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

Immunohistochemical Demonstration of the pGlu79 α-Synuclein Fragment in Alzheimer's Disease and Its Tg2576 Mouse Model. The deposition of β-amyloid peptides and of α-synuclein proteins is a neuropathological hallmark in the brains of Alzheimer's disease (AD) and Parkinson's disease (PD) subjects, respectively. However, there is accumulative evidence that both proteins are not exclusive for their clinical entity but instead co-exist and interact with each other. Here, we investigated the presence of a newly identified, pyroglutamate79-modified α-synuclein variant (pGlu79-aSyn)-along with the enzyme matrix metalloproteinase-3 (MMP-3) and glutaminyl cyclase (QC) implicated in its formation-in AD and in the transgenic Tg2576 AD mouse model. In the human brain, pGlu79-aSyn was detected in cortical pyramidal neurons, with more distinct labeling in AD compared to control brain tissue. Using immunohistochemical double and triple labelings and confocal laser scanning microscopy, we demonstrate an association of pGlu79-aSyn, MMP-3 and QC with β-amyloid plaques. In addition, pGlu79-aSyn and QC were present in amyloid plaque-associated reactive astrocytes that were also immunoreactive for the chaperone heat shock protein 27 (HSP27). Our data are consistent for the transgenic mouse model and the human clinical condition. We conclude that pGlu79-aSyn can be generated extracellularly or within reactive astrocytes, accumulates in proximity to β-amyloid plaques and induces an astrocytic protein unfolding mechanism involving HSP27.

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Trichomes on female reproductive tract: rapid diversification and underlying gene regulatory network in Drosophila suzukii and its related species. The ovipositors of some insects are external female genitalia, which have their primary function to deliver eggs. Drosophila suzukii and its sibling species D. subpulchrella are known to have acquired highly sclerotized and enlarged ovipositors upon their shifts in oviposition sites from rotting to ripening fruits. Inside the ovipositor plates, there are scale-like polarized protrusions termed "oviprovector scales" that are likely to aid the mechanical movement of the eggs. The size and spatial distribution of the scales need to be rearranged following the divergence of the ovipositors. In this study, we examined the features of the oviprovector scales in D. suzukii and its closely related species. We also investigated whether the scales are single-cell protrusions comprised of F-actin under the same conserved gene regulatory network as the well-characterized trichomes on the larval cuticular surface.

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Diversity, equity, and inclusion in nursing education: Strategies and processes to support inclusive teaching. Developing a climate for academic nursing that engages inclusive teaching requires the sustained effort of faculty and leadership. Nursing faculty engage inclusive teaching practices in the day-to-day learning environment, thereby training nurses and future leaders who are capable of addressing complex and diverse health care systems and population-centered needs. Actualizing the personal and professional commitment of faculty to inclusive teaching requires structure and strategies. This paper presents the use of multi-level institutional strategies and processes that supported faculty efforts to integrate DEI focused primarily on inclusive teaching into the curriculum at the University of Michigan School of Nursing. While best practices can vary by institution, we believe the institutional strategies, processes, lessons learned, and resources presented here can assist other academic institutions and nursing faculty as we all work to build a more inclusive nursing classroom and address systems and population-centered needs.

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Building Critical Care Capacity in a Low-Income Country. Critical illness is common throughout the world and is associated with high costs of care and resource intensity. The Corona virus disease 2019 (COVID-19) pandemic created a sudden surge of critically ill patients, which in turn led to devastating effects on health care systems worldwide and more so in Africa. This narrative report describes how an attempt was made at bridging the existing gaps in quality of care for critically ill patients at national and regional levels for COVID and the postpandemic era in a low income country.

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Integrated healthcare approach can curb the increasing cases of cryptococcosis in Africa. Cryptococcosis is a neglected tropical infection and a major cause of morbidity and mortality, especially in HIV-positive persons in Africa. Efforts to manage HIV infection have not had any significant impact on the fatalities due to cryptococcosis. An integrated healthcare approach that includes universal care coverage for Africans, expanded national care guidelines to include CrAg screening for vulnerable groups in all African countries, collaborative research, infection surveillance, and data sharing within Africa will mark a turnaround point.

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Racial differences in circulating mitochondria-derived peptides may contribute to prostate cancer health disparities. The mitochondrial genome has small open reading frames (sORF) which produce measurable mitochondrial-derived peptides (MDPs), including humanin, SHLP2, and MOTS-c. Previously, among men undergoing prostate biopsy, we found higher serum SHLP2 was linked with lower prostate cancer (PC) risk in European American men (EAM), while null associations were found in African American men (AAM). Here, in different patients undergoing prostate biopsy, we tested the link between SHLP2, humanin and MOTS-c and PC risk by race.

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Public awareness and use of 997 emergency medical service phone number during the COVID-19 pandemic. Emergency medical services (EMSs) are an important element of the healthcare system as it provides an opportunity to respond to critical medical conditions and save people's lives. In Saudi Arabia, EMS is offered via the EMS phone number "997" and mobile application "Asefny".

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A temporal gradient of cytonuclear coordination of chaperonins and chaperones during RuBisCo biogenesis in allopolyploid plants. Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) has long been studied from many perspectives. As a multisubunit (large subunits [LSUs] and small subunits[SSUs]) protein encoded by genes residing in the chloroplast ( rbcL ) and nuclear ( rbcS ) genomes, RuBisCo also is a model for cytonuclear coevolution following allopolyploid speciation in plants. Here, we studied the genomic and transcriptional cytonuclear coordination of auxiliary chaperonin and chaperones that facilitate RuBisCo biogenesis across multiple natural and artificially synthesized plant allopolyploids. We found similar genomic and transcriptional cytonuclear responses, including respective paternal-to-maternal conversions and maternal homeologous biased expression, in chaperonin/chaperon-assisted folding and assembly of RuBisCo in different allopolyploids. One observation is about the temporally attenuated genomic and transcriptional cytonuclear evolutionary responses during early folding and later assembly process of RuBisCo biogenesis, which were established by long-term evolution and immediate onset of allopolyploidy, respectively. Our study not only points to the potential widespread and hitherto unrecognized features of cytonuclear evolution but also bears implications for the structural interaction interface between LSU and Cpn60 chaperonin and the functioning stage of the Raf2 chaperone.

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Actinomycetospora soli sp. nov., isolated from the rhizosphere soil of Averrhoa carambola L. A novel actinobacterium, designated strain SF1 T , was isolated from the rhizosphere soil of a star fruit plant ( Averrhoa carambola L.) collected from Bangkok, Thailand, and its taxonomic position was evaluated. The strain showed morphological, chemotaxonomic and phylogenetic characteristics consistent with its classification in the genus Actinomycetospora . Strain SF1 T was an aerobic, Gram-stain-positive and non-motile actinobacterium. Growth occurred at 15-35 °C, at pH 4.0-12.0 and in the presence of 0-10 % (w/v) NaCl. The 16S rRNA gene sequence of strain SF1 T showed the highest similarity to Actinomycetospora chiangmaiensis YIM 0006 T (99.5 %), Actinomycetospora corticicola 014-5 T (98.8 %) and Actinomycetospora endophytica A-T 8314 T (98.8 %). The genome sequencing revealed a genome size of 6.52 Mbp and a DNA G+C content of 74.0 %. In addition, the average nucleotide identity values between strain SF1 T and reference strains, A. chiangmaiensis DSM 45062 T , A. corticicola DSM 45772 T and A. endophytica TBRC 5722 T , were found to be 86.1, 86.5 and 79.7 %, respectively, and the level of digital DNA-DNA hybridization between them were 32.4, 32.4 and 23.3 %, respectively. The whole-cell hydrolysates of strain SF1 T contained meso -diaminopimelic acid as the diagnostic diamino acid, with arabinose, galactose, glucose and ribose as whole-cell sugars. The predominant menaquinone was MK-8(H 4 ). Major cellular fatty acids were iso-C 16 : 0 and a summed feature consisting of C 16 : 1 ω6 c /C 16 : 1 ω7 c . Characterization based on chemotaxonomic, phylogenetic, phenotypic and genomic evidence demonstrated that strain SF1 T represents a novel species of the genus Actinomycetospora , for which the name Actinomycetospora soli sp. nov. is proposed. The type strain is strain SF1 T (=TBRC 15166 T = NBRC 115295 T ).

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Parenting sense of competence and its predictors among primiparous women: a longitudinal study in China. Parenting sense of competence significantly affects the quality of parenting behaviours and healthy infant development. However, primiparous women without parenting experience may lack confidence and feel stress. This study aimed to explore the status of parenting sense of competence and identify its predictors among primiparous women.

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Activated partial thromboplastin time-based clot waveform analysis enables measurement of very low levels of factor IX activity in patients with severe hemophilia B. The precise measurement of very low levels of factor IX activity (FIX:C < 1 IU/dL) is essential for understanding clinical severity and risk of inhibitor development in patients with severe hemophilia B (Pw-SHB). However, such measurement sensitivity has not yet been achieved. We aimed to establish a measurement method using clot waveform analysis (CWA). Residual FIX:C by adding anti-FIX monoclonal antibody, FIX:C by adding recombinant (r)FIX to the commercial Pw-SHB plasmas, and FIX:C in our Pw-SHB were determined by CS-2000i ™ /CS-2400 ™ , followed by analysis of CWA parameters. The presence of anti-FIX antibody in the commercial Pw-SHB plasmas significantly decreased coagulation potential compared to its absence. The addition of rFIX to these innate plasma samples produced significant changes in three parameters upon adding FIX:C at 0.1-1 IU/dL, supporting the presence of trace FIX:C in Pw-SHB. Therefore, appropriate FIX-depleted plasma containing minimum residual FIX:C was chosen from reference curves of FIX:C (0.01-1 IU/dL). Among patients with untreated Pw-SHB, two had FIX:C 0.6-0.7 IU/dL and two had lower than detectable levels using FIX-depleted plasma. One of the latter had detectable trough levels post-rFIX administration. In conclusion, CWA enabled measurement of very low levels of FIX:C using appropriate FIX-deficient plasma.

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Understanding Community Participation in Rural Health Care: A Participatory Learning and Action Approach. Community participation is one of the founding pillars of primary health care. However, due to various reasons, we are yet to achieve complete integration of this component into the health system functioning in India. The objective of our study was to do a formative assessment of community participation in a rural healthcare setting by adopting participatory learning action (PLA). technique. The study participants included frontline health workers and members from local governing institutions of rural areas. The study design is qualitative in nature with a participatory approach. A number of three PLA techniques have been used as a part of this study to recognize available resources for community participation, address its barriers and facilitators, and finally devise a time-line-based action plan. Based on the this, a conceptual framework for community participation pertaining to the rural healthcare system has been developed. This study highlights the importance of understanding the psychosocial aspects of community participation among various stakeholders involved in rural health care. Lessons learned from this PLA study will be helpful in the integration of community-based participatory approach within grassroot level healthcare planning and service delivery.

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Development and internal validation of a risk model for hyperuricemia in diabetic kidney disease patients. This research aimed to identify independent risk factors for hyperuricemia (HUA) in diabetic kidney disease (DKD) patients and develop an HUA risk model based on a retrospective study in Ningbo, China.

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The development of an automated machine learning pipeline for the detection of Alzheimer's Disease. Although Alzheimer's disease is the most prevalent form of dementia, there are no treatments capable of slowing disease progression. A lack of reliable disease endpoints and/or biomarkers contributes in part to the absence of effective therapies. Using machine learning to analyze EEG offers a possible solution to overcome many of the limitations of current diagnostic modalities. Here we develop a logistic regression model with an accuracy of 81% that addresses many of the shortcomings of previous works. To our knowledge, no other study has been able to solve the following problems simultaneously: (1) a lack of automation and unbiased removal of artifacts, (2) a dependence on a high level of expertise in data pre-processing and ML for non-automated processes, (3) the need for very large sample sizes and accurate EEG source localization using high density systems, (4) and a reliance on black box ML approaches such as deep neural nets with unexplainable feature selection. This study presents a proof-of-concept for an automated and scalable technology that could potentially be used to diagnose AD in clinical settings as an adjunct to conventional neuropsychological testing, thus enhancing efficiency, reproducibility, and practicality of AD diagnosis.

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A new prognostic marker in patients undergoing Hartmann's procedure for acute tumoral obstruction of the left colon. In acute obstructive left-sided colorectal cancers (AOLCRC), damage to the colon wall may occur as a result of distension of the colon segments proximal to the tumor. In this study, we aimed to evaluate the relationship between the ratio of dilated colon diameter (CD) to lumbar vertebral corpus diameter on preoperative abdominal computed tomography (CT) scan in patients undergoing Hartmann's Procedure (HP) and post-operative complications.

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Endocrine modulation of primary chemosensory neurons regulates Drosophila courtship behavior. The decision to engage in courtship depends on external cues from potential mates and internal cues related to maturation, health, and experience. Hormones allow for coordinated conveyance of such information to peripheral tissues. Here, we show Ecdysis-Triggering Hormone (ETH) is critical for courtship inhibition after completion of copulation in Drosophila melanogaster. ETH deficiency relieves post-copulation courtship inhibition (PCCI) and increases male-male courtship. ETH appears to modulate perception and attractiveness of potential mates by direct action on primary chemosensory neurons. Knockdown of ETH receptor (ETHR) expression in GR32A-expressing neurons leads to reduced ligand sensitivity and elevated male-male courtship. We find OR67D also is critical for normal levels of PCCI after mating. ETHR knockdown in OR67D-expressing neurons or GR32A-expressing neurons relieves PCCI. Finally, ETHR silencing in the corpus allatum (CA), the sole source of juvenile hormone, also relieves PCCI; treatment with the juvenile hormone analog methoprene partially restores normal post-mating behavior. We find that ETH, a stress-sensitive reproductive hormone, appears to coordinate multiple sensory modalities to guide Drosophila male courtship behaviors, especially after mating.

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The future of long-acting agents for preexposure prophylaxis. The main reason for the failure of oral preexposure prophylaxis (PrEP) regimens for HIV is poor adherence. Intramuscular cabotegravir was recently approved for PrEP, and a number of other long-acting antiretroviral formulations and products are currently in clinical development. This includes subcutaneous and intravenous injections, implants, and microarray (microneedle) patches, as well as extended duration oral drugs. The success and future uptake of these products will depend on a variety of factors.

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Aseptic meningitis in multisystem inflammatory syndrome in children associated with coronavirus disease 2019: a case report. As the coronavirus disease 2019 infections are still ongoing, there is an increasing number of case reports and case series with various manifestations of life-threatening multisystem inflammatory syndrome in children . Our case aims to remind all providers to scrutinize for clinical manifestations, including neurological symptoms, which may mimic aseptic meningitis.

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Effect of Protein-Protein Interactions on Translational Diffusion of Spheroidal Proteins. One of the commonly accepted approaches to estimate protein-protein interactions (PPI) in aqueous solutions is the analysis of their translational diffusion. The present review article observes a phenomenological approach to analyze PPI effects via concentration dependencies of self- and collective translational diffusion coefficient for several spheroidal proteins derived from the pulsed field gradient NMR (PFG NMR) and dynamic light scattering (DLS), respectively. These proteins are rigid globular α-chymotrypsin (ChTr) and human serum albumin (HSA), and partly disordered α-casein (α-CN) and β-lactoglobulin (β-Lg). The PPI analysis enabled us to reveal the dominance of intermolecular repulsion at low ionic strength of solution (0.003-0.01 M) for all studied proteins. The increase in the ionic strength to 0.1-1.0 M leads to the screening of protein charges, resulting in the decrease of the protein electrostatic potential. The increase of the van der Waals potential for ChTr and α-CN characterizes their propensity towards unstable weak attractive interactions. The decrease of van der Waals interactions for β-Lg is probably associated with the formation of stable oligomers by this protein. The PPI, estimated with the help of interaction potential and idealized spherical molecular geometry, are in good agreement with experimental data.

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Effect of CB2 Stimulation on Gene Expression in Pediatric B-Acute Lymphoblastic Leukemia: New Possible Targets. Acute lymphoblastic leukemia type B (B-ALL) is the most common kind of pediatric leukemia, characterized by the clonal proliferation of type B lymphoid stem cells. Important progress in ALL treatments led to improvements in long-term survival; nevertheless, many adverse long-term consequences still concern the medical community. Molecular and cellular target therapies, together with immunotherapy, are promising strategies to overcome these concerns. Cannabinoids, enzymes involved in their metabolism, and cannabinoid receptors type 1 (CB1) and type 2 (CB2) constitute the endocannabinoid system, involved in inflammation, immune response, and cancer. CB2 receptor stimulation exerts anti-proliferative and anti-invasive effects in many tumors. In this study, we evaluated the effects of CB2 stimulation on B-ALL cell lines, SUP-B15, by RNA sequencing, Western blotting, and ELISA. We observe a lower expression of CB2 in SUP-B15 cells compared to lymphocytes from healthy subjects, hypothesizing its involvement in B-ALL pathogenesis. CB2 stimulation reduces the expression of CD9 , SEC61G , TBX21, and TMSB4X genes involved in tumor growth and progression, and also negatively affects downstream intracellular pathways. Our findings suggest an antitumor role of CB2 stimulation in B-ALL, and highlight a functional correlation between CB2 receptors and specific anti-tumoral pathways, even though further investigations are needed.

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FedMSA: A Model Selection and Adaptation System for Federated Learning. Federated Learning (FL) enables multiple clients to train a shared model collaboratively without sharing any personal data. However, selecting a model and adapting it quickly to meet user expectations in a large-scale FL application with heterogeneous devices is challenging. In this paper, we propose a model selection and adaptation system for Federated Learning (FedMSA), which includes a hardware-aware model selection algorithm that trades-off model training efficiency and model performance base on FL developers' expectation. Meanwhile, considering the expected model should be achieved by dynamic model adaptation, FedMSA supports full automation in building and deployment of the FL task to different hardware at scale. Experiments on benchmark and real-world datasets demonstrate the effectiveness of the model selection algorithm of FedMSA in real devices (e.g., Raspberry Pi and Jetson nano).

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Sharing resources to advance translational research. The publication of Resource articles is essential for the dissemination of novel, or substantially enhanced, tools, techniques, disease models, datasets and resources. By sharing knowledge and resources in a globally accessible manner, we can support human disease research to accelerate the translation of fundamental discoveries to effective treatments or diagnostics for diverse patient populations. To promote and encourage excellence in Resource articles, Disease Models & Mechanisms (DMM) is launching a new 'Outstanding Resource Paper Prize'. To celebrate this, we highlight recent outstanding DMM Resource articles that have the ultimate goal of benefitting of human health.

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[Clinical effect of fetal reduction by intracranial and intrathoracic KCl injection]. To evaluate the feasibility and effectiveness of fetal reduction by transabdominal intracranial KCl injection for multifetal pregnancies in the early second trimester.

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Exploring the coating of 3D-printed insulating substrates with conductive composites: a simple, cheap and versatile strategy to prepare customized high-performance electrochemical sensors. The development of 3D-printed electrochemical sensors by fused deposition modeling (FDM) has been increasing exponentially in the last five years. In this context, commercial conductive filaments composed of a blend of carbon particles ( e.g. , graphene or carbon black (CB)) and insulating thermoplastic polymers ( e.g. , polylactic acid (PLA) or acrylonitrile butadiene styrene (ABS)) have been widely used for electrode fabrication. However, such materials may be expensive and the electrodes when used "as-printed" exhibit poor electrochemical performance as a function of the low content of conductive particles in the composition (∼10 to 20 wt%), which requires one or more post-treatment steps ( e.g. polishing, chemical, electrochemical, and photochemical) to reach good electrochemical performance. In this technical note a less used approach to produce "ready-to-use" electrochemical platforms based on 3D printing is explored, which consists of the coating of 3D-printed insulating substrates with homemade conductive composites. To demonstrate the potentiality of this alternative protocol, 3D-printed ABS insulating substrates at two geometries were coated in a highly loaded graphite (55 wt%) homemade composite (G-ABS) and evaluated for the detection of the ferri/ferrocyanide redox probe and model analytes in stationary and hydrodynamic 3D-printed systems (nitrite in micro-flow injection analysis/μFIA and paracetamol in batch injection analysis/BIA, respectively). The analytical parameters acquired with the coated electrodes were comparable to those obtained using conventional electrodes (glassy carbon, boron-doped diamond and carbon screen-printed) and 3D-printed sensors fabricated with commercial filaments. Moreover, the inclusion of carbon black in the fluid conductive composite was demonstrated as a perspective to obtain modified coated 3D-printed surfaces easily for the first time. This alternative "do it yourself" strategy is promising for the large-scale production of very cheap (US$ 0.08) and high-performance electrodes based on FDM 3D printing. Moreover, this approach dispenses the acquisition of commercial conductive filaments and the laborious development of homemade filaments.

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Prevalence, co-morbidities, and in-hospital mortality of patients hospitalized with alcohol-associated hepatitis in the United States from 2015 to 2019. The goals of our study are to determine the most recent trends in hospitalization, mortality, and healthcare utilization among hospitalized patients with alcohol-associated hepatitis (AH) in the United States.

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Early-life residential exposure to moisture damage is associated with persistent wheezing in a Finnish birth cohort. Moisture damage increases the risk for respiratory disorders in childhood. Our aim was to determine whether early age residential exposure to inspector-observed moisture damage or mold is associated with different wheezing phenotypes later in childhood.

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An Unusual U2AF2 Inhibits Splicing and Attenuates the Virulence of the Human Protozoan Parasite Entamoeba histolytica . E. histolytica is the etiological agent of intestinal amebiasis and liver abscesses, which still poses public health threat globally. Metronidazole is the drug of choice against amebiasis. However, metronidazole-resistant amoebic clinical isolates and strains have been reported recently, challenging the efforts for amebiasis eradication. In search of alternative treatments, E. histolytica transcriptomes have shown the association of genes involved in RNA metabolism with the virulence of the parasite. Among the upregulated genes in amoebic liver abscesses are the splicing factors EhU2AF2 and a paralog of EhSF3B1. For this reason and because EhU2AF2 contains unusual KH-QUA2 (84KQ) motifs in its lengthened C-terminus domain, here we investigated how the role of EhU2AF2 in pre-mRNA processing impacts the virulence of the parasite. We found that 84KQ is involved in splicing inhibition/intron retention of several virulence and non-virulence-related genes. The 84KQ domain interacts with the same domain of the constitutive splicing factor SF1 (SF1KQ), both in solution and when SF1KQ is bound to branchpoint signal RNA probes. The 84KQ-SF1KQ interaction prevents splicing complex E to A transition, thus inhibiting splicing. Surprisingly, the deletion of the 84KQ domain in EhU2AF2 amoeba transformants increased splicing and enhanced the in vitro and in vivo virulence phenotypes. We conclude that the interaction of the 84KQ and SF1KQ domains, probably involving additional factors, tunes down Entamoeba virulence by favoring intron retention.

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Pollinator and floral odor specificity among four synchronopatric species of Ceropegia (Apocynaceae) suggests ethological isolation that prevents reproductive interference. Possession of flowers that trap fly pollinators is a conservative trait within the genus Ceropegia, in which pollination systems can be generalized or highly specialized. However, little is known about the role of plant-pollinator interactions in the maintenance of species boundaries. This study examined the degree of plant-pollinator specialization and identified the parameters responsible for specificity among four co-occurring Ceropegia species with overlapping flowering times. All investigated plant species were functionally specialized on pollination by Chloropidae and/or Milichiidae flies and each Ceropegia species was, in turn, ecologically highly specialized on only two pollinating fly morphospecies, though one plant species appeared more generalist. Species-specific fly attraction was due to the differences between plant species in floral scents, floral morphology, colour patterns, and presence of other functional structures, e.g., vibratile trichomes, which were shown to contribute to pollinator attraction in one study species. The combination of these olfactory and visual cues differentially influenced pollinator preferences and thus hindered heterospecific visitation. Furthermore, a pollinator exchange experiment also highlighted that species integrity is maintained through efficient ethological isolation (pollinator attraction). The mechanical isolation mediated by the fit between floral morphology and size and/or shape of fly pollinators appears less pronounced here, but whether or not the morphological match between male (pollinium) and female (guide rails) reproductive organs can impede hybridization remains to be investigated.

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Microdomain Protein Nce102 Is a Local Sensor of Plasma Membrane Sphingolipid Balance. Sphingolipids are essential building blocks of eukaryotic membranes and important signaling molecules that are regulated tightly in response to environmental and physiological inputs. While their biosynthetic pathway has been well-described, the mechanisms that facilitate the perception of sphingolipid levels at the plasma membrane remain to be uncovered. In Saccharomyces cerevisiae, the Nce102 protein has been proposed to function as a sphingolipid sensor as it changes its plasma membrane distribution in response to sphingolipid biosynthesis inhibition. We show that Nce102 redistributes specifically in regions of increased sphingolipid demand, e.g., membranes of nascent buds. Furthermore, we report that the production of Nce102 increases following sphingolipid biosynthesis inhibition and that Nce102 is internalized when excess sphingolipid precursors are supplied. This finding suggests that the total amount of Nce102 in the plasma membrane is a measure of the current need for sphingolipids, whereas its local distribution marks sites of high sphingolipid demand. The physiological role of Nce102 in the regulation of sphingolipid synthesis is demonstrated by mass spectrometry analysis showing reduced levels of hydroxylated complex sphingolipids in response to heat stress in the nce102 Δ deletion mutant. We also demonstrate that Nce102 behaves analogously in the widespread human fungal pathogen Candida albicans, suggesting a conserved principle of local sphingolipid control across species. IMPORTANCE Microorganisms are challenged constantly by their rapidly changing environment. To survive, they have developed diverse mechanisms to quickly perceive stressful situations and adapt to them appropriately. The primary site of both stress sensing and adaptation is the plasma membrane. We identified the yeast protein Nce102 as a marker of local sphingolipid levels and fluidity in the plasma membrane. Nce102 is an important structural and functional component of the membrane compartment Can1 (MCC), a plasma membrane microdomain stabilized by a large cytosolic hemitubular protein scaffold, the eisosome. The MCC/eisosomes are widely conserved among fungi and unicellular algae. To determine if Nce102 carries out similar functions in other organisms, we analyzed the human fungal pathogen Candida albicans and found that Nce102 responds to sphingolipid levels also in this organism, which has potential applications for the development of novel therapeutic approaches. The presented study represents a valuable model for how organisms regulate plasma membrane sphingolipids.

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Exploring Structure-Sensitive Relations for Small Species Adsorption Using Machine Learning. Accurate prediction of adsorption energies on heterogeneous catalyst surfaces is crucial to predicting reactivity and screening materials. Adsorption linear scaling relations have been developed extensively but often lack accuracy and apply to one adsorbate and a single binding site type at a time. These facts undermine their ability to predict structure sensitivity and optimal catalyst structure. Using machine learning on nearly 300 density functional theory calculations, we demonstrate that generalized coordination number scaling relations hold well for oxygen- and high-valency carbon-binding species but fail for others. We reveal that the valency and the electronic coupling of a species with the surface, along with the site type and its coordination environment, are critical for small species adsorption. The model simultaneously predicts the adsorption energy and preferred site and significantly outperforms linear scalings in accuracy. It can expose the structure sensitivity of chemical reactions and enable enhanced catalyst activity via engineering particle shape and facet defects. The generality of our methodology is validated by training the model with transition metal data and transferring it to predict adsorption energies on single-atom alloys.

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Using Vis-NIR Spectroscopy for Predicting Quality Compounds in Foods. Over the past four decades, near-infrared reflectance spectroscopy (NIRS) has become one of the most attractive and used technique for analysis as it allows for fast and simultaneous qualitative and quantitative characterization of a wide variety of food samples [...].

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A comprehensive evaluation of polygenic score and genotype imputation performances of human SNP arrays in diverse populations. Regardless of the overwhelming use of next-generation sequencing technologies, microarray-based genotyping combined with the imputation of untyped variants remains a cost-effective means to interrogate genetic variations across the human genome. This technology is widely used in genome-wide association studies (GWAS) at bio-bank scales, and more recently, in polygenic score (PGS) analysis to predict and stratify disease risk. Over the last decade, human genotyping arrays have undergone a tremendous growth in both number and content making a comprehensive evaluation of their performances became more important. Here, we performed a comprehensive performance assessment for 23 available human genotyping arrays in 6 ancestry groups using diverse public and in-house datasets. The analyses focus on performance estimation of derived imputation (in terms of accuracy and coverage) and PGS (in terms of concordance to PGS estimated from whole-genome sequencing data) in three different traits and diseases. We found that the arrays with a higher number of SNPs are not necessarily the ones with higher imputation performance, but the arrays that are well-optimized for the targeted population could provide very good imputation performance. In addition, PGS estimated by imputed SNP array data is highly correlated to PGS estimated by whole-genome sequencing data in most cases. When optimal arrays are used, the correlations of PGS between two types of data are higher than 0.97, but interestingly, arrays with high density can result in lower PGS performance. Our results suggest the importance of properly selecting a suitable genotyping array for PGS applications. Finally, we developed a web tool that provides interactive analyses of tag SNP contents and imputation performance based on population and genomic regions of interest. This study would act as a practical guide for researchers to design their genotyping arrays-based studies. The tool is available at: https://genome.vinbigdata.org/tools/saa/ .

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Evaluation of Three Clinical Prediction Tools to Predict Mortality in Hospitalized Patients with Lassa Fever. Lassa fever is a viral hemorrhagic illness with a case fatality rate for hospitalized patients as high as 69%. Identifying cases before they progress to serious illness can lead to earlier treatment and improved clinical outcomes. Three existing clinical prediction tools were evaluated on their ability to predict the in-hospital mortality in Lassa fever: the quick Sequential Organ Failure Assessment (qSOFA), the Modified Early Warning System (MEWS), and the Universal Vital Assessment (UVA). This was a retrospective cohort study of patients admitted to the dedicated Lassa fever ward of the Kenema Government Hospital in Sierra Leone between May 2013 and December 2019. Data among three serology groups were analyzed: Lassa antigen-positive (Ag+) regardless of IgM status, Lassa Ag- and IgM+, and Lassa Ag- and IgM- cases. There were 123 cases of suspected Lassa fever included in this study. Abnormalities in respiratory rate, oxygenation status, mental status, and serum markers of kidney and liver dysfunction were more likely seen in the Ag+ group, which had an in-hospital mortality of 85.7%. For the Lassa Ag+ group, the sensitivity and positive predictive value of qSOFA ≥ 2 was 70.6% and 92.3%, MEWS ≥ 5 was 96.9% and 86.1%, and UVA ≥ 5 was 60.0% and 100.0%. The MEWS and UVA scores show potential for use in Lassa fever, but there is opportunity for future development of a tool that includes the clinical and laboratory markers specific to Lassa fever.

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Neural Network Based on Health Monitoring Electrical Equipment Fault and Biomedical Diagnosis. In order to improve the accuracy of electrical equipment failure diagnosis and keep electrical equipment operating safely and efficiently, this paper proposes to design an electrical equipment failure diagnosis system based on a neural network, analyze the faults of electrical equipment and their causes, and establish knowledge base according to relevant data and expert judgment. The fault knowledge base was introduced into the neural network operation structure, and the fault diagnosis results were classified step by step through multiple subnetworks. In data preprocessing, in order to avoid the redundancy of primary fault information features, the principal component heuristic attribute reduction algorithm was used to select the fault data samples optimally. The neural network learning algorithm is used to calculate the forward direction and error rate of the initial error data, and the reliability function is used to optimize the initial weight threshold of the neural network, propagating the error backwards and high. Experimental results show that adding attribute reduction improves error classification performance, avoids the problem of local minima through neural network operation, and has fewer iteration steps, lower average error, and higher accuracy of fault diagnosis, reaching 95.6%.

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Main Retailers In Which Mexican Households Acquire Their Food Supply. To describe the frequency of food and beverages purchased made by Mexican households at different types of grocery retailers.

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[Chronic diarrhea caused by a novel mutation of STAT3 gene in a child]. 6月龄患儿以腹泻、呕吐起病，临床表现为排稀水样便并次数增多，营养不良，双肾多发结石，胃肠镜示慢性浅表性胃窦炎、慢性结肠炎，十二指肠降段黏膜病理示固有层多量淋巴细胞、浆细胞浸润伴绒毛萎缩。全外显子测序发现STAT3基因c.1516G>A（p.E506K）杂合错义突变，为自发变异。该突变未曾见报道，可能是儿童慢性腹泻新发致病突变。该患儿改无乳糖深度水解配方喂养及对症支持治疗后排便正常，体重逐渐增加，双肾结石变小。.

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Mechanistic insights on novel small molecule allosteric activators of cGMP-dependent protein kinase PKG1α. cGMP-dependent protein kinase (PKG) represents a compelling drug target for treatment of cardiovascular diseases. PKG1 is the major effector of beneficial cGMP signaling which is involved in smooth muscle relaxation and vascular tone, inhibition of platelet aggregation and signaling that leads to cardioprotection. In this study, a novel piperidine series of activators previously identified from an ultrahigh-throughput screen were validated to directly bind partially activated PKG1α and subsequently enhance its kinase activity in a concentration-dependent manner. Compounds from initial optimization efforts showed an ability to activate PKG1α independent of the endogenous activator, cGMP. We demonstrate these small molecule activators mimic the effect of cGMP on the kinetic parameters of PKG1α by positively modulating the K M of the peptide substrate and negatively modulating the apparent K M for ATP with increase in catalytic efficiency, k cat . In addition, these compounds also allosterically modulate the binding affinity of cGMP for PKG1α by increasing the affinity of cGMP for the high-affinity binding site (CNB-A) and decreasing the affinity of cGMP for the low-affinity binding site (CNB-B). We show the mode of action of these activators involves binding to an allosteric site within the regulatory domain, near the CNB-B binding site. To the best of our knowledge, these are the first reported non-cGMP mimetic small molecules shown to directly activate PKG1α. Insights into the mechanism of action of these compounds will enable future development of cardioprotective compounds that function through novel modes of action for the treatment of cardiovascular diseases.

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Food web and metabolic interactions of the lung inhabitants Streptococcus pneumoniae and Pseudomonas aeruginosa. Bacteria that successfully adapt to different substrates and environmental niches within the lung and overcome the immune defence can cause serious lung infections. Such infections are generally complex, and recognized as polymicrobial in nature. Both Pseudomonas aeruginosa and Streptococcus pneumoniae can cause chronic lung infections and were both detected in cystic fibrosis (CF) lung at different stages. In this study, single and dual species cultures of Pseudomonas aeruginosa and Streptococcus pneumoniae were studied under well-controlled planktonic growth conditions. Under pH-controlled conditions, both species apparently benefited from the presence of the other. In co-culture with P. aeruginosa, S. pneumoniae grew efficiently under aerobic conditions, whereas in pure S. pneumoniae culture, growth inhibition occurred in bioreactors with dissolved oxygen concentrations above the microaerobic range. Lactic acid and acetoin that are produced by S. pneumoniae were efficiently utilized by P. aeruginosa. In pH-uncontrolled co-cultures, the low pH triggered by S. pneumoniae assimilation of glucose and lactic acid production negatively affected the growth of both strains. Nevertheless, ammonia production improved significantly, and P. aeruginosa growth dominated at later growth stages. This study revealed unreported metabolic interactions of two important pathogenic microorganisms and shed new lights into pathophysiology of bacterial lung infection.

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The Moral Significance of Aesthetics in Nature Imagery. To solicit support for nature and wildlife conservation, mission-driven organizations rely on professional nature and wildlife imagery in their media outlets and campaigns. We investigated whether-and if so, why-the aesthetics of images increase social media engagement (e.g., number of likes) and the extent to which images elicit moral concern for nature and wildlife. In Study 1 ( N = 782 U.S. adults), we trained a neural network to predict image aesthetics in National Geographic's Instagram data and identified image-specific attributes that influence aesthetics. We found that image aesthetics predicted engagement with the Instagram posts. In Study 2 ( N = 775 U.S. adults), we established the causal effect of aesthetics on engagement and moral concern, which is explained by self-transcendent emotions (awe and inspiration) and purity associated with an image. Study 3 ( N = 406 U.S. adults) replicated the results, showing that our key effects were stronger for individuals who place higher importance on beauty. By demonstrating the moral significance of image aesthetics, we highlight the potential of the beauty of nature to invigorate global conservation efforts.

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Plastics are a new threat to Palau's coral reefs. Plastic pollution of the oceans has long been an ongoing and growing problem. Single-use plastic (plastic bags and microbeads) is responsible for most of this pollution. In recent years, studies have highlighted the importance of the size of plastic particles, and the impact of this pollution source on the environment. We determined the concentration of small marine plastics in seawater, sediments and beach sand around a pristine reef area (Republic of Palau) using very simple tools (plankton net, sieves, organic matter degradation, density separation, Nile red fluorochrome). In this study, we succeeded in detecting microplastic (MPs) particles and microplastic fibers, but also nanoplastic (NPs). These three types of particles were found in all samples with a large heterogeneity, from 0.01 to 0.09 particles L-1 and 0.17 to 32.13 particles g-1 DW for MPs in seawater, sediments and sand, respectively. Even when NPs were identified, the amounts of NPs were underestimated and varied from 0.09 to 0.43 particles L-1 in seawater and from 1.08 to 71.02 particles g-1 DW in sediment and sand, respectively. These variations could be attributed to the environmental characteristics of the different sites. This study shows that plastic pollution must be considered in environmental studies even in the most pristine locations. It also shows that NPs pollution is related to the amount of MPs found at the sites. To understand the effects of this plastic pollution, it is necessary that the next toxicological studies take into account the effects of this fraction that makes up the NPs.

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Advances in encapsulating gonadotropin-releasing hormone agonists for controlled release: a review. Gonadotropin-releasing hormone (GnRH) agonists are peptides consisting of nine or ten amino acid residues. GnRH agonists have been applied in the therapy of sexual hormone disorders like prostate cancer, endometriosis, uterine myoma, central precious puberty, and in-vitro fertility. Treatment is achieved by continuous hormone intake and long-term agonists administration, which is usually associated with poor patient compliance. Because GnRH agonists that are administered with the parenteral route are broken down by peptidase, their half-life is short. As a result, developing sustained release for the drug delivery system is significant. Even though some drugs have been successfully delivered with long-acting release microspheres and approved by the Food and Drug Administration (FDA), some challenges remain. This review highlighted current approaches to encapsulate GnRH agonists into delivery systems and strategies encountered during the loading process. Moreover, the following sections provide strategies to improve the release profile, and animal and human studies were summarised.

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Common and unique neural activities in subclinical depression and major depressive disorder indicate the development of brain impairments in different depressive stages. Subclinical depression (SD) and major depressive disorder (MDD) can be considered as the early and late stages of depression, but the characteristics of intrinsic neural activity in different depressive stages are largely unknown.

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Identification and Antibiotic Susceptibility of Eggerthella lenta in Bloodstream Infections. The identification and antibiotic susceptibility of two clinical isolates of Eggerthella lenta from bloodstream infections were determined. This microorganism is rarely pathogenic, and the findings are presented here to promote the detection and awareness of this infection. The bacteria were obtained from one patient with pressure sores and another with a malignant gastric tumor. Smears were prepared, stained, and examined by microscopy. Single colonies were analyzed by Gram staining, MALDI-TOF MS, and the 16S rRNA gene sequencing. Antibiotic sensitivity was assessed by the agar dilution method. The bacilli were found to be Gram-positive, and the MS results showed 99.8% homology with E. lenta . It was confirmed by gene sequencing. Antibiotic susceptibility tests demonstrated that E. lenta was sensitive to piperacillin-tazobactam, ampicillin-sulbactam, imipenem, meropenem, metronidazole, clindamycin, and vancomycin. This study could increase awareness of this rare infection.

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Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells. SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy is only moderate, and improved treatment strategies are urgently needed. To accomplish this goal, we devised a strategy to identify compounds that act synergistically with remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput screening in the presence of submaximal remdesivir concentrations, using a human lung epithelial cell line infected with a clinical isolate of SARS-CoV-2. This identified 20 approved drugs that act synergistically with remdesivir, many with favorable pharmacokinetic and safety profiles. Strongest effects were observed with established antivirals, Hepatitis C virus nonstructural protein 5A (HCV NS5A) inhibitors velpatasvir and elbasvir. Combination with their partner drugs sofosbuvir and grazoprevir further increased efficacy, increasing remdesivir's apparent potency > 25-fold. We report that HCV NS5A inhibitors act on the SARS-CoV-2 exonuclease proofreader, providing a possible explanation for the synergy observed with nucleoside analog remdesivir. FDA-approved Hepatitis C therapeutics Epclusa® (velpatasvir/sofosbuvir) and Zepatier® (elbasvir/grazoprevir) could be further optimized to achieve potency and pharmacokinetic properties that support clinical evaluation in combination with remdesivir.

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Hondrosarcoma of the chest with intraabdominal distribution (case report). A rare clinical observation of chondrosarcoma metastasis into the abdominal cavity with a specific metastatic ascitic fluid is presented. Chondrosarcomas that occur as a result of malignant transformation of benign chondroma are quite rare. Even less often in the literature, cases of chondrosarcoma metastases are described, especially in a peritoneum with the presence of metastatic ascites. The article describes a case of metastatic ascites in a 38-year old patient with chondrosarcoma, which developed against the background of previously resected rib chords. The article describes the cytological signs of chondrosarcoma in ascitic fluid.

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Metformin alleviates neurocognitive impairment in aging via activation of AMPK/BDNF/PI3K pathway. Slowing down age-related neurocognitive impairment has been a challenge. We evaluated the therapeutic effects of metformin in D-galactose-induced aging. Additionally, we studied the potential molecular mechanisms that could be responsible for metformin's anti-aging effects. Thirty male rats were equally divided into: 1-control group, which received saline solution, 2-D-galactose (D-gal) group, which received D-galactose (100 mg/kg/day) by gastric lavage for eight weeks, and 3-D-galactose + Metformin (D-gal + Met) treated group, which received D-galactose + metformin (200 mg/kg/day) by gastric lavage for eight weeks. Neurocognitive assessment was done. Measurement of inflammatory, oxidative stress, and BDNF biomarkers was performed. AMPK and PI3K genes expression were assessed. Hippocampal tissues were dissected for histopathological and immunohistochemical studies. D-gal resulted in neurocognitive impairments, elevation of inflammatory biomarkers, altered oxidative stress markers, decreased BDNF, decreased expression of synaptophysin and Bcl2 with increased expression of Caspase-3, and down-regulation of AMPK and PI3K genes. Neurodegenerative changes were present in the hippocampus. Metformin restored significantly D-gal induced neurodegenerative changes. We concluded that metformin could alleviate age-induced neurocognitive deficit via amelioration of neuroinflammation, attenuation of oxidative stress, reduction of apoptosis, as well as promotion of synaptic plasticity. These mechanisms could be mediated via the activation of the AMPK/BDNF/PI3K pathway.

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Exclusive breastmilk pumping: A concept analysis. To analyze and examine the concept of exclusive breast pumping (EP).

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Design of SARS-CoV-2 Main Protease Inhibitors Using Artificial Intelligence and Molecular Dynamic Simulations. Drug design is a time-consuming and cumbersome process due to the vast search space of drug-like molecules and the difficulty of investigating atomic and electronic interactions. The present paper proposes a computational drug design workflow that combines artificial intelligence (AI) methods, i.e., an evolutionary algorithm and artificial neural network model, and molecular dynamics (MD) simulations to design and evaluate potential drug candidates. For the purpose of illustration, the proposed workflow was applied to design drug candidates against the main protease of severe acute respiratory syndrome coronavirus 2. From the ∼140,000 molecules designed using AI methods, MD analysis identified two molecules as potential drug candidates.

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Universal or Personalized Mesenchymal Stem Cell Therapies: Impact of Age, Sex, and Biological Source. Mesenchymal stem/stromal cells (MSCs) hold great promise for the treatment of autoimmune conditions given their immunomodulatory properties. Based on the low immunogenicity of MSCs, it is tempting to consider the expansion of MSCs from a "universal donor" in culture prior to their allogeneic applications for immediate care. This raises the critical question of the criteria we should use to select the best "universal donor". It is also imperative we compare the "universal" approach with a "personalized" one for clinical value. In addition to the call for MHC-matching, recent studies suggest that factors including age, sex, and biological sources of MSCs can have significant impact on therapy outcome. Here, we will review findings from these studies, which shed light on the variables that can guide the important choice of "universal" or "personalized" MSC therapy for autoimmune diseases.

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Biochemical and molecular responses of Rosa damascena mill. cv. Kashan to salicylic acid under salinity stress. Today, salinity stress is one of the most important abiotic stresses in the world, because it causes damage to many agricultural products and reduces their yields. Oxidative stress causes tissue damages in plants, which occurs with the production of reactive oxygen species (ROS) when plants are exposed to environmental stresses such as salinity. Today, it is recommended to use compounds that increase the resistance of plants to environmental stresses and improve plant metabolic activities. Salicylic acid (SA), as an intracellular and extracellular regulator of the plant response, is known as one of these effective compounds. Damask rose (Rosa damascena Mill.) is a medicinal plant from the Rosaceae, and its essential oils and aromatic compounds are used widely in the cosmetic and food industries in the world. Therefore, considering the importance of this plant from both medicinal and ornamental aspects, for the first time, we investigated one of the native cultivars of Iran (Kashan). Since one of the most important problems in Damask rose cultivation is the occurrence of salinity stress, for the first time, we investigated the interaction of several levels of NaCl salinity (0, 4, 8, and 12 ds m - 1 ) with SA (0, 0.5, 1, and 2 mM) as a stress reducer.

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Systematic review on active treatment for urinary fistula after partial nephrectomy. Urinary fistula is expected to become more frequent in urological practice as a result of expanding indication of partial nephrectomy given it's oncological results equivalent to those of radical nephrectomy but at a lower risk of progression to chronic kidney disease, lower cardiovascular morbidity, and overall mortality.

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Digest: Recent movement of a flicker hybrid zone. What biotic and abiotic factors drive hybrid zone movement? By resampling a classic hybrid zone between two subspecies of woodpeckers, Aguillon and Rohwer documented a westward shift that may be attributed to changes in land use or climate. These findings highlight the increasing influence of anthropogenic activities on hybridization events.

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Genome-Based Assessment of Antimicrobial Resistance and Virulence Potential of Isolates of Non-Pullorum/Gallinarum Salmonella Serovars Recovered from Dead Poultry in China. Paratyphoid avian salmonellosis is considered one of the leading causes of poultry death, resulting in significant economic losses to poultry industries worldwide. In China, especially in Shandong province, the leading producer of poultry products, several recurrent outbreaks of avian salmonellosis have been reported during the last decade where the precise causal agent remains unknown. Moreover, the establishment of earlier and more accurate recognition of pathogens is a key factor to prevent the further dissemination of resistant and/or hypervirulent clones. Here, we aim to use whole-genome sequencing combined with in silico toolkits to provide the genomic features of the antimicrobial resistance and virulence potential of 105 regionally representative non-Pullorum/Gallinarum Salmonella isolates recovered from dead poultry between 2008 and 2019 in Shandong, China. Additionally, phenotypic susceptibility to a panel of 15 antibiotics representing 11 classes was assessed by the broth microdilution method. In this study, we identified eight serovars and nine multilocus sequence typing (MLST) types, with Salmonella enterica serovar Enteritidis sequence type 11 (ST11) being the most prevalent (84/105; 80%). Based on their phenotypic antimicrobial resistance, 77.14% of the isolates were defined as multidrug resistant (≥3 antimicrobial classes), with the detection of one S. Enteritidis isolate that was resistant to the 11 classes. The highest rates of resistance were observed against nalidixic acid (97.14%) and ciprofloxacin (91.43%), followed by ampicillin (71.43%), streptomycin (64.77%), and tetracycline (60%). Genomic characterization revealed the presence of 41 resistance genes, with an alarmingly high prevalence of bla TEM-1B (60%), in addition to genomic mutations affecting the DNA gyrase ( gyrA ) and DNA topoisomerase IV ( parC ) genes, conferring resistance to quinolones. The prediction of plasmid replicons detected 14 types, with a dominance of IncFIB(S)_1 and IncFII(S)_1 (87.62% for both), while the IncX1 plasmid type was considered the key carrier of antimicrobial resistance determinants. Moreover, we report the detection of critical virulence genes, including cdtB , rck , sodCI , pef , and spv , in addition to the typical determinants for Salmonella pathogenicity island 1 (SPI-1) and SPI-2. Furthermore, phylogenomic analysis revealed the detection of three intra-farm and five inter-farm transmission events. Overall, the detection of Salmonella isolates presenting high antimicrobial resistance and harboring different critical virulence genes is of major concern, which requires the urgent implementation of effective strategies to mitigate non-Pullorum/Gallinarum avian salmonellosis. IMPORTANCE Avian salmonellosis is one of the leading global causes of poultry death, resulting in substantial economic losses in China (constituting 9% of overall financial losses). In Shandong province, a top poultry producer (30% of the overall production in China, with 15% being exported to the world), extensive outbreaks of avian salmonellosis have been reported in the past decade where the causal agents or exact types remain rarely addressed. From approximately 2008 to 2019, over 2,000 Salmonella strains were isolated and identified from dead poultry during routine surveillance of 95 poultry farms covering all 17 cities in Shandong. Approximately 1,500 isolates were confirmed to be of non-Pullorum/Gallinarum Salmonella serovars. There is an urgent need to understand the mechanisms behind the implication of zoonotic Salmonella serovars in systemic infections of poultry. Here, we analyzed populations of clinically relevant isolates of non-Pullorum/Gallinarum Salmonella causing chicken death in China by a whole-genome sequencing approach and determined that antimicrobial-resistant Salmonella Enteritidis remained the major cause in the past decades.

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Maxillofacial Skeleton and Facial Anatomy. In this article, we discuss the anatomy and development of the face. One should become familiar with the layers, muscles, vessels, and nerves of the face. Embryologic development of the face and supporting structures is also discussed. Additionally, different clinical manifestation of facial paralysis is highlighted.

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Effects of Obstructive Sleep Apnea-Hypopnea Syndrome and Cognitive Function in Ischemic Stroke Based on Linear Regression Equation. The objective of this research is to study the effect of obstructive sleep apnea-hypopnea syndrome on cognitive function of stroke. Based on linear regression equation and Montreal Cognitive Assessment Scale, the degree of cognitive impairment in OSAHS patients was evaluated and the influencing factors of OSAHS-induced cognitive impairment and the correlation between the degree of OSAHS and cognitive impairment were explored. The results are as follows: about 68% of OSAHS patients have cognitive dysfunction, and the incidence of cognitive dysfunction is positively correlated with OSAHS; cognitive impairment of OSAHS patients was associated with age, obesity, years of schooling, and intermittent nocturnal hypoxia or hypoventilation; the severity of cognitive dysfunction of OSAHS patients was positively correlated with age and obesity but negatively correlated with education level; Logistic regression analysis results showed that there were three factors that were finally entered into the regression equation, namely, LSaO2, BMI, and AHI, and the Logistic regression equation obtained was as follows: Logist P = -0.109 X 1 + 0.785 X 2 + 1.228 X 3 . This study helps clinical workers to detect and intervene the impaired cognitive ability of patients with OSAHS early, so as to reduce the incidence and mortality of related complications and improve the quality of life of patients.

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Long-term spatial variation of algal blooms extracted using the U-net model from 10 years of GOCI imagery in the East China Sea. Long-term satellite missions could help to provide insights into spatial and temporal variations in algal blooms. However, the traditional reflectance-based method has limitations in regards to determining the available threshold for algal bloom detection among the time-varying observation conditions. In terms of extracting useful information from long-term data series precisely and efficiently, the deep learning method has shown its superiority over traditional algorithms in batch data processing. In this study, a U-net model for algal bloom extraction along the coast of the East China Sea was developed using GOCI images. The U-net model was trained with two different datasets that were constructed with six-band channels (all visible bands from GOCI imagery) and RGB-band channels (bands of 443, 555, and 680 nm from GOCI imagery). The quantitative assessment from the U-net models suggests that the U-net model trained with the six-band channel datasets outperformed the RGB-band channel datasets, with increases of 23.6%, 18.1%, and 12.5% in terms of accuracy, precision, and F-score, respectively. The validation map derived from the U-net model trained with six-band channel datasets also showed considerable matching with the ground-truth maps. By using the U-net model, the occurrence of algal blooms was automatically extracted from GOCI images. A 10-year time series of GOCI data collected between 2011 and 2020 was derived using an output-trained U-net model to explore spatial variation along the coast of the ECS. It was found that the most affected areas of the algal blooms varied by year, but were mainly located in the Zhoushan and Zhejiang coasts. Additionally, by performing principal component analysis on the daily meteorological data during April and August 2011-2020, factors related to algal bloom occurrence were discussed.

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Noncoding RNAs: Regulating the crosstalk between tumor-associated macrophages and gastrointestinal cancer. Gastrointestinal (GI) cancers, one of the most lethal cancers nowadays, have caused millions of deaths. The tumor microenvironment (TME) is a complex ecosystem containing multiple cells, such as immune cells, cancer cells, and endothelial cells. Tumor-associated macrophages (TAMs), the predominant cells infiltrating the TME, have been verified to play a crucial role in regulating tumor progression. Noncoding RNAs (ncRNAs) are involved in mediating tumor-infiltrating immune cells, including TAMs. GI cancer cells produce various ncRNAs to modulate TAM infiltration and polarization. Meanwhile, ncRNAs play a pivotal role in macrophage and cancer cell metabolic reprogramming. Furthermore, macrophages mediate the impact of ncRNAs on chemoresistance, metastasis, and progression of GI cancer. In this review, we summarize recent research advances in the crosstalk between macrophages and GI cancer regulated by ncRNAs. Moreover, we propose the promising role of ncRNAs as potential targets and prognostic biomarkers in cancer treatment, hoping to facilitate the identification of new targets for immunotherapy.

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TGFBR3 supports anoikis through suppressing ATF4 signaling. Epithelial morphogenesis and oncogenic transformation can cause loss of cell adhesion, and detached cells are eliminated by anoikis. Here, we reveal that transforming growth factor β receptor 3 (TGFBR3) acts as an anoikis mediator through the coordination of activating transcription factor 4 (ATF4). In breast cancer tissues, TGFBR3 is progressively lost, but elevated TGFBR3 is associated with a histologic subtype characterized by cellular adhesion defects. Dissecting the impact of extracellular matrix (ECM) deprivation, we demonstrate that ECM loss promotes TGFBR3 expression, which in turn causes differentiation of cell aggregates, conferring a low-adhesion phenotype, and drives the intrinsic apoptotic pathway. We demonstrate that inhibition of TGFBR3 impairs epithelial anoikis by activating ATF4 signaling. These preclinical findings provide a rationale for therapeutic inhibition of ATF4 in the subgroup of breast cancer patients with low TGFBR3 expression.

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Social network analysis of Staphylococcus aureus carriage in a general youth population. Staphylococcus aureus carriage increases the risk of infection. We used social network analysis to evaluate whether contacts have the same S. aureus genotype indicating direct transmission or whether contagiousness is an indirect effect of contacts sharing the same lifestyle or characteristics.

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Transcriptome analysis reveals the roles of phytohormone signaling in tea plant (Camellia sinensis L.) flower development. Tea plant (Camellia sinensis (L.) O. Kuntze) is an important economic tea crop, but flowering will consume a lot of nutrients of C. sinensis, which will seriously affect the nutritional growth of C. sinensis. However, there are few studies on the development mechanism of C. sinensis flower, and most studies focus on a single C. sinensis cultivar.

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An accelerated approach of biogas production through a two-stage BioH 2 /CH 4 continuous anaerobic digestion system from Napier grass. Napier grass found to be greatest potential for gaseous bioenergy production. The biohydrogen and biomethane productions from untreated Napier grass in single and two-stage continuous bioreactors was evaluated using anaerobic digestion technology. The bioreactors were fed Napier grass with organic loading rate (OLR) of 0.5, 1.0 and 2.0 kg VS/m 3 -d, respectively. The hydrogen, methane, and energy yields were evaluated. The methane yield of single-stage system was 282.08 CH 4 /g vS with OLR of 0.5 kg VS/m 3 -d. For two-stage system, the biohydrogen and biomethane yields were 90.06 mL H 2 /g vS and 367.00 mL CH 4 /g vS with OLRs of 1.0 and 0.5 kg VS/m 3 -d, respectively. The energy yields of single and two-stage systems were 13.14 and 10.10 kJ/g vS respectively. The peak OLR of Napier grass was 0.5 kg VS/m 3 -d for the two-stage system whereas the total energy recovery was 30 % higher than the single-stage system.

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Perceptions and attitudes of ICU physicians toward antibiotics prescribing and resistance: A cross-sectional study. Antibiotic resistance is a major emphasis in intensive care units (ICUs). Better understanding of ICU physicians' perceptions, attitudes, and knowledge about antimicrobial prescribing practices could facilitate more effective interventions in fighting antimicrobial resistance in Egyptian ICUs and establishing a proper Antimicrobial Stewardship Program.

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International prevalence of consultation with a naturopathic practitioner: a systematic review and meta-analysis. Naturopathy is a traditional medicine system informed by codified philosophies and principles, and an emphasis on non-pharmacologic therapeutic interventions. While naturopathy is practised by approximately 75 000-100 000 000 naturopathic practitioners in at least 98 countries, little is known about the international prevalence of history of consultation with a naturopathic practitioner. This study reports a systematic review and meta-analysis of studies describing the global prevalence of history of consultation with a naturopathic practitioner by the general population.

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Hydrogen Bond-Mediated Supramolecular Polymeric Nanomedicine with pH/Light-Responsive Methotrexate Release and Synergistic Chemo-/Photothermal Therapy. Complete cancer cure and healing are still difficult, owing to its complexity and heterogeneity. Integration of supramolecular forces, for example, hydrogen bonds (H-bonds), to anti-cancer nanomedicine affords new scaffolds for biomedical material decoration, featuring the advantages of dynamic property and easier processability. Here, we target the construction of H-bond-mediated supramolecular polymer micelles, loaded with a chemotherapeutic drug along with a photothermal agent for synergistic chemo-/photothermal therapies (CT/PTT). To do so, we design and synthesize an amphiphilic ABA-type triblock copolymer, bearing H-bonding moiety (barbiturate, Ba) within the middle hydrophobic B block. The presence of pendant Ba moieties within the hydrophobic core promotes the loading capability of methotrexate (MTX) and transportation stability, benefitting from the formation of specific Ba/MTX H-bonding interactions. IR780, a photothermal agent, concomitantly encapsulated via hydrophobic interactions, facilitates the development of a synergistic CT/PTT modalities, where MTX can be released on demand owing to the dissociation of Ba/MTX H-bonding interactions induced by elevated temperature. Such H-bonding nanomedicine possesses enhanced drug loading capacity and transport performance and can also trigger stimuli-responsive drug release in the tumor zone. We believe that H-bonded nanomedicines provide a fine toolbox that is conducive to attaining biomedical requirements with remarkable values in theranostics that are highly promising in clinical applications.

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Clinical Effectiveness of Herbal Oral Care Products in Periodontitis Patients: A Systematic Review. The use of herbal products in oral cavity has shown an increased popularity and potential benefits due to their additional anti-inflammatory and antioxidant properties as well as the lack of side effects related to their use.

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Pharmacokinetic evaluation and relative bioavailability pilot study of fidaxomicin in healthy Chinese subjects: An open, randomized, single-dose, cross-over study. To compare the pharmacokinetic (PK) characteristics, investigate relative bioavailability, and provide data for potential additional bioequivalence trials between generic fidaxomicin (test (T) formulation) and the original brand (reference (R) formulation) in healthy Chinese subjects.

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Development of an acellular nerve cap xenograft for neuroma prevention. Neuroma formation following limb amputation is a prevalent and debilitating condition that can deeply affect quality of life and productivity. Several approaches exist to prevent or treat neuromas; however, no approach is either consistently reliable or surgically facile, with high rates of neuroma occurrence and/or recurrence. The present study describes the development and testing of a xenogeneic nerve cap graft made from decellularized porcine nerve. The grafts were tested in vitro for cellular removal, cytotoxicity, mechanical properties, and morphological characteristics. The grafts were then tested in rat sciatic nerve gap reconstruction and nerve amputation models for 8 weeks. Gross morphology, electrophysiology, and histopathology assessments were performed to determine the ability of the grafts to limit pathologic nerve regrowth. In vitro testing showed well decellularized and demyelinated nerve cap graft structures without any cytotoxicity from residual reagents. The grafts had a proximal socket for the proximal nerve stump and longitudinally oriented internal pores. Mechanical and surgical handling properties suggested suitability for implantation as a nerve graft. Following 8 weeks in vivo, the grafts were well integrated with the proximal and distal nerve segments without evidence of fibrotic adhesions to the surrounding tissues or bulbous outgrowth of the nerve. Electrophysiology revealed absence of nerve conduction within the remodeled nerve cap grafts and significant downstream muscle atrophy. Histologic evaluation showed well organized but limited axonal regrowth within the grafts without fibrous overgrowth or neuromatous hypercellularity. These results provide proof of concept for a novel xenograft-based approach to neuroma prevention.

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Rituximab in myasthenia gravis: efficacy, associated infections and risk of induced hypogammaglobulinemia. The aim of this study is to evaluate the long-term efficacy, safety, and impact on immunoglobulin G (IgG) levels of rituximab in patients with myasthenia gravis (MG). A retrospective, observational study of drug-refractory MG patients treated with rituximab was done. The MG Foundation of America postintervention status (MGFA-PIS) was used to evaluate clinical response. Serum IgG levels were determined at baseline and post-treatment. Hypogammaglobulinemia was defined as IgG<7g/L. Thirty patients were included, 12 with anti-MuSK and 18 with anti-AChR antibodies. Mean (SD) follow-up was 85.5 (48) months. All 12 MuSK+ patients but only six (33%) AChR+ patients achieved minimal manifestations or remission (p<0.01). Nine severe infections were observed in five patients (17%). One patient was diagnosed with progressive multifocal leukoencephalopathy. At baseline, two patients (2/24; 8%) had hypogammaglobulinemia. During follow-up, hypogammaglobulinemia was observed in 60% (3/5) of patients who developed an infection and in 33% (7/21) who did not. Two of these patients died of infection-related complications. This study supports the effectiveness of rituximab in patients with MG, especially those with anti-MuSK antibodies. Severe infections may appear after rituximab treatment and hypogammaglobulinemia might play a role on it. A standard protocol would be needed to closely monitor IgG levels in MG patients treated with rituximab.

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Long-term effects of lower versus higher oxygenation levels in adult ICU patients-A systematic review. Oxygen therapy is a common treatment in the intensive care unit (ICU) with both potentially desirable and undesirable long-term effects. This systematic review aimed to assess the long-term outcomes of lower versus higher oxygenation strategies in adult ICU survivors.

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Role of oxidative stress in induction of trans-differentiation of neutrophils in patients with rheumatoid arthritis. Rheumatoid arthritis (RA) is an autoimmune disorder whose etiopathology involves an interplay between genetic and environmental factors, with oxidative stress being a key contributory factor. This study aimed to establish the impact, if any, of an oxidative, pro-inflammatory milieu upon trans-differentiation of neutrophils and disease progression. In the synovial fluid (SF) and peripheral blood sourced from patients with RA ( n = 40) along with healthy controls ( n = 25), the proportion of neutrophil-dendritic (N-DC) cell hybrids, i.e. CD66b + /CD83 + was characterized in terms of their antigen presentation (HLA-DR, CD80, andCD86) and cell adhesion and migration (ICAM-1, VCAM-1, and CD62L) properties, along with their ability to generate reactive oxygen species (ROS). In the SF of RA cases, the raised levels of circulating and intra-neutrophilic pro-inflammatory cytokines/chemokines were accompanied by an enhanced proportion of CD66b + neutrophils, that co-expressed features of antigen presenting cells (APCs) namely CD83, HLA-DR, CD80, CD86, ICAM-1, VCAM-1, and decreased CD62L. These N-DCs as compared to canonical neutrophils demonstrated a higher generation of ROS, and their frequency positively correlated with disease activity score (DAS28). An ex-vivo functional assay validated that oxidative stress supported trans-differentiation and could be attenuated by a free radical scavenger. Taken together, the pro-inflammatory microenvironment in the SF of patients with RA coupled with a higher generation of ROS promoted the trans-differentiation of neutrophils into N-DCs, suggesting the inclusion of anti-oxidants as an add-on therapeutic strategy to limit trans-differentiation.

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Analysis of the Possibility of Using Cenospheres in the Production of Cement Mortars for Use in an Elevated Temperature Environment. The topic of research included in this article was the evaluation of the influence of cenospheres on selected parameters of mortar cement. Samples were designed as CEM I 42.5 R Portland cement with the application of different additive amounts. In the experimental work, the consistency, compressive strength, and bending strength were tested after 28 and 56 days of maturation, and after heating temperatures of 20, 300, 500, and 700 °C. The compressive strength was tested on half beams (40 × 40 × 160 mm). Using the obtained results, the properties of the mortars were compared. The research confirmed the possibility of producing cenosphere-modified cement mortars. Cenospheres used in the preparation of cement mortar negatively affected the bending and compressive strength with increasing temperature (20, 300, 500, 700 °C) and increasing content of this additive (10, 20, 30%).

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Graphium septentrionicolus Page amp; Treadaway, 2013 (Lepidoptera: Papilionidae) is a distinct species. After molecular and morphological analyses, the taxon septentrionicolus Page Treadaway, 2013 is shown to be a distinct species, and Graphium adonarensis (Rothschild, 1896) is placed as conspecific with Graphium sarpedon (Linnaeus, 1758). Graphium huangshanensis Wu Ma, 2016 syn. nov. is synonymised with G. septentrionicolus.

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Improving Dietary Intake of Essential Nutrients Can Ameliorate Inflammation in Patients with Diabetic Foot Ulcers. Diabetic foot ulcers (DFUs) are classified as chronic wounds and are one of the most common complications of diabetes. In chronic wounds, management of inflammation is a key step in treatment. Nutrition plays an important role in managing and controlling inflammation. This study evaluated the effects of nutrition supplementation and education on inflammatory biomarkers in patients with DFUs. Eligible patients with foot ulcers were randomly assigned to either a treatment ( n = 15) or control group ( n = 14). Both groups received standard care for wound treatment from the clinic; however, the treatment group was also provided with nutritional supplementation and education. Plasma concentrations of inflammatory biomarkers, namely C-reactive protein (CRP), interleukin 6 (IL6), interleukin 10 (IL10), and tristetraprolin (TTP), were evaluated at baseline and every four weeks, until complete wound closure had occurred or up to 12 weeks. The mean plasma concentration of IL6 significantly decreased in the treatment group ( p = 0.001). The interaction between time and group was not statistically significant for the mean plasma concentrations of CRP, IL10, and TTP during the 12 weeks of the study. The results of this study showed the positive effects of nutritional intervention on controlling inflammation in DFU patients. More clinical trials with a larger population and longer duration of time are needed to confirm our results.

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Heart rate and age modulate retinal pulsatile patterns. Theoretical models of retinal hemodynamics showed the modulation of retinal pulsatile patterns (RPPs) by heart rate (HR), yet in-vivo validation and scientific merit of this biological process is lacking. Such evidence is critical for result interpretation, study design, and (patho-)physiological modeling of human biology spanning applications in various medical specialties. In retinal hemodynamic video-recordings, we characterize the morphology of RPPs and assess the impact of modulation by HR or other variables. Principal component analysis isolated two RPPs, i.e., spontaneous venous pulsation (SVP) and optic cup pulsation (OCP). Heart rate modulated SVP and OCP morphology (p FDR < 0.05); age modulated SVP morphology (p FDR < 0.05). In addition, age and HR demonstrated the effect on between-group differences. This knowledge greatly affects future study designs, analyses of between-group differences in RPPs, and biophysical models investigating relationships between RPPs, intracranial, intraocular pressures, and cardiovascular physiology.

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Application of High-Efficiency Cell Expansion and High-Throughput Drug Sensitivity Screening for Leukemia Treatment. This study is to assess the clinical value of in vitro primary cell high-efficiency expansion and high-throughput drug sensitivity screening (HEHDS) system in leukemia, and we evaluated a cohort of 121 patients with acute myeloid leukemia (AML) and 27 patients with acute lymphoblastic leukemia (ALL) using HEHDS. Bone marrow aspirates were collected from patients with leukemia. Purified leukemic cancer cells were obtained, cultured, and screened with a panel of 247 FDA-approved compounds by HEHDS technology. Ninety-six patients received HEHDS-guided therapy while 52 patients who were subjected to physician directed therapy served as controls. ALL patients who received treatment guided by HEHDS showed higher rate of complete remission (CR) than that of patients in the non-HEHDS group (90.91% vs. 56.25%). Similarly, AML patients received HEHDS-guided therapy were found to have greater CR rate, when compared with patients who received physician-directed therapy (45.88% vs. 25%). There was a significantly higher rate of CR in HEHDS-guided therapy group compared to the non-HEHDS group. The application of HEHDS could be beneficial for leukemia treatment.

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Association between a dietary pattern high in saturated fatty acids, dietary energy density, and sodium with coronary heart disease. This study aimed to determine the association between dietary pattern (DP) and coronary heart disease (CHD) among high-risk adults as determined by metabolic syndrome (MetS) criteria in Malaysia. This cross-sectional study involved 365 participants with (CHD = 178; non-CHD = 187) who were recruited from selected health clinics. Dietary intake was measured using a 189-item semi-quantitative foods frequency questionnaire (FFQ) whilst anthropometry and clinical data were measured by trained researcher and biochemical data were obtained from medical records. The reduced rank regression (RRR) method was used to derive DPs scores and binary logistic regression was used to assess the associations between identified DPs and CHD. The main DP found in this study was characterised by "high saturated fatty acid (SFA), high dietary energy density (DED), high sodium". This DP, which is attributed to high consumption of coconut-based dishes, fast foods and snacks, rice dishes, fat spread, seasoning sauces, salted and processed foods, and low intake of fruits, green leafy vegetables, white rice and other vegetables were associated with CHD (OR:1.32, 95% CI:1.03, 1.69) p value = 0.026 when, adjusted for age, sex, race, education level, household income, family history of CHD, marital status, smoking status, physical activity, stress level and BMI. This study suggests that individuals with a DP of high SFA, high DED, and high sodium have a significantly increased likelihood of having CHD compared to those who do not practice this DP.

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The use of formal care for dementia from a professional perspective: a scoping review. The progressive character of dementia usually leads to a continuously increasing need for support. There is some evidence of late use of professional support during the disease course. We aim to provide an overview of aspects influencing access and use of formal care in dementia from the perspective of health and social care professionals. Additionally, the perspectives of professionals and people with dementia/informal carers will be compared.

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Nuances of Septal Deviation Repair. Septoplasty is one of the most common procedures performed by facial plastic surgeons. Surgical decision-making surrounding septal deviation repair centers around the location of deviation and need for dorsal and/or caudal septal correction. Endonasal approaches are often adequate and external approaches are utilized for significant L-strut involvement. For severe deformities, extracorporeal septoplasty and anterior septal reconstruction can be utilized. We present an overview of septal deviation repair with technical nuances and advanced reconstruction techniques.

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Absence of Figla-like Gene Is Concordant with Femaleness in Cichlids Harboring the LG1 Sex-Determination System. Oreochromis niloticus has been used as a reference genome for studies of tilapia sex determination (SD) revealing segregating genetic loci on linkage groups (LGs) 1, 3, and 23. The master key regulator genes (MKR) underlying the SD regions on LGs 3 and 23 have been already found. To identify the MKR in fish that segregate for the LG1 XX/XY SD-system, we applied short variant discovery within the sequence reads of the genomic libraries of the Amherst hybrid stock, Coptodon zillii and Sarotherodon galilaeus , which were aligned to a 3-Mbp-region of the O. aureus genome. We obtained 66,372 variants of which six were concordant with the XX/XY model of SD and were conserved across these species, disclosing the male specific figla-like gene. We further validated this observation in O. mossambicus and in the Chitralada hybrid stock. Genome alignment of the 1252-bp transcript showed that the figla-like gene's size was 2664 bp, and that its three exons were capable of encoding 99 amino acids including a 45-amino-acid basic helix-loop-helix domain that is typical of the ovary development regulator- factor-in-the-germline-alpha ( FIGLA ). In Amherst gonads, the figla-like gene was exclusively expressed in testes. Thus, the figla-like genomic presence determines male fate by interrupting the female developmental program. This indicates that the figla-like gene is the long-sought SD MKR on LG1.

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Occupations and their impact on the spreading of COVID-19 in urban communities. The current pandemic has disproportionally affected the workforce. To improve our understanding of the role that occupations play in the transmission of COVID-19, we analyse real-world network data that were collected in Bucharest between August 1st and October 31st 2020. The data record sex, age, and occupation of 6895 patients and the 13,272 people they have interacted with, thus providing a social network from an urban setting through which COVID-19 has spread. Quite remarkably, we find that medical occupations have no significant effect on the spread of the virus. Instead, we find common transmission chains to start with infected individuals who hold jobs in the private sector and are connected with non-active alters, such as spouses, siblings, or elderly relatives. We use relational hyperevent models to assess the most likely homophily and network effects in the community transmission. We detect homophily with respect to age and anti-homophily with respect to sex and employability. We note that, although additional data would be welcomed to perform more in-depth network analyses, our findings may help public authorities better target under-performing vaccination campaigns.

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Highly Efficient Red/NIR-Emissive Fluorescent Probe with Polarity-Sensitive Character for Visualizing Cellular Lipid Droplets and Determining Their Polarity. Lipid droplets (LDs), which are ubiquitous organelles existing in almost all eukaryotic cells, have attracted a lot of attention in the field of cell biology over the last decade. For the biological study of LDs via fluorescence imaging, the superior LD fluorescent probes with environmental polarity-sensitive character are highly desired and powerful but are very scarce. Herein, we have newly developed such a kind of fluorescent probe named LDs-Red which enables us to visualize LDs and to further reveal their polarity information. This fluorescent probe displays the advantages of intense red/near-infrared emission, high LD staining specificity, and good photostability; thus, it would be very useful for LD fluorescence imaging application. As a result, the three-dimensional confocal imaging to visualize spatial distribution of LDs and the multicolor confocal imaging to simultaneously observe LDs and other cellular organelles have been realized using this new LD fluorescent probe. Furthermore, the polarity-sensitive emission character of this probe enables us to quantitatively determine the LD polarity via spectral scan imaging. Consequently, the cancer cells (HepG2, HeLa, and Panc02) displaying lower polarity of LDs than the normal cells (L929, U251, and HT22) have been systematically demonstrated. In addition, this polarity-sensitive probe displaying shorter fluorescence wavelengths in cancer cells than in normal cells has an important and potential ability to distinguish them.

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Proteome-wide analysis of the hippocampus in adolescent male mice with learning and memory impairment caused by chronic ethanol exposure. Alcohol consumption may cause various impairments in the brain. The hippocampus is particularly vulnerable to alcohol exposure, which may cause learning and memory deficits. Recently, proteomics analysis has become a popular approach to explore the pathogenesis of various diseases. The present study was conducted to investigate protein expression alteration in the hippocampus and to identify the molecular mechanisms underlying ethanol-induced learning and memory impairments. Mouse models of chronic ethanol intoxication were established by intragastrical administration for 28 consecutive days, and hippocampal neuronal damage was assessed by Nissl staining. Recognition memory was evaluated by Novel object recognition and Morris water maze tests, and hippocampus tissues were collected for label-free quantitative proteomics and analyzed using bioinformatics methods. Our study showed that chronic ethanol exposure prompted marked changes in protein expression in the hippocampus. We identified 32 differentially expressed proteins, of which 21 were upregulated and 11 downregulated. Gene Ontology analysis suggested that the identified differentially proteins were mainly involved in cytoskeleton and signal transduction mechanisms. Further verification using Western blotting and real-time quantitative PCR revealed that the hippocampal CTSL (cathepsin L), and PVALB (Parvalbumin) showed strongest expression changes, the latter being specifically expressed in GABAergic interneurons. These two proteins might serve as candidate protein biomarkers, providing new prospects for the diagnosis and treatment of ethanol-induced learning and memory disorders.

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Development of a new toolbox for mouse PET-CT brain image analysis fully based on CT images and validation in a PD mouse model. Automatic analysis toolboxes are popular in brain image analysis, both in clinical and in preclinical practices. In this regard, we proposed a new toolbox for mouse PET-CT brain image analysis including a new Statistical Parametric Mapping-based template and a pipeline for image registration of PET-CT images based on CT images. The new templates is compatible with the common coordinate framework (CCFv3) of the Allen Reference Atlas (ARA) while the CT based registration step allows to facilitate the analysis of mouse PET-CT brain images. From the ARA template, we identified 27 volumes of interest that are relevant for in vivo imaging studies and provided binary atlas to describe them. We acquired 20 C57BL/6 mice with [18F]FDG PET-CT, and 12 of them underwent 3D T2-weighted high-resolution MR scans. All images were elastically registered to the ARA atlas and then averaged. High-resolution MR images were used to validate a CT-based registration pipeline. The resulting method was applied to a mouse model of Parkinson's disease subjected to a test-retest study (n = 6) with the TSPO-specific radioligand [18F]VC701. The identification of regions of microglia/macrophage activation was performed in comparison to the Ma and Mirrione template. The new toolbox identified 11 (6 after false discovery rate adjustment, FDR) brain sub-areas of significant [18F]VC701 uptake increase versus the 4 (3 after FDR) macro-regions identified by the Ma and Mirrione template. Moreover, these 11 areas are functionally connected as found by applying the Mouse Connectivity tool of ARA. In conclusion, we developed a mouse brain atlas tool optimized for PET-CT imaging analysis that does not require MR. This tool conforms to the CCFv3 of ARA and could be applied to the analysis of mouse brain disease models.

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Value of computed tomography Hounsfield units in predicting pedicle screw loosening in the thoracic spine. We evaluated the feasibility of using the Hounsfield unit (HU) value of the vertebral body to predict screw loosening in the thoracic spine. Consecutive patients who underwent thoracic spinal fusion surgery (from 2014 to 2020) were retrospectively identified. Patients with pedicle screw loosening in the upper instrumented vertebra (UIV) on postoperative computed tomography were included in the "loosening" group. The control group comprised an equal number of age-, sex-, and UIV-matched patients without screw loosening. Preoperative HU values at the UIV and lumbar T-scores were compared between the groups; receiver operating characteristic curves were constructed for HU values and T-scores to predict screw loosening, and the best cutoff values were determined. The same statistical analyses were performed for each subgroup, i.e., upper (T1-T4) and lower (T9-T12) thoracic levels. Forty-six patients each were included in the loosening and control groups. A significant between-group difference of HU values was noted for the lower thoracic UIV (loosening = 99.3, control = 126.3; p = 0.02) but not for the upper thoracic UIV (loosening = 171.8, control = 146.0, p = 0.70). T-scores did not differ between the groups for the lower (p = 0.14) and upper (p = 0.56) thoracic UIV. For the lower thoracic UIV, the area under the receiver operating characteristic curve was 0.660 for HUs (p = 0.01; 95% confidence interval [CI] 0.541-0.766) and 0.601 (p = 0.13; 95% CI 0.480-0.713) for T-scores. The optimal cutoff value for HUs was 126.3. Using this cutoff, HU values showed a better positive predictive value, negative predictive value, and accuracy compared to T-scores in predicting screw loosening.

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An Observational Study on the Use of a Patient Navigator to Help Improve Outcomes in Patients on Chronic Opioids. In the United States, the prevalence of opioid use disorders has increased in recent years along with an attendant rise in the incidence of chronic pain disorders and prescription opioid use. Patient navigation services have been used to improve health outcomes in cancer and other chronic disease states, but it is unclear whether the implementation of patient navigation services can facilitate improved outcomes among patients receiving chronic opioid therapy.

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Food Insecurity in a Sample of Informal Caregivers in 4 Southern US States. Given the disproportionate burden of food insecurity in the southern US states and the high prevalence of caregiving in this area, we assessed caregiving-related predictors of food insecurity among caregivers in 4 southern US states.

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Dietary emulsifier glycerol monodecanoate affects the gut microbiota contributing to regulating lipid metabolism, insulin sensitivity and inflammation. Glycerol monodecanoate (GMD) is a medium-chain monoacylglycerol that possesses emulsifying and antibacterial properties. The common emulsifiers carboxymethylcellulose and polysorbate-80 have been reported to cause intestinal microbiota dysbiosis and metabolic disturbances. Glycerol monolaurate (GML), another medium-chain monoacylglycerol, is often used as an emulsifier and could improve metabolism by regulating the gut microbiota. However, research on the effects of GMD on the metabolism and gut microbiota remains scarce. Mice were fed a normal chow diet with or without GMD (150, 800, and 1600 mg kg -1 ) for 22 weeks. Metabolism indicators and related genes, gut microbiota, and fecal SCFAs were analyzed. The results demonstrated that GMD significantly improved insulin sensitivity, reduced the serum LPS level, and decreased pro-inflammation cytokines including IL-1β, tumor necrosis factor (TNF), and monocyte chemotactic protein 1 (MCP-1). Additionally, 150 and 1600 mg kg -1 GMD could significantly lower the blood glucose content. 1600 mg kg -1 GMD improved cholesterol metabolism and related gene expression compared to 150 and 800 mg kg -1 GMD. Moreover, 150 and 800 mg kg -1 GMD up-regulated the abundance of Lactobacillus and Turicibacter , while 1600 mg kg -1 GMD significantly up-regulated the abundance of Bifidobacterium . Our findings indicated that different doses of GMD had inconsistent effects on lipid metabolism by differentially altering the gut microbiota composition. Meanwhile, all doses of GMD showed excellent effects on increasing insulin sensitivity and improving inflammation.

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Reversible cerebral artery constriction accompanied with stroke-like episode in MELAS: A case series. The pathophysiology of stroke-like episode (SLE) in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was uncertain, though mitochondrial metabolic crisis of cortical neurons and mitochondrial proliferation in small vessels of brain have been considered. However, the involvement of major cerebral vessels was debated. We aimed to investigate whether major cerebral vessels participate in SLE.

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Validity of the Functioning Assessment Short Tests (FAST), in patients with schizophrenia. Functional impairment in schizophrenia is one of the main features of the disorder and implies a great impact on the patient's quality of life. The Brief Functioning Assessment Scale (FAST), originally validated in bipolar disorder, has also been validated for its application in other mental disorders. However, we only found one study on the reliability and validity of the Brazilian version in schizophrenia. The purpose of this study was to analyze the psychometric properties of the Spanish version of the FAST in patients diagnosed with schizophrenia.

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Lef1 is transcriptionally activated by Klf4 and suppresses hyperoxia-induced alveolar epithelial cell injury. Bronchopulmonary dysplasia (BPD) is a long-term respiratory condition. More than a quarter of extremely premature newborns are harmed by BPD. At present, there are no apparent effective drugs or treatments for the condition. In this study, we aimed to investigate the functional role and mechanism of lymphoid enhancer-binding factor 1 ( Lef1 ) in BPD in vitro .

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Activation of PGRN/MAPK axis stimulated by the hypoxia-conditioned mesenchymal stem cell-derived HIF-1α facilitates osteosarcoma progression. Progranulin (PGRN) is an important survival factor in the progression of multiple cancers.

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Curating the gnomAD database: Report of novel variants in the thyroid peroxidase gene using in silico bioinformatics algorithms and a literature review. Thyroid peroxidase (TPO) is a membrane-bound glycoprotein located at the apical side of the thyroid follicular cells that catalyzes both iodination and coupling of iodotyrosine residues within the thyroglobulin molecule, leading to the synthesis of thyroid hormone. Variants in TPO cause congenital hypothyroidism (CH) by iodide organification defect and are commonly inherited in an autosomal recessive fashion. In the present work, we report a detailed population analysis and bioinformatic prediction of the TPO variants indexed in the Genome Aggregation Database (gnomAD) v2.1.1. The proportion of missense cysteine variants and nonsense, frameshift, and splice acceptor/donor variants were analyzed in each ethnic group (European (Non-Finnish), European (Finnish), African/African Americans, Latino/Admixed American, East Asian, South Asian, Ashkenazi Jewish, Other). The results showed a clear predominance of frameshift variants in the East Asian (82%) and European (Finnish) (75%) population, whereas the splice site variants predominate in African/African Americans (99.46%), Other (96%), Latino/Admixed American (94%), South Asian (86%), European (Non-Finnish) (56%) and Ashkenazi Jewish (56%) populations. The analysis of the distribution of the variants indexed in gnomAD v2.1.1 database revealed that most missense variants identified in the An peroxidase domain map in exon 8, followed by exons 11, 7 and 9, and finally in descending order by exons 10, 6, 12 and 5. In total, 183 novel TPO variants were described (13 missense cysteine's variants, 158 missense variants involving the An peroxidase domain and 12 splicing acceptor or donor sites variants) which were not reported in the literature and that would have deleterious effects on prediction programs. In the gnomAD v2.1.1 population, the estimated prevalence of heterozygous carriers of the potentially damaging variants was 1:77. In conclusion, we provide an updated and curated reference source of new TPO variants for application in clinical diagnosis and genetic counseling. Also, this work contributes to elucidating the molecular basis of CH associated with TPO defects.

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Unraveling the Complex Chirality Evolution in DNA-Assembled High-Order, Hybrid Chiroplasmonic Superstructures from Multi-Scale Chirality Mechanisms. Hierarchical, chiral hybrid superstructures of chromophores and nanoparticles are expected to give rise to intriguing unveiled chiroptical responses originating from the complex chiral interactions among the components. Herein, DNA origami cavity that could self-assemble into one-dimensional (1D) DNA tubes was employed as a scaffold to accurately organize metal nanoparticles and chromophores. The chiral interactions were studied at the level of individual hybrid particles and their 1D hybrid superstructures. Complex chirality mechanisms involving global structural chirality, plasmon-induced circular dichroism (PICD) and exciton-coupled circular dichroism (ECCD) were disentangled. The multiplexed CD spectrum superposition revealed the chirality evolution at different length scales. These results can offer a model for boosting the theoretical understanding of classical-quantum hybrid systems, and would inspire the future design of optically-active substances across length scales.

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Prevalence and factors associated with latent autoimmune diabetes in adults (LADA): a cross-sectional study. The Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressive Type 1 diabetes subgroup with onset during middle age. Studies report that about 10% of adults initially diagnosed with clinical Type 2 diabetes (T2D) have LADA. Inappropriate diagnosis and mismanagement of the LADA can increase the risk of diabetic complications, which affect the quality of life and is the cause of increased mortality. In low-income countries setting, data regarding the magnitude of LADA is limited. We carried out this study to estimate the burden of misdiagnosed LADA among T2D patients in selected health facilities in Dar es Salaam and to bring awareness to the use of Glutamic Acid Decarboxylase (GAD) autoantibody in screening for LADA.

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Enhanced Ambient Sensing Environment-A New Method for Calibrating Low-Cost Gas Sensors. Accurate calibration of low-cost gas sensors is, at present, a time consuming and difficult process. Laboratory calibration and field calibration methods are currently used, but laboratory calibration is generally discounted due to poor transferability, and field methods requiring several weeks are standard. The Enhanced Ambient Sensing Environment (EASE) method described in this article, is a hybrid of the two, combining the advantages of a laboratory calibration with the increased accuracy of a field calibration. It involves calibrating sensors inside a duct, drawing in ambient air with similar properties to the site where the sensors will operate, but with the added feature of being able to artificially increases or decrease pollutant levels, thus condensing the calibration period required. Calibration of both metal-oxide (MOx) and electrochemical (EC) gas sensors for the measurement of NO 2 and O 3 (0-120 ppb) were conducted in EASE, laboratory and field environments, and validated in field environments. The EC sensors performed marginally better than MOx sensors for NO 2 measurement and sensor performance was similar for O 3 measurement, but the EC sensor nodes had less node inter-node variability and were more robust. For both gasses and sensor types the EASE calibration outperformed the laboratory calibration, and performed similarly to or better than the field calibration, whilst requiring a fraction of the time.

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Maternal exposure to PM 2.5 disrupting offspring spermatogenesis through induced sertoli cells apoptosis via inhibin B hypermethylation in mice. Particulate Matter 2.5 (PM 2.5 ) disrupts endocrine functions and may negatively affect sperm quality and quantity in males; however, the long-term effects and potential mechanisms of this effect are unknown. This study aimed to investigate the epigenetic mechanism of maternal exposure to PM 2.5 -induced inhibin B hypermethylation in male offspring. In this experiment design, pregnant C57BL/6 mice were treated with two doses of PM 2.5 (4.8 and 43.2 mg/kg bw). The membrane control group was given a sampling membrane and the control group received nothing. Following the formation of the vaginal plug, intratracheal instillation of PM 2.5 was administered every three days until delivery of the pups. To assess the effect of PM 2.5 in vitro, TM4 cells, a Sertoli-like cell line, was treated with different concentrations (0, 25, 50, 100 μg/mL) of PM 2.5 for 24 h. The results displayed that Sperm motility, as well as the number of adult offspring, was decreased in the PM 2.5 exposed group relative to the untreated controls. Increased vacuolization was observed in the Sertoli cells of mice that were exposed to PM 2.5 in utero. The levels of inhibin and testosterone were reduced and the levels of LH and FSH increased in the PM 2.5 groups relative to the untreated controls. In vitro, PM 2.5 resulted in cell cycle inhibition as well as increased apoptosis in TM4 cells. Moreover, PM 2.5 -induced inhibin B hypermethylation and activation of the p21/Cleaved Caspase-3 pathway resulted in TM4 cell apoptosis that was rescued through the use of a DNA methylation inhibitor. Together, our data suggest that prenatal exposure to PM 2.5 results in inhibin B hypermethylation and can activate the p21/Cleaved Caspase-3 pathway, resulting in Sertoli cell apoptosis, aberrant secretion of androgen binding protein, and decreased testosterone, thus resulting in the inhibition of spermatogenesis.

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New potential treatment for cardiovascular disease through modulation of hemoglobin oxygen binding curve: Myo-inositol trispyrophosphate (ITPP), from cancer to cardiovascular disease. The human body is a highly aerobic organism, which needs large amount of oxygen, especially in tissues characterized by high metabolic demand, such as the heart. Inadequate oxygen delivery underlies cardiovascular diseases, such as coronary artery disease, heart failure and pulmonary hypertension. Hemoglobin, the oxygen-transport metalloprotein in the red blood cells, gives the blood enormous oxygen carrying capacity; thus oxygen binding to hemoglobin in the lungs and oxygen dissociation in the target tissues are crucial points for oxygen delivery as well as potential targets for intervention. Myo-inositol trispyrophosphate (ITPP) acts as an effector of hemoglobin, shifting the oxygen dissociation curve to the right and increasing oxygen release in the target tissues, especially under hypoxic conditions. ITPP has been successfully used in cancer studies, demonstrating anti-cancer properties due to prevention of tumor hypoxia. Currently it is being tested in phase 2 clinical trials in humans with various tumors. First preclinical evidence also indicates that it can successfully alleviate myocardial hypoxia and prevent adverse left ventricular and right ventricular remodeling in post-myocardial infarction heart failure and pulmonary hypertension. The aim of the article is to summarize the current knowledge on ITTP, as well as to determine the prospects for its potential use in the treatment of many cardiovascular disorders.

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Microneedles: One-Plane Bevel-Tipped Fabrication by 3D-Printing Processes. This article presents microneedles analyses where the design parameters studied included length and inner and outer diameter ranges. A mathematical model was also used to generalize outer and inner diameter ratios in the obtained ranges. Following this, the range of inner and outer diameters was completed by mechanical simulations, ranging from 30 μm to 134 μm as the inner diameter range and 208 μm to 250 μm as the outer diameter range. With these ranges, a mathematical model was made using fourth-order polynomial regressions with a correlation of 0.9993, ensuring a safety factor of four in which von Misses forces of the microneedle are around 17.931 MPa; the ANSYS software was used to analyze the mechanical behavior of the microneedles. In addition, the microneedle concept was made by 3D printing using a bio-compatible resin of class 1. The features presented by the microneedle designed in this study make it a promising option for implementation in a transdermal drug-delivery device.

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Affinity and Valence Impact the Extent and Symmetry of Phase Separation of Multivalent Proteins. Biomolecular self-assembly spatially segregates proteins with a limited number of binding sites (valence) into condensates that coexist with a dilute phase. We develop a many-body lattice model for a three-component system of proteins with fixed valence in a solvent. We compare the predictions of the model to experimental phase diagrams that we measure in vivo, which allows us to vary specifically a binding site's affinity and valency. We find that the extent of phase separation varies exponentially with affinity and increases with valency. Valency alone determines the symmetry of the phase diagram.

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High sorbic acid resistance of Penicillium roqueforti is mediated by the SORBUS gene cluster. Penicillium roqueforti is a major food-spoilage fungus known for its high resistance to the food preservative sorbic acid. Here, we demonstrate that the minimum inhibitory concentration of undissociated sorbic acid (MICu) ranges between 4.2 and 21.2 mM when 34 P. roqueforti strains were grown on malt extract broth. A genome-wide association study revealed that the six most resistant strains contained the 180 kbp gene cluster SORBUS, which was absent in the other 28 strains. In addition, a SNP analysis revealed five genes outside the SORBUS cluster that may be linked to sorbic acid resistance. A partial SORBUS knock-out (>100 of 180 kbp) in a resistant strain reduced sorbic acid resistance to similar levels as observed in the sensitive strains. Whole genome transcriptome analysis revealed a small set of genes present in both resistant and sensitive P. roqueforti strains that were differentially expressed in the presence of the weak acid. These genes could explain why P. roqueforti is more resistant to sorbic acid when compared to other fungi, even in the absence of the SORBUS cluster. Together, the MICu of 21.2 mM makes P. roqueforti among the most sorbic acid-resistant fungi, if not the most resistant fungus, which is mediated by the SORBUS gene cluster.

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Title/Abstract stringlengths 45 11.7k	T001 int64 0 1	T002 int64 0 1	T004 int64 0 1	T005 int64 0 1	T007 int64 0 1	T013 int64 0 1	T019 int64 0 1	T020 int64 0 1	T022 int64 0 1	T023 int64 0 1	T025 int64 0 1	T026 int64 0 1	T028 int64 0 1	T029 int64 0 1	T031 int64 0 1	T033 int64 0 1	T037 int64 0 1	T040 int64 0 1	T041 int64 0 1	T043 int64 0 1	T044 int64 0 1	T045 int64 0 1	T046 int64 0 1	T047 int64 0 1	T048 int64 0 1	T052 int64 0 1	T054 int64 0 1	T055 int64 0 1	T057 int64 0 1	T058 int64 0 1	T059 int64 0 1	T060 int64 0 1	T061 int64 0 1	T062 int64 0 1	T063 int64 0 1	T065 int64 0 1	T067 int64 0 1	T070 int64 0 1	T073 int64 0 1	T074 int64 0 1	T078 int64 0 1	T079 int64 0 1	T081 int64 0 1	T093 int64 0 1	T097 int64 0 1	T098 int64 0 1	T099 int64 0 1	T102 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	T125 int64 0 1	T126 int64 0 1	T129 int64 0 1	T130 int64 0 1	T131 int64 0 1	T168 int64 0 1	T170 int64 0 1	T184 int64 0 1	T191 int64 0 1	T192 int64 0 1	T196 int64 0 1	T197 int64 0 1	T201 int64 0 1	T204 int64 0 1
Immunohistochemical Demonstration of the pGlu79 α-Synuclein Fragment in Alzheimer's Disease and Its Tg2576 Mouse Model. The deposition of β-amyloid peptides and of α-synuclein proteins is a neuropathological hallmark in the brains of Alzheimer's disease (AD) and Parkinson's disease (PD) subjects, respectively. However, there is accumulative evidence that both proteins are not exclusive for their clinical entity but instead co-exist and interact with each other. Here, we investigated the presence of a newly identified, pyroglutamate79-modified α-synuclein variant (pGlu79-aSyn)-along with the enzyme matrix metalloproteinase-3 (MMP-3) and glutaminyl cyclase (QC) implicated in its formation-in AD and in the transgenic Tg2576 AD mouse model. In the human brain, pGlu79-aSyn was detected in cortical pyramidal neurons, with more distinct labeling in AD compared to control brain tissue. Using immunohistochemical double and triple labelings and confocal laser scanning microscopy, we demonstrate an association of pGlu79-aSyn, MMP-3 and QC with β-amyloid plaques. In addition, pGlu79-aSyn and QC were present in amyloid plaque-associated reactive astrocytes that were also immunoreactive for the chaperone heat shock protein 27 (HSP27). Our data are consistent for the transgenic mouse model and the human clinical condition. We conclude that pGlu79-aSyn can be generated extracellularly or within reactive astrocytes, accumulates in proximity to β-amyloid plaques and induces an astrocytic protein unfolding mechanism involving HSP27.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Trichomes on female reproductive tract: rapid diversification and underlying gene regulatory network in Drosophila suzukii and its related species. The ovipositors of some insects are external female genitalia, which have their primary function to deliver eggs. Drosophila suzukii and its sibling species D. subpulchrella are known to have acquired highly sclerotized and enlarged ovipositors upon their shifts in oviposition sites from rotting to ripening fruits. Inside the ovipositor plates, there are scale-like polarized protrusions termed "oviprovector scales" that are likely to aid the mechanical movement of the eggs. The size and spatial distribution of the scales need to be rearranged following the divergence of the ovipositors. In this study, we examined the features of the oviprovector scales in D. suzukii and its closely related species. We also investigated whether the scales are single-cell protrusions comprised of F-actin under the same conserved gene regulatory network as the well-characterized trichomes on the larval cuticular surface.	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Diversity, equity, and inclusion in nursing education: Strategies and processes to support inclusive teaching. Developing a climate for academic nursing that engages inclusive teaching requires the sustained effort of faculty and leadership. Nursing faculty engage inclusive teaching practices in the day-to-day learning environment, thereby training nurses and future leaders who are capable of addressing complex and diverse health care systems and population-centered needs. Actualizing the personal and professional commitment of faculty to inclusive teaching requires structure and strategies. This paper presents the use of multi-level institutional strategies and processes that supported faculty efforts to integrate DEI focused primarily on inclusive teaching into the curriculum at the University of Michigan School of Nursing. While best practices can vary by institution, we believe the institutional strategies, processes, lessons learned, and resources presented here can assist other academic institutions and nursing faculty as we all work to build a more inclusive nursing classroom and address systems and population-centered 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	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
Building Critical Care Capacity in a Low-Income Country. Critical illness is common throughout the world and is associated with high costs of care and resource intensity. The Corona virus disease 2019 (COVID-19) pandemic created a sudden surge of critically ill patients, which in turn led to devastating effects on health care systems worldwide and more so in Africa. This narrative report describes how an attempt was made at bridging the existing gaps in quality of care for critically ill patients at national and regional levels for COVID and the postpandemic era in a low income country.	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	0	0	0	0	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 healthcare approach can curb the increasing cases of cryptococcosis in Africa. Cryptococcosis is a neglected tropical infection and a major cause of morbidity and mortality, especially in HIV-positive persons in Africa. Efforts to manage HIV infection have not had any significant impact on the fatalities due to cryptococcosis. An integrated healthcare approach that includes universal care coverage for Africans, expanded national care guidelines to include CrAg screening for vulnerable groups in all African countries, collaborative research, infection surveillance, and data sharing within Africa will mark a turnaround point.	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Racial differences in circulating mitochondria-derived peptides may contribute to prostate cancer health disparities. The mitochondrial genome has small open reading frames (sORF) which produce measurable mitochondrial-derived peptides (MDPs), including humanin, SHLP2, and MOTS-c. Previously, among men undergoing prostate biopsy, we found higher serum SHLP2 was linked with lower prostate cancer (PC) risk in European American men (EAM), while null associations were found in African American men (AAM). Here, in different patients undergoing prostate biopsy, we tested the link between SHLP2, humanin and MOTS-c and PC risk by race.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Public awareness and use of 997 emergency medical service phone number during the COVID-19 pandemic. Emergency medical services (EMSs) are an important element of the healthcare system as it provides an opportunity to respond to critical medical conditions and save people's lives. In Saudi Arabia, EMS is offered via the EMS phone number "997" and mobile application "Asefny".	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	1	0	0	0	1	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
A temporal gradient of cytonuclear coordination of chaperonins and chaperones during RuBisCo biogenesis in allopolyploid plants. Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) has long been studied from many perspectives. As a multisubunit (large subunits [LSUs] and small subunits[SSUs]) protein encoded by genes residing in the chloroplast ( rbcL ) and nuclear ( rbcS ) genomes, RuBisCo also is a model for cytonuclear coevolution following allopolyploid speciation in plants. Here, we studied the genomic and transcriptional cytonuclear coordination of auxiliary chaperonin and chaperones that facilitate RuBisCo biogenesis across multiple natural and artificially synthesized plant allopolyploids. We found similar genomic and transcriptional cytonuclear responses, including respective paternal-to-maternal conversions and maternal homeologous biased expression, in chaperonin/chaperon-assisted folding and assembly of RuBisCo in different allopolyploids. One observation is about the temporally attenuated genomic and transcriptional cytonuclear evolutionary responses during early folding and later assembly process of RuBisCo biogenesis, which were established by long-term evolution and immediate onset of allopolyploidy, respectively. Our study not only points to the potential widespread and hitherto unrecognized features of cytonuclear evolution but also bears implications for the structural interaction interface between LSU and Cpn60 chaperonin and the functioning stage of the Raf2 chaperone.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Actinomycetospora soli sp. nov., isolated from the rhizosphere soil of Averrhoa carambola L. A novel actinobacterium, designated strain SF1 T , was isolated from the rhizosphere soil of a star fruit plant ( Averrhoa carambola L.) collected from Bangkok, Thailand, and its taxonomic position was evaluated. The strain showed morphological, chemotaxonomic and phylogenetic characteristics consistent with its classification in the genus Actinomycetospora . Strain SF1 T was an aerobic, Gram-stain-positive and non-motile actinobacterium. Growth occurred at 15-35 °C, at pH 4.0-12.0 and in the presence of 0-10 % (w/v) NaCl. The 16S rRNA gene sequence of strain SF1 T showed the highest similarity to Actinomycetospora chiangmaiensis YIM 0006 T (99.5 %), Actinomycetospora corticicola 014-5 T (98.8 %) and Actinomycetospora endophytica A-T 8314 T (98.8 %). The genome sequencing revealed a genome size of 6.52 Mbp and a DNA G+C content of 74.0 %. In addition, the average nucleotide identity values between strain SF1 T and reference strains, A. chiangmaiensis DSM 45062 T , A. corticicola DSM 45772 T and A. endophytica TBRC 5722 T , were found to be 86.1, 86.5 and 79.7 %, respectively, and the level of digital DNA-DNA hybridization between them were 32.4, 32.4 and 23.3 %, respectively. The whole-cell hydrolysates of strain SF1 T contained meso -diaminopimelic acid as the diagnostic diamino acid, with arabinose, galactose, glucose and ribose as whole-cell sugars. The predominant menaquinone was MK-8(H 4 ). Major cellular fatty acids were iso-C 16 : 0 and a summed feature consisting of C 16 : 1 ω6 c /C 16 : 1 ω7 c . Characterization based on chemotaxonomic, phylogenetic, phenotypic and genomic evidence demonstrated that strain SF1 T represents a novel species of the genus Actinomycetospora , for which the name Actinomycetospora soli sp. nov. is proposed. The type strain is strain SF1 T (=TBRC 15166 T = NBRC 115295 T ).	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Parenting sense of competence and its predictors among primiparous women: a longitudinal study in China. Parenting sense of competence significantly affects the quality of parenting behaviours and healthy infant development. However, primiparous women without parenting experience may lack confidence and feel stress. This study aimed to explore the status of parenting sense of competence and identify its predictors among primiparous women.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Activated partial thromboplastin time-based clot waveform analysis enables measurement of very low levels of factor IX activity in patients with severe hemophilia B. The precise measurement of very low levels of factor IX activity (FIX:C < 1 IU/dL) is essential for understanding clinical severity and risk of inhibitor development in patients with severe hemophilia B (Pw-SHB). However, such measurement sensitivity has not yet been achieved. We aimed to establish a measurement method using clot waveform analysis (CWA). Residual FIX:C by adding anti-FIX monoclonal antibody, FIX:C by adding recombinant (r)FIX to the commercial Pw-SHB plasmas, and FIX:C in our Pw-SHB were determined by CS-2000i ™ /CS-2400 ™ , followed by analysis of CWA parameters. The presence of anti-FIX antibody in the commercial Pw-SHB plasmas significantly decreased coagulation potential compared to its absence. The addition of rFIX to these innate plasma samples produced significant changes in three parameters upon adding FIX:C at 0.1-1 IU/dL, supporting the presence of trace FIX:C in Pw-SHB. Therefore, appropriate FIX-depleted plasma containing minimum residual FIX:C was chosen from reference curves of FIX:C (0.01-1 IU/dL). Among patients with untreated Pw-SHB, two had FIX:C 0.6-0.7 IU/dL and two had lower than detectable levels using FIX-depleted plasma. One of the latter had detectable trough levels post-rFIX administration. In conclusion, CWA enabled measurement of very low levels of FIX:C using appropriate FIX-deficient plasma.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Understanding Community Participation in Rural Health Care: A Participatory Learning and Action Approach. Community participation is one of the founding pillars of primary health care. However, due to various reasons, we are yet to achieve complete integration of this component into the health system functioning in India. The objective of our study was to do a formative assessment of community participation in a rural healthcare setting by adopting participatory learning action (PLA). technique. The study participants included frontline health workers and members from local governing institutions of rural areas. The study design is qualitative in nature with a participatory approach. A number of three PLA techniques have been used as a part of this study to recognize available resources for community participation, address its barriers and facilitators, and finally devise a time-line-based action plan. Based on the this, a conceptual framework for community participation pertaining to the rural healthcare system has been developed. This study highlights the importance of understanding the psychosocial aspects of community participation among various stakeholders involved in rural health care. Lessons learned from this PLA study will be helpful in the integration of community-based participatory approach within grassroot level healthcare planning and service delivery.	0	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	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
Development and internal validation of a risk model for hyperuricemia in diabetic kidney disease patients. This research aimed to identify independent risk factors for hyperuricemia (HUA) in diabetic kidney disease (DKD) patients and develop an HUA risk model based on a retrospective study in Ningbo, China.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The development of an automated machine learning pipeline for the detection of Alzheimer's Disease. Although Alzheimer's disease is the most prevalent form of dementia, there are no treatments capable of slowing disease progression. A lack of reliable disease endpoints and/or biomarkers contributes in part to the absence of effective therapies. Using machine learning to analyze EEG offers a possible solution to overcome many of the limitations of current diagnostic modalities. Here we develop a logistic regression model with an accuracy of 81% that addresses many of the shortcomings of previous works. To our knowledge, no other study has been able to solve the following problems simultaneously: (1) a lack of automation and unbiased removal of artifacts, (2) a dependence on a high level of expertise in data pre-processing and ML for non-automated processes, (3) the need for very large sample sizes and accurate EEG source localization using high density systems, (4) and a reliance on black box ML approaches such as deep neural nets with unexplainable feature selection. This study presents a proof-of-concept for an automated and scalable technology that could potentially be used to diagnose AD in clinical settings as an adjunct to conventional neuropsychological testing, thus enhancing efficiency, reproducibility, and practicality of AD diagnosis.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
A new prognostic marker in patients undergoing Hartmann's procedure for acute tumoral obstruction of the left colon. In acute obstructive left-sided colorectal cancers (AOLCRC), damage to the colon wall may occur as a result of distension of the colon segments proximal to the tumor. In this study, we aimed to evaluate the relationship between the ratio of dilated colon diameter (CD) to lumbar vertebral corpus diameter on preoperative abdominal computed tomography (CT) scan in patients undergoing Hartmann's Procedure (HP) and post-operative complications.	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0
Endocrine modulation of primary chemosensory neurons regulates Drosophila courtship behavior. The decision to engage in courtship depends on external cues from potential mates and internal cues related to maturation, health, and experience. Hormones allow for coordinated conveyance of such information to peripheral tissues. Here, we show Ecdysis-Triggering Hormone (ETH) is critical for courtship inhibition after completion of copulation in Drosophila melanogaster. ETH deficiency relieves post-copulation courtship inhibition (PCCI) and increases male-male courtship. ETH appears to modulate perception and attractiveness of potential mates by direct action on primary chemosensory neurons. Knockdown of ETH receptor (ETHR) expression in GR32A-expressing neurons leads to reduced ligand sensitivity and elevated male-male courtship. We find OR67D also is critical for normal levels of PCCI after mating. ETHR knockdown in OR67D-expressing neurons or GR32A-expressing neurons relieves PCCI. Finally, ETHR silencing in the corpus allatum (CA), the sole source of juvenile hormone, also relieves PCCI; treatment with the juvenile hormone analog methoprene partially restores normal post-mating behavior. We find that ETH, a stress-sensitive reproductive hormone, appears to coordinate multiple sensory modalities to guide Drosophila male courtship behaviors, especially after mating.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1
The future of long-acting agents for preexposure prophylaxis. The main reason for the failure of oral preexposure prophylaxis (PrEP) regimens for HIV is poor adherence. Intramuscular cabotegravir was recently approved for PrEP, and a number of other long-acting antiretroviral formulations and products are currently in clinical development. This includes subcutaneous and intravenous injections, implants, and microarray (microneedle) patches, as well as extended duration oral drugs. The success and future uptake of these products will depend on a variety of factors.	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	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
Aseptic meningitis in multisystem inflammatory syndrome in children associated with coronavirus disease 2019: a case report. As the coronavirus disease 2019 infections are still ongoing, there is an increasing number of case reports and case series with various manifestations of life-threatening multisystem inflammatory syndrome in children . Our case aims to remind all providers to scrutinize for clinical manifestations, including neurological symptoms, which may mimic aseptic meningitis.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Effect of Protein-Protein Interactions on Translational Diffusion of Spheroidal Proteins. One of the commonly accepted approaches to estimate protein-protein interactions (PPI) in aqueous solutions is the analysis of their translational diffusion. The present review article observes a phenomenological approach to analyze PPI effects via concentration dependencies of self- and collective translational diffusion coefficient for several spheroidal proteins derived from the pulsed field gradient NMR (PFG NMR) and dynamic light scattering (DLS), respectively. These proteins are rigid globular α-chymotrypsin (ChTr) and human serum albumin (HSA), and partly disordered α-casein (α-CN) and β-lactoglobulin (β-Lg). The PPI analysis enabled us to reveal the dominance of intermolecular repulsion at low ionic strength of solution (0.003-0.01 M) for all studied proteins. The increase in the ionic strength to 0.1-1.0 M leads to the screening of protein charges, resulting in the decrease of the protein electrostatic potential. The increase of the van der Waals potential for ChTr and α-CN characterizes their propensity towards unstable weak attractive interactions. The decrease of van der Waals interactions for β-Lg is probably associated with the formation of stable oligomers by this protein. The PPI, estimated with the help of interaction potential and idealized spherical molecular geometry, are in good agreement with experimental data.	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	1	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Effect of CB2 Stimulation on Gene Expression in Pediatric B-Acute Lymphoblastic Leukemia: New Possible Targets. Acute lymphoblastic leukemia type B (B-ALL) is the most common kind of pediatric leukemia, characterized by the clonal proliferation of type B lymphoid stem cells. Important progress in ALL treatments led to improvements in long-term survival; nevertheless, many adverse long-term consequences still concern the medical community. Molecular and cellular target therapies, together with immunotherapy, are promising strategies to overcome these concerns. Cannabinoids, enzymes involved in their metabolism, and cannabinoid receptors type 1 (CB1) and type 2 (CB2) constitute the endocannabinoid system, involved in inflammation, immune response, and cancer. CB2 receptor stimulation exerts anti-proliferative and anti-invasive effects in many tumors. In this study, we evaluated the effects of CB2 stimulation on B-ALL cell lines, SUP-B15, by RNA sequencing, Western blotting, and ELISA. We observe a lower expression of CB2 in SUP-B15 cells compared to lymphocytes from healthy subjects, hypothesizing its involvement in B-ALL pathogenesis. CB2 stimulation reduces the expression of CD9 , SEC61G , TBX21, and TMSB4X genes involved in tumor growth and progression, and also negatively affects downstream intracellular pathways. Our findings suggest an antitumor role of CB2 stimulation in B-ALL, and highlight a functional correlation between CB2 receptors and specific anti-tumoral pathways, even though further investigations are needed.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
FedMSA: A Model Selection and Adaptation System for Federated Learning. Federated Learning (FL) enables multiple clients to train a shared model collaboratively without sharing any personal data. However, selecting a model and adapting it quickly to meet user expectations in a large-scale FL application with heterogeneous devices is challenging. In this paper, we propose a model selection and adaptation system for Federated Learning (FedMSA), which includes a hardware-aware model selection algorithm that trades-off model training efficiency and model performance base on FL developers' expectation. Meanwhile, considering the expected model should be achieved by dynamic model adaptation, FedMSA supports full automation in building and deployment of the FL task to different hardware at scale. Experiments on benchmark and real-world datasets demonstrate the effectiveness of the model selection algorithm of FedMSA in real devices (e.g., Raspberry Pi and Jetson nano).	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Sharing resources to advance translational research. The publication of Resource articles is essential for the dissemination of novel, or substantially enhanced, tools, techniques, disease models, datasets and resources. By sharing knowledge and resources in a globally accessible manner, we can support human disease research to accelerate the translation of fundamental discoveries to effective treatments or diagnostics for diverse patient populations. To promote and encourage excellence in Resource articles, Disease Models & Mechanisms (DMM) is launching a new 'Outstanding Resource Paper Prize'. To celebrate this, we highlight recent outstanding DMM Resource articles that have the ultimate goal of benefitting of human health.	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
[Clinical effect of fetal reduction by intracranial and intrathoracic KCl injection]. To evaluate the feasibility and effectiveness of fetal reduction by transabdominal intracranial KCl injection for multifetal pregnancies in the early second trimester.	0	0	0	0	0	0	0	0	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	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
Exploring the coating of 3D-printed insulating substrates with conductive composites: a simple, cheap and versatile strategy to prepare customized high-performance electrochemical sensors. The development of 3D-printed electrochemical sensors by fused deposition modeling (FDM) has been increasing exponentially in the last five years. In this context, commercial conductive filaments composed of a blend of carbon particles ( e.g. , graphene or carbon black (CB)) and insulating thermoplastic polymers ( e.g. , polylactic acid (PLA) or acrylonitrile butadiene styrene (ABS)) have been widely used for electrode fabrication. However, such materials may be expensive and the electrodes when used "as-printed" exhibit poor electrochemical performance as a function of the low content of conductive particles in the composition (∼10 to 20 wt%), which requires one or more post-treatment steps ( e.g. polishing, chemical, electrochemical, and photochemical) to reach good electrochemical performance. In this technical note a less used approach to produce "ready-to-use" electrochemical platforms based on 3D printing is explored, which consists of the coating of 3D-printed insulating substrates with homemade conductive composites. To demonstrate the potentiality of this alternative protocol, 3D-printed ABS insulating substrates at two geometries were coated in a highly loaded graphite (55 wt%) homemade composite (G-ABS) and evaluated for the detection of the ferri/ferrocyanide redox probe and model analytes in stationary and hydrodynamic 3D-printed systems (nitrite in micro-flow injection analysis/μFIA and paracetamol in batch injection analysis/BIA, respectively). The analytical parameters acquired with the coated electrodes were comparable to those obtained using conventional electrodes (glassy carbon, boron-doped diamond and carbon screen-printed) and 3D-printed sensors fabricated with commercial filaments. Moreover, the inclusion of carbon black in the fluid conductive composite was demonstrated as a perspective to obtain modified coated 3D-printed surfaces easily for the first time. This alternative "do it yourself" strategy is promising for the large-scale production of very cheap (US$ 0.08) and high-performance electrodes based on FDM 3D printing. Moreover, this approach dispenses the acquisition of commercial conductive filaments and the laborious development of homemade filaments.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0	0	1	0	0	0
Prevalence, co-morbidities, and in-hospital mortality of patients hospitalized with alcohol-associated hepatitis in the United States from 2015 to 2019. The goals of our study are to determine the most recent trends in hospitalization, mortality, and healthcare utilization among hospitalized patients with alcohol-associated hepatitis (AH) in the United States.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Early-life residential exposure to moisture damage is associated with persistent wheezing in a Finnish birth cohort. Moisture damage increases the risk for respiratory disorders in childhood. Our aim was to determine whether early age residential exposure to inspector-observed moisture damage or mold is associated with different wheezing phenotypes later in childhood.	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
An Unusual U2AF2 Inhibits Splicing and Attenuates the Virulence of the Human Protozoan Parasite Entamoeba histolytica . E. histolytica is the etiological agent of intestinal amebiasis and liver abscesses, which still poses public health threat globally. Metronidazole is the drug of choice against amebiasis. However, metronidazole-resistant amoebic clinical isolates and strains have been reported recently, challenging the efforts for amebiasis eradication. In search of alternative treatments, E. histolytica transcriptomes have shown the association of genes involved in RNA metabolism with the virulence of the parasite. Among the upregulated genes in amoebic liver abscesses are the splicing factors EhU2AF2 and a paralog of EhSF3B1. For this reason and because EhU2AF2 contains unusual KH-QUA2 (84KQ) motifs in its lengthened C-terminus domain, here we investigated how the role of EhU2AF2 in pre-mRNA processing impacts the virulence of the parasite. We found that 84KQ is involved in splicing inhibition/intron retention of several virulence and non-virulence-related genes. The 84KQ domain interacts with the same domain of the constitutive splicing factor SF1 (SF1KQ), both in solution and when SF1KQ is bound to branchpoint signal RNA probes. The 84KQ-SF1KQ interaction prevents splicing complex E to A transition, thus inhibiting splicing. Surprisingly, the deletion of the 84KQ domain in EhU2AF2 amoeba transformants increased splicing and enhanced the in vitro and in vivo virulence phenotypes. We conclude that the interaction of the 84KQ and SF1KQ domains, probably involving additional factors, tunes down Entamoeba virulence by favoring intron retention.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Pollinator and floral odor specificity among four synchronopatric species of Ceropegia (Apocynaceae) suggests ethological isolation that prevents reproductive interference. Possession of flowers that trap fly pollinators is a conservative trait within the genus Ceropegia, in which pollination systems can be generalized or highly specialized. However, little is known about the role of plant-pollinator interactions in the maintenance of species boundaries. This study examined the degree of plant-pollinator specialization and identified the parameters responsible for specificity among four co-occurring Ceropegia species with overlapping flowering times. All investigated plant species were functionally specialized on pollination by Chloropidae and/or Milichiidae flies and each Ceropegia species was, in turn, ecologically highly specialized on only two pollinating fly morphospecies, though one plant species appeared more generalist. Species-specific fly attraction was due to the differences between plant species in floral scents, floral morphology, colour patterns, and presence of other functional structures, e.g., vibratile trichomes, which were shown to contribute to pollinator attraction in one study species. The combination of these olfactory and visual cues differentially influenced pollinator preferences and thus hindered heterospecific visitation. Furthermore, a pollinator exchange experiment also highlighted that species integrity is maintained through efficient ethological isolation (pollinator attraction). The mechanical isolation mediated by the fit between floral morphology and size and/or shape of fly pollinators appears less pronounced here, but whether or not the morphological match between male (pollinium) and female (guide rails) reproductive organs can impede hybridization remains to be investigated.	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	0	1
Microdomain Protein Nce102 Is a Local Sensor of Plasma Membrane Sphingolipid Balance. Sphingolipids are essential building blocks of eukaryotic membranes and important signaling molecules that are regulated tightly in response to environmental and physiological inputs. While their biosynthetic pathway has been well-described, the mechanisms that facilitate the perception of sphingolipid levels at the plasma membrane remain to be uncovered. In Saccharomyces cerevisiae, the Nce102 protein has been proposed to function as a sphingolipid sensor as it changes its plasma membrane distribution in response to sphingolipid biosynthesis inhibition. We show that Nce102 redistributes specifically in regions of increased sphingolipid demand, e.g., membranes of nascent buds. Furthermore, we report that the production of Nce102 increases following sphingolipid biosynthesis inhibition and that Nce102 is internalized when excess sphingolipid precursors are supplied. This finding suggests that the total amount of Nce102 in the plasma membrane is a measure of the current need for sphingolipids, whereas its local distribution marks sites of high sphingolipid demand. The physiological role of Nce102 in the regulation of sphingolipid synthesis is demonstrated by mass spectrometry analysis showing reduced levels of hydroxylated complex sphingolipids in response to heat stress in the nce102 Δ deletion mutant. We also demonstrate that Nce102 behaves analogously in the widespread human fungal pathogen Candida albicans, suggesting a conserved principle of local sphingolipid control across species. IMPORTANCE Microorganisms are challenged constantly by their rapidly changing environment. To survive, they have developed diverse mechanisms to quickly perceive stressful situations and adapt to them appropriately. The primary site of both stress sensing and adaptation is the plasma membrane. We identified the yeast protein Nce102 as a marker of local sphingolipid levels and fluidity in the plasma membrane. Nce102 is an important structural and functional component of the membrane compartment Can1 (MCC), a plasma membrane microdomain stabilized by a large cytosolic hemitubular protein scaffold, the eisosome. The MCC/eisosomes are widely conserved among fungi and unicellular algae. To determine if Nce102 carries out similar functions in other organisms, we analyzed the human fungal pathogen Candida albicans and found that Nce102 responds to sphingolipid levels also in this organism, which has potential applications for the development of novel therapeutic approaches. The presented study represents a valuable model for how organisms regulate plasma membrane sphingolipids.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Exploring Structure-Sensitive Relations for Small Species Adsorption Using Machine Learning. Accurate prediction of adsorption energies on heterogeneous catalyst surfaces is crucial to predicting reactivity and screening materials. Adsorption linear scaling relations have been developed extensively but often lack accuracy and apply to one adsorbate and a single binding site type at a time. These facts undermine their ability to predict structure sensitivity and optimal catalyst structure. Using machine learning on nearly 300 density functional theory calculations, we demonstrate that generalized coordination number scaling relations hold well for oxygen- and high-valency carbon-binding species but fail for others. We reveal that the valency and the electronic coupling of a species with the surface, along with the site type and its coordination environment, are critical for small species adsorption. The model simultaneously predicts the adsorption energy and preferred site and significantly outperforms linear scalings in accuracy. It can expose the structure sensitivity of chemical reactions and enable enhanced catalyst activity via engineering particle shape and facet defects. The generality of our methodology is validated by training the model with transition metal data and transferring it to predict adsorption energies on single-atom alloys.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1	0	0
Using Vis-NIR Spectroscopy for Predicting Quality Compounds in Foods. Over the past four decades, near-infrared reflectance spectroscopy (NIRS) has become one of the most attractive and used technique for analysis as it allows for fast and simultaneous qualitative and quantitative characterization of a wide variety of food samples [...].	0	0	0	0	0	0	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	1	0	0	0	0	0	0	0	0
A comprehensive evaluation of polygenic score and genotype imputation performances of human SNP arrays in diverse populations. Regardless of the overwhelming use of next-generation sequencing technologies, microarray-based genotyping combined with the imputation of untyped variants remains a cost-effective means to interrogate genetic variations across the human genome. This technology is widely used in genome-wide association studies (GWAS) at bio-bank scales, and more recently, in polygenic score (PGS) analysis to predict and stratify disease risk. Over the last decade, human genotyping arrays have undergone a tremendous growth in both number and content making a comprehensive evaluation of their performances became more important. Here, we performed a comprehensive performance assessment for 23 available human genotyping arrays in 6 ancestry groups using diverse public and in-house datasets. The analyses focus on performance estimation of derived imputation (in terms of accuracy and coverage) and PGS (in terms of concordance to PGS estimated from whole-genome sequencing data) in three different traits and diseases. We found that the arrays with a higher number of SNPs are not necessarily the ones with higher imputation performance, but the arrays that are well-optimized for the targeted population could provide very good imputation performance. In addition, PGS estimated by imputed SNP array data is highly correlated to PGS estimated by whole-genome sequencing data in most cases. When optimal arrays are used, the correlations of PGS between two types of data are higher than 0.97, but interestingly, arrays with high density can result in lower PGS performance. Our results suggest the importance of properly selecting a suitable genotyping array for PGS applications. Finally, we developed a web tool that provides interactive analyses of tag SNP contents and imputation performance based on population and genomic regions of interest. This study would act as a practical guide for researchers to design their genotyping arrays-based studies. The tool is available at: https://genome.vinbigdata.org/tools/saa/ .	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	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
Evaluation of Three Clinical Prediction Tools to Predict Mortality in Hospitalized Patients with Lassa Fever. Lassa fever is a viral hemorrhagic illness with a case fatality rate for hospitalized patients as high as 69%. Identifying cases before they progress to serious illness can lead to earlier treatment and improved clinical outcomes. Three existing clinical prediction tools were evaluated on their ability to predict the in-hospital mortality in Lassa fever: the quick Sequential Organ Failure Assessment (qSOFA), the Modified Early Warning System (MEWS), and the Universal Vital Assessment (UVA). This was a retrospective cohort study of patients admitted to the dedicated Lassa fever ward of the Kenema Government Hospital in Sierra Leone between May 2013 and December 2019. Data among three serology groups were analyzed: Lassa antigen-positive (Ag+) regardless of IgM status, Lassa Ag- and IgM+, and Lassa Ag- and IgM- cases. There were 123 cases of suspected Lassa fever included in this study. Abnormalities in respiratory rate, oxygenation status, mental status, and serum markers of kidney and liver dysfunction were more likely seen in the Ag+ group, which had an in-hospital mortality of 85.7%. For the Lassa Ag+ group, the sensitivity and positive predictive value of qSOFA ≥ 2 was 70.6% and 92.3%, MEWS ≥ 5 was 96.9% and 86.1%, and UVA ≥ 5 was 60.0% and 100.0%. The MEWS and UVA scores show potential for use in Lassa fever, but there is opportunity for future development of a tool that includes the clinical and laboratory markers specific to Lassa fever.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Neural Network Based on Health Monitoring Electrical Equipment Fault and Biomedical Diagnosis. In order to improve the accuracy of electrical equipment failure diagnosis and keep electrical equipment operating safely and efficiently, this paper proposes to design an electrical equipment failure diagnosis system based on a neural network, analyze the faults of electrical equipment and their causes, and establish knowledge base according to relevant data and expert judgment. The fault knowledge base was introduced into the neural network operation structure, and the fault diagnosis results were classified step by step through multiple subnetworks. In data preprocessing, in order to avoid the redundancy of primary fault information features, the principal component heuristic attribute reduction algorithm was used to select the fault data samples optimally. The neural network learning algorithm is used to calculate the forward direction and error rate of the initial error data, and the reliability function is used to optimize the initial weight threshold of the neural network, propagating the error backwards and high. Experimental results show that adding attribute reduction improves error classification performance, avoids the problem of local minima through neural network operation, and has fewer iteration steps, lower average error, and higher accuracy of fault diagnosis, reaching 95.6%.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Main Retailers In Which Mexican Households Acquire Their Food Supply. To describe the frequency of food and beverages purchased made by Mexican households at different types of grocery retailers.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	1	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
[Chronic diarrhea caused by a novel mutation of STAT3 gene in a child]. 6月龄患儿以腹泻、呕吐起病，临床表现为排稀水样便并次数增多，营养不良，双肾多发结石，胃肠镜示慢性浅表性胃窦炎、慢性结肠炎，十二指肠降段黏膜病理示固有层多量淋巴细胞、浆细胞浸润伴绒毛萎缩。全外显子测序发现STAT3基因c.1516G>A（p.E506K）杂合错义突变，为自发变异。该突变未曾见报道，可能是儿童慢性腹泻新发致病突变。该患儿改无乳糖深度水解配方喂养及对症支持治疗后排便正常，体重逐渐增加，双肾结石变小。.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0	0
Mechanistic insights on novel small molecule allosteric activators of cGMP-dependent protein kinase PKG1α. cGMP-dependent protein kinase (PKG) represents a compelling drug target for treatment of cardiovascular diseases. PKG1 is the major effector of beneficial cGMP signaling which is involved in smooth muscle relaxation and vascular tone, inhibition of platelet aggregation and signaling that leads to cardioprotection. In this study, a novel piperidine series of activators previously identified from an ultrahigh-throughput screen were validated to directly bind partially activated PKG1α and subsequently enhance its kinase activity in a concentration-dependent manner. Compounds from initial optimization efforts showed an ability to activate PKG1α independent of the endogenous activator, cGMP. We demonstrate these small molecule activators mimic the effect of cGMP on the kinetic parameters of PKG1α by positively modulating the K M of the peptide substrate and negatively modulating the apparent K M for ATP with increase in catalytic efficiency, k cat . In addition, these compounds also allosterically modulate the binding affinity of cGMP for PKG1α by increasing the affinity of cGMP for the high-affinity binding site (CNB-A) and decreasing the affinity of cGMP for the low-affinity binding site (CNB-B). We show the mode of action of these activators involves binding to an allosteric site within the regulatory domain, near the CNB-B binding site. To the best of our knowledge, these are the first reported non-cGMP mimetic small molecules shown to directly activate PKG1α. Insights into the mechanism of action of these compounds will enable future development of cardioprotective compounds that function through novel modes of action for the treatment of cardiovascular diseases.	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	1	1	1	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Food web and metabolic interactions of the lung inhabitants Streptococcus pneumoniae and Pseudomonas aeruginosa. Bacteria that successfully adapt to different substrates and environmental niches within the lung and overcome the immune defence can cause serious lung infections. Such infections are generally complex, and recognized as polymicrobial in nature. Both Pseudomonas aeruginosa and Streptococcus pneumoniae can cause chronic lung infections and were both detected in cystic fibrosis (CF) lung at different stages. In this study, single and dual species cultures of Pseudomonas aeruginosa and Streptococcus pneumoniae were studied under well-controlled planktonic growth conditions. Under pH-controlled conditions, both species apparently benefited from the presence of the other. In co-culture with P. aeruginosa, S. pneumoniae grew efficiently under aerobic conditions, whereas in pure S. pneumoniae culture, growth inhibition occurred in bioreactors with dissolved oxygen concentrations above the microaerobic range. Lactic acid and acetoin that are produced by S. pneumoniae were efficiently utilized by P. aeruginosa. In pH-uncontrolled co-cultures, the low pH triggered by S. pneumoniae assimilation of glucose and lactic acid production negatively affected the growth of both strains. Nevertheless, ammonia production improved significantly, and P. aeruginosa growth dominated at later growth stages. This study revealed unreported metabolic interactions of two important pathogenic microorganisms and shed new lights into pathophysiology of bacterial lung infection.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
The Moral Significance of Aesthetics in Nature Imagery. To solicit support for nature and wildlife conservation, mission-driven organizations rely on professional nature and wildlife imagery in their media outlets and campaigns. We investigated whether-and if so, why-the aesthetics of images increase social media engagement (e.g., number of likes) and the extent to which images elicit moral concern for nature and wildlife. In Study 1 ( N = 782 U.S. adults), we trained a neural network to predict image aesthetics in National Geographic's Instagram data and identified image-specific attributes that influence aesthetics. We found that image aesthetics predicted engagement with the Instagram posts. In Study 2 ( N = 775 U.S. adults), we established the causal effect of aesthetics on engagement and moral concern, which is explained by self-transcendent emotions (awe and inspiration) and purity associated with an image. Study 3 ( N = 406 U.S. adults) replicated the results, showing that our key effects were stronger for individuals who place higher importance on beauty. By demonstrating the moral significance of image aesthetics, we highlight the potential of the beauty of nature to invigorate global conservation efforts.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Plastics are a new threat to Palau's coral reefs. Plastic pollution of the oceans has long been an ongoing and growing problem. Single-use plastic (plastic bags and microbeads) is responsible for most of this pollution. In recent years, studies have highlighted the importance of the size of plastic particles, and the impact of this pollution source on the environment. We determined the concentration of small marine plastics in seawater, sediments and beach sand around a pristine reef area (Republic of Palau) using very simple tools (plankton net, sieves, organic matter degradation, density separation, Nile red fluorochrome). In this study, we succeeded in detecting microplastic (MPs) particles and microplastic fibers, but also nanoplastic (NPs). These three types of particles were found in all samples with a large heterogeneity, from 0.01 to 0.09 particles L-1 and 0.17 to 32.13 particles g-1 DW for MPs in seawater, sediments and sand, respectively. Even when NPs were identified, the amounts of NPs were underestimated and varied from 0.09 to 0.43 particles L-1 in seawater and from 1.08 to 71.02 particles g-1 DW in sediment and sand, respectively. These variations could be attributed to the environmental characteristics of the different sites. This study shows that plastic pollution must be considered in environmental studies even in the most pristine locations. It also shows that NPs pollution is related to the amount of MPs found at the sites. To understand the effects of this plastic pollution, it is necessary that the next toxicological studies take into account the effects of this fraction that makes up the NPs.	0	0	0	0	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Advances in encapsulating gonadotropin-releasing hormone agonists for controlled release: a review. Gonadotropin-releasing hormone (GnRH) agonists are peptides consisting of nine or ten amino acid residues. GnRH agonists have been applied in the therapy of sexual hormone disorders like prostate cancer, endometriosis, uterine myoma, central precious puberty, and in-vitro fertility. Treatment is achieved by continuous hormone intake and long-term agonists administration, which is usually associated with poor patient compliance. Because GnRH agonists that are administered with the parenteral route are broken down by peptidase, their half-life is short. As a result, developing sustained release for the drug delivery system is significant. Even though some drugs have been successfully delivered with long-acting release microspheres and approved by the Food and Drug Administration (FDA), some challenges remain. This review highlighted current approaches to encapsulate GnRH agonists into delivery systems and strategies encountered during the loading process. Moreover, the following sections provide strategies to improve the release profile, and animal and human studies were summarised.	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	1	1	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Common and unique neural activities in subclinical depression and major depressive disorder indicate the development of brain impairments in different depressive stages. Subclinical depression (SD) and major depressive disorder (MDD) can be considered as the early and late stages of depression, but the characteristics of intrinsic neural activity in different depressive stages are largely unknown.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Identification and Antibiotic Susceptibility of Eggerthella lenta in Bloodstream Infections. The identification and antibiotic susceptibility of two clinical isolates of Eggerthella lenta from bloodstream infections were determined. This microorganism is rarely pathogenic, and the findings are presented here to promote the detection and awareness of this infection. The bacteria were obtained from one patient with pressure sores and another with a malignant gastric tumor. Smears were prepared, stained, and examined by microscopy. Single colonies were analyzed by Gram staining, MALDI-TOF MS, and the 16S rRNA gene sequencing. Antibiotic sensitivity was assessed by the agar dilution method. The bacilli were found to be Gram-positive, and the MS results showed 99.8% homology with E. lenta . It was confirmed by gene sequencing. Antibiotic susceptibility tests demonstrated that E. lenta was sensitive to piperacillin-tazobactam, ampicillin-sulbactam, imipenem, meropenem, metronidazole, clindamycin, and vancomycin. This study could increase awareness of this rare infection.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells. SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy is only moderate, and improved treatment strategies are urgently needed. To accomplish this goal, we devised a strategy to identify compounds that act synergistically with remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput screening in the presence of submaximal remdesivir concentrations, using a human lung epithelial cell line infected with a clinical isolate of SARS-CoV-2. This identified 20 approved drugs that act synergistically with remdesivir, many with favorable pharmacokinetic and safety profiles. Strongest effects were observed with established antivirals, Hepatitis C virus nonstructural protein 5A (HCV NS5A) inhibitors velpatasvir and elbasvir. Combination with their partner drugs sofosbuvir and grazoprevir further increased efficacy, increasing remdesivir's apparent potency > 25-fold. We report that HCV NS5A inhibitors act on the SARS-CoV-2 exonuclease proofreader, providing a possible explanation for the synergy observed with nucleoside analog remdesivir. FDA-approved Hepatitis C therapeutics Epclusa® (velpatasvir/sofosbuvir) and Zepatier® (elbasvir/grazoprevir) could be further optimized to achieve potency and pharmacokinetic properties that support clinical evaluation in combination with remdesivir.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hondrosarcoma of the chest with intraabdominal distribution (case report). A rare clinical observation of chondrosarcoma metastasis into the abdominal cavity with a specific metastatic ascitic fluid is presented. Chondrosarcomas that occur as a result of malignant transformation of benign chondroma are quite rare. Even less often in the literature, cases of chondrosarcoma metastases are described, especially in a peritoneum with the presence of metastatic ascites. The article describes a case of metastatic ascites in a 38-year old patient with chondrosarcoma, which developed against the background of previously resected rib chords. The article describes the cytological signs of chondrosarcoma in ascitic fluid.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Metformin alleviates neurocognitive impairment in aging via activation of AMPK/BDNF/PI3K pathway. Slowing down age-related neurocognitive impairment has been a challenge. We evaluated the therapeutic effects of metformin in D-galactose-induced aging. Additionally, we studied the potential molecular mechanisms that could be responsible for metformin's anti-aging effects. Thirty male rats were equally divided into: 1-control group, which received saline solution, 2-D-galactose (D-gal) group, which received D-galactose (100 mg/kg/day) by gastric lavage for eight weeks, and 3-D-galactose + Metformin (D-gal + Met) treated group, which received D-galactose + metformin (200 mg/kg/day) by gastric lavage for eight weeks. Neurocognitive assessment was done. Measurement of inflammatory, oxidative stress, and BDNF biomarkers was performed. AMPK and PI3K genes expression were assessed. Hippocampal tissues were dissected for histopathological and immunohistochemical studies. D-gal resulted in neurocognitive impairments, elevation of inflammatory biomarkers, altered oxidative stress markers, decreased BDNF, decreased expression of synaptophysin and Bcl2 with increased expression of Caspase-3, and down-regulation of AMPK and PI3K genes. Neurodegenerative changes were present in the hippocampus. Metformin restored significantly D-gal induced neurodegenerative changes. We concluded that metformin could alleviate age-induced neurocognitive deficit via amelioration of neuroinflammation, attenuation of oxidative stress, reduction of apoptosis, as well as promotion of synaptic plasticity. These mechanisms could be mediated via the activation of the AMPK/BDNF/PI3K pathway.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Exclusive breastmilk pumping: A concept analysis. To analyze and examine the concept of exclusive breast pumping (EP).	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	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
Design of SARS-CoV-2 Main Protease Inhibitors Using Artificial Intelligence and Molecular Dynamic Simulations. Drug design is a time-consuming and cumbersome process due to the vast search space of drug-like molecules and the difficulty of investigating atomic and electronic interactions. The present paper proposes a computational drug design workflow that combines artificial intelligence (AI) methods, i.e., an evolutionary algorithm and artificial neural network model, and molecular dynamics (MD) simulations to design and evaluate potential drug candidates. For the purpose of illustration, the proposed workflow was applied to design drug candidates against the main protease of severe acute respiratory syndrome coronavirus 2. From the ∼140,000 molecules designed using AI methods, MD analysis identified two molecules as potential drug candidates.	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	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
Universal or Personalized Mesenchymal Stem Cell Therapies: Impact of Age, Sex, and Biological Source. Mesenchymal stem/stromal cells (MSCs) hold great promise for the treatment of autoimmune conditions given their immunomodulatory properties. Based on the low immunogenicity of MSCs, it is tempting to consider the expansion of MSCs from a "universal donor" in culture prior to their allogeneic applications for immediate care. This raises the critical question of the criteria we should use to select the best "universal donor". It is also imperative we compare the "universal" approach with a "personalized" one for clinical value. In addition to the call for MHC-matching, recent studies suggest that factors including age, sex, and biological sources of MSCs can have significant impact on therapy outcome. Here, we will review findings from these studies, which shed light on the variables that can guide the important choice of "universal" or "personalized" MSC therapy for autoimmune diseases.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Biochemical and molecular responses of Rosa damascena mill. cv. Kashan to salicylic acid under salinity stress. Today, salinity stress is one of the most important abiotic stresses in the world, because it causes damage to many agricultural products and reduces their yields. Oxidative stress causes tissue damages in plants, which occurs with the production of reactive oxygen species (ROS) when plants are exposed to environmental stresses such as salinity. Today, it is recommended to use compounds that increase the resistance of plants to environmental stresses and improve plant metabolic activities. Salicylic acid (SA), as an intracellular and extracellular regulator of the plant response, is known as one of these effective compounds. Damask rose (Rosa damascena Mill.) is a medicinal plant from the Rosaceae, and its essential oils and aromatic compounds are used widely in the cosmetic and food industries in the world. Therefore, considering the importance of this plant from both medicinal and ornamental aspects, for the first time, we investigated one of the native cultivars of Iran (Kashan). Since one of the most important problems in Damask rose cultivation is the occurrence of salinity stress, for the first time, we investigated the interaction of several levels of NaCl salinity (0, 4, 8, and 12 ds m - 1 ) with SA (0, 0.5, 1, and 2 mM) as a stress reducer.	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Systematic review on active treatment for urinary fistula after partial nephrectomy. Urinary fistula is expected to become more frequent in urological practice as a result of expanding indication of partial nephrectomy given it's oncological results equivalent to those of radical nephrectomy but at a lower risk of progression to chronic kidney disease, lower cardiovascular morbidity, and overall mortality.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Digest: Recent movement of a flicker hybrid zone. What biotic and abiotic factors drive hybrid zone movement? By resampling a classic hybrid zone between two subspecies of woodpeckers, Aguillon and Rohwer documented a westward shift that may be attributed to changes in land use or climate. These findings highlight the increasing influence of anthropogenic activities on hybridization events.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Genome-Based Assessment of Antimicrobial Resistance and Virulence Potential of Isolates of Non-Pullorum/Gallinarum Salmonella Serovars Recovered from Dead Poultry in China. Paratyphoid avian salmonellosis is considered one of the leading causes of poultry death, resulting in significant economic losses to poultry industries worldwide. In China, especially in Shandong province, the leading producer of poultry products, several recurrent outbreaks of avian salmonellosis have been reported during the last decade where the precise causal agent remains unknown. Moreover, the establishment of earlier and more accurate recognition of pathogens is a key factor to prevent the further dissemination of resistant and/or hypervirulent clones. Here, we aim to use whole-genome sequencing combined with in silico toolkits to provide the genomic features of the antimicrobial resistance and virulence potential of 105 regionally representative non-Pullorum/Gallinarum Salmonella isolates recovered from dead poultry between 2008 and 2019 in Shandong, China. Additionally, phenotypic susceptibility to a panel of 15 antibiotics representing 11 classes was assessed by the broth microdilution method. In this study, we identified eight serovars and nine multilocus sequence typing (MLST) types, with Salmonella enterica serovar Enteritidis sequence type 11 (ST11) being the most prevalent (84/105; 80%). Based on their phenotypic antimicrobial resistance, 77.14% of the isolates were defined as multidrug resistant (≥3 antimicrobial classes), with the detection of one S. Enteritidis isolate that was resistant to the 11 classes. The highest rates of resistance were observed against nalidixic acid (97.14%) and ciprofloxacin (91.43%), followed by ampicillin (71.43%), streptomycin (64.77%), and tetracycline (60%). Genomic characterization revealed the presence of 41 resistance genes, with an alarmingly high prevalence of bla TEM-1B (60%), in addition to genomic mutations affecting the DNA gyrase ( gyrA ) and DNA topoisomerase IV ( parC ) genes, conferring resistance to quinolones. The prediction of plasmid replicons detected 14 types, with a dominance of IncFIB(S)_1 and IncFII(S)_1 (87.62% for both), while the IncX1 plasmid type was considered the key carrier of antimicrobial resistance determinants. Moreover, we report the detection of critical virulence genes, including cdtB , rck , sodCI , pef , and spv , in addition to the typical determinants for Salmonella pathogenicity island 1 (SPI-1) and SPI-2. Furthermore, phylogenomic analysis revealed the detection of three intra-farm and five inter-farm transmission events. Overall, the detection of Salmonella isolates presenting high antimicrobial resistance and harboring different critical virulence genes is of major concern, which requires the urgent implementation of effective strategies to mitigate non-Pullorum/Gallinarum avian salmonellosis. IMPORTANCE Avian salmonellosis is one of the leading global causes of poultry death, resulting in substantial economic losses in China (constituting 9% of overall financial losses). In Shandong province, a top poultry producer (30% of the overall production in China, with 15% being exported to the world), extensive outbreaks of avian salmonellosis have been reported in the past decade where the causal agents or exact types remain rarely addressed. From approximately 2008 to 2019, over 2,000 Salmonella strains were isolated and identified from dead poultry during routine surveillance of 95 poultry farms covering all 17 cities in Shandong. Approximately 1,500 isolates were confirmed to be of non-Pullorum/Gallinarum Salmonella serovars. There is an urgent need to understand the mechanisms behind the implication of zoonotic Salmonella serovars in systemic infections of poultry. Here, we analyzed populations of clinically relevant isolates of non-Pullorum/Gallinarum Salmonella causing chicken death in China by a whole-genome sequencing approach and determined that antimicrobial-resistant Salmonella Enteritidis remained the major cause in the past decades.	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Maxillofacial Skeleton and Facial Anatomy. In this article, we discuss the anatomy and development of the face. One should become familiar with the layers, muscles, vessels, and nerves of the face. Embryologic development of the face and supporting structures is also discussed. Additionally, different clinical manifestation of facial paralysis is highlighted.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Effects of Obstructive Sleep Apnea-Hypopnea Syndrome and Cognitive Function in Ischemic Stroke Based on Linear Regression Equation. The objective of this research is to study the effect of obstructive sleep apnea-hypopnea syndrome on cognitive function of stroke. Based on linear regression equation and Montreal Cognitive Assessment Scale, the degree of cognitive impairment in OSAHS patients was evaluated and the influencing factors of OSAHS-induced cognitive impairment and the correlation between the degree of OSAHS and cognitive impairment were explored. The results are as follows: about 68% of OSAHS patients have cognitive dysfunction, and the incidence of cognitive dysfunction is positively correlated with OSAHS; cognitive impairment of OSAHS patients was associated with age, obesity, years of schooling, and intermittent nocturnal hypoxia or hypoventilation; the severity of cognitive dysfunction of OSAHS patients was positively correlated with age and obesity but negatively correlated with education level; Logistic regression analysis results showed that there were three factors that were finally entered into the regression equation, namely, LSaO2, BMI, and AHI, and the Logistic regression equation obtained was as follows: Logist P = -0.109 X 1 + 0.785 X 2 + 1.228 X 3 . This study helps clinical workers to detect and intervene the impaired cognitive ability of patients with OSAHS early, so as to reduce the incidence and mortality of related complications and improve the quality of life of patients.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Long-term spatial variation of algal blooms extracted using the U-net model from 10 years of GOCI imagery in the East China Sea. Long-term satellite missions could help to provide insights into spatial and temporal variations in algal blooms. However, the traditional reflectance-based method has limitations in regards to determining the available threshold for algal bloom detection among the time-varying observation conditions. In terms of extracting useful information from long-term data series precisely and efficiently, the deep learning method has shown its superiority over traditional algorithms in batch data processing. In this study, a U-net model for algal bloom extraction along the coast of the East China Sea was developed using GOCI images. The U-net model was trained with two different datasets that were constructed with six-band channels (all visible bands from GOCI imagery) and RGB-band channels (bands of 443, 555, and 680 nm from GOCI imagery). The quantitative assessment from the U-net models suggests that the U-net model trained with the six-band channel datasets outperformed the RGB-band channel datasets, with increases of 23.6%, 18.1%, and 12.5% in terms of accuracy, precision, and F-score, respectively. The validation map derived from the U-net model trained with six-band channel datasets also showed considerable matching with the ground-truth maps. By using the U-net model, the occurrence of algal blooms was automatically extracted from GOCI images. A 10-year time series of GOCI data collected between 2011 and 2020 was derived using an output-trained U-net model to explore spatial variation along the coast of the ECS. It was found that the most affected areas of the algal blooms varied by year, but were mainly located in the Zhoushan and Zhejiang coasts. Additionally, by performing principal component analysis on the daily meteorological data during April and August 2011-2020, factors related to algal bloom occurrence were discussed.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Noncoding RNAs: Regulating the crosstalk between tumor-associated macrophages and gastrointestinal cancer. Gastrointestinal (GI) cancers, one of the most lethal cancers nowadays, have caused millions of deaths. The tumor microenvironment (TME) is a complex ecosystem containing multiple cells, such as immune cells, cancer cells, and endothelial cells. Tumor-associated macrophages (TAMs), the predominant cells infiltrating the TME, have been verified to play a crucial role in regulating tumor progression. Noncoding RNAs (ncRNAs) are involved in mediating tumor-infiltrating immune cells, including TAMs. GI cancer cells produce various ncRNAs to modulate TAM infiltration and polarization. Meanwhile, ncRNAs play a pivotal role in macrophage and cancer cell metabolic reprogramming. Furthermore, macrophages mediate the impact of ncRNAs on chemoresistance, metastasis, and progression of GI cancer. In this review, we summarize recent research advances in the crosstalk between macrophages and GI cancer regulated by ncRNAs. Moreover, we propose the promising role of ncRNAs as potential targets and prognostic biomarkers in cancer treatment, hoping to facilitate the identification of new targets for immunotherapy.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
TGFBR3 supports anoikis through suppressing ATF4 signaling. Epithelial morphogenesis and oncogenic transformation can cause loss of cell adhesion, and detached cells are eliminated by anoikis. Here, we reveal that transforming growth factor β receptor 3 (TGFBR3) acts as an anoikis mediator through the coordination of activating transcription factor 4 (ATF4). In breast cancer tissues, TGFBR3 is progressively lost, but elevated TGFBR3 is associated with a histologic subtype characterized by cellular adhesion defects. Dissecting the impact of extracellular matrix (ECM) deprivation, we demonstrate that ECM loss promotes TGFBR3 expression, which in turn causes differentiation of cell aggregates, conferring a low-adhesion phenotype, and drives the intrinsic apoptotic pathway. We demonstrate that inhibition of TGFBR3 impairs epithelial anoikis by activating ATF4 signaling. These preclinical findings provide a rationale for therapeutic inhibition of ATF4 in the subgroup of breast cancer patients with low TGFBR3 expression.	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	1	0	0	1	0	0	1	0	0	0	0	0	0	1	0	0	0	0
Social network analysis of Staphylococcus aureus carriage in a general youth population. Staphylococcus aureus carriage increases the risk of infection. We used social network analysis to evaluate whether contacts have the same S. aureus genotype indicating direct transmission or whether contagiousness is an indirect effect of contacts sharing the same lifestyle or characteristics.	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Transcriptome analysis reveals the roles of phytohormone signaling in tea plant (Camellia sinensis L.) flower development. Tea plant (Camellia sinensis (L.) O. Kuntze) is an important economic tea crop, but flowering will consume a lot of nutrients of C. sinensis, which will seriously affect the nutritional growth of C. sinensis. However, there are few studies on the development mechanism of C. sinensis flower, and most studies focus on a single C. sinensis cultivar.	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	0	0
An accelerated approach of biogas production through a two-stage BioH 2 /CH 4 continuous anaerobic digestion system from Napier grass. Napier grass found to be greatest potential for gaseous bioenergy production. The biohydrogen and biomethane productions from untreated Napier grass in single and two-stage continuous bioreactors was evaluated using anaerobic digestion technology. The bioreactors were fed Napier grass with organic loading rate (OLR) of 0.5, 1.0 and 2.0 kg VS/m 3 -d, respectively. The hydrogen, methane, and energy yields were evaluated. The methane yield of single-stage system was 282.08 CH 4 /g vS with OLR of 0.5 kg VS/m 3 -d. For two-stage system, the biohydrogen and biomethane yields were 90.06 mL H 2 /g vS and 367.00 mL CH 4 /g vS with OLRs of 1.0 and 0.5 kg VS/m 3 -d, respectively. The energy yields of single and two-stage systems were 13.14 and 10.10 kJ/g vS respectively. The peak OLR of Napier grass was 0.5 kg VS/m 3 -d for the two-stage system whereas the total energy recovery was 30 % higher than the single-stage system.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Perceptions and attitudes of ICU physicians toward antibiotics prescribing and resistance: A cross-sectional study. Antibiotic resistance is a major emphasis in intensive care units (ICUs). Better understanding of ICU physicians' perceptions, attitudes, and knowledge about antimicrobial prescribing practices could facilitate more effective interventions in fighting antimicrobial resistance in Egyptian ICUs and establishing a proper Antimicrobial Stewardship Program.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
International prevalence of consultation with a naturopathic practitioner: a systematic review and meta-analysis. Naturopathy is a traditional medicine system informed by codified philosophies and principles, and an emphasis on non-pharmacologic therapeutic interventions. While naturopathy is practised by approximately 75 000-100 000 000 naturopathic practitioners in at least 98 countries, little is known about the international prevalence of history of consultation with a naturopathic practitioner. This study reports a systematic review and meta-analysis of studies describing the global prevalence of history of consultation with a naturopathic practitioner by the general population.	0	0	0	0	0	0	0	0	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
Hydrogen Bond-Mediated Supramolecular Polymeric Nanomedicine with pH/Light-Responsive Methotrexate Release and Synergistic Chemo-/Photothermal Therapy. Complete cancer cure and healing are still difficult, owing to its complexity and heterogeneity. Integration of supramolecular forces, for example, hydrogen bonds (H-bonds), to anti-cancer nanomedicine affords new scaffolds for biomedical material decoration, featuring the advantages of dynamic property and easier processability. Here, we target the construction of H-bond-mediated supramolecular polymer micelles, loaded with a chemotherapeutic drug along with a photothermal agent for synergistic chemo-/photothermal therapies (CT/PTT). To do so, we design and synthesize an amphiphilic ABA-type triblock copolymer, bearing H-bonding moiety (barbiturate, Ba) within the middle hydrophobic B block. The presence of pendant Ba moieties within the hydrophobic core promotes the loading capability of methotrexate (MTX) and transportation stability, benefitting from the formation of specific Ba/MTX H-bonding interactions. IR780, a photothermal agent, concomitantly encapsulated <i>via</i> hydrophobic interactions, facilitates the development of a synergistic CT/PTT modalities, where MTX can be released on demand owing to the dissociation of Ba/MTX H-bonding interactions induced by elevated temperature. Such H-bonding nanomedicine possesses enhanced drug loading capacity and transport performance and can also trigger stimuli-responsive drug release in the tumor zone. We believe that H-bonded nanomedicines provide a fine toolbox that is conducive to attaining biomedical requirements with remarkable values in theranostics that are highly promising in clinical applications.	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0
Clinical Effectiveness of Herbal Oral Care Products in Periodontitis Patients: A Systematic Review. The use of herbal products in oral cavity has shown an increased popularity and potential benefits due to their additional anti-inflammatory and antioxidant properties as well as the lack of side effects related to their use.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pharmacokinetic evaluation and relative bioavailability pilot study of fidaxomicin in healthy Chinese subjects: An open, randomized, single-dose, cross-over study. To compare the pharmacokinetic (PK) characteristics, investigate relative bioavailability, and provide data for potential additional bioequivalence trials between generic fidaxomicin (test (T) formulation) and the original brand (reference (R) formulation) in healthy Chinese subjects.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Development of an acellular nerve cap xenograft for neuroma prevention. Neuroma formation following limb amputation is a prevalent and debilitating condition that can deeply affect quality of life and productivity. Several approaches exist to prevent or treat neuromas; however, no approach is either consistently reliable or surgically facile, with high rates of neuroma occurrence and/or recurrence. The present study describes the development and testing of a xenogeneic nerve cap graft made from decellularized porcine nerve. The grafts were tested in vitro for cellular removal, cytotoxicity, mechanical properties, and morphological characteristics. The grafts were then tested in rat sciatic nerve gap reconstruction and nerve amputation models for 8 weeks. Gross morphology, electrophysiology, and histopathology assessments were performed to determine the ability of the grafts to limit pathologic nerve regrowth. In vitro testing showed well decellularized and demyelinated nerve cap graft structures without any cytotoxicity from residual reagents. The grafts had a proximal socket for the proximal nerve stump and longitudinally oriented internal pores. Mechanical and surgical handling properties suggested suitability for implantation as a nerve graft. Following 8 weeks in vivo, the grafts were well integrated with the proximal and distal nerve segments without evidence of fibrotic adhesions to the surrounding tissues or bulbous outgrowth of the nerve. Electrophysiology revealed absence of nerve conduction within the remodeled nerve cap grafts and significant downstream muscle atrophy. Histologic evaluation showed well organized but limited axonal regrowth within the grafts without fibrous overgrowth or neuromatous hypercellularity. These results provide proof of concept for a novel xenograft-based approach to neuroma prevention.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0
Rituximab in myasthenia gravis: efficacy, associated infections and risk of induced hypogammaglobulinemia. The aim of this study is to evaluate the long-term efficacy, safety, and impact on immunoglobulin G (IgG) levels of rituximab in patients with myasthenia gravis (MG). A retrospective, observational study of drug-refractory MG patients treated with rituximab was done. The MG Foundation of America postintervention status (MGFA-PIS) was used to evaluate clinical response. Serum IgG levels were determined at baseline and post-treatment. Hypogammaglobulinemia was defined as IgG<7g/L. Thirty patients were included, 12 with anti-MuSK and 18 with anti-AChR antibodies. Mean (SD) follow-up was 85.5 (48) months. All 12 MuSK+ patients but only six (33%) AChR+ patients achieved minimal manifestations or remission (p<0.01). Nine severe infections were observed in five patients (17%). One patient was diagnosed with progressive multifocal leukoencephalopathy. At baseline, two patients (2/24; 8%) had hypogammaglobulinemia. During follow-up, hypogammaglobulinemia was observed in 60% (3/5) of patients who developed an infection and in 33% (7/21) who did not. Two of these patients died of infection-related complications. This study supports the effectiveness of rituximab in patients with MG, especially those with anti-MuSK antibodies. Severe infections may appear after rituximab treatment and hypogammaglobulinemia might play a role on it. A standard protocol would be needed to closely monitor IgG levels in MG patients treated with rituximab.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Long-term effects of lower versus higher oxygenation levels in adult ICU patients-A systematic review. Oxygen therapy is a common treatment in the intensive care unit (ICU) with both potentially desirable and undesirable long-term effects. This systematic review aimed to assess the long-term outcomes of lower versus higher oxygenation strategies in adult ICU survivors.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	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
Role of oxidative stress in induction of trans-differentiation of neutrophils in patients with rheumatoid arthritis. Rheumatoid arthritis (RA) is an autoimmune disorder whose etiopathology involves an interplay between genetic and environmental factors, with oxidative stress being a key contributory factor. This study aimed to establish the impact, if any, of an oxidative, pro-inflammatory milieu upon trans-differentiation of neutrophils and disease progression. In the synovial fluid (SF) and peripheral blood sourced from patients with RA ( n = 40) along with healthy controls ( n = 25), the proportion of neutrophil-dendritic (N-DC) cell hybrids, i.e. CD66b + /CD83 + was characterized in terms of their antigen presentation (HLA-DR, CD80, andCD86) and cell adhesion and migration (ICAM-1, VCAM-1, and CD62L) properties, along with their ability to generate reactive oxygen species (ROS). In the SF of RA cases, the raised levels of circulating and intra-neutrophilic pro-inflammatory cytokines/chemokines were accompanied by an enhanced proportion of CD66b + neutrophils, that co-expressed features of antigen presenting cells (APCs) namely CD83, HLA-DR, CD80, CD86, ICAM-1, VCAM-1, and decreased CD62L. These N-DCs as compared to canonical neutrophils demonstrated a higher generation of ROS, and their frequency positively correlated with disease activity score (DAS28). An ex-vivo functional assay validated that oxidative stress supported trans-differentiation and could be attenuated by a free radical scavenger. Taken together, the pro-inflammatory microenvironment in the SF of patients with RA coupled with a higher generation of ROS promoted the trans-differentiation of neutrophils into N-DCs, suggesting the inclusion of anti-oxidants as an add-on therapeutic strategy to limit trans-differentiation.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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 the Possibility of Using Cenospheres in the Production of Cement Mortars for Use in an Elevated Temperature Environment. The topic of research included in this article was the evaluation of the influence of cenospheres on selected parameters of mortar cement. Samples were designed as CEM I 42.5 R Portland cement with the application of different additive amounts. In the experimental work, the consistency, compressive strength, and bending strength were tested after 28 and 56 days of maturation, and after heating temperatures of 20, 300, 500, and 700 °C. The compressive strength was tested on half beams (40 × 40 × 160 mm). Using the obtained results, the properties of the mortars were compared. The research confirmed the possibility of producing cenosphere-modified cement mortars. Cenospheres used in the preparation of cement mortar negatively affected the bending and compressive strength with increasing temperature (20, 300, 500, 700 °C) and increasing content of this additive (10, 20, 30%).	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Graphium septentrionicolus Page amp; Treadaway, 2013 (Lepidoptera: Papilionidae) is a distinct species. After molecular and morphological analyses, the taxon septentrionicolus Page Treadaway, 2013 is shown to be a distinct species, and Graphium adonarensis (Rothschild, 1896) is placed as conspecific with Graphium sarpedon (Linnaeus, 1758). Graphium huangshanensis Wu Ma, 2016 syn. nov. is synonymised with G. septentrionicolus.	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	1
Improving Dietary Intake of Essential Nutrients Can Ameliorate Inflammation in Patients with Diabetic Foot Ulcers. Diabetic foot ulcers (DFUs) are classified as chronic wounds and are one of the most common complications of diabetes. In chronic wounds, management of inflammation is a key step in treatment. Nutrition plays an important role in managing and controlling inflammation. This study evaluated the effects of nutrition supplementation and education on inflammatory biomarkers in patients with DFUs. Eligible patients with foot ulcers were randomly assigned to either a treatment ( n = 15) or control group ( n = 14). Both groups received standard care for wound treatment from the clinic; however, the treatment group was also provided with nutritional supplementation and education. Plasma concentrations of inflammatory biomarkers, namely C-reactive protein (CRP), interleukin 6 (IL6), interleukin 10 (IL10), and tristetraprolin (TTP), were evaluated at baseline and every four weeks, until complete wound closure had occurred or up to 12 weeks. The mean plasma concentration of IL6 significantly decreased in the treatment group ( p = 0.001). The interaction between time and group was not statistically significant for the mean plasma concentrations of CRP, IL10, and TTP during the 12 weeks of the study. The results of this study showed the positive effects of nutritional intervention on controlling inflammation in DFU patients. More clinical trials with a larger population and longer duration of time are needed to confirm our results.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Heart rate and age modulate retinal pulsatile patterns. Theoretical models of retinal hemodynamics showed the modulation of retinal pulsatile patterns (RPPs) by heart rate (HR), yet in-vivo validation and scientific merit of this biological process is lacking. Such evidence is critical for result interpretation, study design, and (patho-)physiological modeling of human biology spanning applications in various medical specialties. In retinal hemodynamic video-recordings, we characterize the morphology of RPPs and assess the impact of modulation by HR or other variables. Principal component analysis isolated two RPPs, i.e., spontaneous venous pulsation (SVP) and optic cup pulsation (OCP). Heart rate modulated SVP and OCP morphology (p FDR < 0.05); age modulated SVP morphology (p FDR < 0.05). In addition, age and HR demonstrated the effect on between-group differences. This knowledge greatly affects future study designs, analyses of between-group differences in RPPs, and biophysical models investigating relationships between RPPs, intracranial, intraocular pressures, and cardiovascular physiology.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Application of High-Efficiency Cell Expansion and High-Throughput Drug Sensitivity Screening for Leukemia Treatment. This study is to assess the clinical value of in vitro primary cell high-efficiency expansion and high-throughput drug sensitivity screening (HEHDS) system in leukemia, and we evaluated a cohort of 121 patients with acute myeloid leukemia (AML) and 27 patients with acute lymphoblastic leukemia (ALL) using HEHDS. Bone marrow aspirates were collected from patients with leukemia. Purified leukemic cancer cells were obtained, cultured, and screened with a panel of 247 FDA-approved compounds by HEHDS technology. Ninety-six patients received HEHDS-guided therapy while 52 patients who were subjected to physician directed therapy served as controls. ALL patients who received treatment guided by HEHDS showed higher rate of complete remission (CR) than that of patients in the non-HEHDS group (90.91% vs. 56.25%). Similarly, AML patients received HEHDS-guided therapy were found to have greater CR rate, when compared with patients who received physician-directed therapy (45.88% vs. 25%). There was a significantly higher rate of CR in HEHDS-guided therapy group compared to the non-HEHDS group. The application of HEHDS could be beneficial for leukemia treatment.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Association between a dietary pattern high in saturated fatty acids, dietary energy density, and sodium with coronary heart disease. This study aimed to determine the association between dietary pattern (DP) and coronary heart disease (CHD) among high-risk adults as determined by metabolic syndrome (MetS) criteria in Malaysia. This cross-sectional study involved 365 participants with (CHD = 178; non-CHD = 187) who were recruited from selected health clinics. Dietary intake was measured using a 189-item semi-quantitative foods frequency questionnaire (FFQ) whilst anthropometry and clinical data were measured by trained researcher and biochemical data were obtained from medical records. The reduced rank regression (RRR) method was used to derive DPs scores and binary logistic regression was used to assess the associations between identified DPs and CHD. The main DP found in this study was characterised by "high saturated fatty acid (SFA), high dietary energy density (DED), high sodium". This DP, which is attributed to high consumption of coconut-based dishes, fast foods and snacks, rice dishes, fat spread, seasoning sauces, salted and processed foods, and low intake of fruits, green leafy vegetables, white rice and other vegetables were associated with CHD (OR:1.32, 95% CI:1.03, 1.69) p value = 0.026 when, adjusted for age, sex, race, education level, household income, family history of CHD, marital status, smoking status, physical activity, stress level and BMI. This study suggests that individuals with a DP of high SFA, high DED, and high sodium have a significantly increased likelihood of having CHD compared to those who do not practice this DP.	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	1	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0
The use of formal care for dementia from a professional perspective: a scoping review. The progressive character of dementia usually leads to a continuously increasing need for support. There is some evidence of late use of professional support during the disease course. We aim to provide an overview of aspects influencing access and use of formal care in dementia from the perspective of health and social care professionals. Additionally, the perspectives of professionals and people with dementia/informal carers will be compared.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nuances of Septal Deviation Repair. Septoplasty is one of the most common procedures performed by facial plastic surgeons. Surgical decision-making surrounding septal deviation repair centers around the location of deviation and need for dorsal and/or caudal septal correction. Endonasal approaches are often adequate and external approaches are utilized for significant L-strut involvement. For severe deformities, extracorporeal septoplasty and anterior septal reconstruction can be utilized. We present an overview of septal deviation repair with technical nuances and advanced reconstruction techniques.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Absence of Figla-like Gene Is Concordant with Femaleness in Cichlids Harboring the LG1 Sex-Determination System. Oreochromis niloticus has been used as a reference genome for studies of tilapia sex determination (SD) revealing segregating genetic loci on linkage groups (LGs) 1, 3, and 23. The master key regulator genes (MKR) underlying the SD regions on LGs 3 and 23 have been already found. To identify the MKR in fish that segregate for the LG1 XX/XY SD-system, we applied short variant discovery within the sequence reads of the genomic libraries of the Amherst hybrid stock, Coptodon zillii and Sarotherodon galilaeus , which were aligned to a 3-Mbp-region of the O. aureus genome. We obtained 66,372 variants of which six were concordant with the XX/XY model of SD and were conserved across these species, disclosing the male specific figla-like gene. We further validated this observation in O. mossambicus and in the Chitralada hybrid stock. Genome alignment of the 1252-bp transcript showed that the figla-like gene's size was 2664 bp, and that its three exons were capable of encoding 99 amino acids including a 45-amino-acid basic helix-loop-helix domain that is typical of the ovary development regulator- factor-in-the-germline-alpha ( FIGLA ). In Amherst gonads, the figla-like gene was exclusively expressed in testes. Thus, the figla-like genomic presence determines male fate by interrupting the female developmental program. This indicates that the figla-like gene is the long-sought SD MKR on LG1.	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Occupations and their impact on the spreading of COVID-19 in urban communities. The current pandemic has disproportionally affected the workforce. To improve our understanding of the role that occupations play in the transmission of COVID-19, we analyse real-world network data that were collected in Bucharest between August 1st and October 31st 2020. The data record sex, age, and occupation of 6895 patients and the 13,272 people they have interacted with, thus providing a social network from an urban setting through which COVID-19 has spread. Quite remarkably, we find that medical occupations have no significant effect on the spread of the virus. Instead, we find common transmission chains to start with infected individuals who hold jobs in the private sector and are connected with non-active alters, such as spouses, siblings, or elderly relatives. We use relational hyperevent models to assess the most likely homophily and network effects in the community transmission. We detect homophily with respect to age and anti-homophily with respect to sex and employability. We note that, although additional data would be welcomed to perform more in-depth network analyses, our findings may help public authorities better target under-performing vaccination campaigns.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Highly Efficient Red/NIR-Emissive Fluorescent Probe with Polarity-Sensitive Character for Visualizing Cellular Lipid Droplets and Determining Their Polarity. Lipid droplets (LDs), which are ubiquitous organelles existing in almost all eukaryotic cells, have attracted a lot of attention in the field of cell biology over the last decade. For the biological study of LDs via fluorescence imaging, the superior LD fluorescent probes with environmental polarity-sensitive character are highly desired and powerful but are very scarce. Herein, we have newly developed such a kind of fluorescent probe named LDs-Red which enables us to visualize LDs and to further reveal their polarity information. This fluorescent probe displays the advantages of intense red/near-infrared emission, high LD staining specificity, and good photostability; thus, it would be very useful for LD fluorescence imaging application. As a result, the three-dimensional confocal imaging to visualize spatial distribution of LDs and the multicolor confocal imaging to simultaneously observe LDs and other cellular organelles have been realized using this new LD fluorescent probe. Furthermore, the polarity-sensitive emission character of this probe enables us to quantitatively determine the LD polarity via spectral scan imaging. Consequently, the cancer cells (HepG2, HeLa, and Panc02) displaying lower polarity of LDs than the normal cells (L929, U251, and HT22) have been systematically demonstrated. In addition, this polarity-sensitive probe displaying shorter fluorescence wavelengths in cancer cells than in normal cells has an important and potential ability to distinguish them.	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Proteome-wide analysis of the hippocampus in adolescent male mice with learning and memory impairment caused by chronic ethanol exposure. Alcohol consumption may cause various impairments in the brain. The hippocampus is particularly vulnerable to alcohol exposure, which may cause learning and memory deficits. Recently, proteomics analysis has become a popular approach to explore the pathogenesis of various diseases. The present study was conducted to investigate protein expression alteration in the hippocampus and to identify the molecular mechanisms underlying ethanol-induced learning and memory impairments. Mouse models of chronic ethanol intoxication were established by intragastrical administration for 28 consecutive days, and hippocampal neuronal damage was assessed by Nissl staining. Recognition memory was evaluated by Novel object recognition and Morris water maze tests, and hippocampus tissues were collected for label-free quantitative proteomics and analyzed using bioinformatics methods. Our study showed that chronic ethanol exposure prompted marked changes in protein expression in the hippocampus. We identified 32 differentially expressed proteins, of which 21 were upregulated and 11 downregulated. Gene Ontology analysis suggested that the identified differentially proteins were mainly involved in cytoskeleton and signal transduction mechanisms. Further verification using Western blotting and real-time quantitative PCR revealed that the hippocampal CTSL (cathepsin L), and PVALB (Parvalbumin) showed strongest expression changes, the latter being specifically expressed in GABAergic interneurons. These two proteins might serve as candidate protein biomarkers, providing new prospects for the diagnosis and treatment of ethanol-induced learning and memory disorders.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Development of a new toolbox for mouse PET-CT brain image analysis fully based on CT images and validation in a PD mouse model. Automatic analysis toolboxes are popular in brain image analysis, both in clinical and in preclinical practices. In this regard, we proposed a new toolbox for mouse PET-CT brain image analysis including a new Statistical Parametric Mapping-based template and a pipeline for image registration of PET-CT images based on CT images. The new templates is compatible with the common coordinate framework (CCFv3) of the Allen Reference Atlas (ARA) while the CT based registration step allows to facilitate the analysis of mouse PET-CT brain images. From the ARA template, we identified 27 volumes of interest that are relevant for in vivo imaging studies and provided binary atlas to describe them. We acquired 20 C57BL/6 mice with [<sup>18</sup>F]FDG PET-CT, and 12 of them underwent 3D T2-weighted high-resolution MR scans. All images were elastically registered to the ARA atlas and then averaged. High-resolution MR images were used to validate a CT-based registration pipeline. The resulting method was applied to a mouse model of Parkinson's disease subjected to a test-retest study (n = 6) with the TSPO-specific radioligand [<sup>18</sup>F]VC701. The identification of regions of microglia/macrophage activation was performed in comparison to the Ma and Mirrione template. The new toolbox identified 11 (6 after false discovery rate adjustment, FDR) brain sub-areas of significant [<sup>18</sup>F]VC701 uptake increase versus the 4 (3 after FDR) macro-regions identified by the Ma and Mirrione template. Moreover, these 11 areas are functionally connected as found by applying the Mouse Connectivity tool of ARA. In conclusion, we developed a mouse brain atlas tool optimized for PET-CT imaging analysis that does not require MR. This tool conforms to the CCFv3 of ARA and could be applied to the analysis of mouse brain disease models.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Value of computed tomography Hounsfield units in predicting pedicle screw loosening in the thoracic spine. We evaluated the feasibility of using the Hounsfield unit (HU) value of the vertebral body to predict screw loosening in the thoracic spine. Consecutive patients who underwent thoracic spinal fusion surgery (from 2014 to 2020) were retrospectively identified. Patients with pedicle screw loosening in the upper instrumented vertebra (UIV) on postoperative computed tomography were included in the "loosening" group. The control group comprised an equal number of age-, sex-, and UIV-matched patients without screw loosening. Preoperative HU values at the UIV and lumbar T-scores were compared between the groups; receiver operating characteristic curves were constructed for HU values and T-scores to predict screw loosening, and the best cutoff values were determined. The same statistical analyses were performed for each subgroup, i.e., upper (T1-T4) and lower (T9-T12) thoracic levels. Forty-six patients each were included in the loosening and control groups. A significant between-group difference of HU values was noted for the lower thoracic UIV (loosening = 99.3, control = 126.3; p = 0.02) but not for the upper thoracic UIV (loosening = 171.8, control = 146.0, p = 0.70). T-scores did not differ between the groups for the lower (p = 0.14) and upper (p = 0.56) thoracic UIV. For the lower thoracic UIV, the area under the receiver operating characteristic curve was 0.660 for HUs (p = 0.01; 95% confidence interval [CI] 0.541-0.766) and 0.601 (p = 0.13; 95% CI 0.480-0.713) for T-scores. The optimal cutoff value for HUs was 126.3. Using this cutoff, HU values showed a better positive predictive value, negative predictive value, and accuracy compared to T-scores in predicting screw loosening.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
An Observational Study on the Use of a Patient Navigator to Help Improve Outcomes in Patients on Chronic Opioids. In the United States, the prevalence of opioid use disorders has increased in recent years along with an attendant rise in the incidence of chronic pain disorders and prescription opioid use. Patient navigation services have been used to improve health outcomes in cancer and other chronic disease states, but it is unclear whether the implementation of patient navigation services can facilitate improved outcomes among patients receiving chronic opioid therapy.	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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Food Insecurity in a Sample of Informal Caregivers in 4 Southern US States. Given the disproportionate burden of food insecurity in the southern US states and the high prevalence of caregiving in this area, we assessed caregiving-related predictors of food insecurity among caregivers in 4 southern US states.	0	0	0	0	0	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	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dietary emulsifier glycerol monodecanoate affects the gut microbiota contributing to regulating lipid metabolism, insulin sensitivity and inflammation. Glycerol monodecanoate (GMD) is a medium-chain monoacylglycerol that possesses emulsifying and antibacterial properties. The common emulsifiers carboxymethylcellulose and polysorbate-80 have been reported to cause intestinal microbiota dysbiosis and metabolic disturbances. Glycerol monolaurate (GML), another medium-chain monoacylglycerol, is often used as an emulsifier and could improve metabolism by regulating the gut microbiota. However, research on the effects of GMD on the metabolism and gut microbiota remains scarce. Mice were fed a normal chow diet with or without GMD (150, 800, and 1600 mg kg -1 ) for 22 weeks. Metabolism indicators and related genes, gut microbiota, and fecal SCFAs were analyzed. The results demonstrated that GMD significantly improved insulin sensitivity, reduced the serum LPS level, and decreased pro-inflammation cytokines including IL-1β, tumor necrosis factor (TNF), and monocyte chemotactic protein 1 (MCP-1). Additionally, 150 and 1600 mg kg -1 GMD could significantly lower the blood glucose content. 1600 mg kg -1 GMD improved cholesterol metabolism and related gene expression compared to 150 and 800 mg kg -1 GMD. Moreover, 150 and 800 mg kg -1 GMD up-regulated the abundance of Lactobacillus and Turicibacter , while 1600 mg kg -1 GMD significantly up-regulated the abundance of Bifidobacterium . Our findings indicated that different doses of GMD had inconsistent effects on lipid metabolism by differentially altering the gut microbiota composition. Meanwhile, all doses of GMD showed excellent effects on increasing insulin sensitivity and improving inflammation.	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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Reversible cerebral artery constriction accompanied with stroke-like episode in MELAS: A case series. The pathophysiology of stroke-like episode (SLE) in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was uncertain, though mitochondrial metabolic crisis of cortical neurons and mitochondrial proliferation in small vessels of brain have been considered. However, the involvement of major cerebral vessels was debated. We aimed to investigate whether major cerebral vessels participate in SLE.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Validity of the Functioning Assessment Short Tests (FAST), in patients with schizophrenia. Functional impairment in schizophrenia is one of the main features of the disorder and implies a great impact on the patient's quality of life. The Brief Functioning Assessment Scale (FAST), originally validated in bipolar disorder, has also been validated for its application in other mental disorders. However, we only found one study on the reliability and validity of the Brazilian version in schizophrenia. The purpose of this study was to analyze the psychometric properties of the Spanish version of the FAST in patients diagnosed with schizophrenia.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lef1 is transcriptionally activated by Klf4 and suppresses hyperoxia-induced alveolar epithelial cell injury. Bronchopulmonary dysplasia (BPD) is a long-term respiratory condition. More than a quarter of extremely premature newborns are harmed by BPD. At present, there are no apparent effective drugs or treatments for the condition. In this study, we aimed to investigate the functional role and mechanism of lymphoid enhancer-binding factor 1 ( Lef1 ) in BPD in vitro .	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	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Activation of PGRN/MAPK axis stimulated by the hypoxia-conditioned mesenchymal stem cell-derived HIF-1α facilitates osteosarcoma progression. Progranulin (PGRN) is an important survival factor in the progression of multiple cancers.	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Curating the gnomAD database: Report of novel variants in the thyroid peroxidase gene using in silico bioinformatics algorithms and a literature review. Thyroid peroxidase (TPO) is a membrane-bound glycoprotein located at the apical side of the thyroid follicular cells that catalyzes both iodination and coupling of iodotyrosine residues within the thyroglobulin molecule, leading to the synthesis of thyroid hormone. Variants in TPO cause congenital hypothyroidism (CH) by iodide organification defect and are commonly inherited in an autosomal recessive fashion. In the present work, we report a detailed population analysis and bioinformatic prediction of the TPO variants indexed in the Genome Aggregation Database (gnomAD) v2.1.1. The proportion of missense cysteine variants and nonsense, frameshift, and splice acceptor/donor variants were analyzed in each ethnic group (European (Non-Finnish), European (Finnish), African/African Americans, Latino/Admixed American, East Asian, South Asian, Ashkenazi Jewish, Other). The results showed a clear predominance of frameshift variants in the East Asian (82%) and European (Finnish) (75%) population, whereas the splice site variants predominate in African/African Americans (99.46%), Other (96%), Latino/Admixed American (94%), South Asian (86%), European (Non-Finnish) (56%) and Ashkenazi Jewish (56%) populations. The analysis of the distribution of the variants indexed in gnomAD v2.1.1 database revealed that most missense variants identified in the An peroxidase domain map in exon 8, followed by exons 11, 7 and 9, and finally in descending order by exons 10, 6, 12 and 5. In total, 183 novel TPO variants were described (13 missense cysteine's variants, 158 missense variants involving the An peroxidase domain and 12 splicing acceptor or donor sites variants) which were not reported in the literature and that would have deleterious effects on prediction programs. In the gnomAD v2.1.1 population, the estimated prevalence of heterozygous carriers of the potentially damaging variants was 1:77. In conclusion, we provide an updated and curated reference source of new TPO variants for application in clinical diagnosis and genetic counseling. Also, this work contributes to elucidating the molecular basis of CH associated with TPO defects.	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Unraveling the Complex Chirality Evolution in DNA-Assembled High-Order, Hybrid Chiroplasmonic Superstructures from Multi-Scale Chirality Mechanisms. Hierarchical, chiral hybrid superstructures of chromophores and nanoparticles are expected to give rise to intriguing unveiled chiroptical responses originating from the complex chiral interactions among the components. Herein, DNA origami cavity that could self-assemble into one-dimensional (1D) DNA tubes was employed as a scaffold to accurately organize metal nanoparticles and chromophores. The chiral interactions were studied at the level of individual hybrid particles and their 1D hybrid superstructures. Complex chirality mechanisms involving global structural chirality, plasmon-induced circular dichroism (PICD) and exciton-coupled circular dichroism (ECCD) were disentangled. The multiplexed CD spectrum superposition revealed the chirality evolution at different length scales. These results can offer a model for boosting the theoretical understanding of classical-quantum hybrid systems, and would inspire the future design of optically-active substances across length 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	0	0	0	0	0	0	0	1	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
Prevalence and factors associated with latent autoimmune diabetes in adults (LADA): a cross-sectional study. The Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressive Type 1 diabetes subgroup with onset during middle age. Studies report that about 10% of adults initially diagnosed with clinical Type 2 diabetes (T2D) have LADA. Inappropriate diagnosis and mismanagement of the LADA can increase the risk of diabetic complications, which affect the quality of life and is the cause of increased mortality. In low-income countries setting, data regarding the magnitude of LADA is limited. We carried out this study to estimate the burden of misdiagnosed LADA among T2D patients in selected health facilities in Dar es Salaam and to bring awareness to the use of Glutamic Acid Decarboxylase (GAD) autoantibody in screening for LADA.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Enhanced Ambient Sensing Environment-A New Method for Calibrating Low-Cost Gas Sensors. Accurate calibration of low-cost gas sensors is, at present, a time consuming and difficult process. Laboratory calibration and field calibration methods are currently used, but laboratory calibration is generally discounted due to poor transferability, and field methods requiring several weeks are standard. The Enhanced Ambient Sensing Environment (EASE) method described in this article, is a hybrid of the two, combining the advantages of a laboratory calibration with the increased accuracy of a field calibration. It involves calibrating sensors inside a duct, drawing in ambient air with similar properties to the site where the sensors will operate, but with the added feature of being able to artificially increases or decrease pollutant levels, thus condensing the calibration period required. Calibration of both metal-oxide (MOx) and electrochemical (EC) gas sensors for the measurement of NO 2 and O 3 (0-120 ppb) were conducted in EASE, laboratory and field environments, and validated in field environments. The EC sensors performed marginally better than MOx sensors for NO 2 measurement and sensor performance was similar for O 3 measurement, but the EC sensor nodes had less node inter-node variability and were more robust. For both gasses and sensor types the EASE calibration outperformed the laboratory calibration, and performed similarly to or better than the field calibration, whilst requiring a fraction of the time.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
Maternal exposure to PM 2.5 disrupting offspring spermatogenesis through induced sertoli cells apoptosis via inhibin B hypermethylation in mice. Particulate Matter 2.5 (PM 2.5 ) disrupts endocrine functions and may negatively affect sperm quality and quantity in males; however, the long-term effects and potential mechanisms of this effect are unknown. This study aimed to investigate the epigenetic mechanism of maternal exposure to PM 2.5 -induced inhibin B hypermethylation in male offspring. In this experiment design, pregnant C57BL/6 mice were treated with two doses of PM 2.5 (4.8 and 43.2 mg/kg bw). The membrane control group was given a sampling membrane and the control group received nothing. Following the formation of the vaginal plug, intratracheal instillation of PM 2.5 was administered every three days until delivery of the pups. To assess the effect of PM 2.5 in vitro, TM4 cells, a Sertoli-like cell line, was treated with different concentrations (0, 25, 50, 100 μg/mL) of PM 2.5 for 24 h. The results displayed that Sperm motility, as well as the number of adult offspring, was decreased in the PM 2.5 exposed group relative to the untreated controls. Increased vacuolization was observed in the Sertoli cells of mice that were exposed to PM 2.5 in utero. The levels of inhibin and testosterone were reduced and the levels of LH and FSH increased in the PM 2.5 groups relative to the untreated controls. In vitro, PM 2.5 resulted in cell cycle inhibition as well as increased apoptosis in TM4 cells. Moreover, PM 2.5 -induced inhibin B hypermethylation and activation of the p21/Cleaved Caspase-3 pathway resulted in TM4 cell apoptosis that was rescued through the use of a DNA methylation inhibitor. Together, our data suggest that prenatal exposure to PM 2.5 results in inhibin B hypermethylation and can activate the p21/Cleaved Caspase-3 pathway, resulting in Sertoli cell apoptosis, aberrant secretion of androgen binding protein, and decreased testosterone, thus resulting in the inhibition of spermatogenesis.	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	1	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
New potential treatment for cardiovascular disease through modulation of hemoglobin oxygen binding curve: Myo-inositol trispyrophosphate (ITPP), from cancer to cardiovascular disease. The human body is a highly aerobic organism, which needs large amount of oxygen, especially in tissues characterized by high metabolic demand, such as the heart. Inadequate oxygen delivery underlies cardiovascular diseases, such as coronary artery disease, heart failure and pulmonary hypertension. Hemoglobin, the oxygen-transport metalloprotein in the red blood cells, gives the blood enormous oxygen carrying capacity; thus oxygen binding to hemoglobin in the lungs and oxygen dissociation in the target tissues are crucial points for oxygen delivery as well as potential targets for intervention. Myo-inositol trispyrophosphate (ITPP) acts as an effector of hemoglobin, shifting the oxygen dissociation curve to the right and increasing oxygen release in the target tissues, especially under hypoxic conditions. ITPP has been successfully used in cancer studies, demonstrating anti-cancer properties due to prevention of tumor hypoxia. Currently it is being tested in phase 2 clinical trials in humans with various tumors. First preclinical evidence also indicates that it can successfully alleviate myocardial hypoxia and prevent adverse left ventricular and right ventricular remodeling in post-myocardial infarction heart failure and pulmonary hypertension. The aim of the article is to summarize the current knowledge on ITTP, as well as to determine the prospects for its potential use in the treatment of many cardiovascular disorders.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Microneedles: One-Plane Bevel-Tipped Fabrication by 3D-Printing Processes. This article presents microneedles analyses where the design parameters studied included length and inner and outer diameter ranges. A mathematical model was also used to generalize outer and inner diameter ratios in the obtained ranges. Following this, the range of inner and outer diameters was completed by mechanical simulations, ranging from 30 μm to 134 μm as the inner diameter range and 208 μm to 250 μm as the outer diameter range. With these ranges, a mathematical model was made using fourth-order polynomial regressions with a correlation of 0.9993, ensuring a safety factor of four in which von Misses forces of the microneedle are around 17.931 MPa; the ANSYS software was used to analyze the mechanical behavior of the microneedles. In addition, the microneedle concept was made by 3D printing using a bio-compatible resin of class 1. The features presented by the microneedle designed in this study make it a promising option for implementation in a transdermal drug-delivery device.	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	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
Affinity and Valence Impact the Extent and Symmetry of Phase Separation of Multivalent Proteins. Biomolecular self-assembly spatially segregates proteins with a limited number of binding sites (valence) into condensates that coexist with a dilute phase. We develop a many-body lattice model for a three-component system of proteins with fixed valence in a solvent. We compare the predictions of the model to experimental phase diagrams that we measure in vivo, which allows us to vary specifically a binding site's affinity and valency. We find that the extent of phase separation varies exponentially with affinity and increases with valency. Valency alone determines the symmetry of the phase diagram.	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	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
High sorbic acid resistance of Penicillium roqueforti is mediated by the SORBUS gene cluster. Penicillium roqueforti is a major food-spoilage fungus known for its high resistance to the food preservative sorbic acid. Here, we demonstrate that the minimum inhibitory concentration of undissociated sorbic acid (MICu) ranges between 4.2 and 21.2 mM when 34 P. roqueforti strains were grown on malt extract broth. A genome-wide association study revealed that the six most resistant strains contained the 180 kbp gene cluster SORBUS, which was absent in the other 28 strains. In addition, a SNP analysis revealed five genes outside the SORBUS cluster that may be linked to sorbic acid resistance. A partial SORBUS knock-out (>100 of 180 kbp) in a resistant strain reduced sorbic acid resistance to similar levels as observed in the sensitive strains. Whole genome transcriptome analysis revealed a small set of genes present in both resistant and sensitive P. roqueforti strains that were differentially expressed in the presence of the weak acid. These genes could explain why P. roqueforti is more resistant to sorbic acid when compared to other fungi, even in the absence of the SORBUS cluster. Together, the MICu of 21.2 mM makes P. roqueforti among the most sorbic acid-resistant fungi, if not the most resistant fungus, which is mediated by the SORBUS gene cluster.	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0