bluuebunny/crossref_metadata_2025_split huggingface dataset:
Derivation of anthropometric-based equations to predict lean body mass composition of cancer patients
Authors: Carey Autumn B. , Felix Ashley S. , Huling Jared D. , Odei James B. , Coss Christopher C. , Ning Xia , Donneyong Macarius M. 
Published: July 2021

ABSTRACTBackgroundLean body mass (LBM) composition of cancer patients is a predictor of chemotherapy-related adverse events and overall cancer survival. However, clinicians lack validated algorithms that can be applied to measure the LBM of cancer patients to facilitate accurate chemotherapy dosing. Our goal was to develop LBM predictive equations using routinely measured anthropometric measures among cancer patients.MethodsWe leveraged the 1999-2006 National Health and Nutrition Examination Survey (NHANES) data cycles containing information on self-reported cancer diagnosis, LBM measures based on dual-energy x-ray absorptiometry (DXA) and several anthropometric and demographic factors. We restricted our analysis to participants who had been diagnosed with cancer at the time of surveys. The data was randomly split to 75%:25% to train and test predictive models. Least absolute shrinkage and selection operator (LASSO) models were used to predict LBM based on anthropometric and demographic factors, overall and separately among sex and sex-by-race/ethnic subgroups. LBM measured directly with DXA served as the gold standard for assessing the predictive abilities (correlations [R2] and the Root Mean Square Error [RMSE]) of the derived LBM-algorithms. We further compared the correlations between both DXA-based LBM and predicted LBM and urine creatinine levels, a known biomarker of muscle mass.ResultsWe identified 1,777 cancer patients with a median age of 71 (interquartile range [IQR]: 60-80) years. The most parsimonious model comprised of height and weight, which accurately predicted LBM overall (R2=0.86, RMSE =2.26). The predictive abilities of these models varied across sex-by-race/ethnic groups. The magnitude of correlations between derived LBM-algorithm and urine creatinine levels were larger compared to those measured between DXA-based LBM and urine creatinine levels (R2=0.30 vs. R2=0.17)ConclusionsWe successfully developed a simple sex-specific and sex-by-race/ethnicity-specific models to accurately predict the LBM of cancer patients by using only height and weight. The simplicity and high accuracy of these models make them inexpensive alternatives to measuring the LBM of cancer patients. Data on the LBM of cancer patients could help guide optimal chemotherapy dose selection among cancer patients.
Predicting age from hearing test results with machine learning reveals the genetic and environmental factors underlying accelerated auditory aging
Authors: Goallec Alan Le , Diai Samuel , Vincent Théo , Patel Chirag J. 
Published: July 2021

AbstractWith the aging of the world population, age-related hearing loss (presbycusis) and other hearing disorders such as tinnitus become more prevalent, leading to reduced quality of life and social isolation. Unveiling the genetic and environmental factors leading to age-related auditory disorders could suggest lifestyle and therapeutic interventions to slow auditory aging. In the following, we built the first machine learning-based hearing age predictor by training models to predict chronological age from hearing test results (root mean squared error=7.10±0.07 years; R-Squared=31.4±0.8%). We defined hearing age as the prediction outputted by the model on unseen samples, and accelerated auditory aging as the difference between a participant’s hearing age and age. We then performed a genome wide association study [GWAS] and found that accelerated hearing aging is 14.1±0.4% GWAS-heritable. Specifically, accelerated auditory aging is associated with 662 single nucleotide polymorphisms in 243 genes (e.gOR2B4P, involved in smell perception). Similarly, it is associated with biomarkers (e.g cognitive tests), clinical phenotypes (e.g chest pain), diseases (e.g depression), environmental (e.g smoking, sleep) and socioeconomic (e.g income, education, social support) variables. The hearing age predictor could be used to evaluate the efficiency of emerging rejuvenation therapies on hearing.
Untargeted saliva metabolomics reveals COVID-19 severity
Authors: Frampas Cecile F. , Longman Katie , Spick Matt P. , Lewis Holly M. , Costa Catia D. S. , Stewart Alex , Dunn-Walters Deborah , Greener Danni , Evetts George E. , Skene Debra , Trivedi Drupad , Pitt Andrew R. , Hollywood Katherine , Barran Perdita , Bailey Melanie J. 
Published: July 2021

ABSTRACTBackgroundThe COVID-19 pandemic is likely to represent an ongoing global health issue given the potential for vaccine escape and the low likelihood of eliminating all reservoirs of the disease. Whilst diagnostic testing has progressed at pace, there is an unmet clinical need to develop tests that are prognostic, to triage the high volumes of patients arriving in hospital settings. Recent research has shown that serum metabolomics has potential for prognosis of disease progression.1In a hospital setting, collection of saliva samples is more convenient for both staff and patients, and therefore offers an alternative sampling matrix to serum. We demonstrate here for the first time that saliva metabolomics can reveal COVID-19 severity.Methods88 saliva samples were collected from hospitalised patients with clinical suspicion of COVID-19, alongside clinical metadata. COVID-19 diagnosis was confirmed using RT-PCR testing. COVID severity was classified using clinical descriptors first proposed by SR Knight et al. Metabolites were extracted from saliva samples and analysed using liquid chromatography mass spectrometry.ResultsIn this work, positive percent agreement of 1.00 between a PLS-DA metabolomics model and the clinical diagnosis of COVID severity was achieved. The negative percent agreement with the clinical severity diagnosis was also 1.00, for overall percent agreement of 1.00.ConclusionsThis research demonstrates that liquid chromatography-mass spectrometry can identify salivary biomarkers capable of separating high severity COVID-19 patients from low severity COVID-19 patients in a small cohort study.
Evaluation of Clinical Job Demands, Job Resources, and a Novel Intervention on Measures of Health Care Worker Stress at a Community Hospital Pre and Post COVID-19
Authors: Sels Jessica , Carroll Dylan , Duffee Doug 
Published: July 2021

AbstractObjectiveTo explore the relationship and identity of Health Care Worker stressors to a measure of perceived burnout and to a novel intervention tool.Participants and MethodsFrom July 2019 to June 2020, we surveyed Health Care Workers (HCW) pre and post COVID19 in an independent local community hospital for burnout with the Health Care Provider Wellness Assessment tool. Linear regression and means comparison were used to identify overall job demand and resource perception with burnout, unique stressor portraits by provider subtype and mean survey scores between those who did or did not voluntarily complete at least 14 days of a 28 day novel self-help intervention tool.ResultsRegarding the pre COVID-19 data, of 73 respondents, there was statistically significant (p<.01) correlation between overall job demands (directly) and resources (inversely) with burnout intensity. With respect to the HCW stressor characteristic analyses there was statistical significance (p<.05) between the mean frequency occurrence of the top 5 stressors identified by respondent subtype when compared to the mean occurrence of overall individual responses within the corresponding subtype. Finally, although limited by a low number of respondents, the intervention tool analysis suggested a therapeutic trend toward disruption of the stress-burnout relationship. Regarding the post COVID-19 data, 18 respondents did not show statistically significant characterizable stressor portraits (ie stressors were present but not patternable).ConclusionUnique stressor portraits were identified by HCW subtype which correlated with more intense burnout self-perception. Additionally, there was a trend toward self-help tool efficacy in mitigating burnout.
Yuel: Compound-Protein Interaction Prediction with High Generalizability
Authors: Wang Jian , Dokholyan Nikolay V. 
Published: July 2021

ABSTRACTVirtual drug screening has the potential to revolutionize the stagnant drug discovery field due to its low cost and fast speed. Predicting binding affinities between small molecules and the protein target is at the core of computational drug screening. Deep learning-based approaches have recently been adapted to predict binding affinities and claim to achieve high prediction accuracy in their tests, however, we show that current approaches are not reliable for virtual drug screening due to the lack of generalizability, i.e. the ability to predict interactions between unknown proteins and unknown small molecules. To address this shortcoming, we develop a compound-protein interaction predictor, Yuel. Upon comprehensive tests on various datasets, we find that out of all the deep-learning approaches surveyed, only Yuel can predict interactions between unknown compounds and unknown proteins. Additionally, Yuel can also be utilized to identify compound atoms and proteins residues that are involved in the binding.
Stimulus-induced narrowband gamma oscillations are test-retest reliable in healthy elderly in human EEG
Authors: Kumar Wupadrasta Santosh , Manikandan Keerthana , Murty Dinavahi V.P.S. , Ramesh Ranjini Garani , Purokayastha Simran , Javali Mahendra , Rao Naren Prahalada , Ray Supratim 
Published: July 2021

AbstractVisual stimulus-induced narrowband gamma oscillations in electroencephalogram (EEG) recordings have been recently shown to be compromised in subjects with Mild Cognitive Impairment or Alzheimer’s Disease (AD), suggesting that gamma could be an inexpensive and easily accessible biomarker for early diagnosis of AD. However, to use gamma as a biomarker, its characteristics should remain consistent across multiple recordings, even when separated over long intervals. Previous magnetoencephalography studies in young subjects have reported that gamma power remains consistent over recordings separated by a few weeks to months. Here, we assessed the consistency of slow (20-35 Hz) and fast gamma (36-66 Hz) oscillations induced by static full-field gratings in male (N=20) and female (N=20) elderly subjects (>49 years) in EEG recordings separated by more than a year, and tested the consistency in the magnitude of gamma power, its temporal evolution and spectral profile. Gamma oscillations had distinct spectral and temporal characteristics across subjects, which remained consistent across recordings (average intraclass correlation, ICC of ∼0.7). Alpha oscillations (8-12 Hz) and steady-state-visually-evoked-potentials (SSVEPs) were also found to be reliable. We further tested how EEG features can be used to identify two recordings as belonging to the same versus different subjects and found high classifier performance (area under ROC curve of ∼0.89), with the temporal evolution of slow gamma and spectral profile emerging as the most informative features. These results suggest that EEG gamma oscillations are reliable across recordings and can be used as a clinical biomarker as well as a potential tool for subject identification.Significance statementWe demonstrate the reliability of stimulus-induced gamma oscillations in elderly humans for the first time in EEG. Since gamma has recently been shown to be compromised in patients with Mild Cognitive Impairment or early Alzheimer’s Disease (AD), together these results mark the first steps towards an EEG based clinical biomarker for early diagnosis of AD. We observed high reliability in the power spectrum, gamma power and its temporal characteristics, within the test-retest period of one year. Alpha and steady-state-visually-evoked potential power were also found to be reliable. These spectral and temporal features could also be used to identify EEG recordings as belonging to the same versus different subjects with high performance, suggesting a potentially key role in subject identification also.
Involvement of sensory neuron-TRPV4 in acute and chronic itch behaviors
Authors: Fang Quan , Wang Zilong , Suttle Abbie , Chen Yong 
Published: July 2021

ABSTRACTItch, particularly chronic itch, negatively impacts patients’ physical, social, and psychological well-being, leading to deterioration in their quality of life. Limited understanding of itch mechanisms hinders the development of effective antipruritic treatments.TRPV4, a multimodally activated nonselective cation channel, has been detected in sensory neurons of dorsal root and trigeminal ganglion (DRG, TG) and skin cells (e.g. keratinocytes, mast cells, and macrophages). Recent evidence from experimental and clinical relevant studies has implicated that TRPV4 in skin cells plays an important role in both acute and chronic itch. In contrast, little is known whether TRPV4 in sensory neurons directly contributes to scratching behaviors. Here we used sensory neuron-Trpv4 conditional knockout (cKO) mice to address this question. Our results showed that TRPV4 in sensory neurons contributes to scratching behavior evoked by histaminergic (histamine and 48/80) and partial histaminergic (5-HT), but not non-histaminergic (SLIGRL and CQ) pruritogens. Moreover, we observed that TRPV4 in sensory neurons is required for dry skin, but not allergic contact dermatitis, -associated chronic itch. These findings suggest that neuronal-TRPV4 might be specific for some forms of acute and chronic itch.
Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors
Authors: Foster Jessica B. , Griffin Crystal , Rokita Jo Lynne , Stern Allison , Brimley Cameron , Rathi Komal , Lane Maria V. , Buongervino Samantha N. , Smith Tiffany , Madsen Peter J. , Martinez Daniel , Wechsler-Reya Robert J. , Karikó Katalin , Storm Phillip B. , Barrett David M. , Resnick Adam C. , Maris John M. , Bosse Kristopher R. 
Published: July 2021

AbstractPediatric brain tumors are the leading cause of cancer death in children with an urgent need for innovative therapies. Here we show that the cell surface oncoprotein glypican 2 (GPC2) is highly expressed on multiple lethal pediatric brain tumors, including medulloblastomas, embryonal tumors with multi-layered rosettes, other CNS embryonal tumors, as well as definable subsets of highly malignant gliomas. To target GPC2 on these pediatric brain tumors with adoptive cellular therapies and mitigate potential inflammatory neurotoxicity, we developed four mRNA chimeric antigen receptor (CAR) T cell constructs using the highly GPC2-specific fully human D3 single chain variable fragment. First, we validated and prioritized these CARs using in vitro cytotoxicity and T cell degranulation assays with GPC2-expressing neuroblastoma cells. Next, we expanded the testing of the two most potent GPC2-directed CAR constructs prioritized from these studies to GPC2-expressing medulloblastoma and high-grade glioma cell lines, showing significant GPC2-specific cell death in multiple models. Finally, locoregional delivery bi-weekly of two to four million GPC2-directed mRNA CAR T cells induced significant and sustained tumor regression in two orthotopic medulloblastoma models, and significantly prolonged survival in an aggressive orthotopic thalamic diffuse midline glioma model. No GPC2-directed CAR T cell related neurologic or systemic toxicity was observed. Taken together, these data show that GPC2 is a highly differentially expressed cell surface protein on multiple malignant pediatric brain tumors that can be targeted safely with local delivery of mRNA CAR T cells.One Sentence SummaryGlypican 2 is expressed on the surface of multiple pediatric brain tumors and can be successfully targeted with mRNA chimeric antigen receptor T cells.
Microchromosomes are building blocks of bird, reptile and mammal chromosomes
Authors: Waters Paul D. , Patel Hardip R. , Ruiz-Herrera Aurora , Álvarez-González Lucía , Lister Nicholas C. , Simakov Oleg , Ezaz Tariq , Kaur Parwinder , Frere Celine , Grützner Frank , Georges Arthur , Graves Jennifer A. Marshall 
Published: July 2021

AbstractMicrochromosomes, once considered unimportant shreds of the chicken genome, are gene rich elements with a high GC content and few transposable elements. Their origin has been debated for decades. We used cytological and whole genome sequence comparisons, and chromosome conformation capture, to trace their origin and fate in genomes of reptiles, birds and mammals. We find that microchromosomes as well as macrochromosomes are highly conserved across birds, and share synteny with single small chromosomes of the chordate amphioxus, attesting to their origin as elements of an ancient animal genome. Turtles and squamates (snakes and lizards) share different subsets of ancestral microchromosomes, having independently lost microchromosomes by fusion with other microchromosomes or macrochromosomes. Patterns of fusions were quite different in different lineages.Cytological observations show that microchromosomes in all lineages are spatially separated into a central compartment at interphase and during mitosis and meiosis. This reflects higher interaction between microchromosomes than with macrochromosomes, as observed by chromosome conformation capture, and suggests some functional coherence. In highly rearranged genomes fused microchromosomes retain most ancestral characteristics, but these may erode over evolutionary time; surprisingly de novo microchromosomes have rapidly adopted high interaction.Some chromosomes of early branching monotreme mammals align to several bird microchromosomes, suggesting multiple microchromosome fusions in a mammalian ancestor. Subsequently multiple rearrangements fueled the extraordinary karyotypic diversity of therian mammals.Thus microchromosomes, far from being aberrant genetic elements, represent fundamental building blocks of amniote chromosomes, and it is mammals, rather than reptiles, that are atypical.Significance StatementGenomes of birds and reptiles, but not mammals, consist of a few large chromosomes and many tiny microchromosomes. Once considered unimportant shreds of the genome, microchromosomes are gene rich and highly conserved among bird and reptiles, and share homology with one or more of the tiny chromosomes of an invertebrate that diverged from the vertebrate lineage 684 million years ago. Microchromosomes interact strongly and crowd together at the centre of cells, suggesting functional coherence. Many microchromosomes have been lost independently in turtles, snakes and lizards as they have fused with each other, or with larger chromosomes. In mammals they have completely disappeared, yet some chromosomes of the basal platypus line up with several microchromosomes, suggesting that they are the building blocks of the atypically variable chromosomes of mammals.
Genome-wide association study reveals putative bacterial risk factors for cavitary Mycobacterium avium complex lung disease
Authors: Yano Hirokazu , Nishiuchi Yukiko , Arikawa Kentaro , Ota Atsushi , Miki Mari , Maruyama Fumito , Kida Hiroshi , Kitada Seigo , Iwamoto Tomotada 
Published: July 2021

ABSTRACTMycobacterium avium complex (MAC) lung disease is a slowly progressive disease, and its increasing incidence has garnered increased research interests. Cavitary MAC lung disease is associated with a higher mortality rate. Though genetic studies have unraveled the human risk factors, the role of microbial factors on pathogenesis behind the disease remains elusive. In this study, M. avium isolates were collected from sputum specimens of 109 distinct Japanese patients with or without a cavity (60 with a cavity and 49 without cavity) in a hospital located in Osaka prefecture. M. avium genomes were sequenced and searched for DNA motifs associated with cavity formation using a bacterial GWAS. Excluding known macrolide resistance mutations; cavity formation was found to be primarily associated with variants of cytochrome P450 of the CYP139 family, type I polyketide synthase Pks13, and the promoter region of an operon encoding membrane-anchored protease FtsH and folate synthesis pathway enzymes. Cavity risk variants at these three loci were frequent in the MahEastAsia2 lineage among the six lineages detected in M. avium global populations. Furthermore, the study demonstrated a correlation between the cavity risk promoter variant and increased sulfamethoxazole/trimethoprim resistance. Together, these findings suggest that natural variation in the biosynthesis and maintenance processes of M. avium membrane components influences the disease type of MAC lung disease. Although further validation is needed, the bacterial genetic markers listed in the present study could contribute to prognosis prediction based on bacterial genotyping and help develop treatment strategies in the future.IMPORTANCENontuberculous mycobacterial lung disease is of great concern in countries with an increasingly aging population. The disease types can largely be classified into non-cavitary nodular bronchiectasis and cavitary diseases (fibrocavitary, nodular bronchiectasis with cavity) that require different treatment strategies depending on the causal agents. Several studies have reported human risk factors for the disease; however, little efforts were made to investigate the risk factors in nontuberculous mycobacteria. Moreover, molecular genetics experiments have been difficult to search for virulence factors in M. avium, which the population genomics approaches could overcome. Here, the GWAS results suggested variants in three chromosomal loci associated with mycobacterial membrane components as risk factors for cavitary MAC lung disease. These findings could help develop treatment strategies for MAC lung disease in the future.