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Bo-Chieh Chang,1 Meng-Hsuan Kuo,1 Chi-Hui Lee,1 Ya-Lan Chu,1 Kuang-Peng Chen,2 Chun-Liong Tung,2 Ya-Hui Yang,3 Chuan-Sheng Hung,4 Jui-Hsiu Tsai,2,5 Hung-Yi Chuang6 1Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; 2Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; 3Department of Long-Term Care and Health Management, Cheng Shiu University, Kaohsiung, Taiwan; 4Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5School of Medicine, Tzu Chi University, Hualien, Taiwan; 6Department of Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Jui-Hsiu Tsai, Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Min-Sheng Road, Dalin Town, Chiayi, 622, Taiwan, Email faanvangogh@gmail.comIntroduction: Poor adherence to antipsychotics in patients with schizophrenia is a leading cause of relapse and functional deterioration. Long-acting injectable paliperidone may reduce relapse risks, health-care utilisation, and health-care costs in these patients.Methods: In this 24-month mirror-image study, we compared health-care utilization and costs before and after the initiation of paliperidone palmitate 3-monthly (PP3M) treatment in patients with schizophrenia spectrum disorders. Before the initiation of PP3M, the patients received paliperidone 1-monthly (PP1M) treatment. The primary study outcomes were changes in health-care utilisation and costs over the study period.Results: This study included 34 patients with schizophrenia spectrum disorders. During the 12-months period after the initiation of PP3M treatment, the mean duration of hospitalisation decreased from 57.7 to 28.5 days (p = 0.03). Moreover, significant reductions were noted in emergency room visits (PP1M vs PP3M: 0.3 vs 0.0, respectively; p = 0.05) and health-care costs (PP1M vs PP3M: 107,328.8 vs 57,848.6, respectively; p = 0.03).Conclusion: PP3M may significantly reduce hospitalisation duration, emergency room visits, and health-care costs in patients with schizophrenia.Keywords: schizophrenia, long-acting injectable antipsychotics, paliperidone palmitate, health-care cost, health-care utilisation

Objective: To examine the association between frequency of assisting with home meal preparation and fruit and vegetable preference and self-efficacy for making healthier food choices among grade 5 children in Alberta, Canada.Design: A cross-sectional survey design was used. Children were asked how often they helped prepare food at home and rated their preference for twelve fruits and vegetables on a 3-point Likert-type scale. Self-efficacy was measured with six items on a 4-point Likert-type scale asking children their level of confidence in selecting and eating healthy foods at home and at school.Setting: Schools (n =151) located in Alberta, Canada.Subjects: Grade 5 students (n = 3398).Results: A large majority (83-93 %) of the study children reported helping in home meal preparation at least once monthly. Higher frequency of helping prepare and cook food at home was associated with higher fruit and vegetable preference and with higher self-efficacy for selecting and eating healthy foods.Conclusions: Encouraging children to be more involved in home meal preparation could be an effective health promotion strategy. These findings suggest that the incorporation of activities teaching children how to prepare simple and healthy meals in health promotion programmes could potentially lead to improvement in dietary habits. [ABSTRACT FROM AUTHOR]

In hospitalized patients, acute kidney injury (AKI) is an important adverse event associated with high mortality and medical costs. Accurate diagnosis and timely management of AKI are essential for improving the outcomes of in-hospital AKI, and delayed diagnosis or misdiagnosis hinders advancements in AKI care. To ameliorate this problem, several electronic AKI alert systems have been proposed but have shown inconsistent effects on AKI outcomes. Before electronic systems can improve AKI outcomes, it is important to confirm their diagnostic accuracy. The purposes of the present study were to establish an easy-to-construct computerized algorithm for the diagnosis of renal impairment and to test its accuracy. The present study retrospectively included 1551 patients hospitalized in Wanfang Hospital with serum creatinine (SCr) levels > 1.3 mg/dL. A computerized algorithm was constructed to identify AKI events and chronic kidney disease (CKD) in these patients. Previous SCr tests were reviewed to define baseline SCr levels. A SCr level increased > 1.5 times from baseline was defined as AKI. An estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m 2 for > 90 days was defined as CKD. Discharge diagnoses made by the attending physicians were defined as "clinician's diagnoses." The researcher's diagnoses, made by experienced nephrologists according to the same criteria, were the gold standard to which the computerized algorithms and the clinician's diagnoses were compared. The diagnoses made by the computerized algorithm and clinician were compared with the researcher's diagnoses to define their accuracy. Among the included patients, the mean age was 73.0 years; in-hospital mortality was 14.8%, and AKI was present in 28.6% of patients. Regarding the diagnostic accuracy for AKI, the computerized algorithm achieved a sensitivity of 85.6% and a specificity of 98.8%. The main cause of false-negative (FN) AKI diagnosis was AKI occurring prior to the outpatient visit, before the indexed hospitalization. Regarding the diagnostic accuracy for CKD, the computerized algorithm achieved a sensitivity of 94.7% and specificity of 100%. The main cause of FN CKD diagnosis was the lack of previous eGFR records. The computerized algorithm exhibited significantly superior accuracy compared to the clinician's diagnoses for both AKI (95.0% vs. 57.0%) and CKD (96.5% vs. 73.6%). We developed a simple and easy-to-construct computerized algorithm for the diagnosis of renal impairment that demonstrated significantly improved diagnostic accuracy for AKI and CKD compared to that of clinicians. In the future, an algorithmic approach for the differential diagnosis of AKI and a decision guide should be incorporated into this system., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Osteoporotic vertebral compression fractures (OVCF) significantly affect older adults, leading to considerable morbidity and healthcare costs. Despite the known health risks of morbid obesity, its impact on surgical outcomes of OVCF remains underexplored. This study examines the influence of morbid obesity on the clinical outcomes of patients undergoing vertebral augmentation procedures, specifically vertebroplasty (VP) or kyphoplasty (KP)., Methods: We analyzed data from the National Inpatient Sample (NIS) for hospitalized patients aged 60 years or older undergoing VP or KP for OVCF from 2005 to 2020. Morbid obesity was defined as a body mass index (BMI) above 40 kg/m². The primary outcomes assessed in-hospital mortality, discharge destinations, hospital stays, costs, and complications. Logistic and linear regressions adjusted for confounders were used to determine the impact of morbid obesity on these outcomes., Results: The analysis included 4734 patients. Patients with morbid obesity accounted for 30.1% of the study sample. After adjustment for relevant demographic and clinical confounders, morbid obesity was significantly associated with increased risks of unfavorable discharge (adjusted OR (aOR): 1.24, 95% confidence interval (CI): 1.08-1.42, P=0.002) and overall complication (aOR=1.15, 95% CI 1.01 to 1.30, P=0.041), including venous thromboembolism (VTE; aOR=1.57, 95% CI 1.07 to 2.30, P=0.020, P=0.003), urinary tract infection (aOR=1.35, 95% CI 1.14 to 1.60, P=0.001), and acute kidney injury (AKI; aOR: 1.47, 95% CI 1.21 to 1.78, P<0.001)., Conclusions: Morbid obesity is associated with an increased risk of adverse short-term outcomes in patients undergoing VP or KP for OVCF, including unfavorable discharge and specific complications. These findings contribute insights to preoperative risk stratification and encourage clinicians to be more vigilant in managing this high-risk population. Further prospective research is still needed to confirm these associations and develop effective interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The development of a inhaled nanodrug delivery assessment platform is crucial for advancing treatments for chronic lung diseases. Traditional in vitro models and commercial aerosol systems fail to accurately simulate the complex human respiratory patterns and mucosal barriers. To address this, we have developed the breathing mucociliary-on-a-chip (BMC) platform, which replicates mucociliary clearance and respiratory dynamics in vitro. This platform allows for precise analysis of drug deposition and penetration, providing critical insights into how liposomes and other nanocarriers interact with lung tissues under various airflow conditions. Our results reveal that liposomes penetrate deeper into the cellular layer under high shear stress, with both static and dynamic airflows distinctly affecting their drug release rates. The BMC platform integrates dynamic inhalation systems with mucociliary clearance functionality, enabling a comprehensive evaluation of drug delivery efficacy. This approach highlights the importance of airflow dynamics in optimizing inhalable nanodrug delivery systems, improving nanocarrier design, and tailoring drug dosages and release strategies. The BMC platform represents a significant advancement in the field of inhaled nanodrug delivery, offering a more accurate and reliable method for assessing the performance of therapies. By providing a detailed understanding of drug interactions with lung tissues, this platform supports the development of personalized inhaled therapies and offers promising strategies for treating pulmonary diseases and advancing nanodrug development.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue's stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without "packing foam-like" extracellular matrix.

Chlorination of ammonia or chloramine-containing waters induces breakpoint chlorination reactions, producing a hydroxyl radical (•OH), but enhances the formation of undesirable N -nitrosamines. The prevailing view attributes •OH formation to a nitrosyl intermediate derived from the hydrolysis of dichloramine, but this pathway is unlikely at neutral or acidic pH. This study reveals a novel mechanism where •OH is generated via interactions between trichloramine (NCl 3 ) and dichloramine (NHCl 2 ), which also form nitrosation agents. Our experiments demonstrated that the NCl 3 -NHCl 2 interaction degrades micropollutants with kinetics 2-3 times faster than breakpoint chlorination. Using electron paramagnetic resonance, we detected •OH in the NCl 3 -NHCl 2 reaction. Micropollutant removal was unimpaired under low dissolved oxygen (O 2(aq) ) conditions, aligning with negligible O 2(aq) changes during the NCl 3 -NHCl 2 reaction and suggesting O 2(aq) does not participate in •OH formation. Using benzene as a probe in 18 O-labeled H 2 O, we confirmed water contributes to the oxygen source of •OH in NCl 3 -NHCl 2 interactions, through which parallel reactions occur, leading to the formation of one mole of •OH alongside 1.92 mol of N 2 . A kinetic model developed in this study accurately predicted •OH and N 2 and demonstrated the NCl 3 -NHCl 2 interaction as the primary pathway for •OH formation in breakpoint chlorination, providing new insights into breakpoint chemistry.

Background: Yezo virus (YEZV) is an emerging tick-borne pathogen, which was initially reported in Japan in 2021. Only one patient had been reported in China so far. We aimed to describe the epidemiological, clinical, and laboratory findings of a series of patients, and to characterise the viral genomes of YEZV., Methods: In this active surveillance and genomic analysis, we conducted active surveillance at Mudanjiang Forestry Central Hospital, Heilongjiang Province of northeast China. Participants were eligible for inclusion if they sought medical care for a recent tick bite between May 1 and July 31, in 2022 and 2023, and between May 1 and July 10, in 2024. We collected sera from participants to detect YEZV infection by meta-transcriptomic sequencing, real-time RT-PCR, and indirect immunofluorescence assay. We isolated YEZV by cell culture and characterised the pathogen by morphological and phylogenetic analyses., Findings: A series of 18 patients with YEZV infection (12 male and six female; median age 53 years, IQR 45-60) were identified among 988 participants. The patients presented with fever (18 patients, 100%), headache (ten patients, 56%), dizziness (nine patients, 50%), malaise (three patients, 17%), lumbago (three patients, 17%), and cough (three patients, 17%). Nine (50%) patients had rash around the tick bite site and four (22%) had lymphadenopathy. Nine (50%) patients had gastrointestinal symptoms, and five (28%) had neurological symptoms. We observed leukopenia in ten (63%) and thrombocytopenia in five (31%) of 16 assessed patients. Elevated hepatic transaminase concentrations were identified in 13 (72%) of all 18 patients, lactate dehydrogenase or α-hydroxybutyric dehydrogenase in nine (50%), serum amyloid protein A in 13 (72%), and hypersensitive C-reactive protein in ten (56%). Eight (7%) of 119 Ixodes persulcatus ticks removed from participants were positive for YEZV. Three YEZV strains were isolated from the sera of patients. Ten viral genomes were obtained from five patients, a blood-sucking I persulcatus removed from a participant, and four host-questing tick samples collected in the areas where patients were identified or in the adjacent region. Phylogenetic analyses revealed that YEZVs in either patients or ticks were divided into two clades, each with distinct mutations., Interpretation: Awareness of YEZV infection is important and clinicians should consider the virus when diagnosing patients with suitable symptoms., Funding: National Key Research and Development Program of China., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The study aimed to examine effects of (-)-epigallocatechin-3-gallate (EGCG) on energy metabolism and mitochondrial dynamics in mouse model of renal injury caused by doxorubicin (DOX). Here, mice were divided into Control group, EGCG-only treated group, DOX group, and three doses of EGCG plus DOX groups. Our results showed that EGCG behaved beneficial effects against kidney injury via attenuation of pathological changes in kidney tissue, which was confirmed by reducing serum creatinine (SCr), blood urea nitrogen (BUN), and apoptosis. Subsequently, changes in reactive oxygen species generation, malondialdehyde content, and activities of antioxidant enzymes were considerably ameliorated in EGCG + DOX groups when compared to DOX group. Furthermore, EGCG-evoked renal protection was associated with increases of mitochondrial membrane potential and decreases of mitochondrial fission protein Dynamin-related protein 1 (Drp1). Moreover, changing glycolysis into mitochondrial oxidative phosphorylation was observed, evidenced by controlling activities of malate dehydrogenase (MDH) and hexokinase (HK) in EGCG + DOX groups when compared to DOX group, indicating that reprogramming energy metabolism was linked to EGCG-induced renal protection in mice. Therefore, EGCG was demonstrated to have a protective effect against kidney injury by reducing oxidative damage, metabolic disorders, and mitochondrial dysfunction, suggesting that EGCG has potential as a feasible strategy to prevent kidney injury., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Coral polyps are composed of four tissues; however, their characteristics are largely unexplored. Here we report biological characteristics of tentacles (Te), mesenterial filaments (Me), body wall (Bo), and mouth with pharynx (MP), using comparative genomic, morpho-histological, and transcriptomic analyses of the large-polyp coral, Fimbriaphyllia ancora. A draft F. ancora genome assembly of 434 Mbp was created. Morpho-histological and transcriptomic characterization of the four tissues showed that they have distinct differences in structure, primary cellular composition, and transcriptional profiles. Tissue-specific, highly expressed genes (HEGs) of Te are related to biological defense, predation, and coral-algal symbiosis. Me expresses multiple digestive enzymes, whereas Bo expresses innate immunity and biomineralization-related molecules. Many receptors for neuropeptides and neurotransmitters are expressed in MP. This dataset and new insights into tissue functions will facilitate a deeper understanding of symbiotic biology, immunology, biomineralization, digestive biology, and neurobiology in corals., (© 2024. The Author(s).)

Background and Aim: An early and accurate diagnosis of ampullary neoplasia is crucial; however, sampling bias is still a major concern. New-generation endocytoscopy enables real-time visualization of cellular structures and enables an accurate pathological prediction; however, its feasibility for small ampullary lesions has never been investigated., Methods: We developed a novel endocytoscopic (EC) classification system for ampullary lesions after an expert review and agreement from five experienced endoscopists and one pathologist. We then consecutively enrolled a total of 43 patients with an enlarged ampulla (< 3 cm), all of whom received an endocytoscopic examination. The feasibility of endocytoscopy was evaluated, and the performance of the EC classification system was then correlated with the final histopathology., Results: In five cases (11.6%), the endocytoscope could not approach the ampulla, and these cases were defined as technical failure. Among the remaining 38 patients, 8 had histopathology-confirmed adenocarcinoma, 15 had adenoma, and 15 had non-neoplastic lesions. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification system to diagnose ampullary neoplasias were 95.7%, 86.7%, 91.7%, 92.9%, and 92.1%, respectively. Moreover, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification to diagnose ampullary cancer were 62.5%, 100%, 100%, 90.9%, and 92.1%, respectively. One case with intra-ampullary papillary-tubular carcinoma was classified as having a non-neoplastic lesion by endocytoscopy., Conclusions: Endocytoscopy and the novel EC classification system demonstrated good feasibility to discriminate ampullary neoplasias from non-neoplastic lesions and may be useful for optical biopsies of clinically suspicious ampullary lesions., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Sarcomas of the cervical spine with osteolytic lesions and intradural extension are extremely uncommon. This is a case report of a woman in her late 30s who had experienced numbness and gradual weakness of her four limbs. MRI with enhanced T1-weighted contrast showed a heterogeneously enhancing intradural extramedullary mass lesion over C2-C4 levels compressing the spinal cord. Over the corresponding levels, the computed tomography scan showed an osteolytic lesion. Surgical intervention was performed under intraoperative neuromonitoring. Histopathological findings demonstrated a low-grade tumor with round to ovoid nuclei with a moderate amount of eosinophilic cytoplasm with minimal nuclear pleomorphism. Next-generation sequencing technology was employed and findings revealed PTCH1::GLI1 and GLI1::KDM2B fusion with strongly positive findings on GLI1 immunohistochemical staining. The final diagnosis was GLI1 fusion sarcoma. The patient recovered well under multidisciplinary treatment with stringent follow-up, which are required for this rare disease entity., (© 2023 Japanese Society of Neuropathology.)

Background: Many diseases may be caused by pathogens and oxidative stress resulting from carcinogens. Earlier studies have highlighted the antimicrobial and antioxidant effects of plant essential oils (EO). It is crucial to effectively utilize agricultural waste to achieve a sustainable agricultural economy and protect the environment. The present study aimed to evaluate the potential benefits of EO extracted from the discarded peels of Citrus depressa Hayata (CD) and Citrus microcarpa Bunge (CM), synonyms of Citrus deliciosa Ten and Citrus japonica Thunb, respectively., Results: Gas chromatography-mass spectrometry analysis revealed that the main compounds in CD-EO were (R)-(+)-limonene (38.97%), γ-terpinene (24.39%) and linalool (6.22%), whereas, in CM-EO, the main compounds were (R)-(+)-limonene (48.00%), β-pinene (13.60%) and γ-terpinene (12.07%). CD-EO exhibited inhibitory effects on the growth of common microorganisms, including Candida albicans, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. However, CM-EO showed only inhibitory effects on E. coli. Furthermore, CD-EO exhibited superior antioxidant potential, as demonstrated by its ability to eliminate 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis-3-ethylbenzthiazoline-6-sulfonate free radicals. Furthermore, CD-EO at a concentration of 100 μg mL -1 significantly inhibited 12-O-tetradecanoylphorbol-13-acetate-induced cancer transformation in mouse epidermal JB6 P+ cells (P < 0.05), possibly by up-regulating protein expression of nuclear factor erythroid 2-related factor 2 and its downstream antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1 and UGT1A., Conclusion: These findings suggest that CD-EO exhibits inhibitory effects on pathogenic microorganisms, possesses antioxidant properties and has cancer chemopreventive potential. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Diabetes is a leading cause of death, according to statistics published by the Department of Health, Executive Yuan of Taiwan. In modern medicine, diabetes can be controlled using various medications; however, some drugs often have undesirable side effects. It therefore became a goal to find plant-based material that can reduce glucose concentration in the blood while reducing the incidence of complications and not causing side effects. Alpha-glucosidase inhibitors (AGIs) are effective glucose-lowering medicines and are enzymes essential to carbohydrate digestion. Inhibition of α-glucosidase leads to a delayed and reduced rise in postprandial blood glucose levels. This study evaluates the inhibitory effect of mixed extracts of Psidium guajava L. and Morus alba L. leaves on α-glucosidase activity and postprandial hyperglycemia in normal and diabetic rats. The inhibition of α-glucosidase activity was assayed in vitro. Half maximal inhibitory concentration ( IC 50 ) values of Psidium guajava L. and Morus alba L. were 2.25 and 0.1 mg/mL, respectively. The IC 50 value of a commercial anti-hyperglycemic agent (Glucobay) is 6.41 mg/mL. The IC 50 value of a mixture of extracts of Psidium guajava L. and Morus alba L. was 0.07 mg/mL. In cytotoxicity tests, survival percentages and shape did not significantly affect the murine embryonic liver cell line (BNL CL.2) when treated with varying concentrations of mixture extracts for varying periods of time. In summary, Psidium guajava L. and Morus alba L. showed positive anti-diabetes activity and suggested promising potential for alternative functional foods for diabetes mellitus (DM) patients., Competing Interests: The authors declare no competing financial interests., (© 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: This study aimed to investigate clinicopathological and molecular tumour features associated with intratumoral pks + Escherichia coli (pks + E.coli + ), pks + E.coli - (non-E.coli bacteria harbouring the pks island), Enterotoxigenic Bacteroides fragilis (ETBF) and Fusobacterium nucleatum (F. nucleatum)., Methods: We screened 1697 tumour-derived DNA samples from the Australasian Colorectal Cancer Family Registry, Melbourne Collaborative Cohort Study and the ANGELS study using targeted PCR., Results: Pks + E.coli + was associated with male sex (P < 0.01) and APC:c.835-8 A > G somatic mutation (P = 0.03). The association between pks + E.coli + and APC:c.835-8 A > G was specific to early-onset CRCs (diagnosed<45years, P = 0.02). The APC:c.835-A > G was not associated with pks + E.coli - (P = 0.36). F. nucleatum was associated with DNA mismatch repair deficiency (MMRd), BRAF:c.1799T>A p.V600E mutation, CpG island methylator phenotype, proximal tumour location, and high levels of tumour infiltrating lymphocytes (Ps < 0.01). In the stratified analysis by MMRd subgroups, F. nucleatum was associated with Lynch syndrome, MLH1 methylated and double MMR somatic mutated MMRd subgroups (Ps < 0.01)., Conclusion: Intratumoral pks + E.coli + but not pks + E.coli - are associated with CRCs harbouring the APC:c.835-8 A > G somatic mutation, suggesting that this mutation is specifically related to DNA damage from colibactin-producing E.coli exposures. F. nucleatum was associated with both hereditary and sporadic MMRd subtypes, suggesting the MMRd tumour microenvironment is important for F. nucleatum colonisation irrespective of its cause., (© 2024. The Author(s).)

Genetic susceptibility to familial colorectal cancer (CRC), including for individuals classified as Familial Colorectal Cancer Type X (FCCTX), remains poorly understood. We describe a multi-generation CRC-affected family segregating pathogenic variants in both BRCA1, a gene associated with breast and ovarian cancer and RNF43, a gene associated with Serrated Polyposis Syndrome (SPS). A single family out of 105 families meeting the criteria for FCCTX (Amsterdam I family history criteria with mismatch repair (MMR)-proficient CRCs) recruited to the Australasian Colorectal Cancer Family Registry (ACCFR; 1998-2008) that underwent whole exome sequencing (WES), was selected for further testing. CRC and polyp tissue from four carriers were molecularly characterized including a single CRC that underwent WES to determine tumor mutational signatures and loss of heterozygosity (LOH) events. Ten carriers of a germline pathogenic variant BRCA1:c.2681&#95;2682delAA p.Lys894ThrfsTer8 and eight carriers of a germline pathogenic variant RNF43:c.988 C > T p.Arg330Ter were identified in this family. Seven members carried both variants, four of which developed CRC. A single carrier of the RNF43 variant met the 2019 World Health Organization (WHO 2019 ) criteria for SPS, developing a BRAF p.V600 wildtype CRC. Loss of the wildtype allele for both BRCA1 and RNF43 variants was observed in three CRC tumors while a LOH event across chromosome 17q encompassing both genes was observed in a CRC. Tumor mutational signature analysis identified the homologous recombination deficiency (HRD)-associated COSMIC signatures SBS3 and ID6 in a CRC for a carrier of both variants. Our findings show digenic inheritance of pathogenic variants in BRCA1 and RNF43 segregating with CRC in a FCCTX family. LOH and evidence of BRCA1-associated HRD supports the importance of both these tumor suppressor genes in CRC tumorigenesis., (© 2023. The Author(s).)

Hidradenitis suppurativa (HS), recognized as a chronic and debilitating skin disease, presents significant challenges in both diagnosis and treatment. This review explores the clinical manifestations, genetic landscape, and molecular mechanisms underlying HS. The disease's association with a predisposing genetic background, obesity, smoking, and skin occlusion underscores the complexity of its etiology. Genetic heterogeneity manifests in sporadic, familial, and syndromic forms, with a focus on mutations in the γ-secretase complex genes, particularly NCSTN. The dysregulation of immune mediators, including TNF-α, IL-17, IL-1β, and IL-12/23, plays a crucial role in the chronic inflammatory nature of HS. Recent advancements in genetic research have identified potential therapeutic targets, leading to the development of anti-TNF-α, anti-IL-17, anti-IL-1α, and anti-IL-12/23 therapies and JAK inhibitors. These interventions offer promise in alleviating symptoms and improving the quality of life for HS patients.

Introduction: Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnancy. However, studies of activating molecule of Beclin1-regulated autophagy (Ambra1) affecting the insulin substrate receptor 1/phosphatidylinositol 3 kinase/protein kinase B (IRS-1/PI3K/Akt) signalling pathway in GDM have not been reported. The aim of the study was to detect the difference of Ambra1 expression in the placenta of normal pregnant women and GDM patients., Material and Methods: An in vitro model of gestational diabetes mellitus was established by inducing HTR8/Svneo cells from human chorionic trophoblast layer with high glucose. The changes of cell morphology were observed by inverted microscope, and the expression levels of Ambra1 gene and protein in model cells were detected. After this, Ambra1 gene was silenced by shRNA transfection, and PI3K inhibitor was added to detect changes in Ambra1, autophagy, and insulin (INS) signalling pathways., Results: The protein expression levels of Ambra1, Bcl-2 interacting protein (Beclin-1), and microtubule-associated proteins 1A/1B light chain 3B (LC3-II) in the placentas of GDM pregnant women were higher than those of normal pregnant women. High glucose induces morphological changes in HTR8/Svneo cells and increases Ambra1 transcription and translation levels. sh-Ambra1 increased survival of HTR8/SvNEO-HG cells and inhibited Ambra1, Beclin1, and LC3-II transcription and translation levels. Also, sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels and inhibited the IRS-1/PI3K/Akt signalling pathway and its resulting autophagy., Conclusions: sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels to reduce autophagy in gestational diabetes.

Background: Multimorbidity and polypharmacy increase the risk of hospitalization in older adults receiving potentially inappropriate medication (PIM). The current study compared the ability of PIM-Taiwan, PRISCUS, and Beers criteria to predict 90-day rehospitalization in older patients with and without PIM. Methods: The retrospective cohort study used Taiwan's Longitudinal Health Insurance Database to retrieve quarterly information about prescribed medication for adults aged ≥65 years hospitalized between 2001 and 2018. We analyzed the association of PIM with 90-day rehospitalization using logistic regression. Results: The study cohort included 206,058 older adults (mean age: 72.5 years). In the analysis, 133,201 (64.6%), 97,790 (47.5%), and 147,450 (71.6%), were identified as having PIM exposure in PIM-Taiwan, PRICUS, and Beers criteria, respectively. PIM-Taiwan criteria found exposure to PIM affecting the cardiovascular (adjusted OR [aOR] 1.37, 95% confidence interval [CI] = 1.32-1.41), gastrointestinal (aOR 1.26, 95% CI = 1.23-1.30), central nervous (aOR 1.11, 95% CI = 1.08-1.14), and respiratory (aOR 1.16, 95% CI = 1.12-1.20) systems significantly increased the risk of 90-day rehospitalization, after adjustment for covariates. In PRISCUS criteria, exposure to PIM affecting the respiratory (aOR 1.48, 95% CI = 1.41-1.56), central nervous (aOR 1.12, 95% CI = 1.09-1.15), and cardiovascular (aOR 1.20, 95% CI = 1.16-1.24) systems significantly increased the risk. In Beers criteria, exposure to PIM affecting the cardiovascular (aOR 1.37, 95% CI = 1.32-1.41), gastrointestinal (aOR 1.38, 95% CI = 1.35-1.42), central nervous (aOR 1.18, 95% CI = 1.15-1.21), endocrine (aOR 1.10, 95% CI = 1.06-1.15), and respiratory (aOR 1.09, 95% CI = 1.04-1.13) systems significantly increased the risk. Patients with 90-day rehospitalization had higher rates of the potentially harmful drug-drug interaction (DDI) pairs of serotonin syndrome (n = 19; 48.8%), QT prolongation (n = 4; 30.8%), extrapyramidal symptoms (EPS) (n = 102; 24.5%), and hypokalemia (n = 275; 20.1%). Conclusion: Beers criteria was more efficient in predicting 90-day rehospitalization among older adults experiencing PIM in Taiwan than either PIM-Taiwan or PRISCUS. The risk of 90-day rehospitalization was associated with the potentially harmful DDI classes of serotonin syndrome, QT prolongation, EPS, and hypokalemia., 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 Hsieh, Huang, Yang, Ho, Chen, Tung, Chu and Tsai.)

Fermentation of fruits offers a diverse range of flavors, smells, and colors. Colored fruits are rich in naturally occurring pigments, such as betacyanin. Hence, they are considered to possess powerful antioxidant activities. However, in wine production, such pigments often diversify the flavor and color of the wine. The objective of this study was to compare the quality of two types of wines: a single-fruit (pitaya) wine and a mixed-fruit wine that contains watermelon ( Citrullus lanatus ), mint ( Mintha spicata ), and pitaya ( Hylocereus costaricensis ). In this study, fresh pitaya, watermelon, and mint leaves were fermented using Saccharomyces cerevisiae . Juice extracts underwent fermentation at room temperature for 7 days under dark conditions. Physicochemical changes, such as pH, sugar content, specific gravity, and alcohol content, were observed daily. The antioxidant activities were measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the ferric reducing antioxidant power (FRAP) assay, and total phenolic contents (TPCs). After 14 days of fermentation, the alcohol contents of mixed and pitaya wine were 11.22% (v/v) and 11.25%, respectively. The total sugar content of the mixed wine was 8.0 °Brix, while that of pitaya wine was 7.0 °Brix. Moreover, pitaya wine exhibited a higher TPC (22.7 mg GAE/100 g D.W.), and better FRAP (3578 μmole/L) and DPPH scavenging ability (80.2%) compared to the mixed wine with a TPC of 21.4 mg GAE/100 g D.W., FRAP of 2528 μmole/L, and DPPH of 75.6%., while the addition of watermelon and mint did not change the alcohol percentage contents of wine., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: Starting enzyme replacement therapy (ERT) before severe irreversible muscular damage occurs is important in infantile-onset Pompe disease (IOPD). This long-term follow-up study demonstrates our diagnostic and treatment strategies for IOPD and compares our clinical outcomes with those of other medical centres., Methods: In this long-term follow-up study, we analysed the outcomes of very early ERT with premedication hydrocortisone in patients with IOPD. Out of 1 228 539 infants screened between 1 January 2010 and 28 February 2021, 33 newborns had confirmed IOPD in Taipei Veterans General Hospital. Twenty-six were regularly treated and monitored at Taipei Veterans General Hospital. Echocardiographic parameters, biomarkers, IgG antibodies against alglucosidase alpha, pulmonary function variables and developmental status were all assessed regularly over an average follow-up duration of 6.18±3.14 years. We compared the long-term treatment outcomes of our patients with those of other research groups., Results: The average age at ERT initiation was 9.75±3.17 days for patients with classic IOPD. The average of the latest antialglucosidase alpha IgG titre was 669.23±1159.23. All enrolled patients had normal heart sizes, motor milestones, cognitive function and pulmonary function that were near-normal to normal. Compared with patients in other studies, our patients had better outcomes in all aspects., Conclusion: Very early ERT using our rapid diagnostic and treatment strategy enabled our patients with IOPD to have better outcomes than patients in other medical centres., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bakanae disease caused by Fusarium fujikuroi is an increasing threat to rice production. The infected plants show symptoms such as elongation, slenderness, chlorosis, a large leaf angle, and even death. Bakanae disease is traditionally managed by seed treatment. However, fungicide-resistant F. fujikuroi isolates have emerged in several Asian areas, including Taiwan. This study aimed to identify new bakanae resistance quantitative trait loci (QTLs) and provide molecular markers to assist future breeding., Results: A population of F 2:9 recombinant inbred lines (RILs) was derived from the cross between an elite japonica Taiwanese cultivar 'Taikeng 16 (TK16)' and an indica variety 'Budda'. 'Budda' was found highly resistant to all 24 representative isolates of the F. fujikuroi population in Taiwan. For the RIL population, 6,492 polymorphic single nucleotide polymorphisms (SNPs) spanning the rice genome were obtained by genotyping-by-sequencing (GBS) technique, and the disease severity index (DSI) was evaluated by inoculation with a highly virulent F. fujikuroi isolate Ff266. Trait-marker association analysis of 166 RILs identified two QTLs in 'Budda'. qBK2.1 (21.97-30.15 Mb) is a novel and first bakanae resistance QTL identified on chromosome 2. qBK1.8 (5.24-8.66 Mb) partially overlaps with the previously reported qBK1.3 (4.65-8.41 Mb) on chromosome 1. The log of odds (LOD) scores of qBK1.8 and qBK2.1 were 4.75 and 6.13, accounting for 4.9% and 8.1% of the total phenotypic variation, respectively. 64 RILs carrying both qBK1.8 and qBK2.1 showed lower DSI (7%) than the lines carrying only qBK1.8 (15%), only qBK2.1 (13%), or none of the two QTLs (21%). For the future application of identified QTLs, 11 KBioscience competitive allele-specific PCR (KASP) markers and 3 insertion-deletion (InDel) markers were developed., Conclusions: Compared to other important rice diseases, knowledge of bakanae resistance has been insufficient, which limited the development and deployment of resistant cultivars. The discovery of qBK2.1 has provided a new source of bakanae resistance. The resistant RILs inheriting good plant type, good taste, and high yield characteristics from 'TK16' can be used as good resistance donors. Our newly developed markers targeting qBK2.1 and qBK1.8 can also serve as an important basis for future fine-mapping and resistance breeding., (© 2023. The Author(s).)

Background and Aims: For EUS-guided fine-needle biopsy sampling (EUS-FNB) of solid pancreatic lesions (SPLs), the role of sampling strategy between targeted biopsy sampling and wide sampling has not been reported. This study aimed to investigate the benefits of the 2 sampling techniques on EUS-FNB using rapid on-site evaluation., Methods: Patients with SPLs were prospectively enrolled and randomly assigned (1:1) to undergo EUS-FNB using either contrast guidance or the fanning technique. The primary outcome was the total number of passes required to establish a diagnosis, and secondary outcomes were overall diagnostic accuracy and adverse event rates., Results: One hundred eighteen patients were enrolled from February 2019 to January 2021, with 59 patients assigned to each group. There was no significant difference in the total number of passes required to establish a diagnosis between the contrast and fanning groups (median, 1 [interquartile range, 1-1] vs 1 [interquartile range, 1-2], respectively; P = .629). The sensitivity, specificity, and diagnostic accuracy in the contrast group was 100%, 66.7%, and 98.3% and in the fanning group 100%, 100%, and 100%, respectively (P = 1). An SPL <4 cm (odds ratio, 2.47; 95% confidence interval, 1.05-5.81; P = .037) and macroscopic visible core length >1 cm (odds ratio, 2.89; 95% confidence interval, 1.07-7.84; P = .037) were independently associated with increased cytologic and histologic accuracy., Conclusions: The diagnostic accuracy of EUS-FNB with the fanning technique for SPLs was comparable with the contrast guidance technique. Without additional cost, EUS-FNB with the fanning technique may be preferred for SPLs. (Clinical trial registration number: NCT04924725.)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Ticks are the most important obligate blood-feeding vectors of human pathogens. With the advance of high-throughput sequencing, more and more bacterial community and virome in tick has been reported, which seems to pose a great threat to people., Methods: A total of 14 skin specimens collected from tick-bite patients with mild to severe symptoms were analyzed through meta-transcriptomic sequencings., Results: Four bacteria genera were both detected in the skins and ticks, including Pseudomonas, Acinetobacter, Corynebacterium and Propionibacterium, and three tick-associated viruses, Jingmen tick virus (JMTV), Bole tick virus 4 (BLTV4) and Deer tick mononegavirales-like virus (DTMV) were identified in the skin samples. Except of known pathogens such as pathogenic rickettsia, Coxiella burnetii and JMTV, we suggest Roseomonas cervicalis and BLTV4 as potential new agents amplified in the skins and then disseminated into the blood. As early as 1 day after a tick-bite, these pathogens can transmit to skins and at most four ones can co-infect in skins., Discussion: Advances in sequencing technologies have revealed that the diversity of tick microbiome and virome goes far beyond our previous understanding. This report not only identifies three new potential pathogens in humans but also shows that the skin barrier is vital in preventing horizontal transmissions of tick-associated bacteria or virus communities to the host. It is the first research on patients' skin infectome after a tick bite and demonstrates that more attention should be paid to the cutaneous response to prevent tick-borne illness., 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 Zhang, Zheng, Chu, Cui, Wei, Bian, Liu, Yao, Jiang, Huo, Yuan, Li, Zhao, Li, Wang, Wei, Zhu, Chen, Gao, Wang, Ye, Song, Jiang, Lam, Ni and Jia.)

Introduction: Optimal treatment of hepatocellular carcinoma (HCC) beyond the Milan criteria is in debate. We aimed to identify candidates for surgical resection (SR) in Barcelona Clinic Liver Cancer (BCLC)-A/B HCC beyond the Milan criteria with survival benefit., Methods: Patients with BCLC-A/B HCC beyond the Milan criteria at the National Taiwan University Hospital during 2005 and 2019 were screened, and those who received transarterial chemoembolization (TACE) or SR were consecutively included. The tumor burden was classified by the seven-eleven criteria into low (≤7), intermediate (7-11), or high (>11). Multivariable Cox proportional hazard regression analysis was used for outcome prediction., Results: Overall, 474 patients who received SR ( n = 247) and TACE ( n = 227) were enrolled. Patients who underwent SR were significantly younger with better liver reserve. There were 76 (31%) and 129 (57%) deaths in the SR and TACE groups after a median follow-up of 3.9 and 2.1 years, respectively. The seven-eleven criteria could distinguish median overall survival (OS) among low ( n = 149), intermediate ( n = 203), and high ( n = 122) tumor burden groups (7.7 vs. 6.9 vs. 2.8 years, respectively, p < 0.001). Patients receiving SR had a significantly higher median OS compared with TACE in those with intermediate (8.2 vs. 2.6 years, p < 0.001) and high (5.6 vs. 1.5 years, p = 0.001) tumor burden. After adjustment for age, sex, and liver reserve, SR was predictive for better OS in intermediate (adjusted hazard ratio [aHR]: 0.45, 95% confidence interval [CI]: 0.27-0.75) and high tumor burden groups (aHR: 0.54, 95% CI: 0.32-0.92). The survival benefit of SR especially confines to patients within 3 tumors., Conclusions: In patients with BCLC-A/B HCC beyond the Milan criteria with tumor burden beyond the up-to-7 criteria but within 3 tumors, SR has better OS than TACE and should be considered in resectable patients., Competing Interests: T.-H.S. received research grant from Gilead Sciences and was on speaker's bureaus for AbbVie, Bayer, Bristol-Myers Squibb, Gilead Sciences, Merck Sharp and Dohme, and Takeda. J.-H.K. has served as a consultant for AbbVie, Gilead Sciences, Merck Sharp and Dohme, and Roche and on speaker's bureaus for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Merck Sharp, and Dohme. Others declare no conflict of interests., (Copyright © 2023 by The Author(s). Published by S. Karger AG, Basel.)

This study aimed to investigate the anti-obesity effects of Coptis chinensis (CC), BALASAN (combinational guava leaf extract and mulberry leaf extract), and CC/BALASAN (CC/BAL) on high-fat diet-induced obese C57BL/6 mice and to explore possible mediating mechanisms in 3T3-L1 pre-adipocytes. Oil red-O stain was used to test the effects of CC, BALASAN, and CC/BAL on the differentiation of 3T3-L1 pre-adipocytes. Additionally, real-time PCR was used to detect the expression of genes involved in adipocyte differentiation and inflammation-related genes in adipose tissue of mice that were fed a high-fat diet. CC, BALASAN, and CC/BAL inhibited the differentiation of 3T3-L1 pre-adipocytes and exhibited excellent inhibitory ability against the expression of PPARγ and RXRα genes associated with adipocyte differentiation. Replenishing mice with a high-fat diet with CC, BALASAN, and CC/BAL reduced body weight gaining and blood glucose and plasma cholesterol levels. CC also effectively reduced liver weight, whereas BALASAN and CC/BAL had no inhibitory effect. In addition, CC effectively inhibited the expression of C/EBP-α in adipose tissue. Interestingly, BALASAN not only inhibited the expression of C/EBP-α, but also that of PPARγ, RXRα, and TNFα. Such data indicated that CC, BALASAN, and CC/BAL may have potentially beneficial effects against obesity and associated metabolic disorders by down-regulating the PPARγ/RXRα pathway., Competing Interests: The authors declare no competing financial interest., (© 2023 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Nipa ( Nypa fruticans Wurmb.) is an important mangrove palm species, but it is understudied due to lack of information on genetic patterns within its distribution range. In this study, we identified 18 informative microsatellite markers to assess genetic variations among local populations in the Indo-West Pacific (IWP). Results showed population stratification based on high genetic differentiation (F ST = 0.22131) with the Mantel test indicating significance to isolation-by-distance. We found a pronounced differentiation between the west populations in Sri Lanka and east populations in Southeast Asia. The east populations around the South China Sea were more genetically similar than those along the Malacca Strait and Java Sea. These genetic clines were shaped by ocean circulations and seasonal monsoon reversals as plausible factors. The Malacca Strait was confirmed as both a genetic and a geographic barrier rather than a corridor according to the Monmonier plot. Simulations of directional migration indicated a statistically strong contemporary genetic connectivity from west to east where Sri Lankan immigrants were detected as far as central Philippines via long-distance dispersal. This is the first report on the recent migration patterns of nipa using microsatellites. Assignment of first-generation (F 0 ) immigrants suggested Mainland Southeast Asia as a melting pot due to the admixture associated with excess of homozygosity. The western populations were recent expansions that emerged in rapid succession based on a phylogram as supported by footprints of genetic drift based on bottleneck tests., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mantiquilla, Shiao, Lu, Sridith, Sidique, Liyanage, Chu, Shih and Chiang.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can be effectively controlled by rapid and accurate identification of SARS-CoV-2-infected cases through large-scale screening. Hypercube pooling polymerase chain reaction (PCR) is frequently used as a pooling technique because of its high speed and efficiency. We attempted to implement the hypercube pooling strategy and found it had a large quantization effect. This raised two questions: is hypercube pooling with edge = 3 actually the optimal strategy? If not, what is the best edge and dimension? We used a C++ program to calculate the expected number of PCR tests per patient for different values of prevalence, edge, and dimension. The results showed that every edge had a best performance range. Then, using C++ again, we created a program to calculate the optimal edge and dimension required for pooling samples when entering prevalence into our program. Our program will be provided as freeware in the hope that it can help governments fight the SARS-CoV-2 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Liao, Fuh, Weng, Wang, Chen, Huang, Chen, Chu, Chen, Yeh, Yu, Wu, Lin, Liou, Wu and Liaw.)

Distal radius orientation is important in evaluating Colles' fracture. In most cases, the wrist was protected by a bandage, splint, or cast. Therefore, it was difficult for the radiology technician to take perfect anteroposterior and lateral view radiographs. In this study, we build a mathematical model and calculate the pronation angle needed to produce dorsal tilt, which is a volar tilt in a perfect lateral view radiograph. The formulas are all incorporated into Excel to facilitate usage., 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., (© 2022 Chen, Wu, Liao, Fuh, Chen, Weng, Wang, Chen, Huang, Chen, Chu, Yeh, Yu, Wu, Lin, Liou, Wu and Liaw.)

Background: Household air pollution (HAP) from cooking with solid fuels has been associated with adverse respiratory effects, but most studies use surveys of fuel use to define HAP exposure, rather than on actual air pollution exposure measurements., Objective: To examine associations between household and personal fine particulate matter (PM 2.5 ) and black carbon (BC) measures and respiratory symptoms., Methods: As part of the Prospective Urban and Rural Epidemiology Air Pollution study, we analyzed 48-h household and personal PM 2.5 and BC measurements for 870 individuals using different cooking fuels from 62 communities in 8 countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Self-reported respiratory symptoms were collected after monitoring. Associations between PM 2.5 and BC exposures and respiratory symptoms were examined using logistic regression models, controlling for individual, household, and community covariates., Results: The median (interquartile range) of household and personal PM 2.5 was 73.5 (119.1) and 65.3 (91.5) μg/m 3 , and for household and personal BC was 3.4 (8.3) and 2.5 (4.9) x10 -5  m -1 , respectively. We observed associations between household PM 2.5 and wheeze (OR: 1.25; 95%CI: 1.07, 1.46), cough (OR: 1.22; 95%CI: 1.06, 1.39), and sputum (OR: 1.26; 95%CI: 1.10, 1.44), as well as exposure to household BC and wheeze (OR: 1.20; 95%CI: 1.03, 1.39) and sputum (OR: 1.20; 95%CI: 1.05, 1.36), per IQR increase. We observed associations between personal PM 2.5 and wheeze (OR: 1.23; 95%CI: 1.00, 1.50) and sputum (OR: 1.19; 95%CI: 1.00, 1.41). For household PM 2.5 and BC, associations were generally stronger for females compared to males. Models using an indicator variable of solid versus clean fuels resulted in larger OR estimates with less precision., Conclusions: We used measurements of household and personal air pollution for individuals using different cooking fuels and documented strong associations with respiratory symptoms., (Copyright © 2022. Published by Elsevier Inc.)

Background: Endovascular thrombectomy (EVT) for acute ischemic stroke via direct carotid puncture (DCP) has been commonly reported as case reports and series in the literature. However, the reported procedural risk and therapeutic outcome associated with this approach were variable. In this study, we aim to establish the role and safety profile of this alternative access technique by describing our single-center experience and conducting a comprehensive review of the literature., Methods: We conducted a retrospective review of consecutive patients at our center with large vessel occlusion (LVO) treated between 2018 and 2020 with DCP access. In addition, a literature review of studies published from 2012-2021 following PRISMA guidelines was conducted., Results: During the 3-year period, 11 patients with LVO were treated with EVT using DCP technique in our local cohort. A total of 216 cases were found in the literature search. A combined total of 227 cases were reviewed separately and collectively. Combining the data, DCP access was successfully achieved in 93.3% of the cases; 76.6% achieved satisfactory recanalization (mTICI ≥2b). DCP-related complications were seen in 20.3% of cases. A total of 32.4% patients were functionally independent (mRS ≤2) upon follow-up., Conclusions: Results from the literature review and our experience illustrate DCP as a feasible approach for EVT. The role of DCP as a bailout is iterated despite a higher complication risk, which may be imperative in low-volume stroke centers. Further studies to evaluate the role of DCP as a primary vascular access technique for EVT in selected cases could be explored., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Magnesium (Mg 2+ ), an essential structural component of chlorophyll, is absorbed from the soil by roots and transported to shoots to support photosynthesis in plants. However, the molecular mechanisms underlying root-to-shoot Mg 2+ translocation remain largely unknown. We describe here the identification of four plasma membrane (PM)-localized transporters, named Mg 2+ release transporters (MGRs), that are critical for root-to-shoot Mg transport in Arabidopsis. Functional complementation assays in a Mg 2+ -uptake-deficient bacterial strain confirmed that these MGRs conduct Mg 2+ transport. PM-localized MGRs (MGR4, MGR5, MGR6, and MGR7) were expressed primarily in root stellar cells and participated in the xylem loading step of the long-distance Mg 2+ transport process. In particular, MGR4 and MGR6 played a major role in shoot Mg homeostasis, as their loss-of-function mutants were hypersensitive to low Mg 2+ but tolerant to high Mg 2+ conditions. Reciprocal grafting analysis further demonstrated that MGR4 functions in the root to determine shoot Mg 2+ accumulation and physiological phenotypes caused by both low- and high-Mg 2+ stress. Taken together, our study has identified the long-sought transporters responsible for root-to-shoot Mg 2+  translocation in plants., (Copyright © 2022 The Author. Published by Elsevier Inc. All rights reserved.)

Black Carbon (BC) is an important component of household air pollution (HAP) in low- and middle- income countries (LMICs), but levels and drivers of exposure are poorly understood. As part of the Prospective Urban and Rural Epidemiological (PURE) study, we analyzed 48-hour BC measurements for 1187 individual and 2242 household samples from 88 communities in 8 LMICs (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Light absorbance (10 -5  m -1 ) of collected PM 2.5 filters, a proxy for BC concentrations, was calculated via an image-based reflectance method. Surveys of household/personal characteristics and behaviors were collected after monitoring. The geometric mean (GM) of personal and household BC measures was 2.4 (3.3) and 3.5 (3.9)·10 -5  m -1 , respectively. The correlation between BC and PM 2.5 was r = 0.76 for personal and r = 0.82 for household measures. A gradient of increasing BC concentrations was observed for cooking fuels: BC increased 53% (95%CI: 30, 79) for coal, 142% (95%CI: 117, 169) for wood, and 190% (95%CI: 149, 238) for other biomass, compared to gas. Each hour of cooking was associated with an increase in household (5%, 95%CI: 3, 7) and personal (5%, 95%CI: 2, 8) BC; having a window in the kitchen was associated with a decrease in household (-38%, 95%CI: -45, -30) and personal (-31%, 95%CI: -44, -15) BC; and cooking on a mud stove, compared to a clean stove, was associated with an increase in household (125%, 95%CI: 96, 160) and personal (117%, 95%CI: 71, 117) BC. Male participants only had slightly lower personal BC (-0.6%, 95%CI: -1, 0.0) compared to females. In multivariate models, we were able to explain 46-60% of household BC variation and 33-54% of personal BC variation. These data and models provide new information on exposure to BC in LMICs, which can be incorporated into future exposure assessments, health research, and policy surrounding HAP and BC., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: Although androgen deprivation therapy (ADT) and androgen receptor (AR) signaling inhibitors are effective in metastatic prostate cancer, resistance occurs in most patients. This phase I/II trial assessed the safety, pharmacokinetic impact, and efficacy of the glucocorticoid receptor (GR) antagonist mifepristone in combination with enzalutamide for castration-resistant prostate cancer (CRPC)., Patients and Methods: One hundred and six patients with CRPC were accrued. Phase I subjects were treated with enzalutamide monotherapy at 160 mg per day for 28 days to allow steady-state accumulation. Patients then entered the dose escalation combination portion of the study. In phase II, patients were randomized 1:1 to either receive enzalutamide alone or enzalutamide plus mifepristone. The primary endpoint was PSA progression-free survival (PFS), with radiographic PFS, and PSA response rate (RR) as key secondary endpoints. Circulating tumor cells were collected before randomization for exploratory translational biomarker studies., Results: We determined a 25% dose reduction in enzalutamide, when added to mifepristone, resulted in equivalent drug levels compared with full-dose enzalutamide and was well tolerated. However, the addition of mifepristone to enzalutamide following a 12-week enzalutamide lead-in did not delay time to PSA, radiographic or clinical PFS. The trial was terminated early due to futility., Conclusions: This is the first prospective trial of dual AR-GR antagonism in CRPC. Enzalutamide combined with mifepristone was safe and well tolerated but did not meet its primary endpoint. The development of more specific GR antagonists combined with AR antagonists, potentially studied in an earlier disease state, should be explored., (©2022 American Association for Cancer Research.)

The long-lasting co-evolution of ticks with pathogens results in mutual adaptation. Blood-feeding is one of the critical physiological behaviors that have been associated with the tick microbiome; however, most knowledge was gained through the study of laboratory-reared ticks. Here we detached Ixodes persulcatus ticks at different stages of blood-feeding from human patients and performed high-throughput transcriptomic analysis on them to identify their virome and genes differentially expressed between flat and fully fed ticks. We also traced bloodmeal sources of those ticks and identified bats and three other potential mammalian hosts, highlighting the public health significance. We found Jingmen tick virus and 13 putative new viruses belonging to 11 viral families, three of which even exhibited high genetic divergence from viruses previously reported in the same tick species from the same geographic region. Furthermore, differential expression analysis suggested a downregulation of antioxidant genes in the fully fed I. persulcatus ticks, which might be related to bloodmeal-related redox homeostasis. Our work highlights the significance of active surveillance of tick viromes and suggests a role of reactive oxygen species (ROS) in modulating changes in the microbiome during blood-feeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Ning, Zheng, Chu, Cui, Zhang, Guo, Wei, Liu, Sun, Ye, Jiang, Yuan, Li, Bian, Bell-Sakyi, Wang, Jiang, Song, Cao, Tsan-Yuk Lam, Ni and Jia.)

Pulmonary sequelae following COVID-19 pneumonia have been emerging as a challenge; however, suitable cell sources for studying COVID-19 mechanisms and therapeutics are currently lacking. In this paper, we present a standardized primary alveolar cell culture method for establishing a human alveolar epithelium model that can recapitulate viral infection and cellular plasticity. The alveolar model is infected with a SARS-CoV-2 pseudovirus, and the clinically relevant features of the viral entry into the alveolar type-I/II cells, cytokine production activation, and pulmonary surfactant destruction are reproduced. For this damaged alveolar model, we find that the inhibition of Wnt signaling via XAV939 substantially improves alveolar repair function and prevents subsequent pulmonary fibrosis. Thus, the proposed alveolar cell culture strategy exhibits potential for the identification of pathogenesis and therapeutics in basic and translational research., (© 2022. The Author(s).)

Introduction: Use of polluting cooking fuels generates household air pollution (HAP) containing health-damaging levels of fine particulate matter (PM 2.5 ). Many global epidemiological studies rely on categorical HAP exposure indicators, which are poor surrogates of measured PM 2.5 levels. To quantitatively characterize HAP levels on a large scale, a multinational measurement campaign was leveraged to develop household and personal PM 2.5 exposure models., Methods: The Prospective Urban and Rural Epidemiology (PURE)-AIR study included 48-hour monitoring of PM 2.5 kitchen concentrations (n = 2,365) and male and/or female PM 2.5 exposure monitoring (n = 910) in a subset of households in Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania and Zimbabwe. PURE-AIR measurements were combined with survey data on cooking environment characteristics in hierarchical Bayesian log-linear regression models. Model performance was evaluated using leave-one-out cross validation. Predictive models were applied to survey data from the larger PURE cohort (22,480 households; 33,554 individuals) to quantitatively estimate PM 2.5 exposures., Results: The final models explained half (R 2  = 54%) of the variation in kitchen PM 2.5 measurements (root mean square error (RMSE) (log scale):2.22) and personal measurements (R 2  = 48%; RMSE (log scale):2.08). Primary cooking fuel type, heating fuel type, country and season were highly predictive of PM 2.5 kitchen concentrations. Average national PM 2.5 kitchen concentrations varied nearly 3-fold among households primarily cooking with gas (20 μg/m 3 (Chile); 55 μg/m 3 (China)) and 12-fold among households primarily cooking with wood (36 μg/m 3 (Chile)); 427 μg/m 3 (Pakistan)). Average PM 2.5 kitchen concentration, heating fuel type, season and secondhand smoke exposure were significant predictors of personal exposures. Modeled average PM 2.5 female exposures were lower than male exposures in upper-middle/high-income countries (India, China, Colombia, Chile)., Conclusion: Using survey data to estimate PM 2.5 exposures on a multinational scale can cost-effectively scale up quantitative HAP measurements for disease burden assessments. The modeled PM 2.5 exposures can be used in future epidemiological studies and inform policies targeting HAP reduction., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/purpose: To investigate the impact of pharmaceutical care programs for the management of contraindicated drug-drug interactions (DDIs) in direct-acting antivirals (DAAs) therapy., Methods: A prospective observational study was performed at Dalin Tzu Chi Hospital between January 2018 and December 2019. Pharmacists screened DDIs for all hepatitis C patients before DAA therapy. The study outcome included the frequency of contraindicated DDIs, acceptance rate, and cost avoidance of the pharmaceutical care program., Results: A total of 1053 patients were enrolled in the study, with a mean age of 67.1 ± 11.9 years. Most patients received therapy with sofosbuvir/ledipasvir (37.1%; n = 391), elbasvir/grazoprevir (23.8%; n = 251), or glecaprevir/pibrentasvir (21.1%; n = 222). A total of 796 (75.6%) patients received at least one co-medication, with the average number of co-medications being 5.2 per patient (SD: 4.4/patient). In total, 1356 DDIs were identified, with the average DDIs per patient of 1.3 (SD: 1.7). For patients with contraindicated DDIs (2%, n = 102), statins and amiodarone were the most common co-medications. Physicians often accepted pharmacists' recommendations (acceptance rate of 72.5%) or withheld co-medication to avoid severe adverse drug events (ADEs). The estimated cost avoidance of preventable ADEs was USD 14,033 for contraindicated DDIs with pharmaceutical care programs., Conclusion: The implementation of pharmaceutical care programs in DAA therapy provides a favorable outcome and substantial cost avoidance., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This study evaluates the whole airway abnormalities of long-term treated late-onset Pompe disease (LOPD) patients, with interventions using the flexible bronchoscope (FB). As a retrospective study, we follow up with our five LOPD patients treated with Myozyme from 2012 to 2021 regularly, but with a focus on the whole airway abnormalities of these patients visualized through FB. The long-term clinical outcomes and relevant airway symptoms were assessed. Pulmonary function test and polysomnography were performed to evaluate the degree of respiratory compromise. All patients in the study had varying degrees of airway collapsibility, pulmonary complications, sleep apnea syndrome, and facial anomalies. Pulmonary function could preserve after Myozyme treatment, but potential deterioration thereafter. This is the first study that focuses on airway abnormalities and pulmonary complications in long-term treated LOPD patients using FB. Despite years of Myozyme treatment, we still observed airway abnormalities in these patients. In our series, the pulmonary complications seem more obvious than those observed in patients with infantile-onset Pompe disease, which might be related to the late diagnosis and treatment. We might recommend that FB could provide dynamic evaluation and interventions of airway abnormalities simultaneously. Early diagnosis of respiratory dysfunction is a critical prognostic factor of the long-term outcome of treated LOPD patients., (© 2021 Wiley Periodicals LLC.)

A laser beam rider is a large-scale optical structure designed so that it is attracted toward the optical axis, while also affording forward propulsion via radiation pressure along the beam path. Such structures form the basis of laser-driven light sails. Experimental measurements are described whereby a thin diffractive axicon film is shown to exhibit a natural restoring force when its axis is displaced from the optical axis. This effect is attributed to the optical momentum change of diffracted light. Whereas continuous illumination supports harmonic motion, modulated illumination is shown to support both parametric gain and parametric damping. The 12.7µ m period photopolymer axicon grating was suspended in a vacuum torsion oscillator and irradiated with a 1.5 W near-infrared laser modulated at a period of 38 s.

In this study, different probiotics commonly used to produce fermented dairy products were inoculated independently for Chenopodium formosanum Koidz. fermentation. The strain with the highest level of antioxidant activity was selected and the fermentation process was further optimized via response surface methodology (RSM). Lactobacillus plantarum BCRC 11697 was chosen because, compared to other lactic acid bacteria, it exhibits increased free radical scavenging ability and can produce more phenolic compounds, DPPH (from 72.6% to 93.2%), and ABTS (from 64.2% to 76.9%). Using RSM, we further optimize the fermentation protocol of BCRC 11697 by adjusting the initial fermentation pH, agitation speed, and temperature to reach the highest level of antioxidant activity (73.5% of DPPH and 93.8% of ABTS). The optimal protocol (pH 5.55, 104 rpm, and 24.4°C) resulted in a significant increase in the amount of phenolic compounds as well as the DPPH and ABTS free radical scavenging ability of BCRC 11697 products. The IC50 of the DPPH and ABTS free radical scavenging ability were 0.33 and 2.35 mg/mL, respectively, and both protease and tannase activity increased after RSM. An increase in lower molecular weight (<24 kDa) protein hydrolysates was also observed. Results indicated that djulis fermented by L. plantarum can be a powerful source of natural antioxidants for preventing free radical-initiated diseases., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Circulating tumor cells (CTC) are under investigation as a minimally invasive liquid biopsy that may improve risk stratification and treatment selection. CTCs uniquely allow for digital pathology of individual malignant cell morphology and marker expression. We compared CTC features and T-cell counts with survival endpoints in a cohort of patients with metastatic genitourinary cancer treated with combination immunotherapy., Experimental Design: Markers evaluated included pan-CK/CD45/PD-L1/DAPI for CTCs and CD4/CD8/Ki-67/DAPI for T cells. ANOVA was used to compare CTC burden and T-cell populations across timepoints. Differences in survival and disease progression were evaluated using the maximum log-rank test., Results: From December 2016 to January 2019, 183 samples from 81 patients were tested. CTCs were found in 75% of patients at baseline. CTC burden was associated with shorter overall survival (OS) at baseline ( P = 0.022), but not on-therapy. Five morphologic subtypes were detected, and the presence of two specific subtypes with unique cellular features at baseline and on-therapy was associated with worse OS (0.9-2.3 vs. 28.2 months; P < 0.0001-0.013). Increasing CTC heterogeneity on-therapy had a trend toward worse OS ( P = 0.045). PD-L1 + CTCs on-therapy were associated with worse OS ( P < 0.01, cycle 2). Low baseline and on-therapy CD4/CD8 counts were also associated with poor OS and response category., Conclusions: Shorter survival may be associated with high CTC counts at baseline, presence of specific CTC morphologic subtypes, PD-L1 + CTCs, and low %CD4/8 T cells in patients with metastatic genitourinary cancer. A future study is warranted to validate the prognostic utility of CTC heterogeneity and detection of specific CTC morphologies., (©2020 American Association for Cancer Research.)