tbuckley/cabot-search huggingface dataset:
A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis
Authors: Alfredo Torres, M. Angélica Michea, Ákos Végvári, Marion Arce, Valentina Pérez, Marcela Alcota, Alicia Morales, Rolando Vernal, Mauricio Budini, Roman A. Zubarev, Fermín E. González
Journal: International Journal of Oral Science (2024)

Abstract Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases, yet its association with progressive periodontitis remains unexplored. To investigate the involvement and significance of ferroptosis in periodontitis progression, we assessed sixteen periodontitis-diagnosed patients. Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid (GCF) collection was performed for further analyses. Clinical metrics, proteomic data, in silico methods, and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis. Subsequent western blot analyses validated key findings. Finally, a single-cell RNA sequencing (scRNA-seq) dataset (GSE164241) for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression. Periodontitis progression was identified as occurring at a faster rate than traditionally thought. GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles. In addition, specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins, including SNCA, CA1, HBB, SLC4A1, and ANK1 was strongly associated with the clinical progression status of periodontitis. Moreover, we found specific proteins - drivers or suppressors - associated with ferroptosis (SNCA, FTH1, HSPB1, CD44, and GCLC), revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis. Additionally, the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis. Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients, which offer new insights into the molecular mechanisms of progressive periodontal disease. These findings may lead to novel diagnostic and therapeutic strategies.
A plasma protein-based risk score to predict hip fractures
Authors: Thomas R. Austin, Maria Nethander, Howard A. Fink, Anna E. Törnqvist, Diana I. Jalal, Petra Buzkova, Joshua I. Barzilay, Laura Carbone, Maiken E. Gabrielsen, Louise Grahnemo, Tianyuan Lu, Kristian Hveem, Christian Jonasson, Jorge R. Kizer, Arnulf Langhammer, Kenneth J. Mukamal, Robert E. Gerszten, Bruce M. Psaty, John A. Robbins, Yan V. Sun, Anne Heidi Skogholt, John A. Kanis, Helena Johansson, Bjørn Olav Åsvold, Rodrigo J. Valderrabano, Jie Zheng, J. Brent Richards, Eivind Coward, Claes Ohlsson
Journal: Nature Aging (2024)

Abstract As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Trøndelag Health Study validation cohorts using the same aptamer-based platform. When transferred to an antibody-based proteomic platform in a UK Biobank validation cohort, the proteomic risk score was strongly associated with hip fractures (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53–1.77). The proteomic risk score, but not available polygenic risk scores for fractures or bone mineral density, improved the C-index beyond the fracture risk assessment tool (FRAX), which integrates information from clinical risk factors (C-index, FRAX 0.735 versus FRAX + proteomic risk score 0.776). The developed proteomic risk score constitutes a new tool for stratifying patients according to hip fracture risk; however, its improvement in hip fracture discrimination is modest and its clinical utility beyond FRAX with information on femoral neck bone mineral density remains to be determined.
METLIN-CCS Lipid Database: An authentic standards resource for lipid classification and identification
Authors: Erin S. Baker, Winnie Uritboonthai, Aries Aisporna, Corey Hoang, Heino M. Heyman, Lisa Connell, Damien Olivier-Jimenez, Martin Giera, Gary Siuzdak
Journal: Nature Metabolism (2024)
Heterogeneity in the definition of major adverse kidney events: a scoping review
Authors: Akinori Maeda, Ryota Inokuchi, Rinaldo Bellomo, Kent Doi
Journal: Intensive Care Medicine (2024)

Acute kidney injury (AKI) is associated with persistent renal dysfunction, the receipt of dialysis, dialysis dependence, and mortality. Accordingly, the concept of major adverse kidney events (MAKE) has been adopted as an endpoint for assessing the impact of AKI. However, applied criteria or observation periods for operationalizing MAKE appear to vary across studies. To evaluate this heterogeneity for MAKE evaluation, we performed a systematic scoping review of studies that employed MAKE as an AKI endpoint. Four major academic databases were searched, and we identified 122 studies with increasing numbers over time. We found marked heterogeneity in applied criteria and observation periods for MAKE across these studies, with some even lacking a description of criteria. Moreover, 13 different observation periods were employed, with 30 days and 90 days as the most common. Persistent renal dysfunction was evaluated by estimated glomerular filtration rate (34%) or serum creatinine concentration (48%); however, 37 different definitions for this component were employed in terms of parameters, cut-off criteria, and assessment periods. The definition for the dialysis component also showed significant heterogeneity regarding assessment periods and duration of dialysis requirement (chronic vs temporary). Finally, MAKE rates could vary by 7% [interquartile range: 1.7-16.7%] with different observation periods or by 36.4% with different dialysis component definitions. Our findings revealed marked heterogeneity in MAKE definitions, particularly regarding component assessment and observation periods. Dedicated discussion is needed to establish uniform and acceptable standards to operationalize MAKE in terms of selection and applied criteria of components, observation period, and reporting criteria for future trials on AKI and related conditions.
Design and Application of an in Situ Traceable NO Donor for Promoting the Healing of Wound Infections
Authors: Shasha Wang, Jiexiang Zhan, Xiaojun Zhou, Chuanglong He, Peng Wei, Tao Yi
Journal: Advanced Healthcare Materials (2024)

Therapies for wound infections require medications with antibacterial and wound-healing functions. However, it remains a challenge to produce a single drug that can perform dual functions. Nitric oxide (NO), with its antibacterial and wound-healing activities, is an ideal solution to address this challenge. However, many controlled-release strategies for NO rely on external probes for tracing the release in situ, making it difficult to precisely assess the location and magnitude. To address this issue, this study describes a novel NO donor, DHU-NO1, capable of efficiently releasing NO under mild conditions (450 nm illumination). Simultaneously, DHU-NO1 generates the fluorophore Azure B (AZB), which enables direct, non-consumptive tracing of the NO release by monitoring the fluorescence and absorption changes in AZB. Given that NO can be conveniently traced, the amount of released NO can be controlled during biological applications, thereby allowing both functions of NO to be performed. When applied to the affected area, DHU-NO1, illuminated by both a simple light-emitting diode (LED) light source and natural light, achieves significant antibacterial effects against wound infections and promotes wound healing in mice. This study offers a novel and effective approach for treating wound infections.
Sacubitril/valsartan for the treatment of non‐obstructive hypertrophic cardiomyopathy: An open label randomized controlled trial (<scp>SILICOFCM</scp>)
Authors: Lazar Velicki, Dejana Popovic, Nduka C. Okwose, Andrej Preveden, Milorad Tesic, Maria Tafelmeier, Sarah J. Charman, Fausto Barlocco, Guy A. MacGowan, Petar M. Seferovic, Nenad Filipovic, Arsen Ristic, Iacopo Olivotto, Lars S. Maier, Djordje G. Jakovljevic
Journal: European Journal of Heart Failure (2024)

Sacubitril/valsartan treatment reduces mortality and hospitalizations in heart failure with reduced ejection fraction but has limited application in hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the effect of sacubitril/valsartan on peak oxygen consumption (VO
Challenges in monitoring the quality of care in multiple sclerosis—authors' reply
Authors: Isabel Voigt, Stefanie Fischer, Undine Proschmann, Urszula Konofalska, Peggy Richter, Hannes Schlieter, Thomas Berger, Sven G Meuth, Hans-Peter Hartung, Katja Akgün, Tjalf Ziemssen
Journal: The Lancet Regional Health - Europe (2024)
<scp>SUGP2</scp> p.(<scp>Arg639Gln</scp>) variant is involved in the pathogenesis of hemochromatosis via the <scp>CIRBP</scp>/<scp>BMPER</scp> signaling pathway
Authors: Yanmeng Li, Anjian Xu, Susu Liu, Wei Zhang, Donghu Zhou, Qin OuYang, Huaduan Zi, Bei Zhang, Ning Zhang, Wei Geng, Yiming Zhou, Weijia Duan, Xiaoming Wang, Xinyan Zhao, Xiaojuan Ou, Changfa Fan, Jidong Jia, Jian Huang
Journal: American Journal of Hematology (2024)

Abstract Pathogenic variants in HFE and non‐ HFE genes have been identified in hemochromatosis in different patient populations, but there are still a certain number of patients with unexplained primary iron overload. We recently identified in Chinese patients a recurrent p.(Arg639Gln) variant in SURP and G‐patch domain containing 2 (SUGP2), a potential mRNA splicing‐related factor. However, the target gene of SUGP2 and affected iron‐regulating pathway remains unknown. We aimed to investigate the pathogenicity and underlying mechanism of this variant in hemochromatosis. RNA‐seq analysis revealed that SUGP2 knockdown caused abnormal alternative splicing of CIRBP pre‐mRNA, resulting in an increased normal splicing form of CIRBP V1, which in turn increased the expression of BMPER by enhancing its mRNA stability and translation. Furthermore, RNA‐protein pull‐down and RNA immunoprecipitation assays revealed that SUGP2 inhibited splicing of CIRBP pre‐mRNA by a splice site variant at CIRBP c.492 and was more susceptible to CIRBP c.492 C/C genotype. Cells transfected with SUGP2 p.(Arg639Gln) vector showed up‐regulation of CIRBP V1 and BMPER expression and down‐regulation of pSMAD1/5 and HAMP expression. CRISPR‐Cas9 mediated SUGP2 p.(Arg622Gln) knock‐in mice showed increased iron accumulation in the liver, higher total serum iron, and decreased serum hepcidin level. A total of 10 of 54 patients with hemochromatosis (18.5%) harbored the SUGP2 p.(Arg639Gln) variant and carried CIRBP c.492 C/C genotype, and had increased BMPER expression in the liver. Altogether, the SUGP2 p.(Arg639Gln) variant down‐regulates hepcidin expression through the SUGP2/CIRBP/BMPER axis, which may represent a novel pathogenic factor for hemochromatosis.
Current status of community resources and priorities for weed genomics research
Authors: Jacob Montgomery, Sarah Morran, Dana R. MacGregor, J. Scott McElroy, Paul Neve, Célia Neto, Martin M. Vila-Aiub, Maria Victoria Sandoval, Analia I. Menéndez, Julia M. Kreiner, Longjiang Fan, Ana L. Caicedo, Peter J. Maughan, Bianca Assis Barbosa Martins, Jagoda Mika, Alberto Collavo, Aldo Merotto, Nithya K. Subramanian, Muthukumar V. Bagavathiannan, Luan Cutti, Md. Mazharul Islam, Bikram S. Gill, Robert Cicchillo, Roger Gast, Neeta Soni, Terry R. Wright, Gina Zastrow-Hayes, Gregory May, Jenna M. Malone, Deepmala Sehgal, Shiv Shankhar Kaundun, Richard P. Dale, Barend Juan Vorster, Bodo Peters, Jens Lerchl, Patrick J. Tranel, Roland Beffa, Alexandre Fournier-Level, Mithila Jugulam, Kevin Fengler, Victor Llaca, Eric L. Patterson, Todd A. Gaines
Journal: Genome biology (2024)

Abstract Weeds are attractive models for basic and applied research due to their impacts on agricultural systems and capacity to swiftly adapt in response to anthropogenic selection pressures. Currently, a lack of genomic information precludes research to elucidate the genetic basis of rapid adaptation for important traits like herbicide resistance and stress tolerance and the effect of evolutionary mechanisms on wild populations. The International Weed Genomics Consortium is a collaborative group of scientists focused on developing genomic resources to impact research into sustainable, effective weed control methods and to provide insights about stress tolerance and adaptation to assist crop breeding.
Plasma proteomics analysis of patients with chronic spontaneous urticaria reveals significant associations with key disease characteristics but not with response to omalizumab treatment
Authors: Misbah Noshela Ghazanfar, Valdemaras Petrosius, Jennifer Astrup Sørensen, Ditte Georgina Zhang, Zarqa Ali, Marcus Maurer, Emek Kocatürk, Valdemar Wendelboe Nielsen, Simonas Savickas, Ulrich auf dem Keller, Erwin M. Schoof, Simon Francis Thomsen
Journal: Allergy (2024)

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Data S1. Data S2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Risk of death, major adverse cardiac events and relapse in patients with bullous pemphigoid treated with systemic or topical corticosteroids
Authors: Khalaf Kridin, Katja Bieber, Artem Vorobyev, Eva Lotta Moderegger, Gema Hernandez, Enno Schmidt, Ralf J Ludwig
Journal: British Journal of Dermatology (2024)

Abstract Background According to current guidelines, systemic or topical corticosteroids are both recommended as first-line treatments for bullous pemphigoid (BP). There is evidence to suggest that topical application may be associated with a lower risk of mortality. However, there is a lack of comprehensive large-scale data comparing mortality rates, as well as the risk of major adverse cardiac events (MACE), infections and relapse, between systemic and topical corticosteroid treatments. Objectives To evaluate the risk of death, MACE, infections and relapse in patients with BP treated with systemic or topical corticosteroids. Methods A population-based retrospective cohort study was performed using the TriNetX US Collaborative Network. As a measure against bias, propensity score matching for age, sex, 10 diseases and 6 medications was done, and 3 sensitivity analyses were conducted. Results All-time risk of death was increased in US patients with BP exposed to any dose of systemic corticosteroids (n = 2917) vs. patients treated with topical clobetasol propionate [n = 2932; hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.28–1.58 (P &amp;lt; 0.001)]. This was consistent in time-stratified analysis (1- and 3-year mortality rates) and in analysis contrasting prednisone (equivalent) doses of 1–10 mg (low) or 30–100 mg (medium–high) systemic corticosteroid to topical treatment. The increased risk of death in US patients with BP exposed to any dose of systemic corticosteroids vs. topical treatment was accompanied by increased risks for MACE (HR 1.33, 95% CI 1.08–1.64; P = 0.008) and infections (HR 1.33, 95% CI 1.15–1.54; P &amp;lt; 0.001). The risk of continued disease or relapse was decreased in patients treated with systemic vs. topical corticosteroids (HR 0.85, 95% CI 0.77–0.94; P = 0.002). Results regarding mortality and continued disease or relapse persisted in three sensitivity analyses. Potential limitations included the retrospective data collection, bias for treatment selection and miscoding. Conclusions Pending validation in prospective studies, where feasible – and despite the heightened risk of relapse – topical corticosteroid treatment may be advantageous over systemic corticosteroid treatment owing to its significantly lower risk of death.
The impact of high‐salt diet on asthma in humans and mice: Effect on specific T‐cell signatures and microbiome
Authors: Stephanie Musiol, Carla P. Harris, Silvia Gschwendtner, Amy Burrell, Yacine Amar, Benjamin Schnautz, Dennis Renisch, Sonja C. Braun, Stefan Haak, Michael Schloter, Carsten B. Schmidt‐Weber, Christina E. Zielinski, Francesca Alessandrini
Journal: Allergy (2024)

Abstract Background The rise in asthma has been linked to different environmental and lifestyle factors including dietary habits. Whether dietary salt contributes to asthma incidence, remains controversial. We aimed to investigate the impact of higher salt intake on asthma incidence in humans and to evaluate underlying mechanisms using mouse models. Methods Epidemiological research was conducted using the UK Biobank Resource. Data were obtained from 42,976 participants with a history of allergies. 24‐h sodium excretion was estimated from spot urine, and its association with asthma incidence was assessed by Cox regression, adjusting for relevant covariates. For mechanistic studies, a mouse model of mite‐induced allergic airway inflammation (AAI) fed with high‐salt diet (HSD) or normal‐salt chow was used to characterize disease development. The microbiome of lung and feces (as proxy for gut) was analyzed via 16S rRNA gene based metabarcoding approach. Results In humans, urinary sodium excretion was directly associated with asthma incidence among females but not among males. HSD‐fed female mice displayed an aggravated AAI characterized by increased levels of total IgE, a T H 2‐T H 17‐biased inflammatory cell infiltration accompanied by upregulation of osmosensitive stress genes. HSD induced distinct changes in serum short chain fatty acids and in both gut and lung microbiome, with a lower Bacteroidetes to Firmicutes ratio and decreased Lactobacillus relative abundance in the gut, and enriched members of Gammaproteobacteria in the lung. Conclusions High dietary salt consumption correlates with asthma incidence in female adults with a history of allergies. Female mice revealed HSD‐induced T‐cell lung profiles accompanied by alterations of gut and lung microbiome.
The transplantation of the gut microbiome of fat-1 mice protects against colonic mucus layer disruption and endoplasmic reticulum stress induced by high fat diet
Authors: Amina Bourragat, Quentin Escoula, Sandrine Bellenger, Olivier Zemb, Martin Beaumont, Killian Chaumonnot, Jean-Pierre Farine, Emmanuel Jacotot, Aline Bonnotte, Laure Avoscan, Jeanine Lherminier, Kangjia Luo, Michel Narce, Jérôme Bellenger
Journal: Gut Microbes (2024)

High-fat diets alter gut barrier integrity, leading to endotoxemia by impacting epithelial functions and inducing endoplasmic reticulum (ER) stress in intestinal secretory goblet cells. Indeed, ER stress, which is an important contributor to many chronic diseases such as obesity and obesity-related disorders, leads to altered synthesis and secretion of mucins that form the protective mucus barrier. In the present study, we investigated the relative contribution of omega-3 polyunsaturated fatty acid (PUFAs)-modified microbiota to alleviating alterations in intestinal mucus layer thickness and preserving gut barrier integrity. Male fat-1 transgenic mice (exhibiting endogenous omega-3 PUFAs tissue enrichment) and wild-type (WT) littermates were fed either an obesogenic high-fat diet (HFD) or a control diet. Unlike WT mice, HFD-fed fat-1 mice were protected against mucus layer alterations as well as an ER stress-mediated decrease in mucin expression. Moreover, cecal microbiota transferred from fat-1 to WT mice prevented changes in the colonic mucus layer mainly through colonic ER stress downregulation. These findings highlight a novel feature of the preventive effects of omega-3 fatty acids against intestinal permeability in obesity-related conditions.
The protective role of commensal gut microbes and their metabolites against bacterial pathogens
Authors: Liqin Cheng, Mário S. P. Correia, Shawn M. Higdon, Fabricio Romero Garcia, Ioanna Tsiara, Enrique Joffré, Åsa Sjöling, Fredrik Boulund, Elisabeth Lissa Norin, Lars Engstrand, Daniel Globisch, Juan Du
Journal: Gut Microbes (2024)

Multidrug-resistant microorganisms have become a major public health concern around the world. The gut microbiome is a gold mine for bioactive compounds that protect the human body from pathogens. We used a multi-omics approach that integrated whole-genome sequencing (WGS) of 74 commensal gut microbiome isolates with metabolome analysis to discover their metabolic interaction with Salmonella and other antibiotic-resistant pathogens. We evaluated differences in the functional potential of these selected isolates based on WGS annotation profiles. Furthermore, the top altered metabolites in co-culture supernatants of selected commensal gut microbiome isolates were identified including a series of dipeptides and examined for their ability to prevent the growth of various antibiotic-resistant bacteria. Our results provide compelling evidence that the gut microbiome produces metabolites, including the compound class of dipeptides that can potentially be applied for anti-infection medication, especially against antibiotic-resistant pathogens. Our established pipeline for the discovery and validation of bioactive metabolites from the gut microbiome as novel candidates for multidrug-resistant infections represents a new avenue for the discovery of antimicrobial lead structures.