Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial.

OBJECTIVE: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. METHODS: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. RESULTS: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. CONCLUSION: Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Uric acid elevation in pediatric patients with dilated cardiomyopathy and prediction of mortality.

Background and aims: Pediatric dilated cardiomyopathy (DCM) is a primary cause of heart failure, highlighting the urgent need for effective prognostic markers. Methods: We performed a single-center retrospective study involving 145 children diagnosed with DCM, with a median follow-up period of 4.0 months (interquartile range: 6.2-108.4 months). The relationship between serum uric acid (SUA) levels and all-cause mortality was assessed using Kaplan-Meier survival curves, multivariate Cox proportional hazard models, and restricted cubic spline (RCS) models. Results: Of the 145 children with DCM (median age 5.7 years; 61.4% male), 45 (31%) died within 1 year, and 65 (44.8%) died during the maximum follow-up period. In adjusted multivariate Cox regression models, each log2 SUA increase was linked to a higher risk of 1-year mortality [hazard ratio (HR), 2.66; 95% confidence interval (CI), 1.41-5.01] and overall mortality (HR, 1.97; 95% CI, 1.15-3.37). The highest SUA tertile showed a greater risk of mortality at 1 year (HR, 4.26; 95% CI: 1.5-12.06) and during the maximum follow-up (HR, 2.56; 95% CI: 1.06-6.16) compared with the lowest tertile. RCS models indicated an inverted L-shaped association between baseline SUA levels and overall mortality risk, with age-stratified analyses revealing a linear and U-shaped relationship in children ≤10 and >10 years, respectively. Further age-stratified analyses highlighted the modifying effect of age on this association. Conclusion: Elevated SUA levels are a significant predictor of mortality in pediatric DCM, with a pronounced impact on children under 10 years of age. Therefore, SUA levels could serve as potential biomarkers for risk stratification in this population.

Versatile stochastic model for predictive KMC simulation of fcc metal nanostructure evolution with realistic kinetics.

Stochastic lattice-gas models provide the natural framework for analysis of the surface diffusion-mediated evolution of crystalline metal nanostructures on the appropriate time scale (often 101-104 s) and length scale. Model behavior can be precisely assessed by kinetic Monte Carlo simulation, typically incorporating a rejection-free algorithm to efficiently handle the broad range of Arrhenius rates for hopping of surface atoms. The model should realistically prescribe these rates, or the associated barriers, for a diversity of local surface environments. However, commonly used generic choices for barriers fail, even qualitatively, to simultaneously describe diffusion for different low-index facets, for terrace vs step edge diffusion, etc. We introduce an alternative Unconventional Interaction-Conventional Interaction formalism to prescribe these barriers, which, even with few parameters, can realistically capture most aspects of behavior. The model is illustrated for single-component fcc metal systems, mainly for the case of Ag. It is quite versatile and can be applied to describe both the post-deposition evolution of 2D nanostructures in homoepitaxial thin films (e.g., reshaping and coalescence of 2D islands) and the post-synthesis evolution of 3D nanocrystals (e.g., reshaping of nanocrystals synthesized with various faceted non-equilibrium shapes back to 3D equilibrium Wulff shapes).

Link between remnant cholesterol and the reversion to normoglycemia in Chinese adults with prediabetes: a 5-year cohort study.

Despite the clear association between remnant cholesterol (RC)and diabetes risk, no study to date has examined the relationship between RC and reversal of prediabetes to normoglycemia. This retrospective cohort study included a total of 15,023 patients with prediabetes who underwent a physical examination between 2010 and 2016. The link between initial RC levels and the reversion from prediabetes to normoglycemia was analyzed using the Cox proportional-hazards regression model. Additionally, the study explored the possible relationship between RC and the probability of returning normoglycemia by applying Cox proportional hazards regression models with cubic spline functions. To address competing risks, a multivariate Cox regression analysis was undertaken, treating the onset of diabetes as a competing risk event for reversing prediabetes to normoglycemia. Additionally, the study incorporated extensive subgroup analyses alongside multiple sensitivity analyses, enhancing the reliability and robustness of the results. After adjusting for covariates, the findings indicated that RC was inversely associated with the likelihood of reverting to normoglycemia (per 5 mg/dL increase, HR = 0.918, 95% CI 0.909-0.927). The analysis also revealed a nonlinear relationship between RC and normoglycemia reversion, with an inflection point at 51.08 mg/dL. For RC values below this inflection point (RC < 50.08 mg/dL), the HR for the probability of returning to normoglycemia was 0.907 (95% CI 0.897-0.917 per 5 mg/dL). Additionally, the competing risks model demonstrated a negative relationship between RC and the reversal of prediabetes to normoglycemia (SHR = 0.92, 95% CI 0.91-0.93). Sensitivity analyses confirmed the robustness and stability of these results. This study demonstrated a negative and non-linear association between RC and the probability of reversion to normoglycemia in Chinese adults with prediabetes. By actively intervening to reduce RC levels, at least to below 51.08 mg/dL, further reduction of RC may significantly increase the probability of returning to normoglycemia from prediabetes.

Hypoxia-inducible factor-1α can reverse the Adriamycin resistance of breast cancer adjuvant chemotherapy by upregulating transferrin receptor and activating ferroptosis.

Breast cancer is a common malignant tumor in women. Ferroptosis, a programmed cell death pathway, is closely associated with breast cancer and its resistance. The transferrin receptor (TFRC) is a key factor in ferroptosis, playing a crucial role in intracellular iron accumulation and the occurrence of ferroptosis. This study investigates the influence and significance of TFRC and its upstream transcription factor hypoxia-inducible factor-1α (HIF1α) on the efficacy of neoadjuvant therapy in breast cancer. The differential gene obtained from clinical samples through genetic sequencing is TFRC. Bioinformatics analysis revealed that TFRC expression in breast cancer was significantly greater in breast cancer tissues than in normal tissues, but significantly downregulated in Adriamycin (ADR)-resistant tissues. Iron-responsive element-binding protein 2 (IREB2) interacts with TFRC and participates in ferroptosis. HIF1α, an upstream transcription factor, positively regulates TFRC. Experimental results indicated higher levels of ferroptosis markers in breast cancer tissue than in normal tissue. In the TAC neoadjuvant regimen-sensitive group, iron ion (Fe2+) and malondialdehyde (MDA) levels were greater than those in the resistant group (all p < .05). Expression levels of TFRC, IREB2, FTH1, and HIF1α were higher in breast cancer tissue compared to normal tissue. Additionally, the expression of the TFRC protein in the TAC neoadjuvant regimen-sensitive group was significantly higher than that in the resistant group (all p < .05), while the difference in the level of expression of IREB2 and FTH1 between the sensitive and resistant groups was not significant (p > .05). The dual-luciferase assay revealed that HIF1α acts as an upstream transcription factor of TFRC (p < .05). Overexpression of HIF1α in ADR-resistant breast cancer cells increased TFRC, Fe2+, and MDA content. After ADR treatment, the cell survival rate decreased significantly, and ferroptosis could be reversed by the combined application of Fer-1 (all p < .05). In conclusion, ferroptosis and chemotherapy resistance are correlated in breast cancer. TFRC is a key regulatory factor influenced by HIF1α and is associated with chemotherapy resistance. Upregulating HIF1α in resistant cells may reverse resistance by activating ferroptosis through TFRC overexpression.

Real-Time KMC Simulation of Vacancy-Mediated Intermixing in Au@Ag Octahedral Core-Cubic Shell Nanocrystals with Ab Initio-Guided Kinetics.

Utilization of core-shell rather than monometallic nanocrystals (NCs) facilitates fine-tuning of NC properties for applications. However, compositional evolution via intermixing can degrade these properties prompting recent experimental studies. We develop an atomistic-level stochastic model for vacancy-mediated intermixing exploiting a formalism which allows incorporation at an ab initio density functional theory level of not just the thermodynamics of vacancy formation, but also relevant diffusion barriers for a vast number of possible local environments (in the core and in the shell, at the interface, and in the intermixed phase). This facilitates a predictive treatment and comprehensive understanding of intermixing on the relevant time scale (e.g., 101-103 s). In contrast, previous modeling at the atomistic level utilized only unrealistic generic prescriptions of barriers or employed simplified continuum treatments. For Au@Ag octahedral core-cubic shell NCs, our modeling not only captures the experimentally observed rate or time scale for intermixing of ∼100 s at 450 °C for 60 nm NCs, but also elucidates the underlying rate controlling processes and the effective intermixing barrier.

Changes in the recent three decades and survey on the current status of surgical treatment for esophageal cancer in China.

BACKGROUND: To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated. METHODS: We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs. RESULTS: A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two-field lymph node dissection including the para-recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation. CONCLUSIONS: Currently, in China, minimally invasive surgery-oriented multimodality treatment, including complete two-field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades.

DNA-encoded probe-based assay for profiling plant kinase activities.

Elucidating kinase-substrate relationships is pivotal for deciphering cellular signaling mechanisms, yet it remains challenging due to the complexity of kinase networks. Herein, we report the development of a versatile DNA-based kinase assay platform for high-throughput profiling of plant protein kinase activities and substrate preferences. Our approach employs DNA-linked peptide substrates, facilitating quantitative and specific kinase activity detection through next-generation DNA sequencing. Leveraging DNA barcodes as quantitative readouts, our approach establishes a high-throughput, sensitive, and specific platform for dissecting kinase-substrate networks in plants, representing a powerful tool for elucidating signaling mechanisms in plants.

Association between excessive alcohol consumption and incident diabetes mellitus among Japanese based on propensity score matching.

The available evidence on the connection between excessive alcohol consumption and diabetes is controversial. Therefore, the primary objective of this investigation was to examine the connection between excessive alcohol consumption and incident diabetes in a Japanese population through the utilization of propensity score matching (PSM) analysis. Our retrospective cohort study encompassed a sample of 15,464 Japanese individuals who were initially free of diabetes between the years 2004 and 2015. The study utilized comprehensive medical records of individuals who underwent a physical examination. Employing a one:one PSM analysis, the current research included 2298 individuals with and without excessive alcohol consumption. Furthermore, a doubly robust estimation method was employed to ascertain the connection between excessive alcohol consumption and diabetes. The findings revealed that individuals with excessive alcohol consumption exhibited a 73% higher likelihood of developing diabetes (HR = 1.73, 95% CI 1.08-2.77). Furthermore, upon adjusting for variables, the PSM cohort demonstrated that individuals with excessive alcohol consumption had a 78% increased risk of developing diabetes in comparison to those with non-excessive alcohol consumption (HR = 1.78, 95% CI 1.08-2.93). Individuals with excessive alcohol consumption were found to have a 73% higher risk of developing diabetes compared to those with non-excessive alcohol consumption, even after controlling for propensity score (HR = 1.73, 95% CI 1.08-2.78). Participants in the PSM cohort with excessive alcohol consumption had a 73% higher risk of developing diabetes than those with non-excessive alcohol consumption after controlling for confounding factors. These findings underscore the importance of alcohol consumption guidelines aimed at reducing excessive drinking. Clinicians should be vigilant in screening for alcohol use in patients, particularly those at risk for diabetes, and provide appropriate counseling and resources to support alcohol reduction.

Non-negligible ultrasonographic findings in sarcoid myositis: A case series and literature review.

Sarcoid myositis is a rare and often debilitating extrapulmonary manifestation of sarcoidosis that can be difficult to recognize without a prior sarcoidosis diagnosis. Sarcoidosis with muscle nodules or masses as the first symptom is the least common form, occurring in approximately 0.5%-2.3% of cases. This article presents four middle-aged female patients who initially sought medical attention for a lower limb mass. Ultrasound examinations revealed consistent characteristic changes indicative of myositis. All patients underwent ultrasound-guided muscle biopsy and were diagnosed with sarcoidosis. Therefore, ultrasonography plays a pivotal role as the primary diagnostic tool for the early detection of sarcoid myositis.

Relationship between Baseline Serum Potassium and 1-Year Readmission in Pediatric Patients with Heart Failure: A Retrospective Cohort Study.

Pediatric heart failure (HF) is associated with high readmission rates, but the optimal serum potassium range for this population remains unclear. In this single-center retrospective cohort study, 180 pediatric patients hospitalized for HF between January 2016 and January 2022 were stratified into low-potassium (<3.7 mmol/L), middle-potassium (3.7-4.7 mmol/L), and high-potassium (≥4.7 mmol/L) groups based on the distribution of potassium levels in the study population. The primary outcome was readmission for HF within 1 year of discharge. Cox regression and restricted cubic spline models were used to assess the association between potassium levels and 1-year HF readmission rates. Notably, 38.9% of patients underwent 1 or more 1-year readmissions for HF within 1 year. The high-potassium group had a significantly higher readmission frequency than the middle-potassium group. In multivariate Cox regression models, potassium levels of ≥4.7 mmol/L were independently associated with increased 1-year readmission risk. A J-shaped relationship was observed between baseline potassium levels and 1-year readmission risk, with the lowest risk at 4.1 mmol/L. In pediatric patients with HF, a serum potassium level ≥ 4.7 mmol/L was independently associated with increased 1-year readmission risk. Maintaining potassium levels within a narrow range may improve outcomes in this population.

The Root Extract of Rosa multiflora Ameliorates Nonalcoholic Steatohepatitis Development via Blockade of De Novo Lipogenesis and Inflammation.

Nonalcoholic steatohepatitis (NASH) is characterized by severe inflammation and fibrosis due to an excessive accumulation of triglycerides (TGs) in the liver with a dysregulated de novo lipogenesis (DNL) pathway. In this study, we aimed to evaluate the effectiveness of YC-1102, an extract obtained from the roots of Rosa multiflora, as a nutritional supplement in a diet-induced NASH mouse model. C57BL/6 wild-type mice were fed a fructose, palmitate, and cholesterol (FPC)-containing diet for 16 weeks to induce experimental NASH. A daily oral gavage of YC-1102 and obetichoic acid (OCA) was conducted for 9 weeks. After sacrifice, disease parameters related to hepatic lipids, inflammation, and fibrosis were evaluated. The treatment with YC-1102 significantly decreased the liver/body weight ratio, epididymal fat weight, and plasma ALT and AST levels, which are indicators of NASH injuries. YC-1102 attenuated hepatic lipid accumulation by inhibiting the transcription of DNL genes in the livers exhibiting NASH. Additionally, we found that YC-1102 blocked the development of hepatic inflammation and fibrosis by directly disturbing macrophage activation, resulting in an amelioration of hepatic fibrosis. Our findings suggest that YC-1102 could ameliorate NASH progression by inhibiting uncontrolled DNL and inflammation.

Mapping adipocyte interactome networks by HaloTag-enrichment-mass spectrometry.

Mapping protein interaction complexes in their natural state in vivo is arguably the Holy Grail of protein network analysis. Detection of protein interaction stoichiometry has been an important technical challenge, as few studies have focused on this. This may, however, be solved by artificial intelligence (AI) and proteomics. Here, we describe the development of HaloTag-based affinity purification mass spectrometry (HaloMS), a high-throughput HaloMS assay for protein interaction discovery. The approach enables the rapid capture of newly expressed proteins, eliminating tedious conventional one-by-one assays. As a proof-of-principle, we used HaloMS to evaluate the protein complex interactions of 17 regulatory proteins in human adipocytes. The adipocyte interactome network was validated using an in vitro pull-down assay and AI-based prediction tools. Applying HaloMS to probe adipocyte differentiation facilitated the identification of previously unknown transcription factor (TF)-protein complexes, revealing proteome-wide human adipocyte TF networks and shedding light on how different pathways are integrated.

Diurnally asymmetric cloud cover trends amplify greenhouse warming.

Surface air temperature (SAT) is a key indicator of climate change. Variations in cloud cover affect SAT by interacting with radiation. During daytime, clouds tend to cool the surface by blocking sunlight, while nighttime clouds warm the surface by trapping longwave radiation. Here, we show that, on the global scale, cloud cover, particularly low-level cloudiness, exhibits diurnally asymmetric trends in a warming climate. Cloud fraction on average decreases more during the day than at night. Climate models indicate that the diurnally asymmetric cloud cover variation is mainly driven by trends in the lower tropospheric stability and is largely attributed to the increasing greenhouse gases rather than natural variability. This asymmetry, therefore, turns out to be an amplifier of surface warming, by both decreasing the daytime cloud shortwave albedo effect and increasing the nighttime cloud longwave greenhouse effect.

Three-Pillar Expansive Craniotomy in Children with Acute Ruptured Supratentorial Brain Arteriovenous Malformations.

OBJECTIVE: Acute rupture and hemorrhage of pediatric brain arteriovenous malformations (AVMs) may lead to cerebral herniation or intractable intracranial hypertension, necessitating emerging surgical interventions to alleviate intracranial pressure. However, there is still controversy regarding the timing of treatment for ruptured AVMs. This study aimed to assess the feasibility of utilizing three-pillar expansive craniotomy (3PEC) at different times during the treatment of pediatric ruptured supratentorial AVMs. METHODS: A retrospective analysis was conducted on all consecutive cases of acute rupture in supratentorial AVM children who underwent 3PEC at a single institution from 2020 to 2022. General information, clinical characteristics, radiological data, and prognosis were reviewed and analyzed. RESULTS: Thirteen children were included in the analysis. The intracranial pressure of all patients decreased to below 15 mmHg within 10 days. The expansion volume of the cranial cavity of the patients increased by 18.3 cm3 (95% confidence interval, 10.2-26.3; P < 0.001) compared to the hematoma volume. None of the patients required decompressive craniectomy due to intractable intracranial hypertension caused by cerebral swelling. The median waiting period for patients with delayed AVMs treatment was 8 days, during which no rebleeding occurred. CONCLUSIONS: Emergency intervention with 3PEC in children experiencing acutely ruptured supratentorial AVMs appears to be feasible. For children requiring delayed management of the AVMs, 3PEC may diminish the risk of rebleeding during the waiting period and shorten the waiting period.

Stabilization of EREG via STT3B-mediated N-glycosylation is critical for PDL1 upregulation and immune evasion in head and neck squamous cell carcinoma.

Dysregulated Epiregulin (EREG) can activate epidermal growth factor receptor (EGFR) and promote tumor progression in head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underlying EREG dysregulation remain largely unknown. Here, we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues. Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway. Of note, we found that N-glycosylation of EREG was essential for its stability, membrane location, biological function, and upregulation of its downstream target PDL1 in HNSCC. EREG was glycosylated at N47 via STT3B glycosyltransferases, whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG. Consistently, knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells. Moreover, treatment of HNSCC cells with NGI-1, an inhibitor of STT3B, blocked STT3B-mediated glycosylation of EREG, leading to its degradation and suppression of PDL1. Finally, combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo. Taken together, STT3B-mediated N-glycosylation is essential for stabilization of EREG, which mediates PDL1 upregulation and immune evasion in HNSCC.

Spatiotemporal variations and source on black carbon over Chongqing, China: Long-term changes and observational experiments.

Black carbon (BC), as a critical light-absorbing constituent within aerosols, exerts profound effects on atmospheric radiation balance, climate, air quality and human health, etc. And it is also a long-standing focus in rapidly developing megacities. So, this study primarily focuses on investigating the variation characteristics and underlying causes of BC in Chongqing (31,914,300 population), which is one of the municipalities directly under the central government of China, serving as a pivotal economic hub in southwest China. Utilizing MERRA-2 reanalysis data, we examined the long-term changes of atmospheric BC over Chongqing 20 years (from 2002 to 2021). Moreover, BC mass concentration observations were conducted using an Aethalometer (AE-33) from March 15 to June 14, 2021 in Liangping District, Chongqing. The statistical analysis over the last 20 years reveals an annual mean BC concentration in Chongqing of 3.42 ± 0.20 µg/m3, exhibiting growth from 2002 to 2008, followed by a decline from 2008 to 2021. Monthly concentration displays a "U-shaped" trend, with the lowest values occurring in summer and the highest in winter. Due to topographical and meteorological influences, local emissions primarily contribute to BC pollution, characterized by a spatial distribution pattern of high in the west and low in the east. Ground observation indicates a distinct dual-peaked pattern in the diurnal variation of BC, with peak concentrations aligning with periods of high traffic emissions. The variation in BC is significantly influenced by meteorological conditions (wind, temperature, atmospheric boundary layer) and local pollution sources (predominantly traffic). Furthermore, extreme events analysis suggests that local emissions and regional transport (with higher contributions from Chongqing and the Sichuan Basin) predominantly contributed to BC pollution. This study effectively makes up for the deficiency in analyzing the distribution and sources of BC pollution in Chongqing, providing valuable scientific insights for the atmospheric environment of megacities.