bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALOHA: Aggregated local extrema splines for high-throughput dose-response analysis
Authors: Davidson Sarah E. , Wheeler Matthew W. , Auerbach Scott S. , Sivaganesan Siva , Medvedovic Mario 
Published: March 2021

AbstractComputational methods for genomic dose-response integrate dose-response modeling with bioinformatics tools to evaluate changes in molecular and cellular functions related to pathogenic processes. These methods use parametric models to describe each gene’s dose-response, but such models may not adequately capture expression changes. Additionally, current approaches do not consider gene co-expression networks. When assessing co-expression networks, one typically does not consider the dose-response relationship, resulting in ‘co-regulated’ gene sets containing genes having different dose-response patterns. To avoid these limitations, we develop an analysis pipeline called Aggregated Local Extrema Splines for High-throughput Analysis (ALOHA), which computes individual genomic dose-response functions using a flexible class Bayesian shape constrained splines and clusters gene co-regulation based upon these fits. Using splines, we reduce information loss due to parametric lack-of-fit issues, and because we cluster on dose-response relationships, we better identify co-regulation clusters for genes that have co-expressed dose-response patterns from chemical exposure. The clustered pathways can then be used to estimate a dose associated with a pre-specified biological response, i.e., the benchmark dose (BMD), and approximate a point of departure dose corresponding to minimal adverse response in the whole tissue/organism. We compare our approach to current parametric methods and our biologically enriched gene sets to cluster on normalized expression data. Using this methodology, we can more effectively extract the underlying structure leading to more cohesive estimates of gene set potency.
Perception of effort during an isometric contraction is influenced by prior muscle lengthening or shortening
Authors: Kozlowski Benjamin , Pageaux Benjamin , Hubbard Emma F. , St. Peters Benjamin , Millar Philip J. , Power Geoffrey A. 
Published: March 2021

AbstractPurposeFollowing a shortening or lengthening muscle contraction, the torque produced in the isometric steady state is distinctly lower (residual torque depression; rTD) or higher (residual torque enhancement; rTE), respectively, compared to a purely isometric contraction at the same final muscle length and level of activation. This is referred to as the history dependence of force. When matching a given torque level, there is greater muscle activation (electromyography; EMG) following shortening and less activation following lengthening. Owing to these differences in neuromuscular activation, it is unclear whether perception of effort is altered by the history dependence of force.MethodsExperiment 1 tested whether perception of effort differed between the rTD and rTE state when torque was matched. Experiment 2 tested whether perception of effort differed between the rTD and rTE state when EMG was matched. Finally, experiment 3 tested whether EMG differed between the rTD and rTE state when perception of effort was matched.ResultsWhen torque was matched, both EMG and perception of effort were higher in the rTD compared to rTE state. When EMG was matched, torque was lower in the rTD compared to rTE state while perception of effort did not differ between the two states. When perception of effort was matched, torque was lower in the rTD compared to rTE state and EMG did not differ between the two states.ConclusionThe combined results from these experiments indicate that the history dependence of force alters one’s perception of effort, dependent on the level of motor command.
The truncate soft-shell clam,Mya truncata, as a biomonitor of municipal wastewater exposure and historical anthropogenic impacts in the Canadian Arctic
Authors: Schaefer Christina M , Deslauriers David , Jeffries Ken M 
Published: March 2021

AbstractMunicipal wastewater is a large source of pollution to Canadian waters, yet its effects on Arctic marine ecosystems remains relatively unknown. We characterized the impacts of municipal wastewater from a growing northern community, Iqaluit, Nunavut on the Arctic truncate soft-shell clam,Mya truncata. Clams were sampled from six locations that varied in proximity to the wastewater treatment plant and shell biogeochemical analysis revealed that clams nearest the wastewater treatment plant had slower growth rates, lower carbon and oxygen stable isotope ratios, and elevated concentrations of copper and lead. A parallel analysis on mRNA expression profiles characterizedM. truncata’s physiological response to wastewater effluent. Clams nearest the wastewater treatment plant had significantly lower mRNA expression of genes associated with metabolism, antioxidants, molecular chaperones, and phase I and II detoxification, but had heightened mRNA expression in genes coding for enzymes that bind and remove contaminants. These results demonstrated a biological response to Iqaluit’s wastewater effluent and highlightM. truncata’s potential to act as a biomonitor of municipal wastewater along Canadian Arctic coastlines.
Ultra-sensitive isotope probing to quantify activity and substrate assimilation in microbiomes
Authors: Kleiner Manuel , Kouris Angela , Jensen Marlene , D’Angelo Grace , Liu Yihua , Korenek Abigail , Tolić Nikola , Sachsenberg Timo , McCalder Janine , Lipton Mary S. , Strous Marc 
Published: March 2021

AbstractStable isotope probing (SIP) approaches are a critical tool in microbiome research to determine associations between species and substrates. The application of these approaches ranges from studying microbial communities important for global biogeochemical cycling to host-microbiota interactions in the intestinal tract. Current SIP approaches, such as DNA-SIP or nanoSIMS, are limited in terms of sensitivity, resolution or throughput. Here we present an ultra-sensitive, high-throughput protein-based stable isotope probing approach (Protein-SIP), which cuts cost for labeled substrates by ∼90% as compared to other SIP and Protein-SIP approaches and thus enables isotope labeling experiments on much larger scales and with higher replication. It allows for the determination of isotope incorporation into microbiome members with species level resolution using standard metaproteomics LC-MS/MS measurements. The analysis has been implemented as an open-source application (https://sourceforge.net/projects/calis-p/). We demonstrate sensitivity, precision and accuracy using bacterial cultures and mock communities with different labeling schemes. Furthermore, we benchmark our approach against two existing Protein-SIP approaches and show that in the low labeling range used our approach is the most sensitive and accurate. Finally, we measure translational activity using 18O heavy water labeling in a 63-species community derived from human fecal samples grown on media simulating two different diets. Activity could be quantified on average for 27 species per sample, with 9 species showing significantly higher activity on a high protein diet, as compared to a high fiber diet. Surprisingly, among the species with increased activity on high protein were severalBacteroidesspecies known as fiber consumers. Apparently, protein supply is a critical consideration when assessing growth of intestinal microbes on fiber, including fiber based prebiotics. In summary, we demonstrate that our Protein-SIP approach allows for the ultra-sensitive (0.01% to 10% label) detection of stable isotopes of elements found in proteins, using standard metaproteomics data.
Non-severe SARS-CoV-2 infection is characterised by very early T cell proliferation independent of type 1 interferon responses and distinct from other acute respiratory viruses
Authors: Chandran Aneesh , Rosenheim Joshua , Nageswaran Gayathrie , Swadling Leo , Pollara Gabriele , Gupta Rishi K , Guerra-Assuncao Jose Afonso , Woolston Annemarie , Ronel Tahel , Pade Corrina , Gibbons Joseph , De Estrada Blanca Sanz-Magallon Duque , de Massy Marc Robert , Whelan Matthew , Semper Amanda , Brooks Tim , Altmann Daniel M , Boyton Rosemary J , McKnight Áine , Manisty Charlotte , Treibel Thomas Alexander , Moon James , Tomlinson Gillian S , Maini Mala K , Chain Benjamin M , Noursadeghi Mahdad ,   COVIDsortium Investigators
Published: March 2021

AbstractThe correlates of natural protective immunity to SARS-CoV-2 in the majority who experience asymptomatic infection or non-severe disease are not fully characterised, and remain important as new variants emerge. We addressed this question using blood transcriptomics, multiparameter flow cytometry and T cell receptor (TCR) sequencing spanning the time of incident infection. We identified a type 1 interferon (IFN) response common to other acute respiratory viruses, and a cell proliferation response that discriminated SARS-CoV-2 from other viruses. These responses peaked by the time the virus was first detected, and in some preceded virus detection. Cell proliferation was most evident in CD8 T cells and associated with rapid expansion of SARS-CoV-2 reactive TCRs. We found an equally rapid increase in immunoglobulin transcripts, but circulating virus-specific antibodies lagged by 1-2 weeks. Our data support a protective role for rapid induction of type 1 IFN and CD8 T cell responses to SARS-CoV-2.
Prevalence and risk factors of internet gaming disorder and problematic internet use before and during the COVID-19 pandemic: A large online survey of Japanese adults
Authors: Oka Taiki , Hamamura Toshitaka , Miyake Yuka , Kobayashi Nao , Honjo Masaru , Kawato Mitsuo , Kubo Takatomi , Chiba Toshinori 
Published: March 2021

AbstractInternet gaming disorder (IGD) and problematic internet use (PIU) are becoming increasingly detrimental in modern society, with serious consequences for daily functioning. IGD and PIU may be exacerbated by lifestyle changes imposed by the coronavirus 2019 (COVID-19) pandemic. This study investigated changes in IGD and PIU during the pandemic and risk factors for them. This study is a part of a larger online study on problematic smartphone use in Japan, originally planned in 2019, and expanded in August 2020 to include the impact of COVID-19. 51,246 adults completed an online survey during the pandemic (August 2020), in Japan. Of these, 3,938 had also completed the survey before the onset of the pandemic (December, 2019) and were used as the study population to determine how the pandemic has influenced IGD and PIU. IGD was assessed using the Internet Gaming Disorder Scale (IGDS). PIU was measured using the Compulsive Internet Use Scale (CIUS). The prevalence of probable IGD during COVID-19 was 4.1% [95%CI, 3.9% to 4.2%] overall (N=51,246), and 8.6% among younger people (age < 30), higher than reported before the pandemic (1 - 2.5%). Probable PIU was 7.8% [95%CI, 7.6% to 8.1%] overall, and 17.0% [95%CI, 15.9% to 18.2%] among younger people, also higher than reported before the pandemic (3.2 - 3.7%). Comparisons before and during the pandemic, revealed that probable IGD prevalence has increased 1.6 times, and probable PIU prevalence by 1.5 times (IGD:t3937= 5.93,p< .001, PIU:t3937= 6.95,p< .001). Youth (age < 30) and COVID-19 infection were strongly associated with IGD exacerbation (odds ratio, 2.10 [95%CI, 1.18 to 3.75] and 5.67 [95%CI, 1.33 to 24.16]). Internet gaming disorder and problematic internet use appear to be aggravated by the pandemic. In particular, younger persons and people infected with COVID-19 are at higher risk for Internet Gaming Disorder. Prevention of these problems is needed.
Primary Care for Homeless Veterans: A Systematic Review of the Homeless Patient Aligned Care Team (HPACT)
Authors: Rosenthal David , Howell Benjamin A. , Johnson Erin , Frumento Katherine Stemmer , Tsai Jack 
Published: March 2021

AbstractBackgroundIn 2011, the Veterans Health Administration (VHA) implemented homeless-tailored primary care medical home models, called the Homeless Patient Aligned Care Teams (HPACT) to improve care for homeless Veterans. The aim of this study was to describe the existing peer-reviewed literature on HPACTs by systematically reviewing studies published since 2011 to date.MethodsWe conducted a systematic review of peer-reviewed studies published from 2011 to June 2019 to evaluate the literature since the inception of the VHA’s Homeless PACT program implementation. We included original research articles evaluating the Homeless PACT and excluded those that did not contain original data.ResultsOf 379 studies screened, 20 studies met our inclusion criteria and were included for analysis. Given wide variability in research designs and outcome measures, a narrative review was conducted. The 20 included studies were categorized into 3 groups: Early HPACT pilot implementations; Association of HPACT clinics with quality and utilization; and Specialized programs within HPACTs. Observational findings suggest reductions in emergency department utilization, improvements in primary care treatment utilization, engagement, and patient experience; but limited rigorous studies exist beyond single site pilots and a few large observational cohort studies.DiscussionThe HPACT model has been successfully implemented in VHA medical centers throughout the country with multiple studies showing increased primary care engagement and improved patient experience; however, further studies are needed about quality, utilization and whether the model can be implemented outside the VHA system.Registration Number/Funding sourcenone
Association of Heart Failure Subtypes and Atrial fibrillation: Data from the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Nji Miriam A.M. , Solomon Scott D. , Chen Lin Yee , Shah Amil M. , Soliman Elsayed Z. , Alam Aniqa , Subramanya Vinita , Alonso Alvaro 
Published: March 2021

ABSTRACTAimsTo determine the prevalence and incidence of AF among HF subtypes in a biracial community-based cohort.MethodsWe studied 6,496 participants in the Atherosclerosis Risk in Community study (mean age, 75.8±5.3, 59% women, 23% black) who attended the 2011-2013 visit. HF was identified from physician adjudicated diagnosis, hospital discharges, and self-report. HF subtypes were based on echocardiography. A left ventricular ejection fraction <40% represents HF with reduced ejection fraction (HFrEF), 40%-49% for HF with midrange ejection fraction (HFmEF), and ≥50% for HF with preserved ejection fraction (HFpEF). AF was ascertained through 2017 from study electrocardiograms, hospital discharges, and death certificates. Confounder-adjusted logistic regression and Cox models were used to estimate associations of HF subtype with prevalent and incident AF.ResultsAmong eligible participants, 393 had HF (HFpEF=232, HFmEF=41, HFrEF=35 and unclassified HF =85) and 735 had AF. Compared to those without HF, all HF subtypes were more likely to have prevalent AF [odds ratio (95% confidence interval (CI)) 7.4 (5.6-9.9) for HFpEF, 8.1 (4.3-15.3) for HFmEF, 10.0 (5.0-20.2) for HFrEF, 8.8 (5.6-14.0) for unclassified HF]. Among participants without AF at baseline (n=5,761), 610 of them developed AF. Prevalent HF was associated with increased risk of AF [hazard ratio (95%CI) 2.3 (1.6-3.3) for HFpEF, 4.6 (2.4-8.6) for HFmEF, 3.8 (1.8-8.2) for HFrEF, 2.3 (0.9-5.6) for unclassified HR].ConclusionAF and HF frequently co-occur, with small differences by HF subtype, underscoring the importance of understanding the interplay of these two epidemics and evaluating shared preventive and therapeutic strategies.
Coping with COVID-19 Pandemic: A Population-Based Study in Bangladesh
Authors: Hossain K M Amran , Saunders Karen , Sakel Mohamed , Walton Lori Maria , Raigangar Veena , Uddin Zakir , Hossain Mohammad Anwar , Islam Asma , Ahmed Faruq , Faruqui Rafey , Tasnim Tamanna , Rana Shohag , Shafin Rubayet , Ahmed Md. Shahoriar , Haque Md. Obaidul , Kabir Md. Feroz , Hossain Mohammad Sohrab , Jahid Iqbal Kabir , Yasmin Mst. Hosneara , Chakrovorty Sonjit Kumar , Hossain Md. Shahadat , Paul Joty 
Published: March 2021

ABSTRACTThis study aims to investigate coping strategies used by Bangladeshi citizens during the COVID-19 pandemic.DesignProspective, cross-sectional survey of adults (N=2001) living in Bangladesh.MethodsParticipants were interviewed for socio-demographic data and completed the Bengali translated Brief-COPE Inventory. Statistical data analysis was conducted using SPSS (Version 20).ResultsParticipants (N=2001), aged 18 to 86 years, were recruited from eight administrative divisions within Bangladesh (mean age 31.85±14.2 years). Male to female participant ratio was 53.4% (n=1074) to 46.6% (n=927). Higher scores were reported for approach coping styles (29.83±8.9), with lower scores reported for avoidant coping styles (20.83 ± 6.05). Humor coping scores were reported at 2.68±1.3 and religion coping scores at 5.64±1.8. Both men and women showed similar coping styles. Multivariate analysis found a significant relationship between male gender and both humor and avoidant coping (p <.01). Male gender was found to be inversely related to both religion and approach coping (p <.01). Marital status and education were significantly related to all coping style domains (p<.01). Occupation was significantly related to approach coping (p <.01). Rural and urban locations differed significantly in participant coping styles (p <.01). Factor analysis revealed two cluster groups (Factor 1 and 2) comprised of unique combinations from all coping style domains.ConclusionParticipants in this study coped with the COVID-19 pandemic by utilizing a combination of coping strategies. Factor 1 revealed both avoidant and approach coping strategies and Factor 2 revealed a combination of humor and avoidant coping strategies. Overall, a higher utilization of approach coping strategies was reported, which has previously been associated with better physical and mental health outcomes. Religion was found to be a coping strategy for all participants. Future research may focus on understanding resilience in vulnerable populations, including people with disability or with migrant or refugee status in Bangladesh.
The plastid genome characteristics of a moth orchid (Phalaenopsis wilsoniii, Orchidaceae)
Authors: Xia KeKe , Liu Ding-Kun , Wang Jie-Yu 
Published: March 2021

AbstractPhalaenopsis wilsonii is a typical deciduous species in the horticulturally well-known genus,Phalaenopsis. Tshi species is belonging to the sectionAphyllaein moth orchid, and is endemic to South China. Although theAphyllaesection display the deciduous feature that is unique in this genus, their genetic information is still insufficient and limited them as breeding parent in moth orchid. Here, we reported and characterized the complete chloroplast genome forPhalaenopsis wilsonii. We found the total size of the chloroplast genome was 145,373 bp, constituting of a large single copy (LSC) region (84,996 bp), a small single-copy region (10,668 bp) and two inverted repeats (IRs) regions (24,855 bp). Based on homologous searching on database, we annotated 76 protein-coding genes, 38 tRNA, and 8 rRNA. The phylogenetic reconstruction revealed thatP. wilsoniishow the closest relationship withP. lowiiwithin subgenusParishianae.
Spermiogenesis alterations in the absence of CTCF revealed by single cell RNA sequencing
Authors: Torres-Flores Ulises , Díaz-Espinosa Fernanda , López-Santaella Tayde , Rebollar-Vega Rosa , Vázquez-Jiménez Aarón , Taylor Ian J. , Ortiz-Hernández Rosario , Echeverría Olga M. , Vázquez-Nin Gerardo H. , Gutierrez-Ruiz María Concepción , De la Rosa-Velázquez Inti Alberto , Resendis-Antonio Osbaldo , Hernández-Hernandez Abrahan 
Published: March 2021

AbstractCTCF is an architectonical protein that organizes the genome inside the cell nucleus in almost all eukaryotic cells. There is evidence that CTCF plays a critical role during spermatogenesis as its depletion produces abnormal sperm and infertility. However, the defects produced by the absence of CTCF throughout spermatogenesis have not been characterized. In this work, we performed single cell RNA sequencing in spermatogenic cells without CTCF. We uncovered defects in transcriptional programs that explain the severity of the damage in the produced sperm. At early stages of spermatogenesis, transcriptional alterations are mild. As germ cells go throughout the specialization stage or spermiogenesis, transcriptional profiles become more altered. We found spermatid defects that support the alterations in the transcriptional profiles, and thus we conclude that CTCF depletion alters several transcriptional profiles mostly during spermiogenesis. Our data highlights the importance of CTCF at the different stages of spermatogenesis.
Rapid characterization of spike variants via mammalian cell surface display
Authors: Javanmardi Kamyab , Chou Chia-Wei , Terrace Cynthia I. , Annapareddy Ankur , Kaoud Tamer S. , Guo Qingqing , Lutgens Josh , Zorkic Hayley , Horton Andrew P. , Gardner Elizabeth C. , Nguyen Giaochau , Boutz Daniel R. , Goike Jule , Voss William N. , Kuo Hung-Che , Dalby Kevin N , Gollihar Jimmy D. , Finkelstein Ilya J. 
Published: March 2021

AbstractThe SARS-CoV-2 spike (S) protein is a critical component of subunit vaccines and a target for neutralizing antibodies. Spike is also undergoing immunogenic selection with clinical variants that increase infectivity and partially escape convalescent plasma. Here, we describe spike display, a high-throughput platform to rapidly characterize glycosylated spike ectodomains across multiple coronavirus-family proteins. We assayed ∼200 variant SARS-CoV-2 spikes for their expression, ACE2 binding, and recognition by thirteen neutralizing antibodies (nAbs). An alanine scan of all five N-terminal domain (NTD) loops highlights a public class of epitopes in the N1, N3, and N5 loops that are recognized by most of the NTD-binding nAbs. Some clinical NTD substitutions abrogate binding to these epitopes but are circulating at low frequencies around the globe. NTD mutations in variants of concern B.1.1.7 (United Kingdom), B.1.351 (South Africa), B.1.1.248 (Brazil), and B.1.427/B.1.429 (California) impact spike expression and escape most NTD-targeting nAbs. However, two classes of NTD nAbs still bind B.1.1.7 spikes and neutralize in pseudoviral assays. B.1.351 and B.1.1.248 include compensatory mutations that either increase spike expression or increase ACE2 binding affinity. Finally, B.1.351 and B.1.1.248 completely escape a potent ACE2 peptide mimic. We anticipate that spike display will accelerate antigen design, deep scanning mutagenesis, and antibody epitope mapping for SARS-CoV-2 and other emerging viral threats.
Extracellular vesicles synchronize cellular phenotypes of differentiating cells
Authors: Minakawa Tomohiro , Matoba Tetsuya , Yamashita Jun K. 
Published: March 2021

ABSTRACTDuring embryonic development, cells differentiate in a coordinated manner, aligning their fate decisions and differentiation stages with those of surrounding cells. However, little is known about the mechanisms that regulate this synchrony. Here we show that cells in close proximity synchronize their differentiation stages and cellular phenotypes with each other via extracellular vesicle (EV)-mediated cellular communication. We previously established a mouse embryonic stem cell (ESC) line harboring an inducible constitutively active protein kinase A (CA-PKA) gene and found that the ESCs rapidly differentiated into mesoderm after PKA activation. In the present study, we performed a co-culture of control ESCs and PKA-ESCs, finding that both ESCs rapidly differentiated in synchrony even when PKA was activated only in PKA-ESCs, a phenomenon we named “Phenotypic Synchrony of Cells (PSyC)”. We further demonstrated PSyC was mediated by EVs containing miR-132. PKA-ESC-derived EVs and miR-132-containing artificial nano-vesicles similarly enhanced mesoderm and cardiomyocyte differentiation in ESCs and ex vivo embryos, respectively. PSyC is a new form of cell-cell communication mediated by EV regulation of neighboring cells and could be broadly involved in tissue development and homeostasis.