bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell response to Listeria infection
Authors: Corre Morgane , Boehm Volker , Besic Vinko , Kurowska Anna , Viry Anouk , Mohammad Ammara , Sénamaud-Beaufort Catherine , Thomas-Chollier Morgane , Lebreton Alice 
Published: November 2023

Abstract
Cell autonomous responses to intracellular bacteria largely depend on reorganization of gene expression. To gain isoform-level resolution of these modes of regulation, we combined long- and short-read transcriptomic analyses of the response of intestinal epithelial cells to infection by the foodborne pathogen Listeria monocytogenes. Among the most striking isoform-based types of regulation, expression of the cellular stress response regulator CIRBP (cold-inducible RNA-binding protein) and of several SRSFs (serine/arginine-rich splicing factors) switched from canonical transcripts to nonsense-mediated decay-sensitive isoforms by inclusion of ‘poison exons’. We showed that damage to host cell membranes caused by bacterial pore-forming toxins (listeriolysin O, perfringolysin, streptolysin or aerolysin) led to the dephosphorylation of SRSFs via the inhibition of the kinase activity of CLK1, thereby driving CIRBP alternative splicing. CIRBP isoform usage was found to have consequences on infection, since selective repression of canonical CIRBP reduced intracellular bacterial load while that of the poison exon-containing isoform exacerbated it. Consistently, CIRBP-bound mRNAs were shifted towards stress-relevant transcripts in infected cells, with increased mRNA levels or reduced translation efficiency for some targets. Our results thus generalize the alternative splicing of CIRBP and SRSFs as a common response to biotic or abiotic stresses by extending its relevance to the context of bacterial infection.
ZEBRA: a hierarchically integrated gene expression atlas of the murine and human brain at single-cell resolution
Authors: Flotho Matthias , Amand Jérémy , Hirsch Pascal , Grandke Friederike , Wyss-Coray Tony , Keller Andreas , Kern Fabian 
Published: November 2023

Abstract
The molecular causes and mechanisms of neurodegenerative diseases remain poorly understood. A growing number of single-cell studies have implicated various neural, glial, and immune cell subtypes to affect the mammalian central nervous system in many age-related disorders. Integrating this body of transcriptomic evidence into a comprehensive and reproducible framework poses several computational challenges. Here, we introduce ZEBRA, a large single-cell and single-nucleus RNA-seq database. ZEBRA integrates and normalizes gene expression and metadata from 33 studies, encompassing 4.2 million human and mouse brain cells sampled from 39 brain regions. It incorporates samples from patients with neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and Multiple sclerosis, as well as samples from relevant mouse models. We employed scVI, a deep probabilistic auto-encoder model, to integrate the samples and curated both cell and sample metadata for downstream analysis. ZEBRA allows for cell-type and disease-specific markers to be explored and compared between sample conditions and brain regions, a cell composition analysis, and gene-wise feature mappings. Our comprehensive molecular database facilitates the generation of data-driven hypotheses, enhancing our understanding of mammalian brain function during aging and disease. The data sets, along with an interactive database are freely available at https://www.ccb.uni-saarland.de/zebra.
Sarcopenia and mild kidney dysfunction and risk of all-cause and cause-specific mortality in older adults
Authors: Wu Gan , Hu Qiong , Huang Zhenhe , Lai Zhihan , Wang Xiaojie , Cai Miao , Lin Hualiang 
Published: November 2023

ABSTRACT

Background
Sarcopenia has been identified as a risk factor for increased mortality in individuals with CKD. However, when considering individuals with mild kidney dysfunction prior to CKD, the impact of sarcopenia on adverse outcomes, particularly mortality, remains uncertain.

Methods
This study included 323 801 participants from the UK Biobank. Mild kidney dysfunction was defined as estimated glomerular filtration rate between 60 and 89.9 mL/min/1.73 m2, and sarcopenia was defined according to the criteria of the 2019 European Working Group of Sarcopenia in Older People. Cox proportional hazard models with inverse probability weighting and competing risk models were used for analysis.

Results
During a median follow-up of 11.8 years, 20 146 participants died from all causes. Compared with participants with normal kidney function and without sarcopenia, those with mild kidney dysfunction or sarcopenia had significantly increased risks of all-cause mortality [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.12–1.19; HR 1.29, 95% CI 1.20–1.37]; those with both mild kidney dysfunction and sarcopenia had an even higher risk of all-cause mortality (HR 1.61, 95% CI 1.52–1.71), with a significant overall additive interaction (relative risk due to interaction 0.17, 95% CI 0.05–0.29). Further subgroup analyses revealed that the associations of probable sarcopenia with all-cause and cause-specific mortality (non-accidental cause, non-communicable diseases and cancer) were stronger among participants with mild kidney dysfunction than those with normal kidney function.

Conclusions
The study indicates that sarcopenia and mild kidney dysfunction synergistically increase the risk of all-cause and cause-specific mortality. Early recognition and improvement of mild kidney function or sarcopenia in older people may reduce mortality risk but would require more prospective confirmation.
Increased Levels of Caspase-1 and IL-1β Among Adults With Persistent Immune Activation After 12 Years of Suppressive Antiretroviral Therapy in the Infectious Diseases Institute HIV Treatment Cohort
Authors: Nabatanzi Rose , Ssekamatte Phillip , Castelnuovo Barbara , Kambugu Andrew , Nakanjako Damalie 
Published: November 2023

Abstract

Background
We sought evidence of activated pyroptosis and the inflammasome pathways among human immunodeficiency virus (HIV)–infected adults after 12 years of suppressive antiretroviral therapy (ART) and persistent immune activation in the Infectious Diseases Institute HIV treatment cohort in Uganda.

Methods
In a cross-sectional study, using peripheral blood mononuclear cells of HIV-infected individuals with high and low immune activation (CD4/CD8+CD38+HLA-DR+ cells) relative to HIV-negative reference group, caspase-1 expression was measured using flow cytometry and plasma interleukin 18 and interleukin 1β (IL-1β) levels using enzyme-linked immunosorbent assay.

Results
There was higher expression of caspase-1 by CD4 T cells of ART-treated individuals with high immune activation relative to those with lower immune activation (P = .04). Similarly, plasma levels of IL-1β were higher among ART-treated individuals with high immune activation levels relative to those with low immune activation levels (P = .009). We observed a low positive correlation between caspase-1 expression by CD4/CD8 T cells and immune activation levels (r = 0.497 and r = 0.329, respectively).

Conclusions
Caspase-1 and IL-1β were high among individuals with high immune activation despite 12 years of suppressive ART. There is a need to further understand the role of persistent abortive infection and the latent HIV reservoir characteristics as drivers of persistent activation and inflammation and to subsequently intervene to prevent the complications of chronic immune activation during long-term ART.
Interprofessional Education: An Innovative Approach to Increase the Human Immunodeficiency Virus Workforce
Authors: Person Anna K , Harris Sadie J , Burdge Jennifer , Blue Amy V , Leedy Nicole E , Villacorta Evelyn , Justo Julie Ann , Black Erik , Janelle Jennifer , Ahuja Divya , Chastain Cody A 
Published: November 2023

Abstract
Ending the human immunodeficiency virus (HIV) epidemic relies on a robust clinical workforce. The Southeast AIDS Education and Training Center's interprofessional education program is a novel approach to increasing the interest and ability of early health professional learners to provide high-quality, comprehensive, person-first care for people with HIV.
Key Points: Interprofessional education (IPE) focusing on multidisciplinary care for people with HIV can serve as a novel way to increase the HIV workforce. This brief report describes the IPE program of the Southeast AIDS Education and Training Center.
Impact of In-house Candida auris Polymerase Chain Reaction Screening on Admission on the Incidence Rates of Surveillance and Blood Cultures With C. auris and Associated Cost Savings
Authors: Rosa Rossana , Jimenez Adriana , Andrews David , Dinh Huy , Parra Katiuska , Martinez Octavio , Abbo Lilian M 
Published: November 2023

Abstract

Background
The impact of strategies for rapid diagnostic screening of Candida auris on hospital operations has not been previously characterized. We describe the implementation of in-house polymerase chain reaction (PCR) testing on admission for screening of colonization with C. auris, associated process improvements, and financial impact.

Methods
This study was conducted across an integrated health system. Patients were tested based on risk factors for C. auris carriage. Pre-intervention, the PCR was sent out to a reference laboratory, and postintervention was performed in-house. Changes in the incidence rates (IRs) of C. auris present on admission (CA-POA) and C. auris hospital-onset fungemia (CA-HOF) were assessed using interrupted time series analysis. The economic impact on isolation and testing costs was calculated.

Results
Postintervention, the IR of CA-POA doubled (IRR, 2.57; 95% CI, 1.16–5.69; P = .02) compared with the pre-intervention period. The baseline rate of CA-HOF was increasing monthly by 14% (95% CI, 1.05–1.24; P = .002) pre-intervention, while during the postintervention period there was a change in slope with a monthly decrease in IR of 13% (95% CI, 0.80–0.99; P = .02). The median turnaround time (TAT) of the results (interquartile range) was reduced from 11 (8–14) days to 2 (1–3) days. Savings were estimated to be between $772 513.10 and $3 730 480.26.

Conclusions
By performing in-house PCR for screening of C. auris colonization on admission, we found a doubling of CA-POA rates, a subsequent decrease in CA-HOF rates, reduced TAT for PCR results, and more efficient use of infection control measures. In-house testing was cost-effective in a setting of relatively high prevalence among individuals with known risk factors.
Immune Control in Repeated Babesia microti Infection in a Patient With B-Cell Deficiency
Authors: Little Jessica S , Oakley Miranda S , Thorner Anna R , Johnston Demerise , Majam Victoria , Liakos Alexis D , Novack Lewis A , Zheng Hong , Meredith Scott , Chou Chao-Kai , Newton Benjamin R , Soiffer Robert J , Krause Peter J , Baden Lindsey R , Kumar Sanjai 
Published: November 2023

Abstract
The immunology of human babesiosis is poorly investigated. We present a comprehensive investigation of a 75-year-old man with B-cell deficiency who experienced 3 episodes of babesiosis over a 6-year period. Slowly evolving clinical immunity was observed, as evidenced by milder clinical symptoms and lower peak parasite burden after each subsequent babesiosis episode. The patient exhibited several striking immunologic findings. First, the patient had exceptionally high Babesia microti–specific antibodies despite very few circulating B cells, which predominantly coexpressed CD27 (memory marker) and CD95 (death receptor). Second, we demonstrated the presence of long-lasting NK cells and expansion of T memory stem cells. Third, levels of the IP-10 cytokine directly correlated with parasite burden. These results raise fundamental questions on the priming, maintenance, and location of a B-cell population that produces high antibody levels in the face of severe B-cell deficiency. Our results should invoke interest among researchers to study the immunology and pathogenesis of human babesiosis.
Statutes and Contracts as Founts of Formal Reasoning
Authors: Summers Robert S 
Published: November 2023

Abstract
In this essay, which I dedicate to my friend and co-author, Professor Patrick Atiyah, I seek to demonstrate that, in American law, the overall level of formality of those reasons for decision (or other action) that derive from contracts is generally lower than the formality of reasons deriving from statutes. I also explore the importance of this fact, and here and there speculate on the explanations for it. I provide brief accounts of the varieties of formality involved, as well. I believe these efforts, which are partially programmatic, enable us to understand somewhat more fully the distinctive nature of statutes and contracts (which I here consider to be a type of law), and the special character of the reasoning that these types of law generate.
Confucian Welfarism: Intellectual Origins of Solidarity for Health and Welfare Systems
Authors: Yeh Ming-Jui 
Published: November 2023

Abstract
Solidarity is presumed to underpin the redistributive health and welfare systems in modern democracies; however, it is often considered a Western—or more specifically, European—concept. While health and welfare systems have been transplanted successfully to many non-Western developed countries, whether the solidarity necessary for such systems exists or is intellectually available remains under debate. Using an East Asian country with the Confucian tradition as an illustrative case, I first argue that the Confucian tradition has special theoretical and sociological importance for health and welfare solidarity. Then, through investigating the classic Confucian writings, I propose transformed interpretations of the essential concepts of Confucian thought, namely filial piety, benevolent governance and the mandate of heaven. With these interpretations, the differentiated family-based solidarity and the people-rooted thought in Confucianism could be reimagined to fit with the modern liberal-democratic political regime and welfare arrangements. I call this model Confucian welfarism, which I argue could form the intellectual origins of solidarity for people who believe in or have an affinity to Confucian ethos.
The sustainability of trade in wild plants—A data-integration approach tested on critically endangered Nardostachys jatamansi
Authors: Smith-Hall Carsten , Pyakurel Dipesh , Meilby Henrik , Pouliot Mariève , Ghimire Puspa L , Ghimire Suresh , Madsen Sofia T , Paneru Yagya R , Subedi Bhishma P , Timoshyna Anastasiya , Treue Thorsten 
Published: November 2023

Abstract
While the demand for many products from wild-harvested plants is growing rapidly, the sustainability of the associated plant trade remains poorly understood and understudied. We integrate ecological and trade data to advance sustainability assessments, using the critically endangered Nardostachys jatamansi in Nepal to exemplify the approach and illustrate the conservation policy gains. Through spatial distribution modeling and structured interviews with traders, wholesalers, and processors, we upscale district-level trade data to provincial and national levels and compare traded amounts to three sustainable harvest scenarios derived from stock and yield data in published inventories and population ecology studies. We find increased trade levels and unsustainable harvesting focused in specific subnational geographical locations. Data reported in government records and to CITES did not reflect estimated trade levels and could not be used to assess sustainability. Our results suggest that changing harvesting practices to promote regeneration would allow country-wide higher levels of sustainable harvests, simultaneously promoting species conservation and continued trade of substantial economic importance to harvesters and downstream actors in the production network. The approach can be applied to other plant species, with indication that quick and low-cost proxies to species distribution modeling may provide acceptable sustainability estimates at aggregated spatial levels.
Engineering of a phosphotriesterase with improved stability and enhanced activity for detoxification of the pesticide metabolite malaoxon
Authors: Job Laura , Köhler Anja , Testanera Mauricio , Escher Benjamin , Worek Franz , Skerra Arne 
Published: November 2023

Abstract
Organophosphorus (OP) pesticides are still widely applied but pose a severe toxicological threat if misused. For in vivo detoxification, the application of hydrolytic enzymes potentially offers a promising treatment. A well-studied example is the phosphotriesterase of Brevundimonas diminuta (BdPTE). Whereas wild-type BdPTE can hydrolyse pesticides like paraoxon, chlorpyrifos-oxon and mevinphos with high catalytic efficiencies, kcat/KM &gt;2 × 107 M−1 min−1, degradation of malaoxon is unsatisfactory (kcat/KM ≈ 1 × 104 M−1 min−1). Here, we report the rational engineering of BdPTE mutants with improved properties and their efficient production in Escherichia coli. As result, the mutant BdPTE(VRNVVLARY) exhibits 37-fold faster malaoxon hydrolysis (kcat/KM = 4.6 × 105 M−1 min−1), together with enhanced expression yield, improved thermal stability and reduced susceptibility to oxidation. Therefore, this BdPTE mutant constitutes a powerful candidate to develop a biocatalytic antidote for the detoxification of this common pesticide metabolite as well as related OP compounds.
Carbon dynamics in long-term starving poplar trees—the importance of older carbohydrates and a shift to lipids during survival
Authors: Helm Juliane , Muhr Jan , Hilman Boaz , Kahmen Ansgar , Schulze Ernst-Detlef , Trumbore Susan , Herrera-Ramírez David , Hartmann Henrik 
Published: November 2023

Abstract
Carbon (C) assimilation can be severely impaired during periods of environmental stress, like drought or defoliation, making trees heavily dependent on the use of C reserve pools for survival; yet, the dynamics of reserve use during periods of reduced C supply are still poorly understood. We used stem girdling in mature poplar trees (Populus tremula L. hybrids), a lipid-storing species, to permanently interrupt the phloem C transport and induced C shortage in the isolated stem section below the girdle and monitored metabolic activity during three campaigns in the growing seasons of 2018, 2019 and 2021. We measured respiratory fluxes (CO2 and O2), non-structural carbon concentration, the respiratory substrate (based on isotopic analysis and CO2/O2 ratio) and the age of the respiratory substrate (based on radiocarbon analysis). Our study shows that poplar trees can survive long periods of reduced C supply from the canopy by switching in metabolism from recent carbohydrates to older storage pools with a potential mixture of respiratory substrates, including lipids. This mechanism of stress resilience can explain why tree decline may take many years before death occurs.
Bladder Repair with Irrigation and Debridement and Open Reduction Internal Fixation of the Anterior Pelvic Ring is Safe and Decreases Risk of Infection in Pelvic Ring Injuries with Extraperitoneal Bladder Ruptures
Authors: Saiz Augustine M. , O’Donnell Edmond , Kellam Patrick , Cleary Courtney , Moore Ximia , Schultz Blake J , Mayer Ryan , Amin Adeet , Gary Joshua , Warner Stephen J , Routt Milton L. , Eastman Jonathan G. 
Published: November 2023

Abstract

Objective:
To determine the incidence of infection in nonoperative versus operative management of extraperitoneal bladder ruptures in patients with pelvic ring injuries.

Setting:
Two level 1 trauma centers.

Design:
A retrospective cohort study of two prospectively collected trauma registries.
Patients/Participants: Of 1127 patients with operative pelvic ring injuries, 68 (6%) had extraperitoneal bladder ruptures.

Main Outcome Measurements:
Primary outcome was the incidence and associated risk factors of deep pelvic infection requiring return to OR for surgical debridement. Secondary outcomes included quality of reduction, other complications, and radiographic union.

Results:
Of the 68 patients with extraperitoneal bladder ruptures in the setting of an operative pelvic ring injury, 55 had bladder repair and 13 did not. Of those 13 without repair, none had ORIF of the anterior pelvic ring. Patients without bladder repair had an increased odds of infection 17-fold compared to patients who did have a repair performed (OR 16.9, 95% CI 1.75 – 164, P = 0.01). Other associated factors for deep pelvic infection included use of suprapubic catheter (P < 0.02) and a closed reduction of the anterior ring (P < 0.01). Patients undergoing anterior ring ORIF and bladder repair had improved reductions and no increased infection risk.

Conclusions:
Operative repair of extraperitoneal bladder ruptures decreases risk of infection in patients with pelvic ring injuries. Additionally, ORIF of the anterior pelvic ring does not increase risk of infection and results in better reductions compared to closed reduction. Treatment algorithms for these combined injuries should consider recommending early bladder repair and anterior pelvic ORIF.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Effect of Cervicothoracic Junction LIV Selection on Posterior Cervical Fusion Mechanical Failure
Authors: Labrum Joseph T. , Waddell William H. , Gupta Rishabh , Coronado Rogelio A. , Hymel Alicia , Steinle Anthony , Abtahi Amir M. , Stephens Byron F. 
Published: November 2023

Study Design:
Systematic review and Meta-analysis.

Objective:
Analyze and summarize literature evaluating the role of C7, T1, and T2 lowest instrumented vertebra (LIV) selection in posterior cervical fusion (PCF) and if this affects the progression of mechanical failure and revision surgery.

Summary of Background Data:
Literature evaluating mechanical failure and adjacent segment disease in the setting of PCF at or nearby the cervicothoracic junction (CTJ) remains limited with studies reporting conflicting results.

Materials and Methods:
Two reviewers conducted a detailed systematic review using EMBASE, PubMed, Web of Science, and Google Scholar on June 28, 2021, for primary research articles comparing revision and complication rates for posterior fusions ending in the lower cervical spine (C7) and upper thoracic spine (T1–T2). The initial systematic database yielded 391 studies, of which 10 met all inclusion criteria. Random effects meta-analyses compared revision and mechanical failure rates between patients with an LIV above the CTJ and patients with an LIV below the CTJ.

Results:
Data from 10 studies (total sample=2001, LIV above CTJ=1046, and LIV below CTJ=955) were meta-analyzed. No differences were found between the 2 cohorts for all-cause revision [odds ratio (OR)=0.75, 95% CI=0.42–1.34, P<0.0001] and construct-specific revision (OR=0.62, 95% CI=0.25–1.53, P<0.0001). The odds of total mechanical failure in the LIV below CTJ cohort compared with the LIV above CTJ cohort were significantly lower (OR=0.38, 95% CI=0.18–0.81, P<0.0001).

Conclusion:
The results show patients with PCFs ending below the CTJ have a lower risk of undergoing total mechanical failure compared with fusions ending above the CTJ. This is important information for both physicians and patients to consider when planning for operative treatment.

Level of Evidence:
Level I.