Diet affects inflammatory arthritis: a Mendelian randomization study of 30 dietary patterns causally associated with inflammatory arthritis.

Background: The causal associations between dietary intake and the risk and severity of Inflammatory Arthritis (IA) are currently unknown. Objective: In this study, we aimed to investigate the causal relationship between nine dietary categories (30 types of diet) and IA using Mendelian randomization (MR). Methods: We analyzed data from 30 diets and IA in a genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that could influence the results of MR analyses were screened out through the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. SNPs were analyzed through two-sample bidirectional MR using inverse variance weighting, MR-Egger regression, and weighted median method. The multiplicity and heterogeneity of SNPs were assessed using MR-Egger intercept term tests and Cochran's Q tests. FDR correction was used to correct the p-values. Results: IVW results showed that Beef intake [Odds ratio (OR) = 2.862; 95% confidence interval (CI), 1.360-6.021, p = 0.006, p_fdr < 0.05] was positively associated with rheumatoid arthritis(RA); Dried fruit intake (OR = 0.522; 95% CI, 0.349-0.781, p = 0.002, p_fdr < 0.05), and Iron intake (OR = 0.864; 95%CI, 0.777-0.960, p = 0.007, p_fdr < 0.05) were negatively associated with RA, all of which were evidence of significance. Fresh fruit intake (OR = 2.528. 95% CI, 1.063-6.011, p = 0.036, p_fdr > 0.05) was positively associated with psoriatic arthritis (PsA); Cheese intake (OR = 0.579; 95% CI, 0.367-0.914, p = 0.019, p_fdr > 0.05) was negatively associated with PsA; both were suggestive evidence. Processed meat intake (OR = 0.238; 95% CI, 0.100-0.565, p = 0.001, p_fdr < 0.05) was negatively associated with reactive arthritis (ReA), a protective factor, and significant evidence. All exposure data passed the heterogeneity check (Cochrane's Q test p > 0.05) and no directional pleiotropy was detected. Leave-one-out analyses demonstrated the robustness of the causal relationship in the positive results. Conclusion: Our study presents genetic evidence supporting a causal relationship between diet and an increased risk of IA. It also identifies a causal relationship between various dietary modalities and different types of IA. These findings have significant implications for the prevention and management of IA through dietary modifications.

Evaluating the Rates of Mortality and Cardiac Catheterization Using High-Sensitivity Troponin and Conventional Troponin Assays.

Non-ST segment elevation myocardial infarction (NSTEMI) is an acute coronary syndrome event where myocardial ischemia is present, with an increase of cardiac troponins without an elevation of the ST segment. One of the fundamental measures used to diagnose or rule out acute coronary syndrome (ACS) is troponin levels in the blood. Troponin is a broad term used for the category of muscle contraction regulatory proteins and is commonly measured during ACS evaluation. Troponin I is only released by cardiac tissue, while some assay measurements will also pick up troponin released by skeletal muscle injury. This retrospective observational study was performed investigating troponin assays and how they relate to patient's outcomes. The troponin assays used in this Miami hospital where the database of patients was collected between 2018 and 2023 were troponin I (cTnI), the conventional troponin assay, and the newer high-sensitivity troponin I assay (hs-cTn). In this observational study patients who received an admitting diagnosis of NSTEMI corroborated by an independent cardiologist had their respective troponin assay levels included. Patients found to have ECG changes significant for non-ischemic pathologies, or echocardiogram findings suggestive of myocardial dysfunction not clinically correlated to an ACS were excluded from the study. A total of 75 patients were included in this study and the mean age was 75.97 ±14.72 years, with a presentation of chest pain, dyspnea and general weakness recorded in 59% (n = 45) of patients. The median time between troponin samples was 6.63 hours across both assays and hs-cTn showed a 4.99% increase in variation between samples while cTnI had a decrease of 2.53%. The study objective is to support whether there is a difference in rates of cardiac catheterization or mortality based on the type of troponin testing. There was no significant association found between, the type of troponin assay used during hospital admission, and the outcomes of catheterization and death (p > 0.009).

Serum uric acid and high-sensitivity C-reactive protein levels among people living with HIV on dolutegravir and ritonavir-boosted atazanavir-based antiretroviral therapy: a comparative cross-sectional study.

Background: After the introduction of antiretroviral therapy, the care given to people living with HIV has become complicated by the appearance of comorbidities as a result of HIV and HAART toxicities, in which cardiovascular disease got the most attention. So, this study aimed to assess serum uric acid and high-sensitivity C-reactive protein levels among people living with HIV on dolutegravir (DTG) and ritonavir-boosted atazanavir (ATV/r)-based therapy. Methods: An institutional-based comparative cross-sectional study was conducted from November 4, 2021, to January 4, 2022. An equal number of dolutegravir- and ritonavir-boosted atazanavir-treated patients (n = 86 each) were enrolled. A consecutive sampling method was used to select participants. Data were entered into Epidata version 4.6, exported to SPSS version 25.0, and analyzed using Chi-square, Student's t-test, Mann-Whitney U-test, and logistic regression. Statistical significance was set at p < 0.05. Results: The prevalence of hyperuricemia and high-sensitivity C-reactive protein levels ≥2 mg/L were 46.5% (40/86) and 24.4% (21/86) in the DTG group, and 30.2% (26/86) and 44.2 (38/86) in the ATV/r group, respectively. When compared to ATV/r, a higher mean level of uric acid was found among DTG-based regimens (5.38 mg/dL). Duration of ART (AOR = 2, 95% CI: 1.2, 4.4) and DTG-based regimen (AOR = 1.9, 95% CI: 1.04, 3.8) were significant predictors of developing hyperuricemia. ATV/r-based regimen (AOR = 3, 95% CI: 1.5, 8.3) and high waist circumference (AOR = 2.5, 95% CI: 1, 3.5) were significantly associated with increased high-sensitivity C-reactive protein levels. Conclusion: It is observed that DTG-based and ATV/r-based ART are associated with hyperuricemia and increased high-sensitivity C-reactive protein levels, respectively. Therefore, it is important to consider and evaluate serum uric acid and high-sensitivity C-reactive protein levels in patients taking DTG and ATV/r-based ART, as well as among those on HAART for years and with a higher waist circumference, so as to detect and prevent early the risk of having CVD.

Advances in molecular basis of response to immunotherapy for penile cancer: better screening of responders.

Penile cancer is a rare malignant tumor of the male urinary system. The treatment benefit of standard first-line chemotherapy is not ideal for patients with locally advanced or metastatic lymph nodes. Immunotherapy has brought new treatment strategies and opportunities for patients with penile cancer. At present, clinical studies on immunotherapy for penile cancer have been reported, and the results show that it is effective but not conclusive. With the development of immunotherapy and the progress of molecular research technology, we can better screen the immunotherapy response population and explore new combination treatment regimens to evaluate the best combination regimen and obtain the optimal treatment options, which is also an important research direction for the immunotherapy of penile cancer in the future.

Computational modeling and uncertainty prediction of hyperelastic constitutive responses of damaged brain tissue under different temperature and strain rates.

The effect of strain rate and temperature on the hyperelastic material stress-strain characteristics of the damaged porcine brain tissue is evaluated in this present work. The desired constitutive responses are obtained using the commercially available finite element (FE) tool ABAQUS, utilizing 8-noded brick elements. The model's accuracy has been verified by comparing the results from the previously published literature. Further, the stress-strain behavior of the brain tissue is evaluated by varying the damages at various strain rates and temperatures (13, 20, 27, and 37°C) under compression test. Additionally, the sensitivity analysis of the model is computed to check the effect of input parameters, that is, the temperature, strain rate, and damages on the material properties (shear modulus). The modeling and discussion sections enumerate the inclusive features and model capabilities.

Application of the international system for reporting serous fluid cytopathology on pleural effusion cytology with paired pleural biopsy: A new insight and novel approach on risk of malignancy.

INTRODUCTION: The risk of malignancy (ROM) remains an area of interest for further evaluation in reporting systems including in International System for reporting serous fluid cytopathology (TIS), which is a standardized system for reporting effusion cytology. Herein, we report our findings in further investigation of ROM in TIS by studying on paired pleural effusion specimens and corresponding pleural biopsies with emphasis on negative for malignancy, and atypia of undetermined significance categories. MATERIALS AND METHODS: The  Johns Hopkins Hospital pathology database was retrospectively searched for patients with a pleural biopsy (PBX) and a paired pleural effusion (PF) cytology specimens over a 4-year period. We employed the TIS categories. The following statistical parameters were evaluated: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ROM. RESULTS: A total of 223 patient cases were included. Effusions TIS reclassification and ROM were as follows: 1.8% non-diagnostic (ROM 75%), 75.8% negative for malignancy (ROM 23%), 4.9% atypical cells of undetermined significance (ROM 45%), 2.2% suspicious for malignancy (ROM 80%), and 15.2% malignant (ROM 100%). Overall accuracy, sensitivity, specificity, PPV and NPV were calculated and were 79.4%, 45%, 97.7%, 91.2% and 77%, respectively. Among, discordant cases diagnosed negative for malignancy on PF and positive for malignancy on PBX, there were significant number of lymphomas, mesotheliomas, and sarcomas. Lung cancer was the most common carcinoma; however, rare types of carcinomas were noted. Cells blocks and immunohistochemistry (IHC) studies were utilized to confirm either malignant conditions or rule out malignancy in both cell blocks and histology biopsies. CONCLUSION: This study demonstrates the high specificity and ROM for 'malignant' and 'suspicious for malignancy' categories in the TIS reporting system and highlights the modest negative predictive value for the 'negative for malignancy' category. Although Tissue biopsies are usually considered as 'gold standard', any definitive diagnosis of malignancy of body fluid should be considered positive for malignancy in further clinical decision-making.

Resistance exercise breaks during prolonged sitting augment the blood flow response to a subsequent oral glucose load in sedentary adults.

Sitting-induced impairments in postprandial blood flow are an important link between sedentary behaviour and cardiometabolic disease risk. The objective of this work was to examine the effects of resistance exercise breaks (REB) performed every 30 min during an otherwise sedentary 3-h period on the vasodilatory response to a subsequent oral glucose load in sedentary adults. Twenty-four sedentary adults (27 ± 7 years, 16 females) completed two conditions. Fasting blood glucose, insulin, popliteal artery blood flow (PABF) and gastrocnemius perfusion were measured immediately before standardized breakfast consumption. After breakfast, the 3-h REB or uninterrupted (SIT) intervention period commenced. Participants sat at a workstation, and popliteal artery shear rate (PASR) was measured 60 and 120 min into this period. In the REB condition, participants performed a 3-min REB (3 × [20 s squats, 20 s high knees, 20 s calf raises]) every 30 min. Following the intervention period, baseline measurements were repeated. Participants then consumed a 75 g glucose beverage, and PABF and perfusion were measured every 30-60 min for the following 120 min. Relative to SIT, REB increased PASR at 60 min (+31.4 ± 9.2/s, P = 0.037) and 120 min (+37.4 ± 10.2/s, P = 0.019) into the intervention period. Insulin and glucose increased (P < 0.001) in response to glucose consumption, with no differences between conditions (P ≥ 0.299). In response to the glucose load, perfusion (1.57 vs. 1.11 mL/100 mL/min, P = 0.023) and PABF (+45.3 ± 11.8 mL/min, P = 0.001) were greater after REB versus SIT. Performing 3-min REB every 30 min during an otherwise sedentary 3-h period augmented leg blood flow responses to an oral glucose load. HIGHLIGHTS: What is the central question of this study? Can 3-min resistance exercise breaks (REB) performed during an otherwise sedentary 3-h period augment the vasodilatory response to a subsequent oral glucose load in sedentary adults? What is the main finding and its importance? Performing 3-min REB, which included squats, high knees, and calf raises, every 30 min augmented lower limb blood flow responses to a subsequent oral glucose load compared to 3 h of uninterrupted sitting in sedentary adults. Sitting-induced impairment in postprandial vasodilatory function has been identified as a link between sedentary behaviour and cardiometabolic disease. Thus, the current study presents a potentially effective strategy to offset this risk.

Insulin sensitivity, disposition index and insulin clearance in cystic fibrosis: a cross-sectional study.

AIMS/HYPOTHESIS: The aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency. METHODS: In a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups. We used three different oral minimal models to assess insulin secretion, insulin sensitivity and insulin clearance during the OGTT. We evaluated insulin secretion using total secretion (Φ total), first-phase secretion (Φ dynamic) and second-phase secretion (Φ static) from the model, and we estimated the disposition index by multiplying Φ total and insulin sensitivity. RESULTS: Among 61 participants (NGT 21%, EGI 33%, IGT 16%, CFRD 30%), insulin secretion indices (Φ total, dynamic and static) were significantly lower in the CFRD group compared with the other groups. Insulin sensitivity declined with worsening in glucose tolerance (p value for trend <0.001) and the disposition index declined between NGT and EGI and between IGT and CFRD. Those with CFRD had elevated insulin clearance compared with NGT (p=0.019) and low insulin secretion (Φ total) was also associated with high insulin clearance (p<0.001). CONCLUSIONS/INTERPRETATION: In individuals with PI-CF, disposition index declined with incremental impairment in glucose tolerance due to a reduction in both insulin secretion and insulin sensitivity. Moreover in CF, reduced insulin secretion was associated with higher insulin clearance.

Ultra-high-sensitive plasmonic sensor based on asymmetric hexagonal nano-ring resonator for cancer detection.

A highly sensitive sensor based on two metal-insulator-metal waveguides coupled to an asymmetric hexagonal nano-ring resonator detecting cancerous cells is proposed. This novel design is utilized to facilitate the sensing of human cells. The sensing mechanism of the presented optical structure can act as a refractive index measurement in biological, chemical, biomedical diagnosis, and bacteria detection, which leads to achieving high sensitivity in the structure. The main goal is to achieve the highest sensitivity concerning the optimum design. As a result, the sensitivity of the designed topology reaches a maximum value of about 1800 nm/RIU (nm/refractive index unit) by controlling the angle of the resonator. It is evident that the sensitivity parameter is improved, and the reason for the increase in sensitivity is due to the asymmetry of the resonator, which has an 81 % increase in sensitivity compared to the symmetrical resonator, especially for blood cancer cells. The maximum quality factor obtains 131.65 with a FOM of 90.4 (RIU-1). The sensing performance of this proposed structure is numerically investigated using the finite difference time domain (FDTD) method with the perfectly matched layer (PML). Accordingly, the suggested high sensitivity sensor makes this structure a promising therapeutic candidate for sensing applications that can be used in on-chip optical devices to produce highly complex integrated circuits.

A New Approach Refined Probabilistic Health Risk Assessment of Shaoguan Smelter Based on Microenvironment - Guangdong Province, China, 2021.

Introduction: This study introduces a novel method for developing an advanced exposure conceptual model tailored for health risk assessment, focusing on microenvironments. Methods: The research was conducted at a major smelter in China to assess the health risks associated with trace metals (TMs) pollutants in the facility and the surrounding soil. Results: Deterministic risk assessment indicated that cobalt, cadmium, antimony, manganese, arsenic, plumbum, and mercury (Co, Cd, Sb, Mn, As, Pb, and Hg) necessitated further evaluation through probabilistic risk assessment to assess potential health risks to residents. The 95% quantile concentrations of other TMs were found to be within acceptable health risk limits. For the probabilistic risk assessment, exposure parameters such as body weight, respiration rate, and exposure duration were collected using a questionnaire. This targeted assessment of the residential microenvironment revealed it as the site of the highest carcinogenic (CR) and non-carcinogenic risks (NCR), with values ranging from 2.84×10-5 to 6.7×10-5 and 1.59 to 5.57, respectively. Conclusion: The primary contaminants posing the greatest health risks in residential and industrial areas have been identified as As, Pb, and Mn. The probabilistic health risk model, which focuses on microenvironmental factors, yields more precise results and offers a valuable tool for managing soil health risks.

Trait-Anxious People Take Longer to Search for Happy Faces in the Presence of Neutral and Fearful Distractors.

A large body of evidence suggests that processing of affective information is typically disrupted in anxiety. It has also been hypothesized that anxious individuals are less able to evaluate contextual cues and to respond in an adaptive way to stress. In the present study, 25 participants (16 females; 9 males) scoring high (scores of 45 or above) and 26 participants (13 females; 13 males) scoring low (scores of 35 and below) on a standardized measure of trait anxiety performed an emotion search task to investigate attentional biases when the task provides an explicit emotional context. An emotional context was set in each block by asking participants to look as quickly as possible at a face expressing a specific emotion, while eye movements were being recorded. On each trial, two faces appeared, one of them expressing the target emotion and the other one expressing a distractor emotion. High trait-anxious participants showed slower response times (time to look at the instructed emotion), regardless of the affective context, compared to the control group. Additionally, we found slower responses to happy faces (positive context) in the anxious group in the presence of neutral and fearful distractors. Cognitive control may therefore be disrupted in anxiety, as anxious people take longer to process (search for) happy faces, presumably because attentional resources are drawn by neutral and fearful distractors. Those differences were not observed in a simple reaction times task, which suggests that attentional biases, and not differential processing of low-level facial features, are responsible for those differences.

Screening, epidemic trends and drug sensitivity analysis of nontuberculous mycobacteria in a local area of China.

OBJECTIVE: To analyze the isolation rate, prevalence trends, species distribution, and drug sensitivity of non-tuberculous mycobacteria (NTM) in Anhui Province, providing a reference for diagnosis and treatment strategies. METHODS: Specimens from suspected mycobacterial infection patients at Anhui Chest Hospital (including outpatients and inpatients) from January 2021 to December 2023 were cultured. Identified NTM strains were analyzed for species distribution and drug sensitivity. RESULTS: Of 10,519 mycobacteria strains cultured, 1,589 were NTM (15.11%). The top four species were Mycobacterium intracellulare (75.36%), Mycobacterium abscessus (11.78%), Mycobacterium kansasii (7.09%), and Mycobacterium avium (2.85%). NTM strains showed high sensitivity to amikacin and clarithromycin (≥90%) and significant sensitivity to rifabutin, moxifloxacin, and rifampicin (89.03%-79.61%). They exhibited high resistance to imipenem/cilastatin, sulfamethoxazole, minocycline, and doxycycline (≥95%). CONCLUSION: NTM isolation rates in Anhui have remained stable, with the predominant species being M. intracellulare, M. kansasii, M. abscessus, and M. avium. NTM strains are highly sensitive to amikacin, clarithromycin, rifabutin, moxifloxacin, and rifampicin. These findings can guide diagnosis, treatment strategies, and drug selection for NTM disease in Anhui Province.

Drug sensitivity testing during dental pulp-dentin complex repair: its effect on treatment outcome and prognosis.

OBJECTIVE: To assess the efficacy of targeted therapy based on drug sensitivity testing (DST) results in patients with acute pulpitis (AP). METHODS: A total of 80 cases of AP were included retrospectively and divided into two groups: control (Ctrl) group (conventional drug palliative therapy, n=40) and experimental (Exp) group (DST + non-resistant drugs, n=40). The clinical data and laboratory examination data of patients, including bacterial culture data, drug sensitivity test results, Ca and P contents in dental pulp, visual analogue scale (AVS), treatment satisfaction, and dental pulp incidence, were collected and analyzed. RESULTS: Prevotella melaninogenica, Fusobacterium nucleatum, and Porphyromonas gingivalis exhibited higher resistance rates (RS) to penicillin and amoxicillin but no resistance to imipenem and metronidazole. The content of Ca and P in the dental pulp of the Exp group patients was significantly higher than that of the Ctrl group (P=0.006). The total response rate (95% vs. 77.5%, P=0.018) and overall patient satisfaction (92.5% vs. 80%, P=0.021) were also significantly higher in the Exp group than in the Ctrl group. Additionally, when the follow-up duration exceeded 1 year, the incidence of dental pulp reactions in the Exp group was significantly lower than that of the Ctrl group (P=0.026). CONCLUSIONS: These findings suggest that Gram-negative anaerobes are the predominant oral pathogens in patients with AP. Imipenem and metronidazole demonstrate the most effective anti-infective properties against these anaerobes. Utilizing DST to select non-resistant drugs for treatment prior to therapy effectively enhances clinical outcomes for patients with AP.

Prognostic significance of the hs-CRP/Alb ratio for cardiovascular events in patients with end-stage renal disease undergoing maintenance hemodialysis.

OBJECTIVE: To evaluate the predictive power of the high-sensitivity C-reactive protein (hs-CRP) to albumin (Alb) ratio for cardiovascular events in patients receiving maintenance hemodialysis (MHD) for end-stage renal disease (ESRD). METHODS: This retrospective study enrolled 202 ESRD patients undergoing MHD at Bobai County People's Hospital from November 2020 to November 2022, with follow-up extending to November 2023. Patients were divided into two groups based on the occurrence of cardiovascular events during follow-up: the occurrence group (n = 92) and the non-occurrence group (n = 110). Clinical data were compared between these groups. Independent risk factors for cardiovascular events post-MHD were identified using a multivariate logistic regression model. The hs-CRP/Alb ratio's predictive utility was assessed through receiver operating characteristic (ROC) curve analysis, establishing an optimal cutoff value. A decision tree prediction model was developed to further delineate the probability of cardiovascular events. RESULTS: The occurrence group was older and had a longer duration of dialysis compared to the non-occurrence group (P < 0.05). They also showed a higher prevalence of diabetic and hypertensive nephropathy and a higher proportion of smokers (all P < 0.05). Notably lower levels of hemoglobin (HGB), triglycerides, total cholesterol, low-density lipoprotein, albumin (Alb), and calcium were detected (all P < 0.05), whereas ß2-microglobulin (ß2-mg), hs-CRP, phosphorus, and the hs-CRP/Alb ratio were markedly increased (all P < 0.05). Multivariate analysis revealed diabetic nephropathy or hypertensive nephropathy, a high hs-CRP/Alb ratio, and elevated phosphorus levels as risk factors for cardiovascular events, while high hemoglobin levels were protective (P < 0.05). The ROC analysis indicated the hs-CRP/Alb ratio (AUC = 0.884) outperformed other predictors with an optimal cutoff at 0.111. Patients with a hs-CRP/Alb ratio ≥ 0.111 were found to have a 29-fold increased risk of cardiovascular events (95% CI: 11.304-74.842). CONCLUSION: The hs-CRP/Alb ratio is a significant predictive biomarker for cardiovascular events in ESRD patients undergoing MHD. An elevated hs-CRP/Alb ratio is associated with an increased risk of cardiovascular events, underscoring its utility in this patient population.

Ferroptosis-related LINC02535/has-miR-30c-5p/EIF2S1 axis as a novel prognostic biomarker involved in immune infiltration and progression of PDAC.

BACKGROUND: PDAC, also known as pancreatic ductal adenocarcinoma, is often diagnosed at a late stage due to nonspecific symptoms and a distinct lack of reliable biomarkers for timely diagnosis. Ferroptosis, a novel non-apoptotic cell death mode discovered in recent years, is strongly linked to the progression of PDAC and the evasion of the immune system. The objective of this study is to discover a novel ceRNA biomarker associated with ferroptosis and investigate its possible molecular mechanisms and therapeutic potential in PDAC. METHODS: Based on the FerrDb and TCGA databases, the R survival package was used to screen for ferroptosis-related mRNAs associated with PDAC prognosis. The ferroptosis-related ceRNA network was identified by miRTarBase, miRNet, and starBase and visualized using Cytoscape. The LASSO regression analysis was used to build a risk model associated with ceRNA. Additionally, we investigated the correlation between the ceRNA axis and the infiltration of immune cells in PDAC by employing the ssGSEA algorithm. Spearman correlation analysis was used to investigate the association between the ceRNA network and the expression levels of immune checkpoint genes in PDAC. The prediction of potential medications for PAAD patients with high risk scores was conducted using the R package oncoPredict and the Genomics of Drug Sensitivity in Cancer (GDSC) repository. Expression levels of LINC02535 in clinical specimens and PDAC cell lines were determined using qRT-PCR. CCK-8, colony formation, EdU, wound healing, and transwell assays were performed to assess the impact of reducing LINC02535 on the growth, migration, and invasion of PDAC cell lines BxPC3 and PANC1. RESULTS: We first discovered a new LINC02535/miR-30c-5p/EIF2S1 axis associated with ferroptosis and created a prognostic nomogram for predicting overall survival. Meanwhile, the risk scores of the LINC02535/miR-30c-5p/EIF2S1 axis associated with ferroptosis were linked to immune subtypes in PDAC. The high immune infiltration subtype exhibited elevated ceRNA risk scores and EIF2S1 expression. The correlation analysis revealed a positive correlation between ceRNA risk scores and four immune cells, namely Activated CD4 T cell, Memory B cell, Neutrophil, and Type 2 T helper cell, as well as four immune checkpoint genes, namely CD274, HAVCR2, PDCD1LG2, and TIGIT. The analysis of drug sensitivity indicated that individuals with a high-risk score may exhibit greater sensitivity to inhibitors targeting MEK1/2 compared to those with a low-risk score. In our validation experiments, it was observed that the expression of LINC02535 was increased in both PDAC tissues and cell lines. Additionally, the inhibition of LINC02535 resulted in decreased proliferation, migration, and invasion of PDAC cells. Rescue experiments demonstrated that LINC02535 promoted PDAC cell growth and metastasis by upregulating EIF2S1 expression. CONCLUSION: To summarize, a novel ferroptosis-associated LINC02535/miR-30c-5p/EIF2S1 ceRNA network for PDAC patients was established. The analysis of this network's functionality offers potential insights for clinical decision-making and the advancement of precision medicine.

Treating heart failure by targeting the vagus nerve.

Increased sympathetic and reduced parasympathetic nerve activity is associated with disease progression and poor outcomes in patients with chronic heart failure. The demonstration that markers of autonomic imbalance and vagal dysfunction, such as reduced heart rate variability and baroreflex sensitivity, hold prognostic value in patients with chronic heart failure despite modern therapies encourages the research for neuromodulation strategies targeting the vagus nerve. However, the approaches tested so far have yielded inconclusive results. This review aims to summarize the current knowledge about the role of the parasympathetic nervous system in chronic heart failure, describing the pathophysiological background, the methods of assessment, and the rationale, limits, and future perspectives of parasympathetic stimulation either by drugs or bioelectronic devices.

Detection of residual pluripotent stem cells in cell therapy products utilizing droplet digital PCR: an international multisite evaluation study.

The presence of residual undifferentiated pluripotent stem cells (PSCs) in PSC-derived cell therapy products (CTPs) is a major safety issue for their clinical application, due to the potential risk of PSC-derived tumor formation. An international multidisciplinary multisite study to evaluate a droplet digital PCR (ddPCR) approach to detect residual undifferentiated PSCs in PSC-derived CTPs was conducted as part of the Health and Environmental Sciences Institute Cell Therapy-TRAcking, Circulation & Safety Technical Committee. To evaluate the use of ddPCR in quantifying residual iPSCs in a cell sample, different quantities of induced pluripotent stem cells (iPSCs) were spiked into a background of iPSC-derived cardiomyocytes (CMs) to mimic different concentrations of residual iPSCs. A one step reverse transcription ddPCR (RT-ddPCR) was performed to measure mRNA levels of several iPSC-specific markers and to evaluate the assay performance (precision, sensitivity, and specificity) between and within laboratories. The RT-ddPCR assay variability was initially assessed by measuring the same RNA samples across all participating facilities. Subsequently, each facility independently conducted the entire process, incorporating the spiking step, to discern the parameters influencing potential variability. Our results show that a RT-ddPCR assay targeting ESRG, LINC00678, and LIN28A genes offers a highly sensitive and robust detection of impurities of iPSC-derived CMs and that the main contribution to variability between laboratories is the iPSC-spiking procedure, and not the RT-ddPCR. The RT-ddPCR assay would be generally applicable for tumorigenicity evaluation of PSC-derived CTPs with appropriate marker genes suitable for each CTP.

Spatio-temporal characteristics and multi-scale risk identification of pollution load based on sensitivity analysis in small watersheds located in Tuojiang River Basin, China.

High-quality development of water resources supports high-quality socio-economic development. High-quality development connects high-quality life, and clarifying the key management contents of small watersheds plays an important role in building ecologically clean small watersheds and promoting regional production and life. Previous research on pollution loads has focused on examining the impact of various external drivers on pollution loads but still lacks research on the impact of changes in pollution sources themselves on pollution loads. In this study, sensitivity analysis was used to determine the impact of changes from different sources on the total pollution loads, which can recognize the critical pollution sources. We first employed the pollutant discharge coefficient method to quantify non-point source pollution loads in the small watershed in the upstream Tuojiang River basin from 2010 to 2021. Then, combination sensitivity analysis with Getis-Ord Gi* was used to identify the critical sources and their crucial areas at the global, districts (counties), and towns (streets) scales, respectively. The results indicate: (1) The pollution loads of COD, NH3-N, TN, and TP all show a decreasing trend, reducing by 18.3%, 16.2%, 18.6%, and 28.1% from 2010 to 2021, respectively; (2) Livestock and poultry breeding pollution source is the most critical source for majority areas across watershed; (3) High-risk areas are mainly concentrated in Jingyang district and its subordinate towns (streets). There is a trend of low-pollution risk areas transitioning to high-pollution risk areas, with high-risk areas predominantly concentrated in the southeast and exhibiting a noticeable phenomenon of pollution load spilling around. This study can promote other similar small watersheds, holding significant importance for non-point source pollution control in small watersheds.

Cyber dating abuse perpetration and victimization among Chinese college students with a history of peer phubbing: psychological resilience moderates the indirect effect of rejection sensitivity.

BACKGROUND: As emerging adults are increasingly reliant on instant messaging applications for communication with romantic partners, cyber dating abuse perpetration (CDAP) and victimization (CDAV) have proliferated. This has aroused the high attention of researchers. This study aimed to explore the mechanism of the influence of peer phubbing on CDAP and CDAV in Chinese context. METHODS: 566 Chinese college students (average age of 19.31 years, 47.7% females) were investigated with the generic scale of being phubbed, rejection sensitivity questionnaire, Chinese version of resilience scale and cyber dating abuse questionnaire. The data were analyzed by using a moderated mediation model with SPSS and the PROCESS. RESULTS: The results revealed that: (1) peer phubbing had a significant positive predictive effect on CDAP (ß = .32, p < .001) and CDAV (ß = .43, p < .001) respectively. (2) Rejection sensitivity played a partial mediating role both between peer phubbing and CDAP (indirect effect = .12, 95% CI = [.05, .18], accounting for 37.5%) and CDAV (indirect effect = .09, 95% CI = [.05, .14], accounting for 20.9%. (3) The first half (ß = - .27, p < .001) of the indirect effect of peer phubbing on CDAP and CDAV are weakened by psychological resilience, and the direct paths were also weakened by psychological resilience(ß = - .13, p < .001;ß = - .16, p < .001). CONCLUSION: These findings highlight the importance of discerning the mechanisms moderating the mediated paths linking peer phubbing to CDAP and CDAV. The results also underline the importance of implementing measures and interventions to use the protective role of psychological resilience on college students' CDAP and CDAV.

Pan-cancer analyses reveal the molecular and clinical characteristics of TET family members and suggests that TET3 maybe a potential therapeutic target.

The Ten-Eleven Translocation (TET) family genes are implicated in a wide array of biological functions across various human cancers. Nonetheless, there is a scarcity of studies that comprehensively analyze the correlation between TET family members and the molecular phenotypes and clinical characteristics of different cancers. Leveraging updated public databases and employing several bioinformatics analysis methods, we assessed the expression levels, somatic variations, methylation levels, and prognostic values of TET family genes. Additionally, we explored the association between the expression of TET family genes and pathway activity, tumor microenvironment (TME), stemness score, immune subtype, clinical staging, and drug sensitivity in pan-cancer. Molecular biology and cytology experiments were conducted to validate the potential role of TET3 in tumor progression. Each TET family gene displayed distinct expression patterns across at least ten detected tumors. The frequency of Single Nucleotide Variant (SNV) in TET genes was found to be 91.24%, primarily comprising missense mutation types, with the main types of copy number variant (CNV) being heterozygous amplifications and deletions. TET1 gene exhibited high methylation levels, whereas TET2 and TET3 genes displayed hypomethylation in most cancers, which correlated closely with patient prognosis. Pathway activity analysis revealed the involvement of TET family genes in multiple signaling pathways, including cell cycle, apoptosis, DNA damage response, hormone AR, PI3K/AKT, and RTK. Furthermore, the expression levels of TET family genes were shown to impact the clinical staging of tumor patients, modulate the sensitivity of chemotherapy drugs, and thereby influence patient prognosis by participating in the regulation of the tumor microenvironment, cellular stemness potential, and immune subtype. Notably, TET3 was identified to promote cancer progression across various tumors, and its silencing was found to inhibit tumor malignancy and enhance chemotherapy sensitivity. These findings shed light on the role of TET family genes in cancer progression and offer insights for further research on TET3 as a potential therapeutic target for pan-cancer.