bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consultagene: Pre- and Post-Pandemic Experience with a Web-based Platform and Remote Delivery of Genetic Services
Authors: Worley Kim C. , Riconda Daniel Lee , Wallis Amy M. , Shaw Chad A. , Holder Chris M. , Nassef Salma A. , Darilek Sandra , Lalani Seema R. , Magoulas Pilar L. , Huguenard Sarah M. , Lee Brendan H. L. 
Published: January 2021

AbstractChanges in genetics and genomics sequencing in recent years have created increased demand for genetics professionals, including clinical geneticists and genetic counselors. A significant workforce shortage of these professionals has become widely recognized. This shortage is driven by several factors, including the increased role of genetics in healthcare due to precision medicine initiatives and demand outside of medical practices in clinical and direct-to-consumer genetic testing companies that require genetics professionals for education and counseling.We developed the Consultagene virtual platform for delivery of genetic care, counseling, and education to address some of these issues that have become global challenges in the field of clinical genetics and to bridge existing gaps at the point of care. The platform provides access to specific content based upon the referral indication including educational videos and resource links, allows document sharing, health and history information gathering and appointment scheduling with persistent access to the materials via secure data infrastructure. Having the platform coupled with access to our tele- and video consultation service allows clients convenient on-demand access to genetic education and services as needed.This report describes the Consultagene platform development and use prior to and during the COVID-19 pandemic, some of the identified strengths and weaknesses of such a platform, and the current applications in the new environment where telemedicine practice has rapidly expanded.Topic SummaryConsultagene is the first academic virtual platform to integrate a comprehensive range of genetics services including genetics education, genetics consultation, and genetic counseling. Consultagene addresses the increasing demands and unmet, evolving needs for genetic services due to widely available genomic sequencing and the platform seamlessly adapted to the pandemic-induced adjustments to clinical practice.
Interpretable machine learning prediction of all-cause mortality
Authors: Qiu Wei , Chen Hugh , Dincer Ayse Berceste , Lundberg Scott , Kaeberlein Matt , Lee Su-In 
Published: January 2021

AbstractPrior studies on all-cause mortality traditionally use linear models; however, growing field of explainable artificial intelligence (XAI) can improve prediction accuracy over traditional linear models using complex machine learning (ML) models while still revealing novel insights. We propose the IMPACT (Interpretable Machine learning Prediction of All-Cause morTality) framework that implements and explains complex, non-linear ML models by combining a tree ensemble mortality prediction model and a principled XAI technique. We apply IMPACT to the NHANES (1999-2014) dataset, which enables us to understand different subpopulations according to shorter or longer term mortality and younger and older individuals. Our IMPACT models have higher predictive accuracy than popular pre-existing mortality risk scores and biological ages. Using individualized feature importance scores, we discover novel risk predictors (e.g., arm circumference) and interactions between risk predictors (e.g., serum chloride with age and/or gender). Furthermore, IMPACT provides a novel perspective of reference intervals and may suggest that the widely accepted reference intervals for serum albumin, mean cell volume and platelet count may in fact be sub-optimal for health. Finally, in order to ensure that our models are useful to as broad of a community as possible, we develop and publish a variety of explainable risk scores usable by individuals with and without medical expertise. The predictive accuracy of IMPACT combined with the capability of discovering mortality risk predictors and complex relationships demonstrates the value and utility of XAI in epidemiologic study design.
ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 Patients
Authors: Karakike Eleni , Dalekos George N. , Koutsodimitropoulos Ioannis , Saridaki Maria , Pourzitaki Chryssa , Papathanakos Georgios , Kotsaki Antigone , Chalvatzis Stamatios , Dimakopoulou Vasiliki , Vechlidis Nikolaos , Paramythiotou Elisabeth , Avgoustou Christina , Ioakeimidou Aikaterini , Kouriannidi Elli , Komnos Apostolos , Neou Evangelia , Rovina Nikoletta , Stefanatou Eleni , Milionis Haralampos , Nikolaidis George , Koutsoukou Antonia , Damoraki Georgia , Dimopoulos George , Zoumpos Vassileios , Eugen-Olsen Jesper , Akinosoglou Karolina , Gatselis Nikolaos K. , Koulouras Vasilios , Gkeka Eleni , Markou Nikolaos , Netea Mihai G. , Giamarellos-Bourboulis Evangelos J. 
Published: January 2021

ABSTRACTRationaleMacrophage activation syndrome (MAS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19.ObjectiveTo investigate the outcome of personalized immunotherapy in critical COVID-19.MethodsIn this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score ≥2 or ARDS by SARS-CoV-2 were screened for MAS (ferritin more than 4420 ng/ml) and CID (ferritin ≤4420 ng/ml and low expression of HLA-DR on CD14-monocytes). Patients with MAS and CID with increased aminotransferases were assigned to intravenous anakinra; those with CID and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints.Measurements and Main ResultsThe primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6, soluble urokinase plasminogen activator receptor (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment.ConclusionsBiomarkers may guide favourable anakinra responses in critically ill patients with COVID-19.Trial RegistrationClinicalTrials.gov, NCT04339712
Management of conductive deafness from Otitis Media with Effusion (known as ‘glue ear’) in children using bone conduction headsets when grommet operations were unavailable during COVID-19
Authors: Brown T Holland , O’Connor Isobel Fitzgerlad , Bewick Jessica , Morley Colin 
Published: January 2021

AbstractBackgroundOtitis Media with Effusion (OME) causing hearing impairments affects ∼1 in 10 children starting school in UK/ Europe. 80% have at least one episode with most having conductive hearing loss. Studies showed children with OME hear better with bone conducting headsets. During COVID-19 we investigated whether children with deafness secondary OME, without access to audiology or grommet surgery, could be aided with bone conduction kits and the HearGlueEar app.MethodsStarting July 2020, during COVID-19, children aged 3-11 years with OME and on a grommet waiting list were invited to a single arm, prospective study. They received the kit, instructions and HearGlueEar app by post. By 3 weeks parents were asked to charge and pair the devices, attend a remote consultation and complete an OMQ-14 questionnaire. Remote follow-up lasted 3 months. Outcomes: ability to use the equipment, complete the questionnaire about child’s hearing and behaviour before and with the equipment, declining grommet surgery or where deafness resolved, and give opinion about the intervention.Findings26 children enrolled. Families used the kit at home and school. Most found remote consultations positive and convenient. OMQ-14 responses were 90% positive. Comments were: “Other people have said, wow his speech is clearer.”, “It is making a real difference at home.”, “He said over and over again, “I can hear everybody, wow, wow, wow.”, “It is no exaggeration to say this has made an astronomical improvement to his quality of life”. One child reported “I can hear my best friend again”. “She is getting on really well with the headphones - pairing them with the iPad at home is simply brilliant.” Three families continued with the headset to avoid grommets.InterpretationPosting a bone conduction kit, HearGlueEar app and remote consultation is effective support for children with deafness secondary to OME.FundingNone
Data Resource Profile: thousands of circulating RNA profiles of pre-clinical samples from the Janus Serum Bank Cohort
Authors: Langseth Hilde , Umu Sinan Ugur , Bucher-Johannessen Cecilie , Babigumira Ronnie , Leithaug Magnus , Lauritzen Marianne , Vineis Paolo , Ursin Giske , Lyle Robert , Rounge Trine B 
Published: January 2021

AbstractThere is justified optimism regarding the use of miRNAs as early detection biomarkers of cancer. They are well characterized and are involved in all the hallmarks of cancer. Less is known about the role of most other non-coding RNA (ncRNAs) classes in normal physiology and tumorigenesis. The JanusRNA dataset consist of circulating RNA profiles of pre-clinical samples from 1631 cancer patients and 673 cancer-free controls. We studied eight cancer types including cancer of the: lung, colon, rectum, prostate, breast, testis, ovaries and gallbladder. JanusRNA has its origin from the large population-based Janus Serum Bank Cohort which consists of 318 628 Norwegians. The dataset combines information from the complete nationwide cancer registry, RNA sequencing profiles from 1631 cancer patients and 673 cancer-free controls, as well as data on lifestyle, anthropometry and biochemical measurements from national health surveys. The Janus Serum Bank is specifically suited for studies of early detection and risk biomarkers of cancer, since samples are collected nationwide over a large time span, pre-clinically and cancer occurs at different points in time after blood draw. We used a nested case-control design, selecting both cases and controls among the Janus cohort members. We restricted our selection to cases with at least one sample collected within 10 years prior to cancer diagnosis. We selected 673 cancer-free Janus participants for comparison of RNA levels with the cancer cases. The controls were frequency matched to the case group on sex, age at blood donation and date of blood donation. The JanusRNA dataset has been used to investigate the natural variation of circulating RNAs in cancer-free individuals. This data resource was also used in a study of variation in RNA expression associated with common traits like age, sex, smoking, BMI and physical activity in cancer-free individuals. RNA dynamics in lung and testicular carcinogenesis throughout a 10-year follow-up has also been studied.
Role of FYVE and Coiled-Coil Domain Autophagy Adaptor 1 in severity of COVID-19 infection
Authors: Smieszek Sandra P. , Przychodzen Bartlomiej , Polymeropoulos Christos , Polymeropoulos Vasilios , Polymeropoulos Mihael H. 
Published: January 2021

AbstractCoronaviruses remodel intracellular membranes to form specialized viral replication compartments, such as double-membrane vesicles where viral RNA genome replication takes place. Understanding the factors affecting host response is instrumental to design of therapeutics to prevent or ameliorate the course of infection.As part of explorative tests in hospitalized patients with confirmed COVID-19 infection participating in ODYSSEY trial, we obtained samples for whole genome sequencing analysis as well as for viral genome sequencing. Based on our data, we confirm one of the strongest severity susceptibility locus thus far reported in association with severe COVID-19: 3p21.31 locus with lead variant rs73064425. We further examine the associated region. Interestingly based on LD analysis we report 3 coding mutations within one gene in the region of FYVE and Coiled-Coil Domain Autophagy Adaptor 1 (FYCO1). We specifically focus on the role of FYCO1 modifiers and gain-of-function variants. We report the associations between the region and clinical characteristics in this severe set of COVID-19 patients.We next analyzed expression profiles of FYCO1 across all 466 compounds tested. We selected only those results that showed a significant reduction of expression of FYCO1. The most significant candidate was indomethacin – an anti-inflammatory that could potentially downregulate FYCO1. We hypothesize that via its direct effects on efficiency of viral egress, it may serve as a potent therapeutic decreasing the replication and infectivity of the virus. Clinical studies will be needed to examine the therapeutic utility of indomethacin and other compounds downregulating FYCO1 in COVID-19 infection and other strains of betacoronaviruses.
Assessing the lockdown effect from excess mortalities
Authors: Weber Alexej 
Published: January 2021

AbstractBackground and AimsThe reported case numbers of COVID-19 are often used to estimate the growth rate of infections. We use the excess mortality instead to show the effect of most restrictive non-pharmaceutical interventions (mrNPIs) as compared to less restrictive NPIs (lrNPIs) concerning growth rate and death counts.MethodsWe estimate the COVID-19 growth rate for Austria, France, Germany, Italy, Netherlands, South Korea, Spain, Sweden, UK and USA from the excess mortality. We use the average growth rate obtained for Sweden and South Korea, the only countries with lrNPIs only, to estimate additional death numbers in the other countries, had mrNPIs not been applied.ResultsThe growth rate estimated from excess mortality decreased faster for countries with mrNPIs than for Sweden and South Korea, suggesting that the mrNPIs do have a non-negligible effect. Implementing lrNPIs instead of mrNPIs results in up to 3 times higher death numbers. This is not visible when the growth rate is calculated using the reported case numbers of COVID-19 instead of the excess mortality.ConclusionThe conclusion for the spreading of COVID-19 obtained from reported COVID-19 cases in previous studies are most likely biased. Using our method, a more realistic estimate of the growth rate is obtained. Conclusions made for the reproduction number derived from the reported case numbers, such as the apparent insignificance of mrNPIs (lockdowns), might therefore be wrong and will have to be reevaluated using the growth rates obtained with our method.
Exploring domains, clinical implications and environmental associations of a deep learning marker of biological ageing
Authors: Gialluisi Alessandro , Di Castelnuovo Augusto , Costanzo Simona , Bonaccio Marialaura , Persichillo Mariarosaria , Magnacca Sara , De Curtis Amalia , Cerletti Chiara , Donati Maria Benedetta , de Gaetano Giovanni , Capobianco Enrico , Iacoviello Licia 
Published: January 2021

AbstractDeep Neural Networks (DNN) have been recently developed for the estimation of Biological Age (BA), the hypothetical underlying age of an organism, which can differ from its chronological age (CA). Although promising, these population-specific algorithms warrant further characterization and validation, since their biological, clinical and environmental correlates remain largely unexplored.Here, an accurate DNN was trained to compute BA based on 36 circulating biomarkers in an Italian population (N=23,858; age≥35 years; 51.7% women). This estimate was heavily influenced by markers of metabolic, heart, kidney and liver function. The resulting Δage (BA-CA) significantly predicted mortality and hospitalization risk for all and specific causes. Slowed biological aging (Δage<0) was associated with higher physical and mental wellbeing, healthy lifestyles (e.g. adherence to Mediterranean diet) and higher socioeconomic status (educational attainment, household income and occupational status), while accelerated aging (Δage>0) was associated with smoking and obesity. Together, lifestyles and socioeconomic variables explained □48% of the total variance in Δage, potentially suggesting the existence of a genetic basis.These findings validate blood-based biological aging as a marker of public health in adult Italians and provide a robust body of knowledge on its biological architecture, clinical implications and potential environmental influences.
FILER: large-scale, harmonized FunctIonaL gEnomics Repository
Authors: Kuksa Pavel P. , Gangadharan Prabhakaran , Katanic Zivadin , Kleidermacher Lauren , Amlie-Wolf Alexandre , Lee Chien-Yueh , Qu Liming , Greenfest-Allen Emily , Valladares Otto , Leung Yuk Yee , Wang Li-San 
Published: January 2021

AbstractMotivationQuerying massive collections of functional genomic and annotation data, linking and summarizing the query results across data sources and data types are important steps in high-throughput genomic and genetic analytical workflows. However, accomplishing these steps is difficult because of the heterogeneity and breadth of data sources, experimental assays, biological conditions (e.g., tissues, cell types), data types, and file formats.ResultsFunctIonaL gEnomics Repository (FILER) is a large-scale, harmonized functional genomics data catalog uniquely providing: 1) streamlined access to >50,000 harmonized, annotated functional genomic and annotation datasets across >20 integrated data sources, >1,100 biological conditions/tissues/cell types, and >20 experimental assays; 2) a scalable, indexing-based genomic querying interface; 3) ability for users to analyze and annotate their own experimental data against reference datasets. This rich resource spans >17 Billion genomic records for both GRCh37/hg19 and GRCh38/hg38 genome builds. FILER scales well with the experimental (query) data size and the number of reference datasets and data sources. When evaluated on large-scale analysis tasks, FILER demonstrated great efficiency as the observed running time for querying 1000x more genomic intervals (106vs. 103) against all 7×109hg19 FILER records increased sub-linearly by only a factor of 15x. Together, these features facilitate reproducible research and streamline querying, integrating, and utilizing large-scale functional genomics and annotation data.Availability and implementationFILER can be 1) freely accessed athttps://lisanwanglab.org/FILER, 2) deployed on cloud or local servers (https://bitbucket.org/wanglab-upenn/FILER), and 3) integrated with other pipelines using provided scripts.Contactlswang@pennmedicine.upenn.edu
Effects of Task Demands on Neural Correlates of Acoustic and Semantic Processing in Challenging Listening Conditions
Authors: Devaraju Dhatri S. , Kemp Amy , Eddins David A. , Shrivastav Rahul , Chandrasekaran Bharath , Wray Amanda Hampton 
Published: January 2021

AbstractPurposeListeners shift their listening strategies to prioritize lower-level acoustic information and higher-level semantic information in challenging listening conditions. However, the neural mechanisms underlying different strategies are unclear. The current study examined the extent to which encoding of lower-level acoustic cues is modulated by task demand and relationships with the higher-level semantic processing.MethodElectroencephalography (EEG) was acquired while participants listened to sentences in noise that contained either higher or lower probability final words. Task difficulty was modulated by time available to process responses. Cortical tracking of speech - neural correlates of acoustic temporal envelope processing - were estimated using temporal response functions (TRFs).ResultsTask difficulty did not affect cortical tracking of temporal envelope of speech under challenging listening conditions. No correlations were observed between the cortical tracking of temporal envelope of speech and semantic processes, even after controlling for the effect of individualized signal-to-noise ratios.ConclusionsCortical tracking of temporal envelope of speech and semantic processing are differentially influenced by task difficulty. While increased task demands modulated higher-level semantic processing, cortical tracking of temporal envelope of speech may be influenced by task difficulty primarily when the demand is manipulated in terms of acoustic properties of the stimulus, consistent with an emerging perspective in speech perception.
Proteins observed in scalp hair from preschool children
Authors: Singhal Kratika , Leib Ryan D. , Rovnaghi Cynthia R. , Xenochristou Maria , Aghaeepour Nima , Chien Allis S. , Tam Grace K-Y. , Ruiz Monica O. , Dinakarpandian Deendayal , Anand Kanwaljeet J. S. 
Published: January 2021

ABSTRACTEarly childhood experiences have long-lasting effects on subsequent mental and physical health, education, and employment. Measurement of these effects relies on insensitive behavioral signs, subjective assessments by adult observers, neuroimaging and neurophysiological studies, or remote epidemiologic outcomes. Despite intensive search, no biomarkers for developmental changes in the brain have been identified. We analyzed scalp hair from healthy children and their mothers using an unbiased proteomics platform to reveal 1368 hair proteins commonly observed in children, 1438 proteins commonly observed in mothers, and 1288 proteins observed sporadically in individual subjects. Mothers showed higher numbers of peptide spectral matches and hair proteins compared to children, with important age-related differences between mothers and children. Age-related differences were also observed in children, with differential protein expression patterns between younger (2 years and below) and older children (3-5 years). Boolean analyses showed greater conservation of hair protein patterns between mothers and their biological children as compared to mothers and unrelated children. The top 5% proteins driving population variability represent biological pathways associated with brain development, immune signaling, and stress response regulation. Non-structural proteins observed in scalp hair may include promising biomarkers to investigate the developmental changes associated with early childhood experiences.One Sentence SummaryThe non-structural proteins observed in scalp hair from preschool children show evidence for heritability, reflect biological functions such as brain development, or immune function and regulation of stress responses, and exhibit age- and sex-related differences across periods of early childhood development.
Achieving natural behavior in a robot using neurally inspired hierarchical control
Authors: Barter Joseph W. , Yin Henry H. 
Published: January 2021

AbstractTerrestrial locomotion presents tremendous computational challenges on account of the enormous degrees of freedom in legged animals, and the complex and unpredictable properties of the natural environment and the effectors. Yet the nervous system can achieve locomotion with ease. Here we introduce a quadrupedal robot capable of goal-directed posture control and locomotion over rough terrain. The underlying control architecture is a hierarchical network of simple negative feedback control systems inspired by the organization of the vertebrate nervous system. Without using an internal model or feedforward planning, and without any training, our robot shows robust posture control and locomotor behavior in novel environments with unpredictable disturbances.