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Yen-Hao Chen,1– 4 Wan-Ting Huang,5 Wen-Chin Lee,6 Ching-Mei Chen,5 Fu-Jen Cheng,7 Chia-Te Kung,7 Chin-Chou Wang,8 Liang-Jen Wang,9 Yu-Che Ou,10 Shau-Hsuan Li1 1Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 2School of Medicine, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 3School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan; 4Department of Nursing, School of Nursing, Fooyin University, Kaohsiung, 831, Taiwan; 5Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 6Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 7Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 8Department of Occupational Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 9Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 10Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, TaiwanCorrespondence: Shau-Hsuan Li, Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, 833, Taiwan, Email lee.a0928@msa.hinet.netBackground: The aim of this study was to investigate the role of phthalate in patients with esophageal squamous cell carcinoma (ESCC).Methods: A total of 116 ESCC patients and 58 controls without any known histories of malignancies were enrolled. All eight urine phthalate metabolites were measured to assess phthalate levels. Clinical and urine phthalate metabolite profiles were compared between subgroups to identify differences, and the effects of phthalates on clinical ESCC outcomes were also examined.Results: The concentrations of some urine phthalate metabolites were higher in the ESCC group than in the control group, including mono-(3-carboxypropyl) phthalate (MCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). Higher concentrations of urine phthalate metabolites were associated with clinical T3–T4 status. Patients with higher concentration of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and MEOHP had lower 1-year and 2-year overall survival (OS) rates than those with lower concentrations of these metabolites in our univariate analysis. Multivariate analysis showed that urinary MEHP of ≥ 3 μg/L and clinical stage IVB were independent prognostic factors for worse OS.Conclusion: The results of our study showed that urine phthalate metabolites are elevated in ESCC patients and associated with advanced tumor stage, and that a high urinary concentration of MEHP is an independent prognostic factor of worse OS.Keywords: phthalate, esophageal cancer, squamous cell carcinoma, survival

Ting-Yu Hsu,1 Chi-Yung Cheng,1,2,* I-Min Chiu,1,2 Chun-Hung Richard Lin,2 Fu-Jen Cheng,1 Hsiu-Yung Pan,1 Yu-Jih Su,3 Chao-Jui Li1,* 1Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; 3Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Chi-Yung Cheng; Chao-Jui Li, Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan, Tel +886-7-7317123 ext. 8415, Email qzsecawsxd@gmail.com; chaojui@cgmh.org.twBackground: The global aging population presents a significant challenge, with older adults experiencing declining physical and cognitive abilities and increased vulnerability to chronic diseases and adverse health outcomes. This study aims to develop an interpretable deep learning (DL) model to predict adverse events in geriatric patients within 72 hours of hospitalization.Methods: The study used retrospective data (2017– 2020) from a major medical center in Taiwan. It included non-trauma geriatric patients who visited the emergency department and were admitted to the general ward. Data preprocessing involved collecting prognostic factors like vital signs, lab results, medical history, and clinical management. A deep feedforward neural network was developed, and performance was evaluated using accuracy, sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC). Model interpretation utilized the Shapley Additive Explanation (SHAP) technique.Results: The analysis included 127,268 patients, with 2.6% experiencing imminent intensive care unit transfer, respiratory failure, or death during hospitalization. The DL model achieved AUCs of 0.86 and 0.84 in the validation and test sets, respectively, outperforming the Sequential Organ Failure Assessment (SOFA) score. Sensitivity and specificity values ranged from 0.79 to 0.81. The SHAP technique provided insights into feature importance and interactions.Conclusion: The developed DL model demonstrated high accuracy in predicting serious adverse events in geriatric patients within 72 hours of hospitalization. It outperformed the SOFA score and provided valuable insights into the model’s decision-making process. Keywords: explainable machine learning, deep learning algorithm, adverse events, mortality

Our previous studies have revealed a correlation between urinary phthalates (PAE) metabolites and parabens and PM 2.5 exposure and susceptibility to attention-deficit/hyperactivity disorder (ADHD) in school-age children. Our goal was to examine the relationships between urinary organophosphate flame retardants (OPFRs) and their metabolites and the susceptibility to ADHD in the same cohort of children. We recruited 186 school children, including 132 with ADHD and 54 normal controls, living in southern Taiwan to investigate five OPFRs (1,3-dichloro-2-propyl phosphate (TDCPP), tri-n-butyl phosphate (TnBP), tris (2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPHP)) and five OPFR metabolites (bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-n-butyl phosphate (DNBP), bis(2-chloroethyl) hydrogen phosphate (BCEP), di-(2-butoxyethyl) phosphate (DBEP), and diphenyl phosphate (DPHP)) in urine. ADHD patients' behavioral symptoms and neuropsychological function were assessed using the Swanson, Nolan, and Pelham Version IV Scale (SNAP-IV) and the Conners' Continuous Performance Test 3rd Edition (Conners CPT3), respectively. BCEP was predominant among urinary OPFRs and the metabolites in both the ADHD and control groups. ADHD children had significantly higher levels of urinary BDCPP, BCEP, DBEP, DPHP, TCEP, TBEP, TNBP, TPHP, and Σ 10 OPFR compared to the controls. After controlling for age, gender, body mass index, PM 2.5 exposure scenarios, and urinary phthalate metabolites, parabens, bisphenol-A and creatinine, levels of urinary BDCPP, TDCPP, and TBEP in ADHD children showed significant and dose-dependent effects on core behavioral symptoms of inattention. DNBP levels were positively correlated with neuropsychological deficits (CPT detectability, omission, and commission), while urinary DPHP in ADHD children were negatively related to CPT detectability and commission. Hyperactivity and impulsivity were not correlated with urinary OPFRs and their metabolites in ADHD children. In conclusion, the ADHD symptom of inattention and CPT performance may be closely associated with certain urinary OPFRs and their metabolites, independent of urinary PAE metabolites, parabens, and bisphenol-A in school-age-ADHD children., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: How-Ran Chao reports financial support was provided by National Science and Technology Council. How-Ran Chao reports a relationship with National Science and Technology Council that includes: funding grants. If there are other authors, they 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Abdominal aortic aneurysm (AAA) often remains undetected until rupture due to limited access to diagnostic ultrasound. This trial evaluated a deep learning (DL) algorithm to guide AAA screening by novice nurses with no prior ultrasonography experience. Ten nurses performed 15 scans each on patients over 65, assisted by a DL object detection algorithm, and compared against physician-performed scans. Ultrasound scan quality, assessed by three blinded expert physicians, was the primary outcome. Among 184 patients, DL-guided novices achieved adequate scan quality in 87.5% of cases, comparable to the 91.3% by physicians (p = 0.310). The DL model predicted AAA with an AUC of 0.975, 100% sensitivity, and 97.8% specificity, with a mean absolute error of 2.8 mm in predicting aortic width compared to physicians. This study demonstrates that DL-guided POCUS has the potential to democratize AAA screening, offering performance comparable to experienced physicians and improving early detection., (© 2024. The Author(s).)

Incense-burning smoke is a deleterious air pollutant that initiates cytotoxic effects by inducing apoptosis in lung epithelial cells and also acts as a risk factor for lung cancers. Auramine, an ingredient of incense smoke, has been implicated in tumor progression and cellular sensitivity in non-small cell lung cancer (NSCLC) towards anti-cancer agents through unclear mechanisms. Tumor protein p53 (TP53)-activated long intergenic non-coding RNA-p21 (lincRNA-p21) undertakes a pivotal role in regulating cell apoptosis and chemosensitivity. TP53 mutations prevalent in 50% of NSCLC, contribute to diminished therapeutic efficacy. However, the influence of auramine on chemotherapy-induced lincRNA-p21 expression and apoptosis in NSCLC with different TP53 genetic statuses remains unexplored. This study disclosed that both wild-type p53 (wtp53) and mutant p53 (mutp53) mediate lincRNA-p21 expression, albeit through distinct promoter enhancers, p53-response element (p53RE) and non-B DNA structure G-quadruplex (GQ), respectively. Intriguingly, auramine functions as an effective stabilizer of the GQ structure, augmenting mutp53-mediated lincRNA-p21 expression and enhancing apoptosis and cellular sensitivity to chemotherapy in mutp53-expressing NSCLC cells. These findings suggest a mechanism by which mutp53, in the presence of auramine, is endowed with tumor-suppressing function akin to wtp53, thereby aiding in combating chemoresistance in NSCLC cells harboring TP53 mutations., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Humans are extensively exposed to organophosphate flame retardants (OPFRs), an emerging group of organic contaminants with potential nephrotoxicity. Nevertheless, the estimated daily intake (EDI) and prognostic impacts of OPFRs have not been assessed in individuals with chronic kidney disease (CKD). In this 2-year longitudinal study of 169 patients with CKD, we calculated the EDIs of five OPFR triesters from urinary biomonitoring data of their degradation products and analyzed the effects of OPFR exposure on adverse renal outcomes and renal function deterioration. Our analysis demonstrated universal OPFR exposure in the CKD population, with a median EDI ΣOPFR of 360.45 ng/kg body weight/day (interquartile range, 198.35-775.94). Additionally, our study revealed that high tris(2-chloroethyl) phosphate (TCEP) exposure independently correlated with composite adverse events and composite renal events (hazard ratio [95 % confidence interval; CI]: 4.616 [1.060-20.096], p = 0.042; 3.053 [1.075-8.674], p = 0.036) and served as an independent predictor for renal function deterioration throughout the study period, with a decline in estimated glomerular filtration rate of 4.127 mL/min/1.73 m 2 (95 % CI, -8.127--0.126; p = 0.043) per log ng/kg body weight/day of EDI TCEP . Furthermore, the EDI TCEP and EDI ΣOPFR were positively associated with elevations in urinary 8-hydroxy-2'-deoxyguanosine and kidney injury molecule-1 during the study period, indicating the roles of oxidative damage and renal tubular injury in the nephrotoxicity of OPFR exposure. To conclude, our findings highlight the widespread OPFR exposure and its possible nephrotoxicity in the CKD population., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure., Methods: The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation., Results: The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2-butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2-butoxyethyl) phosphate (r = 0.88, p < 0.01). Patients with TBEP in their urine had higher percentage of wild-type EGFR and the detection of TBEP was associated with a reduced likelihood of mutant EGFR expression., Conclusions: OPFR exposure was prevalent in lung cancer patients, with TBEP detection identified as a factor with lower EGFR mutation expression. This study contributes to the understanding of OPFR exposure in lung cancer patients and underscores the significance of TBEP in evaluating EGFR mutation in this population., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Antibiotic resistance has emerged as a global concern. Xiyanping injection (XYP), a traditional Chinese medicine injection, has been extensively utilized for the treatment of suppurative acute tonsillitis (SAT) in China, exhibiting clinical efficacy. Consequently, there is a need for further evaluation of the potential effectiveness and safety of this treatment. This meta-analysis consolidated data from multiple independent studies to assess the overall treatment efficacy of XYP as adjuvant therapy in patients with SAT. Methods: The search for randomized controlled trials (RCTs) encompassed databases from their inception to 1 April 2024, including the Cochrane Library, PubMed, Embase, SinoMed, CNKI, Wanfang, VIP, and CBM. Data extraction, methodological quality assessment, and meta-analysis were performed independently by two researchers. Review Manager 5.4 was used for data analysis. Various tools were employed for assessment, including forest plots to visualize results, funnel plots to detect publication bias, trial sequential analysis to estimate sample size, and GRADE to evaluate evidence quality. Results: A comprehensive analysis of 32 RCTs involving 4,265 cases was conducted. When compared to conventional treatments (CTs; β-lactams/clindamycin hydrochloride injection/ribavirin) alone, the combination of XYP with CTs demonstrated significant reductions in symptom duration. This included sore throat (MD = -21.08, 95% CI: -24.86 to -17.29, p < 0.00001), disappearance of tonsillar redness and swelling (mean difference [MD] = -20.28, 95% confidence interval [CI]: -30.05 to -10.52, p < 0.0001), tonsil purulent discharge (MD = -22.40, 95% CI: -28.04 to -16.75, p < 0.00001), and normalization of temperature (MD = -19.48, 95% CI: -22.49 to -16.47, p < 0.00001). Furthermore, patients receiving CTs combined with XYP exhibited lower levels of interleukin-6 (MD = -7.64, 95% CI: 8.41 to -6.87, p < 0.00001) and interleukin-8 (MD = -5.23, 95% CI: -5.60 to -4.86, p < 0.00001) than those receiving CTs alone. Additionally, the combination therapy significantly improved the recovery rate (relative risk [RR] = 1.55, 95% CI: 1.37 to 1.77, p < 0.00001), white blood cell count recovery rate (RR = 1.13, 95% CI: 1.04 to 1.23, p = 0.004), and disappearance rate of tonsillar redness and swelling (RR = 0.51, 95% CI: 1.14 to 1.38, p < 0.00001), with no significant increase in adverse events (RR = 0.47, 95% CI: 0.20 to 1.10, p = 0.08). Conclusion: The current systematic review and meta-analysis tentatively suggest that the combination of XYP and CTs yields superior clinical outcomes for patients with SAT compared to CTs alone, with a favorable safety profile. Nonetheless, these findings warrant further confirmation through more rigorous RCTs, given the notable heterogeneity and publication bias observed in the included studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=296118, identifier CRD42022296118., 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. The reviewer XA declared a shared parent affiliation with the author(s) to the handling editor at the time of review., (Copyright © 2024 Cheng, Lyu, Wang and Xie.)

Lung cancer stands as a major contributor to cancer-related fatalities globally, with cigarette smoke playing a pivotal role in its development and metastasis. Cigarette smoke is also recognized as a risk factor for bone loss disorders like osteoporosis. However, the association between cigarette smoke and another bone loss disorder, lung cancer osteolytic bone metastasis, remains largely uncertain. Our Gene Set Enrichment Analysis (GSEA) indicated that smokers among lung cancer patients exhibited higher expression levels of bone turnover gene sets. Both The Cancer Genome Atlas (TCGA) database and our clinic samples demonstrated elevated expression of the osteolytic factor IL-6 in ever-smokers with bone metastasis among lung cancer patients. Our cellular experiments revealed that benzo[α]pyrene (B[α]P) and cigarette smoke extract (CSE) promoted IL-6 production and cell migration in lung cancer. Activation of the PI3K, Akt, and NF-κB signaling pathways was involved in cigarette smoke-augmented IL-6-dependent migration. Additionally, cigarette smoke lung cancer-secreted IL-6 promoted osteoclast formation. Importantly, blocking IL-6 abolished cigarette smoke-facilitated lung cancer osteolytic bone metastasis in vivo . Our findings provide evidence that cigarette smoke is a risk factor for osteolytic bone metastasis. Thus, inhibiting IL-6 may be a valuable therapeutic strategy for managing osteolytic bone metastasis in lung cancer patients who smoke., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Breast cancer stands as the predominant malignancy and primary cause of cancer-related mortality among females globally. Approximately 25% of breast cancers exhibit HER2 overexpression, imparting a more aggressive tumor phenotype and correlating with poor prognoses. Patients with metastatic breast cancer receiving HER2 tyrosine kinase inhibitors (HER2 TKIs), such as Lapatinib, develop acquired resistance within a year, posing a critical challenge in managing this disease. Here, we explore the potential of Artemisia argyi, a Chinese herbal medicine known for its anti-cancer properties, in mitigating HER2 TKI resistance in breast cancer. Analysis of the Cancer Genome Atlas (TCGA) revealed diminished expression of transmembrane serine protease 2 (TMPRSS2), a subfamily of membrane proteolytic enzymes, in breast cancer patients, correlating with unfavorable outcomes. Intriguingly, lapatinib-responsive patients exhibited higher TMPRSS2 expression. Our study unveiled that the compounds from Artemisia argyi, eriodictyol, and umbelliferone could inhibit the growth of lapatinib-resistant HER2-positive breast cancer cells. Mechanistically, they suppressed HER2 kinase activation by enhancing TMPRSS2 activity. Our findings propose TMPRSS2 as a critical determinant in lapatinib sensitivity, and Artemisia argyi emerges as a potential agent to overcome lapatinib via activating TMPRSS2 in HER2-positive breast cancer. This study not only unravels the molecular mechanisms driving cell death in HER2-positive breast cancer cells induced by Artemisia argyi but also lays the groundwork for developing novel inhibitors to enhance therapy outcomes., (© 2024 Wiley Periodicals LLC.)

Magnetic impurities in superconductors are of increasing interest due to emergent Yu-Shiba-Rusinov (YSR) states and Majorana zero modes for fault-tolerant quantum computation. However, a direct relationship between the YSR multiple states and magnetic anisotropy splitting of quantum impurity spins remains poorly characterized. By using scanning tunneling microscopy, we systematically resolve individual transition-metal (Fe, Cr, and Ni) impurities induced YSR multiplets as well as their Zeeman effects in the K 3 C 60 superconductor. The YSR multiplets show identical d orbital-like wave functions that are symmetry-mismatched to the threefold K 3 C 60 (1 1 1) host surface, breaking point-group symmetries of the spatial distribution of YSR bound states in real space. Remarkably, we identify an unprecedented fermion-parity-preserving quantum phase transition between ground states with opposite signs of the uniaxial magnetic anisotropy that can be manipulated by an external magnetic field. These findings can be readily understood in terms of anisotropy splitting of quantum impurity spins, and thus elucidate the intricate interplay between the magnetic anisotropy and YSR multiplets., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Although many cohort studies have reported that long-term exposure to particulate matter (PM) causes lung cancer, the molecular mechanisms underlying the PM-induced increases in lung cancer progression remain unclear. We applied the lung cancer cell line A549 (Parental; A549.Par) to PM for an extended period to establish a mimic PM-exposed lung cancer cell line, A549.PM. Our results indicate that A549.PM exhibits higher cell growth and proliferation abilities compared to A549.Par cells in vitro and in vivo . The RNA sequencing analysis found amphiregulin (AREG) plays a critical role in PM-induced cell proliferation. We observed that PM increases AREG-dependent lung cancer proliferation through glutamine metabolism. In addition, the EGFR/PI3K/AKT/mTOR signaling pathway is involved in PM-induced solute carrier family A1 member 5 (SLC1A5) expression and glutamine metabolism. Our findings offer important insights into how lung cancer proliferation develops upon exposure to PM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Injection molding is a highly nonlinear procedure that is easily influenced by various external factors, thereby affecting the stability of the product's quality. High-speed injection molding is required for production due to the rapid cooling characteristics of thin-walled parts, leading to increased manufacturing complexity. Consequently, establishing appropriate process parameters for maintaining quality stability in long-term production is challenging. This study selected a hot runner mold with a thin wall fitted with two external sensors, a nozzle pressure sensor and a tie-bar strain gauge, to collect data regarding the nozzle peak pressure, the timing of peak pressure, the viscosity index, and the clamping force difference value. The product weight was defined as the quality indicator, and a standardized parameter optimization process was constructed, including injection speed, V / P switchover point, packing, and clamping force. Finally, the optimized process parameters were applied to the adaptive process control experiments using the developed control system operated within the micro-controller unit (MCU). The results revealed that the control system effectively stabilized the product weight variation and standard deviation of 0.677% and 0.0178 g, respectively.

Organophosphate flame retardants (OPFRs) are emerging environmental pollutants that can be detected in water, dust, and biological organisms. Certain OPFRs can disrupt lipid metabolism in animal models and cell lines. However, the effects of OPFRs on human lipid metabolism remain unclear. We included 1,580 participants (≥20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between OPFR exposure and lipid metabolism biomarkers. After adjusting for confounding factors, results showed that one-unit increases in the log levels of diphenyl phosphate (DPhP) (regression coefficient = -5.755; S.E. = 2.289; p  = 0.023) and log bis-(1-chloro-2-propyl) phosphate (BCPP) (regression coefficient = -4.637; S.E. = 2.019; p  = 0.036) were negatively associated with the levels of total cholesterol (TC) in all participants. One-unit increases in the levels of DPhP (regression coefficient = -2.292; S.E. = 0.802; p  = 0.012), log bis (1,3-dichloro-2-propyl) phosphate (BDCPP) (regression coefficient = -2.046; S.E. = 0.825; p  = 0.026), and log bis-2-chloroethyl phosphate (BCEP) (regression coefficient = -2.604; S.E. = 0.704; p  = 0.002) were negatively associated with the levels of high-density lipoprotein cholesterol (HDL-C). With increasing quartiles of urine BDCPP levels, the mean TC levels significantly decreased in all participants ( p value for trend = 0.028), and quartile increases in the levels of DPhP ( p value for trend = 0.01), BDCPP ( p value for trend = 0.001), and BCEP ( p value for trend<0.001) were negatively corelated with HDL-C, with approximately 5.9, 9.9, and 12.5% differences between the upper and lower quartiles. In conclusion, DPhP, BDCPP, and BCEP were negatively related to HDL-C concentration, whereas DPhP and BCPP levels were negatively associated with TC level. Thus, exposure to OPFRs may interfere with lipid metabolism., 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 Cheng, Tsai, Huang, Kung, Huang, You, Li, Wang, Lee and Pan.)

Introduction: The objective of this multi-center retrospective cohort study was to devise a predictive tool known as RAPID-ED. This model identifies non-traumatic adult patients at significant risk for cardiac arrest within 48 hours post-admission from the emergency department., Methods: Data from 224,413 patients admitted through the emergency department (2016-2020) was analyzed, incorporating vital signs, lab tests, and administered therapies. A multivariable regression model was devised to anticipate early cardiac arrest. The efficacy of the RAPID-ED model was evaluated against traditional scoring systems like National Early Warning Score (NEWS) and Modified Early Warning Score (MEWS) and its predictive ability was gauged via the area under the receiver operating characteristic curve (AUC) in both hold-out validation set and external validation set., Results: RAPID-ED outperformed traditional models in predicting cardiac arrest with an AUC of 0.819 in the hold-out validation set and 0.807 in the external validation set. In this critical care update, RAPID-ED offers an innovative approach to assessing patient risk, aiding emergency physicians in post-discharge care decisions from the emergency department. High-risk score patients (≥13) may benefit from early ICU admission for intensive monitoring., Conclusion: As we progress with advancements in critical care, tools like RAPID-ED will prove instrumental in refining care strategies for critically ill patients, fostering an improved prognosis and potentially mitigating mortality rates., 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., (© 2024 The Authors.)

Background: The effect of alcohol consumption on trauma remains controversial. The effects of alcohol on hemorrhage and peritonitis after blunt abdominal trauma have rarely been discussed. This study aimed to explore the effects of acute alcohol intoxication on the clinical characteristics, injury patterns, and outcomes in a surgical blunt bowel mesenteric injury (BBMI) cohort., Methods: A retrospective data analysis was performed using trauma cases of patients who had been tested for alcohol and had surgically proven BBMI from a Trauma Registry System from 2009 to 2021. Patients were grouped according to their positive blood alcohol concentration (BAC; >0.5% vs. no BAC; less than 0.5% no BAC) upon arrival at the emergency department (ED). The injury characteristics, physiological parameters, and outcomes with respect to post-injury complications and mortality were assessed., Results: In total, 142 patients with surgical BBMI were included. Of these, 116 and 26 patients were assigned to the BAC-negative and BAC-positive groups, respectively. The overall injury severity, injury pattern, and age were comparable between the groups. The patients in the BAC-positive group had a significantly lower systolic blood pressure (99 mmHg vs. 119 mmHg; p = 0.046), worse shock index (0.96 vs. 0.82; p = 0.048), and lower percentage and number of packed red blood cells transfused (34.6% vs. 57.8%; p = 0.032 and 0 U vs. 2 U; p = 0.031) than those in the BAC-negative group. Additionally, although not statistically significant, patients in the BAC-positive group had lower leukocyte counts (9,700 cells/mm 3 vs. 11,600 cells/mm 3 ; p = 0.165 ) at the ED. However, significantly reduced percentages of leukocytes ≥ 12,000 cells/mm 3 (26.9% vs. 48.3%; p = 0.048) and ≥ 12,000 or ≤ 4,000 cells/mm 3 (26.9% vs. 50.9%; p = 0.027) were observed in the BAC-positive group at the ED. Furthermore, the 30-day mortality rate did not show statistically significant differences, and there was a higher incidence of bowel-related mortality in the BAC-positive group (11.5% vs. 1.7%, p = 0.043)., Conclusions: For patients with BBMI arriving alive to the hospital, acute alcohol consumption was associated with significantly worse hemodynamic parameters, interfered inflammation status, and higher bowel related mortality rate., (© 2024. The Author(s).)

Objective: The study was performed to explore the association between blood lipids and cognitive impairment in patients with type 2 diabetes mellitus (T2DM)., Methods: This study included 336 patients with T2DM. Relevant clinical data including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A1, apolipoprotein B were collected, and the Mini-Mental State Examination (MMSE) score and Montreal Cognitive Assessment (MoCA) score were used to assess the cognitive function in patients with T2DM., Results: Serum apolipoprotein A1 levels were significantly increased in T2DM patients with cognitive impairment compared with T2DM patients without cognitive impairment (p = 0.017). Serum apolipoprotein A1 levels were significantly negatively correlated with MoCA score (r = - 0.143, p = 0.009) and MMSE score (r = - 0.132, p = 0.016) in patients with T2DM. In multivariable-adjusted regression model, serum apolipoprotein A1 was independently associated with cognitive impairment in patients with T2DM (OR = 5.201, p = 0.024)., Conclusion: Serum apolipoprotein A1 is associated with cognitive impairment in patients with T2DM, but not TC, TG, HDL-C, LDL-C, and apolipoprotein B, indicating that increased serum apolipoprotein A1 may be a risk factor of cognitive impairment in patients with T2DM., (© 2023. The Author(s).)

Background: Organophosphate flame retardants (OPFRs) are commonly used in various consumer products to prevent fire hazards. However, OPFRs have been linked to several health problems, including cancer. This study aimed to investigate the association between urine levels of OPFRs and endometrial cancer (EC), and to explore the correlation between concentrations of parent OPFR compounds and their metabolites., Methods: Urine samples from 76 EC patients and 76 healthy controls were collected and analyzed for the levels of five common parent OPFRs and their respective metabolites. Propensity score matching was applied to account for differences in baseline characteristics between the two participant groups. Significantly higher levels of OPFRs in EC patients were identified, and logistic regression models were used to determine whether elevated OPFRs were associated with EC and to explore whether any lifestyle behaviors contributed to the increased OPFR levels. Spearman's rank correlation coefficients between the concentrations of the parent compounds and their metabolites were calculated., Results: Out of the ten OPFRs studied, the median urine levels of bis(1,3-dichloro-2-propyl) phosphate (BDCPP), tris(2-butoxyethyl) phosphate (TBEP), and di-(2-butoxyethyl) phosphate (DBEP) were significantly higher in EC patients compared to healthy controls. After matching 41 patients with 41 controls, multiple logistic regression analysis revealed that only BDCPP (OR 4.274; 95% CI 1.172-15.592) was an independent factor associated with EC. A lifestyle questionnaire survey found that urine BDCPP levels were related to age (OR 4.294; 95% CI 1.015-18.164), meals eaten out (OR 4.238; 95% CI 1.454-12.354), and consumption of chilled-ready meals (OR 0.118; 95% CI 0.014-0.985). A positive correlation was only observed between the concentrations of TBEP and its metabolite DBEP; other correlations were not significant., Conclusion: We concluded that higher urine BDCPP level was an independent factor associated with EC, and higher BDCPP levels were related to aging, more meals eaten out, and fewer chilled-ready meals. These findings highlight the potential hazard of long-term OPFR exposure on the development of EC.

The management of blunt abdominopelvic trauma with combined hemoperitoneum and pelvic fractures is challenging for trauma surgeons. Although angioembolization can achieve hemostasis in most visceral organ injuries and pelvic fractures after blunt abdominal trauma, it cannot effectively control hemorrhage in patients with blunt bowel mesenteric injury (BBMI). This study aimed to determine the risk factors associated with hemodynamically unstable patients with BBMI and to test the hypothesis that pelvic fracture is an independent risk factor for patients with unstable BBMI and concomitant pelvic fracture to guide the therapeutic sequence for difficult-to-manage patients. This retrospective study reviewed the data of hospitalized patients with trauma between 2009 and 2021 and included 158 adult patients with surgically proven BBMI. The patients were divided on the basis of the presence of a shock episode before emergency laparotomy. The shock group included 44.3% of all patients in the study (n = 70). Clinical injury severity and prognosis for patients in the shock group were poorer than those for patients in the non-shock group, and more invasive treatments and transfusions were performed for patients in the shock group than for those in the non-shock group. Pelvic fractures were more frequently associated with the shock group than with the non-shock group (21.4% vs. 5.7%; p = 0.003). In multivariate analysis, the presence of intracerebral hemorrhage (odds ratio [OR] = 10.87, 95% confidence intervals [CIs]: 1.70-69.75) and rib fracture (OR = 5.94, 95% CIs = 1.06-33.45) was identified as an independent predictor of shock, whereas the effect of pelvic fracture did not achieve statistical significance (OR = 2.94, 95% CIs = 0.66-13.13) after adjusting for confounding factors. For patients with BBMI, outcomes need to be improved during early diagnosis, and treatments should be expeditiously performed on the basis of the rapid identification of unstable hemodynamic status. Our results support the recommendation of emergency laparotomy in unstable patients with concomitant pelvic fractures, followed by damage control TAE if needed.

Chondrosarcoma is the second most common type of bone cancer. At present, the most effective clinical course of action is surgical resection. Cisplatin is the chemotherapeutic medication most widely used for the treatment of chondrosarcoma; however, its effectiveness is severely hampered by drug resistance. In the current study, we compared cisplatin-resistant chondrosarcoma SW1353 cells with their parental cells via RNA sequencing. Our analysis revealed that glutamine metabolism is highly activated in resistant cells but glucose metabolism is not. Amphiregulin (AR), a ligand of the epidermal growth factor receptor, enhances glutamine metabolism and supports cisplatin resistance in human chondrosarcoma by promoting NADPH production and inhibiting reactive oxygen species (ROS) accumulation. The MEK, ERK, and NrF2 signaling pathways were shown to regulate AR-mediated alanine-serine-cysteine transporter 2 (ASCT2; also called SLC1A5) and glutaminase (GLS) expression as well as glutamine metabolism in cisplatin-resistant chondrosarcoma. The knockdown of AR expression in cisplatin-resistant chondrosarcoma cells was shown to reduce the expression of SLC1A5 and GLS in vivo . These results indicate that AR and glutamine metabolism are worth pursuing as therapeutic targets in dealing with cisplatin-resistant human chondrosarcoma., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Organophosphate flame retardants (OPFRs) are ubiquitous in the environment. The compositions and concentrations of different OPFRs metabolites vary in different environments depending on different human activities. The objective of the present study was to evaluate the exposure of different age groups to OPFRs in Taiwan., Methods: Volunteers provided urine samples and responded to questionnaires including demographic factors, underlying disease, lifestyle information, and occupation from October 2021 to January 2022. OPFR measurements were performed using a Waters Acquity Ultra-Performance Liquid Chromatography system coupled with a Waters Xevo TQ-XS mass spectrometer., Results: A total of 391 volunteers (74 children and 317 adults) were enrolled in this study. The concentrations (presented as μg/g creatinine) of bis(1,3-dichloro-2-propyl) phosphate (BDCPP, p  = 0.029) and tri-n-butyl phosphate (TNBP, p  = 0.008) were higher in the adult group, while the concentrations of bis-2-chloroethyl phosphate (BCEP, p  = 0.024), diphenyl phosphate (DPHP, p  < 0.001), tris(1,3-dichloro-2-propyl) phosphate (TDCPP, p  = 0.009), and Tris(2-butoxyethyl) phosphate (TBEP, p  = 0.007) were higher in the child group. Compared with school age children (>6 years), the concentration of di(2-n-butoxyethyl) phthalate (DBEP, 1.14 vs. 0.20 μg/g creatinine, p  = 0.001), DPHP (1.23 vs. 0.54 μg/g creatinine, p  = 0.036), TBEP (1.63 vs. 0.29 μg/g creatinine, p  < 0.001), and the sum of OPFR metabolites (ΣOPFRs, 6.58 vs. 2.04 μg/g creatinine, p  < 0.001) were statistically higher in preschool-aged children. After adjusting for confounding factors, pre-school age [odds ratio (OR): 4.579, 95% confidence interval (CI): 1.389-13.115] and current smoker (OR: 5.328, 95%CI: 1.858-14.955) were independently associated with the risk of ΣOPFRs higher than 90 percentile., Conclusion: This study revealed the distribution of different OPFRs metabolites in children and adults. DBEP, DPHP, TBEP, and ΣOPFR were higher in preschool-aged children. Pre-school age and current smoking status were independent risk factors for ΣOPFRs higher than 90 percentile., 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 © 2023 Cheng, Wang, Pan, Chen, Huang, Li, Wang, Wang, Lee, Tsai, Ou and Kung.)

Background: Artemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A. argyi and its constituents in reducing the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated in this study., Results: Among the phytochemicals in A. argyi, eriodictyol and umbelliferone were identified to target transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) proteins, the essential factors for the cellular entry of SARS-CoV-2, in both FRET-based enzymatic assays and molecular docking analyses. These two ingredients of A. argyi suppressed the infection of ACE2-expressed HEK-293 T cells with lentiviral-based pseudo-particles (Vpp) expressing wild-type and variants of SARS-CoV-2 spike (S) protein (SARS-CoV-2 S-Vpp) via interrupting the interaction between S protein and cellular receptor ACE2 and reducing the expressions of ACE2 and TMPRSS2. Oral administration with umbelliferone efficiently prevented the SARS-CoV-2 S-Vpp-induced inflammation in the lung tissues of BALB/c mice., Conclusions: Eriodictyol and umbelliferone, the phytochemicals of Artemisia argyi, potentially suppress the cellular entry of SARS-CoV-2 by preventing the protein binding activity of the S protein to ACE2., (© 2023. The Author(s).)

ST-segment elevation myocardial infarction (STEMI), one of the primary factors leading to global mortality, has been shown through epidemiological studies to have a relationship with short-term exposure to air pollutants; however, the association between air pollutants and the outcome of STEMI has not been well studied. The aim of this study was to estimate the impact of air pollutants on the outcomes of STEMI. Data on particulate matter <2.5 μm (PM 2.5 ), <10 μm (PM 10 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) at each of the 11 air monitoring stations in Kaohsiung City were collected between 1 January 2012 and 31 December 2017. Medical records of non-trauma patients aged > 20 years who had presented to the Emergency Department (ED) with a principal diagnosis of STEMI were extracted. The primary outcome measure was in-hospital mortality. After adjusting for potential confounders and meteorological variables, we found that an increase in the interquartile range (IQR) in NO 2 was associated with an elevated risk of in-hospital mortality in patients with STEMI. Moreover, there was an observed higher risk of in-hospital mortality associated with an increase in the IQR of NO 2 during the warm season, specifically in lag 3 (3 days prior to the onset, OR = 3.266; 95%CI: 1.203-8.864, p = 0.02). Conversely, an IQR increase in PM 10 was associated with an increased risk of in-hospital mortality in patients with STEMI in lag 3 (OR = 2.792; 95%CI: 1.115-6.993, p = 0.028) during the cold season. Our study suggests that exposure to NO 2 (during the warm season) and PM 10 (during the cold season) may contribute to a higher risk of poor prognosis in patients with STEMI.

Background: Organophosphate flame retardants (OPFRs) are widely distributed in the environment and their metabolites are observed in urine, but little is known regarding OPFRs in a broad-spectrum young population from newborns to those aged 18 years., Objectives: Investigate urinary levels of OPFRs and OPFR metabolites in Taiwanese infants, young children, schoolchildren, and adolescents within the general population., Methods: Different age groups of subjects (n=136) were recruited from southern Taiwan to detect 10 OPFR metabolites in urine samples. Associations between urinary OPFRs and their corresponding metabolites and potential health status were also examined., Results: The mean level of urinary Σ 10 OPFR in this broad-spectrum young population is 2.25 μg/L (standard deviation (SD) of 1.91 μg/L). Σ 10 OPFR metabolites in urine are 3.25 ± 2.84, 3.06 ± 2.21, 1.75 ± 1.10, and 2.32 ± 2.29 μg/L in the age groups comprising of newborns, 1-5 year-olds, 6-10 year-olds, and 11-18 year-olds, respectively, and borderline significant differences were found in the different age groups ( p =0.125). The OPFR metabolites of TCEP, BCEP, DPHP, TBEP, DBEP, and BDCPP predominate in urine and comprise more than 90% of the total. TBEP was highly correlated with DBEP in this population (r=0.845, p <0.001). The estimated daily intake (EDI) of Σ 5 OPFRs (TDCPP, TCEP, TBEP, TNBP, and TPHP) was 2,230, 461, 130, and 184 ng/kg bw/day for newborns, 1-5 yr children, 6-10 yr children, and 11-17 yr adolescents, respectively. The EDI of Σ 5 OPFRs for newborns was 4.83-17.2 times higher than the other age groups. Urinary OPFR metabolites are significantly correlated with birth length and chest circumference in newborns., Conclusion: To our knowledge, this is the first investigation of urinary OPFR metabolite levels in a broad-spectrum young population. There tended to be higher exposure rates in both newborns and pre-schoolers, though little is known about their exposure levels or factors leading to exposure in the young population. Further studies should clarify the exposure levels and factor relationships., 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 © 2023 Chen, Chen, Tsai, Lu, You, Chen, Huang, Tsai, Cheng, Kung, Li, Wang, Ou, Lee, Chang, Hashim, Chao and Wang.)

There has been a long-standing debate about the mechanism of the unusual superconductivity in alkali-intercalated fullerides. In this Letter, using high-resolution angle-resolved photoemission spectroscopy, we systematically investigate the electronic structures of superconducting K&#95;{3}C&#95;{60} thin films. We observe a dispersive energy band crossing the Fermi level with the occupied bandwidth of about 130 meV. The measured band structure shows prominent quasiparticle kinks and a replica band involving the Jahn-Teller active phonon modes, which reflects strong electron-phonon coupling in the system. The electron-phonon coupling constant is estimated to be about 1.2, which dominates the quasiparticle mass renormalization. Moreover, we observe an isotropic nodeless superconducting gap beyond the mean-field estimation (2Δ/k&#95;{B}T&#95;{c}≈5). Both the large electron-phonon coupling constant and large reduced superconducting gap suggest a strong-coupling superconductivity in K&#95;{3}C&#95;{60}, while the electronic correlation effect is suggested by the observation of a waterfall-like band dispersion and the small bandwidth compared with the effective Coulomb interaction. Our results not only directly visualize the crucial band structure but also provide important insights into the mechanism of the unusual superconductivity of fulleride compounds.

Importance: Early awareness of Kawasaki disease (KD) helps physicians administer appropriate therapy to prevent acquired heart disease in children. However, diagnosing KD is challenging and relies largely on subjective diagnosis criteria., Objective: To develop a prediction model using machine learning with objective parameters to differentiate children with KD from other febrile children., Design, Setting, and Participants: This diagnostic study included 74 641 febrile children younger than 5 years who were recruited from 4 hospitals, including 2 medical centers and 2 regional hospitals, between January 1, 2010, and December 31, 2019. Statistical analysis was performed from October 2021 to February 2023., Main Outcomes and Measures: Demographic data and laboratory values from electronic medical records, including complete blood cell count with differential, urinalysis, and biochemistry, were collected as possible parameters. The primary outcome was whether the febrile children fulfilled the diagnostic criteria of KD. The supervised eXtreme Gradient Boosting (XGBoost) machine learning method was applied to establish a prediction model. The confusion matrix and likelihood ratio were used to evaluate the performance of the prediction model., Results: This study included a total of 1142 patients with KD (mean [SD] age, 1.1 [0.8] years; 687 male patients [60.2%]) and 73 499 febrile children (mean [SD] age, 1.6 [1.4] years; 41 465 male patients [56.4%]) comprising the control group. The KD group was predominantly male (odds ratio, 1.79; 95% CI, 1.55-2.06) with younger age (mean difference, -0.6 years [95% CI, -0.6 to -0.5 years]) compared with the control group. The prediction model's best performance in the testing set was able to achieve 92.5% sensitivity, 97.3% specificity, 34.5% positive predictive value, 99.9% negative predictive value, and a positive likelihood ratio of 34.0, which indicates outstanding performance. The area under the receiver operating characteristic curve of the prediction model was 0.980 (95% CI, 0.974-0.987)., Conclusions and Relevance: This diagnostic study suggests that results of objective laboratory tests had the potential to be predictors of KD. Furthermore, these findings suggested that machine learning with XGBoost can help physicians differentiate children with KD from other febrile children in pediatric emergency departments with excellent sensitivity, specificity, and accuracy.

The injection-molding process is a non-linear process, and the product quality and long-term production stability are affected by several factors. To stabilize the product quality effected by these factors, this research establishes a standard process parameter setup procedure and an adaptive process control system based on the data collected by a nozzle pressure sensor and a tie-bar strain gauge to achieve this goal. In this research, process parameters such as the V/P switchover point, injection speed, packing pressure, and clamping force are sequentially optimized based on the characteristics of the pressure profile. After the optimization process, this research defines the standard quality characteristics through the optimized process parameters and combines it with the adaptive process control system in order to achieve the purpose of automatic adjustment of the machine and maintain high-quality production. Finally, three different viscosity materials are used to verify the effectiveness of the optimization procedure and the adaptive process control system. With the system, the variation of product weight was reduced to 0.106%, 0.092%, and 0.079%, respectively.

Background: Several risk scores have been developed to predict and analyze in-hospital mortality and short- and long-term outcomes of ST-elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (PPCI); these can classify patients as having a high or low risk of death or complications., Objective: To compare the prognostic precision of four risk scores for predicting in-hospital mortality in patients with STEMI treated with PPCI., Methods: We performed a retrospective cohort analysis of patients with STEMI who underwent PPCI between 2012 and 2019 ( N  = 1346). GRACE (Global Registry of Acute Cardiac Events), CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications), Zwolle, and TIMI (Thrombolysis in Myocardial Infarction) risk scores were calculated for each patient according to different variables. We evaluated the predictive accuracy of these scores for in-hospital mortality using the C statistic, which was obtained using logistic regression and receiver operating characteristic curves., Results: The GRACE, CADILLAC, Zwolle, and TIMI risk scores all had good predictive precision for in-hospital mortality, with C statistics ranging from 0.842 to 0.923. The GRACE and CADILLAC risk scores were found to be superior., Conclusions: All GRACE, CADILLAC, Zwolle, and TIMI risk scores showed a high predictive value for in-hospital mortality due to all causes in patients with STEMI treated with PPCI. The GRACE and CADILLAC risk scores revealed a better accuracy for predicting in-hospital mortality than the Zwolle and TIMI risk scores., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Chih-Hwa Wang et al.)

Blood glucose (BG) monitoring is important for critically ill patients, as poor sugar control has been associated with increased mortality in hospitalized patients. However, constant BG monitoring can be resource-intensive and pose a healthcare burden in clinical practice. In this study, we aimed to develop a personalized machine-learning model to predict dysglycemia from electrocardiogram (ECG) data. We used the Medical Information Mart for Intensive Care III database as our source of data and obtained more than 20 ECG records from each included patient during a single hospital admission. We focused on lead II recordings, along with corresponding blood sugar data. We processed the data and used ECG features from each heartbeat as inputs to develop a one-class support vector machine algorithm to predict dysglycemia. The model was able to predict dysglycemia using a single heartbeat with an AUC of 0.92 ± 0.09, a sensitivity of 0.92 ± 0.10, and specificity of 0.84 ± 0.04. After applying 10 s majority voting, the AUC of the model's dysglycemia prediction increased to 0.97 ± 0.06. This study showed that a personalized machine-learning algorithm can accurately detect dysglycemia from a single-lead ECG.

Background: Hyperkalemia is a critical condition, especially in intensive care units. So far, there have been no accurate and noninvasive methods for recognizing hyperkalemia events on ambulatory electrocardiogram monitors., Objective: This study aimed to improve the accuracy of hyperkalemia predictions from ambulatory electrocardiogram (ECG) monitors using a personalized transfer learning method; this would be done by training a generic model and refining it with personal data., Methods: This retrospective cohort study used open source data from the Waveform Database Matched Subset of the Medical Information Mart From Intensive Care III (MIMIC-III). We included patients with multiple serum potassium test results and matched ECG data from the MIMIC-III database. A 1D convolutional neural network-based deep learning model was first developed to predict hyperkalemia in a generic population. Once the model achieved a state-of-the-art performance, it was used in an active transfer learning process to perform patient-adaptive heartbeat classification tasks., Results: The results show that by acquiring data from each new patient, the personalized model can improve the accuracy of hyperkalemia detection significantly, from an average of 0.604 (SD 0.211) to 0.980 (SD 0.078), when compared with the generic model. Moreover, the area under the receiver operating characteristic curve level improved from 0.729 (SD 0.240) to 0.945 (SD 0.094)., Conclusions: By using the deep transfer learning method, we were able to build a clinical standard model for hyperkalemia detection using ambulatory ECG monitors. These findings could potentially be extended to applications that continuously monitor one's ECGs for early alerts of hyperkalemia and help avoid unnecessary blood tests., (©I-Min Chiu, Jhu-Yin Cheng, Tien-Yu Chen, Yi-Min Wang, Chi-Yung Cheng, Chia-Te Kung, Fu-Jen Cheng, Fei-Fei Flora Yau, Chun-Hung Richard Lin. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 05.12.2022.)

Organophosphate flame retardants (OPFRs) are emerging and widespread environmental pollutants with potential health hazards, including nephrotoxicity. However, the exposure patterns and nephrotoxic potential of OPFRs are yet to be investigated in patients with chronic kidney disease (CKD). We conducted a cross-sectional study involving 166 patients with CKD stratified by estimated glomerular filtration rate (eGFR) and severity of proteinuria. The urinary concentrations of 10 OPFR compounds were measured to evaluate the exposure patterns. Clinical and urinary OPFR profiles were compared among subgroups to identify whether the OPFR compounds were independently correlated with eGFR and proteinuria. Additionally, lifestyle factors were compared among subgroups stratified by median concentrations of urinary OPFR compounds associated with renal disease severity. This study revealed universal exposure to OPFRs in the CKD population, with an overall urinary detection rate of 98.80 %. Furthermore, after adjusting for covariates, the urinary concentration of bis(2-chloroethyl) phosphate (BCEP) was identified as an independent predictor of lower eGFR (low vs high eGFR, odds ratio (OR) (95 % confidence interval (CI)), 1.761 (1.032-3.005) per log μg/g creatinine, p = 0.038), and the urinary concentration of bis(2-butoxyethyl) phosphate (BBOEP) was independently correlated with overt proteinuria in CKD patients (with vs without overt proteinuria, OR (95 % CI), 1.813 (1.065-3.086) per log μg/g creatinine, p = 0.028). Moreover, frequent seafood consumption was negatively correlated with urinary BCEP concentration (high vs low BCEP, OR (95 % CI), 0.455 (0.228-0.908), p = 0.025), and age was inversely associated with urinary BBOEP concentration (high vs low BBOEP, OR (95 % CI), 0.968 (0.937-0.999) per year, p = 0.048). In conclusion, our investigation highlights the extensive exposure to OPFRs and the independent association between renal disease severity and urinary BCEP/BBOEP concentrations in the CKD population, indicating the nephrotoxic potential of these pollutants., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Exposure to fine particulate matter with an aerodynamic diameter of ≤2.5 μm (PM 2.5 ) is associated with adverse health effects. This study aimed to evaluate the toxic effects of the constituents of PM 2.5 on mouse kidneys., Methods: We collected PM 2.5 near an industrial complex located in southern Kaohsiung, Taiwan, that was divided into water extract and insoluble particles. Male C57BL/6 mice were divided into five groups: control, low- and high-dose insoluble particle exposure, and low- and high-dose water extract exposure. Biochemical analysis, Western blot analysis, histological examination, and immunohistochemistry were performed to evaluate the impact of PM 2.5 constituents on mice kidneys., Results: PM 2.5 was collected from January 1, 2021, to February 8, 2021, from an industrial complex in Kaohsiung, Taiwan. Metallic element analysis showed that Pb, Ni, V, and Ti were non-essential metals with enrichment factors >10. Polycyclic aromatic hydrocarbon and nitrate polycyclic aromatic hydrocarbon analyses revealed that the toxic equivalents are, in the order, benzo(a)pyrene (BaP), indeno(1,2,3-cd) pyrene (IP), dibenzo(a,h)anthracene (DBA), and benzo(b)fluoranthene (BbF), which are potential carcinogens. Both water extract and insoluble particle exposure induced inflammatory cytokine upregulation, inflammatory cell infiltration, antioxidant activity downregulation, and elevation of kidney injury molecule 1 (KIM-1) level in mouse kidneys. A dose-dependent effect of PM 2.5 water extract and insoluble particle exposure on angiotensin converter enzyme 2 downregulation in mouse kidneys was observed., Conclusion: We found that water-soluble extract and insoluble particles of PM 2.5 could induce oxidative stress and inflammatory reactions, influence the regulation of renin-angiotensin system (RAS), and lead to kidney injury marker level elevation in mouse kidneys. The lowest-observed-adverse-effect level for renal toxicity in mice was 40 μg water-soluble extract/insoluble particle inhalation per week, which was approximately equal to the ambient PM 2.5 concentration of 44 μg/m 3 for mice., 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Cigarette smoking is the main risk factor for lung cancer. MSCs in the TME promoting tumor angiogenesis, growth, and metastasis. SIBLING proteins enable cancer cells to extend, invade and metastasize., Objectives: Cigarette smoke promotes the progression and metastasis of lung cancer, although how this occurs is poorly understood. We evaluated the impact of whether cigarette smoking motivates SIBLING protein expression and is involved in MSC-mediated lung tumor metastasis., Methods: We investigated the expression of OPN in the Gene Expression Omnibus (GEO) databases and confirmed the results by immunohistochemistry (IHC), qPCR and Western blotting (WB) of lung cancer cells and tissues. The effect of OPN on the recruitment and adhesion of mesenchymal stem cells (MSCs) to lung cancer cells and lung cancers metastasis was investigated by Transwell, adhesion assays. A series of in vitro and in vivo experiments were conducted to demonstrate the mechanisms by which OPN modulates recruitment and adhesion of MSCs to lung cancer cells and lung cancer metastasis., Results: Cigarette smoke extract (CSE) and benzo[α]pyrene (B[α]P) increased levels of OPN expression and facilitated the recruitment and adhesion of MSCs to lung cancer cells via JAK2/STAT3 signaling. We also observed that OPN promotes tumor-associated MSC (TA-MSC) formation through the OPN receptor (integrins αvβ1, αvβ3, αvβ5 or CD44), inducing lung cancer cell migration and invasion. In an orthotopic mouse model of lung cancer, increases in OPN expression promoted by cigarette smoke upregulated MSC recruitment and facilitated lung cancer metastasis. Knockdown of OPN expression inhibited cigarette smoke-induced lung cancer metastasis in vivo., Conclusion: Cigarette smoke increases OPN expression through the JAK2/STAT3 signaling pathway to attract MSC cell recruitment and promote lung cancer metastasis. Our findings offer important insights into how lung cancer metastasis develops in smokers., (Copyright © 2022. Production and hosting by Elsevier B.V.)

This study systematically evaluated the efficacy and safety of Ganshuang Granules in the treatment of liver injury, so as to provide a new choice for patients with liver injury. CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, and Web of Science were systematically searched for the randomized controlled trial(RCT) of Ganshuang Granules in the treatment of liver injury. RevMan 5.4 was employed to perform the Meta-analysis of the included RCT according to the Cochrane Handbook 5.1. A total of 3 005 patients were included in 38 RCTs, including 1 536 patients in the observation group and 1 469 in the control group. The results of Meta-analysis showed that Ganshuang Granules combined with conventional therapy was superior to the therapy in the control group in reducing alanine aminotransferase(ALT)(MD=-24.12, 95%CI[-32.17,-16.07], P&lt;0.000 01), aspartate aminotransferase(AST)(MD=-23.24, 95%CI[-29.70,-16.78], P&lt;0.000 01), total bilirubin(TBiL)(MD=-12.42, 95%CI[-14.62,-10.22], P&lt;0.000 01), and gamma-glutamyl transpeptidase(GGT)(MD=-21.32, 95%CI[-33.61,-9.03], P=0.000 7). Compared with the control group, the observation group had witnessed a significant increase in albumin(ALB)(MD=4.94, 95%CI[4.44, 5.45], P&lt;0.000 01). No significant adverse reactions were observed. According to the available data, Ganshuang Granules combined with conventional therapy can effectively recover the levels of ALT, AST, TBiL, GGT, and ALB in patients with liver injury. Nevertheless, high-quality RCT is still needed to further verify the findings of this study.

Background: ST-segment elevation myocardial infarction (STEMI) is a leading cause of death worldwide. A shock index (SI), modified SI (MSI), delta-SI, and shock index-C (SIC) are known predictors of STEMI. This retrospective cohort study was designed to compare the predictive value of the SI, MSI, delta-SI, and SIC with thrombolysis in myocardial infarction (TIMI) risk scales. Method: Patients > 20 years old with STEMI who underwent percutaneous coronary intervention (PCI) were included. Receiver operating characteristic (ROC) curve analysis with the Youden index was performed to calculate the optimal cutoff values for these predictors. Results: Overall, 1552 adult STEMI cases were analyzed. The thresholds for the emergency department (ED) SI, MSI, SIC, and TIMI risk scales for in-hospital mortality were 0.75, 0.97, 21.00, and 5.5, respectively. Accordingly, ED SIC had better predictive power than the ED SI and ED MSI. The predictive power was relatively higher than TIMI risk scales, but the difference did not achieve statistical significance. After adjusting for confounding factors, the ED SI > 0.75, MSI > 0.97, SIC > 21.0, and TIMI risk scales > 5.5 were statistically and significantly associated with in-hospital mortality of STEMI. Compared with the ED SI and MSI, SIC (>21.0) had better sensitivity (67.2%, 95% CI, 58.6−75.9%), specificity (83.5%, 95% CI, 81.6−85.4%), PPV (24.8%, 95% CI, 20.2−29.6%), and NPV (96.9%, 95% CI, 96.0−97.9%) for in-hospital mortality of STEMI. Conclusions: SIC had better discrimination ability than the SI, MSI, and delta-SI. Compared with the TIMI risk scales, the ACU value of SIC was still higher. Therefore, SIC might be a convenient and rapid tool for predicting the outcome of STEMI., Competing Interests: The authors declare no conflict of interest.

Tris(2-butoxyethyl) phosphate (TBEP) is one of the most abundant organophosphate flame retardants in the environment. This study aimed to evaluate the effect of TBEP exposure during adolescence on male reproductive function in adult rats. Male Sprague-Dawley rats were treated with 20 and 200 mg/kg body weight of TBEP or corn oil from postnatal day (PND) 42 to PND 105. A significant increase in the proportion of sperm with abnormal morphology (flattened head and bent tail) and superoxide anion (O 2 -. ) production in the sperm of the 200 mg/kg treated group was observed (p < 0.05). Excessive production of sperm hydrogen peroxide (H 2 O 2 ) was found in both the 20 and 200 mg/kg treatment groups (p < 0.05). Disruption of testicular structure was observed in the 20 and 200 mg/kg treated groups and seminiferous tubule degeneration was observed in the 200 mg/kg treated group. Our study demonstrated the adverse effects of TBEP on male reproductive function in rats., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Carbon monoxide poisoning (COP), resulting from accidental and intentional exposure, is a leading cause of fatal poisoning worldwide. Except for early death, neurological sequelae are common and impose a large burden on patients, caregivers, and the society., Materials and Methods: This retrospective study included patients who visited the emergency departments (EDs) of the medical institutes of Chang Gung Memorial Hospital after COP with a carboxyhemoglobin level > 10% between January 2009 and October 2018. Patients who experienced out-of-hospital cardiac arrest (OHCA) were excluded. Poor outcome was defined as mortality or a Glasgow coma scale (GCS) <13 at discharge. Stepwise regression analysis was performed, and a receiver operating characteristic (ROC) curve was applied to analyze our newly created scoring system for prognosis prediction., Results: This study enrolled 1171 patients. Fire scene (F) (aOR, 20.635; 95% CI, 8.345-51.023), intentional CO exposure (I) (aOR, 2.634; 95% CI, 1.335-5.196), respiratory failure (R) (aOR, 9.944; 95% CI, 5.533-17.873), every point of reduced GCS (E) (aOR, 1.253; 95% CI, 1.186-1.323), and diabetes mellitus (D) (aOR, 2.749; 95% CI, 1.201-6.292) were identified as predictors of poor outcomes. The FIRED score was created., Conclusion: The FIRED score could predict the outcomes of non-OHCA patients with a carboxyhemoglobin level > 10% after COP using five factors that can be obtained by history taking and basic examination. An FIRED score ≥ 10 was associated with a poor outcome (sensitivity, 89.6%; specificity, 82.4%; AUC0.930)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Stroke is a leading cause of death, and air pollution is associated with stroke hospitalization. However, the susceptibility factors are unclear. Retrospective studies from 2014 to 2018 in Kaohsiung, Taiwan, were analyzed. Adult patients (>17 years) admitted to a medical center with stroke diagnosis were enrolled and patient characteristics and comorbidities were recorded. Air pollutant measurements, including those of particulate matter (PM) with aerodynamic diameters < 10 μm (PM10) and < 2.5 μm (PM2.5), nitrogen dioxide (NO2), and ozone (O3), were collected from air quality monitoring stations. During the study period, interquartile range (IQR) increments in PM2.5 on lag3 and lag4 were 12.3% (95% CI, 1.1−24.7%) and 11.5% (95% CI, 0.3−23.9%) concerning the risk of stroke hospitalization, respectively. Subgroup analysis revealed that the risk of stroke hospitalization after exposure to PM2.5 was greater for those with advanced age (≥80 years, interaction p = 0.045) and hypertension (interaction p = 0.034), after adjusting for temperature and humidity. A dose-dependent effect of PM2.5 on stroke hospitalization was evident. This is one of few studies focusing on the health effects of PM2.5 for patients with risk factors of stroke. We found that patients with risk factors, such as advanced age and hypertension, are more susceptible to PM2.5 impacts on stroke hospitalization.

The level and composition of air pollution have changed during the coronavirus disease 2019 (COVID-19) pandemic. However, the association between air pollution and pediatric respiratory disease emergency department (ED) visits during the COVID-19 pandemic remains unclear. The study was retrospectively conducted between 2017 and 2020 in Kaohsiung, Taiwan, from 1 January 2020 to 1 May 2020, defined as the period of the COVID-19 pandemic, and 1 January 2017 to 31 May 2019, defined as the pre-COVID-19 pandemic period. We enrolled patients under 17 years old who visited the ED in a medical center and were diagnosed with respiratory diseases such as pneumonia, asthma, bronchitis, and acute pharyngitis. Measurements of particulate matter (PM) with aerodynamic diameters of <10 μm (PM10) and < 2.5 μm (PM2.5), nitrogen dioxide (NO2), and Ozone (O3) were collected. During the COVID-19 pandemic, an increase in the interquartile range of PM2.5, PM10, and NO2 levels was associated with increases of 72.5% (95% confidence interval [CI], 50.5−97.7%), 98.0% (95% CI, 70.7−129.6%), and 54.7% (95% CI, 38.7−72.6%), respectively, in the risk of pediatric respiratory disease ED visits on lag 1, which were greater than those in the pre-COVID-19 pandemic period. After adjusting for temperature and humidity, the risk of pediatric respiratory diseases after exposure to PM2.5 (inter p = 0.001) and PM10 (inter p < 0.001) was higher during the COVID-19 pandemic. PM2.5, PM10, and NO2 may play important roles in pediatric respiratory events in Kaohsiung, Taiwan. Compared with the pre-COVID-19 pandemic period, the levels of PM2.5 and PM10 were lower; however, the levels were related to a greater increase in ED during the COVID-19 pandemic.

This research developed an adaptive control system for injection molding process. The purpose of this control system is to adaptively maintain the consistency of product quality by minimize the mass variation of injection molded parts. The adaptive control system works with the information collected through two sensors installed in the machine only-the injection nozzle pressure sensor and the temperature sensor. In this research, preliminary experiments are purposed to find master pressure curve that relates to product quality. Viscosity index, peak pressure, and timing of the peak pressure are used to characterize the pressure curve. The correlation between product quality and parameters such as switchover position and injection speed were used to produce a training data for back propagation neural network (BPNN) to compute weight and bias which are applied on the adaptive control system. By using this system, the variation of part weight is maintained to be as low as 0.14%.

Background. Out-of-hospital cardiac arrest (OHCA) remains a challenge for emergency physicians, given the poor prognosis. In 2020, MIRACLE2, a new and easier to apply score, was established to predict the neurological outcome of OHCA. Objective. The aim of this study is to compare the discrimination of MIRACLE2 score with cardiac arrest hospital prognosis (CAHP) score for OHCA neurologic outcomes. Methods. This retrospective cohort study was conducted between January 2015 and December 2019. Adult patients (>17 years) with cardiac arrest who were brought to the hospital by an emergency medical service crew were included. Deaths due to trauma, burn, drowning, resuscitation not initiated due to pre-ordered “do not resuscitate” orders, and patients who did not achieve return of spontaneous circulation were excluded. Receiver operating characteristic curve analysis with Youden Index was performed to calculate optimal cut-off values for both scores. Results. Overall, 200 adult OHCA cases were analyzed. The threshold of the MIRACLE2 score for favorable neurologic outcomes was 5.5, with an area under the curve (AUC) value of 0.70 (0.61−0.80, p < 0.001); the threshold of the CAHP score was 223.4, with an AUC of 0.77 (0.68−0.86, p < 0.001). On setting the MIRACLE2 score cut-off value, we documented 64.7% sensitivity (95% confidence interval [CI], 56.9−71.9%), 66.7.0% specificity (95% CI, 48.2−82.0%), 90.8% positive predictive value (PPV; 95% CI, 85.6−94.2%), and 27.2% negative predictive value (NPV; 95% CI, 21.4−33.9%). On establishing a CAHP cut-off value, we observed 68.2% sensitivity (95% CI, 60.2−75.5%), 80.6% specificity (95% CI, 62.5−92.6%), 94.6% PPV (95% CI, 88.6%−98.0%), and 33.8% NPV (95% CI, 23.2−45.7%) for unfavorable neurologic outcomes. Conclusions. The CAHP score demonstrated better discrimination than the MIRACLE2 score, affording superior sensitivity, specificity, PPV, and NPV; however, the CAHP score remains relatively difficult to apply. Further studies are warranted to establish scores with better discrimination and ease of application.

This study systematically sorted out the evidence data of the safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM) of Reyanning Mixture in the treatment of acute upper respiratory tract infection(heat-toxin attacking lung syndrome) with the qualitative and quantitative evaluation methods adopted. Based on evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, pharmacoeconomics, and health technology evalua-tion(HTA), the clinical value of Reyanning Mixture was evaluated using multi-criteria decision analysis(MCDA) model, Chinese patent medicine clinical evidence, and value evaluation software(CSC v2.0). The SRS monitoring data, Meta-analysis, and other safety evidence showed that the main adverse reactions of Reyanning Mixture were nausea, diarrhea, and rash, and no serious adverse reactions were found. The pharmacovigilance system was sound, and the system was perfect. There was no recall, notification, or interview for unqualified products. Based on the existing research, the evidence was sufficient, and the risk was controllable. Hence, its safety was grade A. Meta-analysis showed that in the treatment of acute upper respiratory tract infection, Reyanning Mixture combined with Amoxicillin Capsules was better than Amoxicillin Capsules alone in shortening the complete fever relief time and improving the cure rate. Besides, it was superior to Shuanghuanglian Granules in shortening the complete fever relief time, cough relief time, nasal congestion relief time, and pharyngeal congestion relief time. The Meta-analysis was conducted based on AMSTAR standard, and its ove-rall quality was proved good. The evidence quality in GRADE system evaluation was medium and low. The quality of evidence was medium, and the clinical value was obvious. Hence, its effectiveness was grade A. The results of pharmacoeconomic research showed that compared with Amoxicillin Capsules, Reyanning Mixture alone or in combination with Amoxicillin Capsules had cost-effectiveness advantages in the treatment of acute upper respiratory tract infection, and the results were stable in sensitivity analysis. According to the CASP economic evaluation checklist, the research problems were clear and the results were reliable. As revealed by the comprehensive evaluation, the evidence quality was sufficient and the result was clear. Its economy was grade B. Reyanning Mixture had multiple therapeutic targets like anti-virus, anti-bacteria, antipyresis, and anti-cough, with good clinical innovation. There were many innovative initiatives in ensuring drug supply, especially at the grass roots, drug safety, and effectiveness, and also multiple innovative contributions to production technology, quality control, scientific and technological research and development, and enterprise management and marketing. Therefore, its innovation was grade B. The dosage form of Reyanning was mixture, which made it convenient for storage and transportation. The usage was easy to be mastered and accepted by doctors and nurses, exhibiting good suitability for clinicians, nurses, pharmacists, and patients who received this drug and basically meeting the needs of clinical medication. The suitability was grade B. The average daily cost of this drug was 8.082 yuan, and the price was low. The treatment cost accounted for a small proportion of the annual disposable income of urban and rural residents, indicating that it was affordable. Reyanning Mixture was available in 31 provinces, cities and autonomous regions, covering 6 910 hospitals. The allocation of hospitals at all levels was more than 50%. There was no shortage or supply restriction of medicinal material resources. The annual production capacity was sufficient to meet the supply demand, so its accessibility was grade A. Reyanning Mixture, sourced from &quot;pneumonia Ⅲ&quot;, has been subjected to a real-world study of its clinical application, with 4 367 cases involved, and the characteristic of TCM was grade B. The comprehensive evaluation results demonstrated that the clinical value score of Reyanning Mixture in the treatment of acute upper respiratory tract infection(heat-toxin attacking lung syndrome) was 0.80, making it rated class A. According to the Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021), it is recommended to convert it into the relevant policy results of basic clinical medication management according to the procedures.

Emergency care is a critical area of medicine whose outcomes are influenced by the time, availability, and accuracy of contextual information. The success of critical or emergency care is determined by the quality and accuracy of the information received during the emergency call and the data collected during emergency transportation. The Internet of Things (IoT) consists of many smart devices and components that communicate via their connection to the Internet, which is used to collect data with sensors that obtain personal health parameters. In the past, most health measurement systems were based on a single dedicated orientation, and few systems had multiple devices on the same platform. In addition to traditional health measurement technologies, most such systems use centralized data transmission, which means that health measurement data have become the exclusive intellectual asset of the system developer. Therefore, this study develops an IoT-based message-broker system that is deployed and demonstrated for five health devices: blood oxygen, blood pressure, forehead temperature, body temperature, and body weight sensors. A central controller accessed by radio-frequency identification (RFID) collects clients' health profiles on the cloud platform. All collected data can be quickly shared, analyzed, and visualized, and the health devices can be changed, added to, and removed reliably when the requirements change. Additionally, following the message queuing telemetry transport (MQTT) protocol, all devices can communicate with each other and be integrated into a higher-level health measurement standard (such as blood pressure plus weight or body temperature plus blood oxygen). We implement a smart healthcare monitoring system (SHMS) and verify its reliability. We use MQTT to establish an open communication format that other organizations can follow to perform individual patient vital sign monitoring in potential applications. The robustness and flexibility of this research can be verified through the addition of other systems. Through this structure, more large-scale health detection devices can be integrated into the method proposed in this research in the future. Personal RFID or health insurance cards can be used for personal services or in medical institutions, and the data can easily be shared through the mechanism of this research. Such information sharing will enable the utilization of medical resources to be maximized., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Yung-Chung Tsao et al.)

Targeting protein kinase C (PKC) family was found to repress the migration and resistance of non-small cell lung cancer cells to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, none of the PKC inhibitors has been approved for anticancer therapy yet due to the limited efficacy in clinical trials, and the underlying mechanisms remain unclear. l-lactic acidosis, a common condition comprising high l-lactate concentration and acidic pH in the tumor microenvironment, has been known to induce tumor metastasis and drug resistance. In this study, l-lactic acid was found to reverse the inhibitory effects of pan-PKC inhibitors GO6983 on PKC activity, cell migration, and EGFR-TKI resistance, but these effects were not affected by the modulators of lactate receptor GPR81. Interestingly, blockade of lactate transporters, monocarboxylate transporter-1 and -4 (MCT1 and MCT4), attenuated the intracellular level of GO6983, and its inhibitory effect on PKC activity, suggesting that lactic acid promotes the resistance to PKC inhibitors by competing for the uptake through these transporters rather than by activating its receptor, GPR81. Our findings explain the underlying mechanisms of the limited response of PKC inhibitors in clinical trials., (© 2021 Wiley Periodicals LLC.)

The microscopic understanding of high-temperature superconductivity in cuprates has been hindered by the apparent complexity of crystal structures in these materials. We used scanning tunneling microscopy and spectroscopy to study the electron-doped copper oxide compound Sr 1- x Nd x CuO 2 , which has only bare cations separating the CuO 2  planes and thus the simplest infinite-layer structure of all cuprate superconductors. Tunneling conductance spectra of the major CuO 2 planes in the superconducting state revealed direct evidence for a nodeless pairing gap, regardless of variation of its magnitude with the local doping of trivalent neodymium. Furthermore, three distinct bosonic modes are observed as multiple peak-dip-hump features outside the superconducting gaps and their respective energies depend little on the spatially varying gaps. As well as the bosonic modes, with energies identical to those of the external, bending and stretching phonons of copper oxides, our findings reveal the origin of the bosonic modes in lattice vibrations rather than spin excitations., (© The Author(s) 2021. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Background: Exposure to glufosinate ammonium, an herbicide used worldwide, can cause CNS and respiratory toxicities. This study aimed to analyze acute human glufosinate ammonium poisoning., Materials and Methods: This multicenter retrospective cohort study involved five medical institutes affiliated with the Chang Gung Memorial Hospital system. Patients with glufosinate ammonium exposure visiting the emergency department (ED) between January 2008 and December 2020 were included., Results: In total, 95 patients were enrolled. Compared to exposure via the non-oral route, patients exposed orally (n = 61) had lower GCS scores, higher mortality rates, and longer hospital lengths of stay (P-value: <0.001, 0.002, and < 0.001, respectively). In the subgroup analysis among oral exposure patients, the survival group had a lower amount of estimated glufosinate ingestion than the non-survival group (10.5 [3.4-27] vs. 40.5 [27-47.3] g, P-value: 0.022), lower rate of substance co-exposure (9 [19.6%] vs. 10 [66.7%] P-value: 0.001), and lower rate of paraquat co-exposure (0 [0%] vs. 7 [46.7%] P < 0.001) compared with the mortality group. In the orally-exposed and non-paraquat co-exposure patients (n = 54), age > 70 years and GCS score < 9 at triage presented a high sensitivity (100.00%, 95% CI: 63.06-100.00%) and medium specificity (58.70%, 95% CI: 43.23-73.00%) in predicting mortality., Conclusion: Old age, change in consciousness, and paraquat co-exposure were associated with higher mortality in human glufosinate poisoning. Age > 70 years and GCS score < 9 at triage could be predictors of mortality in patients with acute oral glufosinate poisoning., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)