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Chia-Yu Huang,1,2 Mei-Yao Wu,3– 5 Ming-Cheng Huang,2,3 Teng-Shun Yu,6,7 Peter Karl Mayer,3,8,&ast; Hung-Rong Yen2,3,5,8,9,&ast; 1Department of Family Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; 2Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 3Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; 4School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 5Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; 6Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; 7College of Medicine, China Medical University, Taichung, Taiwan; 8International Master Program in Acupuncture, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 9Chinese Medicine Research Center, China Medical University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hung-Rong Yen, School of Chinese Medicine, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, North District, Taichung, 404, Taiwan, ext. 3001 Fax +886-4-22365141, Email hungrongyen@mail.cmu.edu.twPurpose: Disability is the comorbidity of dementia for which there is no available preventive measure. The aim of this study was to investigate the association between acupuncture treatment and the risk of disability development in dementia patients.Patients and Methods: A cohort study was performed using a nationwide health database in Taiwan. The included dementia patients were divided into acupuncture and non-acupuncture cohorts based on whether they received acupuncture treatment during the follow-up period. The variables in the two cohorts were controlled by 1:1 propensity-score matching. The difference in disability development in dementia patients between the acupuncture and non-acupuncture cohorts was also analyzed. Subgroup analyses were performed using socioeconomic variables, comorbidities and anti-dementia agents (donepezil, rivastigmine, galantamine and memantine) used for dementia treatment.Results: A total of 9,760 dementia patients met our inclusion criteria, and patients were divided into an equal number (n=2,422) of acupuncture and non-acupuncture groups, respectively, after 1:1 propensity-score matching. The dementia patients had a lower risk of disability development after acupuncture treatment than those who did not receive acupuncture treatment (adjusted hazard ratio 0.65, 95% confidence interval 0.60– 0.70, p < 0.001). The results were independent of basic variables or comorbidities in the two cohorts. Patients who did not use anti-dementia agents had a lower risk of developing disability after receiving acupuncture intervention than those who used anti-dementia agents.Conclusion: Our results revealed the relationship between acupuncture intervention and decreased risk of developing disability in dementia patients. The results are useful for dementia treatment, trial design and further planning of care programs.Keywords: acupuncture, disability, dementia, traditional Chinese medicine

Objective: Abnormal uterine bleeding (AUB) is a prevalent condition in reproductive-aged women that significantly decreases the quality of life. A thorough history is necessary to determine the causes of AUB, which were categorized by the AUB System 2 (PALM-COEIN). AUB has been associated with retained intrauterine objects. However, studies regarding AUB caused by retained stitches of the cervical cerclage were limited., Case Report: We present two cases of AUB caused by retained stitches of the cervical cerclage. Both cases were successfully treated by removing the retained stitches by hysteroscopy., Conclusion: A comprehensive history is crucial to AUB evaluation, especially a previous history of iatrogenic processes, such as intrauterine device placement, retained cerclage stitches, or other foreign bodies., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Alcohol use disorder (AUD) is recognized as a chronic relapsing disorder. Alcohol Relapse Risk Scale (ARRS), a multidimensionally self-rating scale, was developed initially by the Japanese to assess the risk of alcohol reuse. The study aimed to validate the reliability and factor structure of the Chinese version of the ARRS (C-ARRS) for patients with AUD. A total of 218 patients diagnosed with AUD according to DSM-5 were recruited for self-administering C-ARRS. We assessed the internal consistency of C-ARRS using Cronbach's α coefficients and examined the factor structure through confirmatory factor analysis (CFA). Additionally, we investigated the concurrent validity by correlating C-ARRS with the Visual Analog Scale of Alcohol Craving (VAS), Penn Alcohol Craving Score (PACS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scores. CFA demonstrated inadequate data fit for the original 32-item C-ARRS, prompting the development of a revised 27-item version consisting of 6 subscales with satisfactory model fit estimates. The 27-item C-ARRS exhibited favorable internal consistency, with Cronbach's α ranging from 0.611 to 0.798, along with adequate factor loadings. The 27-item C-ARRS scores displayed significant correlations with the scores of VAS, PACS, BDI and BAI (p < .001). Our results indicated favorable reliability and factor structure of the 27-item C-ARRS. The significant correlation between the 27-item C-ARRS and clinical measures (such as depression, anxiety, and craving) demonstrates satisfactory concurrent validity. These observations collectively support the feasibility of using 27-item C-ARRS to assess the risk of alcohol relapse in patients with AUD., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Alcohol use disorder (AUD) is associated with imbalanced bone turnover and psychological symptoms, but the relationship between bone and brain remains unclear. The study analyzed serum levels of a bone formation marker, procollagen type 1 N-terminal propeptide (P1NP), and bone resorption marker, C-terminal telopeptide of type I collagen (CTX-1), in AUD patients before and after 2 weeks of alcohol withdrawal and investigated their correlation with psychological symptoms., Methods: Ninety patients with AUD and 117 healthy controls were recruited. P1NP and CTX-1 levels were measured using Enzyme-Linked Immunosorbent Assay. The Penn Alcohol Craving Scale (PACS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were assessed in the AUD group at baseline, week 1, and week 2 of withdrawal., Results: Baseline CTX-1 levels, along with the CTX-1/P1NP and P1NP/CTX-1 ratio, were higher in the AUD group than controls. Over the 2-week withdrawal, PACS, BDI, and BAI scores demonstrated significant reductions. P1NP (p < 0.001) and P1NP/CTX-1 ratio increased (p < 0.001), while CTX-1/P1NP ratio decreased (p < 0.001), indicating a propensity toward bone formation. Univariate analysis revealed that reductions in PACS, BDI, and BAI scores during withdrawal correlated with increased P1NP levels and decreased CTX-1/P1NP ratios. However, multivariate analysis indicated that only PACS score reductions correlated with these changes., Conclusions: Bone metabolism shifted toward increased bone formation and decreased bone resorption during 2-week alcohol withdrawal. The correlation between improvements in bone turnover markers and reduction in craving scores during withdrawal supports the concept of the bone-brain axis., (© 2024 Research Society on Alcohol.)

Acupuncture is widely accepted as a therapeutic treatment by patients and healthcare providers globally. The safety record has been well established in acupuncture practice although some rare adverse events (AEs) were reported in the literature. While acupuncture-related AEs are generally defined as any undesirable event that occurs in patients during acupuncture treatment that may or may not be associated with the treatment, acupuncture-related adverse reactions (ARs) are defined as any undesirable or harmful reaction induced by trained practitioners practicing acupuncture treatment with standard doses. In this review, we clarify the relationship between AEs and ARs. Furthermore, we compile a list of acupuncture-related AEs reported in systematic reviews and meta-analysis articles. We find that serious acupuncture-related AEs are rare, with serious AEs occurring at a rate of approximately 0.04-0.08 per 10,000 treatments. The most likely serious AEs are pneumothorax, central and peripheral nerve injuries, heart injuries, abdominal organ injuries, infections, and needle breakage. Commonly reported minor AEs include bruising, hematoma, or bleeding at the needling site, as well as vasovagal reactions such as tiredness, dizziness, fainting, or residual pain at insertion points. The analysis identifies contributing factors for serious AEs being deep needle penetration, incorrect acupoint selection, and improper needle manipulation. It also addresses infections caused by contaminated needles, environmental factors, and inadequate skin disinfection. Moreover, other serious AEs, like needle breakage, are mostly due to aggressive manipulation and repeated reheating. Importantly, most acupuncture-related AEs are preventable. To avoid such AEs, acupuncturists in clinical practice should carefully select needling areas, be aware of cautions and contraindications of acupuncture, maintain safe acupuncture depth and hygiene, and strictly adhere to standard operating procedures.

Background: Ketamine has emerged as a prominent substance of misuse. Leptin, an adipocyte-derived polypeptide hormone, has been implicated in the development of addiction. Sex-specific changes in leptin levels have been demonstrated following acute ketamine administration; the persistence of long-term ketamine use on leptin levels is uncertain. Objectives: To assess the sex-difference of leptin levels, and their persistence, in individuals with ketamine use disorder (KUD) compared to healthy controls. Methods: Plasma leptin levels were measured in 62 healthy controls (37 males, 25 females) and 68 participants with KUD (50 males, 18 females) on the first day (baseline) and after 1 and 2 weeks of abstinence. As leptin levels are affected by body mass index (BMI), BMI-adjusted leptin (leptin/BMI ratio) was also examined. Mixed model for repeated measures was used to examine changes after ketamine abstinence. Results: Compared to same-sex controls, female, but not male, participants with KUD demonstrated lower leptin levels and leptin/BMI ratio at baseline, week 1, and week 2 (leptin levels: p  = .001, 0.006 and 0.032, respectively; leptin/BMI ratio: p  = .004, 0.022, and 0.09, respectively). Repeated measures showed that leptin levels and the leptin/BMI ratio increased after 2 weeks of abstinence in male participants with KUD ( p  = .002 and 0.011, respectively), but females did not show such an increase ( p  > .05). Conclusions: Sex-specific differences were observed in leptin levels and the leptin/BMI ratio in individuals with KUD compared to controls. Lower leptin levels in females with KUD persisted after 2 weeks of abstinence.

Background: Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery., Methods: The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014-2018; ClinicalTrials.gov #NCT02119182) enrolled subjects who presented to trauma centre and received head computed tomography within 24-h (h) post-TBI. We performed a secondary data analysis in subjects aged ≥17-years with hospitalisation. Clinical characteristics, surgery type/timing, hospital and six-month outcomes were reported., Findings: Of 2032 subjects (age: mean = 41.4-years, range = 17-89-years; male = 71% female = 29%), 260 underwent cranial surgery, comprising 65% decompressive craniectomy, 23% craniotomy, 12% other surgery. Subjects with surgery (vs. without surgery) presented with worse neurological injury (median Glasgow Coma Scale = 6 vs. 15; midline shift ≥5 mm: 48% vs. 2%; cisternal effacement: 61% vs. 4%; p < 0.0001). Median time-to-craniectomy/craniotomy was 1.8 h (interquartile range = 1.1-5.0 h), and 67% underwent intracranial pressure monitoring. Seventy-three percent of subjects with decompressive craniectomy and 58% of subjects with craniotomy had ≥3 intracranial lesion types. Decompressive craniectomy (vs. craniotomy) was associated with intracranial injury severity (median Rotterdam Score = 4 vs. 3, p < 0.0001), intensive care length of stay (median = 13 vs. 4-days, p = 0.0002), and six-month unfavourable outcome (62% vs. 30%; p = 0.0001). Earlier time-to-craniectomy was associated with intracranial injury severity., Interpretation: In a large representative cohort of patients hospitalised with TBI, surgical decision-making and time-to-surgery aligned with intracranial injury severity. Multifocal TBIs predominated in patients with cranial surgery. These findings summarise current TBI surgical practice across US trauma centres and provide the foundation for analyses in targeted subpopulations., Funding: National Institute of Neurological Disorders and Stroke; US Department of Defense; Neurosurgery Research and Education Foundation., Competing Interests: AMD declares: grant funding from the Mercatus Center at George Mason University (not related to the current work). DKM declares: grant funding from United Kingdom National Institute for Health Research (not related to the current work). KKWW declares: is a shareholder of Gryphon Bio, Inc. (not related to the current work). All other authors declare no conflict of interest., (© 2024 The Author(s).)

Background: Individuals using methamphetamine (METH) may experience psychosis, which usually requires aggressive treatment. Studies of the neural correlates of METH-associated psychosis (MAP) have focused predominantly on the default mode network (DMN) and cognitive control networks. We hypothesize that METH use alters global functional connections in resting-state brain networks and that certain cross-network connections could be associated with psychosis., Methods: We recruited 24 healthy controls (CRL) and 54 men with METH use disorder (MUD) who were then divided into 25 without psychosis (MNP) and 29 with MAP. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), evaluating (1) large-scale alterations in regional-wise resting-state functional connectivity (rsFC) across 11 brain networks and (2) associations between rsFC and psychotic symptom severity., Results: The MUD group exhibited greater rsFC between the salience network (SN)-DMN, and subcortical network (SCN)-DMN compared to the CRL group. The MAP group exhibited decreased rsFC in the sensory/somatomotor network (SMN)-dorsal attention network (DAN), SMN-ventral attention network (VAN), SMN-SN, and SMN-auditory network (AN), whereas the MNP group exhibited increased rsFC in the SMN-DMN and the frontoparietal network (FPN)-DMN compared to CRL. Additionally, the MAP group exhibited decreased rsFC strength between the SMN-DMN, SMN-AN, SMN-FPN, and DMN-VAN compared to the MNP group. Furthermore, across the entire MUD group, the PANSS-Positive subscale was negatively correlated with the DMN-FPN and FPN-SMN, while the PANSS-Negative subscale was negatively correlated with the DMN-AN and SMN-SMN., Conclusion: MUD is associated with altered global functional connectivity. In addition, the MAP group exhibits a different brain functional network compared to the MNP group., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Sophora flavescens is often used in traditional Chinese medicine for skin issues, diarrhea, and vaginal itching (Plant names have been checked with http://www.the/plant/list.org on Feb 22nd, 2024). Oxymatrine (OY), a major bioactive compound from Sophora flavescens, is commonly used in China to treat ulcerative colitis, but its mechanisms are still unclear., Aim of the Study: Recent studies have found that the crosstalk between ferroptosis and inflammation is an important mechanism in the pathogenesis of UC. The aim of this study was to investigate the potential underlying mechanisms of OY treatment on DSS-induced ulcerative colitis, specifically focusing on the processes of ferroptosis and inflammation., Materials and Methods: Bioinformatics methods were used to identify key targets of OY for ferroptosis and inflammation in ulcerative colitis, based on GEO data and FerrDb database. Then, 4% DSS solution was used to induce UC model. OY's impact on morphological changes was assessed using colon views, Hematoxylin and eosin (HE) staining, and transmission electron microscopy (TEM). Ferroptosis phenotype index and inflammations factors were detected by ELISA or chem-bio detection kits. The screen out hub related genes about ferroptosis and inflammation were verified by RT-PCR, immunohistochemistry (IHC), and western blotting (WB) respectively., Results: Bioinformatics results show that there are 16 key target genes involved in ferroptosis and inflammation interaction of OY treatment for UC, such as IL6, NOS2, IDO1, SOCS1, and DUOX. The results of animal experiments show that OY could depress inflammatory factors (IL-1β, IL-6, TNF-α, HMGB1, and NLRP3) and reduce iron deposition (Fe 2+ , GSH). Additionally, OY suppressed the hub genes or proteins expression involved in ferroptosis and inflammation, including IL-1β, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2., Conclusion: This present study combines bioinformatics, molecular biology, and animal experimental research evidently demonstrated that OY attenuates UC by improving ferroptosis and inflammation, mainly target to the expression of IL-1β, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2., Competing Interests: Declaration of competing interest All authors declared no potential conflicts of interest with respect to research, authorship, and publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to examine the association between constipation and mild cognitive impairment (MCI); and further elucidate the possible mechanisms involved. A cross-sectional study was conducted among community-dwelling elders (N = 789) in Nanning, China. Trained research staffs collected detailed information through questionnaires and physical examinations. A Bayesian network model was used to explore the hypothesized causal path. Synergistic effects of constipation with infrequent fruit consumption, inactive physical exercise, or history of stroke were observed in the risks of MCI occurrence. The Bayesian network model analyses showed 3 hypothesized causal-association paths leading to MCI occurrence. Among these, constipation, history of stroke, and years of schooling were directly related to the occurrence of MCI. Years of schooling indirectly affected MCI through infrequent fruit consumption and constipation; or through inactive physical exercises and history of stroke. This study demonstrates a direct association between constipation and increased risks of MCI., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Immunotherapy has revolutionized cancer treatment, but the lack of a reliable predictive biomarker for treatment response remains a challenge. Alpha-1,6-Mannosylglycoprotein 6-β-N-Acetylglucosaminyltransferase 5 (MGAT5) is a key regulator of complex N-glycan synthesis, and its dysregulation is associated with cancer progression. The lectin Phaseolus vulgaris leukoagglutinin (PHA-L) specifically binds to mature MGAT5 products. Previous studies have indicated elevated PHA-L staining in head and neck squamous cell carcinoma (HNSCC), which implies increased activity of MGAT5. However, the specific role of MGAT5 in HNSCC remains unclear. In this study, we found significantly higher PHA-L staining and MGAT5 expression in HNSCC tumors compared to adjacent non-tumor tissues. Using a mass spectrometry (MS)-based glycoproteomic approach, we identified 163 potential protein substrates of MGAT5. Functional analysis revealed that protein substrates of MGAT5 regulated pathways related to T cell proliferation and activation. We further discovered that PD-L1 was among the protein substrates of MGAT5, and the expression of MGAT5 protected tumor cells from cytotoxic T lymphocyte (CTL) killing. Treatment of nivolumab alleviated the protective effects of MGAT5 on CTL activity. Consistently, patients with MGAT5-positive tumors showed improved responses to immunotherapy compared to those with MGAT5-negative tumors. Using purified PD-L1 from HNSCC cells and a glycoproteomic approach, we further deciphered that the N35 and N200 sites carry the majority of complex N-glycans on PD-L1. Our findings highlight the critical role of MGAT5-mediated branched N-glycans on PD-L1 in modulating the interaction with the immune checkpoint receptor PD-1. Consequently, we propose that MGAT5 could serve as a biomarker to predict patients' responses to anti-PD-1 therapy. Furthermore, targeting the branched N-glycans at N35 and N200 of PD-L1 may lead to the development of novel diagnostic and therapeutic approaches., (© 2024. The Author(s).)

Due to their underdeveloped physiological maturity, preterm infants often face challenges related to sucking, breathing, and swallowing coordination during initial feeding. This lack of coordination may lead to episodes of apnea and choking, resulting in unstable vital signs. Preterm infants with this issue must gradually learn oral feeding skills appropriate to their developmental stage. Registered nurses play a critical role in assessing the right time to transition from tube to oral feeding and in providing a safe and positive oral feeding experience. In this article, three validated assessment tools for feeding premature infants are introduced, accompanied by clinical research data demonstrating their use in clinical practice. These three tools include: (1) the Neonatal Oral Motor Assessment Scale, which is applied to evaluate oral motor skills using observations of nonnutritive sucking and the sucking state during the two minutes before feeding; (2) the Premature Oral Feeding Readiness Assessment Scale, which is used to assess readiness for oral feeding in preterm infants; and (3) the Early Feeding Skills assessment, which is used to evaluate the oral feeding skills of preterm infants. These tools aid nurses in helping preterm infants achieve independent oral feeding, facilitating earlier discharge and return to home. The clinical implications and effectiveness of these tools are also discussed to provide to nurses the means and confidence necessary to apply them appropriately in clinical settings.

The employment of migrant care workers provides a remedy to face the challenges of increased demand for care of older adults. A scoping review aimed to identify, categorize, and summarize the existing knowledge about migrant care workers' working experiences in long-term care facilities. Identifying gaps in the literature can inform future research. Five electronic databases were searched in April 2024 in addition to a manual search for articles published in English. Forty-five articles were reviewed. A few studies described migrant care assistants' main tasks as assisting physical care and care assistants' characteristics grouped into personal and acquired qualities to provide good quality care. Migrant care workers experienced work satisfaction, achievement, adaptability and adjustment, organizational support, work burden, sense of loneliness, low wages, low social status, and loss of profession. They faced challenges involving inadequate knowledge of palliative care, communication and language barriers, cultural and religious differences, and health concerns. Friendly and discriminatory relationships were found between migrant care workers and stakeholders. Existing evidence regarding the experiences of migrant care workers in delivering palliative care to dying residents or facilitating death preparation is limited. Additionally, there is a notable absence of data from the perspectives of employers and residents on discrimination issues. Further research is necessary to investigate these areas., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Ketamine can induce persisting psychosis in a subset of individuals who use it chronically and heavily. Previously, we found that the psychopathology and cognitive impairments in patients with ketamine dependence (KD) exhibiting persistent psychosis (KPP) bear resemblances with schizophrenia, albeit with less severity in those with no persistent psychosis (KNP). Furthermore, we also showed that patients with KD had higher blood levels of neurofilament light chain (NFL), a biomarker for neuroaxonal injury, compared to healthy controls. In this study, we aimed to investigate the differences in NFL levels between patients with KPP and KNP while comparing the levels of individuals with schizophrenia and healthy controls., Methods: We enrolled 64 treatment-seeking ketamine-dependent patients (53 with KNP and 11 with KPP), 37 medication-free patients with schizophrenia, and 80 healthy controls. Blood NFL levels were measured by single molecule array immunoassay., Results: NFL levels were highest in the KPP subgroup, followed by the KNP subgroup, and then the schizophrenia and control groups (mean ± SD: 24.5 ± 24.7, 12.9 ± 10.9, 9.2 ± 12.2, and 6.2 ± 2.2 pg/mL, respectively), with no significant difference observed between the schizophrenia and control groups., Conclusions: We found that KD is associated with higher NFL levels compared to schizophrenia, with the KPP subgroup showing the most consistent alterations. The observation of accentuated neuroaxonal pathology in individuals with KPP implies that this clinical manifestation is associated with a specific neurobiological phenotype, despite prior evidence suggesting syndromal similarity between schizophrenia and KPP., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Green chemistry has been a rising topic in environmental sustainability, with a focus on the waste and consumption reduction of chemical and biomedical industries. Traditional chemical handling processes require tools that contact chemical reagents to produce vast amounts of residues and disposals. This study presents a contactless chemical mixing system that integrates acoustic droplet ejection and levitation techniques. First, the acoustic droplet ejection system creates a droplet in mid-air from a designated liquid reservoir by focusing acoustic energy at the liquid-air junction. The droplet levitation system captures and transports the droplet along a predetermined path by shifting the focal points of the acoustic standing waves. This facilitates contactless mixing of chemicals in a defined ratio. Notably, this study employs piezoelectric discs in an acoustic droplet ejection system to eject droplets from liquids. The relationship between the duration of the driving bursts and height and size of ejected droplets was also investigated. The proposed acoustic standing wave levitation system captures droplets with weights between 2.8 and 5.2 mg. To assess the reliability of the proposed system, 25 droplets were sequentially generated and transported to the mixing well without failure. The root mean square error between the collected and expected liquid weights was only 0.098 mg. The proposed system offers a promising solution for reducing waste and promoting environmentally friendly practices in chemical and biomedical laboratories., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Chih-Hsien Huang reports financial support was provided by National Science and Technology Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Relational autonomy is an alternative concept of autonomy in which an individual is recognized as embedded into society and influenced by relational factors. Social context, including social location, political structure, and social forces, significantly influence an agent to develop and exercise autonomy skills. The relational approach has been applied in clinical practice to identify relational factors impacting patient autonomy and decision-making, yet there is a knowledge gap in how these factors influence the demonstration of relational autonomy in the context of medical decisions of adults., Objective: The present study targeted the existing knowledge of what and how relational factors impact individuals making medical decisions using the theoretical framework of relational autonomy., Methods: A meta-synthesis study was utilized. Four electronic databases, including Embase, OVID Medline, CINAHL, and PubMed, were searched, along with gray literature and reference lists, to identify relevant studies., Results: 23 studies reporting 21 qualitative and two mixed-method studies were reviewed. Four themes emerged from the qualitative findings: (1) supportive relationships facilitate an individual's relational autonomy; (2) obtaining comprehensive information from broader sources helps individuals exercise relational autonomy; (3) undue family pressure impedes the exercising of patient relational autonomy; and (4) healthcare providers' dominant voice hampers the demonstration of relational autonomy., Conclusions: Applying relational autonomy to assist adults in making well-considered decisions is essential. The meta-synthesis suggests establishing a supportive relationship between individuals, healthcare providers, and family. A supportive relationship will allow healthcare providers to make judgments in line with an individual's values and wishes with the aim of promoting relational autonomy. Advance care planning was proposed as the effective solution to obtain a consensus between individuals and their families while respecting an individual's values and preferences. Furthermore, it is considered crucial for healthcare providers to appreciate an individual's values and incorporate their preferences into recommendations., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Evidence-based literature recognizes that the different degrees of agreement between a child self-report and a proxy-report depend on the characteristics of the domains, the child's age and illness, the proxy's own perspective on QoL, and family attendance during the child's hospitalization. This study aims to determine the degree of agreement between proxy-reports and child self-reports on quality of life (QoL) for children with hematologic malignancy ranging in age from 5 to 18 years who are undergoing treatment. We retrieved clinical QoL data from a study titled "Dynamic change in QoL for Vietnamese children with hematologic malignancy" from April 2021 to December 2022. To evaluate the magnitude of agreement between self-reports and proxy-reports, intraclass correlation coefficients (ICCs) for 259 pairs of measurements were quantified. Using independent t tests, the mean differences between self-reports and proxy-reports were tested. Moderate agreement was consistent through all age groups for five subscales, including physical, psychosocial, pain, nausea, and procedural anxiety (ICCs ranged from 0.53 to 0.74). The weakest agreement appeared in two groups, subjects aged 5-7 years and 13-18 years on six domains (school, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication) (-0.01 to 0.49). Child self-rating was consistently higher than that of proxies for the physical, emotional, and nausea domains among children aged 5-7 years and for procedural anxiety, treatment anxiety, and cognitive problems among children aged 8-12 years.    Conclusion: The agreement level of self-reports and proxy-reports was differently distributed by child age and the PedsQL domains. The proxy children agreement on QoL among children with hematologic malignancy was divergent according to the different age groups, which could potentially be explained by proxy-child bonding at different stages of childhood development. Our recommendation for future studies is to explore children's age as a potential factor influencing proxy agreement on QoL among children with cancer. What is Known: • Children and their proxies may think differently about quality of life (QoL). • Comparing two sources of data (i.e., child and proxy) on aspects of QoL can help identify the discrepancies between children's perceptions of their QoL and their parents' perceptions. This can be useful in terms of identifying potential areas for improvement or concern and may also be helpful in making decisions about treatment and care. What is New: • Our study results demonstrated that proxies who comprised children aged 5-7 years or 13-18 years reported differently among domains that cannot be expressed verbally or with body language, including cognitive problems, perceived physical appearance, and communication. • Children generally perceived their QoL to be better than their proxies. Therefore, a more comprehensive understanding of children's QoL may require the consideration of multiple sources of data from various perspectives., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort., Methods: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury., Results: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months., Conclusions: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed., Level of Evidence: IV., Trial Registration Number: NCT02119182., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Polycystic ovary syndrome (PCOS) is a female endocrine disorder with metabolic issues. Hyperandrogenism combined with hyperinsulinemia exacerbates the reproductive, metabolic, and inflammatory problems in PCOS patients. The etiology of PCOS is unclear. Patient-specific induced pluripotent stem cells (iPSCs) offer a promising model for studying disease mechanisms and conducting drug screening. Here, we aim to use mesenchymal progenitor cells (MPCs) derived from PCOS iPSCs to explore the mechanism of PCOS. We compared the transcriptome profiles of PCOS and healthy control (HC) iPSC-derived MPCs (iPSCMs). Moreover, we assess the impact of androgens on iPSCMs. In the comparison between PCOS and HC, the expression levels of 1026 genes were significantly different. A gene set enrichment analysis (GSEA) revealed that adipogenesis- and metabolism-related genes were downregulated, whereas inflammation-related genes were upregulated in the PCOS iPSCMs. Dysregulation of the TGF-β1 and Wnt signaling pathways was observed in the PCOS iPSCMs. Furthermore, there was impaired adipogenesis and decreased lipolysis in the PCOS iPSCMs-derived adipocytes. With testosterone treatment, genes related to metabolism were upregulated in the HC iPSCMs but downregulated in the PCOS iPSCMs. The impact of testosterone varied among HCs and PCOS iPSCMs, possibly because of a genetic predisposition toward PCOS. This study found specific signaling pathways that could serve as therapeutic targets for PCOS.

Asphyxiated neonates often undergo therapeutic hypothermia (TH) to reduce morbidity and mortality. Since both perinatal asphyxia (PA) and TH influence physiology, altered pharmacokinetics (PK) and pharmacodynamics (PD) are expected. Given that TH is the standard of care for PA with moderate to severe hypoxic-ischemic encephalopathy, disentangling the effect of PA versus TH on PK/PD is not possible in clinical settings. However, animal models can provide insights into this matter. The (neonatal) Göttingen Minipig, the recommended strain for nonclinical drug development, was selected as translational model. Four drugs-midazolam (MDZ), fentanyl (FNT), phenobarbital (PHB), and topiramate (TPM)-were intravenously administered under four conditions: control (C), therapeutic hypothermia (TH), hypoxia (H), and hypoxia plus TH (H+TH). Each group included six healthy male neonatal Göttingen Minipigs anesthetized for 24 hours. Blood samples were drawn at 0 (predose) and 0.5, 2, 2.5, 3, 4, 4.5, 6, 8, 12, and 24 hours post drug administration. Drug plasma concentrations were determined using validated bioanalytical assays. The PK parameters were estimated through compartmental and noncompartmental PK analysis. The study showed a statistically significant decrease in FNT clearance (CL; 66% decrease), with an approximately threefold longer half-life (t 1/2 ) in the TH group. The H+TH group showed a 17% reduction in FNT CL, with a 62% longer t 1/2 compared with the C group; however, it was not statistically significant. Although not statistically significant, trends toward lower CL and longer t 1/2 were observed in the TH and H+TH groups for MDZ and PHB. Additionally, TPM demonstrated a 28% decrease in CL in the H group compared with controls. SIGNIFICANCE STATEMENT: The overarching goal of this study using the neonatal Göttingen Minipig model was to disentangle the effects of systemic hypoxia and TH on PK using four model drugs. Such insights can subsequently be used to inform and develop a physiologically based pharmacokinetic model, which is useful for drug exposure prediction in human neonates., (Copyright © 2024 by The Author(s).)

Diabetic retinopathy (DR), which can cause vision loss, may progress faster with poor glycemic control and oxidative stress. This study aims to examine how dietary patterns and glycemic control biomarkers relate to retinopathy risk in type 2 diabetes patients. In this study, we enrolled diabetic patients with retinopathy (DR) ( n = 136) and without retinopathy (no DR) ( n = 466) from a cohort of participants in the "Blood Pressure Control to Reduce the Risk of Type 2 Diabetic Nephropathy Study". Hemoglobin A1c (HbA1c) and malondialdehyde were defined as elevated when their levels reached ≥8.5% and ≥2/3 (16.2 μm), respectively. Dietary data were collected by a food frequency questionnaire. Dietary patterns were identified by factor analysis. Elevated HbA1c was significantly correlated with increased risk of DR (OR: 2.12, 95% CI: 1.14-3.93, p = 0.017). In subjects with a high animal protein and processed food dietary pattern (≥highest tertile score) or a low vegetable intake pattern (

Background: Evaluating the risk of relapse is a pivotal step in the treatment of patients with methamphetamine use disorder (MUD). The 30-item Stimulant Relapse Risk Scale (SRRS) was originally developed in Japan to meet the demand. This study examined the reliability, validity, and factor structure of the Chinese version of the SRRS for patients with MUD., Methods: 247 patients with MUD self-rated the Chinese version of the SRRS. Cronbach's alpha coefficients and inter-item correlation analysis were used to assess the internal consistency reliability. Construct validity was determined through confirmatory factor analysis (CFA), and concurrent validity was examined using the visual analogue scale (VAS) for drug craving and the severity of dependence scale (SDS). We followed the participants for 1 year and assessed the predictive validity based on the correlation of the scores of the Chinese version of the SRRS with the relapse rate within 3, 6, and 12 months of follow-up., Results: CFA revealed satisfactory model fit estimates for the 22-item Chinese version of the SRRS that consisted of four subscales. The four-factored 22-item Chinese version of the SRRS had adequate internal consistency with Cronbach's alphas ranging from 0.76 to 0.92. The 22-item Chinese version of the SRRS scores were significantly correlated with the VAS and SDS scores as well as the relapse rate within 3, 6, and 12 months, indicating good concurrent and predictive validity of this scale. The receiver operating characteristic curve revealed a cutoff score of 40 could discriminate between participants with (SDS score ≥ 4) and without (SDS score < 4) methamphetamine dependence (area under the curve = 0.71, p < 0.01)., Conclusions: The 22-item Chinese version of the SRRS that consists of four subscales is a valid and reliable instrument to assess the relapse risk in patients with MUD., (© 2024. The Author(s).)

Objective: The clinical manifestations of methamphetamine (METH)-associated psychosis (MAP) and acute paranoid schizophrenia (SCZ) are similar. This study aims to assess regional cerebral blood flow (rCBF) in individuals who use METH and in those with SCZ using the MRI arterial spin labeling (ASL) technique., Methods: We prospectively recruited 68 participants and divided them into four groups: MAP (N = 15), SCZ (N = 13), METH users with no psychosis (MNP; N = 22), and normal healthy controls (CRL; N = 18). We measured rCBF using an MRI three-dimensional pseudo-continuous ASL sequence. Clinical variables were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS). Group-level rCBF differences were analyzed using a two-sample t-test., Results: Decreased rCBF was found in the precuneus, premotor cortex, caudate nucleus, dorsolateral prefrontal cortex, and thalamus in the MNP group compared with the CRL group. The MAP group had significantly decreased rCBF in the precuneus, hippocampus, anterior insula, inferior temporal gyrus, inferior orbitofrontal gyrus, and superior occipital gyrus compared with the MNP group. Increased rCBF in the precuneus and premotor cortex was seen in the MAP group compared with the SCZ group. rCBF in the precuneus and premotor cortex significantly correlated negatively with the PANSS but correlated positively with BACS scores in the MAP and SCZ groups., Conclusion: METH exposure was associated with decreased rCBF in the precuneus and premotor cortex. Patients with MAP exhibited higher rCBF than those with SCZ, implying preserved insight and favorable outcomes. rCBF can therefore potentially serve as a diagnostic approach to differentiate patients with MAP from those with SCZ., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Previous studies have shown a growing need for pediatric palliative care, but there is a lack of knowledge in many countries concerning prevalence of service use among children and young adults with life-limiting conditions. This study aimed to estimate (1) the annual prevalence of children and young adults with a life-limiting condition, and (2) their specialized palliative care and other healthcare utilization., Methods: Data from the Health and Welfare Data Science Center in Taiwan were used. All children and young adults aged 0-25 years recorded in inpatient or outpatient data, and infants aged < 1 year in death data with a life-limiting condition diagnostic code from 2008 to 2017 were recruited. Poisson regression was used to estimate the crude and adjusted relative risk of prevalence of life-limiting conditions with 95% confidence intervals, adjusted for age and sex, and to evaluate the trend in prevalence of each life-limiting diagnostic groups, in specialized palliative care and other service use., Results: Data contained 236,250 individuals with a life-limiting condition, of which oncological and congenital abnormalities were the most common. There was an annualized increase over 10 years in the prevalence of life-limiting conditions of 36.4%, from 45,311 cases (59.4 per 10,000 population) to 52,226 cases (81.0 per 10,000 population), with the highest prevalence in individuals aged 21-25 years. All diagnostic groups showed significant increases in prevalence (p < .001) with the exception of oncology, circulatory, and "other" group. Specialized palliative care services, including family consultation, shared care, home visits have increased in use over time (p < .001), while inpatient hospice has slightly decreased. The highest prevalence of healthcare use was for traditional Chinese medicine (237.1 per 1,000 population in 2017), but this decreased over time (p < .001)., Conclusions: Due to a growing trend towards multidisciplinary care, healthcare professionals and policymakers must engage and take action to expand specialized palliative care and integrate delivery of other healthcare services. Traditional Chinese medicine having a decreasing slope, yet still the highest prevalence of use, needs further attention., (© 2024. The Author(s).)

With improvements in living standards, the demand for antibacterial self-cleaning coatings has significantly increased. In this work, self-cleaning coatings with antibacterial properties were fabricated by spray-coating a composite of fluorinated acrylic resin and Ag/SiO 2 nanoparticles with quaternary ammonium salts. The synergistic action of the quaternary ammonium salts and silver nanostructures caused the coating to show a dual antibacterial effect. The Ag/SiO 2 nanoparticles roughened the coating's surface and, in combination with the fluorinated chains, provided the surface a superhydrophobic self-cleaning property with a contact angle of 156° and a sliding angle of less than 2°. Notably, the composite coating withstood 100 abrasion cycles without losing its superhydrophobicity and the contact angle is still exceeded 150° after 60 h of immersion solutions with different pH values, demonstrating outstanding wear resistance and acid/alkali stability. The incorporation of nanostructured antibacterial agents was effective in improving the roughness and antibacterial properties of the low-surface-energy resin, resulting in a self-cleaning antibacterial composite coating. This method may pave a new route for the design of functional coating materials with excellent overall performance.

Isolated traumatic subarachnoid hemorrhage (tSAH) after traumatic brain injury (TBI) on head computed tomography (CT) scan is often regarded as a "mild" injury, with reduced need for additional workup. However, tSAH is also a predictor of incomplete recovery and unfavorable outcome. This study aimed to evaluate the characteristics of CT-occult intracranial injuries on brain magnetic resonance imaging (MRI) scan in TBI patients with emergency department (ED) arrival Glasgow Coma Scale (GCS) score 13-15 and isolated tSAH on CT. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (TRACK-TBI; enrollment years 2014-2019) enrolled participants who presented to the ED and received a clinically-indicated head CT within 24 h of TBI. A subset of TRACK-TBI participants underwent venipuncture within 24 h for plasma glial fibrillary acidic protein (GFAP) analysis, and research MRI at 2-weeks post-injury. In the current study, TRACK-TBI participants age ≥17 years with ED arrival GCS 13-15, isolated tSAH on initial head CT, plasma GFAP level, and 2-week MRI data were analyzed. In 57 participants, median age was 46.0 years [quartile 1 to 3 (Q1-Q3): 34-57] and 52.6% were male. At ED disposition, 12.3% were discharged home, 61.4% were admitted to hospital ward, and 26.3% to intensive care unit. MRI identified CT-occult traumatic intracranial lesions in 45.6% (26 of 57 participants; one additional lesion type: 31.6%; 2 additional lesion types: 14.0%); of these 26 participants with CT-occult intracranial lesions, 65.4% had axonal injury, 42.3% had subdural hematoma, and 23.1% had intracerebral contusion. GFAP levels were higher in participants with CT-occult MRI lesions compared with without (median: 630.6 pg/mL, Q1-Q3: [172.4-941.2] vs. 226.4 [105.8-436.1], p  = 0.049), and were associated with axonal injury (no: median 226.7 pg/mL [109.6-435.1], yes: 828.6 pg/mL [204.0-1194.3], p  = 0.009). Our results indicate that isolated tSAH on head CT is often not the sole intracranial traumatic injury in GCS 13-15 TBI. Forty-six percent of patients in our cohort (26 of 57 participants) had additional CT-occult traumatic lesions on MRI. Plasma GFAP may be an important biomarker for the identification of additional CT-occult injuries, including axonal injury. These findings should be interpreted cautiously given our small sample size and await validation from larger studies.

Clinical studies examining the effects of vitamin D on cognition have reported inconsistent results. To date, no comprehensive study has examined this effect on the basis of sample characteristics or intervention model-related factors. This systematic review and meta-analysis of randomized controlled trials investigated the effects of vitamin D supplementation on global cognitive function and specific cognitive domains. This review was preregistered in the PROSPERO database (CRD42021249908) and comprised 24 trials enrolling 7557 participants (mean age: 65.21 years; 78.54% women). The meta-analysis revealed that vitamin D significantly influenced global cognition (Hedges' g = 0.128, p = .008) but not specific cognitive domains. A subgroup analysis indicated that the effect size of vitamin D was stronger for vulnerable populations (Hedges' g = 0.414) and those with baseline vitamin D deficiency (Hedges' g = 0.480). On the basis of subgroup analyses in studies without biological flaws (Hedges' g = 0.549), we suggest that an intervention model should correct baseline vitamin D deficiency. Our results indicate that vitamin D supplementation has a small but significant positive effect on cognition in adults., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The skeletal muscle is the largest organ in mammals and is the primary motor function organ of the body. Our previous research has shown that long non-coding RNAs (lncRNAs) are significant in the epigenetic control of skeletal muscle development. Here, we observed progressive upregulation of lncRNA 4930581F22Rik expression during skeletal muscle differentiation. Knockdown of lncRNA 4930581F22Rik hindered skeletal muscle differentiation and resulted in the inhibition of the myogenic markers MyHC and MEF2C. Furthermore, we found that lncRNA 4930581F22Rik regulates myogenesis via the ERK/MAPK signaling pathway, and this effect could be attenuated by the ERK-specific inhibitor PD0325901. Additionally, in vivo mice injury model results revealed that lncRNA 4930581F22Rik is involved in skeletal muscle regeneration. These results establish a theoretical basis for understanding the contribution of lncRNAs in skeletal muscle development and regeneration., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Published by Elsevier Ltd.)

Background/aim: In hepatocellular carcinoma (HCC) treatment, radiotherapy (RT) stands as a pivotal approach, yet the emergence of radioresistance poses a formidable challenge. This study aimed to explore the potential synergy between quetiapine and RT for HCC treatment., Materials and Methods: A Hep3B xenograft mouse model was used, the investigation tracked tumor progression, safety parameters, and molecular mechanisms., Results: The findings revealed a synergistic anti-HCC effect when quetiapine was coupled with RT that prolonged tumor growth time and a significantly higher growth inhibition rate compared to the control group. Safety assessments indicated minimal pathological changes, suggesting potential of quetiapine in mitigating RT-induced alterations in liver and kidney functions. Mechanistically, the combination suppressed metastasis and angiogenesis-related proteins, while triggering the activation of apoptosis-related proteins via targeting Epidermal growth factor receptor (EGFR)-mediated signaling., Conclusion: The potential of the quetiapine and RT combination is emphasized, offering enhanced anti-HCC efficacy, a safety profile, and positioning quetiapine as a radiosensitizer for HCC treatment., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To discuss several techniques of hysteroscopic surgery for complete septate uterus., Case Report: A 40-year-old female with unexplained primary infertility was diagnosed with complete septate uterus with septate cervix. Hysteroscopic incision of complete septate uterus was performed by using ballooning technique. The patient conceived naturally shortly after the operation and delivered a healthy, term infant., Conclusion: Hysteroscopic incision of complete septate uterus is a safe and prompt way of metroplasty. With the knowledge obtained from a pre-operative MRI, it can be completed without laparoscopy and the need for hospitalization., Competing Interests: Conflicts of interest The authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Bipolar disorder (BD) is a severe mental disorder related to neurocognitive deficits. Exposure to childhood trauma is associated with worse cognitive performance. Different compositions of childhood trauma in BD and their impacts on cognition are rarely reported., Methods: We used the Brief Assessment of Cognition in Affective Disorders (BAC-A) to assess cognitive performance and the Chinese version of the Short Form of the Childhood Trauma Questionnaire (C-CTQ-SF) to assess childhood trauma experience among 55 euthymic BD patients. Cluster analysis was applied to dissect their childhood trauma experiences, which revealed three distinct clusters: a low trauma group, neglect-focus group, and multiple-trauma-experience group. We compared the cognitive function between the three clusters and used a generalized linear model to evaluate the impact of childhood neglect on cognitive domains., Results: The neglect-focus cluster showed prominent exposures to physical and emotional neglect (41.8%). BD patients in this cluster performed worse in BAC-A compared with patients in the multiple trauma cluster, especially in working memory and processing speed. The neglect-focus group revealed a significant negative effect on the composite score (ß = -0.904, p = 0.025) and working memory (ß = -1.150, p = 0.002) after adjusting sex, age, education year, BMI and total psychotropic defined daily dose., Conclusions: Distinct patterns of childhood trauma experience are seen in BD patients and are related with different cognitive profiles. Early exposure of neglect-focus trauma was associated with the worst cognitive performance in current study. Further studies investigating the intensity of the neglect, as well as individual resilience and coping mechanisms in BD, are warranted., (© 2024. The Author(s).)

Background: Cognitive impairment is a growing problem with increasing burden in global aging. Older adults with major depressive disorder (MDD) have higher risk of dementia. Neurofilament light chain (NfL) has been proven as a potential biomarker in neurodegenerative disease, including dementia. We aimed to investigate the association between cognitive deficits and NfL levels in older adults with MDD., Methods: In this cross-sectional study, we enrolled 39 MDD patients and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer's type, as controls, from a tertiary psychiatric hospital. Both groups were over age 65 and with matched Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and each cognitive domain., Results: In the MDD group, participants had higher rate of family psychiatry history and current alcohol use habit compared with controls. Control group of neurocognitive disorders showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits clustered with that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster., Conclusions: We noted the negative correlation between NfL levels and cognition in MDD patients clustered with neurodegenerative disorder, Alzheimer's type. NfL could be a promising candidate as a biomarker to predict subtype of patients in MDD to develop cognitive decline. Further longitudinal studies and within MDD cluster analysis are required to validate our findings for clinical implications., (© 2024. The Author(s).)

Objective: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH model performances in a contemporary cohort of US patients., Methods: The prospective 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years 2014-2018) enrolled subjects aged ≥ 17 years who presented to level I trauma centers and received head CT within 24 hours of TBI. Data were extracted from the subjects who met the model criteria (for IMPACT, Glasgow Coma Scale [GCS] score 3-12 with 6-month Glasgow Outcome Scale-Extended [GOSE] data [n = 441]; for CRASH, GCS score 3-14 with 2-week mortality data and 6-month GOSE data [n = 831]). Analyses were conducted in the overall cohort and stratified on the basis of TBI severity (severe/moderate/mild TBI defined as GCS score 3-8/9-12/13-14), age (17-64 years or ≥ 65 years), and the 5 top enrolling sites. Unfavorable outcome was defined as GOSE score 1-4. Original IMPACT and CRASH model coefficients were applied, and model performances were assessed by calibration (intercept [< 0 indicated overprediction; > 0 indicated underprediction] and slope) and discrimination (c-statistic)., Results: Overall, the IMPACT models overpredicted mortality (intercept -0.79 [95% CI -1.05 to -0.53], slope 1.37 [1.05-1.69]) and acceptably predicted unfavorable outcome (intercept 0.07 [-0.14 to 0.29], slope 1.19 [0.96-1.42]), with good discrimination (c-statistics 0.84 and 0.83, respectively). The CRASH models overpredicted mortality (intercept -1.06 [-1.36 to -0.75], slope 0.96 [0.79-1.14]) and unfavorable outcome (intercept -0.60 [-0.78 to -0.41], slope 1.20 [1.03-1.37]), with good discrimination (c-statistics 0.92 and 0.88, respectively). IMPACT overpredicted mortality and acceptably predicted unfavorable outcome in the severe and moderate TBI subgroups, with good discrimination (c-statistic ≥ 0.81). CRASH overpredicted mortality in the severe and moderate TBI subgroups and acceptably predicted mortality in the mild TBI subgroup, with good discrimination (c-statistic ≥ 0.86); unfavorable outcome was overpredicted in the severe and mild TBI subgroups with adequate discrimination (c-statistic ≥ 0.78), whereas calibration was nonlinear in the moderate TBI subgroup. In subjects ≥ 65 years of age, the models performed variably (IMPACT-mortality, intercept 0.28, slope 0.68, and c-statistic 0.68; CRASH-unfavorable outcome, intercept -0.97, slope 1.32, and c-statistic 0.88; nonlinear calibration for IMPACT-unfavorable outcome and CRASH-mortality). Model performance differences were observed across the top enrolling sites for mortality and unfavorable outcome., Conclusions: The IMPACT and CRASH models adequately discriminated mortality and unfavorable outcome. Observed overestimations of mortality and unfavorable outcome underscore the need to update prognostic models to incorporate contemporary changes in TBI management and case-mix. Investigations to elucidate the relationships between increased survival, outcome, treatment intensity, and site-specific practices will be relevant to improve models in specific TBI subpopulations (e.g., older adults), which may benefit from the inclusion of blood-based biomarkers, neuroimaging features, and treatment data.

Background: Tumour vascular normalisation therapy advocates a balance between pro-angiogenic factors and anti-angiogenic factors in tumours. Artemisinin (ART), which is derived from traditional Chinese medicine, has been shown to inhibit tumour growth; however, the relationship between ART and tumour vascular normalisation in oral squamous cell carcinoma (OSCC) has not been previously reported., Methods: Different concentrations(0 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg)of ART were used to treat the xenograft nude mice model of OSCC. The effects of ART on migration and proliferation of OSCC and human umbilical vein endothelial cells (HUVEC) cells were detected by scratch assay and CCK-8 assay. OSCC cells with macrophage migration inhibitory factor (MIF) silenced were constructed to explore the effect of MIF., Results: Treatment with ART inhibited the growth and angiogenesis of OSCC xenografts in nude mice and downregulated vascular endothelial growth factor (VEGF), IL-8, and MIF expression levels. ART reduced the proliferation, migration, and tube formation of HUVEC, as well as the expression of VEGFR1 and VEGFR2. When the dose of ART was 50 mg/kg, vascular normalisation of OSCC xenografts was induced. Moreover, VEGF and IL-8 were needed in rhMIF restoring tumour growth and inhibit vascular normalisation after the addition of rhMIF to ART-treated cells., Conclusion: Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF-signalling pathway., (© 2022 Wiley Periodicals LLC.)

Background: Clozapine is the primary antipsychotic (APD) for treatment-resistant schizophrenia (TRS). However, only 40% of patients with TRS respond to clozapine, constituting a subgroup of clozapine-resistant patients. Recently, the neuropeptide orexin-A was shown to be involved in the pathophysiology of schizophrenia. This study evaluated the association of orexin-A levels with the clozapine response in patients with TRS., Methods: We recruited 199 patients with schizophrenia, including 37 APD-free and 162 clozapine-treated patients. Clozapine-treated patients were divided into clozapine-responsive ( n  = 100) and clozapine-resistant ( n  = 62) groups based on whether they had achieved psychotic remission defined by the 18-item Brief Psychiatric Rating Scale (BPRS-18). We compared blood orexin-A levels among the three groups and performed regression analysis to determine the association of orexin-A level with treatment response in clozapine-treated patients. We also explored the correlation between orexin-A levels and cognitive function, assessed using the CogState Schizophrenia Battery., Results: Clozapine-responsive patients had higher orexin-A levels than clozapine-resistant and APD-free patients. Orexin-A level was the only factor significantly associated with treatment response after adjustment. Orexin-A levels were negatively correlated with BPRS-18 full scale and positive, negative, and general symptoms subscale scores. We also observed a positive correlation between orexin-A levels and verbal memory, visual learning and memory, and working memory function., Conclusions: This cross-sectional study showed that higher levels of orexin-A are associated with treatment response to clozapine in patients with TRS. Future prospective studies examining changes in orexin-A level following clozapine treatment and the potential benefit of augmenting orexin-A signaling are warranted., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neurofilament light chain (NFL), as a measure of neuroaxonal injury, has recently gained attention in alcohol dependence (AD). Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme which metabolizes the alcohol breakdown product acetaldehyde. An ALDH2 single nucleotide polymorphism (rs671) is associated with less ALDH2 enzyme activity and increased neurotoxicity. We examined the blood NFL levels in 147 patients with AD and 114 healthy controls using enzyme-linked immunosorbent assay and genotyped rs671. We also followed NFL level, alcohol craving and psychological symptoms in patients with AD after 1 and 2 weeks of detoxification. We found the baseline NFL level was significantly higher in patients with AD than in controls (mean  ±  SD: 264.2  ±  261.8 vs. 72.1 ± 35.6 pg/mL, p < 0.001). The receiver operating characteristic curve revealed that NFL concentration could discriminate patients with AD from controls (area under the curve: 0.85; p < 0.001). The NFL levels were significantly reduced following 1 and 2 weeks of detoxification, with the extent of reduction correlated with the improvement of craving, depression, and anxiety (p < 0.001). Carriers with the rs671 GA genotype, which is associated with less ALDH2 activity, had higher NLF levels either at baseline or after detoxification compared with GG carriers. In conclusion, plasma NFL level was increased in patients with AD and reduced after early abstinence. Reduction in NFL level corroborated well with the improvement of clinical symptoms. The ALDH2 rs671 polymorphism may play a role in modulating the extent of neuroaxonal injury and its recovery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: To demonstrate that acupuncture is beneficial for decreasing the risk of ischaemic stroke in patients with rheumatoid arthritis (RA)., Design: A propensity score-matched cohort study., Setting: A nationwide population-based study., Participants: Patients with RA diagnosed between 1 January 1997 and 31 December 2010, through the National Health Insurance Research Database in Taiwan., Interventions: Patients who were administered acupuncture therapy from the initial date of RA diagnosis to 31 December 2010 were included in the acupuncture cohort. Patients who did not receive acupuncture treatment during the same time interval constituted the no-acupuncture cohort., Primary Outcome Measures: A Cox regression model was used to adjust for age, sex, comorbidities, and types of drugs used. We compared the subhazard ratios (SHRs) of ischaemic stroke between these two cohorts through competing-risks regression models., Results: After 1:1 propensity score matching, a total of 23 226 patients with newly diagnosed RA were equally subgrouped into acupuncture cohort or no-acupuncture cohort according to their use of acupuncture. The basic characteristics of these patients were similar. A lower cumulative incidence of ischaemic stroke was found in the acupuncture cohort (log-rank test, p<0.001; immortal time (period from initial diagnosis of RA to index date) 1065 days; mean number of acupuncture visits 9.83. In the end, 341 patients in the acupuncture cohort (5.95 per 1000 person-years) and 605 patients in the no-acupuncture cohort (12.4 per 1000 person-years) experienced ischaemic stroke (adjusted SHR 0.57, 95% CI 0.50 to 0.65). The advantage of lowering ischaemic stroke incidence through acupuncture therapy in RA patients was independent of sex, age, types of drugs used, and comorbidities., Conclusions: This study showed the beneficial effect of acupuncture in reducing the incidence of ischaemic stroke in patients with RA., Competing Interests: Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Hospital length of stay (HLOS) is a metric of injury severity, resource utilization, and healthcare access. Recent evidence has shown an association between Medicaid insurance and increased HLOS after traumatic brain injury (TBI). This study aims to validate the association between Medicaid and prolonged HLOS after TBI using the National Trauma Data Bank., Methods: National Trauma Data Bank Trauma Quality Programs Participant Use Files (2003-2021) were queried for adult patients with TBI using traumatic intracranial injury ICD-9/ICD-10 codes. Patients with complete HLOS, age, sex, race, insurance payor, Glasgow Coma Scale, Injury Severity Score, and discharge disposition data were included (N = 552 949). Analyses were stratified by TBI severity using Glasgow Coma Scale. HLOS was coded into Tiers according to percentiles within TBI severity categories (Tier 1: 1-74th; 2: 75-84th; 3: 85-94th; 4: 95-99th). Multivariable logistic regressions evaluated associations between insurance payor and prolonged (Tier 4) HLOS, controlling for sociodemographic, Injury Severity Score, cranial surgery, and discharge disposition variables. Adjusted odds ratios (aOR) and 95% CI were reported., Results: HLOS Tiers consisted of 0-19, 20-27, 28-46, and ≥47 days (Tiers 1-4, respectively) in severe TBI (N = 103 081); 0-15, 16-21, 22-37, and ≥38 days in moderate TBI (N = 39 904); and 0-7, 8-10, 11-19, and ≥20 days in mild TBI (N = 409 964). Proportion of Medicaid patients increased with Tier ([Tier 1 vs Tier 4] severe: 16.0% vs 36.1%; moderate: 14.1% vs 31.6%; mild TBI: 10.2% vs 17.4%; all P < .001). On multivariable analyses, Medicaid was associated with prolonged HLOS (severe TBI: aOR = 2.35 [2.19-2.52]; moderate TBI: aOR = 2.30 [2.04-2.61]; mild TBI: aOR = 1.75 [1.67-1.83]; reference category: private/commercial)., Conclusion: This study supports Medicaid as an independent predictor of prolonged HLOS across TBI severity strata. Reasons may include different efficacies in care delivery and reimbursement, which require further investigation. Our findings support the development of discharge coordination pathways and policies for Medicaid patients with TBI., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: The Penn Alcohol Craving Scale (PACS) is a five-item, single-dimension questionnaire that is used to measure a patient's alcohol craving. We sought to develop the Chinese version of the PACS (PACS-C) and assess its reliability and validity., Methods: A total of 160 Taiwanese patients with alcohol use disorder were enrolled in this study. The internal consistency and concurrent validity of the PASC-C with the visual analogue scale (VAS) for craving, the Yale-Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd), and the Severity of Alcohol Dependence Questionnaire (SADQ) were assessed. The test-retest reliability of the PASC-C was evaluated 1 day after the baseline measurements. Confirmatory factor analysis (CFA) was performed to examine the psychometric properties of the PACS-C., Results: The PACS-C exhibited good internal consistency (Cronbach's α=0.95) and test-retest reliability (r=0.97). This scale showed high correlations with the VAS (r=0.81) and YBOCS-hd (r=0.81 and 0.79 for the obsession and compulsion subscales, respectively), and moderate correlation with the SADQ-C (r=0.47). Furthermore, CFA results revealed that the PACS-C had good fit indices under various models., Conclusion: The PACS-C appears to be a reliable and valid tool for assessing alcohol craving in patients with alcohol use disorder in Taiwan.

Cells in the tumor microenvironment (TME) communicate via membrane-bound and secreted proteins, which are mostly glycosylated. Altered glycomes of malignant tumors influence behaviors of stromal cells. In this study, we showed that the loss of core-1 β1,3-galactosyltransferase (C1GALT1)-mediated O-glycosylation suppressed tumor growth in syngeneic head and neck cancer mouse models. O-glycan truncation in tumor cells promoted the M1 polarization of macrophages, enhanced T-cell-mediated cytotoxicity, and reduced interleukin-6 (IL-6) levels in the secretome. Proteasomal degradation of IL-6 was controlled by the O-glycan at threonine 166. Both IL-6/IL-6R blockade and O-glycan truncation in tumor cells induced similar pro-inflammatory phenotypes in macrophages and cytotoxic T lymphocytes (CTLs). The combination of the O-glycosylation inhibitor itraconazole and anti-programmed cell death protein 1 (anti-PD-1) antibody effectively suppressed tumor growth in vivo. Collectively, our findings demonstrate that O-glycosylation in tumor cells governs their crosstalk with macrophages and CTLs. Thus, targeting O-glycosylation successfully reshapes the TME and consequently enhances the efficacy of anti-PD-1 therapy., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Importance: Due to insufficient smoking cessation apps for persons living with HIV, our study focused on designing and testing the Sense2Quit app, a patient-facing mHealth tool which integrated visualizations of patient information, specifically smoking use., Objectives: The purpose of this paper is to detail rigorous human-centered design methods to develop and refine visualizations of smoking data and the contents and user interface of the Sense2Quit app. The Sense2Quit app was created to support tobacco cessation and relapse prevention for people living with HIV., Materials and Methods: Twenty people living with HIV who are current or former smokers and 5 informaticians trained in human-computer interaction participated in 5 rounds of usability testing. Participants tested the Sense2Quit app with use cases and provided feedback and then completed a survey., Results: Visualization of smoking behaviors was refined through each round of usability testing. Further, additional features such as daily tips, games, and a homescreen were added to improve the usability of the app. A total of 66 changes were made to the Sense2Quit app based on end-user and expert recommendations., Discussion: While many themes overlapped between usability testing with end-users and heuristic evaluations, there were also discrepancies. End-users and experts approached the app evaluation from different perspectives which ultimately allowed us to fill knowledge gaps and make improvements to the app., Conclusion: Findings from our study illustrate the best practices for usability testing for development and refinement of an mHealth-delivered consumer informatics tool for improving tobacco cessation yet further research is needed to fully evaluate how tools informed by target user needs improve health outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

DNA was extracted from tissue samples from specimens of newly-collected Bathynomuskensleyi from Queensland and subsequently the COI and 16S rRNA sequences were successfully cloned. The holotype of B.kensleyi was also sampled for COI only. Comparison of the sequences showed that, for the COI sequences, B.jamesi and B.kensleyi have more than 59 different DNA positions amongst 596 known reading sequences. The Kimura two parameter (K2P) distance analysis confirmed that B.jamesi and B.kensleyi are two species. Indian records of Bathynomus are reviewed and three of the four identified species from India are shown to be misidentifications. Bathynomusdecemspinosus , B.doederlini and B.kensleyi are found to not occur in India and the only accepted record is that of Bathynomuskeablei Lowry & Dempsey, 2006. We conclude that, based on molecular analysis and morphological comparisons, the correct species identity of Indian species other than Bathynomuskeablei remains unknown., Competing Interests: No conflict of interest to declare Disclaimer: This article is (co-)authored by any of the Editors-in-Chief, Managing Editors or their deputies in this journal., (Ming-Chih Huang, Niel L Bruce.)

Background: Methamphetamine use disorder (MUD) is a worldwide health concern. The hypothalamic orexin system regulates stress response and addictive behaviors. The genetic variation in the hypocretin receptor 2 (HCRTR2), rs2653349, is associated with substance use disorder. Objectives: We explored the gene-environment (GxE) interaction of rs2653349 and adverse childhood experiences (ACEs) associated with MUD susceptibility. Methods: Four hundred and one individuals (336 males, 65 females) with MUD and 348 healthy controls (288 males, 60 females) completed a self-report questionnaire evaluating ACEs, encompassing childhood abuse and household dysfunction categories, and were genotyped for SNP rs2653349. Methamphetamine use variables were collected using the Diagnostic Interview for Genetic Studies. We used regression analyses to assess the GxE effect on MUD risk. Results: The MUD group had a comparable genotypic distribution for rs2653349 to the control group, albeit with a higher prevalence and number of types of ACEs, correlating with an increased MUD risk ( p  < .05). No significant genetic impact of rs2653349 on MUD risk was found. However, we observed a GxE interaction effect between the minor allele of rs2653349 and the number of childhood abuse or household dysfunction types, correlating with a reduced MUD risk (OR = -0.71, p  = .04, Benjamini-Hochberg adjusted p  = .08 and OR = -0.59, p  = .045, Benjamini-Hochberg adjusted p  = .09, respectively). Conclusion: HCRTR2 SNP rs2653349 has no significant impact on MUD risk, but ACEs may increase this risk. GxE results suggest that rs2653349 could offer protection against developing MUD in individuals experiencing multiple types of ACEs.