bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic DNA Methylation in Diabetic Chronic Complications in Patients With Type 2 Diabetes Mellitus
Authors: Wang Xixi , Yang Wenhong , Zhu Yunyan , Zhang Shiyu , Jiang Miao , Hu Ji , Zhang Hong-Hong 
Published: June 2022

AimTo explore the relationship between genomic DNA methylation and diabetic chronic complications.Methods299 patients with type 2 diabetes mellitus (T2DM) hospitalized in the Second Affiliated Hospital of Soochow University were enrolled. We divided the patients into different complications groups and corresponding non-complication groups. Clinical and biochemical parameters were compared between the two groups. The level of genomic DNA methylation in leukocytes was determined by high-performance liquid chromatography-tandem mass spectrometry.Results(1) Age, duration of diabetes, creatinine (Cr), blood urea nitrogen (BUN), genomic DNA methylation, 24- hour urine total protein (24-hUTP), and intima-media thickness (IMT) were significantly higher in the carotid plaque (CP) group. Waist-to-hip ratio (WHR), body mass index (BMI), estimated glomerular- filtration rate (eGFR), and albumin (Alb) were significantly lower in the CP group. Gender, age and BMI were the influencing factors of CP. (2) Age, duration, Cr, BUN, urinary microalbumin creatinine ratio (UACR), systolic blood pressure (SBP), TCSS, and 24- hUTP were significantly higher in the diabetic retinopathy (DR) group. eGFR, 2h postprandial C- peptide, and Alb were lower in the DR group. Age, duration, Cr, Alb, SBP, and the presence of DN were the influencing factors of DR. (3) Age, duration, HbA1c, BUN, TCSS, SBP, and IMT(R) were significantly higher in the diabetic nephropathy (DN) group. 2h postprandial C-peptide, and Alb were lower in the DN group. HbA1c, BUN, DR, and HBP were the influencing factors of DN. (4) Age, duration, total cholesterol (TC), low-density lipoprotein (LDL-C), triglyceride (TG), Cr, BUN, uric acid (UA), and SBP were significantly higher in the diabetic peripheral neuropathy (DPN) group. The level of genomic DNA methylation and eGFR were significantly lower in the DPN group. Age, duration, LDL-C, UA, the presence of DR, and the genomic DNA methylation level were the influencing factors for DPN. Incorporating the level of genomic DNA methylation into the prediction model could improve the ability to predict DPN on the basis of conventional risk factors.ConclusionLow level of genomic DNA methylation is a relatively specific risk factor for DPN in patients with T2DM and not a contributing factor to the other chronic complications.
Lifestyle or Environmental Influences and Their Interaction With Genetic Susceptibility on the Risk of LADA
Authors: Carlsson Sofia 
Published: June 2022

BackgroundLADA is a common form of diabetes described as a mix between type 1 and type 2 diabetes. Understanding of how genes and environmental factors interact in the development of LADA is central for future efforts to prevent the disease. This review aims to synthesize the literature on lifestyle factors linked to LADA risk and discuss their potential interaction with genetic susceptibility.FindingsCurrent knowledge on environmental risk factors for LADA is primarily based on observational data from Scandinavian populations. Increasing evidence suggest that lifestyle factors promoting type 2 diabetes such as obesity, sedentariness, low birth weight and smoking, is implicated in the risk of LADA. Data from mendelian randomization studies support that the link between LADA and obesity, low birth weight and smoking is causal. Limited evidence indicates that dietary factors including consumption of red meat, coffee and sweetened beverages may increase the risk while consumption of alcohol and omega-3 fatty acids may reduce the risk. Several lifestyle factors, including smoking and obesity, seem to interact with human leukocyte antigen genes associated with autoimmunity, conferring much stronger effects on disease risk among those exposed to both factors.SummaryAvailable studies suggest that lifestyle modification has the potential for prevention of LADA, particularly for individuals with high risk of disease such as those with genetic susceptibility. Research into risk factors of LADA is however limited, confirmations are warranted, many factors remain to be explored, and there is a need for intervention studies to assess causality
Identification of Immune-Related Subtypes and Characterization of Tumor Microenvironment Infiltration in Kidney Renal Clear Cell Carcinoma
Authors: Qin Huisheng , Wang Tiancheng , Zhang Hui 
Published: June 2022

Background: Tumor microenvironment (TME) plays indisputable role in the progression of cancers. Immune cell infiltration (ICI) in TME was related to the prognosis of tumor patients. In this paper, we identified the pattern of immune-related ICI subtypes based on the TME immune infiltration pattern.Methods: The data from kidney renal clear cell carcinoma data (KIRC) was downloaded from the TCGA database. The distinct ICI subtypes were identified using CIBERSORT and ESTIMATE algorithms. The gene subgroups were identified based on DEGs in ICI subtypes. The single sample gene set enrichment analysis (ssGSEA) was used to ascertain the ICI score. Kaplan-Meier curve with log-rank test was conducted to analyze the survival probability of patients with KIRC in different subtypes.Results: The patients with high ICI scores exhibited a longer survival time and lower expression of checkpoint-related and immune activity-related genes. The high ICI score clusters were positively related to TMB. The patients in the low TMB subgroups have a favorable prognosis. The prediction ICI score did not affect the TMB status, and the low TMB subgroups + low/high ICI score subgroups exhibited better survival.Conclusion: In all, the tumor immune microenvironment, ICI score, and TMB were important determinants of KIRC patients’ survival outcomes. The TMB + ICI score may be a potential biomarker for predicting the prognosis of patients and for targeted immunotherapies to treating KIRC.
Extracellular CIRP Promotes GPX4-Mediated Ferroptosis in Sepsis
Authors: Shimizu Junji , Murao Atsushi , Nofi Colleen , Wang Ping , Aziz Monowar 
Published: June 2022

Sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern (DAMP) that promotes inflammation and induces cell death via apoptosis, NETosis, and/or pyroptosis. Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxide on cellular membranes. We hypothesize that eCIRP induces ferroptosis in macrophages and lung tissue during sepsis. RAW 264.7 cells stimulated with recombinant murine (rm) CIRP significantly decreased the expression of glutathione peroxidase 4 (GPX4), a negative regulator of ferroptosis, and increased lipid reactive oxygen species (ROS) in a TLR4 dependent manner. In TLR4-/- peritoneal macrophages, depression of GPX4 expression and increase in lipid ROS levels were attenuated after rmCIRP-treatment compared to WT macrophages. rmCIRP also induced cell death in RAW 264.7 cells which was corrected by the ferroptosis inhibitor, ferrostatin-1 (Fer-1). Intraperitoneal injection of rmCIRP decreased GPX4 expression and increased lipid ROS in lung tissue, whereas the increase of lipid ROS was reduced by Fer-1 treatment. GPX4 expression was significantly decreased, while malondialdehyde (MDA), iron levels, and injury scores were significantly increased in lungs of WT mice after cecal ligation and puncture (CLP)-induced sepsis compared to CIRP-/- mice. Treatment with C23, a specific eCIRP inhibitor, in CLP mice alleviated the decrease in GPX4 and increase in MDA levels of lung tissue. These findings suggest that eCIRP induces ferroptosis in septic lungs by decreasing GPX4 and increasing lipid ROS. Therefore, regulation of ferroptosis by targeting eCIRP may provide a new therapeutic approach in sepsis and other inflammatory diseases.
Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells From Acute Myocardial Infarction
Authors: Qian Jun , Gao Yanhua , Lai Yan , Ye Zi , Yao Yian , Ding Keke , Tong Jing , Lin Hao , Zhu Guoqi , Yu Yunan , Ding Haoran , Yuan Deqiang , Chu Jiapeng , Chen Fei , Liu Xuebo 
Published: June 2022

BackgroundAcute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive.MethodsTen AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells.ResultsWe identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory-related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell–cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture.ConclusionsOur studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.
The Association Between Psoriasis and Risk of Cardiovascular Disease: A Mendelian Randomization Analysis
Authors: Gao Ning , Kong Minjian , Li Xuebiao , Zhu Xian , Wei Dongdong , Ni Ming , Wang Yifan , Hong Ze , Dong Aiqiang 
Published: June 2022

BackgroundA large number of observational studies showed that patients with psoriasis have a higher risk of cardiovascular disease (CVD), but most studies did not fully adjust for confounding factors, so it is not clear whether the risk of CVD is directly attributed to psoriasis. We used Mendelian randomization (MR) to evaluate the potential causal relationship between psoriasis and CVD.MethodsWe used genetic instruments from the genome-wide association study (GWAS) of European descent for psoriasis to investigate its relationship with CVD. Inverse variance-weighted (IVW) MR analyses were used for the primary analysis. In addition, a variety of other methods were used to replicate the analysis.ResultsThe fixed-effects IVW method indicated that genetic susceptibility to psoriasis was associated with a higher risk of heart failure (HF) [odds ratio (OR) = 1.04; 95% CI, 1.01–1.06, P = 2.72E-03], atrial fibrillation (AF) (OR = 1.04; 95% CI, 1.02–1.07, P = 3.27E-04), myocardial infarction (MI) (OR = 1.07; 95% CI, 1.01–1.12, P = 0.01), valvular heart disease (VHD) (OR = 1.001; 95% CI, 1.000–1.002, P = 1.85E-03), and large artery stroke (LAS) (OR = 1.11; 95% CI, 1.05–1.18, P = 5.37E-04) but not with the other two subtypes of ischemic stroke (IS) [cardioembolic stroke (CES) (OR = 1.03; 95% CI, 0.98–1.07, P = 0.27) and small vessel stroke (SVS) (OR = 1.00; 95% CI, 0.95–1.07), P = 0.88)]. Sensitivity analysis found weak evidence of horizontal diversity and heterogeneity to ensure the stability of the results.ConclusionOur study provided evidence for a potential causal link between psoriasis and CVD. These findings partly suggest that early monitoring of cardiovascular risk in patients with psoriasis is intentional.
Sub-Nano Pt/β-FeOOH Quantum Dots for Photocatalytic Removal of Toluene: Catalyst Design, Preparation, and Benefits
Authors: Pei Mengxi , Lv Shangchun , Liu Yishui , Si Zhichun , Wu Xiaodong , Ran Rui , Weng Duan , Kang Feiyu 
Published: June 2022

Photocatalytic removal of organic pollutants under solar irradiation at room temperature is considered an energy-saving technique of environmental remediation. However, photocatalysis is impeded by the poor response to visible light and fast charge recombination. In this work, sub-nano Pt/β-FeOOH quantum dots (QDs) were designed to shorten the charge migration path and obtain wide light harvesting. Interestingly, the crystalline β-FeOOH QDs can be obtained by loading sub-nano Pt particles via a reconstruction mechanism of amorphous FeOOH induced by H2 spillover, which facilitates the fast kinetics of charge transition and benefits the oxygen-rich surface of the catalyst for photocatalytic oxidation reactions. Moreover, the Pt-VO-Fe interfaces were proved to be the most active sites for the activation of O2. As a result, the catalyst exhibits a predominant photocatalytic performance in toluene oxidation, achieving a TOFPt of 0.591 min−1 at room temperature under visible light irradiation. This work provides a new perspective on the design and preparation of nanocatalysts for high-efficient photocatalysis under visible light irradiation.
Balancing Benefits and Risks of Indomethacin in the Management of Antenatal Bartter Syndrome: A Case Report
Authors: Alajjuri Omar Ala' , Samaha Mayar Essam , Honemeyer Ulrich , Mohammed Ghada , Mousa Noha A. 
Published: June 2022

BackgroundBartter syndrome, a very rare inherited renal tubular disorder, characterized by urinary salt wastage, hypokalemia, polyuria, and metabolic alkalosis, may manifest antenatally as severe isolated polyhydramnios. Indomethacin is known to reduce salt wastage and subsequent polyhydramnios during pregnancy; however, it reduces the Ductus Arteriosus diameter among other potential complications, such as inhibition of gastrointestinal perfusion and increasing the risk of renal toxicity.CaseA 36-year-old multigravida presented with severe isolated polyhydramnios at 30 weeks of gestation. Based on a history of a previous pregnancy affected with Bartter syndrome, indomethacin was initiated. Amniotic fluid volume and Ductus Arteriosus diameter were monitored. As evidence lacks on optimal dose and duration of indomethacin, multiple-dose adjustments were made to reduce the amniotic fluid volume while maintaining normal Ductus Arteriosus diameter. Progressive polyhydramnios led to Cesarean section at 34+ weeks of gestation resulting in a healthy fetus diagnosed with Bartter syndrome in the early neonatal period.ConclusionWe share our experience in the adjustment of the dose and duration of Indomethacin therapy in the treatment of severe polyhydramnios associated with antenatal Bartter syndrome. Amniotic fluid index, Ductus Arteriosus diameter, and umbilical artery doppler work together as key indicators to guide the success and safety of the therapy.
Integrated Analysis of the Alterations in Gut Microbiota and Metabolites of Mice Induced After Long-Term Intervention With Different Antibiotics
Authors: Zhang Nan , Liu Jun , Chen Zhiyun , Chen Ning , Gu Fangyan , He Qiushui 
Published: June 2022

ObjectivesWe aimed to study the effect of antibiotic-induced disruption of gut microbiome on host metabolomes and inflammatory responses after long-term use of antibiotics.MethodsA total of three groups of 3-week-old female C57BL/6 mice (n = 44) were continuously treated with vancomycin (VAN), polymyxin B (PMB), or water, respectively, for up to 28 weeks. Fecal samples collected at different time points were analyzed by bacterial 16S rRNA gene sequencing and untargeted metabolomics by ultraperformance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS). Serum cytokines (IFN-γ, IL-2, IL-10, IL-13, IL-17A, and TNF-α) were determined by multiplex immunoassay.ResultsTreatment by VAN or PMB did not affect the average body weight of mice. However, a heavier caecum observed in VAN-treated mice. Compared with PMB-treated and control mice, VAN treatment induced more rapid dysbiosis of gut microbiota and dysmetabolism. Instead of Bacteroides, VAN-treated mice had a compositional shift to Proteobacteria and its species Escherichia coli and Verrucomicrobia and its species Akkermansia muciniphila. The shift was accompanied by decreased richness and diversity in microbiota. PMB-treated mice had an increased Firmicutes, and the diversity was shortly increased and further decreased to the baseline. Decreased levels of short-chain and long-chain fatty acids, bile acids, L-arginine, dopamine, L-tyrosine, and phosphatidylcholine (all p &lt; 0.05) were observed in VAN-treated mice. In contrast, significantly increased levels of amino acids including L-aspartic acid, beta-alanine, 5-hydroxy-L-tryptophan, L-glutamic acid, and lysophosphatidylcholines (all p &lt; 0.05) were found. These changes occurred after 3-week treatment and remained unchanged up to 28 weeks. For PMB-treated mice, metabolites involved in the metabolic pathway of vitamin B6 were decreased, whereas glycocholic acid and chenodeoxycholic acid were increased (all p &lt; 0.05). After 8-week treatment, VAN-treated mice had significantly higher levels of serum IFN-γ, IL-13, and IL-17A, and PMB-treated mice had higher levels of IL-13 and IL-17 compared to control mice. At 28-week treatment, only IL-17A remained high in PMB-treated mice.ConclusionThis study showed that the antibiotic-induced alterations in gut microbiota contribute to host inflammatory responses through the change in metabolic status, which are likely related to the type, rather than timing of antibiotic used.
Targeted Intraoperative Radiotherapy (TARGIT-IORT) for Early-Stage Invasive Breast Cancer: A Single Institution Experience
Authors: Brown Andrea , Buss Elizabeth J. , Chin Christine , Liu Gaotong , Lee Shing , Rao Roshni , Taback Brett , Wiechmann Lisa , Horowitz David , Choi Julie C. , Katz Leah M. , Connolly Eileen P. 
Published: June 2022

Purpose/ObjectiveWe present our single-institution experience in the management of invasive breast cancer with targeted intraoperative radiotherapy (TARGIT-IORT), focusing on patient suitability for IORT determined by the American Society for Radiation Oncology (ASTRO) Accelerated Partial Breast Irradiation (APBI) consensus guidelines.Materials/MethodsWe identified 237 patients treated for biopsy-proven early-stage invasive breast cancer using low energy x-ray TARGIT-IORT at the time of lumpectomy between September 2013 and April 2020 who were prospectively enrolled in an institutional review board (IRB) approved database. We retrospectively reviewed preoperative and postoperative clinicopathologic factors to determine each patient’s ASTRO APBI suitability (suitable, cautionary or unsuitable) according to the 2017 consensus guidelines (CG). Change in suitability group was determined based on final pathology. Kaplan-Meier methods were used to estimate the survival probability and recurrence probability across time.Results237 patients were included in this analysis, based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable, 46 (19.4%) were cautionary and none were deemed unsuitable. Suitability classification changed in 95 (40%) patients based on final pathology from lumpectomy. Increasing preoperative lesion size or a body mass index (BMI) ≥ 30 kg/m2 were significant predictors for suitability group change. Forty-one (17.3%) patients received additional adjuvant whole breast radiotherapy after TARGIT-IORT. At a median follow up of 38.2 months (range 0.4 – 74.5), five (2.1%) patients had ipsilateral breast tumor recurrences (IBTR), including two (0.8%) true local recurrences defined as a recurrence in the same quadrant as the initial lumpectomy bed with the same histology as the initial tumor. IBTR occurred in 1/103 (0.09%) patient in the post-op suitable group, 4/98 (4.08%) patients in the post-op cautionary group, and no patients in the post-op unsuitable group. At 3-years, the overall survival rate was 98.4% and the local recurrence free survival rate was 97.1%.ConclusionThere is a low rate of IBTR after TARGIT-IORT when used in appropriately selected patients. Change in suitability classification pre to postoperatively is common, highlighting a need for further investigation to optimize preoperative patient risk stratification in this setting. Patients who become cautionary or unsuitable based on final pathology should be considered for additional adjuvant therapy.
Prognostic Impact of Serum CRP Level in Head and Neck Squamous Cell Carcinoma
Authors: Zhang Yaoting , Gu Dongsheng 
Published: June 2022

ObjectiveThis study evaluated the association of pretreatment serum C-reactive protein (CRP) level with prognosis in patients with head and neck squamous cell carcinoma (HNSCC).MethodsWithin a single-center retrospective study, HNSCC patients receiving treatment between 2014 and 2016 were analyzed regarding the prognostic value of CRP serum levels. X-Tile software was used to determine the optimal cutoff value of serum CRP level. The log-rank test and Kaplan–Meier method were used to assess the effects of CRP level on prognosis in patients with HNSCC. Univariate and multivariate analyses (enter method) using a Cox proportional hazards model were utilized to identify prognostic indicators of progression-free survival (PFS) as the primary outcome and overall survival (OS) as the secondary outcome.ResultsA total of 221 patients with HNSCC were assessed for eligibility, and 208 cases were included in the analysis. The HNSCC patients in the low-group (CRP ≤11.3 mg/L) showed better survival than those in the high-group (CRP &gt; 11.3 mg/L). The univariate and multivariate analyses showed that N1-3 stage and a high serum CRP level (&gt;11.3 mg/L) were unfavorable prognostic factors for PFS and OS in patients with HNSCC.ConclusionSerum CRP level is an independent prognostic marker for patients with HNSCC. CRP level could be regarded as a novel prognostic factor for HNSCC patients.