bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of pre-exposure of antibiotic prophylaxis for leptospirosis: protocol for a systematic review and meta-analysis
Authors: Rashuamán-Conche Benny , Loli-Guevara Silvana , Rodriguez-López Ethel , Alva-Díaz Carlos 
Published: November 2021

ABSTRACTIntroductionLeptospirosis is the most widespread zoonosis in the world. It represents a public health problem especially in tropical and subtropical regions, but it is also present in temperate regions. Spirochetes from leptospira genus cause the disease, they affect humans as an intermediate host. About pre-exposure prophylaxis for people at risk, antibiotics such as doxycycline or azithromycin were used to prevent the development of leptospirosis and its related adverse outcomes. However, the evidence about the efficacy and safety of this intervention is limited.ObjectivesTo determine whether pre-exposure antibiotic administration prevents infection, hospitalization, or mortality from leptospirosis, without causing severe adverse effects.MethodsWe propose to do a systematic review and meta-analysis. We will search in Pubmed (Medline), Embase.com, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science, LILACS and ClinicalTrials.gov. Individual randomized controlled trials, non-randomized controlled trials, cohorts, and cases-control studies will be included according to the inclusion and exclusion criteria set. The flow chart for selecting studies to be included will be presented in accordance with the PRISMA guide. The methodological quality of the studies will be evaluated by duplicate. Subsequently, the qualitative analysis of the data will be carried out and the feasibility of a quantitative meta-analysis will be evaluated. Finally, a summary of findings table will be presented according to the feasibility of the meta-analysis.ResultsThe results will be published in a peer-reviewed journal.ConclusionThis systematic review will sum up-to-date evidence about the efficacy and safety of pre-exposure antibiotic prophylaxis for preventing laboratory-confirmed leptospirosis, hospitalization and mortality.
Patient experience with healthcare: Feedback for a ‘Post COVID-19 clinic’ at a tertiary care center in rural area
Authors: Garg Alpana , Subramain Maran , Barlow Patrick B , Garvin Lauren , Hoth Karin F , Dukes Kimberly , Hoffman Richard M , Comellas Alejandro P. 
Published: November 2021

AbstractPurposePost-acute sequelae of SARS-CoV-2 (PASC) is a complex condition with multisystem involvement. We assessed patients’ perspectives and experience with a PASC clinic established at University of Iowa in June 2020.MethodsWe conducted a mixed-method survey in June 2021 to ask PASC clinic patients about 1) PASC symptoms and their impact on physical and mental health, and cognition using the PROMIS Global Health and Cognitive Function abilities items, and 2) satisfaction with clinic services and referrals, barriers to care, and recommended support resources.FindingsNinety-seven patients (97/277, 35% response rate) completed the survey. Most were women (67%, n=65/97), Caucasian (93%, n=90/97) and received outpatient care during acute COVID-19 illness (79%). Fifty percent reported wait time of 1-3 months and 40% traveled >1 hour for appointment. The most common symptoms >3 months from initial infection were fatigue (77%), “brain fog” (73%), exercise intolerance (73%), anxiety (63%), sleep difficulties (56%) and depression (44%). Qualitative analysis of open-ended answers added valuable context to quantitative results. A minority of patients reported significantly reduced functioning (≥1.5 SD below mean) of their physical health (22.5%), mental health (15.9%) and cognitive abilities (17.6%). Satisfaction with clinical services was high though participants identified barriers to care including scheduling delays and financial concerns. Respondents suggested potential strategies for optimizing recovery including continuity of care, a co-located multispecialty clinic and being provided with timely information from emerging research.ConclusionOur study reports high PASC symptom burden, its impact on health and patient experience with healthcare. It is important that primary healthcare professionals listen to patients with empathy and support them during recovery. Healthcare systems and policymakers should focus on accessible, comprehensive, and patient-centered integrated care.
Classifying progression status statements from radiology exams among non-small cell lung cancer patients using natural language processing
Authors: Davoudi Anahita , Yu Shun , Doucette Abigail , Gabriel Peter , Miller Mark , Williams Heather , Desai Heena , Le Anh , Stoeckert Christian J , Maxwell Kara , Mowery Danielle L. 
Published: November 2021

AbstractAlthough NLP has been used to support cancer research more broadly, the development of NLP algorithms to extract evidence of progression from clinical notes to support lung cancer research is still in its infancy. In this study, we trained supervised machine learning classifiers using rich semantic features to detect and classify statements of progression status from radiology exams. Our progression status classifier achieves high F1-scores for detecting and discerning progression (0.80), stable (0.82), and not relevant (0.92) sentences, demonstrating promising performance. We are actively integrating these extractions with structured electronic health record data using ontologies to instantiate a longitudinal model of progression among non-small cell lung cancer patients.
Homeostatic control of c-di-AMP synthase (MsDisA) and hydrolase (MsPDE) fromMycobacterium smegmatis
Authors: Gautam Sudhanshu , Mahapa Avisek , Yeramala Lahari , Gandhi Apoorv , Krishnan Sushma , Vinothkumar Kutti R. , Chatterji Dipankar 
Published: November 2021

AbstractCyclic-di-nucleotide based secondary messengers regulate various physiological processes including the stress responses in bacteria. In the past decade, cyclic diadenosine monophosphate (c-di-AMP) has emerged as a crucial second messenger, implicated in fatty acid metabolism, antibiotic resistance, biofilm formation, virulence, DNA repair, ion homeostasis, sporulation etc. The level of c-di-AMP is maintained in the cell by the action of two opposing enzymes, namely diadenylate cyclase (DAC) and phosphodiesterase (PDE). In mycobacteria, this molecule is essential for its regulatory role in bacterial physiology and host-pathogen interactions. However, such modulation of c-di-AMP remains to be explored inMycobacterium smegmatis. Here, we systematically characterised the c-di-AMP synthase (MsDisA) and a hydrolase (MsPDE) fromM. smegmatisat different pH and osmolytic conditionsin vitro. Our biochemical assays show that the MsDisA activity is enhanced during the alkaline stress and c-di-AMP is readily produced without any intermediates. At pH 9.4, the MsDisA promoter activityin vivoincreases significantly, strengthening this observation. However, under physiological conditions, the activity of MsDisA was moderate with the formation of intermediates. To get further insights into the structural characteristics, we determined the cryo-EM structure of the MsDisA, revealing some interesting features. Biochemical analysis of individual domains shows that the N-terminal minimal region alone can form a functional octamer. Altogether, our results reveal the biochemical and structural regulation of mycobacterial c-di-AMP in response to various environmental stress.
Parapatric speciation with recurrent gene flow of two sexual dichromatic pheasants
Authors: Li Zheng , Zhou Jie , Gao Minzhi , Liang Wei , Dong Lu 
Published: November 2021

AbstractBackgroundUnderstanding speciation has long been a fundamental goal of evolutionary biology. It is widely accepted that speciation requires an interruption of gene flow to generate strong reproductive isolation between species, in which sexual selection may play an important role by generating and maintaining sexual dimorphism. The mechanism of how sexual selection operated in speciation with gene flow remains an open question and the subject of many research. Two species in genus Chrysolophus, Golden pheasant (C. pictus) and Lady Amherst’s pheasant (C. amherstiae), which both exhibit significant plumage dichromatism, are currently parapatric in the southwest China with several hybrid recordings in field.MethodsIn this research, we estimated the pattern of gene flow during the speciation of two pheasants using the Approximate Bayesian Computation (ABC) method based on the multiple genes data. With a new assembled de novo genome of Lady Amherst’s pheasant and resequencing of widely distributed individuals, we reconstructed the demographic history of the two pheasants by pairwise sequentially Markovian coalescent (PSMC).ResultsThe results provide clear evidence that the gene flow between the two pheasants were consistent with the prediction of isolation with migration model for allopatric populations, indicating that there was long-term gene flow after the initially divergence (ca. 2.2 million years ago), and further support the secondary contact when included the parapatric populations since around 30 ka ongoing gene flow to now, which might be induced by the population expansion of the Golden pheasant in late Pleistocene.ConclusionsThe results of the study support the scenario of speciation between Golden pheasant (C. pictus) and Lady Amherst’s pheasant (C. amherstiae) with cycles of mixing-isolation-mixing due to the dynamics of natural selection and sexual selection in late Pleistocene that provide a good research system as evolutionary model to test reinforcement selection in speciation.
The annotation and analysis of complex 3D plant organs using 3DCoordX
Authors: Vijayan Athul , Strauss Soeren , Tofanelli Rachele , Mody Tejasvinee Atul , Lee Karen , Tsiantis Miltos , Smith Richard S. , Schneitz Kay 
Published: November 2021

AbstractA fundamental question in biology concerns how molecular and cellular processes become integrated during morphogenesis. In plants, characterization of 3D digital representations of organs at single-cell resolution represents a promising approach to addressing this problem. A major challenge is to provide organ-centric spatial context to cells of an organ. We developed several general rules for the annotation of cell position and embodied them in 3DCoordX, a user-interactive computer toolbox implemented in the open-source software MorphoGraphX. It enables rapid spatial annotation of cells even in highly curved biological shapes. With the help of 3DCoordX we obtained new insight by analyzing cellular growth patterns in organs of several species. For example, the data indicated the presence of a basal cell proliferation zone in the ovule primordium of Arabidopsis thaliana. Proof-of-concept analyses suggested a preferential increase in cell length associated with neck elongation in the archegonium of Marchantia polymorpha and variations in cell volume linked to central morphogenetic features of a trap of the carnivorous plant Utricularia gibba. Our work demonstrates the broad applicability of the developed strategies as they provide organ-centric spatial context to cellular features in plant organs of diverse shape complexity.
Balancing selection and the crossing of fitness valleys in structured populations: diversification in the gametophytic self-incompatibility system
Authors: Stetsenko Roman , Brom Thomas , Castric Vincent , Billiard Sylvain 
Published: November 2021

AbstractThe self-incompatibility locus (S-locus) of flowering plants displays a striking allelic diversity. How such a diversity has emerged remains unclear. In this paper, we performed numerical simulations in a finite island population genetics model to investigate how population subdivision affects the diversification process at a S-locus, given that the two-genes architecture typical of S-loci involves the crossing of a fitness valley. We show that population structure slightly reduces the parameter range allowing for the diversification of self-incompatibility haplotypes (S-haplotypes), but at the same time also increases the number of these haplotypes maintained in the whole metapopulation. This increase is partly due to a higher rate of diversification and replacement of S-haplotypes within and among demes. We also show that the two-genes architecture leads to a higher diversity in structured populations compared with a simpler genetic architecture where new S-haplotypes appear in a single mutation step. Overall, our results suggest that population subdivision can act in two opposite directions: it renders S-haplotypes diversification easier, although it also increases the risk that the self-incompatibility system is lost.
Unifying Single-Channel Permeability from Rare-Event Sampling and Steady-State Flux
Authors: Lin Yi-Chun , Luo Yun Lyna 
Published: November 2021

AbstractVarious all-atom molecular dynamics (MD) simulation methods have been developed to compute free energies and crossing rates of ions and small molecules through ion channels. However, a systemic comparison across different methods is scarce. Using a carbon nanotube as a model of small conductance ion channel, we computed the single-channel permeability for potassium ion using umbrella sampling, Markovian milestoning, and steady-state flux under applied voltage. We show that a slightly modified inhomogeneous solubility-diffusion equation yields a single-channel permeability consistent with the mean first passage time (MFPT)-based method. For milestoning, applying cylindrical and spherical bulk boundary conditions yield consistent MFPT if factoring in the effective bulk concentration. The sensitivity of the MFPT to the output frequency of collective variables is highlighted using the convergence and symmetricity of the inward and outward MFPT profiles. The consistent transport kinetic results from all three methods demonstrated the robustness of MD-based methods in computing ion channel permeation. The advantages and disadvantages of each technique are discussed, focusing on the future applications of milestoning in more complex systems.
Cohesion in male singing behavior predicts group reproductive output in a social songbird
Authors: Perkes Ammon , Anderson H. Luke , Gros-Louis Julie , Schmidt Marc , White David 
Published: November 2021

SummaryAll social groups require organization to function optimally. Group organization is often shaped by social ‘rules’, which function to manage conflict, discourage cheating, or promote cooperation1–5. If social rules promote effective social living, then the ability to learn and follow these rules may be expected to influence individual and group-level fitness. However, such links can rarely be tested, due to the complexity of the factors mediating social systems and the difficulty of gathering data across multiple groups. Songbirds offer an opportunity to investigate the link between social rules and reproductive output because most of their social interactions are mediated by song, a well-studied and readily quantifiable behavior6,7. Using observations from 19 groups of brown-headed cowbirds (Molothrus ater) studied across 15 years, we find evidence for a previously undocumented social rule: cohesive group transitions between dominance- and courtship-related singing. Comparing across groups, the degree of cohesion in male singing behavior predicts the reproductive output of their group. Experimental manipulation of group structure via the introduction of juvenile males to captive flocks reduced group cohesion and adult male reproductive success. Taken together, these results demonstrate that cohesion in group behavioral states can affect both individual and group-level reproductive success, suggesting that selection can act not only on individual-level traits, but also on an individual’s ability and opportunity to participate effectively in organized social interactions. Social cohesion could therefore be an unappreciated force affecting social evolution in many diverse systems.
Evolutionary and spike-timing-dependent reinforcement learning train spiking neuronal network motor control
Authors: Haşegan Daniel , Deible Matt , Earl Christopher , D’Onofrio David , Hazan Hananel , Anwar Haroon , Neymotin Samuel A 
Published: November 2021

AbstractDespite being biologically unrealistic, artificial neural networks (ANNs) have been successfully trained to perform a wide range of sensory-motor behaviors. In contrast, the performance of more biologically realistic spiking neuronal network (SNN) models trained to perform similar behaviors remains relatively suboptimal. In this work, we aimed at pushing the field of SNNs forward by exploring the potential of different learning mechanisms to achieve optimal performance. Inspired by biological learning mechanisms operating at multiple timescales, we used spike-timing-dependent reinforcement learning (STDP-RL) and evolutionary strategy (EVOL) with SNNs to solve the CartPole reinforcement learning (RL) control problem. Though the role of STDP-RL in biological systems is well established, several other mechanisms, though not fully understood, work in concert during learning in vivo. Recreating accurate models that capture the interaction of STDP-RL with these diverse learning mechanisms is extremely difficult. EVOL is an alternative method, and has been successfully used in many studies to fit model neural responsiveness to electrophysiological recordings and in some cases for classification problems. One advantage of EVOL is that it may not need to capture all interacting components of synaptic plasticity, and thus provides a better alternative to STDP-RL. Here, we compared the performance of each algorithm after training, which revealed EVOL as a powerful method to training SNNs to perform sensory-motor behaviors. Our modeling opens up new capabilities for SNNs in RL and could serve as a testbed for neurobiologists aiming to understand multi-timescale learning mechanisms and dynamics in neuronal circuits.
A Proteome-Wide Map of Chaperone-Assisted Protein Refolding in the Cytosol
Authors: To Philip , Xia Yingzi , Devlin Taylor , Fleming Karen G. , Fried Stephen D. 
Published: November 2021

AbstractThe journey by which proteins navigate their energy landscapes to their native structures is complex, involving (and sometimes requiring) many cellular factors and processes operating in partnership with a given polypeptide chain’s intrinsic energy landscape. The cytosolic environment and its complement of chaperones play critical roles in granting proteins safe passage to their native states; however, the complexity of this medium has generally precluded biophysical techniques from interrogating protein folding under cellular-like conditions for single proteins, let alone entire proteomes. Here, we develop a limited-proteolysis mass spectrometry approach paired with an isotope-labeling strategy to globally monitor the structures of refolding E. coli proteins in the cytosolic medium and with the chaperones, GroEL/ES (Hsp60) and DnaK/DnaJ/GrpE (Hsp70/40). GroEL can refold the majority (85%) of the E. coli proteins for which we have data, and is particularly important for restoring acidic proteins and proteins with three to five domains, trends that come to light because our assay measures the structural outcome of the refolding process itself, rather than indirect measures like binding or aggregation. For the most part, DnaK and GroEL refold a similar set of proteins, supporting the view that despite their vastly different structures, these two chaperones both unfold misfolded states, as one mechanism in common. Finally, we identify a cohort of proteins that are intransigent to being refolded with either chaperone. The data support a model in which chaperone-nonrefolders have evolved to fold efficiently once and only once, co-translationally, and remain kinetically trapped in their native conformations.
Unsupervised cell functional annotation for single-cell RNA-Seq
Authors: Li Dongshunyi , Ding Jun , Bar-Joseph Ziv 
Published: November 2021

AbstractOne of the first steps in the analysis of single cell RNA-Sequencing data (scRNA-Seq) is the assignment of cell types. While a number of supervised methods have been developed for this, in most cases such assignment is performed by first clustering cells in low-dimensional space and then assigning cell types to different clusters. To overcome noise and to improve cell type assignments we developed UNIFAN, a neural network method that simultaneously clusters and annotates cells using known gene sets. UNIFAN combines both, low-dimensional representation for all genes and cell specific gene set activity scores to determine the clustering. We applied UNIFAN to human and mouse scRNA-Seq datasets from several different organs. As we show, by using knowledge on gene sets, UNIFAN greatly outperforms prior methods developed for clustering scRNA-Seq data. The gene sets assigned by UNIFAN to different clusters provide strong evidence for the cell type that is represented by this cluster making annotations easier.Softwarehttps://github.com/doraadong/UNIFAN
Incident heart failure and myocardial infarction in sodium-glucose cotransporter 2 versus dipeptidyl peptidase-4 inhibitor users
Authors: Zhou Jiandong , Lee Sharen , Kit Leung Keith Sai , Chung Wai Abraham Ka , Liu Tong , Liu Ying , Chang Dong , Wong Wing Tak , Kei Wong Ian Chi , Yung Cheung Bernard Man , Zhang Qingpeng , Tse Gary 
Published: November 2021

AbstractObjectivesTo compare the rates of major cardiovascular adverse events in sodium-glucose cotransporter-2 inhibitors (SGLT2I) and dipeptidyl-peptidase-4 inhibitors (DPP4I) users in a Chinese population.BackgroundSGLT2I and DPP4I are increasingly prescribed for type 2 diabetes mellitus patients. However, few population-based studies are comparing their effects on incident heart failure or myocardial infarction.MethodsThis was a population-based retrospective cohort study using the electronic health record database in Hong Kong, including type 2 diabetes mellitus patients receiving either SGLT2I or DPP4I between January 1st, 2015, to December 31st, 2020. Propensity-score matching was performed in a 1:1 ratio based on demographics, past comorbidities, non-SGLT2I/DPP4I medications with nearest-neighbor matching (caliper=0.1). Univariable and multivariable Cox models were used to identify significant predictors for new onset heart failure, new onset myocardial infarction, cardiovascular mortality, and all-cause mortality. Sensitivity analyses with competing risk models and multiple propensity score matching approaches were conducted. Subgroup age and gender analyses were presented.ResultsA total of 41994 patients (58.89% males, median admission age at 58 years old, interquartile rage [IQR]: 51.2-65.3) were included in the study cohorts with a median follow-up duration of 5.6 years (IQR: 5.32-5.82). After adjusting for significant demographics, past comorbidities, medication prescriptions and biochemical results, SGLT2I users have a significantly lower risk for myocardial infarction (hazard ratio [HR]: 0.34, 95% confidence interval [CI]: [0.28, 0.41], P < 0.0001), cardiovascular mortality (HR: 0.53, 95% CI: [0.38, 0.74], P = 0.0002) and all-cause mortality (HR: 0.21, 95% CI: [0.18, 0.25], P= 0.0001) under multivariable Cox regression. However, the risk for heart failure is comparable (HR: 0.87, 95% CI: [0.73, 1.04], P= 0.1343).ConclusionsSGLT2 inhibitors are protective against adverse cardiovascular events compared to DPP4I. The prescription of SGLT2I is preferred especially for males and patients aged 65 or older to prevent cardiovascular risks.