bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual color mesoscopic imaging reveals spatiotemporally heterogeneous coordination of cholinergic and neocortical activity
Authors: Lohani Sweyta , Moberly Andrew H. , Benisty Hadas , Landa Boris , Jing Miao , Li Yulong , Higley Michael J. , Cardin Jessica A. 
Published: December 2020

AbstractVariation in an animal’s behavioral state is linked to fluctuations in brain activity and cognitive ability. In the neocortex, state-dependent control of circuit dynamics may reflect neuromodulatory influences including acetylcholine (ACh). While early literature suggested ACh exerts broad, homogeneous control over cortical function, recent evidence indicates potential anatomical and functional segregation of cholinergic signaling. Additionally, it is unclear whether states as defined by different behavioral markers reflect heterogeneous cholinergic and cortical network activity. We performed simultaneous, dual-color mesoscopic imaging of both ACh and calcium across the neocortex of awake mice to investigate their relationships with behavioral variables. We find that increasing arousal, categorized by different motor behaviors, is associated with spatiotemporally dynamic patterns of cholinergic release and enhanced large-scale network correlations. Overall, our findings demonstrate that ACh provides a highly dynamic and spatially heterogeneous signal that links fluctuations in behavior to functional reorganization of cortical networks.
Defective myelination in an RNA polymerase III mutant leukodystrophic mouse
Authors: Merheb Emilio , Cui Min-Hui , DuBois Juwen C. , Branch Craig A. , Gulinello Maria , Shafit-Zagardo Bridget , Moir Robyn D. , Willis Ian M. 
Published: December 2020

AbstractRNA polymerase (Pol) III synthesizes abundant short non-coding RNAs that have essential functions in protein synthesis, secretion and other processes. Despite the ubiquitous functions of these RNAs, mutations in Pol III subunits cause Pol III-related leukodystrophy, an early-onset neurodegenerative disease. The basis of this neural sensitivity and the mechanisms of disease pathogenesis are unknown. Here we show that mice expressing pathogenic mutations in the largest Pol III subunit,Polr3a, specifically in Olig2-expressing cells, have impaired growth and developmental delay, deficits in cognitive, sensory and fine sensorimotor function, and hypomyelination in multiple regions of the cerebrum and spinal cord. In contrast, the gross motor defects and cerebellar hypomyelination that are common features of severely affected patients are absent in the mice, suggesting a relatively mild form of the disease in this conditional model. Our results show that disease pathogenesis in the mice involves defects that reduce both the number of mature myelinating oligodendrocytes and the ability of these cells to produce a myelin sheath of normal thickness. Thus, the findings suggest cell-specific roles for Pol III in the development and/or survival of oligodendrocytes as well as their function in myelination.Significance StatementPathogenic mutations in subunits of RNA polymerase (Pol) III cause a prevalent autosomal recessive form of leukodystrophy. However, understanding of the mechanisms of pathogenesis, including how ubiquitously-expressed Pol III mutations affect primarily the central nervous system, has been limited by the absence of an animal model of the disease. We show that conditional knock-in of pathogenicPolr3amutations in the Olig2 lineage in mice results in growth, neurobehavioral and hypomyelination phenotypes reflecting a subset of clinical features of Pol III-related leukodystrophy patients. Myelination defects in the mice identify neural-specific roles for Pol III transcription. The phenotypes of Pol III-related leukodystrophic mice enable genetic and pharmacological approaches aimed at mitigating the consequences of this disease in humans.
Cross-neutralization of SARS-CoV-2 by HIV-1 specific broadly neutralizing antibodies and polyclonal plasma
Authors: Mishra Nitesh , Kumar Sanjeev , Singh Swarandeep , Bansal Tanu , Jain Nishkarsh , Saluja Sumedha , Palanichamy Jayanth Kumar , Mir Riyaz A. , Sinha Subrata , Luthra Kalpana 
Published: December 2020

AbstractCross-reactive epitopes (CREs) are similar epitopes on viruses that are recognized or neutralized by same antibodies. The S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated. Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses. In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined. These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize. As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2. Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2. Collectively, our observations suggest that human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile.ImportanceIn the current ongoing COVID-19 pandemic, neutralizing antibodies have been shown to be a critical feature of recovered patients. HIV-1 bnAbs recognize extensively diverse cross-reactive epitopes and tolerate diversity within their core epitope. Given the unique nature of HIV-1 bnAbs and their ability to recognize and/or accommodate viral glycans, we reasoned that the glycan shield of SARS-CoV-2 spike protein can be targeted by HIV-1 specific bnAbs. Herein, we showed that HIV-1 specific antibodies cross-react and neutralize SARS-CoV-2. Understanding cross-reactive neutralization epitopes of antibodies generated in divergent viral infections will provide key evidence for engineering so called super-antibodies (antibodies that can potently neutralize diverse pathogens with similar antigenic features). Such cross-reactive antibodies can provide a blueprint upon which synthetic variants can be generated in the face of future pandemics.
The acute effects of aerobic exercise on sensorimotor adaptation in chronic stroke
Authors: Mackay Christopher P , Brauer Sandra G , Kuys Suzanne S , Schaumberg Mia A , Leow Li-Ann 
Published: December 2020

AbstractSensorimotor adaptation, or the capacity to adapt movement to changes in the moving body or environment, is a form of motor learning that is important for functional independence (e.g., regaining stability after slips or trips). Aerobic exercise can acutely improve many forms of motor learning in healthy adults. It is not known, however, whether acute aerobic exercise has similar positive effects on sensorimotor adaptation in stroke survivors as it does in healthy individuals.PurposeThe aim of this study was to determine whether acute aerobic exercise promotes sensorimotor adaptation in people post stroke.MethodsA single-blinded crossover study. Participants attended two separate sessions at the university campus, completing an aerobic exercise intervention in one session and a resting control condition in the other session. Sensorimotor adaptation was assessed before and after each session. Participants were twenty people with chronic stroke. Intervention completed was treadmill exercise at mod-high intensity for 30 minutes.ResultsResults demonstrated that acute aerobic exercise in chronic stroke survivors significantly increased sensorimotor adaptation from pre to post treadmill intervention.ConclusionThese results indicate a potential role for aerobic exercise to promote the recovery of sensorimotor function in chronic stroke survivors.
Harnessing Electronic Health Records to Study Emerging Environmental Disasters: A Proof of Concept with Perfluoralkyl Substances (PFAS)
Authors: Boland Mary Regina , Davidson Lena M. , Canelón Silvia P. , Meeker Jessica , Penning Trevor , Holmes John H , Moore Jason H 
Published: December 2020

ABSTRACTObjectiveEnvironmental disasters are anthropogenic catastrophic events that affect health. Famous disasters include the Chernobyl and Fukushima-Daiichi nuclear meltdowns, which had disastrous health consequences. Traditional methods for studying environmental disasters are costly and time-intensive. We propose the use of Electronic Health Records (EHR) and informatics methods to study the health effects of emergent environmental disasters in a cost-effective manner.Materials and MethodsAn emergent environmental disaster is exposure to Perfluoralkyl Substances (PFAS) in the Philadelphia area. Penn Medicine (PennMed) comprises multiple hospitals and facilities within the Philadelphia Metropolitan area, including over three thousand PFAS-exposed women living in one of the highest PFAS exposure areas nationwide. We developed a high-throughput method that utilizes only EHR data to evaluate the disease risk in this heavily exposed population.ResultsWe replicated all five disease/conditions implicated by PFAS exposure, including hypercholesterolemia, proteinuria, thyroid disease, kidney disease and colitis, either directly or via closely related diagnoses.DiscussionUsing EHRs coupled with informatics enables the health impacts of environmental disasters to be more easily studied in large cohorts versus traditional methods that rely on interviews and expensive serum-based testing. By reducing cost and increasing the diversity of individuals included in studies, we can overcome many of the hurdles faced by previous studies, including a lack of racial and ethnic diversity.ConclusionThis proof-of-concept study confirms that EHRs can be used to study human health and disease impacts of environmental disasters and produces equivalent disease-exposure knowledge to prospective epidemiology studies while remaining cost-effective.KEY MESSAGESElectronic Health Records can be used for studying health effects of environmental exposuresPFAS exposure - disease associations were mainly replicated using EHRsEHRs represent a cost-effective method to augment traditional epidemiology studies
SCENTinel 1.0: development of a rapid test to screen for smell loss
Authors: Parma Valentina , Hannum Mackenzie E. , O’Leary Maureen , Pellegrino Robert , Rawson Nancy E. , Reed Danielle R. , Dalton Pamela H. 
Published: December 2020

AbstractBackgroundCommercially available smell tests are primarily used in research or in-depth clinical evaluations, but are too costly and lengthy for population surveillance in health emergencies like COVID-19. We developed the SCENTinel 1.0 test which rapidly evaluates three olfactory functions (detection, intensity, and identification). We tested whether self-administering the SCENTinel 1.0 test discriminates between individuals with smell loss or average smell ability (normosmics), and provides comparable performance as the validated and standardized NIH Toolbox® Odor Identification Test in normosmics.MethodsUsing Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1.0 performance of a group of self-reported anosmics (N=111, 47±13yo, F=71%,) and normosmics (N=154, 47±14yo, F=74%), as well as individuals reporting other smell disorders (e.g., hyposmia, parosmia; N=42, 55±10yo, F=67%).ResultsNinety-four percent of normosmics met our SCENTinel 1.0 accuracy criteria, while only 10% of anosmics and 64% of individuals with other smell disorders did. Overall performance on SCENTinel 1.0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC=0.95, Sensitivity=0.72, Specificity=0.94). Odor intensity provided the best single-feature predictor to classify normosmics. Among normosmics, 92% met the accuracy criteria at both SCENTinel 1.0 and the NIH Toolbox® Odor Identification Test.ConclusionsSCENTinel 1.0 is a practical test able to discriminate individuals with smell loss and is likely to be useful in many clinical situations, including COVID-19 symptom screening.
A Systematic Review and Meta-Analysis of the Incidence Rate of Takayasu Arteritis
Authors: Rutter Megan , Bowley Jonathan , Lanyon Peter C. , Grainge Matthew J. , Pearce Fiona A. 
Published: December 2020

AbstractObjectivesTakayasu arteritis (TAK), is a rare autoimmune rheumatic disease causing large vessel vasculitis. Onset is typically between the ages of 20-30. It is associated with substantial morbidity and mortality, notably due to its effects on the cardiovascular system. It has a poorly understood global epidemiology. Our objective was to systematically review the available evidence in order to calculate the incidence rate of TAK.MethodsThree databases (Medline, PubMed and Embase) were searched in November 2019 and the results were screened by two reviewers. A random effects meta-analysis was then conducted in R to calculate the overall incidence rate. Heterogeneity was assessed using I2. The quality of the studies was assessed using an adapted Newcastle-Ottawa scale. Further sub-group analyses were performed by quality, sex, research setting and geographical location. Publication bias was assessed using a Begg’s funnel plot.ResultsThe incidence rate for TAK per million person-years with 95% confidence intervals was 1.11 per million person years (95% CI 0.75 – 1.65). The heterogeneity in the data was extremely high in all analyses, which suggests that there was considerable variation in incidence rates across the different populations studied. TAK was found to be more common in women (incidence rate 2.01 per million person-years, 95% CI 1.39-2.90).ConclusionsTAK is an extremely rare disease. It affects women more commonly than men. There is considerable variation in the incidence rate between populations. We suggest that future research should focus on discrete populations in order to better identify genetic and environmental risk factors.
Environmental monitoring shows SARS-CoV-2 contamination of surfaces in food plants
Authors: Ming Ziwen , Han Sukkyun , Deng Kai , Ha Youngsil , Kim SungSoo , Reyes Enrique , Zhao Yu , Dobritsa Anatoly , Wu Meiting , Zhang Dandan , Cox David P , Joyner Emma , Kulasekara Hemantha , Kim Seong Hong , Jang Yong Seog , Fowler Curtis , Fei Xing , Akasaki Hikari , Themeli Eni , Agapov Alexander , Bruneau Dylan , Tran Thao , Szczesny Cameron , Kienzle Casey , Tenney Kristina , Geng Hao , Samadpour Mansour 
Published: December 2020

ABSTRACTThe SARS-CoV-2 pandemic has presented new challenges to food manufacturers. In addition to preventing the spread of microbial contamination of food, with SARS-CoV-2, there is an additional focus on preventing SARS-CoV-2 infections in food plant personnel. During the early phase of the pandemic, several large outbreaks of Covid-19 occurred in food manufacturing plants resulting in deaths and economic loss. In March of 2020, we assisted in implementation of environmental monitoring programs for SARS-CoV-2 in 116 food production facilities. All participating facilities had already implemented measures to prevent symptomatic personnel from coming to work. During the study period, from March 17, 2020 to September 3, 2020, 1.23% of the 22,643 environmental samples tested positive for SARS-CoV-2, suggesting that infected individuals are actively shedding virus. Virus contamination was commonly found on frequently touched surfaces. Most plants managed to control their environmental contamination when they became aware of the positive findings. Comparisons of the personnel test results to environmental contamination in one plant showed a good correlation between the two. Our work illustrates that environmental monitoring for SARS-CoV-2 can be used as a surrogate for identifying the presence of asymptomatic and pre-symptomatic personnel in workplaces and may aid in controlling infection spread.HighlightsEnvironmental contamination by SARS-CoV-2 virus was detected in food plantsOut of 22,643 environmental swabs, 278 (1.23%) were positive for SARS-CoV-2Frequently touched surfaces had the most contaminationSurface testing for SARS-CoV-2 may indicate presence of asymptomatic carriers
A Decision Analytics Model to Optimize Investment in Interventions Targeting the HIV PrEP Cascade of Care
Authors: Jenness Samuel M. , Knowlton Gregory , Smith Dawn K. , Marcus Julia L. , Anderson Emeli J. , Siegler Aaron J. , Jones Jeb , Sullivan Patrick S. , Enns Eva 
Published: December 2020

ABSTRACTObjectivesGaps between recommended and actual levels of HIV preexposure prophylaxis (PrEP) use remain among men who have sex with men (MSM). Interventions can address these gaps, but it is unknown how public health initiatives should invest prevention funds into these interventions to maximize their population impact.DesignWe used a stochastic network-based HIV transmission model for MSM in the Atlanta area paired with an economic budget optimization model.MethodsThe model simulated MSM participating in up to three real-world PrEP cascade interventions designed to improve initiation, adherence, or persistence. The primary outcome was infections averted over 10 years. The budget optimization model identified the investment combination under different budgets that maximized this outcome given intervention costs from a payer perspective.ResultsFrom the base 15% PrEP coverage level, the three interventions could increase coverage to 27%, resulting in 12.3% of infections averted over 10 years. Uptake of each intervention was interdependent: maximal use of the adherence and persistence interventions depended on new PrEP users generated by the initiation intervention. As the budget increased, optimal investment involved a mixture of the initiation and persistence interventions, but not the adherence intervention. If adherence intervention costs were halved, the optimal investment was roughly equal across interventions.ConclusionsInvestments into the PrEP cascade through initiatives should account for the interactions of the interventions as they are collectively deployed. Given current intervention efficacy estimates, the total population impact of each intervention may be improved with greater total budgets or reduced intervention costs.
Prevalence trends of diabetes subgroups in US: A data-driven analysis spanning three decades from NHANES (1988-2018)
Authors: Antonio-Villa Neftali Eduardo , Fernández-Chirino Luisa , Vargas-Vázquez Arsenio , Fermín-Martinez Carlos A. , Aguilar-Salinas Carlos A. , Bello-Chavolla Omar Yaxmehen 
Published: December 2020

ABSTRACTAIMSData-driven diabetes subgroups were proposed as an alternative to address diabetes heterogeneity. However, changes in trends for these subgroups have not been reported. Here, we analyzed trends of diabetes subgroups, stratified by sex, race, education level, age categories and time since diabetes diagnosis in the U.S.METHODSWe used data from consecutive NHANES cycles spanning the 1988-2018 period. Diabetes subgroups (mild obesity-related [MOD], severe-insulin deficient [SIDD], severe-insulin resistant [SIRD], and mild age-related diabetes [MARD]) were classified using validated self-normalizing neural networks. Severe autoimmune-diabetes (SAID) was assessed for NHANES-III. Prevalence was estimated using examination sample weights considering bi-cyclic changes (BC) to evaluate trends and changes over time.RESULTSDiabetes prevalence in the US increased from 7.5% (95%CI 7.1-7.9) in 1988-1989 to 13.9% (95%CI 13.4-14.4) in 2016-2018 (BC 1.09%, 95%CI 0.98-1.31, p<0.001). Non-Hispanic Blacks had the highest prevalence. Overall, MOD, MARD, and SIDD had an increase during the studied period. Particularly, Non-Hispanic Blacks had sharp increases in MARD and SIDD, Mexican Americans in SIDD, and non-Hispanic Whites in MARD. Males, subjects with secondary/high school, and adults aged 40-64 years had the highest increase in MOD prevalence. Trends in diabetes subgroups sustained after stratifying time since diabetes diagnosis.CONCLUSIONSPrevalence of diabetes and its subgroups in the U.S. have increased from 1988-2018. These trends were different across sex, ethnicities, education, and age categories, indicating significant heterogeneity in diabetes within the U.S. Obesity burden, population aging, socioeconomic disparities, and lifestyle aspects could be implicated in the uprising trends of diabetes in the U.S.
BAP1 activity regulates PcG occupancy and global chromatin condensation counteracting diffuse PCGF3/5-dependent H2AK119ub1 deposition
Authors: Conway Eric , Rossi Federico , Tamburri Simone , Ponzo Eleonora , Ferrari Karin Johanna , Zanotti Marika , Fernandez-Perez Daniel , Manganaro Daria , Rodighiero Simona , Pasini Diego 
Published: December 2020

AbstractBAP1 is recurrently mutated or deleted in a large number of diverse cancer types, including mesothelioma, uveal melanoma and hepatocellular cholangiocarcinoma. BAP1 is the catalytic subunit of the Polycomb Repressive De-Ubiquitination complex (PR-DUB) which removes PRC1 mediated H2AK119ub1. We and others have shown that H2AK119ub1 is essential for maintaining transcriptional repression and contributes to PRC2 chromatin recruitment. However, the precise relationship between BAP1 and PRC1 remains mechanistically elusive. Using embryonic stem cells, we show that a major function of BAP1 is to restrict H2AK119ub1 deposition to target sites. This increases the stability of PcG complexes with their targets and prevents diffuse accumulation of H2AK119ub1 and H3K27me3 modifications. Loss of BAP1 results in a broad increase in H2AK119ub1 levels that are primarily dependent on PCGF3/5-PRC1 complexes with a mechanism that is reminiscent of X-chromosome inactivation. Increased genome-wide H2AK119ub1 levels titrates away PRC2 from its targets and stimulates diffuse H3K27me3 accumulation across the genome. This decreases the activity of PcG repressive machineries at physiological targets and induces a general compaction of the entire chromatin. Our findings provide evidences for a unifying model that resolves the apparent contradiction between BAP1 catalytic activity and its rolein vivo, uncovering molecular vulnerabilities that could be useful for BAP1-related pathologies.