The Determinants of Mental Illness Self-Management for Patients With Schizophrenia and Type 2 Diabetes: A Self-Determination Theory Approach.

AIM: This study based on self-determination theory aimed to assess the relationship between motivation, competence in diabetes management and perceived autonomy support respectively and mental illness self-management; furthermore, the authors intended to explore the determinants of mental illness self-management for patients with schizophrenia and diabetes. DESIGN: This was a cross-sectional study. METHODS: One hundred ten participants were recruited at the psychiatric hospital and assessed with the Illness Management and Recovery Scale, the Treatment Self-Regulation Questionnaire, the Perceived Competence Scale for Diabetes and the Health-Care Climate Questionnaire. RESULTS: Patients with lower educational levels, who were admitted to the chronic ward, were unemployed, had lower motivation in illness management, lower competence in diabetes management and perceived lower autonomy support all had lower mental illness self-management. Competence in diabetes management, employment status, autonomy support, educational levels and living alone were the determinants of mental illness self-management. CONCLUSION: Recovery from schizophrenia and comorbid diabetes is an enduring and complicated process requiring support from healthcare providers. Health professionals should assess the levels of illness self-management and provide integrated care interventions for patients with schizophrenia and diabetes, helping them manage both conditions. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: The illness management programme could apply to patients with schizophrenia and diabetes and address patients' characteristics such as low levels of education, living alone and being unemployed while additionally promoting motivation and competence, and providing supporting autonomy. REPORTING METHOD: The STROBE checklist was followed. PATIENT OR PUBLIC CONTRIBUTION: Patients with schizophrenia and diabetes were recruited for this study and voluntarily completed the questionnaire.

Investigation of electrocatalysis for tiered-tower micro-electro-mechanical-system-based biosensors: application in the early detection of the thrombosis factor trimethylamine N-oxide.

Trimethylamine N-oxide (TMAO) has been recognized as a biomarker for the early detection of thrombosis. However, testing for TMAO typically requires expensive laboratory equipment and skilled technicians, making it unsuitable for home care pre-screening. To enable its widespread use in home applications, it is crucial to develop a scalable and sensitive device capable of catalyzing TMAO metabolism with a specific enzyme that is tailored for point-of-care use. This study presents an investigation of a MEMS-based two-tiered-tower biosensor array with a detection limit of 0.1 µM for TMAO, aiming to diagnose chronic metabolic diseases using urine or serum samples. Based on the augmented Cole-Cole model, the proposed parameters R_catalyzed, C_catalyzed, and Rp_catalyzed can predict the catalytic impedance of enzymatic activities such as the redox effects of analytes and characterize the small-signal current caused by catalysis. The proposed MEMS biosensor, integrated with a readout circuitry, demonstrates a high sensitivity of 41 ADC counts per µM TMAO (or 4.5 mV µM-1 TMAO), a response time of 1 second, a repetition rate of 98.9%, and a drift over time of 0.5 mV. The sensor effectively distinguishes TMAO based on minute capacitance changes induced by the TorA enzyme, resulting in a discernible distinction of 10.6%. These measurements were successfully compared to conventional cyclic voltammetry (CV) results, showing a variance of only 0.024%. The proposed biosensor is well-suited for pre-screening thrombosis factors for the early detection and prevention of thrombosis in point-of-care applications. The device is cost-effective, lightweight, and demonstrates excellent performance, with a conversion rate of 88% of TMAO and a selectivity rate of 97% for the by-product TMA, allowing for the prediction of cardiovascular risks.

A comprehensive molecular phylogeny of the genus Sylvirana (Anura: Ranidae) highlights unrecognized diversity, revised classification and historical biogeography.

The genus Sylvirana includes 12 species widely distributed in South China and Southeast Asia. The phylogenetic relationships and species diversity for Sylvirana and allied genera remain unresolved and controversial due to insufficient data and incomplete taxon sampling. Using a combined dataset of mitochondrial genes (16S and COI) and 101 nuclear genes obtained through the amplicon sequence capture approach, we generated the most comprehensive phylogenetic analysis for the genus Sylvirana to date, inferring diversity, phylogenetic relationships, and historical biogeography with unprecedented levels of taxon and geographic sampling. Our results conservatively reveal six undescribed species, mostly distributed in peninsular Indochina. Phylogenetic analyses strongly support the non-monophyly of Sylvirana with respect to Pterorana. Additionally, phylogenetic results place Sylvirana guentheri and Pelophylax lateralis into genus Humerana, supporting the inclusion of Hylarana latouchii, Papurana milleti, and Hylarana attigua within Pterorana + Sylvirana. The long-disputed species of Hylarana bannanica (previously Sylvirana) cluster with genus Papurana. Because the results of multiple non-monophyletic genera create taxonomic confusion, we suggest relegating all genera to subgenus rank of Hylarana. Sylvirana is a junior synonym of the Pterorana. Biogeographically, we trace the origin of Pterorana to Southeast Asia during the early Miocene, with subsequent dispersal thereafter. Our study shows that climatic changes may have profoundly influenced the diversification of Pterorana during the Miocene.

Non-Linear Association Between Climatic Parameters and Bell's Palsy Prevalence of Hospital Outpatients: An Ecological Proof in Kunshan, Suzhou, China.

Objective: This study aimed to explore the relationship between climatic parameters and the daily cases of Bell's palsy (BP) among hospital outpatients, providing ecological evidence for understanding BP etiology and prevention. Methods: Retrospective analysis was conducted on data from 2187 BP patients who attended Kunshan First People's Hospital Outpatient Clinic from January 1, 2020, to December 31, 2022. Meteorological data, including temperature, relative humidity, precipitation, wind speed, sunshine duration, and atmospheric pressure, were collected and combined with daily BP case records. Additionally, air quality index was used as a covariate. Results: The number of new BP cases among outpatients showed a negative correlation with average daily temperature. A nonlinear relationship between daily average temperature and BP cases was observed through the generalized additive model (GAM). A significant negative correlation was identified between daily average temperature and BP cases, with inflection points at temperatures above 4.2°C, suggesting a potential decrease in BP risk with temperature rise beyond this threshold. Conclusion: This study provides ecological evidence of a link between climatic factors and BP occurrence. Temperature demonstrated a significant nonlinear negative correlation with daily BP incidence, highlighting temperature and cold exposure as key targets for BP prevention in Kunshan.

Comparative risk of infection of medications used for type 2 diabetes.

INTRODUCTION: Glucose-lowering drugs pose a potential infection risk among individuals with type 2 diabetes. The U.S. Food and Drug Administration has issued safety warnings regarding increased risks of urinary tract infections (UTIs) and genital infections with sodium-glucose cotransporter 2 (SGLT2) inhibitors. However, the infection risk associated with other glucose-lowering drugs remains unclear. We conducted a PubMed database search to review the infection risk of glucose-lowering drugs, focusing on meta-analysis of randomized controlled trials. AREAS COVERED: We described the infection risks associated with SGLT2 inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucose-like peptide-1 receptor agonists, metformin, and thiazolidinediones, covering infections of the genitourinary, respiratory, and gastrointestinal systems, including skin and soft tissue infections (SSTIs). EXPERT OPINION: SGLT2 inhibitors are associated with a higher genital infection risk, while their UTI risk remains inconclusive. DPP-4 inhibitors could be a treatment option for those intolerant to SGLT2 inhibitors, given their lower genital infection risk compared to placebo. Uncertainty persists regarding the risks of respiratory infections, gastroenteritis, and SSTIs with SGLT2 inhibitors. Limited evidence is available regarding the impact of DPP-4 inhibitors on respiratory infections. Additional research is needed to determine the comparative infection risk of other glucose-lowering drugs.

Genes Selectively Expressed in Rat Organs.

Background: Understanding organic functions at a molecular level is important for scientists to unveil the disease mechanism and to develop diagnostic or therapeutic methods. Aims: The present study tried to find genes selectively expressed in 11 rat organs, including the adrenal gland, brain, colon, duodenum, heart, ileum, kidney, liver, lung, spleen, and stomach. Materials and Methods: Three normal male Sprague-Dawley (SD) rats were anesthetized, their organs mentioned above were harvested, and RNA in the fresh organs was extracted. Purified RNA was reversely transcribed and sequenced using the Solexa high-throughput sequencing technique. The abundance of a gene was measured by the expected value of fragments per kilobase of transcript sequence per million base pairs sequenced (FPKM). Genes in organs with the highest expression level were sought out and compared with their median value in organs. If a gene in the highest expressed organ was significantly different (p < 0.05) from that in the medianly expressed organ, accompanied by q value < 0.05, and accounted for more than 70% of the total abundance, the gene was assumed as the selective gene in the organ. Results & Discussion: The Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) pathways were enriched by the highest expressed genes. Based on the criterion, 1,406 selective genes were screened out, 1,283 of which were described in the gene bank and 123 of which were waiting to be described. KEGG and GO pathways in the organs were partly confirmed by the known understandings and a good portion of the pathways needed further investigation. Conclusion: The novel selective genes and organic functional pathways are useful for scientists to unveil the mechanisms of the organs at the molecular level, and the selective genes' products are candidate disease markers for organs.

Associations of different types of statins with the risk of open-angle glaucoma: a systematic review and network meta-analysis.

PURPOSE: Previous studies implied that different types of statins may pose divergent impacts on the risk of glaucoma onset. This study aimed to comprehensively evaluate the effects of various statins on the risk of glaucoma occurrence. METHODS: PubMed, Cochrane CENTRAL, Embase, and Web of Science were searched from February 1994 to February 2024. We included studies that investigated the effects of various types of statins, fibrates, ezetimibe, cholestyramine, niacin, PCSK9 inhibitors, omega-3 fatty acids, and any cholesterol-lowering medications on glaucoma onset or progression. The revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) and the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-1) tool were used to assess the quality of randomized controlled trials (RCTs) and non-RCTs, respectively. The frequentist network meta-analysis framework was utilized to evaluate the comparative effectiveness, with the random effects model applied. RESULTS: This network meta-analysis comprised 12 studies, encompassing 262,217 individuals and including cholesterol-lowering medications such as statins, fibrates, ezetimibe, cholestyramine, niacin, and omega-3 fatty acids. Our findings demonstrate that comparing to the placebo, rosuvastatin (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.03 to 1.46), simvastatin (RR, 1.21; 95% CI, 1.02 to 1.43), and pravastatin (RR, 1.20; 95% CI, 1.01 to 1.43) increased the risk of glaucoma onset with statistical significance. CONCLUSION: Rosuvastatin, simvastatin, and pravastatin were each associated with a significantly increased risk of glaucoma onset. We advise medical practitioners to exercise caution when prescribing these specific statins for patients who are at risk of developing glaucoma. KEY MESSAGES: What is known Previous studies have suggested a link between statins and the risk of developing glaucoma. However, there is still ongoing debate regarding the specific effects of each type of statin on the onset of glaucoma. What is new This network meta-analysis comprehensively evaluated the effects of various statins on the risk of glaucoma onset. Rosuvastatin, simvastatin, and pravastatin were associated with a significantly increased risk of glaucoma onset.

[Distribution Characteristics and Risk Assessment of Organophosphates in Water and Sediment in Dongting Lake].

Organophosphates （OPEs） are widely used as flame retardants and additives and thus are commonly detected in the environment. In order to explore their environmental behavior, the concentrations of 13 OPEs in the surface water and sediment of Dongting Lake were analyzed using UPLC-MS/MS. The results showed that 11 OPEs were detected, with detection frequencies of 5.26%-100% and 58.3%-100%, and the concentrations of OPEs were 2.06-2 028 ng·L-1 and 19.6-2 232 ng·g-1 in water and sediment, respectively. Overall, contamination concentrations were ranked in descending order as follows： inflowing rivers, lake area, and outlet, whereas the spatial distribution of concentrations in sediment was inversely proportional to hydrodynamics. The concentration of OPEs in Dongting Lake was at a high level compared with that of domestic and foreign lakes. Among the detected 11 OPEs, tri-iso-butyl phosphate （TnBP） and （TiBP） were dominant in water, accounting for 52.3% and 22.4% of ∑OPEs, respectively. TPhP was the dominant OPEs in sediment, accounting for 31.2% of ∑OPEs. The correlation and principal component analysis indicated that OPEs pollution in Dongting Lake was mainly affected by industrial production emissions, fishery aquaculture, and atmospheric deposition. The assessment results of the risk entropy showed that most of the detected OPEs in water had relatively low ecological risks, whereas the ecological risk of 2-ethylhexyl diphenyl phosphate （EHDPP） at some sampling points requires further attention.

Ensartinib in the treatment of anaplastic lymphoma kinase-positive locally advanced or metastatic patients with lung squamous or adenosquamous carcinoma: A real-world, retrospective study.

AIM: To report the efficacy and safety of ensartinib, an anaplastic lymphoma kinase (ALK) inhibitor, in treating patients with ALK-positive advanced lung squamous cell carcinoma (LUSC) or lung adenosquamous carcinoma (LASC) in China. METHODS: This retrospective study analyzed data for 36 advanced-stage patients with ALK-positive LUSC (cohort A) and 13 patients with ALK-positive LASC (cohort B) between December 16, 2020 and December 16, 2021. All patients received once-daily ensartinib 225 mg. Outcome analysis included the demographic characteristics, tumor response, progression-free survival (PFS), and treatment-related adverse events (TRAE). RESULTS: Among the 49 patients, the majority were under 65 years old (73.5%), non-smokers (85.7%), had an Eastern Cooperative Oncology Group Performance Status of 0-1 (77.6%), and were at stage IV (71.4%). All patients were included in the efficacy and safety analysis. Seven PFS events were reported in cohort A while no patients experienced PFS events in cohort B. The median PFS was not estimable for both cohorts. In cohort A, the objective response rate (ORR) was 63.9%, and the disease control rate (DCR) was 83.3%. In the cohort B, the ORR was 76.9% and the DCR was 100.0%. Rash was the only TRAE reported in the cohort A (8.3%) and cohort B (23.1%). No patients had grade 3 or higher TRAE. CONCLUSION: Ensartinib has been tentatively proven favorable efficacy and tolerability in the treatment of patients with ALK-positive advanced LUSC or LASC in the real-world. However, confirmatory studies are still needed in larger sample sizes.

The Impact of the COVID-19 Pandemic on Orthodontic Adult Patients' Characteristics and Decision on Orthodontic Appliance.

Purpose: There is an overall paucity of data examining the specific details of orthodontic patients' patterns or orthodontic service disruptions possibly influenced by COVID-19 pandemic. Therefore, this study aimed to explore the impact of the COVID-19 pandemic on orthodontic clinic disruption regarding the change in adult patients' characteristics and decisions of orthodontic treatment devices. Patients and Methods: A retrospective sample of 311 patients receiving orthodontic treatment from 2018 to 2022 were collected and divided into two groups: before (n = 167) and during (n = 144) the COVID-19 pandemic. Demographics, dental indices, the index of complexity outcome and need (ICON), and the degree of treatment difficulty were analyzed. Results: There were fewer students among patients during the COVID-19 pandemic than before (24.5% versus 35.9%, P = 0.036). Compared with patients before the pandemic, more patients selected ceramic brackets or Invisalign during the pandemic (P = 0.022). There were higher percentage of class I dental malocclusions among patients during than before the COVID-19 pandemic (P = 0.044). Moreover, the ICON score and the score of the degree of treatment difficulty were both significantly lower for patients during than before the COVID-19 pandemic (63.9±14.0 versus 58.3±15.3, P=0.001 and 7.4±2.6 versus 6.8±2.6, P=0.049, respectively). Conclusion: The COVID-19 pandemic influenced the characteristics and decisions of orthodontic patients. Those who still came to the orthodontic clinic despite the COVID-19 outbreak may have been those with less malocclusion severity and treatment difficulty. Besides, during the time of covid-19 pandemic, more patients chose ceramic bracket and Invisalign as their orthodontic treatment device rather than conventional or self-ligating metal brackets.

Evaluating micronized adipose tissue niche and artificial dermis grafts following nonmelanoma skin cancer excision: a pilot study.

BACKGROUND: Recently, micronized adipose tissue (MAT) grafts have shown promising results in wound healing, including diabetic ulcers. OBJECTIVE: To assess the possibility of using 3D printed MAT niche grafts in the management of skin and soft tissue defects resulting from non-melanoma skin cancer (NMSC) resections. MATERIALS AND METHODS: A retrospective feasibility study was conducted on patients with skin and soft tissue defects resulting from NMSC resections. Twenty-one patients were treated using either artificial dermis (n = 11) or MAT niche (n = 10) grafting. Healing time and POSAS scores were compared. The Mann-Whitney U test and the Pearson chi-square test were used in statistical analysis to compare between and within groups based on preoperative and postoperative measurements. RESULTS: Wounds in the MAT niche group reepithelialized significantly faster than those in the artificial dermis group (mean [SD] 39.2 [11.4] days vs 63.7 [34.8] days; P = .04). In the 21 scar parameters evaluated, the MAT niche group demonstrated significantly superior outcomes in only 2 parameters based on operator assessment scores: relief (mean [SD] 1.6 [0.7] vs 2.2 [0.6]; P = .047) and scar contracture (mean [SD] 1.3 [0.5] vs 2.5 [1.0]; P = .011). CONCLUSION: This study proves the feasibility of exploring the effects of MAT niche grafting following NMSC excision on healing time and specific parameters of scarring, including scar relief and scar contracture.

The underlying neuropsychological and neural correlates of the impaired Chinese reading skills in children with attention deficit hyperactivity disorder.

Impaired basic academic skills (e.g., word recognition) are common in children with Attention Deficit Hyperactivity Disorder (ADHD). The underlying neuropsychological and neural correlates of impaired Chinese reading skills in children with ADHD have not been substantially explored. Three hundred and two children with ADHD (all medication-naïve) and 105 healthy controls underwent the Chinese language skill assessment, and 175 also underwent fMRI scans (84 ADHD and 91 controls). Between-group and mediation analyses were applied to explore the interrelationships of the diagnosis of ADHD, cognitive dysfunction, and impaired reading skills. Five ADHD-related brain functional networks, including the default mode network (DMN) and the dorsal attention network (DAN), were built using predefined regions of interest. Voxel-based group-wise comparisons were performed. The ADHD group performed worse than the control group in word-level reading ability tests, with lower scores in Chinese character recognition (CR) and word chains (WS) (all P < 0.05). With full-scale IQ and sustained attention in the mediation model, the direct effect of ADHD status on the CR score became insignificant (P = 0.066). The underlying neural correlates for the orthographic knowledge (OT) and CR differed between the ADHD and the control group. The ADHD group tended to recruit more DMN regions to maintain their reading performance, while the control group seemed to utilize more DAN regions. Children with ADHD generally presented impaired word-level reading skills, which might be caused by impaired sustained attention and lower IQ. According to the brain functional results, we infer that ADHD children might utilize a different strategy to maintain their orthographic knowledge and character recognition performance.

Systolic blood pressure as a critical mediator in the association between adult height and 25-year risk of stroke.

BACKGROUND: Adult height is associated with the risk of stroke. However, the underlying mechanism remains unclear. We explored the mediating role of metabolic factors in the association between adult height and stroke incidence. METHODS: We used data from 3306 community-dwelling participants with complete information on adult height, metabolic factors, and 25-year cardiovascular outcomes. Participants were classified into three adult height groups based on sex-specific height quartiles: short (Q1), average (Q2-Q3), and tall (Q4). The primary endpoint was the occurrence of cardiovascular disease, including coronary artery disease and stroke. RESULTS: Taller adult height was associated with a lower risk of stroke. Compared with the short group the risk of stroke reduced with taller height with a hazard ratio (HR) of 0.68 in the average group (95% confidence interval [CI]: 0.50-0.93), and 0.45 in the tall group (95% CI: 0.31-0.65). Low systolic blood pressure was considered as a protective mediator in the effect of adult height on the risk of stroke in the average (HR: 0.86; 95% CI: 0.82-0.93) and the tall group (HR: 0.85; 95% CI: 0.78-0.91). Systolic blood pressure significantly contributed to height-related stroke risk (proportion mediated: 0.41; 95% CI: 0.19-1.56). CONCLUSIONS: This study found an inverse association between adult height and stroke risk, which is partly driven by lower systolic blood pressure. These findings highlight the importance of systolic blood pressure management as a potential preventive strategy against stroke.

Sodium Glucose Transporter 2 Inhibitors Versus Metformin on Cardiovascular and Renal Outcomes in Patients With Diabetes With Low Cardiovascular Risk: A Nationwide Cohort Study.

BACKGROUND: This study investigated whether initial SGLT2 (sodium-glucose cotransporter 2) inhibitor-based treatment is superior to metformin-based regimens as a primary prevention strategy among low-risk patients with diabetes. METHODS AND RESULTS: In this nationwide cohort study, a total of 38 496 patients with diabetes with low cardiovascular risk were identified (age 62.0±11.6 years, men 50%) from January 1 to December 31, 2016. Patients receiving SGLT2 inhibitors-based and metformin-based regimens were 1:2 matched by propensity score. Study outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, stroke, and progression to end-stage renal disease. Compared with 1928 patients receiving metformin-based regimens, 964 patients receiving SGLT2 inhibitor-based regimens had similar all-cause mortality (hazard ratio [HR], 0.75 [95% CI, 0.51-1.12]), cardiovascular death (HR, 0.69 [95% CI, 0.25-1.89]), hospitalization for heart failure (HR, 1.06 [95% CI, 0.59-1.92]), stroke (HR, 0.78 [95% CI, 0.48-1.27]), and progression to end-stage renal disease (HR, 0.88 [95% CI, 0.32-2.39]). However, SGLT2 inhibitors were associated with a lower risk of all-cause mortality (HR, 0.47 [95% CI, 0.23-0.99]; P for interaction=0.008) and progression to end-stage renal disease (HR, 0.22 [95% CI, 0.06-0.82]; P for interaction=0.04) in patients under the age of 65. CONCLUSIONS: In comparison to metformin-based regimens, SGLT2 inhibitor-based regimens showed a similar risk of all-cause mortality and adverse cardiorenal events. SGLT2 inhibitors might be considered as first-line therapy in select low-risk patients, for example, younger patients with diabetes.

Rapid and Direct Detection of Trimethylamine N-oxide Using an Off-Chip Capacitance Biosensor with Readout SoC for Early-Stage Thrombosis and Cardiovascular Disease.

A demonstration of an off-chip capacitance array sensor with a limit of detection of 1 µM trimethylamine N-oxide (TMAO) to diagnose a chronic metabolism disease in urine is presented. The improved Cole-Cole model is employed to determine the parameters of R_catalyzed, C_catalyzed, and Rp_catalyzed, enabling the prediction of the catalytic resistance of enzyme, reduction effects of the analyte, and characterize the small signal alternating current properties of ionic strength caused by catalysis. Based on the standard solutions, we investigate the effects of pixel geometry parameters, driving electrode width, and sensing electrode width on the electrical field change of the off-chip capacitance sensor; the proposed off-chip sensor with readout system-on-chip exhibits a high sensitivity of 21 analog-to-digital converter counts/µM TMAO (or 2.5 mV/µM TMAO), response time of 1 s, repetition of 98.9%, and drift over time of 0.5 mV. The proposed off-chip sensor effectively discriminates TMAO in a phosphate-buffered saline solution based on minute changes in capacitance induced by the TorA enzyme, resulting in a discernible 2.15% distinction. These measurements have been successfully corroborated using the conventional cyclic voltammetry method, demonstrating a mere 0.024% variance. The off-chip sensor is crafted with a specific focus on detecting TMAO, achieved by excluding any reduction reactions between the TMAO-specific enzyme TorA and the compounds creatine and creatinine present in urine. This deliberate omission ensures that the sensor's attention remains solely on TMAO, thereby enhancing its precision in achieving accurate and reliable TMAO detection.

Multimodal Integrative Genomics and Pathology Analyses in Neoadjuvant Nivolumab Treatment for Intermediate and Locally Advanced Hepatocellular Carcinoma.

Introduction: Immunotherapy has resulted in pathologic responses in hepatocellular carcinoma (HCC), but the benefits and molecular mechanisms of neoadjuvant immune checkpoint blockade are largely unknown. Methods: In this study, we evaluated the efficacy and safety of preoperative nivolumab (anti-PD-1) in patients with intermediate and locally advanced HCC and determined the molecular markers for predicting treatment response. Results: Between July 2020 and November 2021, 20 treatment-naive HCC patients with intermediate and locally advanced tumors received preoperative nivolumab at 3 mg/kg for 3 cycles prior to surgical resection. Nineteen patients underwent surgical resection on trial. Seven (36.8%) of the 19 patients had major pathologic tumor necrosis (≥60%) in the post-nivolumab resection specimens, with 3 having almost complete (>90%) tumor necrosis. The tumor necrosis was hemorrhagic and often accompanied by increased or dense immune cell infiltrate at the border of the tumors. None of the patients developed major adverse reactions contradicting hepatectomy. RNA-sequencing analysis on both pre-nivolumab tumor biopsies and post-nivolumab resected specimens showed that, in cases with major pathologic necrosis, the proportion of CD8 T cells in the HCC tissues predominantly increased after treatment. Moreover, to investigate noninvasive biomarker for nivolumab response, we evaluated the copy number variation (CNV) using target-panel sequencing on plasma cell-free DNA of the patients and derived a CNV-based anti-PD-1 score. The score correlated with the extent of tumor necrosis and was validated in a Korean patient cohort with anti-PD-1 treatment. Conclusion: Neoadjuvant nivolumab demonstrated promising clinical activity in intermediate and locally advanced HCC patients. We also identified useful noninvasive biomarker predicting responsiveness.

The impact of sodium-glucose co-transporter-2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation.

AIMS: The effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase-4 inhibitors (DPP4i). MATERIALS AND METHODS: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. RESULTS: After up to 5 years of follow-up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51-0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24-0.82). SGLT2i was related to reduced risks of AF-related hospitalisation (HR: 0.72, 95% CI: 0.56-0.93), stroke (HR: 0.75, 95% CI: 0.60-0.94), and all-cause death (HR: 0.33, 95% CI: 0.24-0.44). The protective effects were consistent irrespective of the concurrent use of non-vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. CONCLUSIONS: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF-related hospitalisation, stroke, and all-cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

A bivalent inhibitor against TDRD3 to suppress phase separation of methylated G3BP1.

The formation of membrane-less organelles is driven by multivalent weak interactions while mediation of such interactions by small molecules remains an unparalleled challenge. Here, we uncovered a bivalent inhibitor that blocked the recruitment of TDRD3 by the two methylated arginines of G3BP1. Relative to the monovalent inhibitor, this bivalent inhibitor demonstrated an enhanced binding affinity to TDRD3 and capability to suppress the phase separation of methylated G3BP1, TDRD3, and RNAs, and in turn inhibit the stress granule growth in cells. Our result paves a new path to mediate multivalent interactions involved in SG assembly for potential combinational chemotherapy by bivalent inhibitors.