucial role of beliefs and justifications for the expression of aversive personality. Whereas research focusing on stable dispositions has long attributed ethically and socially aversive behavior to an array of aversive (or "dark") traits, other approaches from social-cognitive psychology and behavioral economics have emphasized the crucial role of social norms and situational justifications that allow individuals to uphold a positive self-image despite their harmful actions. We bridge these research traditions by focusing on the common core of aversive traits (the dark factor of personality [D]) and its defining aspect of involving diverse beliefs that serve to construct justifications. In particular, we theoretically specify the processes by which D is expressed in aversive behavior-namely, through diverse beliefs and the justifications they serve. In six studies (total N > 25,000) we demonstrate (a) that D involves higher subjective justifiability of those aversive behaviors that individuals high in D are more likely to engage in, (b) that D uniquely relates to diverse descriptive and injunctive beliefs-related to distrust (e.g., cynicism), hierarchy (e.g., authoritarianism), and relativism (e.g., normlessness)-that serve to justify aversive behavior, and (c) a theoretically derived pattern of moderations and mediations supporting the view that D accounts for aversive behavior because it fosters subjective justifiability thereof-at least in part owing to certain beliefs and the justifications they afford. More generally, our findings highlight the role of (social) cognitions within the conceptual definitions of personality traits and processes through which they are expressed in behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).	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	0	0
Ability to Care in Acute Situations-The Influence of Simulation-Based Education on New Graduate Nurses. Simulation-based education is frequently used in transition programs for new graduate nurses. Simulation-based education is implemented as a measure to practice nursing skills, gain experience, and prepare nurses for caring in challenging situations, such as acute situations. However, concerns about the data supporting the use of simulation are obtained from small studies that do not use validated measurement scales.	0	0	0	0	0	0	0	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Perspectives on using bacteriophages in biogerontology research and interventions. With the development of materials engineering, gerontology-related research on new tools for diagnostic and therapeutic applications, including precision and personalised medicine, has expanded significantly. Using nanotechnology, drugs can be precisely delivered to organs, tissues, cells, and cell organelles, thereby enhancing their therapeutic effects. Here, we discuss the possible use of bacteriophages as nanocarriers that can improve the safety, efficiency, and sensitivity of conventional medical therapies. Phages are a new class of targeted-delivery vectors, which can carry high concentrations of cargo and protect other nontargeted cells from the senescent cell killing effects of senolytics. Bacteriophages can also be subjected to chemical and/or genetic modifications that would acquire novel properties and improve their ability to detect senescent cells and deliver senolytics. Phage research in experimental biogerontology will also develop strategies to efficiently deliver senolytics, target senescent cells, activate extrinsic apoptosis pathways in senescent cells, trigger immune cells to recognise senescent cells, induce autophagy, promote cell and tissue regeneration, inhibit senescence-associated secretory phenotype (SASP) by senomorphic activity, stimulate the properties of mild stress-inducing hormetic agents and hormetins, and modulate the gut microbiome.	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	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
Mapping and understanding of correlated electroencephalogram (EEG) responses to the newsvendor problem. Decision-making is one of the most critical activities of human beings. To better understand the underlying neurocognitive mechanism while making decisions under an economic context, we designed a decision-making paradigm based on the newsvendor problem (NP) with two scenarios: low-profit margins as the more challenging scenario and high-profit margins as the less difficult one. The EEG signals were acquired from healthy humans while subjects were performing the task. We adopted the Correlated Component Analysis (CorrCA) method to identify linear combinations of EEG channels that maximize the correlation across subjects ([Formula: see text]) or trials ([Formula: see text]). The inter-subject or inter-trial correlation values (ISC or ITC) of the first three components were estimated to investigate the modulation of the task difficulty on subjects' EEG signals and respective correlations. We also calculated the alpha- and beta-band power of the projection components obtained by the CorrCA to assess the brain responses across multiple task periods. Finally, the CorrCA forward models, which represent the scalp projections of the brain activities by the maximally correlated components, were further translated into source distributions of underlying cortical activity using the exact Low Resolution Electromagnetic Tomography Algorithm (eLORETA). Our results revealed strong and significant correlations in EEG signals among multiple subjects and trials during the more difficult decision-making task than the easier one. We also observed that the NP decision-making and feedback tasks desynchronized the normalized alpha and beta powers of the CorrCA components, reflecting the engagement state of subjects. Source localization results furthermore suggested several sources of neural activities during the NP decision-making process, including the dorsolateral prefrontal cortex, anterior PFC, orbitofrontal cortex, posterior cingulate cortex, and somatosensory association cortex.	0	0	0	0	0	0	0	0	0	0	0	1	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	0	0	0	0	0	0	0	0	0	0	0	0	0
Seronegative Autoimmune Limbic Encephalitis: A Case Report. Autoimmune encephalitis (AE) is an immune-mediated disorder of the central nervous system (CNS). Its definitive diagnosis relies on the identification of a specific antibody. Autoimmune limbic encephalitis (LE) is a subset of AE characterized by inflammation of the limbic cerebral cortex. Cognitive decline, behavioral disturbance, and seizures are its cardinal manifestations. We present the case of a 70-year-old man with subacute progressive gait imbalance, cognitive impairment, and psychiatric manifestations. Extensive serum and cerebrospinal fluid (CSF) investigations did not reveal any abnormality. Autoimmune and paraneoplastic encephalitis antibody panels were negative. Magnetic resonance imaging (MRI) and positron emission tomography (PET) brain scans suggested LE. He responded well to immunotherapy. This case illustrates that AE must be suspected in the appropriate setting, even in the absence of a specific antibody. These patients should be given the benefit of early immunotherapy.	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	0	0	0
Self-sealing MEMS spray-nozzles to prevent bacterial contamination of portable inhalers for aqueous drug delivery. Pulmonary drug delivery by portable inhalers is the gold standard in lung disease therapy. An increasing focus on environmentally friendly inhalation currently spurs the development of propellant-free devices. However, the absence of propellants in the drug creates a need for suitable sealing systems that can ensure the pathogenic safety of devices. Traditionally, liquid drug inhalers incorporate a spray nozzle and a separate check valve. Here we show a fully integrated MEMS-based spray system for aqueous drug solutions and demonstrate its bacterial safety. The device comprises a thin silicon membrane with spray orifices, which self-seal against a compliant parylene valve seat underneath. This sealing system prevents bacterial ingrowth in its default closed state, while actuation lifts the membrane from the valve seat upon pressurization and sprays an inhalable aerosol from the nozzles. To seal against bacterial contamination effectively, we found that a contact force between the valve seat and the membrane (featuring the spray nozzles) is needed. In our testing, both self-sealing and an otherwise identical unvalved version of the spray chip can be bacterially safe in continued use when thoroughly cleaned of excess fluids and subjected to low bacterial loads for brief periods. However, when directly exposed to [Formula: see text] CFU/ml of our test organism Citrobacter rodentium for 24 h, unvalved systems become contaminated in nearly 90% of cases. In contrast, self-sealing spray chips reduced contamination probability by 70%. This development may enable preservative-free drug formulations in portable inhalers that use propellant-free aqueous drug solutions.	0	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0	0	0
PD-1 is expressed in cytotoxic granules of NK cells and rapidly mobilized to the cell membrane following recognition of tumor cells. The contribution of the T cell-related inhibitory checkpoint PD-1 to the regulation of NK cell activity is still not clear with contradictory results concerning its expression and role in the modulation of NK cell cytotoxicity. We provide novel key findings on the mechanism involved in the regulation of PD-1 expression on NK cell membrane and its functional consequences for the elimination of cancer cells. In contrast to freshly isolated NK cells from cancer patients, those from healthy donors did not express PD-1 on the cell membrane. However, when healthy NK cells were incubated with tumor target cells, membrane PD-1 expression increased, concurrent with the CD107a surface mobilization. This finding suggested that PD-1 was translocated to the cell membrane during NK cell degranulation after contact with target cells. Indeed, cytosolic PD-1 was expressed in freshly-isolated-NK cells and partly co-localized with CD107a and GzmB, confirming that membrane PD-1 corresponded to a pool of preformed PD-1. Moreover, NK cells that had mobilized PD-1 to the cell membrane presented a significantly reduced anti-tumor activity on PD-L1-expressing-tumor cells in vitro and in vivo , which was partly reversed by using anti-PD-1 blocking antibodies. Our results indicate that NK cells from healthy individuals express cytotoxic granule-associated PD-1, which is rapidly mobilized to the cell membrane after interaction with tumor target cells. This novel finding helps to understand how PD-1 expression is regulated on NK cell membrane and the functional consequences of this expression during the elimination of tumor cells, which will help to design more efficient NK cell-based cancer immunotherapies.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0
Acts of appetite: neural circuits governing the appetitive, consummatory, and terminating phases of feeding. The overconsumption of highly caloric and palatable foods has caused a surge in obesity rates in the past half century, thereby posing a healthcare challenge due to the array of comorbidities linked to heightened body fat accrual. Developing treatments to manage body weight requires a grasp of the neurobiological basis of appetite. In this Review, we discuss advances in neuroscience that have identified brain regions and neural circuits that coordinate distinct phases of eating: food procurement, food consumption, and meal termination. While pioneering work identified several hypothalamic nuclei to be involved in feeding, more recent studies have explored how neuronal populations beyond the hypothalamus, such as the mesolimbic pathway and nodes in the hindbrain, interconnect to modulate appetite. We also examine how long-term exposure to a calorically dense diet rewires feeding circuits and alters the response of motivational systems to food. Understanding how the nervous system regulates eating behaviour will bolster the development of medical strategies that will help individuals to maintain a healthy body weight.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	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
Tailoring Cu 2+ -loaded electrospun membranes with antibacterial ability for guided bone regeneration. Copper (Cu)-loaded electrospun membranes were tailored for guided bone regeneration (GBR), targeting the stimulation of innate cells active in bone growth and the prevention of bacterial infections. Functional GBR membranes were produced via an electrospinning set-up using a silk-based solution associated with polyethylene oxide (Silk/PEO - control). Experimental groups were loaded with copper oxide using varying weight percentages (0.05 % to 1 % of CuO). The morphological, structural, chemical, and mechanical properties of membranes were evaluated. Direct and indirect in vitro cytocompatibility experiments were performed with primary human bone mesenchymal stem cells and primary human umbilical vein endothelial cells. The antibacterial potential of membranes was tested with Staphylococcus aureus and Fusobacterium nucleatum biofilm. CuO was successfully incorporated into membranes as clusters without compromising their mechanical properties for clinical applicability. Increased Cu concentrations generated membranes with thinner nanofibers, greater pore areas, and stronger antimicrobial effect (p < 0.01). Cu 2+ ion was released from the nanofiber membranes during 1 week, showing higher release in acidic conditions. CuO 0.1 % and CuO 0.05 % membranes were able to support and stimulate cell adhesion and proliferation (p < 0.05), and favor angiogenic responses of vascular cells. In addition, detailed quantitative and qualitative analysis determined that amount of the attached biofilm was reduced on the tailored functional Cu 2+ -loaded GBR membrane. Importantly, these qualities represent a valuable strategy to improve the bone regeneration process and diminish the risk of bacterial infections.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Novel GRIA2 variant in a patient with atypical autism spectrum disorder and psychiatric symptoms: a case report. As sequencing technology has advanced in recent years, a series of synapse-related gene variants have been reported to be associated with autism spectrum disorders (ASDs). The α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor is a subtype of the ionotropic glutamate receptor, whose number or composition changes can regulate the strength and plasticity of synapses.	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	0	0
Nurse preceptors' orientation competence and associated factors-A cross-sectional study. To identify distinct orientation competence profiles amongst nurse preceptors and explain the associated factors.	0	0	0	0	0	0	0	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[Prevention and management of pegaspargase associated-toxicities (excluding coagulation abnormalities). Recommendations of the French Society of Children and Adolescent Cancers (Leukemia committee)]. Pegaspargase (Oncaspar®), a pegylated form of native Escherichia Coli-derived L-asparaginase is an essential component chemotherapy used in the treatment of acute lymphoblastic leukemia (ALL) in pediatric and adult patients. Its particular toxicity profile requires a specific management to improve safety and tolerability and optimize treatment outcome and therefore survival. Within the framework of workshops of practice harmonization of the French Society of Children and Adolescent Cancers, diagnostic and management of the most commonly occuring toxicities (excluding coagulation abnormalities) during Pegaspargase treatment were reviewed according to the analysis of published studies.	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	1	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Is the chemical and mechanical ageing of clear aligners during use the reason why predicted results don't always align with final clinical outcomes? Data sources The online databases of Scopus, Web of Science, ScienceDirect, PubMed, ProQuest and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP), from inception to September 2021, were searched with no restrictions to identify eligible studies measuring the changes in surface morphology, chemical and mechanical properties of clear aligners before and after intraoral usage.Study selection Only studies investigating changes in Smart Track (LD30) material met the inclusion criteria. In vitro studies, studies with a sample size of less than ten, studies not assessing the properties of aligners after usage and those assessing the old material of Invisalign were excluded.Data extraction and synthesis Two reviewers independently assessed the studies, and disagreements were resolved through consultation with a third reviewer. Data was pooled using Review Manager (RevMan) version 5.3. Inconsistency test (I2) was used to examine heterogeneity between studies. Meta-analysis was performed based on a random-effects model. Qualitative synthesis was used to assess outcomes from a single study or where different outcome measures were used between studies.Results Two randomised non-control studies and two cohort studies met the inclusion criteria and were included in this systematic review. All included studies were judged to have a moderate risk of bias when assessed using Cochrane collaboration tools (RoB 2 and ROBINS-I). Qualitative assessment of all studies showed LD30 exhibited changes in surface morphology after clinical usage. Mechanical properties were analysed using the pooled estimate of data from 70 aligners. Significant decreases in both Martens hardness (SMD = -3.37; 95% CI [-6.24, -0.52]; P = 0.02) and indentation modulus (SMD = -2.41; 95% CI [-3.39, -1.43]; P = 0.02) indicate changes in mechanical properties before and after usage.Conclusions Within the limitations of the included studies, the authors concluded that LD30 exhibited changes in surface morphology, chemical and mechanical properties during usage, which may have an impact on the differences between predicted and final clinical results. There is currently insufficient evidence to precisely determine the best material that could serve treatment needs.	0	0	0	0	0	0	0	0	0	0	0	0	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
Biofilm with highly heterogeneous interior structure for pollutant removal: Effects of individual extracellular polymeric substance. For the first time, this study reveals the effects of an individual component of extracellular polymeric substances on the substrate consumption rates by the embedded cells based on the highly heterogeneous interior structures of a working biofilm. The flow-across mode in operation established a boundary-layer flow field with high transport resistance, making the uniformly structured model valid. Conversely, the flow field of the flow-through mode is determined by 46% jointly by proteins and β-d-glucopyranose polysaccharides. The substrate consumption rates hindered by β-d-glucopyranose polysaccharide is up to 60% over the 20%-40% biofilm height from the bottom, much lower than expected by the uniformly structured models. The strategies to maximize the biofilm performance have been suggested.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	0	0	0
Using the Multidimensional AIMES to Estimate Connection-to-Nature in an Australian Population: A Latent Class Approach to Segmentation. Individuals can interact and develop multiple connections to nature (CN) which have different meanings and reflect different beliefs, emotions, and values. Human population are not homogenous groups and often generalised approaches are not effective in increasing connectedness to nature. Instead, target-group specific approaches focusing on different segments of the population can offer a promising approach for engaging the public in pro-environmental behaviours. This research employed latent class analysis to identify subgroups of individuals in a large, representative sample ( n = 3090) of an Australian region. Three groups were identified using the AIMES measure of CN with its focus on five types of connection to nature. The high CN group comprised about one-third (35.4%) of participants while the group with the lowest profile of scores contained around a fifth (18.6%) of participants. The majority (46.0%) of participants registered CN levels between the high and low groups. These classes were then regressed on predictor variables to further understand differences between the groups. The largest, consistent predictors of class membership were biocentric and social-altruistic value orientations, stronger intentions to perform pro-environmental behaviours in public (e.g., travel on public transport), the amount of time spent in nature, and the age of participants.	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	0	0
Analytical and Preformulation Characterization Studies of Human Papillomavirus Virus-Like Particles to Enable Quadrivalent Multi-Dose Vaccine Formulation Development. Introducing multi-dose formulations of Human Papillomavirus (HPV) vaccines will reduce costs and enable improved global vaccine coverage, especially in low- and middle-income countries. This work describes the development of key analytical methods later utilized for HPV vaccine multi-dose formulation development. First, down-selection of physicochemical methods suitable for multi-dose formulation development of four HPV (6, 11, 16, and 18) Virus-Like Particles (VLPs) adsorbed to an aluminum adjuvant (Alhydrogel®, AH) was performed. The four monovalent AH-adsorbed HPV VLPs were then characterized using these down-selected methods. Second, stability-indicating competitive ELISA assays were developed using HPV serotype-specific neutralizing mAbs, to monitor relative antibody binding profiles of the four AH-adsorbed VLPs during storage. Third, concentration-dependent preservative-induced destabilization of HPV16 VLPs was demonstrated by addition of eight preservatives found in parenterally administered pharmaceuticals and vaccines, as measured by ELISA, dynamic light scattering, and differential scanning calorimetry. Finally, preservative stability and effectiveness in the presence of vaccine components were evaluated using a combination of RP-UHPLC, a microbial growth inhibition assay, and a modified version of the European Pharmacopoeia assay (Ph. Eur. 5.1.3). Results are discussed in terms of analytical challenges encountered to identify and develop high-throughput methods that facilitate multi-dose formulation development of aluminum-adjuvanted protein-based vaccine candidates.	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	0	0	0	0	0	0	0	0	0	1	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
mRNA COVID-19 vaccines were linked to myocarditis at 28 d (0.15 to 10 excess events/100 000 vaccinated persons). Karlstad Ø, Hovi P, Husby A, et al. SARS-CoV-2 vaccination and myocarditis in a Nordic cohort study of 23 million residents. JAMA Cardiol. 2022;7:600-12. 35442390.	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	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	0	0	0	1	0
Trpc6 gain-of-function disease mutation enhances phosphatidylserine exposure in murine platelets. Platelets enhance coagulation by exposing phosphatidylserine (PS) on their cell surface in response to strong agonist activation. Transient receptor potential channels, including TRPC6, have been implicated in the calcium influx central to this process. Here, we characterize the effect of a Trpc6 gain-of-function (GOF) disease-associated, and a dominant negative (DN), mutation on murine platelet activation. Platelets from mice harboring Trpc6E896K/E896K (GOF) and Trpc6DN/DN mutations were subject to in vitro analysis. Trpc6E896K/E896K and Trpc6DN/DN mutant platelets show enhanced and absent calcium influx, respectively, upon addition of the TRPC3/6 agonist GSK1702934A (GSK). GSK was sufficient to induce integrin αIIbβ3 activation, P-selection and PS exposure, talin cleavage, and MLC2 phosphorylation in Trpc6E896K/E896K, but not in wild-type, platelets. Thrombin-induced calcium influx and PS exposure were enhanced, and clot retraction delayed, by GOF TRPC6, while no differences were noted between wild-type and Trpc6DN/DN platelets. In contrast, Erk activation upon GSK treatment was absent in Trpc6DN/DN, and enhanced in Trpc6E896K/E896K, platelets, compared to wild-type. The positive allosteric modulator, TRPC6-PAM-C20, and fluoxetine maintained their ability to enhance and inhibit, respectively, GSK-mediated calcium influx in Trpc6E896K/E896K platelets. The data demonstrate that gain-of-function mutant TRPC6 channel can enhance platelet activation, including PS exposure, while confirming that TRPC6 is not necessary for this process. Furthermore, the results suggest that Trpc6 GOF disease mutants do not simply increase wild-type TRPC6 responses, but can affect pathways not usually modulated by TRPC6 channel activity, displaying a true gain-of-function phenotype.	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Recyclable polysaccharide/stimuli-responsive polymer composites and their applications in water remediation. The use of composites of stimuli-responsive polymers with polysaccharides during water remediation has gained impetus in recent years. The applications of composites of polysaccharides (chitosan, cellulose and cyclodextrin) with stimuli-responsive polymers (CO 2 -, thermo-, light-, and pH-responsive polymers) were reviewed in this paper. These smart composites have tuneable physicochemical properties that enable them to form tailor-made adsorbents for the adsorption of pollutants from water. Adsorption and desorption of pollutants can be switched on and off by adjusting appropriate stimuli without the use of toxic organic solvents. The polysaccharide/stimuli-responsive polymer-based adsorbents, therefore, can be easily recovered during water remediation by adjusting the stimuli, and this makes them to be eco-friendly and recyclable. These attributes of the polysaccharide/stimuli-responsive polymer-based composites were explored in detail in this review. In addition, the challenges associated with the use of these smart composites as well as their future prospects were also articulated in this paper.	0	0	0	0	0	0	0	0	0	0	0	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	1	0	0	1	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0
A commercial ARHGEF17/TEM4 antibody cross-reacts with Nuclear Mitotic Apparatus protein 1 (NuMA). The Rho family Guanine nucleotide exchange factor (GEF) ARHGEF17 (also known as TEM4) is a large protein with only 3 annotated regions: an N-terminal actin-binding domain, a Rho-specific dbl homology (DH)- pleckstrin homology (PH) type GEF domain and a seven bladed β propeller fold at the C-terminus with unknown function. TEM4 has been implicated in numerous activities that rely on regulation of the cytoskeleton including cell migration, cell-cell junction formation and the spindle assembly checkpoint during mitosis. Here we have assessed the specificity of a TEM4 polyclonal antibody that has been commonly used as a Western blotting and immunocytochemistry probe for TEM4 in mammalian cells. We find that this antibody, in addition to its intended target, cross-reacts with the Nuclear Mitotic Apparatus Protein 1 (NuMA) in Western blotting and immunoprecipitation, and detects NuMA preferentially in immunocytochemistry. This cross-reactivity, with an abundant chromatin- and mitotic spindle-associated factor, is likely to affect the interpretation of experiments that make use of this antibody probe, in particular by immunocytochemistry and immunoprecipitation.	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	1	0	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0
Diagnostic performance of serum calprotectin in discriminating active from inactive ulcerative colitis in an outpatient setting. There are limited and conflicting data on the value of serum calprotectin (sCp) in discriminating active from inactive disease activity in ulcerative colitis (UC). Faecal calprotectin (fCp), sCp, serum C-reactive protein (sCRP) and platelets were compared in patients with UC who had clinically active (n = 29) and clinically inactive (n = 42) disease. Serum calprotectin was measured with Bühlmann<sup>®</sup> (BMN sCp) and Immunodiagnostik<sup>TM</sup> (IDK sCp) assays. Median (interquartile range) fCp was higher in active than inactive disease [1004 (466-1922) versus 151 (55-280) µg/g; <i>p</i> < 0.0001). BMN sCp [4534 (3387-6416) versus 4031 (2401-5414) ng/mL; <i>p</i> = 0.1825], IDK sCp [4531 (2920-6433) versus 3307 (2104-4789) ng/mL; <i>p</i> = 0.1065], sCRP [ 4 (2-8) versus 2 (1-4) mg/L; <i>p</i> = 0.0638) and platelets [269 (233-331) versus 280 (227-325) ×10<sup>-9</sup>/L; <i>p</i> = 0.8055] were similar in active and inactive disease respectively. The area under the receiver operator characteristics curves with 95% confidence limits were 0.85 (0.76-0.94) for fCp, 0.61 (0.47-0.74) for BMN sCp, 0.61 (0.48-0.75) for IDK sCp, 0.69 (0.56-0.81) for sCRP and 0.52 (0.38-0.66) for blood platelets. Faecal calprotectin is the optimum biomarker for discriminating between active and inactive UC. The diagnostic performance of sCp, irrespective of assay, and systemic biomarkers was poor; of these sCRP performed best.	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	1	0	0	0	0	0	0	0	0	0	0	0	0
Driven by notifications - exploring the effects of badge notifications on user experience. Notification badges are an unexplored category of visual feedback to which we are continuously exposed. This study aims to deepen knowledge on the topic by measuring the behavioral effects of notification badges on a large sample of smartphone users. More precisely, the goal of the study is to observe if the presence of notification badges increases the frequency of clicks on apps. More than 1000 participants were involved in a remote between-subjects experiment, allocated into fifteen equinumerous groups of comparison. Each participant was presented with a smartphone screen displaying fifteen app icons and just one badge notification. Participants were asked to perform a remote user test called First Impression Click Test: a methodology that indicates where they would click first to accomplish a given task (i.e., Where would you click first on this screen?). Our results show a large increase in the number of clicks on apps with notification badges compared to those without notification badges and suggest the important ability of these small affordances to attract attention and stimulate action. Based on the evidence provided, our findings have practical implications for user experience design.	0	0	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Preclinical platforms to study therapeutic efficacy of human γδ T cells. Gamma delta (γδ) T lymphocytes are promising candidate for adoptive T cell therapy, however, their treatment efficacy is not satisfactory. Vδ2 T cells are unique to primates and few suitable models are available to assay their anti-tumour function.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0	0	1	0	0	0	0	0
CCL20/CCR6 axis mediates macrophages to promote proliferation and migration of ESCs by blocking autophagic flux in endometriosis. Endometriosis (EMs) is a common benign gynecological disease that affects approximately 10% of females of reproductive age. Endometriosis ectopic lesions could recruit macrophages, which in turn facilitates endometriosis progression. Several studies have indicated that CCL20 derived from macrophages activates the expression of CCR6 in several cells and induces cell proliferation and migration. However, the function of the CCL20/CCR6 axis in the interactions between macrophages and endometriotic stromal cells (ESCs) in EMs has yet to be elucidated.	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	1	0	0	0	0	0	0	0	0	1	1	0	0	0	0
Bacterial membrane vesicles in inflammatory bowel disease. Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation with no cure. The intestine is fundamental in controlling human health. Disruption of the microbial ecosystem in the intestine is considered an important cause of IBD. The interaction between the host and microbiota significantly impacts the intestinal epithelial barrier and immune function. Bacterial membrane vesicles (MVs) are vital participants in bacteria-bacteria and host-microbiota communication. Currently, MVs have been found to exhibit many important regulating effects for intestinal microecology and have excellent application potential in clinical disease therapies. In the present review, we review the current knowledge on MVs, and specifically focus on gut bacterial MVs and their roles in the IBD. In addition, we summarized the potential utility of MVs as a novel therapeutic approach in IBD patients.	1	0	0	0	0	0	0	1	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Self-Assembly of Optimally Packed Cylindrical Clusters inside Spherical Shells. Systems with short-range attraction and long-range repulsion can form ordered microphases in bulk and under confinement. Using grand canonical Monte Carlo simulations, we study a colloidal system with competing interactions under confinement in narrow spherical shells at thermodynamic conditions at which the hexagonal phase of cylindrical clusters is stable in bulk. We observe spontaneous formation of different ordered structures. The results of the simulations are in a very good agreement with the predictions of a simple mathematical model based on the geometry and optimal packing of colloidal clusters. The results of the simulations and the explanation provided by a relatively simple geometric model may be helpful in manufacturing copolymer nanocapsules and may indicate possible ways of coiling DNA strands on spherical objects.	0	0	0	0	0	0	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	1	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
The tribe Cybalomiini (Lepidoptera: Pyraloidea, Crambidae, Glaphyrinae) of sub-Saharan Africa. The Cybalomiini (Crambidae, Glaphyrinae) of Africa south of the Sahara are revised. One new genus Melouia is described, 26 new species: Crambicybolomia similis, Goniophysetis aarviki, G. cuthberti, Trichophysetis collinsi, T. vumbensis, T. foveolatae, T. zariensis, T. samueli, T. ethiopica, T. mossi, T. trilinealis, T. cataracta, Melouia krooni, M. aspidophoralis, Ptychopseustis maesi, P. sharporum, P. baringensis, P. abyssinica, P. catherinae, P. butleri, P. fuscalis, P. beccarii, P. sinualis, P. umbroterminalis, P. brunneoflavalis, and P. suffusalis are described and one new synonymy is declared.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Future prospect of "Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients". Recently, we read the article "Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients" with interest, and it is preliminary suggested that gut microbiota is closely related to therapeutic effect of nivolumab. Based on the meaningful results of this article, several valuable research directions are proposed to enhance the therapeutic effect of immune checkpoint inhibitors on advanced hepatocellular carcinoma.	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	0	0	0	0	0	0	0	0	0	0	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
Myopia and BMI: a nationwide study of 1.3 million adolescents. This study analyzed the association between adolescent BMI and myopia severity.	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	0	0	0
Three-dimensional echo decorrelation monitoring of radiofrequency ablation in ex vivo bovine liver. Three-dimensional (3D) echo decorrelation imaging was investigated for monitoring radiofrequency ablation (RFA) in ex vivo bovine liver. RFA experiments (N = 14) were imaged by 3D ultrasound using a matrix array, with in-phase and quadrature complex echo volumes acquired about every 11 s. Tissue specimens were then frozen at -80 °C, sectioned, and semi-automatically segmented. Receiver operating characteristic (ROC) curves were constructed for assessing ablation prediction performance of 3D echo decorrelation with three potential normalization approaches, as well as 3D integrated backscatter (IBS). ROC analysis indicated that 3D echo decorrelation imaging is potentially a good predictor of local RFA, with the best prediction performance observed for globally normalized decorrelation. Tissue temperatures, recorded by four thermocouples integrated into the RFA probe, showed good correspondence with spatially averaged decorrelation and statistically significant but weak correlation with measured echo decorrelation at the same spatial locations. In tests predicting ablation zones using a weighted K-means clustering approach, echo decorrelation performed better than IBS, with smaller root mean square volume errors and higher Dice coefficients relative to measured ablation zones. These results suggest that 3D echo decorrelation and IBS imaging are capable of real-time monitoring of thermal ablation, with potential application to clinical treatment of liver tumors.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Acute pancreatitis in 60 Iranian children: do pediatricians follow the new guidelines in diagnosis and management of acute pancreatitis? The incidence of acute pancreatitis in children is increasing, but causes and diagnostic and therapeutic methods are various in different centers. The aim of this study was to investigate the common causes and routine diagnostic and therapeutic methods of acute pancreatitis in children in a pediatric gastrointestinal referral center and its accordance with existing guidelines.	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	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
In Vitro Assessment of Poly-N-Vinylpyrrolidone/Acrylic Acid Nanoparticles Biocompatibility in a Microvascular Endothelium Model. An amphiphilic copolymer of N-vinyl-2-pyrrolidone and acrylic acid-namely, p(VP-AA)-OD6000 (p(VP-AA))-was synthesized to prepare p(VP-AA) nanoparticles (NPs). Furthermore, the copolymer was linked with CFSE, and the so-prepared nanoparticles were loaded with the DiI dye to form D nanoparticles (DNPs). In this study, as demonstrated by immunofluorescence microscopy, immunofluorescence, and confocal microscopy, DNPs were readily taken up by human microvascular endothelial cells (HMEC-1) cells in a concentration-dependent manner. Upon uptake, both the CFSE dye (green stain) and the DiI dye (red stain) were localized to the cytoplasm of treated cells. Treatment with p(VP-AA) did not affect the viability of normal and challenged with LPS, HMEC-1 cells at 0.010 mg/mL and induced a dose-dependent decrease of these cells' viability at the higher concentrations of 0.033 and 0.066 mg/mL ( p ≤ 0.01; p ≤ 0.001, respectively). Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon p(VP-AA) NPs treatment by assessing the expression of adhesion molecules (E-Selectin, ICAM-1, and V-CAM). NPs treatments at concentrations utilized ( p = NS) did not affect individual adhesion molecules' expression. p(VP-AA) NPs do not activate the endothelium and do not affect its viability at pharmacologically relevant concentrations.	0	0	0	0	0	0	0	0	0	0	0	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	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0
The anatomy of social dynamics in escape rooms. From sport and science production to everyday life, higher-level pursuits demand collaboration. Despite an increase in the number of data-driven studies on human behavior, the social dynamics of collaborative problem solving are still largely unexplored with network science and other computational and quantitative tools. Here we introduce escape rooms as a non-interventional and minimally biased social laboratory, which allows us to capture at a high resolution real-time communications in small project teams. Our analysis portrays a nuanced picture of different dimensions of social dynamics. We reveal how socio-demographic characteristics impact problem solving and the importance of prior relationships for enhanced interactions. We extract key conversation rules from motif analysis and discuss turn-usurping gendered behavior, a phenomenon particularly strong in male-dominated teams. We investigate the temporal evolution of signed and group interactions, finding that a minimum level of tense communication might be beneficial for collective problem solving, and revealing differences in the behavior of successful and failed teams. Our work unveils the innovative potential of escape rooms to study teams in their complexity, contributing to a deeper understanding of the micro-dynamics of collaborative team processes.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0
A systematic review and meta-analysis on the association between ambient air pollution and pulmonary tuberculosis. There is inconclusive evidence on the association between ambient air pollution and pulmonary tuberculosis (PTB) incidence, tuberculosis-related hospital admission and mortality. This review aimed to assess the extent to which selected air pollutants are associated to PTB incidence, hospital admissions and mortality. This was a systematic review of studies published in English from January 1st, 1946, through May 31st, 2022, that quantitatively assessed the association between PM 2.5 , PM 10 , NO 2 , SO 2 , CO, O 3 and the incidence of, hospital admission or death from PTB. Medline, Embase, Scopus and The Cochrane Library were searched. Extracted data from eligible studies were analysed using STATA software. Random-effect meta-analysis was used to derive pooled adjusted risk and odds ratios. A total of 24 studies (10 time-series, 5 ecologic, 5 cohort, 2 case-control, 1 case cross-over, 1 cross-sectional) mainly from Asian countries were eligible and involved a total of 437,255 tuberculosis cases. For every 10 μg/m 3 increment in air pollutant concentration, there was a significant association between exposure to PM 2.5 (pooled aRR = 1.12, 95% CI: 1.06-1.19, p < 0.001, N = 6); PM 10 (pooled aRR = 1.06, 95% CI: 1.01-1.12, p = 0.022, N = 8); SO 2 (pooled aRR = 1.08, 95% CI: 1.04-1.12, p < 0.001, N = 9); and the incidence of PTB. There was no association between exposure to CO (pooled aRR = 1.04, 95% CI: 0.98-1.11, p = 0.211, N = 4); NO 2 (pooled aRR = 1.08, 95% CI: 0.99-1.17, p = 0.057, N = 7); O 3 (pooled aRR = 1.00, 95% CI: 0.99-1.02, p = 0.910, N = 6) and the incidence of PTB. There was no association between the investigated air pollutants and mortality or hospital admissions due to PTB. Overall quality of evidence was graded as low (GRADE approach). Exposure to PM 2.5 , PM 10 and SO 2 air pollutants was found to be associated with an increased incidence of PTB, while exposure to CO, NO 2 and O 3 was not. There was no observed association between exposure to these air pollutants and hospital admission or mortality due to PTB. The quality of the evidence generated, however, remains low. Addressing the tuberculosis epidemic by 2030 as per the 4th Sustainable Development Goal may require a more rigorous exploration of this association.	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	1	0	0	0	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
Illness perceptions and outcome in multiple sclerosis: A systematic review of the literature. According to Leventhal's self-regulation model, ill people construct personal representations of their disease, namely illness perceptions, which impact their coping strategies and the emotional response to their condition. Since these representations develop in the social environment, the individuals' perceptions may also be related to the opinions of their caregivers. This systematic review aims at synthesising and critically appraising literature pertaining the relationship between illness perceptions and outcome in persons with multiple sclerosis and their caregivers. A literature search was conducted in MEDLINE, PsycINFO, and CINAHL. Only papers with the following characteristics were included: quantitative studies; written in English or Italian; published from 1992; investigating the relationship between illness perceptions and any outcome in persons with multiple sclerosis and/or their caregivers; using validated scales assessing illness perceptions. Twenty papers were included and appraised through the 16-item Quality Assessment Tool for Studies with Diverse Designs. The quality of the papers was acceptable. Eighteen out of 20 papers reported the existence of a moderate effect size when analysing the relationship between illness perceptions and outcome, whereby "positive" perceptions (e.g. stronger beliefs of control) related to better outcomes, while "negative" ones (e.g. attribution of negative consequences to the disease) related to worse outcome.	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	0	0	0
Current appetite influences relative differences in the expected satiety of foods for momentary, but not hypothetical, expected satiety assessments. Research has shown that expected satiety is highly associated with portion-size selection and can vary (kcal-for-kcal) significantly between foods. However, research has not adequately investigated whether current appetite influences relative differences in the expected satiety of foods. This is important to explore to better understand how current motivational state influences food choice and portion selection. This study used 'hypothetical' and 'momentary' expected-satiety assessments to understand whether methods requiring a reflection on current motivational state [momentary] versus more hypothetical considerations when assessing expected satiety can influence the interpretation of results. It was hypothesised that current appetite would only influence relative differences in expected satiety between foods for momentary, but not hypothetical, expected satiety assessments. Participants (n = 54) were shown images of twelve foods, once when hungry and once when full. In each case, they selected a portion for each food to 1) match the expected satiety of a fixed-portion 'standard' food [hypothetical], and 2) stave off hunger until their next meal [momentary]. Results showed that the relative between-food comparison of expected satiety was stable for hypothetical (p=.73) but not momentary assessments (p<.001) suggesting that while current motivational state may influence food choice and portion selection in the moment, more generalised comparisons of the satiating abilities of foods (learned over a longer period) remain stable. This is important 1) for methods in future studies, as immediate dietary intake does not appear to influence hypothetical expected satiety, thus dietary control is not necessary before participants undertake these assessments, and 2) as it confirms that difficulties associated with dietary regulation may not be due to inaccurate hypothetical judgements about foods, but instead appear to be influenced by contextual nuances that occur in the moment.	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	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
Prenatal exposure to bisphenol S and bisphenol A differentially affects male reproductive system in the adult offspring. Early exposure to bisphenol may result in adverse reproductive health in later life. The use of bisphenol S (BPS) has increased considerably after bisphenol A (BPA) is regulated worldwide. However, little is known about the fetal exposure to BPS compared with BPA and its effects on the reproductive system in the adult male offspring. Here, we investigated the effects of orally administered BPS and BPA (0.4, 4.0, 40.0 μg/kg bw/d) during gestation (gD4-21) on testicular development by evaluating the sperm DNA damage & methylation and testicular functions in the 90 d Wistar rats. Male offspring prenatally exposed to BPS (0.4 μg/kg) had higher plasma testosterone than BPA and control. The testis histology reveals thickened membrane by producing a wide interstitial gap between seminiferous tubules, increased testicular inflammation, oxidative stress, TIMP-1 expression, and decreased VCAM-1 expression. BPS promotes apoptosis by up-regulating IL-6, cleaved caspases, and a spike in sperm DNA fragmentation. Prenatal BPS exposure reduces sperm motility mediated via impaired PI3K-AKT signaling and increases testicular TEX11 expression in the offspring. Exposure of the fetus to BPS interferes developmental programming of the male reproductive system in the offspring. BPS could be an equally potent endocrine disruptor affecting male reproductive functions.	0	0	0	0	1	1	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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Rising abuse of veterinary drugs. There has been a significant increase in veterinary drugs found on toxicology screens and postmortem analyses, especially in the Northeast region of the US. This article details the effects and treatment of two common culprits: xylazine and tiletamine-zolazepam.	0	0	0	0	0	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[<sup>18</sup> F]FDG brain uptake of C57Bl/6 male mice is affected by locomotor activity after cocaine use: A small animal positron emission tomography study. We verified if cocaine-induced peripheral activation might disrupt [<sup>18</sup> F]FDG brain uptake after a cocaine challenge and suggested an optimal protocol to measure cocaine-induced brain metabolic alterations in mice. C57Bl/6 male mice were injected with [<sup>18</sup> F]FDG and randomly separated into three groups. Groups 1 and 2 were kept conscious after [<sup>18</sup> F]FDG administration and after 5 min received saline or cocaine (20 mg/kg). The animals in group 1 (n = 5) were then evaluated in the open field for 30 min and those from group 2 (n = 6) were kept alone in a home cage for the same period. Forty-five minutes after [<sup>18</sup> F]FDG administration, images were acquired for 30 min. Group 3 (n = 6) was kept anesthetized and image acquisition started immediately after tracer injection, for 75 min. Saline (Day 1) or cocaine (Day 2) was injected 5 min after starting acquisition. Another set of animals (n = 5) were treated with cocaine every other day for 10 days or saline (n = 6) and were scanned with the dynamic protocol to verify its efficacy. [<sup>18</sup> F]FDG uptake increased after cocaine administration when compared to baseline only in animals kept under anesthesia. No brain effect of cocaine was observed in animals submitted to the open field or kept in the home cage. The use of anesthesia is essential to visualize cocaine-induced changes in brain metabolism by [<sup>18</sup> F]FDG PET, providing an interesting preclinical approach to investigate naïve subjects and enabling a bidirectional translational science approach for better understanding of cocaine use disorder.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1	1	0	0	0	0	0	0	0	0	0	0
Indirect calculation of LDL using thirteen equations in Pakistani population. Owing to the atherogenic properties, low density lipoprotein cholesterol (LDL-C) is the primary target for treatment and diagnosis of cardiovascular diseases (CVDs), hence accurate measurement of LDL-C is critical. Despite the availability of direct measurement assays for LDL-C, it is routinely calculated by Friedewald equation in clinical settings in Pakistan mostly due to financial constraints. However, the validity of this equation is impacted by several factors, therefore several other equations have been developed for the calculation of LDL-C.	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	0	0	0
Time Line of Occlusion for Intracranial Aneurysms Treated with the Pipeline Embolization Device. Rates of aneurysm occlusion following treatment with flow-diverting stents have been quantified at predefined time points in clinical trials, but data characterizing the continuous temporal progression of aneurysm occlusion are lacking. This study used real-world variability in timing of angiographic follow-up to characterize the time line of aneurysm occlusion following treatment with the Pipeline embolization device (PED).	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	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	1	0	0	0	0	0	0
Biological sample donation and informed consent for neurobiobanking: Evidence from a community survey in Ghana and Nigeria. Genomic research and neurobiobanking are expanding globally. Empirical evidence on the level of awareness and willingness to donate/share biological samples towards the expansion of neurobiobanking in sub-Saharan Africa is lacking.	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	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
Sublethal and lethal Cd toxicity in soybean roots specifically affects the metabolome, Cd binding to proteins and cellular distribution of Cd. Soybean (Glycine max (L.) Merr.) plants were exposed to various Cd concentrations from background and low non-toxic (0.5-50 nM) via sublethally toxic (< 550 nM) to highly, ultimately lethally toxic (3 µM) concentrations. Plants were cultivated hydroponically for 10 weeks until pod development stage of the control plants. The threshold and mechanism of sublethal Cd toxicity was investigated by metabolomics and metalloproteomics (HPLC-ICP-MS) measuring metal binding to proteins in the harvested roots. Spatial distribution of Cd was revealed by µXRF-CT. Specific binding of Cd to proteins already at 50 nM Cd revealed the likely high-affinity protein binding targets in roots, identified by protein purification from natural abundance. This revealed allantoinase, aquaporins, peroxidases and protein disulfide isomerase as the most likely high-affinity targets of Cd binding. Cd was deposited in cortex cell vacuoles at sublethal and bound to the cell walls of the outer cortex and the vascular bundle at lethal Cd. Cd binding to proteins likely inhibits them, and possibly induces detoxification mechanisms, as verified by metabolomics: allantoic acid and allantoate increased due to sublethal Cd toxicity. Changes of the Cd binding pattern indicated a detoxification strategy at lower Cd, but saturated binding sites at higher Cd concentrations.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Genomic insights into the emergence and spread of NDM-1-producing Vibrio spp. isolates in China. Carbapenemase-producing Vibrio spp., which exhibit an XDR phenotype, have become increasingly prevalent and pose a severe threat to public health.	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	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
The Occurrence of Squalene in Human Milk and Infant Formula. (1) Background: The aim of the conducted research was to analyze the squalene content in infants' food. (2) Methods: The experimental material included human milk collected from 100 women from Poland and three different infant formulas. The breast milk fat was extracted according to the Rose-Gottlieb method (AOAC), while the squalene content was determined using the high-performance liquid chromatography (HPLC) method. (3) Results: The highest amount of squalene was identified in the milk of women aged 18-25 ( p < 0.05), and its content in milk decreased with the age of lactating women. Moreover, the greatest amount of squalene was identified in milk from the first lactation period (colostrum), while in mature milk, its content was more than two times lower. There was a correlation between breastfeeding BMI and the squalene content in milk (r = 0.78). (4) Conclusions: The conducted research shows that the level of squalene in human milk depends on physiological factors such as the lactation period and individual factors (age, BMI). The results of the conducted research indicate that breast milk is richer in squalene than modified milk. This study shows the importance of breastfeeding and indicates the superiority of breast milk over infant formulas.	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	1	0	0	0	0	0	0	0	0
Search and rescue incidents among persons 65 years and older in the USA: Examination of factors associated with death. Older people are vulnerable to becoming lost from home, especially if alone and in unfamiliar environments. Incidents of older persons becoming lost are frequently reported and often requiring a search and rescue (SAR) response. Becoming lost is distressing to the person concerned, their carer, and family and may result in physical injury and/or death. This study examined what factors are associated with death among older persons reported lost from home.	0	0	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	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The Brain Protein Acylation System Responds to Seizures in the Rat Model of PTZ-Induced Epilepsy. Abnormal energy expenditure during seizures and metabolic regulation through post-translational protein acylation suggest acylation as a therapeutic target in epilepsy. Our goal is to characterize an interplay between the brain acylation system components and their changes after seizures. In a rat model of pentylenetetrazole (PTZ)-induced epilepsy, we quantify 43 acylations in 29 cerebral cortex proteins; levels of NAD + ; expression of NAD + -dependent deacylases (SIRT2, SIRT3, SIRT5); activities of the acyl-CoA-producing/NAD + -utilizing complexes of 2-oxoacid dehydrogenases. Compared to the control group, acylations of 14 sites in 11 proteins are found to differ significantly after seizures, with six of the proteins involved in glycolysis and energy metabolism. Comparing the single and chronic seizures does not reveal significant differences in the acylations, pyruvate dehydrogenase activity, SIRT2 expression or NAD + . On the contrary, expression of SIRT3, SIRT5 and activity of 2-oxoglutarate dehydrogenase (OGDH) decrease in chronic seizures vs. a single seizure. Negative correlations between the protein succinylation/glutarylation and SIRT5 expression, and positive correlations between the protein acetylation and SIRT2 expression are shown. Our findings unravel involvement of SIRT5 and OGDH in metabolic adaptation to seizures through protein acylation, consistent with the known neuroprotective role of SIRT5 and contribution of OGDH to the Glu/GABA balance perturbed in epilepsy.	0	0	0	0	0	0	0	0	0	0	1	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Effect of acetone fraction of Ottelia alismoides on the G2/M cell cycle arrest and apoptosis in the human carcinoma cell lines. The North-eastern parts of India have immense therapeutic floras, Ottelia alismoides is an aquatic plant that has been in use for a long time in traditional medicine for treating diseases like cancer, tuberculosis, diabetes, febrifuge, hemorrhoids, and rubefacient. In lung and skin carcinoma cells with a high rate of proliferation and metastasis including drug resistance and non-specific target activity, generates important challenges towards their treatment strategy. Thus, finding novel therapeutic targets to treat lung and skin cancer progression is essential to enhance the patients' survival with treatment.	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	1	0	0	0	0	0
Cigarette Smoking Among US Adults With Selected Chronic Diseases Associated With Smoking, 2010-2019. People who smoke cigarettes are at greater risk of developing chronic diseases and related complications. Our study provides recent estimates and trends in cigarette smoking among people with respiratory and cardiovascular diseases, cancers, and diabetes.	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	1	0	0	0	0	0
ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies. Alzheimer's disease (AD) is the most common cause of dementia worldwide, and its prevalence is rapidly increasing due to extended lifespans. Among the increasing number of genetic risk factors identified, the apolipoprotein E (APOE) gene remains the strongest and most prevalent, impacting more than half of all AD cases. While the ε4 allele of the APOE gene significantly increases AD risk, the ε2 allele is protective relative to the common ε3 allele. These gene alleles encode three apoE protein isoforms that differ at two amino acid positions. The primary physiological function of apoE is to mediate lipid transport in the brain and periphery; however, additional functions of apoE in diverse biological functions have been recognized. Pathogenically, apoE seeds amyloid-β (Aβ) plaques in the brain with apoE4 driving earlier and more abundant amyloids. ApoE isoforms also have differential effects on multiple Aβ-related or Aβ-independent pathways. The complexity of apoE biology and pathobiology presents challenges to designing effective apoE-targeted therapeutic strategies. This review examines the key pathobiological pathways of apoE and related targeting strategies with a specific focus on the latest technological advances and tools.	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	0	0	0	0	0	0	0	0
Enhancement of transdermal permeation of cannabinoids and their pharmacodynamic evaluation in rats. The objective of the present study was to enhance the transdermal permeation of cannabinoids: cannabidiol (CBD), cannabigerol (CBG) and tetrahydrocannabivarin (THCV) using chemical permeation enhancer approach and evaluate them for their anti-inflammatory effect in vivo in a paw edema model in rats. Cannabinoids gel formulations were developed using FDA approved inactive ingredients: lactic acid (LA), polyethylene glycol-400 (PEG-400), N-methyl-2 pyrrolidone (NMP), dimethyl sulfoxide (DMSO). In vitro skin permeation testing (IVPT) showed flux of ∼ 13.25 μg/cm 2 /h for CBD, ∼9.38 μg/cm 2 /h for CBG and ∼ 51.74 μg/cm 2 /h for THCV. Additionally, IVPT study showed cumulative drug permeation of 610.96 ± 88.92 μg/cm 2 , 432.09 ± 35.59 μg/cm 2 and 2384.44 ± 42.22 μg/cm 2 from CBD, CBG and THCV gel formulations respectively. Further, effect of excipients on cannabinoid permeation showed that, formulation containing lactic acid, NMP and DMSO showed significantly (p < 0.0001) enhanced flux of cannabinoids as compared to formulation without LA, NMP and DMSO. In vivo studies showed that paw edema was significantly (p < 0.0001) reduced in the groups containing CBD, CBG, THCV as compared to control and placebo formulation. In conclusion, flux of CBD, CBG and THCV was significantly enhanced using chemical permeation enhancers approach which helped in reducing rat paw edema.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	0	0	0	0
The Purified Siderophore from Streptomyces tricolor HM10 Accelerates Recovery from Iron-Deficiency-Induced Anemia in Rats. Iron-deficiency-induced anemia is associated with poor neurological development, including decreased learning ability, altered motor functions, and numerous pathologies. Siderophores are iron chelators with low molecular weight secreted by microorganisms. The proposed catechol-type pathway was identified based on whole-genome sequences and bioinformatics tools. The intended pathway consists of five genes involved in the biosynthesis process. Therefore, the isolated catechol-type siderophore (Sid) from Streptomyces tricolor HM10 was evaluated through an anemia-induced rat model to study its potential to accelerate recovery from anemia. Rats were subjected to an iron-deficient diet (IDD) for 42 days. Anemic rats (ARs) were then divided into six groups, and normal rats (NRs) fed a standard diet (SD) were used as a positive control group. For the recovery experiment, ARs were treated as a group I; fed an IDD (AR), group II; fed an SD (AR + SD), group III, and IV, fed an SD with an intraperitoneal injection of 1 μg Sid Kg -1 (AR + SD + Sid1) and 5 μg Sid Kg -1 (AR + SD + Sid5) twice per week. Group V and VI were fed an iron-enriched diet (IED) with an intraperitoneal injection of 1 μg Sid Kg -1 (AR + IED + Sid1) and 5 μg Sid Kg -1 (AR + IED + Sid5) twice per week, respectively. Weight gain, food intake, food efficiency ratio, organ weight, liver iron concentration (LIC) and plasma (PIC), and hematological parameters were investigated. The results showed that ~50-60 mg Sid L -1 medium could be producible, providing ~25-30 mg L -1 purified Sid under optimal conditions. Remarkably, the AR group fed an SD with 5 μg Sid Kg -1 showed the highest weight gain. The highest feed efficiency was observed in the AR + SD + Sid5 group, which did not significantly differ from the SD group. Liver, kidneys, and spleen weight indicated that diet and Sid concentration were related to weight recovery in a dose-dependent manner. Liver iron concentration (LIC) in the AR + IED + Sid1 and AR + IED + Sid5 groups was considerably higher than in the AR + SD + Sid1 AR + SD + Sid5 groups or the AR + SD group compared to the AR group. All hematological parameters in the treated groups were significantly closely attenuated to SD groups after 28 days, confirming the efficiency of the anemia recovery treatments. Significant increases were obtained in the AR + SD + Sid5 and AR + IED + Sid5 groups on day 14 and day 28 compared to the values for the AR + SD + Sid1 and AR + IED + Sid1 groups. The transferrin saturation % (TSAT) and ferritin concentration (FC) were significantly increased with time progression in the treated groups associatively with PIC. In comparison, the highest significant increases were noticed in ARs fed IEDs with 5 μg Kg -1 Sid on days 14 and 28. In conclusion, this study indicated that Sid derived from S. tricolor HM10 could be a practical and feasible iron-nutritive fortifier when treating iron-deficiency-induced anemia (IDA). Further investigation focusing on its mechanism and kinetics is needed.	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	0	0	0
The Top 100 Most Cited Scientific Papers in the Public, Environmental & Occupational Health Category of Web of Science: A Bibliometric and Visualized Analysis. (1) Background: The main basis for the public recognition of the merits of scientists has always been the system of scientific publications and citations. Our goal is to identify and analyze the most cited articles in the Public, Environmental & Occupational Health category. (2) Methods: We searched the Web of Science for all articles published in the "Public, Environmental & Occupational Health" category up to March 2022 and selected the 100 most cited articles. We recorded the number of citations, the journal, the year of publication, quartile, impact factor, institution, country, authors, topic, type of publication and collaborations. (3) Results: 926,665 documents were analyzed. The top 100 had 401,620 citations. The journal with the most articles was the Journal of Clinical Epidemiology and the one with the highest number of citations was Medical Care. The year with the highest number of articles in the top 100 was 1998. The country with the highest percentage of publications was the USA and the most productive institution was Harvard. The most frequent keywords were bias, quality, and extension. The largest collaboration node was between the USA, Canada, Germany, Spain, Australia, France, and Sweden. (4) Conclusions: This bibliometric study on Public, Environmental & Occupational Health provides valuable information not only to identify topics of interest in the analyzed category, but also to identify the differences in the topics they 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	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
Enhanced Robustness of the Mouse Retinal Circadian Clock Upon Inherited Retina Degeneration. Daily biological rhythms are fundamental to retinal physiology and visual function. They are generated by a local circadian clock composed of a network of cell type/layer-specific, coupled oscillators. Animal models of retinal degeneration have been instrumental in characterizing the anatomical organization of the retinal clock. However, it is still unclear, among the multiple cell-types composing the retina, which ones are essential for proper circadian function. In this study, we used a previously well-characterized mouse model for autosomal dominant retinitis pigmentosa to examine the relationship between rod degeneration and the retinal circadian clock. This model carries the P23H mutation in rhodopsin, which induces mild rod degeneration in heterozygous and rapid loss of photoreceptors in homozygous genotypes. By measuring PER2::LUC bioluminescence rhythms, we show that the retinal clock in <i>P23H/+</i> heterozygous mice displays circadian rhythms with significantly increased robustness and amplitude. By treating retinal explants with L-α aminoadipic acid, we further provide evidence that this enhanced rhythmicity might involve activation of Müller glial cells.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	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
Analysis of Complications and Recipients' and Graft Survival in Patients 60 Years of Age and Older in the Long-Term Follow-up Period After Kidney Transplant: A Single-Center, Paired Kidney Analysis. Long-term results of kidney transplant (KTx) in older patients may differ from younger recipients owing to increased cardiovascular comorbidities. The study aimed to analyze surgical and nonsurgical complications that develop in the long-term follow-up period after KTx, and factors that influence results of KTx in recipients aged 60 years and older (≥60) compared with younger recipients (<60).	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	0	0	0	0	0	0	0	0	0	0	0	0
Toxicological assessment compilation of selected examples of raw materials for homeopathic and anthroposophic medicinal products - Part 2. The present successor article comprises more than 180 substances representing a continuative compilation of toxicologically evaluated starting materials prompted by the wide use and high number of homeopathic and anthroposophic medicinal products (HMP) on the market together with the broad spectrum of active substances of botanical, mineral, chemical or animal origin contained therein, and by the equally important requirement of applying adequate safety principles as with conventional human medicinal products in line with the European regulatory framework. The February 2019 issue of the Regulatory Toxicology and Pharmacology journal includes the antecedent article bearing the same title and entailing safety evaluations of more than 170 raw materials processed in HMP. This part 2 article highlights scientific evaluation following recognized methods used in toxicology with a view to drug-regulatory authority's assessment principles and practice in the context of HMP, and offers useful systematic, scientifically substantiated and simultaneously pragmatic approaches in differentiated HMP risk assessment. As a unique feature, both articles provide the most extensive publicly available systematic compilation of a considerable number of substances processed in HMP as a transparent resource for applicants, pharmaceutical manufacturers, the scientific community and healthcare authorities to actively support regulatory decision making in practice.	0	0	0	0	0	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
Standardized Methods Using EUS-guided Fine-needle Biopsy and a Minimal Medium Creates Three Pancreatic Cancer Organoids. Recently, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has been conducted for diagnosing pancreatic ductal adenocarcinoma (PDAC), after which obtained samples were used in organoid cultures. However, no standardized method for PDAC organoid cultures exists. Therefore, to standardize or simplify sample collection and culture methods for PDAC organoids, we performed a floating culture using non-minced specimens obtained by EUS-FNB in a minimal medium, lacking growth factors or inhibitors for pancreatic organoids.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Global transcriptome analyses and regulatory mechanisms in Halothece sp. PCC 7418 exposed to abiotic stresses. Halotolerant species are of interest since they occur naturally in environments with excess toxic ions. The cyanobacterium Halothece sp. PCC 7418 (hereafter referred to as Halothece) exhibits remarkable halotolerance and was used to examine stress-responsive regulatory mechanisms. The effects of five different stimuli on Halothece transcriptomes were examined using RNA sequencing. In response to diverse stresses, there were both common and stress-specific transcriptional responses. A common upregulated gene set under all stresses consisted of nine differentially expressed genes (DEGs). We also found that osmotic stress elicited the largest set of DEGs. Salt- and osmotic-responsive regulatory mechanisms shared common pathways. DEGs that were upregulated under salt stress encoded proteins involved in photosynthesis and related machineries. Furthermore, DEGs encoding two-component system (TCS) factors, transcriptional factors, scaffolds for protein-protein interactions, transporters, protein turnover factors, and lipid biosynthesis enzymes were also identified under salt stress. Notably, one-carbon (1C) metabolism factors, glycine betaine (GB) synthesis enzymes, and GB transporters were upregulated under salt stress. Metabolic analyses revealed that GB accumulated under salt stress, while mycosporine-2-glycine (M2G) accumulated under salt or osmotic stress. None of the nutrient starvations induced GB nor M2G accumulation. These results suggested that GB and M2G are two osmoprotectants that contribute to halotolerance. Based on our results, we proposed regulatory mechanisms that are crucial for halotolerance, which are coordinated with the GB, M2G, 1C, amino acid, and central carbon interlinking metabolic pathways. 1C metabolism directly fulfills the high metabolite requirements for halotolerance together with the ancillary role of several metabolic pathways.Key Points• Global transcriptome surveys together with molecular and metabolite analyses provide insights into regulatory networks that are crucial for halotolerance• Regulatory networks that are crucial for halotolerance coordinated with the two key osmoprotectants, one carbon, amino acid, and central carbon interlinking metabolic pathways• The findings have translational relevance in genomic and transcriptomic mechanisms of halotolerance.	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	1	0	1	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
T cells dominate peripheral inflammation in a cross-sectional analysis of obesity-associated diabetes. Myeloid cells dominate metabolic disease-associated inflammation (metaflammation) in mouse obesity, but the contributions of myeloid cells to the peripheral inflammation that fuels sequelae of human obesity are untested. This study used unbiased approaches to rank contributions of myeloid and T cells to peripheral inflammation in people with obesity across the spectrum of metabolic health.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0
COVID-19 increases the risk for the onset of atrial fibrillation in hospitalized patients. COVID-19 is associated with significant extrapulmonary symptoms. Myocardial involvement has been described for infections with SARS-CoV-2 which may lead to an increase in morbidity and mortality. The objective of our study was to investigate the association of COVID-19 and atrial fibrillation (AF) or atrial flutter (AFl) in hospitalized patients. This retrospective study used electronic medical records to detect patients with COVID-19 and their comorbidities within the Mass General Brigham hospital system. All patients ≥ 18 years who were hospitalized and received a PCR test for SARS-CoV-2 were screened for inclusion as well as patients from a pre-pandemic cohort. We matched on common risk factors for AF and then used multivariable logistic regression to estimate the odds for AF or AFl. Of 78,725 patients eligible for analysis, 11,004 COVID-19 negative patients were matched to 3,090 COVID-19 positive patients and 5005 pre-pandemic patients were matched to 2283 COVID-19 positive patients. After adjusting for demographics and comorbidities, COVID-19 positive patients had 1.19 times the odds (95% CI 1.00, 1.41) of developing AF compared to COVID-19 negative patients and 1.57 times the odds (95% CI 1.23, 2.00) of developing AF compared to pre-pandemic patients. Our study demonstrated an increased risk for AF, directing the attention for improved screening and treatment regimens for the sequelae of COVID-19. While COVID-19 continues to affect many people around the world, AF may be a significant cause for morbidity and mortality. Adequate detection and treatment of AF is essential to reduce the burden of disease.	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	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
[Characteristics and influencing factors of soil nitrification potential in coastal salinized farmland]. Understanding the nitrification capacity of coastal saline farmland soils and its main drivers is of great significance to regulate soil nitrification and improve the utilization efficiency of nitrogen fertilization in farmland. Using a combination of field investigations and laboratory analyses, we examined farmland soil nitrification potential and soil physical, chemical, and biological properties in the coastal muddy tidal flat saline soil area (Dongying and Dongtai). We established the correlation between soil properties and soil nitrification potential with multiple stepwise regression analyses and structural equation modeling (SEM). The results showed that soil pH value was relatively stable and other soil properties and soil nitrification potential varied in coastal saline farmland. The soil nitrification potential ranged from 0.04 to 10.42 mg·kg -1 ·d -1 and decreased with the increases of soil salinization level. Soil nitrification potential had the strongest correlation with soil organic matter, cation exchange capacity, and Cl - , with the correlation coefficient being 0.409, 0.397 and -0.337, respectively. The results of multiple stepwise regression analysis showed that Na + , silt, cation exchange capacity, and CO 3 2- +HCO 3 - were the main influencing factors of soil nitrification potential. The results from the SEM analysis suggested that Na + , silt, cation exchange capacity, and CO 3 2- +HCO 3 - directly affected soil nitrification potential, and soil organic matter, clay, Cl - and SO 4 2- had indirect effects. In all, soil Na + and cation exchange capacity were the two main factors affecting nitrification. Adjusting soil NaCl content and cation exchange capacity was an effective means of regulating soil nitrification.	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	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hepatitis B core-related antigen: Are we near a treatment endpoint? Different serological and virological markers in chronic hepatitis B patients guide staging of viral infection, and initiation and response to therapy. Due to the persistence of intrahepatic covalently closed circular DNA (cccDNA) in the hepatocyte nucleus, hepatitis B is not curable. Even after undetectable hepatitis B virus DNA levels, the persistence of hepatitis B surface antigen and novel markers such as hepatitis B core-related antigen (HBcrAg) indicate the persistence of intrahepatic cccDNA. In this study, HBcrAg levels at baseline and after 24 and 48 wk of antiviral therapy predicted hepatitis B e antigen seroconversion. Due to the poor sensitivity of assays and detectable levels in HBsAg-negative patients, the long-term utility of HBcrAg needs future research.	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	0	0	0
Integrated Transcriptome and Targeted Metabolite Analysis Reveal miRNA-mRNA Networks in Low-Light-Induced Lotus Flower Bud Abortion. Most Nelumbo nucifera (lotus) flower buds were aborted during the growing season, notably in low-light environments. How lotus produces so many aborted flower buds is largely unknown. An integrated transcriptome and targeted metabolite analysis was performed to reveal the genetic regulatory networks underlying lotus flower bud abortion. A total of 233 miRNAs and 25,351 genes were identified in lotus flower buds, including 68 novel miRNAs and 1108 novel genes. Further enrichment analysis indicated that sugar signaling plays a potential central role in regulating lotus flower bud abortion. Targeted metabolite analysis showed that trehalose levels declined the most in the aborting flower buds. A potential regulatory network centered on miR156 governs lotus flower bud abortion, involving multiple miRNA-mRNA pairs related to cell integrity, cell proliferation and expansion, and DNA repair. Genetic analysis showed that miRNA156-5p-overexpressing lotus showed aggravated flower bud abortion phenotypes. Trehalose-6-P synthase 1 (TPS1), which is required for trehalose synthase, had a negative regulatory effect on miR156 expression. TPS1 -overexpression lotus showed significantly decreased flower bud abortion rates both in normal-light and low-light environments. Our study establishes a possible genetic basis for how lotus produces so many aborted flower buds, facilitating genetic improvement of lotus' shade tolerance.	0	1	0	0	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	1	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Multisite phosphorylation and binding alter conformational dynamics of the 4E-BP2 protein. Intrinsically disordered proteins (IDPs) play critical roles in regulatory protein interactions, but detailed structural/dynamic characterization of their ensembles remain challenging, both in isolation and when they form dynamic "fuzzy" complexes. Such is the case for mRNA cap-dependent translation initiation, which is regulated by the interaction of the predominantly folded eukaryotic initiation factor 4E (eIF4E) with the intrinsically disordered eIF4E binding proteins (4E-BPs) in a phosphorylation-dependent manner. Single-molecule Förster resonance energy transfer showed that the conformational changes of 4E-BP2 induced by binding to eIF4E are non-uniform along the sequence; while a central region containing both motifs that bind to eIF4E expands and becomes stiffer, the C-terminal region is less affected. Fluorescence anisotropy decay revealed a non-uniform segmental flexibility around six different labeling sites along the chain. Dynamic quenching of these fluorescent probes by intrinsic aromatic residues measured via fluorescence correlation spectroscopy report on transient intra- and inter-molecular contacts on nanosecond-to-microsecond timescales. Upon hyperphosphorylation, which induces folding of ∼40 residues in 4E-BP2, the quenching rates decreased at most labeling sites. The chain dynamics around sites in the C-terminal region far away from the two binding motifs significantly increased upon binding to eIF4E, suggesting that this region is also involved in the highly dynamic 4E-BP2:eIF4E complex. Our time-resolved fluorescence data paint a sequence-level rigidity map of three states of 4E-BP2 differing in phosphorylation or binding status and distinguish regions that form contacts with eIF4E. This study adds complementary structural and dynamics information to recent studies of 4E-BP2, and it constitutes an important step toward a mechanistic understanding of this important IDP via integrative modeling.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	0	0
Prevalence and gender distribution of trichotillomania: A systematic review and meta-analysis. Epidemiological studies have provided varying prevalence estimates of trichotillomania (TTM) and other hair-pulling behaviors. We performed a systematic review and meta-analysis to provide data-driven prevalence estimates of TTM and hair-pulling. PubMed, PsycInfo and Embase were searched on June 2020 (updated in November 2021). Studies reporting the frequency of TTM defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria or hair-pulling behaviors were included. Prevalence data was extracted for both genders, and female-to-male odds ratios (OR) were computed for TTM and any hair-pulling behaviors. Data were pooled through random-effects meta-analyses. Of the 713 records identified through database searches, 30 studies involving 38,526 participants were included. Meta-analyses indicated TTM had a prevalence of 1.14% (95% CI 0.66%, 1.96%), while any hair-pulling behavior had a prevalence of 8.84% (95% CI 6.33%, 12.20%). Meta-analyses demonstrated females were at an increased risk of any hair-pulling when noticeable hair loss was required (OR = 2.23, 95% CI 1.60, 3.10, p < 0.0001), but not of any hair-pulling when noticeable hair loss was not required (OR = 0.90, 95% CI 0.72, 1.64, p = 0.33). Meta-analyses did not indicate female preponderance in TTM (k = 10; N = 22,775; OR = 1.29; 95% CI 0.91, 1.83; I 2 = 28%, p = 0.15), although there was considerable heterogeneity across studies. This study demonstrates that TTM impacts ∼1% of the population, while general hair-pulling behaviors affects ∼8%, highlighting the significant public health impact of this understudied condition. Additional research should clarify the gender distribution of TTM in epidemiological samples.	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	0	0
Maternity Healthscapes: Conceptualization and Index Development. This article provides a conceptualization and an index of the multidimensional concept of maternity healthscapes (MHS).	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	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
Elucidation of Key Interactions between VirF and the <i>virB</i> Promoter in Shigella flexneri Using E. coli MarA- and GadX-Based Homology Models and <i>In Vitro</i> Analysis of the DNA-Binding Domains of VirF and MarA. Infection with <i>Shigella</i>, the organism responsible for the diarrheal disease shigellosis, leads to approximately 200,000 deaths globally annually. Virulence of this pathogen is primarily controlled by the DNA-binding transcriptional activator VirF. This AraC family protein activates transcription of two major virulence genes, <i>virB</i> and <i>icsA</i>, which lead to the pathogen's ability to invade and spread within colonic epithelial cells. While several AraC proteins have been studied, few studies of VirF's binding to its DNA promoters have been reported, and VirF's three-dimensional structure remains unsolved. Here, we used structures of two E. coli VirF homologs, GadX and MarA-<i>marRAB</i>, to generate homology models of the VirF DNA-binding domain in free and DNA-bound conformations. We conducted alanine scanning mutagenesis on seven residues within MarA that make base-specific interactions with its promoter, <i>marRAB</i>, and the corresponding residues within VirF (identified by sequence and structural homologies). <i>In vitro</i> DNA-binding assays studying both wild-type and mutant MarA and VirF proteins identified residues important for binding to the <i>marRAB</i> and <i>virB</i> promoters, respectively. Comparison of the effects of these DNA-binding domain mutants validated our MarA-based homology model, allowing us to identify crucial interactions between VirF and the <i>virB</i> promoter. Proteins with mutations to helix 3 within both MarA(W42A, R46A) and MalE-VirF(R192A, K193A) exhibited significant reductions in DNA binding, while the effects of mutations in helix 6 varied. This suggests the shared importance of helix 3 in the binding to these promoters, while helix 6 is transcription factor specific. These results can inform further development of virulence-targeting inhibitors as an alternative to traditional antimicrobial drug design. <b>IMPORTANCE</b> Globally, infection with Shigella flexneri is a leading cause of bacterial dysentery, particularly affecting children under the age of 5 years. The virulence of this pathogen makes it highly infectious, allowing it to spread easily within areas lacking proper sanitation or access to clean drinking water. VirF is a DNA-binding transcription factor that activates S. flexneri virulence once the bacteria infect the human colon. Development of drugs that target VirF's DNA-binding activity can be an effective treatment to combat shigellosis as an alternative or addition to traditional antibiotics. Due to the lack of structural data, analysis of VirF's DNA-binding activity is critical to the development of potent VirF inhibitors.	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	0	0	0	0	0	0	0
Microcystic elongated and fragmented (MELF) pattern of invasion: Molecular features and prognostic significance in the PORTEC-1 and -2 trials. Microcystic, elongated fragmented (MELF) pattern of myometrial invasion is a distinct histologic feature occasionally seen in low-grade endometrial carcinomas (EC). The prognostic relevance of MELF invasion was uncertain due to conflicting data, and it had not yet appropriately been studied in the context of the molecular EC classification. We aimed to determine the relation of MELF invasion with clinicopathological and molecular characteristics, and define its prognostic relevance in early-stage low/intermediate risk EC.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
NK cell immunometabolism as target for liver cancer therapy. Natural killer (NK) cells are being used effectively as a potential candidate in tumor immunotherapy. However, the migration and transport of NK cells to solid tumors is inadequate. NK cell dysfunction, tumor invasiveness, and metastasis are associated with altered metabolism of NK cells in the liver cancer microenvironment. However, in liver cancers, metabolic impairment of NK cells is still not understood fully. Evidence from various sources has shown that the interaction of NK cell's immune checkpoints with its metabolic checkpoints is responsible for the regulation of the development and function of these cells. How immune checkpoints contribute to metabolic programming is still not fully understood, and how this can be beneficial needs a better understanding, but they are emerging to be incredibly compelling to rebuilding the function of NK cells in the tumor. It is expected to represent a potential aim that focuses on improving the efficacy of therapies based on NK cells for treating liver cancer. Here, the recent advancements made to understand the NK cell's metabolic reprogramming in liver cancer have been summarized, along with the possible interplay between the immune and the metabolic checkpoints in NK cell function. Finally, an overview of some potential metabolic-related targets that can be used for liver cancer therapy treatment has been 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	0	0	0	0	0	0	0	0	0	0	0	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
Cytoophidia coupling adipose architecture and metabolism. Tissue architecture determines its unique physiology and function. How these properties are intertwined has remained unclear. Here we show that the metabolic enzyme CTP synthase (CTPS) form filamentous structures termed cytoophidia along the adipocyte cortex in Drosophila adipose tissue. Loss of cytoophidia, whether due to reduced CTPS expression or a point mutation that specifically abrogates its polymerization ability, causes impaired adipocyte adhesion and defective adipose tissue architecture. Moreover, CTPS influences integrin distribution and dot-like deposition of type IV collagen (Col IV). Col IV-integrin signaling reciprocally regulates the assembly of cytoophidia in adipocytes. Our results demonstrate that a positive feedback signaling loop containing both cytoophidia and integrin adhesion complex couple tissue architecture and metabolism in Drosophila adipose tissue.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	0	0	0	0
Protocol for the generation of HIV-1 genomic RNA with altered levels of N 6 -methyladenosine. N 6 -methyladenosine (m 6 A) modification of human immunodeficiency virus type 1 (HIV-1) RNA plays a critical role in regulating viral replication and evasion of innate immunity. Here, we describe a protocol for the production of HIV-1 with altered m 6 A levels by manipulating the expression of m 6 A demethylases in HIV-1 producer cells. RNA from purified virions is analyzed by northern blot and dot blot for m 6 A levels prior to use in downstream assays to determine the function of m 6 A modification of viral RNA. For complete details on the use and execution of this protocol, please refer to Chen et al. (2021).	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	0	0	0
Gold nanoparticles targeting the autophagy-lysosome system to combat the inflammation-compromised osteogenic potential of periodontal ligament stem cells: From mechanism to therapy. Although substantial data indicate that the osteogenic potential of periodontal ligament stem cells (PDLSCs) is compromised under inflammatory conditions, the underlying mechanism remains largely unexplored. In this study, we found that both the autophagy levels and autophagic flux levels were decreased in PDLSCs incubated under inflammatory conditions (I-PDLSCs). Based on the increased expression of LC3 II (at an autophagy level) and decreased accumulation of LC3 II (at an autophagic flux level) in I-PDLSCs, we speculated that the disruption of I-PDLSC autophagy arose from dysfunction of the cellular autophagy-lysosome system. Subsequently, our hypothesis was demonstrated by inhibited autophagosome-lysosome fusion, damaged lysosomal function, and suppressed activation of transcription factor EB (TFEB, a master regulator of the autophagy-lysosome system) in I-PDLSCs and verified by TFEB overexpression in I-PDLSCs. We found that gold nanoparticle (Au NP) treatment rescued the osteogenic potential of I-PDLSCs by restoring the inflammation-compromised autophagy-lysosome system. In this context, Au NP ceased to be effective when TFEB was knocked down in PDLSCs. Our data demonstrate the crucial role of the autophagy-lysosome system in cellular osteogenesis under inflammatory conditions and suggest a new target for rescuing inflammation-induced cell dysfunction using nanomaterials to aid cell biology and tissue regeneration.	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	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
Implementation of a Night-Float Curriculum: Impact on Intern Confidence over Time. Formal nighttime education is becoming increasingly necessary as more internal medicine (IM) residency programs adopt night-float rotations (NFRs); however, the efficacy of an NFR curriculum throughout an academic year and which topics in an NFR curriculum increase trainee confidence are unknown. We implemented a 12-module, self-paced NFR curriculum for 76 postgraduate year-1 residents at an academic IM residency program. We evaluated the impact of this curriculum on postgraduate year-1 residents' clinical confidence, as well as longitudinal efficacy of the curriculum.	0	0	0	0	0	0	0	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0