bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferring the heritability of bacterial traits in the era of machine learning
Authors: Mai T Tien , Lees John A , Gladstone Rebecca A , Corander Jukka 
Published: March 2023

Abstract Quantification of heritability is a fundamental desideratum in genetics, which allows an assessment of the contribution of additive genetic variation to the variability of a trait of interest. The traditional computational approaches for assessing the heritability of a trait have been developed in the field of quantitative genetics. However, the rise of modern population genomics with large sample sizes has led to the development of several new machine learning-based approaches to inferring heritability. In this article, we systematically summarize recent advances in machine learning which can be used to infer heritability. We focus on an application of these methods to bacterial genomes, where heritability plays a key role in understanding phenotypes such as antibiotic resistance and virulence, which are particularly important due to the rising frequency of antimicrobial resistance. By designing a heritability model incorporating realistic patterns of genome-wide linkage disequilibrium for a frequently recombining bacterial pathogen, we test the performance of a wide spectrum of different inference methods, including also GCTA. In addition to the synthetic data benchmark, we present a comparison of the methods for antibiotic resistance traits for multiple bacterial pathogens. Insights from the benchmarking and real data analyses indicate a highly variable performance of the different methods and suggest that heritability inference would likely benefit from tailoring of the methods to the specific genetic architecture of the target organism.Availability and implementationThe R codes and data used in the numerical experiments are available at: https://github.com/tienmt/her_MLs.
‘Synergistic selection’: a cooperative model of evolution
Authors: Corning Peter A 
Published: March 2023

AbstractMany developments over the past few decades have undermined the central tenets of the so-called ‘Modern Synthesis’ in evolutionary biology—including its narrow focus on genetic mutations and other molecular level factors as a prime source of innovation in evolution and a deeply competitive model of biological change. It is now apparent that cooperative (synergistic) effects of various kinds, at all ‘levels’ of living systems, have played a major causal role in shaping the overall trajectory of life on Earth, and that living systems themselves have been purposeful participants (‘agents’) and co-developers in this process.
Freshwater protected areas can preserve high-performance phenotypes in populations of a popular sportfish
Authors: Zolderdo A J , Abrams A E I , Lawrence M J , Reid C H , Suski C D , Gilmour K M , Cooke S J 
Published: March 2023

Abstract
Recreational fishing has the potential to cause evolutionary change in fish populations; a phenomenon referred to as fisheries-induced evolution. However, detecting and quantifying the magnitude of recreational fisheries selection in the wild is inherently difficult, largely owing to the challenges associated with variation in environmental factors and, in most cases, the absence of pre-selection or baseline data against which comparisons can be made. However, exploration of recreational fisheries selection in wild populations may be possible in systems where fisheries exclusion zones exist. Lakes that possess intra-lake freshwater protected areas (FPAs) can provide investigative opportunities to evaluate the evolutionary impact(s) of differing fisheries management strategies within the same waterbody. To address this possibility, we evaluated how two physiological characteristics (metabolic phenotype and stress responsiveness) as well as a proxy for angling vulnerability, catch-per-unit-effort (CPUE), differed between populations of largemouth bass (Micropterus salmoides) inhabiting long-standing (&gt;70 years active) intra-lake FPAs and adjacent, open access, main-lake areas. Fish from FPA populations had significantly higher aerobic scope (AS) capacity (13%) and CPUE rates compared with fish inhabiting the adjacent main-lake areas. These findings are consistent with theory and empirical evidence linking exploitation with reduced metabolic performance, supporting the hypothesis that recreational fishing may be altering the metabolic phenotype of wild fish populations. Reductions in AS are concerning because they suggest a reduced scope for carrying out essential life-history activities, which may result in fitness level implications. Furthermore, these results highlight the potential for unexploited FPA populations to serve as benchmarks to further investigate the evolutionary consequences of recreational fishing on wild fish and to preserve high-performance phenotypes.
The potential of dynamic 99mTc-sestamibi cadmium zinc telluride-single-photon emission computed tomography camera assessing myocardial flow reserve in patients with heart failure with preserved ejection fraction
Authors: Yoshida Satoya , Unno Kazumasa , Nanasato Mamoru , Niimi Takanaga , Inukai Kohei , Morisaki Hidenori , Hattori Tomoki , Hirose Miku , Hayashi Takumi , Uchida Noriya , Simoda Masahiro , Oishi Hideo , Ando Monami , Hirayama Kenshi , Takenaka Masaki , Maeda Mayuho , Yoshida Ruka , Ogura Yasuhiro , Suzuki Hirohiko , Furusawa Kenji , Morimoto Ryota , Kato Katsuhiko , Isobe Satoshi , Yoshida Yukihiko , Murohara Toyoaki 
Published: March 2023

AbstractAimsCoronary microvascular dysfunction (CMD) is related to the pathophysiology, mortality, and morbidity of heart failure with preserved ejection fraction (HFpEF). A novel single-photon emission computed tomography (SPECT) camera with cadmium zinc telluride (CZT) detectors allows for the quantification of absolute myocardial blood flow and myocardial flow reserve (MFR) in patients with coronary artery disease. However, the potential of CZT-SPECT assessing for CMD has never been evaluated in patients with HFpEF.Methods and resultsThe clinical records of 127 consecutive patients who underwent dynamic CZT-SPECT were retrospectively reviewed. Rest and stress scanning were started simultaneously with 3 and 9 MBq/kg of 99mTc-sestamibi administration, respectively. Dynamic CZT-SPECT imaging data were analysed using a net-retention model with commercially available software. Transthoracic echocardiography was performed in all patients. The MFR value was significantly lower in the HFpEF group (mean ± SEM = 2.00 ± 0.097) than that in the non-HFpEF group (mean ± SEM = 2.74 ± 0.14, P = 0.0004). A receiver operating characteristic analysis indicated that if a cut-off value of 2.525 was applied, MFR could efficiently distinguish HFpEF from non-HFpEF. Heart failure with preserved ejection fraction had a consistently low MFR, regardless of the diastolic dysfunction score. Heart failure with preserved ejection fraction patients with MFR values lower than 2.075 had a significantly higher incidence of heart failure exacerbation.ConclusionMyocardial flow reserve assessed by CZT-SPECT was significantly reduced in patients with HFpEF. A lower MFR was associated with a higher hospitalization rate in these patients. Myocardial flow reserve assessed by CZT-SPECT has the potential to predict future adverse events and stratify the severity of disease in patients with HFpEF.
Upper gastrointestinal bleeding in adults treated with veno-arterial extracorporeal membrane oxygenation: a cohort study
Authors: Stern Jules , Dupuis Claire , Kpeglo Hervé , Reuter Jean , Vinclair Camille , Para Marylou , Nataf Patrick , Pelletier Anne-Laure , de Montmollin Etienne , Bouadma Lila , Timsit Jean-François , Sonneville Romain 
Published: March 2023

AbstractOBJECTIVESUpper gastrointestinal bleeding (UGIB) is a common complication in adults treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock or cardiac arrest. We aimed to determine risk factors, prevalence and outcomes associated with VA-ECMO-associated UGIB in adult patients.METHODSWe conducted a retrospective cohort study (2014–2022) on consecutive VA-ECMO patients in the medical and infectious disease intensive care unit of Bichat-Claude Bernard University Hospital, Paris, France. UGIB was defined as (i) an overt bleeding (haematemesis, melena, haematochezia) or (ii) acute anaemia associated with a lesion diagnosed on upper gastrointestinal endoscopy. VA-ECMO-associated UGIB was defined as an UGIB occurring during VA-ECMO, or up to 10 days after decannulation in patients weaned off extracorporeal membrane oxygenation (ECMO). Cause-specific models were used to identify factors associated with UGIB and death, respectively.RESULTSAmong the 455 patients included, 48 (10%) were diagnosed with UGIB after a median of 12 [7; 23] days following ECMO cannulation. Mortality occurred in 36 (75%) patients with UGIB and 243 (60%) patients without. UGIB patients had longer intensive care unit stays (32 [19; 60] vs 18 [7; 37] days; P &lt; 0.01), longer ECMO (14 [9; 18] vs 7 [4; 11] days; P &lt; 0.01) and mechanical ventilation durations (21 [16; 36] vs 10 [5; 20] days; P &lt; 0.01), as compared to non-UGIB patients. Ninety upper gastrointestinal endoscopies were performed, and the most frequent lesions detected were gastro-duodenal ulcers (n = 23, 26%), leading to 11/90 therapeutic procedures. By multivariable analysis, a history of peptic ulcer [cause-specific hazard ratio (CSHR) 2.93, 95% confidence interval (CI) [1.01; 8.51]], a dual antiplatelet therapy (CSHR 2.0, 95% CI [1.07; 3.72]) and extracorporeal cardiopulmonary resuscitation (CSHR 2.78, 95% CI [1.42; 5.45]) were independently associated with an increased risk of UGIB.CONCLUSIONSIn adult patients under VA-ECMO, a history of gastric ulcer, dual antiplatelet therapy and extracorporeal cardiopulmonary resuscitation were independently associated with an increased risk of UGIB. This study highlights the potential role of acute ischaemia–reperfusion injury in the pathophysiology of VA-ECMO-associated UGIB.
Intrapericardial long non-coding RNA–Tcf21 antisense RNA inducing demethylation administration promotes cardiac repair
Authors: Zhu Dashuai , Liu Shuo , Huang Ke , Li Junlang , Mei Xuan , Li Zhenhua , Cheng Ke 
Published: March 2023

Abstract

Aims
Epicardium and epicardium-derived cells are critical players in myocardial fibrosis. Mesenchymal stem cell–derived extracellular vesicles (EVs) have been studied for cardiac repair to improve cardiac remodelling, but the actual mechanisms remain elusive. The aim of this study is to investigate the mechanisms of EV therapy for improving cardiac remodelling and develop a promising treatment addressing myocardial fibrosis.

Methods and results
Extracellular vesicles were intrapericardially injected for mice myocardial infarction treatment. RNA-seq, in vitro gain- and loss-of-function experiments, and in vivo studies were performed to identify targets that can be used for myocardial fibrosis treatment. Afterward, a lipid nanoparticle–based long non-coding RNA (lncRNA) therapy was prepared for mouse and porcine models of myocardial infarction treatment. Intrapericardial injection of EVs improved adverse myocardial remodelling in mouse models of myocardial infarction. Mechanistically, Tcf21 was identified as a potential target to improve cardiac remodelling. Loss of Tcf21 function in epicardium-derived cells caused increased myofibroblast differentiation, whereas forced Tcf21 overexpression suppressed transforming growth factor-β signalling and myofibroblast differentiation. LncRNA–Tcf21 antisense RNA inducing demethylation (TARID) that enriched in EVs was identified to up-regulate Tcf21 expression. Formulated lncRNA–TARID-laden lipid nanoparticles up-regulated Tcf21 expression in epicardium-derived cells and improved cardiac function and histology in mouse and porcine models of myocardial infarction.

Conclusion
This study identified Tcf21 as a critical target for improving cardiac fibrosis. Up-regulating Tcf21 by using lncRNA–TARID-laden lipid nanoparticles could be a promising way to treat myocardial fibrosis. This study established novel mechanisms underlying EV therapy for improving adverse remodelling and proposed a lncRNA therapy for cardiac fibrosis.
Residence in Peripheral Regions and Low Socioeconomic Status Are Associated With Worse Outcomes of Inflammatory Bowel Diseases: A Nationwide Study From the epi-IIRN
Authors: Ledder Oren , Harel Sasha , Lujan Rona , Friss Chagit , Orlanski-Meyer Esther , Yogev Dotan , Loewenberg Weisband Yiska , Greenfeld Shira , Kariv Revital , Lederman Natan , Matz Eran , Schwartz Doron , Focht Gili , Dotan Iris , Turner Dan 
Published: March 2023

Abstract

Background
Timely access to quality medical care impacts patient outcomes in inflammatory bowel disease (IBD). In a nationwide study from the epidemiology group of the Israeli IBD research nucleus we aimed to assess the impact of residence and socioeconomic status (SES) on disease outcomes.

Methods
We utilized data from the 4 health maintenance organizations in Israel, representing 98% of the population. Regions were defined as central, northern and southern; SES was graded from lowest to highest (from 1 to 4) as per Israel Central Bureau of Statistics. The primary outcome was steroid dependency, with secondary outcomes of surgeries and biologic therapy use.

Results
A total of 28 216 IBD patients were included: 15 818 (56%) Crohn’s disease (CD) and 12 398 (44%) ulcerative colitis; 74%, 12% and 14% resided in central, southern, and northern Israel, respectively (SES 1: 21%, SES 4: 12%). Lower SES was associated with steroid dependency (20% in SES 1 vs 12% in SES 4 in CD; P &lt; .001; and 18% vs 12% in ulcerative colitis; P &lt; .001), and higher surgery rates (12% vs 7%; P &lt; .001, and 1.4% vs 0.7%; P = .115, respectively). There were higher steroid dependency and CD surgery rates in peripheral vs central regions. In multivariable models, both SES and peripheral region were independently associated with poorer outcomes.

Conclusions
We found that lower SES and peripheral residence were associated with deleterious outcomes in IBD. This should be considered by policymakers and should encourage strategies for improving outcomes in populations at risk.
Evaluation of a Delta-9-Tetrahydrocannabinol Carboxylic Acid (Δ9-THC-COOH) Immunoassay and a Gas Chromatography–Mass Spectrometry (GC-MS) Method for the Detection of Delta-8-Tetrahydrocannabinol Carboxylic Acid (Δ8-THC-COOH)
Authors: Baird Serena N , Frazee Clinton C , Garg Uttam 
Published: March 2023

Abstract

Background
Delta-8 tetrahydrocannabinol (Δ8-THC) is a naturally occurring or synthetically prepared cannabinoid that elicits psychological and physiological experiences commonly reported for its more infamous isomer, delta-9 tetrahydrocannabinol (Δ9-THC). Unlike Δ9-THC, Δ8-THC products are generally legal under federal law and there has been a rise in their usage. One of the main targets for detection and quantitation of Δ9-THC is its inactive metabolite, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THC-COOH).

Methods
This study evaluated the ability of the currently used Δ9-THC-COOH immunoassay and gas chromatography–mass spectrometry (GC-MS) methods to detect 11-nor-9-carboxy-Δ8-tetrahydrocannabinol (Δ8-THC-COOH) and distinguish it from Δ9-THC-COOH.

Results
The EMIT II Plus® Cannabinoid immunoassay for Δ9-THC-COOH with a cutoff of 20 ng/mL showed positive results for Δ8-THC-COOH with concentrations of 30 ng/mL or higher. Although many of the ion fragments generated by mass spectrometry were found to overlap between the 2 compounds, the GC-MS method presently used to quantify Δ9-THC-COOH separated the 2 compounds sufficiently to identify them independently by relative retention time.

Conclusion
Current immunoassays and GC-MS methods should be evaluated for the ability to detect and distinguish the presence of Δ8-THC-COOH.
CRISPR-Cas12a-based genome editing and transcriptional repression for biotin synthesis inPseudomonas mutabilis
Authors: Zhao Jiarun , Zuo Siqi , Huang Lei , Lian Jiazhang , Xu Zhinan 
Published: March 2023

AbstractAimsTo establish a dual-function clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a system combined genome editing and transcriptional repression for multiplex metabolic engineering of Pseudomonas mutabilis.Materials and resultsThis CRISPR-Cas12a system consisted of two plasmids that enabled single gene deletion, replacement, and inactivation with efficiency &gt;90% for most targets within 5 days. With the guidance of truncated crRNA containing 16 bp spacer sequences, a catalytically active Cas12a could be employed to repress the expression of the reporter gene eGFP up to 66.6%. When bdhA deletion and eGFP repression were tested simultaneously by transforming a single crRNA plasmid and Cas12a plasmid, the knockout efficiency reached 77.8% and the expression of eGFP was decreased by &gt;50%. Finally, the dual-functional system was demonstrated to increase the production of biotin by 3.84-fold, with yigM deletion and birA repression achieved simultaneously.ConclusionsThis CRISPR-Cas12a system is an efficient genome editing and regulation tool to facilitate the construction of P. mutabilis cell factories.
The pharmacological mechanism of Xiaoyaosan polysaccharide reveals improvement of CUMS-induced depression-like behavior by carbon source-triggered butyrate-producing bacteria
Authors: Xiong Linlin , Wu Yanning , Shu Qinglong , Xiong Wei 
Published: March 2023

AbstractAimsHere, regulatory effects of Xiaoyaosan polysaccharide on entire intestinal flora and butyrate-producing bacteria were investigated to reveal their pharmacological mechanism serving as bacterial-derived carbon sources for regulating intestinal microecology during the treatment of chronic unpredictable mild stress (CUMS)-induced depression in rats.Methods and resultsThe effects were measured by analyzing depression-like behavior, intestinal flora, butyrate-producing bacteria diversity, and fecal butyrate content. After intervention, CUMS rats exhibited alleviated depression and increased body weight, sugar water consumption rate, and performance index in the open-field test (OFT). The abundance of dominant phyla, such as Firmicutes and Bacteroidetes, and dominant genera, such as Lactobacillus and Muribaculaceae, was regulated to restore the diversity and abundance of the entire intestinal flora to a healthy level. The polysaccharide enriched the diversity of butyrate-producing bacteria, increased the abundance of the butyrate-producing bacteria Roseburia sp. and Eubacterium sp., reduced the abundance of Clostridium sp., increased the distribution of Anaerostipes sp., Mediterraneibacter sp., and Flavonifractor sp., and subsequently increased the content of butyrate in the intestine.ConclusionsThese findings suggest that the Xiaoyaosan polysaccharide alleviates unpredictable mild stress-induced depression-like chronic behavior in rats by regulating the composition and abundance of the entire intestinal flora, restoring the diversity of butyrate-producing bacteria, and increasing the butyrate levels.
Modern Pandemics: Recession and Recovery
Authors: Ma Chang , Rogers John , Zhou Sili 
Published: March 2023

Abstract
We examine the immediate and bounce-back effects from six modern health crises that preceded Covid-19. Time-series models for a large cross-section of economies indicate that real GDP growth falls by around 2 percentage points in affected economies relative to unaffected economies in the year of the outbreak. Bounce-back in GDP growth is rapid and strong, especially when compared to non-health crises. Unemployment for less educated workers is higher and exhibits more persistence, and there is significantly greater persistence in female unemployment than male. Moreover, the negative initial effects of pandemics and bounce-back are economically contagious through international trade. The negative effects on GDP and unemployment are felt less in economies with larger first-year responses in government spending, especially on health care. Our estimates imply that the impact effect of the Covid-19 shock on world GDP growth is approximately four standard deviations worse than the average past pandemic.
Trophic Path of Marked Exuviae Within Colonies ofCoptotermes gestroi(Blattodea: Rhinotermitidae)
Authors: Tong Reina L , Choi Eun-Kyung , Ugarelli Kelly , Chouvenc Thomas , Su Nan-Yao 
Published: March 2023

AbstractNitrogen, a limiting growth factor in wood-feeding insects, was hypothesized to play a role in the recently discovered behavior of subterranean termites returning to the nest to molt. Coptotermes gestroi (Wasmann) exuviae is approximately 11% N by dry weight, and therefore a potentially rich source of recyclable nitrogen. Exuviae from a C. gestroi colony were marked with immunoglobulin G (IgG) and were fed to two-year-old C. gestroi colonies. IgG-marked exuviae were detected with an enzyme-linked immunosorbent assay. The IgG marker was later detected in every caste and life stage except first-instar larvae (L1). The proportion of individuals positive for the marker varied by caste, with the queens always being positive for the marker. The queens and second-or-higher-instar workers (W2+) had significantly higher concentrations of the marker than the eggs and L1. The trophic path of exuviae includes individuals that directly fed on marked exuviae (workers and possibly second-instar larvae) and individuals that secondarily received marked exuviae through trophallaxis (queens, kings, and soldiers). This study described the trophic path of consumed exuviae and demonstrated its role in the recycling of nitrogen in a subterranean termite. Molting at the central nest may be an efficient means to transfer nitrogen from shed exuviae to recipients and may be a nitrogen recycling behavior conserved from a termite ancestor.
Predicting interstellar radiation fields from chemical evolution models
Authors: Romero M , Corcho-Caballero P , Millán-Irigoyen I , Mollá M , Ascasibar Y 
Published: March 2023

ABSTRACT
We present a self-consistent prediction of the interstellar radiation field (ISRF), from the extreme ultraviolet (EUV) to submm range, based on two chemical evolution models of a Milky-Way-like galaxy . To this end, we develop a new tool called mixclask to include gas emission, absorption, and scattering from the photoionization code cloudy in the Monte Carlo radiative transfer code skirt. Both algorithms are invoked iteratively, until the physical properties of the interstellar medium (ISM) converge. We have designed a first test, reminiscent of a H ii region, and we find that the results of mixclask are in good agreement with a spherically symmetric cloudy simulation. Both MWG models based on chemical evolution codes give results broadly consistent with previous empirical models reported in the literature for the ISRF of our Galaxy, albeit they systematically underestimate the mid-infrared emission. We also find significant differences between our two models in the whole ultraviolet range, not fully explored in previous ISRF models. These results show the feasibility of our method of combining radiative transfer with chemical evolution models: there is increased predictive power and the ISRF obtained provides further constraints on the model parameters. python source code to implement our method is publicly available at https://github.com/MarioRomeroC/Mixclask.