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Preventing the progression of acute pancreatitis (AP) to severe acute pancreatitis (SAP) is crucial for AP patients. The use of clinical parameters in laboratory facilities for predicting SAP can be rapid, efficient, and cost-effective. This study aimed to investigate the predictive and prognostic value of collected clinical detection parameters, such as serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels, and their ratios, such as ALP-to-hemoglobin (Hb) and LDH-to-Hb ratios, for the prediction of SAP occurrence, complications, and mortality. In all, 50 healthy controls (CON), 455 patients with mild acute pancreatitis (MAP), 127 patients with moderately severe acute pancreatitis (MSAP), and 93 patients with SAP were included in the study. Thirty clinical parameters were collected, measured, compared, and analyzed. The ratios of ALP/Hb and LDH/Hb were subsequently calculated and evaluated with respect to gender and age and whether they could predict SAP occurrence, complications, and mortality. The results revealed that 15 parameters were significant for the prediction of AP. Furthermore, the following 6 indicators are associated with the occurrence of SAP: ALP, ALP/Hb, LDH, LDH/Hb, CRP, and blood glucose. Among these parameters, the predictive abilities of ALP/Hb and LDH/Hb for SAP were most effective. However, they fail to differentiate between MAP and MSAP or gender in SAP patients. Positive correlations were only observed between the levels of these indicators and age at onset of SAP. In addition, receiver operating characteristic (ROC) curves were generated to predict SAP incidence rates, complications, and mortality. The area under the curve (AUC) values for the ALP/Hb ratio ranged from 0.7097 to 0.7837, whereas those for the LDH/Hb ratio ranged from 0.5043 to 0.7778. These findings suggest that ALP and LDH alone or in combination with Hb possess unique predictive characteristics that may serve as independent factors for predicting SAP occurrence, complications, and mortality; of these, the ALP/Hb ratio is especially predictive of SAP mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aims to investigate the effect of Epstein-Barr virus (EBV) reactivation or EBV reactivation with dexamethasone (DXM) in patients with adverse drug reactions (ADRs) through evaluating the levels of monocyte, macrophage M2/M1, and cytokines, and investigating whether expression of EBV receptor EphA2 could specifically influence EBV activation in ADRs. We performed a prospective longitudinal study to analyze the monocytes, macrophages, M2/M1 ratio, and cytokines, including interleukin (IL)-4, IL-13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IFN-β, C-X-C motif chemokine ligand (CXCL)9, and CXCL10, in patients with maculopapular exanthema (MPE) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and control groups after disease onset. Skin biopsy samples from these patients were subjected to hematoxylin and eosin (H&E) staining to examine tissue architecture and inflammatory cell infiltration, as well as Epstein-Barr virus-encoded RNA (EBER) staining to detect the presence of EBV within the skin lesions. Peripheral blood mononuclear cells collected from these patients were co-cultured with EBV or EBV combined with DXM to assess the impact on monocytes, macrophages, the M2/M1 ratio, and the associated cytokine profile. Furthermore, we sought to identify which cytokines might be crucial in mediating the interaction between the M2/M1 ratio and EBV. EPhA2 expression was evaluated to determine its role in the reactivation of EBV and its correlation with increased viral load in MPE and SJS/TEN patients. Selective depletion of macrophages occurred during the acute stage of SJS/TEN, while a shift towards M2 macrophages was observed in MPE. Both IFN-β and CXCL9 levels were elevated in MPE and SJS/TEN. Additionally, our study demonstrated the presence of EBV in the skin lesions of SJS/TEN and MPE patients through H&E and EBER staining, confirming EBV's involvement in these conditions. Activation of EBV and EBV combined with DXM led to a shift from M1 to M2 macrophages, accompanied by increased levels of IL-4, IFN-γ, and CXCL9 in MPE and SJS/TEN, compared to healthy individuals. Specifically, EBV combined with DXM primarily drove IFN-γ and IL-4 expansions in MPE, while CXCL9 was predominantly elevated in SJS/TEN. The increased IL-4 levels were associated with the relative rise in EBV viral loads after EBV combined with DXM stimulation. Furthermore, EphA2 expression in monocytes was significantly higher in SJS/TEN and MPE patients compared to controls, with further increases on EBV stimulation. This elevation in EPhA2 correlated with increased EBV viral load, particularly in MPE and SJS/TEN patients. The gradual shift from M1 to M2 cell development observed during the clinical course of MPE and SJS/TEN is mediated by the predominance of EBV and EBV with DXM at the acute stage, leading to elevated IL-4, IFN-γ, and CXCL9 levels, which may exacerbate allergic reactions. The elevation in EPhA2 correlated with increased EBV viral load, particularly in MPE and SJS/TEN patients, suggesting that adverse drug reactions may induce EPhA2 expression, facilitating EBV replication and activation. EphA2 could thus serve as an indicator of EBV activation and a marker for assessing the risk of EBV in patients with adverse drug reactions., (© 2024 Japanese Dermatological Association.)

Competing Interests: Declarations. Conflicts of interest: None.

Background: The use of mechanical cardiopulmonary resuscitation device has been very prevalent in out-of-hospital cardiac arrest rescue. This study aimed to investigate whether the timing of mechanical cardiopulmonary resuscitation device set-up correlated with the the outcome of cardiac arrest patients., Methods: We retrospectively reviewed adult nontrauma cardiac arrest cases in New Taipei City, Taiwan, from January to December 2022. Demographic data, intervention-related factors, and the time variables of mechanical cardiopulmonary resuscitation were collected. The outcomes included the return of spontaneous circulation and 24-hour survival. We compared patients who achieved spontaneous circulation and those who did not with univariate and multivariable regression analyses., Results: In total, 1680 patients who received mechanical cardiopulmonary resuscitation were included in the analysis. Reducing the time interval from manual chest compression initiation to device setup was independently associated with the return of spontaneous circulation and 24-hour survival, especially in the subgroup of patients of initial shockable rhythm. Receiver operating characteristic analysis revealed that the outcome of patients with an initial shockable rhythm could be predicted by the mechanical cardiopulmonary resuscitation setup time, with areas under the curve of 60.8% and 63.9% for ROSC and 24-hour survival, respectively. The cutoff point was 395.5 s for patients with an initial shockable rhythm., Conclusion: A positive correlation was found between early mechanical cardiopulmonary resuscitation intervention and the outcomes of out-of-hospital cardiac arrest patients. The time between manual chest compression and device setup could predict the return of spontaneous circulation and 24-hour survival in the subgroup of patients with initially shockable rhythm with the optimal cutoff point at 395.5 s., (© 2024. The Author(s).)

The optimal prehospital blood pressure in patients following traumatic brain injury (TBI) remains controversial. We aimed to assess the association between the systolic blood pressure (SBP) at emergency department triage and patient outcomes following isolated moderate-to-severe TBI. We conducted a cross-national multicenter retrospective cohort study using the Pan-Asia Trauma Outcomes Study database from January 1, 2016, to November 30, 2018. The enrollees were adult patients with isolated moderate-to-severe TBI defined by the International Classification of Diseases code, a Glasgow Coma Scale (GCS) <13 at triage, and a nonhead Abbreviated Injury Scale ≤3. The studied variables were SBPs at triage categorized into different ranges. The primary outcome was 30-day mortality, and the secondary outcome was poor functional status at hospital discharge defined by the modified Rankin Scale ≥4. Multivariable logistic regression was applied to adjust for confounders including country, sex, age, mechanism of injury, prehospital vascular access, respiratory rate, GCS, oxygen saturation, intubation, Injury Severity Score, head surgery, intensive care unit admission, and length of hospital stay. Subgroup analyses were performed on different severity of TBI. A total of 785 patients (median age, 42 years; male patients 77.5%; mean SBP at triage, 136.3 ± 33.1 mmHg) were included in the primary analysis. The lowest 30-day mortality rate existed in patients with SBP of 100-119 mmHg. Taking it as baseline, the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of SBP <100 mmHg, 120-139 mmHg, 140-159 mmHg, and ≥160 mmHg were 7.05 (2.51-19.78), 3.14 (1.14-8.65), 2.91 (1.04-8.17), and 3.28 (1.14-9.42). As for the secondary outcome, the aORs and 95% CIs were 1.36 (0.68-2.68) of <100 mmHg, 0.99 (0.57-1.70) of 120-139 mmHg, 1.23 (0.67-2.25) of 140-159 mmHg, and 1.52 (0.78-2.95) of ≥160 mmHg. Subgroup analyses revealed trends of the best outcomes in both moderate and severe TBI patients with SBP 100-119 mmHg, whereas statistical significance appeared only in patients with severe TBI. SBP of 110-119 mmHg at triage is associated with the lowest 30-day mortality in patients following isolated moderate-to-severe TBI and possibly related to a better functional outcome.

The use of an earth-abundant and inexpensive iron complex as a catalyst, coupled with near-infrared (NIR) light as the energy source, for radical reactions with alkyl halides has been far less developed. In this study, we report NIR light-mediated iron(I) dimer-catalyzed radical cascade reactions of fluoroalkyl bromides for the synthesis of ring-fused quinazolinones bearing a difluoromethyl group. In this process, the 3-bromo-1,10-phenanthroline ligand facilitates the reactivity of [CpFe(CO) 2 ] 2 , thereby improving the efficiency of the reaction.

Background: Clinical nursing care is an essential element in pediatric oncology. The body of research interventions targeting pediatric oncology patients and their families has grown in recent years. However, no reviews are currently available on nursing interventions for pediatric oncology., Aim: The aim was to develop a comprehensive overview of the available nursing interventions for pediatric oncology patients and their families, outline the characteristics of the interventions, and identify any knowledge gaps., Methods: This review was conducted in accordance with the JBI guidelines for scoping reviews. Citations were retrieved from the following databases: Scopus, PubMed, CINAHL, PsycINFO, and Embase. The following inclusion criteria were applied: peer-reviewed studies written in English, Danish, Norwegian, or Swedish from 2000 onward and reporting on pediatric patients with cancer and/or family members of a pediatric patient with cancer who received non-pharmacological and non-procedural nursing interventions provided by a pediatric oncology hospital service. Eligible studies were screened by title and abstract, and in full text by two independent reviewers. Critical appraisal was achieved using the Mixed Methods Appraisal Tool., Findings: Among 2762 references, 26 studies met the inclusions criteria, comprising 25 unique nursing interventions. 89 % had been published from 2013 onward, reflecting the rapid changes occurring in pediatric oncology treatment. 36 % were qualitative, 58 % were quantitative and 8 % employed mixed methods. The studies were characterized by considerable diversity in terms of intervention content, components, timing of delivery, and delivery mode. 60 % of the interventions were targeted parents among whom mothers were highly overrepresented (75 %). 16 % adopted a family-centered focus., Conclusion: This review contributes to building a more comprehensive understanding of the evidence base within pediatric oncology nursing research. This field is evolving and holds the potential to support families with childhood cancer across various phases of their treatment trajectory. However, a clear need exists to develop and test interventions with a genuinely family-centered focus, targeting both patients and family members. A considerable gap exists in reporting of the intervention development process and intervention characteristics. Improving the reporting of intervention development is needed to enhance research quality and facilitate subsequent adaptation or upscaling of interventions for use in other populations and contexts., Tweetable Abstract: Nursing interventions can support families with childhood cancer but future intervention studies need to enhance transparency in reporting @IJNSjournal., 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 Ltd.. All rights reserved.)

Background: The prognostic and therapeutic implications of endothelial cells (ECs) heterogeneity in prostate cancer (PCa) are poorly understood., Methods: We investigated associations of EC heterogeneity with PCa recurrence and castration resistance in 8 bulk transcriptomic and 4 single-cell RNA-seq cohorts. A recurrence-associated EC (RAEC) signature was constructed by comparing 11 machine learning algorithms through nested cross-validation. Functional relevances of RAEC-specific genes were also tested., Results: A subset of ECs was significantly associated with recurrence in primary PCa and named RAECs. RAECs were characteristic of tip and immature cells and were enriched in migration, angiogenesis, and collagen-related pathways. We then developed an 18-gene RAEC signature (RAECsig) representative of RAECs. Higher RAECsig scores independently predicted tumor recurrence and performed better or comparably compared to clinicopathological factors and commercial gene signatures in multiple PCa cohorts. Of the 18 RAECsig genes, FSCN1 was upregulated in ECs from PCa with higher Gleason scores; and the silencing of FSCN1, TMEME255B, or GABRD in ECs either attenuated tube formation or inhibited PCa cell proliferation. Finally, higher RAECsig scores predicted castration resistance in both primary and castration-resistant PCa., Conclusion: This study establishes an endothelial signature that links a subset of ECs to prostate cancer recurrence and castration resistance., (© 2024. The Author(s).)

Objectives: Following current cardiopulmonary resuscitation (CPR) guidelines, which recommend chest compressions at "the center of the chest," ~50% of patients experiencing out-of-hospital cardiac arrest (OHCA) undergo aortic valve (AV) compression, obstructing blood flow. We used resuscitative transesophageal echocardiography (TEE) to elucidate the impact of uncompressed vs. compressed AV on outcomes of adult patients experiencing OHCA., Design: Prospective observational cohort study., Setting: Single center., Patients: This study included adult OHCA patients undergoing resuscitative TEE in the emergency department. Patients were categorized into AV uncompressed or AV compressed groups based on TEE findings., Interventions: None., Measurements and Main Results: The primary outcome was sustained return of spontaneous circulation (ROSC). The secondary outcomes included end-tidal co2 (Et co2 ) during CPR, any ROSC, survival to ICU and hospital discharge, post-resuscitation withdrawal, and favorable neurologic outcomes at discharge. Additional analyses on intra-arrest arterial blood pressure (ABP) were also conducted. The sample size was pre-estimated at 37 patients/group. From October 2020 to January 2023, 76 patients were enrolled, 39 and 37 in the AV uncompressed and AV compressed groups, respectively. Intergroup baseline characteristics were similar. Compared with the AV compressed group, the AV uncompressed group had a higher probability of sustained ROSC (53.8% vs. 24.3%; adjusted odds ratio [aOR], 4.72; p = 0.010), any ROSC (56.4% vs. 32.4%; aOR, 3.30; p = 0.033), and survival to ICU (33.3% vs. 8.1%; aOR, 6.74; p = 0.010), and recorded higher initial diastolic ABP (33.4 vs. 11.5 mm Hg; p = 0.002) and a larger proportion achieving diastolic ABP greater than 20 mm Hg during CPR (93.8% vs. 33.3%; p < 0.001). The Et co2 , post-resuscitation withdrawal, and survival to discharge revealed no significant intergroup differences. No patients were discharged with favorable neurologic outcomes. Uncompressed AV seemed critical for sustained ROSC across all subgroups., Conclusions: Absence of AV compression during OHCA resuscitation is associated with an increased chance of ROSC and survival to ICU. However, its effect on long-term outcomes remains unclear., Competing Interests: Drs. Cheng and Tsai disclosed work for hire. Dr. Sun received funding from the Far Eastern Memorial Hospital (PI20200001). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions. However, the patho-genesis of hypoglycaemic counterregulation is still unclear. Glucagon-like peptide-1 (GLP-1) and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus (T1DM). The role of GLP-1 in counterregulatory dys-function during hypoglycaemia in patients with T1DM has not been reported., Aim: To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice., Methods: T1DM was induced in C57BL/6J mice using streptozotocin, followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia (DH5). Immunofluorescence, Western blot, and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon (GCG) secretion. The GLP-1 receptor agonist GLP-1(7-36) or the antagonist exendin (9-39) were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice., Results: The expression levels of intestinal GLP-1 and its receptor (GLP-1R) were significantly increased in DH5 mice. Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex, leading to dysfunction of adrenal counterregulation during hypoglycaemia. DH5 mice showed increased pancreatic δ-cell mass, cAMP levels in δ cells, and plasma somatostatin concentrations, while cAMP levels in pancreatic α cells and plasma GCG levels decreased. Furthermore, GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group. Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway., Conclusion: Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia, leading to reduced appetite and compromised secretion of adrenaline, noradrenaline, and GCG during hypo-glycaemia., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant health challenge, characterized by its widespread prevalence, intricate natural progression and multifaceted pathogenesis. Although NAFLD initially presents as benign fat accumulation, it may progress to steatosis, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Mesenchymal stem cells (MSCs) are recognized for their intrinsic self-renewal, superior biocompatibility, and minimal immunogenicity, positioning them as a therapeutic innovation for liver diseases. Therefore, this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways, including glycolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics, and support the development of MSC-based therapy in the treatment of NAFLD., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To compare the effectiveness of intraosseous versus intravenous vascular access in the treatment of adult patients with out-of-hospital cardiac arrest., Design: Cluster randomised controlled trial., Setting: The VICTOR (Venous Injection Compared To intraOsseous injection during resuscitation of patients with out-of-hospital cardiac arrest) trial involved emergency medical service agencies with all four advanced life support ambulance teams in Taipei City, Taiwan. The enrolment period spanned 6 July 2020 to 30 June 2023 and was temporarily suspended between 20 May 2021 and 31 July 2021 owing to the covid-19 pandemic., Participants: Adult (age 20-80 years) patients with non-traumatic out-of-hospital cardiac arrest., Interventions: Biweekly randomised clusters of four participating advanced life support ambulance teams were assigned to insert either intravenous or intraosseous access., Main Outcome Measures: The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation, sustained return of spontaneous circulation (≥2 hours), and survival with favourable neurological outcomes (cerebral performance category score ≤2) at hospital discharge., Results: Among 1771 enrolled patients, 1732 (741 in the intraosseous group and 991 in the intravenous group) were included in the primary analysis (median age 65.0 years; 1234 (71.2%) men). In the intraosseous group, 79 (10.7%) patients were discharged alive, compared with 102 (10.3%) patients in the intravenous group (odds ratio 1.04, 95% confidence interval 0.76 to 1.42; P=0.81). The odds ratio of intraosseous versus intravenous access was 1.23 (0.89 to 1.69; P=0.21) for pre-hospital return of spontaneous circulation, 0.92 (0.75 to 1.13; P=0.44) for sustained return of spontaneous circulation, and 1.17 (0.82 to 1.66; P=0.39) for survival with favourable neurological outcomes., Conclusions: Among adults with non-traumatic out-of-hospital cardiac arrest, initial attempts to establish vascular access through the intraosseous route did not result in different outcomes compared with intravenous access in terms of the proportion of patients surviving to hospital discharge, pre-hospital return of spontaneous circulation, sustained return of spontaneous circulation, and favourable neurological outcomes., Trial Registration: NCT04135547ClinicalTrials.gov NCT04135547., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: this study was supported by the Taiwan Ministry of Science and Technology, National Science and Technology Council, and National Taiwan University Hospital, Yun-Lin Branch; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Fish cells, such as grass carp ( Ctenopharyngodon idella ) kidney (CIK) cells, are harder to transfect than mammalian cells. There is a need for an efficient gene delivery system for fish cells. Here, we used CIK cell line as a model to develop a strategy to enhance RNA and plasmid DNA transfection efficiency using a nanocarrier generated from α-lactalbumin (α-NC). α-NC absorbed nucleic acid cargo efficiently and exhibited low cytotoxicity. Plasmid transfection was more efficient with α-NC than with liposomal transfection reagents. We used α-NC to co-transfect Tol2 transposase mRNA and a plasmid containing Cas9 and GFP, generating a stable transgenic CIK cell line. Genome and RNA sequencing revealed that the Cas9 and GFP fragments were successfully inserted into the genome of CIK cells and efficiently transcribed. In this study, we established an efficient transfection system for fish cells using α-NC, simplifying the process of generating stable transgenic fish cell lines., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Pancreatic cancer (PC) is a malignant tumor possessing high mortality. The role of transcription factor Forkhead Box F2 (FOXF2) in PC remains unverified. The current study investigated the roles of FOXF2 in developing PC in vitro and in vivo . A xenograft tumor model was constructed with nude mice injected using FOXF2‑overexpressing PC cells or FOXF2‑silenced PC cells. High FOXF2 expression significantly enhanced the proliferation ability of PC cells in vitro and pancreatic tumor growth in vivo . The cell cycle analysis indicated that transition of G1‑S phase was promoted by FOXF2. The cell cycle‑associated proteins cyclin D1, CDK2, phosphorylated (p)‑CDK2 and p‑RB were upregulated in the FOXF2‑overexpressing cells and downregulated in the cells with FOXF2 knockdown. Flow cytometric analysis and Hoechst staining showed that the percentage of apoptotic cells was significantly increased after FOXF2 was silenced. FOXF2 knockdown promoted expression of pro‑apoptotic proteins (Bad, Bax and cleaved caspase‑3) while suppressing the anti‑apoptotic proteins (Bcl‑2 and Bcl‑xl) at the protein level. FOXF2 improved the migration and invasion of PC cells in vitro . Moreover, luciferase and chromatin immunoprecipitation assays revealed that FOXF2 binds to the MSI2 promoter, promoting its transcriptional expression. FOXF2 knockdown inhibited the MSI2 protein translation while enhancing the translation of NUMB protein, suppressing PC development in vivo . MSI2 silencing reversed the promotive effect mediated by FOXF2 on cell proliferation. These results demonstrated that FOXF2 is essential in PC progression, and the potential mechanism includes regulating MSI2 transcription.

Objective: The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or slow down the progression, the commonly used estimated glomerular filtration rate (eGFR) based on serum creatinine may be influenced by factors unrelated to kidney function. Therefore, there is a need to identify novel biomarkers that can more accurately assess renal function in T2D patients. In this study, we employed an interpretable machine-learning framework to identify plasma metabolomic features associated with GFR in T2D patients., Methods: We retrieved 1626 patients with type 2 diabetes (T2D) in Liaoning Medical University First Affiliated Hospital (LMUFAH) as a development cohort and 716 T2D patients in Second Affiliated Hospital of Dalian Medical University (SAHDMU) as an external validation cohort. The metabolite features were screened by the orthogonal partial least squares discriminant analysis (OPLS-DA). We compared machine learning prediction methods, including logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The Shapley Additive exPlanations (SHAP) were used to explain the optimal model., Results: For T2D patients, compared with the normal or elevated eGFR group, glutarylcarnitine (C5DC) and decanoylcarnitine (C10) were significantly elevated in GFR mild reduction group, and citrulline and 9 acylcarnitines were also elevated significantly (FDR<0.05, FC > 1.2 and VIP > 1) in moderate or severe reduction group. The XGBoost model with metabolites had the best performance: in the internal validate dataset (AUROC=0.90, AUPRC=0.65, BS=0.064) and external validate cohort (AUROC=0.970, AUPRC=0.857, BS=0.046). Through the SHAP method, we found that C5DC higher than 0.1μmol/L, Cit higher than 26 μmol/L, triglyceride higher than 2 mmol/L, age greater than 65 years old, and duration of T2D more than 10 years were associated with reduced GFR., Conclusion: Elevated plasma levels of citrulline and a panel of acylcarnitines were associated with reduced GFR in T2D patients, independent of other conventional risk factors., 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 An, Zhang, Xue, Luo, Li, Fang and Zong.)

Background and Importance: This study compared the on-scene Glasgow Coma Scale (GCS) and the GCS-motor (GCS-M) for predictive accuracy of mortality and severe disability using a large, multicenter population of trauma patients in Asian countries., Objective: To compare the ability of the prehospital GCS and GCS-M to predict 30-day mortality and severe disability in trauma patients., Design: We used the Pan-Asia Trauma Outcomes Study registry to enroll all trauma patients >18 years of age who presented to hospitals via emergency medical services from 1 January 2016 to November 30, 2018., Settings and Participants: A total of 16,218 patients were included in the analysis of 30-day mortality and 11 653 patients in the analysis of functional outcomes., Outcome Measures and Analysis: The primary outcome was 30-day mortality after injury, and the secondary outcome was severe disability at discharge defined as a Modified Rankin Scale (MRS) score ≥4. Areas under the receiver operating characteristic curve (AUROCs) were compared between GCS and GCS-M for these outcomes. Patients with and without traumatic brain injury (TBI) were analyzed separately. The predictive discrimination ability of logistic regression models for outcomes (30-day mortality and MRS) between GCS and GCS-M is illustrated using AUROCs., Main Results: The primary outcome for 30-day mortality was 1.04% and the AUROCs and 95% confidence intervals for prediction were GCS: 0.917 (0.887-0.946) vs. GCS-M:0.907 (0.875-0.938), P  = 0.155. The secondary outcome for poor functional outcome (MRS ≥ 4) was 12.4% and the AUROCs and 95% confidence intervals for prediction were GCS: 0.617 (0.597-0.637) vs. GCS-M: 0.613 (0.593-0.633), P  = 0.616. The subgroup analyses of patients with and without TBI demonstrated consistent discrimination ability between the GCS and GCS-M. The AUROC values of the GCS vs. GCS-M models for 30-day mortality and poor functional outcome were 0.92 (0.821-1.0) vs. 0.92 (0.824-1.0) ( P  = 0.64) and 0.75 (0.72-0.78) vs. 0.74 (0.717-0.758) ( P  = 0.21), respectively., Conclusion: In the prehospital setting, on-scene GCS-M was comparable to GCS in predicting 30-day mortality and poor functional outcomes among patients with trauma, whether or not there was a TBI., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Previous investigations have shown a positive relationship between baseball pitching velocity and the kinetic chain involved in pitching motion. However, no study has examined the influence of finger characteristics on pitching velocity and rate of spin via a sensor-embedded baseball., Methods: Twenty-one pitchers volunteered and were recruited for this study. An experimental baseball embedded with a force sensor and an inertial measurement unit was designed for pitching performance measurement. Finger length and strength were measured as dependent variables. Spin rate and velocity were independent variables. Pearson product-moment correlations (r) and intraclass correlation coefficients (ICCs) determined the relationship between finger characteristics and pitching performance., Results: Finger length discrepancy, two-point pinch strength, index finger RFD (rate of force development), middle finger impulse, and force discrepancy had significant correlations with spin rate (r = 0.500~0.576, p ≤ 0.05). Finger length discrepancy, two-point pinch, three-point pinch strength, index and middle finger RFD, middle finger impulse, and force combination had significant correlations with fastball pitching velocity (r = 0.491~0.584, p ≤ 0.05)., Conclusions: Finger length discrepancy, finger pinch strength, and pitching finger force including maximal force and RFD may be factors that impact fastball spin rate and fastball pitching velocity.

Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Here, we report that PTEN deficiency induced Krüppel-like factor 5 (KLF5) acetylation and that interruption of KLF5 acetylation orchestrated intricate interactions between cancer cells and CAFs that enhance FGF receptor 1 (FGFR1) signaling and promote tumor growth. Deacetylated KLF5 promoted tumor cells to secrete TNF-α, which stimulated inflammatory CAFs to release FGF9. CX3CR1 inhibition blocked FGFR1 activation triggered by FGF9 and sensitized PTEN-deficient prostate cancer to the AKT inhibitor capivasertib. This study reveals the role of KLF5 acetylation in reprogramming CAFs and provides a rationale for combined therapies using inhibitors of AKT and CX3CR1.

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective: Our objective was to determine whether there is an association between adverse childhood experiences (ACEs) and lifetime history of early childhood mild head or neck injury and concussion in a nationally representative US cohort., Setting and Design: This is a cross-sectional study using data from the Adolescent Brain Cognitive Development (ABCD) Study (data release 3.0), a prospective investigation of child brain development and health., Participants: There were 11 878 children aged 9 or 10 years at baseline, recruited from 21 school-based sites in the United States. After excluding children with missing questionnaires for the primary exposure variable and children with severe brain injuries involving more than 30-minute loss of consciousness, the final sample size was 11 230 children., Measures: The primary exposure variable was ACEs. We measured eight ACEs: sexual abuse, physical abuse, emotional neglect, parent domestic violence, parent substance use disorder, parental mental illness, parent criminal involvement, and parent divorce. The primary outcomes were head or neck injury and concussion, measured using the Ohio State University Traumatic Brain Injury Screen-Identification Method Short Form., Results: The sample ( N = 11 230) was 52% boys with a mean age of 9.9 years (SD = 0.62 years). The racial and ethnic makeup was reflective of national demographics. Having a higher overall ACE count was associated with higher odds of head or neck injury, with greater odds with more ACEs reported. Children with 2 ACEs had 24% greater odds of head or neck injury (AOR = 1.24, 95% confidence interval [CI] = 1.06-1.45) and 64% greater odds of concussion (AOR = 1.64, 95% CI = 1.18-2.22), and children with 4 or more ACEs had 70% greater odds of head or neck injury (AOR = 1.7, 95% CI = 1.14, 2.49) and 140% greater odds of concussion (AOR = 2.4, 95% CI = 1.15-4.47). The individual ACE categories of sexual abuse, parent domestic violence, parental mental illness, and parent criminal involvement were significantly associated with increased risk of head or neck injury and parental mental illness with increased risk of concussion., Conclusions and Relevance: ACEs are associated with early childhood mild head or neck injury and concussion and should be integrated in head injury prevention and intervention efforts., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/purpose: This review aimed to investigate the effect of crew ratios of on-scene advanced life support (ALS)-trained personnel on patients with out-of-hospital cardiac arrest (OHCA)., Methods: We systematically searched PubMed, Ovid EMBASE, and the Cochrane Central Register of Controlled Trials databases from the inception date until September 30, 2022, for eligible studies. Two reviewers independently screened the studies for relevance, extracted data, and quality. We compared the effect of the ratio of on-scene ALS-trained personnel >50 % to those with a ratio ≤50 % among prehospital personnel on the clinical outcomes of OHCA patients. The primary outcome was survival-to-discharge and secondary outcomes were any return of spontaneous circulation (ROSC), sustained ROSC (≥2 h), and favourable neurological outcome at discharge (cerebral performance category scores: 1 or 2). Pooled odds ratios (ORs) were calculated, and the certainty of evidence was assessed., Results: From 10,864 references, we identified four non-randomised studies, including 16,475 patients. Two studies were performed in Japan and two in Taiwan. There were significant differences in survival-to-discharge (OR: 1.24, 95 % confidence interval [CI]: 1.07-1.44, I 2 : 7 %), any ROSC (OR:1.22, 95 % CI: 1.04-1.43, I 2 : 74 %) and sustained ROSC (OR: 1.39, 95 % CI: 1.16-1.65, I 2 : 40 %), but insignificant differences in favourable neurological outcome at discharge. The overall certainty of evidence was rated as very low for all outcomes., Conclusion: Prehospital ALS care with a ratio of on-scene ALS-trained personnel >50 % could improve OHCA patient outcomes than crew ratios ≤50 %. Further studies are required to reach a robust conclusion., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Purpose: To develop a contrast-enhanced ultrasound (CEUS) clinic-radiomics nomogram for individualized assessment of Ki-67 expression in hepatocellular carcinoma (HCC)., Methods: A retrospective cohort comprising 310 HCC individuals who underwent preoperative CEUS (using SonoVue) at three different centers was partitioned into a training set, a validation set, and an external test set. Radiomics signatures indicating the phenotypes of the Ki-67 were extracted from multiphase CEUS images. The radiomics score (Rad-score) was calculated accordingly after feature selection and the radiomics model was constructed. A clinic-radiomics nomogram was established utilizing multiphase CEUS Rad-score and clinical risk factors. A clinical model only incorporated clinical factors was also developed for comparison. Regarding clinical utility, calibration, and discrimination, the predictive efficiency of the clinic-radiomics nomogram was evaluated., Results: Seven radiomics signatures from multiphase CEUS images were selected to calculate the Rad-score. The clinic-radiomics nomogram, comprising the Rad-score and clinical risk factors, indicated a good calibration and demonstrated a better discriminatory capacity compared to the clinical model (AUCs: 0.870 vs 0.797, 0.872 vs 0.755, 0.856 vs 0.749 in the training, validation, and external test set, respectively) and the radiomics model (AUCs: 0.870 vs 0.752, 0.872 vs 0.733, 0.856 vs 0.729 in the training, validation, and external test set, respectively). Furthermore, both the clinical impact curve and the decision curve analysis displayed good clinical application of the nomogram., Conclusion: The clinic-radiomics nomogram constructed from multiphase CEUS images and clinical risk parameters can distinguish Ki-67 expression in HCC patients and offer useful insights to guide subsequent personalized treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The phenolic aldehyde syringaldehyde (SA) has been shown to have an antihyperglycemic effect in diabetic rats due to increased glucose utilization and insulin sensitivity. To understand the direct effect of SA on the GLP-1 receptor, STZ-induced diabetic rats were used. The levels of pro-inflammatory cytokines, liver enzymes, and renal function were measured using specific ELISA kits. The mechanisms of SA effects were investigated using CHO-K1 cells, pancreatic Min-6 cells, and cardiomyocyte H9c2 cells. The results indicated that the antihyperglycemic effect of SA in diabetic rats was abolished by blocking the GLP-1 receptor with an antagonist. SA has a direct effect on the GLP-1 receptor when using CHO-K1 cells transfected with the exogenous GLP-1 receptor gene. In addition, SA stimulated insulin production in Min-6 cells by activating GLP-1 receptors. SA caused a dose-dependent rise in GLP-1 receptor mRNA levels in cardiac H9c2 cells. These in vitro results support the notion that SA has a direct effect on the GLP-1 receptor. Otherwise, SA inhibited the increase of pro-inflammatory cytokines, including interleukins and tumor TNF-α, in type 1 diabetic rats in a dose-dependent manner. Moreover, as with liraglutide, SA reduced plasma lipid profiles, including total cholesterol and triglyceride, in mixed diet-induced type 2 diabetic rats. Intriguingly, chronic treatment with SA (as with liraglutide) reversed the functions of both the liver and the kidney in these diabetic rats. SA displayed less efficiency in reducing body weight and food consumption compared to liraglutide. In conclusion, SA effectively activates GLP-1 receptors, resulting in a reduction in diabetic-related complications in rats. Therefore, it is beneficial to develop SA as a chemical agonist for clinical applications in the future.

Background: Immunohistochemistry (IHC) is an essential technique in surgical and clinical pathology for detecting diagnostic, prognostic, and predictive biomarkers for personalized cancer therapy. However, the lack of standardization and reference controls results in poor reproducibility, and a reliable tool for IHC quantification is urgently required. The objective of this study was to describe a novel approach in which H3F3B (histone H3, family 3B) can be used as an internal reference standard to quantify protein expression levels using IHC., Methods: The authors enrolled 89 patients who had human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). They used a novel IHC-based assay to measure protein expression using H3F3B as the internal reference standard. H3F3B was uniformly expressed at the protein level in all tumor regions in cancer tissues. HER2 expression levels were measured with the H-score using HALO software., Results: Kaplan-Meier analysis indicated that, among patients who had HER2-positive BC in The Cancer Genome Atlas data set and the authors' data set, the subgroup with low HER2 expression had a significantly better prognosis than the subgroup with high HER2 expression. Furthermore, the authors observed that HER2 expression levels were precisely evaluated using the proposed method, which can classify patients who are at higher risk of HER2-positive BC to receive trastuzumab-based adjuvant therapy. Dual-color IHC with H3F3B is an excellent tool for internal and external quality control of HER2 expression assays., Conclusions: The proposed IHC-based quantification method accurately assesses HER2 expression levels and provides insights for predicting clinical prognosis in patients with HER2-positive BC who receive trastuzumab-based adjuvant therapy., (© 2024 American Cancer Society.)

Cutaneous drug reactions (CDRs) are common drug-induced allergic reactions that cause severe consequences in HIV/AIDS patients. The CCL17/CCR4 axis is involved in the immune mechanism of allergic diseases, but its role in the CDRs has not been determined. Here, we aimed to determine the role of the CCL17/CCR4 axis and the underlying mechanism involved in CDRs. In this study, the serum cytokine levels in patients with CDR and healthy controls were measured. The CCL17-triggered allergic profile was screened via a PCR array. Apoptosis of keratinocytes cocultured with CCL17-stimulated Th2 cells was analyzed by flow cytometry. An NVP-induced rat CDR model was established, and dynamic inflammatory factor levels and Th2 cells in the peripheral blood of the rats were measured. Rat skin lesions and signaling pathways in Th2 cells were also analyzed. We showed that the serum CCL17 level was significantly upregulated in CDR patients (P = 0.0077), and the Th2 cell subgroup was also significantly elevated in the CDR rats. The CCL17/CCR4 axis induces Th2 cells to release IL-4 and IL-13 via the ERK/STAT3 pathway. The CCR4 antagonist compound 47 can alleviate rash symptoms resulting from NVP-induced drug eruption, Th2 cell subgroup, IL-4, and IL-13 and inhibit keratinocyte apoptosis. Taken together, these findings indicate that the CCL17/CCR4 axis mediates CDR via the ERK/STAT3 pathway in Th2 cells and type 2 cytokine-induced keratinocyte apoptosis., 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.)

This study investigates the influence of the quality of the "deep squat" movement, adapted from the Functional Movement Screen (FMS) system, on the lower extremity movement pattern during baseball throwing, and its potential impact on throwing performance and propulsion efficiency. Twenty-two baseball players were recruited and categorized into two groups: 13 in the high-score squat group (HSS) and 9 in the low-score squat group (LSS), based on their deep squat screening results. This research explored disparities in ball velocity, propulsion efficiency, propulsion ground reaction force (GRF) characteristics, and throwing kinematics between these two groups. The findings revealed no significant difference in ball velocity between the groups. However, the LSS group demonstrated a lower propulsion GRF efficiency ( p < 0.030, ES = 0.46), along with a higher vertical peak GRF ( p < 0.002, ES = 0.66). In the pivot leg, the HSS group exhibited significantly lower impulse forces in the Impulse Fresultant ( p < 0.035, ES = 0.45), throwing direction ( p < 0.049, ES = 0.42), and vertical direction ( p < 0.048, ES = 0.42). Additionally, the contribution to the ball velocity of the pivot leg was significantly greater in the HSS group, along with significantly better efficiency in Impulse Fresultant ( p < 0.035, ES = 0.45), throwing direction ( p < 0.053, ES = 0.41), and vertical direction ( p < 0.032, ES = 0.46). In the leading leg, the HSS group demonstrated significantly lower impulse forces in the Impulse Fresultant ( p < 0.001, ES = 0.69), throwing direction ( p < 0.007, ES = 0.58), and vertical direction ( p < 0.001, ES = 0.70). Moreover, the contribution to the ball velocity of the leading leg was significantly greater in the HSS group, accompanied by significantly better efficiency in Impulse Fresultant ( p < 0.003, ES = 0.63), throwing direction ( p < 0.005, ES = 0.60), and vertical direction ( p < 0.021, ES = 0.49). In conclusion, this study suggests that squat screening is a valuable tool for assessing propulsion efficiency. Coaches and trainers should be mindful of players with low squat quality but high throwing performance, as they may face increased impact and injury risks in the future.

Background: Major trauma is a leading cause of unexpected death globally, with increasing age-adjusted death rates for unintentional injuries. Field triage schemes (FTSs) assist emergency medical technicians in identifying appropriate medical care facilities for patients. While full FTSs may improve sensitivity, step-by-step field triage is time-consuming. A simplified FTS (sFTS) that uses only physiological and anatomical criteria may offer a more rapid decision-making process. However, evidence for this approach is limited, and its performance in identifying all age groups requiring trauma center resources in Asia remains unclear., Methods: We conducted a multinational retrospective cohort study involving adult trauma patients admitted to emergency departments in the included countries from 2016 to 2020. Prehospital and hospital data were reviewed from the Pan-Asia Trauma Outcomes Study database. Patients aged ≥18 years transported by emergency medical services were included. Patients lacking data regarding age, sex, physiological criteria, or injury severity scores were excluded. We examined the performance of sFTS in all age groups and fine-tuned physiological criteria to improve sFTS performance in identifying high-risk trauma patients in different age groups., Results: The sensitivity and specificity of the physiological and anatomical criteria for identifying major trauma (injury severity score ≥ 16) were 80.6% and 58.8%, respectively. The modified sFTS showed increased sensitivity and decreased specificity, with more pronounced changes in the young age group. Adding the shock index further increased sensitivity in both age groups., Conclusions: sFTS using only physiological and anatomical criteria is suboptimal for Asian adult patients with trauma of all age groups. Adjusting the physiological criteria and adding a shock index as a triage tool can improve the sensitivity of severely injured patients, particularly in young age groups. A swift field triage process can maintain acceptable sensitivity and specificity in severely injured patients., Competing Interests: Declaration of Competing Interest This study received no financial support and there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: To prevent school injuries, thorough epidemiological data is an essential foundation. We aimed to investigate the characteristics of school injuries in Asia and explore risk factors for major trauma., Methods: This retrospective study was conducted in the participating centers of the Pan-Asian Trauma Outcome Study from October 2015 to December 2020. Subjects who reported "school" as the site of injury were included. Major trauma was defined as an Injury Severity Score (ISS) value of ≥16., Results: In total, 1305 injury cases (1.0% of 127,715 events) occurred at schools. Among these, 68.2% were children. Unintentional injuries were the leading cause and intentional injuries comprised 7.5% of the cohort. Major trauma accounted for 7.1% of those with documented ISS values. Multivariable regression revealed associations between major trauma and factors, including age, intention of injury (self-harm), type of injury (traffic injuries, falls), and body part injured (head, thorax, and abdomen). Twenty-two (1.7%) died, with six deaths related to self-harm. Females represented 28.4% of injuries but accounted for 40.9% of all deaths., Conclusions: In Asia, injuries at schools affect a significant number of children. Although the incidence of injuries was higher in males, self-inflicted injuries and mortality cases were relatively higher in females., Impact: Epidemiological data and risk factors for major trauma resulting from school injuries in Asia are lacking. This study identified significant risk factors for major trauma occurring at schools, including age, intention of injury (self-harm), injury type (traffic injuries, falls), and body part injured (head, thoracic, and abdominal injuries). Although the incidence of injuries was higher in males, the incidence of self-harm injuries and mortality rates were higher in females. The results of this would make a significant contribution to the development of prevention strategies and relative policies concerning school injuries., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

This study aims to investigate the different ground reaction force (GRF) characteristics from different stride types. This study included 30 Taiwanese elite college and professional baseball pitchers. Each pitcher was classified into one of the following stride types: tall and fall (TF), dip and drive (DD), or mixed (MX). Our findings indicated that DD pitchers pressed their bodies forward earlier than TF pitchers. In contrast, the GRF of the pivot leg of TF pitchers increased slowly in the first half of the stride phase and continued to increase even after the stride leg touched the ground. This type of continuous pressing in TF was different from that in DD and MX pitchers, which decreased rapidly into the arm-cocking & acceleration phases. We conclude that the lower extremities were used differently by TF, DD and MX pitchers. This information could serve as a training guideline for coaches and pitchers to enhance training effectiveness, while simultaneously lowering injury risks.

Objective: We aimed to determine the reliability of using the Fibrosis-4 (FIB-4) index in COVID-19 patients without underlying liver illness., Method: We employed multivariate logistic regression to identify variables that exhibited statistically significant influence on the ultimate outcome. Multilayer perceptron analysis was employed to develop a prediction model for the FIB-4 index concerning ICU admission and intubation rates. However, the scarcity of cases rendered the assessment of the mortality rate unfeasible. We plotted ROC curves to analyze the predictive strength of the FIB-4 index across various age groups., Result: In univariate logistic regression, only the FIB-4 index and respiratory rate demonstrated statistical significance on all poor outcomes. The FIB-4 index for mortality prediction had an ROC and AUC of 0.863 (95% CI: 0.781-0.9444). It demonstrates predictive power across age groups, particularly for age ≥65 (AUC: 0.812, 95% CI: 0.6571-0.9673) and age <65 (AUC: 0.878, 95% CI: 0.8012-0.9558). Its sensitivity for intubation and ICU admission prediction is suboptimal., Conclusion: FIB-4 index had promising power in prediction of mortality rate in all age groups., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chien Chieh Hsieh reports article publishing charges was provided by Far Eastern Memorial Hospital. 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Out-of-hospital cardiac arrest (OHCA) is a significant public health issue worldwide and is associated with low survival rates and poor neurological outcomes. The generation of optimal coronary perfusion pressure (CPP) via high-quality chest compressions is a key factor in enhancing survival rates. However, it is often challenging to provide adequate CPP in real-world cardiopulmonary resuscitation (CPR) scenarios. Based on animal studies and human trials on improving CPP in patients with nontraumatic OHCA, resuscitative endovascular balloon occlusion of the aorta (REBOA) is a promising technique in these cases. This study aims to investigate the benefits of REBOA adjunct to CPR compared with conventional CPR for the clinical management of nontraumatic OHCA., Methods: This is a parallel-group, randomized, controlled, multinational trial that will be conducted at two urban academic tertiary hospitals in Korea and Taiwan. Patients aged 20-80 years presenting with witnessed OHCA will be enrolled in this study. Eligible participants must fulfill the inclusion criteria, and written informed consent should be collected from their legal representatives. Patients will be randomly assigned to the intervention (REBOA-CPR) or control (conventional CPR) group. The intervention group will receive REBOA and standard advanced cardiovascular life support (ACLS). Meanwhile, the control group will receive ACLS based on the 2020 American Heart Association guidelines. The primary outcome is the return of spontaneous circulation (ROSC). The secondary outcomes include sustained ROSC, survival to admission, survival to discharge, neurological outcome, and hemodynamic changes., Discussion: Our upcoming trial can provide essential evidence regarding the efficacy of REBOA, a mechanical method for enhancing CPP, in OHCA resuscitation. Our study aims to determine whether REBOA can improve treatment strategies for patients with nontraumatic OHCA based on clinical outcomes, thereby potentially providing valuable insights and guiding further advancements in this critical public health area., Trial Registration: ClinicalTrials.gov NCT06031623. Registered on September 9, 2023., (© 2024. The Author(s).)

DNA methylation and chromatin accessibility play important roles in gene expression, but their function in subgenome expression dominance remains largely unknown. We conducted comprehensive analyses of the transcriptome, DNA methylation, and chromatin accessibility in liver and muscle tissues of allotetraploid common carp, aiming to reveal the function of epigenetic modifications in subgenome expression dominance. A noteworthy overlap in differential expressed genes (DEGs) as well as their functions was observed across the two subgenomes. In the promoter and gene body, the DNA methylation level of the B subgenome was significantly different than that of the A subgenome. Nevertheless, differences in DNA methylation did not align with changes in homoeologous biased expression across liver and muscle tissues. Moreover, the B subgenome exhibited a higher prevalence of open chromatin regions and greater chromatin accessibility, in comparison to the A subgenome. The expression levels of genes located proximally to open chromatin regions were significantly higher than others. Genes with higher chromatin accessibility in the B subgenome exhibited significantly elevated expression levels compared to the A subgenome. Contrastingly, genes without accessibility exhibited similar expression levels in both subgenomes. This study contributes to understanding the regulation of subgenome expression dominance in allotetraploid common carp.

The aim of this study is to analyze the effect of serum metabolites on diabetic nephropathy (DN) and predict the prevalence of DN through a machine learning approach. The dataset consists of 548 patients from April 2018 to April 2019 in the Second Affiliated Hospital of Dalian Medical University (SAHDMU). We select the optimal 38 features through a least absolute shrinkage and selection operator (LASSO) regression model and a 10-fold cross-validation. We compare four machine learning algorithms, including extreme gradient boosting (XGB), random forest, decision tree, and logistic regression, by AUC-ROC curves, decision curves, and calibration curves. We quantify feature importance and interaction effects in the optimal predictive model by Shapley additive explanation (SHAP) method. The XGB model has the best performance to screen for DN with the highest AUC value of 0.966. The XGB model also gains more clinical net benefits than others, and the fitting degree is better. In addition, there are significant interactions between serum metabolites and duration of diabetes. We develop a predictive model by XGB algorithm to screen for DN. C2, C5DC, Tyr, Ser, Met, C24, C4DC, and Cys have great contribution in the model and can possibly be biomarkers for DN., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Jing-Mei Yin et al.)

Hypercapnia, elevation of the partial pressure of CO2 in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions and that elevated CO2 increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs). We also show that zinc finger homeobox 3 (Zfhx3) - a mammalian ortholog of zfh2, which mediates hypercapnic immune suppression in Drosophila - is expressed in mouse and human macrophages. Deletion of Zfhx3 in the myeloid lineage blocked the suppressive effect of hypercapnia on immune gene expression in AMØs and decreased viral replication, inflammatory lung injury, and mortality in hypercapnic mice infected with influenza A virus. To our knowledge, our results establish Zfhx3 as the first known mammalian mediator of CO2 effects on immune gene expression and lay the basis for future studies to identify therapeutic targets to interrupt hypercapnic immunosuppression in patients with advanced lung disease.

The infertile electromagnetic (EM) attenuating behavior of carbon material makes the improvement of its performance remain a significant challenge. Herein, a facile and low-cost strategy radically distinct from the prevalent approaches by constructing polar covalent bonds between sp 2 -hybridized and sp 3 -hybridized carbon atoms to introduce strong dipolar polarization is proposed. Through customizing and selectively engineering the N moieties conjugated with carbon rings, the microstructure of the as-synthesized 2D nanosheet is gradually converted with the partial transition from sp 3 carbons to sp 2 carbons, where the electric dipoles between them are also tuned. Supported by the DFT calculations, a progressively enhanced sp 2 ─sp 3 C─C dipolar polarization is caused by this controllable structure evolution, which is demonstrated to contribute dominantly to the total dielectric loss. By virtue of this unduplicated loss behavior, a remarkable effective absorption bandwidth (EAB) beyond -10 dB of 8.28 GHz (2.33 mm) and an ultrawide EAB beyond -5 dB of 13.72 GHz (4.93 mm) are delivered, which upgrade the EM performance of carbon material to a higher level. This study not only demonstrates the huge perspective of sp 2 ─sp 3 -hybridized carbon in EM elimination but also gives pioneering insights into the carbon-carbon polarization mechanism for guiding the development of advanced EM absorption materials., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Introduction: Timely diagnosis of patients affected by an emerging infectious disease plays a crucial role in treating patients and avoiding disease spread. In prior research, we developed an approach by using machine learning (ML) algorithms to predict serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on clinical features of patients visiting an emergency department (ED) during the early coronavirus 2019 (COVID-19) pandemic. In this study, we aimed to externally validate this approach within a distinct ED population., Methods: To create our training/validation cohort (model development) we collected data retrospectively from suspected COVID-19 patients at a US ED from February 23-May 12, 2020. Another dataset was collected as an external validation (testing) cohort from an ED in another country from May 12-June 15, 2021. Clinical features including patient demographics and triage information were used to train and test the models. The primary outcome was the confirmed diagnosis of COVID-19, defined as a positive reverse transcription polymerase chain reaction test result for SARS-CoV-2. We employed three different ML algorithms, including gradient boosting, random forest, and extra trees classifiers, to construct the predictive model. The predictive performances were evaluated with the area under the receiver operating characteristic curve (AUC) in the testing cohort., Results: In total, 580 and 946 ED patients were included in the training and testing cohorts, respectively. Of them, 98 (16.9%) and 180 (19.0%) were diagnosed with COVID-19. All the constructed ML models showed acceptable discrimination, as indicated by the AUC. Among them, random forest (0.785, 95% confidence interval [CI] 0.747-0.822) performed better than gradient boosting (0.774, 95% CI 0.739-0.811) and extra trees classifier (0.72, 95% CI 0.677-0.762). There was no significant difference between the constructed models., Conclusion: Our study validates the use of ML for predicting COVID-19 in the ED and demonstrates its potential for predicting emerging infectious diseases based on models built by clinical features with temporal and spatial heterogeneity. This approach holds promise for scenarios where effective diagnostic tools for an emerging infectious disease may be lacking in the future., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. This work was supported with grants from National Health Research Institutes (NHRI), Taiwan (NHRI-EX112-11137PI), and National Science and Technology Council (NSTC), Taiwan (109-2823-8-002-013-CV). The funders had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. There are no conflicts of interest to declare.

Background/purpose: To develop a prediction model for emergency medical technicians (EMTs) to identify trauma patients at high risk of deterioration to emergency medical service (EMS)-witnessed traumatic cardiac arrest (TCA) on the scene or en route., Methods: We developed a prediction model using the classical cross-validation method from the Pan-Asia Trauma Outcomes Study (PATOS) database from 1 January 2015 to 31 December 2020. Eligible patients aged ≥18 years were transported to the hospital by the EMS. The primary outcome (EMS-witnessed TCA) was defined based on changes in vital signs measured on the scene or en route. We included variables that were immediately measurable as potential predictors when EMTs arrived. An integer point value system was built using multivariable logistic regression. The area under the receiver operating characteristic (AUROC) curve and Hosmer-Lemeshow (HL) test were used to examine discrimination and calibration in the derivation and validation cohorts., Results: In total, 74,844 patients were eligible for database review. The model comprised five prehospital predictors: age <40 years, systolic blood pressure <100 mmHg, respiration rate >20/minute, pulse oximetry <94%, and levels of consciousness to pain or unresponsiveness. The AUROC in the derivation and validation cohorts was 0.767 and 0.782, respectively. The HL test revealed good calibration of the model (p = 0.906)., Conclusion: We established a prediction model using variables from the PATOS database and measured them immediately after EMS personnel arrived to predict EMS-witnessed TCA. The model allows prehospital medical personnel to focus on high-risk patients and promptly administer optimal treatment., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.