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Glioblastoma (GBM) is the most common primary malignant brain tumor, with a median overall survival of less than 2 years and a nearly 100% mortality rate under standard therapy that consists of surgery followed by combined radiochemotherapy. Therefore, new therapeutic strategies are urgently needed. The success of chimeric antigen receptor (CAR) T cells in hematological cancers has prompted preclinical and clinical investigations into CAR-T-cell treatment for GBM. However, recent trials have not demonstrated any major success. Here, we delineate existing challenges impeding the effectiveness of CAR-T-cell therapy for GBM, encompassing the cold (immunosuppressive) microenvironment, tumor heterogeneity, T-cell exhaustion, local and systemic immunosuppression, and the immune privilege inherent to the central nervous system (CNS) parenchyma. Additionally, we deliberate on the progress made in developing next-generation CAR-T cells and novel innovative approaches, such as low-intensity pulsed focused ultrasound, aimed at surmounting current roadblocks in GBM CAR-T-cell therapy.

Cancers and neurological disorders are two major types of diseases in humans. We developed the concept called the “Aberrant Cell Cycle Disease (ACCD)” due to the accumulating evidence that shows that two different diseases share the common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncoprotein activation and tumor suppressor (TS) inactivation, which are associated with both tumor growth in cancers and neuronal death in neurological disorders. Therefore, some cancer therapies (e.g., kinase/oncogene inhibition and TS elevation) can be leveraged for neurological treatments. MicroRNA (miR/miRNA) provides a new style of drug-target binding. For example, a single tumor suppressor miRNA (TS-miR/miRNA) can bind to and decrease tens of target kinases/oncogenes, producing much more robust efficacy to block cell cycle re-entry than inhibiting a single kinase/oncogene. In this review, we summarize the miRNAs that are altered in both cancers and neurological disorders, with an emphasis on miRNA drugs that have entered into clinical trials for neurological treatment.

Introduction: The epidemic of gun violence in the United States (US) is exacerbated by frequent mass shootings. In 2021, there were 698 mass shootings in the US, resulting in 705 deaths and 2,830 injuries. This is a companion paper to a publication in JAMA Network Open, in which the nonfatal outcomes of victims of mass shootings have been only partially described. Methods: We gathered clinical and logistic information from 31 hospitals in the US about 403 survivors of 13 mass shootings, each event involving greater than 10 injuries, from 2012–19. Local champions in emergency medicine and trauma surgery provided clinical data from electronic health records within 24 hours of a mass shooting. We organized descriptive statistics of individual-level diagnoses recorded in medical records using International Classification of Diseases codes, according to the Barell Injury Diagnosis Matrix (BIDM), a standardized tool that classifies 12 types of injuries within 36 body regions. Results: Of the 403 patients who were evaluated at a hospital, 364 sustained physical injuries—252 by gunshot wound (GSW) and 112 by non-ballistic trauma—and 39 were uninjured. Fifty patients had 75 psychiatric diagnoses. Nearly 10% of victims came to the hospital for symptoms triggered by, but not directly related to, the shooting, or for exacerbations of underlying conditions. There were 362 gunshot wounds recorded in the Barell Matrix (1.44 per patient). The Emergency Severity Index (ESI) distribution was skewed toward higher acuity than typical for an emergency department (ED), with 15.1% ESI 1 and 17.6% ESI 2 patients. Semi-automatic firearms were used in 100% of these civilian public mass shootings, with 50 total weapons for 13 shootings (Route 91 Harvest Festival, Las Vegas. 24). Assailant motivations were reported to be associated with hate crimes in 23.1%. Conclusion: Survivors of mass shootings have substantial morbidity and characteristic injury distribution, but 37% of victims had no GSW. Law enforcement, emergency medical systems, and hospital and ED disaster planners can use this information for injury mitigation and public policy planning. The BIDM is useful to organize data regarding gun violence injuries. We call for additional research funding to prevent and mitigate interpersonal firearm injuries, and for the National Violent Death Reporting System to expand tracking of injuries, their sequelae, complications, and societal costs.

The choline-containing phospholipid, phosphatidylcholine (PtdCho) is the most common mammalian phospholipid found in cell membrane (Ide et al., 2013). It is also a component of intracellular signalling pathways (Cui and Houweling, 2002). Herein is described a measure of the rate of accumulation of choline by lipid soluble PtdCho and lyso-Ptdcho which can further be discriminated by chromatographic analysis (Smith and Phyu, 2016). Determination of the accumulation of [3H-methyl]-choline into water-soluble components is also described. The procedure could be used to measure the effect of drugs and other factors on choline incorporation into phospholipids. After exposure of cells to test conditions (e.g., drugs) adherent cells in tissue culture flasks are incubated with radiolabelled [3H-methyl]-choline in medium for 15 min (pulse). The [3H-methyl]-choline is then rapidly removed and incubation continued in the presence of non-radioactive medium (chase). Cellular distribution of [3H-methyl] is then determined by cell fractionation and measurement of radioactivity in the lipid and non-lipid cellular components.

Aims: To examine the cardiovascular safety of combining glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with aspirin in individuals with obesity, both with and without type 2 diabetes (T2D)., Materials and Methods: This propensity score matched cohort study analysed data from 2 946 579 individuals with obesity, with and without T2D, using the TriNetX US and Global dataset. Participants were categorized into four matched groups: those receiving GLP-1 RA plus aspirin versus those receiving GLP-1 RA alone, for both diabetic and non-diabetic individuals. Cardiovascular outcomes and adverse events were evaluated over 5 years using Cox proportional hazards models., Results: Individuals with obesity treated with GLP-1 RAs plus aspirin showed significantly higher risks of various cardiovascular events compared to those on GLP-1 RAs alone. In non-diabetic obese individuals, the combination therapy increased risks of hypertensive heart diseases (HR 1.40, 95% CI 1.15-1.60), ischaemic heart disease (HR 2.39, 95% CI 1.92-2.97) and heart failure (HR 1.97, 95% CI 1.54-2.53). Similar patterns were observed in individuals with T2D. Atrial fibrillation and cardiac arrhythmias showed increasing hazard ratios over time. The combination therapy also led to more frequent adverse events, including gastrointestinal bleeding., Conclusions: The combination of GLP-1 RAs with aspirin in individuals with obesity, both with and without T2D, was associated with increased cardiovascular risks compared to GLP-1 RA monotherapy. These findings suggest that there may be risks associated with the combined use of these treatments and highlight the need for further research into this possible complication with regard to treatment., (© 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background : Hallux valgus is a common forefoot disorder with hundreds of proposed management techniques. Distal chevron osteotomy with a modified McBride procedure has been traditionally recommended for mild hallux valgus because of its simple and less invasive nature with fewer complications, faster recovery, and reliable outcomes. In recent years, the indications for this procedure have expanded to include hallux valgus with severe deformities. This study aims to compare the radiographic outcomes of the surgical treatment for moderate versus severe hallux valgus patients from the perspective of sesamoid bone reduction. Materials and Methods : A retrospective review of medical records identified 99 feet from 94 patients that were treated with distal chevron osteotomy with a modified McBride procedure. These feet were divided by the preoperative hallux valgus angle and intermetatarsal angle into the moderate and severe groups. Results : Postoperative radiographic parameters significantly improved in both groups after treatment, indicating adequate deformity correction. Improvement in the sesamoid position was better in the moderate group compared to that in the severe group. The recurrence rate in the severe group was higher than that in the moderate group without statistical significance. Conclusions : Based on the radiographic results of the postoperative position following sesamoid reduction, the distal chevron osteotomy with a modified McBride procedure is effective for treating moderate hallux valgus deformities. However, this treatment strategy may be associated with a higher recurrence rate in cases of severe hallux valgus deformity. A complete reduction in the sesamoids should be emphasized during the management of severe hallux valgus deformity.

Metabolic syndrome (MetS) is a global health concern with spatial disparities, especially in disadvantaged neighborhoods. This study aimed to examine the association between area-level socioeconomic deprivation, the availability of medical resources in disadvantaged areas such as the Cijin district, and the prevalence of MetS in Taiwan. We used two representative secondary cross-sectional datasets, including physical examinations and lifestyle surveys from 2016 to 2020, sourced from the Taiwan Biobank and the Cijin District Adult Lifestyle and Health Survey. Our findings indicate that residing in the Cijin district, characterized by socioeconomic deprivation and limited medical resources, is associated with significantly higher odds of MetS (aOR = 1.45, 95% CI = 1.28-1.64, p <0.001). Additionally, living in areas with medium (aOR = 1.12, 95% CI = 1.07-1.17, p <0.001) and high area-level socioeconomic deprivation indexes (aOR = 1.13, 95% CI = 1.01-1.25, p <0.001) is linked to a higher likelihood of MetS. Conversely, residing in high medical resource availability index areas is associated with a lower risk of MetS (aOR = 0.92, 95% CI = 0.86-0.99, p = 0.026). We found a link between socioeconomic deprivation and limited medical resources, especially in disadvantaged areas such as the Cijin district, contributing to a higher MetS risk. Residents in these areas often struggle to access healthcare and preventive care. Addressing these disparities requires comprehensive public health initiatives and targeted policy interventions to improve residents' well-being., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background: Impaired mitochondrial protein import machinery leads to phenotypically heterogeneous diseases. Here, we report a recurrent homozygous missense variant in the gene that encodes the translocase of outer mitochondrial membrane 7 (TOMM7) in nine patients with microcephaly, short stature, facial dysmorphia, atrophic macular scarring, and moyamoya disease from seven unrelated families., Methods: To prove the causality of the TOMM7 variant, mitochondrial morphology, proteomics, and respiration were investigated in CRISPR/Cas9-edited iPSCs-derived endothelial cells. Cerebrovascular defects and mitochondrial respiration were also examined in CRISPR/Cas9-edited zebrafish., Findings: iPSC-derived endothelial cells with homozygous TOMM7 p.P29L showed increased TOM7 stability, enlarged mitochondria, increased senescence, and defective tube formation. In addition, proteomic analysis revealed a reduced abundance of mitochondrial proteins involved in ATP synthesis or coordinating TCA cycle and gluconeogenesis. Moreover, mitochondrial respiration was slightly decreased while ATP production from glycolysis was significantly increased. Furthermore, deletion of tomm7 in zebrafish caused craniofacial and cerebrovascular defects that recapitulated human phenotypes. Notably, homozygous iPSCs differentially expressed genes involved in glycolysis and response to hypoxia. Finally, the metabolic imbalance was evidenced by decreased oxygen consumption, increased level of hexokinase 2, and enhanced glycolysis in endothelial cells derived from the patient's iPSCs., Interpretation: These results revealed the essential role of TOMM7 in balancing cellular sources of energy production at both proteomic and transcriptomic levels and provided the molecular mechanisms through which TOMM7 p.P29L variant leads to an autosomal recessive microcephalic osteodysplastic dwarfism with moyamoya disease., Funding: This work is supported by National Science and Technology Council grants and National Cheng Kung University Hospital., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Triple negative breast cancer (TNBC) is characterized by high heterogenicity and aggressiveness and autophagy plays a complicated role in cancer development. Zingerone is reported to possess multiple pharmacological activities, including antitumors. This study explored the biological role and the relevant mechanisms of zingerone in TNBC. Following zingerone treatment, the viability of normal breast cancer cells MCF-10A and TNBC cells (MDA-MB-231 and MDA-MB-468) was detected with CCK-8 assay. The proliferation, migration and invasion of TNBC cells were detected with colony formation, wound healing, and transwell assays. Western blot was used to detect the expressions of migration-, apoptosis- and autophagy-related proteins. Flow cytometry was used to detect the cell apoptotic level and immunofluorescence assay measured the autophagy. The experimental data revealed that zingerone with varying concentrations suppressed cell viability, proliferation, migration and invasion while promoting the apoptosis in TNBC, which might be mediated by autophagy activation. Besides, zingerone decreased HDAC1 expression in TNBC cells and regulated autophagy via HDAC1. Collectively, zingerone impeded the malignant progression of TNBC via inducing HDAC1-mediated autophagy., (© 2024 Wiley Periodicals LLC.)

Bone mineral density (BMD) is a crucial indicator of osteoporosis. Bioelectrical impedance analysis (BIA) introduces a new method for assessing body composition, specifically BMD measurement. Compared with existing ultrasound and dual-energy X-ray absorptiometry for BMD screening and diagnosis, BIA has the advantages of safety, convenience and speed. However, the accuracy of BIA for BMD measurement needs to be explored. This study aimed to evaluate the accuracy of the novel BIA technique in conducting whole-body BMD assessments in the general population of Taiwan. Overall, 318 healthy adults in Taiwan (37.67 ± 19.44 years of age; 145 male and 173 female patients) were included. Whole-body BMD was measured via foot-to-foot BIA-StarBIA-201 (StarBIA Meditek Co. LTD, Taichung, Taiwan) and the dual-energy X-ray absorptiometry (DXA) Lunar Prodigy technology (GE Medical Systems, Madison, WI, USA). Linear regression analysis, Pearson's correlation coefficient, the Bland-Altman plot, and paired t tests were used. The whole-body BMDs measured by BIA and DXA were 1.139 ± 0.124 g/cm 2 and 1.202 ± 0.168 g/cm 2 , respectively. The regression equation was y = 1.057x + 0.063. The Pearson correlation coefficient, mean difference, and limits of agreement were r = 0.737, - 0.053 g/cm 2 , and - 0.290-0.165 g/cm 2 , respectively. The regression equation was y = 1.057x + 0.063. The Pearson correlation coefficient, mean difference, and limits of agreement were r = 0.737 (p < 0.001), - 0.053 g/cm 2 , and - 0.290-0.165 g/cm 2 , respectively. Standing BIA was correlated with the DXA gold standard for estimating whole-body BMD in adults; however, its interchangeability remains limited. The potential bias in the measurement results of this study represents a current challenge with BIA compared with that of DXA, and there is still room for improvement. The convenient BIA method for measuring whole-body BMD may be useful in the application of primary screening and future development of BMD assessment methods. BIA is widely used to measure body composition, but its application to the measurement of BMD represents a novel technological breakthrough., Competing Interests: Declarations. Competing interests: The authors have read the journal’s policy and have the following competing interests: Dr. Kuen-Chang Hsieh was employed by a commercial company, StarBIA Meditek Co. Ltd., during this study. This does not alter our adherence to Nature Research policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. All other authors have no conflicts of interest to declare. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (© 2024. The Author(s).)

Aim: We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D)., Materials and Methods: In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event., Results: After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions., Conclusions: In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population., (© 2024 John Wiley & Sons Ltd.)

Background: Ovarian cancer is the most lethal gynecological cancer. As the primary treatment, chemotherapy has a response rate of only 60-70% in advanced stages, and even lower as a second-line treatment. Despite guideline recommendations, which drugs will be most effective remains unclear. Thus, a strategy to prioritize chemotherapy options is urgently needed. Cancer organoids have recently emerged as a method for in vitro drug testing. However, limited clinical correlations have been assessed with test results from cancer organoids, particularly in gynecological cancers. We therefore aimed to generate patient-derived organoids (PDOs) of ovarian cancer, to assess their drug sensitivities and correlations with patient clinical outcomes., Methods: PDOs were generated from fresh tumors obtained during surgical resection, which was then cultured under matrix gel and appropriate growth factors. Morphological and molecular characterization of PDOs were assessed by phase contrast microscopy and paraffin-embedded histopathology. Expressions of PAX8, TP53, WT1, CK7, and CK20 were tested by immunohistochemical staining and compared with parental tumor tissues and the human protein atlas database. PDOs were subjected to in vitro drug testing to determine drug sensitivity using Titer-Glo ® 3D Cell Viability Assay. PDO viability was measured, and area under the curve calculated, to compare responses to various compounds. Correlations were calculated between selected patients' clinical outcomes and in vitro drug testing results., Results: We established 31 PDOs. Among them, 28 PDOs can be expanded, including 15, 11, and 2 from ovarian, endometrial, and cervical cancers, respectively. The PDOs preserved the histopathological profiles of their originating tumors. In vitro drug testing of 10 ovarian cancer PDOs revealed individual differential responses to recommended drugs, and interpersonal heterogeneity in drug sensitivity, even with the same histology type. Among four patients who were platinum sensitive, resistant, or refractory, PDO drug responses correlated well with their clinical courses., Conclusion: In vitro drug testing using ovarian cancer organoids is feasible and correlates well with patient clinical responses. These results may facilitate development of precision chemotherapy and personalized screening for repurposed or new drugs., (© 2024. The Author(s).)

Background: Patient-prosthesis mismatch (PPM) after surgical aortic valve replacement for severe aortic stenosis has a significant effect on survival. Few studies have identified the risk factors for PPM and related outcomes. This study investigated these risk factors and clarified the outcomes., Methods: This study enrolled consecutive patients who underwent aortic valve replacement surgery between January 2010 and June 2020 in our hospital. Data on clinical profiles, prosthesis types, echocardiographic parameters before and after surgery, and clinical outcomes including the composite of all-cause mortality and redo valve replacement were collected. We defined moderate and severe PPM as an effective orifice area index value of ≤ 0.85 and ≤ 0.65 cm 2 /m 2 , respectively, measured postoperatively through echocardiography. Potential risk factors for PPM and clinical outcomes were evaluated., Results: A total of 185 patients were enrolled. Body surface area (BSA; 1.68 ± 0.02 vs. 1.62 ± 0.01 m 2 , p = 0.036), renal insufficiency (32.50% vs. 11.70%, p = 0.026), and aortic annulus diameter (1.99 ± 0.05 vs. 2.17 ± 0.03 cm, p = 0.013) were statistically significant risk factors for severe PPM. The primary outcome was observed in 30.00% and 15.86% of the patients with and without severe PPM, respectively (log-rank p = 0.023). Multivariate Cox proportional hazards analysis indicated that severe PPM was a risk factor for the primary outcome (hazard ratio: 2.688, 95% confidence interval: 1.094-6.622, p = 0.031)., Conclusions: Our study demonstrated that large BSA, renal insufficiency, and small annulus diameter were risk factors for severe PPM after aortic valve replacement surgery. Severe PPM was associated with worse clinical outcomes., Competing Interests: All authors have no conflicts of interest to declare. All authors have seen and agree with the contents of the manuscript. We certify that the submission is original work and is not under review at any other publication.

Objective: To investigate the relationships of sleep patterns and respiratory disturbance index (RDI) with key physiological parameters (height, body mass index (BMI), bone age (BA), and IGF-1 levels) in children aged 6 to 16 years with self-perceived short stature., Methods: For this cross-sectional study, conducted from October 2019 to November 2021, 238 children aged 6 to 16 years with self-perceived short stature were enrolled. The primary outcomes of sleep patterns and the RDI were non-invasively collected at home using the LARGAN Health AI-Tech Sleep Apnea and Sleep Quality Examination System, which operates based on polygraphy. Additionally, various physiological parameters, including height, BMI, bone age, and IGF-1 levels, were measured to assess their associations with sleep patterns and RDI., Results: Significant age-related reductions were observed in both the total and deep sleep durations. Children aged 6-9 years averaged 8.5 ± 1.0 h of total sleep, which decreased to 8.1 ± 1.1 h in ages 10-11 and further to 7.5 ± 0.9 h in ages 12-16 ( p < 0.0001). Deep sleep followed a similar pattern, decreasing from 4.4 ± 1.1 h in the youngest group to 3.3 ± 1.0 h in the oldest ( p < 0.0001). Notably, girls experienced significantly longer deep sleep than boys, averaging 4.0 ± 1.2 h compared to 3.6 ± 1.2 h ( p = 0.0153). In a multivariable regression analysis, age (beta = 4.89, p < 0.0001) and RDI (beta = -0.54, p = 0.0022) were significantly associated with body height. Age and deep sleep duration (beta = -0.02, p = 0.0371) were significantly associated with BMI., Conclusions: The results demonstrate significant age-related decreases in the total and deep sleep duration among children with self-perceived short stature, along with a notable association between RDI and body height and an association between deep sleep duration and BMI. These findings suggest that sleep disturbances in pediatric endocrine patients are intricately linked with physiological growth parameters. The identified correlations underline the importance of monitoring sleep patterns in this demographic to better understand the impact of endocrine disorders on developmental health. Further research is needed to explore interventions that could alleviate these sleep disturbances, thereby potentially improving outcomes for the affected children.

Background: Obesity is a major health concern worldwide. Previous studies have suggested that phthalate plasticizers are obesogens. However, the relationship between early-life phthalate exposure and long-term obesity development remains unknown., Objective: We investigated the association between prenatal phthalate exposure and children's body mass index (BMI) patterns in an 18-year birth cohort follow-up study in Taiwan., Methods: Our analytical lab quantified seven phthalate metabolites in maternal urine during pregnancy using quantitative liquid chromatography-tandem mass spectrometry. In addition, we calculated BMI z scores for participated children at each follow-up, utilized trajectory analysis to describe children's BMI z-score patterns at 2-18 years of age, and adopted generalized estimating equations (GEE) and multivariate logistic regression models to assess the association between prenatal phthalate exposure and BMI z scores in children., Results: A total of 208 mother-child pairs were included in the analysis. Maternal urinary diethyl phthalate (DEP) metabolites were associated with the increase of BMI z scores in children aged 2-18 years in the GEE model. Doubled maternal urinary ∑mDEHP (3 mono hexyl-metabolites of di-ethyl-hexyl phthalate (DEHP) increased the risk of children being in the stable-high BMI trajectory group until the age of eighteen., Impact Statement: We observed that BMI trajectories of children remained stable after the age of 5 years. During each follow-up, a higher frequency of overweight or obese was observed in children, ranging from 15.9% to 35.6% for girls and 15.2-32.0% for boys, respectively. Prenatal phthalate exposure was associated with increasing BMI z scores in children. Prenatal DEHP exposure was associated with a stable-high BMI trajectory in children up to the age of 18 years., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The association between short-term changes in serum magnesium level and risk of in-hospital mortality was investigated in patients with acute myocardial infarction (AMI). In this retrospective cohort study, data of 2,716 patients with AMI were extracted from the Medical Information Mart for Intensive Care (MIMIC-III and MIMIC-IV) database for 2001-2012. Univariate and multivariate Cox proportional hazards models were used to explore the association between serum magnesium level and short-term change and in-hospital mortality in patients with AMI. In addition, subgroups according to age, gender, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score (SAPS-II) were also analysed. In total, 504 (18.6%) patients died in hospital. After adjusting for covariates, all AMI patients with high magnesium levels at ICU admission (HR=1.03, 95% CI: 0.83-1.27) or 48 hours after ICU admission (all p<0.05), or those demonstrating a change in magnesium level within the first 48 hours of ICU stay (all p<0.05) were shown to have a high risk of in-hospital mortality. Moreover, this correlation was retained irrespective of age, gender, SOFA score, and SAPS-II (all p<0.05). Serum magnesium levels at different time points after ICU admission and change in serum magnesium level during the first 48 hours were associated with in-hospital mortality in patients with AMI, indicating that clinical attention should be paid to short-term changes in serum magnesium levels regarding treatment adjustment, which may further reduce the risk of mortality.

Ten-eleven translocation 1 (TET1) is a methylcytosine dioxygenase involved in active DNA demethylation. In our previous study, we demonstrated that TET1 reprogrammed the ovarian cancer epigenome, increased stem properties, and activated various regulatory networks, including metabolic networks. However, the role of TET1 in cancer metabolism remains poorly understood. Herein, we uncovered a demethylated metabolic gene network, especially oxidative phosphorylation (OXPHOS). Contrary to the concept of the Warburg effect in cancer cells, TET1 increased energy production mainly using OXPHOS rather than using glycolysis. Notably, TET1 increased the mitochondrial mass and DNA copy number. TET1 also activated mitochondrial biogenesis genes and adenosine triphosphate production. However, the reactive oxygen species levels were surprisingly decreased. In addition, TET1 increased the basal and maximal respiratory capacities. In an analysis of tricarboxylic acid cycle metabolites, TET1 increased the levels of α-ketoglutarate, which is a coenzyme of TET1 dioxygenase and may provide a positive feedback loop to modify the epigenomic landscape. TET1 also increased the mitochondrial complex I activity. Moreover, the mitochondrial complex I inhibitor, which had synergistic effects with the casein kinase 2 inhibitor, affected ovarian cancer growth. Altogether, TET1-reprogrammed ovarian cancer stem cells shifted the energy source to OXPHOS, which suggested that metabolic intervention might be a novel strategy for ovarian cancer treatment.

Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumor. Currently, the predominant clinical treatment is the combination of surgical resection with concurrent radiotherapy and chemotherapy, using temozolomide (TMZ) as the primary chemotherapy drug. Lidocaine, a widely used amide‑based local anesthetic, has been found to have a significant anticancer effect. It has been reported that aberrant hepatocyte growth factor (HGF)/mesenchymal‑epithelial transition factor (MET) signaling plays a role in the progression of brain tumors. However, it remains unclear whether lidocaine can regulate the MET pathway in GBM. In the present study, the clinical importance of the HGF/MET pathway was analyzed using bioinformatics. By establishing TMZ‑resistant cell lines, the impact of combined treatment with lidocaine and TMZ was investigated. Additionally, the effects of lidocaine on cellular function were also examined and confirmed using knockdown techniques. The current findings revealed that the HGF/MET pathway played a key role in brain cancer, and its activation in GBM was associated with increased malignancy and poorer patient outcomes. Elevated HGF levels and activation of its receptor were found to be associated with TMZ resistance in GBM cells. Lidocaine effectively suppressed the HGF/MET pathway, thereby restoring TMZ sensitivity in TMZ‑resistant cells. Furthermore, lidocaine also inhibited cell migration. Overall, these results indicated that inhibiting the HGF/MET pathway using lidocaine can enhance the sensitivity of GBM cells to TMZ and reduce cell migration, providing a potential basis for developing novel therapeutic strategies for GBM.

Background: Preoperative estimation of the volume of the left atrium (LA) and epicardial adipose tissue (EAT) on computed tomography (CT) images is associated with an increased risk of atrial fibrillation (AF) recurrence. We aimed to design a deep learning-based workflow to provide reliable automatic segmentation of the atria, pericardium, and EAT for future applications in the management of AF., Methods: This study enrolled 157 patients with AF who underwent first-time catheter ablation between January 2015 and December 2017 at Taipei Veterans General Hospital. Three-dimensional (3D) U-Net models of the LA, right atrium (RA), and pericardium were used to develop a pipeline for total, LA-EAT, and RA-EAT automatic segmentation. We defined fat within the pericardium as tissue with attenuation between -190 and -30 HU and quantified the total EAT. Regions between the dilated endocardial boundaries and endocardial walls of the LA or RA within the pericardium were used to detect voxels attributed to fat, thus estimating LA-EAT and RA-EAT., Results: The LA, RA, and pericardium segmentation models achieved Dice coefficients of 0.960 ± 0.010, 0.945 ± 0.013, and 0.967 ± 0.006, respectively. The 3D segmentation models correlated well with the ground truth for the LA, RA, and pericardium ( r = 0.99 and p < 0.001 for all). The Dice coefficients of our proposed method for EAT, LA-EAT, and RA-EAT were 0.870 ± 0.027, 0.846 ± 0.057, and 0.841 ± 0.071, respectively., Conclusion: Our proposed workflow for automatic LA, RA, and EAT segmentation using 3D U-Nets on CT images is reliable in patients with AF., Competing Interests: Conflicts of interest: Dr. Shih-Ann Chen, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: Osteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations., Methods: We selected 8115 patients with osteoporosis (T-score ≤ - 2.5) and 55,942 healthy individuals (T-score > - 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic reticulum (ER) stress, inflammasome activation, and osteoclastogenesis. An in vitro model of GD patient's cells treated with adeno-associated virus 9 (AAV9)-GBA1 to assess GBA1 enzyme activity, chitotriosidase activity, ER stress, and osteoclast differentiation. Longitudinal dual-energy X-ray absorptiometry (DXA) data tracking bone density in patients with Gaucher disease (GD) undergoing enzyme replacement therapy (ERT) over an extended period., Results: The GBA1 gene variant rs11264345 was significantly associated [P < 0.002, Odds Ratio (OR) = 1.06] with an increased risk of bone disease. Upregulation of Calnexin, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) was positively associated with osteoclastogenesis in patients with GD. In vitro AAV9-GBA1 treatment of GD patient cells led to enhanced GBA1 enzyme activity, reduced chitotriosidase activity, diminished ER stress, and decreased osteoclast differentiation. Long-term bone density data suggests that initiating ERT earlier in GD leads to greater improvements in bone density., Conclusions: Elevated ER stress and inflammasome activation are indicative of osteoporosis development, suggesting the need for clinical monitoring of patients with GD. Furthermore, disease-associated variant in the GBA1 gene may constitute a risk factor predisposing specific populations to osteoporosis., (© 2024. The Author(s).)

Background/aim: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder characterized by sphingomyelin accumulation causing progressive lung disease, respiratory failure, and death., Patients and Methods: This retrospective observational study used the TriNetX database of electronic health records for 15,108 patients with ASMD from 2000-2020. After exclusions, 8,980 individuals were followed for 10 or 20 years. Outcomes included incidence and prevalence of respiratory disorders. Associations of age, sex and race were assessed., Results: Nearly all respiratory outcomes increased significantly over 20 versus 10 years. Other respiratory disorders, specified respiratory disorders and secondary pulmonary hypertension exhibited the greatest increases, reflecting progressive lung damage in ASMD. While outcomes were poor overall, older age, male sex, and racial minority status associated with greater risks, indicating differences in disease progression or care., Conclusion: This study confirms the progressive nature of ASMD and need for close monitoring and treatment of pulmonary complications to reduce long-term morbidity and mortality. Genetic testing enabling diagnosis even for milder, adult-onset forms is critical to optimize outcomes., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Silver-Russell syndrome (SRS; OMIM #180860) is a clinically and genetically heterogeneous imprinting disorder characterized by prenatal and postnatal growth failure. The aim of this study was to identify the epigenotype-phenotype correlations in these patients using quantitative DNA methylation analysis. Methods: One hundred and eighty-three subjects clinically suspected of having SRS were referred for diagnostic testing by the methylation profiling of H19 -associated imprinting center (IC) 1 and imprinted PEG1/MEST regions using methylation-specific high-resolution melting analysis and methylation quantification with the MassARRAY assay. Correlations between quantitative DNA methylation status and clinical manifestations of the subjects according to the Netchine-Harbison (N-H) clinical scoring system for SRS were analyzed. Results: Among the 183 subjects, 90 had a clinical diagnosis of SRS [N-H score ≥ 4 (maximum = 6)] and 93 had an SRS score < 4. Molecular lesions were detected in 41% (37/90) of the subjects with a clinical diagnosis of SRS, compared with 3% (3/93) of those with an N-H score < 4. The IC1 methylation level was negatively correlated with the N-H score. The molecular diagnosis rate was positively correlated with the N-H score. Thirty-one subjects had IC1 hypomethylation (IC1 methylation level <35% by the MassARRAY assay), seven had maternal uniparental disomy 7, and two had pathogenic copy number variants. Among the 90 subjects with an N-H score ≥ 4, the IC1 methylation level was significantly different between those with or without some clinical SRS features, including birth length ≤ 10th centile, relative macrocephaly at birth, normal cognitive development, body asymmetry, clinodactyly of the fifth finger, and genital abnormalities. Conclusions: This study confirmed the suitability of the N-H clinical scoring system as clinical diagnostic criteria for SRS. Quantitative DNA methylation analysis using the MassARRAY assay can improve the detection of epigenotype-phenotype correlations, further promoting better genetic counseling and multidisciplinary management for these patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background/aim: X-linked hypophosphatemia (XLH), the most common form of hereditary rickets, results from loss-of-function mutations in the phosphate-regulating PHEX gene. Elevated fibroblast growth factor 23 (FGF23) contributes to hypophosphatemia in XLH. This study aimed to characterize PHEX variants and serum FGF23 profiles in Taiwanese patients with XLH., Patients and Methods: We retrospectively reviewed the records of 102 patients clinically suspected of having hypophosphatemic rickets from 2006 to 2022. Serum intact Fibroblast growth factor-23 (iFGF23) levels were measured on clinic visit days. PHEX mutations were identified using Sanger sequencing, and negative cases were analyzed using whole-exome sequencing., Results: The majority (92.1%) of patients exhibited elevated FGF23 compared with normal individuals. Among 102 patients, 44 distinct PHEX mutations were identified. Several mutations recurred in multiple unrelated Taiwanese families. We discovered a high frequency of novel PHEX mutations and identified variants associated with extreme FGF23 elevation and tumorigenesis., Conclusion: Our findings revealed the PHEX genotypic variants and FGF23 levels in Taiwanese patients with XLH. These results are crucial given the recent approval of burosumab, a monoclonal FGF23 antibody, for XLH therapy. This study provides key insights into the clinical management of XLH in Taiwan., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We presented the case of a patient with non-ST-elevation myocardial infarction with coronary arteries of an anomalous origin, an interarterial course of the LMCA, a unique wide-angle "right" main bifurcation lesion, and a high SYNTAX score. Management with contemporary PCI and imaging may be an alternative to surgery., 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., (© 2023 Su, Ko and Lee.)

Background/aim: Fabry disease, an X-linked lysosomal storage disorder, causes progressive globotriaosylceramide accumulation in cells throughout the body. Characteristic multiorgan manifestations include renal dysfunction (Fabry nephropathy) and associated urinary tract complications. Enzyme replacement therapy (ERT) has been available since 2001, but contemporary real-world data are lacking regarding Fabry nephropathy risks and treatment outcomes., Patients and Methods: This retrospective cohort study analyzed electronic medical records data for 10,637 Fabry disease patients from the TriNetX research database. Kidney and urinary tract outcomes were evaluated over two decades, 2000-2010 and 2011-2020. Outcomes assessed included chronic kidney disease (CKD), urinary tract infections, urinary incontinence, obstruction, renal insufficiency, and end-stage renal disease (ESRD)., Results: The prevalence of stage 4-5 CKD nearly doubled between 2000-2010 and 2011-2020, while ESRD prevalence rose over 4-fold. Incidence rates showed similar marked elevations across renal and urologic complications. Females and Black patients experienced disproportionate escalations in kidney and urinary tract morbidity., Conclusion: This large cohort study revealed significantly increased Fabry nephropathy and associated urologic complications over the past two decades, contradicting expectations of reduced morbidity with ERT availability. The findings highlight needs to optimize screening, treatment strategies, monitoring practices, and address disparities to curb rising disease burden and improve patient outcomes., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Turner syndrome confers increased cancer susceptibility; however, large-scale epidemiological evidence is lacking. This study aimed to analyze the incidence and prevalence of various malignancies in patients with Turner syndrome over 20 years of age to inform screening strategies., Patients and Methods: We performed a retrospective cohort analysis of 11,502 patients with Turner syndrome from 2000 to 2020 utilizing the TriNetX research network database. The outcomes encompassed the incidence and prevalence of 20 cancers. Stratified analyses were used to evaluate variations in age, sex, and race., Results: Key findings demonstrated markedly elevated risks of breast (1.7%), colon (1.0%), renal (0.4%), gonadoblastoma (0.4%), and other cancers. Significant demographic variations were observed in the incidence of cancers, such as gonadoblastoma, renal, and colon cancer., Conclusion: This large real-world study offers novel insights into the spectrum of cancer risk across adulthood in Turner syndrome. Our findings elucidate Turner syndrome's complex cancer phenotype to inform clinical decision-making, prognostication, and tailored screening strategies to ultimately advance patient care., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The search for new redox-active organic materials (ROMs) is essential for the development of sustainable energy-storage solutions. In this study, we present a new class of cyclobuta[ b ]quinoxaline-1,2-diones or squaric acid quinoxalines (SQXs) as highly promising candidates for ROMs featuring exceptional stability and high redox potentials. While simple 1,2- and 1,3-squaric acid amides (SQAs), initially reported by Hünig and coworkers decades ago, turned out to exhibit low stability in their radical cation oxidation states, we demonstrate that embedding the nitrogen atoms into a quinoxaline heterocycle leads to robust two-electron SQX redox systems. A series of SQX compounds, as well as their corresponding radical cations, were prepared and fully characterized, including EPR spectroscopy, UV-vis spectroscopy, and X-ray diffraction. Based on the promising electrochemical properties and high stability of the new ROM, we developed SQX-functionalized polymers and investigated their physical and electrochemical properties for energy-storage applications. These polymers showed remarkable thermal stability well above 200 °C with reversible redox properties and potentials of about 3.6 V vs Li + /Li. By testing the galvanostatic cycling performance in half-cells with lithium-metal counter electrodes, a styrene-based polymer with SQX redox side groups showed stable cycling for single-electron oxidation for more than 100 cycles. These findings render this new class of redox-active polymers as highly promising materials for future energy-storage applications.

Aims: To analyse the genome-wide association study (GWAS) data of patients with type 1 diabetes mellitus (T1D) in order to develop a risk score for the genetic effects on T1D risk and age at diagnosis in the Taiwanese population., Materials and Methods: We selected 610 patients with T1D and 2511 healthy individuals from an electronic medical record database of more than 300 000 individuals with genetic information, analysed their GWAS data, and developed a polygenic risk score (PRS)., Results: The PRS, based on 149 selected single-nucleotide polymorphisms, could effectively predict T1D risk. A PRS increase was associated with increased T1D risk (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.72-2.55). Moreover, a 1-unit increase in standardized T1D PRS decreased the age at diagnosis by 0.74 years. Combined PRS and human leukocyte antigen (HLA) DQA1*03:02-DQA1*05:01 genotypes could accurately predict T1D risk. In multivariable models, HLA variants and PRS were independent risk factors for T1D risk (OR 3.76 [95% CI 1.54-9.16] and 1.71 [95% CI 1.37-2.13] for HLA DQA1*03:02-DQA1*05:01 and PRS, respectively). In a limited study population of those aged ≤18 years, PRS remained significantly associated with T1D risk. The association between T1D PRS and age at diagnosis was more obvious among males and patients aged ≤18 years., Conclusions: Polygenic risk score and HLA variations enable personalized risk estimates, enhance newborn screening efficiency for ketoacidosis prevention, and addresses the gap in data on T1D prediction in isolated Asian populations., (© 2023 John Wiley & Sons Ltd.)

Background/aim: Gaucher disease (GD) is a rare lysosomal storage disorder that can involve the lungs and pulmonary vasculature. The long-term effects of GD on respiratory health remain unclear due to limited data on the natural history of this disease. We analyzed electronic health records for 11,004 patients with GD over 10-20 years to determine the incidence of pulmonary hypertension (PH), lung disease, and other respiratory comorbidities and better understand disease course to guide management., Patients and Methods: We conducted a retrospective cohort study using the TriNetX research database of 130 million international patients. The incidence of primary/secondary PH, pulmonary heart disease, interstitial/obstructive/restrictive lung disease, pulmonary hemorrhage, and pulmonary embolism was assessed in patients with GD from 2000-2020., Results: Incidence rates of all conditions assessed increased from 10 to 20 years of follow-up. Excess risk of PH, lung disease, and pulmonary hemorrhage was significantly higher in GD patients after 20 versus 10 years., Conclusion: Extended follow-up in GD is associated with substantially higher risks of PH, lung disease and other respiratory comorbidities, highlighting the need for close monitoring and early intervention to mitigate long-term pulmonary decline. Improved understanding of mechanisms driving respiratory deterioration can support the development of novel treatments to optimize outcomes in this population at high risk of pulmonary morbidity and mortality., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Individuals with Down syndrome are at a higher risk of cardiac, renal, and other health issues due to a complex disease physiology. However, few data exist on long-term disease risks to guide prevention and care. We aimed to determine the 10-year incidence of cardiac, renal, and urinary tract complications in Down syndrome versus matched controls., Methods: This retrospective cohort study utilized a large collaborative database. We identified 32,444 patients with Down syndrome and matched controls, excluding those with pre-follow-up target events. Covariates included demographics, lifestyle factors, and comorbidities. Outcomes were ischemic heart disease, hypertension, hypothyroidism, epilepsy, urinary tract infections and chronic kidney disease. We calculated unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression and plotted Kaplan-Meier survival curves., Findings: Over 10 years, Down syndrome patients showed a 3.7-fold higher ischemic heart disease risk (95% CI: 3.0-4.6) and a 1.6-fold higher hypertension risk (95% CI: 1.4-1.8) versus controls. Hypothyroidism (HR = 2.0; 95% CI: 1.7-2.4), epilepsy (HR = 4.5; 95% CI: 3.5-5.8), and urinary tract infection (HR = 3.9; 95% CI: 3.4-4.6) risks were also higher. Chronic kidney disease risk was 2.7-fold greater (95% CI: 2.1-3.5). Survival analysis confirmed a significantly higher incidence of all outcomes in Down syndrome ( p < 0.0001)., Interpretation: This large study found major health challenges in Down syndrome, with risks 3- to 5-fold higher for chronic conditions versus matched controls over 10 years. Though survival remains high with proper care, focusing resources on the prevention and management of complications in this high-risk group can optimize well-being across the lifespan. Future research accounting for limitations here would provide definitive estimates of disease risk in Down syndrome to guide targeted health strategies.

Lithium metal is a promising anode material for next-generation high-energy-density batteries but suffers from low stripping/plating Coulombic efficiency and dendritic growth particularly at sub-zero temperatures. Herein, a poorly-flammable, locally concentrated ionic liquid electrolyte with a wide liquidus range extending well below 0 °C is proposed for low-temperature lithium metal batteries. Its all-anion Li + solvation and phase-nano-segregation solution structure are sustained at low temperatures, which, together with a solid electrolyte interphase rich in inorganic compounds, enable dendrite-free operation of lithium metal anodes at -20 °C and 0.5 mA cm -2 , with a Coulombic efficiency of 98.9 %. As a result, lithium metal batteries coupling thin lithium metal anodes (4 mAh cm -2 ) and high-loading LiNi 0.8 Co 0.15 Al 0.05 O 2 cathodes (10 mg cm -2 ) retain 70 % of the initial capacity after 100 cycles at -20 °C. These results, as a proof of concept, demonstrate the applicability of locally concentrated ionic liquid electrolytes for low-temperature lithium metal batteries., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

To comprehensively clarify the pollution characteristics of persistent toxic substances, the Soil and Air Monitoring Program Phase III (SAMP-III) was conducted in 2019 in China. In total, 154 surface soil samples were collected across China, and 30 unsubstituted polycyclic aromatic hydrocarbons (U-PAHs) and 49 methylated PAHs (Me-PAHs) were analyzed in this study. The mean concentrations of total U-PAHs and Me-PAHs were 540 ± 778 and 82.0 ± 132 ng/g dw, respectively. Northeastern China and Eastern China are the two regions of concern with high PAH and BaP equivalency levels. Compared with SAMP-I (2005) and SAMP-II (2012), an obvious upward temporal trend followed by a downward trend of PAH levels was observed in the past 14 years for the first time. The mean concentrations of 16 U-PAHs were 377 ± 716, 780 ± 1010, and 419 ± 611 ng/g dw in surface soil across China for the three phases, respectively. Considering rapid economic growth and energy consumption, an increasing trend from 2005 to 2012 was expected. From 2012 to 2019, the PAH levels in soils across China decreased by 50 %, which was consistent with the decline in PAH emissions. The period of reduction of PAHs in surface soil coincided with the implementation of Air and Soil Pollution Control Actions in China after 2013 and 2016, respectively. Along with the pollution control actions in China, the pollution control of PAHs and the increase in soil quality can be expected in the near future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

As sisters and sociologists, we shared an unnerving experience of sexual harassment in one of our preliminary field sites. Our research pursuits split thereafter, with one of us leaning into questions of gender and sexuality and the other steering clear. Despite our diverging interests, we both encountered discomforting moments that raise questions about what data we render surplus in our analysis. In this article, we draw on ethnographic and interviewing data from our respective projects to conceptualize "discomforting surplus" as ethnographic data that we omit from our analyses. We offer two types of discomforting surpluses: those that reveal dissonance between our actions and self-conceptions, and those that seem not just uncomfortable, but inconsequential. We mine these discomforting surpluses, calling for introspection about our subject positions and the potential benefits of trying out analytical frames we have ignored. We conclude with practical suggestions for reflecting meaningfully on our relationships to the field and engaging in thought experiments that center discomforting surplus. These contradictions, omissions, and unnerving questions in ethnographic research are important to grapple with as we encounter a push for greater transparency and open science., 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 Su and Su.)

Purpose: There is no consensus on the selection of appropriate prophylactic tube feeding in patients with head and neck squamous cell carcinoma (HNSCC) undergoing concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the effect of prophylactic tube feeding in patients with HNSCC who presented with a high Mallampati score and underwent CCRT., Methods: We prospectively enrolled 185 consecutive patients with stage II to IVa HNSCC and a pre-treatment Mallampati score of 3 or 4 who received CCRT between August 2017 and December 2018 with follow-up data collected retrospectively. Patients were divided to either with or without prophylactic tube feeding group for comparison of treatment tolerance, toxicities, and quality of life(QOL). Propensity score matching (PSM) was used to achieve balanced covariates across the two groups., Results: Of the cohort, 52 (28.1%) and 133 (71.9%) patients were allocated to the prophylactic and non-prophylactic tube feeding groups, respectively. Before and after PSM, patients in the tube feeding group had a significantly lower incidence of incomplete radiotherapy, incompletion of chemotherapy, emergency room visits, and grade 3 or higher infection, and improved symptoms of quality of life after CCRT than those in the non-tube feeding group., Conclusion: Prophylactic tube feeding was associated with better treatment tolerance, safety profiles, and quality of life in patients with HNSCC and high Mallampati scores who underwent CCRT. Therefore, Mallampati score might serve as a clinical tool for proactive selection of patients receiving prophylactic tube feeding in HNSCC patients upon receiving CCRT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Birth defects (BDs) are the main causes of mortality and disability in infants and children. Associations between maternal diabetes mellitus (DM), including gestational DM (GDM) and pregestational DM (type 1 or type 2), and the risk of BDs have been reported. This study aims to determine the relationship between maternal DM and BDs and to investigate whether reducing the incidence of DM can decrease the incidence of BDs., Methods: We identified all births in Taiwan from the National Birth Defects Surveillance Program between January 1, 2010, and December 31, 2014. Information on the infants' characteristics (sex, gestational age, and birth weight) and mothers' characteristics (age, parity, and associated diseases, including DM) were obtained from the National Birth Registry and National Health Insurance Research Database (NHIRD) in Taiwan. BDs were coded according to the International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) codes 740-759., Results: Multiple logistic regression analysis with adjusted odds ratio (aOR) and 95% confidence interval (95% CI) for all BDs showed that the aOR (95% CI) was 1.002 (0.965-1.041), and the p -value was 0.9139 in the GDM group. In the type 1 DM group, the aOR (95% CI) was 1.748 (1.110-2.754), and the p -value was 0.016. In the type 2 DM group, the aOR (95%CI) was 1.175 (1.005-1.375), 1.331 (1.196-1.482), and 1.391 (1.216-1.592), and the p -value was 0.0437, <0.0001, and <0.0001 for the duration of mothers with type 2 DM <2, 2 to 5, >5 years, respectively., Conclusion: Mothers with pregestational DM (type 1 or type 2) increase the incidence of BD. Appropriate maternal glycemic control may achieve good pregnancy and perinatal outcomes., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Purpose: Phthalates are ubiquitous endocrine disruptors that can affect pubertal development in children. The association of fetal and childhood levels of phthalates with pubertal development were explored., Methods: We conduct a population-based birth cohort study to investigate the association between prenatal and childhood exposure to phthalates and pubertal development. Initially, a total of 445 children were recruited from 2000 to 2001, of which 90 children were followed for 15 years which measurements of urine and development assessed at 2, 5, 8, 11, and 14 years. We defined higher Tanner stage as the 14-year-old Tanner stage ≥ 4 and 5 for boys and girls, respectively. A logistic regression analysis was conducted to estimate the crude and adjusted odds ratio of a higher Tanner stage at 14 years old. The Pearson correlation coefficient and multiple linear regression were used to estimate the association of testicular volume, uterine volume, ovarian volume, and blood hormones at 14 years of age with the log-transformed concentration of phthalates at 2, 5, 8, 11, and 14 years., Results: In boys, a significantly different geometric mean of mono-benzyl phthalate (MBzP) was observed in 11-year-olds; 6.82 and 2.96 in the lower Tanner stage group and higher Tanner stage group. In girls, a significant difference in the geometric mean of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in 11-year-olds and mono-ethyl phthalate (MEP) in 2-year-olds was observed; MEHHP was 32.97 and 18.13 in the lower Tanner stage group and higher Tanner stage group, and MEP was 26.54 and 65.74 in the lower Tanner stage group and higher Tanner stage group, respectively. Uterine volume at 14 years old was negatively associated with several phthalate metabolites (MEHP at 8 years old, MnBP at 8 years old, MBzP at 14 years old, MMP prenatally, MMP at 8 years old, and MEP at 8 years old) after adjusting for covariates. However, no significant correlations were found between phthalate metabolites and ovarian or testicular volume., Conclusion: Phthalate exposure at certain time points may influence the reproductive development of children during puberty; however, further studies should be conducted to determine the causal nature of this association., 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 Su, Huang, Wang and Chang.)

Background: Pancreatic cancer can induce a hypercoagulable state which may lead to clinically apparent thrombosis. However, the effect of anticoagulants remains ambiguous. This study aimed to investigate the potential effect of long-term systemic anticoagulant usage on hospitalization outcomes of patients with pancreatic cancer. Methods: This retrospective study extracted all data from the U.S. Nationwide Inpatient Sample (NIS) database from 2005 to 2018. We included hospitalized adults ≥18 years old with a pancreatic cancer diagnosis identified by International Classification of Diseases ninth revision (ICD-9) and tenth revision (ICD-10) codes. We utilized diagnostic codes ICD9 V58.61 and ICD10 Z79.01, i.e., 'long-term use of anticoagulant', to identify individuals who were on a long-term systemic anticoagulant. The study cohort were then further grouped as being with or without long-term systemic use of an anticoagulant. Propensity score matching was performed to balance the characteristics of the two groups. The risks of life-threatening events, e.g., acute myocardial infarction (AMI), acute heart failure (AHF), sepsis, shock, and acute kidney injury (AKI), in-hospital death, and prolonged length of stay (LOS) in the hospital were compared between the groups by univariable and multivariable logistic regression analyses. Results: The study population consisted of 242,903 hospitalized patients with pancreas cancer, 6.5% ( n = 15,719) of whom were on long-term systemic anticoagulants. A multivariable regression analysis showed that long-term systemic anticoagulant use was independently associated with lower odds of sepsis (aOR: 0.81, 95% CI: 0.76-0.85), shock (aOR: 0.59, 95% CI: 0.51-0.68), AKI (aOR: 0.86, 95% CI: 0.81-0.91), in-hospital mortality (aOR: 0.65, 95% CI: 0.60-0.70), and prolonged LOS (aOR: 0.84, 95% CI: 0.80-0.89). Conclusions: Long-term systemic anticoagulant use is associated with better clinical outcomes in terms of decreased risks of some life-threatening events, in-hospital death, and prolonged LOS among hospitalized patients with pancreatic cancer in the U.S.