T-cell receptor diversity and allergen sensitivity in childhood asthma and atopic dermatitis.

BACKGROUND: Childhood allergies of asthma and atopic dermatitis (AD) involve an overactive T-cell immune response triggered by allergens. However, the impact of T-cell receptor (TCR) repertoires on allergen sensitization and their role in mediating different phenotypes of asthma and AD in early childhood remains unclear. METHODS: A total of 78 children, comprising 26 with asthma alone, 26 with AD alone, and 26 healthy controls (HC), were enrolled. TCR repertoire profiles were determined using a unique molecular identifier system for next-generation sequencing. Integrative analyses of their associations with allergen-specific IgE levels and allergies were performed. RESULTS: The diversity in TCR alpha variable region (TRAV) genes of TCR repertoires and complementarity determining region 3 (CDR3) clonality in TRAV/TRBV (beta) genes were significantly higher in children with AD compared with those with asthma and HC (p < .05). Compared with HC, the expression of TRAV13-1 and TRAV4 genes was significantly higher in both asthma and AD (p < .05), with a significant positive correlation with mite-specific IgE levels (p < .01). In contrast, TRBV7-9 gene expression was significantly lower in both asthma and AD (p < .01), with this gene showing a significant negative correlation with mite-specific IgE levels (p < .01). Furthermore, significantly higher TRAV8-3 gene expression, positively correlated with food-specific IgE levels, was found in children with AD compared with those with asthma (p < .05). CONCLUSION: Integrated TCR repertoires analysis provides clinical insights into the diverse TCR genes linked to antigen specificity, offering potential for precision immunotherapy in childhood allergies.

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving fixed-dose pangenotypic direct-acting antivirals.

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.

The Preparation and Dust Suppression Performance Evaluation of Iron Ore Tailing-Based Cementitious Composites.

In order to comprehensively utilize iron ore tailings (IOTs), the possibility of using IOTs as raw materials for the preparation of cementitious composites (IOTCCs) was investigated, and IOTCC was further applied to mine interface pollution control. The mechanical properties, hydration products, wind erosion resistance, and freeze-thaw (F-T) cycle resistance of IOTCCs were evaluated rigorously. The activity index of iron tailings increased from 42% to 78% after grinding for 20 s. The IOTCC was prepared by blending 86% IOT, 10% ground granulated blast-furnace slag (GGBS), and 4% cement clinker. Meanwhile, the hydration products mainly comprised ettringite, calcium hydroxide, and C-S-H gel, and they were characterized via XRD, IR, and SEM. It was observed that ettringite and C-S-H gel were principally responsible for the strength development of IOTCC mortars with an increase in curing time. The results show that the kaolinite of the tailings was decomposed largely after mechanical activation, which promoted the cementitious property of IOT.

Understanding the Disparities of PM2.5 Air Pollution in Urban Areas via Deep Support Vector Regression.

In densely populated urban areas, PM2.5 has a direct impact on the health and quality of residents' life. Thus, understanding the disparities of PM2.5 is crucial for ensuring urban sustainability and public health. Traditional prediction models often overlook the spillover effects within urban areas and the complexity of the data, leading to inaccurate spatial predictions of PM2.5. We propose Deep Support Vector Regression (DSVR) that models the urban areas as a graph, with grid center points as the nodes and the connections between grids as the edges. Nature and human activity features of each grid are initialized as the representation of each node. Based on the graph, DSVR uses random diffusion-based deep learning to quantify the spillover effects of PM2.5. It leverages random walk to uncover more extensive spillover relationships between nodes, thereby capturing both the local and nonlocal spillover effects of PM2.5. And then it engages in predictive learning using the feature vectors that encapsulate spillover effects, enhancing the understanding of PM2.5 disparities and connections across different regions. By applying our proposed model in the northern region of New York for predictive performance analysis, we found that DSVR consistently outperforms other models. During periods of PM2.5 surges, the R-square of DSVR reaches as high as 0.729, outperforming non-spillover models by 2.5 to 5.7 times and traditional spatial metric models by 2.2 to 4.6 times. Therefore, our proposed model holds significant importance for understanding disparities of PM2.5 air pollution in urban areas, taking the first steps toward a new method that considers both the spillover effects and nonlinear feature of data for prediction.

Machine learning-based longitudinal prediction for GJB2-related sensorineural hearing loss.

BACKGROUND: Recessive GJB2 variants, the most common genetic cause of hearing loss, may contribute to progressive sensorineural hearing loss (SNHL). The aim of this study is to build a realistic predictive model for GJB2-related SNHL using machine learning to enable personalized medical planning for timely intervention. METHOD: Patients with SNHL with confirmed biallelic GJB2 variants in a nationwide cohort between 2005 and 2022 were included. Different data preprocessing protocols and computational algorithms were combined to construct a prediction model. We randomly divided the dataset into training, validation, and test sets at a ratio of 72:8:20, and repeated this process ten times to obtain an average result. The performance of the models was evaluated using the mean absolute error (MAE), which refers to the discrepancy between the predicted and actual hearing thresholds. RESULTS: We enrolled 449 patients with 2184 audiograms available for deep learning analysis. SNHL progression was identified in all models and was independent of age, sex, and genotype. The average hearing progression rate was 0.61 dB HL per year. The best MAE for linear regression, multilayer perceptron, long short-term memory, and attention model were 4.42, 4.38, 4.34, and 4.76 dB HL, respectively. The long short-term memory model performed best with an average MAE of 4.34 dB HL and acceptable accuracy for up to 4 years. CONCLUSIONS: We have developed a prognostic model that uses machine learning to approximate realistic hearing progression in GJB2-related SNHL, allowing for the design of individualized medical plans, such as recommending the optimal follow-up interval for this population.

Comparison of diagnostic performance among Abbott RealTime HCV Genotyping II, Abbott HCV Genotype plus RUO, and Roche Cobas HCV Genotyping assays for hepatitis C virus genotyping.

Comparison of diagnostic accuracy for commercial hepatitis C virus (HCV) genotyping (Abbott RealTime HCV Genotyping II, Roche Cobas Genotyping) and investigational Abbott HCV Genotype plus RUO assays designed to discriminate genotype (GT)-1a, 1b or 6 in cases of ambiguous GT from the Abbott commercial assay remains limited. 743 HCV-viremic samples were subjected to analysis using Abbott and Roche commercial as well as Abbott HCV Genotype plus RUO assays. Next-generation sequencing (NGS) targeting core region was employed as the reference standard. Diagnostic accuracy was reported as the number of participants (percentages) along with 95% confidence intervals (CIs). Using NGS, 741 samples (99.7%) yielded valid genotyping results. The diagnostic accuracies were 97.6% (95% CI: 96.1%-98.5%) and 95.3% (95% CI: 93.4%-96.6%) using Abbott and Roche commercial assays (p = 0.0174). Abbott commercial assay accurately diagnosed HCV GT-6a and 6w, whereas Roche commercial assay accurately diagnosed HCV GT-6a. Both assays demonstrated low accuracies for HCV GT-6b, 6e, 6g, and 6n. Abbott HCV Genotype plus RUO assay discriminated 13 of the 14 samples (92.9%; 95% CI: 64.2%-99.6%) that yielded ambiguous GT. Both assays were capable of diagnosing mixed HCV infections when the minor genotype comprised >8.4% of the viral load. The diagnostic performance of commercial HCV genotyping assays is commendable. Abbott assay demonstrated superior performance compared to Roche assay in diagnosing HCV GT-6. Abbott HCV Genotype plus RUO assay aids in discriminating ambiguous GT. Both commercial assays are proficient in diagnosing mixed HCV infections at a cut-off viral load of 8.4% in minor genotype.

Co-culture of STRO1 + human gingival mesenchymal stem cells and human umbilical vein endothelial cells in 3D spheroids: enhanced in vitro osteogenic and angiogenic capacities.

Stem cell spheroid is a promising graft substitute for bone tissue engineering. Spheroids obtained by 3D culture of STRO1+ Gingival Mesenchymal Stem Cells (sGMSCs) (sGMSC spheroids, GS) seldom express angiogenic factors, limiting their angiogenic differentiation in vivo. This study introduced a novel stem cell spheroid with osteogenic and angiogenic potential through 3D co-culture of sGMSCs and Human Umbilical Vein Endothelial Cells (HUVECs) (sGMSC/HUVEC spheroids, GHS). GHS with varying seeding ratios of sGMSCs to HUVECs (GHR) were developed. Cell fusion within the GHS system was observed via immunofluorescence. Calcein-AM/PI staining and chemiluminescence assay indicated cellular viability within the GHS. Furthermore, osteogenic and angiogenic markers, including ALP, OCN, RUNX2, CD31, and VEGFA, were quantified and compared with the control group comprising solely of sGMSCs (GS). Incorporating HUVECs into GHS extended cell viability and stability, initiated the expression of angiogenic factors CD31 and VEGFA, and upregulated the expression of osteogenic factors ALP, OCN, and RUNX2, especially when GHS with a GHR of 1:1. Taken together, GHS, derived from the 3D co-culture of sGMSCs and HUVECs, enhanced osteogenic and angiogenic capacities in vitro, extending the application of cell therapy in bone tissue engineering.

Integrating Genome-wide Polygenic Risk Scores with Non-genetic Models to Predict Surgical Site Infection after Total Knee Arthroplasty Using United Kingdom Biobank Data.

BACKGROUND: Prediction of the risk of developing surgical site infection (SSI) in patients following total knee arthroplasty (TKA) is of clinical importance. Genetic susceptibility is involved in developing TKA-related SSI. Previously reported models for predicting SSI were constructed using non-genetic risk factors without incorporating genetic risk factors. To address this issue, we performed a genome-wide association study (GWAS) using the UK Biobank database. METHODS: Adult patients who underwent primary TKA (n = 19,767) were analyzed and divided into SSI (n = 269) and non-SSI (n = 19,498) cohorts. Non-genetic covariates, including demographic data and preoperative comorbidities, were recorded. Genetic variants associated with SSI were identified by GWAS and included to obtain standardized polygenic risk scores (zPRS, an estimate of genetic risk). Prediction models were established through analyses of multivariable logistic regression and the receiver operating characteristic (ROC) curve. RESULTS: There were four variants (rs117896641, rs111686424, rs8101598, and rs74648298) achieving genome-wide significance that were identified. The logistic regression analysis revealed seven significant risk factors: increasing zPRS, decreasing age, men, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, and peripheral vascular disease. The areas under the ROC curve (AUC) were 0.628 and 0.708 when zPRS (model 1) and non-genetic covariates (model 2) were used as predictors, respectively. The AUC increased to 0.76 when both zPRS and non-genetic covariates (model 3) were used as predictors. A risk-prediction nomogram was constructed based on model 3 to visualize the relative effect of statistically significant covariates on the risk of SSI and predict the probability of developing SSI. Age and zPRS were the top two covariates that contributed to the risk, with younger age and higher zPRS associated with higher risks. CONCLUSION: Our GWAS identified four novel variants that were significantly associated with susceptibility to SSI following TKA. Integrating genome-wide zPRS with non-genetic risk factors improved the performance of the model in predicting SSI.

Moonlighting glyceraldehyde-3-phosphate dehydrogenase of Lactobacillus gasseri inhibits keratinocyte apoptosis and skin inflammation in experimental atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood. OBJECTIVE: Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management. METHODS: In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines. RESULTS: L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. CONCLUSION: The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.

Hepatitis B Virus Status and Clinical Outcomes in IgA Nephropathy.

Introduction: Immunoglobulin A nephropathy (IgAN) has been reported to coexist with hepatitis B virus (HBV) infection. Despite the clinical significance of this association, there is a lack of comprehensive research investigating the impact of various common conditions following HBV infection and the potential influence of anti-HBV therapy on the progression of IgAN. Methods: We investigated 3 distinct states of HBV infection, including chronic HBV infection, resolved HBV infection, and the deposition of hepatitis B antigens in renal tissue, in a follow-up database of 1961 patients with IgAN. IgAN progression was defined as a loss of estimated glomerular filtration rate (eGFR) >40%. Multivariable cause-specific hazards models to analyze the relationship between HBV states and IgAN progression. Results: Chronic HBV infection was identified as an independent risk factor for IgAN progression, supported by both prematching analysis (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.06-2.44; P = 0.024) and propensity-score matching analysis (HR, 1.74; 95% CI 1.28-2.37; P < 0.001). Conversely, resolved HBV infection showed no significant association with IgAN progression (HR, 1.01; 95% CI 0.67-1.52; P = 0.969). Moreover, the presence of HBV deposition in the kidneys and the utilization of anti-HBV therapy did not appear to be significant risk factors for renal outcomes (P > 0.05). Conclusion: Chronic HBV infection is an independent risk factor for IgAN progression, whereas resolved HBV infection is not. In patients with IgAN, management of concurrent chronic HBV infection should be enhanced. The presence of HBV deposition in the kidneys and the use of anti-HBV medications do not impact the kidney disease progression in patients with IgAN with concurrent HBV infection.

Synaptotagmins family affect glucose transport in retinal pigment epithelial cells through their ubiquitination-mediated degradation and glucose transporter-1 regulation.

BACKGROUND: Synaptotagmins (SYTs) are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and hormones. However, few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy (DR) through Ca2+/glucose transporter-1 (GLUT1) and the possible regulatory mechanism of SYTs. AIM: To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR. METHODS: DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells (ARPE-19). Bioinformatics analysis, reverse transcriptase-polymerase chain reaction, Western blot, flow cytometry, ELISA, HE staining, and TUNEL staining were used for analysis. RESULTS: Six differentially expressed proteins (SYT2, SYT3, SYT4, SYT7, SYT11, and SYT13) were found between the DR and control groups, and SYT4 was highly expressed. Hyperglycemia induces SYT4 overexpression, manipulates Ca2+ influx to induce GLUT1 fusion with the plasma membrane, promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake, induces ARPE-19 cell apoptosis, and promotes DR progression. Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR, resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane, and these effects were blocked by oe-Parkin treatment. Moreover, dysregulation of the myelin transcription factor 1 (Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process, and this process was inhibited in the oe-MYT1-treated group. CONCLUSION: Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.

Cost-Effectiveness of Diabetic Retinopathy Screening for Newly Diagnosed Type 2 Diabetic Patients: A Nationwide Population-based Propensity Score-Matched Cohort Study.

AIMS: This study investigated the association between the frequency of screening for diabetic retinopathy (DR) versus the development of DR and corresponding medical expenses among patients newly diagnosed with type 2 diabetes mellitus (T2DM). METHODS: This longitudinal, population-based study used the Taiwan National Health Insurance Research Database (2004 to 2020) as a data source. Propensity score matching (PSM) (sex, age, comorbidities and concurrent medication use) was employed in the grouping of T2DM patients according to different frequency of DR screening. Outcome measures included the proportion of patients who developed DR, who received DR treatment, and the associated medical expenses and hospitalizations. RESULTS: The 17-year cohort included 337,046 patients. After PSM, three groups each containing 35,739 patients were assembled and analyzed. Compared to low-frequency screening, high-frequency screening was more effective in detecting patients requiring treatment; however, the net cost for treatment was significantly lower. Standard-frequency screening appears to provide the best balance in terms of DR detection, diagnosis interval, the risk of DR-related hospitalization, and DR treatment costs. CONCLUSIONS: In this real-world cohort study covering all levels of the healthcare system, infrequent screening was associated with delayed diagnosis and elevated treatment costs, while a fundus screening interval of 1-2 years proved optimal in terms of detection and medical expenditures.

The mediating role of perceived social support on the relationship between lack of occupational coping self-efficacy and implicit absenteeism among intensive care unit nurses: a multicenter cross­sectional study.

BACKGROUND: Implicit absenteeism is very common among nurses. Poor perceived social support of intensive care unit nurses has a negative impact on their mental and physical health. There is evidence that lack of occupational coping self-efficacy can promote implicit absenteeism; however, the relationship between lack of occupational coping self-efficacy in perceived social support and implicit absenteeism of intensive care unit nurses is unclear. Therefore, this study aimed to evaluate the role of perceived social support between lack of occupational coping self-efficacy and implicit absenteeism of intensive care unit nurses, and to provide reliable evidence to the management of clinical nurses. METHODS: A cross-sectional study of 517 intensive care unit nurses in 10 tertiary hospitals in Sichuan province, China was conducted, of which 474 were valid questionnaires with a valid recovery rate of 91.6%. The survey tools included the Chinese version of Implicit Absenteeism Scale, the Chinese version of Perceived Social Support Scale, the Chinese version of Occupational Coping Self-Efficacy Scale and the Sociodemographic characteristics. Descriptive analysis and Pearson correlation analysis were performed using SPSS version 22.0, while the mediating effects were performed using AMOS version 24.0. RESULTS: The average of intensive care unit nurses had a total implicit absenteeism score of (16.87 ± 3.98), in this study, the median of intensive care unit nurses' implicit absenteeism score was 17, there were 210 intensive care unit nurses with low implicit absenteeism (44.3%) and 264 ICU nurses with high implicit absenteeism (55.7%). A total perceived social support score of (62.87 ± 11.61), and a total lack of occupational coping self-efficacy score of (22.78 ± 5.98). The results of Pearson correlation analysis showed that implicit absenteeism was negatively correlated with perceived social support (r = -0.260, P < 0.001) and positively correlated with lack of occupational coping self-efficacy (r = 0.414, P < 0.001). In addition, we found that perceived social support plays a mediating role in lack of occupational coping self-efficacy and implicit absenteeism [ß = 0.049, 95% CI of (0.002, 0.101)]. CONCLUSIONS: Intensive care unit nurses had a high level of implicit absenteeism with a moderate level of perceived social support and lack of occupational coping self-efficacy. Nursing managers should pay attention to the nurses those who were within low levels of social support and negative coping strategies, and take measures to reduce intensive care unit nurses' professional stress, minimize implicit absenteeism.

Impact of Hearing Aids on Language Outcomes in Preschool Children With Mild Bilateral Hearing Loss.

This study aimed to investigate the role of hearing aid (HA) usage in language outcomes among preschool children aged 3-5 years with mild bilateral hearing loss (MBHL). The data were retrieved from a total of 52 children with MBHL and 30 children with normal hearing (NH). The association between demographical, audiological factors and language outcomes was examined. Analyses of variance were conducted to compare the language abilities of HA users, non-HA users, and their NH peers. Furthermore, regression analyses were performed to identify significant predictors of language outcomes. Aided better ear pure-tone average (BEPTA) was significantly correlated with language comprehension scores. Among children with MBHL, those who used HA outperformed the ones who did not use HA across all linguistic domains. The language skills of children with MBHL were comparable to those of their peers with NH. The degree of improvement in audibility in terms of aided BEPTA was a significant predictor of language comprehension. It is noteworthy that 50% of the parents expressed reluctance regarding HA use for their children with MBHL. The findings highlight the positive impact of HA usage on language development in this population. Professionals may therefore consider HAs as a viable treatment option for children with MBHL, especially when there is a potential risk of language delay due to hearing loss. It was observed that 25% of the children with MBHL had late-onset hearing loss. Consequently, the implementation of preschool screening or a listening performance checklist is recommended to facilitate early detection.

Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.

BACKGROUND: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. METHODS: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. RESULTS: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). CONCLUSIONS: Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

Development of a thermotaxis and rheotaxis microfluidic device for motile spermatozoa sorting.

Male infertility is a pervasive global reproductive challenge, primarily attributed to a decline in semen quality. Addressing this concern, there has been a growing focus on spermatozoa sorting in assisted reproductive technology. This study introduces a groundbreaking development in the form of a thermotaxis and rheotaxis microfluidic (TRMC) device designed for efficient motile spermatozoa sorting within a short 15-min timeframe. The TRMC device mimics the natural sperm sorting mechanism of the oviduct, selecting spermatozoa with superior motility and DNA integrity. The experimental outcomes demonstrate a remarkable enhancement in the percentage of progressive spermatozoa following sorting, soaring from 3.90% to an impressive 96.11% when subjected to a temperature decrease from 38 °C to 35 °C. Notably, sperm motility exhibited a substantial 69% improvement. The TRMC device exhibited a commendable recovery rate of 60.93%, surpassing current clinical requirements. Furthermore, the sorted spermatozoa displayed a notable reduction in the DNA fragmentation index to 6.94%, signifying a substantial 90% enhancement in DNA integrity. This remarkable advancement positions the TRMC device as highly suitable for applications in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), offering a promising solution to male infertility challenges.

A Self-Delivery Nanodrug Simultaneously Inhibits COX-2/PGE2 Mediated Inflammation and Downregulates PD-L1 to Boost Photoimmunotherapy.

Phototherapy promotes anti-tumor immunity by inducing immunogenic cell death (ICD), However, the accompanying inflammatory responses also trigger immunosuppression, attenuating the efficacy of photo-immunotherapy. Herein, they co-assembled a cell-membrane targeting chimeric peptide C16-Cypate-RRKK-PEG8-COOH (CCP) and anti-inflammatory diclofenac (DA) to develop a nanodrug (CCP@DA) that both enhances the immune effect of phototherapy and weakens the inflammation-mediated immunosuppression. CCP@DA achieves cell membrane-targeting photodynamic and photothermal synergistic therapies to damage programmed death ligand 1 (PD-L1) and induce a strong ICD to activate anti-tumor response. Simultaneously, the released DA inhibits the cycoperoxidase-2 (COX-2)/prostaglandin E2 (PGE2) pathway in tumor cells to inhibit pro-tumor inflammation and further down-regulate PD-L1 expression to relieve the immunosuppressive microenvironment. CCP@DA significantly inhibited tumor growth and inflammation both in vitro and in vivo, while maintaining a potent anti-tumor immune response. Additionally, it exhibits excellent anti-metastatic capabilities and prolongs mouse survival time with a single dose and low levels of near-infrared (NIR) light exposure. This work provides a valuable strategy to control the therapy-induced inflammation for high-efficiency photoimmunotherapy.

Corrigendum: Distinct characteristics and prognosis of IgA nephropathy patients with nephrotic syndrome: a propensity score-matched cohort study.

[This corrects the article DOI: 10.3389/fmed.2024.1344219.].

Enlarged perivascular spaces in alcohol-related brain damage induced by dyslipidemia.

Perivascular spaces (PVSs) as the anatomical basis of the glymphatic system, are increasingly recognized as potential imaging biomarkers of neurological conditions. However, it is not clear whether enlarged PVSs are associated with alcohol-related brain damage (ARBD). We aimed to investigate the effect of long-term alcohol exposure on dyslipidemia and the glymphatic system in ARBD. We found that patients with ARBD exhibited significantly enlargement of PVSs in the frontal cortex and basal ganglia, as well as a notable increased levels of total cholesterol (TC) and triglycerides (TG). The anatomical changes of the glymphatic drainage system mentioned above were positively associated with TC and TG. To further explore whether enlarged PVSs affects the function of the glymphatic system in ARBD, we constructed long alcohol exposure and high fat diet mice models. The mouse model of long alcohol exposure exhibited increased levels of TC and TG, enlarged PVSs, the loss of aquaporin-4 polarity caused by reactive astrocytes and impaired glymphatic drainage function which ultimately caused cognitive deficits, in a similar way as high fat diet leading to impairment in glymphatic drainage. Our study highlights the contribution of dyslipidemia due to long-term alcohol abuse in the impairment of the glymphatic drainage system.

Increased Long-Term Risk of Dementia in Patients With Carbon Monoxide Poisoning: A Systematic Review and Meta-Analysis of Cohort Studies.

OBJECTIVE: To assess whether carbon monoxide (CO) poisoning increases the incidence of dementia. METHODS: We searched the Cochrane Library, PubMed, and EMBASE from inception to 14 August 2022. Two authors independently selected studies, assessed the quality of included studies, and extracted data. Any disagreement was resolved by discussion with a third author. Only cohort study with an enough follow-up period was included for systematic reviews and meta-analysis. RESULTS: Thirty-three full texts were initially searched, but only three studies met our inclusion criteria, and they were comprised of 134,563 participants who were initially free of dementia. The follow-up period ranged from 9 to 12 years. We found that CO poisoning increased the risk of dementia incidence (adjusted hazard ratio 2.61, 95% confidence interval 1.56 to 4.36, p=0.0003). Subgroup analysis showed that the increased dementia risk was significant in males but not in females, and the highest risk was in young age group, followed by in middle age group, but not in the old one. CONCLUSION: Overall the evidence from prospective cohort studies supported a link between CO exposure and an increased dementia risk, although all the included studies were limited to Taiwanese population.