bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subepicardial adipose genes contribute to the deterioration of heart failure preserved ejection fraction
Authors: Zhang Ruiying , Wang Man , Lang Yuheng , Zhang Jiaqi , Wang Yuchao , Zheng Han , Zheng Yue , Zhou Bingyang 
Published: February 2025

BackgroundThe mortality of patients with acute myocardial infarction (MI) raised rapidly in last decade and obesity are becoming the major cause to CAD progression, thus inducing heart failure preserved ejection fraction (HFpEF). However, why visceral adipocytes show different effects on healthy and ageing cardiomyocytes is less known.MethodsGSE251971 was downloaded and Venn diagram between visceral adipocyte genes genes and DEGs was performed to obtain visceral adipocyte-associated DEGs in heart failure. Protein-protein interaction (PPI) network was constructed to obtain the hub genes utilizing the Cytoscape plugin Cytohubba. The hub genes and their interactions were analyzed using NetworkAnalyst 3.0 and for validation, the hub genes expressions were analyzed using Single-cell sequencing data, cell lines and human sub-epicardial tissues and blood samples.ResultsUsing Venn diagram, 71 visceral adipocyte-associated DEGs were identified. Nine hub genes were obtained, including OGN, SELL, FOS, NKG7, LOX, HBB, CXCL9, CP and ALOX5. Single-cell sequencing demonstrated all hub genes were highly expressed in human hypertrophic cardiomyopathy and ischemic cardiomyopathy patients with end-stage heart failure. The related OGN, FOS, NKG7 and ALOX5 mRNA expressions were significantly highly expressed in sub-epicardial tissues in HFpEF patients. AUCs of OGN, FOS and ALOX5 were 0.902, 0.795 and 0.730, and the AUC of joint ROC of OGN, FOS and ALOX5 was 0.946. Additionally, FOS, ALOX5 and OGN expressions were increased at follow up 1 year recurrence, while decreased at follow up 2 year recurrence. Mechanically, FOS and ALOX5 were highly expressed in macrophages under hypoxia, while OGN was highly expressed in fibroblasts under hypoxia. SASPs, including IL1α, IL1β, IL6 and TNFα, decreased in hypoxic macrophages after FOS and ALOX5 knockdown or both. Also, SASPs decreased in hypoxic fibroblasts after OGN knockdown. These results suggested that FOS, ALOX5 and OGN may affect cell senescence after hypoxia, thus inducing myocardial infarction and HFpEF progression.ConclusionThe screened hub genes, including OGN, FOS and ALOX5, were validated using single-cell sequencing data, cell lines and human samples, which can be therapeutic targets for the treatment to cell senescence under hypoxia and prediction to heart failure progression to HFpEF.
Transduction of hematopoietic stem and progenitor cells by an MECP2 lentiviral vector improves Rett syndrome phenotypes
Authors: Anderson Joseph S. , Silverman Jill L. , Lodigiani Alyse L. , Barbaduomo Camilla M. , Beegle Julie R. 
Published: February 2025

IntroductionRett Syndrome is a genetic neurodevelopmental disorder caused by decreased levels of MeCP2. Due to mutations in the MECP2 gene, insufficient MeCP2 protein levels lead to clinical phenotypes including the loss of normal movement, decreased communication, seizures, sleep disorders, and breathing problems. Currently there is no cure for Rett Syndrome and the only means to help patients is palliative care directed to their specific symptoms. Therefore, novel therapies need to be developed to alleviate disease phenotypes by restoring normal MECP2 expression. An autologous hematopoietic stem cell and gene therapy approach for Rett syndrome may offer a benefit to affected patients by systemic delivery of functional MeCP2, including to affected neurons in the central nervous system.MethodsIn our current experiments, we evaluated the therapeutic effect of MECP2 lentiviral vector transduced human CD34+ hematopoietic stem and progenitor cells after transplantation into an immunodeficient mouse model of Rett syndrome.ResultsWe observed improvement of Rett syndrome-related phenotypes including the reversion toward normal motor abilities in an open field assay for total activity, horizontal activity, and vertical rearing activity, and an increased latency to fall in a rotarod assay. An increased level of MeCP2 protein was also observed in the brain tissue of transplanted mice.DiscussionBy providing functional MeCP2 to affected cells, our results highlight the ability of this strategy to improve Rett syndrome phenotypes. These proof-of-concept studies demonstrate the potential use of a stem cell gene therapy approach as a novel treatment for Rett syndrome patients.
Outcomes of transsphenoidal surgery for pituitary adenomas in Spain: a retrospective multicenter study
Authors: Paja Miguel , Soto Alfonso , Hanzu Felicia A. , Guerrero-Pérez Fernando , Cámara Rosa , Moure Dolores , Gálvez Ángeles , Simó-Servat Andreu , Villar-Taibo Rocío , Calatayud María , Vicente Almudena , Recio-Córdova Jose M. , Serra Guillermo , Martín Rojas-Marcos Patricia , Parra-Ramírez Paola , Araujo-Castro Marta , Librizzi Soledad , Irigaray Ana , Ollero Dolores , Aznar Silvia , Muñoz Fernando , Aulinas Anna , González-Fernández Laura , García-Centeno Rogelio , Egaña Nerea , González-Vidal Tomás , Menéndez Edelmiro , Delgado Ana M. , Abarca Javier , Sottile Johana , Picó Antonio M. , Novo Cristina , Ortiz Isabel , Tenorio Carmen , de León Ricardo , de Pablos-Velasco Pedro , Crespo Cristina , Peñalver David , Díaz-Soto Gonzalo , Puig-Domingo Manel , Biagetti Betina 
Published: February 2025

BackgroundThe outcomes of transsphenoidal surgery (TSS) for pituitary adenoma (PA) depend on many factors, including the availability of an expert team and the volume of surgeries performed. Data on the outcomes of TSS for PA are scarce in our country. TESSPAIN evaluates TSS outcomes in Spanish centers to assess the influence of surgical volume and specialized neurosurgical teams on success and complication rates.MethodsA retrospective, nationwide, study of Spanish centers performing TSS between January 2018 and December 2022. Centers were classified as high volume (HV) [n=11, defined as centers with recognized expertise in Spain or those performing more than 25 TSS/year] or non-HV. Data collection included surgical success rates, complications, and pituitary adenoma resectability (R-PA). Additional analyses evaluated the impact of dedicated neurosurgical teams (DNT) within HV centers.ResultsA total of 2815 TSS from 29 Spanish centers were included (1421 NSPA, 436 GH-secreting, 323 Cushing’s disease, 127 PRL-secreting and 25 TSH-secreting PA). The overall success rate was 50.5%, 76.8% for R-PA. HV centers had a higher overall success rate (53.1 vs. 47.7%; p=0.03). Better TSS outcomes for NSPA accounted for this difference. The overall TSS complication rate was 22.1%, which was higher for NSPA than for SPA (25.0 vs. 17.7%). The overall complication rate of TSS for PA was significantly higher in non-HV centers than in HV centers (24 vs 20.4.0; p &lt;0.01). Centers with a DNT showed a trend to higher success rate in R-PA, while having a lower overall incidence of complications in TSS for PA than HV centers without a DNT (18.5 vs. 23.0; p=0.058), mainly reducing the rate of permanent ADH deficiency in all TSS for PA (2.7 vs. 8.4%; p&lt;0.001).ConclusionHigher surgical volume and DNT are associated with improved TSS outcomes for PA in Spain. Our results support the recommendation of concentration of pituitary surgery in a reduced number of centers of expertise in our country in order to improve the success rate and reduce complications, mainly postoperative ADH deficiency.
Infections and antibiotic use in early childhood have limited importance in developing manifest type 1 diabetes – The ABIS cohort study
Authors: Bélteky Malin , Wahlberg Jeanette , Ludvigsson Johnny 
Published: February 2025

AimsTo investigate the effect of early childhood infections and antibiotic use on the risk of type 1 diabetes in a general population cohort.Research Design and MethodsThe All Babies In Southeast Sweden (ABIS) cohort followed 16 428 children from birth. Questionnaires collected at 1 year (n=11 093), 3 years (n=8 890) and 5 years of age (n=7 445) included data on infections and antibiotic use and were validated against national registers. After a mean follow-up of 25 years, 168 individuals have been diagnosed with type 1 diabetes (1.0% of the original cohort, aged 1-24.5 years).ResultsThere were few significant differences in type or frequency of early childhood infections or antibiotic use between cases with type 1 diabetes and the reference group (remaining individuals who did not develop type 1 diabetes) after adjusting for sex, heredity and socioeconomic status. A small number of type 1 diabetes children (4.8% compared to 0.8% of the reference group) reported six or more episodes of gastroenteritis in the 1-3-year age group, resulting in an adjusted odds ratio (aOR) of 8.21; 95% CI 2.70-25.01, p&lt;0.001. Cases of type 1 diabetes with an increased genetic risk (n=91) reported fewer episodes of the common cold between 1 and 3 years of age compared to the reference group (aOR 0.27; 0.13-0.58, p&lt;0.001). Individuals with type 1 diabetes without risk-associated HLA alleles (n=14) reported a higher frequency of pneumonia in the 1–3- and 3–5-year age group (aOR 26.08; 6.29-108.17, p&lt;0.001 and aOR 35.63; 4.10-309.96, p=0.001 respectively), and had more viral and total infections registered in the National Patient Register from 0-5 years (aOR 5.72; 1.59-20.57, p=0.008 and aOR 18.71; 1.95-179.55, p=0.01).ConclusionsChildhood infections could increase the risk of developing type 1 diabetes in a small group of individuals without risk-associated HLA alleles, but this was not seen in the majority with HLA-risk. More research is required for this overlooked population, including screening and prevention trials. The association to frequent gastrointestinal infections in the first years of life needs to be reproduced in other studies to be confirmed.
Effect of plant spacing on the soil properties and fertility of Pinus sylvestris var. mongolica plantations in sandy land of the agro-pastoral ecotone in northern China
Authors: Guo Xinyu , Yang Guang , Ma Yunxia , Qiao Shi , Chen Haoyu , Liu Feng , Ma Shuai 
Published: February 2025

Duolun County in Inner Mongolia, a typical agro-pastoral ecotone, serves as an important ecological barrier in northern China. To combat windblown sand and land degradation, the government has established extensive P. sylvestris var. mongolica Litv. plantations. This study investigated the effects of three afforestation modes (2 m × 6 m, 2 m × 3 m, and 1 m × 1 m), which were used as treatments, and unafforested bare sandy land as a control, on soil physicochemical properties and soil fertility. The results showed that row spacing significantly affected soil characteristics and soil fertility. With an increase in plant row spacing, the content of coarse particles decreased, while fine particle content, soil water and nutrient levels, and soil porosity increased. Additionally, the bulk density of the soil decreased, particularly in the topsoil. However, planting P. sylvestris var. mongolica in sandy land increased the soil’s electrical conductivity, which declined with wider spacing. Soil fertility of different types of plantation forests was evaluated using the soil quality index (SQI) and grey relation analysis (GRA) combined with the minimum dataset (MDS), and the results showed that: 2 m × 6 m &gt; 2 m × 3 m &gt; 1 m × 1 m &gt; bare sandy land. The results of the two evaluation systems were consistent and their TDS (total dataset) and the MDS in the two evaluation systems were significantly positively correlated (SQI: P &lt; 0.05, R2 = 0.9384). GRA: P &lt; 0.05, R2 = 0.8929). Compared with bare sand, the soil bulk density and pH of 2 m × 6 m plantation was 13.72% and 4.02% lower; the soil water content and total porosity were 49.75% and 27.88% higher; the soil organic matter, total N, P, and K were 250.99%, 136%, 100%, and 19.53% higher; the available N, P, and K were 29.95%, 94.3%, and 12.71% higher; and the clay, silt and very fine sand contents were 242.55%, 343.1%, and 17.21% higher, respectively. These findings indicate that the development of soil characteristics and fertility accumulation are not ideal when the planting density is larger, among the above three afforestation modes, 2 m × 6 m plantation forests can better improve the soil characteristics and fertility quality of sandy soils.
LINC00461 SNPs rs933647 and rs201864123 modify the risk of adenoid hypertrophy susceptibility for children in South China
Authors: Hou Chao , Luo Xilian , Wan Xin , Chen Kaining , Xian Zhongren , Xu Kaixiong , Zeng Yingjia , Wang Chenlu , Yang Wan , Zheng Zilin , Lin Yueling , Lu Zhaojin , Chen Yanqiu , Che Di , Gu Xiaoqiong 
Published: February 2025

BackgroundAdenoidal hypertrophy (AH) is commonly observed in childhood and closely linked to obstructive sleep apnea (OSA). Despite the high prevalence of AH, its pathophysiological mechanisms remain incompletely understood. We attempt to explore this issue from a genetic perspective. Elevated levels of LINC00461 have been identified in OSA tissues. We aimed to explore the relationship between susceptibility to adenoid hypertrophy and LINC00461 gene polymorphisms.MethodsWe genotyped the LINC00461 single nucleotide polymorphisms (SNPs) rs933647 and rs201864123 in 546 AH patients and 574 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between the SNPs and AH risk. The SIPI (Susceptible-Infected-Protected-Infected) method was utilized to analyze SNP-SNP interactions between rs933647 and rs201864123.ResultsOur study found that the rs933647 GA polymorphism was associated with an increased risk of AH. Similarly, the T allele of SNP rs201864123 increased AH risk in southern Chinese children. Furthermore, SIPI analysis demonstrated an interaction between these SNPs associated with adenoid hypertrophy risk.ConclusionThe LINC00461 rs933647 GA genotype and rs201864123 T variant may contribute to the susceptibility of AH in the child population of China.
Impaired immune reconstitution in HIV infection: the role of CD4+ T-cell-associated NKG2D ligands, CD4+ T-cell subsets imbalance, and immune function deficiency
Authors: Xu Qianqian , Zhang Qiuyue , Xu Peng , Zhang Tong , Wu Hao , Zhang Xin , Moog Christiane , Su Bin 
Published: February 2025

ObjectiveThe role of natural killer (NK) cells, which mediate innate immunity, in the immune reconstitution of people living with HIV (PLWH) remains unclear. Our previous research indicated that early activation of CD56dimCD16dim/- NK cells plays an important role in the recovery of CD4+ T cells in immunological non-responders (INRs) after ART. This study mainly focuses on the profiles of cell receptors and their relative ligands for NK cells and CD4+ T cells exhibited on INRs and immunological responders (IRs) in order to analyze the impact of differential immune status on immune reconstitution in PLWH receiving ART.MethodsThis study included 66 PLWH who had been on ART for 4 years, comprising 32 INRs and 34 IRs. Using flow cytometry, we examined the expression of cell receptors and ligands for NK cells and CD4+ T cells in PBMCs, as well as the differentiation of CD4+ T cells.ResultsThe expression of NKG2D ligands, including MICA/B and ULBP2-5, on CD4+ T cells in INRs is elevated prior to ART. Further research found that the expression of CD95 on MICA/B+CD4+ T cells and ULBP2-5+CD4+ T cells was higher in INRs before ART compared to IRs. Simultaneously, the percentages of death receptor CD95 expression on MICA/B+CD4+ T cells and on ULBP2-5+CD4+ T cells before ART were negatively correlated with CD4+ T-cell counts and ΔCD4. Among the CD4+ T-cell subsets, an imbalance persists in the CD4+ Tcm and CD4+ Temra subsets in both INRs and IRs, before or after ART. CD4+ T cells exhibit elevated levels of activation, proliferation, exhaustion, and apoptosis prior to ART initiation. However, CD4+ T-cell activation and proliferation normalize post-ART, while apoptosis and exhaustion levels remain significantly elevated. Regardless of ART, the anti-apoptotic capacity of CD4+ T cells in INRs is still lower than that of IRs and healthy controls (HCs). Before ART, the frequency of CD31 expression on naive CD4+ T cells in INRs is lower than that in IRs and HCs. Following ART, the amounts of CD31+ Tn from CD4+ T cells remain impaired in both INRs and IRs compared to HCs.ConclusionThe upregulation of related ligands for the NKG2D receptor on CD4+ T cells in INRs is associated with increased susceptibility of CD4+ T cells to NK cell-mediated killing. CD95 may plays an important role in poor recovery of CD4+ T cells co-expressing NKG2D-related ligands. The imbalance in CD4+ Tcm and CD4+ Temra subset homeostasis and impaired CD31 expression on naive CD4+ T cells in INRs are associated with poor immune reconstitution outcomes.
Two rare mutations in homozygosity synergize to silence TREX1 in Aicardi-Goutières syndrome
Authors: Rubin Tamar , Bernier Stéphane , Hoon Lim Lily Siok , Salman Michael S. , Leung Edward , Mhanni Aziz , Marles Sandra , Greenberg Cheryl , Perez Anna , Sun Yichun , Angers Isabelle , Vinh Donald C. , Roussel Lucie 
Published: February 2025

BackgroundAicardi-Goutières syndrome (AGS) is a rare monogenic type I interferonopathy characterized by dysregulated inflammation and tissue damage that primarily affects the central nervous system. AGS is genetically diverse, with pathogenic variants across multiple genes, including TREX1, which drives excessive type I interferon (IFN) production.ObjectiveThis study investigated the genetic and molecular mechanisms underlying AGS in a family of two affected children, focusing on the role of TREX1 variants in protein expression and dysregulation of the interferon pathway.MethodsGenomic sequencing data were used to identify TREX1 variants in the affected children. Functional assays in patient-derived lymphoblastoid cells (LCLs) and cell line models were used to evaluate TREX1 expression and activation of the cGAS-STING pathway.ResultsTwo homozygous TREX1 variants were identified in two affected children. Functional analyses showed that both variants are required to mirror the near-absent protein levels observed in LCL and to cause excessive activation of IRF3 in cGAS-STING pathway in response to cytosolic DNA stimulation.ConclusionTo our knowledge, our findings demonstrate, for the first time, the compound effect of two rare homozygous variants account for AGS. This also reiterates the importance of molecular and functional assessments of genomic variants identified by sequencing.
Research status and hotspots of hypothermia and human diseases: a bibliometric analysis
Authors: Li Wei-Xuan , Han Na-Na , Ji Qian-Yu , Dong Xue-Tong , Lu Chao-Long , Wang Song-Jun 
Published: February 2025

BackgroundHypothermia has been strongly associated with human diseases; it affects life safety. Therapeutic hypothermia generates good results for certain diseases, without serious complications. In clinical practice, research on the treatment of hypothermia and severe hypothermia-induced diseases have achieved fruitful results. However, no bibliometric analysis has been conducted. In this study, we explored the research status and hotspots of hypothermia and human diseases by conducting a bibliometric analysis.MethodsArticles on hypothermia and human diseases were collected from the Web of Science Core Collection. From 1 January 2005 to 31 August 2024, A total of 1,553 articles were retrieved. After excluding irrelevant articles, 706 articles were analyzed.ResultsThe United States and China published the maximum number of research articles on hypothermia and human diseases. Among institutes, Johns Hopkins University and Harvard University published the maximum number of research articles. Scholars, including Ishikawa Takaki, Maeda Hitoshi, and Michiue Tomomi, constituted a highly productive group of authors. The journal, Therapeutic Hypothermia and Temperature Management published the highest number of articles, and Nature Reviews Drug Discovery had the highest impact factor. Cluster analysis of all keywords primarily focused on the following research directions: (i) hypothermia-related injury, (ii) hypothermia treatment, and (iii) the mechanism underlying hypothermia.ConclusionThis bibliometric study comprehensively summarizes the impact of hypothermia on human diseases and the research overview of the use of moderate hypothermia for treatment. This paper clarifies the research status, frontiers and hotspots, and also puts forward new insights for hypothermia research: strengthen research cooperation to improve the depth of research, increase support for areas with insufficient medical conditions; in the future, single-cell multiomics technology will be used to explore cell types sensitive to different low temperatures and corresponding molecular mechanisms; non-coding RNA regulation will be used to achieve precision treatment of hypothermia diseases; Organoids will be an important object of hypothermia research. These research insights can provide reference for researchers.
Global burden and trends of viral hepatitis among women of childbearing age from 1990 to 2021
Authors: Yang Shaojie , Zhong Lin , Huang Lu , Lin Shengyuan , Li Yubin 
Published: February 2025

BackgroundThe burden and trends of viral hepatitis in women of childbearing age (WCBA) are rarely quantified. This study aimed to assess the global, regional, and national incidence and prevalence rates among WCBA from 1990 to 2021.MethodsFrom 1990 to 2021, we retrieved data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 on the incidence and prevalence of hepatitis A, B, C, and E for WCBA. Estimated annual percent change in the age-standardized incidence and prevalence rates were calculated to quantify the temporal trend.ResultsIn 2021, it was estimated that there were 42,266,708 new cases and 109,107,759 prevalent cases of viral hepatitis among WCBA globally. AHA had the highest incidence rate, while CHB had the highest prevalence rate globally. Notably, AHA and AHE were emerging in low-endemic regions. Generally, the burden of viral hepatitis decreased with higher SDI levels, except for AHA. Between 1990 and 2021, the global age-standardized incidence rate for viral hepatitis among WCBA decreased annually by −1.11% for acute hepatitis A (AHA), −1.24% for AHB, and −0.18% for AHC, −0.34% for AHE, with more significant reductions observed for chronic hepatitis B (CHB) and CHC at −1.33% and −0.29%, respectively. Furthermore, the burden of viral hepatitis continued to rise in lower-SDI regions, and the proportion of younger individuals affected increased as SDI decreased.ConclusionsAlthough the incidence and prevalence rates of viral hepatitis have decreased in recent decades, notable regional and demographic disparities remain. These concerning trends are especially pronounced in low-SDI regions, making it essential to tackle the disparities in healthcare resource allocation for WCBA across areas with varying SDI levels.