bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mosaics of climatic stress across species' ranges: tradeoffs cause adaptive evolution to limits of climatic tolerance
Authors: Parmesan Camille , Singer Michael C. 
Published: February 2022

Studies in birds and trees show climatic stresses distributed across species' ranges, not only at range limits. Here, new analyses from the butterflyEuphydryas edithareveal mechanisms generating these stresses: geographic mosaics of natural selection, acting on tradeoffs between climate adaptation and fitness traits, cause some range-central populations to evolve to limits of climatic tolerance, while others remain resilient. In one ecotype, selection for predator avoidance drives evolution to limits of thermal tolerance. In a second ecotype, the endangered Bay Checkerspot, selection on fecundity drives evolution to the climate-sensitive limit of ability to complete development within the lifespans of ephemeral hosts, causing routinely high mortality from insect–host phenological asynchrony. The tradeoff between maternal fecundity and offspring mortality generated similar values of fitness on different dates, partly explaining why fecundity varied by more than an order of magnitude. Evolutionary response to the tradeoff rendered climatic variability the main driver of Bay Checkerspot dynamics, and increases in this variability, associated with climate change, were a key factor behind permanent extinction of a protected metapopulation. Finally, we discuss implications for conservation planning of our finding that adaptive evolution can reduce population-level resilience to climate change and generate geographic mosaics of climatic stress.This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.
Effects of species interactions on the potential for evolution at species' range limits
Authors: Alexander Jake M. , Atwater Daniel Z. , Colautti Robert I. , Hargreaves Anna L. 
Published: February 2022

Species’ ranges are limited by both ecological and evolutionary constraints. While there is a growing appreciation that ecological constraints include interactions among species, like competition, we know relatively little about how interactions contribute to evolutionary constraints at species' niche and range limits. Building on concepts from community ecology and evolutionary biology, we review how biotic interactions can influence adaptation at range limits by impeding the demographic conditions that facilitate evolution (which we term a ‘demographic pathway to adaptation’), and/or by imposing evolutionary trade-offs with the abiotic environment (a ‘trade-offs pathway’). While theory for the former is well-developed, theory for the trade-offs pathway is not, and empirical evidence is scarce for both. Therefore, we develop a model to illustrate how fitness trade-offs along biotic and abiotic gradients could affect the potential for range expansion and niche evolution following ecological release. The model shows that which genotypes are favoured at species' range edges can depend strongly on the biotic context and the nature of fitness trade-offs. Experiments that characterize trade-offs and properly account for biotic context are needed to predict which species will expand their niche or range in response to environmental change.This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.
Understanding the biology of species' ranges: when and how does evolution change the rules of ecological engagement?
Authors: Bridle Jon , Hoffmann Ary 
Published: February 2022

Understanding processes that limit species' ranges has been a core issue in ecology and evolutionary biology for many decades, and has become increasingly important given the need to predict the responses of biological communities to rapid environmental change. However, we still have a poor understanding of evolution at range limits and its capacity to change the ecological ‘rules of engagement’ that define these communities, as well as the time frame over which this occurs. Here we link papers in the current volume to some key concepts involved in the interactions between evolutionary and ecological processes at species' margins. In particular, we separate hypotheses about species’ margins that focus on hard evolutionary limits, which determine how genotypes interact with their environment, from those concerned with soft evolutionary limits, which determine where and when local adaptation can persist in space and time. We show how theoretical models and empirical studies highlight conditions under which gene flow can expand local limits as well as contain them. In doing so, we emphasize the complex interplay between selection, demography and population structure throughout a species' geographical and ecological range that determines its persistence in biological communities. However, despite some impressively detailed studies on range limits, particularly in invertebrates and plants, few generalizations have emerged that can predict evolutionary responses at ecological margins. We outline some directions for future work such as considering the impact of structural genetic variants and metapopulation structure on limits, and the interaction between range limits and the evolution of mating systems and non-random dispersal.This article is part of the theme issue ‘Species’ ranges in the face of changing environments (Part II)’.
Optimal intervention strategies for minimizing total incidence during an epidemic
Authors: Britton Tom , Leskelä Lasse 
Published: February 2022

AbstractThis article considers the minimization of the total number of infected individuals over the course of an epidemic in which the rate of infectious contacts can be reduced by time-dependent nonpharmaceutical interventions. The societal and economic costs of interventions are taken into account using a linear budget constraint which imposes a trade-off between short-term heavy interventions and long-term light interventions. We search for an optimal intervention strategy in an infinite-dimensional space of controls containing multiple consecutive lockdowns, gradually imposed and lifted restrictions, and various heuristic controls based for example on tracking the effective reproduction number. Mathematical analysis shows that among all such strategies, the global optimum is achieved by a single constant-level lockdown of maximum possible magnitude. Numerical simulations highlight the need of careful timing of such interventions, and illustrate their benefits and disadvantages compared to strategies designed for minimizing peak prevalence. Rather counterintuitively, adding restrictions prior to the start of a well-planned intervention strategy may even increase the total incidence.
Automated identification of unstandardized medication data: A scalable and flexible data standardization pipeline using RxNorm on GEMINI multicenter hospital data
Authors: Waters Riley , Malecki Sarah , Lail Sharan , Mak Denise , Saha Sudipta , Jung Hae Young , Razak Fahad , Verma Amol 
Published: February 2022

ABSTRACTObjectivePatient data repositories often assemble medication data from multiple sources, necessitating standardization prior to analysis. We implemented and evaluated a medication standardization procedure for use with a wide range of pharmacy data inputs across all drug categories, which supports research queries at multiple levels of granularity.MethodsThe GEMINI-RxNorm system automates the use of multiple RxNorm tools in tandem with other datasets to identify drug concepts from pharmacy orders. GEMINI-RxNorm was used to process 2,090,155 pharmacy orders from 245,258 hospitalizations between 2010 and 2017 at 7 hospitals in Ontario, Canada. The GEMINI-RxNorm system matches drug-identifying information from pharmacy data (including free-text fields) to RxNorm concept identifiers. A user interface allows researchers to search for drug terms and returns the relevant original pharmacy data through the matched RxNorm concepts. Users can then manually validate the predicted matches and discard false positives. We designed the system to maximize recall (sensitivity) and enable excellent precision (positive predictive value) with minimal manual validation. We compared the performance of this system to manual coding (by a physician and pharmacist) of 13 medication classes.ResultsManual coding was performed for 1,948,817 pharmacy orders and GEMINI-RxNorm successfully returned 1,941,389 (99.6%) orders. Recall was greater than 98.5% in all 13 drug classes, and the F-Measure and precision remained above 90.0% in all drug classes, facilitating efficient manual review to achieve 100.0% precision. GEMINI-RxNorm saved time substantially compared to manual standardization, reducing the time taken to review a pharmacy order row from an estimated 30 seconds to 5 seconds and reducing the number of rows needed to be reviewed by up to 99.99%.Discussion and ConclusionGEMINI-RxNorm presents a novel combination of RxNorm tools and other datasets to enable accurate, efficient, flexible, and scalable standardization of pharmacy data. By facilitating efficient minimal manual validation, the GEMINI-RxNorm system can allow researchers to achieve near-perfect accuracy in medication data standardization.
SPECIFICATIONS OF THE ACMG/AMP VARIANT CURATION GUIDELINES FOR MYOCILIN: RECOMMENDATIONS FROM THE CLINGEN GLAUCOMA EXPERT PANEL
Authors: Burdon Kathryn P , Graham Patricia , Hadler Johanna , Hulleman John D , Pasutto Francesca , Boese Erin A , Craig Jamie E , Fingert John H , Hewitt Alex W , Siggs Owen M , Whisenhunt Kristina , Young Terri L , Mackey David A , Dubowsky Andrew , Souzeau Emmanuelle 
Published: February 2022

ABSTRACTThe standardization of variant curation criteria is essential for accurate interpretation of genetic results and clinical care of patients. The variant curation guidelines developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015 are widely used but are not gene specific. To address this issue, the Clinical Genome Resource (ClinGen) Variant Curation Expert Panels (VCEP) have been tasked with developing gene-specific variant curation guidelines. The Glaucoma VCEP was created to develop rule specifications for genes associated with primary glaucoma, including myocilin (MYOC), the most common cause of Mendelian glaucoma. Of the 28 ACMG/AMP criteria, the Glaucoma VCEP adapted 15 rules to MYOC, and deemed 13 rules not applicable. Key specifications included determining minor allele frequency thresholds, developing an approach to counting probands and segregations, and reviewed functional assays. The rules were piloted on 81 variants and led to a change in classification in 38% of those that were classified in ClinVar with functional evidence influencing the classification of 18 variants. The standardized variant curation guidelines for MYOC provide a framework for the consistent application of the rules between laboratories, to improve MYOC genetic testing in the management of glaucoma.
Factors Associated with Food Insecurity among Pregnant Women in Gedeo Zone Public Hospitals, Southern Ethiopia
Authors: Areba Abriham Shiferaw , Haile Arega , Abire Belayneh Genoro , Debela Berhanu Gidisa , Legesse Miheret Tesfu , Andarge Sewitemariam Desalegn , Kanno Girum Gebremeskel , Gondol Belay Negassa , Abame Desta Erkalo 
Published: February 2022

AbstractBackgroundFood insecurity refers to a lack of consistent access to sufficient food for active, better health. Around two billion people worldwide suffer from food insecurity and hidden hunger. Food insecurity and associated factors among pregnant women in Gedeo Zone Public Hospitals, Southern Ethiopia, are the focus of this study.MethodFrom May to June 2021 G.C. institutional-based cross-sectional study was conducted among pregnant women in Gedeo zone public hospitals. A sample of 506 women has been used, and a multistage cluster sampling technique was used. An adjusted odds ratio (AOR) and their 95% confidence intervals (CI) were calculated to determine the association between various factors and outcomes. A p-value of less than 0.05 was considered significant in multivariable regression.ResultsFood insecurity was found to be prevalent in 67.4% of pregnant mothers. The results of a multivariable logistic regression revealed that pregnant women from rural areas [AOR=0.532, 95 % CI: 0.285, 0.994], married [AOR=0.232, 95% CI: 0.072, 0.750], have a secondary education [AOR=0.356, 95%CI: 0.154, 0.822], and be employed [AOR=0.453, 95% CI: 0.236, 0.872], income between 1000 and 2000 [AOR=0.163, 95% CI: 0.066, 0.399], and income greater than 2000 [AOR=0.125, 95% CI: 0.053,0.293], the wealth index middle and rich [AOR=0.441, 95% CI: 0.246, 0.793] were significant predictors of food insecurity among pregnant mothers [AOR=0.24, 95 % CI: 0.128, 0.449].ConclusionThe study area had a high prevalence of food insecurity. Food insecurity was reduced in those who lived in rural areas, were married, had a secondary education, earned between 1000 and 2000 ETB and more than 2000 ETB, and had a wealth index of middle and rich.
Effects of bilateral sequential theta-burst stimulation on functional connectivity in treatment-resistant depression: first results
Authors: Stöhrmann Peter , Godbersen Godber Mathis , Reed Murray Bruce , Unterholzner Jakob , Klöbl Manfred , Baldinger-Melich Pia , Vanicek Thomas , Hahn Andreas , Lanzenberger Rupert , Kasper Siegfried , Kranz Georg S. 
Published: February 2022

AbstractBackgroundPrevious studies suggest that transcranial magnetic stimulation exerts antidepressant effects by altering functional connectivity (FC). However, knowledge about this mechanism is still limited. Here, we aimed to investigate the effect of bilateral sequential theta-burst stimulation (TBS) on FC in treatment-resistant depression (TRD) in a sham-controlled longitudinal study.MethodsTRD patients (n = 20) underwent a three-week treatment of intermittent TBS of the left and continuous TBS of the right dorsolateral prefrontal cortex (DLPFC). Upon this trial’s premature termination, 15 patients had received active TBS and five patients sham stimulation. Resting-state functional magnetic resonance imaging was performed at baseline and after treatment. FC (left and right DLPFC) was estimated for each participant, followed by group statistics (T-tests). Furthermore, depression scores were analyzed (linear mixed models analysis) and tested for correlation with FC.ResultsBoth groups exhibited reductions of depression scores, however, there was no significant main effect of group, or group and time. Anticorrelations between DLPFC and the subgenual cingulate cortex (sgACC) were observed for baseline FC, corresponding to changes in depression severity. Treatment did not significantly change DLPFC-sgACC connectivity, but significantly reduced FC between the left stimulation target and bilateral anterior insula.ConclusionsOur data is compatible with previous reports on the relevance of anticorrelation between DLPFC and sgACC for treatment success. Furthermore, FC changes between left DLPFC and bilateral anterior insula highlight the effect of TBS on the salience network.LimitationsDue to the limited sample size, results should be interpreted with caution and are of exploratory nature.
Periductal bile acid exposure causes cholangiocyte injury and fibrosis
Authors: Dotan Miri , Fried Sophia , Har-Zahav Adi , Shamir Raanan , Wells Rebecca G , Waisbourd-Zinman Orith 
Published: February 2022

AbstractIntroductionBile duct integrity is essential for the maintenance of the structure and function of the biliary tree. We previously showed that cholangiocyte injury in a toxic model of biliary atresia leads to increased monolayer permeability. Increased epithelial permeability was also shown in other cholangiopathies. We hypothesized that after initial cholangiocyte injury, leakage of bile acids into the duct submucosa propagates cholangiocyte damage and fibrosis. We thus aimed to determine the impact of bile acid exposure on cholangiocytes and the potential therapeutic effect of a non-toxic bile acid.Materials and methodsExtrahepatic bile duct explants were isolated from adult and neonatal BALB/c mice. Explants were cultured with or without glycochenodeoxycholic acid and ursodeoxycholic acid. They were then fixed and stained.ResultsExplants treated with glycochenodeoxycholic acid demonstrated cholangiocyte injury with monolayer disruption and partial lumen obstruction compared to control ducts. Masson’s trichrome stains revealed increased collagen fibers. Myofibroblast marker α-SMA stains were significantly elevated in the periductal region. The addition of ursodeoxycholic acid resulted in decreased cholangiocyte injury and reduced fibrosis.ConclusionsBile acid leakage into the submucosa after initial cholangiocyte injury may serve as a possible mechanism of disease propagation and progressive fibrosis in cholangiopathies.
Characterization of small fiber neuropathy in hypermobile Ehlers Danlos Syndrome
Authors: Fernandez Aurore , Aubry-Rozier Bérengère , Vautey Mathieu , Berna Chantal , Suter Marc R. 
Published: February 2022

Hypermobile Ehlers Danlos Syndrome (hEDS)/hypermobility spectrum disorders (HSD) are incapacitating and painful syndromes involving a generalized connective tissue disorder with joint hypermobility and musculoskeletal complications. A neuropathic component is clinically likely given frequent burning sensations, hypoesthesia, or allodynia. Small fiber neuropathy (SFN) refers to the dysfunction or damage of A-δ and C-fibers, which relay thermal and nociceptive information as well as mediating autonomic function. SFN has been suggested by prior studies in hEDS but these early findings (case series N≤20) with sole reliance on intraepidermal nerve fiber density (IENFD) called for a larger sample combined with functional testing.In this retrospective chart extraction from 79 hEDS/HSD patients referred to a pain center due to neuropathic pain or dysautonomia, both functional (Quantitative Sensory Testing (QST), N=79) and structural (IENFD, N=69) evaluations of small nerve fibers were analyzed in combination with clinical data and standardized questionnaires.All the patients reported moderate to severe pain interfering with daily life. A decreased thermal detection (QST) was shown in 55/79 patients (70%) and a decreased IENFD in 54/69 patients (78%). Hence a small fiber neuropathy (both abnormal IENFD and QST) was definite in 40/69 patients (58%), possible in 23/69 patients (33%) and excluded in only 6/69 patients (9%).These results add strong evidence for a peripheral neuropathic contribution to pain symptoms in hEDS/HSD, in addition to the known nociceptive and central sensitization components. Such neuropathic contribution could raise the hypothesis of a neurological cause of hEDS, the only EDS syndrome still without a known genetic cause. Hence, our data is leading the way to a better stratification of this very heterogeneous population, which could improve symptom management and expand pathophysiological research.
Community engaged tick surveillance and tickMAP as a public health tool to track the emergence of ticks and tick-borne diseases in New York
Authors: Hart Charles E , Bhaskar Jahnavi Reddy , Reynolds Erin , Hermance Meghan , Earl Martin , Mahoney Matthew , Martinez Ana , Petzlova Ivona , Esterly Allen T , Thangamani Saravanan 
Published: February 2022

ABSTRACTA community engaged passive surveillance program was utilized to acquire ticks and associated information throughout New York state. Ticks were speciated and screened for several tick-borne pathogens. Of these ticks, only I. scapularis was commonly infected with pathogens of human relevance, including B. burgdorferi, B. miyamotoi, A. phagocytophilum, B. microti, and Powassan virus. In addition, the geographic and temporal distribution of tick species and pathogens was determined. This enabled the construction of a powerful visual analytical mapping tool, tickMAP to track the emergence of ticks and tick-borne pathogens in real-time. The public can use this tool to identify hot-spots of disease emergence, clinicians for supportive evidence during differential diagnosis, and researchers to better understand factors influencing the emergence of ticks and tick-borne diseases in New York. Overall, we have created a community-engaged tick surveillance program and an interactive visual analytical tickMAP that other regions could emulate to provide real-time tracking and an early warning for the emergence of tick-borne diseases.
Spatial Correlation of Left Atrial Low Voltage Substrate in Sinus Rhythm versus Atrial Fibrillation: Identifying the Pathological Substrate Irrespective of the Rhythm
Authors: Nairn Deborah , Eichenlaub Martin , Lehrmann Heiko , Müller-Edenborn Björn , Chen Juan , Huang Taiyuan , Nagel Claudia , Sánchez Jorge , Luongo Giorgio , Arentz Thomas , Dössel Olaf , Jadidi Amir , Loewe Axel 
Published: February 2022

AbstractBackgroundLow voltage substrate (LVS) identified during electroanatomical mapping is a potential target for atrial fibrillation (AF) ablation. However, it is not clear how the location and extent of LVS correlate between mapping in sinus rhythm (SR) and AF.Objectives(1) Identify voltage dissimilarities between mapping in SR and AF. (2) Identification of regional voltage thresholds that improve cross-rhythm sub-strate detection. (3) Comparison of LVS between SR and native vs. induced AF.MethodsForty-one ablation-naive persistent AF patients underwent high-density voltage mapping in SR and AF. Each patient’s voltage information was mapped to a joint geometry for analysis. Global and regional voltage thresholds in AF were identified which best match LVS<0.5mV and <1.0mV in SR. Additionally, the correlation between SR-LVS with induced vs. native AF LVS was assessed.ResultsSubstantial voltage differences (median: 0.52, IQR: 0.33-0.69, max: 1.19mV) with predominance of the posterior/inferior LA wall exist between the rhythms. An AF threshold of 0.34mV for the entire atrium provides an accuracy, sensitivity and specificity of 69%, 67% and 69% to identify SR-LVS<0.5mV, respectively. Lower thresholds for the posterior wall (0.27 mV) and inferior wall (0.3mV) result in higher spatial concordance to SR-LVS (4% and 7% increase). Concordance with SR-LVS was higher for induced AF compared to native AF (AUC: 0.80 vs. 0.73). AF-LVS<0.5mV corresponds to SR-LVS<0.97mV using high-definition mapping (AUC: 0.73).ConclusionThe proposed voltage thresholds during AF maximise the consistency of LVS identification as determined during SR. Regional thresholds can further improve concordance.