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Background and Objective: Concern has been expressed over the cardiovascular risks associated with rosiglitazone and pioglitazone. This study investigates the association between oral antihyperglycaemics (rosiglitazone, pioglitazone, sulfonylureas and metformin) with myocardial infarction, congestive heart failure, angina pectoris, stroke and transient ischaemic attack.Methods: We used Taiwan's 2000-5 National Health Insurance database to conduct a population-based, retrospective cohort study of 473 483 newly diagnosed patients with type 2 diabetes mellitus. We classified study patients into five basic groups based on the agents they were prescribed during the study period: (i) rosiglitazone monotherapy; (ii) pioglitazone monotherapy; (iii) sulfonylurea-based therapy; (iv) metformin-based therapy; and (v) sulfonylurea and metformin-based therapy. Cox proportional hazards models were used to evaluate the association between the use of rosiglitazone or pioglitazone and the occurrence of cardiovascular events.Results: Patients receiving rosiglitazone monotherapy were at higher risk for any cardiovascular event (hazard ratio [HR] 1.89; 95% CI 1.57, 2.28), myocardial infarction (HR 2.09; 95% CI 1.36, 3.24), angina pectoris (HR 1.79; 95% CI 1.39, 2.30) and transient ischaemic attack (HR 2.57; 95% CI 1.33, 4.96) than those receiving metformin monotherapy. Overall, add-on rosiglitazone and pioglitazone were associated with comparable cardiovascular risk. Based on our point estimates, pioglitazone as an add-on therapy was found to have a favourable, but nonsignificant, effect on outcome.Conclusions: Our findings extend the evidence from current literature to a real-world setting and support data from clinical trials that the disadvantages or harm caused by thiazolidinediones, especially rosiglitazone, may outweigh their benefits in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

An artificial intelligence (AI)-enabled electrocardiogram (ECG) model has been developed in a healthy adult population to predict ECG biological age (ECG-BA). This ECG-BA exhibited a robust correlation with chronological age (CA) in healthy adults and additionally significantly enhanced the prediction of aging-related diseases' onset in adults with subclinical diseases. The model showed particularly strong predictive power for cardiovascular and non-cardiovascular diseases such as stroke, coronary artery disease, peripheral arterial occlusive disease, myocardial infarction, Alzheimer's disease, osteoarthritis, and cancers. When combined with CA, ECG-BA improved diagnostic accuracy and risk classification by 21% over using CA alone, notably offering the greatest improvements in cancer prediction. The net reclassification improvement significantly reduced misclassification rates for disease onset predictions. This comprehensive study validates ECG-BA as an effective supplement to CA, advancing the precision of risk assessments for aging-related conditions and suggesting broad implications for enhancing preventive healthcare strategies, potentially leading to better patient outcomes., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Ethnopharmacological Relevance: The current treatment for diabetic nephropathy (DN) is inadequate, and there is an urgent need for an effective and minimally adverse alternative therapy. Da-Chai-Hu Decoction (DCHD) is a time-honored herbal remedy from Chinese medicine, boasting a legacy spanning more than 1800 years. Clinical observations suggest that it may provide therapeutic benefits for individuals with type 2 diabetes mellitus (T2DM). Nonetheless, the specific advantages of DCHD in relation to DN and the mechanisms through which it operates are still not well understood., Aim of the Study: This research aims to investigate whether DCHD can avert renal damage in mice with T2DM and to elucidate the mechanisms by which DCHD combats DN through the integration of metabolomics and network pharmacology., Materials and Methods: The beneficial effects of DCHD on DN was initially evaluated using a renal injury model in T2DM mice. Subsequently, untargeted metabolomics analysis was utilized to investigate the potential mechanisms of DCHD against DN. Additionally, UPLC-HR MS/MS was employed to identify the chemical components in DCHD and the absorption components in DCHD-treated plasma. Network pharmacology and our newly proposed function-guided and network-based complementary methodology (FNICM) was utilized to predict the potential pathway of DCHD intervention in DN. Finally, the core pathway was validated through Western blotting analysis and ELISA., Results: A total of 260 chemical components were detected in DCHD, and 41 absorption components were found in DCHD-treated plasma by UPLC-HR MS/MS for the first time. Additionally, In vivo experiments revealed that DCHD exerts the ability to regulate the disorder in glucose/lipid metabolism and improves kidney dysfunction. Furthermore, a comprehensive analysis utilizing non-targeted urine metabolomics and the FNICM method identified a total of 33 differential metabolites, which were categorized as core metabolites. Lastly, combined FNICM, network pharmacology and experimental pharmacology studies suggest that DCHD may regulate the AGEs/RAGE/AKT pathways in combating DN., Conclusions: The results indicate that DCHD treats DN through the inhibition of the AGEs/RAGE/AKT pathway and by regulating metabolic profiles., 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.)

Radical-initiated functionalization of bicyclo[1.1.0]butanes (BCBs) is a straightforward approach to accessing diverse cyclobutane derivatives. However, selective C(sp 3 )-H functionalization at the C2 position of BCBs remains scarce. Herein, a mild protocol for the hydrogen-evolution of C2 C(sp 3 )-H phosphorylation with BCBs enabled by photoinduced cobaloxime catalysis was realized in a regio- and diastereoselective manner. This oxidant- and additional photocatalyst-free method enabled C(sp 3 )-H phosphorylation with a wide range of BCBs and diarylphosphine oxides. The mechanism was studied via control experiments and DFT calculation. Moreover, the efficiency of this approach was highlighted in the synthesis of high-value, structurally complex molecules.

With contemporary anesthetic drugs, the efficacy of general anesthesia is assured. Health-economic and clinical objectives are related to reductions in the variability in dosing, variability in recovery, etc. Consequently, meta-analyses for anesthesiology research would benefit from quantification of ratios of standard deviations of log-normally distributed variables (e.g., surgical duration). Generalized confidence intervals can be used, once sample means and standard deviations in the raw, time, scale, for each study and group have been used to estimate the mean and standard deviation of the logarithms of the times (i.e., "log-scale"). We examine the matching of the first two moments versus also using higher-order terms, following Higgins et al. 2008 and Friedrich et al. 2012. Monte Carlo simulations revealed that using the first two moments 95% confidence intervals had coverage 92%-95%, with small bias. Use of higher-order moments worsened confidence interval coverage for the log ratios, especially for coefficients of variation in the time scale of 50% and for larger n = 50 $$ \left(n=50\right) $$ sample sizes per group, resulting in 88% coverage. We recommend that for calculating confidence intervals for ratios of standard deviations based on generalized pivotal quantities and log-normal distributions, when relying on transformation of sample statistics from time to log scale, use the first two moments, not the higher order terms., (© 2025 The Author(s). Pharmaceutical Statistics published by John Wiley & Sons Ltd.)

Background: Undetected atrial fibrillation (AF) poses a significant risk of stroke and cardiovascular mortality. However, diagnosing AF in real-time can be challenging as the arrhythmia is often not captured instantly. To address this issue, a deep-learning model was developed to diagnose AF even during periods of arrhythmia-free windows., Methods: The proposed method introduces a novel approach that integrates clinical data and electrocardiograms (ECGs) using a colorization technique. This technique recolors ECG images based on patients' demographic information while preserving their original characteristics and incorporating color correlations from statistical data features. Our primary objective is to enhance atrial fibrillation (AF) detection by fusing ECG images with demographic data for colorization. To ensure the reliability of our dataset for training, validation, and testing, we rigorously maintained separation to prevent cross-contamination among these sets. We designed a Dual-input Mixed Neural Network (DMNN) that effectively handles different types of inputs, including demographic and image data, leveraging their mixed characteristics to optimize prediction performance. Unlike previous approaches, this method introduces demographic data through color transformation within ECG images, enriching the diversity of features for improved learning outcomes., Results: The proposed approach yielded promising results on the independent test set, achieving an impressive AUC of 83.4%. This outperformed the AUC of 75.8% obtained when using only the original signal values as input for the CNN. The evaluation of performance improvement revealed significant enhancements, including a 7.6% increase in AUC, an 11.3% boost in accuracy, a 9.4% improvement in sensitivity, an 11.6% enhancement in specificity, and a substantial 25.1% increase in the F1 score. Notably, AI diagnosis of AF was associated with future cardiovascular mortality. For clinical application, over a median follow-up of 71.6 ± 29.1 months, high-risk AI-predicted AF patients exhibited significantly higher cardiovascular mortality (AF vs. non-AF; 47 [18.7%] vs. 34 [4.8%]) and all-cause mortality (176 [52.9%] vs. 216 [26.3%]) compared to non-AF patients. In the low-risk group, AI-predicted AF patients showed slightly elevated cardiovascular (7 [0.7%] vs. 1 [0.3%]) and all-cause mortality (103 [9.0%] vs. 26 [6.4%]) than AI-predicted non-AF patients during six-year follow-up. These findings underscore the potential clinical utility of the AI model in predicting AF-related outcomes., Conclusions: This study introduces an ECG colorization approach to enhance atrial fibrillation (AF) detection using deep learning and demographic data, improving performance compared to ECG-only methods. This method is effective in identifying high-risk and low-risk populations, providing valuable features for future AF research and clinical applications, as well as benefiting ECG-based classification studies., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board (2017–10-009BC) at Taipei Veterans General Hospital, Taipei, Taiwan. All methods were carried out following the regulations of the Institutional Review Board. The Internal Review Board of Taipei Veterans General Hospital granted an exemption from the need to secure informed consent due to the thorough de-identification of patient data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Pancreatic development is a complex process vital for maintaining metabolic balance, requiring intricate interactions among different cell types and signaling pathways. Fibroblast growth factor receptors 2b (FGFR2b)-ligands signaling from adjacent mesenchymal cells is crucial in initiating pancreatic development and differentiating exocrine and endocrine cells through a paracrine mechanism. However, the precise critical time window that affects pancreatic development remains unclear. To explore the roles of FGFR2b-ligands and identify the narrow window of time during which FGFR2b-ligand signaling affects pancreatic development, we used an inducible mouse model to control the expression of soluble dominant-negative FGFR2b (sFGFR2b) at various stages of pancreatic development. Our findings revealed a significant effect of FGFR2b-ligand signaling on epithelial morphology, lumen formation, and pancreatic branching during primary and secondary transition stages. Additionally, sFGFR2b expression reduced the number of Pdx1+ progenitor cells and altered the pancreatic islet structure. Furthermore, we examined the effect of mutation in FGF10, an FGFR2b ligand, on embryonic pancreatic β-cell function. FGF10 null mutant embryos exhibited reduced pancreatic size and a decrease number of islet-like structure. Although neonatal mice with haploinsufficiency for FGF10 exhibited abnormal glucose tolerance test results, indicating a potential diabetes predisposition, these abnormalities normalized with age, aligning with observations in wild type mice. Our study underscores the critical role of FGFR2b-ligand signaling in pancreatic development and postnatal islet function, offering insights into potential therapeutic targets for pancreatic disorders., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: All animal studies were performed at the Animal Institute of Wenzhou University according to the protocols approved by the Laboratory Animal Ethics Committee of Wenzhou University and Laboratory Animal Centre of Wenzhou University (approval no.WZU-013). The study adhered to the ethical guidelines and regulations for the care and use of laboratory animals, ensuring that all procedures minimized pain and distress to the animals. Consent to participate: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: Diabetic cognitive impairment (DCI), considered one of the most severe and commonly overlooked complications of diabetes, has shown inconsistent findings regarding the metabolic profiles in DCI patients. This systematic review and meta-analysis aimed to identify dysregulated metabolites as potential biomarkers for early DCI, providing valuable insights into the underlying pathophysiological mechanisms., Materials and Methods: A systematic search of four databases, namely PubMed, Embase, Web of Science and Cochrane, was conducted up to March 2024. Subsequently, a qualitative review of clinical studies was performed followed by a meta-analysis of metabolite markers. Finally, the sources of heterogeneity were explored through subgroup and sensitivity analyses., Results: A total of 774 unique publications involving 4357 participants and the identification of multiple metabolites were retrieved. Of these, 13 clinical studies reported metabolite differences between the DCI and control groups. Meta-analysis was conducted for six brain metabolites and two metabolite ratios. The results revealed a significant increase in myo-inositol (MI) concentration and decreases in glutamate (Glu), Glx (glutamate and glutamine) and N-acetylaspartate/creatine (NAA/Cr) ratios in DCI, which have been identified as the most sensitive metabolic biomarkers for evaluating DCI progression. Notably, brain metabolic changes associated with cognitive impairment are more pronounced in type 2 diabetes mellitus than in type 1 diabetes mellitus, and the hippocampus emerged as the most sensitive brain region regarding metabolic changes associated with DCI., Conclusions: Our results suggest that MI, Glu, and Glx concentrations and NAA/Cr ratios within the hippocampus may serve as metabolic biomarkers for patients with early-stage DCI., (© 2024 John Wiley & Sons Ltd.)

Functional capacity is an important objective health metric, and relies on the maintenance of physiological homeostasis. Autonomic nervous system is known to coordinates the maintenance of multi-organ homeostasis. The objective of this study was to examine the association of autonomic nervous system function with functional capacity in adults aged 55 years and older. A cohort of 542 adults (mean age of 70.1 years) received repeated measurements of heart rate variability, an autonomic nervous system function marker, and chair rise time, a functional capacity measure. Linear mixed models analysis showed that 1 SD lower powers in low-frequency range at baseline was associated with a 0.11 (95% CI 0.01-0.21) s/year faster increase in chair rise time during the follow-up, whereas 1 SD increase in powers in high-frequency range and 1 SD decrease in the ratio of powers in low-frequency range to powers in high-frequency range during the follow-up were associated with a 0.22 (95% CI 0.06-0.39) s and 0.17 (95% CI 0.01-0.33) s increase in chair rise time. In conclusion, autonomic nervous system function and its changes were longitudinally associated with changes in functional capacity in older adults., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We report a case of unilateral serous choroidal effusion in a patient without prior glaucoma surgeries that developed within 1 week of starting topical dorzolamide. A Caucasian female in her 60s with a history of severe primary open-angle glaucoma in the left eye without prior glaucoma surgeries developed irritation and subsequently blurry vision in her left eye within 1 week of starting topical dorzolamide 2% in the left eye only. Funduscopic exam and B-scan ultrasound demonstrated a serous choroidal effusion in the nasal and temporal periphery. After discontinuing dorzolamide and initiating prednisolone and cycloplegic agents, the choroidal effusions fully resolved after 2 weeks, and vision returned to baseline. Choroidal effusion can occur as a result of an idiosyncratic reaction to topical dorzolamide even in patients without prior glaucoma surgeries. Immediate cessation of dorzolamide and treatment with steroid and cycloplegic agents result in good vision recovery for dorzolamide-induced choroidal effusion., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Postoperative delirium may be mediated by perioperative systemic- and neuro-inflammation. By inhibiting the pro-inflammatory actions of plasmin, tranexamic acid (TXA) may decrease postoperative delirium. To explore this hypothesis, we modified an ongoing randomised trial of TXA, adding measures of postoperative delirium, cognitive function, systemic cytokines, and astrocyte activation., Methods: Adults undergoing elective posterior lumbar fusion randomly received intraoperative intravenous TXA (n=43: 10 mg kg -1 loading dose, 2 mg kg -1 h -1 infusion) or Placebo (n=40). Blood was collected pre- and at 24 h post-operatively (n=32) for biomarkers of systemic inflammation (cytokines) and astrocyte activation (S100B). Participants had twice daily delirium assessments using the 3-minute diagnostic interview for Confusion Assessment Method (n=65). Participants underwent 4 measures of cognitive function preoperatively and during post-discharge follow-up., Results: Delirium incidence in the TXA group (7/32=22%) was not significantly less than in the Placebo group (11/33=33%); P =0.408, absolute difference=11%, relative difference=33%, effect size = -0.258 (95% CI -0.744 to 0.229). In the Placebo group (n=16), delirium severity was associated with the number of instrumented vertebral levels ( P =0.001) and with postoperative interleukin -8 and -10 concentrations ( P =0.00008 and P =0.005, respectively) and these associations were not significantly modified by TXA. In the Placebo group, delirium severity was associated with S100B concentration ( P =0.0009) and the strength of the association was decreased by TXA ( P =0.002)., Conclusions: A potential 33% relative decrease in postoperative delirium incidence justifies an adequately powered clinical trial to determine if intraoperative TXA decreases delirium in adults undergoing lumbar fusion., Competing Interests: Declaration of interests The authors declare that they have no conflict of interest.

Background: Cancer patients' vulnerability to QT prolongation contradicts certain anti-cancer drug usage. Until now, the QT prolongation's impact on CV mortality in cancer patients remains unclear, potentially biasing therapeutic decisions., Methods: This retrospective observational cohort included adult cancer patients with an electrocardiogram (ECG) performed in a tertiary hospital in Taiwan. The first performed ECGs after cancer diagnosis (n = 59,568) were analyzed. The corrected QT intervals by Bazett (QTcB), Fridericia (QTcFri), and Framingham (QTcFra) formulae were used to predict the 90-day and one-year CV mortality according to the Taiwan death registry., Results: The AUC of QTcB (90 days: 0.70, 1 year: 0.68) for predicting CV mortality was better than QTcFri and QTcFra (90 days: 0.63 and 0.50, 1 year: 0.65 and 0.56). Using the restricted cubic spline regression model adjusted by age and comorbidities, QTcB increased a significant but trivial risk of CV mortality at 90 days (hazard ratio, 1.007, P = 0.02) and one year (1.006, P < 0.01). Compared to those with QTcB < 500ms, the patients with QTcB ≥ 500ms were older and had more comorbidities and mortalities within one year. The incidence of sudden death and ventricular arrhythmias was only 0.2%. After adjusting for comorbidities, QTcB was neither associated with 90-day nor one-year CV mortality. In the patients already with QTcB ≥ 500ms, the patients receiving the unexpected uses of QT-prolonging drugs were not associated with higher one-year CV mortality than those without (P = 0.14)., Conclusions: Rather than a prolonged QT interval per se, comorbidities contributed to CV mortality and irreversible outcomes in cancer patients., (© 2024. The Author(s).)

Introduction: Colorectal cancer leads to peritoneal metastasis in 8-15 % of cases and necessitates treatments, such as hyperthermic intraperitoneal chemotherapy (HIPEC). However, HIPEC may result in perioperative complications, some often overlooked, such as abdominal compartment syndrome., Case Presentation: A 52-year-old female with colorectal cancer and peritoneal metastasis underwent debulking surgery followed by HIPEC. During HIPEC, a sudden increase in airway pressure and severe hypotension were noted. Pneumothorax with abdominal compartment syndrome (ACS) was suspected and HIPEC was terminated. Despite intravenous fluids and vasopressors, she experienced circulatory and respiratory collapse. Laparotomy sutures were promptly removed, which effectively alleviated the intra-abdominal hypertension and immediately restored the vital signs. An inadequately repaired diaphragm defect was identified and repaired. A chest tube was inserted for pleural effusion., Discussion: ACS is characterized by an increase in abdominal cavity pressure above 20 mmHg, leading to end-organ damage. It can mimic physiological effects of HIPEC and result in adverse outcomes. Early detection of ACS is essential, especially when complicated by pneumothorax from diaphragmatic tumor dissection. The closed technique for HIPEC, while efficient, can increase the risk of ACS and requires careful management., Conclusions: This case underscores the complexity of HIPEC and the importance of promptly identifying and managing ACS during the procedure. Monitoring intra-abdominal pressure during HIPEC is essential. Thoroughly check for iatrogenic injuries, including the diaphragm, is crucial before starting before HIPEC., Competing Interests: Conflict of interest statement None declared., (Copyright © 2024. Published by Elsevier Ltd.)

Type 2 diabetes mellitus (T2DM) is a prevalent health challenge faced by countries worldwide. In this study, we propose a novel large language multimodal models (LLMMs) framework incorporating multimodal data from clinical notes and laboratory results for diabetes risk prediction. We collected five years of electronic health records (EHRs) dating from 2017 to 2021 from a Taiwan hospital database. This dataset included 1,420,596 clinical notes, 387,392 laboratory results, and more than 1505 laboratory test items. Our method combined a text embedding encoder and multi-head attention layer to learn laboratory values, and utilized a deep neural network (DNN) module to merge blood features with chronic disease semantics into a latent space. In our experiments, we observed that integrating clinical notes with predictions based on textual laboratory values significantly enhanced the predictive capability of the unimodal model in the early detection of T2DM. Moreover, we achieved an area greater than 0.70 under the receiver operating characteristic curve (AUC) for new-onset T2DM prediction, demonstrating the effectiveness of leveraging textual laboratory data for training and inference in LLMs and improving the accuracy of new-onset diabetes prediction., (© 2024. The Author(s).)

Diabetic peripheral neuropathy (DPN) is a significant and frequent complication of diabetes. Bu-Yang-Huan-Wu Decoction (BHD) is a classic traditional Chinese herbal prescription that is commonly used in modern clinical practice for the effective treatment of DPN, but the underlying mechanism is not yet clearly defined. The chemical constituents of BHD were characterized by UPLC-Q-Orbitrap HR MS/MS, and a total of 101 chemical components were identified, including 30 components absorbed into blood. An interaction network of "compound-target-disease" interactions was constructed based on the compounds detected absorbed in blood and their corresponding targets of diabetic neuropathy acquired from disease gene databases, and the possible biological targets and potential signalling pathways of BHD were predicted via network pharmacology analysis. Subsequently, methylglyoxal-induced (MGO-induced) Schwann cells (SCs) were used to identify the active ingredients in blood components of BHD and verify the molecular mechanisms of BHD. Through network topological analysis, 30 shared targets strongly implicated in the anti-DPN effects of BHD were identifed. Combined network pharmacology and in vitro cellular analysis, we found that the active ingredient of BHD may treat DPN by modulating the AGEs/RAGE pathway. This study provides valuable evidence for future mechanistic studies and potential therapeutic applications for patients with DPN., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Objectives: Thin endometrium (TE) compromises endometrial receptivity, often leading to implantation failure and lower clinical pregnancy rates. As autologous platelet-rich plasma (PRP) emerges as a potential remedy, the present study focused on its therapeutic effects on TE in infertile women who underwent frozen embryo transfer., Study Design: Patients with TE who underwent frozen embryo transfer treatment in our hospital were included. To diminish individual variability, a self-controlled series approach was used. Two menstrual study cycles were arranged for each participant before the actual embryo transfer cycle; PRP treatment was conducted in the second cycle. Key metrics analyzed included endometrial thickness and the expression of specific endometrial biomarkers including HOXA-10, Ki67, and αvβ3 integrin. Transvaginal ultrasound was employed to measure endometrial thickness on Days 11 and 14, and an endometrial biopsy was conducted on progesterone Day 5 of the first two cycles. Pregnancy outcomes were observed after the embryo transfer cycle., Results: PRP treatment significantly increased the median endometrial thickness, from 5.8 mm to 6.5 mm (P = 0.0066). Additionally, PRP treatment resulted in a statistically significant increase in the H-score for all endometrial markers. Importantly, during the subsequent embryo transfer cycle with PRP treatment, two patients successfully achieved pregnancies, both culminating in live births., Conclusions: These findings emphasize the potential of PRP in improving endometrial conditions, especially for individuals grappling with thin endometrium issues, as underscored by this self-comparison methodology., 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: To investigate (1) lateral atlantoaxial articulation (LAA) morphology in patients with basilar invagination (BI) with atlantoaxial dislocation (AAD) and healthy individuals and its relationship with the severity of dislocation and (2) the effect of the LAA morphology on reduction degree (RD) after surgery., Methods: In this retrospective propensity score matching case-control study, imaging and baseline data of 62 patients with BI and AAD from 2011 to 2022 were collected. Six hundred thirteen  participants without occipitocervical junctional deformity served as controls. Logistic regression and receiver operating characteristic (ROC) curve were used for analysis., Results: The age, BMI and sex did not differ significantly between the two groups after propensity score matching. Sagittal slope angle (SSA) and coronal slope angle (CSA) was lower and greater, respectively, in the patient group than in the control group. A negative SSA value usually indicates anteverted LAA. Regression analysis revealed a significant negative correlation between SSA and severity of dislocation. However, no relationship was found between CSA and the severity of dislocation. The multivariate logistic regression analysis revealed that minimum-SSA emerged as an independent predictor of satisfactory reduction (RD ≥ 90%). The ROC curve demonstrated an area under the curve of 0.844, with a cut-off value set at -40.2., Conclusion: SSA in patients group was significantly smaller and more asymmetric than that in the control group. Dislocation severity was related to SSA but not to CSA. Minimum-SSA can be used as a predictor of horizontal RD after surgery., (© 2024. The Author(s).)

Abstract: This study aims to explore the value of real-time strain elastography (RTE) and contrast-enhanced ultrasonography (CEUS) in the diagnosis of breast BI-RADS 4 lesions. It collected 85 cases (totaling 85 lesions) diagnosed with breast BI-RADS 4 through routine ultrasound from October 2020 to December 2022 in Huangshan City People's Hospital. All lesions underwent RTE and CEUS examination before surgery, and the ImageJ software was used to measure the periphery of lesion images in the enhancement peak mode and grayscale mode to calculate the contrast-enhanced ultrasound area ratio. The diagnostic capabilities of single-modal and multimodal ultrasound examination for the malignancy of breast BI-RADS 4 lesions were compared using the receiver operating characteristic curve; the Spearman correlation analysis was adopted to evaluate the correlation between multimodal ultrasound and CEUS area ratio. As a result, among the 85 lesions, 51 were benign, and 34 were malignant. The areas under the curve (AUCs) of routine ultrasound (US), US + RTE, US + CEUS, and US + RTE + CEUS were 0.816, 0.928, 0.953, and 0.967, respectively, with the combined method showing a higher AUC than the single application. The AUC of the CEUS area ratio diagnosing breast lesions was 0.888. There was a strong positive correlation (r = 0.819, P < 0.001) between the diagnostic performance of US + RTE + CEUS and the CEUS area ratio. In conclusion, based on routine ultrasound, the combination of RTE and CEUS can further improve the differential diagnosis of benign and malignant lesions in breast BI-RADS 4., Competing Interests: Competing interests: All of the authors had no any personal, financial, commercial, or academic conflicts of interest separately., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In tuberculosis (TB), chest radiography (CXR) patterns are highly variable, mimicking pneumonia and many other diseases. This study aims to evaluate the efficacy of Google teachable machine, a deep neural network-based image classification tool, to develop algorithm for predicting TB probability of CXRs. The training dataset included 348 TB CXRs and 3806 normal CXRs for training TB detection. We also collected 1150 abnormal CXRs and 627 normal CXRs for training abnormality detection. For external validation, we collected 250 CXRs from our hospital. We also compared the accuracy of the algorithm to five pulmonologists and radiological reports. In external validation, the AI algorithm showed areas under the curve (AUC) of 0.951 and 0.975 in validation dataset 1 and 2. The accuracy of the pulmonologists on validation dataset 2 showed AUC range of 0.936-0.995. When abnormal CXRs other than TB were added, AUC decreased in both human readers (0.843-0.888) and AI algorithm (0.828). When combine human readers with AI algorithm, the AUC further increased to 0.862-0.885. The TB CXR AI algorithm developed by using Google teachable machine in this study is effective, with the accuracy close to experienced clinical physicians, and may be helpful for detecting tuberculosis by CXR., (© 2024. The Author(s).)

Modern anesthetic drugs ensure the efficacy of general anesthesia. Goals include reducing variability in surgical, tracheal extubation, post-anesthesia care unit, or intraoperative response recovery times. Generalized confidence intervals based on the log-normal distribution compare variability between groups, specifically ratios of standard deviations. The alternative statistical approaches, performing robust variance comparison tests, give P-values, not point estimates nor confidence intervals for the ratios of the standard deviations. We performed Monte-Carlo simulations to learn what happens to confidence intervals for ratios of standard deviations of anesthesia-associated times when analyses are based on the log-normal, but the true distributions are Weibull. We used simulation conditions comparable to meta-analyses of most randomized trials in anesthesia, n ≈ 25 and coefficients of variation ≈ 0.30 . The estimates of the ratios of standard deviations were positively biased, but slightly, the ratios being 0.11% to 0.33% greater than nominal. In contrast, the 95% confidence intervals were very wide (i.e., > 95% of P ≥ 0.05). Although substantive inferentially, the differences in the confidence limits were small from a clinical or managerial perspective, with a maximum absolute difference in ratios of 0.016. Thus, P < 0.05 is reliable, but investigators should plan for Type II errors at greater than nominal rates., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Treatment options for pregnant women with immune thrombocytopenia (ITP) who do not respond to first-line treatment are limited. Few studies have reported the use of recombinant human thrombopoietin (rhTPO) for this subset of patients., Aims: To investigate the efficacy and safety of rhTPO in ITP during pregnancy and determine obstetric outcomes and predictors of treatment response., Methods: From July 2013 to October 2022, the data of 81 pregnant women with ITP and a platelet count < 30 × 10 9 /L who did not respond to steroids and/or intravenous immunoglobulin were retrospectively analysed. Of these patients, 33 received rhTPO treatment (rhTPO group) while 48 did not (control group). Baseline characteristics, haematological disease outcomes before delivery, obstetric outcomes, and adverse events were compared between groups. In the rhTPO group, a generalised estimating equation (GEE) was used to investigate the factors influencing the response to rhTPO treatment., Results: The baseline characteristics were comparable between both groups (P > 0.05, both). Compared with controls, rhTPO patients had higher platelet counts (median [interquartile range]: 42 [21.5-67.5] vs. 25 [19-29] × 10 9 /L, P = 0.002), lower bleeding rate (6.1% vs. 25%, P = 0.027), and lower platelet transfusion rate before delivery (57.6% vs. 97.9%, P < 0.001). Gestational weeks of delivery (37.6 [37-38.4] vs 37.1 [37-37.2] weeks, P = 0.001) were longer in the rhTPO group than in the control group. The rates of caesarean section, postpartum haemorrhage, foetal or neonatal complications, and complication types in both groups were similar (all P > 0.05). No liver or renal function impairment or thrombosis cases were observed in the rhTPO group. GEE analysis revealed that the baseline mean platelet volume (MPV) (odds ratio [OR]: 0.522, P = 0.002) and platelet-to-lymphocyte ratio (PLR) (OR: 1.214, P = 0.025) were predictors of response to rhTPO treatment., Conclusion: rhTPO may be an effective and safe treatment option for pregnancies with ITP that do not respond to first-line treatment; it may have slightly prolonged the gestational age of delivery. Patients with a low baseline MPV and high baseline PLR may be more responsive to rhTPO treatment. The present study serves as a foundation for future research., (© 2023. The Author(s).)

Objective: We investigated the correlation between glycemic control status and depressive symptoms in type 2 diabetes elderly., Methods: A total of 1527 participants with type 2 diabetes aged 55 years and older from the Healthy Aging Longitudinal Study in Taiwan study were included in this cross-sectional study. The Center for Epidemiologic Studies Depression Scale (CESD) (20 items) score of ≥16 was indicative of depressive symptoms. The participants were divided into HbA1c ≥ 6.5% and < 6.5% representing the glycemic control. Multiple logistic regression (MLR) and Generalized linear model (GLM) were used., Results: The MLR analysis showed that the low HbA1c group had significant two-fold increased odds of depressive symptoms compared to the high HbA1c group (OR 1.89, 95% CI 1.17-3.05). The risk of depressive symptoms was lower among males (OR 0.49, 95% CI 0.30-0.80) and those with higher BMI (OR 0.93, 95% CI 0.86-1.00); whereas the risk was higher among those who lived alone (OR 2.37, 95% CI 1.31-4.27) and with ADL disability (OR 3.01, 95% CI 1.85-4.89). The GLM showed that the dimension of depressive affect reached statistical significance with lower HbA1c., Conclusion: This nationwide community-based study shows that depressive symptoms are associated with lower HbA1C, reminding us that more attention should be paid to the presence of depressive symptoms in those with lower HbA1C. Further research is needed to clarify the causal relationship., Competing Interests: Declaration of Competing Interest None of the authors reported a conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The COVID-19 pandemic has had an enormous impact on society and the medical environment in Taiwan in 2022. As pregnant women with COVID-19 are at higher risk for multiple complications, Taiwan needs a COVID-19 specialized maternity unit to improve the quality of maternal and neonatal care., Materials and Methods: We share our experience with specialized maternity unit for pregnant women with COVID-19 at the National Cheng Kung University Hospital, where we can have careful evaluation, safe birth, and comprehensive postpartum care., Results: Our COVID-19 specialized maternity unit enrolled 253 pregnant women with COVID-19, 90 (35.6%) pregnant women were admitted to the specialized maternity unit, and 71 (28.1%) pregnant women gave birth during hospitalization in two months. All pregnant women recovery well and real-time polymerase chain reaction tests on all infants were negative for COVID-19., Conclusion: A specialized maternity unit can provide pregnant women with a safe birth environment, immediate maternity care, and high medical quality. It can also help health workers in non-specialized maternity units deal with COVID-19-related psychological stress. Therefore, setting up one specialized maternity unit in the city during the pandemic should be guardedly considered., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: Detecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker., Methods: We adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies., Results: A considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed., Conclusions: The measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Population health monitoring based on the Internet of Medical Things (IoMT) is becoming an important application trend healthcare improvement. This work aims to develop an autonomous network architecture, collecting sensor data with a cluster topology, forwarding information through relay nodes, and applying edge computing and transmission scheduling for network scalability and operational efficiency. The proposed distributed network architecture incorporates data compression technologies and effective scheduling algorithms for handling the transmission scheduling of various physiological signals. Compared to existing scheduling mechanisms, the experimental results depict the network performance and show that in analyzing the delay and jitter, the proposed WFQ-based algorithms have reduced the delay and jitter ratio by about 40% and 19.47% compared to LLQ with priority queueing scheme, respectively. The experimental results also demonstrate that the proposed network topology is more effective than the direct path transmission approach in terms of energy consumption, which suggests that the proposed network architecture may improve the development of medical applications with body area networks such that the goal of self-organizing population health monitoring can be achieved.

Background: Veno-venous extracorporeal membrane oxygenation (ECMO) was successfully performed for the rescue of an adult patient with severe acute respiratory distress syndrome (ARDS) induced by fulminant psittacosis, and then a near-fatal pulmonary embolism (PE) and cardiac arrest (CA) of the same patient was cured through catheter-directed thrombolysis., Case Presentation: A 51-year-old female patient was admitted to the hospital on September 10, 2021 due to slurred speech, weakness in lower limbs, dizziness, and nausea. Subsequently, she developed confusion and was transferred to the intensive care unit (ICU), where she received anti-shock, antibiotics, invasive mechanical ventilation (IMV), and veno-venous ECMO due to the diagnosis of severe pneumonia, severe ARDS, and septic shock based on comprehensive physical examination, laboratory tests, and imaging findings. The metagenomic next-gengeration sequencing ( m -NGS) in the bronchoalveolar lavage fluid (BALF) suggested that the pathogen was chlamydia psittaci, so the antibiotics were adjusted to doxycycline combined with azithromycin. After withdrawal from ECMO, ultrasound (US) re-examination of the left lower limb revealed inter-muscular vein thrombosis, following which heparin was replaced by subcutaneous injection of 0.4ml enoxaparin sodium twice daily for anti-coagulation therapy. After withdrawal from IMV, the patient suffered sudden CA and successful cardiopulmonary resuscitation (CPR), and emergency pulmonary angiography (PA) was performed to show bilateral main pulmonary artery embolism. After immediate catheter-directed thrombolysis and placement of an inferior vena cava filter, the patient's condition gradually stabilized., Conclusions: Veno-venous ECMO can be successfully performed as an emergency life-saving treatment for patients with severe ARDS induced by fulminant psittacosis, and during ECMO regular examinations should be conducted to detect and manage thrombosis in time, thereby avoiding the occurrence of near-fatal PE and CA., 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.)

Purpose: This study used data from a national birth cohort study to investigate the duration of internet use at the age of 12 years among children diagnosed with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disabilities (IDs) and learning disabilities (LDs) at the age of five and a half years (66 months) to understand whether an ADHD, ASD, ID and LD diagnosis in childhood increases the risk of problematic internet use (PIU) in adolescence. Furthermore, the pathway relationship of dissociative absorptive trait with PIU and these diagnoses was also investigated., Methods: The 5.5- and 12-year-old Taiwan Birth Cohort Study dataset was used (N = 17,694)., Results: More boys were diagnosed with LDs, IDs, ADHD and ASD; however, girls were at increased likelihood of PIU. ID and ASD diagnoses were not associated with increasing PIU likelihood. However, children who had been diagnosed with LDs and ADHD, along with higher dissociative absorptive trait, had an indirectly increased likelihood of PIU in adolescence., Conclusions: Dissociative absorption was found to be a mediating factor between childhood diagnosis and PIU and can be used as a screening indicator in prevention programs to reduce the duration and severity of PIU in children diagnosed with ADHD and LDs. Furthermore, with the increased prevalence of smartphone usage in adolescents, education policy-makers should pay greater attention to the issue of PIU in female adolescents., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

1,3-Functionalized cyclobutane structural motifs are ubiquitous in natural products and pharmaceuticals. Photoinduced alkylation of bicyclo[1.1.0]butanes (BCBs) offers a step-economical strategy for accessing 1,3-functionalized cyclobutane motifs. Herein, we disclose a general and mild photocatalytic protocol of bromoallylation and alkylation of BCBs in a metal, additive-free manner by using the same photocatalyst, 2-isopropylthioxanthone, in different catalytic roles. Furthermore, the synthetic utility of these products was illustrated in the synthesis of various valuable and complex cyclobutane derivatives.

A frontal sinus cutaneous fistula (FSCF) is a rare and challenging condition. Remarkable advancements in endonasal endoscopic surgery (EES) have enabled the treatment paradigm for a FSCF to gradually shift from open procedures to ESS. Nevertheless, the experience of EES for a post-trephination-related FSCF is rare, especially in patients with a pronounced frontal recess (FR) ossification. Here, we report an endoscopic strategy for successfully treating a post-trephination-related FSCF with complete ipsilateral FR neo-osteogenesis. Through two surgical corridors created by the modified mini-Lothrop procedure and an ipsilateral frontal osteotomy window, we established a patent drainage pathway from the affected side to the opposite side. This strategy may prevent potential orbital and cranial base injuries from affecting the ossified region of the ipsilateral FR. Moreover, in addition to the advantage of aesthetic outcomes, the procedure allows a single-stage surgery and facilitates the debridement and surveillance of the wound through the drainage pathway postoperatively. In conclusion, this technique could be a feasible endoscopic strategy for a FSCF, regardless of the severity of the FR ossification., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The first carbonatotellurites, AKTeO 2 (CO 3 ) (A = Li, Na), have been successfully synthesized by using boric acid as the mineralizer. AKTeO 2 (CO 3 ) (A = Li, Na) crystallize in the monoclinic space group P 2 1 / n (no. 14), and their structures exhibit the novel zero-dimensional (0D) [Te 2 C 2 O 10 ] 4- clusters, in which two [TeO 4 ] 4- groups form a [Te 2 O 6 ] 4- dimer via edge-sharing, with each side of the dimer attached by a [CO 3 ] 2- group via a Te-O-C bridge. The alkali metal cations occupy the voids between the 0D clusters and maintain the charge balance. The ultraviolet-visible-near-infrared diffuse reflectance spectra show that the short absorption cut-off edges of LiKTeO 2 (CO 3 ) (LKTC) and NaKTeO 2 (CO 3 ) (NKTC) are 248 and 240 nm, respectively, and LKTC exhibits the largest experimental band gap (4.58 eV) among all of the tellurites containing the π-conjugated anionic groups reported. Theoretical calculations revealed that they exhibit moderate birefringences of 0.029 and 0.040@1064 nm, respectively.

Background: Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk., Methods: This prospective cohort study included 3928 adults aged ≥ 55 years without systemic inflammation in the baseline examination of the Healthy Aging Longitudinal Study in Taiwan, which started in 2009. Each participant received leukocyte mitochondrial DNA copy number measurement using a fluorescence-based quantitative polymerase chain reaction at baseline, serum high-sensitivity C-reactive protein measurements at baseline and the follow-up examination five years later, and the ascertainment of all-cause death (until November 30, 2021). The relationships among the leukocyte mitochondrial DNA copy number, longitudinal serum high-sensitivity C-reactive protein levels, and time to all-cause mortality were examined using the joint longitudinal and survival modeling analysis., Results: Of the 3928 participants (mean age: 69 years; 2060 [52%] were women), 837 (21%) died during follow-up. In the adjusted analysis, one standard deviation lower natural log-transformed baseline leukocyte mitochondrial DNA copy number was associated with an increase of 0.05 (95% confidence interval [CI], 0.02 to 0.08) standard deviation in serum high-sensitivity C-reactive protein in subsequent years. An increase of 1 standard deviation in instantaneous high-sensitivity C-reactive protein levels was associated with a hazard ratio (HR) for all-cause mortality of 1.22 (95% CI, 1.14 to 1.30). Similar results were obtained after further adjusting for baseline high-sensitivity C-reactive protein levels (HR [95% CI], 1.27 [1.16 to 1.38]) and after excluding those with serum high-sensitivity C-reactive protein above 10 mg/L (HR [95% CI], 1.21[1.11 to 1.31]) or 3 mg/L (HR [95% CI], 1.19 [1.06 to 1.31]) during follow-up., Conclusions: A lower leukocyte mitochondrial DNA copy number was associated with persistently higher high-sensitivity C-reactive protein levels. Moreover, these higher time-varying high-sensitivity C-reactive protein levels were instantaneously associated with a higher risk of death., (© 2022. The Author(s).)

Background: Police officers are a high-stress group with special job characteristics, and the Chinese police management system places particularly high demands on police officers. Whether the influence of job demands on officers' job burnout can be deduced to general stress response needs to be verified. Based on the JD-R model, the study aims to explore the impact of job demands on police stress response, whether job autonomy as a job resource has a moderating effect, and whether basic psychological needs mediate this effect., Methods: A total of 251 police officers in a district-level public security bureau of China, were surveyed using Chinese-language versions of the Job Demands Scale, the Stress Response Scale, the Job Autonomy Scale, and the Basic Psychological Needs Scale. The mediating effect of basic psychological needs and the moderating effect of job autonomy were tested by regression analysis and bootstrap test., Results: Job demands increase police officers' stress response, and job autonomy does not play a buffer role but enhances this impact, and job demands can partially reduce the police stress response through the satisfaction of basic psychological needs, that is, there is a masking effect of basic psychological needs., Conclusions: Adjusting and optimizing the ratio of job demands and autonomy in police work to provide high guidance under high demands is of great value to reduce the negative stress responses among police officers., (© 2022. The Author(s).)

Objective: To explore the effect of curcumin on the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/endometrial expression of glucose 4 (GLUT4) signalling pathway and its regulator, phosphatase and tensin homolog (PTEN), in a rat model of polycystic ovarian syndrome (PCOS)., Methods: PCOS model was induced by letrozole intragastric administration. Sprague-Dawley rats were randomized into 4 groups according to a random number table: (1) control group; (2) PCOS group, which was subjected to PCOS and received vehicle; (3) curcumin group, which was subjected to PCOS and treated with curcumin (200 mg/kg for 2 weeks); and (4) curcumin+LY294002 group, which was subjected to PCOS, and treated with curcumin and LY294002 (a specific PI3K inhibitor). Serum hormone levels (17 β-estradiol, follicle stimulating hormone, luteinizing hormone, progesterone, and testosterone) were measured by enzyme linked immunosorbent assay, and insulin resistance (IR) was assessed using the homeostasis model assessment of IR. Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination. Expression levels of key transcriptional regulators and downstream targets, including IRS1, PI3K, protein kinase B (AKT), GLUT4, and PTEN, were measured via reverse transcription polymerase chain reaction and Western blot, respectively., Results: The PCOS group showed impaired ovarian morphology and function. Compared with the PCOS group, curcumin treatment exerted ovarioprotective effects, down-regulated serum testosterone, restored IR, inhibited inflammatory cell infiltration in ovarian tissues, decreased IRS1, PI3K, and AKT expressions, and up-regulated GLUT4 and PTEN expressions in PCOS rats (P<0.05 or P<0.01). In contrast, IRS1, PI3K, AKT, and PTEN expression levels were not significantly different between PCOS and curcumin+LY294002 groups (P>0.05)., Conclusion: The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions, in which, PTEN, a new target, may play a role in regulating the IRS1/PI3K/GLUT4 pathway., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

In this work, we develop a wireless sensor-integrated face mask using Au@SnO 2 nanoparticle-modified conductive fibers based on augmented reality (AR) technology. AR technology enables the overlay of real objects and environments with virtual 3D objects and allows virtual interactions with real objects to create desired meanings. With the help of the AR system, the size of the mask could be precisely estimated and then manufactured using 3D printing technology. The body temperature sensor and respiratory sensor were integrated into the mask so that vital parameters of the human body could be continuously monitored without removing the personal protective equipment. Furthermore, the outer part of the mask consists of conductive fabric modified with Au@SnO 2 core-shell nanoparticle additives, which enhanced the filtration efficiency of airborne aerosols. A significant improvement in the filtration efficiency of particulate matter 2.5 was observed after applying an external voltage to the conductive textiles. A smartwatch with a heart rate sensor was paired with the mask to display sensor data on the mask through wireless transmission. Therefore, this sensor-integrated mask system with AR technology provides the first line of defense to combat global threats from pathogens and air pollutants., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: The automatic coding of clinical text documents by using the International Classification of Diseases, 10th Revision (ICD-10) can be performed for statistical analyses and reimbursements. With the development of natural language processing models, new transformer architectures with attention mechanisms have outperformed previous models. Although multicenter training may increase a model's performance and external validity, the privacy of clinical documents should be protected. We used federated learning to train a model with multicenter data, without sharing data per se., Objective: This study aims to train a classification model via federated learning for ICD-10 multilabel classification., Methods: Text data from discharge notes in electronic medical records were collected from the following three medical centers: Far Eastern Memorial Hospital, National Taiwan University Hospital, and Taipei Veterans General Hospital. After comparing the performance of different variants of bidirectional encoder representations from transformers (BERT), PubMedBERT was chosen for the word embeddings. With regard to preprocessing, the nonalphanumeric characters were retained because the model's performance decreased after the removal of these characters. To explain the outputs of our model, we added a label attention mechanism to the model architecture. The model was trained with data from each of the three hospitals separately and via federated learning. The models trained via federated learning and the models trained with local data were compared on a testing set that was composed of data from the three hospitals. The micro F 1 score was used to evaluate model performance across all 3 centers., Results: The F 1 scores of PubMedBERT, RoBERTa (Robustly Optimized BERT Pretraining Approach), ClinicalBERT, and BioBERT (BERT for Biomedical Text Mining) were 0.735, 0.692, 0.711, and 0.721, respectively. The F 1 score of the model that retained nonalphanumeric characters was 0.8120, whereas the F 1 score after removing these characters was 0.7875-a decrease of 0.0245 (3.11%). The F 1 scores on the testing set were 0.6142, 0.4472, 0.5353, and 0.2522 for the federated learning, Far Eastern Memorial Hospital, National Taiwan University Hospital, and Taipei Veterans General Hospital models, respectively. The explainable predictions were displayed with highlighted input words via the label attention architecture., Conclusions: Federated learning was used to train the ICD-10 classification model on multicenter clinical text while protecting data privacy. The model's performance was better than that of models that were trained locally., (©Pei-Fu Chen, Tai-Liang He, Sheng-Che Lin, Yuan-Chia Chu, Chen-Tsung Kuo, Feipei Lai, Ssu-Ming Wang, Wan-Xuan Zhu, Kuan-Chih Chen, Lu-Cheng Kuo, Fang-Ming Hung, Yu-Cheng Lin, I-Chang Tsai, Chi-Hao Chiu, Shu-Chih Chang, Chi-Yu Yang. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 10.11.2022.)

16p13.11 copy number variants (CNVs) have been associated with autism, schizophrenia, psychosis, intellectual disability, and epilepsy. The majority of 16p13.11 deletions or duplications occur within three well-defined intervals, and despite growing knowledge of the functions of individual genes within these intervals, the molecular mechanisms that underlie commonly observed clinical phenotypes remain largely unknown. Patient-derived, induced pluripotent stem cells (iPSCs) provide a platform for investigating the morphological, electrophysiological, and gene-expression changes that result from 16p13.11 CNVs in human-derived neurons. Patient derived iPSCs with varying sizes of 16p13.11 deletions and familial controls were differentiated into cortical neurons for phenotypic analysis. High-content imaging and morphological analysis of patient-derived neurons demonstrated an increase in neurite branching in patients compared with controls. Whole-transcriptome sequencing revealed expression level changes in neuron development and synaptic-related gene families, suggesting a defect in synapse formation. Subsequent quantification of synapse number demonstrated increased numbers of synapses on neurons derived from early-onset patients compared to controls. The identification of common phenotypes among neurons derived from patients with overlapping 16p13.11 deletions will further assist in ascertaining common pathways and targets that could be utilized for screening drug candidates. These studies can help to improve future treatment options and clinical outcomes for 16p13.11 deletion patients., Competing Interests: MS reports grant support from Novartis, Biogen, Astellas, Aeovian, Bridgebio, and Aucta. He has served on Scientific Advisory Boards for Novartis, Roche, Regenxbio, SpringWorks Therapeutics, Jaguar Therapeutics, and Alkermes. JG-H has been a consultant to Alkermes, Sunovion, and Neurocrine pharmaceuticals and has equity in and serves as founding head of the scientific advisory board of Mightier/Neuromotion Labs, makers of emotional regulation training video games. The remaining 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 © 2022 Buttermore, Anderson, Chen, Makhortova, Kim, Wafa, Dwyer, Micozzi, Winden, Zhang, Han, Kleiman, Brownstein, Sahin and Gonzalez-Heydrich.)

Background: Epigenetics exerts a vital role in the onset and development of renal cell carcinoma (RCC). Mounting evidence has shed light on the significance of human immune system in response to tumor infiltrating T cells. Hereby, we sought to unmask the immunomodulatory role of histone deacetylase 3 (HDAC3) and its potential upstream molecule, programmed cell death 5 (PDCD5) in RCC., Methods: RCC and adjacent non-cancerous tissues were clinically resected from 58 patients, in which the expression profile of microRNA-195-5p (miR-195-5p), PDCD5, HDAC3, and serum glucocorticoid-inducible kinase 1 (SGK1) was determined by RT-qPCR and Western blot analysis. Their relations were investigated by a series of luciferase assays in combination with ChIP and co-IP. RCC cells (A498) were intervened using gain- and loss-of-function approaches, followed by cell proliferation evaluation. After co-culture with CD3 + T cells, flow cytometry and interferon-γ (IFN-γ) determination were performed. A xenograft tumor mouse model was developed for in vivo validation., Results: PDCD5 was downregulated in RCC tissues and A498 cells. Upregulation of HDAC3, as well as of SGK1, resulted in suppression of A498 cell proliferation and promotion of T cell activation as evidenced by higher IFN-γ expression. Re-expression of PDCD5 downregulated HDAC3, causing a subsequent upregulation of miR-195-5p, while miR-195-5p could inversely modulate its target gene, SGK1. The regulatory mechanism appeared to be functional in vivo., Conclusion: Our results highlight the possible manipulation by PDCD5 on RCC cell proliferation and T cell activation, which provides new clues to better understand the immune balance in RCC progression., (© 2022. The Author(s).)

Background: Interleukin (IL)-34 is a pro-inflammatory cytokine involved in tumor development. The role of IL-34 in the proliferation and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) remains to be investigated., Aim: To investigate whether and how IL-34 affects the proliferation of GC cells and EMT., Methods: Using immunohistochemical staining, the expression of IL-34 protein was detected in 60 paired GC and normal paracancerous tissues and the relationship between IL-34 and clinicopathological factors was analyzed. The expression of IL-34 mRNA and protein in normal gastric epithelial cell lines and GC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Stable IL-34 knockdown and overexpression in AGS cell lines were established by lentiviral infection and validated by qRT-PCR and western blotting. The cholecystokinin-8 assay, clone formation assay, cell scratch assay, and transwell system were used to detect GC cell proliferation, clone formation, migration, and invasion capacity, respectively. The effects of IL-34 on the growth of GC transplant tumors were assessed using a subcutaneous transplant tumor assay in nude mice. The effects of IL-34 on the expression level of EMT-associated proteins in AGS cells were examined by western blotting., Results: Expression of IL-34 protein and mRNA was higher in GC cell lines than in GES-1 cells. Compared to matched normal paraneoplastic tissues, the expression of IL-34 protein was higher in 60 GC tissues, which was correlated with tumor size, T-stage, N-stage, tumor, node and metastasis stage, and degree of differentiation. Knockdown of IL-34 expression inhibited the proliferation, clone formation, migration, and invasion of AGS cells, while overexpression of IL-34 promoted cell proliferation, clone formation, migration, and invasion. Furthermore, the reduction of IL-34 promoted the expression of E-cadherin in AGS cells but inhibited the expression of vimentin and N-cadherin. Overexpression of IL-34 inhibited E-cadherin expression but promoted expression of vimentin and N-cadherin in AGS cells. Overexpression of IL-34 promoted the growth of subcutaneous transplanted tumors in nude mice., Conclusion: IL-34 expression is increased in GC tissues and cell lines compared to normal gastric tissues or cell lines. In GC cells, IL-34 promoted proliferation, clone formation, migration, and invasion by regulating EMT-related protein expression cells. Interference with IL-34 may represent a novel strategy for diagnosis and targeted therapy of GC., Competing Interests: Conflict-of-interest statement: There is no conflict of interest in this study., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: A national birth cohort study was used to investigate whether high-risk family factors at 1.5-year-olds can increase the risk of attention-deficit/hyperactivity disorder (ADHD) diagnosis when children reach 5.5 years. The pathway relationship of high-risk family factors, children's developmental conditions, risk of autism spectrum disorder (ASD), and diagnosis of intellectual disability (ID), learning disability (LD), and ASD was also investigated., Methods: The 1.5-, 3- and 5.5-year-old Taiwan Birth Cohort Study (TBCS) dataset was used (N = 19,185). The high-risk familial factor was measured using five questions assessing whether parents are currently unmarried, unemployed, do not have any social insurance, perceive a "very heavy" economic childcare burden, and at least one of the parents has a disability certification. Developmental conditions were assessed using the Taiwan Birth Cohort Study-Developmental Instrument (TBCS-DI), and ASD risk was measured using the Modified Checklist of Autism in Toddlers. Data on ADHD, ID, LD, and ASD diagnoses were collected at age 5.5. The odds ratio model investigated whether children from families with high-risk factors at 1.5-years were at increased risk of ADHD, ID, LD, or ASD diagnosis at 5.5-years, compared to those children from families without such risks. Structural equation modeling investigated the logistic regression pathway relationship of high-risk familial characteristics, children's developmental conditions, autism screening, and diagnosis., Results: In the national birth cohort dataset of 19,185 children, 2070 (10.8%) met at least one of the high-risk familial factors. Children who met one high-risk familial factor had a 1.21-fold increased risk for ADHD diagnosis, 1.36-fold increased risk for LD diagnosis, and 1.80-fold increased risk for ASD diagnosis, compared to children from families without risks. High-risk familial factors directly increased the risk of ADHD and ID diagnosis, and indirectly increased the risk of ADHD, ID, LD, and ASD diagnosis through the mediating factor of children's development., Conclusions: Children who met more high-risk familial characteristics were at higher risk of ADHD, ID, LD, and ASD diagnosis. Development at three years was predictive of diagnosis at 5.5 years. Thus, developmental screening at age three is vital for interventions. Preventive, family-focused, and/or child-rearing services for at-risk families are important for improving outcomes for these children and their families., 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 © 2022 Lung, Chen, Shen and Shu.)