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Background and Aims: Accessible noninvasive screening tools for metabolic dysfunction-associated steatotic liver disease (MASLD) are needed. We aim to explore the performance of a deep-learning based artificial intelligence (AI) model in distinguishing the presence of MASLD using 12-lead electrocardiogram (ECG)., Methods: This is a retrospective study of adults diagnosed with MASLD in Olmsted County, Minnesota, between 1996 and 2019. Both cases and controls had ECGs performed within 6 years before and 1 year after study entry. An AI-based ECG model using a convolutional neural network was trained, validated, and tested in 70%, 10% and 20% of the cohort, respectively. External validation was performed in an independent cohort from Mayo Clinic Enterprise. The primary outcome was the performance of ECG to identify MASLD, alone or when added to clinical parameters., Results: 3,468 MASLD cases and 25,407 controls were identified. The AI-ECG model predicted the presence of MASLD with an area under the curve (AUC) of 0.69 (original cohort) and 0.62 (validation cohort). The performance was similar or superior to age- and sex-adjusted models using body mass index (BMI) (AUC=0.71), presence of diabetes, hypertension or hyperlipidemia (AUC=0.68) or diabetes alone (AUC=0.66). The model combining ECG, BMI, diabetes, and alanine aminotransferase had the highest AUC (0.76 (original); 0.72 (validation))., Conclusion: This is a proof-of-concept study that an AI-based ECG model can detect MASLD with a comparable or superior performance as compared to the models using a single clinical parameter but not superior to the combination of clinical parameters. ECG can serve as another screening tool for MASLD in the non-hepatology space., (Copyright © 2024. Published by Elsevier Inc.)

Background: The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality., Objectives: This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS., Methods: Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period., Results: Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150)., Conclusions: This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities., Competing Interests: Funding Support and Author Disclosures Dr Templin has received institutional grants from Abbott Vascular, Medtronic, and SMT; and has received consulting grants from Biotronik, Microport, and Innova. Dr Airaksinen has received grants or has contracts with the Finnish Foundation for Cardiovascular Research; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Pfizer, Boehringer Ingelheim, and AstraZeneca. Dr Bauersachs has received grants from or has contracts with Abiomed, CVRx, Norgine, Roche, and Zoll; holds patents PCT/EP2007/008772 and PCT/EP2009/051986 for microRNA and downstream targets for diagnostics and therapeutic purposes; has received consulting fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Edwards, Norgine, Novartis, Pfizer, Roche, and Vifor; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cardior, CVRx, Norgine, Novartis, Pfizer, and Vifor. Dr Boehm has received grants from or has contracts with Deutsche Forschungsgemeinschaft research support (DFG, SFB-TTR 219, S-01); has received speaker honoraria from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Novartis, Servier, and Vifor; and is on the advisory board of Amgen, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Pfizer, ReCor, Servier, and Vifor. Dr Ferreira has received payments for lectures, presentations, speakers bureaus, manuscript writing, or educational events from A Menarini, Medinfar, Bayer, AstraZeneca, Biotronik, and Medtronic; and has received payments for participation on a Data Safety Monitoring Board or Advisory Board from Medtronic. Dr Dichtl has received consulting fees from Reata. Dr Kaiser has received consulting fees from the Swiss Federal Office of Public Health; and has received support for attending meetings and/or travel from Medtronic, Abbott, and Europa Organization. Dr Kobza has received institutional grants on behalf of the Luzerner Kantonsspital from Biosense Webster, Boston Scientific, Biotronik, Medtronik, and Sis-Medical; and has received consulting fees from Biosense Webster, Biotronik, and Medtronic. Dr Koenig has received grants and provision of reagents to the institution from Singulex, Dr.Beckmann Pharma, Abbott, and Roche Diagnostics; has received consulting fees from AstraZeneca, Novartis, Amgen, Pfizer, The Medicines Company, DalCor Pharmaceuticals, Kowa, Corvidia Therapeutics, OMEICOS, Daiichi-Sankyo, Novo Nordisk, New Amsterdam Pharma, TenSixteen Bio, Esperion, and Genentech; and has received lecture fees from Bristol Myers Squibb, Novartis, Amgen, Berlin-Chemie, Sanofi, and AstraZeneca. Dr Lüscher has received research or educational grants to the institution from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Novo Nordisk, Sanofi, and Vifor; is the president elect of the European Society of Cardiology; is chairman of the research committee of the Swiss Heart Foundation; is President of the Board of the Zurich Heart House; and is Trustee of the London Heart House. Dr Karakas has received grants or has contracts with Vifor Pharma and Daiichi-Sankyo; has received consulting fees or payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Vifor, Pharmacosmos, and Sphingotec; and has received equipment, materials, drugs, medical writing, gifts or other services from Sphingotec and Vifor Pharma. Dr Niederseer has received consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Gerson Lehmann Group (GLG) Consulting, Novo Nordisk, Pfizer and Zoll; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Novo Nordisk, and Pfizer; and has received support for attending meetings and/or travel from Abbott, Amgen, Bayer, and Novo Nordisk. Dr Roffi has received institutional research grants from Boston Scientific, Cordis, Terumo, Biotronik, and Medtronic. Dr Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years; the Department of Cardiology (University Hospital of Zurich/University of Zurich), however, reports research, educational, and/or travel grants from Abbott, Abiomed, Alexion, Amgen, AstraZeneca, At the Limits Ltd, Bayer, Berlin Heart, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Concept Medical, Corteria, CSL, Daiichi-Sankyo, Diatools AG, Edwards Lifesciences, Guidant Europe NV, Hamilton Health Sciences, IHF, Innosuisse, Johnson/Johnson, Kaneka Corporation, Kantar, Kiniksa, Labormedizinisches Zentrum, MedAlliance, Medical Education Global Solutions, Medtronic, MicroPort, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, RecorMedical, Roche Diagnostics, Roche Pharma, Sahajanand IN, Sanofi, Sarstedt AG, Servier, SIS Medical, Sorin CRM SAS, SSS International Clinical Research, Stromal, Terumo Deutschland, Trama Solutions, V-Wave, Vascular Medical, Vifor, Wissens Plus, and ZOLL. Prof Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years; remuneration for the time spent in the following consulting activities were made directly to the University of Zurich and do not impact on his personal remuneration: AstraZeneca (IMC), Bayer, Boehringer Ingelheim, Citi Research, Klub Class, Novo Nordisk, Radcliffe Group, Stiftung Pfizer Forschungspreis, and Vifor; remuneration for the following lectures were made directly to the University of Zurich and do not impact on his personal remuneration: Abbott, Amgen, AstraZeneca (A+ Science AB), Bayer (At the Limits), Boehringer Ingelheim, Boston Scientific (CCE Services), Brigham and Women’s Hospital Boston, C.T.I GmbH, FomF, Hôpitaux Universitaires des Genève (GECORE), Luzerner Kantonsspital, Sanofi-Aventis, Servier, Medcon, Medscape (WebMD), Medtronic, Medworld, Novartis, Roche, Ruwag, Swiss Heart Failure Academy, The Hong Kong Heart Failure Society, Trama Solutions SL, Inselspital Bern, Charité–Universitätsmedizin Berlin (Medical Education Global Solutions), Romanian Society of Cardiology, ÖKG Österreichische Gesellschaft für Kardiologie, and Zoll; has received support for attending meetings and/or travel from AstraZeneca (IMC/A+ Science AB), Boehringer Ingelheim, Centro Hospitaler de Vila Nova de Gaia, C.T.I. GmbH (Universitätsklinikum Düsseldorf), European Society of Cardiology, Monocle, Novartis, Spektar Putovanja, Austrian Heart Failure Association, and Heart Failure Association of the ESC; remuneration for following Advisory Boards were made directly to the University of Zurich and do not impact on his personal remuneration: Bayer, Roche, IMC/AstraZeneca, and Amgen; and he has received secretarial and administrative support of the HFA for his role as President/Past-President for 2018 to 2020. Dr Schunkert has received consulting fees from Amgen, Daiichi-Sankyo, Merck Sharp and Dohme, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Servier; has received honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and support for attending meetings and/or travel from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Merck Sharp and Dohme, Novartis, Sanofi Aventis, Servier, and Synlab; and has received honoraria for his participation on a Data Safety Monitoring Board or Advisory Board of Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Amgen. Dr Wolfrum has received consulting fees from NVT/Biosensors as well as payments for lectures, presentations, speakers bureaus, manuscript writing, or educational events from NVT/Biosensors; and has equities in Hi-D Imaging, Winterthur, Switzerland. Dr Crea has received personal fees from Amgen, AstraZeneca, Abbott, Menarini, Chiesi, and Daiichi-Sankyo, outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The rapid development of ocean exploration and underwater robot technology has put forward new requirements for underwater sensing methods, which can be used for hydrodynamic characteristics perception, underwater target tracking, and even underwater cluster communication. Here, inspired by the specialized undulated surface structure of the seal whisker and its ability to suppress vortex-induced vibration, a multidirectional hydrodynamic sensor based on biomimetic whisker array structure and magnetic 3D self-decoupling theory is introduced. The magnetic-based sensing method enables wireless connectivity between the magnetic functional structures and electronics, simplifying device design and endowing complete watertightness. The 3D self-decoupling capability enables the sensor, like a seal or other organisms, to perceive arbitrary whisker motions caused by the action of water flow without complex calibration and additional sensing units. The whisker sensor is capable of detecting a variety of hydrodynamic information, including the velocity (RMSE < 0.061 m s -1 ) and direction of the steady flow field, the frequency (error < 0.05 Hz) of the dynamic vortex wake, and the orientation (error < 7°) of the vortex wake source, demonstrating its extensive potential for underwater environmental perception and communication, especially in deep sea conditions., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: It is essential to develop new biomarker with effective prognostic roles because of the unclear clinical use of the current community-acquired pneumonia (CAP) predictors., Aim: To evaluate the association between serum activin A levels and prognosis in CAP patients., Methods: A total of 168 CAP individuals grouped according to the severity and prognosis of illness condition, and 48 healthy individuals as the control group were enrolled in this study. Circulating concentrations of activin A were measured using enzyme-linked immunoassays. The interaction between activin A levels and etiologies of CAP was determined. Based on the severity of CAP, 110 patients (65.48%) were categorized into group-I, 42 (25%) cases were grouped into group-II, and 16 (9.52%) cases were categorized into group-III., Results: Serum activin A levels were higher in patients with CAP than controls, but independent of etiology. Moreover, the scores of Pneumonia Severity Index (PSI) and CURB-65 positively correlated with the increasing levels of serum activin A, and were at their highest peak in individuals in group-III ( P < 0.001). Combining activin A with CURB-65 or PSI was more effective in improving predictive property ( P < 0.01). According to Cox proportional regression analysis, after adjusting clinical parameters, we confirmed that activin A showed a powerful predictive property for hospital mortality in CAP patients ( P < 0.001)., Conclusion: Higher level of serum activin A was associated with poor prognosis of CAP. Activin A can be used as a more valuable biomarker of prognosis in CAP patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Artificial intelligence (AI) electrocardiogram (ECG) analysis can enable detection of hyperkalemia. In this validation, we assessed the algorithm's performance in two high acuity settings., Methods: An emergency department (ED) cohort (February to August 2021) and a mixed intensive care unit (ICU) cohort (August 2017 to February 2018) were identified and analyzed separately. For each group, pairs of laboratory-collected potassium and 12 lead ECGs obtained within 4 hours of each other were identified. The previously developed AI ECG algorithm was subsequently applied to leads 1 and 2 of the 12 lead ECGs to screen for hyperkalemia (potassium >6.0 mEq/L)., Results: The ED cohort (N=40,128) had a mean age of 60 years, 48% were male, and 1% (N=351) had hyperkalemia. The area under the curve (AUC) of the AI-enhanced ECG (AI-ECG) to detect hyperkalemia was 0.88, with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive likelihood ratio (LR+) of 80%, 80%, 3%, 99.8%, and 4.0, respectively, in the ED cohort. Low-eGFR (<30 ml/min) subanalysis yielded AUC, sensitivity, specificity, PPV, NPV, and LR+ of 0.83, 86%, 60%, 15%, 98%, and 2.2, respectively, in the ED cohort. The ICU cohort (N=2636) had a mean age of 65 years, 60% were male, and 3% (N=87) had hyperkalemia. The AUC for the AI-ECG was 0.88 and yielded sensitivity, specificity, PPV, NPV, and LR+ of 82%, 82%, 14%, 99%, and 4.6, respectively in the ICU cohort. Low-eGFR subanalysis yielded AUC, sensitivity, specificity, PPV, NPV, and LR+ of 0.85, 88%, 67%, 29%, 97%, and 2.7, respectively in the ICU cohort., Conclusions: The AI-ECG algorithm demonstrated a high NPV, suggesting that it is useful for ruling out hyperkalemia, but a low PPV, suggesting that it is insufficient for treating hyperkalemia.

Many microbes accumulate energy storage molecules such as triglycerides (TAG) and starch during nutrient limitation. In eukaryotic green algae grown under nitrogen-limiting conditions, triglyceride accumulation is coupled with chlorosis and growth arrest. In this study, we show that reactive oxygen species (ROS) actively accumulate during nitrogen limitation in the microalga Chlorella sorokiniana . Accumulation of ROS is mediated by the downregulation of genes encoding ROS-quenching enzymes, such as superoxide dismutases, catalase, peroxiredoxin, and glutathione peroxidase-like, and by the upregulation of enzymes involved in generating ROS, such as NADPH oxidase, xanthine oxidase, and amine oxidases. The expression of genes involved in ascorbate and glutathione metabolism is also affected under this condition. ROS accumulation contributes to the degradation of monogalactosyl diacylglycerol (MGDG) and thylakoid membrane remodeling, leading to chlorosis. Quenching ROS under nitrogen limitation reduces the degradation of MGDG and the accumulation of TAG. This work shows that ROS accumulation, membrane remodeling, and TAG accumulation under nitrogen limitation are intricately linked in the microalga C. sorokiniana., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vijayan, Wase, Liu, Morse, Zhang and Riekhof.)

Purpose: SHR-A1811 is an antibody-drug conjugate composed of an anti-human epidermal growth factor receptor 2 (HER2) antibody trastuzumab, a cleavable linker, and a topoisomerase I inhibitor payload. We assessed the safety, tolerability, antitumor activity, and pharmacokinetics of SHR-A1811 in heavily pretreated HER2-expressing or mutated advanced solid tumors., Methods: This global, multi-center, first-in-human, phase I trial was conducted at 33 centers. Patients who had HER2-expressing or mutated unresectable, advanced, or metastatic solid tumors and were refractory or intolerant to standard therapies were enrolled. SHR-A1811 was administered intravenously at doses ranging from 1.0 to 8.0 mg/kg once every 3 weeks. The primary end points were dose-limiting toxicity, safety, and the recommended phase II dose., Results: From September 7, 2020, to February 27, 2023, 307 patients who had undergone a median of three (IQR, 2-5) previous treatment regimens in the metastatic setting received SHR-A1811 treatment. As of data cutoff (February 28, 2023), one patient from the 6.4 mg/kg group experienced dose-limiting toxicities (pancytopenia and colitis). The most common grade 3 or higher adverse events (AEs) included decreased neutrophil count (119 [38.8%]) and decreased WBC count (70 [22.8%]). Interstitial lung disease occurred in only eight (2.6%) patients. Serious AEs and deaths occurred in 70 (22.8%) and 13 (4.2%) patients, respectively. SHR-A1811 led to objective responses in 59.9% (184/307) of all patients, 76.3% (90/118) of HER2-positive breast cancer, 60.4% (55/91) of HER2 low-expressing breast cancer, and 45.9% (39/85 with evaluable tumor responses) of the 98 nonbreast tumors., Conclusion: SHR-A1811 exhibited acceptable tolerability, promising antitumor activity, and a favorable pharmacokinetic profile in heavily pretreated advanced solid tumors. The recommended phase II dose of 4.8 or 6.4 mg/kg was selected for various tumor types.

Background: Pheochromocytoma-induced takotsubo syndrome (Pheo-TTS) significantly increases the risk of adverse events for inpatient. The early identification of risk factors at admission is crucial for effective risk stratification and minimizing complications in Pheo-TTS patients., Methods: We conducted a systematic review combined with hierarchical cluster and feature importance analysis of demographic, clinical and laboratory data upon admission, alongside in-hospital complication data for Pheo-TTS patients. We analyzed cases published in PubMed and Embase from 2 May 2006 to 27 April 2023., Results: Among 172 Pheo-TTS patients, cluster analysis identified two distinct groups: a chest pain dominant (CPD) group (n = 86) and a non-chest pain dominant (non-CPD) group (n = 86). The non-CPD group was characterized by a younger age (44.0 ± 15.2 vs . 52.4 ± 14.4, p < 0.001), a higher prevalence of neurological/psychiatric disorders (53.5% vs . 32.6%), and increased presentation of dyspnea (87.2% vs . 17.4%), pulmonary rales (59.3% vs . 8.1%), and tachycardia (77.9% vs . 30.2%). Additionally, they exhibited more atypical takotsubo syndrome (TTS) imaging phenotypes (55.8% vs . 36.5%, all p < 0.05). The non-CPD group experienced more than a 2-fold increase for in-hospital adverse events compared to the CPD group (70.9% vs . 30.2%, p < 0.001). After adjusting for confounding factors, the absence of chest pain (odds ratio [OR] = 0.407, 95% confidence interval [CI] 0.169-0.979, p = 0.045), the presence of abdominal symptoms (OR = 3.939, 95% CI 1.770-8.766, p = 0.001), pulmonary rales (OR = 4.348, 95% CI 1.857-10.179, p = 0.001), and atypical TTS imaging phenotype (OR = 3.397, 95% CI 1.534-7.525, p = 0.003) remained as independent predictors of in-hospital complications., Conclusions: Clinical manifestations and imaging features at admission help to predict in-hospital complications for Pheo-TTS patients., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Purpose: To evaluate the value of preoperative intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and conventional MRI indicators in identifying sarcomatoid dedifferentiation in renal cell carcinoma (RCC) and tumor thrombus., Methods: From September 2016 to April 2023, consecutive patients with RCC and tumor thrombus who received routine MRI examination and IVIM-DWI before radical resection were enrolled prospectively. Kaplan-Meier method with log-rank test was used to calculate and compare the survival probability. The preoperative imaging features were analyzed. Univariate and multivariable logistic regression analyses were employed to identify independent predictors of sarcomatoid dedifferentiation. The predictive ability was evaluated by receiver operating characteristic (ROC) curves., Results: Twenty-two patients (15.3%) of the 144 patients in the training set (median age, 58.0 years [IQR, 52.0-65.0 years]; 108 men) and 11 patients (22.4%) of the 49 patients in the test set (median age, 58.0 years [IQR, 53.0-63.0 years]; 38 men) had sarcomatoid dedifferentiated tumors. Patients with sarcomatoid-differentiated tumors had poor progress-free survival in the training set and test set (P < 0.001 and P = 0.007). f value (P = 0.011), mN stage (P = 0.007), and necrosis (P = 0.041) were independent predictors for predicting sarcomatoid dedifferentiation in the training set. The model combining conventional MRI features and f value had AUCs of 0.832 (95% CI 0.755-0.909) and 0.825 (95% CI 0.702-0.948) in predicting sarcomatoid dedifferentiation in the training set and test set., Conclusion: It is feasible to preoperatively identify sarcomatoid dedifferentiation based on IVIM-DWI and conventional MR imaging indicators., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The purpose of this preliminary investigation into the pathogenesis of pre-eclampsia was to screen the differential proteins in the serum of pregnant women with normal pregnancy and early-onset pre-eclampsia using isobaric tags for relative and absolute quantitation (iTRAQ), so as to identify serum biomarkers for the early diagnosis of pre-eclampsia., Methods: We examined the peripheral serum of 58 normal pregnant women and 42 pregnant women with early-onset pre-eclampsia using iTRAQ; the differentially expressed proteins were screened for bioinformatics analysis; and the expression of candidate proteins human leukocyte antigen-1 (HLA-1) and β2-microglobulin (β2M) in placental tissues was detected using western blot., Results: We identified a total of 63 differential proteins in the serum of patients from the normal control group and the pre-eclampsia group, and this included 24 up-regulated proteins and 39 down-regulated proteins. The western blot results of placental tissue showed reduced HLA-1 expression (1.12 ± 0.23) in the placenta in the pre-eclampsia group as compared with the normal control group (1.34 ± 0.22). Consistent with the results observed in the serum, β2M in the placenta in the pre-eclampsia group was significantly elevated (1.05 ± 0.47) in comparison with the normal group (0.75 ± 0.33) (P < 0.05)., Conclusion: In this study, we found that iTRAQ technology was useful for identifying differentially expressed proteins in the peripheral serum of pregnant women with pre-eclampsia, and that HLA-1 and β2M, which may be involved in the occurrence of pre-eclampsia, show promise as predictive markers of pre-eclampsia., (© 2023 International Federation of Gynecology and Obstetrics.)

Simultaneous multiplexed analysis can provide comprehensive information for disease diagnosis. However, the current multiplex methods rely on sophisticated barcode technology, which hinders its wider application. In this study, an ultrasimple size encoding method is proposed for multiplex detection using a wedge-shaped microfluidic chip. Driving by negative pressure, microparticles are naturally arranged in distinct stripes based on their sizes within the chip. This size encoding method demonstrates a high level of precision, allowing for accuracy in distinguishing 3-5 sizes of microparticles with a remarkable accuracy rate of up to 99%, even the microparticles with a size difference as small as 0.5 μm. The entire size encoding process is completed in less than 5 min, making it ultrasimple, reliable, and easy to operate. To evaluate the function of this size encoding microfluidic chip, three commonly co-infectious viruses' nucleic acid sequences (including complementary DNA sequences of HIV and HCV, and DNA sequence of HBV) are employed for multiplex detection. Results indicate that all three DNA sequences can be sensitively detected without any cross-interference. This size-encoding microfluidic chip-based multiplex detection method is simple, rapid, and high-resolution, its successful application in serum samples renders it highly promising for potential clinical promotion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Catalpol (CAT) has various pharmacological activities and plays a protective role in cerebral ischemia. It has been reported that CAT played a protective role in cerebral ischemia by upregulaing NRF1 expression. Bioinformatics analysis reveals that NRF1 can be used as a transcription factor to bind to the histone acetyltransferase KAT2A. However, the role of KAT2A in cerebral ischemia remains to be studied. Therefore, we aimed to investigate the role of CAT in cerebral ischemia and its related mechanism., Methods: In vitro, a cell model of oxygen and glucose deprivation/reperfusion (OGD/R) was constructed, followed by evaluation of neuronal injury and the expression of METTL3, Beclin-1, NRF1, and KAT2A. In vivo, a MCAO rat model was prepared by means of focal cerebral ischemia, followed by assessment of neurological deficit and brain injury in MCAO rats. Neuronal autophagy was evaluated by observation of autophagosomes in neurons or brain tissues by TEM and detection of the expression of LC3 and p62., Results: In vivo, CAT reduced the neurological function deficit and infarct volume, inhibited neuronal apoptosis in the cerebral cortex, and significantly improved neuronal injury and excessive autophagy in MCAO rats. In vitro, CAT restored OGD/R-inhibited cell viability, inhibited cell apoptosis, LDH release, and neuronal autophagy. Mechanistically, CAT upregulated NRF1, NRF1 activated METTL3 via KAT2A transcription, and METTL3 inhibited Beclin-1 via m 6 A modification., Conclusion: CAT activated the NRF1/KAT2A/METTL3 axis and downregulated Beclin-1 expression, thus relieving neuronal injury and excessive autophagy after cerebral ischemia., (© 2024. The Author(s).)

Sensor faults are one of the most common faults that cause performance degradation or functional loss in permanent magnet traction drive systems (PMTDSs). To quickly diagnose faulty sensors, this paper proposes a real-time joint diagnosis method for multi-sensor faults based on structural analysis. Firstly, based on limited monitoring signals on board, a structured model of the system was established using the structural analysis method. The isolation and detectability of faulty sensors were analyzed using the Dulmage-Mendelsohn decomposition method. Secondly, the minimum collision set method was used to calculate the minimum overdetermined equation set, transforming the higher-order system model into multiple related subsystem models, thereby reducing modeling complexity and facilitating system implementation. Next, residual vectors were constructed based on multiple subsystem models, and fault detection and isolation strategies were designed using the correlation between each subsystem model and the relevant sensors. The validation results of the physical testing platform based on online fault data recordings showed that the proposed method could achieve rapid fault detection and the localization of multi-sensor faults in PMTDS and had a good application value.

A key strength of echocardiography lies in its integration of comprehensive spatiotemporal cardiac imaging data in real-time, to aid frontline or bedside patient risk stratification and management. Nonetheless, its acquisition, processing, and interpretation are known to all be subject to heterogeneity from its reliance on manual and subjective human tracings, which challenges workflow and protocol standardization and final interpretation accuracy. In the era of advanced computational power, utilization of machine learning algorithms for big data analytics in echocardiography promises reduction in cost, cognitive errors, and intra- and inter-observer variability. Novel spatiotemporal deep learning (DL) models allow the integration of temporal arm information based on unlabeled pixel echocardiographic data for convolution of an adaptive semantic spatiotemporal calibration to construct personalized 4D heart meshes, assess global and regional cardiac function, detect early valve pathology, and differentiate uncommon cardiovascular disorders. Meanwhile, data visualization on spatiotemporal DL prediction models helps extract latent temporal imaging features to develop advanced imaging biomarkers in early disease stages and advance our understanding of pathophysiology to support the development of personalized prevention or treatment strategies. Since portable echocardiograms have been increasingly used as point-of-care imaging tools to aid rural care delivery, the application of these new spatiotemporal DL techniques show the potentials in streamlining echocardiographic acquisition, processing, and data analysis to improve workflow standardization and efficiencies, and provide risk stratification and decision supporting tools in real-time, to prompt the building of new imaging diagnostic networks to enhance rural healthcare engagement., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Background: Respiratory conditions are major physical triggers of takotsubo syndrome (TTS) and portend worse outcomes. However, data on TTS in patients with coronavirus disease-2019 infection (COVID-19) are limited., Methods: We searched PubMed, Embase, and Cochrane Library databases for case reports for the period 2019-2022 describing TTS in patients with COVID-19 pneumonia (TTS-COVID). We summarized the clinical data and outcomes and compared them to those in patients with TTS with an acute respiratory disease other than COVID-19 as a trigger (TTS-acute respiratory disease) and those with TTS with no respiratory disease (TTS-no respiratory disease)., Results: The mortality rate was higher in those with TTS-COVID (26.0%) than those with TTS-acute respiratory disease (5.7%) or TTS-no respiratory disease (4.2%; P < 0.001 for both). The proportion of men was higher in TTS-COVID (33.3%) than it was in TTS-no respiratory disease (9.1%; P < 0.001). The manifestations of TTS in COVID patients were atypical (dyspnea [70.3%] and cough [40.6%]); few had chest pain (23.4%). Cardiovascular risk factors were common in the TTS-COVID cohort, but fewer patients were on cardioprotective medications in this group than in the other 2 groups. Level of catecholamine use was higher in the TTS-COVID group (37.7%) than it was in the TTS-no respiratory disease (10.9%; P < 0.001) group. Apical ballooning (72.6%) was the most common TTS subtype, and basal segment type was seen in 11.0% of TTS-COVID patients., Conclusions: COVID-19 patients who developed TTS had high mortality rates and unique features, compared with those in the TTS-acute respiratory disease group or the TTS-no respiratory disease group. Understanding the pathophysiology of TTS in COVID-19 may help prevent TTS and direct therapy in this setting., (© 2024 The Authors.)

Fluorescence in situ hybridization (FISH) is a powerful cytogenetic method used to precisely detect and localize nucleic acid sequences. This technique is proving to be an invaluable tool in medical diagnostics and has made significant contributions to biology and the life sciences. However, the number of cells is large and the nucleic acid sequences are disorganized in the FISH images taken using the microscope. Processing and analyzing images is a time-consuming and laborious task for researchers, as it can easily tire the human eyes and lead to errors in judgment. In recent years, deep learning has made significant progress in the field of medical imaging, especially the successful application of introducing the attention mechanism. The attention mechanism, as a key component of deep learning, improves the understanding and interpretation of medical images by giving different weights to different regions of the image, enabling the model to focus more on important features. To address the challenges in FISH image analysis, we combined medical imaging with deep learning to develop the SEAM-Unet++ automated cell contour segmentation algorithm with integrated attention mechanism. The significant advantage of this algorithm is that it improves the accuracy of cell contours in FISH images. Experiments have demonstrated that by introducing the attention mechanism, our method is able to segment cells that are adherent to each other more efficiently.

The microfluidic chip-based nucleic acid detection method significantly improves the sensitivity since it precisely controls the microfluidic flow in microchannels. Nonetheless, significant challenges still exist in improving the detection efficiency to meet the demand for rapid detection of trace substances. This work provides a novel magnetic herringbone (M-HB) structure in a microfluidic chip, and its advantage in rapid and sensitive detection is verified by taking complementary DNA (cDNA) sequences of human immunodeficiency virus (HIV) detection as an example. The M-HB structure is designed based on controlling the magnetic field distribution in the micrometer scale and is formed by accumulation of magnetic microbeads (MMBs). Hence, M-HB is similar to a nanopore microstructure, which has a higher contact area and probe density. All of the above is conducive to improving sensitivity in microfluidic chips. The M-HB chip is stable and easy to form, which can linearly detect cDNA sequences of HIV quantitatively ranging from 1 to 20 nM with a detection limit of 0.073 nM. Compared to the traditional herringbone structure, this structure is easier to form and release by controlling the magnetic field, which is flexible and helps in further study. Results show that this chip can sensitively detect the cDNA sequences of HIV in blood samples, demonstrating that it is a powerful platform to rapidly and sensitively detect multiple nucleic acid-related viruses of infectious diseases.

Objective: To explore the potential mechanism of Yougui Wan on deformed lumbar intervertebral disk structure in rats., Methods: Thirty male Sprague-Dawley rats were randomly divided into 3 groups, with 10 rats in each group. The animals in the blank control group were healthy rats without specific treatment, and those in the model group and traditional Chinese medicine (TCM) group were used to establish the intervertebral disk degeneration (IDD) model by puncturing the annulus. Four weeks after modeling, rats in the TCM group were administered Yougui Wan by gavage for 2 consecutive weeks. Serum interleukin-6 (IL-10), macrophage migration inhibitory factor (MIF) and tumor necrosis factor alpha (TNF-α) levels were measured by ELISA, and the protein expression levels of collagen II and Notch1 in intervertebral disk tissues were examined by Western blotting. Apoptosis was detected by the TUNEL method., Results: Compared with those in the blank group, IL-10, MIF and TNF-α levels in the model group and TCM group were increased (P < 0.05), the protein expression levels of collagen II were decreased, and the protein expression levels of Notch1 were increased. Compared with those in the model group, the levels of IL-10 in the TCM group were increased (P < 0.05), the levels of MIF and TNF-α were decreased (P < 0.05), the protein expression levels of collagen II were increased, and the protein expression levels of Notch1 were decreased., Conclusion: Yougui Wan can inhibit the inflammatory response in IDD rats, reduce the degradation of extracellular matrix, reduce apoptosis in nucleus pulposus cells, and alleviate intervertebral disk degeneration. The mechanism may be related to the regulation of the Notch signaling pathway., (© 2024. The Author(s).)

Background: Cisplatin (CDDP)-based chemotherapy is a standard first-line treatment for metastatic bladder cancer (BCa) patients, and chemoresistance remains a major challenge in clinical practice. Circular RNAs (circRNAs) have emerged as essential regulators in carcinogenesis and cancer progression. However, the role of circRNAs in mediating CDDP chemosensitivity has yet to be well elucidated in BCa., Methods: CircSTX6 (hsa&#95;circ&#95;0007905) was identified by mining the public circRNA datasets and verified by Sanger sequencing, agarose gel electrophoresis, RNase R treatment and qRT-PCR assays. Then, function experiments were performed to evaluate the effects of circSTX6 on BCa metastasis. Luciferase reporter assay, RNA pull-down, RNA immunoprecipitation (RIP), RNA stability assay, Fluorescence in situ hybridization (FISH) and Immunofluorescence (IF) were conducted to evaluate the interaction among circSTX6, miR-515-3p, PABPC1 and SUZ12. Animal experiments were performed to explore the function of circSTX6 in tumor metastasis and CDDP sensitivity., Results: We identified that circSTX6 was significantly upregulated in clinical samples and cells of BCa. Functionally, circSTX6 promoted cell migration and invasion both in vitro and in vivo. Mechanistically, circSTX6 could act as a miR-515-3p sponge and abolish its effect on SUZ12. Moreover, circSTX6 was confirmed to increase the stability of SUZ12 mRNA by interacting with a mRNA stabilizer PABPC1 and subsequently promote the expression of SUZ12. Importantly, silencing of circSTX6 improved the chemosensitivity of CDDP-resistant bladder cancer cells to CDDP. Furthermore, in vivo analysis supported that knockdown of circSTX6 attenuated CDDP resistance in BCa tumors., Conclusion: These studies demonstrate that circSTX6 plays a pivotal role in BCa metastasis and chemoresistance, and has potential to serve as a therapeutic target for treatment of BCa., (© 2023. The Author(s).)

Purpose: To determine the optimal cut-off value of Ki-67 for predicting the survival of patients with clear cell renal cell carcinoma (ccRCC) and tumor thrombus and to explore the correlation between Ki-67 expression and pathological features., Patients and Methods: We retrospectively analyzed Ki-67 immunohistochemical staining of ccRCC and tumor thrombus resected from February 2006 to February 2022. The survival rate was evaluated using the Kaplan-Meier method. The optimal cut-off value of the Ki-67 expression for predicting survival was determined by the minimum P-value method. Clinicopathological data were compared based on Ki-67 status (low versus high expression). Univariate and multivariate Cox regression analysis was used to explore independent predictors., Results: A total of 202 patients (median age, 58 years [IQR, 52-65 years], 147 men) with ccRCC and tumor thrombus were included in the study. The optimal cut-off value of Ki-67 for predicting survival was 30%. 159 (78.7%) and 43 (21.3%) patients were included in the low-expression and high-expression groups. Patients with Ki-67 high expression had significantly worse recurrence-free survival (P < 0.001) and cancer-specific survival (P < 0.001). Ki-67 high expression was associated with adverse pathological features, including tumor necrosis, ISUP nuclear grade, sarcomatoid differentiation, perirenal fat invasion, renal pelvis invasion, and inferior vena cava wall invasion (all P < 0.050). Ki-67 expression ≥ 30% (P = 0.016), tumor side (P = 0.003), diabetes (P = 0.040), blood loss (P = 0.016), inferior vena cava wall invasion (P = 0.016), and sarcomatoid differentiation (P = 0.014) were independent predictors of cancer-specific survival., Conclusion: The optimal cut-off level of Ki-67 in predicting the prognosis of ccRCC and tumor thrombus was 30%. The high expression of Ki-67 was associated with the aggressive pathological phenotype and poor prognosis., Competing Interests: Declaration of Competing Interest No potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Venous tumor thrombus (VTT) consistency of renal cell carcinoma (RCC) is an important consideration in nephrectomy plus thrombectomy. However, evaluation of VTT consistency through preoperative MR imaging is lacking., Purpose: To evaluate VTT consistency of RCC through intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters (D t , D p , f, and ADC) and the apparent diffusion coefficient (ADC) value., Study Type: Retrospective., Population: One hundred and nineteen patients (aged 55.8 ± 11.5 years, 85 male) with histologically-proven RCC and VTT who underwent radical resection., Field Strength/sequences: 3.0-T; two-dimensional single-shot diffusion-weighted echo planar imaging sequence at 9 b-values (0-800 s/mm 2 )., Assessment: IVIM parameters and ADC values of the primary tumor and the VTT were calculated. The VTT consistency (friable vs. solid) was determined through intraoperative findings of two urologists. The accuracy of VTT consistency classification based on the individual IVIM parameters of primary tumors and of VTT, and based on models combining parameters, was assessed. Type of operation, intra-operative blood loss, and operation length were recorded., Statistical Tests: Shapiro-Wilk test; Mann-Whitney U test; Student's t-test; Chi-square test; Receiver operating characteristic (ROC) analysis. Statistical significance level was P < 0.05., Results: Of the enrolled 119 patients, 33 patients (27.7%) had friable VTT. Patients with friable VTT were significantly more likely to experience open surgery, have significantly more intraoperative blood loss, and significantly longer operative duration. The area under the ROC curve (AUC) values of D t of the primary tumor and VTT in classifying VTT consistency were 0.758 (95% CI 0.671-0.832) and 0.712 (95% CI 0.622-0.792), respectively. The AUC value of the model combining D p and D t of VTT was 0.800 (95% CI 0.717-0.868). Furthermore, the AUC of the model combining D p and D t of VTT and D t of the primary tumor was 0.886 (95% CI 0.814-0.937)., Conclusion: IVIM-derived parameters had the potential to predict VTT consistency of RCC., Evidence Level: 3 Technical Efficacy: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Aims: ECG abnormalities are often the first signs of arrhythmogenic right ventricular cardiomyopathy (ARVC) and we hypothesized that an artificial intelligence (AI)-enhanced ECG could help identify patients with ARVC and serve as a valuable disease-detection tool., Methods and Results: We created a convolutional neural network to detect ARVC using a 12-lead ECG. All patients with ARVC who met the 2010 task force criteria and had disease-causative genetic variants were included. All case ECGs were randomly assigned in an 8:1:1 ratio into training, validation, and testing groups. The case ECGs were age- and sex-matched with control ECGs at our institution in a 1:100 ratio. Seventy-seven patients (51% male; mean age 47.2 ± 19.9), including 56 patients with PKP2, 7 with DSG2, 6 with DSC2, 6 with DSP, and 2 with JUP were included. The model was trained using 61 case ECGs and 5009 control ECGs; validated with 7 case ECGs and 678 control ECGs and tested in 22 case ECGs and 1256 control ECGs. The sensitivity, specificity, positive and negative predictive values of the model were 77.3, 62.9, 3.32, and 99.4%, respectively. The area under the curve for rhythm ECG and median beat ECG was 0.75 and 0.76, respectively., Conclusion: Our study found that the model performed well in excluding ARVC and supports the concept that the AI ECG can serve as a biomarker for ARVC if a larger cohort were available for network training. A multicentre study including patients with ARVC from other centres would be the next step in refining, testing, and validating this algorithm., Competing Interests: Conflict of interest: No conflicts of interests related to this algotihm. However, KCS, SJA, ZIA and PAF are co-inventors on AI-ECG algorithms via Mayo Clinic and could benefit from their commercialization., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The spatiotemporal deep convolutional neural network (DCNN) helps reduce echocardiographic readers' erroneous 'judgement calls' on Takotsubo syndrome (TTS). The aim of this study was to improve the interpretability of the spatiotemporal DCNN to discover latent imaging features associated with causative TTS pathophysiology., Methods and Results: We applied gradient-weighted class activation mapping analysis to visualize an established spatiotemporal DCNN based on the echocardiographic videos to differentiate TTS (150 patients) from anterior wall ST-segment elevation myocardial infarction (STEMI, 150 patients). Forty-eight human expert readers interpreted the same echocardiographic videos and prioritized the regions of interest on myocardium for the differentiation. Based on visualization results, we completed optical flow measurement, myocardial strain, and Doppler/tissue Doppler echocardiography studies to investigate regional myocardial temporal dynamics and diastology. While human readers' visualization predominantly focused on the apex of the heart in TTS patients, the DCNN temporal arm's saliency visualization was attentive on the base of the heart, particularly at the atrioventricular (AV) plane. Compared with STEMI patients, TTS patients consistently showed weaker peak longitudinal displacement (in pixels) in the basal inferoseptal (systolic: 2.15 ± 1.41 vs. 3.10 ± 1.66, P < 0.001; diastolic: 2.36 ± 1.71 vs. 2.97 ± 1.69, P = 0.004) and basal anterolateral (systolic: 2.70 ± 1.96 vs. 3.44 ± 2.13, P = 0.003; diastolic: 2.73 ± 1.70 vs. 3.45 ± 2.20, P = 0.002) segments, and worse longitudinal myocardial strain in the basal inferoseptal (-8.5 ± 3.8% vs. -9.9 ± 4.1%, P = 0.013) and basal anterolateral (-8.6 ± 4.2% vs. -10.4 ± 4.1%, P = 0.006) segments. Meanwhile, TTS patients showed worse diastolic mechanics than STEMI patients (E'/septal: 5.1 ± 1.2 cm/s vs. 6.3 ± 1.5 cm/s, P < 0.001; S'/septal: 5.8 ± 1.3 cm/s vs. 6.8 ± 1.4 cm/s, P < 0.001; E'/lateral: 6.0 ± 1.4 cm/s vs. 7.9 ± 1.6 cm/s, P < 0.001; S'/lateral: 6.3 ± 1.4 cm/s vs. 7.3 ± 1.5 cm/s, P < 0.001; E/E': 15.5 ± 5.6 vs. 12.5 ± 3.5, P < 0.001)., Conclusion: The spatiotemporal DCNN saliency visualization helps identify the pattern of myocardial temporal dynamics and navigates the quantification of regional myocardial mechanics. Reduced AV plane displacement in TTS patients likely correlates with impaired diastolic mechanics., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

MicroRNAs (miRNAs) are essential to the tumour growth and metastasis of several cancers. However, the implied functions of miR-211-5p in pancreatic cancer (PC) remains poorly known. In the present study, we discovered that miR-211-5p was a significantly downregulated miRNA in PC tissues compared to adjacent non-tumour tissues. Moreover, we revealed that miR-211-5p overexpression suppressed the proliferation and metastasis of PC cells. Mechanistically, miR-211-5p directly bond to 3'UTR of bone morphogenetic protein-2 (BMP2) and negatively regulated its expression. Rescue experiments showed that the biological function of miR-211-5p was reversed by BMP-2 overexpression in PC cells. Clinical data indicated that BMP2 expression was negatively correlated with miR-211-5p levels in PC patients. Our study provided evidence that miR-211-5p served as a significant suppressor in PC, provided potential targets for prognosis and treatment of patients with PC.

Aims: Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles., Methods and Results: A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85-0.92), a sensitivity of 0.85 (0.78-0.95) and a specificity of 0.76 (0.74-0.79) in the internal validation cohort and an AUC of 0.82 (0.73-0.91), a sensitivity of 0.74 (0.61-0.87) and a specificity of 0.79 (0.77-0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort., Conclusion: A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim: Contrast-enhanced cardiac magnetic resonance (Ce-CMR) and Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) are frequently utilized in clinical practice to assess myocardial viability. However, studies evaluating direct comparison between Ce-CMR and FDG-PET have a smaller sample size, and no clear distinction between the two imaging modalities has been defined. To address this gap, we conducted a meta-analysis of studies comparing Ce-CMR and FDG-PET for the assessment of myocardial viability., Methods: We searched PubMed, EMBASE, Scopus, and Web of Science databases from their inception to 4/20/2022 with search terms "viability" AND "heart diseases" AND "cardiac magnetic resonance imaging" AND "positron-emission tomography." We extracted patient characteristics, segment level viability assessment according to Ce-CMR and FDG-PET, and change in regional wall motion abnormalities (RWMA) at follow-up., Results: We included four studies in the meta-analysis which provided viability assessment with Ce-CMR and FDG-PET in all patients and change in RWMA at follow-up. There were 82 patients among the four included studies, and 585 segments were compared for viability assessment. There were 59 (72%) males, and mean age was 65 years. The sensitivity (95% confidence interval-CI) and specificity (CI) of Ce-CMR for predicting myocardial recovery were 0.88 (0.66-0.96) and 0.64 (0.49-0.77), respectively. The sensitivity (CI) and specificity (CI) of FDG-PET for predicting myocardial recovery were 0.91 (0.63-0.99) and 0.67 (0.49-0.81), respectively., Conclusion: FDG-PET and Ce-CMR have comparable diagnostic parameters in myocardial viability assessment and are consistent with prior research., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Purpose: To evaluate the clinical outcomes of lenvatinib plus PD-1 inhibitors (LP) and regorafenib (R) in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure., Methods: From June 2018 to September 2021, 68 patients from a single center who received lenvatinib combined with PD-1 inhibitors or regorafenib after sorafenib treatment failure were analyzed. The tumor response and survival outcomes were compared between the LP group and R group. Prognostic factors for OS and PFS were determined using Cox proportional hazard regression models., Results: The ORR increased in the LP group (19.5% vs 7.4%, p =0.294), and the DCR was better in the R group (73.2% vs 44.4%, p =0.017). Additionally, median PFS and OS were not significantly different between the LP group and R two groups in survival analysis (PFS: 5.3 months vs 3.0 months, p =0.633; OS: 11.8 months vs 8.0 months, p =0.699). The common adverse events (≥grade 3) were hand-foot skin reactions (13.1%). In multivariate analyses, AFP≥400 ng/mL and ECOG PS 2 were independent risk factors for poor prognosis., Conclusion: The LP group appeared to have a trend of greater tumor response and a higher disease control rate than the R group among patients with sorafenib-resistant HCC, although PFS and OS did not differ significantly between the two groups., Competing Interests: The authors state that there are no potential conflicts of interest in this article., (© 2023 Xu et al.)

Influenza virus, existing many subtypes, causes a huge risk of people health and life. Different subtypes bring a huge challenge for detection and treatment, thus simultaneous detection of multiple influenza virus subtypes plays a key role in fight against this disease. In this work, three kinds of influenza virus subtypes are one-step detection based on microbead-encoded microfluidic chip. HIN1, H3N2 and H7N3 were simultaneously captured only by microbeads of different magnetism and sizes, and they were further treated by magnetic separation and enriched through the magnetism and size-dependent microfluidic structure. Different subtypes of influenza virus could be linearly encoded in different detection zones of microfluidic chip according to microbeads of magnetism and size differences. With the high-brightness quantum dots (QDs) as label, the enriched fluorescence detection signals were further read online from linearly encoded strips, obtaining high sensitivity with detection limit of HIN1, H3N2, H7N3 about 2.2 ng/mL, 3.4 ng/mL and 2.9 ng/mL. Moreover, a visual operation interface, microcontroller unit and two-way syringe pump were consisted of a miniaturized detection device, improving the detection process automation. And this assay showed strong specificity. This method improves a new way of multiple pathogens detection using microbead-encoded technologies in the microfluidic chip., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

At present, the research of business environment is limited to conducting surveys on specific groups or measuring data from official databases. The assessment of the business environment largely depends on public perception. Aiming to explore the public perception of business environment, this paper organically combines the big data text mining and sentiment analysis (SA). The results show that the combination of big data text mining and SA can reflect the theme characteristics, reduce the bias of sentiment and text analysis, and clearly show the public perception of the business environment. The empirical study found that the public perception of business environment depends on not only the four dimensions of business environment, but also the influence of public opinion that cannot be ignored. The public's low recognition of the business environment in Heilongjiang Province mainly includes backward economic development, serious brain drain, low government efficiency, imperfect policies, administrative law enforcement, regional climate and urban construction. In order to solve these problems, it is necessary to improve the high-standard market system to promote economic development, enhance the efficiency of government services, improve government policies, effectively enhance law enforcement, strengthen infrastructure construction and promote cultural innovation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Ethnopharmacological Relevance: Yi Qi Huo Xue Fang (YQHXF) is an effective formula for treating cerebral ischemic stroke (CIS). However, its active ingredients and mechanism of action remain unclear., Aim of the Study: This study aimed to reveal the mechanism of action of YQHXF in the treatment of ischemic stroke based on network pharmacology and experimental validation., Materials and Methods: This study identified the chemical components in YQHXF and the components absorbed by rat serum based on UPLC-Q-TOF/MS technology and used network pharmacology to predict key candidate targets. A protein-protein-interaction (P-P-I) network was constructed using String 11.0 database and Cytoscape, and R software for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Finally, molecular docking combined with animal experiments was used to verify network pharmacology results., Results: This study identified and confirmed 36 chemical components of YQHXF and five chemical ingredients that were absorbed into the blood of rats and screened 66 key candidate targets. All targets in the P-P-I network were mainly related to inflammation and vascular processes. KEGG enrichment results revealed that these 66 key candidate targets were primarily involved in the "AGE-RAGE signaling pathway," "TNF-α signaling pathway, and "T cell receptor signaling pathway." Molecular docking results revealed that Prostaglandin-endoperoxidase synthase 2(PTGS-2), Nitric oxide synthase, endothelial (NOS3), and peroxisome proliferator-activated receptor gamma (PPARG) were more stably bound to their active ingredients. Animal experiments demonstrated that YQHXF promoted M2 polarization, inhibited M1 polarization in microglia, and promoted angiogenesis, which may be related to the PPARG pathway., Conclusion: This study revealed the key active components and effective targets of YQHXF, identified the mechanism of action of YQHXF, laid the foundation for further research on YQHXF, and provided ideas for developing new drugs for CIS., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To evaluate whether venous tumor thrombus (VTT) consistency is a risk factor for the patient's prognosis with renal cell carcinoma (RCC)., Materials and Methods: A total of 190 RCC patients with VTT, who were treated at Department of Urology, Chinese PLA General Hospital, were retrospectively analyzed in this study. The baseline clinical characteristics, postoperative outcomes, and pathological findings were analyzed. Tumor thrombus was classified as solid and friable based on their respective characteristics. Survival curves were estimated using the Kaplan-Meier survival curve analysis, and univariable and multivariable cox proportional hazard regression models were used., Results: Among the total 190 patients included in this study, 145 (76.3%) patients had solid VTT, and 45 (23.7%) patients had friable VTT in their renal veins and inferior vena cava (IVC). There were no significant differences in the age, gender, BMI, symptoms, complex diseases, tumor side, tumor size, TNM stage, Mayo stage, tumor grade, sarcomatous differentiation, pelvic invasion, and sinus fat invasion of patients. Solid VTT consistency was more likely to have a capsule as compared to those with friable VTT (P = 0.007). Kaplan-Meier survival curve analysis demonstrated no statistically significant differences in the overall survival (OS) (P = 0.973) and progression-free survival (PFS) (P = 0.667) of patients. Moreover, VTT consistency was not associated with OS (P = 0.706) of PFS (P = 0.504) in multivariate cox regression analysis., Conclusions: RCC VTT consistency was not a prognostic risk factor for predicting the OS and PFS of patients., (© 2023. Italian Society of Surgery (SIC).)

The loading of homogeneous catalysts with support can dramatically improve their performance in olefin polymerization. However, the challenge lies in the development of supported catalysts with well-defined pore structures and good compatibility to achieve high catalytic activity and product performance. Herein, we report the use of an emergent class of porous material-covalent organic framework material (COF) as a carrier to support metallocene catalyst-Cp 2 ZrCl 2 for ethylene polymerization. The COF-supported catalyst demonstrates a higher catalytic activity of 31.1×10 6  g mol -1  h -1 at 140 °C, compared with 11.2×10 6  g mol -1  h -1 for the homogenous one. The resulting polyethylene (PE) products possess higher weight-average molecular weight (M w ) and narrower molecular weight distribution (Ð) after COF supporting, that is, M w increases from 160 to 308 kDa and Ð drops from 3.3 to 2.2. The melting point (T m ) is also increased by up to 5.2 °C. Moreover, the PE product possesses a characteristic filamentous microstructure and demonstrates an increased tensile strength from 19.0 to 30.7 MPa and elongation at break from 350 to 1400 % after catalyst loading. We believe that the use of COF carriers will facilitate the future development of supported catalysts for highly efficient olefin polymerization and high-performance polyolefins., (© 2023 Wiley-VCH GmbH.)

Objective: To investigate clinical features and outcomes of Chinese patients with Takotsubo syndrome (TTS)., Methods: We established the first Chinese Registry of Takotsubo Syndrome (ChiTTS Registry) and analyzed demographic, clinical, therapeutical, and outcome data to characterize clinical and outcome features of Chinese TTS patients., Results: In 112 enrolled patients in the ChiTTS registry from 02/01/2016 to 12/28/2021, the mean age was 59.4 ± 18.7 years old, and 27.7% were men. A total of 41.1% patients experienced respiratory and circulatory complications during hospitalization, and 17.3% patients developed cardiogenic shock. Physical triggers, dyspnea, tachycardia, and younger age (< 70 years old) predicted in-hospital complications. The MACCE rate during follow up was 13.9% per patient per year and the rate of all-cause death was 12.8% per patient per year. TTS patients with in-hospital complications developed more long-term MACCE (24.6% vs. 6.6% per patient-year, P < 0.001) and higher all-cause mortality (21.9% vs. 6.6% per patient-year, P = 0.001) than those without. The Kaplan-Meier survival analysis showed that more MACCE occurred in TTS patients with tachycardia during 3-year follow-up (HR 4.18; 95% CI 1.80-9.74; log-rank test P < 0.001). Among all medications at discharge, only beta-blocker was associated with reduced long-term MACCE (HR: 0.35; 95% CI: 0.12-0.996; P = 0.049)., Conclusion: We investigated clinical and outcome features of patients in the first Chinese TTS Registry. Tachycardiac TTS patients developed more inpatient and long-term adverse cardiovascular events., Competing Interests: Declaration of Competing Interest All authors of this article declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: Fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) and cardiac magnetic resonance (CMR) are frequently used advanced cardiac imaging to diagnose cardiac sarcoidosis (CS). We conducted a meta-analysis and systematic review to compare diagnostic parameters of FDG-PET and CMR in the diagnosis of cardiac sarcoidosis (CS)., Methods: We searched PubMed, EMBASE, and Scopus databases from their inception to 9/30/2021 with search terms "cardiac sarcoidosis" AND "cardiac magnetic resonance imaging" AND "positronemission tomography". We extracted patient characteristics, results of the FDG-PET and CMR, and adverse outcomes from the included studies. Adverse outcomes served as a reference standard for the evaluation of FDG-PET and CMR., Results: We included 4 studies in the meta-analysis which provided adverse outcomes and all patients underwent FDG-PET and CMR. There were 237 patients, 60.3% male, and ages ranged from 50-53 years. There were 45 events in 237 patients from four studies included in the meta-analyses. The pooled sensitivity (95% confidence interval-CI) and specificity (CI) of CMR in predicting an adverse event were 0.94 (0.79-0.98) and 0.49 (0.40-0.59), respectively. The pooled sensitivity (CI) and specificity (CI) of FDG-PET in predicting an adverse event were 0.51 (0.26-0.75) and 0.60 (0.35-0.81), respectively., Conclusion: CMR was more sensitive but less specific than FDG-PET in predicting adverse events; however, the study population and definition of a positive test need to be considered while interpreting the results., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: In patients with advanced clear cell renal cell carcinoma, despite the undoubted benefits from immune checkpoint inhibitor (ICI)-based therapies over monotherapies of angiogenic/mTOR inhibitors in the intention-to-treat population, approximately a quarter of the patients can scarcely gain advantage from ICIs, prompting the search for predictive biomarkers for patient selection., Methods: Clinical and multi-omic data of 2428 ccRCC patients were obtained from The Cancer Genome Atlas (TCGA, n = 537), JAVELIN Renal 101 (avelumab plus axitinib vs. sunitinib, n = 885), and CheckMate-009/010/025 (nivolumab vs. everolimus, n = 1006)., Results: BAP1 mutations were associated with large progression-free survival (PFS) benefits from ICI-based immunotherapies over sunitinib/everolimus (pooled estimate of interaction HR = 0.71, 95% CI 0.51-0.99, P = 0.045). Using the top 20 BAP1 mutation-associated differentially expressed genes (DEGs) generated from the TCGA cohort, we developed the BAP1-score, negatively correlated with angiogenesis and positively correlated with multiple immune-related signatures concerning immune cell infiltration, antigen presentation, B/T cell receptor, interleukin, programmed death-1, and interferon. A high BAP1-score indicated remarkable PFS benefits from ICI-based immunotherapies over angiogenic/mTOR inhibitors (avelumab plus axitinib vs. sunitinib: HR = 0.55, 95% CI 0.43-0.70, P < 0.001; nivolumab vs. everolimus: HR = 0.72, 95% CI 0.52-1.00, P = 0.045), while these benefits were negligible in the low BAP1-score subgroup (HR = 1.16 and 1.02, respectively)., Conclusion: In advanced ccRCCs, the BAP1-score is a biologically and clinically significant predictor of immune microenvironment and the clinical benefits from ICI-based immunotherapies over angiogenic/mTOR inhibitors, demonstrating its potential utility in optimizing the personalized therapeutic strategies in patients with advanced ccRCC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: To explore the therapeutic efficacy of percutaneous kyphoplasty (PKP) combined with zoledronic acid (ZOL) in postmenopausal women and adult men with osteoporotic vertebral compression fracture (OVCF)., Materials and Methods: A total of 238 patients with OVCF were randomly assigned to the control or ZOL group: 119 patients were treated with only PKP (control group), and 119 were treated with ZOL infusion after PKP (ZOL group). Clinical, radiological and laboratory indices were evaluated at follow-up., Results: The visual analog scale (VAS) score and Oswestry Disability Index (ODI) were significantly higher in both groups post-treatment than at baseline (all p < 0.01). The bone mineral density (BMD) of the proximal femoral neck and height of the injured vertebra were significantly increased after treatment compared with before treatment, and the Cobb angle of the injured vertebra was significantly decreased in both groups (all p < 0.01). However, the bone metabolism indices (type I procollagen amino-terminal peptide (PINP), beta type I collagen carboxy-terminal peptide (β-CTX), and osteocalcin in the N-terminal molecular fragment (NMID)) were significantly lower post-treatment than at baseline in only the ZOL group (all p < 0.01). The VAS score, ODI, BMD, PINP level, β-CTX level, NMID level, vertebral height and Cobb angle of the injured vertebra were significantly higher in the ZOL group than in the control group (all p < 0.01). There were no significant differences in the postoperative bone cement leakage rate between the two groups. At follow-up, new OVCFs were experienced by 16 patients in the control group and 2 patients in the ZOL group (p < 0.01)., Conclusion: The therapeutic efficacy of PKP combined with ZOL for primary OVCF is clinically beneficial and warrants further study., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic stress induces depression- and anxiety-related behaviors, which are common mental disorders accompanied not only by dysfunction of the brain but also of the intestine. Activating transcription factor 4 (ATF4) is a stress-induced gene, and we previously show that it is important for gut functions; however, the contribution of the intestinal ATF4 to stress-related behaviors is not known. Here, we show that chronic stress inhibits the expression of ATF4 in gut epithelial cells. ATF4 overexpression in the colon relieves stress-related behavioral alterations in male mice, as measured by open-field test, elevated plus-maze test, and tail suspension test, whereas intestine-specific ATF4 knockout induces stress-related behavioral alterations in male mice. Furthermore, glutamatergic neurons are inhibited in the paraventricular thalamus (PVT) of two strains of intestinal ATF4-deficient mice, and selective activation of these neurons alleviates stress-related behavioral alterations in intestinal ATF4-deficient mice. The highly expressed gut-secreted peptide trefoil factor 3 (TFF3) is chosen from RNA-Seq data from ATF4 deletion mice and demonstrated decreased in gut epithelial cells, which is directly regulated by ATF4. Injection of TFF3 reverses stress-related behaviors in ATF4 knockout mice, and the beneficial effects of TFF3 are blocked by inhibiting PVT glutamatergic neurons using DREADDs. In summary, this study demonstrates the function of ATF4 in the gut-brain regulation of stress-related behavioral alterations, via TFF3 modulating PVT neural activity. This research provides evidence of gut signals regulating stress-related behavioral alterations and identifies possible drug targets for the treatment of stress-related behavioral disorders.

The cellular and molecular actions of general anesthetics to induce anesthesia state and also cellular signaling changes for subsequent potential "long term" effects remain largely elusive. General anesthetics were reported to act on voltage-gated ion channels and ligand-gated ion channels. Here we used single-cell RNA-sequencing complemented with whole-cell patch clamp and calcium transient techniques to examine the gene transcriptome and ion channels profiling of sevoflurane and propofol, both commonly used clinically, on the human fetal prefrontal cortex (PFC) mixed cell cultures. Both propofol and sevoflurane at clinically relevant dose/concentration promoted "microgliosis" but only sevoflurane decreased microglia transcriptional similarity. Propofol and sevoflurane each extensively but transiently (<2 h) altered transcriptome profiling across microglia, excitatory neurons, interneurons, astrocytes and oligodendrocyte progenitor cells. Utilizing scRNA-seq as a robust and high-through put tool, our work may provide a comprehensive blueprint for future mechanistic studies of general anesthetics in clinically relevant settings., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Background Limited data are available for postpartum hypertension prediction after preeclampsia. Methods and Results We examined the association between maternal serum chemerin levels in patients with preeclampsia and blood pressure (BP) levels after delivery in a prospective birth cohort of 15 041 singleton pregnant women. A total of 310 cases among 322 patients with preeclampsia (follow-up rate, 96.3%) were followed up during a mean 2.8 years after delivery. Compared with matched uncomplicated controls (n=310), serum chemerin measured at ≈35 gestational weeks was significantly increased in preeclampsia (171.8±49.2 versus 140.2±53.5 ng/mL; P <0.01) and positively correlated with the occurrence of postpartum hypertension, defined as either BP ≥130/80 mm Hg (per 1-SD increase: odds ratio [OR], 4.01 [95% CI, 2.77-5.81]) or as BP ≥140/90 mm Hg (per 1-SD increase: OR, 1.70 [95% CI, 1.28-2.25]) in patients with preeclampsia. The addition of chemerin levels improved the predictive performance of the clinical variable-derived prediction models for postpartum hypertension (for BP ≥130/80 mm Hg: area under the curve, 0.903 [95% CI, 0.869-0.937], Δ area under the curve, 0.070, P <0.001; for BP ≥140/90 mm Hg: area under the curve, 0.852 [95% CI, 0.803-0.902], Δ area under the curve, 0.030, P =0.002). The decision curve analysis revealed a net benefit of the chemerin-based prediction model for postpartum BP ≥130/80 mm Hg. Conclusions This study provides the first evidence supporting the independent predictive role of third-trimester maternal chemerin levels for postpartum hypertension after preeclampsia. Future study is warranted for external validation of this finding.

The goal when imaging bioprocesses with optical microscopy is to acquire the most spatiotemporal information with the least invasiveness. Deep neural networks have substantially improved optical microscopy, including image super-resolution and restoration, but still have substantial potential for artifacts. In this study, we developed rationalized deep learning (rDL) for structured illumination microscopy and lattice light sheet microscopy (LLSM) by incorporating prior knowledge of illumination patterns and, thereby, rationally guiding the network to denoise raw images. Here we demonstrate that rDL structured illumination microscopy eliminates spectral bias-induced resolution degradation and reduces model uncertainty by five-fold, improving the super-resolution information by more than ten-fold over other computational approaches. Moreover, rDL applied to LLSM enables self-supervised training by using the spatial or temporal continuity of noisy data itself, yielding results similar to those of supervised methods. We demonstrate the utility of rDL by imaging the rapid kinetics of motile cilia, nucleolar protein condensation during light-sensitive mitosis and long-term interactions between membranous and membrane-less organelles., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The Chemokine-like factor ( CKLF )-like MARVEL transmembrane domain-containing ( CMTM ) family, comprising nine members, is involved in the tumorigenesis and progression of various cancers. However, the expression profiles and clinical significance of CMTM family members in hepatocellular carcinoma (HCC) are not fully clarified. In this study, the RNA-sequencing and clinical data were downloaded from The Cancer Genome Atlas (TCGA) databases. The Kaplan-Meier method and the Cox proportional hazards regression analysis were used to evaluate the prognostic significance of CMTM family members. Single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were employed to explore the relationship between CMTM family genes and the tumor microenvironment in HCC. Finally, the prognostic CMTM family gene expression was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining in clinical HCC tissue specimens. The results indicated that, compared with normal tissues, the expression of CKLF , CMTM1 , CMTM3 , CMTM4 , CMTM7 , and CMTM8 were significantly upregulated in HCC, while the expression of CMTM2 , CMTM5 , and CMTM6 were significantly downregulated in HCC. Univariate and multivariate Cox regression analysis demonstrated that CKLF was an independent prognostic biomarker for the overall survival (OS) of HCC patients. In HCC, the expression of CKLF was found to be correlated with immune cell infiltration, immune-related functions, and immune checkpoint genes. The qRT-PCR and IHC confirmed that CKLF was highly expressed in HCC. Overall, this research suggested that CKLF is involved in immune cell infiltration and may serve as a critical prognostic biomarker, which provides new light on the therapeutics for HCC.

To evaluate the pharmacokinetic effects of SHR3680 on repaglinide and bupropion and its metabolite hydroxybupropion., Methods: A single-centre, open-label, single-arm, fixed-sequence clinical trial in 18 patients with prostate cancer., Results: After a single oral dose of 0.5 mg repaglinide and SHR3680, geometric mean peak plasma concentration (C max ) of plasma repaglinide was 14.240 and 5.887 ng/mL, geometric mean area under the concentration-time curve (AUC 0-t )was 20.577 and 7.320 h ng/mL, geometric mean AUC 0-∞ was 20.949 and 7.451 h ng/mL, mean half-life (t 1/2 ) was 1.629 and 1.195 hours, and geometric mean oral clearance (CL/F) was 23.867 and 67.107 L/h, respectively. After a single oral administration of 150 mg bupropion and SHR3680, geometric mean C max of plasma bupropion was 85.430 and 33.747 ng/mL, geometric mean AUC 0-t was 1003.896 and 380.158 h ng/mL, geometric mean AUC 0-∞ was 1038.054 and 401.387 h ng/mL, mean t 1/2 was 22.533 and 17.733 hours, and geometric mean CL/F was 144.501 and 373.705 L/h, respectively. The plasma geometric mean C max of its main active metabolic hydroxybupropion was 268.113 and 177.318 ng/mL, geometric mean AUC 0-t was 14 283.087 and 5420.219 h ng/mL, geometric mean AUC 0-∞ was 15 218.158 and 5364.625 h ng/mL, mean t 1/2 were 36.069 and 16.688 hours, and geometric mean CL/F was 8.623 L/h and 27.961 L/h, respectively., Conclusion: Coadministration of SHR3680 with repaglinide or bupropion significantly shortened the elimination half-lives, significantly increased the apparent clearance rate, and significantly decreased the in vivo exposure of repaglinide, bupropion and hydroxybupropion compared with single administration of repaglinide or bupropion., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Lysosomal amino acid accumulation is implicated in several diseases, but its role in insulin resistance, the central mechanism to type 2 diabetes and many metabolic diseases, is unclear. In this study, we show the hepatic expression of lysosomal membrane protein solute carrier family 7 member 14 (SLC7A14) is increased in insulin-resistant mice. The promoting effect of SLC7A14 on insulin resistance is demonstrated by loss- and gain-of-function experiments. SLC7A14 is further demonstrated as a transporter resulting in the accumulation of lysosomal γ-aminobutyric acid (GABA), which induces insulin resistance via inhibiting mTOR complex 2 (mTORC2)'s activity. These results establish a causal link between lysosomal amino acids and insulin resistance and suggest that SLC7A14 inhibition may provide a therapeutic strategy in treating insulin resistance-related and GABA-related diseases and may provide insights into the upstream mechanisms for mTORC2, the master regulator in many important processes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to investigate early oncologic outcomes in patients with adrenocortical carcinoma (ACC) with venous invasion (VI) treated using both open and mini-invasive approaches., Patients and Materials: We conducted a retrospective analysis of 4 international referral center databases, including all the patients undergoing adrenalectomy for ACC with VI from January 2007 to March 2020. According to CT scan or MRI, the tumor thrombus was classified into four levels: (1) adrenal vein invasion; (2) renal vein invasion; (3) infra-hepatic Inferior vena cava (IVC); and (4) retro-hepatic IVC. In addition, we divided our patients into patients who had undergone open surgery and mini-invasive surgery., Results: We identified 20 patients with a median follow-up of 12 months. The median tumor size was 110mm. ENSAT stage was II in 4 patients, III in 13 patients, and IV in 3 patients. Tumor thrombus extended in the adrenal vein (n=5), renal vein (n=1), infra-hepatic IVC (n=9), or into the retro-hepatic IVC (n=5). Ten patients were treated with a mini-invasive approach. The patient treated with an open approach reported a more aggressive disease. The two groups did not differ in surgical margins, surgical time, blood losses, complications, and length of stay. The prognosis resulted worse in the patient undergoing open. Kaplan-Meier analysis indicated a difference in OS for the patients stratified by ENSAT stage (Log-rank p=0.011); we also reported a difference in DFS for patients stratified for thrombus extension (p=0.004) and ENSAT stage (p<0.001)., Conclusion: The DFS of patients with VI from ACC is influenced by the staging and the extension of the venous invasion; the staging influences the OS. The mini-invasive approach seems feasible in selected patients; however, further studies investigating the oncological outcomes are needed. A mini-invasive approach for adrenal tumors with venous invasion is an explorable option in very selected patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest., Materials and Methods: Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed., Results: Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up., Conclusions: Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.

Background: As one of the major diagnostic criteria in Musculoskeletal Infection Society, the microbiological diagnosis of periprosthetic joint infection (PJI) performed by analyzing periprosthetic tissue culture is recommended. The goal of this study was to determine if methylene blue (MB) has antibacterial effects that might interfere with microbial culture in vitro., Methods: Eight isolates of reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus pyogenes, and Candida albicans were incubated appropriately on blood agar, China blue agar, or Sabouraud's agar plates at 35 ℃. (Streptococci were cultured in a CO 2 -rich atmosphere.) Each bacterial suspension was formed by 50-fold dilution before the test MB was added. For each strain, bacterial suspension was divided into 3 groups (5 samples each) exposed either MB 0.1%, MB 0.05% or sterile non-bacteriostatic 0.45% saline. The antimicrobial property of MB was determined by measuring the bacterial density on agar plates incubated for 24 h and comparing it with controls unexposed to MB., Results: Exposure to MB 0.1% or MB 0.05% negatively affected microbial viability in vitro. Of the diluted form of MB exposure, reference strains of S. hominis and A. baumannii resulted in fewer colony-forming units compared with the sterile saline control. MB concentration was significantly negatively correlated with CFU counts of S. hominis and A. baumannii strains. The antibacterial property of MB 0.1% or MB 0.05% appears to affect the ability to culture the organism in in vitro assays., Conclusion: MB 0.1% or MB 0.05% has strong antimicrobial activities against some commonly encountered bacterial strains in PJI in vitro. To further evaluate its potential antibacterial usefulness in clinical applications, the next studies are needed to assess the ability of MB to affect the ability to culture the pathogens in vivo, especially in periprosthetic tissue., (© 2022. The Author(s).)

Emerging acoustic bioassembly represents an attractive strategy to build cellular closely-packed organotypic constructs in a tunable manner for biofabrication. However, simultaneously assemble heterogeneous cell types into heterocellular functional units with spatially-defined cell arrangements, such as complementary and sandwich cytoarchitectures, remains a long-lasting challenge. To overcome this challenge, herein we present an acoustic differential bioassembly technique to assemble different cell types at the distinct positions of the acoustic field based on their inherent physical characteristics including cellular size and buoyant density. Specifically, different cell types can be differentially assembled beneath the nodal or the antinode regions of the Faraday wave to form complementary cytoarchitectures, or be selectively positioned at the center or edge area beneath either the nodal or the antinode regions to form sandwich cytoarchitectures. Using this technique, we assemble human induced pluripotent stem cell-derived liver spheroids and endothelial cells into hexagonal cytoarchitectures in vitro to mimic the cord and sinusoid structures in the hepatic lobules. This hepatic lobule model reconstitutes liver metabolic and synthetic functions, such as albumin secretion and urea production. Overall, the acoustic differential bioassembly technique facilitates the construction of human relevant in vitro organotypic models with spatially-defined heterocellular architectures, and can potentially find wide applications in tissue engineering and regenerative medicine., (Creative Commons Attribution license.)

Introduction: Atherosclerosis is the leading cause of cardiovascular disease (CVD), which is one of the most common causes of morbidity and mortality worldwide. Lipid accumulation and inflammation play a crucial role in the pathogenesis of atherosclerosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging lipid-lowering agent reported as a potential anti-inflammation effect in the prevention of CVD. However, the anti-inflammatory effect is still elusive. Therefore, a systematic review and meta-analysis is needed to analyse the anti-inflammatory effect of PCSK9 inhibitors on atherosclerosis in practice., Methods and Analysis: This protocol was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. We will include double-blind, randomised controlled trials that reported changes in the levels of inflammatory markers, with an intervention arm of PCSK9 inhibitors and a treatment duration of more than 2 weeks. The following databases will be mainly searched from 1 January 2003 to the formal search date: PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials. The primary aim is to assess the effect of PCSK9 inhibitors on inflammatory markers, including circulating inflammatory markers such as C-reactive protein, high-sensitivity C-reactive protein, white cell counts, IL-1β, IL-6 and TNF-α and local inflammatory markers such as the most diseased segment target-to-background ratio of the index vessel in adult patients with atherosclerosis. We will assess the quality of evidence, heterogeneity and report bias following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions., Ethics and Dissemination: Due to the systematic review being based on published studies, no ethics approval is required. The study results will be presented at international conferences and published in a peer-reviewed journal., Prospero Registration Number: CRD42022297710., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim is to evaluate the diagnostic value of Activin A levels in serum and pleural fluid on Parapneumonic Pleural Effusion (PPE)., Methods: The authors collected serum and pleural fluid from 86 PPE and 37 Non-PPE (NPPE) patients. Including Activin A, levels of biomarkers such as Lactate Dehydrogenase (LDH), Procalcitonin (PCT), and C-Reactive Protein (CRP) were measured. All factors were calculated for association with days after admission. The diagnostic potential of biomarkers on PPE was considered by Receiver Operating Characteristic (ROC) curve analysis., Results: Levels of Activin A in serum and pleural fluid of PPE patients were significantly higher than those of the NPPE patients. Moreover, concentrations of Activin A in pleural fluid showed a more obvious relevant days after admission. ROC curve analysis found that Activin A in pleural fluid had AUCs of 0.899 with 93% sensitivity and 84% specificity for PPE diagnosis., Conclusion: Activin A in pleural fluid correlated with disease severity could act to diagnose PPE., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)