bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virus infection significantly decreases insect fitness: a meta-analysis
Authors: Cesar Cássia Siqueira , Miranda Vitória Horvath , Silveira Elielson Rodrigo , de Oliveira Thiago Assis , Cogni Rodrigo 
Published: January 2025

AbstractOrganisms are constantly at risk of being infected by pathogens such as viruses. Adaptations against viral infection include immune defenses encoded within the host genome and associations with defensive symbionts such asWolbachia. Wolbachiais widely spread among insects, and its success in nature may be due to its antiviral effects, which can benefit hosts if viruses significantly reduce host fitness. Here, we conducted a meta-analysis to assess the degree to which viral infection affects the fitness of insect hosts, and which factors may influence the impact of viral infection on hosts such as if the insect host is a vector or not of viruses that cause diseases in humans and plants, and if the insect is a new or a natural host of a specific virus. We gathered 1,040 effect sizes from 150 studies. Our results show that viruses significantly reduce host fitness, especially their survival. The decrease in host fitness is higher in non-vector than in vector insects, and we found no difference in fitness decrease caused by viral infection between new and natural hosts. Moreover, we found that fitness effects caused by viruses vary between host order and fitness components. In conclusion, our results show that viruses exert severe harmful effects on hosts by decreasing their fitness. In this context, harboring symbionts that confer antiviral protection, such asWolbachia, can be highly advantageous for hosts, enhancing their fitness. Conversely,Wolbachiacan benefit from the presence of viruses, facilitating its spread in insect populations by offering antiviral protection.
The metabolic enzyme GYS1 condenses with NONO/p54nrbin the nucleus to spatiotemporally regulate glycogenesis and myogenic differentiation
Authors: Peng Shujun , Li Canrong , Wang Yifan , Yi Yuguo , Chen Xinyu , Yin Yujing , Yang Fan , Chen Fengzhi , Ouyang Yingyi , Xu Haolun , Chen Baicheng , Shi Haowen , Li Qingrun , Zhao Yu , Feng Lin , Gan Zhenji , Xie Xiaoduo 
Published: January 2025

AbstractAccumulating evidence indicates that metabolic enzymes can directly couple metabolic signals to transcriptional adaptation and cell differentiation. Glycogen synthase 1 (GYS1), the key metabolic enzyme for glycogenesis, is a nucleocytoplasmic shuttling protein compartmentalized in the cytosol and nucleus. However, the spatiotemporal regulation and biological function of nuclear GYS1 (nGYS1) microcompartments remain unclear. Here, we show that GYS1 dynamically reorganizes into nuclear condensates under conditions of glycogen depletion or transcription inhibition. nGYS1 complexes with the transcription factor NONO/p54nrband undergoes liquid-liquid phase separation to form biomolecular condensates, leading to its nuclear retention and inhibition of glycogen biosynthesis. Compared to their wild-type littermates, Nono-deficient mice exhibit exercise intolerance, higher muscle glycogen content, and smaller myofibers. Additionally, Gys1 or Nono deficiency prevents C2C12 differentiation and cardiotoxin-induced muscle regeneration in mice. Mechanistically, nGYS1 and NONO co-condense with the myogenic transcription factor MyoD and preinitiation complex (PIC) proteins to form transcriptional condensates, driving myogenic gene expression during myoblast differentiation. These results reveal the spatiotemporal regulation and subcellular function of nuclear GYS1 condensates in glycogenesis and myogenesis, providing mechanistic insights into glycogenoses and muscular dystrophy.
Regulation of cell cycle by the novel GATA1/TAL1/Sphingomyelin Synthase 1 (SGMS1) transcriptional axis. Implications for anti-leukemic strategies
Authors: Raza Yasharah , Moorthi Sitapriya , Yu Gui-Qin , Chiappone Sam , Vacchi-Suzzi Caterina , Luberto Chiara 
Published: January 2025

ABSTRACTSphingomyelin Synthase 1 (gene name:SGMS1) participates in regulation of sphingolipid levels by synthesizing sphingomyelin from ceramide and phosphatidylcholine. Evidence have supported SGMS1’s functions in regulating proliferation, cell cycle, cell death and migration. While its functions have begun to be explored, very little is known about upstream regulators. Here, we demonstrate thatSGMS1is a direct gene target of the GATA1-TAL1 transcriptional complex in K562 erythroleukemic cells. A predicted GATA1 consensus DNA binding sequence was identified with in a newly characterized alternativeSGMS1promoter (TSS-7 promoter) and ChIP analysis confirmed GATA1 occupancy on the promoter. Down-regulation of GATA1 in K562 cells significantly decreased SGMS1 expression and enzymatic activity, and ChIP-Seq analysis from ENCODE showed colocalized peaks for GATA1 and TAL1(a well-established GATA1 DNA binding partner) on theSGMS1gene. Analysis of publicly available datasets shows that elevatedGATA1, TAL1andSGMS1expression not only clusters GATA1 positive chronic myelogenous leukemia cells (like K562), but also selectively identifies acute erythrocytic and megakaryocytic leukemias (M6 and M7 AML, respectively). Microarray gene expression analysis after down-regulation ofSGMS1in M6 AML Hel cells revealed alteration of genes regulating G2/M check point and mitotic spindle formation. This phenotype was functionally confirmed by the significant delay in G2/M cell cycle progression of cells withSGMS1downregulation and sensitization to the clinically relevant anti-mitotic agent, Taxol. Altogether, these results identifySGMS1as a novel target of GATA1/TAL1 transcriptional complex and they support a role for the GATA1/TAL1/SGMS1 axis in regulating transit through G2/M. Importantly, results also point to combination of anti-mitotic agents and inhibition of SGMS1 as a potential novel therapeutic approach against the aggressive and resilient M6 AMLs.KEY POINTSThe Sphingomyelin Synthase 1 gene (SGMS1) is a novel direct target of GATA1 and TAL1.HighSGMS1levels are associated with highGATA1/TAL1expression and regulate cell cycle progression through the G2/M checkpoint in GATA1+erythroleukemic Acute Myeloid Leukemia Hel cells.HighSGMS1is associated with lower probability of survival of patients with Acute Myeloid Leukemia and down-regulation of SGMS1 co-operates with microtubule targeting agents to induce cytotoxicity in GATA1 positive AML Hel cells.
Primate-specific microRNA-1202 regulates dopaminergic neurogenesis by targeting APC2 and modulates WNT/β-catenin signaling pathway in midbrain organoid
Authors: Long Xiaohang , Cao Dandan , Chan See-Wing , Hao Suyu , Liu Lingxiao , Chan Wai-Yee , Cheung Hoi-Hung 
Published: January 2025

ABSTRACTMicroRNAs (miRNAs) are generally evolutionarily conserved, but a small number of them are found exclusively in primates. MiR-1202 is a primate-specific miRNA that was previously revealed as being involved in major depression disorder (MDD). Moreover, the genomic locus where miR-1202 locates (6q25.3) is strongly associated with recurrent early-onset MDD and neurodevelopmental disorder. We hypothesize that miR-1202 plays a unique role in the brain in fine-tuning the transcriptional network that governs neurogenesis. Here, we reported that microdeletion of miR-1202 resulted in retarded organoid growth but enhanced dopaminergic (DA) neuron differentiation in midbrain organoids. Integrated analysis of miRNA-interacting targets and transcriptional changes in miR-1202 knockout cells revealed that APC2, a negative regulator of canonical WNT/β-catenin pathway, was a downstream target of miR-1202. Knockdown of APC2 resulted in attenuated DA neurogenesis, in contrast to the enhanced DA neurogenesis in miR-1202 knockout cells. Treatments of the brain organoids with antidepressants increased miR-1202 expression and simultaneously inhibited APC2 expression. Consistently, APC2 expression was found to increase in MDD patients. Our results suggest that miR-1202 regulates dopamine neurogenesis by inhibiting the APC2/WNT signaling pathway, which plays a distinct role in the midbrain-hindbrain regional patterning during the early development of the central nervous system.
Exome Sequencing for Head and Neck Cancer Predisposition Genes
Authors: Yu Yao , Feng Bingjian , Chang Chun-Pin , Bell Russell , Wood Austin , Sturgis Erich , Li Guojun , Olshan Andrew , Chen Chien-Jen , Lou Pen-Jen , Hsu Wan-Lun , Cessna Melissa , Witt Benjamin , Neklason Deb , Hashibe Mia , Huff Chad , Tavtigian Sean 
Published: January 2025

AbstractIntroductionWhile common variants have been studied for head and neck cancer (HNC) risk and exome sequencing has been conducted for head and neck tumor tissue samples, large-scale studies of exome sequencing on head and neck cancer risk have not been conducted. Our study aimed to identify head and neck cancer predisposition genes with exome sequencing and to assess interactions between the head and neck cancer susceptibility genes and tobacco use.MethodsWe conducted a case-control analysis to identify germline susceptibility genes for HNC risk. We used whole-exome sequencing data in Phase 1, targeted gene sequencing data in Phase 2 (2,134 HNC cases and 2,072 controls), and publicly available whole-exome sequencing data from the UK Biobank database. We conducted a gene-based association analysis and estimated the effect size of known and novel HNC susceptibility genes and pathways.ResultsSix known cancer predisposition genes reached nominal significance (p < 0.05), includingBRCA1,BRCA2,RAD51B,BAP1,APC, andMUTYH. Additionally, we identified 21 novel HNC risk genes with meta p-value < 0.05. LoF variants inBRCA1(OR=5.0, 95% CI: 1.72-14.57),BRCA2(OR=2.56, 95% CI: 1.22-5.41), andMUTYH(OR=4.84, 95% CI: 1.01-13.86) exhibited significantly elevated effect sizes.APC, BRCA2, and the DNA repair gene set exhibited borderline interactions with smoking, with synergy indices and 95% confidence intervals of 1.92 [0.98, 3.75], 1.77 [0.91, 3.46], and 1.57 [0.97, 2.54], respectively.ConclusionsWe observed associations with HNC risk for DNA repair pathway genes associated with breast cancer and polyposis colorectal cancer predisposition genes. Potential interactions between these genes and tobacco smoking were also identified. Our study utilized targeted gene sequencing and whole-exome sequencing approaches to identify cancer susceptibility genes, while further studies are needed to confirm the associations observed with HNC risk.
Optimal control and cost-effectiveness analysis of mitigation strategies for monkeypox virus infection in the presence of routine interventions
Authors: Naandam Samuel M. , Chataa Paul , Nikingbong Christopher , Adom-Konadu Agnes 
Published: January 2025

AbstractEmpirical evidence substantiates the pivotal role of vaccination in eradicating monkeypox virus (Mpox) infections. Mathematical modeling serves as a crucial tool for identifying strategies to curtail the disease’s proliferation. This study introduces a comprehensive mathematical framework for analyzing the dynamics of monkeypox transmission, incorporating imperfect vaccination and immunity degradation post-recovery. The theoretical constructs of positivity and boundedness are employed to confirm the model’s well-posedness. The next-generation matrix approach is utilized to calculate the control reproduction number (ℛc), and the equilibrium points of the model are identified. The investigation demonstrates that the disease-free equilibrium is both locally and globally asymptotically stable, while the endemic equilibrium is proven to exhibit global asymptotic stability as well. Sensitivity analyses of parameters influencing ℛcare performed using Latin Hypercube Sampling (LHS) and Partial Rank Correlation Coefficients (PRCC). Furthermore, the model is extended to incorporate time-dependent interventions, including the administration of high-efficacy vaccines, the quarantine of exposed individuals, and the treatment of infected individuals. The model’s qualitative findings are reinforced through numerical simulations, which validate the effectiveness of various control strategies in suppressing monkeypox spread among susceptible, exposed, and infected populations. Simulations without vaccination controls reveal an initial surge in exposed and infected cases, followed by gradual containment over time. The findings highlight the critical importance of vaccination as a pharmaceutical intervention, though its effectiveness is hindered by challenges such as viral mutations, the diminishing efficacy of vaccines, and limited vaccination resources. These constraints underscore the necessity of adopting integrated intervention measures, especially as instances of reinfection post-vaccination and treatment of infected cases have been documented in several studies. Policymakers are thus encouraged to employ a balanced and pragmatic approach when easing other preventive measures for monkeypox. Additionally, a cost-effectiveness analysis was performed to determine the most economical strategy for controlling monkeypox transmission. The results indicate that the optimal control strategy involves combining high-efficacy vaccination with the quarantine of exposed individuals, demonstrating superior cost-effectiveness among the examined interventions.
Online General Exercise Management (GEM) Program for patients with Breast Cancer-Related Lymphedema: A Protocol for a Pilot Randomized Controlled Trial
Authors: Arinaga Yoko , Sato Fumiko , Miyata Satoshi , Piller Neil , Ohtake Tohru 
Published: January 2025

ABSTRACTBackgroundBreast cancer-related lymphedema (BCRL) requires a lifetime commitment to self-care.AimsThis is a study protocol for a pilot parallel-group randomized controlled trial which will assess the effectiveness of an online version of the General Exercise Management (GEM) program for patients with BCRL.MethodsSixty patients will be recruited through online advertisements and randomly allocated to either an intervention or control group. The intervention group will be provided with an educational program on standard self-care for BCRL as well as the GEM program, while the control group will receive only the self-care education program. Both groups will participate in a six-month online program, perform daily self-checks and participate in monthly small-group sessions. All participants, session facilitators and a statistical analyst will be blinded to group allocation.Anticipated ResultsThe primary expected outcome is a reduction of BCRL symptoms, and the secondary outcomes are health-related quality of life and self- care adherence improvements.ConclusionsThe findings will inform further investigation in a Phase III trial.Declaration of InterestAll authors declare that they have no competing financial interests.This study was approved by the Institutional Review Board of Fukushima Medical University Hospital (REC2024-068) and registered with UMIN-CTR (UMIN000055357).
Estimating the Global Market Size for Disease-Modifying Therapies in Epilepsy Caused by Haploinsufficiency
Authors: Pérez-Palma Eduardo , Brünger Tobias , Lhatoo Samden , Zhang Guo-Qiang , Nascimento Fabio A , Lal Dennis 
Published: January 2025

AbstractImportanceHaploinsufficiency, a condition where a single functional copy of a gene is insufficient to maintain normal physiological function due to a mutation, represents the most prevalent disease mechanism underlying genetic epilepsies, particularly developmental and epileptic encephalopathies (DEEs). Current therapies for these patients primarily address symptoms and fail to alter the disease trajectory. Given the prospect of targeted gene therapies, accurately quantifying the burden of these disorders is paramount for optimizing resource allocation in patient care and facilitating the development of novel disease-modifying therapies.ObjectiveTo estimate the global and U.S. incidence and prevalence of epilepsy caused by haploinsufficiency.Design, Setting, and ParticipantsFirst, we identified epilepsy genes, focusing on autosomal dominant genes with a high likelihood of haploinsufficiency. Second, we utilized a statistical framework to estimate the birth incidence of patients with protein-truncating variants in these genes, incorporating gene-specific mutation rates and birth rate data. Finally, we calculated prevalence by multiplying annual incidence by an effective disease duration, considering factors like sudden unexpected death in epilepsy.Main Outcomes and MeasuresBirth incidence and prevalence of epilepsy attributable tode novoprotein-truncating variants in haploinsufficient genes.ResultsAn estimated 228.81 (90% CI: 206.21–241.93) cases of haploinsufficiency-related epilepsy occur per 100,000 live births globally. This translates to approximately 313,595 new cases annually worldwide and 8,736 in the United States. The estimated global prevalence is 14,343,840 individuals.Conclusions and RelevanceThis study provides the first data-driven estimates of the of haploinsufficiency-related epilepsy burden, highlighting a substantial population potentially benefiting from gene-targeting therapies. These findings have significant implications for research prioritization, resource allocation, and the development of precision medicine approaches for treating these severe neurological disorders.
Identifying socio-economic barriers to antibiotic resistance stewardship in the Dairy Industry in LICs and LMICs
Authors: Singh Harshita , Singh Awanish Kumar , Singh Gargi 
Published: January 2025

AbstractAntibiotic resistance (ABR) is a severe global public health threat, particularly in low- and middle-income countries (LICs and LMICs), where socio-economic and infrastructural factors impede effective ABR management. Here, we identify critical challenges, including disparity in the volume of research related to ABR stewardship for the dairy industry, that hinder the success of national action plans in LICs and LMICs. We conducted a literature review to pinpoint specific challenges to ABR stewardship in LICs and LMICs and employed generalised linear models to evaluate the predictive influence of dairy-related, socio-economic, and environmental factors on progress in antimicrobial resistance stewardship using TrACSS scores. We ascertained six key themes in otherwise interconnected challenges that critically limit ABR stewardship in LICs and LMICs: (i) lack of awareness among stakeholders, (ii) ineffective regulations, (iii) insufficient surveillance and monitoring, (iv) inadequate veterinary health infrastructure, (v) economic constraints, and (vi) certain cultural beliefs and traditional practices. Generalised linear regression models confirmed that effective surveillance, robust health and diagnostic infrastructure, and economic affluence significantly determine the progress of ABR stewardship in a country, as reported by TrACSS scores. However, the substantially sparse knowledge on the impact of dairy farms on environmental resistome generated in LICs and LMICs raises the concern that the interventions for the dairy industry in these countries are not informed by the actual local and national conditions.
Transcriptomic analysis of chronic chikungunya in the Reunionese CHIKGene cohort uncovers a shift in gene expression more than 10 years after infection
Authors: Gérardin Patrick , Medina-Santos Raissa , Le Clerc Sigrid , Bruneau Léa , Maillot Adrien , Labib Taoufik , Rahmouni Myriam , Spadoni Jean-Louis , Meyniel Jean-Philippe , Cornet Clémence , Lefebvre Cécile , El Jahrani Nora , Savara Jakub , Mathew Mano Joseph , Fontaine Christine , Payet Christine , Ah-You Nathalie , Chabert Cécile , Mussard Corinne , Porcherat Sylvaine , Medjane Samir , Noirel Josselin , Marimoutou Catherine , Hocini Hakim , Zagury Jean-François 
Published: January 2025

AbstractAimIn 2005-2006, a chikungunya epidemic of unprecedented magnitude hit Reunion Island, which raised a public health concern through the substantial proportions of long-lasting manifestations. To understand the pathophysiology underlying chronic chikungunya (CC), we designed the CHIKGene cohort study and collected blood samples from 133 subjects diagnosed with CC and from 86 control individuals that had recovered within 3 months, 12-to-15 years after exposure.MethodsWe conducted bulk RNAseq analysis on peripheral blood mononuclear cells to find differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) and gene ontologies to uncover top-level enriched terms associated with DEGs, and weighted gene correlation network analysis (WGCNA) to elucidate underlying cellular processes.ResultsAmong 1549 DEGs, gene expression analysis identified 10 top genes includingNR4A2andTRIM58(upregulated in CC),IGHG3andIGHV3-49(downregulated in CC) linked to immune regulation,OSBP2(upregulated in CC) andSEMA6B(downregulated in CC) linked to neuronal homeostasis and axon guidance, respectively. GSEA and WGCNA unveiled cellular processes such as "Metabolism of RNA" and "Cell Cycle”.ConclusionsThis study uncovers a shift in gene expression of CC subjects.IGHG3andIGHV3-49gene shut-offs spotlight the importance of neutralizing antibodies against chikungunya virus in the progression to chronic disease. Human diseases associations highlight connections to rheumatoid arthritis, nervous and cardiac systems. GSEA and WGCNA bounce the hypotheses of a persistent viral reservoir or an increased susceptibility to RNA viral pathogens with new onset infections. Together, our findings might offer potential targets for therapeutic options aimed at alleviating chronic chikungunya.
araCNA: Somatic copy number profiling using long-range sequence models
Authors: Visscher Ellen , Yau Christopher 
Published: January 2025

AbstractSomatic copy number alterations (CNAs) are hallmarks of cancer. Current algorithms that call CNAs from whole genome sequenced (WGS) data have not exploited deep learning methods owing to computational scaling limitations. Here, we present a novel deep-learning approach, araCNA, trained only on simulated data that can accurately predict CNAs in real WGS cancer genomes. araCNA uses novel transformer alternatives (e.g Mamba) to handle genomic-scale sequence lengths (∼1M) and learn long-range interactions. Results are extremely accurate on simulated data, and this zero-shot approach is on par with existing methods when applied to 50 WGS samples from the cancer genome atlas. Notably, our approach requires only a tumour sample and not a matched normal sample, has fewer markers of overfitting, and performs inference in only a few minutes. araCNA demonstrates how domain knowledge can be used to simulate training sets that harness the power of modern machine learning in biological applications.