A case report of severe pulmonary arterial hypertension after nivolumab, an IgG4 anti-PD1 monoclonal antibody.

Background: Pulmonary hypertension has been increasingly reported in association with immunotherapy, but generally lacking invasive haemodynamic confirmation in literature. We present the first case of pulmonary arterial hypertension following nivolumab confirmed with invasive haemodynamic measurements. Case summary: A 65-year-old male with gastro-oesophageal adenocarcinoma developed progressive dyspnoea with exertion, decreasing exercise tolerance after receiving nivolumab for seven months. He was admitted with acute hypoxaemic respiratory failure after syncope at home. The patient was diagnosed with pulmonary arterial hypertension (PAH) with pre-capillary aetiology with right heart catheterization (RHC): mean pulmonary artery pressure 49 mmHg, pulmonary capillary wedge pressure 7 mmHg, and cardiac index 1.3 L/min/m2. Based on serial echocardiograms, the development of PAH appeared to be associated with nivolumab. The patient died of cardiac arrest 3 days after admission. Discussion: Progressive unexplained dyspnoea after receiving programmed cell death protein 1 monoclonal antibody should prompt clinicians to consider PAH and RHC.

Effects of Prepartum L-Tryptophan Supplementation on the Postpartum Performance of Holstein Cows.

The negative energy balance occurring in the periparturient period of cows will impede their health and postpartum performance. To target this issue, L-tryptophan was supplied to the prepartum cows. The results showed that L-tryptophan supplementation significantly increased the serum melatonin level and was accompanied with increases in SOD activity, IL-10 and colostrum IgA levels as well as decreases in MDA and IL-6 levels compared to the control cows. The incidence of postpartum diseases was significantly lower and the pregnancy rate was significantly higher in cows fed L-tryptophan than in the control group. A striking observation was that prepartum L-tryptophan supplementation not only improved the milk production but also the quality compared to the control cows. In general, supplementation with L-tryptophan in the prepartum period can improve the postpartum reproduction and lactation performance of cows to some extent.

Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

A new gold(I) phosphine complex induces apoptosis in prostate cancer cells by increasing reactive oxygen species.

Thioredoxin reductase (TrxR) is a pivotal regulator of redox homeostasis. It is frequently overexpressed in various cancer cells, including prostate cancer, making it a promising target for the development of anti-cancer drugs. In this study, we screened a series of newly designed complexes of gold(I) phosphine. Specifically, Compound 5 exhibited the highest cytotoxicity against prostate cancer cells and demonstrated stronger antitumor effects than commonly used drugs, such as cisplatin and auranofin. Importantly, our mechanistic study revealed that Compound 5 effectively inhibits the TrxR system in vitro. Additionally, Compound 5 promoted intracellular accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction and irreversible apoptosis in prostate cancer cells. Our in vivo xenograft study further demonstrated that Compound 5 has excellent antitumor activity against prostate cancer cells, but does not cause severe side effects. These findings provide a promising lead Compound for the development of novel antitumor agents targeting prostate cancer and offer a valuable tool for investigating biological pathways involving TrxR and ROS modulation.

Development and evaluation of a deep learning framework for the diagnosis of malnutrition using a 3D facial points cloud: A cross-sectional study.

BACKGROUND: The feasibility of diagnosing malnutrition using facial features has been validated. A tool to integrate all facial features associated with malnutrition for disease screening is still demanded. This work aims to develop and evaluate a deep learning (DL) framework to accurately determine malnutrition based on a 3D facial points cloud. METHODS: A group of 482 patients were studied in this perspective work. The 3D facial data were obtained using a 3D camera and represented as a 3D facial points cloud. A DL model, PointNet++, was trained and evaluated using the points cloud as inputs and classified the malnutrition states. The performance was evaluated with the area under the receiver operating characteristic curve, accuracy, specificity, sensitivity, and F1 score. RESULTS: Among the 482 patients, 150 patients (31.1%) were diagnosed as having moderate malnutrition and 54 patients (11.2%) as having severe malnutrition. The DL model achieved the performance with an area under the receiver operating characteristic curve of 0.7240 ± 0.0416. CONCLUSION: The DL model achieved encouraging performance in accurately classifying nutrition states based on a points cloud of 3D facial information of patients with malnutrition.

Utilizing support vector machines to foster sustainable development and innovation in the clean energy sector via green finance.

As the global demand for clean energy continues to grow, the sustainable development of clean energy projects has become an important topic of research. in order to optimize the performance and sustainability of clean energy projects, this work explores the environmental and economic benefits of the clean energy industry. through the use of Support Vector Machine (SVM) Multi-factor models and a bi-level multi-objective approach, this work conducts comprehensive assessment and optimization. with wind power base a as a case study, the work describes the material consumption of wind turbines, transportation energy consumption and carbon dioxide (CO2) emissions, and infrastructure material consumption through descriptive statistics. Moreover, this work analyzes the characteristics of different wind turbine models in depth. On one hand, the SVM multi-factor model is used to predict and assess the profitability of Wind Power Base A. On the other hand, a bi-level multi-objective approach is applied to optimize the number of units, internal rate of return within the project, and annual average equivalent utilization hours of the Wind Power Base A. The research results indicate that in March, the WilderHill New Energy Global Innovation Index (NEX) was 0.91053, while the predicted value of the SVM multi-factor model was 0.98596. The predicted value is slightly higher than the actual value, demonstrating the model's good grasp of future returns. The cumulative rate of return of Wind Power Base A is 18.83%, with an annualized return of 9.47%, exceeding the market performance by 1.68%. Under the optimization of the bi-level multi-objective approach, the number of units at Wind Power Base A decreases from the original 7004 to 5860, with total purchase and transportation costs remaining basically unchanged. The internal rate of return of the project increases from 8% to 9.3%, and the annual equivalent utilization hours increase to 2044 h, comprehensively improving the investment return and utilization efficiency of the wind power base. Through optimization, significant improvements are achieved in terAs the global demand for clean energy continues to grow, the sustainable development of clean energy projects has become an important topic of research. In order to optimize the performance and sustainability of clean energy projects, this work explores the environmental and economic benefits of the clean energy industry. Through the use of Support Vector Machine (SVM) multi-factor models and a bi-level multi-objective approach, this work conducts comprehensive assessment and optimization. With Wind Power Base A as a case study, the work describes the material consumption of wind turbines, transportation energy consumption and carbon dioxide (CO2) emissions, and infrastructure material consumption through descriptive statistics. Moreover, this work analyzes the characteristics of different wind turbine models in depth. On one hand, the SVM multi-factor model is used to predict and assess the profitability of Wind Power Base A. On the other hand, a bi-level multi-objective approach is applied to optimize the number of units, internal rate of return within the project, and annual average equivalent utilization hours of the Wind Power Base A. The research results indicate that in March, the WilderHill New Energy Global Innovation Index (NEX) was 0.91053, while the predicted value of the SVM multi-factor model was 0.98596. The predicted value is slightly higher than the actual value, demonstrating the model's good grasp of future returns. The cumulative rate of return of Wind Power Base A is 18.83%, with an annualized return of 9.47%, exceeding the market performance by 1.68%. Under the optimization of the bi-level multi-objective approach, the number of units at Wind Power Base A decreases from the original 7004 to 5860, with total purchase and transportation costs remaining basically unchanged. The internal rate of return of the project increases from 8% to 9.3%, and the annual equivalent utilization hours increase to 2044 h, comprehensively improving the investment return and utilization efficiency of the wind power base. Through optimization, significant improvements are achieved in terms of the number of units, internal rate of return within the project, and annual average equivalent utilization hours at Wind Power Base A. The number of units decreases to 5860, with total purchase and transportation costs remaining basically unchanged, the internal rate of return increases to 9.3%, and annual equivalent utilization hours increase to 2044 h. Energy consumption and CO2 emissions are significantly reduced, with energy consumption decreasing by 0.68 × 109 kgce and CO2 emissions decreasing by 1.29 × 109 kg. The optimization effects are mainly concentrated in the production and installation stages, with emission reductions achieved through the recycling and disposal of materials consumed in the early stages. In terms of investment benefits, environmental benefits are enhanced, with a 13.93% reduction in CO2 emissions. Moreover, there is improved energy efficiency, with the energy input-output ratio increasing from 7.73 to 9.31. This indicates that the Wind Power Base A project has significant environmental and energy efficiency advantages in the clean energy industry. This work innovatively provides a comprehensive assessment and optimization scheme for clean energy projects and predicts the profitability of Wind Power Base A using SVM multi-factor models. Besides, this work optimizes key parameters of the project using a bi-level multi-objective approach, thus comprehensively improving the investment return and utilization efficiency of the wind power base. This work provides innovative methods and strong data support for the development of the clean energy industry, which is of great significance for promoting sustainable development under the backdrop of green finance.

A non-invasive method to determine core temperature for cats and dogs using surface temperatures based on machine learning.

BACKGROUND: Rectal temperature (RT) is an important index of core temperature, which has guiding significance for the diagnosis and treatment of pet diseases. OBJECTIVES: Development and evaluation of an alternative method based on machine learning to determine the core temperatures of cats and dogs using surface temperatures. ANIMALS: 200 cats and 200 dogs treated between March 2022 and May 2022. METHODS: A group of cats and dogs were included in this study. The core temperatures and surface body temperatures were measured. Multiple machine learning methods were trained using a cross-validation approach and evaluated in one retrospective testing set and one prospective testing set. RESULTS: The machine learning models could achieve promising performance in predicting the core temperatures of cats and dogs using surface temperatures. The root mean square errors (RMSE) were 0.25 and 0.15 for cats and dogs in the retrospective testing set, and 0.15 and 0.14 in the prospective testing set. CONCLUSION: The machine learning model could accurately predict core temperatures for companion animals of cats and dogs using easily obtained body surface temperatures.

Capsaicin attenuates Porphyromonas gingivalis-suppressed osteogenesis of periodontal ligament stem cells via regulating mitochondrial function and activating PI3K/AKT/mTOR pathway.

BACKGROUND AND OBJECTIVE: Prevention of periodontal bone resorption triggered by Porphyromonas gingivalis (P. gingivalis) is crucial for dental stability. Capsaicin, known as the pungent ingredient of chili peppers, can activate key signaling molecules involved in osteogenic process. However, the effect of capsaicin on osteogenesis of periodontal ligament stem cells (PDLSCs) under inflammation remains elusive. METHODS: P. gingivalis culture suspension was added to mimic the inflammatory status after capsaicin pretreatment. The effects of capsaicin on the osteogenesis of PDLSCs, as well as mitochondrial morphology, Ca2+ level, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and osteogenesis-regulated protein expression levels were analyzed. Furthermore, a mouse experimental periodontitis model was established to evaluate the effect of capsaicin on alveolar bone resorption and the expression of osteogenesis-related proteins. RESULTS: Under P. gingivalis stimulation, capsaicin increased osteogenesis of PDLSCs. Not surprisingly, capsaicin rescued the damage to mitochondrial morphology, decreased the concentration of intracellular Ca2+ and ROS, enhanced MMP and activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The in vivo results showed that capsaicin significantly attenuated alveolar bone loss and augmented the expression of bone associated proteins. CONCLUSION: Capsaicin increases osteogenesis of PDLSCs under inflammation and reduces alveolar bone resorption in mouse experimental periodontitis.

BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial.

OBJECTIVES: This study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients with systemic lupus erythematosus (SLE) with lupus nephritis (LN). METHODS: This is a single-arm open-label multicentre phase 1 study of BCMA and CD19-directed cCAR in patients suffering from SLE/LN with autoantibodies produced by B cells and plasma/long-lived plasma cells. In this clinical trial, we sequentially assigned biopsy-confirmed (classes III-V) LN patients to receive 3×106 cCAR cells/kg postcessation of all SLE medications and conditioning. The primary endpoint of safety and toxicity was assessed. Complete immune reset was indicated by B cell receptor (BCR) deep sequencing and flow cytometry analysis. Patient 11 (P11) had insufficient lymphocyte counts and was underdosed as compassionate use. RESULTS: P1 and P2 achieved symptom and medication-free remission (MFR) from SLE and complete remission from lymphoma. P3-P13 (excluding P11) received an initial dose of 3×106 cCAR cells /kg and were negative for all autoantibodies, including those derived from long-lived plasma cells, 3 months post-cCAR and the complement returned to normal levels. These patients achieved symptom and MFR with post-cCAR follow-up to 46 months. Complete recovery of B cells was seen in 2-6 months post-cCAR. Mean SLE Disease Activity Index 2000 reduced from 10.6 (baseline) to 2.7 (3 months), and renal function significantly improved in 10 LN patients ≤90 days post-cCAR. cCAR T therapy was well tolerant with mild cytokine-release syndrome. CONCLUSIONS: Data suggest that cCAR therapy was safe and effective in inducing MFR and depleting disease-causing autoantibodies in patients with SLE.

Differential Impact of 0.01% and 0.05% Atropine Eyedrops on Ocular Surface in Young Adults.

Purpose: To evaluate the effect of low-concentration (0.01% and 0.05%) atropine eyedrops on ocular surface characteristics in young adults. Methods: Twenty-six myopic students aged 18 to 30 years were randomly assigned to receive either 0.01% or 0.05% atropine once nightly for 14 days, followed by cessation, with a ≥14-day interval between each administration. Assessments were conducted one, two, seven, and 14 days after using atropine with corresponding timepoints after atropine cessation. Tear meniscus height and first and average noninvasive keratograph tear film breakup time (NIKBUT-first, NIKBUT-average) were measured using Keratograph 5M, whereas the objective scatter index (OSI) was measured by OQAS II devices; the ocular surface disease index (OSDI) score was also obtained. Results: The mean OSI peaked after two days of administration of 0.05% atropine (ß = 0.51, P = 0.001), accompanied by significant decreases in NIKBUT-first (ß = -7.73, P < 0.001) and NIKBUT-average (ß = -8.10, P < 0.001); the OSDI peaked after 14 days (ß = 15.41, P < 0.001). The above parameters returned to baseline one week after atropine discontinuation (all P > 0.05). NIKBUT-first and NIKBUT-average reached their lowest points after 14 days of 0.01% atropine administration (NIKBUT-first: ß = -4.46, P = 0.005; NIKBUT-average: ß = -4.42, P = 0.001), but those significant changes were diminished once atropine treatment stopped. Conclusions: Young adult myopes experienced a significant but temporary impact on the ocular surface with 0.05% atropine administration, whereas 0.01% atropine had a minimal effect. Translational Relevance: The investigation of the ocular surface effects of different concentrations of atropine may inform evidence-based clinical decisions regarding myopia control in young adults.

CLCA1 exacerbates lung inflammation via p38 MAPK pathway in acute respiratory distress syndrome.

Recent research has revealed that airway epithelial calcium-activated chloride channel-1 (CLCA1) is implicated in the inflammation of multiple human respiratory diseases, but the specific role in acute respiratory distress syndrome (ARDS) remains unknown. To investigate the role of CLCA1 in ARDS, 80 participants, including 26 ARDS patients, 26 patients with community-acquired pneumonia (CAP) and 28 control subjects, were enrolled in this study. As the result shows, the level of CLCA1 was significantly increased in ARDS patients and positively correlated with neutrophil infiltration and the poor prognosis of ARDS. Then, the level of CLCA1 also elevated in the LPS-induced ARDS mouse model, and the administration of CLCA1 significantly regulated the phenotypes of ARDS in mice, such as lung injury score, BALF protein concentration, neutrophils infiltration and the secretions of inflammatory factors. Furthermore, administration of CLCA1 substantially altered the phosphorylation of p38 in the ARDS mouse model, whereas repressing the expression of CLCA1 or inhibiting the activation of p38 both alleviated the inflammatory response of ARDS. In summary, CLCA1 was notably correlated with ARDS and exacerbated the ARDS phenotypes through the p38 MAPK pathway.

Alterations in brain functional connectivity in patients with mild cognitive impairment: A systematic review and meta-analysis of functional near-infrared spectroscopy studies.

Emerging evidences suggest that cognitive deficits in individuals with mild cognitive impairment (MCI) are associated with disruptions in brain functional connectivity (FC). This systematic review and meta-analysis aimed to comprehensively evaluate alterations in FC between MCI individuals and healthy control (HC) using functional near-infrared spectroscopy (fNIRS). Thirteen studies were included in qualitative analysis, with two studies synthesized for quantitative meta-analysis. Overall, MCI patients exhibited reduced resting-state FC, predominantly in the prefrontal, parietal, and occipital cortex. Meta-analysis of two studies revealed a significant reduction in resting-state FC from the right prefrontal to right occipital cortex (standardized mean difference [SMD] = -.56; p < .001), left prefrontal to left occipital cortex (SMD = -.68; p < .001), and right prefrontal to left occipital cortex (SMD = -.53; p < .001) in MCI patients compared to HC. During naming animal-walking task, MCI patients exhibited enhanced FC in the prefrontal, motor, and occipital cortex, whereas a decrease in FC was observed in the right prefrontal to left prefrontal cortex during calculating-walking task. In working memory tasks, MCI predominantly showed increased FC in the medial and left prefrontal cortex. However, a decreased in prefrontal FC and a shifted in distribution from the left to the right prefrontal cortex were noted in MCI patients during a verbal frequency task. In conclusion, fNIRS effectively identified abnormalities in FC between MCI and HC, indicating disrupted FC as potential markers for the early detection of MCI. Future studies should investigate the use of task- and region-specific FC alterations as a sensitive biomarker for MCI.

Temperature-Dependent Selectivity and Detection of Hidden Carbon Deposition in Methane Oxidation.

Reaction products in heterogeneous catalysis can be detected either on the catalyst surface or in the gas phase after desorption. However, if atoms are dissolved in the catalyst bulk, then reaction channels can become hidden. This is the case if the dissolution rate of the deposits is faster than their formation rate. This might lead to the underestimation or even overlooking of reaction channels such as, e.g., carbon deposition during hydrocarbon oxidation reactions, which is problematic as carbon can have a significant influence on the catalytic activity. Here, we demonstrate how such hidden deposition channels can be uncovered by carefully measuring the product formation rates in the local gas phase just above the catalyst surface with time-resolved ambient pressure X-ray photoelectron spectroscopy. As a case study, we investigate methane oxidation on a polycrystalline Pd catalyst in an oxygen-lean environment at a few millibar pressure. By ramping the temperature between 350 and 525 °C, we follow the time evolution of the different reaction pathways. Only in the oxygen mass-transfer limit do we observe CO production, while our data suggests that carbon deposition also happens outside this limit.

Metabolome Profiling of Malignant Ascites Identifies Candidate Metabolic Biomarkers of Hepatocellular Carcinoma.

BACKGROUND: Malignant ascites is one of the severe complications of hepatocellular carcinoma, which can be regarded as a unique tumor microenvironment of hepatocellular carcinoma. The identification of novel biomarkers in malignant ascites could be crucial to differentiate patients with hepatocellular carcinoma and cirrhotic ascites. OBJECTIVE: The study aimed to distinguish the metabolomics of malignant ascites in patients with hepatocellular carcinoma from that of non-malignant ascites (cirrhotic ascites). METHODS: Liquid chromatography-mass spectrometry was performed to analyze the differentially distributed biomarkers in patients with malignant ascites and hepatocellular carcinoma (n = 39), as well as in patients with cirrhotic ascites, which were taken as controls (n = 36). RESULTS: A total of 20 differential metabolites associated with malignant ascites were identified, of which 8 metabolites were upregulated and 12 metabolites were downregulated (ratio < 0.5 or > 1.5, respectively). Moreover, pathway and enrichment analyses revealed nitrogen metabolism, urea cycle, phenylalanine, and tyrosine metabolism to be implicated in the formation of malignant ascites in patients with hepatocellular carcinoma. CONCLUSION: Our results suggest that the key factors associated with pathways, such as arachidonic acid, phenylalanine, and glutamic acid pathways, are potential ascitic fluidbased biomarkers for differentiating hepatocellular carcinoma with cirrhosis ascites; the results also provide a clinical pathophysiological interpretation of biomarkers and metabolic pathways relevant to disease status.

Cyanuric Acid-Assisted Synthesis of Hierarchical Amorphous Carbon Nitride Assembled by Ultrathin Oxygen-Doped Nanosheets for Excellent Photocatalytic Hydrogen Generation.

Amorphous carbon nitride with typical short-range order arrangement as an effective photocatalyst is worth exploring but remains a great challenge because its disordered structure induces severe recombination of photogenerated charge carriers. Herein, for the first time, we demonstrate that a hierarchical amorphous carbon nitride (HACN) with structural oxygen incorporation can be synthesized via a cyanuric acid-assisted melem hydrothermal process, accompanied by freeze-drying and pyrolysis. The complex composed of melem and cyanuric acid exhibiting a unique 3D self-supporting skeleton and significant phase transformation is responsible for the formation of an interconnected hierarchical framework and amorphous structure for HACN. These features are beneficial to enhance its visible light harvesting by the multiple-reflection effect within the architecture consisting of more exposed porous nanosheets and introducing a long band tail absorption. The well-designed morphology, band tail state, and oxygen doping effectively inhibit rapid band-to-band recombination of the photogenerated electrons and holes and facilitate subsequent separation. Accordingly, the HACN catalyst exhibits exceptional visible light (λ > 420 nm)-driven photoreduction for hydrogen production with a rate of 82.4 µmol h-1, which is 21.7 and 9.5 times higher than those of melem-derived carbon nitride and crystalline nanotube carbon nitride counterparts, respectively, and significantly surpasses those of most reported amorphous carbon nitrides. Our controlling of rearrangement of the in situ supramolecular self-assembly of melem oligomer using cyanuric acid directly instructs the development of highly efficient amorphous photocatalysts for converting solar energy into hydrogen fuel.

COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is among the most common deadly tumors but still lacks specific biomarkers for diagnosis, prognosis, and treatment guidance. The COP9 signalosome (COPS) is an essential regulator of the ubiquitin conjugation pathway upregulated in various cancers. We evaluated the contributions of COPS subunits to HCC tumorigenesis and their utility for prognosis. We comprehensively evaluated the tumor expression pattern and tumorigenic functions of COPS subunits using The Cancer Genome Atlas (TCGA), The Human Protein Atlas and immunohistochemistry. Kaplan-Meier, Cox regression, ROC curve, and nomogram analyses were used to assess the predictive values of COPS subunits for clinical outcome. Expression levels of COPS subunits were significantly upregulated in HCC tissues, which predicted shorter overall survival (OS). Further, Cox regression analysis identified COPS5, COPS7B, and COPS9 as independent prognostic biomarkers for OS. High mutation rates were also found in COPS subunits. Functional network analysis indicated that COPS and neighboring genes regulate 'protein neddylation', 'protein deneddylation', and 'protein ubiquitination'. The COPS PPI included strong interactions with p53, CUL1/2/3/4, and JUN. Moreover, the correlations between COPS subunit expression levels and tumor immune cell infiltration rates were examined using TIMER, TISIDB, ssGSEA, and ESTIMATE packages. COPS subunits expression levels were positively correlated with specific tumor immune cell infiltration rates, immunoregulator expression levels, and microsatellite instability in HCC. Finally, knockout of COPS6 and COPS9 in HCC cells reduced while overexpression enhanced proliferation rate and metastasis capacity. Our study revealed that COPS potential biomarker for unfavorable HCC prognosis and indicators of immune infiltration, tumorigenicity, and metastasis.

Photoplethysmography based atrial fibrillation detection: a continually growing field.

Objective. Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with significant health ramifications, including an elevated susceptibility to ischemic stroke, heart disease, and heightened mortality. Photoplethysmography (PPG) has emerged as a promising technology for continuous AF monitoring for its cost-effectiveness and widespread integration into wearable devices. Our team previously conducted an exhaustive review on PPG-based AF detection before June 2019. However, since then, more advanced technologies have emerged in this field.Approach. This paper offers a comprehensive review of the latest advancements in PPG-based AF detection, utilizing digital health and artificial intelligence (AI) solutions, within the timeframe spanning from July 2019 to December 2022. Through extensive exploration of scientific databases, we have identified 57 pertinent studies.Significance. Our comprehensive review encompasses an in-depth assessment of the statistical methodologies, traditional machine learning techniques, and deep learning approaches employed in these studies. In addition, we address the challenges encountered in the domain of PPG-based AF detection. Furthermore, we maintain a dedicated website to curate the latest research in this area, with regular updates on a regular basis.

Effect of eye-tracking-based attention training for patients with poststroke cognitive impairment: a study protocol for a prospective, single-blinded, single-centre, randomised controlled trial in China.

INTRODUCTION: Poststroke cognitive impairment (PSCI) is a common dysfunction that places a great burden on patients who had stroke and their families. Approximately 46%-92% of stroke survivors experience some degree of attention problems after a stroke. Improving attention is considered the core of successfully improving cognitive function and reintegrating patients into daily life. Eye tracking technology provides real-time feedback and accurate monitoring of cognitive processing, and using this technology to introduce attention training may improve patient treatment outcomes. The main purpose of this study was to investigate whether eye-tracking-based attention training has a positive effect on patients with PSCI. METHODS AND ANALYSIS: This study is a prospective randomised controlled trial. We will recruit 48 patients with PSCI referred to the Department of Rehabilitation Medicine at West China Hospital, Sichuan University, in Southwest China. The participants will be randomly distributed into two groups. Both groups will undergo conventional rehabilitation for 3 weeks, and the intervention group will receive 3 weeks of eye-tracking-based attention training (20-30 min/day). The primary outcome will be the patients' cognitive function, measured by the Montreal Cognitive Assessment. The secondary outcomes will be the patients' attention, independence of daily activities and event-related potential. These outcomes will be assessed at baseline, at the end of treatment (3 weeks) and at follow-up (1 month and 3 months after treatment). We will report the statistics and estimations using 95% CI. ETHICS AND DISSEMINATION: This trial received ethics approval from the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (2023 review No. 258). The results from this study will be disseminated via academic publication. TRIAL REGISTRATION NUMBER: ChiCTR2300068727.

Minimally invasive procedures for right side infective endocarditis: A targeted literature review.

INTRODUCTION: Right-side infective endocarditis (RSIE) is caused by microorganisms and develops into intracardiac and extracardiac complications with high in-hospital and 1-year mortality. Treatments involve antibiotic and surgical intervention. However, those presenting with extremes e.g. heart failure, or septic shock who are not ideal candidates for conventional medical therapy might benefit from minimally invasive procedures. OBJECTIVE: This review summarizes existing observational studies that reported minimally invasive procedures to debulk vegetation due to infective endocarditis either on valve or cardiac implantable electronic devices. METHODS: A targeted literature review was conducted to identify studies published in PubMed/MEDLINE, EMBASE, and Cochrane Central Database from January 1, 2015 to June 5, 2023. The efficacy and/or effectiveness of minimally invasive procedural interventions to debulk vegetation due to RSIE were summarized following PRISMA guidelines. RESULTS: A total of 11 studies with 208 RSIE patients were included. There were 9 studies that assessed the effectiveness of the AngioVac system and 2 assessed the Penumbra system. Overall procedure success rate was 87.9%. Among 8 studies that reported index hospitalization, 4 studies reported no death, while the other 4 studies reported 10 deaths. CONCLUSIONS: This study demonstrates that multiple systems can provide minimally invasive procedure options for patients with RSIE with high procedural success. However, there are mixed results regarding complications and mortality rates. Further large cohort studies or randomized clinical trials are warranted to assess and/or compare the efficacy and safety of these systems.

Generation of Functional and Mature Sympathetic Neurons from Human Pluripotent Stem Cells via a Neuroepithelial Route.

The sympathetic nervous system (SNS) is a crucial branch of the autonomic nervous system (ANS) that is responsible for regulating visceral function and various physiological processes. Dysfunction of the SNS can lead to various diseases, such as hypertension and metabolic disorders. However, obtaining sympathetic neurons from human tissues for research is challenging. The current research aimed at recapitulating the process of human sympathetic neuron development and achieved the successful establishment of a stepwise, highly efficient in vitro differentiation protocol. This protocol facilitated the generation of functional and mature sympathetic neurons from human pluripotent stem cells (hPSCs) using a chemical-defined induction medium. Initially, each differentiation stage was refined to derive sympathoadrenal progenitors (SAPs) from hPSCs through neural epithelial cells (NECs) and trunk neural crest stem cells (NCSCs). hPSC-derived SAPs could be expanded in vitro for at least 12 passages while maintaining the expression of SAP-specific transcription factors and neuronal differentiation potency. SAPs readily generated functional sympathetic neurons (SymNs) when cultured in the neuronal maturation medium for 3-4 weeks. These SymNs expressed sympathetic markers, exhibited electrophysiological properties, and secreted sympathetic neurotransmitters. More importantly, we further demonstrated that hPSC-derived SymNs can efficiently regulate the adipogenesis of human adipose-derived stem cells (ADSCs) and lipid metabolism in vitro. In conclusion, our study provided a simple and robust protocol for generating functional sympathetic neurons from hPSCs, which may be an invaluable tool in unraveling the mechanisms of SNS-related diseases.