bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Experience of an American Academic Ophthalmology Department During the COVID-19 Pandemic
Authors: Kuo Irene C. 
Published: February 2022

Background and Objectives:
To describe the experience of a large American academic ophthalmology department from the start of the COVID-19 pandemic to the early recovery phase in Summer 2020.

Methods:
Retrospective review; description of approaches taken by our academic medical center and department regarding supply chain issues, protection of doctors and staff, elimination of nonurgent care, calls for staff and faculty deployment, and reopening. Comparison of surgical and clinic volumes in suburban locations versus the main campus; analysis of volumes compared with pre-pandemic periods.

Results:
At our medical center, screening and precautions (such as the mask policy) continued to evolve from March through August 2020. Ophthalmologists were not allowed to use N95 respirators except in rare circumstances. Surgical and clinic volume dropped at both urban and suburban locations, but surgery rebounded more quickly at suburban surgery centers once elective procedures resumed. Mandates from administration were not always attainable.

Conclusions:
During respiratory pandemics such as COVID-19, medical centers should adopt protective measures that are consistent across inpatient and outpatient sectors and consistent with other institutions. Our department's large presence outside the urban center where the main hospital is located allowed faster return of clinical care overall. In the event of another pandemic, a central budget rather than individual divisional budgets should be used for purchase of protective equipment for health care workers of an academic center. Because outpatient care provides important continuity of care and keeps patients away from emergency departments and hospitals, perhaps outpatient care does not have to be curtailed to the extent it was in Spring-Summer 2020, provided that outpatient health care workers have sufficient staff and equipment and the above measures are in place.
Circular noncoding RNA circ_0007865, serves as a competing endogenous RNA, targeting the miR-214-3p/FKBP5 axis to regulate oxygen-glucose deprivation-induced injury in brain microvascular endothelial cells
Authors: Liu Jinghua , Zhang Hong , Di Kuiyi , Hou Liying , Yu Shanshan 
Published: February 2022

Background
Ischemic stroke (IS) is a major cause of permanent morbidity and lifelong disability worldwide. Circular RNA (circRNA) circ_0007865 has been reported to be upregulated in acute ischemic stroke (AIS) patients. Also, AIS patients exhibited increased death of human brain microvascular endothelial cells (HBMECs). This study is designed to explore the role and mechanism of circ_0007865 in the oxygen-glucose deprivation (OGD)-induced cell damage in AIS.

Methods
Circ_0007865, microRNA-214-3p (miR-214-3p), and FK506-binding protein 5 (FKBP5) levels were detected by real-time quantitative PCR. Cell proliferative angiogenesis, migration, and apoptosis were assessed by Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, colony formation, tube formation, wound healing, transwell, and flow cytometry assays. B-cell lymphoma-2 (Bcl-2), Bcl-2-related X protein (Bax), cleaved caspase-3, and FKBP5 protein levels were determined by western blot assay. The binding relationship between miR-214-3p and circ_0007865 or FKBP5 was predicted by StarBase, and verified by a dual-luciferase reporter, RNA pull-down assay.

Results
Circ_0007865 and FKBP5 were increased, and miR-214-3p was decreased in OGD-treated HBMECs. Furthermore, the silencing of circ_0007865 could promote cell proliferative angiogenesis, migration, and inhibit apoptosis in OGD-triggered HBMECs in vitro. Mechanically, circ_0007865 acted as a sponge of miR-214-3p to regulate FKBP5.

Conclusion
According to these results, circ_0007865 deficiency could attenuate OGD-induced HBMEC damage by modulating the miR-214-3p/FKBP5 axis, hinting at a promising therapeutic target for future acute IS therapy.
Results From the REsCue Trial: A Randomized Controlled Trial with Extended-Release Calcifediol in Symptomatic Outpatients with COVID-19
Authors: Bishop Charles W. , Ashfaq Akhtar , Melnick Joel Z. , Vazquez-Escarpanter Enrique , Fialkow Jonathan A. , Strugnell Stephen A. , Choe John , Kalantar-Zadeh Kamyar , Federman Noah C. , Ng David , Adams John S. 
Published: February 2022

ABSTRACTImportanceThe benefit of vitamin D treatment for coronavirus disease 2019 (COVID-19) remains unclear.ObjectiveTo investigate the effect of raising serum total 25-hydroxyvitamin D (25D) to 50-100 ng/mL with oral extended-release calcifediol (ERC) on time to symptom resolution in mild to moderate COVID-19.Design, Setting, and ParticipantsA multicenter, randomized, double-blind, placebo-controlled study evaluated treatment of 160 outpatients with COVID-19 diagnosed between November 2020 and October 2021.InterventionsPatients were treated for 4 weeks with ERC (30 mcg/capsule; 300 mcg on Days 1-3 and 60 mcg on Days 4-27) or placebo.Outcome MeasuresPrimary endpoints were raising serum 25D to ≥50 ng/mL at Day 14 and resolution time for five aggregated symptoms. Secondary endpoints included resolution time for aggregated and individual symptoms as a function of serum 25D and changes in clinical biomarkers.Results171 subjects randomized, 160 treated and 134 (65 ERC and 69 placebo) retained. Average age was 43 (range: 18-71); 59% female, 92% White, 80% Hispanic, 7% African-American, 1% Other, 76% overweight, 40% obese, 26% comorbidities, mean baseline 25D of 37±1 (SE) ng/mL. ERC increased mean 25D to 82±4 ng/mL (p<0.001) by Day 7; 88% of subjects attained a level ≥50 ng/mL; the placebo group trended lower. Resolution time for five aggregated symptoms was unchanged by ERC given that two composite non-respiratory symptoms responded poorly. Prespecified analyses showed that respiratory symptoms tended to resolve earlier when serum 25D levels reached ≤50 ng/mL, but statistical significance was limited by small sample size and non-compliance: 25D increased in seven placebo subjects (unauthorized supplementation) and none occurred in five ERC subjects (failure to dose). A post-hoc composite of three respiratory symptoms (trouble breathing, chest congestion and dry or hacking cough) resolved 3.0 days faster when 25D was elevated at Days 7 and 14 (p<0.05); chest congestion resolved 4.0 days faster with 25D increases of ≥25 ng/mL (p<0.05). Safety concerns including hypercalcemia were absent with ERC treatment.Conclusions and RelevanceERC was effective in increasing serum 25D in outpatients with COVID-19, which may have accelerated resolution of respiratory symptoms suggesting mitigation of COVID-19 pneumonia risk, findings which warrant further study.
Whole-Brain Map of Top-down afferent Inputs to Nucleus Accumbens of the Mouse
Authors: Xu Tonghui , Wu Jialiang , Chen Zhilong , Li Zhao 
Published: February 2022

ABSTRACTNucleus accumbens (NAc) is an important part of basal ganglia and receives major transsynaptic inputs from medial prefrontal cortex (mPFC), basolateral amygdala nucleus (BL) and hippocampus (HPC). The neural circuits formed by mPFC, BL, HPC with NAc are closely related to diverse brain functions such as decision-making, social behavior, reward seeking behavior and aggressive behavior. However, a lack of information about network structure of NAc top-down afference has limited our understanding of mechanisms of these functions. Here, we systematically analyzed whole brain patterns of inputs to mPFC/HPC/BL-NAc projectors via using (TRIO) labeling strategy. We found that the upstream input patterns between mPFC-core and mPFC-shell projections, BL-core and BL-shell projections, HPC-core and HPC-shell projections were similar. The projections from mPFC and BL to NAc receive a wide range of inputs, while the projections from HPC to NAc receive convergent inputs. Furthermore, all of mPFC/HPC/BL-NAc projectors receive considerable inputs from respective local regions. This study lays a foundation for further analysis of complex NAc functional mechanisms.
Interactions between genes altered during cardiotoxicity and neurotoxicity in zebrafish revealed using induced network modules analysis
Authors: Kagoo R Andrea , Sharma Ankush , Bhargava Anamika 
Published: February 2022

ABSTRACTZebrafish has become a prominent model organism to study toxicology due to its genomic similarity to humans, optical clarity, well defined developmental stages, short generation time and cost-effective maintenance. It also provides a shorter time frame for in vivo toxicology evaluation compared to mammalian experimental systems. As manufacturing processes and development of new synthetic compounds increase to keep pace with the expanding global demand, environmental health and the effects of toxicant exposure are emerging as critical public health concerns. Owing to this, in this study, we analyzed the impact of such chemical induced toxicity in zebrafish. We first searched the literature comprehensively for genes that were modulated during neurotoxicity and cardiotoxicity in zebrafish and then studied the interactions between those genes using induced network modules analysis of the database ConsensusPathDB. The induced network modules analysis helps to study gene interactions through various types of interactions like gene regulatory, biochemical, genetic and protein interactions. A constant communication between the heart and the brain is an important physiological phenomenon. Therefore, we also analyzed the interactions among genes that are modulated simultaneously during cardiotoxicity and neurotoxicity. This study has led us to identify some potential predictive biomarkers for neurotoxicity and cardiotoxicity in zebrafish.
High rates of spontaneous chromosomal duplications unravel dosage compensation by translational regulation
Authors: Krasovec Marc , Merret Remy , Sanchez Frédéric , Sanchez-Brosseau Sophie , Piganeau Gwenaël 
Published: February 2022

ABSTRACTWhile duplications have long been recognized as a fundamental process driving major evolutionary innovations, direct estimations of spontaneous chromosome duplication rates, leading to aneuploid karyotypes, are scarce. Here, we provide the first estimations of spontaneous chromosome duplication rates in six unicellular eukaryotic species from mutation accumulation (MA) experiments. The spontaneous chromosome duplication rates reach 1×10−4to 1×10−3per genome per generation, which is ~4 to ~50 times less frequent than spontaneous point mutations per genome, whereas chromosome duplication events can affect 1 to 7% of the total genome size. Comparative transcriptomics between MA lines with different chromosome duplications reveals a strong positive correlation between RNA expression rate and DNA copy number. However, comparative analyses of the translation rate of mRNAs estimated by polysome profiling unravel a chromosome specific dosage compensation mechanism. In particular, one chromosome with a gene average of 2.1 excess of mRNAs is compensated by an average of ~0.7 decrease in translation rates. Altogether, our results are consistent with previous observations of a chromosome dependent effect of dosage compensation and provide evidence that it may occur during translation. These results support the existence of a yet unknown post-transcriptional mechanism orchestrating the modification of translation of hundreds of transcripts from genes located on duplicated regions in eukaryotes.
Physiological causes and biogeographic consequences of thermal optima in the hypoxia tolerance of marine ectotherms
Authors: Endress Martin-Georg A. , Boag Thomas H. , Burford Benjamin P. , Penn Justin L. , Sperling Erik A. , Deutsch Curtis A. 
Published: February 2022

AbstractThe minimum O2 needed to fuel the demand of aquatic animals is commonly observed to increase with temperature, driven by accelerating metabolism. However, recent measurements of critical O2 thresholds (‘Pcrit’) reveal more complex patterns, including those with a minimum at an inter-mediate thermal ‘optimum’. To discern the prevalence, physiological drivers, and biogeographic manifestations of such curves, we analyze new experimental and biogeographic data using a general dynamic model of aquatic water breathers. The model simulates the transfer of oxygen from ambient water, through a boundary layer and into animal tissues driven by temperature-dependent rates of metabolism, diffusive gas exchange, and ventilatory and circulatory systems with O2-protein binding. We find that a thermal optimum in Pcrit can arise even when all physiological rates increase steadily with temperature. This occurs when O2 supply at low temperatures is limited by a process that is more temperature sensitive than metabolism, but becomes limited by a less sensitive process at warmer temperatures. Analysis of species respiratory traits suggests this scenario is not uncommon in marine biota, with ventilation and circulation limiting supply under cold conditions and diffusion limiting supply at high temperatures. Using biogeographic data, we show that species with these physiological traits inhabit lowest O2 waters near the optimal temperature for hypoxia tolerance, and are restricted to higher O2 at temperatures above and below this optimum. Our results imply that O2 tolerance can decline under both cold and warm conditions, and thus may influence both poleward and equatorward species range limits.Significance StatementPhysiology shapes the ecology, biogeography, and climate responses of marine species. In aquatic ectotherms, accelerating metabolism and lowered oxygen availability generally result in increasing oxygen limitation with warming. Here we present evidence for thermal optima in hypoxia tolerance of diverse species that is explained by a dynamical model of organismal physiology. Our results indicate that this potentially widespread bidirectional pattern explains species biogeographic limits in cold and warm waters. It can be understood using a generalized Metabolic Index of O2 supply to demand, which captures the variable observed trends between temperature and species hypoxia sensitivity. Oxygen limitation of aerobic metabolism in cold water has far-reaching implications for marine biogeography and species migrations under climate change.
A scalable and unbiased discordance metric with H+
Authors: Dyjack Nathan , Baker Daniel N. , Braverman Vladimir , Langmead Ben , Hicks Stephanie C. 
Published: February 2022

AbstractA standard unsupervised analysis is to cluster observations into discrete groups using a dissimilarity measure, such as Euclidean distance. If there does not exist a ground-truth label for each observation necessary for external validity metrics, then internal validity metrics, such as the tightness or consistency of the cluster, are often used. However, the interpretation of these internal metrics can be problematic when using different dissimilarity measures as they have different magnitudes and ranges of values that they span. To address this problem, previous work introduced the ‘scale-agnostic’ G+ discordance metric, however this internal metric is slow to calculate for large data. Furthermore, we show that G+ varies as a function of the proportion of observations in the predicted cluster labels (group balance), which is an undesirable property.To address this problem, we propose a modification of G+, referred to as H+, and demonstrate that H+ does not vary as a function of group balance using a simulation study and with public single-cell RNA-sequencing data. Finally, we provide scalable approaches to estimate H+, which are available in the fasthplus R package.
Priority effects determine how dispersal affects biodiversity in seasonal metacommunities
Authors: Zou Heng-Xing , Rudolf Volker H. W. 
Published: February 2022

AbstractThe arrival order of species frequently determines the outcome of their interactions. This phenomenon, called the priority effect, is ubiquitous in nature and determines local community structure, but we know surprisingly little about how it influences biodiversity across different spatial scales. Here, we use a seasonal metacommunity model to show that biodiversity patterns and the homogenizing effect of high dispersal depend on the specific mechanisms underlying priority effects. When priority effects are only driven by positive frequency dependence, dispersal-diversity relationships are sensitive to initial conditions but generally show a hump-shaped relationship: biodiversity declines when dispersal rates become high and allow the dominant competitor to exclude other species across patches. When spatiotemporal variation in phenological differences alters species’ interaction strengths (trait-dependent priority effects), local, regional, and temporal diversity are surprisingly insensitive to variation in dispersal, regardless of the initial numeric advantage. Thus, trait-dependent priority effects can strongly reduce the effect of dispersal on biodiversity, preventing the homogenization of metacommunities. Our results suggest an alternative mechanism that maintains local and regional diversity without environmental heterogeneity, highlighting that accounting for the mechanisms underlying priority effects is fundamental to understanding patterns of biodiversity.
Developmental emergence of sleep rhythms enables long-term memory capabilities in Drosophila
Authors: Poe Amy R. , Zhu Lucy , McClanahan Patrick D. , Szuperak Milan , Anafi Ron C. , Thum Andreas S. , Cavanaugh Daniel J. , Kayser Matthew S. 
Published: February 2022

AbstractIn adulthood, sleep-wake rhythms are one of the most prominent behaviors under circadian control. However, during early life, sleep is spread across the 24-hour day (1–4). The mechanism through which sleep rhythms emerge, and the consequent advantage conferred to a juvenile animal, are unknown. In 2nd instar Drosophila larvae (L2), like human infants, sleep is not under circadian control (5). Here, we identify the precise developmental timepoint when the circadian clock begins to regulate sleep in Drosophila, leading to the emergence of sleep rhythms at the early 3rd instar stage (L3). At this stage, a cellular connection forms between DN1a clock neurons and arousalpromoting Dh44 neurons, bringing arousal under clock control to drive the emergence of circadian sleep. Finally, we demonstrate that L3 but not L2 larvae exhibit long-term memory (LTM) of an aversive cue, and that this LTM depends upon deep sleep generated once sleep rhythms begin. We propose that the developmental emergence of circadian sleep enables more complex cognitive processes, including the onset of enduring memories.
Spatial Organization of Neuron-Astrocyte Interactions in the Somatosensory Cortex
Authors: Baraibar Andrés M. , Belisle Lindsey , Marsicano Giovanni , Matute Carlos , Mato Susana , Araque Alfonso , Kofuji Paulo 
Published: February 2022

ABSTRACTMicrocircuits in the neocortex are functionally organized along layers and columns, which are the fundamental modules of cortical information processing. While the function of cortical microcircuits has focused on neuronal elements, much less is known about the functional organization of astrocytes and their bidirectional interaction with neurons. Here we show that CB1R-mediated astrocyte activation by neuron-released endocannabinoids elevate astrocyte Ca2+ levels, stimulate ATP/adenosine release as gliotransmitters, and transiently depress synaptic transmission in layer 5 pyramidal neurons at relatively distant synapses (>20 µm) from the stimulated neuron. This astrocyte-mediated heteroneuronal synaptic depression occurred between pyramidal neurons within a cortical column and was absent in neurons belonging to adjacent cortical columns. Moreover, this form of heteroneuronal synaptic depression occurs between neurons located in particular layers, following a specific connectivity pattern that depends on a layer-specific neuron-to-astrocyte signaling. These results unravel the existence of astrocyte-mediated non-synaptic communication between cortical neurons, and that this communication is column- and layer-specific, which adds further complexity to the intercellular signaling processes in the cortex.
Monotreme-specific conserved proteins derived from retroviral reverse transcriptase
Authors: Kitao Koichi , Miyazawa Takayuki , Nakagawa So 
Published: February 2022

AbstractEndogenous retroviruses (ERVs) have played an essential role in the evolution of mammals. Many ERV-derived genes are reported in the therians that are involved in placental development. However, the contribution of the ERV-derived genes in monotremes, which are oviparous mammals, remains to be uncovered. Here, we conducted a comprehensive search for possible ERV-derived genes in platypus and echidna genomes and identified three reverse transcriptase-like genes named RTOM1, 2, and 3. They were found to be clustered in the GRIP2 intron. Phylogenetic analysis revealed that RTOM1, 2, and 3 are strongly conserved between these species, and they were generated by tandem duplications before the divergence of platypus and echidna. The RTOM transcripts were specifically expressed in the testis, suggesting the physiological importance of RTOM genes. This is the first study reporting monotreme-specific de novo gene candidates derived from ERVs, which provides new insights into the unique evolution of monotremes.
Investigations into the emergent properties of gene-to-phenotype networks across cycles of selection: A case study of shoot branching in plants
Authors: Powell Owen M. , Barbier Francois , Voss-Fels Kai P. , Beveridge Christine , Cooper Mark 
Published: February 2022

AbstractPredictive breeding is now widely practised in crop improvement programs and has accelerated selection response (i.e., the amount of genetic gain between breeding cycles) for complex traits. However, world food production needs to increase further to meet the demands of the growing human population. The prediction of complex traits with current methods can be inconsistent across different genetic, environmental, and agronomic management contexts because the complex relationships between genomic and phenotypic variation are not well accounted for. Therefore, developing gene-to-phenotype network models for traits that integrate the knowledge of networks from systems biology, plant and crop physiology with population genomics has been proposed to close this gap in predictive modelling. Here, we develop a gene-to-phenotype network for shoot branching, a critical developmental pathway underpinning harvestable yield for many crop species, as a case study to explore the value of developing gene-to-phenotype networks to enhance understanding of selection responses. We observed that genetic canalization is an emergent property of the complex interactions among shoot branching gene-to-phenotype network components, leading to the accumulation of cryptic genetic variation, reduced selection responses, and large variation in selection trajectories across populations. As genetic canalization is expected to be pervasive in traits, such as grain yield, that result from interactions among multiple genes, traits, environments, and agronomic management practices, the need to model traits in crop improvement programs as outcomes of gene-to-phenotype networks is highlighted as an emerging opportunity to advance our understanding of selection response and the efficiency of developing resilient crops for future climates.