bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary retensioning of a tether-based device for transapical transcatheter mitral valve implantation
Authors: Beyer Martin , Muller David , De Marco Federico , Badhwar Vinay , Obadia Jean-Francois , Praz Fabien , Modine Thomas , Tonino Pim , Dahle Gry , Cerillo Alfredo , Ludwig Sebastian , Conradi Lenard 
Published: December 2023

Abstract

OBJECTIVES
Relevant paravalvular leakage (PVL) due to prosthesis dislodgement is a rare but potentially severe complication after transcatheter mitral valve implantation (TMVI). Due to the epicardial anchoring mechanism of the Tendyne® TMVI system, repositioning of the valve stent may be possible by retensioning of the tether. This multicentre study aimed to investigate the procedural and short-term safety as well as efficacy of retensioning manoeuvres.

METHODS
From 2017 to 2021, N = 18 patients who underwent secondary tether retensioning were identified. Baseline, procedural and follow-up data were available from N = 11 patients and analysed according to the Mitral Valve Research Consortium definitions. Continuous variables are shown as median with interquartile range.

RESULTS
All patients [age 75 years (73.5, 85.0), 64% male (N = 7), EuroSCORE II 6.2% (5.8, 11.6)] presented with post-procedural PVL [63.6% (N = 7) with PVL ≥3+]. Of these, 54% (N = 6) showed signs of haemolysis. The majority were severely symptomatic [New York Heart Association ≥III (91%, N = 10)]. Procedural outcomes revealed no acute complications and no mortality. At discharge, PVL was completely eliminated in 91% (N = 10) of patients with 1 case of remaining moderate PVL. At 30 days, Mitral Valve Research Consortium device success was achieved in 82% (N = 9) of patients. Two patients required open surgical mitral valve replacement due to persistent and recurrent PVL. In 89% (N = 8) of patients with successful retensioning procedure, New York Heart Association class was I/II. There was no 30-day mortality.

CONCLUSIONS
This multicentre study demonstrates technical feasibility, procedural safety and acute efficacy of retensioning procedures in the majority of patients. The potential to retension the tether in transapical TMVI may provide additional management advantages in populations at high surgical risk.
The System Is Corrupted, and the Mainstream Media Is Lying to us! Exploring the Relation Between Affinity Toward Conspiracy Myths and Alternative News Media Usage
Authors: Vogler Daniel , Rauchfleisch Adrian , Schwaiger Lisa 
Published: December 2023

Abstract
Alternative news media (ANM) have become an important information source for certain audiences. Research shows that ANM usage is linked to a preference for populist parties and the use of digital media. However, ANM existed before the rise of populism and digital media over the last two decades. Thus, we must assume that additional factors are related to ANM usage. To investigate such factors, we conducted a cross-sectional online survey (N = 1,212) of the Swiss population. We analyze how affinity toward conspiracy myths, preference for populist parties, the usage of social media, and the Telegram messenger app are related to ANM usage. The results indicate that people with a high affinity toward conspiracy myths are more likely to use ANM. Different than in previous studies, preference for populist politics is not related to higher ANM usage in Switzerland. Our results suggest that the political context matters when studying ANM usage and that the strong focus on right-wing populism might lead to scholars missing part of the bigger picture. Furthermore, our findings indicate that the use of social media and Telegram, which recently gained relevance as a channel for mobilizing protests during the COVID-19 pandemic, positively connect with ANM consumption.
Enhancing global insight into AMR spread and generation: prospects and limitations of the WHO and quadripartite research agendas
Authors: Fieldman Thomas , Mossialos Elias , Anderson Michael 
Published: December 2023

Abstract
In Summer 2023, the World Health Organisation (WHO) and the Food and Agriculture Organization of the United Nations (FAO)-United Nations Environment Programme (UNEP) WHO-World Organisation for Animal Health (OIE) Quadripartite published two separate research agendas on antimicrobial resistance (AMR). While the publication of these research agendas on AMR creates a significant opportunity to align research priorities internationally, we emphasize a number of limitations. Firstly, the production of two separate AMR research agendas, in human health and One Health, rather than one integrated research agenda, risks the continued deprioritization of the One Health agenda. Furthermore, neither research agenda addressed the need to study the relationship between climate change and AMR despite growing evidence to suggest this may be significant. Finally, there are also missed opportunities in directing the study of appropriate treatment regimens and in clarifying the overall most resource-efficient path to combatting AMR. Moving forward, the international research agenda for AMR needs to be continually redefined in an inclusive, transparent and independent manner. This could be the task of the proposed, but so far not realized, Independent Panel on Evidence for Action against AMR.
Characterization of an ST38 carbapenem-resistant and highly virulent Escherichia coli carrying conjugatively transferable ColV virulence–resistance and blaNDM-5-positive resistance plasmids
Authors: Xu Chen , Li Yunbing , Li Yuanyuan , Huang Lili , Zhou Mi , Xu Yi , Dong Ning 
Published: December 2023

Abstract

Objectives
To characterize an Escherichia coli strain causing bloodstream infection encoding both high-virulence and carbapenem-resistance phenotypes.

Methods
Antimicrobial susceptibility testing, WGS and bioinformatics analysis were performed to characterize strain E1. The function of the ColV plasmid was investigated by the Galleria mellonella infection model, serum killing and macrophage killing assays. The fitness effect of the ColV plasmid was tested by growth curve, plasmid stability tests and the in vitro competition assay. The conjugation assay was performed to test the transferability of the ColV and blaNDM-5-carrying plasmids.

Results
E. coli E1 from bloodstream infection was MDR and highly virulent in the G. mellonella infection model. It belonged to phylogroup D, ST38 and serotype O7:H8. E1 carried a conjugatively transferable IncI1-type blaNDM-5-positive plasmid, which conferred carbapenem resistance, a conjugative IncFIB/FII-type ColV plasmid encoding an array of virulence-associated genes and antibiotic resistance genes blaTEM-1B, strAB and sul2, and seven other plasmids. Co-transfer of the ColV plasmid and the blaNDM-5-positive plasmid was observed. The ColV virulence–resistance hybrid plasmid contributed to the virulence, resistance to serum killing, and macrophage phagocytosis in E. coli E1. The carriage of this ColV plasmid did not constitute an in vitro fitness burden to strain E1 but caused fitness costs to E. coli strain EC600.

Conclusions
The emergence of such a highly virulent and resistant strain with conjugative blaNDM-5-positive and ColV plasmids posed a significant threat to public health. Implementation of control measures is needed to prevent such strains from further disseminating in hospital settings and the community.
A population of Optically Quiescent Quasars from WISE and SDSS
Authors: Greenwell Claire , Gandhi Poshak , Stern Daniel , Lansbury George , Mainieri Vincenzo , Boorman Peter , Toba Yoshiki 
Published: December 2023

ABSTRACT
The growth of active galactic nuclei (AGNs) occurs under some form of obscuration in a large fraction of the population. The difficulty in constraining this population leads to high uncertainties in cosmic X-ray background and galaxy evolution models. Using an SDSS–WISE cross-match, we target infrared luminous AGN (W1 − W2 &gt; 0.8, and monochromatic rest-frame luminosity above λLλ(12 μm) ≈ 3 × 1044 erg s−1), but with passive galaxy-like optical spectra (Optically Quiescent Quasars; OQQs). We find 47 objects that show no significant [O iii]λ5007 emission, a typically strong AGN optical emission line. As a comparison sample, we examine SDSS-selected Type 2 quasars (QSO2s), which show a significant [O iii]λ5007 line by definition. We find a 1:16 ratio of OQQs compared to QSO2s, suggesting that the OQQ duty cycle is likely much shorter than that of QSO2s (though selection biases are not fully quantified). We consider observed properties in comparison with other galaxy types, and examine them for consistency with theories on their intrinsic nature: chiefly (a) a high covering factor for surrounding obscuring matter, preventing the detection of high-ionisation emission lines – ‘cocooned AGN’; or (b) ionized gas being absent on the kpc scales of the Narrow Line Region (NLR), perhaps due to a ‘switching on’ or ‘young’ AGN. OQQs do not obviously fit the standard paradigm for merger-driven AGN and host galaxy evolution, implying we may be missing part of the flow of AGN evolution.
Molecular mechanism of human ISG20L2 for the ITS1 cleavage in the processing of 18S precursor ribosomal RNA
Authors: Ma Yinliang , Wang Jiaxu , He Xingyi , Liu Yuhang , Zhen Shuo , An Lina , Yang Qian , Niu Fumin , Wang Hong , An Boran , Tai Xinyue , Yan Zhenzhen , Wu Chen , Yang Xiaoyun , Liu Xiuhua 
Published: December 2023

Abstract
The exonuclease ISG20L2 has been initially characterized for its role in the mammalian 5.8S rRNA 3′ end maturation, specifically in the cleavage of ITS2 of 12S precursor ribosomal RNA (pre-rRNA). Here, we show that human ISG20L2 is also involved in 18S pre-rRNA maturation through removing the ITS1 region, and contributes to ribosomal biogenesis and cell proliferation. Furthermore, we determined the crystal structure of the ISG20L2 nuclease domain at 2.9 Å resolution. It exhibits the typical αβα fold of the DEDD 3′-5′ exonuclease with a catalytic pocket located in the hollow near the center. The catalytic residues Asp183, Glu185, Asp267, His322 and Asp327 constitute the DEDDh motif in ISG20L2. The active pocket represents conformational flexibility in the absence of an RNA substrate. Using structural superposition and mutagenesis assay, we mapped RNA substrate binding residues in ISG20L2. Finally, cellular assays revealed that ISG20L2 is aberrantly up-regulated in colon adenocarcinoma and promotes colon cancer cell proliferation through regulating ribosome biogenesis. Together, these results reveal that ISG20L2 is a new enzymatic member for 18S pre-rRNA maturation, provide insights into the mechanism of ISG20L2 underlying pre-rRNA processing, and suggest that ISG20L2 is a potential therapeutic target for colon adenocarcinoma.
HMZDupFinder: a robust computational approach for detecting intragenic homozygous duplications from exome sequencing data
Authors: Du Haowei , Dardas Zain , Jolly Angad , Grochowski Christopher M , Jhangiani Shalini N , Li He , Muzny Donna , Fatih Jawid M , Yesil Gozde , Elçioglu Nursel H , Gezdirici Alper , Marafi Dana , Pehlivan Davut , Calame Daniel G , Carvalho Claudia M B , Posey Jennifer E , Gambin Tomasz , Coban-Akdemir Zeynep , Lupski James R 
Published: December 2023

Abstract
Homozygous duplications contribute to genetic disease by altering gene dosage or disrupting gene regulation and can be more deleterious to organismal biology than heterozygous duplications. Intragenic exonic duplications can result in loss-of-function (LoF) or gain-of-function (GoF) alleles that when homozygosed, i.e. brought to homozygous state at a locus by identity by descent or state, could potentially result in autosomal recessive (AR) rare disease traits. However, the detection and functional interpretation of homozygous duplications from exome sequencing data remains a challenge. We developed a framework algorithm, HMZDupFinder, that is designed to detect exonic homozygous duplications from exome sequencing (ES) data. The HMZDupFinder algorithm can efficiently process large datasets and accurately identifies small intragenic duplications, including those associated with rare disease traits. HMZDupFinder called 965 homozygous duplications with three or less exons from 8,707 ES with a recall rate of 70.9% and a precision of 16.1%. We experimentally confirmed 8/10 rare homozygous duplications. Pathogenicity assessment of these copy number variant alleles allowed clinical genomics contextualization for three homozygous duplications alleles, including two affecting known OMIM disease genes EDAR (MIM# 224900), TNNT1(MIM# 605355), and one variant in a novel candidate disease gene: PAAF1.
Increased Cardiometabolic Risk in Healthy Young Adults With Early Life Stress
Authors: Kulak Meghan J. , los Angeles William Lewis-de , Daniels Teresa E. , Mathis Karen J. , Gobin Asi P. , Laumann Laura E. , Beck Quincy , Tyrka Audrey R. 
Published: December 2023

ABSTRACT

Objective
This study aimed to evaluate the relationship between early life stress (ELS) and metabolic risk in healthy young adults and assess the role of health behaviors.

Methods
Young adults aged 18 to 40 years (N = 190) with no medical conditions or medication usage were recruited from the community. Participants with ELS (N = 113) had a history of childhood maltreatment, and most also experienced parental loss (n = 88). Controls (N = 77) had no history of maltreatment or parental loss. Standardized interviews and self-reports assessed demographics, adversity, medical/psychiatric history, and health behaviors. Blood pressure and anthropometrics were measured, and fasting plasma assayed for lipid profiles, glucose, insulin level, and hemoglobin A1c. We calculated both a clinical cut-point and continuous composite metabolic risk score based on clinical risk factors and the mean of z scores of each measure, respectively.

Results
ELS was significantly associated with increased clinical cut-point (β = 0.68, 95% confidence interval [CI] = 0.20–1.17, p = .006) and continuous (β = 0.23, 95% CI = 0.08–0.038, p = .003) composite metabolic risk scores. On sensitivity analysis, the association of ELS with the continuous composite metabolic risk score was reduced to a trend after adjusting for a range of psychosocial and health predictors (β = 0.18, 95% CI = 0.00–0.36, p = .053), with both diet and college graduate status significant in the model.

Conclusions
Healthy young adults with a history of ELS have increased metabolic risk scores as compared with controls. This relationship may be partially due to health behaviors and socioeconomic factors. These findings underline that ELS is an early contributor to metabolic risk.
Integrated-omics profiling unveils the disparities of host defense to ECM scaffolds during wound healing in aged individuals
Authors: Chen Shuai-dong , Chu Chen-yu , Wang Chen-bing , Man Yi 
Published: December 2023

AbstractExtracellular matrix (ECM) scaffold membranes have exhibited promising potential to better the outcomes of wound healing by creating a regenerative microenvironment around. However, when compared to the application in younger individuals, the performance of the same scaffold membrane in promoting re-epithelialization and collagen deposition was observed dissatisfying in aged mice. To comprehensively elucidate the mechanisms underlying this age-related disparity, we conducted an integrated analysis, combing single-cell RNA sequencing (scRNA-Seq) with spatial transcriptomics, to explore the complex cellular niches surrounding the ECM scaffolds. Through intergroup comparative analysis and cell-cell communication, we identified and characterized the senescent SPP1+ macrophages may impede the activation of the type L immune response, thus inhibiting the repair ability of epidermal cells and fibroblasts around the ECM scaffolds. These findings contribute to a deeper understanding of biomaterial applications in varied physiological contexts, thereby paving the way for the development of precision-based biomaterials tailored specifically for aged individuals in future therapeutic strategies.
TRPM8-dependent shaking in mammals and birds
Authors: Selescu Tudor , Bivoleanu Ramona-Andreea , Carstens Mirela Iodi , Manolache Alexandra , Caragea Violeta-Maria , Huțanu Debora-Elena , Meerupally Rathej , Wei Edward T. , Carstens Earl , Zimmermann Katharina , Babes Alexandru 
Published: December 2023

AbstractRemoving water from wet fur or feathers is important for thermoregulation in warm-blooded animals. The “wet dog shake” (WDS) behavior has been largely characterized in mammals but to a much lesser extent in birds. Although it is known that TRPM8 is the main molecular transducer of low temperature in mammals, it is not clear if wetness-induced shaking in furred and feathered animals is dependent on TRPM8. Here, we show that a novel TRPM8 agonist induces WDS in rodents and, importantly, in birds, similar to the shaking behavior evoked by water-spraying. Furthermore, the WDS onset depends on TRPM8, as we show in water-sprayed mice. Overall, our results provide multiple evidence for a TRPM8 dependence of WDS behaviors in all tested species. These suggest that a convergent evolution selected similar shaking behaviors to expel water from fur and feathers, with TRPM8 being involved in wetness sensing in both mammals and birds.
Proliferating CLL cells express high levels of CXCR4 and CD5
Authors: Friedman Daniel , Mehtani Drshika P , Vidler Jennifer B , Patten Piers EM , Hoogeboom Robbert 
Published: December 2023

AbstractChronic Lymphocytic Leukaemia (CLL) is an incurable progressive malignancy of CD5+ B cells with a birth rate between 0.1-1% of the entire clone per day. However, the phenotype and functional characteristics of proliferating CLL cells remain incompletely understood. Here, we stained peripheral blood CLL cells for ki67 and DNA content and found that CLL cells in G1-phase have a CXCR4loCD5hiphenotype, whilst CLL cells in S/G2/M-phase express high levels of both CXCR4 and CD5. Induction of proliferationin vitrousing CD40L stimulation results in high ki67 levels in CXCR4loCD5hicells with CXCR4 expression increasing as CLL cells progress through S and G2/M-phases, whilst CXCR4hiCD5loCLL cells remained quiescent. Dye dilution experiments revealed an accumulation of Ki67hidivided cells in the CXCR4hiCD5hifraction. In Eμ-TCL1 transgenic mice, the CXCR4hiCD5hifraction expressed high levels of ki67 and was expanded in enlarged spleens of diseased animals. Human peripheral blood CXCR4hiCD5hiCLL cells express high levels of IgM and the chemokine receptors CCR7 and CXCR5 and migrated most efficiently towards CCL21. We found higher levels of CXCR4 in patients with progressive disease and the CXCR4hiCD5hifraction was expanded upon clinical relapse. Thus, this study defines the phenotype and functional characteristics of proliferating CLL cells identifying a novel subclonal population that underlies CLL pathogenesis and may drive clinical outcome.
Common genetic variation impacts stress response in the brain
Authors: Seah Carina , Signer Rebecca , Deans Michael , Bader Heather , Rusielewicz Tom , Hicks Emily M. , Young Hannah , Cote Alanna , Townsley Kayla , Xu Changxin , Hunter Christopher J. , McCarthy Barry , Goldberg Jordan , Dobariya Saunil , Holtzherimer Paul E. , Young Keith A. ,   NYSCF Global Stem Cell Array® Team,   Traumatic Stress Brain Research Group, Noggle Scott A. , Krystal John H. , Paull Daniel , Girgenti Matthew J. , Yehuda Rachel , Brennand Kristen J. , Huckins Laura M. 
Published: December 2023

ABSTRACTTo explain why individuals exposed to identical stressors experience divergent clinical outcomes, we determine how molecular encoding of stress modifies genetic risk for brain disorders. Analysis of post-mortem brain (n=304) revealed 8557 stress-interactive expression quantitative trait loci (eQTLs) that dysregulate expression of 915 eGenes in response to stress, and lie in stress-related transcription factor binding sites. Response to stress is robust across experimental paradigms: up to 50% of stress-interactive eGenes validate in glucocorticoid treated hiPSC-derived neurons (n=39 donors). Stress-interactive eGenes show brain region- and cell type-specificity, and, in post-mortem brain, implicate glial and endothelial mechanisms. Stress dysregulates long-term expression of disorder risk genes in a genotype-dependent manner; stress-interactive transcriptomic imputation uncovered 139 novel genes conferring brain disorder risk only in the context of traumatic stress. Molecular stress-encoding explains individualized responses to traumatic stress; incorporating trauma into genomic studies of brain disorders is likely to improve diagnosis, prognosis, and drug discovery.Graphical Abstract
Mappingcis- andtrans-regulatory target genes of human-specific deletions
Authors: Fair Tyler , Pavlovic Bryan J. , Swope Dani , Castillo Octavio E. , Schaefer Nathan K. , Pollen Alex A. 
Published: December 2023

AbstractDeletion of functional sequence is predicted to represent a fundamental mechanism of molecular evolution1,2. Comparative genetic studies of primates2,3have identified thousands of human-specific deletions (hDels), and thecis-regulatory potential of short (≤31 base pairs) hDels has been assessed using reporter assays4. However, how structural variant-sized (≥50 base pairs) hDels influence molecular and cellular processes in their native genomic contexts remains unexplored. Here, we design genome-scale libraries of single-guide RNAs targeting 7.2 megabases of sequence in 6,358 hDels and present a systematic CRISPR interference (CRISPRi) screening approach to identify hDels that modify cellular proliferation in chimpanzee pluripotent stem cells. By intersecting hDels with chromatin state features and performing single-cell CRISPRi (Perturb-seq) to identify theircis- andtrans-regulatory target genes, we discovered 20 hDels controlling gene expression. We highlight two hDels, hDel_2247 and hDel_585, with tissue-specific activity in the brain. Our findings reveal a molecular and cellular role for sequences lost in the human lineage and establish a framework for functionally interrogating human-specific genetic variants.