bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mucociliary Transport Deficiency and Disease Progression in Syrian Hamsters with SARS-CoV-2 Infection
Authors: Li Qian , Vijaykumar Kadambari , Philips Scott E , Hussain Shah S , Huynh Van N , Fernandez-Petty Courtney M , Lever Jacelyn E Peabody , Foote Jeremy B , Ren Janna , Campos-Gómez Javier , Daya Farah Abou , Hubbs Nathaniel W , Kim Harrison , Onuoha Ezinwanne , Boitet Evan R , Fu Lianwu , Leung Hui Min , Yu Linhui , Detchemendy Thomas W , Schaefers Levi T , Tipper Jennifer L , Edwards Lloyd J , Leal Sixto M , Harrod Kevin S , Tearney Guillermo J , Rowe Steven M 
Published: January 2022

AbstractSubstantial clinical evidence supports the notion that ciliary function in the airways plays an important role in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, consequent impaired mucociliary transport (MCT) remains unknown for the intact MCT apparatus from an in vivo model of disease. Using golden Syrian hamsters, a common animal model that recapitulates human COVID-19, we quantitatively followed the time course of physiological, virological, and pathological changes upon SARS-CoV-2 infection, as well as the deficiency of the MCT apparatus using micro-optical coherence tomography, a novel method to visualize and simultaneously quantitate multiple aspects of the functional microanatomy of intact airways. Corresponding to progressive weight loss up to 7 days post-infection (dpi), viral detection and histopathological analysis in both the trachea and lung revealed steadily descending infection from the upper airways, as the main target of viral invasion, to lower airways and parenchymal lung, which are likely injured through indirect mechanisms. SARS-CoV-2 infection caused a 67% decrease in MCT rate as early as 2 dpi, largely due to diminished motile ciliation coverage, but not airway surface liquid depth, periciliary liquid depth, or cilia beat frequency of residual motile cilia. Further analysis indicated that the fewer motile cilia combined with abnormal ciliary motion of residual cilia contributed to the delayed MCT. The time course of physiological, virological, and pathological progression suggest that functional deficits of the MCT apparatus predispose to COVID-19 pathogenesis by extending viral retention and may be a risk factor for secondary infection. As a consequence, therapies directed towards the MCT apparatus deserve further investigation as a treatment modality.
Viability, task switching, and fall avoidance of the simplest dynamic walker
Authors: Patil Navendu S. , Dingwell Jonathan B. , Cusumano Joseph P. 
Published: January 2022

ABSTRACTHumans display great versatility when performing goal-directed tasks while walking. However, the extent to which such versatility helps with fall avoidance remains unclear. We recently demonstrated a functional connection between the motor regulation needed to achieve task goals (e.g. maintaining walking speed) and a simple walker’s ability to reject large disturbances. Here, for the same model, we identify the viability kernel—the state space region in which the walker can step forever via at least one sequence of push-off inputs per state. We further find that only a few basins of attraction of the speed-regulated walker’s steady-state gaits can fully cover the viability kernel. This highlights a potentially important role of task-level motor regulation in fall avoidance. Therefore, we posit an adaptive hierarchical control/regulation strategy that switches between different task-level regulators to avoid falls. Our hierarchical task switching controller only requires a target value of the regulated observable—a ‘task switch’—at each walking step, each chosen from a small, predetermined collection. Because humans have typically already learned to perform such tasks during nominal walking conditions, this suggests that the ‘information cost’ of biologically implementing such controllers for the nervous system, including cognitive demands in humans, could be relatively low.
Transcriptomic and functional genetic evidence for distinct ecophysiological responses across complex life cycle stages
Authors: Freda Philip J. , Toxopeus Jantina , Dowle Edwina J. , Ali Zainab M. , Heter Nicholas , Lambert-Collier Rebekah L. , Sower Isaiah , Tucker Joseph C. , Morgan Theodore J. , Ragland Gregory J. 
Published: January 2022

AbstractOrganisms with complex life cycles demonstrate a remarkable ability to change their phenotypes across development, presumably as an evolutionary adaptation to developmentally variable environments. Developmental variation in environmentally sensitive performance, and thermal sensitivity in particular, has been well documented in holometabolous insects. For example, thermal performance in adults and juvenile stages exhibit little genetic correlation (genetic decoupling) and can evolve independently, resulting in divergent thermal responses. Yet, we understand very little about how this genetic decoupling occurs. We tested the hypothesis that genetic decoupling of thermal physiology is driven by fundamental differences in physiology between life stages, despite a potentially conserved Cellular Stress Response. We used RNAseq to compare transcript expression in response to a cold stressor in Drosophila melanogaster larvae and adults and used RNAi (RNA interference) to test whether knocking down nine target genes differentially affected larval and adult cold tolerance. Transcriptomic responses of whole larvae and adults during and following exposure to -5°C were largely unique both in identity of responding transcripts and in temporal dynamics. Further, we found no relationship between stage-specificity and tissue-specificity of transcripts, suggesting that the differences are not simply driven by differences in tissue composition across development. In addition, RNAi of target genes resulted in largely stage-specific and sometimes sex-specific effects on cold tolerance. The combined evidence suggests that thermal physiology is largely stage-specific at the level of gene expression, and thus natural selection may be acting on different loci during the independent thermal adaptation of different life stages.Summary StatementRNAseq and gene knockout via transgenic RNAi lines suggest that physiological responses to low temperatures are largely distinct across life stages of the fly Drosophila melanogaster.
UbE3-APA: A Bioinformatic Strategy to Elucidate Ubiquitin E3 Ligase Activities in Quantitative Proteomics Study
Authors: Gong Yao , Chen Yue 
Published: January 2022

AbstractMotivationUbiquitination is widely involved in protein homeostasis and cell signaling. Ubiquitin E3 ligases are critical regulators of ubiquitination that recognize and recruit specific ubiquitination targets for the final rate-limiting step of ubiquitin transfer reactions. Understanding the ubiquitin E3 ligase ac-tivities will provide knowledge in the upstream regulator of the ubiquitination pathway and reveal po-tential mechanisms in biological processes and disease progression. Recent advances in mass spec-trometry-based proteomics have enabled deep profiling of ubiquitylome in a quantitative manner. Yet, functional analysis of ubiquitylome dynamics and pathway activity remains challenging.ResultsHere, we developed a UbE3-APA, a computational algorithm and stand-alone python-based software for Ub E3 ligase Activity Profiling Analysis. Combining an integrated annotation database with statistical analysis, UbE3-APA identifies significantly activated or suppressed E3 ligases based on quantitative ubiquitylome proteomics datasets. Benchmarking the software with published quantitative ubiquitylome analysis confirms the genetic manipulation of SPOP enzyme activity through overexpres-sion and mutation. Application of the algorithm in the re-analysis of a large cohort of ubiquitination proteomics study revealed the activation of PARKIN and the co-activation of other E3 ligases in mito-chondria depolarization-induced mitophagy process. We further demonstrated the application of the algorithm in the DIA-based quantitative ubiquitylome analysis.AvailabilitySource code and binaries are freely available for download at URL:https://github.com/Chenlab-UMN/Ub-E3-ligase-Activity-Profiling-Analysis, implemented in python and supported on Linux and MS WindowsContactyuechen@umn.eduSupplementary informationSupplementary data are available.
Pain-related learning signals in the human insula
Authors: Horing Björn , Büchel Christian 
Published: January 2022

AbstractPain is not only a perceptual phenomenon, but also a preeminent learning signal. In reinforcement learning models, prediction errors (PEs) play a crucial role, i.e. the mismatch between expectation and sensory input. In particular, advanced learning models require the representation of different types of PEs, namely signed PEs (whether more or less pain was expected) to specify the direction of learning, and unsigned PEs (the absolute deviation from an expectation) to adapt the learning rate. The insula has been shown to play an important role in pain intensity coding and in signaling surprise. However, mainly unsigned PEs could be identified in the anterior insula. It remains an open question whether these PEs are specific to pain, and whether signed PEs are also represented in the insula.To answer these questions, 47 subjects learned associations of two conditioned stimuli (CS) with four unconditioned stimuli (US; painful heat or loud sound, of one low and one high intensity each) while undergoing functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) measurements. CS-US associations reversed multiple times between intensities and between sensory modalities, generating frequent PEs.SCRs indicated comparable nonspecific characteristics of the two modalities. fMRI analyses focusing on the insular and opercular cortices contralateral to painful stimulation showed that activation in the anterior insula correlated with unsigned intensity PEs. Importantly, this unsigned PE signal was similar for pain and aversive sounds and also modality PEs, indicating an unspecific aversive surprise signal. Conversely, signed pain intensity PE signals were modality-specific and located in the dorsal posterior insula, an area previously implicated in pain intensity processing.Previous studies have identified abnormal insula function and abnormal learning as potential causes of pain chronification. Our findings link these results and suggest one potential mechanism, namely a misrepresentation of learning relevant prediction errors in the insular cortex.
The value of vaccine booster doses to mitigate the global impact of the Omicron SARS-CoV-2 variant
Authors: Hogan Alexandra B , Wu Sean L , Doohan Patrick , Watson Oliver J , Winskill Peter , Charles Giovanni , Barnsley Gregory , Riley Eleanor M , Khoury David S , Ferguson Neil M , Ghani Azra C 
Published: January 2022

AbstractVaccines have played a central role in mitigating severe disease and death from COVID-19 in the past 12 months. However, efficacy wanes over time and this loss of protection is being compounded by the emergence of the Omicron variant. By fitting an immunological model to population-level vaccine effectiveness data, we estimate that neutralizing antibody titres for Omicron are reduced by 3.9-fold (95% CrI 2.9–5.5) compared to the Delta variant. Under this model, we predict that 90 days after boosting with the Pfizer-BioNTech vaccine, efficacy against severe disease (admission to hospital) declines to 95.9% (95% CrI 95.4%–96.3%) against the Delta variant and 78.8% (95% CrI 75.0%–85.1%) against the Omicron variant. Integrating this immunological model within a model of SARS-CoV-2 transmission, we demonstrate that the size of the Omicron wave will depend on the degree of past exposure to infection across the population, with relatively small Omicron waves in countries that previously experienced a large Delta wave. We show that booster doses can have a major impact in mitigating the epidemic peak, although in many settings it remains possible that healthcare capacity could still be challenged. This is particularly the case in “zero-COVID” countries where there is little prior infection-induced immunity and therefore epidemic peaks will be higher. Where dose supply is limited, targeting boosters to the highest risk groups to ensure continued high protection in the face of waning immunity is of greater benefit than giving these doses as primary vaccination to younger age-groups. In many settings it is likely that health systems will be stretched, and it may therefore be necessary to maintain and/or reintroduce some level of NPIs to mitigate the worst impacts of the Omicron variant as it replaces the Delta variant.
Pharmaceutical Payments to Japanese Certificated Hematologists: A Retrospective Analysis of Personal Payments from Pharmaceutical Companies between 2016 and 2019
Authors: Kusumi Eiji , Murayama Anju , Kamamoto Sae , Kawashima Moe , Yoshida Makoto , Saito Hiroaki , Sawano Toyoaki , Yamashita Erika , Tanimoto Tetsuya , Ozaki Akihiko 
Published: January 2022

AbstractBackgroundA growing and significant financial relationship exist between physicians and pharmaceutical companies. However, little is known about the characteristics and trends of personal payments from pharmaceutical companies to hematologists. This study was aimed to evaluate the financial relationship between hematology specialists and pharmaceutical companies in Japan between 2016 and 2019.MethodsDescriptive analyses were performed to evaluate personal payments from 92 major pharmaceutical companies to all board-certificated hematologists in Japan. Furthermore, trend of payments over four years were evaluated by generalized estimating equations.ResultsAmong the 4,183 hematology specialists, 2,706 (64.7%) received a total of US$36,291,434 (¥3,955,766,292). The personal payments were worth $13,411 (standard deviation: $34,856) on average, with a median of $2,471 (Interquartile range: $851 $9,677) over the four-year period, respectively. Only the top 10% of specialists accounted for 76.8% of the total payments. The average payment values constantly increased from $4,259 to $5,574 between 2016 and 2019, with a significant mean annual increase rate of 11.2% (95%CI: 9.1% 13.4%). The proportion of hematology specialists with payments also slightly increased by 1.8% (95%CI: 0.6% 3.0%) per year.ConclusionsMost Japanese board-certified hematology specialists received substantial personal payments. These payments are becoming increasingly more prevalent and greater among hematology specialists.
PLWHA’s Perspective on Community Stigma for Getting Social Support and Improving Life Quality in the Digital Era
Authors: Erwansyah Rio Ady , Rumambo Pandin Moses Glorino 
Published: January 2022

ABSTRACTCommunity stigma against HIV/AIDS is still a problem that must be faced by people living with HIV/AIDS (PLWHA). The existence of stigmatization and discrimination received by PLWHA causes the lack of social support they get. Social support is very important for PLWHA to improve their quality of life. In this digital era where the development of technology and social media is an alternative for PLWHA to get social support online through their community, by sharing information and experiences. This systematic review was conducted through Scopus, Science Direct, ProQuest, and SAGE. The selection of articles followed inclusion criteria, including articles published in the last five years and published in English and discussing perspectives on stigma. Articles published not in English and articles with unclear literature reviews were excluded from this study. The PRISMA flow chart and JBI assessment checklist were used to assess the risk of bias and article quality. 20 relevant articles will be reviewed. The results of the study found that in this digital era PLWHA can take advantage of technological developments and social media to improve their quality of life by getting social support through the online communities they follow.
Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-lead Electrocardiograms
Authors: Wang Xin , Khurshid Shaan , Choi Seung Hoan , Friedman Sam , Weng Lu-Chen , Reeder Christopher , Pirruccello James P. , Singh Pulkit , Lau Emily S. , Venn Rachael , Diamant Nate , Achille Paolo Di , Philippakis Anthony , Anderson Christopher D. , Ho Jennifer E. , Ellinor Patrick T. , Batra Puneet , Lubitz Steven A. 
Published: January 2022

AbstractArtificial intelligence (AI) models applied to 12-lead electrocardiogram (ECG) waveforms can predict atrial fibrillation (AF), a heritable and morbid arrhythmia. We hypothesized that there may be a genetic basis for ECG-AI based risk estimates. We applied an ECG-AI model for predicting incident AF to ECGs from 39,986 UK Biobank participants without AF. We then performed a genome-wide association study (GWAS) of the predicted AF risk. We identified three signals (P<5×10−8) at established AF susceptibility loci marked by the sarcomeric gene TTN, and sodium channel genes SCN5A and SCN10A. We also identified two novel loci near the genes VGLL2 and EXT1. In contrast, a GWAS of risk estimates from a clinical variable model indicated a different genetic profile. Predicted AF risk from an ECG-AI model is influenced by genetic variation implicating sarcomeric, ion channel, and height pathways. ECG-AI models may identify individuals at risk for disease via specific biological pathways.
COVID-19 breakthrough infection after inactivated vaccine induced robust antibody responses and cross-neutralization of SARS-CoV-2 variants, but less immunity against omicron
Authors: Suntronwong Nungruthai , Yorsaeng Ritthideach , Puenpa Jiratchaya , Auphimai Chompoonut , Thongmee Thanunrat , Vichaiwattana Preeyaporn , Kanokudom Sitthichai , Duangchinda Thaneeya , Chantima Warangkana , Pakchotanon Pattarakul , Assawakosri Suvichada , Nilyanimit Pornjarim , Klinfueng Sirapa , Wongsrisang Lakkhana , Srimuan Donchida , Thatsanatorn Thaksaporn , Sudhinaraset Natthinee , Wanlapakorn Nasamon , Poovorawan Yong 
Published: January 2022

AbstractThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of immunity in vaccinated individuals is resulting in increased numbers of SARS-CoV-2 breakthrough infections. This study investigated binding antibody responses and neutralizing activities against SARS-CoV-2 variants in patients with COVID-19 who had been fully vaccinated with CoronaVac (n = 78), individuals who had been fully vaccinated with CoronaVac but had not contracted COVID-19 (n = 170), and individuals who had received AZD1222 as a third vaccination (n = 210). Breakthrough infection was generally detected approximately 88 days after the second CoronaVac vaccination (interquartile range 68–100) days. Blood samples were collected at median of 34 days after infection. Binding antibody levels in sera from patients with breakthrough infection were significantly higher than those in individuals who had received AZD1222 as a third vaccination. However, neutralizing activities against wild-type and variants including alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2) were comparable in patients with breakthrough infections and individuals who received a third vaccination with AZD1222, which activities are exceeding 90%. Omicron (B.1.1.529) was neutralized less effectively by serum from breakthrough infection patients, with a 6.3-fold reduction compared to delta variants. The study suggests that breakthrough infection after two doses of an inactivated vaccine can induce neutralizing antibody against omicron. Further investigation is needed to assess the long-term persistence of antibody against omicron variant.
Outcomes after radioiodine treatment for thyrotoxicosis
Authors: Bolland Mark J , Croxson Michael S 
Published: January 2022

AbstractBackgroundRadioiodine is commonly prescribed as a permanent treatment for thyrotoxicosis. At ADHB, Auckland, New Zealand, radioiodine dose is individualised by the prescribing physician according to patient characteristics.AimsWe investigated the outcomes of this approach.MethodsWe identified all patients receiving radioiodine for thyrotoxicosis at ADHB in 2015 and retrieved relevant clinical details.Results222 patients were prescribed radioiodine: 147 (66%) for Graves’ disease, 58 (26%) for toxic nodular goitre, and 17 (8%) for solitary toxic nodule. For Graves’ disease, 80% had one radioiodine dose (first dose median 550 MBq, range 200-1000 MBq; total dose 200-2400 MBq), 92% had the thyrotoxicosis cured, and 83% required thyroxine post-radioiodine. For toxic nodular goitre, 93% had one dose (median 550 MBq, range 400-1000 MBq, total dose 400-1800 MBq), 93% were cured and 22% required thyroxine. For solitary toxic nodule, all had one dose (median 550 MBq, range 500-550 MBq), all were cured and 35% required thyroxine. In 69/222 (31%) patients (35% of individuals with Graves’ disease, 17% with toxic nodular goitre, and 47% with solitary toxic nodule), the most recent TSH (mean 3.2 years post-radioiodine) was elevated (30% TSH >10 mu/L, 70% TSH 4-10 mu/L).ConclusionsFollowing radioiodine treatment, >90% of individuals have the thyrotoxicosis cured, but hypothyroidism is usual in Graves’ disease and occurs in 22-35% in toxic nodular goitre or solitary toxic nodule. Many individuals taking thyroxine after radioiodine have suboptimally controlled hypothyroidism.
CBioProfiler: a web and standalone pipeline for cancer biomarker and subtype characterization
Authors: Liu Xiaoping , Wang Zisong , Shi Hongjie , Li Sheng , Wang Xinghuan 
Published: January 2022

AbstractCancer is a leading cause of death worldwide, and the identification of biomarkers and subtypes that can predict the long-term survival of cancer patients is essential for their risk stratification, treatment, and prognosis. However, there are currently no standardized tools for exploring cancer biomarkers or subtypes. In this study, we introduce CBioProfiler, a web server and standalone application that includes two pipelines for analyzing cancer biomarkers and subtypes. The cancer biomarker pipeline consists of five modules for identifying and annotating cancer survival-related biomarkers using multiple machine learning survival algorithms. The subtype pipeline includes three modules for data preprocessing, subtype identification using multiple unsupervised machine learning methods, and subtype evaluation and validation. CBioProfiler also includes a novel R package, CuratedCancerPrognosisData, which has reviewed, curated, and integrated gene expression data and clinical data from 268 gene expression studies of 43 common blood and solid tumors, including data from 47,686 clinical samples. The web server is available athttps://www.cbioprofiler.com/andhttps://cbioprofiler.znhospital.cn/CBioProfiler/, and the standalone app and source code can be found athttps://github.com/liuxiaoping2020/CBioProfiler.