Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization.

PURPOSE: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR). METHODS: We applied two-sample MR approaches to assess the association between genetically predicted circulating concentrations of sex hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG)], BMI, and mammographic density phenotypes (dense and non-dense area). We created instrumental variables from large European ancestry-based genome-wide association studies and applied estimates to mammographic density phenotypes in up to 14,000 women of European ancestry. We performed analyses overall and by menopausal status. RESULTS: Genetically predicted BMI was positively associated with non-dense area (IVW: ß = 1.79; 95% CI = 1.58, 2.00; p = 9.57 × 10-63) and inversely associated with dense area (IVW: ß = - 0.37; 95% CI = - 0.51,- 0.23; p = 4.7 × 10-7). We observed weak evidence for an association of circulating sex hormone concentrations with mammographic density phenotypes, specifically inverse associations between genetically predicted testosterone concentration and dense area (ß = - 0.22; 95% CI = - 0.38, - 0.053; p = 0.009) and between genetically predicted estradiol concentration and non-dense area (ß = - 3.32; 95% CI = - 5.83, - 0.82; p = 0.009), although results were not consistent across a range of MR approaches. CONCLUSION: Our findings support a positive causal association between BMI and mammographic non-dense area and an inverse association between BMI and dense area. Evidence was weaker and inconsistent for a causal effect of circulating sex hormone concentrations on mammographic density phenotypes. Based on our findings, associations between circulating sex hormone concentrations and mammographic density phenotypes are weak at best.

Expression and prognostic significance of the PD-1/PD-L1 pathway in AIDS-related non-Hodgkin lymphoma.

OBJECTIVE: Immune tolerance and evasion play a critical role in virus-driven malignancies. However, the phenotype and clinical significance of programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2, in aggressive acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) remain poorly understood, particularly in the Epstein-Barr virus (EBV)-positive subset. METHODS: We used in situ hybridization with EBV-encoded RNA (EBER) to assess the EBV status. We performed immunohistochemistry and flow cytometry analysis to evaluate components of the PD-1/PD-L1/L2 pathway in a multi-institutional cohort of 58 patients with AR-NHL and compared EBV-positive and EBV-negative cases. RESULTS: The prevalence of EBV+ in AR-NHL was 56.9% and was associated with a marked increase in the expression of PD-1/PD-L1/PD-L2 in malignant cells. Patients with AR-NHLs who tested positive for both EBER and PD-1 exhibited lower survival rates compared to those negative for these markers (47.4% vs. 93.8%, p = 0.004). Similarly, patients positive for both EBER and PD-L1 also demonstrated poorer survival (56.5% vs. 93.8%, p = 0.043). Importantly, PD-1 tissue-expression demonstrated independent prognostic significance for overall survival in multivariate analysis and was correlated to elevated levels of LDH (r = 0.313, p = 0.031), increased PD-1+ Tregs (p = 0.006), and robust expression of EBER (r = 0.541, p < 0.001) and PD-L1 (r = 0.354, p = 0.014) expression. CONCLUSIONS: These data emphasize the importance of PD-1-mediated immune evasion in the complex landscape of immune oncology in AR-NHL co-infected with EBV, and contribute to the diagnostic classification and possible definition of immunotherapeutic strategies for this unique subgroup.

The Role of Infiltrated T Lymphocyte in Oral Squamous Cell Carcinoma: Insights into Clinicopathological Characteristics and Prognosis.

Background: To compare and analyze the presence of CD4+ and CD8 + lymphocyte infiltrates in Oral squamous cell carcinoma (OSCC) tissue versus adjacent tissue and their clinical significance. Methods: We enrolled a total of 152 patients diagnosed with OSCC, all of whom had confirmed diagnoses through pathological reports. Clinical and demographics data were extracted from medical records. Tissue microarrays were constructed and immunohistochemical staining for CD4 and CD8 was performed. Findings: The average number of infiltrating CD4+ T cells in OSCC tumor tissue was 1026.22±1163.36 cells/mm2, which did not significantly differ from the count in adjacent tissue, which was 1163.36±1013.23 cells/mm2. However, the number of CD8+ T cell infiltration in tumor tissue was significantly higher than in adjacent tissue (655.25±705.70 vs 504.56±659.26 cells/mm2, p = 0.026). We observed that, among patients who consumed alcohol, the CD4+ T cell infiltration in tumor tissue being significantly lower than that in adjacent tissue (P=0.036). Moreover, the CD8+ T cell infiltration in cancer tissue was significantly higher than in adjacent tissue for T1-2 patients (p=0.005). Patients with higher CD8+ T cell in tumor tissue exhibited significantly improved overall survival (p = 0.043). Multivariate analyses revealed that alcohol consumption had a significant impact on the number of CD4+T lymphocytes in tumor tissue (OR = 0.403, P = 0.033) while T stage was the independent factor affecting CD8+ T lymphocyte infiltration in tumor tissue (OR = 0.459, P = 0.031). Interpretation: OSCC patients with a higher number of CD8+ T lymphocyte infiltration in tumor tissue exhibited an improved prognosis.

Virus surrogates throughout a full-scale advanced water reuse system.

Water reuse as an alternative water supply is increasing throughout the world due to water stress and scarcity; however, there are no standard practices for monitoring virus pathogens in such systems. This study aimed to identify suitable surrogates for virus fate, transport, and removal throughout a water reuse scheme. Various microbial targets (11 viruses, two phage, and three bacteria) were monitored using molecular and culture methods across all treatment stages in a wastewater reclamation facility and advanced water treatment facility. Criteria were established for identifying suitable surrogates, which included reliable detection, observable fate and transport, calculable log-reduction values (LRVs), correlations with other targets, and various morphological types. In total, five viruses (PMMoV, AiV, GII NoV, AdV, FRNA GII) met these stringent criteria and were suggested as potential virus surrogates. These surrogates enabled successful comparison of assigned versus actual LRVs throughout a water reuse scheme. Results suggest that virus pathogens are effectively removed throughout water reuse treatment and the suggested surrogates can be utilized for monitoring treatment performance and ensuring public health safety. This study provides a framework that water utilities across the world can reference for establishing virus monitoring practices.

Protopine protects chondrocytes from undergoing ferroptosis by activating Nrf2 pathway.

Osteoarthritis is a highly prevalent joint disease; however, effective treatments are lacking. Protopine (PTP) is an isoquinoline alkaloid with potent anti-inflammatory and antioxidant properties; however, it has not been studied in osteoarthritis. This study aimed to investigate whether PTP can effectively protect chondrocytes from ferroptosis. Primary mouse chondrocytes were treated with tert-butyl hydroperoxide (TBHP) to simulate oxidative stress in an in vitro model of osteoarthritis. Two concentrations of PTP (10 and 20 µg/mL) were validated for in vitro experiments. Cellular inflammation and metabolism were detected using RT-qPCR and western blotting (WB). Ferroptosis was assessed via WB, qPCR, reactive oxygen species (ROS) levels, lipid ROS, and immunofluorescence staining. In vitro, PTP significantly ameliorated chondrocyte inflammation and cytolytic metabolism and significantly suppressed chondrocyte ferroptosis through the activation of the Nrf2 pathway. The anterior cruciate ligament transection (ACLT) mouse model was used to validate the in vivo effects of PTP. The joint cartilage was assessed using the Osteoarthritis Research Society International (OARSI) score, Safranin O staining, and immunohistochemistry. The intra-articular administration of PTP alleviated cartilage inflammation and ferroptosis, as evidenced by the expression of MMP3, MMP13, COL2A1, GPX4, and Nrf2. Overall, we find that PTP exerted anti-ferroptosis and anti-inflammatory effects on chondrocytes to protect the articular cartilage.

Resveratrol promotes the differentiation of human umbilical cord mesenchymal stem cells into esophageal fibroblasts via AKT signaling pathway.

Objectives: Resveratrol has been implicated in the differentiation and development of human umbilical cord mesenchymal stem cells. The differentiation of into esophageal fibroblasts is a promising strategy for esophageal tissue engineering. However, the pharmacological effect and underlying mechanism of resveratrol on human umbilical cord mesenchymal stem cells differentiation are unknown. Here, we investigated the effects and mechanism of resveratrol on the differentiation of human umbilical cord mesenchymal stem cells. Methods: Using a transwell-membrane coculture system to culture human umbilical cord mesenchymal stem cells and esophageal fibroblasts, we examined how resveratrol act on the differentiation of human umbilical cord mesenchymal stem cells. Immunocytochemistry, Sirius red staining, quantitative real-time PCR, and Western blotting were performed to examine collagen synthesis and possible signaling pathways in human umbilical cord mesenchymal stem cells. Results: We found that resveratrol promoted collagen synthesis and AKT phosphorylation. However, co-treatment of cells with resveratrol and the PI3K inhibitor LY294002 inhibited collagen synthesis and AKT phosphorylation. We demonstrated that resveratrol down-regulated the expression of IL-6, TGF-ß, caspase-9, and Bax by activating the AKT pathway in human umbilical cord mesenchymal stem cell. Furthermore, resveratrol inhibited phosphorylated NF-ĸB in human umbilical cord mesenchymal stem cells. Conclusion: Our data suggest that resveratrol promotes the differentiation of human umbilical cord mesenchymal stem cells into fibroblasts. The underlying mechanism is associated with the downregulation of IL-6 and TGF-ß via the AKT pathway and by inhibiting the NF-ĸB pathway. Resveratrol may be useful for esophageal tissue engineering.

Patients with chronic hepatitis B who have persistently normal alanine aminotransferase or aged < 30 years may exhibit significant histologic damage.

BACKGROUND: The timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged < 30 years is still undetermined. We aimed to elucidate the correlation between liver histology, age, and ALT level in CHB patients and analyze the histological characteristics of the liver among patients with persistently normal ALT or aged < 30 years. METHODS: A retrospective analysis was conducted on 697 treatment-naive CHB patients. Liver biopsies were performed, and significant histological damage was defined as the grade of liver inflammation ≥ G2 and/or fibrosis ≥ S2 based on the Scheuer scoring system. RESULTS: The liver inflammation grades and fibrosis stages correlated positively with age, ALT, AST, GGT levels and negatively with the counts of PLT (all p < 0.050) in HBeAg-positive patients. Higher ALT levels and lower PLT counts were independently associated with significant liver inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients. Furthermore, among those with persistently normal ALT levels, the incidence of significant liver inflammation and fibrosis were 66.1% and 53.7% in HBeAg-positive groups, and 63.0% and 55.5% in HBeAg-negative groups. Moreover, there was no significant difference in the prevalence of significant liver damage between patients aged < 30 years and those aged ≥ 30 years, in both HBeAg-positive (≥ G2 or ≥ S2: 63.8% vs. 75.8%, p = 0.276) and HBeAg-negative (≥ G2 or ≥ S2: 65.9% vs. 72.5%, p = 0.504) groups, among patients with persistently normal ALT levels. CONCLUSIONS: A considerable proportion of CHB patients with persistently normal ALT, including those below the age of 30 years, exhibited significant histological damage. This highlights the importance of initiating early antiviral therapy for HBV-infected individuals, even in the absence of elevated ALT levels.

Soil fungal communities varied across aspects of restored grassland in former mining areas of the Qinghai-Tibet Plateau.

To determine whether different aspects lead to a heterogeneous distribution of soil fungi, we investigated artificially established alpine grasslands in the Muli mining area in the Qinghai-Tibet Plateau. Employing high-throughput sequencing techniques, we analyzed the composition, diversity, and function of soil fungal communities across various aspects (flat, East-facing, South-facing, West-facing, North-facing). We also examined their relationships with environmental factors. Soil fungal communities of restored alpine grasslands differed significantly across aspects in terms of the dominant phyla, classes and species level. Compared with No aspect, the Shannon index of fungi respectively decreased by 2.99%, 19.32%, 19.37% and 10.56% for East aspect, South aspect, West aspect and North aspect, respectively, and the Chao1 index of fungi respectively decreased by-2.44%, 35.50%, 42.15% and 3.21%, respectively. A total of 22 different types of fungi were identified in the study area. Predictive analysis, based on PICRUSt2, indicated that the primary functions of the fungal communities across different aspects were aerobic respiration I (cytochrome c) and aerobic respiration II (cytochrome c). Among the environmental variables, total phosphorus (P) and total nitrogen (N) were the principal factors influencing the fungal community composition.In conclusion, aspect plays a significant role in shaping the composition of fungal communities and also affects their overall diversity.

The Configuration of GRB2 in Protein Interaction and Signal Transduction.

Growth-factor-receptor-binding protein 2 (GRB2) is a non-enzymatic adaptor protein that plays a pivotal role in precisely regulated signaling cascades from cell surface receptors to cellular responses, including signaling transduction and gene expression. GRB2 binds to numerous target molecules, thereby modulating a complex cell signaling network with diverse functions. The structural characteristics of GRB2 are essential for its functionality, as its multiple domains and interaction mechanisms underpin its role in cellular biology. The typical signaling pathway involving GRB2 is initiated by the ligand stimulation to its receptor tyrosine kinases (RTKs). The activation of RTKs leads to the recruitment of GRB2 through its SH2 domain to the phosphorylated tyrosine residues on the receptor. GRB2, in turn, binds to the Son of Sevenless (SOS) protein through its SH3 domain. This binding facilitates the activation of Ras, a small GTPase, which triggers a cascade of downstream signaling events, ultimately leading to cell proliferation, survival, and differentiation. Further research and exploration into the structure and function of GRB2 hold great potential for providing novel insights and strategies to enhance medical approaches for related diseases. In this review, we provide an outline of the proteins that engage with domains of GRB2, along with the function of different GRB2 domains in governing cellular signaling pathways. This furnishes essential points of current studies for the forthcoming advancement of therapeutic medications aimed at GRB2.

The use of individual-based FDG-PET volume of interest in predicting conversion from mild cognitive impairment to dementia.

BACKGROUND: Based on a longitudinal cohort design, the aim of this study was to investigate whether individual-based 18F fluorodeoxyglucose positron emission tomography (18F-FDG-PET) regional signals can predict dementia conversion in patients with mild cognitive impairment (MCI). METHODS: We included 44 MCI converters (MCI-C), 38 non-converters (MCI-NC), 42 patients with Alzheimer's disease with dementia, and 40 cognitively normal controls. Data from annual cognitive measurements, 3D T1 magnetic resonance imaging (MRI) scans, and 18F-FDG-PET scans were used for outcome analysis. An individual-based FDG-PET approach was applied using seven volumes of interest (VOIs), Z transformed using a normal FDG-PET template. Hypometabolism was defined as a Z score < -2 of regional standard uptake value ratio. For the longitudinal cognitive test scores, generalized estimating equations were used. A linear mixed-effects model was used to compare the temporal impact of cortical hypometabolism and cortical thickness degeneration. RESULTS: The clinical follow-up period was 6.6 ± 3.8 years (range 3.1 to 16.0 years). The trend of cognitive decline could differentiate MCI-C from MCI-NC after 3 years of follow-up. In the baseline 18F-FDG-PET scan of the patients with MCI, medial temporal lobe (MTL; 94.7% sensitivity, 80.5% specificity) and posterior cingulate cortex (PCC; 89.5% sensitivity, 73.1% specificity) hypometabolism predicted conversion with high accuracy. 18F-FDG-PET hypometabolism preceded dementia conversion at an interval of 3.70 ± 1.68 years and was earlier than volumetric changes, with the exception of the MTL. CONCLUSIONS: Our finding supports the use of individual-based 18F-FDG-PET analysis to predict MCI conversion to dementia. Reduced FDG-PET metabolism in the MTL and PCC were strongly associated with future cognitive decline in the MCI-C group. Changes in 18F-FDG-PET occurred 1 to 8 years prior to conversion to dementia. Progressive hypometabolism in the PCC, precuneus and lateral temporal lobe, but not MTL, preceded MRI findings at the MCI stage.

Automatic quantitative stroke severity assessment based on Chinese clinical named entity recognition with domain-adaptive pre-trained large language model.

BACKGROUND: Stroke is a prevalent disease with a significant global impact. Effective assessment of stroke severity is vital for an accurate diagnosis, appropriate treatment, and optimal clinical outcomes. The National Institutes of Health Stroke Scale (NIHSS) is a widely used scale for quantitatively assessing stroke severity. However, the current manual scoring of NIHSS is labor-intensive, time-consuming, and sometimes unreliable. Applying artificial intelligence (AI) techniques to automate the quantitative assessment of stroke on vast amounts of electronic health records (EHRs) has attracted much interest. OBJECTIVE: This study aims to develop an automatic, quantitative stroke severity assessment framework through automating the entire NIHSS scoring process on Chinese clinical EHRs. METHODS: Our approach consists of two major parts: Chinese clinical named entity recognition (CNER) with a domain-adaptive pre-trained large language model (LLM) and automated NIHSS scoring. To build a high-performing CNER model, we first construct a stroke-specific, densely annotated dataset "Chinese Stroke Clinical Records" (CSCR) from EHRs provided by our partner hospital, based on a stroke ontology that defines semantically related entities for stroke assessment. We then pre-train a Chinese clinical LLM coined "CliRoberta" through domain-adaptive transfer learning and construct a deep learning-based CNER model that can accurately extract entities directly from Chinese EHRs. Finally, an automated, end-to-end NIHSS scoring pipeline is proposed by mapping the extracted entities to relevant NIHSS items and values, to quantitatively assess the stroke severity. RESULTS: Results obtained on a benchmark dataset CCKS2019 and our newly created CSCR dataset demonstrate the superior performance of our domain-adaptive pre-trained LLM and the CNER model, compared with the existing benchmark LLMs and CNER models. The high F1 score of 0.990 ensures the reliability of our model in accurately extracting the entities for the subsequent automatic NIHSS scoring. Subsequently, our automated, end-to-end NIHSS scoring approach achieved excellent inter-rater agreement (0.823) and intraclass consistency (0.986) with the ground truth and significantly reduced the processing time from minutes to a few seconds. CONCLUSION: Our proposed automatic and quantitative framework for assessing stroke severity demonstrates exceptional performance and reliability through directly scoring the NIHSS from diagnostic notes in Chinese clinical EHRs. Moreover, this study also contributes a new clinical dataset, a pre-trained clinical LLM, and an effective deep learning-based CNER model. The deployment of these advanced algorithms can improve the accuracy and efficiency of clinical assessment, and help improve the quality, affordability and productivity of healthcare services.

Polymerization strategy for cellulose nanocrystals-based photonic crystal films with water resisting property.

Cellulose nanocrystals (CNCs) can form a liquid crystal film with a chiral nematic structure by evaporative-induced self-assembly (EISA). It has attracted much attention as a new class of photonic liquid crystal material because of its intrinsic, unique structural characteristics, and excellent optical properties. However, the CNCs-based photonic crystal films are generally prepared via the physical crosslinking strategy, which present water sensitivity. Here, we developed CNCs-g-PAM photonic crystal film by combining free radical polymerization and EISA. FT-IR, SEM, POM, XRD, TG-DTG, and UV-Vis techniques were employed to characterize the physicochemical properties and microstructure of the as-prepared films. The CNCs-g-PAM films showed a better thermo-stability than CNCs-based film. Also, the mechanical properties were significantly improved, viz., the elongation at break was 9.4 %, and tensile strength reached 18.5 Mpa, which was a much better enhancement than CNCs-based film. More importantly, the CNCs-g-PAM films can resist water dissolution for more than 24 h, which was impossible for the CNCs-based film. The present study provided a promising strategy to prepare CNCs-based photonic crystal film with high flexibility, water resistance, and optical properties for applications such as decoration, light management, and anti-counterfeiting.

Removal efficiency of antibiotic residues, antibiotic resistant bacteria, and genes across parallel secondary settling tank and membrane bioreactor treatment trains in a water reclamation plant.

Antimicrobial resistance is recognized as a potent threat to human health. Wastewater treatment facilities are viewed as hotspots for the spread of antimicrobial resistance. This study provides comprehensive data on the occurrences of 3 different antibiotic resistant opportunistic pathogens (with resistance to up to 5 antibiotics), 13 antibiotic resistant genes and intI1, and 22 different antimicrobial residues in a large water reclamation plant (176 million gallons per day) that runs a conventional Modified Ludzack-Ettinger (MLE) reactor followed by a secondary settling tank (SST) and membrane bioreactor (MBR) in parallel. All the antibiotic resistant bacteria and most of the antibiotic resistance genes were present in the raw influent, ranging from 2.5 × 102-3.7 × 106 CFU/mL and 1.2× 10-1-6.5 × 1010 GCN/mL, respectively. MBR outperformed the SST system in terms of ARB removal as the ARB targets were largely undetected in MBR effluent, with log removals ranging from 2.7 to 6.8, while SST only had log removals ranging from 0.27 to 4.6. Most of the ARG concentrations were found to have significantly higher in SST effluent than MBR permeate, and MBR had significantly higher removal efficiency for most targets (p < 0.05) except for sul1, sul2, blaOXA48, intI1 and 16S rRNA genes (p > 0.05). As for the antibiotic residues (AR), there was no significant removal from the start to the end of the treatment process, although MBR had higher removal efficiencies for azithromycin, chloramphenicol, erythromycin, erythromycin-H2O, lincomycin, sulfamethoxazole and triclosan, compared to the SST system. In conclusion, MBR outperformed SST in terms of ARB and ARGs removal. However low removal efficiencies of most AR targets were apparent.

Bioactive 5/5/5/6 Four-Ring System Iridoids from Plumeria alba L.

Two rare 5/5/5/6 four-ring system iridoids, allamancins A and B (1 and 2) together with one known biogenetically related iridoid derivative, 3-O-methyallamancin (3) were isolated from the flowers of Plumeria alba L. The structures of these iridoid derivatives were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic analysis. The inhibitory activities of compounds 1-3 against nitric oxide (NO) production induced and three cancer cell lines were evaluated in vitro. Compounds 1 and 3 showed inhibitory activities on NO production with IC50 values of 18.3±0.12 and 22.1±0.14 µM, respectively. Compounds 1-3 showed moderate inhibitory activities against cancer cell lines of A549, Hela and MCF-7.

An axon-T cell feedback loop enhances inflammation and axon degeneration.

Inflammation is closely associated with many neurodegenerative disorders. Yet, whether inflammation causes, exacerbates, or responds to neurodegeneration has been challenging to define because the two processes are so closely linked. Here, we disentangle inflammation from the axon damage it causes by individually blocking cytotoxic T cell function and axon degeneration. We model inflammatory damage in mouse skin, a barrier tissue that, despite frequent inflammation, must maintain proper functioning of a dense array of axon terminals. We show that sympathetic axons modulate skin inflammation through release of norepinephrine, which suppresses activation of γδ T cells via the ß2 adrenergic receptor. Strong inflammatory stimulation-modeled by application of the Toll-like receptor 7 agonist imiquimod-causes progressive γδ T cell-mediated, Sarm1-dependent loss of these immunosuppressive sympathetic axons. This removes a physiological brake on T cells, initiating a positive feedback loop of enhanced inflammation and further axon damage.

The association between fear of progression and medical coping strategies among people living with HIV: a cross-sectional study.

BACKGROUND: Due to the chronic nature of HIV, mental health has become a critical concern in people living with HIV (PLWHIV). However, little knowledge exists about the association between fear of progression (FoP) and medical coping modes (MCMs) in PLWHIV in China. METHODS: A cohort of 303 PLWHIV were consecutively enrolled and their demographic, clinical and psychological information was collected. The Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Social Support Rating Scale (SSRS), Internalized HIV Stigma Scale (IHSS) and MCMs Questionnaire were utilized. RESULTS: Of the participants, 215 PLWHIV were classified into the low-level FoP group, and 88 were grouped into the high-level FoP group based on their FoP-Q-SF scores, according to the criteria for the classification of dysfunctional FoP in cancer patients. The high-level group had a higher proportion of acquired immunodeficiency syndrome (AIDS) stage (P = 0.005), lower education levels (P = 0.027) and lower income levels (P = 0.031). Additionally, the high-level group had lower scores in social support (P < 0.001) and its three dimensions, with total SSRS scores showing a negative correlation with two dimensions of FoP-Q-SF, namely physical health (r2 = 0.0409, P < 0.001) and social family (r2 = 0.0422, P < 0.001). Further, the high-level group had higher scores in four dimensions of internalized HIV stigma, and a positive relationship was found to exist between IHSS scores and FoP-Q-SF scores for physical health (r2 = 0.0960, P < 0.001) and social family (r2 = 0.0719, P < 0.001). Social support (OR = 0.929, P = 0.001), being at the AIDS stage (OR = 3.795, P = 0.001), and internalized HIV stigma (OR = 1.028, P < 0.001) were independent factors for FoP. Furthermore, intended MCMs were evaluated. FoP were positively correlated with avoidance scores (r2 = 0.0886, P < 0.001) and was validated as the only factor for the mode of confrontation (OR = 0.944, P = 0.001) and avoidance (OR = 1.059, P = 0.001) in multivariate analysis. CONCLUSION: The incidence of dysfunctional FoP in our study population was relatively high. High-level FoP was associated with poor social support, high-level internalized HIV stigma and a negative MCM among PLWHIV.

Multi-center application of a convolutional neural network for preoperative detection of cavernous sinus invasion in pituitary adenomas.

OBJECTIVE: Cavernous sinus invasion (CSI) plays a pivotal role in determining management in pituitary adenomas. The study aimed to develop a Convolutional Neural Network (CNN) model to diagnose CSI in multiple centers. METHODS: A total of 729 cases were retrospectively obtained in five medical centers with (n = 543) or without CSI (n = 186) from January 2011 to December 2021. The CNN model was trained using T1-enhanced MRI from two pituitary centers of excellence (n = 647). The other three municipal centers (n = 82) as the external testing set were imported to evaluate the model performance. The area-under-the-receiver-operating-characteristic-curve values (AUC-ROC) analyses were employed to evaluate predicted performance. Gradient-weighted class activation mapping (Grad-CAM) was used to determine models' regions of interest. RESULTS: The CNN model achieved high diagnostic accuracy (0.89) in identifying CSI in the external testing set, with an AUC-ROC value of 0.92 (95% CI, 0.88-0.97), better than CSI clinical predictor of diameter (AUC-ROC: 0.75), length (AUC-ROC: 0.80), and the three kinds of dichotomizations of the Knosp grading system (AUC-ROC: 0.70-0.82). In cases with Knosp grade 3A (n = 24, CSI rate, 0.35), the accuracy the model accounted for 0.78, with sensitivity and specificity values of 0.72 and 0.78, respectively. According to the Grad-CAM results, the views of the model were confirmed around the sellar region with CSI. CONCLUSIONS: The deep learning model is capable of accurately identifying CSI and satisfactorily able to localize CSI in multicenters.

Flexible EEG Electrodes with Embedded Pressure Sensors and Customized Interface Towards Comfortable Home EEG Monitoring.

To realize stable and comfortable dry electroencephalography (EEG) recording for home healthcare, a flexible pressure-sensitive electrode (PSE) is proposed, and a dedicated multi-channel pressure sensor interface is developed. The PSE monitors the pressure on the electrode during continuous EEG recording. With the PSE, stable but comfortable electrode-skin contact can be achieved. The analog front-end of the sensor interface is fabricated in 180-nm CMOS, occupying an active area of 0.25 mm2. The flexible sensor exhibited a -2.5 kΩ/kPa sensitivity. The sensor interface enjoyed a large stimulus range of up to 2.65 mApp and showed a resolution of 0.047 - 8.0 mΩ/√Hz. It is digital-compatible, reconfigurable, and area-efficient, which can be migrated into various EEG acquisition integrated circuits and systems.

Prospective observational study of baloxavir marboxil in adults and adolescents with uncomplicated influenza from China.

Introduction: There are limited data on the efficacy of baloxavir marboxil (baloxavir) versus oseltamivir in Chinese patients with influenza A. Methods: This study is an observational real-world investigation encompassing 246 patients (baloxavir, n = 147; oseltamivir, n = 99) confirmed positive for influenza A. The choice between baloxavir and oseltamivir antiviral treatments was determined collaboratively by the clinician and the patient. A thorough comparative analysis was undertaken between the two groups, examining parameters such as the duration of fever and symptoms, viral load dynamics, lymphocyte changes, and enhancements in health-related quality of life (QoL). Results: No significant differences were observed in demographic data between the two groups. The duration of fever was significantly shorter in the baloxavir group (P < 0.001). However, the duration of symptoms was not significant different (P = 0.167). Multivariable Cox analysis showed the independent factors affecting duration of fever were baloxavir treatment (HR = 2.033, P < 0.001), fever on day 1 (HR = 0.741, P = 0.010) and CRP level (HR = 1.009, P = 0.039). Moreover, sex (HR= 0.660, P = 0.019) and monocyte count (HR = 1.355, P = 0.018) were independent factors affecting the duration of symptoms. No significant difference in change of health-related quality of life (P > 0.05), positive rate of viral antigen on day 3 (P = 0.477) between the two groups. Remarkably, a mutation was observed in one case on the third-day after baloxavir treatment compared with first-day, from cysteine to serine at position 384 of the PA subunit. Conclusion: In the clinical setting, baloxavir demonstrated comparable clinical benefits to oseltamivir, establishing its efficacy as an effective antiviral therapy for Chinese patients with influenza.

Light at night exposure and risk of breast cancer: a meta-analysis of observational studies.

Objective: The aim of this meta-analysis is to evaluate the impact of light at night (LAN) exposure on the risk of breast cancer across varying factors. Method: We conducted a systematic search of literature up to July 15, 2023, including PubMed, Cochrane Library, and Embase databases, using keywords related to breast cancer and LAN exposure. Cohort study and case-control study literature on night light exposure and breast cancer risk were included. Statistical analyses were performed using Stata software version 17.0. To address heterogeneity among different studies, we employed a random-effects model for analysis and assessed publication bias using funnel plots and Egger's test. Results: We included 13 case-control and 8 cohort studies with 734,372 participants worldwide. In the Newcastle-Ottawa Scale (NOS) assessments, the average score was 7.43 (ranging from 5 to 9). The overall meta-analysis demonstrated a significant association between exposure to LAN and risk of breast cancer (RR = 1.12; 95% CI: 1.06-1.17; I2 = 31.3%, p < 0.001). In the subgroup analysis, the results of the analysis for study types (case-control studies: RR = 1.16; 95% CI: 1.06-1.27; I2 = 40.4%, p = 0.001; cohort studies: RR = 1.08; 95% CI: 1.04-1.14; I2 = 0.0%, p < 0.001) and the results for light exposure types (outdoor LAN: RR = 1.07; 95% CI: 1.02-1.13; I2 = 30.9%, p = 0.004) are presented. In the analysis conducted for continents, the highest breast cancer risk was observed in the Asian population (Asian: RR = 1.24; 95% CI: 1.15-1.34; I2 = 0.0%, p < 0.001) and in the analysis of estrogen receptor status (ER+: RR = 1.10; 95% CI: 1.03-1.18; I2 = 17.0%, p = 0.005;). We also conducted an analysis on menopausal status and various lifestyles but did not find any statistically significant findings. Conclusion: Our study demonstrates that LAN exposure is associated with an increased risk of breast cancer, particularly in the Asian population. Among the existing hypotheses, the idea that LAN exposure leads to a decrease in melatonin is widely accepted. However, until the mechanism of this effect is clearly elucidated, it is not recommended to take melatonin supplements for breast cancer prevention without medical advice. We hope to conduct more high-quality research, especially concerning the investigation of other environmental confounding factors, to further advance this field.