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The development of synovial membrane-like structures has been described previously only in association with breast implants, the bone-cement interface of hip prostheses, tendon implants, testicular implants, and traumatized skin. Previous investigators have theorized that this phenomenon-referred to as 'synovial metaplasia'-develops in response to gliding trauma. In some cases, these lesions can exhibit a papillary growth pattern. We report 2 unusual cases of oral mucoceles exhibiting papillary synovial metaplasia-like change: the first arising in the lower lip of an 11-year old African-American boy and the second in the lower lip of a 12-year-old European-American girl. We propose that these cases represent a rare and previously undescribed histopathologic variant of the oral mucocele. These lesions should be distinguished from other oral lesions that may exhibit a papillary cystic growth pattern. [ABSTRACT FROM AUTHOR]

The odontogenic keratocyst is a developmental odontogenic cyst most commonly occurring in the jaws. In rare instances, however, this lesion has been reported to occur in the gingival soft tissues. Although most authors have regarded these soft tissue lesions to be peripheral odontogenic keratocysts, others have preferred to regard them as histopathologic variants of the gingival cyst of the adult. We document 2 additional cases occurring in the gingival soft tissues, and we review the existing literature concerning this unusual lesion. Given the distinct microscopic features and possible association with nevoid basal cell carcinoma syndrome, we favor the view that this lesion represents the soft tissue counterpart of the intraosseous odontogenic keratocyst. [ABSTRACT FROM AUTHOR]

The Natural Products Magnetic Resonance Database (NP-MRD; https://np-mrd.org) is a comprehensive, freely accessible, web-based resource for the deposition, distribution, extraction, and retrieval of nuclear magnetic resonance (NMR) data on natural products (NPs). The NP-MRD was initially established to support compound de-replication and data dissemination for the NP community. However, that community has now grown to include many users from the metabolomics, microbiomics, foodomics, and nutrition science fields. Indeed, since its launch in 2022, the NP-MRD has expanded enormously in size, scope, and popularity. The current version of NP-MRD now contains nearly 7× more compounds (281 859 versus 40 908) and 7× more NMR spectra (5.5 million versus 817 278) than the first release. More specifically, an additional 4.6 million predicted spectra and another 11 000 spectra simulated from experimental chemical shifts were deposited into the database. Likewise, the number of NMR raw spectral data depositions has grown from 165 spectra per year to >10 000 per year. As a result of this expansion, the number of monthly webpage views has grown from 55 to 20 000 and the number of monthly visitors has increased from 7 to 2500. To address this growth and to better support the expanding needs of its diverse community of users, many additional improvements to the NP-MRD have been made. These include significant enhancements to the data submission process, notable updates to the database's spectral search utilities and useful additions to support better NMR spectral analysis/prediction. Significant efforts have also been undertaken to remediate and update many of NP-MRD's database entries. This manuscript describes these database improvements and expansion efforts, along with how they have been implemented and what future upgrades to the NP-MRD are planned., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Aim: Transitional care in the emergency department (ED) has the potential to improve outcomes for older patients, but the specific population benefits from it and impact in Taiwan remain unclear. Therefore, we conducted this study., Methods: An interdisciplinary team comprising emergency physicians, dedicated transitional care nurse (TCN), nurse practitioners, nurses, geriatricians, and social workers was established at a tertiary medical center. TCN conducted screenings of ED patients (≥75 years) awaiting hospitalization to identify those in need of social or care support and aid as required. The team held regular meetings to address transitional care challenges. A retrospective analysis was conducted, comparing patients who received transitional care with those who did not, between February 1, 2022, and October 31, 2022, followed by a three-month outcome assessment., Results: We successfully implemented a novel ED transitional care model, involving 183 patients with TCN assistance and 374 patients without. Compared to patients without TCN, those with TCN were older, had more underlying comorbidities, required more nasogastric feeding and Foley indwelling, and had higher rates of hospice and palliative care. The common needs for TCN included providing home care instructions to a foreign caregiver (38.4%), long-term care referral (30.0%), care instructions for family members of older adults in long-term care facilities (26.3%), social worker referral (3.2%), and home healthcare referral (2.1%). Follow-up analysis showed no significant outcome differences between the two cohorts., Conclusion: The model we implemented identified the population benefiting from this service. Despite the frailty of patients receiving TCN, their outcomes were not inferior, suggesting the potential benefits of TCN for this population. Further research is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hsu, Ho, Lin, Tsai, Yang, Hsu, Peng, Hsu, Ho and Huang.)

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer, and immune checkpoint inhibitors (ICIs) have shown efficacy in its treatment. The combination of chemotherapy and ICIs represents a new trend in the standard care for metastatic NPC. In this study, we aim to clarify the immune cell profile and related prognostic factors in the ICI-based treatment of metastatic NPC. Programmed cell death ligand 1 (PD-L1) expression was measured in 81 metastatic tissue samples that had not received prior ICI treatment. The combined positive score (CPS) was positive in 58.0% of the samples, with a statistically significant correlation to median overall survival (OS) (CPS ≥ 1 vs. CPS < 1: 28 vs. 16 months, P = 0.004). For the combination treatment of metastatic NPC, 62 patients were enrolled in a retrospective analysis, yielding a median OS of 39.3 months. The objective response rate for this combination therapy was 71%, with a complete response rate of 45.2%. With a cutoff value of 4.8 for the pre-treated neutrophil-lymphocyte ratio (NLR) in peripheral blood (PB), the difference in median OS was statistically significant ( P = 0.021). Thirty-seven patients received local treatment following the combination therapy of ICIs and chemotherapy, which provided additional survival benefits. Most hyper-responders exhibited a prolonged low NLR (< 3), a high total lymphocyte count, and an undetectable or stable EBV DNA load in PB during treatment. Peripheral blood mononuclear cells (PBMCs) from most patients receiving the combination treatment were rich in PD-1+CD8+ lymphocytes, which showed high expression of both IFN-γ and Granzyme B, demonstrating the ability to kill the EBV-positive NPC cell line and xenografts in vitro and in vivo. Responders also displayed increased levels of CD4+CD45RA-CCR7-CD28+CD57- cells (effector memory cell subset) in peripheral blood. These results indicate that in the context of combined chemotherapy and ICIs, high PD-L1 expression in pre-treated metastatic tumor tissue, a low NLR before treatment, a decrease in NLR after treatment, and local treatment can provide significant benefits for patients with metastatic NPC., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Maintaining proper immune function and hormone status is important for athletes to avoid upper respiratory tract infection (URTI) and insufficient recovery, which is detrimental to sport performance and health. The aim of this study was to evaluate whether three-week supplementation of L-glutamine could benefit the mucosal immunity and hormonal status of combat-sport athletes as well as their rates of upper respiratory tract infection (URTI) and subjective feelings of well-being after intensive training., Methods: Twenty-one combat-sport athletes from the National Taiwan University of Sport were recruited in this study. After intensive training, two groups of the participants were asked to consume powder form of 0.3 g/kg body weight of L-glutamine (GLU group) or maltodextrin (PLA group) with drinking water in a randomized design at the same time every day during 3 weeks. Saliva samples were collected to measure immunoglobulin A (IgA), nitric oxide (NO), testosterone (T) and cortisol (C) before and after three-week supplementation; moreover, Hooper's index questionnaires were completed for wellness assessment. The incidence and duration of URTI were recorded by using a health checklist throughout the entire study period., Results: Supplementation of L-glutamine significantly enhanced the concentrations of IgA and NO in saliva; additionally, the incidence of URTI was significantly reduced. Regarding hormones, T concentration was significantly decreased in the PLA group, whereas C concentration was significantly increased, resulting in a significant decrease of T/C ratio. In contrast, the GLU group showed a significant increase of T/C ratio, while the mood scores of the Hooper's index questionnaire were higher in the PLA group., Conclusions: Three-week supplementation of L-glutamine after intensive training enhanced the mucosal immunity, improved hormonal status and reduced the rate of URTI of combat-sport athletes while feelings of well-being were also enhanced. Therefore, L-glutamine would be beneficial for the sports performance and recovery of athletes.

Aim: This study aimed to explore anesthesia nurses' (ANs) perceptions of roles, competencies, and attitudes towards patient safety culture, along with predictive factors for patient safety culture., Introduction: The 2021 guidelines from the International Council of Nurses aim to ensure global access to safe surgical and anesthesia care by 2030. However, in Taiwan, the roles and competencies of ANs are still evolving. Many have a limited understanding, posing potential risks to patient safety., Methods: A cross-sectional study was conducted, involving ANs from five hospitals within a healthcare foundation. ANs' self-perceived roles and competencies were assessed using a structured questionnaire based on the CanMEDS framework from the International Federation of Nurse Anesthetists. Additionally, data were collected using the Chinese version of the Safety Attitudes Questionnaire. Reporting followed the STROBE guideline., Results: Among 200 ANs, a consensus emerged favored all roles and competencies, with positive attitudes toward patient safety culture. Remarkably, self-perceived competencies, working in regional hospitals, and working in medical centers significantly predicted ANs' attitude toward patient safety culture., Discussion: The study results can assist ANs in gaining a deeper understanding of their roles and competencies. Considering predictive factors, strengthening ANs' competencies may contribute to enhancing patient safety culture., Conclusion and Implication for Nursing and Health Policy: Our results informed nursing leaders and policymakers in Taiwan and other countries regarding ANs' perceptions of roles and competencies. Nurse managers could consider the specific factors influencing ANs' attitudes toward patient safety culture and make great efforts to develop strategies aimed at enhancing their competencies., (© 2024 International Council of Nurses.)

Octocorals, vital components of reef ecosystems, inhabit various marine environments across diverse climate zones, spanning from tropical shallows to frigid deep-sea regions. Certain octocoral species, notably Lobophytum and Sinularia, are particularly intriguing due to their production of diverse metabolites, warranting continuous investigation. Although octocorals played the roles in coral ecosystems, the studies are rare in comparison to scleractinian corals, especially in transcriptomic and genomic data. However, RNA extraction was massively interfered by the polysaccharides and secondary metabolites produced from octocoral holobiont. For this purpose, five lysis buffer systems and two extraction processes were examined for the RNA extraction efficiency in octocorals. We found CTAB/10%SDS as a new method for RNA extraction from six different octocoral genera. Furthermore, our new method is enable to extract RNA with good quality for downstream application such as quantitative PCR and RNA sequencing. Finally, comparative transcriptomic analysis between healthy octocorals and those dark-induced bleaching corals in Lobophytum hsiehi revealed extracellular matrix and immunity-related genes may play the important roles in coral-symbiodinium symbiosis. We believe that this study's findings and the developed RNA extraction method will serve as valuable references for future research, particularly in octocorals., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Acute respiratory failure (ARF) associated with antipsychotic use has been documented through case reports and population-based studies., Objective: To assess whether the recent use of antipsychotics is associated with an increased risk of ARF in U.S. Medicare beneficiaries with chronic obstructive pulmonary disease., Design, Setting, and Participants: Case-crossover study conducted among U.S. Fee-for-Service Medicare beneficiaries with chronic obstructive pulmonary disease hospitalized with ARF, from January 1, 2007, through December 31, 2019., Exposure: Oral antipsychotics., Main Outcome(s) and Measure(s): Adjusted odds ratios (aOR) and 95% confidence intervals (CI) for ARF requiring invasive mechanical ventilation associated with the use of antipsychotics in the case period (days -14 to -1) compared to the control period (days -75 to -88)., Results: We identified 145,018 cases (mean age 69.4 years, 57.2% female). Of these, 2,003 had antipsychotic use only during the case period and 1,728 only during the control period. The aOR of ARF within 14 days after antipsychotic use was 1.13 (95% CI, 1.06, 1.20). The risk increased with increasing age, being statistically significant in patients ages 75-84 years (aOR: 1.37 [95% CI, 1.17, 1.60]) and 85 + years (aOR: 1.50 [95% CI, 1.20, 1.89]), but not in beneficiaries under 75 years of age (aOR 18-49 years: 1.01 [95% CI, 0.85, 1.20]; 50-64 years: 1.03 [95% CI, 0.92, 1.15]; 65-74 years: 1.12 [95% CI, 0.98, 1.27])., Conclusions and Relevance: Recent antipsychotic use by Medicare beneficiaries with chronic obstructive pulmonary disease was associated with an increased risk of ARF in those aged 75 years and older., Competing Interests: Declarations:. Financial Support:: The U.S. Food and Drug Administration funded this study through an interagency agreement with the Centers for Medicare & Medicaid Services (Contract number: GS-10F-0133S). The authors who were employees or contractors of the U.S. Food and Drug Administration and the Centers for Medicare & Medicaid Services played a role in the design; however, other officials at the U.S. Food and Drug Administration and the Centers for Medicare & Medicaid Services had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Conflict of Interest:: Amy Brehm’s spouse owns stocks in Bristol Myers, Abbvie, and Johnson & Johnson. All other authors have no conflicts of interest to disclose. Previous Presentation:: Preliminary results of this work were presented at CHEST Annual Meeting 2022, October 16–19, 2022, Nashville, TN, USA. Disclaimer:: The manuscript was subject to administrative review before submission, but this review did not alter its content. The views expressed are those of the authors and not necessarily those of the Department of Health and Human Services, the U.S. Food and Drug Administration, or the Centers for Medicare & Medicaid Services., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Flooding is a widespread natural disaster that causes tremendous yield losses of global food production. Rice is the only cereal capable of growing in aquatic environments. Direct seeding by which seedlings grow underwater is an important cultivation method for reducing rice production cost. Hypoxic germination tolerance and root growth in waterlogged soil are key traits for rice adaptability to flooded environments. Alternative oxidase (AOX) is a non-ATP-producing terminal oxidase in the plant mitochondrial electron transport chain, but its role in hypoxia tolerance had been unclear. We have discovered that AOX1a is necessary and sufficient to promote germination/coleoptile elongation and root development in rice under flooding/hypoxia. Hypoxia enhances endogenous H 2 O 2 accumulation, and H 2 O 2 in turn activates an ensemble of regulatory genes including AOX1a to facilitate the conversion of deleterious reactive oxygen species to H 2 O 2 in rice under hypoxia. We show that AOX1a and H 2 O 2 act interdependently to coordinate three key downstream events, that is, glycolysis/fermentation for minimal ATP production, root aerenchyma development and lateral root emergence under hypoxia. Moreover, we reveal that ectopic AOX1a expression promotes vigorous root and plant growth, and increases grain yield under regular irrigation conditions. Our discoveries provide new insights into a unique sensor-second messenger pair in which AOX1a acts as the sensor perceiving low oxygen tension, while H 2 O 2 accumulation serves as the second messenger triggering downstream root development in rice against hypoxia stress. This work also reveals AOX1a genetic manipulation and H 2 O 2 pretreatment as potential targets for improving flooding tolerance in rice and other crops., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Despite advancements in targeted therapy, glioblastoma remains a challenging condition with limited treatment options. While surgical techniques and external radiation therapy have improved, the median survival for glioblastoma stands at around 12-18 months, with a 5-year survival rate of only 6.8%. Epithelioid glioblastoma (eGBM) represents a rare subtype within the glioma spectrum. Utilizing patient-derived xenograft (PDX) models in mice offers a promising avenue for drug screening and translational research, particularly for this specific glioblastoma subtype. Establishing a stable PDX model for eGBM revealed consistent genetic abnormalities, including BRAF V600E mutation and CDKN2A deletion, in both primary and PDX tumors. Leveraging a curated drug database, compounds potentially targeting these aberrations were identified. By using the novel PDX platform, the results presented in this study demonstrate that the treatments with Palbociclib or Dabrafenib/Trametinib significantly reduced tumor size. RNA sequencing analysis further validated the responsiveness of the tumors to these targeted therapies. In conclusion, PDX models offer a deeper understanding of eGBM at the genomic level and facilitate the identification of potential therapeutic targets. Further translational studies of this novel PDX model hold promise for advancing the diagnosis and treatment of this specific subtype of glioblastoma., Competing Interests: None., (AJCR Copyright © 2024.)

Cellular bioenergetics and mitochondrial dynamics are crucial for the secretion of insulin by pancreatic beta cells in response to elevated levels of blood glucose. To elucidate the interactions between energy production and mitochondrial fission/fusion dynamics, we combine live-cell mitochondria imaging with biophysical-based modeling and graph-based network analysis. The aim is to determine the mechanism that regulates mitochondrial morphology and balances metabolic demands in pancreatic beta cells. A minimalistic differential equation-based model for beta cells is constructed that includes glycolysis, oxidative phosphorylation, calcium dynamics, and fission/fusion dynamics, with ATP synthase flux and proton leak flux as main regulators of mitochondrial dynamics. The model shows that mitochondrial fission occurs in response to hyperglycemia, starvation, ATP synthase inhibition, uncoupling, and diabetic conditions, in which the rate of proton leakage exceeds the rate of mitochondrial ATP synthesis. Under these metabolic challenges, the propensities of tip-to-tip fusion events simulated from the microscopy images of the mitochondrial networks are lower than those in the control group and prevent the formation of mitochondrial networks. The study provides a quantitative framework that couples bioenergetic regulation with mitochondrial dynamics, offering insights into how mitochondria adapt to metabolic challenges., (© 2024. The Author(s).)

Paraneoplastic leukocytosis (PNL) in genitourinary cancer, though rare, can indicate aggressive behavior and poor outcomes. It has been potentially linked to cancer expressing G-CSF and GM-CSF, along with their respective receptors, exerting an autocrine/paracrine effect. In our study, we successfully established four patient-derived xenograft (PDX) lines and related cell lines from urothelial cancer (UC), conducting next-generation sequencing (NGS) for genetic studies. UC-PDX-LN1, originating from bladder cancer, exhibited two druggable targets - HRAS and ERCC2 - responding well to chemotherapy and targeted therapy, though not to tipifarnib, an HRAS inhibitor. Transcriptome analysis post-treatment illuminated potential mechanisms, with index protein analysis confirming their anticancer pathways. Mice implanted with UC-PDX-LN1 mirrored PNL observed in the patient's original tumor. Cytokine array and RT-PCR analyses revealed high levels of G-CSF and GM-CSF in our PDX and cell lines, along with their presence in culture media and tumor cysts.Leukocytosis within small vessels in and around the tumor, associated with NETosis and thrombus formation, suggested a mechanism wherein secreted growth factors were retained, further fueling tumor growth via autocrine/paracrine signaling. Disrupting this cancer cell-NETosis-thrombosis cycle, we demonstrated that anti-neutrophil or anticoagulant interventions enhanced chemotherapy's antitumor effects or prolonged survival in mice, even though these drugs lacked direct antitumor efficacy when used independently. Clinical observations in bladder cancer patients revealed PNL in 1.61% of cases (35/2162) with associated poor prognosis. These findings propose a novel approach, advocating for the combination of anticancer/NETosis/thrombosis strategies for managing UC patients presenting with PNL in clinical settings., Competing Interests: None., (AJCR Copyright © 2024.)

Background: The Xin-yi-san herbal decoction (XYS) is commonly used to treat patients with allergic rhinitis in Taiwan. Theophylline is primarily oxidized with high affinity by human cytochrome P450 (CYP)1A2, and has a narrow therapeutic index., Purpose: This study aimed to investigate the inhibition of human CYP1A2-catalyzed theophylline oxidation (THO) by XYS and its adverse effects in patients., Methods: Human CYPs were studied in recombinant enzyme systems. The influence of concurrent XYS usage in theophylline-treated patients was retrospectively analyzed., Results: Among the major human hepatic and respiratory CYPs, XYS inhibitors preferentially inhibited CYP1A2 activity, which determined the elimination and side effects of theophylline. Among the herbal components of XYS decoction, Angelicae Dahuricae Radix contained potent THO inhibitors. Furanocoumarin imperatorin was abundant in XYS and Angelicae Dahuricae Radix decoctions, and non-competitively inhibited THO activity with K i values of 77‒84 nM, higher than those (20‒52 nM) of fluvoxamine, which clinically interacted with theophylline. Compared with imperatorin, the intestinal bacterial metabolite xanthotoxol caused weaker THO inhibition. Consistent with the potency of the inhibitory effects, the docking analysis generated Gold fitness values in the order-fluvoxamine > imperatorin > xanthotoxol. During 2017‒2018, 2.6 % of 201,093 theophylline users consumed XYS. After inverse probability weighting, XYS users had a higher occurrence of undesired effects than non-XYS users; in particular, there was an approximately two-fold higher occurrence of headaches (odds ratio (OR), 2.14; 95 % confidence interval (CI), 1.99‒2.30; p < 0.001) and tachycardia (OR, 1.83; 95 % CI, 1.21‒2.77; p < 0.05). The incidence of irregular heartbeats increased (OR, 1.36; 95 % CI, 1.07‒1.72; p < 0.05) only in the theophylline users who took a high cumulative dose (≥ 24 g) of XYS. However, the mortality in theophylline users concurrently taking XYS was lower than that in non-XYS users (OR, 0.24; 95 % CI, 0.14‒0.40; p < 0.001)., Conclusion: XYS contains human CYP1A2 inhibitors, and undesirable effects were observed in patients receiving both theophylline and XYS. Further human studies are essential to reduce mortality and to adjust the dosage of theophylline in XYS users., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objectives: This study assessed the incidence of postfracture radiological temporomandibular joint (TMJ) degeneration in patients with different types of mandibular fractures, focusing on the impact of condylar fractures., Methods: This retrospective review included patients diagnosed as having mandibular fractures from 2016 to 2020 who had undergone initial computed tomography (CT) and a follow-up CT scan at least 1-month postfracture. Patient demographics, fracture details, treatment methods, and radiological signs of TMJ degeneration on CT were analyzed to identify risk factors for postfracture TMJ degeneration, with a focus on condylar head fracture and non-head (condylar neck or base) fractures., Results: The study included 85 patients (mean age: 38.95 ± 17.64 years). The per-patient analysis indicated that the incidence of new radiologic TMJ degeneration on CT was significantly the highest (p < 0.001) in patients with condylar head fractures (90.91%), followed by those with non-head condylar fractures (57.14%), and those without condylar involvement (24.49%). The per-joint analysis indicated nearly inevitable degeneration (93.94%) in 33 TMJs with ipsilateral condylar head fractures. For the remaining 137 TMJs, multivariate logistic regression revealed that other patterns (ipsilateral non-head, contralateral, or both) of condylar fractures (odds ratio (OR) = 3.811, p = 0.007) and the need for open reduction and internal fixation (OR = 5.804, p = 0.005) significantly increased the risk of TMJ degeneration., Conclusions: Ipsilateral non-head condylar fractures and contralateral condylar fractures are associated with a high risk of postfracture TMJ degeneration. Indirect trauma plays a vital role in postfracture TMJ degeneration., (© 2024. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

A valid assessment tool that measures active play is not yet available due to the sporadic and spontaneous nature of play, as well as the potential differences in how active play is understood and measured across different age groups, cultures, and contexts. The purpose of this review was to identify the scope and gaps in the measurement of active play based on data gathered from 68 countries that participated in the Global Matrix (GM) initiative, led by the Active Healthy Kids Global Alliance (AHKGA). GM is the global-level, biennial evaluation system of physical activity related behaviors among children and youth, including the Active Play indicator, and the sources of influence using letter grades (ranging between "A" and "F"). Based on the identified scope and gaps, this study offers recommendations for future research dedicated to the measurement/surveillance of active play. Out of the 68 countries involved in the previous GM (2014-22), 55% of the grades remained unassigned due to insufficient data on the Active Play indicator. The high number of unassigned grades, combined with the absence of valid measurement tool, highlight a need for a standardized measurement tool for improved global data generation of active play among children and youth. Our findings emphasize the need to address challenges in measuring active play. This review offers future considerations, research recommendations specific to the GM initiative, and two sets of age- and location-specific (indoor and outdoor settings) questionnaire items along with guidelines for its use. Together, these elements provide a roadmap for guiding future research and evaluation efforts on active play., (© 2024 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Cannabis is widely used for medicinal and recreational purposes. As a result, there is increased interest in its chemical components and their physiological effects. However, current information on cannabis chemistry is often outdated or scattered across many books and journals. To address this issue, we used modern metabolomics techniques and modern bioinformatics techniques to compile a comprehensive list of >6000 chemical constituents in commercial cannabis. The metabolomics methods included a combination of high- and low-resolution liquid chromatography-mass spectrometry (MS), gas chromatography-MS, and inductively coupled plasma-MS. The bioinformatics methods included computer-aided text mining and computational genome-scale metabolic inference. This information, along with detailed compound descriptions, physicochemical data, known physiological effects, protein targets, and referential compound spectra, has been made available through a publicly accessible database called the Cannabis Compound Database (https://cannabisdatabase.ca). Such a centralized, open-access resource should prove to be quite useful for the cannabis community.

Ethnopharmacological Relevance: The Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits of Ganoderma sinense particularly in addressing pulmonary-related ailments. Ganoderma formosanum, an indigenous subspecies of G. sinense from Taiwan, has demonstrated the same therapeutic properties., Aim of the Study: The aim of this study is to identify bioactive compounds and evaluate the potential of G. formosanum extracts as a novel treatment to alleviate pulmonary fibrosis (PF). Using an in-house drug screening platform, two-stage screening was performed to determine their anti-fibrotic efficacy., Methods and Materials: G. formosanum was fractionated into four partitions by solvents of different polarities. To determine their antifibrotic and pro-apoptotic properties, the fractions were analyzed using two TGF-β1-induced pulmonary fibrosis cell models (NIH-3T3) and human pulmonary fibroblast cell lines, immunoblot, qRT-PCR, and annexin V assays. Subsequently, transcriptomic analysis was conducted to validate the findings and explore possible molecular pathways. The identification of potential bioactive compounds was achieved through UHPLC-MS/MS analysis, while molecular interaction study was investigated by multiple ligands docking and molecular dynamic simulations., Results: The ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-β1-induced fibrotic models. Moreover, the EAF exhibited no discernible cytotoxicity. Untargeted UHPLC-MS/MS analysis identified potential bioactive compounds in EAF, including stearic acid, palmitic acid, and pentadecanoic acid. Multiple ligands docking and molecular dynamic simulations further confirmed that those bioactive compounds possess the ability to inhibit TGF-β receptor 1., Conclusion: Potential bioactive compounds in G. formosanum were successfully extracted and identified in the EAF, whose anti-fibrotic and pro-apoptotic properties could potentially modulate pulmonary fibrosis. This finding not only highlights the EAF's potential as a promising therapeutic candidate to treat pulmonary fibrosis, but it also elucidates how Ganoderma confers pulmonary health benefits as described in the ancient texts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Outcomes for adult patients with a high-grade glioma continue to be dismal and new treatment paradigms are urgently needed. To optimize the opportunity for discovery, we performed a phase 0/1 dose-escalation clinical trial that investigated tumor pharmacokinetics, pharmacodynamics, and single nucleus transcriptomics following combined ribociclib (CDK4/6 inhibitor) and everolimus (mTOR inhibitor) treatment in recurrent high-grade glioma. Patients with a recurrent high-grade glioma (n = 24) harboring 1) CDKN2A / B deletion or CDK4 / 6 amplification, 2) PTEN loss or PIK3CA mutations, and 3) wild-type retinoblastoma protein (Rb) were enrolled. Patients received neoadjuvant ribociclib and everolimus treatment and no dose-limiting toxicities were observed. The median unbound ribociclib concentrations in Gadolinium non-enhancing tumor regions were 170 nM (range, 65 - 1770 nM) and 634 nM (range, 68 - 2345 nM) in patients receiving 5 days treatment at the daily dose of 400 and 600 mg, respectively. Unbound everolimus concentrations were below the limit of detection (< 0.1 nM) in both enhancing and non-enhancing tumor regions at all dose levels. We identified a significant decrease in MIB1 positive cells suggesting ribociclib-associated cell cycle inhibition. Single nuclei RNAseq (snRNA) based comparisons of 17 IDH-wild-type on-trial recurrences to 31 IDH-wild-type standard of care treated recurrences data demonstrated a significantly lower fraction of cycling and neural progenitor-like (NPC-like) malignant cell populations. We validated the CDK4/6 inhibitor-directed malignant cell state shifts using three patient-derived cell lines. The presented clinical trial highlights the value of integrating pharmacokinetics, pharmacodynamics, and single nucleus transcriptomics to assess treatment effects in phase 0/1 surgical tissues, including malignant cell state shifts. ClinicalTrials.gov identifier: NCT03834740 .

The calcified chondroid mesenchymal neoplasm (CCMN) represents a recently recognized tumor type with only 50 well-documented cases in the English-language literature. Herein we report an additional case of CCMN presenting as a large mass in the temporomandibular joint region of a 41-year-old female. A review of previously reported cases and the current case of CCMN shows the following features: 1) average age 52 years (range 14-87 years) and an approximately even sex distribution; 2) most frequently involved sites: distal extremities (including foot, hand, wrist, forearm) (n=41) and temporomandibular joint/temporal/parotid region (n=9); 3) multilobular soft tissue tumor with chondroid to cartilaginous matrix, often grungy or lace-like calcifications, and variable cytologic atypia; 4) frequently detected FN1 rearrangement (n=15), including FN1 fusion with FGFR2 (n=7) or other receptor tyrosine kinases; 5) 2 reported local recurrences (after incomplete excision); 6) no reports of malignant biologic behavior., Competing Interests: Declaration of interests None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A 7-year-old farmed white-tailed deer doe was transported to a Levy County, Florida property and began to decline in health, exhibiting weight loss and pelvic limb weakness. The doe prematurely delivered live twin fawns, both of which later died. The doe was treated with corticosteroids, antibiotics, gastric cytoprotectants, and B vitamins but showed no improvement. The doe was euthanized, and a post mortem examination was performed under the University of Florida's Cervidae Health Research Initiative. We collected lung tissue after the animal was euthanized and performed histological evaluation, using H&E and Ziehl-Neelsen (ZN) staining, and molecular evaluation, using conventional PCR, followed by Sanger sequencing. The microscopic observations of the H&E-stained lung showed multifocal granuloma, while the ZN-stained tissue revealed low numbers of beaded, magenta-staining rod bacteria inside the granuloma formation. Molecular analysis identified the presence of Mycobacterium kansasii . This isolation of a non-tuberculous Mycobacterium in a white-tailed deer emphasizes the importance of specific pathogen identification in cases of tuberculosis-like disease in farmed and free-ranging cervids. We report the first case of M. kansasii infection in a farmed white-tailed deer ( Odocoileus virginianus ) in Florida. Although M. kansasii cases are sporadic in white-tailed deer, it is important to maintain farm biosecurity and prevent farmed cervids from contacting wildlife to prevent disease transmission.

Purpose: Successful participation in taekwondo (TKD) requires athletes to possess quick decision-making abilities and demonstrate technical proficiency during competition. Dehydration, occurring during both training and competition, is widely recognized to have various negative effects., Methods: This study investigated the impact of different levels of dehydration on cognitive function, as measured by the Vienna Test System, and the specific performance of kicking techniques among TKD athletes. Using a randomized crossover design, 12 participants were involved in the study. Before and after 1 hour of training at 80% of maximal heart rate, participants were weighed and provided urine samples. All participants were randomly assigned to 3 different hydration conditions: the euhydrated (EUH) group had unrestricted access to fluid consumption, while the hypohydrated (HYP) and severely HYP (S-HYP) groups experienced reductions of 2.0% and 4.0% of their initial body weight, respectively., Results: The EUH group exhibited better reaction speed in reaction-time test-form S1 than the HYP and S-HYP groups. Notably, the EUH group demonstrated a significantly higher success rate in the front-side kick (EUH 98%, HYP 90%, S-HYP 88%; P < .05). However, the success rates of back roundhouse kick and free head kick were similar among the 3 statuses. Furthermore, postexercise heart rates were found to be significantly higher in the HYP and S-HYP groups compared with the EUH group., Conclusions: This study provides insight into the negative effects of dehydration on cognitive function and TKD-specific performance. It is recommended that TKD athletes maintain optimal hydration levels during training and competition to ensure optimal performance.

Background: COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. This study's objective was to estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children., Methods: This cohort study identified children aged 5-17 years vaccinated with BNT162b2 matched with unvaccinated children. Participants and BNT162b2 vaccinations were identified in Optum and CVS Health insurance administrative claims databases linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Two COVID-19 outcome definitions were evaluated: COVID-19 diagnosis in any medical setting and COVID-19 diagnosis in hospitals/emergency departments (EDs). Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant-specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases., Results: There were 453,655 eligible vaccinated children one-to-one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person-years; CVS Health, 44.1 per 10,000 person-years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID-19 (meta-analyzed VE = 38% [95% CI, 36-40%]) and hospital/ED-diagnosed COVID-19 (meta-analyzed VE = 61% [95% CI, 56-65%]). VE estimates were lowest among children 5-11 years and during the Omicron-variant era., Conclusions: Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID-19 and hospital/ED-diagnosed COVID-19 in children; observed VE estimates differed by age group and variant era., Registration: The study protocol was publicly posted on the BEST Initiative website ( https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol&#95;2022&#95;508.pdf )., (© 2024. The Author(s).)

Aims and Objectives: This study aims to analyse the trends in the incidence, prevalence and medical costs of pressure injuries (PIs) among genders in Taiwan., Background: The treatment of PIs is complex and costly, often leading to complications and increased mortality. This issue significantly impacts healthcare quality and incurs substantial medical and social costs, warranting attention., Methods: A retrospective cohort study was conducted using data from Taiwan's National Health Insurance Database to obtain and calculate the incidence, prevalence, and medical costs of PIs in the country between 2001 and 2015 as well as to analyse high-risk groups and the medical care utilisation of patients following the STROBE reporting guidelines., Results: Between 2001 and 2015, 15,327 incident case of PIs were diagnosed. During the study period, the prevalence rate of PIs per 100,000 population rose from 26.3 to 189.6, with approximately 11.5%-16.3% of patients undergoing surgical debridement. The PIs prevalence rate increased by 7.2-fold, and hospitalisation costs accounted for 91.7%-96.0% of the total medical costs. Patients with older age, comorbidities, poorer financial status and lower education levels were found to be likely to develop PIs. These predisposing factors differed between males and females. The prevalence of PIs was higher in patients ≥75 years old than in patients from other age groups. Moreover, PI-related medical expenses have been increasing annually., Conclusions: In Taiwan, the rising incidence of PIs is driving up medical costs. Effective care and prevention of PIs necessitate a comprehensive plan from the entire healthcare system., Relevance to Clinical Practice: This research fills a gap in the available data on the incidence, prevalence, and medical costs of PIs in Taiwan and Asia., Patient or Public Contribution: The findings can be used to help develop clinical guidelines for preventive education and treatment of PIs., (© 2024 John Wiley & Sons Ltd.)

Bacterial genotoxins damage host cells by targeting their chromosomal DNA. In the present study, we demonstrate that a genotoxin of Salmonella Typhi, typhoid toxin, triggers the senescence-associated secretory phenotype (SASP) by damaging mitochondrial DNA. The actions of typhoid toxin disrupt mitochondrial DNA integrity, leading to mitochondrial dysfunction and disturbance of redox homeostasis. Consequently, it facilitates the release of damaged mitochondrial DNA into the cytosol, activating type I interferon via the cGAS-STING pathway. We also reveal that the GCN2-mediated integrated stress response plays a role in the upregulation of inflammatory components depending on the STING signaling axis. These SASP factors can propagate the senescence effect on T cells, leading to senescence in these cells. These findings provide insights into how a bacterial genotoxin targets mitochondria to trigger a proinflammatory SASP, highlighting a potential therapeutic target for an anti-toxin intervention., (© 2024. The Author(s).)

Bluetongue disease is a reportable animal disease that affects wild and farmed ruminants, including white-tailed deer (WTD). This report documents the clinical findings, ancillary diagnostics, and genomic characterization of a novel reassortant bluetongue virus serotype 2 (BTV-2) strain isolated from a dead Florida farmed WTD in 2022. Our analyses support that this BTV-2 strain likely stemmed from the acquisition of genome segments from co-circulating BTV strains in Florida and Louisiana. In addition, our analyses also indicate that genetically uncharacterized BTV strains may be circulating in the Southeastern USA; however, the identity and reassortant status of these BTV strains cannot be determined based on the VP2 and VP5 genome sequences. Hence, continued surveillance based on complete genome characterization is needed to understand the genetic diversity of BTV strains in this region and the potential threat they may pose to the health of deer and other ruminants., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The effects of coronavirus disease 2019 (COVID-19) primarily concern the respiratory tract and lungs; however, studies have shown that all organs are susceptible to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 may involve multiorgan damage from direct viral invasion through angiotensin-converting enzyme 2 (ACE2), through inflammatory cytokine storms, or through other secondary pathways. This study involved the analysis of publicly accessible transcriptome data from the Gene Expression Omnibus (GEO) database for identifying significant differentially expressed genes related to COVID-19 and an investigation relating to the pathways associated with mitochondrial, cardiac, hepatic, and renal toxicity in COVID-19. Significant differentially expressed genes were identified and ranked by statistical approaches, and the genes derived by biological meaning were ranked by feature importance; both were utilized as machine learning features for verification. Sample set selection for machine learning was based on the performance, sample size, imbalanced data state, and overfitting assessment. Machine learning served as a verification tool by facilitating the testing of biological hypotheses by incorporating gene list adjustment. A subsequent in-depth study for gene and pathway network analysis was conducted to explore whether COVID-19 is associated with cardiac, hepatic, and renal impairments via mitochondrial infection. The analysis showed that potential cardiac, hepatic, and renal impairments in COVID-19 are associated with ACE2, inflammatory cytokine storms, and mitochondrial pathways, suggesting potential medical interventions for COVID-19-induced multiorgan damage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chang, Wei. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Monovalent booster/additional doses of COVID-19 vaccines were first authorized in August 2021 in the United States. We evaluated the real-world effectiveness of receipt of a monovalent booster/additional dose of COVID-19 vaccine compared with receiving a primary vaccine series without a booster/additional dose., Methods: Cohorts of individuals receiving a COVID-19 booster/additional dose after receipt of a complete primary vaccine series were identified in 2 administrative insurance claims databases (Optum, CVS Health) supplemented with state immunization information system data between August 2021 and March 2022. Individuals with a complete primary series but without a booster/additional dose were one-to-one matched to boosted individuals on calendar date, geography, and clinical factors. COVID-19 diagnoses were identified in any medical setting, or specifically in hospitals/emergency departments (EDs). Propensity score-weighted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated with Cox proportional hazards models; vaccine effectiveness (VE) was estimated as 1 minus the HR by vaccine brand overall and within subgroups of variant-specific eras, immunocompromised status, and homologous/heterologous booster status., Results: Across both data sources, we identified 752,165 matched pairs for BNT162b2, 410,501 for mRNA-1273, and 11,398 for JNJ-7836735. For any medically diagnosed COVID-19, meta-analyzed VE estimates for BNT162b2, mRNA-1273, and JNJ-7836735, respectively, were: BNT162b2, 54% (95% CI, 53%-56%); mRNA-1273, 58% (95% CI, 56%-59%); JNJ-7836735, 34% (95% CI, 23%-44%). For hospital/ED-diagnosed COVID-19, VE estimates ranged from 70% to 76%. VE was generally lower during the Omicron era than the Delta era and for immunocompromised individuals. There was little difference observed by homologous or heterologous booster status., Conclusion: The original, monovalent booster/additional doses were reasonably effective in real-world use among the populations for which they were indicated during the study period. Additional studies may be informative in the future as new variants emerge and new vaccines become available.Registration: The study protocol was publicly posted on the BEST Initiative website (https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol&#95;2022&#95;508.pdf)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JBL, WGA, ATK, CB, and MSA are employees of RTI International, an independent nonprofit institute that performs research on behalf of governmental and commercial clients, including manufacturers of COVID-19 vaccines. LP, MM, RPO, JD, RP, JS, LBW, EJB, JDS, GWY, and KLA are employees of Optum and may own stock in UnitedHealth Group. DAD and CNMW are employees of CVS Health, which performs research on behalf of governmental and commercial clients, including manufacturers of COVID-19 vaccines. All other authors have no conflicts to declare., (© 2024 The Authors.)

Objective: To explore the short- and long-term effects of lower-limb endurance training on chronic obstructive pulmonary disease outpatients., Design: Prospective quasi-experimental study., Setting: 1383-bed teaching hospital in Taiwan., Participants: Overall, 69 outpatients diagnosed with chronic obstructive pulmonary disease were enrolled. A total of 60 patients completed the study., Intervention: Training group: Lower-limb endurance training; control group: Education only., Main Measures: The modified medical research council score, chronic obstructive pulmonary disease assessment test score, pulmonary function test, and number of acute exacerbation within a year., Results: The training group showed significant improvement in the chronic obstructive pulmonary disease assessment test total score, modified medical research council score (both P  < 0.001) at third month sustaining to 12th month ( P  < 0.001) and presented less events of acute exacerbation ( P  = 0.011) at 12th month. The chronic obstructive pulmonary disease assessment test decreased by 8 points sustaining to 12th month. The training group presented significant post-training functional capacity improvements in 6-min walking distance, lowest oxygen saturation during 6-min walking test, peak workload, maximum inspiratory/ expiratory pressures, and calf circumference., Conclusions: The lower-limb endurance training improved perceived dyspnea in daily activity and health status after completion of training and sustaining for a year. The lower-limb endurance training alleviated disease impacted on reduced acute exacerbations., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Structuring liquid oils into edible oleogels from natural and abundant plant ingredients has great significance in fields ranging from foods to pharmaceuticals but has proven challenging. Herein, novel bicomponent phytosterol-based oleogels were developed with natural phenolics. Investigating diverse natural phenolics, cinnamic acid (CA) and ethyl ferulate (EF) successfully formed oleogels in combination with phytosterols (PS), where a synergistic effect on the oleogelation and crystallization was observed compared to the corresponding single component formulations. FTIR and UV-vis spectra showed that the gel network was primarily driven by hydrogen bonding and π-π stacking. Furthermore, oscillatory shear demonstrated oleogels featured higher elastic and network structure deformation at molar ratio of 5:5 and 3:7. Moreover, the bicomponent phytosterol-based oleogels displayed partially reversible shear deformation and a reversible solid-liquid transition. Such information was useful for engineering the functional properties of oleogel-based lipidic materials, providing significance for the application in foods, cosmetics and pharmaceuticals industries., 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 Ltd. All rights reserved.)

Background: Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) infection. To test preclinical NPC drugs, we established two patient-derived xenograft (PDX) mouse models, EBV-positive PDX-B13 and EBV-negative PDX-Li41, for drug screening., Methods: Based on next generation sequencing (NGS) studies, PDX-B13 had CCND1 copy number (CN) gain but CDKN2A CN loss, whereas PDX-Li41 had CDKN2A and RB1 CN loss, TSC1 (negative regulator of mTOR) frameshift deletion mutation, and increased activation of mTOR, a serine/threonine kinase that governs metabolism, autophagy, and apoptosis. Increased mTOR was also associated with poor NPC prognosis., Results: Everolimus, an mTOR inhibitor, suppressed tumor growth in the two PDX NPC models and had an additive antitumor effect with palbociclib, a CDK4/6 inhibitor. PDX tumors treated with various drugs or untreated were subjected to RNA sequencing, transcriptome profile analysis, and selective Western blotting to understand the interactions between these drugs and gene expression profiles. Palbociclib also suppressed EB viral nuclear antigen (EBNA1) expression in PDX-B13. Everolimus together with autophagy inhibitor, hydroxychloroquine, had additive anti-tumor effect on PDX-B13 tumor. Immunohistochemistry revealed that high mTOR levels were correlated with poor overall survival in patients with metastatic NPC (N = 90)., Conclusions: High mTOR levels are a poor prognostic factor in NPC, and cell cycle, mTOR and autophagy pathways may serve as therapeutic targets in NPC. In addition, PDX models can be used for efficiently testing potential NPC drugs., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2023. Published by Elsevier Inc.)

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists' awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures.

Genetic studies have identified numerous loci associated with type 2 diabetes (T2D), but the functional roles of many loci remain unexplored. Here, we engineered isogenic knockout human embryonic stem cell lines for 20 genes associated with T2D risk. We examined the impacts of each knockout on β cell differentiation, functions, and survival. We generated gene expression and chromatin accessibility profiles on β cells derived from each knockout line. Analyses of T2D-association signals overlapping HNF4A-dependent ATAC peaks identified a likely causal variant at the FAIM2 T2D-association signal. Additionally, the integrative association analyses identified four genes (CP, RNASE1, PCSK1N, and GSTA2) associated with insulin production, and two genes (TAGLN3 and DHRS2) associated with β cell sensitivity to lipotoxicity. Finally, we leveraged deep ATAC-seq read coverage to assess allele-specific imbalance at variants heterozygous in the parental line and identified a single likely functional variant at each of 23 T2D-association signals., Competing Interests: Declaration of interests S.C. is the co-founder of OncoBeat, LLC and a consultant of Vesalius Therapeutics., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to investigate differences in cervical lymph node image quality on dual-energy computed tomography (CT) scan with datasets reconstructed using filter back projection (FBP), hybrid iterative reconstruction (IR), and deep learning-based image reconstruction (DLIR) in patients with head and neck cancer., Method: Seventy patients with head and neck cancer underwent follow-up contrast-enhanced dual-energy CT examinations. All datasets were reconstructed using FBP, hybrid IR with 30 % adaptive statistical IR (ASiR-V), and DLIR with three selectable levels (low, medium, and high) at 2.5- and 0.625-mm slice thicknesses. Herein, signal, image noise, signal-to-noise ratio, and contrast-to-noise ratio of lymph nodes and overall image quality, artifact, and noise of selected regions of interest were evaluated by two radiologists. Next, cervical lymph node sharpness was evaluated using full width at half maximum., Results: DLIR exhibited significantly reduced noise, ranging from 3.8 % to 35.9 % with improved signal-to-noise ratio (11.5-105.6 %) and contrast-to-noise ratio (10.5-107.5 %) compared with FBP and ASiR-V, for cervical lymph nodes (p < 0.001). Further, 0.625-mm-thick images reconstructed using DLIR-medium and DLIR-high had a lower noise than 2.5-mm-thick images reconstructed using FBP and ASiR-V. The lymph node margins and vessels on DLIR-medium and DLIR-high were sharper than those on FBP and ASiR-V (p < 0.05). Both readers agreed that DLIR had a better image quality than the conventional reconstruction algorithms., Conclusion: DLIR-medium and -high provided superior cervical lymph node image quality in head and neck CT. Improved image quality affords thin-slice DLIR images for dose-reduction protocols in the future., Competing Interests: Author Ai-Chi Chen and Chia-Wei Lee were employed by General Electric (GE) Healthcare. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Quantum key distribution (QKD) promises unconditional security for communication. However, the random choices of the measurement basis in QKD usually result in low key creation efficiency. This drawback is overcome in the differential-phase-shift QKD, provided that each photon can be prepared in a large number of time slots with a proper waveform. In this work we develop a miniature room-temperature 1550-nm single-photon source to generate narrowband single photon in 50 time slots with a nearly optimal waveform for achieving unity key creation efficiency. By utilizing these single photons in the field test, we demonstrate the differential-phase-shift QKD with a key creation efficiency of 97%. Our work shows that the practical QKD can benefit from the narrowband single photons with controllable waveforms.

Objectives: Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats., Methods: The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine., Key Findings: XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3-10 fold. In a dose-dependent manner, XYS and imperatorin (0.1-10 mg/kg) treatments significantly decreased theophylline clearance by 27-33% and 19-56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51-112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27-57%) by XYS was moderate., Conclusions: XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The synthesis of the cell-wall peptidoglycan during bacterial cell division is mediated by a multiprotein machine, called the divisome. The essential membrane protein complex of FtsB, FtsL and FtsQ (FtsBLQ) is at the heart of the divisome assembly cascade in Escherichia coli. This complex regulates the transglycosylation and transpeptidation activities of the FtsW-FtsI complex and PBP1b via coordination with FtsN, the trigger for the onset of constriction. Yet the underlying mechanism of FtsBLQ-mediated regulation is largely unknown. Here, we report the full-length structure of the heterotrimeric FtsBLQ complex, which reveals a V-shaped architecture in a tilted orientation. Such a conformation could be strengthened by the transmembrane and the coiled-coil domains of the FtsBL heterodimer, as well as an extended β-sheet of the C-terminal interaction site involving all three proteins. This trimeric structure may also facilitate interactions with other divisome proteins in an allosteric manner. These results lead us to propose a structure-based model that delineates the mechanism of the regulation of peptidoglycan synthases by the FtsBLQ complex., (© 2023. The Author(s).)

Aims: Brain-derived neurotrophic factor (BDNF) is markedly decreased in heart failure patients. Both BDNF and its receptor, tropomyosin-related kinase receptor (TrkB), are expressed in cardiomyocytes; however, the role of myocardial BDNF signalling in cardiac pathophysiology is poorly understood. Here, we investigated the role of BDNF/TrkB signalling in cardiac stress response to exercise and pathological stress., Methods and Results: We found that myocardial BDNF expression was increased in mice with swimming exercise but decreased in a mouse heart failure model and human failing hearts. Cardiac-specific TrkB knockout (cTrkB KO) mice displayed a blunted adaptive cardiac response to exercise, with attenuated upregulation of transcription factor networks controlling mitochondrial biogenesis/metabolism, including peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). In response to pathological stress (transaortic constriction, TAC), cTrkB KO mice showed an exacerbated heart failure progression. The downregulation of PGC-1α in cTrkB KO mice exposed to exercise or TAC resulted in decreased cardiac energetics. We further unravelled that BDNF induces PGC-1α upregulation and bioenergetics through a novel signalling pathway, the pleiotropic transcription factor Yin Yang 1., Conclusion: Taken together, our findings suggest that myocardial BDNF plays a critical role in regulating cellular energetics in the cardiac stress response., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Chronic fatigue symptoms of jobs are risk factors that may cause errors and lead to occupational accidents. For instance, occupational injuries and traffic accidents stem from overlooking long-term fatigue. According to statistics for fatigue driving, it was found that fatigue driving is one of the main causes of traffic accidents. The resulting decrease in the quality of traffic, as well as impaired traffic flow efficiency and functioning, contributes markedly to the societal costs of fatigue. This article proposes a noninvasive physical method for fatigue detection using a machine vision image algorithm. The main technology was implemented using a software framework based on optimized skin color segmentation and edge detection, as well as eye contour extraction. By integrating machine vision and an optimized Hove transform algorithm, our method mainly identifies fatigue based on the detected target's face, head gestures, mouth aspect ratio (MAR), and eye condition, and then triggers an alarm through an intelligent auxiliary device. Our evaluation results of facial image data analysis showed that with an ideal eye threshold of 0.3, PERCLOS-80 standard, MAR, and head gesture-nod frequency, the method can be used to detect fatigue data accurately and systematically, thereby fulfilling the purpose of alerting a group of high-risk drivers and preventing them from engaging in high-risk activities in an involuntary state.

Background: Metabolic syndrome is characterized by cardiovascular and chronic disease risk factors that cause health problems. Inequalities in medical resources and information present a challenge in this context. Indigenous communities may be unaware of their risk for metabolic syndrome., Aims: This study explored factors associated with metabolic syndrome-related knowledge, attitudes, and behaviors among Taiwanese indigenous communities., Methods: For this descriptive cross-sectional survey, we collected anthropometric data and used a self-administered questionnaire between 1 July 2016, to 31 July 2017, from a convenience sample of an indigenous tribe in eastern Taiwan. The response rate was 92%., Results: The prevalence of metabolic syndrome was as high as 71%, and the average correct knowledge rate was 39.1%. The participants' self-management attitudes were mainly negative, and the self-management behaviors were low in this population. Stepwise regression analysis showed that knowledge, attitude, age, perception of physical condition, and body mass index, which accounted for 65% of the total variance, were the most predictive variables for self-management behaviors., Conclusions: This is the first study to report the relationship between metabolic syndrome knowledge, attitudes, and behaviors in an indigenous population. There is an urgent need to develop safety-based MetS health education programs that can provide access to the right information and enhance self-management approaches to lessen the growing burden of MetS in indigenous communities.

Background: Physical inactivity is a persistent and worsening population health concern in Asia. Led by the Active Healthy Kids Global Alliance, Global Matrix (GM) initiative provides an opportunity to explore how regional and cultural differences across 18 Asian countries relate to physical activity (PA) participation among children and adolescents., Objectives: To synthesize evidence from the GM2.0 to GM4.0 (2016-2022) in Asian countries., Methods: Report Card grades on behavioral/individual and sources of influence indicators were reported from 18 Asian countries. Letter grades were converted into numerical values for quantitative analyses. Based on this, cross-sectional and longitudinal analyses were conducted to investigate patterns and trends. Qualitative evidence synthesis was performed based on Report Card grades and published papers to identify gaps and suggest future recommendations., Results: In total, 18 countries provided grades for at least one round of GM, 12 countries provided grades for at least two rounds, and seven countries provided grades for all three GMs. Of possible grades, 72.8%, 69.2%, and 76.9% of the grades were assigned from GM 2.0 to GM 4.0, respectively. In terms of the Report Card grades, there was a slight decrease in behavioral/individual indicators from "D+" in GM 2.0 to "D-" in GM 3.0 but this reverted to "D" in GM 4.0. For the sources of influence, a "C" grade was given in all three rounds of GM. Longitudinal observation of seven Asian countries that provided grades in all three rounds of GM revealed that grades are generally stable for all indicators with some country-specific fluctuations. In future GM initiatives and research, considerations should be made to provide more accurate and rich data and to better understand contextual challenges in evaluating certain indicators such as Active Transportation, Active Play, and Physical Fitness in particular. Further, macro level factors such as socioeconomic/cultural disparities and gender-specific barriers, ideology, or climate change should also be proactively considered in future research as these factors are becoming increasingly relevant to indicators of GM and United Nation's Sustainable Development Goals., Conclusions: Participation from Asian countries in GM has increased over the years, which demonstrates the region's enthusiasm, capacity, and support for global PA promotion efforts. The efforts to promote a physically active lifestyle among children and adolescents should be a collective interest and priority of the Asia region based on the gaps identified in this paper., (© 2022 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Glucagon-like peptide 1 receptor agonist (GLP-1 RA) is a potent antidiabetic agent with cardiorenal and weight-losing benefits in patients with type 2 diabetes (T2D). The combination of GLP-1 RA with basal insulin has been suggested in several clinical studies as a useful treatment for intensifying insulin therapy in T2D. However, there has been no real-world evidence study comparing the glycemic effects of GLP-1 RAs add-on to background treatment with and without insulin. A retrospective study was performed in 358 patients with T2D who initiated liraglutide or dulaglutide. Among them, 147 patients were prior and concurrent insulin users, and 211 patients were non-insulin users. After 12 months of GLP-1 RA treatment, the changes in hemoglobin A1c (HbA1C) and body weight were evaluated. The effectiveness of GLP-1 RAs on HbA1C reduction was greater in insulin users than non-insulin users at 12 months (−1.17% vs. −0.76%; p = 0.018). There was no significant difference in body weight change between insulin users and non-insulin users at 12 months (−1.42 kg vs. −1.87 kg; p = 0.287). The proportion of responders (decrease of HbA1C > 1%) in insulin users was much higher than that in non-insulin users (48% vs. 37 %; p = 0.04). In insulin users, those who had increased insulin dosage at 12 months had significantly less HbA1C reduction than that of non-increased patients (−0.62% vs. −1.57%; p = 0.001). GLP-1 RAs provide superior glucose-lowering effects in insulin-treated patients compared with non-insulin-treated patients with T2D without significant differences in body weight decrease.

Oxidative phosphorylation (OXPHOS) is an oxygen-dependent process that consumes catabolized nutrients to produce adenosine triphosphate (ATP) to drive energy-dependent biological processes such as excitation-contraction coupling in cardiomyocytes. In addition to in vivo and in vitro experiments, in silico models are valuable for investigating the underlying mechanisms of OXPHOS and predicting its consequences in both physiological and pathological conditions. Here, we compare several prominent kinetic models of OXPHOS in cardiomyocytes. We examine how their mathematical expressions were derived, how their parameters were obtained, the conditions of their experimental counterparts, and the predictions they generated. We aim to explore the general landscape of energy production mechanisms in cardiomyocytes for future in silico models., Competing Interests: The authors declare no conflict of interest.

Aims: A computerized tool and interdisciplinary care were implemented to develop a novel model for older patients with delirium in the emergency department (ED)., Methods: We developed a computerized tool using a delirium triage screen and brief confusion assessment in the hospital information system, performed education for the healthcare providers, and developed a continuous care protocol. Comparisons for outcomes between pre- and post-intervention periods were performed., Results: Compared with the pre-intervention period, patients in the post-intervention period had shorter hospitalization stay, lower expenditure of hospitalization, more likely to return home, lower ED revisits of ≤ 3 days, re-hospitalization of ≤ 14 days, and mortality of ≤ 1 month. All mentioned differences were not statistically significant., Conclusions: A novel model was successfully developed for delirium management in older patients in the ED. Outcome differences were not significant; however, the result is promising, which gives us an important reference in the future., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)