bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for thalassemia carriers among the Han population of childbearing age in Southwestern of China
Authors: Du Yepei , Zhou Cong , Wang Jing , Yang Yanting , Liu Hui 
Published: April 2024

Purpose:Thalassemia is a severe hereditary blood disorder that poses a significant threat to human health and leads to mortality and disability. It is one of the most prevalent monogenic diseases worldwide. The aim of this study was to analyze the molecular epidemiological data of individuals of childbearing age from the Han ethnic group with thalassemia in Southwest China and to explore the application of next-generation sequencing (NGS) technology in screening thalassemia carriers.Methods:The participants were Han males and females of childbearing age who sought medical advice at the West China Second University Hospital, Sichuan University from June 2022 to June 2023. We detected α- and β-thalassemia mutations using full-length capture of the thalassemia genes and NGS technology.Results:In a cohort of 1,093 participants, 130 thalassemia carriers were identified, with an overall detection rate of 11.89% (130/1,093). Among these, 0.91% (10/1,093) had mutations that could not be detected using traditional PCR techniques. The proportions of carriers with α-, β-, and α-complexed β-thalassemia gene mutations were 7.68% (84/1,093), 3.93% (43/1,093), and 0.27% (3/1,093), respectively. We identified a novel HBA2 c.166del variant that has not been previously reported.Conclusion:Using NGS technology, we found that the mutation-carrying rate of thalassemia genes was 11.89% in the Han population of childbearing age in Southwest China. Compared with the results of traditional PCR techniques, NGS detected an additional 0.91% (10/1,093) rare genetic variants. NGS technology should be utilized as the primary screening method for thalassemia carriers among Han nationality people of childbearing age in Southwest China.
Integrative analysis of the lncRNA-miRNA-mRNA interactions in smooth muscle cell phenotypic transitions
Authors: Mahajan Aatish , Hong Junyoung , Krukovets Irene , Shin Junchul , Tkachenko Svyatoslav , Espinosa-Diez Cristina , Owens Gary K. , Cherepanova Olga A. 
Published: April 2024

Objectives: We previously found that the pluripotency factor OCT4 is reactivated in smooth muscle cells (SMC) in human and mouse atherosclerotic plaques and plays an atheroprotective role. Loss of OCT4 in SMC in vitro was associated with decreases in SMC migration. However, molecular mechanisms responsible for atheroprotective SMC-OCT4-dependent effects remain unknown.Methods: Since studies in embryonic stem cells demonstrated that OCT4 regulates long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), making them candidates for OCT4 effect mediators, we applied an in vitro approach to investigate the interactions between OCT4-regulated lncRNAs, mRNAs, and miRNAs in SMC. We used OCT4 deficient mouse aortic SMC (MASMC) treated with the pro-atherogenic oxidized phospholipid POVPC, which, as we previously demonstrated, suppresses SMC contractile markers and induces SMC migration. Differential expression of lncRNAs, mRNAs, and miRNAs was obtained by lncRNA/mRNA expression array and small-RNA microarray. Long non-coding RNA to mRNA associations were predicted based on their genomic proximity and association with vascular diseases. Given a recently discovered crosstalk between miRNA and lncRNA, we also investigated the association of miRNAs with upregulated/downregulated lncRNA-mRNA pairs.Results: POVPC treatment in SMC resulted in upregulating genes related to the axon guidance and focal adhesion pathways. Knockdown of Oct4 resulted in differential regulation of pathways associated with phagocytosis. Importantly, these results were consistent with our data showing that OCT4 deficiency attenuated POVPC-induced SMC migration and led to increased phagocytosis. Next, we identified several up- or downregulated lncRNA associated with upregulation of the specific mRNA unique for the OCT4 deficient SMC, including upregulation of ENSMUST00000140952-Hoxb5/6 and ENSMUST00000155531-Zfp652 along with downregulation of ENSMUST00000173605-Parp9 and, ENSMUST00000137236-Zmym1. Finally, we found that many of the downregulated miRNAs were associated with cell migration, including miR-196a-1 and miR-10a, targets of upregulated ENSMUST00000140952, and miR-155 and miR-122, targets of upregulated ENSMUST00000155531. Oppositely, the upregulated miRNAs were anti-migratory and pro-phagocytic, such as miR-10a/b and miR-15a/b, targets of downregulated ENSMUST00000173605, and miR-146a/b and miR-15b targets of ENSMUST00000137236.Conclusion: Our integrative analyses of the lncRNA-miRNA-mRNA interactions in SMC indicated novel potential OCT4-dependent mechanisms that may play a role in SMC phenotypic transitions.
Evaluation of cytokine profiles related to Mycobacterium tuberculosis latent antigens using a whole-blood assay in the Philippines
Authors: Yasuda Ikkoh , Saludar Naomi Ruth D. , Sayo Ana Ria , Suzuki Shuichi , Yokoyama Akira , Ozeki Yuriko , Kobayashi Haruka , Nishiyama Akihito , Matsumoto Sohkichi , Cox Sharon E. , Tanaka Takeshi , Yamashita Yoshiro 
Published: April 2024

IntroductionThere is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens.Materials and methodsPatients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay.ResultsA total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p &lt; 0.001) and the community exposure group (p &lt; 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p &lt; 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups.ConclusionThe patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.
A novel web-based dynamic prognostic nomogram for gastric signet ring cell carcinoma: a multicenter population-based study
Authors: Jiang Yujuan , Hu Haitao , Shao Xinxin , Li Weikun , Lu Yiming , Liang Jianwei , Tian Yantao 
Published: April 2024

BackgroundGastric signet ring cell carcinoma (GSRCC) is a rare and highly malignant disease with a poor prognosis. To assess the overall survival (OS) and cancer-specific survival (CSS) of patients with GSRCC, prognostic nomograms were developed and validated using common clinical factors.MethodsThis retrospective cohort study included patients diagnosed with GSRCC between 2011 and 2018 from the National Cancer Center (n = 1453) and SEER databases (n = 2745). Prognostic nomograms were established by identifying independent prognostic factors using univariate and multivariate Cox regression analyses. The calibration curve and C-index were used to assess the predictions. The clinical usefulness of the survival prediction model was further evaluated using the DCA and ROC curves. The models were internally validated in the training cohort and externally validated in the validation cohort. Two web servers were created to make the nomogram easier to use.ResultsPatients with GSRCC were divided into training (n = 2938) and validation (n = 1260) cohorts. The nomograms incorporated six predictors: age, race, tumor site, tumor size, N stage, T stage, and AJCC stage. Excellent agreement was observed between the internal and exterior calibration plots for the GSRCC survival estimates. The C-index and area under the ROC curve were roughly greater than 0.7. Both nomograms had adequate clinical efficacy, as demonstrated by the DCA plots. Furthermore, we developed a dynamic web application utilizing the constructed nomograms available at https://jiangyujuan.shinyapps.io/OS-nomogram/ and https://jiangyujuan.shinyapps.io/DynNomapp-DFS/.ConclusionWe developed web-based dynamic nomograms utilizing six independent prognostic variables that assist physicians in estimating the OS and CSS of patients with GSRCC.
Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM
Authors: Rong Dongyun , Su Yushen , Jia Dechao , Zeng Zhirui , Yang Yan , Wei Dalong , Lu Honguan , Cao Yu 
Published: April 2024

BackgroundSkin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for chemotherapy and immunotherapy response in SKCM and explore their association with oxidative stress.MethodsUtilizing TCGA-SKCM RNA-seq data, we employed Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) networks to identify six core genes. Gene co-expression analysis and immune-related analysis were conducted, and specific markers associated with oxidative stress were identified using Gene Set Variation Analysis (GSVA). Single-cell analysis revealed the expression patterns of Oxidative Stress-Associated Genes (OSAG) in the tumor microenvironment. TIDE analysis was employed to explore the association between immune therapy response and OSAG, while CIBERSORT was used to analyze the tumor immune microenvironment. The BEST database demonstrated the impact of the Oxidative Stress signaling pathway on chemotherapy drug resistance. Immunohistochemical staining and ROC curve evaluation were performed to assess the protein expression levels of core genes in SKCM and normal samples, with survival analysis utilized to determine their diagnostic value.ResultsWe identified six central genes associated with SKCM metastasis, among which the expression of DSC2 and DSC3 involved in the oxidative stress pathway was closely related to immune cell infiltration. DSC2 influenced drug resistance in SKMC patients. Furthermore, downregulation of DSC2 and DSC3 expression enhanced the response of SKCM patients to immunotherapy.ConclusionThis study identified two Oxidative Stress-Associated genes as novel biomarkers for SKCM. Additionally, targeting the oxidative stress pathway may serve as a new strategy in clinical practice to enhance SKCM chemotherapy and sensitivity.
FOXP3 full length splice variant is associated with kidney allograft tolerance
Authors: Saleh Qais W. , Mohammadnejad Afsaneh , Tepel Martin 
Published: April 2024

BackgroundProgressive decline of allograft function leads to premature graft loss. Forkhead box P3 (FOXP3), a characteristic gene of T-regulatory cells, is known to be essential for auto-antigen tolerance. We assessed the hypothesis that low FOXP3 mRNA splice variant levels in peripheral blood cells early after transplantation are associated with progressive allograft injury.MethodsBlood samples were prospectively collected from 333 incident kidney transplant recipients on the first and 29th postoperative day. We used quantitative polymerase chain reaction to determine transcripts of 3 isotypes of FOXP3 splice variants, including pre-mature FOXP3 and full length FOXP3 (FOXP3fl). We investigated the association between FOXP3 splice variant levels and the declines in estimated glomerular filtration rate (eGFR) of more than 5ml/min/1.73m2 within the first-year post-transplant using logistic regression.ResultsWe observed lower FOXP3fl levels in recipients with declining eGFR (N = 132) than in recipients with stable eGFR (N = 201), (logarithmic value -4.13 [IQR -4.50 to -3.84] vs -4.00 [4.32 to -3.74], p=0.02). In ad hoc analysis pre-transplant FOXP3fl levels were similar in both groups. The association between FOXP3fl and declining eGFR was confirmed by multivariable analysis adjusted for potential confounding factors (Odds Ratio 0.51, 95% confidence interval 0.28 to 0.91: p=0.02). When stratifying FOXP3fl levels into quartiles, recipients with lower day1 FOXP3fl had the highest rate of declining eGFR (p=0.04).ConclusionLow FOXP3fl splice variant levels at the first postoperative day in kidney transplant recipients were associated with severe decline of eGFR, a well-known surrogate for hard endpoints.
Rare COVID-19 vaccine side effects got lost in the shuffle. Primary cutaneous lymphomas following COVID-19 vaccination: a systematic review
Authors: Olszewska Berenika , Zaryczańska Anna , Nowicki Roman J. , Sokołowska-Wojdyło Małgorzata 
Published: April 2024

IntroductionCOVID-19 vaccines are generally safe and effective; however, they are associated with various vaccine-induced cutaneous side effects. Several reported cases of primary cutaneous lymphomas (CLs) following the COVID-19 vaccination have raised concerns about a possible association. This systematic review aims to investigate and elucidate the potential link between CLs and SARS-CoV-2 vaccines.MethodsWe performed a systematic literature search on PubMed, EBSCO and Scopus from January 01, 2019, to March 01, 2023, and analyzed studies based on determined eligibility criteria. The systematic review was performed based on the PRISMA protocol.ResultsA total of 12 articles (encompassing 24 patients) were included in this analysis. The majority of CLs were indolent cutaneous T-cell lymphomas (CTCLs) (66,7%; 16/24), with Lymphomatoid papulosis (LyP) being the most common type (33,3%; 8/24). Most patients (79,2%; 19/24) developed lesions after receiving the COVID-19 mRNA-based vaccines, and predominantly after the first immunization dose (54,2%; 13/24). The presented CLs cases exhibited a tendency to exacerbate following subsequent COVID-19 vaccinations. Nevertheless, CLs were characterized by a favorable course, leading to remission in most cases.ConclusionThe available literature suggests an association between the occurrence and exacerbation of CLs with immune stimulation following COVID-19 vaccination. We hypothesize that post-vaccine CLs result from an interplay between cytokines and disrupted signaling pathways triggered by vaccine components, concurrently playing a pivotal role in the pathomechanism of CLs. However, establishing a definitive causal relationship between these events is currently challenging, primarily due to the relatively low rate of reported post-vaccine CLs. Nonetheless, these cases should not be disregarded, and patients with a history of lymphoproliferative disorders require post-COVID-19 vaccination monitoring to control the disease’s course.Systematic review registrationwww.researchregistry.com, identifier [1723].
Branched-chain amino acids and the risks of dementia, Alzheimer’s disease, and Parkinson’s disease
Authors: Fu Yidong , Wang Yue , Ren Huiming , Guo Xu , Han Liyuan 
Published: April 2024

BackgroundWe aimed to examine the association between blood levels of Branched-chain amino acids (BCAAs) - specifically isoleucine, leucine, and valine - and the susceptibility to three neurodegenerative disorders: dementia, Alzheimer’s disease (AD), and Parkinson’s disease (PD).MethodsBased on data from the UK Biobank, a Cox proportional hazard regression model and a dose–response relationship were used to analyze the association between BCAAs and the risks of dementia, AD, and PD. We also generated a healthy lifestyle score and a polygenic risk score. Besides, we conducted a sensitivity analysis to ensure the robustness of our findings.ResultsAfter adjusting for multiple covariates, blood concentrations of isoleucine, leucine, and valine were significantly associated with a reduced risk of dementia and AD. This association remained robust even in sensitivity analyses. Similarly, higher levels of isoleucine and leucine in the blood were found to be associated with an increased risk of PD, but this positive correlation could potentially be explained by the presence of covariates. Further analysis using a dose–response approach revealed that a blood leucine concentration of 2.14 mmol/L was associated with the lowest risk of dementia.ConclusionBCAAs have the potential to serve as a biomarker for dementia and AD. However, the specific mechanism through which BCAAs are linked to the development of dementia, AD, and PD remains unclear and necessitates additional investigation.
Patient-centered nutrition education improved the eating behavior of persons with uncontrolled type 2 diabetes mellitus in North Ethiopia: a quasi-experimental study
Authors: Gebreyesus Hagos Amare , Abreha Girmatsion Fisseha , Beshirie Sintayehu Degu , Abera Merhawit Atsbha , Weldegerima Abraha Hailu , Bezabih Afework Mulugeta , Lemma Tefera Belachew , Nigatu Tsinuel Girma 
Published: April 2024

BackgroundImproving the clinical outcome of people with type 2 diabetes mellitus by modifying their eating behavior through nutrition education is an important element of diabetes self-management. Significant data from the literature supports this idea, however in the Ethiopian setting, there is a practice gap. Therefore, the purpose of this study was to assess how patient-centered nutrition education affected the eating behavior and clinical outcomes of people with uncontrolled type 2 diabetes mellitus.MethodIn this quasi-experimental trial, 178 people with uncontrolled type 2 diabetes were purposely assigned to the intervention (n = 89) or control (n = 89) arm. The intervention arm was given patient-centered nutrition education, whereas the control arm received the routine care. Eating behavior and clinical outcome indicators such as HbAc, lipid profile, anthropometric indices, and blood pressure were assessed in both groups at the start and completion of the intervention. All scale variables were tested for normality and log transformed when appropriate. The baseline characteristics of the intervention and control groups were compared using the t-test for continuous variables and the chi-square test for categorical variables. The effect of nutrition education was determined using a difference in differences (DID) approach. P &lt; 0.05 was established as the criterion of significance.ResultFood selection (DID = 15.84, P &lt; 0.001), meal planning (DID = 31.11, P &lt; 0.001), and calorie needs (DID = 37.65, P &lt; 0.001) scores were statistically higher in the nutrition education arm. Furthermore, their overall eating behavior score (DID = 27.06, P &lt; 0.001) was statistically greater than the controls. In terms of clinical outcomes, the overall picture reveals that the intervention did not outperform over the routine care. However, in comparison to the controls, the intervention arm showed clinically significant improvement in HbA1c (DID = −0.258, P = 0.485).ConclusionPatient-centered nutrition education has resulted in positive adjustments in the eating behavior of people with uncontrolled type 2 diabetes mellitus. Furthermore, it has shown a great potential for improving their glycemic control.
Association of temperature management strategy with fever in critically ill children after out-of-hospital cardiac arrest
Authors: Kadden Micah , Zhang Anqing , Shoykhet Michael 
Published: April 2024

ObjectiveTo determine whether ICU temperature management strategy is associated with fever in children with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA).MethodsWe conducted a single-center retrospective cohort study at a quaternary Children's hospital between 1/1/2016–31/12/2020. Mechanically ventilated children (&lt;18 y/o) admitted to Pediatric or Cardiac ICU (PICU/CICU) with ROSC after OHCA who survived at least 72 h were included. Primary exposure was initial PICU/CICU temperature management strategy of: (1) passive management; or (2) warming with an air-warming blanket; or (3) targeted temperature management with a heating/cooling (homeothermic) blanket. Primary outcome was fever (≥38°C) within 72 h of admission.ResultsOver the study period, 111 children with ROSC after OHCA were admitted to PICU/CICU, received mechanical ventilation and survived at least 72 h. Median age was 31 (IQR 6–135) months, 64% (71/111) were male, and 49% (54/111) were previously healthy. Fever within 72 h of admission occurred in 51% (57/111) of patients. The choice of initial temperature management strategy was associated with occurrence of fever (χ2 = 9.36, df = 2, p = 0.009). Fever occurred in 60% (43/72) of patients managed passively, 45% (13/29) of patients managed with the air-warming blanket and 10% (1/10) of patients managed with the homeothermic blanket. Compared to passive management, use of homeothermic, but not of air-warming, blanket reduced fever risk [homeothermic: Risk Ratio (RR) = 0.17, 95%CI 0.03–0.69; air-warming: RR = 0.75, 95%CI 0.46–1.12]. To prevent fever in one child using a homeothermic blanket, number needed to treat (NNT) = 2.ConclusionIn critically ill children with ROSC after OHCA, ICU temperature management strategy is associated with fever. Use of a heating/cooling blanket with homeothermic feedback reduces fever incidence during post-arrest care.
Laser-induced damages to charge coupled devices with combined nanosecond/picosecond short-pulse lasers
Authors: Cao He , Xie Xiaofan , Chang Hao , Li Yunfei , Yue Jianfeng , Yu Yu , Wang Gong , Tang Ziqi , Li Lifang , Wang Yulei , Lu Zhiwei 
Published: April 2024

The research on laser induced breakdown mechanism of charge coupled devices (CCDs) brings new insights into photoelectric countermeasures. So far combined laser irradiation has been proved to be a more effective measure to destroy CCD. Due to the limitation of short-pulse laser combination method, the mechanism of CCD damage caused by combined short-pulse laser remains unexplored. Here, the distribution of temperature and stress field during the interaction between a combined short-pulse laser and a CCD is analyzed. A nanosecond/picosecond combined short-pulse laser system based on Stimulated Brillouin Scattering (SBS) pulse compression technique is designed. The damage threshold (DT) and properties of CCD by combined laser irradiation are characterized. The results show that the complete DT of combined laser induced CCD breakdown is only 103 mJ/cm2, which is only 44% of that of picosecond laser. The main cause of combined short-pulse laser induced CCD breakdown is short circuit (SC) between silicon substrate and silicon electrode.