bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT)
Authors: Fowler Vance G , Das Anita F , Lipka-Diamond Joy , Ambler Jane E , Schuch Raymond , Pomerantz Roger , Cassino Cara , Jáuregui-Peredo Luis , Moran Gregory J , Rupp Mark E , Lachiewicz Anne M , Kuti Joseph L , Wise Robert A , Kaye Keith S , Zervos Marcus J , Nichols W Garrett 
Published: February 2024

Abstract

Background
Novel treatments are needed for Staphylococcus aureus bacteremia, particularly for methicillin-resistant S. aureus (MRSA). Exebacase is a first-in-class antistaphylococcal lysin that is rapidly bactericidal and synergizes with antibiotics.

Methods
In Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase (DISRUPT), a superiority-design phase 3 study, patients with S. aureus bacteremia/endocarditis were randomly assigned to receive a single dose of intravenous exebacase or placebo in addition to standard-of-care antibiotics. The primary efficacy outcome was clinical response at day 14 in the MRSA population.

Results
A total of 259 patients were randomized before the study was stopped for futility based on the recommendation of the unblinded Data Safety Monitoring Board. Clinical response rates at day 14 in the MRSA population (n = 97) were 50.0% (exebacase + antibiotics; 32/64) versus 60.6% (antibiotics alone; 20/33) (P = .392). Overall, rates of adverse events were similar across groups. No adverse events of hypersensitivity related to exebacase were reported.

Conclusions
Exebacase + antibiotics failed to improve clinical response at day 14 in patients with MRSA bacteremia/endocarditis. This result was unexpected based on phase 2 data that established proof-of-concept for exebacase + antibiotics in patients with MRSA bacteremia/endocarditis. In the antibiotics-alone group, the clinical response rate was higher than that seen in phase 2. Heterogeneity within the study population and a relatively small sample size in either the phase 2 or phase 3 studies may have increased the probability of imbalances in the multiple components of day 14 clinical outcome. This study provides lessons for future superiority studies in S. aureus bacteremia/endocarditis.
Clinical Trials Registration.NCT04160468
The association of off-hour vs. on-hour intensive care unit admission time with mortality in patients with cardiogenic shock: a retrospective multi-centre analysis
Authors: Naumann Dominik , Fischer Julius , Gmeiner Jonas , Lüsebrink Enzo , Beer Benedikt N , Grieger Maximilian , Giousouf Atakan , Schrage Benedikt , Stremmel Christopher , Massberg Steffen , Orban Martin , Scherer Clemens 
Published: February 2024

Abstract

Aims
Studies have shown a so-called off-hour effect for many different diseases, but data are scarce concerning cardiogenic shock. We therefore assessed the association of off-hour vs. on-hour intensive care unit admission with 30-day mortality in patients with cardiogenic shock.

Methods and results
In total, 1720 cardiogenic shock patients (666 admitted during off-hours) from two large university hospitals in Germany were included in retrospect. An admission during off-hours was associated with increased 30-day mortality compared to an admission during on-hours [crude mortality 48% vs. 41%, HR 1.17 (1.03–1.33), P = 0.017]. This effect remained significant after propensity score matching (P = 0.023). Neither patients with a combined SCAI stage D and E (P = 0.088) or C (P = 0.548) nor those requiring cardiopulmonary resuscitation (P = 0.114) had a higher mortality at off-hour admission. In contrast, those without veno-arterial extracorporeal membrane oxygenation [HR 1.17 (1.00–1.36), P = 0.049], without acute myocardial infarction [HR 1.27 (1.02–1.56), P = 0.029] or a with combined SCAI stage A and B [HR 2.23 (1.08–4.57), P = 0.025] had an increased mortality at off-hour admission.

Conclusion
Our study showed an increased mortality in patients with cardiogenic shock admitted during off-hours, especially in those with a milder onset of disease. This stresses the importance of a thorough workup of each patient, especially at times of limited resources, the menace of underestimating the severity of cardiogenic shock, and the need for an improved 24×7 available risk stratification.
The Laws of Rollo as a Primitive Constitution for Normandy: Writing and Rewriting Legal History in France during the Seventeenth and Eighteenth Centuries
Authors: Davy Gilduin 
Published: February 2024

Abstract
The laws of Rollo are regularly evoked in seventeenth- and eighteenth-century Norman historiography. As a result of a renaissance of interest in, and the study of, medieval Norman sources, notably the gestae of Dudo of Saint-Quentin and Guillaume of Jumièges, early modern jurists and historians located the legal particularism of Normandy in Rollo’s laws. They exploited these sources in order to preserve Norman rights and liberties and to use the history of their medieval origins to justify ongoing legal provincialism. But as the Revolution approached, the memory of Rollo’s laws also became an essential issue in emerging political and ideological debates, because they served as much to defend absolute monarchy as to challenge it.
Association between cardiovascular disease and risk of female sexual dysfunction: a systematic review and meta-analysis
Authors: Dilixiati Diliyaer , Cao Ruotong , Mao Yishen , Li Yuting , Dilimulati Daniyaer , Azhati Baihetiya , Rexiati Mulati 
Published: February 2024

Abstract

Aims
Female sexual dysfunction (FSD) is a considerably underestimated condition. It has been repeatedly reported that patients with cardiovascular diseases (CVD) may suffer from an increased risk of FSD. However, there is still a lack of comprehensive and systematic evaluation of various CVD and FSD. We aimed to elucidate the association between CVD and FSD through a comprehensive literature review and meta-analysis.

Methods and results
The PubMed, Scopus, Embase, and Cochrane Library databases were systematically searched from inception to 28 February 2023. We identified all relevant studies reporting the risk of FSD in subjects with or without CVD. The associations between CVD and the risk of FSD were assessed by calculating pooled odds ratios (ORs) (cross-sectional studies) and risk ratios (RRs) (longitudinal studies) with 95% CIs. We employed random-effects models to account for potential heterogeneity, and the quality of the included studies was assessed using the Newcastle–Ottawa Scale. Fifty-four articles with 148 946 individuals were included in our meta-analysis. Compared with control subjects, subjects with CVD had a 1.51-fold increased risk of FSD (OR 1.51 95% CI, 1.34–1.69, P &lt; 0.001, heterogeneity I2 = 91.4%, P &lt; 0.001). Subgroup analyses indicated that the association between CVD and FSD remained significant in longitudinal studies (RR 1.50 95% CI, 1.21–1.86, P &lt; 0.001, heterogeneity I2 = 86.7%, P &lt; 0.001). Particularly, hypertension (OR 1.41 95% CI, 1.23–1.62, P &lt; 0.001, heterogeneity I2 = 82.7%, P &lt; 0.001), stroke (OR 1.81 95% CI, 1.54–2.12, P &lt; 0.001, heterogeneity I2 = 0%, P &lt; 0.423), and myocardial infarction (OR 2.07 95% CI, 1.60–2.67, P &lt; 0.001 heterogeneity I2 = 82.4%, P &lt; 0.001) were significantly associated with FSD. Meta-regression revealed that the primary sources of heterogeneity in FSD are attributable to adjustments for covariates, study design, and study population.

Conclusion
Our meta-analysis indicated that patients with CVD suffer from a greater risk of developing FSD. Meanwhile, we validated these findings in longitudinal queues. Notably, conditions such as hypertension, stroke, and myocardial infarction demonstrated a significant association with the incidence of FSD.
Role of electroanatomical mapping–guided superior vena cava isolation in paroxysmal atrial fibrillation patients without provoked superior vena cava triggers: a randomized controlled study
Authors: Dong Yan , Zhao Dongsheng , Chen Xinguang , Shi Linshen , Chen Qiushi , Zhang Haiyan , Yu Yue , Ullah Inam , Kojodjojo Pipin , Zhang Fengxiang 
Published: February 2024

Abstract

Aims
Data about whether empirical superior vena cava (SVC) isolation (SVCI) improves the success rate of paroxysmal atrial fibrillation (PAF) are conflicting. This study sought to first investigate the characteristics of SVC-triggered atrial fibrillation and secondly investigate the impact of electroanatomical mapping–guided SVCI, in addition to circumferential pulmonary vein isolation (CPVI), on the outcome of PAF ablation in the absence of provoked SVC triggers.

Methods and results
A total of 130 patients undergoing PAF ablation underwent electrophysiological studies before ablation. In patients for whom SVC triggers were identified, SVCI was performed in addition to CPVI. Patients without provoked SVC triggers were randomized in a 1:1 ratio to CPVI plus SVCI or CPVI only. The primary endpoint was freedom from any documented atrial tachyarrhythmias lasting over 30 s after a 3-month blanking period without anti-arrhythmic drugs at 12 months after ablation. Superior vena cava triggers were identified in 30 (23.1%) patients with PAF. At 12 months, 93.3% of those with provoked SVC triggers who underwent CPVI plus SVCI were free from atrial tachyarrhythmias. In patients without provoked SVC triggers, SVCI, in addition to CPVI, did not increase freedom from atrial tachyarrhythmias (87.9 vs. 79.6%, log-rank P = 0.28).

Conclusion
Electroanatomical mapping–guided SVCI, in addition to CPVI, did not increase the success rate of PAF ablation in patients who had no identifiable SVC triggers.

Registration
ChineseClinicalTrials.gov: ChiCTR2000034532
Temporal dynamics of microbial transcription in wetted hyperarid desert soils
Authors: León-Sobrino Carlos , Ramond Jean-Baptiste , Coclet Clément , Kapitango Ritha-Meriam , Maggs-Kölling Gillian , Cowan Don A 
Published: February 2024

Abstract
Rainfall is rare in hyperarid deserts but, when it occurs, it triggers large biological responses essential for the long-term maintenance of the ecosystem. In drylands, microbes play major roles in nutrient cycling, but their responses to short-lived opportunity windows are poorly understood. Due to its ephemeral nature, mRNA is ideally suited to study microbiome dynamics upon abrupt changes in the environment. We analyzed microbial community transcriptomes after simulated rainfall in a Namib Desert soil over 7 days. Using total mRNA from dry and watered plots we infer short-term functional responses in the microbiome. A rapid two-phase cycle of activation and return to basal state was completed in a short period. Motility systems activated immediately, whereas competition–toxicity increased in parallel to predator taxa and the drying of soils. Carbon fixation systems were downregulated, and reactivated upon return to a near-dry state. The chaperone HSP20 was markedly regulated by watering across all major bacteria, suggesting a particularly important role in adaptation to desiccated ecosystems. We show that transcriptomes provide consistent and high resolution information on microbiome processes in a low-biomass environment, revealing shared patterns across taxa. We propose a structured dispersal–predation dynamic as a central driver of desert microbial responses to rainfall.
Genome assembly and annotation of the mermithid nematode Mermis nigrescens
Authors: Bhattarai Upendra R , Poulin Robert , Gemmell Neil J , Dowle Eddy 
Published: February 2024

Abstract
Genetic studies of nematodes have been dominated by Caenorhabditis elegans as a model species. A lack of genomic resources has limited the expansion of genetic research to other groups of nematodes. Here, we report a draft genome assembly of a mermithid nematode, Mermis nigrescens. Mermithidae are insect parasitic nematodes with hosts including a wide range of terrestrial arthropods. We sequenced, assembled, and annotated the whole genome of M. nigrescens using nanopore long reads and 10X Chromium link reads. The assembly is 524 Mb in size consisting of 867 scaffolds. The N50 value is 2.42 Mb, and half of the assembly is in the 30 longest scaffolds. The assembly BUSCO score from the eukaryotic database (eukaryota_odb10) indicates that the genome is 86.7% complete and 5.1% partial. The genome has a high level of heterozygosity (6.6%) with a repeat content of 83.98%. mRNA-seq reads from different sized nematodes (≤2 cm, 3.5–7 cm, and &gt;7 cm body length) representing different developmental stages were also generated and used for the genome annotation. Using ab initio and evidence-based gene model predictions, 12,313 protein-coding genes and 24,186 mRNAs were annotated. These genomic resources will help researchers investigate the various aspects of the biology and host–parasite interactions of mermithid nematodes.
GRUR Taskforce IGC: The WIPO Draft International Legal Instrument Relating to Intellectual Property, Genetic Resources and Traditional Knowledge Associated with Genetic Resources – Overview and Analysis
Authors: Würtenberger Gert , Freischem Stephan 
Published: February 2024

Abstract
The German Association for the Protection of Intellectual Property (Deutsche Vereinigung für gewerblichen Rechtsschutz und Urheberrecht e.V., or GRUR) is a non-profit scientific association of professional groups and organisations working in the field of industrial property and copyright. Its members include, in particular, academics, judges, lawyers, patent attorneys and representatives of associations and private companies.
The GRUR Taskforce IGC has been observing the negotiations of the World Intellectual Property Organization’s (WIPO) Intergovernmental Committee on Intellectual Property and Genetic Resources, Traditional Knowledge and Folklore since 2022. This opinion summarises the results of the discussions of the GRUR Taskforce IGC on the WIPO negotiations on a convention on the protection of genetic resources and associated traditional knowledge and on the draft text of a convention.
The role of constraints and information gaps in driving risky medicine purchasing practices in four African countries
Authors: Wagnild Janelle M , Akhter Nasima , Lee Diana , Jayeola Babatunde , Darko Delese Mimi , Adeyeye Moji Christianah , Komeh James P , Nahamya David , Kasim Adetayo , Hampshire Kate 
Published: February 2024

Abstract
Substandard and falsified (SF) medical products pose a major threat to public health and socioeconomic development, particularly in low- and middle-income countries. In response, public education campaigns have been developed to alert consumers about the risks of SF medicines and provide guidance on ‘safer’ practices, along with other demand- and supply-side measures. However, little is currently known about the potential effectiveness of such campaigns while structural constraints to accessing quality-assured medicines persist. This paper analyses survey data on medicine purchasing practices, information and constraints from four African countries (Ghana, Nigeria, Sierra Leone and Uganda; n &gt; 1000 per country). Using multivariate regression and structural equation modelling, we present what we believe to be the first attempt to tease apart, statistically, the effects of an information gap vs structural constraints in driving potential public exposure to SF medicines. The analysis confirms that less privileged groups (including, variously, those in rural settlements, with low levels of formal education, not in paid employment, often women and households with a disability or long-term sickness) are disproportionately potentially exposed to SF medicines; these same demographic groups also tend to have lower levels of awareness and experience greater levels of constraint. Despite the constraints, our models suggest that public health education may have an important role to play in modifying some (but not all) risky practices. Appropriately targeted public messaging can thus be a useful part of the toolbox in the fight against SF medicines, but it can only work effectively in combination with wider-reaching reforms to address higher-level vulnerabilities in pharmaceutical supply chains in Africa and expand access to quality-assured public-sector health services.
Bipedalism and the dawn of uterine fibroids
Authors: Vilos George A , Vilos Angelos G , Burbank Fred 
Published: February 2024

Abstract
The high prevalence and burden of uterine fibroids in women raises questions about the origin of these benign growths. Here, we propose that fibroids should be understood in the context of human evolution, specifically the advent of bipedal locomotion in the hominin lineage. Over the ≥7 million years since our arboreal ancestors left their trees, skeletal adaptations ensued, affecting the pelvis, limbs, hands, and feet. By 3.2 million years ago, our ancestors were fully bipedal. A key evolutionary advantage of bipedalism was the freedom to use hands to carry and prepare food and create and use tools which, in turn, led to further evolutionary changes such as brain enlargement (encephalization), including a dramatic increase in the size of the neocortex. Pelvic realignment resulted in narrowing and transformation of the birth canal from a simple cylinder to a convoluted structure with misaligned pelvic inlet, mid-pelvis, and pelvic outlet planes. Neonatal head circumference has increased, greatly complicating parturition in early and modern humans, up to and including our own species. To overcome the so-called obstetric dilemma provoked by bipedal locomotion and encephalization, various compensatory adaptations have occurred affecting human neonatal development. These include adaptations limiting neonatal size, namely altricial birth (delivery of infants at an early neurodevelopmental stage, relative to other primates) and mid-gestation skeletal growth deceleration. Another key adaptation was hyperplasia of the myometrium, specifically the neomyometrium (the outer two-thirds of the myometrium, corresponding to 90% of the uterine musculature), allowing the uterus to more forcefully push the baby through the pelvis during a lengthy parturition. We propose that this hyperplasia of smooth muscle tissue set the stage for highly prevalent uterine fibroids. These fibroids are therefore a consequence of the obstetric dilemma and, ultimately, of the evolution of bipedalism in our hominin ancestors.
The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis
Authors: Xiong Yan Q , Li Yi , Goncheva Mariya I , Elsayed Ahmed M , Zhu Fengli , Li Liang , Abdelhady Wessam , Flannagan Ronald S , Yeaman Michael R , Bayer Arnold S , Heinrichs David E 
Published: February 2024

Abstract

Background
Staphylococcus aureus is the most common cause of life-threatening endovascular infections, including infective endocarditis (IE). These infections, especially when caused by methicillin-resistant strains (MRSA), feature limited therapeutic options and high morbidity and mortality rates.

Methods
Herein, we investigated the role of the purine biosynthesis repressor, PurR, in virulence factor expression and vancomycin (VAN) treatment outcomes in experimental IE due to MRSA.

Results
The PurR-mediated repression of purine biosynthesis was confirmed by enhanced purF expression and production of an intermediate purine metabolite in purR mutant strain. In addition, enhanced expression of the transcriptional regulators, sigB and sarA, and their key downstream virulence genes (eg, fnbA, and hla) was demonstrated in the purR mutant in vitro and within infected cardiac vegetations. Furthermore, purR deficiency enhanced fnbA/fnbB transcription, translating to increased fibronectin adhesion versus the wild type and purR-complemented strains. Notably, the purR mutant was refractory to significant reduction in target tissues MRSA burden following VAN treatment in the IE model.

Conclusions
These findings suggest that the purine biosynthetic pathway intersects the coordination of virulence factor expression and in vivo persistence during VAN treatment, and may represent an avenue for novel antimicrobial development targeting MRSA.
Emergency Myelopoiesis Distinguishes Multisystem Inflammatory Syndrome in Children From Pediatric Severe Coronavirus Disease 2019
Authors: Roznik Katerina , Andargie Temesgen E , Johnston T Scott , Gordon Oren , Wang Yi , Akindele Nadine Peart , Persaud Deborah , Antar Annukka A R , Manabe Yukari C , Zhou Weiqiang , Ji Hongkai , Agbor-Enoh Sean , Karaba Andrew H , Thompson Elizabeth A , Cox Andrea L 
Published: February 2024

Abstract

Background
Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition caused by recent infection with severe acute respiratory syndrome coronavirus 2, but the underlying immunological mechanisms driving this distinct syndrome are unknown.

Methods
We utilized high-dimensional flow cytometry, cell-free (cf) DNA, and cytokine and chemokine profiling to identify mechanisms of critical illness distinguishing MIS-C from severe acute coronavirus disease 2019 (SAC).

Results
Compared to SAC, MIS-C patients demonstrated profound innate immune cell death and features of emergency myelopoiesis (EM), an understudied phenomenon observed in severe inflammation. EM signatures were characterized by fewer mature myeloid cells in the periphery and decreased expression of HLA-DR and CD86 on antigen-presenting cells. Interleukin 27 (IL-27), a cytokine known to drive hematopoietic stem cells toward EM, was increased in MIS-C, and correlated with immature cell signatures in MIS-C. Upon recovery, EM signatures decreased and IL-27 plasma levels returned to normal levels. Despite profound lymphopenia, we report a lack of cfDNA released by adaptive immune cells and increased CCR7 expression on T cells indicative of egress out of peripheral blood.

Conclusions
Immune cell signatures of EM combined with elevated innate immune cell-derived cfDNA levels distinguish MIS-C from SAC in children and provide mechanistic insight into dysregulated immunity contributing toward MIS-C, offering potential diagnostic and therapeutic targets.
Cytotoxic Lymphocyte-Monocyte Complex Reflects the Dynamics of Coronavirus Disease 2019 Systemic Immune Response
Authors: Lin Jiajia , Bai Shiyu , He Liheng , Yang Ye , Li Xiyue , Luo Liulin , Wang Ying , Chen Ying-ying , Qin Jinhong , Zhong Yi 
Published: February 2024

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a variety of clinical manifestations, many of which originate from altered immune responses, either locally or systemically. Immune cell cross-talk occurs mainly in lymphoid organs. However, systemic cell interaction specific to coronavirus disease 2019 has not been well characterized. Here, by employing single-cell RNA sequencing and imaging flow cytometry analysis, we unraveled, in peripheral blood, a heterogeneous group of cell complexes formed by the adherence of CD14+ monocytes to different cytotoxic lymphocytes, including SARS-CoV-2–specific CD8+ T cells, γδ T cells, and natural killer T cells. These lymphocytes attached to CD14+ monocytes that showed enhanced inflammasome activation and pyroptosis-induced cell death in progression stage; in contrast, in the convalescent phase, CD14+ monocytes with elevated antigen presentation potential were targeted by cytotoxic lymphocytes, thereby restricting the excessive immune activation. Collectively, our study reports previously unrecognized cell–cell interplay in the SARS-CoV-2–specific immune response, providing new insight into the intricacy of dynamic immune cell interaction representing antiviral defense.