Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH).

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

Clinical analysis of lupus miliaris disseminatus faciei: a cross-sectional study and literature review.

Background: The clinical similarity of lupus miliaris disseminatus faciei (LMDF) and other papular granulomatous facial disorders often makes its correct diagnosis challenging. Diagnosis often requires the assistance of pathological examination, and dermoscopy can be used as an auxiliary and non-invasive examination method, however, the current findings remain incomplete. Objectives: This study aimed to summarize the clinical, histopathological and dermoscopic features of LMDF in the Chinese Han population and aiming to provide practical significance to correct diagnosis. Methods: 109 patients of LMDF were collected in the Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University from August 2015 to August 2023. The clinical and histopathological manifestations of all patients, as well as the dermoscopic image features of 44 cases, including background, follicular findings, vessels, and other structures, were summarized and evaluated. Results: The most significant histopathological features of LMDF in 109 cases is epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. The most significant dermoscopic features of LMDF in all 44 cases were orange structureless background (30/44), follicular plug (32/44), follicular white scar-like area (32/44), unspecific linear vessels (24/44), linear vessels with branch (24/44) and white streaks (18/44). Conclusion: Histopathologically, LMDF is characterized by the presence of epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. Dermoscopically, it exhibits a distinctive orange structureless background, follicular plug, follicular white scar-like area, nonspecific linear vessels, linear vessels with branches, and white streaks.

An overview of influenza A virus detection methods: from state-of-the-art of laboratories to point-of-care strategies.

Influenza A virus (IAV), a common respiratory infectious pathogen, poses a significant risk to personal health and public health safety due to rapid mutation and wide host range. To better prevent and treat IAV, comprehensive measures are needed for early and rapid screening and detection of IAV. Although traditional laboratory-based techniques are accurate, they are often time-consuming and not always feasible in emergency or resource-limited areas. In contrast, emerging point-of-care strategies provide faster results but may compromise sensitivity and specificity. Here, this review critically evaluates various detection methods for IAV from established laboratory-based procedures to innovative rapid diagnosis. By analyzing the recent research progress, we aim to address significant gaps in understanding the effectiveness, practicality, and applicability of these methods in different scenarios, which could provide information for healthcare strategies, guide public health response measures, and ultimately strengthen patient care in the face of the ongoing threat of IAV. Through a detailed comparison of diagnostic models, this review can provide a reliable reference for rapid, accurate and efficient detection of IAV, and to contribute to the diagnosis, treatment, prevention, and control of IAV.

Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease.

Amyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non-amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate-limiting step for amyloid-ß production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1-mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment.

Environmental Toxicant Exposure and Depressive Symptoms.

Importance: Recognizing associations between exposure to common environmental toxicants and mental disorders such as depression is crucial for guiding targeted mechanism research and the initiation of disease prevention efforts. Objectives: To comprehensively screen and assess the associations between potential environmental toxicants and depressive symptoms and to assess whether systemic inflammation serves as a mediator. Design, Setting, and Participants: A total of 3427 participants from the 2013-2014 and 2015-2016 waves of the National Health and Nutrition Examination and Survey who had information on blood or urine concentrations of environmental toxicants and depression scores assessed by the 9-item Patient Health Questionnaire (PHQ-9) were included. Statistical analysis was performed from July 1, 2023, to January 31, 2024. Exposures: Sixty-two toxicants in 10 categories included acrylamide, arsenic, ethylene oxide, formaldehyde, iodine, metals, nicotine metabolites, polycyclic aromatic hydrocarbons, volatile organic compound (VOC) metabolites; and perchlorate, nitrate, and thiocyanate. Main Outcomes and Measures: An exposome-wide association study and the deletion-substitution-addition algorithm were used to assess associations with depression scores (PHQ-9 ≥5) adjusted for other important covariates. A mediation analysis framework was used to evaluate the mediating role of systemic inflammation assessed by the peripheral white blood cell count. Results: Among the 3427 adults included, 1735 (50.6%) were women, 2683 (78.3%) were younger than 65 years, and 744 (21.7%) were 65 years or older, with 839 (24.5%) having depressive symptoms. In terms of race and ethnicity, 570 participants (16.6%) were Mexican American, 679 (19.8%) were non-Hispanic Black, and 1314 (38.3%) were non-Hispanic White. We identified associations between 27 chemical compounds or metals in 6 of 10 categories of environmental toxicants and the prevalence of depressive symptoms, including the VOC metabolites N-acetyl-S-(2-hydroxy-3-butenyl)-l-cysteine (odds ratio [OR], 1.74 [95% CI, 1.38, 2.18]) and total nicotine equivalent-2 (OR, 1.42 [95% CI, 1.26-1.59]). Men and younger individuals appear more vulnerable to environmental toxicants than women and older individuals. Peripheral white blood cell count mediated 5% to 19% of the associations. Conclusions and Relevance: In this representative cross-sectional study of adults with environmental toxicant exposures, 6 categories of environmental toxicants were associated with depressive symptoms with mediation by systemic inflammation. This research provides insight into selecting environmental targets for mechanistic research into the causes of depression and facilitating efforts to reduce environmental exposures.

The Intermode Polariton Parametric Scattering Laser in a Strong Coupled Microcavity Via Two-Photon Absorption.

Exciton-polaritons, hybrid quasiparticles from the strong coupling of excitons and cavity photons in semiconductor microcavities, offer a platform for exploring quantum coherence and nonlinear optical properties. The unique polariton parametric scattering (PPS) laser is of interest for its potential in quantum technologies and nonlinear devices. However, direct resonant excitation of polaritons in strong-coupling microcavities is challenging. This study proposes an innovative two-photon absorption (TPA) pump mechanism to address this. We observe TPA-driven PPS lasing in a strongly coupled microcavity at room temperature. High K-value exciton injections promote coherent stimulated emission of polariton scattering through intermode channels. Angle-resolved spectra confirm a TPA process, showing evolution from pump-state to signal-state. Hanbury Brown-Twiss measurement of second-order correlation g2(τ) of signal state indicates a phase transition from a classical thermal state to a quantum coherent state. Theoretical modeling provides insights into the physical mechanisms of PPS. Our work advances nonlinear phenomena exploration in strongly coupled light-matter systems, contributing to quantum polaritonics and nonlinear optics.

Cadmium contamination decreased bacterial network complexity and stability in coastal reclamation areas.

Cadmium(Cd) contamination can exert significantly adverse effects on soil microbiota in reclaimed areas, however, its effects on bacterial network structure are still limitedly understood. Here we collected soil samples from typical reclaimed wetlands (RW) and ditch wetlands (DW) in coastal reclamation areas and examined the effects of Cd contamination on the bacterial network complexity and stability. The results showed that the bacterial networks were destabilized by the Cd contamination, while bacteria in DW soils showed robust invulnerability characterized by higher node constancy and compositional stability compared with RW soils. Soil bacteria resisted Cd stress by forming a network with intensive connections in the module but sparser connections among the modules. Especially, network modularity was higher in DW soils than in RW soils, but made it more vulnerable to nodes removal. In addition, Cd contamination promoted bacterial positive cohesion but decreased negative cohesion in RW soils. Flavobacteriaceae, Xanthomonadaceae, and Alcaligenaceae were identified as core phylotypes, which played pivotal roles in regulating interspecies interactions due to higher contributions to cohesion and significant correlations with soil nutrients. The findings of this work indicate the changes of bacterial network structure and the indispensable role of core phylotypes in regulating interactions and maintaining network sustainability under Cd contamination.

AKT1 Promotes Tumorigenesis and Metastasis by Directly Phosphorylating Hexokinases.

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.

Excess deaths and loss of life expectancy attributed to long-term NO2 exposure in the Chinese elderly.

BACKGROUND: Evidence linking nitrogen dioxide (NO2) air pollution to life span of high-vulnerability older adults is extensively scarce in low- and middle-income countries. This study seeks to quantify mortality risk, excess deaths, and loss of life expectancy (LLE) associated with long-term exposure to NO2 among elderly individuals in China. METHODS: A nationwide dynamic cohort of 20352 respondents ≥65 years old were enrolled from the China Longitudinal Health and Longevity Survey during 2005-2018. Residential exposures to NO2 and co-pollutants were assessed by well-validated spatiotemporal prediction models. A Cox regression model with time-dependent covariates was utilized to quantify the association of all-cause mortality with NO2 exposure, controlling for confounders such as demographics, lifestyle, health status, and ambient temperature. NO2-attributable deaths and LLE were evaluated for the years 2010 and 2020 based on the pooled NO2-mortality relation derived from multi-national cohort investigations. Decomposition analyses were conducted to dissociate net shift in NO2-related deaths between 2010 and 2020 into four primary contributing factors. RESULTS: A total of 14313 deaths were recorded during follow-up of approximately 100 hundred person-years (median 3.6 years). We observed an approximately linear relationship (nonlinear P = 0.882) of NO2 exposure with all-cause death across a broad range from 6.6 to 95.7 µg/m3. Every 10-µg/m3 rise in yearly average NO2 concentration was linked to a hazard ratio (HR) of 1.045 (95% confidence interval [CI]: 1.031-1.059). In the updated meta-analysis of this study and 9 existing cohorts, we estimated a pooled HR of 1.043 (95% CI: 1.023-1.063) for each 10-µg/m3 growth in NO2. Reaching a 10-µg/m3 counterfactual target of NO2 concentration in China could avoid 0.33 (95% empirical CI: 0.19-0.49) million premature deaths and an LLE of 0.40 (95% empirical CI: 0.23-0.59) years in 2010, which greatly dropped to 0.24 (95% empirical CI: 0.14-0.36) million deaths and 0.21 (95% empirical CI: 0.12-0.31) years of LLE in 2020. The net fall in NO2-attributable deaths (-26.8%) between 2010 and 2020 was primarily driven by the declines in both NO2 concentration (-41.6%) and mortality rate (-27.1%) under population growth (+41.0%) and age structure transition (+0.9%). CONCLUSIONS: Our findings provide national evidence for increased risk of premature death and loss of life expectancy attributed to later-life NO2 exposure among the elderly in China. In an accelerated aging society, strengthened clean air actions should be formulated to minimize the health burden and regional inequality in NO2-attributable mortality.

Association between Volatile Organic Compound Exposure and Sex Hormones in Adolescents: The Mediating Role of Serum Albumin.

The associations between VOCs and sex hormones in adolescents remain unclear, and the role of serum albumin in these associations deserves to be explored. We conducted cross-sectional analyses using generalized linear models (GLMs), weighted quantile sum (WQS) regression, and mediation analysis, based on data from 584 adolescents from the National Health and Nutrition Examination Survey (NHANES). The GLM analyses revealed that seven kinds of mVOCs potentially affected sex hormone levels. According to the WQS regression results, 2-aminothiazoline-4-carboxylic acid (ATCA) was the major contributor to the significant associations of mixed mVOC exposure with testosterone, estradiol, and free androgen index in males; N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) was the major contributor to the significant associations of mixed mVOC exposure with sex hormone-binding globulin in males; and N-acetyl-S-(benzyl)-L-cysteine (BMA) was the major contributor to the significant associations of mixed mVOC exposure with the ratio of testosterone to estradiol in females. Moreover, serum albumin could mediate up to 9.2% of the associations between mixed exposure to mVOCs and sex hormones. Our findings could provide a reference for studies on the mechanisms underlying the effects of VOCs on sex hormones in adolescents and emphasize the necessity of reducing exposure to ATCA, AMCC, BMA, and their parent compounds.

Gamma-Tocotrienol Inhibits Proliferation and Growth of HSD17B4-Overexpressing HepG2 Liver Cancer Cells.

INTRODUCTION: Hydroxysteroid 17-beta dehydrogenase 4 (HSD17B4) is involved in the progression of hepatocellular carcinoma (HCC). AIMS: This study aimed to investigate the inhibitory effect of gamma-tocotrienol (γ-T3) on the proliferation and growth of HSD17B4-overexpressing HepG2 cells. METHODS: HepG2 cells were transfected with empty or HSD17B4-overexpressing plasmids, followed by vitamin E (VE) or γ-T3 treatment. MTS assay, Western blotting, qRT-PCR, and flow cytometry were employed to assess cell proliferation, protein expression, mRNA levels, and apoptosis. HSD17B4 interaction with γ-T3 was assessed by quantifying γ-T3 in the collected precipitate of HSD17B4 using anti-flag magnetic beads. Tumor xenografts were established in NSG mice, and tumor growth was monitored. RESULTS: HSD17B4 overexpression significantly promoted HepG2 cell proliferation, which was effectively counteracted by VE or γ-T3 treatment in a dose-dependent manner. VE and γ-T3 did not exert their effects through direct regulation of HSD17B4 expression. Instead, γ-T3 was found to interact with HSD17B4, inhibiting its activity in catalyzing the conversion of estradiol (E2) into estrone. Moreover, γ-T3 treatment led to a reduction in cyclin D1 expression and suppressed key proliferation signaling pathways, such as ERK, MEK, AKT, and STAT3. Additionally, γ-T3 promoted apoptosis in HSD17B4-overexpressing HepG2 cells. In an in vivo model, γ-T3 effectively reduced the growth of HepG2 xenograft tumors. CONCLUSION: In conclusion, our study demonstrates that γ-T3 exhibits potent anti-proliferative and anti-tumor effects against HepG2 cells overexpressing HSD17B4. These findings highlight the therapeutic potential of γ-T3 in HCC treatment and suggest its role in targeting HSD17B4-associated pathways to inhibit tumor growth and enhance apoptosis.

A Novel Multi-modal Population-graph based Framework for Patients of Esophageal Squamous Cell Cancer Prognostic Risk Prediction.

Prognostic risk prediction is pivotal for clinicians to appraise the patient's esophageal squamous cell cancer (ESCC) progression status precisely and tailor individualized therapy treatment plans. Currently, CT-based multi-modal prognostic risk prediction methods have gradually attracted the attention of researchers for their universality, which is also able to be applied in scenarios of preoperative prognostic risk assessment in the early stages of cancer. However, much of the current work focuses only on CT images of the primary tumor, ignoring the important role that CT images of lymph nodes play in prognostic risk prediction. Additionally, it is important to consider and explore the inter-patient feature similarity in prognosis when developing models. To solve these problems, we proposed a novel multi-modal population-graph based framework leveraging CT images including primary tumor and lymph nodes combined with clinical, hematology, and radiomics data for ESCC prognostic risk prediction. A patient population graph was constructed to excavate the homogeneity and heterogeneity of inter-patient feature embedding. Moreover, a novel node-level multi-task joint loss was proposed for graph model optimization through a supervised-based task and an unsupervised-based task. Sufficient experimental results show that our model achieved state-of-the-art performance compared with other baseline models as well as the gold standard on discriminative ability, risk stratification, and clinical utility. The core code is available at https://github.com/wuchengyu123/MPGSurv.

Efficacy of a smartphone application assisting home-based rehabilitation and symptom management for patients with lung cancer undergoing video-assisted thoracoscopic lobectomy: a prospective, single-blinded, randomised control trial (POPPER study).

BACKGROUND: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and post-discharge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation. METHODS: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. We screened 265 patients and randomly assigned 136 equally to the app group and usual care group. The primary outcome was pulmonary function recovery at 30 days postoperatively. Secondary outcomes included symptom burden and interference with daily living (both rated using the MD Anderson Symptom Inventory for Lung Cancer), aerobic exercise intensity, emergency department visits, app-related safety, and satisfaction with the app. FINDINGS: Of the 136 participants, 56.6% were women and their mean age was 61 years. The pulmonary function recovery ratio 1 month after surgery in the app group was significantly higher than that in the usual care group (79.32% vs. 75.73%; P=0.040). The app group also recorded significantly lower symptom burden and interference with daily living scores and higher aerobic exercise intensity after surgery than the usual care group. Thirty-two alerts were triggered in the app group. The highest pulmonary function recovery ratio and aerobic exercise intensity were recorded in those patients who triggered alerts in both groups. INTERPRETATION: Using a smartphone app is an effective approach to accelerate home-based rehabilitation after VATS lobectomy. The symptom alert mechanism of this app could optimise recovery outcomes, possibly driven by patients' increased self-awareness.

Dose-Response Relationship Between Perceived Control and Depression in Patients With Chronic Heart Failure: A Multicenter and Cross-sectional Study.

BACKGROUND: Little is known regarding the relationship between perceived control and depression in patients with chronic heart failure (CHF), particularly in terms of their dose-response relationship. OBJECTIVE: The aim of this study was to explore this relationship based on linear and nonlinear hypotheses and potential subgroup differences in patients with CHF. METHODS: A total of 308 patients with CHF were included in the study. Data on perceived control, depression, and relevant covariates, such as gender, age, New York Heart Association classification, and comorbidity burden, were collected. Logistic regression, Spearman correlation, and restricted cubic spline analysis were used for data analysis. RESULTS: Compared with the patients in the first quartiles of perceived control scores (0-16), those in the other 3 quartiles had a lower risk of depression (odds ratios of 0.29, 0.21, and 0.20, respectively; P < .05). Furthermore, a negative correlation between perceived control and depression (r = -0.317, P < .01) was observed. The restricted cubic spline analysis revealed an "L-shaped" curve relationship between perceived control and the presence of depression (P for nonlinear < .01). Compared with patients with a perceived control within the 5th percentile (10 scores), as the perceived control increased, the risk of depression rapidly decreased from "1" until it reached a threshold (20 scores) and stabilized. This trend remained consistent across the subgroups grouped by gender, age, New York Heart Association classification, and comorbidity burden. CONCLUSIONS: Interventions targeting perceived control may hold valuable implications for reducing the risk of depression in patients with CHF, particularly those who have not yet reached the threshold.

Lead specifically declines tyrosine hydroxylase activity to induce the onset of Parkinson's disease through disrupting dopamine biosynthesis in fly models.

Parkinson's disease (PD) is one of the fastest-growing neurodegenerative diseases and has been linked to the exposure to numerous environmental neurotoxins. Although lead (Pb) exposure has been related to the development of PD, the molecular target of Pb to cause the onset of PD is insufficiently investigated. Herein, we explored the effects of Pb exposure on behavior, pathophysiology, and gene expression of wild-type (WT) fly (Drosophila melanogaster) by comparison with its PD model. After exposure to Pb, the WT flies showed PD-like locomotor impairments and selective loss of dopaminergic (DAergic) neurons, displaying similar phenotypes to fly PD model (PINK1). Transcriptomic analysis showed the similarity in gene expression profiles between Pb treatment WT flies and PINK1 mutant flies. Moreover, Pb exposure resulted in endogenous dopamine deficits in WT flies. Analyses of gene expression and enzyme activity confirmed that Pb exposure reduced tyrosine hydroxylase (TH) activity and led to failure of dopamine synthesis. Furthermore, molecular dynamics simulation confirmed that Pb was adsorbed by TH and subsequently inhibited the enzymatic activity. Exogenous injection of L-dopa and melatonin could partially rescue the pathological phenotypes of Pb-exposed flies and PD fly model. Antagonist injection of microRNA-133, which negatively regulated the expression of TH gene, ultimately rescued in the manifestation of PD phenotypes in flies. Involvement of TH overexpression mutants of fly strongly promoted the resistance to Pb exposure and rescued both behavior and the number of DAergic neurons. Therefore, our study elucidates the Pb molecular target in dopamine pathway and mechanism underlying the risks of Pb exposure on the occurrence of PD at environmentally-relevant concentrations.

Effect of a fall within three months of admission on delirium in critically Ill elderly patients: a population-based cohort study.

BACKGROUND: Delirium is common among elderly patients in the intensive care unit (ICU) and is associated with prolonged hospitalization, increased healthcare costs, and increased risk of death. Understanding the potential risk factors and early prevention of delirium is critical to facilitate timely intervention that may reverse or mitigate the harmful consequences of delirium. AIM: To clarify the effects of pre-admission falls on ICU outcomes, primarily delirium, and secondarily pressure injuries and urinary tract infections. METHODS: The study relied on data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Statistical tests (Wilcoxon rank-sum or chi-squared) compared cohort characteristics. Logistic regression was employed to investigate the association between a history of falls and delirium, as well as secondary outcomes, while Kaplan-Meier survival curves were used to assess short-term survival in delirium and non-delirium patients. RESULTS: Study encompassed 22,547 participants. Delirium incidence was 40%, significantly higher in patients with a history of falls (54.4% vs. 34.5%, p < 0.001). Logistic regression, controlling for confounders, not only confirmed that a history of falls elevates the odds of delirium (OR: 2.11; 95% CI: 1.97-2.26; p < 0.001) but also showed it increases the incidence of urinary tract infections (OR:1.50; 95% CI:1.40-1.62; p < 0.001) and pressure injuries (OR:1.36; 95% CI:1.26-1.47; p < 0.001). Elderly delirium patients exhibited lower 30-, 180-, and 360-day survival rates than non-delirium counterparts (all p < 0.001). CONCLUSIONS: The study reveals that history of falls significantly heighten the risk of delirium and other adverse outcomes in elderly ICU patients, leading to decreased short-term survival rates. This emphasizes the critical need for early interventions and could inform future strategies to manage and prevent these conditions in ICU settings.

Cascade spatial and channel-wise multifusion network with criss cross augmentation for corneal segmentation and reconstruction.

High-quality 3D corneal reconstruction from AS-OCT images has demonstrated significant potential in computer-aided diagnosis, enabling comprehensive observation of corneal thickness, precise assessment of morphological characteristics, as well as location and quantification of keratitis-affected regions. However, it faces two main challenges: (1) prevalent medical image segmentation networks often struggle to accurately process low-contrast corneal regions, which is a vital pre-processing step for 3D corneal reconstruction, and (2) there are no reconstruction methods that can be directly applied to AS-OCT sequences with 180-degree scanning. To combat these, we propose CSCM-CCA-Net, a simple yet efficient network for accurate corneal segmentation. This network incorporates two key techniques: cascade spatial and channel-wise multifusion (CSCM), which captures intricate contextual interdependencies and effectively extracts low-contrast and obscure corneal features; and criss cross augmentation (CCA), which enhances shape-preserved feature representation to improve segmentation accuracy. Based on the obtained corneal segmentation results, we reconstruct the 3D volume data and generate a topographic map of corneal thickness through corneal image alignment. Additionally, we design a transfer function based on the analysis of intensity histogram and gradient histogram to explore more internal cues for better visualization results. Experimental results on CORNEA benchmark demonstrate the impressive performance of our proposed method in terms of both corneal segmentation and 3D reconstruction. Furthermore, we compare CSCM-CCA-Net with state-of-the-art medical image segmentation approaches using three challenging medical fundus segmentation datasets (DRIVE, CHASEDB1, FIVES), highlighting its superiority in terms of segmentation accuracy. The code and models will be made available at https://github.com/qianguiping/CSCM-CCA-Net.

Increased mortality risk from airborne exposure to polycyclic aromatic hydrocarbons.

BACKGROUND: The potential health effects of airborne polycyclic aromatic hydrocarbons (PAHs) among general population remained extensively unstudied. This study sought to investigate the association of short-term exposure to low-level total and 7 carcinogenic PAHs with mortality risk. METHODS: We conducted an individual-level time-stratified case-crossover study in Jiangsu province of eastern China, by investigating over 2 million death cases during 2016-2019. Daily concentrations of total PAH and its 7 carcinogenic species including benzo[a]anthracene (BaA), benzo[a]pyrene (BaP), benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), chrysene (Chr), dibenz[a,h]anthracene (DahA), and indeno[1,2,3-cd]pyrene (IcdP), predicted by well-validated spatiotemporal models, were assigned to death cases according to their residential addresses. We estimated mortality risk associated with short-term exposure to increase of an interquartile range (IQR) for aforementioned PAHs using conditional logistic regression. RESULTS: An IQR increase (16.9 ng/m3) in 2-day (the current and prior day) moving average of total PAH concentration was associated with risk increases of 1.90% (95% confidence interval [CI]: 1.71-2.09) in all-cause mortality, 1.90% (95% CI: 1.70-2.10) in nonaccidental mortality, 2.01% (95% CI: 1.72-2.29) in circulatory mortality, and 2.53% (95% CI: 2.03-3.02) in respiratory mortality. Risk increases of cause-specific mortality ranged between 1.42-1.90% for BaA (IQR: 1.6 ng/m3), 1.94-2.53% for BaP (IQR: 1.6 ng/m3), 2.45-3.16% for BbF (IQR: 2.8 ng/m3), 2.80-3.65% for BkF (IQR: 1.0 ng/m3), 1.36-1.77% for Chr (IQR: 1.8 ng/m3), 0.77-1.24% for DahA (IQR: 0.8 ng/m3), and 2.96-3.85% for IcdP (IQR: 1.7 ng/m3). CONCLUSIONS: This study provided suggested evidence for heightened mortality risk in relation to short-term exposure to airborne PAHs in general population. Our findings suggest that airborne PAHs may pose a potential threat to public health, emphasizing the need of more population-based evidence to enhance the understanding of health risk under the low-dose exposure scenario.

Ultrasmall Polyphenol-NAD+ Nanoparticle-Mediated Renal Delivery for Mitochondrial Repair and Anti-Inflammatory Treatment of AKI-to-CKD Progression.

As a central metabolic molecule, nicotinamide adenine dinucleotide (NAD+) can potentially treat acute kidney injury (AKI) and chronic kidney disease (CKD); however, its bioavailability is poor due to short half-life, instability, the deficiency of targeting, and difficulties in transmembrane transport. Here a physiologically adaptive gallic acid-NAD+ nanoparticle is designed, which has ultrasmall size and pH-responsiveness, passes through the glomerular filtration membrane to reach injured renal tubules, and efficiently delivers NAD+ into the kidneys. With an effective accumulation in the kidneys, it restores renal function, immune microenvironment homeostasis, and mitochondrial homeostasis of AKI mice via the NAD+-Sirtuin-1 axis, and exerts strong antifibrotic effects on the AKI-to-CKD transition by inhibiting TGF-ß signaling. It also exhibits excellent stability, biodegradable, and biocompatible properties, ensuring its long-term safety, practicality, and clinical translational feasibility. The present study shows a potential modality of mitochondrial repair and immunomodulation through nanoagents for the efficient and safe treatment of AKI and CKD.