bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between Chinese visceral adiposity index and cardiometabolic multimorbidity among Chinese middle-aged and older adults: a national cohort study
Authors: Ye Xiaomei , Zhang Guangru , Han Chenyu , Wang Ping , Lu Jiaping , Zhang Min 
Published: March 2024

ObjectiveThis study aimed to explore the association between the Chinese visceral adiposity index (CVAI) and cardiometabolic multimorbidity in middle-aged and older Chinese adults.MethodsThe data used in this study were obtained from a national cohort, the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018 wave). The CVAI was measured using previously validated biomarker estimation formulas, which included sex, age, body mass index, waist circumference, triglycerides, and high-density lipoprotein cholesterol. The presence of two or more of these cardiometabolic diseases (diabetes, heart disease, and stroke) is considered as cardiometabolic multimorbidity. We used Cox proportional hazard regression models to examine the association between CVAI and cardiometabolic multimorbidity, adjusting for a set of covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to show the strength of the associations. We also conducted a subgroup analysis between age and sex, as well as two sensitivity analyses. Receiver operator characteristic curves (ROC) were used to test the predictive capabilities and cutoff value of the CVAI for cardiometabolic multimorbidity.ResultsA total of 9028 participants were included in the final analysis, with a mean age of 59.3 years (standard deviation: 9.3) and women accounting for 53.7% of the sample population. In the fully-adjusted model, compared with participants in the Q1 of CVAI, the Q3 (HR = 2.203, 95% CI = 1.039 – 3.774) and Q4 of CVAI (HR = 3.547, 95% CI = 2.100 – 5.992) were associated with an increased risk of cardiometabolic multimorbidity. There was no evidence of an interaction between the CVAI quartiles and sex or age in association with cardiometabolic multimorbidity (P &gt;0.05). The results of both sensitivity analyses suggested that the association between CVAI and cardiometabolic multimorbidity was robust. In addition, the area under ROC and ideal cutoff value for CVAI prediction of cardiometabolic multimorbidity were 0.685 (95% CI = 0.649-0.722) and 121.388.ConclusionThe CVAI is a valid biomarker with good predictive capability for cardiometabolic multimorbidity and can be used by primary healthcare organizations in the future for early warning, prevention, and intervention with regard to cardiometabolic multimorbidity.
Emergency materials management of petrochemical accidents considering the randomness and uncertainty base on stochastic programming
Authors: Jiang Wei , Yang Yuxiang , Hu Ansen , Liu Yulin , Hong Siyan 
Published: March 2024

Petroleum is the pillar industry of the national economy, but safety accidents are frequent all over the world. The government attaches more importance to the safety production management of enterprises to reduce the occurrence of accidents that infringe on personal safety. The management of emergency supplies, which can effectively respond to the occurrence of safety production accidents, is a key measure for handling emergency accidents. Rapid response to accidents means reducing accident rescue costs and protecting personal and property safety. This paper proposes a material stochastic model with the randomness of accident demand for materials. The enterprise and the government can obtain the material management scheme and the quantitative evaluation standard of accident preventive measures from the model results respectively. The model covers as many accident scenarios as possible through multi-scenario modeling to reduce the impact of accident uncertainty. Finally, the feasibility is proved by an example of a petroleum enterprise in Zhoushan City. When the accident demand fluctuates randomly between 80% and 120%, the model proposes a material management scheme that the dispatching time of materials and the cost in rescue work do not exceed 31.33 min and 11.68 million CNY respectively. With the assistance of the model, the enterprise saves the cost of safe production and improves the efficiency of rescue. The government has strengthened the supervision and evaluation of enterprise safety production management. Finally, the mission of protecting the property and life safety of the people will be realized.
Experimental study of ultra-low IFT foam flooding for low permeability reservoirs
Authors: Lang Liyuan , Zhao Shuang , Liu Lu 
Published: March 2024

Foam flooding is an effective oil displacement technique to improve fluid sweep efficiency and increase oil recovery. The objective of this paper is to investigate the applicability of ultra-low IFT foam flooding for low permeability oil recovery under the conditions of WX reservoir block in Tuha oilfield (84°C, 86,072 mg/L). A modified amphoteric hydroxy sulfobetaine surfactant (Cn-HSB) was formulated as a foaming agent based on the principle of compatibility with crude oil that could achieve the ultra-low interfacial tension (IFT) and strong foamability simultaneously. This is shown to reduce the oil/water dynamic IFT (DIFT) to an ultra-low value of the order of 10−5 mN/m (0.10wt%), as well as produce a foam volume and half-life of 448 mL and 2567 s, respectively. In addition, results of IFT and foam quality tests indicate that the modified Cn-HSB has good thermal stability and excellent salinity-resistance. Moreover, the ultra-low IFT foam flooding has an ideal injectivity and oil displacement efficiency in low permeability porous media that can mobilize the trapped oil in k = 1.50 × 10−3μm2 with a threshold pressure gradient of 0.115 MPa/m. This improves oil displacement efficiency about 15%OOIP. Fundamental knowledge gained from this research gives insight into the application of ultra-low IFT foam flooding in low-permeability reservoirs under a combination of specific reservoir conditions.
The prognostic significance of LncRNA BLACAT1 overexpression in various tumors: a meta-analysis
Authors: Yan Xuefen , Zhang Nana , Wang Gang , Wang Jiaheng 
Published: March 2024

Objective:Recent studies have revealed increasing evidence that the long non-coding RNA bladder cancer associated transcript 1 (LncRNA BLACAT1) plays an essential role in the emergence of different malignancies. This meta-analysis aimed to evaluate the prognostic significance of LncRNA BLACAT1 in various cancers.Methods:Six electronic databases (PubMed, Embase, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese WanFang database) were comprehensively searched for relevant studies. The analysis of overall survival (OS) and clinicopathological characteristics was conducted.Results:Nineteen studies with 1,559 patients were eventually eligible to be included in this meta-analysis. High expression level of LncRNA BLACAT1 was identified to be linked with shorter OS (HR: 2.02, 95% CI: 1.66–2.46, p &lt; 0.001) and PFS (HR: 2.424, 95% CI: 1.827–3.020, p &lt; 0.001) in cancer patients as opposed to low expression levels. Subgroup analysis showed that analysis model (multivariate or univariate), cut-off value (mean or median), sample size (more or fewer than 100), and cancer type had little effect on OS in multiple tumors. Moreover, high LncRNA BLACAT1 expression was associated with positive lymph node metastasis (HR: 2.29, 95% CI: 1.66–3.16, p &lt; 0.00001), advanced clinical stage (HR: 2.29, 95% CI: 1.65–3.19, p &lt; 0.00001) and worse differentiation status (HR: 0.58, 95% CI: 0.37–0.92, p = 0.02), compared to low LncRNA BLACAT1 expression.Conclusion:The findings highlight that high LncRNA BLACAT1 expression might be detrimental and induce a worse prognosis for cancer patients.
Functional analysis of RRAS2 pathogenic variants with a Noonan-like phenotype
Authors: Iida Takaya , Igarashi Arisa , Fukunaga Kae , Aoki Taiga , Hidai Tomomi , Yanagi Kumiko , Yamamori Masahiko , Satou Kazuhito , Go Hayato , Kosho Tomoki , Maki Ryuto , Suzuki Takashi , Nitta Yohei , Sugie Atsushi , Asaoka Yoichi , Furutani-Seiki Makoto , Kimura Tetsuaki , Matsubara Yoichi , Kaname Tadashi 
Published: March 2024

Introduction: RRAS2, a member of the R-Ras subfamily of Ras-like low-molecular-weight GTPases, is considered to regulate cell proliferation and differentiation via the RAS/MAPK signaling pathway. Seven RRAS2 pathogenic variants have been reported in patients with Noonan syndrome; however, few functional analyses have been conducted. Herein, we report two patients who presented with a Noonan-like phenotype with recurrent and novel RRAS2 pathogenic variants (p.Gly23Val and p.Gly24Glu, respectively) and the results of their functional analysis.Materials and methods: Wild-type (WT) and mutant RRAS2 genes were transiently expressed in Human Embryonic Kidney293 cells. Expression of RRAS2 and phosphorylation of ERK1/2 were confirmed by Western blotting, and the RAS signaling pathway activity was measured using a reporter assay system with the serum response element-luciferase construct. WT and p.Gly23Val RRAS2 were expressed in Drosophila eye using the glass multiple reporter-Gal4 driver. Mutant mRNA microinjection into zebrafish embryos was performed, and the embryo jaws were observed.Results: No obvious differences in the expression of proteins WT, p.Gly23Val, and p.Gly24Glu were observed. The luciferase reporter assay showed that the activity of p.Gly23Val was 2.45 ± 0.95-fold higher than WT, and p.Gly24Glu was 3.06 ± 1.35-fold higher than WT. For transgenic flies, the p.Gly23Val expression resulted in no adults flies emerging, indicating lethality. For mutant mRNA-injected zebrafish embryos, an oval shape and delayed jaw development were observed compared with WT mRNA-injected embryos. These indicated hyperactivity of the RAS signaling pathway.Discussion: Recurrent and novel RRAS2 variants that we reported showed increased in vitro or in vivo RAS signaling pathway activity because of gain-of-function RRAS2 variants. Clinical features are similar to those previously reported, suggesting that RRAS2 gain-of-function variants cause this disease in patients.
The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes
Authors: Martínez-Gómez Laura Edith , Martinez-Armenta Carlos , Tusie-Luna Teresa , Vázquez-Cárdenas Paola , Vidal-Vázquez Rosa P. , Ramírez-Hinojosa Juan P. , Gómez-Martín Diana , Vargas-Alarcón Gilberto , Posadas-Sánchez Rosalinda , Fragoso José Manuel , de la Peña Aurora , Rodríguez-Pérez José Manuel , Mata-Miranda Mónica M. , Vázquez-Zapién Gustavo J. , Martínez-Cuazitl Adriana , Martínez-Ruiz Felipe de J. , Zayago-Angeles Dulce M. , Ramos-Tavera Luis , Méndez-Aguilera Alberto , Camacho-Rea María del C. , Ordoñez-Sánchez María L. , Segura-Kato Yayoi , Suarez-Ahedo Carlos , Olea-Torres Jessel , Herrera-López Brígida , Pineda Carlos , Martínez-Nava Gabriela A. , López-Reyes Alberto 
Published: March 2024

IntroductionSerine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes.MethodsTo evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity).ResultsAccording to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02).DiscussionOur data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.
Effect of smoking-related features and 731 immune cell phenotypes on esophageal cancer: a two-sample and mediated Mendelian randomized study
Authors: Yang Kaiqi , Li Shaoya , Ding Yuchen , Meng Xiaodie , Zhang Changhao , Sun Xiujing 
Published: March 2024

IntroductionNumerous observational studies have indicated that smoking is a substantial risk factor for esophageal cancer. However, there is a shortage of research that delves into the specific causal relationship and potential mediators between the two. Our study aims to validate the correlation between smoking-related traits and esophageal cancer while exploring the possible mediating effects of immune factors.MethodsInitially, we conducted bidirectional univariate Mendelian Randomization (MR) analyses to forecast the causal effects linking smoking-related traits and esophageal cancer. Subsequently, we employed a two-step MR analysis to scrutinize immune cell phenotypes that could mediate these effects. Finally, the coefficient product method was employed to determine the precise mediating impact. Additionally, we have refined our sensitivity analysis to ensure the reliability of the outcomes.ResultsAfter analysis, Smoking status: Never had a significant negative association with the incidence of esophageal cancer (inverse-variance weighted (IVW) method, p=1.82e-05, OR=0.10, 95%CI=0.04~0.29). Ever smoked (IVW, p=1.49e-02, OR=4.31, 95%CI=1.33~13.94) and Current tobacco smoking (IVW, p=1.49e-02, OR=4.31, 95%CI=1.33~13.94) showed the promoting effect on the pathogenesis of esophageal cancer. Through further examination, researchers discovered 21 immune cell phenotypes that have a causal relationship with esophageal cancer. After careful screening, two immune cell phenotypes were found to have potential mediating effects. In particular, it was observed that in the case of the preventive effect of Smoking status: Never on esophageal cancer, the absolute count of CD62L plasmacytoid dendritic cells mediated a reduction of 4.21%, while the mediating effect of CD27 in CD20-CD38-B cells was -4.12%. In addition, sensitivity analyses did not reveal significant heterogeneity or level pleiotropy.ConclusionThe study provides new evidence for the causal relationship between smoking-related features and esophageal cancer and proposes immune factors with potential mediating effects. However, this finding needs to be further demonstrated by more extensive clinical studies.
A generalizable and easy-to-use COVID-19 stratification model for the next pandemic via immune-phenotyping and machine learning
Authors: He Xinlei , Cui Xiao , Zhao Zhiling , Wu Rui , Zhang Qiang , Xue Lei , Zhang Hua , Ge Qinggang , Leng Yuxin 
Published: March 2024

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has affected billions of people worldwide, and the lessons learned need to be concluded to get better prepared for the next pandemic. Early identification of high-risk patients is important for appropriate treatment and distribution of medical resources. A generalizable and easy-to-use COVID-19 severity stratification model is vital and may provide references for clinicians.MethodsThree COVID-19 cohorts (one discovery cohort and two validation cohorts) were included. Longitudinal peripheral blood mononuclear cells were collected from the discovery cohort (n = 39, mild = 15, critical = 24). The immune characteristics of COVID-19 and critical COVID-19 were analyzed by comparison with those of healthy volunteers (n = 16) and patients with mild COVID-19 using mass cytometry by time of flight (CyTOF). Subsequently, machine learning models were developed based on immune signatures and the most valuable laboratory parameters that performed well in distinguishing mild from critical cases. Finally, single-cell RNA sequencing data from a published study (n = 43) and electronic health records from a prospective cohort study (n = 840) were used to verify the role of crucial clinical laboratory and immune signature parameters in the stratification of COVID-19 severity.ResultsPatients with COVID-19 were determined with disturbed glucose and tryptophan metabolism in two major innate immune clusters. Critical patients were further characterized by significant depletion of classical dendritic cells (cDCs), regulatory T cells (Tregs), and CD4+ central memory T cells (Tcm), along with increased systemic interleukin-6 (IL-6), interleukin-12 (IL-12), and lactate dehydrogenase (LDH). The machine learning models based on the level of cDCs and LDH showed great potential for predicting critical cases. The model performances in severity stratification were validated in two cohorts (AUC = 0.77 and 0.88, respectively) infected with different strains in different periods. The reference limits of cDCs and LDH as biomarkers for predicting critical COVID-19 were 1.2% and 270.5 U/L, respectively.ConclusionOverall, we developed and validated a generalizable and easy-to-use COVID-19 severity stratification model using machine learning algorithms. The level of cDCs and LDH will assist clinicians in making quick decisions during future pandemics.
HLA molecular mismatches and induced donor-specific tolerance in combined living donor kidney and hematopoietic stem cell transplantation
Authors: Senev Aleksandar , Tambur Anat R. , Kosmoliaptsis Vasilis , Copley Hannah Charlotte , García-Sánchez Cynthia , Usenko Crystal , Ildstad Suzanne T. , Leventhal Joseph R. 
Published: March 2024

IntroductionWe investigated the potential role of HLA molecular mismatches (MM) in achieving stable chimerism, allowing for donor-specific tolerance in patients undergoing combined living donor kidney and hematopoietic stem cell transplantation (HSCT).MethodsAll patients with available DNA samples (N=32) who participated in a phase 2 clinical trial (NCT00498160) where they received an HLA mismatched co-transplantation of living donor kidney and facilitating cell-enriched HSCT were included in this study. High-resolution HLA genotyping data were used to calculate HLA amino acid mismatches (AAMM), Eplet MM, three-dimensional electrostatic mismatch scores (EMS-3D), PIRCHE scores, HLA-DPB1 T-cell epitope group MM, HLA-B leader sequence MM, and KIR ligands MM between the donor and recipient in both directions. HLA MM were analyzed to test for correlation with the development of chimerism, graft vs. host disease (GvHD), de novo DSA, and graft rejection.ResultsFollow-up time of this cohort was 6–13.5 years. Of the 32 patients, 26 developed high-level donor or mixed stable chimerism, followed by complete withdrawal of immunosuppression (IS) in 25 patients. The remaining six of the 32 patients had transient chimerism or no engraftment and were maintained on IS (On-IS). In host versus graft direction, a trend toward higher median number of HLA-DRB1 MM scores was seen in patients On-IS compared to patients with high-level donor/mixed chimerism, using any of the HLA MM modalities; however, initial statistical significance was observed only for the EMS-3D score (0.45 [IQR, 0.30–0.61] vs. 0.24 [IQR, 0.18–0.36], respectively; p=0.036), which was lost when applying the Bonferroni correction. No statistically significant differences between the two groups were observed for AAMM, EMS-3D, Eplet MM, and PIRCHE-II scores calculated in graft versus host direction. No associations were found between development of chimerism and GvHD and non-permissive HLA-DPB1 T-cell epitope group MM, HLA-B leader sequence, and KIR ligands MM.ConclusionOur results suggest an association between HLA-DRB1 molecular mismatches and achieving stable chimerism, particularly when electrostatic quality of the mismatch is considered. The non-permissive HLA-DPB1 T-cell epitope group, HLA-B leader sequence, and KIR ligands MM do not predict chimerism and GvHD in this combined kidney/HSCT transplant patient cohort. Further work is needed to validate our findings.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT00498160, identifier NCT00498160.
Genotype- and sex-specific changes in vital parameters during isoflurane anesthesia in a mouse model of Alzheimer’s disease
Authors: Bratke Sebastian , Schmid Sebastian , Ulm Bernhard , Jungwirth Bettina , Blobner Manfred , Borgstedt Laura 
Published: March 2024

BackgroundThe prevalence of neurodegenerative diseases is increasing as is life expectancy with Alzheimer’s disease accounting for two-thirds of dementia cases globally. Whether general anesthesia and surgery worsen cognitive decline is still a matter of debate and most likely depending on the interplay of various influencing factors. In order to account for this complexity, Alzheimer’s disease animal models have been developed. The Tg2576 model of Alzheimer’s disease is a well-established mouse model exhibiting amyloidopathy and age-dependent sex-specific differences in Alzheimer’s disease symptomology. Yet, data on anesthesia in this mouse model is scarce and a systematic comparison of vital parameters during anesthesia with wild-type animals is missing. In order to investigate the safety of general anesthesia and changes in vital parameters during general anesthesia in Tg2576 mice, we did a secondary analysis of vital parameters collected during general anesthesia in aged Tg2576 mice.MethodsAfter governmental approval (General Administration of the Free State of Bavaria, file number: 55.2-1-54-2532-149-11) 60 mice at 10-12 months of age were exposed to isoflurane (1.6 Vol%) for 120 min, data of 58 mice was analyzed. During general anesthesia, heart rate, respiratory rate, temperature, isoflurane concentration and fraction of inspired oxygen were monitored and collected. Data were analyzed using univariate and multivariate linear mixed regression models.ResultsDuring general anesthesia, heart rate decreased in a sex-specific manner. Respiratory rate decreased and body temperature increased dependent on genotype. However, the changes were limited and all vital parameters stayed within physiological limits.ConclusionIsoflurane anesthesia in the Tg2576 mouse model is safe and does not seem to influence experimental results by interacting with vital parameters. The present study provides information on appropriate anesthesia in order to advance research on anesthesia and AD and could contribute to improving laboratory animal welfare.