bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of metabolic dysfunction–associated steatotic liver disease and fibrosis defined by liver elastography in the United States using National Health and Nutrition Examination Survey 2017-March 2020 and August 2021-August 2023 data
Authors: Unalp-Arida Aynur , Ruhl Constance E. 
Published: December 2024

Background and Aims:
Steatotic liver disease (SLD) is a significant public health burden. Previously, we estimated prepandemic SLD prevalence determined by transient elastography-assessed hepatic steatosis and fibrosis in the United States. We now estimate the prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD) and examine associations with lifestyle, socioeconomic, and other factors.

Approach and Results:
Liver stiffness and controlled attenuation parameters were assessed on 13,538 non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic men and women aged 20 years and over in the National Health and Nutrition Examination Survey 2017 to March 2020 and August 2021 to August 2023. The prevalence of SLD (controlled attenuation parameter >300 dB/m) was 28.7%, fibrosis (liver stiffness >8 kPa) was 11.3%, and MASLD was 25.6%. Between the 2 survey cycles, the age-standardized SLD prevalence was not significantly different, MASLD prevalence decreased (26.8%–23.6%), and fibrosis prevalence increased (10.4%–12.7%). In multivariable-adjusted analysis, both MASLD and fibrosis were associated with diabetes, higher body mass index, higher waist-to-hip ratio, elevated blood pressure, and inversely associated with non-Hispanic Black race-ethnicity. MASLD was also associated with male sex, non-Hispanic Asian race-ethnicity, prediabetes, higher total cholesterol, lower HDL cholesterol, and greater sedentary lifestyle. Fibrosis was also associated with SLD, lower total cholesterol, and less education.

Conclusions:
In the US population, MASLD and fibrosis prevalence are high along with obesity and diabetes. Our findings suggest that early detection of chronic liver disease and targeting lifestyle and other modifiable risk factors may slow disease progression toward advanced fibrosis and cirrhosis.
Comparative analysis of cold-stored apheresis platelet units in additive solution with or without pathogen reduction: Implications of cytochrome c supplementation
Authors: Ekaney Michael L. , Bartl Neal E. , McKillop Iain H. , Evans Susan L. 
Published: December 2024

BACKGROUND
Platelets are limited in supply, and the preservation of platelet function during storage remains challenging. Novel storage approaches are being explored to improve platelet quality, extend shelf life, and reduce risk of infection. This study sought to elucidate platelet function in cold-stored apheresis units in additive solution (platelet additive solution [PAS]) and subjected to pathogen reduction (PR) as well as the impact of cytochrome c (cyt c) supplementation. We hypothesized that the PR would decrease stored platelet function, regardless of cyt c supplementation.

METHODS
Platelet apheresis units (PAS) were collected (N = 5 volunteers) and divided into PR or no PR (PAS) and supplemented with vehicle or cyt c (100 μM). Units were stored at 4°C for 15 days, sequential aliquots were removed, and platelet/mitochondrial respiratory function and biochemical parameters were analyzed.

RESULTS
There was no difference in platelet aggregation in response to adenosine diphosphate between PAS and PR platelets. Aggregation function in response to arachidonic acid was higher in PR versus PAS platelets. Maximum clot strength was not different between PAS and PR from Day 0 to Day 5 but declined in PR platelets on Days 10 and 15. Oxygen consumption declined at the same rate in PAS and PR platelets, while rate of lactate and TCO2 decrease was greater in PR platelets than in PAS platelets. Supplementation with cyt c did not alter platelet function or biochemical parameters in PAS or PR platelets.

CONCLUSION
Platelet additive solution and PR platelets show similar declines in respiratory capacity, and biochemical parameters during cold storage, but PR platelets demonstrated significantly increased arachidonic acid–induced aggregation across all time points. Further understanding this mechanism may provide a means to prolong platelet shelf life.
Penalizing underage alcohol use is associated with lower mortality for young drivers: Use/lose laws and their association with motor vehicle collision mortality
Authors: Shin Gi Jung , Zogg Cheryl K. , Rice William , Xu Ruidi , Castillo-Angeles Manuel , Swain Sonal , Agarwal Suresh K. , Haines Krista L. 
Published: December 2024

BACKGROUND
Motor vehicle collisions (MVC) continue to be a leading cause of mortality for youth in the United States. Since 2010, seven states have revoked mandatory laws that suspended licenses for underage alcohol use, also known as use/lose laws. This study analyzed whether each state’s policy change was associated with increased youth MVC mortality.

METHODS
State mortality data for youth ages 15 years to 20 years in MVCs involving a young driver (i.e., ages 15–20 years) were obtained from the Fatality Analysis Reporting System. Population data was retrieved from the Centers for Disease Control and Prevention’s Wide-ranging ONline Data for Epidemiologic Research. Motor vehicle collisions mortality rates were calculated for each state with a law change per 1,000,000 persons. For difference-in-difference analysis, each state’s youth MVC mortality rates from 3 years prior to the law change were compared with rates from 3 years post-law changes, relative to a national average compiled of states with no law changes.

RESULTS
From 2010 to 2020, seven states revoked one or more of their mandatory use/lose laws. For all states, young driver MVC mortality rates significantly increased after removal of use/lose legislation (South Dakota: 5.4 excess deaths per million (EDPM), Indiana: 5.6 EDPM, Georgia 28.0 EDPM, Oregon: +41.9 EDPM, Pennsylvania: +10.4 EDPM, Delaware: +45.4 EDPM, Illinois +29.2 EDPM, all p < 0.001).

CONCLUSION
Examining mortality rates at the state reveals a significant negative association between penalizing underage alcohol use and young driver MVC deaths. Future legislation and health outcomes analysis should consider state-level differences to retain and develop effective policies that reduce injury-related mortality.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Assessment and Prediction of Clinical Outcomes for ICU-Admitted Patients Diagnosed with Hepatitis: Integrating Sociodemographic and Comorbidity Data
Authors: Alluri Dimple Sushma , Pabon-Rodriguez Felix M. 
Published: December 2024

AbstractHepatitis, a leading global health challenge, contributes to over 1.3 million deaths annually, with hepatitis B and C accounting for the majority of these fatalities. Intensive care unit (ICU) management of patients is particularly challenging due to the complex clinical care and resource demands. This study focuses on predicting Length of Stay (LoS) and discharge outcomes for ICU-admitted hepatitis patients using machine learning models. Despite advancements in ICU predictive analytics, limited research has specifically addressed hepatitis patients, creating a gap in optimizing care for this population. Leveraging data from the MIMIC-IV database, which includes around 94,500 ICU patient records, this study uses sociodemographic details, clinical characteristics, and resource utilization metrics to develop predictive models. Using Random Forest, Logistic Regression, Gradient Boosting Machines, and Generalized Additive Model with Negative Binomial Regression, these models identified medications, procedures, comorbidities, age, and race as key predictors. Total LoS emerged as a pivotal factor in predicting discharge outcomes and location. These findings provide actionable insights to improve resource allocation, enhance clinical decision-making, and inform future ICU management strategies for hepatitis patients.
Multi-Step Pathway Engineering in ProbioticSaccharomyces boulardiifor Abscisic Acid Production in the Gut
Authors: Van Gaever Femke , Vandecruys Paul , Driege Yasmine , Kim Seo Woo , Thevelein Johan M. , Beyaert Rudi , Staal Jens 
Published: December 2024

AbstractThe plant hormone abscisic acid (ABA) has gained attention for its role in animals and humans, particularly due to its protective effects in various immune and inflammatory disorders. Given its high concentrations in fruits like figs, bilberries and apricots, ABA shows promise as a nutraceutical. However scalability, short half-life and cost limit the use of ABA-enriched fruit extracts and synthetic supplements. In this study, we propose an alternative ABA administration method to overcome these challenges. We genetically engineered a strain of the probioticSaccharomyces boulardiito produce and deliver ABA directly to the gut of mice. Using the biosynthesis pathway fromBotrytis cinerea, four genes (bcaba1-4) were integrated intoS. boulardii, enabling ABA production at 30°C, as previously described inSaccharomyces cerevisiae. Introducing an additional cytochrome P450 reductase gene resulted in a 7-fold increase in ABA titers, surpassing previous ABA-producingS. cerevisiaestrains. Supplementation of the ABA-producingS. boulardiiin the diet of mice (at a concentration of 5 x 108CFU/g) led to effective gut colonization but resulted in low serum ABA levels (approximately 1.8 ng/mL). The absence of detectable serum ABA after administration of the ABA-producing probiotic through oral gavage, prompted further investigation to determine the underlying cause. The physiological body temperature (37°C) was identified as a major bottleneck for ABA production. Modifications to enhance the mevalonate pathway flux improved ABA levels at 37°C. However, additional modifications are needed to optimize ABA production before testing this probiotic in disease contexts in mice.
Most Autophagic Cell Death Studies Lack Evidence of Causality
Authors: Ghaseminejad Yasmin , Özkaya Ali Burak 
Published: December 2024

ABSTRACTAutophagy plays a critical role in maintaining cellular homeostasis and is implicated in various physiological and pathological processes, including cancer, neurodegeneration, and metabolic disorders. Although typically associated with cell survival, autophagy has also been proposed to contribute to cell death, referred to as autophagic cell death (ACD). Despite its importance, the identification of ACD remains contentious due to inconsistencies in experimental methodologies and terminological misuse. In this study, we evaluated 104 research articles published in 2022 that claimed to demonstrate ACD. Articles were assessed based on established criteria, including evidence for autophagy, evidence for cell death, exclusion of apoptosis, and experimental designs demonstrating causality. Our findings reveal that only 12.5% of the articles fulfilled all the criteria for ACD, while 37.5% provided only correlation-level evidence. Additionally, 32.7% of the articles relied on viability loss rather than direct evidence of cell death, and 45.0% of studies utilizing autophagy inhibition to prove causality failed to demonstrate actual inhibition of autophagy. Inconsistent terminology was also prevalent, with cases of ‘autophagy-mediated cell death’ being incorrectly classified as ACD and instances where the term ACD was misused as an umbrella term to describe the coexistence of autophagy and cell death, which should have been labeled ‘autophagy-associated cell death.’ These issues highlight a lack of rigor in current practices, with reliance on correlation-level evidence and inappropriate experimental designs undermining the robustness of many studies. This analysis underscores the need for greater rigor in experimental approaches and article revision processes.
The CD4 T cell-independent IgG response during persistent virus infection favors emergence of neutralization-escape variants
Authors: Ayers Katelyn N , Lauver Matthew D , Alexander Kalynn M , Jin Ge , Paraiso Kitt , Ochetto Alyssa , Garg Sonal , Goetschius Daniel J , Hafenstein Susan L , Wang Joseph Che-Yen , Lukacher Aron E 
Published: December 2024

ABSTRACTHow changes in the quality of anti-viral antibody (Ab) responses due to pre-existing or acquired CD4 T cell insufficiency affect virus evolution during persistent infection are unknown. Using mouse polyomavirus (MuPyV), we found that CD4 T cell depletion before infection results in short-lived plasma cells secreting low-avidity antiviral IgG with limited BCR diversity and weak virus-neutralizing ability. CD4 T cell deficiency during persistent infection incurs a shift from a T-dependent (TD) to T-independent (TI) Ab response, resembling the pre-existing TI Ab response. CD4 T cell loss before infection or during persistent infection is conducive for emergence of Ab-escape variants. Cryo-EM reconstruction of complexes of MuPyV virions with polyclonal IgG directly from infected mice with pre-existing or acquired CD4 T cell deficiency enabled visualization of shortfalls in TI IgG binding. By debilitating the antiviral IgG response, CD4 T cell deficiency sets the stage for outgrowth of variant viruses resistant to neutralization.ONE SENTENCE SUMMARYPre-existing and acquired CD4 T cell deficiency facilitates outgrowth of Ab-escape viral variants during persistent infection.
The 1001G+ project: A curated collection ofArabidopsis thalianalong-read genome assemblies to advance plant research
Authors:   The 1001 Genomes Plus Consortium, Alonso-Blanco Carlos C. , Ashkenazy Haim , Baduel Pierre , Bao Zhigui , Becker Claude , Caillieux Erwann , Colot Vincent , Crosbie Duncan , De Oliveira Louna , Fitz Joffrey , Fritschi Katrin , Grigoreva Elizaveta , Guo Yalong , Habring Anette , Henderson Ian , Hou Xing-Hui , Hu Yiheng , Igolkina Anna , Kang Minghui , Kemen Eric , Kersey Paul J. , Kornienko Aleksandra , Lian Qichao , Liu Haijun , Liu Jianquan , Lucke Miriam , Mayjonade Baptiste , Mercier Raphaël , Mollá Morales Almudena , Movilli Andrea , Murray Kevin D. , Naish Matthew , Nordborg Magnus , Rabanal Fernando A. , Roux Fabrice , Schandry Niklas , Schneeberger Korbinian , Schwab Rebecca , Shirsekar Gautam , Sushko Svitlana , Tao Yueqi , Teasdale Luisa , Vorbrugg Sebastian , Weigel Detlef , Xian Wenfei 
Published: December 2024

AbstractArabidopsis thalianawas the first plant for which a high-quality genome sequence became available. The publication of the first reference genome sequence almost 25 years ago was already accompanied by genome-wide data on sequence polymorphisms in another accession, or naturally occurring strain. Since then, inventories of genome-wide diversity have been generated at increasingly precise levels. High-density genotype data forA. thaliana, including those from the 1001 Genomes Project, were key to demonstrating the enormous power of GWAS in inbred populations of wild plants, and the comparison of intraspecific polymorphism with interspecific divergence has illuminated many aspects of plant genome evolution. Over the past decade, an increasing number of nearly complete genome sequences have been published for many more accessions. Here, we highlight the diversity of a curated collection of previously published and so far unpublished genome sequences assembled using different types of long reads, including PacBio Continuous Long Reads (CLR), PacBio High Fidelity (HiFi) reads, and Oxford Nanopore Technologies (ONT) reads. This 1001 Genomes Plus (1001G+) resource is being made available athttp://1001genomes.org. We invite colleagues with yet unpublished genome assemblies fromA. thalianaaccessions to contribute to this effort.
POLO kinase inhibits Protein Phosphatase 1 to promote the Spindle Assembly Checkpoint and prevent aneuploidy
Authors: Moura Margarida , Barbosa João , Pinto Inês , Leça Nelson , Cunha-Silva Sofia , Verza Arianna Esposito , Pedroso Paulo D. , Lemaire Sarah , Duro Joana , Silva Miguel , Oliveira André , Reis Ricardo , Nilsson Jakob , Sunkel Claudio , Musacchio Andrea , Bollen Mathieu , Conde Carlos 
Published: December 2024

SUMMARYProtein phosphatase 1 (PP1) is essential for spindle assembly checkpoint (SAC) silencing and mitotic exit, but its regulation during mitosis remains ill-defined. Here, we demonstratein vitroand inDrosophilacells that the mitotic kinase POLO phosphorylates PP1α87B at a conserved residue (T286) within a pocket implicated in the recognition of RVxF-containing target proteins. Phosphorylation of T286 inhibits PP1α87B binding to the RVxF motif of the SAC kinase MPS1, dampening the dephosphorylation of MPS1 T-loop. Phosphorylation of T286 is dynamically regulated during mitosis. It occurs at unattached/tensionless kinetochores and decreases as chromosomes congress. Expression of phosphomimetic PP1α87BT286Dprevents MPS1 inactivation in metaphase and causes a SAC-dependent delay of anaphase onset. Conversely, an unphosphorylatable PP1α87BT286Amutant impairs MPS1 activation at unattached kinetochores and weakens the SAC.In vivo, larval neuroblasts expressing PP1α87BT286phosphomutants exhibit frequent chromosome mis-segregation and aneuploidy. Thus, our findings identify POLO-mediated phosphorylation of PP1α87B as a critical regulatory strategy that fine-tunes phosphatase activity to ensure a robust and timely SAC and prevent genome instability.
APR-246 & COTI-2 increase chemoradiotherapy sensitivity via ROS-induced DNA damage and ferroptosis in p53 mutant HPV negative head and neck squamous cell carcinoma
Authors: de Bakker Tycho , Cogels Morgane , Iliadi Chrysanthi , Penninckx Sebastien , Martinive Philippe , Gestel Dirk Van 
Published: December 2024

AbstractAbout 80% of patients with HPV negative head and neck squamous cell carcinoma are diagnosed at stage III or IV. In these cases, Surgical resection followed by (chemo-)radiotherapy is the standard treatment for most cases. However, many patients present with unresectable and/or resistant disease and even metastases, limiting therapeutic options. A common molecular defect in these tumours is the deactivation of the tumour suppressor gene TP53, frequently through inactivating mutations. Restoring TP53 function, combined with the standard chemoradiotherapy may enhance the therapeutic outcomes.In this study, the efficacy of two TP53 reactivating compound, APR-246 and COTI-2, was evaluated in combination with chemoradiotherapy on two different human HNSCC cell lines. Results highlight a synergistic effect of the combination treatment, significantly reducing clonogenic survival, spheroid growth and subcutaneous tumour growth in a preclinical murine model. Mechanistic investigation suggests that this effect is linked to redox imbalance caused by the generation of reactive oxygen species. This appears to play a key role in the Fenton reaction, further facilitated by an increase in DMT1 or decrease in FTH1 expression, leading to elevated cytosolic iron and lipid peroxide levels. Additionally, the reactive oxygen species may contribute towards the increase in both single and double strands breaks observed in several western blots. Overall, these results suggest that combining TP53 reactivation with chemoradiotherapy could trigger ferroptosis, improving tumour control in HNSCC.
Expression of Intron-containing HIV-1 RNA Induces NLRP1 Inflammasome Activation in Myeloid Cells
Authors: Jalloh Sallieu , Hughes Ivy K , Akiyama Hisashi , Gojanovich Aldana , Quiñones Andres , Yang Mengwei , Henderson Andrew J. , Mostoslavsky Gustavo , Gummuluru Suryaram 
Published: December 2024

AbstractDespite the success of antiretroviral therapy (ART) in suppressing plasma viremia in people living with human immunodeficiency virus type-1 (HIV-1), persistent viral RNA expression in tissue reservoirs is observed and can contribute to HIV-1-induced immunopathology and comorbidities. Infection of long-lived innate immune cells, such as tissue-resident macrophages and microglia may contribute to persistent viral RNA production and chronic inflammation. We recently reported thatde-novocytoplasmic expression of HIV-1 intron-containing RNA (icRNA) in macrophages and microglia leads to MDA5 and MAVS-dependent innate immune sensing and induction of type I IFN responses, demonstrating that HIV icRNA is a pathogen-associated molecular pattern (PAMP). In this report, we show that cytoplasmic expression of HIV-1 icRNA also induces NLRP1 inflammasome activation and IL-1β secretion in macrophages and microglia in a RLR- and endosomal TLR-independent manner. Infection of both macrophages and microglia with either replication-competent or single-cycle HIV-1 induced IL-1β secretion, which was attenuated when cytoplasmic expression of viral icRNA was prevented. While IL-1β secretion was blocked by treatment with caspase-1 inhibitors or knockdown of NLRP1 or caspase-1 expression in HIV- infected macrophages, overexpression of NLRP1 significantly enhanced IL-1β secretion in an HIV-icRNA-dependent manner. Immunoprecipitation analysis revealed interaction of HIV-1 icRNA, but not multiply-spliced HIV-1 RNA, with NLRP1, suggesting that HIV-1 icRNA sensing by NLRP1 is sufficient to trigger inflammasome activation. Together, these findings reveal a pathway of NLRP1 inflammasome activation induced byde novoexpressed HIV icRNA in HIV- infected myeloid cells.
Comparative sensitivity ofin vitroacute and chronic apical and transcriptomic points of departure for perfluorooctanoic acid in human vascular endothelial cells
Authors: Opacic Marija , Stanic Bojana , Andric Nebojsa 
Published: December 2024

AbstractIn vitrohuman cell models and new approach methodologies offer valuable alternatives to animal testing, providing human-relevant data for chemical risk assessment. However, the impact of exposure duration and biological levels on the sensitivity of responses in human cellsin vitroremains underexplored. In this study, we employed benchmark concentration modeling to derive and compare points of departure (PODs) for apical (A-POD) and transcriptomic (T-POD) changes in human vascular endothelial cells EA.hy926 following short-term (48 h) and long-term (6 and 12 weeks) exposure to 1, 10, and 100 µM and 1, 10, and 100 nM perfluorooctanoic acid (PFOA), respectively. We found that A-POD could not be calculated for short-term exposure; however, A-PODs after 6 and 12 weeks were determined to be 3.7 nM and 5.4 nM, respectively. mRNA sequencing revealed a significant number of differentially expressed genes in PFOA-exposed EA.hy926 cells across all time points. T-POD values after 6 and 12 weeks (4.1 nM and 22.1 nM, respectively) demonstrated greater sensitivity than the acute T-POD (6.3 µM) and were comparable to the chronic A-POD. Functional gene analysis revealed that transcription was a sensitive, yet general molecular pathway affected by acute exposure, while the IL-17 pathway and extracellular matrix and cytokine-cytokine interactions were implicated after 6 and 12 weeks of exposure to PFOA, respectively. In conclusion, chronic PODs proved to be more informative than acute PODs for chemical risk assessment in PFOA-exposed human endothelial cells. Furthermore, transcriptomics data from long-term exposure can elucidate early molecular pathways associated with chemical exposure, highlighting their potential to connect toxicity effects across different biological levels.