bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicians’ perspective on use of immune checkpoint inhibitors and related biomarkers for solid tumors
Authors: Moser Kaitlynn , Soto Michelle , Geba Daniela , Allen Paul , Lindpaintner Klaus 
Published: April 2022

ABSTRACTBackgroundImmune checkpoint inhibitors (ICIs) are a valuable treatment option for patients with malignant tumors, but only selected patients respond to ICIs. Available biomarkers are of limited use in guiding ICI therapy.ObjectiveTo examine clinicians’ perspective on the use of ICIs and biomarkers for treatment of malignant tumors and to identify unmet needs related to their use.MethodsWe conducted in-depth telephone interviews of eight oncologists, and 100 oncologists completed online surveys.ResultsOncologists have a positive attitude toward use of ICIs, and 98% of them prescribe them in all approved indications. Clinicians report that only about half of the patients with solid tumors responded to treatment, overestimated the response rate to ICIs across most types of tumors they treat compared with data in the literature. They ranked the lack of reliability of biomarkers to guide treatment (rating of 4.4 out of 7) as the top challenge with use of ICIs, followed by lack of overall efficacy and toxicity or occurrence of immune-related adverse events. The biomarkers most often used by survey participants were: a comprehensive panel including driver mutations and tumor mutational burden(69% of respondents), programmed cell death ligand-1 (PD-L1) expression (62%), and microsatellite instability (MSI) (56%). Oncologists indicated that they ordered biomarkers for each type of cancer according to their perceived usefulness of each biomarker in predicting the outcomes for ICI therapy, being more likely to use those perceived as useful or very useful.ConclusionClinicians indicate that more reliable therapy-response prediction biomarkers would have a great impact on treatment decisions for patients with solid tumors, reducing unnecessary treatments, side effects, and health care expenditures.
Digital Health Interventions and Quality of Home-based Primary Care for Older Adults: A Scoping Review Protocol
Authors: Silva Isis de Siqueira , Silva Cicera Renata Diniz Vieira , Lopes Rayssa Horacio , Araujo Aguinaldo Jose , Figueiredo Renan Cabral de , Bay Junior Osvaldo de Goes , Lapao Luis Velez , Uchoa Severina Alice da Costa 
Published: April 2022

AbstractIntroductionThe use of digital health interventions has expanded, particularly in home-based primary care (HBPC) following the increase in the older adult population and the need to respond to the higher demand of chronic conditions and health frailties of this population. There was an even greater demand with COVID-19 and subsequent isolation/social distancing measures for this risk group. The objective of this study is to map and identify the uses and types of digital health interventions and their reported impacts on the quality of HBPC for older adults worldwide.Methods and analysisThis is a scoping review protocol which will enable a rigorous, transparent and reliable synthesis of knowledge. The review will be developed in the theoretical perspective of Arksey and O’malley, with updates by Levac et al. and Peters et al. based on the Joanna Briggs Institute manual, and guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Data from whiteliterature will be extracted from multidisciplinary health databases such as: the Virtual Health Library, LILACS, PubMed, Scopus, Web of Science, CINAHL and Embase; while Google Scholar will be used for gray literature. No date limit or language restrictions will be determined. The quantitative data will be analyzed through descriptive statistics and qualitative data through thematic analysis. The results will be submitted to stakeholder consultation for preliminary sharing of the study and will later be disseminated through publication in open access scientific journals, scientific events and academic and community journals. The full scoping review report will present the main impacts, challenges, opportunities and gaps found in publications related to the use of digital technologies in primary home care.DiscussionThe organization of this protocol will increase the methodological rigor, quality, transparency and accuracy of scoping reviews, reducing the risk of bias.
Why is leptospirosis hard to avoid for the impoverished? Deconstructing leptospirosis transmission risk and the drivers of knowledge, attitudes, and practices in a disadvantaged community in Salvador, Brazil
Authors: Palma Fabiana Almerinda G. , Costa Federico , Lustosa Ricardo , Mogaji Hammed O. , de Oliveira Daiana Santos , Souza Fábio Neves , Reis Mitermayer G. , Ko Albert I. , Begon Michael , Khalil Hussein 
Published: April 2022

AbstractSeveral studies have identified socioeconomic and environmental risk factors for infectious disease, but the relationship between these and knowledge, attitudes, and practices (KAP), and more importantly their web of effects on individual infection risk, have not previously been evaluated. We conducted a cross-sectional KAP survey in an urban disadvantaged community in Salvador, Brazil, leveraging on simultaneously collected fine-scale environmental and epidemiological data on leptospirosis transmission. Residents’ knowledge influenced their attitudes which influenced their practices. However, different KAP variables were driven by different socioeconomic and environmental factors; and while improved KAP variables reduced risk, there were additional effects of socioeconomic and environmental factors on risk. For example, males and those of lower socioeconomic status were at greater risk, but once we controlled for KAP, male gender and lower socioeconomic status themselves were not direct drivers of seropositivity. Employment was linked to better knowledge and a less contaminated environment, and hence lower risk, but being employed was independently associated with a higher, not lower risk of leptospirosis transmission, suggesting travel to work as a high risk activity. Our results show how such complex webs of influence can be disentangled. They indicate that public health messaging and interventions should take into account this complexity and prioritize factors that limit exposure and support appropriate prevention practices.
Doctoring Direct-to-Consumer Genetic Tests with DNA Spike-Ins
Authors: Ney Peter , Bhattacharya Arkaprabha , Ward David , Ceze Luis , Kohno Tadayoshi , Nivala Jeff 
Published: April 2022

AbstractDirect-to-consumer (DTC) genetic testing companies have provided personal genotyping services to millions of customers. Customers mail saliva samples to DTC service providers to have their genotypes analyzed and receive back their raw genetic data. Both consumers and the DTC companies use the results to perform ancestry analyses, relative matching, trait prediction, and estimate predisposition to disease, often relying on genetic databases composed of the data from millions of other DTC-genotyped individuals. While the digital integrity risks to this type of data have been explored, we considered whether data integrity issues could manifest upstream of data generation through physical manipulation of DNA samples themselves, for example by adding synthetic DNA to a saliva sample (“spiked samples”) prior to sample processing by a DTC company. Here, we investigated the feasibility of this scenario within the standard DTC genetic testing pipeline. Starting with the purchase of off-the-shelf DTC genetic testing kits, we found that synthetic DNA can be used to precisely manipulate the results of saliva samples genotyped by a popular DTC genetic testing service and that this method can be used to modify arbitrary single nucleotide polymorphisms (SNPs) in multiplex to create customized doctored genetic profiles. This capability has implications for the use of DTC-generated results and the outcomes of their downstream analyses.
Age acquired skewed X Chromosome Inactivation is associated with adverse health outcomes in humans
Authors: Roberts Amy L. , Morea Alessandro , Amar Ariella , Zito Antonino , El-Sayed Moustafa Julia S. , Tomlinson Max , Bowyer Ruth C. E. , Zhang Xinyuan , Christiansen Colette , Costeira Ricardo , Steves Claire J. , Mangino Massimo , Bell Jordana T. , Wong Chloe C.Y. , Vyse Timothy J. , Small Kerrin S. 
Published: April 2022

AbstractBackgroundAgeing is a heterogenous process characterised by cellular and molecular hallmarks, including changes to haematopoietic stem cells, and is a primary risk factor for chronic diseases. X chromosome inactivation (XCI) randomly transcriptionally silences either the maternal or paternal X in each cell of XX,46 females to balance the gene expression with XY,46 males. Age acquired XCI-skew describes the preferential inactivation of one X chromosome across a tissue, which is particularly prevalent in blood tissues of ageing females and yet its clinical consequences are unknown.MethodsWe assayed XCI in 1,575 females from the TwinsUK population cohort and employed prospective, cross-sectional, and intra-twin designs to characterise the relationship of XCI-skew with molecular, cellular, and organismal measures of ageing, and cardiovascular disease risk and cancer diagnosis.ResultsWe demonstrate that XCI-skew is independent of traditional markers of biological ageing and is associated with a haematopoietic bias towards the myeloid lineage. Using an atherosclerotic cardiovascular disease risk score, which captures traditional risk factors, XCI-skew is associated with an increased cardiovascular disease risk both cross-sectionally and within XCI-skew discordant twin pairs. In a prospective 10-year follow-up study, XCI-skew is predictive of future cancer incidence.ConclusionsOur study demonstrates that age acquired XCI-skew captures changes to the haematopoietic stem cell population and has clinical potential as a unique biomarker of chronic disease risk.FundingKSS acknowledges funding from the Medical Research Council (MR/M004422/1 and MR/R023131/1). JTB acknowledges funding from the ESRC (ES/N000404/1). MM acknowledges funding from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London.
Invasion of malaria mosquitoes natural population by parasitic nematodes Dirofilaria along Ob River basin in Western Siberia
Authors: Burlak Vladimir A. , Fedorova Valentina S. , Artemov Gleb N. 
Published: April 2022

AbstractDirofilariasis – is a dangerous disease that affects carnivores, felines, and humans. It is caused by parasitic nematodes Dirofilaria repens and D. immitis. These parasites are carried by blood–sucking mosquitoes. In recent decades the habitat of Dirofilaria in Europe has been expanding dramatically. In the present study, we investigated how malaria mosquitoes had been infected by Dirofilaria in Western Siberia (Russia) in the range between 50° 48’ N (Labytnangi) and 66° 39’ N (Kurota) along the Ob River. The extensiveness of parasite infection varied between 0.4 % and 5.7 %, in three species of malaria mosquitoes: Anopheles beklemishevi, An. daciae, An. messeae, which all are showed effective vectors of D. repens. The results demonstrate the significant role of malaria mosquitoes for dirofilariasis transmission in severe climate conditions of Western Siberia.
Genetic Risk for Attention-Deficit/Hyperactivity Disorder Predicts Cognitive Decline and Development of Alzheimer’s Disease Pathophysiology in Cognitively Unimpaired Older Adults
Authors: Leffa Douglas T. , Ferrari-Souza João Pedro , Bellaver Bruna , Tissot Cécile , Ferreira Pamela C. L. , Brum Wagner S. , Caye Arthur , Lord Jodie , Proitsi Petroula , Martins-Silva Thais , Tovo-Rodrigues Luciana , Tudorascu Dana L. , Villemagne Victor L. , Cohen Annie , Lopez Oscar L. , Klunk William E. , Karikari Thomas K. , Rosa-Neto Pedro , Zimmer Eduardo , Molina Brooke S.G. , Rohde Luis Augusto , Pascoal Tharick A. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2022

AbstractBackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) persists in older age and is postulated to be a risk factor for cognitive impairment and Alzheimer’s Disease (AD). However, this notion relies exclusively on epidemiological associations, and no previous study has linked ADHD with a decline in cognitive performance in older adults or with AD progression. Therefore, this study aimed to determine whether genetic liability for ADHD, as measured by a well-validated ADHD polygenic risk score (ADHD-PRS), is associated with longitudinal cognitive decline and the development of AD pathophysiology in cognitively unimpaired (CU) older adults.MethodsWe calculated a weighted ADHD-PRS in 212 CU individuals without a clinical diagnosis of ADHD (55-90 years) using whole-genome information. These individuals had baseline amyloid-β (Aβ) positron emission tomography, as well as longitudinal cerebrospinal fluid (CSF) phosphorylated tau at threonine 181, structural magnetic resonance imaging, and cognitive assessments for up to 6 years. Linear mixed-effects models were used to test the association of ADHD-PRS with cognition and AD biomarkers.OutcomesHigher ADHD-PRS was associated with greater cognitive decline over 6 years. The combined effect between high ADHD-PRS and brain Aβ deposition on cognitive deterioration was more significant than each individually. Additionally, higher ADHD-PRS was associated with increased CSF p-tau181 levels and frontoparietal atrophy in CU Aβ-positive individuals.InterpretationOur results suggest that genetic liability for ADHD is associated with cognitive deterioration and the development of AD pathophysiology in the CU elderly. These findings indicate that ADHD-PRS might inform the risk of developing cognitive decline in this population.FundingNational Institute of Health and Brain & Behavioral Research Foundation.
Genomic characteristics, virulence and antimicrobial resistance in avian pathogenic Escherichia coli MTR_BAU02 strain isolated from layer farms in Bangladesh
Authors: Ievy Samina , Hoque M. Nazmul , Islam Md. Saiful , Sobur Md. Abdus , Rahman M. Shaminur , Ballah Fatimah Muhammad , Rahman Md. Bahanur , Hassan Jayedul , Rahman Khan Mohammad Ferdousur , Rahman Md. Tanvir 
Published: April 2022

AbstractBackgroundColibacillosis, caused by avian pathogenic Escherichia coli (APEC), is one of the most significant infectious diseases affecting poultry worldwide. APEC is one of the leading causes of mortality and morbidity associated with significant economic losses in the poultry industry.ObjectiveThis study was aimed to determine the genomic diversity, virulence factor genes (VFGs) and antimicrobial resistance (AMR) genes in the APEC isolated from layer chickens using whole-genome sequencing (WGS).MethodAPEC MTR_BAU02 strain was isolated from the sick and dead birds. Genomic DNA from APEC MTR_BAU02 strain was extracted using commercial DNA extraction kit, WGS libraries were prepared using the Nextera™ DNA Flex Library Prep Kit, and finally, paired-end (2 × 250) WGS performed using Illumina MiSeq sequencer.ResultsThe genome size of strain APEC MTR_BAU02 is 4,924,680 bp with a GC content of 51.1% and 4,681 protein-coding sequences. Among the annotated WGS reads, 99.71% reads mapped to Enterobacteriaceae genomes. Based on the phylogenetic analysis of the APEC MTR_BAU02 genome and 99 reference genomes of E. coli, the APEC MTR_BAU02 genome showed sequence similarities with enterotoxigenic E. coli strains isolated from infections of different clinical severity. Metabolic functional annotations detected 380 SEED subsystems including genes coding for carbohydrate metabolism (17.34%), amino acid and derivatives (14.20%), protein metabolism (10.64%), cofactors, vitamins, prosthetic groups and pigments (7.49%), respiration (4.72%), membrane transport (4.49%), stress response (4.47%), motility and chemotaxis (4.46%), and virulence, disease and defense (2.22%). We also detected 92 VFGs and 122 AMR genes in the APEC MTR_BAU02 strain.ConclusionAssessment of these genomic features with functional genomic validation in commonly occurring serogroups of APEC will increase our understanding of the molecular pathogenesis, pave the way to early diagnosis and more effective control of colibacillosis, and improved animal welfare.
A Genome-Wide Association Analysis of Happiness: Consistent Genetic Effects Across the Lifespan and Across Genetic Ancestries in Multiple Cohorts
Authors: Ward Joey , Lyall Laura , Cullen Breda , Strawbridge Rona J. , Zhu Xingxing , Stanciu Ioana , Aman Alisha , Niedzwiedz Claire L. , Anderson Jana , Bailey Mark E. S. , Lyall Donald M. , Pell Jill 
Published: April 2022

AbstractWe present a genome-wide association study of a general happiness measure in 118,851 participants from the UK Biobank. Using BOLT-LMM, we identify 3 significant loci with a heritability estimate of 0.8%. Linkage disequilibrium score regression was performed on the ‘big five’ personality traits finding significant associations with lower neuroticism and higher extraversion and conscientiousness. Using a novel approach, we construct LDpred-inf polygenic risk scores in the Adolescent Brain Cognitive Development (ABCD) cohort and the Add Health cohort. We detected nominally significant associations with several well-being measures in ABCD and significant correlations with a happiness measure in Add Health. Additionally, we tested for associations with several brain regions in a white British subsample of UK Biobank finding significant associations with several brain structure and integrity phenotypes.We demonstrated a genetic basis for general happiness level and brain structure that appears to remain consistent throughout the lifespan and across multiple ancestral backgrounds.Author summaryAt the genetic level, there has been little investigation into whether people may have a baseline happiness level which varies from person to person. Here we perform a genetic analysis in the UK Biobank to identify three genetic loci that associate with general happiness level and preform genetic correlations of our results with the ‘Big Five’ personality traits, identifying significant correlations with neuroticism, conscientiousness and extraversion.We use the resulting summary statistics to create LDpred-inf polygenic risk scores in UK biobank identifying several brain metrics and regions associate with genetic loading for general happiness level. We also use a novel method to create LDpred-inf polygenic risk scores in two other cohorts, ABCD and Add Health. We found significant correlations with an independent happiness measure in Add Health and nominally significant correlations with several well-being measures in ABCD in both those of European Ancestry and all other ancestries found in these cohorts. We also attempted to replicate our UK Biobank MRi finding in ABCD.We conclude there is evidence that individuals have a general happiness level that is in part genetic which spans across age and ancestry.
Distinct regions of H. pylori’s bactofilin CcmA regulate protein-protein interactions to control helical cell shape
Authors: Sichel Sophie R , Bratton Benjamin P , Salama Nina R 
Published: April 2022

AbstractThe helical shape of H. pylori cells promotes robust stomach colonization, however, how the helical shape of H. pylori cells is determined is unresolved. Previous work identified helical-cell-shape-promoting protein complexes containing a peptidoglycan-hydrolase (Csd1), a peptidoglycan precursor synthesis enzyme (MurF), a non-enzymatic homologue of Csd1 (Csd2), non-enzymatic transmembrane proteins (Csd5 and Csd7), and a bactofilin (CcmA). Bactofilins are highly conserved, spontaneously polymerizing cytoskeletal bacterial proteins. We sought to understand CcmA’s function in generating the helical shape of H. pylori cells. Using CcmA deletion analysis, in vitro polymerization, and in vivo co-immunoprecipitation experiments we identified that the bactofilin domain and N-terminal region of CcmA are required for helical cell shape and the bactofilin domain of CcmA is sufficient for polymerization and interactions with Csd5 and Csd7. We also found that CcmA’s N-terminal region inhibits interaction with Csd7. Deleting the N-terminal region of CcmA increases CcmA-Csd7 interactions and destabilizes the peptidoglycan-hydrolase Csd1. Using super-resolution microscopy, we found that Csd5 recruits CcmA to the cell envelope and promotes CcmA enrichment at the major helical axis. Thus, CcmA helps organize cell-shape-determining proteins and peptidoglycan synthesis machinery to coordinate cell wall modification and synthesis, promoting the curvature required to build a helical cell.
SimSearch: A Human-in-the-Loop Learning Framework for Fast Detection of Regions of Interest in Microscopy Images
Authors: Gupta Ankit , Sabirsh Alan , Wählby Carolina , Sintorn Ida-Maria 
Published: April 2022

AbstractObjectiveLarge-scale microscopy-based experiments often result in images with rich but sparse information content. An experienced microscopist can visually identify regions of interest (ROIs), but this becomes a cumbersome task with large datasets. Here we present SimSearch, a framework for quick and easy user-guided training of a deep neural model aimed at fast detection of ROIs in large-scale microscopy experiments.MethodsThe user manually selects a small number of patches representing different classes of ROIs. This is followed by feature extraction using a pre-trained deep-learning model, and interactive patch selection pruning, resulting in a smaller set of clean (user approved) and larger set of noisy (unapproved) training patches of ROIs and background. The pre-trained deep-learning model is thereafter first trained on the large set of noisy patches, followed by refined training using the clean patches.ResultsThe framework is evaluated on fluorescence microscopy images from a large-scale drug screening experiment, brightfield images of immunohistochemistry-stained patient tissue samples, and malaria-infected human blood smears, as well as transmission electron microscopy images of cell sections. Compared to state-of-the-art and manual/visual assessment, the results show similar performance with maximal flexibility and minimal a priori information and user interaction.ConclusionsSimSearch quickly adapts to different data sets, which demonstrates the potential to speed up many microscopy-based experiments based on a small amount of user interaction.SignificanceSimSearch can help biologists quickly extract informative regions and perform analyses on large datasets helping increase the throughput in a microscopy experiment.