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Dysfunctional extracellular matrices (ECM) contribute to aging and disease. Repairing dysfunctional ECM could potentially prevent age-related pathologies. Interventions promoting longevity also impact ECM gene expression. However, the role of ECM composition changes in healthy aging remains unclear. Here we perform proteomics and in-vivo monitoring to systematically investigate ECM composition (matreotype) during aging in C. elegans revealing three distinct collagen dynamics. Longevity interventions slow age-related collagen stiffening and prolong the expression of collagens that are turned over. These prolonged collagen dynamics are mediated by a mechanical feedback loop of hemidesmosome-containing structures that span from the exoskeletal ECM through the hypodermis, basement membrane ECM, to the muscles, coupling mechanical forces to adjust ECM gene expression and longevity via the transcriptional co-activator YAP-1 across tissues. Our results provide in-vivo evidence that coordinated ECM remodeling through mechanotransduction is required and sufficient to promote longevity, offering potential avenues for interventions targeting ECM dynamics.

AIM: The 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. METHODS: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation and the 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.

Abstract: This article focuses on a recently developed formulation based on the noncommutative branch‐cut cosmology, the Wheeler‐DeWitt (WdW) equation, the Hořava–Lifshitz quantum gravity, chaotic and the coupling of the corresponding Lagrangian approach with the inflaton scalar field. Assuming a mini‐superspace of variables obeying the noncommutative Poisson algebra, we examine the impact of the inflaton scalar field on the evolutionary dynamics of the branch‐cut Universe scale factor, characterized by the dimensionless helix‐like function . This scale factor characterizes a Riemannian foliated spacetime that topologically overcomes the primordial singularities. We take the Hořava–Lifshitz action modeled by branch‐cut quantum gravity as our starting point, which depends on the scalar curvature of the branched Universe and its derivatives and which preserves the diffeomorphism property of General Relativity, maintaining compatibility with the Arnowitt–Deser–Misner formalism. We then investigate the sensitivity of the scale factor of the branch‐cut Universe's dynamics.

Inconsistent use of terminology among diverse stakeholders hinders effective communication in micronutrient programs, especially large-scale food fortification (LSFF) which involves stakeholders from different sectors. To align the terminology use, the Micronutrient Data Innovation Alliance (DInA) of the Micronutrient Forum (MNF) created a lexicon of terms related to LSFF and other micronutrient programs. The purpose of this lexicon is to establish a central repository of consensus definitions of key terms to facilitate communication among diverse stakeholders involved in micronutrient programs including public and private sectors, donor agencies, food industries, academic institutions, etc. This paper describes the methodology of lexicon development. Important terms related to micronutrient programs were compiled from multiple sources, including United Nations agencies, program implementation and technical support agencies, relevant websites, and scientific literature. The selection of terms was guided by key micronutrient interventions (fortification, supplementation, dietary diversification) and the program cycle (assessment, planning, implementation, monitoring and evaluation). Definitions of terms were identified from these references and checked for consistency across different sources. For terms with multiple definitions, a modified Delphi method was applied to harmonize the definitions. The first draft lexicon (n = 113 terms) was reviewed by six experts from the University of California, Davis (UCD) and MNF, and second draft (n = 115 terms) was shared with 24 global micronutrient experts for feedback. Fifty-four terms were found to have multiple definitions. Of which, minor modification was made for 12-terms with nominal difference and remaining 42-terms were shared with over 140 micronutrient-experts disseminated via an online survey through newsletters and emails to solicit experts opinions on the most appropriate definition or a modified one. Nineteen legal terms and 83 micronutrient terms (n = 102 terms) were subsequently added. Overall, 39 experts from diverse areas of expertise (LSFF, micronutrient program planning and implementation, surveys and research, policy development, food industry regulations, food safety, and public health nutrition) participated in the online survey. The terms with >75% agreement among experts were considered as final, while the remaining were reviewed again by experts from UCD and MNF until consensus was reached on harmonized definitions. The current lexicon is available online at the DInA-website. and contains 217 terms and will be maintained as a living document. The lexicon will facilitate the ability of key stakeholders of micronutrient programs to evaluate and compare program performance in order to make informed decisions on how to ensure future progress in reducing micronutrient deficiencies.

Data curators play an important role in assessing data quality and take actions that may ultimately lead to better, more valuable data products. This study explores the curation practices of data curators working within US-based data repositories. We performed a survey in January 2021 to benchmark the levels of curation performed by repositories and assess the perceived value and impact of curation on the data sharing process. Our analysis included 95 responses from 59 unique data repositories. Respondents primarily were professionals working within repositories and examined curation performed within a repository setting. A majority 72.6% of respondents reported that data-level curation was performed by their repository and around half reported their repository took steps to ensure interoperability and reproducibility of their repositorys datasets. Curation actions most frequently reported include checking for duplicate files, reviewing documentation, reviewing metadata, minting persistent identifiers, and checking for corrupt/broken files. The most value-add curation action across generalist, institutional, and disciplinary repository respondents was related to reviewing and enhancing documentation. Respondents reported high perceived impact of curation by their repositories on specific data sharing outcomes including usability, findability, understandability, and accessibility of deposited datasets; respondents associated with disciplinary repositories tended to perceive higher impact on most outcomes. Most survey participants strongly agreed that data curation by the repository adds value to the data sharing process and that it outweighs the effort and cost. We found some differences between institutional and disciplinary repositories, both in the reported frequency of specific curation actions as well as the perceived impact of data curation. Interestingly, we also found variation in the perceptions of those working within the same repository regarding the level and frequency of curation actions performed, which exemplifies the complexity of a repository curation work. Our results suggest data curation may be better understood in terms of specific curation actions and outcomes than broadly defined curation levels and that more research is needed to understand the resource implications of performing these activities. We share these results to provide a more nuanced view of curation, and how curation impacts the broader data lifecycle and data sharing behaviors.

The aerobic hyperthermophile "Fervidibacter sacchari" catabolizes diverse polysaccharides and is the only cultivated member of the class "Fervidibacteria" within the phylum Armatimonadota. It encodes 117 putative glycoside hydrolases (GHs), including two from GH family 50 (GH50). In this study, we expressed, purified, and functionally characterized one of these GH50 enzymes, Fsa16295Glu. We show that Fsa16295Glu is a β-1,3-endoglucanase with optimal activity on carboxymethyl curdlan (CM-curdlan) and only weak agarase activity, despite most GH50 enzymes being described as β-agarases. The purified enzyme has a wide temperature range of 4-95°C (optimal 80°C), making it the first characterized hyperthermophilic representative of GH50. The enzyme is also active at a broad pH range of at least 5.5-11 (optimal 6.5-10). Fsa16295Glu possesses a relatively high kcat/KM of 1.82 × 107 s-1 M-1 with CM-curdlan and degrades CM-curdlan nearly completely to sugar monomers, indicating preferential hydrolysis of glucans containing β-1,3 linkages. Finally, a phylogenetic analysis of Fsa16295Glu and all other GH50 enzymes revealed that Fsa16295Glu is distant from other characterized enzymes but phylogenetically related to enzymes from thermophilic archaea that were likely acquired horizontally from "Fervidibacteria." Given its functional and phylogenetic novelty, we propose that Fsa16295Glu represents a new enzyme subfamily, GH50_3.

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao Peoples Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to

Abstract Recurrent ovarian cancer patients, especially those resistant to platinum, lack effective curative treatments. To address this, we conducted a phase 2 clinical trial (NCT02853318) combining pembrolizumab with bevacizumab, to increase T cell infiltration into the tumor, and oral cyclophosphamide, to reduce the number of regulatory T cells. The trial accrued 40 heavily pretreated recurrent ovarian cancer patients. The primary endpoint, progression free survival, was extended to a median of 10.2 months. The secondary endpoints demonstrated an objective response rate of 47.5%, and disease control in 30% of patients for over a year while maintaining a good quality of life. We performed comprehensive molecular, immune, microbiome, and metabolic profiling on samples of trial patients. Here, we show increased T and B cell clusters and distinct microbial patterns with amino acid and lipid metabolism are linked to exceptional clinical responses. This study suggests the immune milieu and host-microbiome can be leveraged to improve antitumor response in future immunotherapy trials.