bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertension Shifts Gut Microbiota and Tryptophan Metabolism in Women
Authors: Shah Shrushti , Mu Chunlong , Shen-Tu Grace , Schlicht Kristina , Forkert Nils , Laudes Matthias , Köfeler Harald , Shearer Jane 
Published: February 2025

ABSTRACTBackgroundHypertension affects over 1.28 billion adults worldwide, including a significant number of women. Although the gut microbiome is implicated in the onset and progression of hypertension, few studies have examined the relationship in middle-aged women.MethodsWithin an established cohort, we investigated the relationship between gut microbiota and its metabolites in normotensive vs. hypertensive middle-aged women (n=108) matched for age (56.6±0.91 years) and body mass index (24.3±0.24 kg/m²). Fecal microbiota analysis was performed using 16S rRNA sequencing and serum metabolites were analyzed using LC-MS/QTOF. Associations between the microbiota, metabolomic alterations and systemic inflammatory cytokines were statistically examined to uncover their interrelationships and potential role in disease progression.ResultsWomen with hypertension had gut dysbiosis with an increased Firmicutes/Bacteroidetes ratio and higher abundances of inflammatory taxa includingAnaerostipesandCollinsella. Untargeted serum metabolomics demonstrated that hypertensive participants had elevated levels of tryptophan, the pro-inflammatory metabolite kynurenine and lower levels of health-promoting indoles produced by the action of gut microbiota on tryptophan (p<0.05). These findings were confirmed in microbiota analysis showing a reduced abundance of indole-producing species (Alistipes shahii,Bacteroides faecichinchillae, Bacteroides stercoris)(p<0.05) suggesting a lower microbial activity of tryptophan-indole metabolism. Furthermore, hypertension increased inflammatory markers including an elevated IL12/IL10 ratio, interferon-γ and tumor necrosis factor-α. The IL-12/IL-10 ratio demonstrated a positive correlation with kynurenine levels, emphasizing the involvement of cytokines and gut microbiota in driving systemic inflammation in hypertension.ConclusionImbalances in microbiota-regulated tryptophan metabolism contribute to systemic inflammation in hypertensive, middle-aged women, presenting a potentially modifiable target for intervention.GRAPHICAL ABSTRACT
Sleep duration, physical activity and cardiometabolic multimorbidity: Findings from the English Longitudinal Study of Ageing
Authors: Kunutsor Setor K. , Laukkanen Jari A. 
Published: February 2025

AbstractBackgroundU-shaped relationships have been demonstrated between sleep duration and several cardiometabolic conditions. However, the association between sleep duration and cardiometabolic multimorbidity (CMM) and the interrelationship with physical activity has not been previously investigated. We aimed to assess the prospective associations of sleep habits (duration and quality) with CMM and the interplay with physical activity.Methods and ResultsWe included 3,428 participants (mean age 63 years at baseline, 44.8% male) free of hypertension, coronary heart disease, diabetes, and stroke at wave 4 from the English Longitudinal Study of Ageing. Sleep habits were assessed by self-reports. Cardiometabolic multimorbidity was defined as the presence of at least two multiple long-term conditions (hypertension, cardiovascular disease, diabetes, and stroke) at wave 10. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression models adjusted for established cardiometabolic risk factors including physical activity. At 15 years follow-up, 206 participants developed CMM. There was an approximate U-shaped trend between sleep duration and the risk of CMM. Compared to participants with sleep duration of 7-8 hrs/day, the multivariable OR (95% CI) for CMM was 1.39 (1.03-1.90) for sleep duration ≤6 hrs/day and 1.05 (0.55-2.00) for sleep duration ≥ 9 hrs/day. The odds of CMM modestly decreased for each additional hour increase in sleep duration in participants with sleep duration ≤6 hrs/day (OR, 0.78, 95% CI: 0.59-1.02). Sleep quality or physical activity was not associated with CMM.ConclusionsShort sleep duration is associated with an increased risk of CMM, which is independent of established cardiometabolic risk factors including physical activity. Importantly, each additional hour of sleep among those with short sleep durations appeared to mitigate CMM risk, underscoring the potential benefits of optimizing sleep duration.
Dysregulation of cell migration by matrix metalloproteinases in geleophysic dysplasia
Authors: Morales Alejo A. , Camarena Vladimir , Peart LéShon , Smithson Sarah , Shaw Lindsay , Webber Lucy , Negron Jose M. , Sola Juan E. , Brady Ann-Christina , Walz Katherina , Wang Gaofeng , Tekin Mustafa 
Published: February 2025

AbstractGeleophysic dysplasia (GD) is characterized by short stature, brachydactyly, joint limitations, a distinctive facial appearance, as well as cardiac and respiratory dysfunction that can be life-threatening. GD is caused by pathogenic variants in theADAMTSL2,FBN1,orLTBP3genes. While dermal fibroblasts derived from affected individuals have shown poor organization of the extracellular matrix (ECM), it remains elusive how the disorganized ECM contributes to GD pathogenesis. To understand the molecular mechanisms in GD, we isolated and characterized primary human dermal fibroblasts from affected individuals withADAMTSL2andFBN1variants. We found that the secretion of ECM proteins including ADAMTSL2, FBN1, and Fibronectin were impaired in GD fibroblasts. Increased cell migration was observed in GD fibroblasts carryingADAMTSL2orFBN1variants, which was associated with up-regulation of MMP-1 and MMP-14, two proteases related to cell mobility. The enhanced cell migration and up-regulation of MMP-1 and MMP-14 were corroborated in mouse primary dermal fibroblasts carrying pathogenic variants inAdamtsl2and in lung and heart tissues fromAdamtsl2-knockoutmice. A pan MMP inhibitor, GM6001, inhibited the migration of GD fibroblasts. Overall, our results suggest that MMP-1/-14 up-regulation play a role in the development of GD and may be utilized as a treatment target.
Nora virus proliferates in dividing intestinal stem cells and sensitizes flies to intestinal infection and oxidative stress
Authors: Franchet Adrien , Haller Samantha , Yamba Miriam , Barbier Vincent , Thomaz-Vieira Angelica , Leclerc Vincent , Becker Stefanie , Lee Kwang-Zin , Orlov Igor , Spehner Danièle , Daeffler Laurent , Ferrandon Dominique 
Published: February 2025

AbstractThe digestive tract represents the most complex interface of an organism with its biotope. Food may be contaminated by pathogens and toxicants while an abundant and complex microbiota strives in the gut lumen. The organism must defend itself against potentially noxious biotic or abiotic stresses while preserving its microbiota, provided it plays a beneficial role. The presence of intestinal viruses adds another layer of complexity. Starting from a differential sensitivity of two lines from the sameDrosophilawild-type strain to ingestedPseudomonas aeruginosa, we report here that the presence of Nora virus in the gut epithelium promotes the sensitivity to this bacterial pathogen as well as to an ingested oxidizing xenobiotic. The genotype, age, nature of the ingested food and to a limited extent the microbiota are relevant parameters that influence the effects of Nora virus on host fitness. Mechanistically, we detect the initial presence of viral proteins essentially in progenitor cells. Upon stress such as infection, exposure to xenobiotics, aging or feeding on a rich-food diet, the virus is then detected in enterocytes, which correlates with a disruption of the intestinal barrier function in aged flies. Finally, we show that the virus proliferates only when ISCs are induced to divide and that blocking either enterocyte apoptosis or JAK/STAT-driven ISC division leads to a drastically reduced Nora virus titer.In conclusion, it is important to check that experimental strains are devoid of intestinal viruses when monitoring survival/life span of fly lines or when investigating the homeostasis of the intestinal epithelium as these viruses can constitute significant confounding factors.
Platform-dependent effects of genetic variants on plasma APOL1 and their implications for kidney disease
Authors: Wang Qingbo S. , Huang Jinguo , Chan Leanne , Haste Nicole , Olsson Niclas , Gaun Aleksandr , McAllister Fiona , Madhireddy Deepthi , Baruch Amos , Melamud Eugene , Baryshnikova Anastasia 
Published: February 2025

AbstractMutations in apolipoprotein L1 (APOL1) are strongly associated with an increased risk of kidney disease in individuals of African ancestry, yet the underlying mechanisms remain largely unknown. Plasma proteomics provides opportunities to elucidate mechanisms of disease by studying the effects of disease-associated variants on circulating protein levels. Here, we examine the genetic drivers of circulating APOL1 in individuals of African and European ancestry from four independent cohorts (UK Biobank, AASK, deCODE and Health ABC) employing three proteomic technologies (Olink, SomaLogic and mass spectrometry). We find that disease-associatedAPOL1G1 and G2 variants are strong pQTLs for plasma APOL1 in Olink and SomaLogic, but the direction of their effects depends on the proteomic platform. We identify an additionalAPOL1missense variant (rs2239785), common in Europeans, exhibiting the same platform-dependent directional discrepancy. Similarly, variants in the kallikrein-kinin pathway (KLKB1,F12,KNG1) and their genetic interactions exhibit strongtrans-pQTL effects for APOL1 measured by Olink, but not SomaLogic. To explain these discrepancies, we propose a model in whichAPOL1mutations and the kallikrein-kinin pathway influence the relative abundance of two distinct APOL1 forms, corresponding to APOL1 bound to trypanolytic factors 1 and 2, which are differentially recognized by different proteomic platforms. We hypothesize that this shift in relative abundance of APOL1 forms may contribute to the development of kidney disease.
Evaluation of Protein Cards: A nutrition education tool for metabolic bariatric surgery
Authors: Acosta Patricia F.C. , Heidl Alexandra J. , Angeles Patricia M. , Farnesi Biagina-Carla , Alcindor Peggy , Alberga Angela S. , Erdstein Julius , Saputra Stephanie , Cohen Tamara R. 
Published: February 2025

AbstractBackgroundMetabolic bariatric surgery (MBS) is a safe, effective treatment for severe obesity and its associated comorbidities. However, adherence to postoperative guidelines, particularly dietary protein intake remains a challenge. This study examined the suitability of theProtein Cards, a protein-focused nutrition education tool developed to support individuals meet their protein requirements during the postoperative diet stages: fluid, purée, soft, and regular diets.MethodsAn online adapted version of the Suitability Assessment of Materials questionnaire was administered from September 2020 to May 2021. Participants were recruited via convenience sampling and advertisement. The tool was rated as “superior”, “adequate” or “not suitable” on content, literacy demand, graphic illustrations, layout and typography, learning stimulation and motivation, and cultural appropriateness, with scores of 2, 1, and 0, respectively.ResultsA total of 442 individuals completed the online survey. Participants were identified as individuals who have undergone MBS (n= 268), caregivers of individuals who completed MBS (n =68), and/or healthcare providers specializing in MBS (n =106). TheProtein Cardsreceived an overall “superior” rating of 73.16%. The tool had a high likelihood of use particularly for the soft diet stage (63.98 ± 20.71). Participants preferred the tool be available as a mobile application (63.46 ± 20.44) followed by paper book (59.42 ± 22.12) format.ConclusionThe development of nutrition education tools is essential for supporting individuals who have undergone MBS in adopting healthy dietary habits, particularly in their meeting protein requirements. Future studies will refine theProtein Cardsand evaluate its usability among individuals post-MBS.
Regional and national estimates of children affected by all-cause and COVID-19-associated orphanhood and caregiver death in Brazil, by age and family circumstance
Authors: Steyn Nicholas , Unwin H Juliette T , Ponmattam Jamie , Villaveces Andrés , Martins Luiza , Sherr Lorraine , Blenkinsop Alexandra , Semenova Elizaveta , Stuart-Brown Alice , Amaral André Victor Ribeiro , Ratmann Oliver , Schnekenberg Ricardo Parolin , Cluver Lucie , Hillis Susan , Rawlings Laura , Barberia Lorena , Souza Andrea Santos , Castro Marcia C , Flaxman Seth 
Published: February 2025

AbstractChildren affected by orphanhood of any cause may benefit from assessment and referral to appropriate services. Timely and accurate data can guide policy. We leveraged new data sources expanding previous reports on national COVID-19-associated orphanhood to estimate national and sub-national numbers of children newly affected by death of parents and co-residing elderly caregivers due to all-causes and to COVID-19-associated causes in 2020-2021 in Brazil.We estimated that 1,300,000 (95% uncertainty interval 1,190,000, 1,430,000) children in Brazil experienced loss of one or multiple parents and/or co-residing caregivers 60+. 673,000 (652,000, 690,000) children were estimated to have lost one or both parents, of which 149,000 (144,000, 154,000) were COVID-19-associated; 635,000 (534,000, 758,000) children were estimated to have lost a co-residing grandparent or other kin, of which 135,000 (85,900, 199,000) were COVID-19-associated.Orphanhood estimates varied across states. The highest all-cause rate of parental orphanhood was in Roraima, at 17.5 (95% uncertainty interval 15.6, 20.6) per 1000 children, and the lowest was in Santa Catarina, at 9.5 (8.7, 10.4) per 1000 children. COVID-19-associated orphanhood was also unevenly distributed, with Mato Grosso experiencing the greatest rate, at 4.4 (3.9, 5.3) per 1000 children, while Pará experienced the lowest rate of 1.4 (1.2, 1.8) per 1000 children.We compared our estimates with administrative data for COVID-19-associated orphanhood (from Brazil’s civil registry offices and manually reviewed death certificates in Campinas) and found that a similar demographic distribution of orphanhood. However, our estimates suggested that administrative sources undercount orphanhood, suggesting that approximately 32% and 56% of total orphanhood was captured in the two datasets, respectively.Our findings highlight the extent of orphanhood in Brazil and the large inequalities between states. Our comparisons with administrative data both validate our model and suggest that strengthening vital registration systems can put children at the center of public health responses globally.
Mini-Seizures: Novel Interictal iEEG Biomarker Capturing Synchronization Network Dynamics at the Epileptogenic Zone
Authors: Monsoor Tonmoy , Kanai Sotaro , Daida Atsuro , Kuroda Naoto , Sinha Prateik , Oana Shingo , Zhang Yipeng , Liu Lawrence , Singh Gaurav , Duan Chenda , Sim Myung Shin , Fallah Aria , Speier William , Asano Eishi , Roychowdhury Vwani , Nariai Hiroki 
Published: February 2025

ABSTRACTEpilepsy affects 1% of the population, with up to one-third of patients being medication-resistant. Surgery is the only curative treatment, yet over one-third of surgical patients fail to achieve seizure freedom due to the lack of a reliable epileptogenic zone (EZ) biomarker. We introduced and validated mini-seizures, frequent hypersynchronization events at EZ hubs that mirror seizure network dynamics, as a novel interictal EEG biomarker. Using a dynamical networks-based model, we analyzed short interictal intracranial EEG from 159 patients across two institutions. Our model, integrating hypersynchronous network properties and clinical data, successfully identified EZ hubs and accurately predicted one-year postoperative seizure outcomes. Our model (mean F1 score: 87%) outperformed the high-frequency oscillations-based model (mean F1 score: 79%) and seizure onset zone resection-status-based model (current clinical standard) (mean F1 score: 78%), supporting its potential as a robust interictal biomarker for EZ localization. Our findings suggest mini-seizures and seizures exist on a continuum of epileptic events, sharing common network properties. Unlike seizure-based analyses that require 1-2 weeks of monitoring to capture spontaneous seizures, mini-seizures provide a rapid alternative using only brief interictal recordings.
Long Covid in Older Adults: Functional Outcomes and Treatment Effectiveness
Authors: Wagner Brittin , Mathers Kate , Norfolk Aaron , Arora Tanishtha 
Published: February 2025

SUMMARYWe describe six-month functional status, hospitalization, and mortality among 23,632 cases of Long Covid in skilled nursing facilities (SNFs) in the US, primarily experienced by adults over 65 years old. We describe outcomes across seven medications used to treat Covid-19 including functional status (ADLs).
Integrating a conceptual consent permission model from the informed consent ontology for software application execution
Authors: Amith Muhammad “Tuan” , He Yongqun , Smith Elise , Harris Marceline , Manion Frank , Tao Cui 
Published: February 2025

AbstractWe developed a simulated process to show a software implementation to facilitate an approach to integrate the Informed Consent Ontology, a reference ontology of informed consent information, to express implicit description and implement conceptual permission from informed consent life cycle. An early study introduced an experimental method to use Semantic Web Rule Language (SWRL) to describe and represent permissions to computational deduce more information from the Informed Consent Ontology (ICO), demonstrated by the use of the All of Us informed consent documents. We show how incomplete information in informed consent documents can be elucidated using a computational model of permissions toward health information technology that integrates ontologies. Future goals entail applying our computational approach for specific sub-domains of the informed consent life cycle, specifically for vaccine informed consent.
Initial leads to combat streptogramin resistance generated from X-ray fragment screening against VatD
Authors: Asthana Pooja , Lee Sonya , MacDonald Christian M. , Seiple Ian , Fraser James S 
Published: February 2025

SummaryStreptogramins are potent antibiotics targeting bacterial ribosome. The synergistic binding of group A and B streptogramins to 50S-ribosome, yields bactericidal effects. However, their efficacy is compromised by resistance mechanisms, including enzymatic acetylation of group A streptogramins by Virginiamycin Acetyl Transferase (Vat) enzymes, which reduces their affinity for ribosomes. Using fragment-based drug discovery we identified starting points for development of VatD inhibitors. X-ray crystallography screening revealed three primary fragment-binding sites on VatD. In the acetyl binding subsite, fragments stabilized distinct conformational states in critical residues, His82 and Trp121. In the antibiotic binding site, two fragments formed interactions that could be leveraged for competitive inhibition. Elaborations of these fragments showed weak inhibition of VatD activity, indicating potential for further optimization. These findings establish initial hits that could restore streptogramin efficacy by targeting VatD directly, providing a structural foundation for inhibitor development against resistant bacterial strains.
Multi-kinesin clusters impart mechanical stress that reveals mechanisms of microtubule breakage in cells
Authors: Geng Qi , Bonilla Andres , Sandwith Siara N. , Verhey Kristen J. 
Published: February 2025

AbstractMicrotubules are cytoskeletal filaments that provide structural support for numerous cellular processes. Despite their high rigidity, microtubules can be dramatically bent in cells and it is unknown how much force a microtubule can withstand before breaking. We find that liquid-liquid phase separation of the kinesin-3 motor KIF1C results in multi-kinesin clusters that entangle neighboring microtubules and impose a high level of mechanical stress that results in microtubule breakage and disassembly. Combining computational simulations and experiments, we show that microtubule fragmentation is enhanced by having a highly processive kinesin motor domain, a stiff clustering mechanism, and sufficient drag force on the microtubules. We estimate a rupture force for microtubules in cells of 70-120 pN, which is lower than previous estimates based onin vitrostudies with taxol-stabilized microtubules. These results indicate that the presence of multiple kinesins on a cargo has the potential to cause microtubule breakage. We propose that mechanisms exist to protect microtubule integrity by releasing either the motor-cargo or motor-microtubule interaction, thereby preventing the accumulation of mechanical stress upon the engagement of multi-motor clusters with microtubules.
Temporal dimensions of a microbial invader in a plant-microbiome feedback model
Authors: Parker William H. , Rakowski Chase J. , Yitbarek Senay 
Published: February 2025

SummaryPlant-soil feedback (PSF) theory leverages the increasingly recognized ecological significance of microbiomes to provide insight into plant coexistence. However, PSF theory generally assumes that microbiomes have static composition and properties. In reality, plant communities are thought to experience high rates of colonization by new microbial strains.Here we use a PSF model to study the conditions under which soil-associated fungi invade a community of two plant species and their associated microbiomes at different stages of assembly. We manipulate fungal colonization timing, initial plant and microbiome evenness, and properties of all actors, then analyze the resulting community structure.Microbial invasion is most successful early in community assembly. However, invasion outcomes are highly variable across colonization timing. We derive an expression showing that the net support for the invader by the plants determines invasion success. When successful, the invader disrupts the negative feedback among the plants and their microbiomes that enables plant coexistence.Our results highlight the importance of plant-microbial interactions in microbial invasion success, as well as the susceptibility of plant coexistence to soil-associated microbial invaders during transient dynamics. Broadly, our approach integrating a host-microbiome framework with time-dependent interactions is promising for predicting biodiversity dynamics in a changing world.