bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically determined telomere length and multiple myeloma risk and outcome
Authors: Giaccherini Matteo , Macauda Angelica , Orciuolo Enrico , Rymko Marcin , Gruenpeter Karolina , Dumontet Charles , Raźny Malgorzata , Moreno Victor , Buda Gabriele , Beider Katia , Varkonyi Judit , Avet-Loiseau Hervé , Martinez-Lopez Joaquín , Marques Herlander , Watek Marzena , Sarasquete Maria Eugenia , Andersen Vibeke , Karlin Lionel , Suska Anna , Kruszewski Marcin , Abildgaard Niels , Dudziński Marek , Butrym Aleksandra , Nagler Arnold , Vangsted Annette Juul , Kadar Katalin , Waldemar Tomczak , Jamroziak Krzysztof , Jacobsen Svend Erik Hove , Ebbesen Lene Hyldahl , Taszner Michał , Mazur Grzegorz , Lesueur Fabienne , Pelosini Matteo , Garcia-Sanz Ramon , Jurczyszyn Artur , Demangel Delphine , Reis Rui Manuel , Iskierka-Jażdżewska Elżbieta , Markiewicz Miroslaw , Gemignani Federica , Subocz Edyta , Zawirska Daria , Druzd-Sitek Agnieszka , Stępień Anna , Alonso M. Henar , Sainz Juan , Canzian Federico , Campa Daniele 
Published: April 2021

AbstractTelomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the “teloscore” in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36–2.11; P = 2.97 × 10−6 for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86–0.99; P = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.
Customizing a self-healing soft pump for robot
Authors: Tang Wei , Zhang Chao , Zhong Yiding , Zhu Pingan , Hu Yu , Jiao Zhongdong , Wei Xiaofeng , Lu Gang , Wang Jinrong , Liang Yuwen , Lin Yangqiao , Wang Wei , Yang Huayong , Zou Jun 
Published: April 2021

AbstractRecent advances in soft materials enable robots to possess safer human-machine interaction ways and adaptive motions, yet there remain substantial challenges to develop universal driving power sources that can achieve performance trade-offs between actuation, speed, portability, and reliability in untethered applications. Here, we introduce a class of fully soft electronic pumps that utilize electrical energy to pump liquid through electrons and ions migration mechanism. Soft pumps combine good portability with excellent actuation performances. We develop special functional liquids that merge unique properties of electrically actuation and self-healing function, providing a direction for self-healing fluid power systems. Appearances and pumpabilities of soft pumps could be customized to meet personalized needs of diverse robots. Combined with a homemade miniature high-voltage power converter, two different soft pumps are implanted into robotic fish and vehicle to achieve their untethered motions, illustrating broad potential of soft pumps as universal power sources in untethered soft robotics.
TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses
Authors: Caronni Nicoletta , Piperno Giulia Maria , Simoncello Francesca , Romano Oriana , Vodret Simone , Yanagihashi Yuichi , Dress Regine , Dutertre Charles-Antoine , Bugatti Mattia , Bourdeley Pierre , Del Prete Annalisa , Schioppa Tiziana , Mazza Emilia Maria Cristina , Collavin Licio , Zacchigna Serena , Ostuni Renato , Guermonprez Pierre , Vermi William , Ginhoux Florent , Bicciato Silvio , Nagata Shigekatzu , Benvenuti Federica 
Published: April 2021

AbstractAcquisition of cell-associated tumor antigens by type 1 dendritic cells (cDC1) is essential to induce and sustain tumor specific CD8+ T cells via cross-presentation. Here we show that capture and engulfment of cell associated antigens by tissue resident lung cDC1 is inhibited during progression of mouse lung tumors. Mechanistically, loss of phagocytosis is linked to tumor-mediated downregulation of the phosphatidylserine receptor TIM4, that is highly expressed in normal lung resident cDC1. TIM4 receptor blockade and conditional cDC1 deletion impair activation of tumor specific CD8+ T cells and promote tumor progression. In human lung adenocarcinomas, TIM4 transcripts increase the prognostic value of a cDC1 signature and predict responses to PD-1 treatment. Thus, TIM4 on lung resident cDC1 contributes to immune surveillance and its expression is suppressed in advanced tumors.
Genetic basis of hypercholesterolemia in adults
Authors: Saadatagah Seyedmohammad , Jose Merin , Dikilitas Ozan , Alhalabi Lubna , Miller Alexandra A. , Fan Xiao , Olson Janet E. , Kochan David C. , Safarova Maya , Kullo Iftikhar J. 
Published: April 2021

AbstractWe investigated monogenic and polygenic causes of hypercholesterolemia in a population-based cohort, excluding secondary hypercholesterolemia, and using an established framework to identify pathogenic variants. We studied 1682 individuals (50.2 ± 8.6 years, 41.3% males) from southeast Minnesota with primary hypercholesterolemia (low-density lipoprotein cholesterol (LDL-C) ≥155 mg/dl in the absence of identifiable secondary causes). Familial hypercholesterolemia (FH) phenotype was defined as a Dutch Lipid Clinic Network (DLCN) score ≥6. Participants underwent sequencing of LDLR, APOB, and PCSK9, and genotyping of 12 LDL-C-associated single-nucleotide variants to construct a polygenic score (PGS) for LDL-C. The presence of a pathogenic/likely pathogenic variant was considered monogenic etiology and a PGS ≥90th percentile was considered polygenic etiology. The mean LDL-C level was 187.3 ± 32.3 mg/dl and phenotypic FH was present in 8.4% of the cohort. An identifiable genetic etiology was present in 17.1% individuals (monogenic in 1.5% and polygenic in 15.6%). Phenotypic and genetic FH showed poor overlap. Only 26% of those who met the clinical criteria of FH had an identifiable genetic etiology and of those with an identifiable genetic etiology only 12.9% met clinical criteria for FH. Genetic factors explained 7.4% of the variance in LDL-C. In conclusion, in adults with primary hypercholesterolemia, 17.1% had an identifiable genetic etiology and the overlap between phenotypic and genetic FH was modest.
Topologically driven linear magnetoresistance in helimagnetic FeP
Authors: Campbell D. J. , Collini J. , Sławińska J. , Autieri C. , Wang L. , Wang K. , Wilfong B. , Eo Y. S. , Neves P. , Graf D. , Rodriguez E. E. , Butch N. P. , Buongiorno Nardelli M. , Paglione J. 
Published: April 2021

AbstractThe helimagnet FeP is part of a family of binary pnictide materials with the MnP-type structure, which share a nonsymmorphic crystal symmetry that preserves generic band structure characteristics through changes in elemental composition. It shows many similarities, including in its magnetic order, to isostructural CrAs and MnP, two compounds that are driven to superconductivity under applied pressure. Here we present a series of high magnetic field experiments on high-quality single crystals of FeP, showing that the resistance not only increases without saturation by up to several hundred times its zero-field value by 35 T, but that it also exhibits an anomalously linear field dependence over the entire range when the field is aligned precisely along the crystallographic c-axis. A close comparison of quantum oscillation frequencies to electronic structure calculations links this orientation to a semi-Dirac point in the band structure, which disperses linearly in a single direction in the plane perpendicular to field, a symmetry-protected feature of this entire material family. We show that the two striking features of magnetoresistance—large amplitude and linear field dependence—arise separately in this system, with the latter likely due to a combination of ordered magnetism and topological band structure.
Characterizing chronological accumulation of comorbidities in healthy veterans: a computational approach
Authors: Hong Julian C. , Hauser Elizabeth R. , Redding Thomas S. , Sims Kellie J. , Gellad Ziad F. , O’Leary Meghan C. , Hyslop Terry , Madison Ashton N. , Qin Xuejun , Weiss David , Bullard A. Jasmine , Williams Christina D. , Sullivan Brian A. , Lieberman David , Provenzale Dawn 
Published: April 2021

AbstractUnderstanding patient accumulation of comorbidities can facilitate healthcare strategy and personalized preventative care. We applied a directed network graph to electronic health record (EHR) data and characterized comorbidities in a cohort of healthy veterans undergoing screening colonoscopy. The Veterans Affairs Cooperative Studies Program #380 was a prospective longitudinal study of screening and surveillance colonoscopy. We identified initial instances of three-digit ICD-9 diagnoses for participants with at least 5 years of linked EHR history (October 1999 to December 2015). For diagnoses affecting at least 10% of patients, we calculated pairwise chronological relative risk (RR). iGraph was used to produce directed graphs of comorbidities with RR > 1, as well as summary statistics, key diseases, and communities. A directed graph based on 2210 patients visualized longitudinal development of comorbidities. Top hub (preceding) diseases included ischemic heart disease, inflammatory and toxic neuropathy, and diabetes. Top authority (subsequent) diagnoses were acute kidney failure and hypertensive chronic kidney failure. Four communities of correlated comorbidities were identified. Close analysis of top hub and authority diagnoses demonstrated known relationships, correlated sequelae, and novel hypotheses. Directed network graphs portray chronologic comorbidity relationships. We identified relationships between comorbid diagnoses in this aging veteran cohort. This may direct healthcare prioritization and personalized care.
Moving towards accurate and early prediction of language delay with network science and machine learning approaches
Authors: Borovsky Arielle , Thal Donna , Leonard Laurence B. 
Published: April 2021

AbstractDue to wide variability of typical language development, it has been historically difficult to distinguish typical and delayed trajectories of early language growth. Improving our understanding of factors that signal language disorder and delay has the potential to improve the lives of the millions with developmental language disorder (DLD). We develop predictive models of low language (LL) outcomes by analyzing parental report measures of early language skill using machine learning and network science approaches. We harmonized two longitudinal datasets including demographic and standardized measures of early language skills (the MacArthur-Bates Communicative Developmental Inventories; MBCDI) as well as a later measure of LL. MBCDI data was used to calculate several graph-theoretic measures of lexico-semantic structure in toddlers’ expressive vocabularies. We use machine-learning techniques to construct predictive models with these datasets to identify toddlers who will have later LL outcomes at preschool and school-age. This approach yielded robust and reliable predictions of later LL outcome with classification accuracies in single datasets exceeding 90%. Generalization performance between different datasets was modest due to differences in outcome ages and diagnostic measures. Grammatical and lexico-semantic measures ranked highly in predictive classification, highlighting promising avenues for early screening and delineating the roots of language disorders.
Characterisation of S. aureus/MRSA CC1153 and review of mobile genetic elements carrying the fusidic acid resistance gene fusC
Authors: Monecke Stefan , Müller Elke , Braun Sascha D. , Armengol-Porta Marc , Bes Michèle , Boswihi Samar , El-Ashker Maged , Engelmann Ines , Gawlik Darius , Gwida Mayada , Hotzel Helmut , Nassar Rania , Reissig Annett , Ruppelt-Lorz Antje , Senok Abiola , Somily Ali M. , Udo Edet E. , Ehricht Ralf 
Published: April 2021

AbstractWhile many data on molecular epidemiology of MRSA are available for North America, Western Europe and Australia, much less is known on the distribution of MRSA clones elsewhere. Here, we describe a poorly known lineage from the Middle East, CC1153, to which several strains from humans and livestock belong. Isolates were characterised using DNA microarrays and one isolate from the United Arab Emirates was sequenced using Nanopore technology. CC1153 carries agr II and capsule type 5 genes. Enterotoxin genes are rarely present, but PVL is common. Associated spa types include t504, t903 and t13507. PVL-positive CC1153-MSSA were found in Egyptian cattle suffering from mastitis. It was also identified among humans with skin and soft tissue infections in Saudi Arabia, France and Germany. CC1153-MRSA were mainly observed in Arabian Gulf countries. Some isolates presented with a previously unknown SCCmec/SCCfus chimeric element in which a mec B complex was found together with the fusidic acid resistance gene fusC and accompanying genes including ccrA/B-1 recombinase genes. Other isolates carried SCCmec V elements that usually also included fusC. Distribution and emergence of CC1153-MRSA show the necessity of molecular characterization of MRSA that are resistant to fusidic acid. These strains pose a public health threat as they combine resistance to beta-lactams used in hospitals as well as to fusidic acid used in the community. Because of the high prevalence of fusC-positive MRSA in the Middle East, sequences and descriptions of SCC elements harbouring fusC and/or mecA are reviewed. When comparing fusC and its surrounding regions from the CC1153 strain to available published sequences, it became obvious that there are four fusC alleles and five distinct types of fusC gene complexes reminiscent to the mec complexes in SCCmec elements. Likewise, they are associated with different sets of ccrA/B recombinase genes and additional payload that might include entire mec complexes or SCCmec elements.
Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach
Authors: Hamano Momoko , Nomura Seitaro , Iida Midori , Komuro Issei , Yamanishi Yoshihiro 
Published: April 2021

AbstractHeart failure is a heterogeneous disease with multiple risk factors and various pathophysiological types, which makes it difficult to understand the molecular mechanisms involved. In this study, we proposed a trans-omics approach for predicting molecular pathological mechanisms of heart failure and identifying marker genes to distinguish heterogeneous phenotypes, by integrating multiple omics data including single-cell RNA-seq, ChIP-seq, and gene interactome data. We detected a significant increase in the expression level of natriuretic peptide A (Nppa), after stress loading with transverse aortic constriction (TAC), and showed that cardiomyocytes with high Nppa expression displayed specific gene expression patterns. Multiple NADH ubiquinone complex family, which are associated with the mitochondrial electron transport system, were negatively correlated with Nppa expression during the early stages of cardiac hypertrophy. Large-scale ChIP-seq data analysis showed that Nkx2-5 and Gtf2b were transcription factors characteristic of high-Nppa-expressing cardiomyocytes. Nppa expression levels may, therefore, represent a useful diagnostic marker for heart failure.
The Coronavirus Health and Impact Survey (CRISIS) reveals reproducible correlates of pandemic-related mood states across the Atlantic
Authors: Nikolaidis Aki , Paksarian Diana , Alexander Lindsay , Derosa Jacob , Dunn Julia , Nielson Dylan M. , Droney Irene , Kang Minji , Douka Ioanna , Bromet Evelyn , Milham Michael , Stringaris Argyris , Merikangas Kathleen R. 
Published: April 2021

AbstractThe COVID-19 pandemic and its social and economic consequences have had adverse impacts on physical and mental health worldwide and exposed all segments of the population to protracted uncertainty and daily disruptions. The CoRonavIruS health and Impact Survey (CRISIS) was developed for use as an easy to implement and robust questionnaire covering key domains relevant to mental distress and resilience during the pandemic. Ongoing studies using CRISIS include international studies of COVID-related ill health conducted during different phases of the pandemic and follow-up studies of cohorts characterized before the COVID pandemic. In the current work, we demonstrate the feasibility, psychometric structure, and construct validity of this survey. We then show that pre-existing mood states, perceived COVID risk, and lifestyle changes are strongly associated with negative mood states during the pandemic in population samples of adults and in parents reporting on their children in the US and UK. These findings are highly reproducible and we find a high degree of consistency in the power of these factors to predict mental health during the pandemic.
Genetic changes are introduced by repeated exposure of Salmonella spiked in low water activity and high fat matrix to heat
Authors: Baert Leen , Gimonet Johan , Barretto Caroline , Fournier Coralie , Jagadeesan Balamurugan 
Published: April 2021

AbstractWGS is used to define if isolates are “in” or “out” of an outbreak and/or microbial root cause investigation. No threshold of genetic differences is fixed and the conclusions on similarity between isolates are mainly based on the knowledge generated from previous outbreak investigations and reported mutation rates. Mutation rates in Salmonella when exposed to food processing conditions are lacking. Thus, in this study, the ability of heat and dry stress to cause genetic changes in two Salmonella serotypes frequently isolated from low moisture foods was investigated. S. enterica serovars S. Agona ATCC 51,957 and S. Mbandaka NCTC 7892 (ATCC 51,958) were repeatedly exposed to heat (90 °C for 5 min) in a low water activity and high fat matrix. No increased fitness of the strains was observed after 10 repeated heat treatments. However, genetic changes were introduced and the number of genetic differences increased with every heat treatment cycle. The genetic changes appeared randomly in the genome and were responsible for a population of diverse isolates with 0 to 28 allelic differences (0 to 38 SNPs) between them. This knowledge is key to interpret WGS results for source tracking investigations as part of a root cause analysis in a contamination event as isolates are exposed to stress conditions.
Differences in digit ratios between gay men who prefer receptive versus insertive sex roles indicate a role for prenatal androgen
Authors: Swift-Gallant Ashlyn , Di Rita Victor , Major Christina A. , Breedlove Christopher J. , Jordan Cynthia L. , Breedlove S. Marc 
Published: April 2021

AbstractAmong non-human mammals, exposure to androgens during critical periods of development leads to gynephilia (attraction to females), whereas the absence or low levels of prenatal androgens leads to androphilia (attraction to males). However, in humans, retrospective markers of prenatal androgens have only been associated with gynephilia among women, but not with androphilia among men. Here, we asked whether an indirect indication of prenatal androgen exposure, 2D:4D, differs between subsets of gay men delineated by anal sex role (ASR). ASR was used as a proxy for subgroups because ASR groups tend to differ in other measures affected by brain sexual differentiation, such as gender conformity. First, we replicated the finding that gay men with a receptive ASR preference (bottoms) report greater gender nonconformity (GNC) compared to gay men with an insertive ASR preference (tops). We then found that Tops have a lower (male-typical) average right-hand digit ratio than Bottoms, and that among all gay men the right-hand 2D:4D correlated with GNC, indicating that a higher (female-typical) 2D:4D is associated with increased GNC. Differences were found between non-exclusive and exclusive same-sex attraction and GNC, and ASR group differences on digit ratios do not reach significance when all non-heterosexual men are included in the analyses, suggesting greater heterogeneity in the development of non-exclusive same-sex sexual orientations. Overall, results support a role for prenatal androgens, as approximated by digit ratios, in influencing the sexual orientation and GNC of a subset of gay men.
Regulator of G protein signaling 17 represents a novel target for treating cisplatin induced hearing loss
Authors: Dhukhwa Asmita , Al Aameri Raheem F. H. , Sheth Sandeep , Mukherjea Debashree , Rybak Leonard , Ramkumar Vickram 
Published: April 2021

AbstractRegulators of G protein signaling (RGS) accelerate the GTPase activity of G proteins to enable rapid termination of the signals triggered by G protein-coupled receptors (GPCRs). Activation of several GPCRs, including cannabinoid receptor 2 (CB2R) and adenosine A1 receptor (A1AR), protects against noise and drug-induced ototoxicity. One such drug, cisplatin, an anticancer agent used to treat various solid tumors, produces permanent hearing loss in experimental animals and in a high percentage of cancer patients who undergo treatments. In this study we show that cisplatin induces the expression of the RGS17 gene and increases the levels of RGS17 protein which contributes to a significant proportion of the hearing loss. Knockdown of RGS17 suppressed cisplatin-induced hearing loss in male Wistar rats, while overexpression of RGS17 alone produced hearing loss in vivo. Furthermore, RGS17 and CB2R negatively regulate the expression of each other. These data suggest that RGS17 mediates cisplatin ototoxicity by uncoupling cytoprotective GPCRs from their normal G protein interactions, thereby mitigating the otoprotective contributions of endogenous ligands of these receptors. Thus, RGS17 represents a novel mediator of cisplatin ototoxicity and a potential therapeutic target for treating hearing loss.