bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem cell-derived cardiomyocytes expressing a dominant negative pacemaker HCN4 channel do not reduce the risk of graft-related arrhythmias
Authors: Wulkan Fanny , Romagnuolo Rocco , Qiang Beiping , Valdman Sadikov Tamilla , Kim Kyung-Phil , Quesnel Elya , Jiang Wenlei , Andharia Naaz , Weyers Jill J. , Ghugre Nilesh R. , Ozcan Bilgehan , Alibhai Faisal J. , Laflamme Michael A. 
Published: July 2024

BackgroundHuman pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) show tremendous promise for cardiac regeneration following myocardial infarction (MI), but their transplantation gives rise to transient ventricular tachycardia (VT) in large-animal MI models, representing a major hurdle to translation. Our group previously reported that these arrhythmias arise from a focal mechanism whereby graft tissue functions as an ectopic pacemaker; therefore, we hypothesized that hPSC-CMs engineered with a dominant negative form of the pacemaker ion channel HCN4 (dnHCN4) would exhibit reduced automaticity and arrhythmogenic risk following transplantation.MethodsWe used CRISPR/Cas9-mediated gene-editing to create transgenic dnHCN4 hPSC-CMs, and their electrophysiological behavior was evaluated in vitro by patch-clamp recordings and optical mapping. Next, we transplanted WT and homozygous dnHCN4 hPSC-CMs in a pig MI model and compared post-transplantation outcomes including the incidence of spontaneous arrhythmias and graft structure by immunohistochemistry.ResultsIn vitro dnHCN4 hPSC-CMs exhibited significantly reduced automaticity and pacemaker funny current (If) density relative to wildtype (WT) cardiomyocytes. Following transplantation with either dnHCN4 or WT hPSC-CMs, all recipient hearts showed transmural infarct scar that was partially remuscularized by scattered islands of human myocardium. However, in contrast to our hypothesis, both dnHCN4 and WT hPSC-CM recipients exhibited frequent episodes of ventricular tachycardia (VT).ConclusionsWhile genetic silencing of the pacemaker ion channel HCN4 suppresses the automaticity of hPSC-CMs in vitro, this intervention is insufficient to reduce VT risk post-transplantation in the pig MI model, implying more complex mechanism(s) are operational in vivo.
Genetic insights of blood lipid metabolites on polycystic ovary syndrome risk: a bidirectional two-sample Mendelian randomization study
Authors: Wang Xinzhe , Han Huawei , Shi Xiuwen , Nie Xiaping , Zhu Rui , Jin Jing , Zhou Huifang 
Published: July 2024

BackgroundPathologically, metabolic disorder plays a crucial role in polycystic ovarian syndrome (PCOS). However, there is no conclusive evidence lipid metabolite levels to PCOS risk.MethodsIn this study, genome-wide association study (GWAS) genetic data for 122 lipid metabolites were used to assign instrumental variables (IVs). PCOS GWAS were derived from a large-scale meta-analysis of 10,074 PCOS cases and 103,164 controls. An inverse variance weighted (IVW) analysis was the primary methodology used for Mendelian randomization (MR). For sensitivity analyses, Cochran Q test, MR-Egger intercept, MR-PRESSO, leave-one-out analysis,and Steiger test were performed. Furthermore, we conducted replication analysis, meta-analysis, and metabolic pathway analysis. Lastly, reverse MR analysis was used to determine whether the onset of PCOS affected lipid metabolites.ResultsThis study detected the blood lipid metabolites and potential metabolic pathways that have a genetic association with PCOS onset. After IVW, sensitivity analyses, replication and meta-analysis, two pathogenic lipid metabolites of PCOS were finally identified: Hexadecanedioate (OR=1.85,95%CI=1.27–2.70, P=0.001) and Dihomo-linolenate (OR=2.45,95%CI=1.30–4.59, P=0.005). Besides, It was found that PCOS may be mediated by unsaturated fatty acid biosynthesis and primary bile acid biosynthesis metabolic pathways. Reverse MR analysis showed the causal association between PCOS and 2-tetradecenoyl carnitine at the genetic level (OR=1.025, 95% CI=1.003–1.048, P=0.026).ConclusionGenetic evidence suggests a causal relationship between hexadecanedioate and dihomo-linolenate and the risk of PCOS. These compounds could potentially serve as metabolic biomarkers for screening PCOS and selecting drug targets. The identification of these metabolic pathways is valuable in guiding the exploration of the pathological mechanisms of PCOS, although further studies are necessary for confirmation.
Impact of energy storage industry development on the low-carbon economy: evidence from China
Authors: Chen Jian , Li Hanzun 
Published: July 2024

Introduction: Facing the problem that it is difficult to reconcile development and carbon reduction in the energy sector, this study explores the impact mechanism of the development of energy storage industry on low-carbon economy from the perspective of the energy trilemma.Methods: Using a moderated two-mediation model and data from 275 cities in China, this study explores the differences in the impact mechanisms of the development of the energy storage industry on the low-carbon economy in different regions of China.Results: This study draws the following conclusions: first, the development of the energy storage industry can promote the green economy by facilitating technical support and the development of new energy industries. Second, financial support can regulate the effect of this mediating role. Third, in China, the contribution of energy storage industry development to green development is significantly higher in the northern region than in the southern region due to the differences in impact mechanisms.Discussion: The results of this study provide an effective path for developing countries to balance energy sector development, security, and low-carbon.
Optimal approaches for COVID-19 control: the use of vaccines and lockdowns across societal groups
Authors: Bonsall Michael B. , Huntingford Chris , Rawson Thomas 
Published: July 2024

BackgroundBy March 2023, the COVID-19 illness had caused over 6.8 million deaths globally. Countries restricted disease spread through non-pharmaceutical interventions (NPIs; e.g. social distancing). More severe “lockdowns” were also required to manage disease spread. Although lockdowns effectively reduce virus transmission, they substantially disrupt economies and individual well-being. Fortunately, the availability of vaccines provides alternative approaches to manage disease spread. Yet, vaccination programs take several months to implement fully, require further time for individuals to develop immunity following inoculation, may not have complete coverage and/or may be imperfectly efficacious against the virus. Given these aspects of a vaccination programme, it is important to understand how NPIs (such as lockdowns) can be used in conjunction with vaccination to achieve public health goals.MethodsWe use mathematical methods to, investigate optimal approaches for vaccination under varying lockdown lengths and/or severities to prevent COVID-19-related deaths exceeding critical thresholds.ResultsWe find that increases in vaccination rate cause a disproportionate decrease in the length and severity lockdowns to keep mortality levels below a critical threshold. With vaccination, severe lockdowns can further reduce infections by up to 89%. Notably, we include simple demographics, modelling three groups: vulnerable, front-line workers, and non-vulnerable. We investigate the sequence of vaccination. One counter-intuitive finding is that even though the vulnerable group is high risk, demographically, this is a small group and critically, per person, vaccination therefore occurs more slowly. Hence vaccinating this group first achieves limited gains in overall disease control.DiscussionImportantly, we conclude that improved disease control may be best achieved by vaccinating the non-vulnerable group coupled with longer and/or more severe NPIs.
Alphacoronaviruses from bats captured in European Russia in 2015 and 2021 are closely related to those of Northern Europe
Authors: Korneenko Elena V. , Samoilov Andrei E. , Chudinov Ivan K. , Butenko Ivan O. , Sonets Ignat V. , Artyushin Ilya V. , Yusefovich Alexander P. , Kruskop Sergei V. , Sinitsyn Sergei O. , Klyuchnikova Ekaterina O. , Gladkikh Anna S. , Dedkov Vladimir G. , Safonova Marina V. , Daszak Peter , Speranskaya Anna S. 
Published: July 2024

IntroductionBats are considered the natural reservoirs of several viruses including coronaviruses (CoVs), two genera of which, alpha- and betacoronaviruses, infect humans. Despite widespread screening of bat samples for novel viruses, information on the diversity of coronaviruses in bats inhabiting Russian territory remains scarce. Here, we analyzed the presence and diversity of alphacoronaviruses (Alpha-CoVs) in bats from European Russia.MethodsFourty three fecal samples from bats of 8 species: P. nathusii, P. kuhlii, M. brandtii, M. daubentonii, N. noctula, V. murinus, M. dasycneme, and P. auritus were taken to study.Results and discussionWe detected Alpha-CoV RdRp gene fragments in 30% (13/43) of samples examined in 75% (6/8) of species sampled. Phylogenetic analysis of RdRp showed that most of the identified Alpha-CoV sequences fall into clades within the Pedacovirus subgenus, with minor clusters of nyctacoviruses or myotacoviruses. We assert that closely related pedacoviruses have been circulating for a long time (from 2015 to 2021) in a large region from European Russia to Northern Europe. We propose that closely related pedacoviruses collected from common areas represent a separate species, which we name NE-Alpha coronavirus, with its host being bats of the genus Pipistrellus that inhabit a region from the European part of Russia to Northern Europe. Among the animals sampled, 4.6% (2/43) carried two Alpha-CoVs related to different subgenera (pedacovirus/myotacovirus or pedacovirus/nyctacovirus) simultaneously. We confirmed the presence of two different Alpha-CoV subgenera related to pedacovirus and nyctacovirus in P. kuhlii captured in 2021 and kept in captivity using whole genome sequencing of these viruses. The presence of two or more coronaviruses in one individual animal host is an essential prerequisite for recombination to occur. We also obtained two Alpha-CoV whole genomes from two specimens of P. nathusii captured in 2015. The genomic organization of BatCoV/MOW15-21 and BatCoV/MOW15-23 was similar to other Alpha-CoVs, but the assembled genomes contained a long insertion in the ORF1ab gene which has not been described in other Alpha-CoVs, except for a single sequence from P. nathusii captured in the Netherlands. We propose that the insertion encodes a previously undescribed domain of unknown function, probably related to the SEA domain superfamily.
Genetic engineering and genome editing technologies as catalyst for Africa’s food security: the case of plant biotechnology in Nigeria
Authors: Adegbaju Muyiwa Seyi , Ajose Titilayo , Adegbaju Ifeoluwa Elizabeth , Omosebi Temitayo , Ajenifujah-Solebo Shakirat Oloruntoyin , Falana Olaitan Yetunde , Shittu Olufunke Bolatito , Adetunji Charles Oluwaseun , Akinbo Olalekan 
Published: July 2024

Many African countries are unable to meet the food demands of their growing population and the situation is worsened by climate change and disease outbreaks. This issue of food insecurity may lead to a crisis of epic proportion if effective measures are not in place to make more food available. Thus, deploying biotechnology towards the improvement of existing crop varieties for tolerance or resistance to both biotic and abiotic stresses is crucial to increasing crop production. In order to optimize crop production, several African countries have implemented strategies to make the most of this innovative technology. For example, Nigerian government has implemented the National Biotechnology Policy to facilitate capacity building, research, bioresource development and commercialization of biotechnology products for over two decades. Several government ministries, research centers, universities, and agencies have worked together to implement the policy, resulting in the release of some genetically modified crops to farmers for cultivation and Commercialization, which is a significant accomplishment. However, the transgenic crops were only brought to Nigeria for confined field trials; the manufacturing of the transgenic crops took place outside the country. This may have contributed to the suspicion of pressure groups and embolden proponents of biotechnology as an alien technology. Likewise, this may also be the underlying issue preventing the adoption of biotechnology products in other African countries. It is therefore necessary that African universities develop capacity in various aspects of biotechnology, to continuously train indigenous scientists who can generate innovative ideas tailored towards solving problems that are peculiar to respective country. Therefore, this study intends to establish the role of genetic engineering and genome editing towards the achievement of food security in Africa while using Nigeria as a case study. In our opinion, biotechnology approaches will not only complement conventional breeding methods in the pursuit of crop improvements, but it remains a viable and sustainable means of tackling specific issues hindering optimal crop production. Furthermore, we suggest that financial institutions should offer low-interest loans to new businesses. In order to promote the growth of biotechnology products, especially through the creation of jobs and revenues through molecular farming.
The global psychological and physical effects of domestic abuse and violence on South Asian women: a qualitative systematic review
Authors: Masih Marina , Wagstaff Christopher , Kaur-Aujla Harjinder 
Published: July 2024

IntroductionThe purpose of this review is to systematically extract and analyse global academic literature to determine the physical and psychological effects of domestic abuse and violence on South Asian women.DesignThis review employs a qualitative systematic approach and thematic analysis to synthesize the narratives of affected women found in the literature. Given that domestic violence is often concealed and downplayed by various social factors, statistical reports and prevalence data offer only a limited view of the issue due to underreporting. Therefore, qualitative literature is deemed more dependable in this subjective domain as it captures and interprets the experiences and meanings within this under-studied group.Data sourcesEmbase, PsycINFO, Google Scholar, Web Of Science, MEDLINE, and ASSIA were searched.Review methodsAll included studies were critically appraised using the CASP tool for qualitative research. Thematic analysis was conducted to develop six themes. Studies excluded did not address the research question, although intersecting population issues could be valuable topics for further research.ResultsThe literature indicates severe mental and physical health consequences of domestic violence and abuse, with some traits persisting long-term. The analysis underscores the significant role of resilience, suggesting that individuals can overcome traumatic social experiences without enduring lifelong labels or a deficit model.ConclusionThe findings provide support for future interventions aimed at recognizing signs of abuse and preventing severe psychological and physical consequences, particularly among South Asian women. Further research is needed to understand the impact on children and other family members affected by the victim's abuse, which falls beyond the scope of this review.
Causal effects of autoimmune diseases on temporomandibular disorders and the mediating pathways: a Mendelian randomization study
Authors: Chen Xin , Cheng Zheng , Xu Junyu , Wang Qianyi , Zhao Zhibai , Jiang Qianglin 
Published: July 2024

BackgroundThe role of autoimmune diseases (ADs) in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder is destructive in TMDs. This Mendelian randomization (MR) study aims to estimate the causal effect of common ADs on TMDs.MethodsGenetic data from published genome-wide association studies for fourteen common ADs, specifically multiple sclerosis (MS, N = 15,283), ankylosing spondylitis (AS, N = 22,647), asthma (N = 408,422), celiac disease (N = 15,283), Graves’ disease (N = 458,620), Hashimoto thyroiditis (N = 395,640), primary biliary cirrhosis (PBC, N = 11,375), primary sclerosing cholangitis (PSC, N = 14,890), psoriasis vulgaris (N = 483,174), rheumatoid arthritis (RA, N = 417,256), systemic lupus erythematosus (SLE, N = 23,210), Type 1 diabetes (T1D, N = 520,580), inflammatory bowel disease (IBD, N = 34,652), and Sjogren’s syndrome (SS, N = 407,746) were collected. Additionally, the latest summary-level data for TMDs (N = 228,812) were extracted from the FinnGen database. The overall effects of each immune traits were assessed via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Finally, 731 immune cell phenotypes (N = 3,757) were analyzed for their mediating role in the significant causality.ResultsUnivariable MR analyses revealed that genetically predicted RA (IVW OR: 1.12, 95% CI: 1.05-1.19, p &lt; 0.001) and MS (IVW OR: 1.06, 95% CI: 1.03-1.10, p = 0.001) were associated with increased risk of TMDs. Two out of 731 immune cell phenotypes were identified as causal mediators in the associations of RA with TMDs, including “CD25++ CD8+ T cell % CD8+ T cell” (mediation proportion: 6.2%) and “CD3 on activated CD4 regulatory T cell” (5.4%). Additionally, “CD127 on granulocyte” mediated 10.6% of the total effect of MS on TMDs. No reverse directions, heterogeneity, and pleiotropy were detected in the analyses (p &gt; 0.05).ConclusionThis MR study provides new evidence regarding the causal impact of genetic predisposition to RA or MS on the increased risk of TMDs, potentially mediated by the modulation of immune cells. These findings highlight the importance for clinicians to pay more attention to patients with RA or MS when consulting for temporomandibular discomfort. The mediating role of specific immune cells is proposed but needs further investigation.
Causal role of immune cells in uveitis: Mendelian randomization study
Authors: Wu Jiahui , Fang Caocao , Zhou Yongwei , Wang Menghua , Li Qiuming , Dong Shuqian 
Published: July 2024

BackgroundUveitis, characterized by inflammation of the iris, ciliary body, and choroid, presents a significant global clinical challenge, contributing substantially to visual impairment. Risk factors include autoimmune diseases and immune cell dysfunctions, yet many remain unidentified. Immune cells, notably T cells, B cells, and monocytes, play pivotal roles in uveitis pathogenesis. While biologic agents show promise, comprehensive studies on immune cell types in ocular diseases are lacking. Genome-wide association studies (GWAS) and Mendelian randomization (MR) present promising avenues to elucidate genetic susceptibilities and causal relationships between immune cell traits and uveitis risk.MethodsTwo-sample MR analysis was used to evaluate the causal relationship between 731 immune cells and uveitis, and genome-wide significance analysis was performed for genetic variation in 731 immune cells traits (P &lt; 5 × 10-8). Immune characteristics include median fluorescence intensity (MFI), relative cell counts (RC), absolute cell counts (AC), and morphological parameters (MP), which were determined by published GWAS, and public data from the IEU Open GWAS database. The main analysis method of MR is inverse variance weighting (IVW). Heterogeneity and horizontal pleiotropy were also assessed.Results5 immunophenotypes, including CD62L-DC %DC, IgD+ CD38dim %B cell, CD3 on CM CD4+T cell, CD3 on CD45RA-CD4 +T cell, and CD3 on CD39+ CD4+ Treg may increase the risk of uveitis. 5 immunophenotypes, including CD11b on CD33dim HLA DR-Myeloid cell, HLA DR on CD33dim HLA DR+ CD11b-myeloid cell, CD14-CD16 + %monocyte, HLA DR on CD14-CD16 + monocyte and PDL-1 on CD14-CD16 + monocyte was negatively associated with the risk of uveitis. Among them, HLA DR on CD14-CD16 + monocyte (OR=0.921, 95%CI =0.875-0.970, P=0.001) and HLA DR on CD33dim HLA DR+ CD11b- (OR=0.879, 95%CI = 0.833-0.927, P=0.00) were negatively associated with the risk of uveitis in bi-direction.ConclusionThese results indicate that 10 immune cells traits are significantly associated with the risk of developing uveitis and 2 of them were strongly associated with uveitis bi-directionally, after excluding the effects of confounding factors such as some immune diseases, which provided new ideas and therapeutic targets for the study of immune mechanism of uveitis.
Dynamic changes in the proximitome of neutral sphingomyelinase-2 (nSMase2) in TNFα stimulated Jurkat cells
Authors: Schöl Marie , Schempp Rebekka , Hennig Thomas , Wigger Dominik , Schumacher Fabian , Kleuser Burkhard , Stigloher Christian , van Ham Marco , Jänsch Lothar , Schneider-Schaulies Sibylle , Dölken Lars , Avota Elita 
Published: July 2024

Ceramides generated by the activity of the neutral sphingomyelinase 2 (nSMase2) play a pivotal role in stress responses in mammalian cells. Dysregulation of sphingolipid metabolism has been implicated in numerous inflammation-related pathologies. However, its influence on inflammatory cytokine-induced signaling is yet incompletely understood. Here, we used proximity labeling to explore the plasma membrane proximal protein network of nSMase2 and TNFα-induced changes thereof. We established Jurkat cells stably expressing nSMase2 C-terminally fused to the engineered ascorbate peroxidase 2 (APEX2). Removal of excess biotin phenol substantially improved streptavidin-based affinity purification of biotinylated proteins. Using our optimized protocol, we determined nSMase2-proximal biotinylated proteins and their changes within the first 5 min of TNFα stimulation by quantitative mass spectrometry. We observed significant dynamic changes in the nSMase2 microenvironment in response to TNFα stimulation consistent with rapid remodeling of protein networks. Our data confirmed known nSMase2 interactors and revealed that the recruitment of most proteins depended on nSMase2 enzymatic activity. We measured significant enrichment of proteins related to vesicle-mediated transport, including proteins of recycling endosomes, trans-Golgi network, and exocytic vesicles in the proximitome of enzymatically active nSMase2 within the first minutes of TNFα stimulation. Hence, the nSMase2 proximal network and its TNFα-induced changes provide a valuable resource for further investigations into the involvement of nSMase2 in the early signaling pathways triggered by TNFα.