bluuebunny/crossref_metadata_2025_split huggingface dataset:
PWAS Hub: exploring gene-based associations of complex diseases with sex dependency
Authors: Zucker Roei , Kelman Guy , Linial Michal 
Published: November 2024

Abstract
The Proteome-Wide Association Study (PWAS) is a protein-based genetic association approach designed to complement traditional variant-based methods like GWAS. PWAS operates in two stages: first, machine learning models predict the impact of genetic variants on protein-coding genes, generating effect scores. These scores are then aggregated into a gene-damaging score for each individual. This score is then used in case-control statistical tests to significantly link to specific phenotypes. PWAS Hub (v1.2) is a user-friendly platform that facilitates the exploration of gene-disease associations using clinical and genetic data from the UK Biobank (UKB), encompassing 500k individuals. PWAS Hub reports on 819 diseases and phenotypes determined by PheCode and ICD-10 clinical codes, each with a minimum of 400 affected individuals. PWAS-derived gene associations were reported for 72% of the tested phenotypes. The PWAS Hub also analyzes gene associations separately for males and females, considering sex-specific genetic effects, inheritance patterns (dominant and recessive), and gene pleiotropy. We illustrated the utility of the PWAS Hub for primary (essential) hypertension (I10), type 2 diabetes mellitus (E11), and specified haematuria (R31) that showed sex-dependent genetic signals. The PWAS Hub, available at pwas.huji.ac.il, is a valuable resource for studying genetic contributions to common diseases and sex-specific effects.
[SNG2], a prion form of Cut4/Apc1, confers non-Mendelian inheritance of heterochromatin silencing defect in fission yeast
Authors: Sharma Suman , Srivastava Suchita , Dubey Rudra Narayan , Mishra Poonam , Singh Jagmohan 
Published: November 2024

Abstract
Prions represent epigenetic regulator proteins that can self-propagate their structure and confer their misfolded structure and function on normally folded proteins. Like the mammalian prion PrPSc, prions also occur in fungi. While a few prions, like Swi1, affect gene expression, none are shown to affect heterochromatin structure and function. In fission yeast and metazoans, histone methyltransferase Clr4/Suv39 causes H3-Lys9 methylation, which is bound by the chromodomain protein Swi6/HP1 to assemble heterochromatin. Earlier, we showed that sng2-1 mutation in the Cut4 subunit of anaphase-promoting complex abrogates heterochromatin structure due to defective binding and recruitment of Swi6. Here, we demonstrate that the Cut4p forms a non-canonical prion form, designated as [SNG2], which abrogates heterochromatin silencing. [SNG2] exhibits various prion-like properties, e.g. non-Mendelian inheritance, requirement of Hsp proteins for its propagation, de novo generation upon cut4 overexpression, reversible curing by guanidine, cytoplasmic inheritance and formation of infectious protein aggregates, which are dissolved upon overexpression of hsp genes. Interestingly, [SNG2] prion imparts an enhanced tolerance to stress conditions, supporting its role in promoting cell survival under environmental stress during evolution.
Crosstalk between paralogs and isoforms influences p63-dependent regulatory element activity
Authors: Baniulyte Gabriele , McCann Abby A , Woodstock Dana L , Sammons Morgan A 
Published: November 2024

Abstract
The p53 family of transcription factors (p53, p63 and p73) regulate diverse organismal processes including tumor suppression, maintenance of genome integrity and the development of skin and limbs. Crosstalk between transcription factors with highly similar DNA binding profiles, like those in the p53 family, can dramatically alter gene regulation. While p53 is primarily associated with transcriptional activation, p63 mediates both activation and repression. The specific mechanisms controlling p63-dependent gene regulatory activity are not well understood. Here, we use massively parallel reporter assays (MPRA) to investigate how local DNA sequence context influences p63-dependent transcriptional activity. Most regulatory elements with a p63 response element motif (p63RE) activate transcription, although binding of the p63 paralog, p53, drives a substantial proportion of that activity. p63RE sequence content and co-enrichment with other known activating and repressing transcription factors, including lineage-specific factors, correlates with differential p63RE-mediated activities. p63 isoforms dramatically alter transcriptional behavior, primarily shifting inactive regulatory elements towards high p63-dependent activity. Our analysis provides novel insight into how local sequence and cellular context influences p63-dependent behaviors and highlights the key, yet still understudied, role of transcription factor paralogs and isoforms in controlling gene regulatory element activity.
Genetic testing in a national cohort of adults with chronic kidney disease of unknown origin
Authors: de Haan Amber , Eijgelsheim Mark , Vogt Liffert , Hoorn Ewout J , Rotmans Joris I , Fortrie Gijs , Marsman Roos F J , Rothuizen Tonia C , Spijker H Siebe , Claus Laura R , Konings Constantijn J A M , Waanders Femke , Doornebal Joan , Kramer Andrea B , Adema Aaltje Y , van der Zwaag Bert , van Eerde Albertien M , Knoers Nine V A M , de Borst Martin H 
Published: November 2024

ABSTRACT

Background
Chronic kidney disease (CKD) remains unexplained in at least 20% of patients. Massively parallel sequencing (MPS) can be a valuable diagnostic tool in patients with unexplained CKD, but prospective data from routine clinical practice are limited. We aimed to determine the diagnostic yield and relevance of MPS-based gene panel testing in patients with unexplained CKD in a real-world context. We additionally examined barriers to implementation of genetic testing.

Methods
In this prospective cohort study, we recruited patients with unexplained CKD (estimated glomerular filtration rate &lt;60 ml/min/1.73 m2 without underlying clinical diagnosis) with onset at &lt;50 years of age who underwent MPS-based multigene panel testing from 11 academic and non-academic hospitals across the Netherlands. In patients with a (likely) pathogenic variant, we verified that the variant likely explained the clinical phenotype. A nationwide online survey was sent to all Dutch nephrologists and residents to investigate potential barriers for gene panel testing.

Results
A diagnostic variant was identified in 59/340 participants (17%). Most common diagnostic variants were in NPHP1 (13 patients), COL4A3 (12 patients), COL4A4 (5 patients), COL4A5 (6 patients) and PAX2 (5 patients). A genetic diagnosis led to at least one clinical consequence in 73% of patients. Main barriers reported by Dutch nephrologists (N = 71) included genetic illiteracy (53%), difficulties with test selection (51%) and a lack of time (43%).

Conclusions
MPS-based multigene panel testing yielded a genetic diagnosis in 17% of patients with unexplained CKD. Our findings support the relevance of MPS in the diagnostic workup of adults with unexplained CKD with onset at &lt;50 years of age. Additionally, our results underline the need to improve genetic education among nephrologists to better the implementation of MPS-based diagnostic testing in clinical practice.
Generating Campaign Awareness With Digital Media: Exploring Factors Associated With Awareness of and Receptivity to FDA’s Fresh Empire Tobacco Prevention Campaign
Authors: Henes Amy , Curry Laurel , Farrelly Matthew , Guillory Jamie , Crichton Andrew , Saunders McKinley , MacMonegle Anna , Mekos Debra , Zhao Xiaoquan , Nonnemaker James , Guo Merrybelle , Wagner Dana E 
Published: November 2024

Abstract

Introduction
We explore factors that were associated with awareness of and receptivity to U.S. Food and Drug Administration’s Fresh Empire tobacco public education campaign.

Aims and Methods
Evaluation data were 10 674 survey responses from 5129 unique respondents who identified with the Hip Hop peer crowd between 2016 and 2019. The sample was predominantly non-Hispanic Black and Hispanic youth. We assessed the outcomes of brand awareness, ad awareness, and perceived ad effectiveness. We used panel regression models to test which demographic and other characteristics—including potential campaign exposure, as measured by impressions assigned to respondents based on their media market of residence and survey completion date—were associated with these outcomes.

Results
Black, non-Hispanic youth; Hispanic youth; and youth with additional non-Hispanic or multiracial identities were more likely to be aware of the Fresh Empire brand and reported higher ad awareness and perceived effectiveness scores than White, non-Hispanic respondents. Among the full sample, respondents with higher Hip Hop scores—indicating greater identification with the Hip Hop peer crowd—reported higher ad awareness. Compared with nonsusceptible never smokers, youth susceptible to smoking reported lower ad awareness and perceived effectiveness scores. Higher potential exposure to campaign broadcast and digital media were both associated with higher ad awareness.

Conclusions
Fresh Empire reached and appealed to a racially and ethnically diverse group of Hip Hop youth. Our findings highlight the ability of digital media to generate campaign awareness among specific youth audiences.

Implications
Understanding factors that contribute to awareness of and positive reactions to the Fresh Empire campaign can inform the development and implementation of future campaigns focused on Hip Hop youth, youth of color, and other underrepresented audiences. Fresh Empire’s success in reaching its audience using primarily digital media demonstrates the potential of digital media campaigns to be effective at reaching specific audiences with tobacco prevention messages.
Unlocking the Cardiovascular Benefits of Walnuts: Insights on Molecular Mechanism From Animal Studies
Authors: Tepavčević Snežana , Zec Manja , Stojiljković Mojca , Bošković Maja , Ćulafić Tijana , Stanković Aleksandra , Romić Snježana , Živković Maja , Korićanac Goran 
Published: November 2024

Abstract
The health-promoting benefits of walnut consumption are substantially ascribed to its fatty acid (FA) profile, which is rich in polyunsaturated FA with an exceptionally high n-3 to n-6 ratio. There are also phytonutrients in walnuts that are linked to health welfare. This review article integrates all studies on the effects of walnuts on the cardiovascular system performed on experimental animals, and thus is a source of data on the mechanisms underlying the observed effects. These studies, which are very diverse in experimental design, indicate that a diet enriched with walnuts or treating animals with walnut extract or chemical constituents of walnuts, has many favorable effects on heart and vascular system function. The cardiovascular effect of walnuts depends on the metabolic status of the organism. Among the cardiovascular effects of walnuts is that they improve the FA profile in the circulation and heart in favor of n-3 polyunsaturated FAs. In addition, a favorable effect on triglyceride and cholesterol status, which reduces cardiovascular disease risk, is observed. Intake of walnuts promotes FA catabolism and has anti-inflammatory, antioxidant, and antiarrhythmic effects. Walnuts also have a beneficial effect on vascular tone, accompanied by a decrease in blood pressure and reduced risk for atherosclerosis. In conclusion, studies on experimental animals encourage the consumption of walnuts as a simple, convenient approach to improve cardiovascular health.
Decoding spatial orientation in planar materials
Authors: Rawal Angela , Kulachenko Artem , Rawal Amit 
Published: November 2024

Abstract
Structural disorder induces energetic fluctuations, leading to variations in energy levels across different scales, with the spatial orientation of structural units playing a pivotal role in shaping the resulting structure-property relationships. In this communication, we derive expressions for higher-order nematic orientation parameters for planar materials analogous to the Hermans orientation parameter used for axially symmetric materials. The measure of anisotropy has been analyzed by integrating the widely used probability density functions representing the orientation distributions in nematic order parameters. These higher-order nematic orientation parameters are essential for accurately determining the ‘true’ orientation distribution function of macromolecules and understanding structure-property relationships in complex planar systems.
Christian Hebraism
Authors: Burnett Stephen 
Published: November 2024

AbstractChristian Hebraism was an expression of Renaissance humanism that became an improbable success story during the sixteenth century. It first emerged in fifteenth-century Italy, but it grew far faster in northern Europe under the stimulus of Erasmus’ call for a return to the sources of Christian faith (ad fontes) and the Protestant idea that beliefs and practices had to be based upon Scripture alone (sola Scriptura). To act upon these ideals, Christians had to learn Hebrew, universities had to create teaching positions in it, authors had to write (and printers had to produce) Latin language books on Hebrew-related subjects, and rulers had to provide support for the new activity. Christian Hebraists produced a philological apparatus, created polyglot Bibles, and mediated information and perspectives from the Jewish tradition of biblical study into Christian theological and confessional thinking during the sixteenth century.
Gravitational collapse of white dwarfs to neutron stars: From initial conditions to explosions with neutrino-radiation hydrodynamics simulations
Authors: Mori Masamitsu , Sawada Ryo , Suwa Yudai , Tanikawa Ataru , Kashiyama Kazumi , Murase Kohta 
Published: November 2024

Abstract
Using general relativistic neutrino-radiation hydrodynamics simulations with the multi-group M1 scheme in one dimension, we investigate the collapse of massive, fully convective, and non-rotating white dwarfs (WDs), which are formed by accretion-induced collapse or merger-induced collapse, and the subsequent explosion. We produce initial WDs in hydrostatic equilibrium, which have super-Chandrasekhar mass and are about to collapse. The WDs have masses of $1.6\, M_{\odot }$ with different initial central densities specifically at $1.0\times 10^{10}$, $4.0\times 10^{9}$, $2.0\times 10^{9}$, and $1.0\times 10^{9}\:\mbox{g}\:\mbox{cm}^{-3}$. First, we examine the stability of initial WD in case weak interactions are turned off. Secondly, we calculate the collapse of WDs with weak interactions. We employ hydrodynamics simulations with Newtonian gravity in the first and second steps. Thirdly, we calculate the formation of neutron stars and accompanying explosions with general relativistic simulations. As a result, WDs with the highest density of $10^{10}\:\mbox{g}\:\mbox{cm}^{-3}$ collapse not by weak interactions but by the photodissociation of the iron, and three WDs with low central densities collapse by the electron capture as expected at the second step and succeed in the explosion with a small explosion energy of $\sim\! 10^{48}\:$erg at the third step. By changing the surrounding environment of WDs, we find that there is a minimum value of ejecta masses, which is $\sim\! 10^{-5}\, M_{\odot }$. With the most elaborate simulations of this kind so far, this value is one to two orders of magnitude smaller than previously reported values and is compatible with the estimated ejecta mass from FRB 121102.
Histone modification H3K27me3 is essential during chilling-induced flowering in Litchi chinensis
Authors: Pan Xifen , Lu Xingyu , Huang Lijie , Hu Zhiqun , Zhuo Maogen , Ji Yanchun , Lin Bingqi , Luo Jianqin , Lü Peitao , Zhou Biyan 
Published: November 2024

Abstract
Litchi (Litchi chinensis), a prominent fruit tree in the Sapindaceae, initiates flowering in response to low autumn and winter temperatures. This study investigates the epigenetic regulation of this process, focusing on the marks histone H3 lysine 27 trimethylation (H3K27me3) and its deposition genes during the chilling-induced floral induction (FId) and initiation stages. Our genomic analysis delineated the H3K27me3 deposition landscape across the prefloral induction (PFId), FId, and floral initiation (FIn) stages. We identified 5,635 differentially H3K27me3-modified genes (DHGs) in buds and 4,801 DHGs in leaves. Integration of the RNA-seq and ChIP-seq datasets identified 1,001 differentially regulated genes (DRGs) in buds and 675 DRGs in leaves, offering insights into the genes potentially targeted by H3K27me3. To probe the functional role of H3K27me3, we employed GSK343, a histone H3 lysine methyltransferase inhibitor. Treatment with GSK343 during the chilling-induced flowering process led to reduced H3K27me3 deposition at the TREHALOSE-6-PHOSPHATE SYNTHASE 1 (LcTPS1) and FRIGIDA (LcFRI) loci, resulting in increased gene expression. This manipulation delayed flowering and reduced flowering rates, confirming the pivotal role of H3K27me3 in chilling-induced flowering in litchi. Gene coexpression network analysis identified SHORT VEGETATIVE PHASE 10 (LcSVP10) as a crucial regulator in litchi flowering. Overexpression of LcSVP10 in Arabidopsis thaliana delayed flowering, indicating a conserved function in flowering time control. Our results elucidate the molecular and epigenetic mechanisms that govern FId in litchi and highlight the potential of epigenetic modifications to regulate flowering time in horticultural plants.
On the edge of the social media landscape: associations with adolescent substance use and moderation by parental rules
Authors: Bozhar Hanan , de Rooij Susanne R , Lok Anja , Vrijkotte Tanja , Larsen Helle 
Published: November 2024

Abstract

Background
Adolescent problematic social media use (PSMU) has been increasing. Digital engagement has been associated with substance use, but little is known about the potential protective role of parents. We investigated whether screen and substance-related parental rules moderated the associations between (problematic) SMU and intake of tobacco, alcohol, hashish/marijuana, and laughing gas.

Methods
We used data from the Amsterdam Born Children and Development study (N = 1787; Mage = 15.86 years; SD = 0.36). Both frequent and problematic SMU in relation to tobacco, alcohol, hashish/marijuana, and laughing gas intake levels; and moderation by perceived parental rules (screen/substances), was tested with ordinal logistic regression models.

Results
PSMU was associated with higher chances of higher substance use levels. Hashish/marijuana use and heavy drinking were less prevalent in adolescents reporting the presence of parental rules on alcohol/drugs, compared to adolescents reporting no rules. Although parental rules on alcohol/drugs, but not screen time, moderated the relationship between PSMU and both hashish/marijuana use and heavy drinking, the moderation effect was modest, especially in mitigating substance use at higher PSMU-scores.

Conclusion
PSMU was positively associated with a wide range of substance use behaviours. The potential significant role of parental rules (alcohol/drugs) mitigating these associations are highlighted.
Impact of Enteral and Parenteral Nutrition on Mortality and Morbidity of Mechanically Ventilated Severely Septic Critically Ill Patients
Authors: Kamal Shams Manal Mohammed , Shalaby Alawady Diaa Eldin , Eldin Abd Elaziz Farouk Kamal , Elhusseini Hassan Muhamad Mamdouh 
Published: November 2024

Abstract

Background
Malnutrition is common among critically ill patients and can negatively affect clinical outcomes. Artificial nutrition and hydration support is considered standard care in critical illness. However, there is considerable variation in nutrition support practice in ICUs.

Aim of the Work
The study aims to investigate the clinical outcomes difference of nutritional support TPN and EN in intubated mechanically ventilated severe septic patients over ICU stay.

Patients and Methods
The study involves 80 patients, and APATCHE and SOFA scores were used to assess clinical outcomes such as survival rate, extubation rate, tracheostomy, and complications.

Results
There is no significant difference between TPN and EN in terms of delivered Kcal and delivered proteins, APATCHE, and SOFA scores. Clinical outcomes such as survival rate and extubation rates are also not different between both groups. However, there were significantly more digestive complications in the early EN group, indicating that PN may be the safer route in some patient groups.

Conclusion
The study concludes that there is no difference in mortality and extubation rate between EN and TPN in intubated mechanically ventilated severe septic patients. However, there were significantly more digestive complications in the early EN group, indicating that PN may be the safer route in some patient groups.
Effect of Exosomes Derived from Mesenchymal Stem Cell on Hepatic Regeneration in Carbon Tetrachloride Induced Acute Liver Injury in Adult Male Albino Rats. Histological Study
Authors: Lotfy Ali Ghada , Abd El Salam Nevert Farid , Abunasef Seham Kamel , Ezzat Samar F 
Published: November 2024

Abstract

Background
Acute liver failure (ALF) is one of the emergency conditions. Carbon tetrachloride (CCl4) has been widely used to induce experimental hepatic damage. Bone marrow mesenchymal stem cell derived (BM-MSC) exosomes are broadly applied to regenerative approaches for various disorders serving the therapeutic effects of MSCs.

Aim of the Work
The study analyzed microscopically and biochemically, the regenerative power of the BM-MSC exosomes on the experimentally induced acute hepatic injury.

Materials and Methods
Fifty-five male adult Wistar albino rats were randomly divided into three groups: Group (I) control group, group II [given a single intraperitoneal injection of carbon tetrachloride (CCl4) (3% vol/vol in olive oil) at 0.05 ml/kg body weight] and group III [given a single tail vein injection of 50 μg of BM-MSC exosomes in 100 μl phosphate buffered saline 24 hours post-CCl4]. The rats were sacrificed after seven days. Biochemical analysis of AST and ALT was performed. Histological examination of liver tissue was performed through light microscopy of hematoxylin and eosin and Masson trichrome stained sections. Transmission electron microscopy (TEM) of liver tissue was carried out. Morphometric and statistical studies were done.

Results
By light microscopy, H&E-stained sections of Group II (CCl4 treated) revealed altered hepatic architecture with focal cellular infiltration. Congestion and dilatation of portal veins with periportal cellular infiltration were detected. Widening and endothelial discontinuity of the central veins and disorganization and obliteration of some blood sinusoids were demonstrated. Most hepatocytes appeared with darkly acidophilic cytoplasm and condensed nuclei, while others appeared with pyknotic nuclei with vacuolated cytoplasm. In Masson trichrome stained sections, there was a significant increase in the collagen fibers around the central veins and portal triads, and between hepatic cords. TEM examination, hepatocytes displayed irregular heterochromatic nuclei and rarified cytoplasm with plenty of lipid droplets. Hepatic stellate cells were devoid of lipid droplets. The epithelial cell lining the bile ductules had few short microvilli Inflammatory cells were seen near the ductular basal border. Biochemically, there was a significant increase in both ALT & AST levels in group II. The exosomes treated group (III) revealed marked amelioration of the previously mentioned histopathological and biochemical changes compared to the control group.

Conclusion
The acute CCl4 induced injury was significantly attenuated by BM-MSC exosomes therapy, and is characterized by an increase in hepatocyte proliferation, significant regression of collagen deposition in the liver tissue and marked attenuation of hepatocellular damage, both structurally and biochemically.