bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study
Authors: Hoertel N. , Sánchez-Rico M. , Gulbins E. , Kornhuber J. , Vernet R. , Beeker N. , Neuraz A. , Blanco C. , Olfson M. , Airagnes G. , Lemogne C. , Alvarado J. M. , Arnaout M. , Cougoule C. , Meneton P. , Limosin F. 
Published: March 2022

Abstract

Aims
To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19).

Methods
A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19. A total of 686 (4.8%) inpatients received a BZRA at hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (standard deviation (s.d.) = 25.4). The study baseline was the date of admission, and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, medical comorbidities and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW).

Results
Over a mean follow-up of 14.5 days (s.d. = 18.1), the primary endpoint occurred in 186 patients (27.1%) who received BZRAs and in 1134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (hazard ratio (HR) = 3.20; 95% confidence interval (CI) = 2.74–3.74; p < 0.01) and in the IPW analysis (HR = 1.61; 95% CI = 1.31–1.98, p < 0.01), with a significant dose-dependent relationship (HR = 1.55; 95% CI = 1.08–2.22; p = 0.02). This association remained significant in sensitivity analyses. Exploratory analyses indicate that most BZRAs may be associated with an increased mortality among patients hospitalised for COVID-19, except for diazepam, which may be associated with a reduced mortality compared with any other BZRA treatment.

Conclusions
BZRA use may be associated with an increased mortality among patients hospitalised for COVID-19, suggesting the potential benefit of decreasing dose or tapering off gradually these medications when possible.
Future Changes of Atmospheric Energy Cycle in CMIP5 Climate Models
Authors: Kanno Yuki , Iwasaki Toshiki 
Published: March 2022

AbstractFuture changes in the atmospheric energy cycle were estimated by using 12 climate models from the fifth phase of the Coupled Model Intercomparison Project (CMIP5) and mass‐weighted isentropic zonal‐mean framework. In this framework, the zonal‐mean available potential energy (AZ) is converted to the zonal‐mean kinetic energy (KZ) through mean‐meridional direct circulations, and KZ is converted to the wave energy (W), the sum of eddy available potential energy and eddy kinetic energy, through wave‐mean flow interactions. The comparison between the late 21st century in a high emission scenario and the late 20th century in the historical scenario indicates a significant increase in AZ and KZ in winter in the Northern Hemisphere (NH) and the Southern Hemisphere (SH). The wave energy significantly decreases in the NH winter but slightly increases in the SH winter. In the NH winter, the stationary wave energy significantly decreases, and the transient wave energy shifts poleward. Global warming reduces the baroclinic instability wave activity, which suppresses the upward Eliassen‐Palm flux and wave‐induced extratropical direct circulation. It decreases the dynamic energy conversion rates C(AZ, KZ) and C(KZ, W). On the other hand, the diabatic wave energy generation rate (QE) is projected to increase, particularly in the SH. The future W change is consistent with the change in the sum of C(KZ, W) and QE. Changes in both the dynamical energy conversion associated with wave‐mean flow interactions and the generation of eddy available potential energy associated with diabatic heating processes are necessary to explain the wave energy change.
Measurement Characterization of Band‐Pass NGD Time Domain of a 101O‐Topology Passive Circuit
Authors: Zhou Xiang , Gu Zhaoyuan , Ji Qizheng , Hu Xiaofeng , Vauché Rémy , Haddad Fayrouz , Murad Nour Mohammad , Frnda Jaroslav , Rahajandraibe Wenceslas , Wan Fayu , Ravelo Blaise 
Published: March 2022

AbstractThe negative group delay (NGD) is one of less familiar electronic functions. So far, the time domain (TD) experimentation of NGD circuits remains a challenging task. This paper investigates an innovative TD measurement of a band‐pass (BP) NGD passive circuit. The topology of the considered BP NGD distributed circuit constituted by transmission line structure having a 101O‐geometrical shape is introduced. After the design description of the 101O‐structure, the NGD response illustrates from simulation and measurement based on S‐parameters. The NGD center frequency, bandwidth, and value are approximately 3.6 GHz, 33 MHz, and −4.9 ns, respectively. The TD measurement experimentation is based on the sine carrier‐modulated microwave signal generation with 50‐ns duration. The 101O‐NGD circuit input and output signals are plotted with innovative synchronization. It was shown from the TD‐simulated and measured results that the BP NGD effect induces an output envelope about 4.2 ns advanced of the test signal input.
Digital plasmonic nanobubble detection for rapid and ultrasensitive virus diagnostics
Authors: Liu Yaning , Ye Haihang , Huynh HoangDinh , Xie Chen , Kang Peiyuan , Kahn Jeffrey S. , Qin Zhenpeng 
Published: March 2022

AbstractRapid and sensitive diagnostics of infectious diseases is an urgent and unmet need as evidenced by the COVID-19 pandemic. Here, we report a strategy, based on DIgitAl plasMONic nanobubble Detection (DIAMOND), to address this need. Plasmonic nanobubbles are transient vapor bubbles generated by laser heating of plasmonic nanoparticles (NPs) and allow single-NP detection. Using gold NPs as labels and an optofluidic setup, we demonstrate that DIAMOND achieves compartment-free digital counting and works on homogeneous immunoassays without separation and amplification steps. DIAMOND allows specific detection of respiratory syncytial virus spiked in nasal swab samples and achieves a detection limit of ~100 PFU/mL (equivalent to 1 RNA copy/µL), which is competitive with digital isothermal amplification for virus detection. Therefore, DIAMOND has the advantages including one-step and single-NP detection, direct sensing of intact viruses at room temperature, and no complex liquid handling, and is a platform technology for rapid and ultrasensitive diagnostics.
DLMM as a lossless one-shot algorithm for collaborative multi-site distributed linear mixed models
Authors: Luo Chongliang , Islam Md. Nazmul , Sheils Natalie E. , Buresh John , Reps Jenna , Schuemie Martijn J. , Ryan Patrick B. , Edmondson Mackenzie , Duan Rui , Tong Jiayi , Marks-Anglin Arielle , Bian Jiang , Chen Zhaoyi , Duarte-Salles Talita , Fernández-Bertolín Sergio , Falconer Thomas , Kim Chungsoo , Park Rae Woong , Pfohl Stephen R. , Shah Nigam H. , Williams Andrew E. , Xu Hua , Zhou Yujia , Lautenbach Ebbing , Doshi Jalpa A. , Werner Rachel M. , Asch David A. , Chen Yong 
Published: March 2022

AbstractLinear mixed models are commonly used in healthcare-based association analyses for analyzing multi-site data with heterogeneous site-specific random effects. Due to regulations for protecting patients’ privacy, sensitive individual patient data (IPD) typically cannot be shared across sites. We propose an algorithm for fitting distributed linear mixed models (DLMMs) without sharing IPD across sites. This algorithm achieves results identical to those achieved using pooled IPD from multiple sites (i.e., the same effect size and standard error estimates), hence demonstrating the lossless property. The algorithm requires each site to contribute minimal aggregated data in only one round of communication. We demonstrate the lossless property of the proposed DLMM algorithm by investigating the associations between demographic and clinical characteristics and length of hospital stay in COVID-19 patients using administrative claims from the UnitedHealth Group Clinical Discovery Database. We extend this association study by incorporating 120,609 COVID-19 patients from 11 collaborative data sources worldwide.
Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma
Authors: Prummel Karin D. , Crowell Helena L. , Nieuwenhuize Susan , Brombacher Eline C. , Daetwyler Stephan , Soneson Charlotte , Kresoja-Rakic Jelena , Kocere Agnese , Ronner Manuel , Ernst Alexander , Labbaf Zahra , Clouthier David E. , Firulli Anthony B. , Sánchez-Iranzo Héctor , Naganathan Sundar R. , O’Rourke Rebecca , Raz Erez , Mercader Nadia , Burger Alexa , Felley-Bosco Emanuela , Huisken Jan , Robinson Mark D. , Mosimann Christian 
Published: March 2022

AbstractThe mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered onhand2in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most,hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafishhand2reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally,hand2loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies.
Integrating central nervous system metagenomics and host response for diagnosis of tuberculosis meningitis and its mimics
Authors: Ramachandran P. S. , Ramesh A. , Creswell F. V. , Wapniarski A. , Narendra R. , Quinn C. M. , Tran E. B. , Rutakingirwa M. K. , Bangdiwala A. S. , Kagimu E. , Kandole K. T. , Zorn K. C. , Tugume L. , Kasibante J. , Ssebambulidde K. , Okirwoth M. , Bahr N. C. , Musubire A. , Skipper C. P. , Fouassier C. , Lyden A. , Serpa P. , Castaneda G. , Caldera S. , Ahyong V. , DeRisi J. L. , Langelier C. , Crawford E. D. , Boulware D. R. , Meya D. B. , Wilson M. R. 
Published: March 2022

AbstractThe epidemiology of infectious causes of meningitis in sub-Saharan Africa is not well understood, and a common cause of meningitis in this region, Mycobacterium tuberculosis (TB), is notoriously hard to diagnose. Here we show that integrating cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) with a host gene expression-based machine learning classifier (MLC) enhances diagnostic accuracy for TB meningitis (TBM) and its mimics. 368 HIV-infected Ugandan adults with subacute meningitis were prospectively enrolled. Total RNA and DNA CSF mNGS libraries were sequenced to identify meningitis pathogens. In parallel, a CSF host transcriptomic MLC to distinguish between TBM and other infections was trained and then evaluated in a blinded fashion on an independent dataset. mNGS identifies an array of infectious TBM mimics (and co-infections), including emerging, treatable, and vaccine-preventable pathogens including Wesselsbron virus, Toxoplasma gondii, Streptococcus pneumoniae, Nocardia brasiliensis, measles virus and cytomegalovirus. By leveraging the specificity of mNGS and the sensitivity of an MLC created from CSF host transcriptomes, the combined assay has high sensitivity (88.9%) and specificity (86.7%) for the detection of TBM and its many mimics. Furthermore, we achieve comparable combined assay performance at sequencing depths more amenable to performing diagnostic mNGS in low resource settings.
Fabrication of X-ray absorption gratings by centrifugal deposition of bimodal tungsten particles in high aspect ratio silicon templates
Authors: Pinzek Simon , Gustschin Alex , Gustschin Nikolai , Viermetz Manuel , Pfeiffer Franz 
Published: March 2022

AbstractGrating-based X-ray imaging employs high aspect ratio absorption gratings to generate contrast induced by attenuating, phase-shifting, and small-angle scattering properties of the imaged object. The fabrication of the absorption gratings remains a crucial challenge of the method on its pathway to clinical applications. We explore a simple and fast centrifugal tungsten particle deposition process into silicon-etched grating templates, which has decisive advantages over conventional methods. For that, we use a bimodal tungsten particle suspension which is introduced into a custom designed grating holder and centrifuged at over 1000×g. Gratings with 45 µm period, 450 µm depth, and 170 mm × 38 mm active area are successfully processed reaching a homogeneous absorber filling. The effective absorbing tungsten thickness in the trenches is 207 µm resulting in a filling ratio of 46.6% compared to a voidless filling. The grating was tested in a Talbot–Lau interferometer designed for clinical X-ray dark-field computed tomography, where visibilities up to 33.6% at 60 kV were achieved.
Resting state fast brain dynamics predict interindividual variability in motor performance
Authors: Roshchupkina Liliia , Wens Vincent , Coquelet Nicolas , de Tiege Xavier , Peigneux Philippe 
Published: March 2022

AbstractMotor learning features rapid enhancement during practice then offline post-practice gains with the reorganization of related brain networks. We hypothesised that fast transient, sub-second variations in magnetoencephalographic (MEG) network activity during the resting-state (RS) reflect early learning-related plasticity mechanisms and/or interindividual motor variability in performance. MEG RS activity was recorded before and 20 min after motor learning. Hidden Markov modelling (HMM) of MEG power envelope signals highlighted 8 recurrent topographical states. For two states, motor performance levels were associated with HMM temporal parameters both in pre- and post-learning resting-state sessions. However, no association emerged with offline changes in performance. These results suggest a trait-like relationship between spontaneous transient neural dynamics at rest and interindividual variations in motor abilities. On the other hand, transient RS dynamics seem not to be state-dependent, i.e., modulated by learning experience and reflect neural plasticity, at least on the short timescale.
First evidence for backcrossing of F1 hybrids in Acropora corals under sperm competition
Authors: Kitanobo Seiya , Iwao Kenji , Fukami Hironobu , Isomura Naoko , Morita Masaya 
Published: March 2022

AbstractAcropora is a species-rich genus of reef-building corals with highly diverse morphologies. Hybridization among intercrossing species potentially influences species diversity within Acropora. However, the mechanisms that allow hybridization/backcrossing remain unknown. Although we tested a limited number of species, we hypothesized that Acropora gametes in the Indo-Pacific may preferentially fertilize conspecific gametes despite their compatibility with heterospecific gametes, leading to infrequent hybridization between potentially intercrossing species. In this study, F1 hybrids of Acropora florida and A. intermedia showed specific fertilization trends. For example, sperm had the ability to backcross with the parental species even in the presence of sperm from the parental species. Also, eggs of the hybrids produced from A. florida eggs and A. intermedia sperm (“FLOint”) exhibited self-fertilization. Since a low ratio of hybridization between A. florida and A. intermedia is predicted, the population size of hybrids should be small. Therefore, self-fertilization would facilitate reproduction of the hybrid in nature, while remaining sperm could outcompete parental species sperm to backcross with eggs. Although we succeeded in breeding two colonies of hybrids, it is reasonable to speculate that hybrids show a high tendency to choose the most efficient sexual reproduction tactics.
Mutations of the DNA repair gene PNKP in a patient with microcephaly, seizures, and developmental delay (MCSZ) presenting with a high-grade brain tumor
Authors: Jiang Bingcheng , Murray Cameron , Cole Bonnie L. , Glover J. N. Mark , Chan Gordon K. , Deschenes Jean , Mani Rajam S. , Subedi Sudip , Nerva John D. , Wang Anthony C. , Lockwood Christina M. , Mefford Heather C. , Leary Sarah E. S. , Ojemann Jeffery G. , Weinfeld Michael , Ene Chibawanye I. 
Published: March 2022

AbstractPolynucleotide Kinase-Phosphatase (PNKP) is a bifunctional enzyme that possesses both DNA 3′-phosphatase and DNA 5′-kinase activities, which are required for processing termini of single- and double-strand breaks generated by reactive oxygen species (ROS), ionizing radiation and topoisomerase I poisons. Even though PNKP is central to DNA repair, there have been no reports linking PNKP mutations in a Microcephaly, Seizures, and Developmental Delay (MSCZ) patient to cancer. Here, we characterized the biochemical significance of 2 germ-line point mutations in the PNKP gene of a 3-year old male with MSCZ who presented with a high-grade brain tumor (glioblastoma multiforme) within the cerebellum. Functional and biochemical studies demonstrated these PNKP mutations significantly diminished DNA kinase/phosphatase activities, altered its cellular distribution, caused defective repair of DNA single/double stranded breaks, and were associated with a higher propensity for oncogenic transformation. Our findings indicate that specific PNKP mutations may contribute to tumor initiation within susceptible cells in the CNS by limiting DNA damage repair and increasing rates of spontaneous mutations resulting in pediatric glioma associated driver mutations such as ATRX and TP53.
Acoustic levitation and rotation of thin films and their application for room temperature protein crystallography
Authors: Kepa Michal. W. , Tomizaki Takashi , Sato Yohei , Ozerov Dmitry , Sekiguchi Hiroshi , Yasuda Nobuhiro , Aoyama Koki , Skopintsev Petr , Standfuss Jörg , Cheng Robert , Hennig Michael , Tsujino Soichiro 
Published: March 2022

AbstractAcoustic levitation has attracted attention in terms of chemical and biochemical analysis in combination with various analytical methods because of its unique container-less environment for samples that is not reliant on specific material characteristics. However, loading samples with very high viscosity is difficult. To expand the scope, we propose the use of polymer thin films as sample holders, whereby the sample is dispensed on a film that is subsequently loaded onto an acoustic levitator. When applied for protein crystallography experiments, rotation controllability and positional stability are important prerequisites. We therefore study the acoustic levitation and rotation of thin films with an aspect ratio (the diameter-to-thickness ratio) of 80–240, which is an order of magnitude larger than those reported previously. For films with empirically optimized shapes, we find that it is possible to control the rotation speed in the range of 1–4 rotations per second while maintaining a positional stability of 12 ± 5 µm. The acoustic radiation force acting on the films is found to be a factor of 26–30 higher than that for same-volume water droplets. We propose use cases of the developed films for protein crystallography experiments and demonstrate data collections for large single crystal samples at room temperature.
Impact of recording length and other arrhythmias on atrial fibrillation detection from wrist photoplethysmogram using smartwatches
Authors: Liao Min-Tsun , Yu Chih-Chieh , Lin Lian-Yu , Pan Ke-Han , Tsai Tsung-Hsien , Wu Yu-Chun , Liu Yen-Bin 
Published: March 2022

AbstractThis study aimed to evaluate whether quantitative analysis of wrist photoplethysmography (PPG) could detect atrial fibrillation (AF). Continuous electrocardiograms recorded using an electrophysiology recording system and PPG obtained using a wrist-worn smartwatch were simultaneously collected from patients undergoing catheter ablation or electrical cardioversion. PPG features were extracted from 10, 25, 40, and 80 heartbeats of the split segments. Machine learning with a support vector machine and random forest approach were used to detect AF. A total of 116 patients were evaluated. We annotated > 117 h of PPG. A total of 6475 and 3957 segments of 25-beat pulse-to-pulse intervals (PPIs) were annotated as AF and sinus rhythm, respectively. The accuracy of the 25 PPIs yielded a test area under the receiver operating characteristic curve (AUC) of 0.9676, which was significantly better than the AUC for the 10 PPIs (0.9453; P < .001). PPGs obtained from another 38 patients with frequent premature ventricular/atrial complexes (PVCs/PACs) were used to evaluate the impact of other arrhythmias on diagnostic accuracy. The new AF detection algorithm achieved an AUC of 0.9680. The appropriate data length of PPG for optimizing the PPG analytics program was 25 heartbeats. Algorithm modification using a machine learning approach shows robustness to PVCs/PACs.
Structural insights into the substrate-bound condensation domains of non-ribosomal peptide synthetase AmbB
Authors: Chu Yuan Kee Melissa-Jane , Bharath Sakshibeedu R. , Wee Sheena , Bowler Matthew W. , Gunaratne Jayantha , Pan Shenquan , Zhang Lianhui , Song Haiwei 
Published: March 2022

AbstractNon-ribosomal peptide synthetases (NRPS) are multi-modular/domain enzymes that catalyze the synthesis of bioactive peptides. A crucial step in the process is peptide elongation accomplished by the condensation (C) domain with the aid of a peptidyl carrier or thiolation (T) domain. Here, we examined condensation reaction carried out by NRPS AmbB involved in biosynthesis of l-2-amino-4-methoxy-trans-3-butenoic acid (AMB) in P. aeruginosa. We determined crystal structures of the truncated T–C bidomain of AmbB in three forms, the apo enzyme with disordered T domain, the holo form with serine linked phosphopantetheine (Ppant) and a holo form with substrate (l-alanine) loaded onto Ppant. The two holo forms feature the T domain in a substrate-donation conformation. Mutagenesis combined with functional assays identified residues essential for the attachment of Ppant, anchoring the Ppant-l-Ala in the donor catalytic channel and the role of the conserved His953 in condensation activity. Altogether, these results provide structural insights into the condensation reaction at the donor site with a substrate-bound C domain of AmbB and lay the foundation for understanding the molecular mechanism of condensation which is crucial for AMB synthesis.