bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circumcision and Sexual Medicine
Authors: Bernaschina-Rivera Sebastián A , López-Chaim Alexandra I , Cordero-Pacheco José A , Fernández-Crespo Raúl , Quesada-Olarte José , Carrión Rafael 
Published: April 2023

Abstract

Introduction
Male circumcision is one of the most frequently performed and debated urological procedures due to its possible implications for sexual health.

Objectives
The objective of this article is to review the literature on male circumcision and reconcile the scientific evidence to improve the quality of care, patient education, and clinician decision-making regarding the effects on sexual function of this procedure.

Methods
A review of the published literature regarding male circumcision was performed on PubMed. The criteria for selecting resources prioritized systematic reviews and cohort studies pertinent to sexual dysfunction, with a preference for recent publications.

Results
Despite the conflicting data reported in articles, the weight of the scientific evidence suggests there is not sufficient data to establish a direct association between male circumcision and sexual dysfunction.

Conclusion
This review provides clinicians with an updated summary of the best available evidence on male circumcision and sexual dysfunction for evidenced-based quality of care and patient education.
Substance abuse and male sexual dysfunction: what lies beneath?
Authors: Mostafa Taymour , Alghobary Moheiddin 
Published: April 2023

Abstract

Introduction
Substance abuse has become a worldwide health problem, leading to numerous consequences such as social problems among family members, abnormal behavior, adverse health effects, and psychological problems as well as economic consequences.

Objectives
We sought to assess the relationship between substance abuse and male sexual health.

Methods
A search was carried out in the following databases: PubMed, MeSH (Medical Subject Headings), Science Direct, Scopus, Cochrane Library, EMBASE, CINAHL, Academic Search Complete, and the Egyptian Knowledge Bank. The following keywords were used to assess the outcomes for relevant associations: illicit drugs, addiction, substance abuse, sexual health, erectile dysfunction, ejaculatory disorders, impotence, orgasm disorders, and sexual performance.

Results
The initial literature search identified a total of 148 articles in all searched databases. After removal of duplicate studies and application of inclusion/exclusion criteria, 75 reported studies were retained for review, including 38 case-control studies and 37 cross-sectional studies. These articles were classified into the following categories according to the type of abused substance addressed: cannabis/marihuana, 16 articles; opioids, 13 articles; heroin, 11 articles; cocaine, 5 articles; tramadol, 6 articles; ketamine, 2 articles; ecstasy, 4 articles; amphetamine, 2 articles; khat, 7 articles; androgen anabolic steroids, 2 articles; and polydrugs, 7 articles. Most of these recruited articles demonstrated a negative impact of the addressed substance on male sexual health, with variable levels.

Conclusion
Substance abuse has negative impacts on male sexual health that should be addressed. More studies conducted with proper methodological and statistical approaches, including logistic regression analysis, are needed to predict the effects of specific substances, considering the rapidly growing effects of non–substance-use disorders on male sexual health.
Pathogenic LRRK2 compromises the subcellular distribution of lysosomes in a Rab12‐RILPL1‐dependent manner
Authors: Ito Kyohei , Araki Miho , Katai Yuta , Nishimura Yuki , Imotani Sota , Inoue Haruki , Ito Genta , Tomita Taisuke 
Published: April 2023

AbstractMutations in leucine‐rich repeat kinase 2 (LRRK2) cause familial Parkinson's disease (PD). Recent studies have shown that LRRK2 physiologically phosphorylates several Rab family proteins including Rab12 and that this phosphorylation is accelerated by the pathogenic mutations in LRRK2, although the significance in the PD pathogenesis remains unknown. Here we examined the effect of the overexpression of LRRK2 on the distribution of organelles in cultured cells and found that lysosomes become clustered in a perinuclear region upon the overexpression of pathogenic mutant LRRK2 in a manner dependent on its kinase activity. The perinuclear clustering of lysosomes was abolished by knocking out RAB12 as well as its effector protein RILPL1. Re‐expression of Rab12 in RAB12 knockout cells suggested that the phosphorylation at Ser106 of Rab12 is required for the perinuclear clustering of lysosomes. Moreover, phosphorylated Rab12 was also accumulated on the clustered lysosomes, and the phosphorylation of Rab12 increased its interaction with RILPL1, leading us to conclude that the increase in the phosphorylation of Rab12 by pathogenic LRRK2 compromised intracellular lysosomal transport via the enhanced interaction of Rab12 with RILPL1. These data suggest the involvement of abnormal regulation of lysosomal transport in the LRRK2‐mediated pathogenesis of PD.
WWC2 expression in the testis: Implications for spermatogenesis and male fertility
Authors: Höffken Verena , Di Persio Sara , Laurentino Sandra , Wyrwoll Margot J. , Terwort Nicole , Hermann Anke , Röpke Albrecht , Oud Manon S. , Wistuba Joachim , Kliesch Sabine , Pavenstädt Hermann J. , Tüttelmann Frank , Neuhaus Nina , Kremerskothen Joachim 
Published: April 2023

AbstractThe family of WWC proteins is known to regulate cell proliferation and organ growth control via the Hippo signaling pathway. As WWC proteins share a similar domain structure and a common set of interacting proteins, they are supposed to fulfill compensatory functions in cells and tissues. While all three WWC family members WWC1, WWC2, and WWC3 are found co‐expressed in most human organs including lung, brain, kidney, and liver, in the testis only WWC2 displays a relatively high expression. In this study, we investigated the testicular WWC2 expression in spermatogenesis and male fertility. We show that the Wwc2 mRNA expression level in mouse testes is increased during development in parallel with germ cell proliferation and differentiation. The cellular expression of each individual WWC family member was evaluated in published single‐cell mRNA datasets of murine and human testes demonstrating a high WWC2 expression predominantly in early spermatocytes. In line with this, immunohistochemistry revealed cytosolic WWC2 protein expression in primary spermatocytes from human testes displaying full spermatogenesis. In accordance with these findings, markedly lower WWC2 expression levels were detected in testicular tissues from mice and men lacking germ cells. Finally, analysis of whole‐exome sequencing data of male patients affected by infertility and unexplained severe spermatogenic failure revealed several heterozygous, rare WWC2 gene variants with a proposed damaging function and putative impact on WWC2 protein structure. Taken together, our findings provide novel insights into the testicular expression of WWC2 and show its cell‐specific expression in spermatocytes. As rare WWC2 variants were identified in the background of disturbed spermatogenesis, WWC2 may be a novel candidate gene for male infertility.
Cardiac PDGFRα+interstitial cells generate spontaneous inward currents that contribute to excitability in the heart
Authors: Zheng Haifeng , Peri Lauren , Ward Grace K. , Sanders Kenton M. , Ward Sean M. 
Published: April 2023

AbstractThe cell types and conductance that contribute to normal cardiac functions remain under investigation. We used mice that express an enhanced green fluorescent protein (eGFP)‐histone 2B fusion protein driven off the cell‐specific endogenous promoter forPdgfrato investigate the distribution and functional role of PDGFRα+cells in the heart. Cardiac PDGFRα+cells were widely distributed within the endomysium of atria, ventricle, and sino‐atrial node (SAN) tissues. PDGFRα+cells formed a discrete network of cells, lying in close apposition to neighboring cardiac myocytes in mouse and Cynomolgus monkey (Macaca fascicularis) hearts. Expression of eGFP in nuclei allowed unequivocal identification of these cells following enzymatic dispersion of muscle tissues. FACS purification of PDGFRα+cells from the SAN and analysis of gene transcripts by qPCR revealed that they were a distinct population of cells that expressed gap junction transcripts,Gja1andGjc1. Cardiac PDGFRα+cells generated spontaneous transient inward currents (STICs) and spontaneous transient depolarizations (STDs) that reversed at 0 mV. Reversal potential was maintained whenECl = −40 mV. [Na+]oreplacement and FTY720 abolished STICs, suggesting they were due to a non‐selective cation conductance (NSCC) carried by TRPM7. PDGFRα+cells also express β2‐adrenoceptor gene transcripts,Adrb2. Zinterol, a selective β2‐receptor agonist, increased the amplitude and frequency of STICs, suggesting these cells could contribute to adrenergic regulation of cardiac excitability. PDGFRα+cells in cardiac muscles generate inward currents via an NSCC. STICs generated by these cells may contribute to the integrated membrane potentials of cardiac muscles, possibly affecting the frequency of pacemaker activity.
MiR‐24‐3p regulates the differentiation of adipose‐derived stem cells toward pericytes and promotes fat grafting vascularization
Authors: Cai Zhongming , Li Zihao , Wei Qing , Yang Fangfang , Li Tian , Ke Chen , He Yucang , Wang Jingping , Ni Binting , Lin Ming , Li Liqun 
Published: April 2023

AbstractAdipose‐derived stem cells (ADSCs) enhance fat graft survival by promoting neovascularization. The mechanism that promotes ADSCs differentiation toward pericytes was not known. We treated ADSCs with conditional medium (CM) from endothelial cells (ECs) or human recombinant transforming growth factor β (TGF‐β) to induce differentiation into pericytes. Pericytes markers, including platelet‐derived growth factor receptor β (PDGFRβ), alpha‐smooth muscle actin (α‐SMA), and desmin, were examined. Pericytes differentiation markers, migration, and their association with ECs were examined in ADSCs transfected with miR‐24‐3p mimics and inhibitors. Bioinformatics target prediction platforms and luciferase assays were used to investigate whether PDGFRβ was directly targeted by miR‐24‐3p. In vivo, fat mixed with ADSCs transfected with miR‐24‐3p mimics or inhibitors was implanted subcutaneously on the lower back region of nude mice. Fat grafts were harvested and analyzed at 2, 4, 6, and 8 weeks. Results showed that endogenous TGF‐β derived from CM from EC or human recombinant TGF‐β promoted migration, association with ECs, and induced expression of pericyte markers (PDGFRβ, α‐SMA, Desmin) in ADSCs. MiR‐24‐3p directly targeted PDGFRβ in ADSCs by lucifer reporter assays. Inhibition of miR‐24‐3p promoted pericytes differentiation, migration, and association with ECs in ADSCs. Inhibition of miR‐24‐3p in ADSCs promoted survival, integrity, adipocyte viability, vascularization, pericytes association with ECs, and reduced fibrosis, whereas overexpression of miR‐24‐3p in ADSCs yielded the opposite results. Collectively, TGF‐β released by ECs induced ADSCs differentiation toward pericytes through miR‐24‐3p. Downregulation of miR‐24‐3p in ADSCs induced survival, integrity, adipocyte viability, vascularization, pericytes association with ECs, and reduced fibrosis after fat grafting.
Knockout of miR‐184 in zebrafish leads to ocular abnormalities by elevating p21 levels
Authors: Zhang Jing , Li Ping , Sun Luqian , Jiang Ning , Guo Wenya , Wang Jungai , Gao Fen , Li Jing , Li Hui , Zhang Jun , Mu Hongmei , Hu Yanzhong , Cui Xiukun 
Published: April 2023

AbstractmiR‐184 is one of the most abundant miRNAs expressed in the lens and corneal tissue. Mutations in the seed region of miR‐184 are responsible for inherited anterior segment dysgenesis. Animal models recapitulating miR‐184‐related anterior segment dysgenesis are still lacking, and the molecular basis of ocular abnormalities caused by miR‐184 dysfunction has not been well elucidated in vivo. In the present study, we constructed a miR‐184−/− zebrafish line by destroying both two dre‐mir‐184 paralogs with CRISPR‐Cas9 technology. Although there were no gross developmental defects, the miR‐184−/− zebrafish displayed microphthalmia and cataract phenotypes. Cytoskeletal abnormalities, aggregation of γ‐crystallin, and lens fibrosis were induced in miR‐184−/− lenses. However, no obvious corneal abnormalities were observed in miR‐184−/− zebrafish. Instead of apoptosis, deficiency of miR‐184 led to aberrant cell proliferation and a robust increase in p21 levels in zebrafish eyes. Inhibition of p21 by UC2288 compromised the elevation of lens fibrosis markers in miR‐184−/− lenses. RNA‐seq demonstrated that levels of four transcriptional factors HSF4, Sox9a, CTCF, and Smad6a, all of which could suppress p21 expression, were reduced in miR‐184−/− eyes. The predicted zebrafish miR‐184 direct target genes (e.g., atp1a3a and nck2a) were identified and verified in miR‐184−/− eye tissues. The miR‐184−/− zebrafish is the first animal model mimicking miR‐184‐related anterior segment dysgenesis and could broaden our understanding of the roles of miR‐184 in eye development.
Recommending Drug Combinations using Reinforcement Learning to target Genes/proteins that cause Stroke: A comprehensive Systematic Review and Network Meta-analysis
Authors: Boush Mahnaz , Kiaei Ali A. , Safaei Danial , Abadijou Sadegh , Salari Nader , Mohammadi Masoud 
Published: April 2023

ABSTRACTObjectives(Importance)Cerebrovascular accident (Stroke) is a term used in medicine to describe cutting off blood supply to a portion of the brain, which causes tissue damage in the brain. Clots of blood that form in the brain’s blood vessels and ruptures in the brain’s blood vessels are the root causes of cerebrovascular accidents. Dizziness, numbness, weakness on one side of the body, and difficulties communicating verbally, writing, or comprehending language are the symptoms of this condition. Smoking, being older and having high blood pressure, diabetes, high cholesterol, heart disease, a history of cerebrovascular accident in the family, atherosclerosis (which is the buildup of fatty material and plaque inside the coronary arteries), or high cholesterol all contribute to an increased risk of having a cerebrovascular accident.(Objective)This paper analyzes available studies on Cerebrovascular accident medication combinations.Evidence acquisition(Data sources)This systematic review and network meta-analysis analyzed the Science Direct, Embase, Scopus, PubMed, Web of Science (ISI), and Google Scholar databases without a lower time limit and up to July 2022. A network meta-analysis examines the efficacy of this drug combination on genes/proteins that serve as progression targets for cerebrovascular accidents.Results and ConclusionIn scenarios 1 through 3, the p-values for the suggested medication combination and Cerebrovascular accident were 0.036633, 0.007763, and 0.003638, respectively. Scenario I is the combination of medications initially indicated for treating a cerebrovascular accident. The recommended combination of medications for cerebrovascular accidents is ten times more effective. This systematic review and network meta-analysis demonstrate that the recommended medication combination decreases the p-value between cerebrovascular accidents and the genes as potential progression targets, thereby enhancing the treatment for cerebrovascular accidents. The optimal combination of medications improves community health and decreases per-person management costs.HighlightsCombined drugs that make the p-value between Stroke and target genes close to 1Using Reinforcement Learning to recommend drug combinationA comprehensive systematic review of recent worksA Network meta-analysis to measure the comparative efficacyConsidered drug interactions
No causal association between inguinal hernia and aortic aneurysm using Mendelian randomization analysis
Authors: Yao Sicheng , Ci Hongbo 
Published: April 2023

AbstractAortic aneurysm (AA) is a serious disease that affects the aging population worldwide. Potential risk factors such as inguinal hernia has been suggested by conventional studies could contribute to AA. The aim of our study was to clarify the causal association between inguinal hernia and AA using Mendelian randomization (MR) analysis. Summary statistics data for the associations of inguinal hernia were derived from a recently published large genome-wide association study including 18,791 inguinal hernia cases and 93,955 controls in UK Biobank. Corresponding data of AA were extracted from FinnGen, comprising 7,603 cases and 317,899 controls. The causal association was assessed using MR-egger, weighted median, and inverse variance weighting methods, and compared to observational estimates previously published. Our analysis found no convincing causal effect between genetically predicted inguinal hernia and the risk of AA (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 0.85–1.31,p= 0.65), AAA (OR = 1.15, 95% CI = 0.92–1.46,p= 0.22), and TAA (OR = 1.05, 95% CI = 0.85–1.30,p= 0.67). The results are in contrast to previous observational evidence suggesting a harmful effect of inguinal hernia.
Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta infections
Authors: Altarawneh Heba N. , Chemaitelly Hiam , Ayoub Houssein H. , Tang Patrick , Hasan Mohammad R. , Yassine Hadi M. , Al-Khatib Hebah A. , Al Thani Asmaa A. , Coyle Peter , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul-Rahim Hanan F. , Nasrallah Gheyath K. , Al-Kuwari Mohamed Ghaith , Butt Adeel A. , Al-Romaihi Hamad Eid , Al-Thani Mohamed H. , Al-Khal Abdullatif , Bertollini Roberto , Abu-Raddad Laith J. 
Published: April 2023

ABSTRACTBackgroundProtection against SARS-CoV-2 symptomatic infection and severe COVID-19 of previous infection, mRNA two-dose vaccination, mRNA three-dose vaccination, and hybrid immunity of previous infection and vaccination were investigated in Qatar for the Alpha, Beta, and Delta variants.MethodsSix national, matched, test-negative, case-control studies were conducted between January 18-December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests.ResultsEffectiveness of previous infection against Alpha, Beta, and Delta reinfection was 89.5% (95% CI: 85.5-92.3%), 87.9% (95% CI: 85.4-89.9%), and 90.0% (95% CI: 86.7-92.5%), respectively. Effectiveness of two-dose BNT162b2 vaccination against Alpha, Beta, and Delta infection was 90.5% (95% CI, 83.9-94.4%), 80.5% (95% CI: 79.0-82.0%), and 58.1% (95% CI: 54.6-61.3%), respectively. Effectiveness of three-dose BNT162b2 vaccination against Delta infection was 91.7% (95% CI: 87.1-94.7%). Effectiveness of hybrid immunity of previous infection and two-dose BNT162b2 vaccination was 97.4% (95% CI: 95.4-98.5%) against Beta infection and 94.5% (95% CI: 92.8-95.8%) against Delta infection. Effectiveness of previous infection and three-dose BNT162b2 vaccination was 98.1% (95% CI: 85.7-99.7%) against Delta infection. All five forms of immunity had >90% protection against severe, critical, or fatal COVID-19 regardless of variant. Similar effectiveness estimates were observed for mRNA-1273.ConclusionsAll forms of natural and vaccine immunity prior to Omicron introduction provided strong protection against infection and severe COVID-19. Hybrid immunity conferred the strongest protection and its level was consistent with previous-infection immunity and vaccine immunity acting independently of each other.
Genetic tools for the study of the mangrove killifish, Kryptolebias marmoratus,an emerging vertebrate model for phenotypic plasticity
Authors: Li Cheng-Yu , Boldt Helena , Parent Emily , Ficklin Jax , James Althea , Anlage Troy J. , Boyer Lena M. , Pierce Brianna R. , Siegfried Kellee , Harris Matthew P. , Haag Eric S. 
Published: April 2023

AbstractKryptolebias marmoratus(Kmar), a teleost fish of the order Cyprinodontiformes, has a suite of unique phenotypes and behaviors not observed in other fishes. Many of these phenotypes are discrete and highly plastic –varying over time within an individual, and in some cases reversible. Kmar and its interfertile sister species,K. hermaphroditus, are the only known self-fertile vertebrates. This unusual sexual mode has the potential to provide unique insights into the regulation of vertebrate sexual development, and also lends itself to genetics. Kmar is easily adapted to the lab and requires little maintenance. However, its internal fertilization and small clutch size limits its experimental use. To support Kmar as a genetic model, we compared alternative husbandry techniques to maximize recovery of early cleavage-stage embryos. We find that frequent egg collection enhances yield, and that protease treatment promotes the greatest hatching successes from diapause. We completed a forward mutagenesis screen and recovered several mutant lines that serve as important tools for genetics in this model. Several will serve as useful viable recessive markers for marking crosses. Importantly, the mutantkissylipslays embryos at twice the rate of wild-type. Combining frequent egg collection with thekissylipsmutant background allows for a substantial enhancement of early embryo yield. These improvements were sufficient to allow experimental analysis of early development and the successful mono- and bi-allelic targeted knockout of an endogenoustyrosinasegene with CRISPR/Cas9 nucleases. Collectively, these tools will facilitate modern developmental genetics in this fascinating fish, leading to future insights into the regulation of plasticity.
Correcting 4sU induced quantification bias in nucleotide conversion RNA-seq data
Authors: Berg Kevin , Lodha Manivel , Garcia Yilliam Cruz , Hennig Thomas , Wolf Elmar , Prusty Bhupesh K , Erhard Florian 
Published: April 2023

AbstractNucleoside analogues like 4-thiouridine (4sU) are used to metabolically label newly synthesized RNA. Chemical conversion of 4sU before sequencing induces T-to-C mismatches in reads sequenced from labelled RNA, allowing to obtain total and labelled RNA expression profiles from a single sequencing library. Cytotoxicity due to extended periods of labelling or high 4sU concentrations has been described, but the effects of extensive 4sU labelling on expression estimates from nucleotide conversion RNA-seq have not been studied. Here, we performed nucleotide conversion RNA-seq with escalating doses of 4sU with short-term labelling (1h) and over a progressive time course (up to 2h) in different cell lines. With high concentrations or at later time points, expression estimates were biased in an RNA half-life dependent manner. We show that bias arose by a combination of reduced mappability of reads carrying multiple conversions, and a global, unspecific underrepresentation of labelled RNA due to impaired reverse transcription efficiency and potentially global reduction of RNA synthesis. We developed a computational tool to rescue unmappable reads, which performed favourably compared to previous read mappers, and a statistical method, which could fully remove remaining bias. All methods developed here are freely available as part of our GRAND-SLAM pipeline and grandR package.