Early identification of stroke through deep learning with multi-modal human speech and movement data.

JOURNAL/nrgr/04.03/01300535-202501000-00031/figure1/v/2024-05-14T021156Z/r/image-tiff Early identification and treatment of stroke can greatly improve patient outcomes and quality of life. Although clinical tests such as the Cincinnati Pre-hospital Stroke Scale (CPSS) and the Face Arm Speech Test (FAST) are commonly used for stroke screening, accurate administration is dependent on specialized training. In this study, we proposed a novel multimodal deep learning approach, based on the FAST, for assessing suspected stroke patients exhibiting symptoms such as limb weakness, facial paresis, and speech disorders in acute settings. We collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements, facial expressions, and speech tests based on the FAST. We compared the constructed deep learning model, which was designed to process multi-modal datasets, with six prior models that achieved good action classification performance, including the I3D, SlowFast, X3D, TPN, TimeSformer, and MViT. We found that the findings of our deep learning model had a higher clinical value compared with the other approaches. Moreover, the multi-modal model outperformed its single-module variants, highlighting the benefit of utilizing multiple types of patient data, such as action videos and speech audio. These results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke, thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.

Bioactivity evaluation and active compounds identification of Symphoricarpos orbiculatus as potential botanical herbicide.

BACKGROUND: Evaluation of herbicidal activity and identification of active compounds are important bases for the development of new botanical herbicides. RESULTS: This study confirmed that Symphoricarpos orbiculatus has high herbicidal activities against mono-dicotyledonous weeds, including Echinochloa crusgalli, Digitaria sanguinalis, Amaranthus retroflexus and Portulaca oleracea. By bioassay-guided isolation, 12 compounds were isolated and identified from S. orbiculatus for the first time, including iridoids: naucledal (K1), loganin (K2), loganigenin (K3), loganin acid (K4), glucologanin (K5) and vogeloside (K6), as well as flavonoids: quercetine (K7), luteolin (K8), nobiletin (K9), astragalin (K10), isorhamnetin 3-d-glucoside (K11) and rutin (K12). Biological assays showed that iridoids are the main active ingredients of S. orbiculatus. The compounds of K5 and K6 could inhibit both the root (IC50 = 37.54 and 38.91 µg mL-1, respectively) and shoot (IC50 = 42.78 and 45.72 µg mL-1, respectively) of Portulaca oleracea, which have a weeding toxicity similar to that of the commercialized plant-based herbicide pelargonic acid. In addition, the results of pot culture assay showed that S. orbiculatus ethanol extracts had high fresh weight control effect against Digitaria sanguinalis and P. oleracea at the concentration of 40 g L-1. After 7 days, both the soil treatment and the stem and leaf spray method resulted in severe leaf necrosis and significant leaf etiolation. CONCLUSION: Symphoricarpos orbiculatus and its herbicidal active compounds have the potential to develop into botanical herbicides, and are first reported in the present study. © 2024 Society of Chemical Industry.

Non-alcoholic fatty liver disease increases the risk of biochemical recurrence in high-grade metastatic prostate cancer patients.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has been reported to be helpful to identify high-risk individuals of developing prostate cancer. Our aim is to investigate the relationship between NAFLD and biochemical recurrence in metastatic prostate cancer patients. METHODS: We retrospectively investigated 602 patients with metastatic prostate cancer receiving the androgen deprivation therapy. Liver fat was estimated with liver-to-spleen ratio by computed tomography (CT) scans. The relationship between NAFLD and biochemical recurrence was investigated with Cox models. The model for biochemical recurrence was adjusted for multiple variables. RESULTS: NAFLD was significantly associated with biochemical recurrence in patients with Gleason score ≥4+3 when adjusting for each of body mass index (hazards ratio [HR] = 1.38; 95% confidence interval [CI] = 1.08-1.77; p = 0.01), visceral adipose tissue (HR = 1.36; 95% CI = 1.07-1.74; p = 0.01), hypertension (HR = 1.41; 95% CI = 1.10-1.80; p = 0.01), and diabetes mellitus (HR = 1.42; 95% CI = 1.11-1.82; p = 0.01), using age and prostate-specific antigen level as potential confounder. The 2-year biochemical recurrence rate in the Gleason score ≥4+3 patients with and without NAFLD was 84.0% (100/119) and 72.2% (130/180), respectively (p = 0.018). The median biochemical recurrence free survival of the Gleason score ≥4+3 patients with and without NAFLD were 17 and 21 months, respectively (p = 0.005). CONCLUSIONS: NAFLD is an independent risk factor for biochemical recurrence in patients with high-grade metastatic prostate cancer. If validated in prospective studies, future research should test whether treatment of NAFLD can lead to better prognosis.

Improved Precision and Safety of Supra-Tentorial Intracranial Hematoma Puncture Using C-Arm CT Four-Dimensional Navigation.

BACKGROUND Spontaneous intracerebral hemorrhage has a high fatality rate within the initial month after onset. This study determined the safety and therapeutic efficacy of minimally invasive puncture for supra-tentorial intracranial hematoma under C-arm computed tomography (CT) 4-dimensional navigation. MATERIAL AND METHODS We retrospectively analyzed 64 patients with supra-tentorial cerebral hemorrhage from June 2020 to May 2023; 31 patients were assigned to the study group (C-arm CT navigation puncture) and 33 patients were in the control group (conventional CT-guided puncture). The analysis focused on assessment of puncture error, postoperative complication rate, and the Glasgow Outcome Scale (GOS) and National Institute of Health Stroke Scale (NIHSS) scores 30 and 90 days after surgery. RESULTS C-arm CT navigation puncture had improved precision, with significantly reduced transverse (3.17±1.75 mm) and longitudinal (1.83±1.21 mm) deviations, compared with the control group (7.88±1.74 mm and 5.50±1.84 mm, respectively; P<0.05). The overall postoperative complication rate was significantly lower in the study group than in the control group (12.90% vs 36.36%, P<0.05). The mean GOS score was higher in the study group than in the control group 30 and 90 days postoperatively (3.42±0.96 and 3.97±0.95 vs 2.94±0.79 and 3.46±0.90, respectively; P<0.05), while the mean NIHSS score was lower in the study group than in the control group 30 and 90 days postoperatively (10.58±6.52 and 5.97±4.55 vs 14.42±8.13 and 9.55±8.31, respectively; P<0.05). CONCLUSIONS Supra-tentorial intracranial hematoma puncture under C-arm CT 4-dimensional navigation is accurate, safe, and beneficial.

Homoharringtonine Inhibits the NOTCH/MYC Pathway and Exhibits Anti-Tumor Effects in T-Cell Acute Lymphoblastic Leukemia.

We report on the antileukemic activity of homoharringtonine (HHT) in T-ALL. We showed that HHT inhibited NOTCH/MYC pathway and induced a significantly longer survival in T-ALL mouse and patient-derived xenograft models, therefore supporting HHT as a promising agent for T-ALL.

A distinct subset of urothelial cells with enhanced EMT features promotes chemotherapy resistance and cancer recurrence by increasing COL4A1-ITGB1 mediated angiogenesis.

Drug resistance and tumor recurrence remain clinical challenges in the treatment of urothelial carcinoma (UC). However, the underlying mechanism is not fully understood. Here, we performed single-cell RNA sequencing and identified a subset of urothelial cells with epithelial-mesenchymal transition (EMT) features (EMT-UC), which is significantly correlated with chemotherapy resistance and cancer recurrence. To validate the clinical significance of EMT-UC, we constructed EMT-UC like cells by introducing overexpression of two markers, Zinc Finger E-Box Binding Homeobox 1 (ZEB1) and Desmin (DES), and examined their histological distribution characteristics and malignant phenotypes. EMT-UC like cells were mainly enriched in UC tissues from patients with adverse prognosis and exhibited significantly elevated EMT, migration and gemcitabine tolerance in vitro. However, EMT-UC was not specifically identified from tumorous tissues, certain proportion of them were also identified in adjacent normal tissues. Tumorous EMT-UC highly expressed genes involved in malignant behaviors and exhibited adverse prognosis. Additionally, tumorous EMT-UC was associated with remodeled tumor microenvironment (TME), which exhibited high angiogenic and immunosuppressive potentials compared with the normal counterparts. Furthermore, a specific interaction of COL4A1 and ITGB1 was identified to be highly enriched in tumorous EMT-UC, and in the endothelial component. Targeting the interaction of COL4A1 and ITGB1 with specific antibodies significantly suppressed tumorous angiogenesis and alleviated gemcitabine resistance of UC. Overall, our findings demonstrated that the driven force of chemotherapy resistance and recurrence of UC was EMT-UC mediated COL4A1-ITGB1 interaction, providing a potential target for future UC treatment.

ß-blockades and the risk of atrial fibrillation in patients with cardiovascular diseases.

Background: ß-blockers have been widely used in patients with extensive cardiovascular disease (CVD) and have provided benefits. However, they are more likely to cause symptomatic bradycardia, hypotension, or glucose metabolism disorders, which may lead to an increased risk of atrial fibrillation (AF), but evidence is lacking. Aims: This study was to analyze the association between the use of ß-blockers and the risk of developing AF. Methods: This nationwide, prospective cohort study utilized data from the 2013-2020 National Health and Nutrition Examination Survey (NHANES). The patients were stratified into a ß-blocker treatment group (n = 2585) and a non-ß-blocker treatment group (n = 8525). Univariate and multivariate logistic regression analyses were performed to identify the relationship between ß-blockades and the risk of AF. Propensity matching analysis was used to balance patient baseline characteristics and to control for confounders. Results: A total of 11,110 subjects were included in this study (mean [SD] age, 59.89 [15.07] years; 5657 [49.7%] males). A total of 111/2585 subjects developed AF in the ß-blocker treatment group, and 75/8525 developed AF in the non-ß-blocker treatment group (incidence rate, 4.2% vs. 0.8%). Compared with the non-ß-blocker group, the ß-blocker group had an increased risk of incident AF (aOR, 2.339; 95% CI, 1.614-3.410). Some sensitivity analyses also revealed consistent findings of increased AF risk associated with ß-blocker treatment. Conclusion: The findings from this study suggest that ß-blocker treatment is associated with an increased risk of incident AF and may help physicians select a modest medication for patients while also assessing the risk of AF.

Impact of coronary collateralization on major adverse cardiovascular and cerebrovascular events after successful recanalization of chronic total occlusion.

Aims: This study aims to investigate the effects of coronary collateral circulation (CCC) on the prognosis of chronic total occlusion (CTO) patients with or without metabolic syndrome (MetS). Methods: The study included 342 CTO patients who underwent successful percutaneous coronary intervention at the People's Hospital of Liaoning Province between 1 February 2021 and 30 September 2023. The Rentrop score was used to assess the status of CCC. The outcome was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of all-cause mortality, cardiac death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR), and non-fatal stroke. Univariate and multivariate logistic analyses were used to investigate the association of CCC, MetS, and MACCEs with odds ratios (ORs) and 95% confidence intervals (CIs). The effect of CCC was further investigated in different MetS, diabetes mellitus (DM), and Syntax score groups. Results: MACCEs were more common in patients with poor CCC compared to those with good CCC (38.74% vs. 16.56%). Statistical differences were found in MACCEs (OR = 3.33, 95% CI: 1.93-5.72), MI (OR = 3.11, 95% CI: 1.73-5.58), TVR (OR = 3.06, 95% CI: 1.70-5.53), and stent thrombosis (OR = 6.14, 95% CI: 2.76-13.65) between the good and poor CCC groups. Poor CCC patients with MetS had a higher incidence of MACCEs (OR = 4.21, 95% CI: 2.05-8.65), non-fatal MI (OR = 4.44, 95% CI: 2.01-9.83), TVR (OR = 3.28, 95% CI: 1.51-7.11), and stent thrombosis (OR = 10.80, 95% CI: 3.11-37.54). Similar findings were also observed in CTO patients with DM and a Syntax score ≥23. Conclusion: Poor CCC could increase the risk of MACCEs in CTO patients, particularly those with MetS, DM, and a Syntax score ≥23. Further prospective, multicenter studies are needed to validate our findings and to explore potential therapeutic interventions.

Intestinal IL-33 promotes microbiota-derived trimethylamine N-oxide synthesis and drives metabolic dysfunction-associated steatotic liver disease progression by exerting dual regulation on HIF-1α.

BACKGROUND AND AIMS: Gut microbiota play a prominent role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). Interleukin-33 (IL-33) is highly expressed at mucosal barrier sites and regulates intestinal homeostasis. Herein, we aimed to investigate the role and mechanism of intestinal IL-33 in MASLD. APPROACH AND RESULTS: In both human and mice with MASLD, hepatic expression of IL-33 and its receptor suppression of tumorigenicity 2 (ST2) showed no significant change compared to controls, while serum soluble ST2 levels in humans, as well as intestinal IL-33 and ST2 expression in mice were significantly increased in MASLD. Deletion of global or intestinal IL-33 in mice alleviated metabolic disorders, inflammation and fibrosis associated with MASLD by reducing intestinal barrier permeability and rectifying gut microbiota dysbiosis. Transplantation of gut microbiota from IL-33 deficiency mice prevented MASLD progression in wild type (WT) mice. Moreover, IL-33 deficiency resulted in a decrease in the abundance of trimethylamine N-oxide (TMAO)-producing bacteria. Inhibition of TMAO synthesis by 3,3-dimethyl-1-butanol (DMB) mitigated hepatic oxidative stress in mice with MASLD. Nuclear IL-33 bound to hypoxia inducible factor-1α (HIF-1α) and suppressed its activation, directly damaging the integrity of intestinal barrier. Extracellular IL-33 destroyed the balance of intestinal Th1/Th17 and facilitated Th1 differentiation through the ST2-Hif1a-Tbx21 axis. Knockout of ST2 resulted in a diminished MASLD phenotype resembling that observed in IL-33 deficiency mice. CONCLUSIONS: Intestinal IL-33 enhanced gut microbiota-derived TMAO synthesis and aggravated MASLD progression through dual regulation on HIF-1α. Targeting IL-33 and its associated microbiota may provide a potential therapeutic strategy for managing MASLD.

The mechanism of bone metabolism in a Sprague Dawley rat model of mandibular osteoradionecrosis.

Background: Osteoradionecrosis (ORN) is a serious complication of radiotherapy for head and neck cancer. There is currently a lack of data on the dynamic expression of genes related to bone remodeling during the development of mandibular ORN. This study aimed to establish an animal model of ORN in Sprague Dawley (SD) rats, detect the expression of genes related to bone metabolism, observe morphological changes, and clarify the mechanism of ORN. Methods: A total of 24 male SD rats in group 1 were randomly divided into four groups (n=6/group): group a, normal control; group b, simple tooth extraction; group c, simple radiation; and group d, radiation extraction group. The right mandible of rats in groups c and d was irradiated with a single dose of 35 Gy. The right mandibles were taken from each group for morphological observation 90 days after irradiation. SD rats in group 2 (n=144) were randomly divided into four groups (in similar fashion to group 1 but with groups a', b', c', and d'). Samples were collected at six time points after irradiation. Histopathological changes were observed, and Western blotting (WB) was used to analyze protein expression. Results: The formation of dead bone and pathological fracture was visible under micro-computed tomography (micro-CT), and tissue biopsy showed late fibrosis repair. In group d', osteogenesis and osteoclasis coexisted in the early irradiation stage. Vascular endothelial growth factor (VEGF) receptor expression was lower in groups c' and d' than in group a'. On day 45, runt-related transcription factor 2 (RUNX2) expression in group d' was lower than that in the other groups. The ratio of receptor activator of nuclear factor-κß ligand to osteoprotegerin (RANKL:OPG) differed significantly among groups b', c', and d' on the 45th day (d' > c' > b'). Conclusions: Radiation and vascular function damage resulted in the lower expression of VEGF. The first 15 days after radiation was mainly characterized by new bone formation. After 15 days, bone resorption increased. Tooth extraction trauma can aggravate the bone metabolism imbalance and promote ORN occurrence. These findings shed light on the mechanism of ORN.

Nomogram of magnetic resonance imaging (MRI) histogram analysis to predict telomerase reverse transcriptase promoter mutation status in glioblastoma.

Background: Telomerase reverse transcriptase promoter (pTERT) status is a strong biomarker to diagnose and predict the prognosis of glioblastoma (GBM). In this study, we explored the predictive value of preoperative magnetic resonance imaging (MRI) histogram analysis in the form of nomogram for evaluating pTERT mutation status in GBM. Methods: The clinical and imaging data of 181 patients with GBM at our hospital between November 2018 and April 2023 were retrospectively assessed. We used the molecular sequencing results to classify the datasets into pTERT mutations (C228T and C250T) and pTERT-wildtype groups. FireVoxel software was used to extract preoperative T1-weighted contrast-enhanced (T1C) histogram parameters of GBM patients. The T1C histogram parameters were compared between groups. Univariate and multivariate logistic regression analyses were used to construct the nomogram, and the predictive efficacy of model was evaluated using calibration and decision curves. Receiver operating characteristic curve was used to assess model performance. Results: Patient age and percentage of unenhanced tumor area showed statistically significant differences between the pTERT mutation and pTERT-wildtype groups (P<0.001). Among the T1C histogram features, the maximum, standard deviation (SD), variance, coefficient of variation (CV), skewness, 5th, 10th, 25th, 95th and 99th percentiles were statistically significantly different between groups (P=0.000-0.040). Multivariate logistic regression analysis showed that age, percentage of unenhanced tumor area, SD and CV were independent risk factors for predicting pTERT mutation status in GBM patients. The logistic regression model based on these four features showed a better sample predictive performance, and the area under the curve (AUC) [95% confidence interval (CI)], accuracy, sensitivity, specificity were 0.842 (0.767-0.917), 0.796, 0.820, and 0.729, respectively. There were no significant differences in the T1C histogram parameters between the C228T and C250T groups (P=0.055-0.854). Conclusions: T1C histogram parameters can be used to evaluate pTERT mutations status in GBM. A nomogram based on conventional MRI features and T1C histogram parameters is a reliable tool for the pTERT mutation status, allowing for non-invasive radiological prediction before surgery.

Synthesis of non-modified near-infrared carbon dots for hypochlorite detection and cell membrane imaging.

Devising carbon dots with long wavelength emission (red light or near infrared), high selectivity and good bio-compatibility is critical in fluorescence detection and imaging, but achieving this goal remains a great challenge. Herein, near-infrared emissive carbon dots (NIR-CDs) with obvious emission characteristic of 653 nm were synthesized through hydrothermally treatment of toluidine bule and gallic acid. Noticeably, the NIR-CDs exhibited excellent selectivity and sensitivity to hypochlorite (ClO-), and the limit of detection is as low as 42.7 nM. The selective recognition reaction between ClO- and the surface functional groups of NIR-CDs inhibits the fluorescence from NIR-CDs. The quenching mechanism was confirmed by fluorescence lifetime decays, FT-IR spectroscopy and UV-vis absorption spectra. More remarkably, the NIR-CDs have rich hydrophilic groups showed lower cytotoxicity, excellent bio-compatibility and specific cell membrane localization ability. The established spectrofluorometric method based on NIR-CDs has been used to determination of ClO- level in tap water sample, the recoveries were 97.7 %-103.3 %. In addition, the NIR-CDs also has been successfully applied for the imaging of cell membrane. The study provides a novel idea for developing NIR ClO- probe as well as cell membrane localization probe based on CDs, which present bright prospects in real water samples monitoring and cell membrane imaging.

Catalyst-Free Extraction of U(VI) in Solution by Tribocatalysis.

Extraction of U(VI) in water is of great significance in energy and environmental fields. However, the traditional methods usually fail due to the indispensable extra addition of catalyst, adsorbent, precipitant, or sacrificial agents, which may lead to enhanced extraction costs and secondary pollution. Here, a new efficient uranium extraction strategy is proposed based on triboelectricity without adding a catalyst or other additives. It is found only under the friction between the microbubbles (generated under ultrasonication) and the water flow, that reactive oxygen species (ROS) can largely be generated, which thus contributes to the solidification of U(VI) from water. In addition, the magnetic field can affect the phase of the product. Under mechanical stirring, the product contains (UO2)O2·2H2O, while which contains UO2(OH)2 and (UO2)O2·4H2O under the magnetic stirring. Quenching experiments are also carried out to explore the influence of environmental factors. Most importantly, it shows great potential in the extraction of U(VI) from seawater. This work proposes a catalyst-free and light-free strategy toward the solidification of U(VI) from water, which avoids the secondary pollution of the catalyst to the environment and is low-cost, and has great potential in the real application.

A pan-TE map highlights transposable elements underlying domestication and agronomic traits in Asian rice.

Transposable elements (TEs) are ubiquitous genomic components and hard to study due to being highly repetitive. Here we assembled 232 chromosome-level genomes based on long-read sequencing data. Coupling the 232 genomes with 15 existing assemblies, we developed a pan-TE map comprising both cultivated and wild Asian rice. We detected 177 084 high-quality TE variations and inferred their derived state using outgroups. We found TEs were one source of phenotypic variation during rice domestication and differentiation. We identified 1246 genes whose expression variation was associated with TEs but not single-nucleotide polymorphisms (SNPs), such as OsRbohB, and validated OsRbohB's relative expression activity using a dual-Luciferase (LUC) reporter assays system. Our pan-TE map allowed us to detect multiple novel loci associated with agronomic traits. Collectively, our findings highlight the contributions of TEs to domestication, differentiation and agronomic traits in rice, and there is massive potential for gene cloning and molecular breeding by the high-quality Asian pan-TE map we generated.

Biochemical indicators, cell apoptosis, and metabolomic analyses of the low-temperature stress response and cold tolerance mechanisms in Litopenaeus vannamei.

The cold tolerance of Litopenaeus vannamei is important for breeding in specific areas. To explore the cold tolerance mechanism of L. vannamei, this study analyzed biochemical indicators, cell apoptosis, and metabolomic responses in cold-tolerant (Lv-T) and common (Lv-C) L. vannamei under low-temperature stress (18 °C and 10 °C). TUNEL analysis showed a significant increase in apoptosis of hepatopancreatic duct cells in L. vannamei under low-temperature stress. Biochemical analysis showed that Lv-T had significantly increased levels of superoxide dismutase (SOD) and triglycerides (TG), while alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH-L), and uric acid (UA) levels were significantly decreased compared to Lv-C (p < 0.05). Metabolomic analysis displayed significant increases in metabolites such as LysoPC (P-16:0), 11beta-Hydroxy-3,20-dioxopregn-4-en-21-oic acid, and Pirbuterol, while metabolites such as 4-Hydroxystachydrine, Oxolan-3-one, and 3-Methyldioxyindole were significantly decreased in Lv-T compared to Lv-C. The differentially regulated metabolites were mainly enriched in pathways such as Protein digestion and absorption, Central carbon metabolism in cancer and ABC transporters. Our study indicate that low temperature induces damage to the hepatopancreatic duct of shrimp, thereby affecting its metabolic function. The cold resistance mechanism of Lv-T L. vannamei may be due to the enhancement of antioxidant enzymes and lipid metabolism.

Association between type 2 diabetes, alcohol intake frequency, age at menarche, and gallbladder cancer: a two-sample Mendelian randomization study.

Background: Gallbladder cancer (GBC) is a rare malignancy of the digestive tract, characterized by a remarkably poor prognosis. Currently, there is a controversy on the relationship between type 2 diabetes (T2D) and GBC. Additionally, no definitive conclusions were established regarding the causal relationships between alcohol intake frequency (AIF), age at menarche (AAM) and GBC. The objective of this study was to elucidate the causal association between T2D, AIF, AAM, and GBC. Methods: Single-nucleotide polymorphisms (SNPs) associated with exposures and outcomes were sourced from the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Study (GWAS) database. Specifically, the data of GBC comprised 907 East Asians (pathological results of all cases were registered into Biobank Japan) and 425,707 SNPs; T2D comprised 655,666 Europeans with 5,030,727 SNPs; AIF comprised 462,346 Europeans and 9,851,867 SNPs; AAM comprised 243,944 Europeans and 9,851,867 SNPs. The measurement of exposure traits is collected uniformly from the UK Biobank (UKB) database and presented in the form of standard deviation (SD) or the logarithmic form of the odds ratio (logOR). We employed a two-sample Mendelian randomization (MR) analysis to discern the causalities between T2D, AIF, AAM, and GBC. Sensitivity analyses were conducted to identify and address potential heterogeneity, horizontal pleiotropy, and outliers. Results: Our findings indicated that T2D reduced GBC risk [odds ratio (OR) =0.044; 95% confidence interval (CI): 0.004-0.55; P=0.015, inverse variance-weighted (IVW)]. However, no causal relationship was observed between AIF (OR =0.158; 95% CI: 5.33E-05 to 466.84; P=0.65, IVW), AAM (OR =0.19; 95% CI: 0.0003-140.34; P=0.62, IVW), and GBC. Sensitivity analysis revealed no evidence of horizontal pleiotropy, heterogeneity, or outliers, suggesting the robustness and reliability of our conclusions. Conclusions: T2D emerged as a potentially protective factor against GBC, whereas neither AIF nor AAM demonstrated a causal relationship with GBC risk. Regulation of glucose metabolism may be one of the methods for preventing GBC.

Impacts of Tumor Stage at Diagnosis and Adjuvant Therapy on Long-Term Survival Outcomes in Patients With Triple-Negative Breast Cancer Achieving Pathologic Complete Response After Neoadjuvant Chemotherapy.

BACKGROUND: It remains unknown whether the tumor stage at initial diagnosis and adjuvant treatments had any impacts on the long-term survival outcomes of patients with triple-negative breast cancer (TNBC) achieving pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT). METHODS: Clinical stage II-III patients with TNBC who achieved pCR after NACT were identified from the Surveillance, Epidemiology, and End Results (SEER) program (SEER cohort) and the National Clinical Research Center for Cancer (Tianjin) in China (TMUCIH cohort). Survival analyses were conducted based on tumor stages and the types of adjuvant treatment received by the patients. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: The TMUCIH cohort comprised 178 patients with a median follow-up of 55.5 months. Two and 3 patients experienced BCSS and OS events, respectively. The SEER cohort included 1218 patients with a median follow-up of 65.5 months, where 53 and 78 patients experienced BCSS and OS events, respectively. Patients diagnosed with stage III disease had significantly higher hazards of death compared to stage II disease (OS: hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.84-6.07; P < .001; BCSS: HR, 2.86; 95% CI, 1.38-5.92; P < .001). Adjuvant systemic and radiation therapy did not confer additional benefits to OS and BCSS. CONCLUSION: Tumor stage at initial diagnosis remains an independent predictor of long-term survival outcomes in patients with TNBC achieving pCR after NACT. Postoperative adjuvant chemotherapy and radiation therapy do not appear to provide additional benefit to their long-term prognosis.

Vertical distribution of microplastics in sediment columns along the coastline of China.

At present, there has been relatively less coverage of microplastics (MPs) pollution in sediment columns, especially across a large geographical span. This study collected sediment columns across 11 provinces along the coastline of China for MPs pollution investigation. The study found higher MPs diversity (Simpson diversity index) in sediment columns than in surface sediments, mostly comprising fiber MPs with dominant transparent and blue colors. Lower MPs pollution was noted in mangrove reserves, while estuarine and coastal areas showed higher pollution levels. Spearman correlation analysis shows that vertical of MPs abundance significantly decreased with depth at 6 of 11 sites. Large-sized MPs with diverse colors in deeper sediments (>40 cm) suggests that burial processes may render MPs more resistant to degradation. Our research highlights varied MPs distribution in coastal sediment, aiding future marine MPs pollution prediction and assessment.

Wearable device-measured moderate to vigorous physical activity and risk of degenerative aortic valve stenosis.

BACKGROUND AND AIMS: Physical activity has proven effective in preventing atherosclerotic cardiovascular disease, but its role in preventing degenerative valvular heart disease (VHD) remains uncertain. This study aimed to explore the dose-response association between moderate to vigorous physical activity (MVPA) volume and the risk of degenerative VHD among middle-aged adults. METHODS: A full week of accelerometer-derived MVPA data from 87 248 UK Biobank participants (median age 63.3, female: 56.9%) between 2013 and 2015 were used for primary analysis. Questionnaire-derived MVPA data from 361 681 UK Biobank participants (median age 57.7, female: 52.7%) between 2006 and 2010 were used for secondary analysis. The primary outcome was the diagnosis of incident degenerative VHD, including aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The secondary outcome was VHD-related intervention or mortality. RESULTS: In the accelerometer-derived MVPA cohort, 555 incident AS, 201 incident AR, and 655 incident MR occurred during a median follow-up of 8.11 years. Increased MVPA volume showed a steady decline in AS risk and subsequent AS-related intervention or mortality risk, levelling off beyond approximately 300 min/week. In contrast, its association with AR or MR incidence was less apparent. The adjusted rates of AS incidence (95% confidence interval) across MVPA quartiles (Q1-Q4) were 11.60 (10.20, 13.20), 7.82 (6.63, 9.23), 5.74 (4.67, 7.08), and 5.91 (4.73, 7.39) per 10 000 person-years. The corresponding adjusted rates of AS-related intervention or mortality were 4.37 (3.52, 5.43), 2.81 (2.13, 3.71), 1.93 (1.36, 2.75), and 2.14 (1.50, 3.06) per 10 000 person-years, respectively. Aortic valve stenosis risk reduction was also observed with questionnaire-based MVPA data [adjusted absolute difference Q4 vs. Q1: AS incidence, -1.41 (-.67, -2.14) per 10 000 person-years; AS-related intervention or mortality, -.38 (-.04, -.88) per 10 000 person-years]. The beneficial association remained consistent in high-risk populations for AS, including patients with hypertension, obesity, dyslipidaemia, and chronic kidney disease. CONCLUSIONS: Higher MVPA volume was associated with a lower risk of developing AS and subsequent AS-related intervention or mortality. Future research needs to validate these findings in diverse populations with longer durations and repeated periods of activity monitoring.

Affective computing for human-machine interaction via a bionic organic memristor exhibiting selective in situ activation.

Affective computing, representing the forefront of human-machine interaction, is confronted with the pressing challenges of the execution speed and power consumption brought by the transmission of massive data. Herein, we introduce a bionic organic memristor inspired by the ligand-gated ion channels (LGICs) to facilitate near-sensor affective computing based on electroencephalography (EEG). It is constructed from a coordination polymer comprising Co ions and benzothiadiazole (Co-BTA), featuring multiple switching sites for redox reactions. Through advanced characterizations and theoretical calculations, we demonstrate that when subjected to a bias voltage, only the site where Co ions bind with N atoms from four BTA molecules becomes activated, while others remain inert. This remarkable phenomenon resembles the selective in situ activation of LGICs on the postsynaptic membrane for neural signal regulation. Consequently, the bionic organic memristor network exhibits outstanding reliability (200 000 cycles), exceptional integration level (210 pixels), ultra-low energy consumption (4.05 pJ), and fast switching speed (94 ns). Moreover, the built near-sensor system based on it achieves emotion recognition with an accuracy exceeding 95%. This research substantively adds to the ambition of realizing empathetic interaction and presents an appealing bionic approach for the development of novel electronic devices.