bluuebunny/crossref_metadata_2025 huggingface dataset:
Printing of liquid metal by laser-induced thermal bubble at the liquid–liquid interface
Authors: Yan Mingyu , Zhang Yanzhen , Zhu Jianhao , Zang Haifeng , Ding Zhuochen , Zhao Xiaodi , Li Runsheng
Published: December 2023

The dynamics of bubbles near a liquid–liquid interface represent a complex multiphase problem with numerous potential applications. This paper utilizes pulsed laser-induced microbubbles at the liquid–liquid interface to achieve the multi-orifice ejection of liquid metal microdroplets that are challenging to achieve with traditional inkjet printing. The study combines the expansion and collapse processes of thermal bubbles at the two-phase liquid interface with the ejection process of liquid metal droplets, unveiling the underlying mechanisms of liquid metal droplet ejection. In this work, the influence of laser parameters on the behavior of thermal bubbles at the liquid–liquid interface and the double-peak pressure effect was investigated. The impact of laser parameters on the ejection behavior of liquid metal droplets was also examined, which provides theoretical support for the wide applications of bubble dynamics at the liquid–liquid interface in the field of liquid metal inkjet printing.
ConvGRU-MHM: a CNN GRU-enhanced MHM for mitigating GNSS multipath
Authors: Tong Runfa , Liu Chao , Tao Yuan , Wang Xiangyang , Sun Jingqiang
Published: December 2023

In high-precision global navigation satellite system (GNSS) short-baseline positioning, multipath is the main source of errors. If the station environment is quasi-static, repeat periods of satellites can be utilized to generate time- or space-dependent multipath models to mitigate multipaths. However, two general problems are associated with the multipath models constructed based on satellite mechanics: (1) an accuracy decrease occurs when the above models are applied to multipath mitigation over a long time-span; (2) when constructing the spatial and temporal grids of the satellite-based spatially dependent multipath model, it is challenging to balance computational efficiency and spatial resolution. We propose a convolutional neural network-gated recurrent unit enhanced multipath hemispherical map (ConvGRU-MHM) in the observational domain to address these problems. The proposed method directly mines the deep features of elevation, azimuth angle, and multipath and the mapping relationship between these to establish a real-time prediction model. The predicted multipath is obtained and returned to the observation equation for multipath mitigation when the real-time position of the satellite is placed in the pre-trained model. We compared the multipath mitigation performance of sidereal filtering and a MHM with that of the ConvGRU-MHM to demonstrate the advantages of the proposed method. The experimental results are as follows: (1) in the short time-span (first 20 d), the mean accuracy improvements of the ConvGRU-MHM in the E/N/U direction performed better than those of the SF and MHM; and (2) in the long-term time (after 50 d), the mean accuracy improvements of the ConvGRU-MHM in the E/N/U direction are higher than that of the SF and MHM by 10%–20%. As a lightweight model, the ConvGRU-MHM can effectively improve the measurement accuracy of GNSS real-time monitoring in fields, such as deformation monitoring and seismic research.
Two-photon Production in Low-velocity Shocks
Authors: Kulkarni S. R. , Shull J. Michael
Published: December 2023

The Galactic interstellar medium abounds in shocks with low velocities v

s
≲ 70 km s−1. Some are descendants of higher velocity shocks, while others start off at low velocity (e.g., stellar bow shocks, intermediate velocity clouds, spiral density waves). Low-velocity shocks cool primarily via Lyα and two-photon continuum, augmented by optical recombination lines (e.g., Hα), forbidden lines of metals and free-bound emission, free–free emission. The dark far-ultraviolet (FUV) sky, aided by the fact that the two-photon continuum peaks at 1400 Å, makes the FUV band an ideal tracer of low-velocity shocks. GALEX FUV images reaffirm this expectation, discovering faint and large interstellar structure in old supernova remnants and thin arcs stretching across the sky. Interstellar bow shocks are expected from fast stars from the Galactic disk passing through the numerous gas clouds in the local interstellar medium within 15 pc of the Sun. Using the bests atomic data available to date, we present convenient fitting formulae for yields of Lyα, two-photon continuum, and Hα for pure hydrogen plasma in the temperature range of 104–105 K. The formulae presented here can be readily incorporated into time-dependent cooling models as well as collisional ionization equilibrium models.
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

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

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

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

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

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 > 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

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

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

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

Extracellular 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

Removing 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

Chronic 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

To 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

Deletion 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.
Benchmarking A Novel Quantitative PCR-based Microbiome Profiling Platform Against Sequencing-based Methods
Authors: Tully Benjamin J. , Finkel Steven E. , Corzett Christopher H.
Published: December 2023

Background

PCR-based diagnostics, predominantly utilized for pathogen detection, have faced challenges in broader microbial profiling due to disparities in genomic data availability. This study addresses this limitation by exploiting the surge in the number of microbial genomes, facilitated by advancements in next-generation sequencing (NGS) and metagenomic-assembled genomes. The primary aim was to develop and validate quantitative PCR (qPCR) assays for a wide range of gut commensals, traditionally overlooked due to inadequate genomic information. We sought to compare the efficacy of these qPCR assays against established NGS microbiome profiling methodologies - 16S amplicon and metagenomic sequencing.

Methods

We designed 110 species-specific qPCR assays for gut commensals using a novel proprietaryin silicopipeline and validated the assays against stool samples from three healthy donors. The quantitative microbiome profiles were compared to taxonomic profiles generated by standard bioinformatic approaches for 16S amplicon and metagenomic sequencing. 16S amplicons were analyzed as amplicon sequence variants produced by DADA2 and metagenomic sequences were analyzed by multiple iterations of MetaPhlAn (versions 2, 3, and 4) and Kraken2/Bracken paired with two different genomic databases. The qPCR assays were assessed for their ability to detect low abundance microbes and their correlation with NGS results, focusing on taxonomic resolution and limits of quantification.

Results

The qPCR assays demonstrated high concordance with advanced metagenomic and the ineffectiveness of 16S amplicon methods to achieve species-level assignments. qPCR microbiome profiles were more highly correlated with the most current bioinformatic methods than the bioinformatics methods were to each other. The profile comparisons also highlight how the continued use of older bioinformatics protocols can limit results and lead to misinterpretation of data. Notably, qPCR identified taxa undetected or underestimated by metagenomic approaches, revealing limitations in current bioinformatics tools for differentiating closely related species and quantifying low abundance taxa.

Conclusions

This study establishes qPCR as a robust tool for large-scale microbiome profiling, offering enhanced accuracy, sensitivity, and quantitative capabilities compared to standard NGS methods. Our findings advocate for the integration of qPCR in standardizing microbiome detection, providing a pathway towards developing human microbiome profiling platforms capable of accurate species quantification. The adoption of qPCR assays could lead to more consistent, reliable, and cost-effective microbiome research and diagnostics.
Auditory High Entropy Response (A-HER): A Novel Paradigm for Studying Brain Processing of Uncertain Information
Authors: Liang Xiaoqi , Zhu Qianyun , Zhang Zhiguo , Hu Zhenxing , Liang Zhen , Li Linling , Zhang Li , Xiao Xuezhen , Huang Gan
Published: December 2023

This paper introduces a novel experimental paradigm - Auditory High Entropy Response (A-HER), which maximizes the information entropy of auditory stimulus sequences. This allows us to study how the brain processes complex information, rather than isolated individual events. Our analysis of the frequency response of the frontal theta rhythm induced by A-HER indicated a significant increase in signal-to-noise ratio and repeatability compared to zero-entropy Auditory Steady-State Response (A-SSR) and low-entropy mismatch negativity (MMN). We further investigated whether the A-HER response was induced by stimulus sequence differences or uncertainty, and studied its propagation rules. Different principles between evoked and entrained were found in A-HER and A-SSR. In conclusion, the A-HER paradigm, by maximizing stimulus sequence uncertainty, offers a new approach to analyzing how the brain processes uncertain information. It has potential for diagnosing and researching neurological and mental diseases, and for brain-computer interfaces, thus potentially impacting neuroscience, cognitive science, and psychology.
Comment on ‘Accumbens cholinergic interneurons dynamically promote dopamine release and enable motivation’
Authors: Taniguchi James , Melani Riccardo , Chantranupong Lynne , Wen Michelle J. , Mohebi Ali , Berke Joshua , Sabatini Bernardo , Tritsch Nicolas
Published: December 2023

Acetylcholine is widely believed to modulate the release of dopamine in the striatum of mammals. Experiments in brain slices clearly show that synchronous activation of striatal cholinergic interneurons is sufficient to drive dopamine release via axo-axonal stimulation of nicotinic acetylcholine receptors. However, evidence for this mechanismin vivohas been less forthcoming. A recent paper ineLife(Mohebiet al., 2023) reported that, in awake behaving rats, optogenetic activation of striatal cholinergic interneurons with blue light readily evokes dopamine release measured with the red fluorescent sensor RdLight1. Here, we show that blue light alone alters the fluorescent properties of RdLight1 in a manner that may be misconstrued as phasic dopamine release, and that this artefactual photoactivation can account for the effects attributed to cholinergic interneurons. Our findings indicate that measurements of dopamine using the red-shifted fluorescent sensor RdLight1 should be interpreted with caution when combined with optogenetics. In light of this and other publications that did not observe large acetylcholine-evoked dopamine transientsin vivo, the conditions under which such release occurs in behaving animals remain unknown.
GABA Increases Sensory Transmission In Monkeys
Authors: Mahrous Amr A. , Liang Lucy , Balaguer Josep-Maria , Ho Jonathan C. , Hari Krishnapriya , Grigsby Erinn M. , Karapetyan Vahagn , Damiani Arianna , Fields Daryl P. , Gonzalez-Martinez Jorge A. , Gerszten Peter C. , Bennett David J. , Heckman C.J. , Pirondini Elvira , Capogrosso Marco
Published: December 2023

Sensory input flow is central to voluntary movements. For almost a century, GABA was believed to modulate this flow by inhibiting sensory axons in the spinal cord to sculpt neural inputs into skilled motor output. Instead, here we show that GABA can also facilitate sensory transmission in monkeys and consequently increase spinal and cortical neural responses to sensory inputs challenging our understanding of generation and perception of movement.
Population genomic analysis reveals high inbreeding in a Hawksbill turtle population nesting in Singapore
Authors: Tiong Regine Hui Yi , Dacanay Justine , Uchida Akira , Desai Archita Sanjay , Kalsi Namrata , Tong Collin , Kim Hie Lim
Published: December 2023

Seven species of marine turtles remain in a world currently threatened by anthropogenic activities and climate change, standing at the precipice of extinction. Urgent conservation endeavours are imperative to safeguard their survival and preserve the biodiversity of marine ecosystems. Yet, genetic studies on these turtles have leaned on restricted genetic markers, such as the mitochondrial control region. The markers could provide incomplete or biased estimations of genetic diversity and population structure, thereby limiting precise conservation strategies. Here, we have generated ade novogenome assembly and high-quality whole-genome population datasets from hawksbill turtles nesting and foraging in Singapore. This initiative aims to contribute to unbiased, fine-resolution genetic data on the species, conducting a comprehensive population genomic study. Our analysis results demonstrated a remarkable enhancement in genetic markers. While we identified five different haplotypes defined by five variants within 69 mitochondrial control region sequences, the analysis of 35 whole genome sequences uncovered approximately 12 million single nucleotide polymorphisms (SNPs). Within the Singapore hawksbill turtle population, our whole-genome analysis revealed a pronounced degree of inbreeding, with most samples sharing at least a first cousin relationship. Furthermore, within a multiple-paternity nest, we identified related parents. Additionally, our inference of demographic history underscored the impact of past climate change on the decreasing hawksbill turtle population. We believe this pioneering study will substantially enhance the field of conservation genetic study of marine turtles.
Development and validation of multivariable predictive models for recurrence and mortality following nonoperative management of sigmoid volvulus
Authors: Loria Anthony , Cai Xueya , Gao Shan , Zhao Tony , Juviler Peter , Li Yue , Cupertino Paula , Fleming Fergal J.
Published: December 2023

Aim

Sigmoid volvulus is a challenging condition, and deciding between elective surgery or expectant management can be complex. The aim of this study was to develop a tool for predicting the risk of recurrent sigmoid volvulus and all‐cause mortality within 1 year following initial nonoperative management.

Method

This is a retrospective cohort study using Medicare claims data from 2016 to 2018 of beneficiaries admitted urgently/emergently for volvulus, undergoing colonic decompression and discharged alive without surgery (excluding those discharged to hospice). The primary outcomes were recurrent sigmoid volvulus and all‐cause mortality within 1 year. Proportional hazards models and logistic regression were employed to identify risk factors and develop prediction equations, which were subsequently validated.

Results

Among the 2078 patients managed nonoperatively, 36.1% experienced recurrent sigmoid volvulus and 28.6% died within 1 year. The prediction model for recurrence integrated age, sex, race, palliative care consultations and four comorbidities, achieving area under the curve values of 0.63 in both the training and testing samples. The model for mortality incorporated age, palliative care consultations and nine comorbidities, with area under the curve values of 0.76 in the training and 0.70 in the testing sample.

Conclusion

This study provides a straightforward predictive tool that utilizes easily accessible data to estimate individualized risks of recurrent sigmoid volvulus and all‐cause mortality for older adults initially managed nonoperatively. The tool can assist clinicians and patients in making informed decisions about such risks. While the accuracy of the calculator was validated, further confirmation through external validation and prospective studies would enhance its clinical utility.
Down‐regulation of miR‐21‐5p by pirfenidone to inhibit fibroblast proliferation in the treatment of acquired tracheal stenosis
Authors: Li Wentao , Huang Pingping , Wei Jinmei , Tan Sen , Liu Guangnan , Yang Qiu , Wang Guangfa
Published: December 2023

Objective

Treatment options for acquired tracheal stenosis (ATS) are limited due to a series of pathophysiological changes including inflammation and cell proliferation. Micro ribonucleic acid‐21‐5p (miR‐21‐5p) may promote the excessive proliferation of fibroblasts. However, various types of fibrosis can be prevented with pirfenidone (PFD). Currently, the effect of PFD on miR‐21‐5p and its biological function has not been clarified. In this study, PFD was evaluated as a potential treatment for ATS by inducing fibroblast proliferation in lipopolysaccharide (LPS)‐induced fibroblasts by targeting miR‐21‐5p.

Methods

For 48 h, 1 g/ml LPS was used to generate fibroblasts in vitro, followed by the separation of cells into four groups: control, PFD, mimic, and mimic + PFD. The Cell Counting Kit‐8 (CCK‐8) technique was adopted to measure the proliferation of fibroblasts. Real‐time quantitative polymerase chain reaction (RT‐qPCR) and Western blot (WB) were used to measure the relative expressions of tumor necrosis factor‐α (TNF‐α), transforming growth factor‐β1 (TGF‐β1), drosophila mothers against decapentaplegic 7 (Smad7) and collagen type I alpha 1(COL1A1) messenger RNA (mRNA) and proteins, respectively.

Results

(1) At 0, 24, 48, and 72 h, fibroblast growth was assessed using the CCK‐8 method. Compared with the control group, the mimic group showed the highest fibroblast viability, and the PFD group showed the lowest fibroblast viability. However, fibroblast viability increased in the mimic + PFD group but decreased in the mimic one. (2) RT‐qPCR and WB showed that the mimic group exhibited a significant up‐regulation in the relative expressions of TNF‐α, TGF‐β1, and COL1A1 mRNA and proteins but a down‐regulation in the relative expression of Smad7 mRNA and protein compared with the control one. In the PFD group, the results were the opposite. Nevertheless, the relative expressions of TNF‐α, TGF‐β1, and COL1A1 mRNA and proteins were increased, whereas that of Smad7 mRNA was decreased in the mimic + PFD group. The change was less in the mimic group.

Conclusion

PFD may have a preventive and curative effect on ATS by inhibiting fibroblast proliferation and the fibrotic process and possibly through down‐regulating miR‐21‐5p and up‐regulating Smad7 and its mediated fibrotic and inflammatory responses.
A meta‐analysis examining the impact of intrawound treatment on reducing deep surgical site infections during instrumented spine surgery
Authors: Zhou Liqiang , Xing Shuxing
Published: December 2023

The purpose of the meta‐analysis was to evaluate and compare the effect of intrawound management on decreasing deep surgical site infections (SSIs) in instrumented spinal surgery (SS). The results of this meta‐analysis were analysed, and the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random or fixed effect models. For the current meta‐analysis, 29 examinations spanning from 2006 to 2022 were included, encompassing 11 181 people who had instrumented SS. Intrawound management had a significantly lower deep SSI when using vancomycin (OR, 0.34; 95% CI, 0.25–0.44, p < 0.001) and povidone‐iodine as intrawound management (OR, 0.24; 95% CI, 0.13–0.42, p < 0.001) compared to control in instrumented SS subjects. The data that was looked at showed that using vancomycin and povidone‐iodine as intrawound management had a much lower deep SSI than using a control group of instrumented SS subjects. However, given that some studies included a small number of subjects, attention should be given to their values.
Repeated-Sprint Training With Blood-Flow Restriction Improves Repeated-Sprint Ability Similarly to Unrestricted Training at Reduced External Loads
Authors: Mckee James R. , Girard Olivier , Peiffer Jeremiah J. , Hiscock Daniel J. , De Marco Kristen , Scott Brendan R.
Published: December 2023

Purpose: This study examined performance and physiological adaptations following 3 weeks of repeated-sprint training (RST) with blood-flow restriction (BFR) or without (non-BFR). Methods: Twenty-six semiprofessional and amateur adult male team-sport players were assessed for repeated-sprint ability, anaerobic capacity, leg lean mass, neuromuscular function, and maximal aerobic capacity before and after RST. Participants completed 9 cycling RST sessions (3 sets of 5–7 × 5-s sprints, 25-s passive recovery, 3-min rest) over a 3-week period with BFR or non-BFR. Results: During RST sessions, the BFR group demonstrated lower mean power output compared with non-BFR (−14.5%; g = 1.48; P = .001). Significant improvements (P < .05) in mean and peak power output during repeated-sprint ability (+4.1%; g = 0.42, and + 2.2%; g = 0.25, respectively) and anaerobic capacity (+4.8%; g = 0.47, and + 4.7%; g = 0.32, respectively) tests, leg lean mass (+2.0%; g = 0.16), and peak aerobic power (+3.3%; g = 0.25) were observed from pretesting to posttesting without any between-groups differences. No significant changes (P > .05) were observed for maximal isometric voluntary contraction and maximal aerobic capacity. Peak rate of force development decreased (P = .003) in both groups following RST (−14.6%; g = 0.65), without any between-groups differences. Conclusions: Repeated-sprint ability, anaerobic capacity, leg lean mass, and peak aerobic power improved following 3 weeks of RST; however, the addition of BFR did not further enhance adaptations. Interestingly, comparable improvements were achieved between groups despite lower external loads experienced during RST sessions with BFR.
Supplemental Material: Paleogene mid-crustal intrusions in the Ruby Mountains–East Humboldt Range metamorphic core complex, northeastern Nevada, USA
Authors: Snoke Arthur W. , al. et
Published: December 2023

File S1: Mineral analyses (amphibole, biotite, and plagioclase). File S2: SHRIMP-RG U-Pb data. File S3: LA-MC-ICP-MS age data and LA-Q-ICP-MS trace-element data with methods. File S4: LA-MC-ICP-MS Hf isotope (zircon) data. File S5: Supporting data and images for zircon geochronology. File S6: 40Ar/39Ar data on hornblende and biotite. File S7: Bulk-rock Sr, Nd, and Pb isotope data. File S8: Oxygen isotope values of quartz and bulk rocks with methods. Whole-rock chemical analyses of rocks of the middle to late Eocene and early Oligocene monzogranitic suite. Refer to U.S. Geological Survey Data Series 244 (du Bray et al., 2007).
Preterm Infant Care Practice among Nurses in Neonatal Care Units of Selected Hospitals of Nepal: A Cross-Sectional Study
Authors: Shrestha Tumla , Bista Archana Pandey , Shrestha Sarala , Regmi Radhika
Published: December 2023

Introduction. Preterm infants (PTIs) are vulnerable to morbidity, disability, and mortality. They require meticulous care for survival and development in neonatal care units (NCUs). PTI care in NCUs is a collaborative and team effort among different health professionals. However, nurses have a key role for quality care. This study aimed to assess nurses’ PTI care practices across different hospitals in Nepal. Methods. A descriptive cross-sectional study was conducted in NCUs of six randomly selected public hospitals in Nepal. After obtaining ethical approval, structured observation was completed among 40 NCU nurses using a practice checklist. After observation, a self-report questionnaire was administered among 102 nurses. Both descriptive and inferential statistics were used for data analysis. Results. The observation and self-reported mean infant care practices were 73.7% and 70.7%, respectively. The overall practice median score and the interquartile range (IQR) were 4.0 (3.5–4.3) with the highest score of (4.5 [4.1–4.7]) for daily supportive care and the lowest score of (2.8 [2.1–3.5]) for pain management. The care practice was strongly associated with the nurse-infant ratio (adjusted odd ratio (aOR) = 18.52, confidence interval (CI) = 5.83–58.77, and p=<0.001) and training status (aOR = 4.95, CI = 1.59–15.39, and p=0.006). Conclusion. Nurses have adequate practice of thermal care, safe oxygen administration, nutritional care, and infection prevention in NCUs, whereas lacking is found regarding developmental supportive care components (sleep promotion and a supportive sensory environment), parental support, and pain management practices. Consideration of the proper nurse-infant ratio and continued professional development opportunities are essential for practice enhancement in NCUs. These findings might be useful to identify the gaps in PTI care practice in NCUs.