bluuebunny/crossref_metadata_2025_split huggingface dataset:
Floral traits underlying mating system differentiation in the wind-pollinated sister species Oryza rufipogon and Oryza nivara
Authors: Grillo Michael , Gutiérrez Andrés 
Published: December 2024

Abstract
The shift from outcrossing to predominantly selfing is one of the most common transitions in plant evolution. This evolutionary shift has received considerable attention from biologists; however, this work has almost exclusively been focused on animal-pollinated systems. Despite the seminal ecological and economic importance of wind-pollinated species, the mechanisms controlling the degree of outcrossing in wind-pollinated taxa remain poorly understood. As a first step toward addressing this issue, we have conducted a comparative study of floral biology between two recently diverged sister species, Oryza rufipogon and Oryza nivara (Poaceae), that are wind-pollinated and possess distinct mating systems with O. rufipogon being outcrossing and O. nivara highly self-fertilized Therefore, these species present an ideal system for exploring mating system evolution in wind-pollinated taxa. We have identified key floral traits that differ between populations of these species and that are associated with mating system divergence including anther length, anther basal pore size, stigma papillae density, panicle shape, panicle exsertion, pollen viability, and early anther dehiscence. Of these traits, large anther basal pore size and early anther dehiscence are hypothesized to confer reliable autogamous selfing in O. nivara. Manipulations of floret number were conducted to partition the role of geitonogamy and autogamy in conferring self-fertilization. This experiment revealed that selfing in O. nivara is consistent with autogamous selfing, whereas O. rufipogon achieves selfing through geitonogamy. This study serves as a model for understanding the floral mechanisms controlling the outcrossing rate in other wind-pollinated systems, most notably other grasses.
VAREANT: a bioinformatics application for gene variant reduction and annotation
Authors: Narayanan Rishabh , DeGroat William , Peker Elizabeth , Zeeshan Saman , Ahmed Zeeshan 
Published: December 2024

Abstract

Motivation
The analysis of high-quality genomic variant data may offer a more complete understanding of the human genome, enabling researchers to identify novel biomarkers, stratify patients based on disease risk factors, and decipher underlying biological pathways. Although the availability of genomic data has sharply increased in recent years, the accessibility of bioinformatic tools to aid in its preparation is still lacking. Limitations with processing genomic data primarily include its large volume, associated computational and storage costs, and difficulty in identifying targeted and relevant information.

Results
We present VAREANT, an accessible and configurable bioinformatic application to support the preparation of variant data into a usable analysis-ready format. VAREANT is comprised of three standalone modules: (i) Pre-processing, (ii) Variant Annotation, (iii) AI/ML Data Preparation. Pre-processing supports the fine-grained filtering of complex variant datasets to eliminate extraneous data. Variant Annotation allows for the addition of variant metadata from the latest public annotation databases for subsequent analysis and interpretation. AI/ML Data Preparation supports the user in creating AI/ML-ready datasets suitable for immediate analysis with minimal pre-processing required. We have successfully tested and validated our tool on numerous variable-sized datasets and implemented VAREANT in two case studies involving patients with cardiovascular diseases.

Availability and implementation
The open-source code of VAREANT is available at GitHub: https://github.com/drzeeshanahmed/Gene_VAREANT
MeSS and assembly_finder: a toolkit for in silico metagenomic sample generation
Authors: Chaabane Farid , Pillonel Trestan , Bertelli Claire 
Published: December 2024

Abstract

Summary
The intrinsic complexity of the microbiota combined with technical variability render shotgun metagenomics challenging to analyze for routine clinical or research applications. In silico data generation offers a controlled environment allowing for example to benchmark bioinformatics tools, to optimize study design, statistical power, or to validate targeted applications. Here, we propose assembly_finder and the Metagenomic Sequence Simulator (MeSS), two easy-to-use Bioconda packages, as part of a benchmarking toolkit to download genomes and simulate shotgun metagenomics samples, respectively. Outperforming existing tools in speed while requiring less memory, MeSS reproducibly generates accurate complex communities based on a list of taxonomic ranks and their abundance.

Availability and implementation
All code is released under MIT License and is available on https://github.com/metagenlab/MeSS and https://github.com/metagenlab/assembly_finder.
Percolation in higher order networks via mapping to chygraphs
Authors: Vazquez Alexei 
Published: December 2024

Abstract
Percolation theory investigates systems of interconnected units, their resilience to damage and their propensity to propagation. For random networks, we can solve the percolation problems analytically using the generating function formalism. Yet, with the introduction of higher order networks, the generating function calculations are becoming difficult to perform and harder to validate. Here, I illustrate the mapping of percolation in higher order networks to percolation in chygraphs. Chygraphs are defined as a set of complexes where complexes are hypergraphs with vertex sets in the set of complexes. In a previous work, I reported the generating function formalism to percolation in chygraphs and obtained an analytical equation for the order parameter. Taking advantage of this result, I recapitulate analytical results for percolation problems in higher order networks and report extensions to more complex scenarios using symbolic calculations. The code for symbolic calculations can be found at github.com/av2atgh/chygraph.
SGLT2 expression in human vasculature and heart correlates with low-grade inflammation and causes eNOS-NO/ROS imbalance
Authors: Mroueh Ali , Algara-Suarez Paola , Fakih Walaa , Gong Dal-Seong , Matsushita Kensuke , Park Sin-Hee , Amissi Said , Auger Cyril , Kauffenstein Gilles , Meyer Nicolas , Ohlmann Patrick , Jesel Laurence , Pieper Michael Paul , Marchandot Benjamin , Morel Olivier , Mazzucotelli Jean-Philippe , Schini-Kerth Valérie B 
Published: December 2024

Abstract

Aims
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a cardioprotective effect in heart failure and myocardial infarction, pathologies often associated with low-grade inflammation. This cross-sectional study aims to investigate whether low-grade inflammation regulates SGLT2 expression and function in human vasculature, heart, and endothelial cells (ECs).

Methods and results
Human internal thoracic artery (ITA), left ventricle (LV) specimens, and cultured porcine coronary artery ECs were used. Expression of target molecules was assessed using RT-qPCR, western blot analysis, and immunofluorescence staining, and the generation of reactive oxygen species (ROS) and nitric oxide (NO) using fluorescent probes. The function of SGLT2 was investigated using empagliflozin and SGLT1 or 2 siRNA. SGLT2 mRNA and protein levels in ITA and LV specimens were correlated with the level of low-grade inflammation, markers of the angiotensin system, and EC activation. SGLT2 staining was observed in the ITA endothelium and smooth muscle, the coronary microcirculation, and cardiomyocytes. Elevated ROS formation in high SGLT2-expressing specimens was reduced by inhibition of the angiotensin system, SGLT2, and TNF-α. Exposure of ECs to IL-1ß, IL-6, and TNF-α led to an increase in SGLT1 and SGLT2 mRNA and protein expression, up-regulation of components of the angiotensin system, enhanced ROS and decreased NO formation, and activation of NF-κB. The stimulatory effect of TNF-α was prevented by N-acetylcysteine and inhibition of the angiotensin system, SGLT2 but not SGLT1, and NF-κB.

Conclusion
Low-grade inflammation is closely associated with SGLT2 expression in human vasculature and heart, and this response contributes to a feedforward mechanism with the AT1R/NADPH oxidase pathway to cause eNOS-NO/ROS imbalance.
Anti-TNF nonresponse in ulcerative colitis: correcting for mucosal drug exposure reveals distinct cytokine profiles
Authors: van Oostrom Joep , Hanzel Jurij , Verstockt Bram , Singh Sharat , Smith Jeffrey , Gecse Krisztina , Mathot Ron , Vermeire Séverine , D’Haens Geert 
Published: December 2024

Abstract

Introduction
It remains unclear why up to 30% of ulcerative colitis (UC) patients do not respond to tumor necrosis factor inhibitors (TNFi). Validated biomarkers for nonresponse (N)R) are lacking. Most studies investigating underlying mechanisms do not differentiate between pharmacokinetic and inflammatory mechanisms. We therefore aimed to develop a framework to correct for mucosal drug exposure (MDE) and applied this to mucosal cytokine profiles previously linked to (N)R.

Methods
In a prospective international cohort, we studied patients with active moderate–severe UC starting TNFi treatment. Patients underwent endoscopy before (baseline) and after induction treatment (follow-up). NR was defined as the absence of Mayo endoscopic subscore improvement by central read or need for colectomy. The ratio of mucosal concentrations of TNFi/TNF was used to define high or low MDE. Mucosal concentrations of interleukin-6 (IL-6), Oncostatin M (OSM), interleukin-10 (IL-10), and interleukin-12/23p40 (IL-12/IL-23p40) were measured.

Results
Fifty-four UC patients were included (43 infliximab, 11 adalimumab) of whom 39 (72%) were endoscopic responders (after a median treatment of 62 days [48–96]). NR with high MDE had high IL-6 at both time points. R with low MDE exhibited low mucosal IL-10 at baseline. At follow-up, high OSM was associated with NR (irrespective of MDE) and high IL-12/IL-23p40 with R.

Conclusions
We incorporated MDE in mucosal cytokine research to avoid bias due to the insufficient presence of anti-TNF. When applied to mucosal cytokines previously linked to (N)R, IL-6 appears to drive inflammation in TNFi-resistant UC patients, while OSM seems to parallel inflammation and does not cause refractoriness.
Selecting the optimal candidates for percutaneous mitral valvuloplasty using multi-modality imaging
Authors: Lee Hee Jeong , Kim Na Young , Kim Dae-Young , Son Jang-Won , Choi Kang-Un , Lee SeonHwa , Kim In-Cheol , Ko Kyu-Yong , Ha Kyung Eun , Gwak Seo-Yeon , Kim Kyu , Seo Jiwon , Kim Hojeong , Shim Chi Young , Ha Jong-Won , Kim Hyungseop , Hong Geu-Ru , Cho Iksung , Suh Young Joo 
Published: December 2024

Abstract

Aims
This study compared echocardiography (echo) and cardiac computed tomography (CT) in measuring the Wilkins score and evaluated the potential added benefit of CT in predicting immediate percutaneous mitral valvuloplasty (PMV) outcomes in rheumatic mitral stenosis (MS) patients deemed eligible for PMV by echo.

Methods and results
From a multicentre registry of 3,140 patients with at least moderate MS, we included 96 patients (age 56.4 ± 11.5 years, 81% female) eligible for PMV based on echo Wilkins score (≤9) who underwent PMV and had measurable CT and echo images. We compared Wilkins scores from both modalities and analysed their relationship with unsuccessful procedural outcomes, defined as sub-optimal post-procedural mitral valve area (&lt;1.5 cm2) or newly developed mitral regurgitation Grade ≥III. The mean CT score was higher than the echo score (8.0 ± 2.4 vs. 7.3 ± 1.2 points, P = 0.005). Procedural success was achieved in 65 (67.7%) patients. Unsuccessful results occurred in 31 patients, primarily in intermediate echo score (7–9 points) group. Among patients with intermediate echo scores, 90% had high CT scores (≥9), which were associated with significantly higher rates of unsuccessful PMV compared with lower CT scores (61.1 vs. 18.9%, P &lt; 0.001).

Conclusion
CT-derived Wilkins scores were higher than echo-derived scores, with the most significant discrepancy in the intermediate echo score group. CT identified a subgroup of patients at higher risk for unsuccessful PMV among those with intermediate echo-based feasibility. Patients with intermediate echo-based PMV feasibility may benefit from CT-based reclassification, potentially improving patient selection and procedural outcomes.
First whole-genome sequence of Triatoma sanguisuga (Le Conte, 1855), vector of Chagas disease
Authors: Peterson Jennifer K , MacDonald Madolyn L , Ellis Vincenzo A 
Published: December 2024

Abstract
Triatoma sanguisuga is the most widespread triatomine bug species in the United States. The species vectors the human parasite Trypanosoma cruzi, which causes Chagas disease. Vector-borne Chagas disease is rarely diagnosed in the United States, but T. sanguisuga has been implicated in a handful of cases. Despite its public health importance, little is known about the genomics or population genetics of T. sanguisuga. Here, we used long-read sequencing to assemble the first whole-genome sequence for T. sanguisuga using DNA extracted from 1 adult specimen from Delaware. The final size of the genome was 1.162 Gb with 77.7× coverage. The assembly consisted of 183 contigs with an N50 size of 94.97 kb. The Benchmarking Universal Single-Copy Ortholog complete score was 99.1%, suggesting a very complete assembly. Genome-wide GC content was 33.56%, and DNA methylation was 18.84%. The genome consists of 62.75% repetitive DNAs and 17,799 predicted coding genes. The assembled T. sanguisuga genome was very close in size and BUSCO score to that of Triatominae species T. dimidiata (1.16 Gb with 99.1% BUSCO score for T. sanguisuga vs 1.22 Gb with 98.7% BUSCO score for T. dimidiata) and slightly larger than that of T. infestans and Rhodnius prolixus (949 Mb with 90.4% BUSCO score and 706 Mb with 96.5% BUSCO score, respectively). The T. sanguisuga genome is the first North American triatomine species genome to be sequenced, allowing for deeper investigations into epidemiologically relevant aspects of triatomines in temperate climates, thus providing potential vector-borne disease management targets and strengthening public health preparedness.
Services and payments associated with the medicare new technology add-on payment program
Authors: Tsuruo Sarah , Schlacter Jamie , Dhruva Sanket S , Ross Joseph S , Horwitz Leora I 
Published: December 2024

Lay Summary
In 2001, the Centers for Medicare and Medicaid Services (CMS) established the New Technology Add-On Payment (NTAP) program to help Medicare patients access costly new technologies. These technologies, approved by the Food and Drug Administration (FDA) must show “substantial clinical improvement” when compared to existing technologies. Recently, the FDA introduced two fast-track approval pathways allowing technologies to skip the “substantial clinical improvement” requirement. In this study, we describe the technologies and payments associated with NTAPs after this policy change.
Molecular Epidemiology of Invasive Group B Streptococcus in South Africa, 2019–2020
Authors: Ntozini Buhle , Walaza Sibongile , Metcalf Benjamin , Hazelhurst Scott , de Gouveia Linda , Meiring Susan , Mogale Dineo , Mtshali Senzo , Ismail Arshad , Ndlangisa Kedibone , Du Plessis Mignon , Quan Vanessa , Chochua Sopio , McGee Lesley , von Gottberg Anne , Wolter Nicole 
Published: December 2024

Abstract

Background
Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and sepsis and an important cause of disease in adults. Capsular polysaccharide and protein-based GBS vaccines are currently under development.

Methods
Through national laboratory-based surveillance, invasive GBS isolates were collected from patients of all ages between 2019 and 2020. Phenotypic serotyping and antimicrobial susceptibility testing were conducted, followed by whole-genome sequencing for analysis of population structure and surface protein and resistance genes.

Results
In total, 1748 invasive GBS cases were reported. Of these, 661 isolates underwent characterization, with 658 yielding both phenotypic and genotypic results. Isolates (n = 658) belonged to 5 clonal complexes (CC1, CC8/10, CC17, CC19, and CC23) and 6 serotypes were detected: III (42.8%), Ia (27.9%), V (11.9%), II (8.4%), Ib (6.7%), and IV (2.3%). Phenotypically, only 1 isolate exhibited reduced penicillin susceptibility (minimum inhibitory concentration 0.25 µg/mL). Phenotypic resistance to erythromycin, clindamycin, and tetracycline was observed in 16.1%, 3.8%, and 91.5% of isolates, respectively. ermTR (34.9%) and mefA/E (30.1%) genes were most common among erythromycin-resistant isolates, while ermB predominated in clindamycin-resistant isolates (32.0%). tetM accounted for 95.8% of tetracycline resistance. All isolates carried at least 1 of the 3 pilus gene clusters, 1 of the 4 homologous alpha/Rib family determinants, and 98% harbored 1 of the serine-rich repeat protein genes. hvgA was found exclusively in CC17 isolates.

Conclusions
In our setting, β-lactam antibiotics remain appropriate for GBS treatment and polysaccharide and protein-based vaccines under development are expected to provide good coverage.
Phage-Encoded Virulence Factor, Gp05, Alters Membrane Phospholipids and Reduces Antimicrobial Susceptibility in Methicillin-Resistant Staphylococcus aureus
Authors: Li Yi , Mishra Nagendra N , Chen Liang , Manna Adhar C , Cheung Ambrose L , Proctor Richard A , Xiong Yan Q 
Published: December 2024

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of endovascular infections. The prophage-encoded protein Gp05 has been identified as a critical virulence factor that contributes to MRSA persistence during vancomycin treatment in an experimental endocarditis model. However, the mechanisms underlying this persistence phenotype remain poorly understood.

Methods
This study investigated the genetic factors contributing to Gp05-associated MRSA persistence utilizing RNA sequencing (RNA-seq) on an isogenic MRSA strain set, including a clinical persistent bacteremia isolate, its chromosomal gp05 deletion mutant, and gp05-complemented strains.

Results
RNA-seq revealed significant downregulation of the GraSR two-component regulatory system and its downstream genes, mprF and dltABCD, in the gp05 deletion mutant compared to the wild-type and gp05-complemented strains. This downregulation led to a substantial shift in membrane phospholipid composition, with an increased phosphatidylglycerol and a corresponding decrease in lysyl-phosphatidylglycerol. These changes resulted in increased susceptibility of the gp05 deletion mutant to human cationic antimicrobial peptide (CAMP) LL-37, neutrophils, and vancomycin. These results were confirmed in an isogenic gp05 overexpression strain set in MRSA JE2 background.

Conclusions
Gp05 modulates MRSA surface phospholipid components and charge, offering new insights into the molecular mechanisms underlying Gp05-mediated persistence in endovascular infections and potential therapeutic targets to combat these infections.
Exit from Regime Complexity? Regional International Organizations under Scrutiny
Authors: Panke Diana , Grundsfeld Lukas , Tverskoi Pawel 
Published: December 2024

Abstract
Regional regime complexity has long been on the rise and carries a series of potential negative effects, such as waste of resources or reduced effectiveness of regional governance. This article investigates a specific strategy of how states cope with regime complexity, namely by exiting regional international organizations (RIOs). We develop hypotheses on how different types of regional regime complexity influence the chances for exits to occur and theorize interaction effects. The analysis reveals that higher levels of membership- and competency-based regime complexity as well as RIO incompatibility increase the likelihood of state withdrawals. In addition, state characteristics moderate this effect and influence who leaves which organization. Most importantly, smaller rather are less able to shape RIO policies and activities and have fewer capacities to implement them and are thus more likely to exit one of the organizations when being member in many overlapping RIOs. By contrast, powerful states can better navigate regime complexity and avoid negative side-effects and are therefore less inclined to withdraw from RIOs in situations of high regional regime complexity.
Polymerization of dietary fructans differentially affects interactions among intestinal microbiota of colitis mice
Authors: Xiao Yaqin , Zhao Qianyun , Ni Dawei , Zhang Xiaoqi , Hao Wei , Yuan Qin , Xu Wei , Mu Wanmeng , Wu Dingtao , Wu Xu , Wang Shengpeng 
Published: December 2024

Abstract
The intestinal microbiota plays a critical role in maintaining human health and can be modulated by dietary interventions and lifestyle choices. Fructans, a dietary carbohydrate, are selectively utilized by the intestinal microbiota to confer health benefits. However, the specific effects of different fructan types on microbial changes and functions remain incompletely understood. Here, we investigated how the intestinal microbiota responds to fructans with varying degrees of polymerization in the context of gut dysbiosis. Both low molecular weight fructo-oligosaccharides and high molecular weight levan suppressed intestinal inflammation in a colitis mouse model, mitigating intestinal fibrosis and dysbiosis. Although both the effects of fructo-oligosaccharides and levan are microbiota-dependent, distinct modulation patterns of the intestinal microbiota were observed based on the molecular weight of the fructans. Levan had a more pronounced and persistent impact on gut microbiota compared to fructo-oligosaccharides. Levan particularly promoted the abundance of Dubosiella newyorkensis, which exhibited preventive effects against colitis. Our findings highlight the importance of polymerization levels of dietary fructans in microbiota alterations and identify Dubosiella newyorkensis as a potential probiotic for treating inflammatory diseases.
Synergistic effects of colistin–rifampin-based triple antimicrobial combination therapy against Carbapenem-resistant Pseudomonas aeruginosa: a time-kill assay
Authors: Kim Si-Ho , Kim Hye Mee , Chung Doo Ryeon , Ko Jae-Hoon , Huh Kyungmin , Cho Sun Young , Kang Cheol-In , Peck Kyong Ran 
Published: December 2024

Abstract

Background
Our research aimed to investigate the potential of in vitro triple antimicrobial synergism against carbapenem-resistant Pseudomonas aeruginosa (CRPA) as a strategy to overcome antimicrobial resistance.

Methods
We used 12 CRPA blood isolates stocked in the Asian Bacterial Bank between 2016 and 2018. All isolates were tested by multi-locus sequencing and carbapenemase multiplex PCR. To assess the antimicrobial interactions, we performed time–kill assays using double or triple combination regimens. These regimens included CST and/or rifampin combined with IPM, MEM, or CZA. The assay was conducted at 1× and 0.5× MICs.

Results
Among the 12 CRPA isolates, nine produced metallo-beta-lactamases (6 IMP-6, 2 VIM-2 and 1 NDM-1). In the time–kill assay, the median viable bacterial count for CST–rifampin was the lowest among double combinations after 24 h incubation (2.25 log cfu/mL at 1× MIC and 3.71 log cfu/mL at 0.5× MIC). In contrast, all triple combinations achieved 0 log cfu/mL at both 1× MIC and 0.5× MIC. Compared with CST–rifampin (synergism: 25% at 1× MIC, 42% at 0.5× MIC; bactericidal: 50% at 1× MIC, 42% at 0.5× MIC), all triple combinations showed greater synergism and bactericidal activity at both 1× MIC (50%–75% for synergism, 75%–83% for bactericidal activity) and 0.5× MIC (58%–75% for both).

Conclusions
Our findings suggest that CST–rifampin-based triple antimicrobial combinations exhibit greater synergy and bactericidal activity in eradicating CRPA compared with double antimicrobial combinations.