bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Computer Vision Platform to Automatically Locate Critical Events in Surgical Videos
Authors: Mascagni Pietro , Alapatt Deepak , Urade Takeshi , Vardazaryan Armine , Mutter Didier , Marescaux Jacques , Costamagna Guido , Dallemagne Bernard , Padoy Nicolas 
Published: January 2021

Objective:
The aim of this study was to develop a computer vision platform to automatically locate critical events in surgical videos and provide short video clips documenting the critical view of safety (CVS) in laparoscopic cholecystectomy (LC).

Background:
Intraoperative events are typically documented through operator-dictated reports that do not always translate the operative reality. Surgical videos provide complete information on surgical procedures, but the burden associated with storing and manually analyzing full-length videos has so far limited their effective use.

Methods:
A computer vision platform named EndoDigest was developed and used to analyze LC videos. The mean absolute error (MAE) of the platform in automatically locating the manually annotated time of the cystic duct division in full-length videos was assessed. The relevance of the automatically extracted short video clips was evaluated by calculating the percentage of video clips in which the CVS was assessable by surgeons.

Results:
A total of 155 LC videos were analyzed: 55 of these videos were used to develop EndoDigest, whereas the remaining 100 were used to test it. The time of the cystic duct division was automatically located with a MAE of 62.8 ± 130.4 seconds (1.95% of full-length video duration). CVS was assessable in 91% of the 2.5 minutes long video clips automatically extracted from the considered test procedures.

Conclusions:
Deep learning models for workflow analysis can be used to reliably locate critical events in surgical videos and document CVS in LC. Further studies are needed to assess the clinical impact of surgical data science solutions for safer laparoscopic cholecystectomy.
Ribavirin Improves NK Cell IFNγ Response During Sofosbuvir-based DAA Therapy in HCV-infected Liver Transplant Recipients
Authors: Adenugba Akinbami , Hornung Matthias , Weigand Kilian , Peschel Georg , Junger Henrik , Kupke Paul , Lang Hauke , Marquardt Jens U. , Zimmermann Tim , Geissler Edward K. , Schlitt Hans J. , Werner Jens M. 
Published: January 2021

Background.
Chronic hepatitis C virus (HCV) infection is characterized by activation of natural killer (NK) cells. Here, we asked whether HCV elimination by sofosbuvir-based direct-acting antivirals (DAAs) and the addition of ribavirin (RBV) improve NK cell function in liver transplant (LTx) recipients.

Methods.
We analyzed NK cell degranulation and interferon (IFN)γ-response along with STAT1 and STAT4 phosphorylation in 29 HCV-infected LTx recipients and 17 HCV-infected patients during DAA treatment.

Results.
Compared with uninfected LTx recipients, NK cells from HCV-infected LTx recipients were polarized toward cytotoxicity with increased CD107a-degranulation (10.1% versus 14.6%; P = 0.0263) and reduced capacity to produce IFNγ (43.0% versus 26.7%; P = 0.0002). The altered phenotype of NK cells in HCV-infected LTx recipients was accompanied by increased STAT1 (44.6% versus 87.4%; P < 0.0001) and STAT1 phosphorylation (0.7% versus 8.9%; P = 0.0005) compared with pSTAT4 IFNα-induction (29.9% versus 17.6%; P = 0.0014). Successful DAA therapy did not affect CD107a-degranulation but decreased STAT1. RBV cotreatment with DAA therapy for HCV increased CD56Bright NK cell IFNγ-responses in LTx recipients (70.9% versus 89.2%; P = 0.002), and this correlated to an increase in the inducibility of pSTAT4 (MFI 157 versus 173; P = 0.0002).

Conclusions.
RBV cotreatment of HCV infection improved pSTAT4-dependent IFNγ-production in NK cells. This is relevant especially for immunocompromised patients such as LTx recipients or patients with end-stage liver disease.
Indoor dust as a matrix for surveillance of COVID-19 outbreaks
Authors: Renninger Nicole , Nastasi Nick , Bope Ashleigh , Cochran Samuel J. , Haines Sarah R. , Balasubrahmaniam Neeraja , Stuart Katelyn , Bivins Aaron , Bibby Kyle , Hull Natalie M. , Dannemiller Karen C. 
Published: January 2021

AbstractOngoing disease surveillance is a critical tool to mitigate viral outbreaks, especially during a pandemic. Environmental monitoring has significant promise even following widespread vaccination among high-risk populations. The goal of this work is to demonstrate molecular SARS-CoV-2 monitoring in bulk floor dust and related samples as a proof-of-concept of a non-invasive environmental surveillance methodology for COVID-19 and potentially other viral diseases. Surface swab, passive sampler, and bulk floor dust samples were collected from rooms of individuals infected with COVID-19, and SARS-CoV-2 was measured with quantitative reverse transcription polymerase chain reaction (RT-qPCR) and two digital PCR (dPCR) methods. Bulk dust samples had geometric mean concentration of 159 copies/mg-dust and ranged from non-detects to 23,049 copies/mg-dust detected using ddPCR. An average of 88% of bulk dust samples were positive for the virus among detection methods compared to 55% of surface swabs and fewer on the passive sampler (19% carpet, 29% polystyrene). In bulk dust, SARS-CoV-2 was detected in 76%, 93%, and 97% of samples measured by qPCR, chip-based dPCR, and droplet dPCR respectively. Detectable viral RNA in the bulk vacuum bags did not measurably decay over 4 weeks, despite the application of a disinfectant before room cleaning. Future monitoring efforts should further evaluate RNA persistence and heterogeneity in dust. This study did not measure virus viability in dust or potential transmission associated with dust. Overall, this work demonstrates that bulk floor dust is a potentially useful matrix for long-term monitoring of viral disease outbreaks in high-risk populations and buildings.ImportanceEnvironmental surveillance to assess pathogen presence within a community is proving to be a critical tool to protect public health, and it is especially relevant during the ongoing COVID-19 pandemic. Importantly, environmental surveillance tools also allow for the detection of asymptomatic disease carriers and for routine monitoring of a large number of people as has been shown for SARS-CoV-2 wastewater monitoring. However, additional monitoring techniques are needed to screen for outbreaks in high-risk settings such as congregate care facilities. Here, we demonstrate that SARS-CoV-2 can be detected in bulk floor dust collected from rooms housing infected individuals. This analysis suggests that dust may be a useful and efficient matrix for routine surveillance of viral disease outbreaks.
Plasma β-amyloid in mild behavioural impairment – neuropsychiatric symptoms on the Alzheimer’s continuum
Authors: Miao Ruxin , Chen Hung-Yu , Gill Sascha , Naude James , Smith Eric E. , Ismail Zahinoor ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2021

AbstractIntroductionSimple markers are required to recognize older adults at higher risk for neurodegenerative disease. Mild behavioural impairment (MBI) and plasma β-amyloid (Aβ) have been independently implicated in the development of incident cognitive decline and dementia. Here we studied the associations between MBI and plasma Aβ42/Aβ40.MethodsParticipants with normal cognition (n = 86) or mild cognitive impairment (n = 53) were selected from the Alzheimer’s Disease Neuroimaging Initiative. MBI scores were derived from Neuropsychiatric Inventory items. Plasma Aβ42/Aβ40ratios were assayed using mass spectrometry. Linear regressions were fitted to assess the association between MBI total score as well as MBI domain scores with plasma Aβ42/Aβ40.ResultsLower plasma Aβ42/Aβ40was associated with higher MBI total score (p= 0.04) and greater affective dysregulation (p =0.04), but not with impaired drive/motivation (p =0.095) or impulse dyscontrol (p =0.29) MBI domains.ConclusionIn persons with normal cognition or mild cognitive impairment, MBI was associated with low plasma Aβ42/Aβ40. Incorporating MBI into case detection can help capture preclinical and prodromal Alzheimer’s disease.
Proteomic and Metabolomic Investigation of COVID-19 Patients with Elevated Serum Lactate Dehydrogenase
Authors: Yan Haixi , Liang Xiao , Du Juping , He Zebao , Wang Yu , Lyu Mengge , Yue Liang , Zhang Fangfei , Xue Zhangzhi , Xu Luang , Ruan Guan , Li Jun , Zhu Hongguo , Xu Jiaqin , Chen Shiyong , Zhang Chao , Lv Dongqing , Lin Zongmei , Shen Bo , Zhu Yi , Qian Biyun , Chen Haixiao , Guo Tiannan 
Published: January 2021

AbstractSerum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID-19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID-19 patients were enrolled to monitor the clinical and laboratory parameters over three weeks. Serum lactate dehydrogenase (LDH) was shown elevated in the COVID-19 patients on admission and declined throughout disease course, and its ability to classify patient severity outperformed other biochemical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high- and low-risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results found COVID-19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels are associated COVID-19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.
Trends in lipid-modifying agent use in 83 countries
Authors: Blais Joseph E , Wei Yue , Yap Kevin KW , Alwafi Hassan , Ma Tian-Tian , Brauer Ruth , Lau Wallis CY , Man Kenneth KC , Siu Chung Wah , Tan Kathryn C , Wong Ian CK , Wei Li , Chan Esther W 
Published: January 2021

ABSTRACTAimsLipid-modifying agents (LMAs) are increasingly used to reduce lipid levels and prevent cardiovascular events, but the magnitude of their consumption in different world regions is unknown. We aimed to describe recent global trends in LMA consumption and to explore the relationship between country-level LMA consumption and cholesterol concentrations.Methods and resultsThis cross-sectional and ecological study used monthly pharmaceutical sales data from January 2008 to December 2018, for 83 countries from the IQVIA Multinational Integrated Data Analysis System, and total and non–high-density lipoprotein (non– HDL) cholesterol concentrations from the NCD Risk Factor Collaboration. The compound annual growth rate (CAGR) was used to assess changes in LMA consumption over time. From 2008 to 2018, the use of LMAs increased from 7,468 to 11,197 standard units per 1000 inhabitants per year (CAGR 4.13%). Statins were the most used class of LMA and their market share increased in 75% of countries between 2008 and 2018. Fibrates were the most consumed nonstatin drugs. From 2013 to 2018, consumption of low-density lipoprotein lowering therapies increased (statins 3.99%; ezetimibe 4.01%; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors 104.47%). Limited evidence supports a clear relationship between country-level changes in LMA consumption and total and non–HDL cholesterol concentrations in 2008 versus 2018.ConclusionSince 2008, global access to LMAs, especially statins, has improved. In line with international lipid guideline recommendations, recent trends indicate growth in the use of statins, ezetimibe, and PCSK9 inhibitors. Country-level patterns of LMA use and total and non–HDL cholesterol varied considerably.
Association of Chronic Acid Suppression and Social Determinants of Health with COVID-19 Infection
Authors: Zhang Bing , Silverman Anna L. , Bangaru Saroja , Arneson Douglas , Dasharathy Sonya , Nguyen Nghia , Rodden Diane , Shih Jonathan , Butte Atul J. , El-Nachef Wael Noor , Boland Brigid S. , Rudrapatna Vivek A. 
Published: January 2021

AbstractAcid suppressants are a widely-used class of medications previously linked to an increased risk of aerodigestive infections. However, prior studies of these medications as potentially reversible risk factors for COVID-19 have been conflicting. We performed a case-control study involving clinician-abstracted data from 900 health records across 3 US medical centers. We incorporated sociobehavioral predictors of infectious exposure using geomapping to publicly-available data. We found no evidence for an association between chronic acid suppression and incident COVID-19 (adjusted odds ratio 1.04, 95% CI: 0.92-1.17, P=0.515). However, we identified several medical and social features as positive (Latinx ethnicity, BMI ≥ 30, dementia, public transportation use, month of the pandemic) and negative (female sex, concurrent solid tumor, alcohol use disorder) predictors of new-onset infection. These results place both medical and social factors on the same scale within the context of the COVID-19 pandemic, and underscore the importance of comprehensive models of disease.
Dynamics on the web: spiders use physical rules to solve complex tasks in mate search and competition
Authors: Haluts Amir , Garza Reyes Sylvia F. , Gorbonos Dan , Jordan Alex , Gov Nir S. 
Published: January 2021

ABSTRACTA long-standing question in animal behaviour is how organisms solve complex tasks. Here we explore how the dynamics of animal behaviour in the ubiquitous tasks of mate-search and competition can arise from a physics-based model of effective interactions. Male orb-weaving spiders of the genusTrichonephilaare faced with the daunting challenge of entering the web of a much larger and potentially cannibalistic female, approaching her, and fending off rival males. The interactions that govern the dynamics of males within the confined two-dimensional arena of the female’s web are dominated by seismic vibrations. This unifying modality allows us to describe the spiders as interacting active particles, responding only to effective forces of attraction and repulsion due to the female and rival males. Our model is based on a detailed analysis of experimental spider trajectories, obtained during the approach of males towards females, and amidst their interactions with rival males of different sizes. The dynamics of ’spider particles’ that emerges from our theory allows us to explain a puzzling relationship between the density of males on the web and the reproductive advantages of large males. Our results provide strong evidence that the simple physical rules at the basis of our model can give rise to complex fitness related behaviours in this system.
The Flowering Time RegulatorFLKControls Pathogen Defense inArabidopsis thaliana
Authors: Fabian Matthew , Gao Min , Zhang Xiao-Ning , Shi Jiangli , Kim Sung-Ha , Patel Priyank , Hu Anna R. , Lu Hua 
Published: January 2021

AbstractPlant disease resistance is a complex process that is maintained in an intricate balance with development. Increasing evidence indicates the importance of post-transcriptional regulation of plant defense by RNA binding proteins. The K homology (KH) repeat is an ancient RNA binding motif found in proteins from diverse organisms. The role of KH domain proteins in pathogen resistance is not well known. From a genetic screen aimed to uncover novel defense genes in Arabidopsis, we identified a new allele of the canonical flowering regulatory gene,FLOWERING LOCUS KH Domain(FLK), encoding a putative triple KH-repeat protein. In addition to late flowering, theflkmutants exhibited decreased resistance to the bacterial pathogenPseudomonas syringaeand increased resistance to the necrotrophic fungal pathogenBotrytis cinerea. We found that theflkmutations compromised basal defense and defense signaling mediated by salicylic acid and led to increased reactive oxygen species (ROS) scavenging, likely throughFLK’s regulation of the ROS scavenging enzyme catalases. RNA-seq data revealed that major defense signaling genes are regulated byFLK, providing a molecular basis forFLK’s contribution to pathogen defense. Together our data support that FLK is a multifunctional protein regulating pathogen defense and development of plants.
The Arabidopsis Calcium Sensor Calmodulin-like 38 Regulates Stress Granule Autophagy and Dynamics during Low Oxygen Stress and Re-aeration Recovery
Authors: Field Sterling , Gulledge Whitney , Roberts Daniel M. 
Published: January 2021

AbstractIn response to the energy crisis resulting from submergence stress and hypoxia, Arabidopsis limits non-essential mRNAs translation, and accumulate cytosolic stress granules (SG). SGs are phase-separated mRNA-protein particles that partition transcripts for various fates: storage, degradation, or return to translation after stress alleviation. Here, it is shown that RNA stress granules are dynamically regulated during hypoxia stress and aerobic recovery via two phases of autophagy that require the AAA+ATPase CDC48 and the calcium sensor Calmodulin-like 38 (CML38). CML38 is a core hypoxia response-protein that associates with hypoxia-induced SGs. We show that CML38 is essential for SG autophagy during extended hypoxia. Further, cml38 mutants show disorganized SG morphology during extended hypoxia, suggesting a role in SG formation and maintenance. We also show that upon the return of aerobic conditions, intracellular calcium and CML38 are necessary for SG breakdown and turnover, and for upregulating autophagy.cml38mutants not only lose these responses, but also have aberrant, sustained autophagosome accumulation during the reoxygenation recovery phase. The findings suggest that CDC48 RNA granule autophagy (“granulophagy”) is conserved in plants, and that the hypoxia-induced calcium sensor CML38 regulates SG autophagy during anaerobic stress as well as during the reprogramming phase associated with reoxygenation.
A bioreactor for controlled electromechanical stimulation of developing scaffold-free constructs
Authors: Van Houten Sarah K. , Bramson Michael T. K. , Corr David T. 
Published: January 2021

ABSTRACTBioreactors are commonly used to apply biophysically-relevant stimulations to tissue-engineered constructs in order to explore how these stimuli influence tissue development, healing, and homeostasis. These bioreactors offer great flexibility as key features of the stimuli (e.g., duty cycle, frequency, amplitude, duration) can be controlled to elicit a desired cellular response. Controlled delivery of mechanical and/or electrical stimulation has been shown to improve the structure and function of engineered tissue constructs, compared to unstimulated controls, for applications in various musculoskeletal soft tissues. However, most bioreactors that apply mechanical and electrical stimulations, do so to a scaffold after the construct has developed, preventing study of the influence these stimuli have on early construct development. Thus, there is a need for a bioreactor that allows the direct application of mechanical and electrical stimulation to constructsas they develop, to enable such exploration and to better mimic key aspects of tissue development. Hence, the objective of this study was to develop and calibrate a bioreactor to deliver precise mechanical and electrical stimulation, either independently or in combination, to developing scaffold-free tissue constructs. Standard Flexcell Tissue Train plates were modified with stainless steel loading pins and stimulating electrodes to integrate direct mechanical and electrical stimulation, respectively, into our established scaffold-free, single-fiber engineering platform. Linear calibration curves were established, then used to apply precise dynamic mechanical and electrical stimulations, over a range of physiologically relevant strains (0.50, 0.70, 0.75, 1.0, 1.5%) and voltages (1.5, 3.5 V), respectively. Once calibrated, applied mechanical and electrical stimulations were not statistically different from their desired target values, and were consistent whether delivered independently or in combination. Indeed, concurrent delivery of mechanical and electrical stimulation resulted in a negligible change in mechanical (< 2%) and electrical (<1%) values, from their independently-delivered values. With this calibrated bioreactor, we can apply precise, controlled, reproducible mechanical and electrical stimulations, alone or in combination, to scaffold-free, tissue engineered constructs as they develop, to explore how these stimuli can be leveraged to advance and accelerate functional tissue engineering in a variety of musculoskeletal soft tissues.IMPACT STATEMENTAs the importance of biophysical stimulation in tissue engineering continues to be recognized and incorporated, this bioreactor provides a platform to further our understanding of the roles independent or combined mechanical and electrical stimulation have in tissue development and functional maturation, and may inform future tissue engineering approaches for clinical applications.
Multi-scale simulations of the T cell receptor reveal its lipid interactions, dynamics and the arrangement of its cytoplasmic region
Authors: Prakaash Dheeraj , Cook Graham P. , Acuto Oreste , Kalli Antreas C. 
Published: January 2021

AbstractThe T cell antigen receptor (TCR-CD3) complex initiates T cell activation following recognition of peptides presented by Major Histocompatibility Complex (pMHC)-encoded proteins. The ligation of pMHC to TCRαβ induces Src family kinases activity via the cytoplasmic tails of the CD3δε, CD3γε and ζζ dimers. The TCR-CD3 topology is well understood, but little is known about its conformational dynamics and arrangement of its cytoplasmic tails, limiting our grasp of the signalling mechanism. Here, we investigated the entire TCR-CD3 embedded in an asymmetric lipid bilayer using molecular modelling and multi-scale molecular dynamics simulations. Our study demonstrates conformational changes in the extracellular and transmembrane domains, and the arrangement of the TCR-CD3 cytoplasmic tails. The TCRαβ variable regions were the most flexible in the extracellular domain. The cytoplasmic tails formed highly interlaced structures while some tyrosine sidechains within the immunoreceptor tyrosine-based activation motifs (ITAMs) of the CD3ε and ζ subunits dynamically penetrated the hydrophobic core of the bilayer. Ionic interactions between the cytoplasmic tails and phosphatidylinositol phosphates (PIP2and PIP3) in the inner leaflet of the lipid bilayer led to the formation of a distinct annular lipid fingerprint around the TCR-CD3 complex. These results combined with available experiential data increase our understanding of the TCR-CD3 activation mechanism and highlight the importance of membrane lipids in regulating T cell activation.Significance statementThe T cell receptor (TCR-CD3) detects antigenic peptides displayed by major histocompatibility complexes (pMHC) to instigate activation of T cell adaptive immunity. Despite significant structural and functional knowledge of TCR-CD3 topology, the membrane interactions and dynamics of its cytoplasmic moieties remain elusive. Interactions of TCR-CD3 cytoplasmic tails with membrane lipids may regulate their phosphorylation by Src-family kinases, the first intracellular event required for T cell activation. Using the static 3D structure of TCR-CD3 resolved by cryo-electron microscopy, we provide novel insights into the protein-lipid interactions of the complete TCR-CD3 embedded in a bilayer closely mimicking its native membrane environment. Our study sheds light on the dynamics of the TCR-CD3 at near-atomic resolution and further aids in deciphering its activation mechanism.