bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analysis of the efficacy of ω-3 polyunsaturated fatty acids when treating patients with polycystic ovary syndrome
Authors: Huang Yue , Zhang Xiang 
Published: September 2023

Objective:
To systematically assess the efficacy of ω-3 polyunsaturated fatty acids (PUFAs) when treating polycystic ovary syndrome (PCOS).

Methods:
This meta-analysis follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. We searched PubMed, EMBASE, ScienceDirect, Cochrane Library, China journal full-text database, VIP full-text Database, Wanfang Database, and Chinese Biomedical Literature Data for clinical trials on ω-3 PUFAs’ efficacy in treating PCOS. Two independent reviewers examined and analyzed studies, resolving inconsistencies through discussion. RevMan5.3 software performed heterogeneity-based fixed and random-effects meta-analysis. We assessed bias using the Cochrane bias risk assessment tool.

Results:
Our meta-analysis included 7 clinical control studies comprising 574 samples to evaluate the impact of ω-3 PUFAs on various metabolic markers in PCOS patients. We observed a significant reduction in total cholesterol (TC) and triglyceride (TG) levels (P < .05), along with a decrease in insulin resistance as measured by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (P < .05). Testosterone (T) levels were also lowered in the study group post-treatment (P < .05). However, no notable effects were found on body mass index (BMI), fasting blood sugar (FBS), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and Ferriman-Gallwey (mFG) scores (P > .05). Publication bias was not detected, enhancing the robustness of our results. Our study suggests that ω-3 PUFAs could be beneficial in managing specific metabolic markers in PCOS, although the results showed marked heterogeneity.

Conclusion:
In PCOS patients, PUFAs can enhance reproductive endocrine, glucose, and lipid levels. However, additional research and extended follow-up are required to confirm this.
A Cross-Sectional Study of Pediatric Feeding Disorder in Children with Cystic Fibrosis
Authors: Bashir Anam , Antos Nicholas , Miller Tami , Challa Sai Alekha , Pan Amy Y. , Gosa Memorie , Silverman Alan , Goday Praveen S. 
Published: September 2023

Background:
The exact prevalence of feeding problems in children with cystic fibrosis (CF) is unknown. Pediatric feeding disorder (PFD) encompasses poor oral intake with associated medical, nutrition, psychosocial, or feeding skill dysfunction. We hypothesized that PFD is common in CF and aimed to categorize feeding dysfunction across various domains in children with CF.

Methods:
An observational cross-sectional study was conducted in children with CF. Data collected included anthropometrics, nutrition data (including need for tube feeding/enteral nutrition [EN] or high-energy beverages, dietary diversity), feeding skills (Pediatric version of the Eating Assessment tool [pEAT]), and psychosocial function (About Your Child’s Eating questionnaire [AYCE] in children 2–17 years of age/Behavioral Pediatric Feeding Assessment Scale [BPFAS] in children 12–23 months of age). PFD was defined as poor oral intake with: (a) pEAT score > 5; and/or (b) AYCE or BPFAS score > 2 standard deviation of normative controls; and/or (c) nutrition dysfunction (body mass index/weight-for-length z score < −1 and/or preference of oral high energy beverages or dependence on EN and/or decreased dietary diversity).

Results:
Of 103 children in the study, 62 (60.1%) had PFD, 7 children (6.8%) were malnourished, 10 needed EN (9.7%), and 30 (29.1%) needed oral high-energy beverages. Dietary diversity was decreased in 42 children (41.5%), 1 child had feeding skill dysfunction, and 11 (10.8%) met criteria for psychosocial dysfunction.

Conclusion:
Almost 2/3rd of children with CF have PFD and many have poor dietary diversity. A significant percentage of children rely on EN and oral supplements, but psychosocial dysfunction is less prevalent.
Direct extrusion of multifascicle prevascularized human skeletal muscle for volumetric muscle loss surgery
Authors: Duong Van Thuy , Dang Thao Thi , Le Van Phu , Le Thi Huong , Nguyen Chanh Trung , Phan Huu Lam , Seo Jongmo , Back Sung Hoon , Koo Kyo-in 
Published: September 2023

AbstractVolumetric skeletal muscle injuries are prevalent, highlighting the imperative need for scaffolds to facilitate the healing process of such wounds. Human skeletal muscle is composed of multiple fascicles, which are parallel bundles of muscle fibres surrounded by a layer of connective tissue that contains blood vessels and nerves. Replicating these structures presents a considerable challenge. Here, we developed a method to fabricate multifascicle human skeletal muscle scaffolds that mimic the natural structure of human skeletal muscle bundles using a seven-barrel nozzle. To form the core material to generate the fascicle structure, human skeletal myoblasts were encapsulated in Matrigel with calcium chloride. Meanwhile, to create the shell that plays a role as the connective tissue structure, human fibroblasts and human umbilical vein endothelial cells within a mixture of porcine muscle decellularized extracellular matrix and sodium alginate at a 95:5 ratio was used. We assessed four types of extruded scaffolds monolithic-monoculture (Mo-M), monolithic-coculture (Mo-C), multifascicle-monoculture (Mu-M), and multifascicle-coculture (Mu-C) to determine the structural effect of muscle mimicking scaffold. The Mu-C scaffold demonstrated cell proliferation, differentiation, vascularization, mechanical properties, and functionality that were superior to those of the other scaffolds. Furthermore, in anin vivomouse model of volumetric muscle loss, the Mu-C scaffold effectively regenerated the tibialis anterior muscle defect, demonstrating its potential for volumetric muscle transplantation. The multibarrel nozzle device was applied to create functional Mu-C muscle scaffolds that structurally mimicked human skeletal muscle. Our nozzle will be further used to produce other volumetric functional tissues, such as tendons and peripheral nerves.
IL-2–induced Stat3 Signaling is Critical for Effector Treg Cell Programming
Authors: Dean Emma C. , Ditoro Daniel F. , Pham Duy , Gao Min , Zindl Carlene L. , Frey Blake , Harbour Stacey N. , Figge David A. , Miller Aidan T. , Glassman Caleb R. , Garcia K. Christopher , Hatton Robin D. , Weaver Casey T. 
Published: September 2023

AbstractMaintenance of immune homeostasis to the intestinal mictrobiota is dependent on a population of effector regulatory T (eTreg) cells that develop from microbiota-reactive induced (i)Treg cells. A cardinal feature of eTreg cells is their production of IL-10, which plays a non-redundant role in immune tolerance of commensal microbes. Here, we identify an unexpected role for IL-2-induced Stat3 signaling to program iTreg cells for eTreg cell differentiation andIl10transcriptional competency. IL-2 proved to be both necessary and sufficient for eTreg cell development – contingent on Stat3 output of the IL-2 receptor coordinate with IL-2 signaling during early Treg cell commitment. Induction of iTreg cell programming in absence of IL-2-induced Stat3 signaling resulted in impaired eTreg cell differentiation and a failure to produce IL-10. An IL-2 mutein with reduced affinity for the IL-2Rγ (γc) chain was found to have blunted IL-2R Stat3 output, resulting in a deficiency ofIl10transcriptional programming that could not be fully rescued by Stat3 signaling subsequent to an initial window of iTreg cell differentiation. These findings expose a heretofore unappreciated role of IL-2 signaling that acts early to program subsequent production of IL-10 by developing eTreg cells, with broad implications for IL-2–based therapeutic interventions in immune-mediated diseases.
Mitochondrial dsRNA from B-ALL cells stimulates mesenchymal stromal cells to become cancer associated fibroblasts
Authors: Burt Richard J. , Dey Aditi , Akarca Ayse , Allen Hermione , Amerikanou Rodothea , Atkinson Samantha , Auty David , Chatzigerou Jenny , Cutler Emily , Guerra-Assuncao Jose Afonso , Kirschner Kristina , Kumari Ruchi , Manji Jiten , Marafiotti Teresa , Fielding Adele K. 
Published: September 2023

AbstractCancer associated fibroblasts (CAF) arising from bone marrow-derived mesenchymal stromal cells (MSC) are prominent in B-precursor acute lymphoblastic leukaemia (B-ALL). We have previously shown that CAF formation is triggered by exposure to reactive oxygen species-inducing chemotherapy and that CAF support chemoresistance by donating mitochondria to the cancer cells, through tunnelling nanotubes. In the present study, we show that exposure of MSC to ALL cell lines, PDX and primary cells or their conditioned media can also trigger CAF formation, in an oncogene-dependent manner. Using bulk RNA sequencing in cell lines, we show that the MSC to CAF transition is accompanied by a robust interferon pathway response and we have validated this finding in primary cells. Using confocal microscopy and flow cytometry, we identify the take up of leukaemia cell-derived mitochondrial dsRNA by MSC as a proximate trigger for the MSC to CAF transition. We show that degradation of dsRNA in ALL cell conditioned media by DMSO ablates the ability of the conditioned media to stimulate MSC to CAF transition. Since we find that only specific primary driver genetic subtypes of B-ALL possess the property to directly generate CAFs, we propose this phenomenon as the first mechanistic insight into the strong relationship between acute lymphoblastic leukaemia genetic subtype and survival outcomes.Key pointsXExposure of MSC to B-precursor ALL cell lines triggers cancer-associated fibroblast formation in an oncogene-dependent mannerThe proximate trigger for CAF formation is ALL-derived mitochondrial double stranded RNA
Determining the effects of temperature on the evolution of bacterial tRNA pools
Authors: Jain Vatsal , Cope Alexander L. 
Published: September 2023

AbstractThe genetic code consists of 61 codon coding for 20 amino acids. These codons are recognized by transfer RNAs (tRNA) that bind to specific codons during protein synthesis. Most organisms utilize less than all 61 possible anticodons due to base pair wobble: the ability to have a mismatch with a codon at its third nucleotide. Previous studies observed a correlation between the tRNA pool of bacteria and the temperature of their respective environments. However, it is unclear if these patterns represent biological adaptations to maintain the efficiency and accuracy of protein synthesis in different environments. A mechanistic mathematical model of mRNA translation is used to quantify the expected elongation rates and error rate for each codon based on an organism’s tRNA pool. A comparative analysis across a range of bacteria that accounts for covariance due to shared ancestry is performed to quantify the impact of environmental temperature on the evolution of the tRNA pool. We find that thermophiles generally have more anticodons represented in their tRNA pool than mesophiles or psychrophiles. Based on our model, this increased diversity is expected to lead to increased missense errors. The implications of this for protein evolution in thermophiles are discussed.SignificanceProtein synthesis is a vital biological process; however, our understanding of the impact of environmental factors, such as temperature, on the evolution of the molecular mechanisms involved in protein synthesis is limited. In this study, we investigated the impact of environmental temperature on the evolution of the tRNA pool. Our analyses revealed that heat-loving bacteria (thermophiles) generally have more anticodons represented in their tRNA pool. Based on a simple model of ribosome elongation, this observed increase in tRNA diversity in thermophiles is expected to also increase the frequency of translation errors. We speculate that the increased diversity of the tRNA pool could be due to the decreased efficiency of wobble base pairing at higher temperatures, necessitating more tRNA with exact codon-anticodon pairings. Our findings provide key insights into the role of the environment in shaping the tRNA pool.
Molecular Dynamics Activation of γ-Secretase for Cleavage of Notch1 Substrate
Authors: Do Hung N. , Malvankar Shweta R. , Wolfe Michael S. , Miao Yinglong 
Published: September 2023

Abstractγ-Secretase is an intramembrane aspartyl protease complex which cleaves the transmembrane domain of over 150 peptide substrates, including amyloid precursor protein (APP) and the Notch family of receptors, via two conserved aspartates D257 and D385 in the Presenilin-1 (PS1) catalytic subunit. However, while the activation of γ-secretase for cleavage of APP has been widely studied, the cleavage of Notch by γ-secretase remains poorly explored. Here, we combined Gaussian accelerated Molecular Dynamics (GaMD) simulations and mass spectrometry (MS) analysis of proteolytic products to present the first dynamic models for cleavage of Notch by γ-secretase. MS showed that γ-secretase cleaved the WT Notch at Notch residue G34, while cleavage of L36F mutant Notch occurred at Notch residue C33. Initially, we prepared our simulation systems starting from the cryoEM structure of Notch-bound γ-secretase (PDB: 6IDF) and failed to capture the proper cleavages of WT and L36F Notch by γ-secretase. We then discovered an incorrect registry of the Notch substrate in the PS1 active through alignment of the experimental structure of Notch-bound (PDB: 6IDF) and APP-bound γ-secretase (PDB: 6IYC). Every residue of APP substrate was systematically mutated to the corresponding Notch residue to prepare a resolved model of Notch-bound γ-secretase complexes. GaMD simulations of the resolved model successfully captured γ-secretase activation for proper cleavages of both WT and L36F mutant Notch. Our findings here provided mechanistic insights into the structural dynamics and enzyme-substrate interactions required for γ-secretase activation for cleavage of Notch and other substrates.
Multiepitope-based vaccine design against DiiA inStreptococcus pneumoniae, An immunoinformatics approach
Authors: Soliman Mariam M. , Sheikhani Dania , Nassar Jihan , Elsabbagh Sherif , Ibrahim Tamer M. 
Published: September 2023

AbstractStreptococcus pneumoniae(SPN) infection has resulted in significant morbidity and mortality worldwide in children and adults. It is responsible for colonizing the human nasopharynx and can also cause diseases, including otitis media, pneumonia, bacteraemia, and meningitis. SPN is exhibiting resistance to multiple antibiotics and current vaccines have a number of limitations including poor immunogenicity and limited effectiveness against all pneumococcal serotypes. Here, we explain the design of a novel multi-epitope vaccine using Dimorphic invasion-involved protein A (DiiA) as a target protein. For designing the vaccine, the sequence of DiiA was obtained and various bioinformatics tools were employed to predict multiple CTL, HTL, B lymphocyte epitopes of DiiA. After evaluating antigenicity, allergenicity, toxicity, and immunogenicity, the most promising epitopes were chosen for constructing the vaccine, followed by an analysis of their physicochemical and immunological characteristics.The prediction, refinement, and validation of the 3D structure of the vaccine were carried out. Molecular docking, molecular dynamic simulation, and immune simulation were executed to examine the binding affinities and biological interactions at the atomic level between the vaccine and Toll-like receptor (TLR4). Vaccine translation, codon optimization were performed and expression efficiency was assessed through an in-silico cloning experiment performed to transfer into pET28a(+) plasmid vector.The obtained results proved that the vaccine maintained structural stability and possessed the capability to stimulate an efficient immune response againstS. pneumoniaeinfection. The constructed vaccine has the potential for subsequent wet lab experimentation, leading to the development of an innovative vaccine.
Mutation rate heterogeneity at the sub-gene scale due to local DNA hypomethylation
Authors: Mas-Ponte David , Supek Fran 
Published: September 2023

AbstractLocal mutation rates are highly heterogeneous across the human genome. This variability was better studied at the scale of megabase-sized chromosomal domains on the one extreme, and at the scale of oligonucleotides at the other extreme. The intermediate, kilobase-scale heterogeneity in mutation risk was less studied. Here, by analyzing thousands of somatic genomes, we considered the hypothesis there are mutation risk gradients along gene bodies, representing a genomic scale spanning roughly 1 kb – 10 kb, and that different mutational mechanisms are differently distributed across gene segments. The main intragenic heterogeneity concerns several kilobases at the transcription start site and further into 5’ ends of gene bodies, which are commonly hypomutated with respect to several mutational signatures, most prominently the ubiquitous mutational signature of C>T changes at CpG dinucleotides. Width and shape of this mutational coldspot at 5’ gene ends is variable across genes, and corresponds to variable interval of lowered DNA methylation across genes. These hypomutated genic intervals correspond to hypomethylation that can originate from various causes, including intragenic enhancers, Polycomb-marked regions, or chromatin loop anchor points. Tissue-specific DNA hypomethylation begets tissue-specific local hypomutation. However, direction of mutation rate effect is inverted for some mutational processes, where signatures of AID/APOBEC3 cytosine deaminase activity are actually increased in hypomethylated regions. Overall, local DNA methylation determines mutation rate heterogeneity at the sub-gene level, and can generate either mutational coldspots or hotspots, depending on the mutagen exposure history of a cell.
Evaluating goodness-of-fit of animal movement models using lineups
Authors: Fieberg John , Freeman Smith , Signer Johannes 
Published: September 2023

AbstractModels of animal movement are frequently fit to animal location data to understand how animals respond to and interact with local environmental features. Several open-source software packages are available for analyzing animal movements and can facilitate parameter estimation, yet there are relatively few methods available for evaluating model goodness-of-fit. We describe how a simple graphical technique, thelineup protocol, can be used to evaluate goodness-of-fit of integrated step-selection analyses and hidden Markov models, but the method can be applied much more broadly. We leverage the ability to simulate data from fitted models, and demonstrate the approach using both methods applied to fisher (Pekania pennanti) data. A variety of responses and movement metrics can be used to evaluate models, and the lineup protocol can be tailored to focus on specific model assumptions or movement features that are of primary interest. Although it is possible to evaluate goodness-of-fit using a formal hypothesis test, the method can also be used in a more exploratory fashion (e.g., to visualize variability in model behavior across stochastic simulations or identify areas where the model could be improved). We provide coded examples and two vignettes to demonstrate the flexibility of the approach and encourage movement ecologists to consider how their models will be applied when choosing appropriate graphical responses for evaluating goodness-of-fit.
Lymphoma B cells remodel bone marrow stromal cell organization and function to induce a supportive cancer-associated fibroblast network
Authors: Dessauge Elise , Brauge Baptiste , Léonard Simon , Roulois David , Monvoisin Céline , Lejeune Thomas , Destin Jérôme , Jouan Florence , Llamas-Gutierrez Francisco , Mourcin Frédéric , Tarte Karin 
Published: September 2023

ABSTRACTBone marrow (BM) involvement is a common feature of lymphomas deriving from germinal-center B cells and is associated with a bad prognosis. In particular, follicular lymphoma (FL) infiltrates the BM in 70% of cases, in association with a remodeling of surrounding tumor microenvironment. Analysis ofin vitro-expanded FL mesenchymal stromal cells (MSCs) revealed an extensive alteration of BM stromal cell phenotypic, transcriptomic, and functional profiles. However, the mechanisms supporting the direct interplay between lymphoma B cells and their permissive stromal nichein situhave not been yet identified. In the current work, we identified in the BM milieu of FL patients a deregulation of soluble and extracellular matrix (ECM) components reflecting inflammation and ectopic differentiation into lymphoid-like stromal cells. We reproduced the same alterations in a murine model of lymphoma B-cell xenograft where a scRNAseq approach identified LepRposMSCs as specifically and progressively reprogramed by tumor B-cell invasion. Analysis of FL BM collected before and after treatment confirmed that BM niche was partly dependent on the continuous contact with tumor B cells. Altogether, this work shed new lights on the kinetic and mechanisms of BM stromal niche reshaping in B-cell lymphoma.
Testing for a role of postzygotic incompatibilities in rapidly speciated Lake Victoria cichlids
Authors: Feller Anna F. , Peichel Catherine L. , Seehausen Ole 
Published: September 2023

AbstractIntrinsic postzygotic hybrid incompatibilities are usually due to negative epistatic interactions between alleles from different parental genomes. While such incompatibilities are thought to be uncommon in speciation with gene flow, they may be important if such speciation results from a hybrid population. Here we aimed to test this idea in the endemic cichlid fishes of Lake Victoria. Hundreds of species have evolved within the lake in <15k years from a hybrid progenitor. While the importance of prezygotic barriers to gene flow is well established in this system, the possible relevance of postzygotic genetic incompatibilities is unknown. We inferred the presence of negative epistatic interactions from systematic patterns of genotype ratio distortions in experimental crosses and wild samples. We then compared the positions of putative incompatibility loci to regions of high genetic differentiation between sympatric sister species as well as between members of clades that may have arisen at the start of this radiation, and further determined if the loci showed fixed differences between the closest living relatives of the lineages ancestral to the hybrid progenitor. Overall, we find little evidence for a major role of intrinsic postzygotic incompatibilities in the Lake Victoria radiation. However, we find putative incompatibility loci significantly more often coinciding with islands of genetic differentiation between species that separated early in the radiation than between the youngest sister species, consistent with the hypothesis that such variants segregated in the hybrid swarm and were sorted between species in the early speciation events.