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Rice production is inherently risky and volatile, and farmers in Bangladesh face a wide range of risks, including weather, pest and disease attacks, interruptions to input supply, and market-associated risks. Moreover, poor farm households often perceive risks in adopting new technology, even though it could improve productivity and food security. Such households are thus caught in a “risk-induced trap” that precludes them from realizing the benefits of technological innovation. Extension service is one way to help farmers improve risk management skills and escape risk-induced traps, but there is limited empirical analysis of its impact in Bangladesh. The objective of the study is to measure the nexus between agricultural extension services, technology adoption, and production risks as well as women empowerment in agriculture index. IFPRI utilized stratified random sampling to determine the 5603 households in 2018 (which is nationally called the BIHS-2018 dataset) from rural and pre-urban areas of Bangladesh. Out of these 5603 households, 2663 households were specifically selected for the study related to rice farming to achieve the main objective of the study. Focusing on rice farming, a moment-based Poisson regression model is estimated with 2SLS and identifies risks associated with key technologies and potential productivity and risk-reducing effects. The results revealed that wealthier households are more likely to adopt technology for minimizing production risk and women's empowerment which can positively affect productivity by mitigating risk. The result revealed a positive and significant difference in WEAI between the AES participant and non-participant group. We find that engagement in agricultural extension services was associated with technology adoption and production risk reduction. The agricultural extension services increased, technology adoption by 4.2 % and decreased production risk by 2.4 %. Based on the findings, it is concluded that more comprehensive extension services can enhance rice production and ameliorate farmers' risk in rice production to some extent.

Abstract The data described in this paper were collected from four jurisdictions in south Asia, Assam and Bihar in India and Punjab and Sindh in Pakistan. The data were collected from farmer households involved in surface water irrigation with the aim of understanding the merits of participatory irrigation management (PIM) in different settings in south Asia. The data were collected using four structured survey instruments, which comprised three paper-based surveys and one online survey collected via tablets. This data can be used by researchers to empirically analyze: overall institutional performance and its relationship to agro-economic variables; drivers of compliance; gender differences and their impact on participation in water groups and perceptions of performance; preferred charging regimes and broader institutional arrangements for managing water at the local level. These data are unique, having been collected simultaneously across the four jurisdictions.

Pakistan’s existential reliance on the Indus River Basin for water security is threatened by population growth, climate change, and increasing intersectoral demands. Pakistan’s National Water Policy of 2018 (NWP) adopts ‘More Crop per Drop’ as a key policy platform. Within the ‘More Crop per Drop’ strategy the NWP mandates banning flood irrigation nationally and introducing high efficiency irrigation systems (HEIS) to save water. The concept of water use efficiency (WUE) and the impact of replacing flood irrigation with HEIS on basin-wide water use are contested in the context of Pakistan. Research is lacking on how this aspect of the ‘More Crop per Drop’ strategy was included in the NWP and the evidence on which it is based. This paper addresses the gap in the literature by presenting the results of a Delphi study exploring the origins of the strategy, identifying the prevalent WUE paradigm in Pakistan, and exploring the level of appreciation of the effects of the strategy on the so-called rebound effect and water security. The study identifies that the NWP was developed mainly by the Water and Power Development Authority supported by provincial water management institutions, influenced by international funding agencies. The study establishes that the irrigation efficiency paradigm (IEP) is the dominant paradigm operating in the water bureaucracy. The farm-scale focus of this paradigm does not account for the basin-level rebound effect or the potential negative impact of the policy on water security. The study also finds that government extension workers are key sources of information for farmers considering the adoption of HEIS. We caution that banning flood irrigation and introducing HEIS in the absence of an appropriate regulatory framework could worsen Pakistan’s water security rather than ‘save’ irrigation water for reallocation and foreshadow additional research to further explore the situation.

Irrigation infrastructure expansion threatens the diversity of freshwater fish worldwide. Irrigation infrastructure creates migration barriers which can block access to important nursery, feeding and spawning habitat. Lao PDR is a landlocked country situated within the Lower Mekong River Basin where there is a substantial dependency on rice and fish for food, income and livelihoods. The country is experiencing an unprecedented boom in irrigation infrastructure investment, with modernisation programs being implemented in every province. Despite significant investment in infrastructure upgrades, and the potential impact on freshwater fish, little consideration has been given to fish passage solutions. In 2008, we commenced a fish passage program in Lao PDR. The intent of this case study is to outline the pivotal elements of the program of knowledge development and transfer, in the context of river connectivity and fisheries management in Lao PDR. We also highlight challenges in international research in development and lessons learned.

Whilst there is theoretical support for the view that there is a negative relationship between intra-firm logistics integration and transaction costs, this has been largely untested in an empirical sense at least. This study remedies this by reporting results from an empirical investigation of the International Multimodal Transport Industry in Vietnam. Extant literature on inter-departmental integration and transaction costs are briefly reviewed. Conceptualized hypotheses are then tested mainly using the Structural Equation Modeling (SEM) technique. Results from this study imply several mechanisms for reducing transaction costs and thus potentially guiding improvements in firm efficiency and performance. The paper also toucheson areas for future research.

The problem of the ‘financial sustainability’ of individual local councils represents the most significant policy question at issue in contemporary debate on Australian local government. This concern with financial sustainability has not only dominated almost all recent local government conferences across Australia, but it has also formed the capstone of several public inquiries into state local government systems. For instance, at the state level, both the South Australian Financial Sustainability Review Board’s (FSRB) (2005) Rising to the Challenge and the Independent Inquiry into the Financial Sustainability of NSW Local Government’ s (LGI) (2006) Are Councils Sustainable were centrally occupied with determining the meaning of financial sustainability in Australian local government and developing measures of financial sustainability. Moreover, the Queensland Local Government Association (LGAQ) (2006) Size, Shape and Sustainability (SSS) program, the Western Australian Local Government Association (WALGA) (2006) Systemic Sustainability Study and the Local Government Association of Tasmania (LGAT) (2007) Review of the Financial Sustainability of Local Government in Tasmania had at their core the problem of assessing financial sustainability in their respective local government systems.

Background: Tolerance to the analgesic effect of opioids complicates the management of persistent pain states. We tested whether the intrathecal infusion of small interfering RNA (siRNA) against β-arrestin 2 would reduce tolerance to chronic morphine use and the severity of precipitated morphine withdrawal.Methods: Intrathecal β-arrestin 2 (2 μg siRNA per 10 μl per rat) was injected once daily for 3 days. Rats then received a continuous intrathecal infusion of morphine (2 nmol h⁻¹) or saline for 7 days. Daily tail-flick (TF) and intrathecal morphine challenge tests were performed to assess the effect of intrathecal β-arrestin 2 siRNA on antinociception and tolerance to morphine. Naloxone withdrawal (2 mg kg⁻¹) was performed to assess morphine dependence.Results: In the daily TF test, the antinociception of intrathecal morphine was increased and maintained in rats receiving β-arrestin 2 siRNA compared with the control group (morphine alone). In the probe response test, rats receiving morphine infusion with β-arrestin 2 siRNA treatment showed a significant left shift in their dose-response curve, as measured by per cent maximal possible effect (MPE), such that the AD₅₀ was significantly decreased by a factor of 5.6 when compared with that of morphine-infused rats. In the naloxone-induced withdrawal tests, rats receiving β-arrestin 2 siRNA injection with morphine infusion showed a significant reduction in four of the six signs of withdrawal.Conclusions: We show here that intrathecal β-arrestin 2 siRNA in rats enhances analgesia and attenuates naloxone-induced withdrawal symptoms. This may warrant further investigation in the context of long-term use of intrathecal opioids for controlling chronic pain. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a prevalent condition in Taiwan, and the incidence of total knee arthroplasty (TKA) is on the rise. This study aimed to evaluate the postoperative results of patients with different degrees of CKD after TKA, using data from the Taiwan National Health Insurance Research Database., Methods: The study analyzed 3078 patients who received TKA from 2012 to 2017, equally divided into three groups: none-CKD, mild CKD (without dialysis), and severe CKD (with dialysis). Propensity score matching was used to minimize selection bias., Results: After TKA, there was no significant difference in the risk of debridement surgery for infection between the three groups (adjusted HR of mild CKD: 0.71 95% CI=0.36-1.38, p=0.3073; adjusted HR of severe CKD: 1.14, 95% CI=0.63-2.06, p=0.6616). However, CKD patients requiring dialysis had a significantly higher risk of mortality (adjusted HR: 1.98, 95% CI=1.57-2.50, p<0.001) and readmission within 90days of any causes (adjusted HR: 1.83, 95% CI=1.48-2.26, p<0.001) than non-CKD and mild CKD patients., Conclusion: Severe CKD patients needing dialysis after TKA have a higher risk of mortality and readmission rates than that of the non-CKD or mild CKD patients. If the patient is in the early stage of CKD, their prognosis after receiving TKA is expected to be as good as non-CKD patients., Level of Evidence: IV; well-designed cohort study., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objectives : This study aimed to examine the relationship between health-related quality of life (HRQoL) and sociodemographic and clinical variables in survivors of head and neck cancer (HNC) treated with radiotherapy, with or without surgery. Materials and Methods : HRQoL was measured using the functional assessment of cancer therapy-head and neck (FACT-H&N) in a cross-sectional survey involving 150 patients. Of these, 60 had nasopharyngeal cancer (NPC), treated exclusively with radiotherapy, while 90 had oral cavity squamous cell cancer (OSCC), undergoing radical surgery followed by adjuvant radiotherapy. Key variables included cancer type, age, gender, partnership status, education, and employment, with additional clinical variables assessed in patients with OSCC. Statistical analyses included multiple regression, ANOVA, and t-tests to explore relationships between variables and HRQoL. Results : Cancer type, surgical treatment, and employment status emerged as significant independent predictors of HRQoL in HNC patients. Patients with NPC reported better HRQoL on three FACT-H&N subscales-social/family well-being, functional well-being, and additional concerns-compared to patients with OSCC. Unemployed individuals exhibited lower HRQoL on four subscales. In patients with OSCC, partnership status and segmental mandibulectomy were found to predict HRQoL independently. Conclusions : This study concludes that cancer type, surgical intervention, and employment status notably influence HRQoL among HNC patients undergoing radiotherapy. In addition, partnership status is a key factor affecting HRQoL in patients with OSCC.

Cerebellum is a key-structure for the modulation of motor, cognitive, social and affective functions, contributing to automatic behaviours through interactions with the cerebral cortex, basal ganglia and spinal cord. The predictive mechanisms used by the cerebellum cover not only sensorimotor functions but also reward-related tasks. Cerebellar circuits appear to encode temporal difference error and reward prediction error. From a chemical standpoint, cerebellar catecholamines modulate the rate of cerebellar-based cognitive learning, and mediate cerebellar contributions during complex behaviours. Reward processing and its associated emotions are tuned by the cerebellum which operates as a controller of adaptive homeostatic processes based on interoceptive and exteroceptive inputs. Lobules VI-VII/areas of the vermis are candidate regions for the cortico-subcortical signaling pathways associated with loss aversion and reward sensitivity, together with other nodes of the limbic circuitry. There is growing evidence that the cerebellum works as a hub of regional dysconnectivity across all mood states and that mental disorders involve the cerebellar circuitry, including mood and addiction disorders, and impaired eating behaviors where the cerebellum might be involved in longer time scales of prediction as compared to motor operations. Cerebellar patients exhibit aberrant social behaviour, showing aberrant impulsivity/compulsivity. The cerebellum is a master-piece of reward mechanisms, together with the striatum, ventral tegmental area (VTA) and prefrontal cortex (PFC). Critically, studies on reward processing reinforce our view that a fundamental role of the cerebellum is to construct internal models, perform predictions on the impact of future behaviour and compare what is predicted and what actually occurs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hyperkalemia, characterized by elevated serum potassium levels, heightens the risk of sudden cardiac death, particularly increasing risk for individuals with chronic kidney disease and end-stage renal disease (ESRD). Traditional laboratory test monitoring is resource-heavy, invasive, and unable to provide continuous tracking. Wearable technologies like smartwatches with electrocardiogram (ECG) capabilities are emerging as valuable tools for remote monitoring, potentially allowing for personalized monitoring with artificial intelligence (AI)-ECG interpretation., Objectives: The purpose of this study was to develop an AI-ECG algorithm to predict serum potassium level in ESRD patients with smartwatch-generated ECG waveforms., Methods: A cohort of 152,508 patients with 293,557 ECGs paired serum potassium levels obtained within 1 hour at Cedars Sinai Medical Center was used to train an AI-ECG model ("Kardio-Net") to predict serum potassium level. The model was further fine-tuned on 4,337 ECGs from 1,463 patients with ESRD using inputs from 12- and single-lead ECGs. Kardio-Net was evaluated in held-out test cohorts from Cedars Sinai Medical Center and Stanford Healthcare (SHC) as well as a prospective international cohort of 40 ESRD patients with smartwatch ECGs at Chang Gung Memorial Hospital., Results: The Kardio-Net, when applied to 12-lead ECGs, identified severe hyperkalemia (>6.5 mEq/L) with an AUC of 0.852 (95% CI: 0.745-0.956) and a mean absolute error (MAE) of 0.527 mEq/L. In external validation at SHC, the model achieved an AUC of 0.849 (95% CI: 0.823-0.875) and an MAE of 0.599 mEq/L. For single-lead ECGs, Kardio-Net detected severe hyperkalemia with an AUC of 0.876 (95% CI: 0.765-0.987) in the primary cohort and had an MAE of 0.575 mEq/L. In the external SHC validation, the AUC was 0.807 (95% CI: 0.778-0.835) with an MAE of 0.740 mEq/L. Using prospectively obtained smartwatch data, the AUC was 0.831 (95% CI: 0.693-0.975), with an MAE of 0.580 mEq/L., Conclusions: We validate a deep learning model to predict serum potassium levels from both 12-lead ECGs and single-lead smartwatch data, demonstrating its utility for remote monitoring of hyperkalemia., Competing Interests: Funding Support and Author Disclosures Dr Chiu has received funding from the National Science and Technology Council in Taiwan (111-2221-E-182A-008-). Drs Chiu and Ouyang have received funding from Apple and the National Institutes of Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

SCA6 patients with the same size CAG repeat allele can vary significantly in age at onset (AAO) and clinical progression. The specific external factors affecting SCA6 have yet to be investigated. We assessed the effect of early life events on AAO, severity, and progression in SCA6 patients using a social determinant of health approach. We performed a survey of biological and social factors in SCA6 patients enrolled in the SCA6 Network at the University of Chicago. AAO of ataxia symptoms and patient-reported outcome measure (PROM) of ataxia were used as primary outcome measures. Least absolute shrinkage and selection operation (LASSO) regressions were used to identify which early life factors are predictive of SCA6 AAO, severity, and progression. Multiple linear regression models were then used to assess the degree to which these determinants influence SCA6 health outcomes. A total of 105 participants with genetically confirmed SCA6 completed the assessments. SCA6 participants with maternal difficulty during pregnancy, active participation in school sports, and/or longer CAG repeats were determined to have earlier AAO. We found a 13.44-year earlier AAO for those with maternal difficulty in pregnancy than those without (p = 0.008) and a 12.31-year earlier AAO for those active in school sports than those who were not (p < 0.001). Higher education attainment was associated with decreased SCA6 severity and slower progression. Early life biological and social factors can have a strong influence on the SCA6 disease course, indicating that non-genetic factors can contribute significantly to SCA6 health outcomes., (© 2024. The Author(s).)

Recent findings in animals have challenged the traditional view of the cerebellum solely as the site of motor control, suggesting that the cerebellum may also be important for learning to predict reward from trial-and-error feedback. Yet, evidence for the role of the cerebellum in reward learning in humans is lacking. Moreover, open questions remain about which specific aspects of reward learning the cerebellum may contribute to. Here we address this gap through an investigation of multiple forms of reward learning in individuals with cerebellum dysfunction, represented by cerebellar ataxia cases. Nineteen participants with cerebellar ataxia and 57 age- and sex-matched healthy controls completed two separate tasks that required learning about reward contingencies from trial-and-error. To probe the selectivity of reward learning processes, the tasks differed in their underlying structure: while one task measured incremental reward learning ability alone, the other allowed participants to use an alternative learning strategy based on episodic memory alongside incremental reward learning. We found that individuals with cerebellar ataxia were profoundly impaired at reward learning from trial-and-error feedback on both tasks, but retained the ability to learn to predict reward based on episodic memory. These findings provide evidence from humans for a specific and necessary role for the cerebellum in incremental learning of reward associations based on reinforcement. More broadly, the findings suggest that alongside its role in motor learning, the cerebellum likely operates in concert with the basal ganglia to support reinforcement learning from reward., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study aimed to assess the impact of the reimbursement regulation of medical devices (Regulation), introduced by the National Health Insurance Administration (NHIA) in 2013, on patients' access to innovative medical devices in Taiwan., Methods: Analysis of the amount of time needed from application for NHIA reimbursement for new medical devices to receiving the decision from NHIA was done using the nonreimbursement product list featured on the NHIA website. Additionally, Welch analysis of variance was used to compare the amount of time it took from application to NHIA with reimbursement decisions made by the NHIA for different nonreimbursement code categories. Further, related Pharmaceutical Benefit Reimbursement Scheme meeting minutes were analyzed to obtain more detailed information concerning medical devices' reimbursement or not., Results: From December 2012 to June 2021, the overall reimbursement percentage was 56.7%, and the average amount of time between application and reimbursement was 856.7 ± 474.7 days. The mandatory reimbursement rate was about 45%. NHIA reimbursement decisions as special medical devices also take a longer amount of time, because the applicants need to agree to the decision (P < .05). The NHIA decision-making process for nonreimbursement medical devices requires a significantly longer amount of time than for general materials (eg, suture, etc) decisions., Conclusions: Although the Regulation resolves payment issues, it also increases the amount of time to reach reimbursement decisions, thus hindering patient access to innovative medical devices. The study suggests that the review process needs to be simplified concerning reimbursement notification, using local real-world data to support reimbursement decisions., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Previous research has identified that people with cerebellar ataxia (CA) showed impaired reward-related decision-making in the Iowa Gambling Task (IGT). To investigate the mechanisms underlying this impairment, we examined CA participants' combination of performance in the IGT, which predominantly tests reward seeking, and the modified IGT (mIGT), which mainly assesses punishment avoidance., Methods: Fifty participants with CA and one hundred controls completed the IGT and mIGT. Task performance in each of the five twenty-trial blocks was compared between groups and the learning rates were assessed with simple linear regressions. Each participant's IGT score and mIGT score were compared., Results: CA participants performed worse than controls in both the IGT and the mIGT, especially in the last block (IGT: -0.24 ± 10.05 vs. 3.88 ± 10.31, p = 0.041; mIGT: 2.72 ± 7.62 vs. 8.65 ± 8.64, p < 0.001). In contrast to the controls, those with CA did not significantly improve their scores over time in either task. Controls performed better in the mIGT than the IGT, while CA participants' scores in the two tasks showed no significant difference. IGT and mIGT performance did not correlate with ataxia severity or depressive symptoms., Conclusion: Individuals with CA showed impaired performance in both the IGT and mIGT, which indicates disruption in both short-term reward seeking and short-term punishment avoidance. Therefore, these results suggest that reduced sensitivity to long-term consequences drives the risky decision-making in CA., (Copyright © 2023. Published by Elsevier B.V.)

Background: The global aging population presents a significant challenge, with older adults experiencing declining physical and cognitive abilities and increased vulnerability to chronic diseases and adverse health outcomes. This study aims to develop an interpretable deep learning (DL) model to predict adverse events in geriatric patients within 72 hours of hospitalization., Methods: The study used retrospective data (2017-2020) from a major medical center in Taiwan. It included non-trauma geriatric patients who visited the emergency department and were admitted to the general ward. Data preprocessing involved collecting prognostic factors like vital signs, lab results, medical history, and clinical management. A deep feedforward neural network was developed, and performance was evaluated using accuracy, sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC). Model interpretation utilized the Shapley Additive Explanation (SHAP) technique., Results: The analysis included 127,268 patients, with 2.6% experiencing imminent intensive care unit transfer, respiratory failure, or death during hospitalization. The DL model achieved AUCs of 0.86 and 0.84 in the validation and test sets, respectively, outperforming the Sequential Organ Failure Assessment (SOFA) score. Sensitivity and specificity values ranged from 0.79 to 0.81. The SHAP technique provided insights into feature importance and interactions., Conclusion: The developed DL model demonstrated high accuracy in predicting serious adverse events in geriatric patients within 72 hours of hospitalization. It outperformed the SOFA score and provided valuable insights into the model's decision-making process., Competing Interests: The authors declare that they have no competing interests., (© 2024 Hsu et al.)

Background: Thoracic ossification of the ligamentum flavum (TOLF), a rare condition more prevalent in East Asia, is managed through open and endoscopic surgical approaches. Determining the superior surgical option remains unclear. This study assesses the safety and clinical outcomes associated with these approaches in TOLF patients., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic literature search up to August 5, 2023, across PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov. We included randomized controlled trials and cohort studies reporting complication rates, mJOA (modified Japanese Orthopedic Association) scores, JOA scores, VAS (Visual Analog Scale) scores, or hospitalization duration for both open and endoscopic surgeries in TOLF patients., Results: We analyzed 37 studies encompassing 1,646 TOLF patients using a random-effects model. Our findings revealed a significant difference in complication rates (overall complication rates: 0.12; 95% CI: 0.07, 0.19; p < 0.01; I2: 69%; quality of evidence: moderate), with lower complication rates in the endoscopy group. However, no significant differences were observed in JOA scores (overall JOA: 8.35; 95% CI: 7.16, 9.54; p = 0.12; I2: 99%; quality of evidence: very low), VAS scores (overall VAS: 1.31; 95% CI: 1.03, 1.59; p = 0.35; I2: 91%; quality of evidence: very low), or hospitalization duration (hospital stay: 10.83 days; 95% CI: 6.86, 14.80; p = 0.35; I2: 91%; quality of evidence: very low) between the open and endoscopic groups., Conclusions: This meta-analysis reports lower complication rates and improved postoperative mJOA scores for endoscopic surgery in TOLF patients compared to open surgery. It represents the first comprehensive evaluation of clinical outcomes and safety of different surgical approaches for TOLF patients. Further randomized controlled trials are essential to validate these findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities., Competing Interests: J.R.B. has received honoraria for continuing medical education (CME) lectures in behavioral neurology & neuropsychiatry (BNNP) and from Novo Nordisk. He has received funding from the National Institutes of Health (NIH), Dementia Alliance of North Carolina, and Alzheimer’s Association for work unrelated to this project. S.J.H. has received honoraria for CME lectures in BNNP. She has received funding from the Sidney R. Baer Jr. Foundation unrelated to this project. S.B. is a partner in and author for Brain Educators LLC, a neuropsychiatry education publisher. He has received honoraria for CME lectures in BNNP and receives a stipend as a psychiatry director of the American Board of Psychiatry and Neurology. B.F.B. receives author royalties from Cambridge University Press; honoraria for scientific advisory board activities for the Tau Consortium, funded by the Rainwater Charitable Foundation; and institutional research grant support from NIH and for clinical trials from Alector, Biogen, Transposon, Cognition Therapeutics, EIP Pharma, and GE Healthcare—all unrelated to this project. A.E.B. receives author royalties from Oxford University Press and Elsevier; investigator-initiated grants from the Alzheimer’s Association, VoxNeuro, and Bristol Myers Squibb; and consulting honorarium from Eli Lilly—all unrelated to this project. M.D.G. has consulted for Gerson Leherman Group and Reata Pharmaceuticals and receives research support from NIH, the National Institute of Neurological Disorders and Stroke (NINDS), and the Michael J. Homer Family Fund. A.E.H. receives honoraria from the American Heart Association as editor-in-chief of Stroke , and from Elsevier as associate editor of PracticeUpdate Neurology , unrelated to this project. S.K.H. has received honoraria for CME lectures from the American Academy of Neurology (AAN) and the Lewy Body Dementia Association. She has received research funding from NIH and the Michael J. Fox Foundation for Parkinson’s Research. I.K. receives funding from NIH and NINDS. J.D.S. is site principal investigator for Biohaven Pharmaceuticals clinical trials NCT03701399, NCT02960893, and NCT03952806; receives royalties from Oxford University Press, Elsevier, MacKeith Press, and Springer; and is the inventor of the Brief Ataxia Rating Scale, Cerebellar Cognitive Affective/Schmahmann Syndrome Scale, Patient Reported Outcome Measure of Ataxia, and Cerebellar Neuropsychiatry Rating Scale, which are licensed to the General Hospital Corporation. C.C.W. has received honoraria for creating educational content for the AAN. R.H.H. is a paid member of the board of trustees for the McKnight Brain Research Foundation and has received funding from NIH, the Department of Defense, and the Chan Zuckerberg Initiative for work unrelated to this project. D.L.P. has received honoraria for CME lectures in BNNP, royalties from Springer for a functional movement disorder textbook, and honoraria from Elsevier for a functional neurological disorder textbook, and is a paid member of the Brain and Behavior editorial board. He has received funding from NIH and the Sidney R. Baer Jr. Foundation unrelated to this project. The remaining authors declare no conflicts of interest., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Fatigue is a prevalent and debilitating symptom in neurological disorders, including spinocerebellar ataxias (SCAs). However, the risk factors of fatigue in the SCAs as well as its impact have not been well investigated., Objectives: To study the prevalence of fatigue in SCAs, the factors contributing to fatigue, and the influence of fatigue on quality of life., Methods: Fatigue was assessed in 418 participants with SCA1, SCA2, SCA3, and SCA6 from the Clinical Research Consortium for the Study of Cerebellar Ataxia using the Fatigue Severity Scale. We conducted multi-variable linear regression models to examine the factors contributing to fatigue as well as the association between fatigue and quality of life., Results: Fatigue was most prevalent in SCA3 (52.6%), followed by SCA1 (36.7%), SCA6 (35.7%), and SCA2 (35.6%). SCA cases with fatigue had more severe ataxia and worse depressive symptoms. In SCA3, those with fatigue had a longer disease duration and longer pathological CAG repeat numbers. In multi-variable models, depressive symptoms, but not ataxia severity, were associated with more severe fatigue. Fatigue, independent of ataxia and depression, contributed to worse quality of life in SCA3 and SCA6 at baseline, and fatigue continued affecting quality of life throughout the disease course in all types of SCA., Conclusions: Fatigue is a common symptom in SCAs and is closely related to depression. Fatigue significantly impacts patients' quality of life. Therefore, screening for fatigue should be considered a part of standard clinical care for SCAs., (© 2024 International Parkinson and Movement Disorder Society.)

Background & Aims: The gut microbiome plays an important role in liver diseases, but its specific impact on biliary atresia (BA) remains to be explored. We aimed to investigate the microbial signature in the early life of patients with BA and to analyze its influence on long-term outcomes., Methods: Fecal samples (n = 42) were collected from infants with BA before and after Kasai portoenterostomy (KPE). The stool microbiota was analyzed using 16S rRNA next-generation sequencing and compared with that of age-matched healthy controls (HCs). Shotgun metagenomic sequencing analysis was employed to confirm the bacterial composition in 10 fecal samples before KPE. The correlation of the microbiome signature with liver function and long-term outcomes was assessed., Results: In the 16S rRNA next-generation sequencing analysis of fecal microbiota, the alpha and beta diversity analyses revealed significant differences between HCs and patients with BA before and after KPE. The difference in microbial composition analyzed by linear discriminant analysis and random forest classification revealed that the abundance of Bifidobacterium longum ( B. longum ) was significantly lower in patients before and after KPE than in HCs. The abundance of B. longum was negatively correlated with the gamma-glutamyltransferase level after KPE ( p < 0.05). Patients with early detectable B. longum had significantly lower total and direct bilirubin 3 months after KPE ( p < 0.005) and had a significantly lower liver transplantation rate (hazard ratio: 0.16, 95% CI 0.03-0.83, p = 0.029). Shotgun metagenomic sequencing also revealed that patients with BA and detectable B. longum had reduced total and direct bilirubin after KPE., Conclusion: The gut microbiome of patients with BA differed from that of HCs, with a notable abundance of B. longum in early infancy correlating with better long-term outcomes., Impact and Implications: Bifidobacterium longum ( B. longum ) is a beneficial bacterium commonly found in the human gut. It has been studied for its potential impacts on various health conditions. In patients with biliary atresia, we found that a greater abundance of B. longum in the fecal microbiome is associated with improved clinical outcomes. This suggests that early colonization and increasing B. longum levels in the gut could be a therapeutic strategy to improve the prognosis of patients with biliary atresia., (© 2024 The Author(s).)

Purpose: Myopic marmosets are known to exhibit significant inner retinal thinning compared to age-matched controls. The purpose of this study was to assess inner retinal activity in marmosets with lens-induced myopia compared to age-matched controls and evaluate its relationship with induced changes in refractive state and eye growth., Methods: Cycloplegic refractive error (Rx), vitreous chamber depth (VCD), and photopic full-field electroretinogram were measured in 14 marmosets treated binocularly with negative contact lenses compared to 9 untreated controls at different stages throughout the experimental period (from 74 to 369 days of age). The implicit times of the a-, b-, d-, and photopic negative response (PhNR) waves, as well as the saturated amplitude (Vmax), semi-saturation constant (K), and slope (n) estimated from intensity-response functions fitted with Naka-Rushton equations were analyzed., Results: Compared to controls, treated marmosets exhibited attenuated b-, d-, and PhNR waves Vmax amplitudes 7 to 14 days into treatment before compensatory changes in refraction and eye growth occurred. At later time points, when treated marmosets had developed axial myopia, the amplitudes and implicit times of the b-, d-, and PhNR waves were similar between groups. In controls, the PhNR wave saturated amplitude increased as the b + d-wave Vmax increased. This trend was absent in treated marmosets., Conclusions: Marmosets induced with negative defocus exhibit early alterations in inner retinal saturated amplitudes compared to controls, prior to the development of compensatory myopia. These early ERG changes are independent of refraction and eye size and may reflect early changes in bipolar, ganglion, amacrine, or glial cell physiology prior to myopia development., Translational Relevance: The early changes in retinal function identified in the negative lens-treated marmosets may serve as clinical biomarkers to help identify children at risk of developing myopia.

Background and Objectives: The Baylor Profound Mental Status Examination (BPMSE) was developed to assess cognitive function in the profound stage of dementia. The Clinical Dementia Rating (CDR) scale has been widely used in measuring functional performance in dementia. We aimed to determine whether cognitive function is related to overall functional impairment in profound dementia., Methods: We selected 864 patients with probable Alzheimer disease (AD) and 25 patients with possible dementia with Lewy Bodies (DLB) cases with profound dementia by Mini-Mental Status Examination or/and clinical global impression. We used BPMSE to measure cognitive function and the CDR sum-of-boxes (CDR-SB) score to determine overall functional status. We used Spearman rank order correlation to examine the univariate association between CDR-SB and BPMSE in the 2 diagnostic groups separately and multivariable regression analysis to investigate whether BPMSE remained associated with functional status after adjustment for age, sex, education, and APOE ε4 genotype. We expected to see an inverse correlation between BPMSE and CDR-SB scores based on the directionality of the rating scale scoring., Results: In both AD and DLB, total BPMSE scores had a significant inverse correlation with CDR-SB scores (AD: r = -0.453, p < 0.001; DLB: r = -0.489, p = 0.013). It is of interest that in DLB, the "attention" domain of BPMSE had the strongest association with CDR-SB ( r = -0.700, p < 0.001) compared with other domains. The multivariable regression models showed that higher BPMSE scores (i.e., better cognitive function) remained significantly correlated with lower CDR-SB scores (i.e., better global function) in AD (CDR-SB: β = -0.340, p < 0.001), but the regression coefficient for BPMSE did not reach significance in the DLB model (CDR-SB: β = -0.298, p = 0.174)., Discussion: In patients with AD and DLB who enter the profound dementia stage, cognitive function is associated with the severity of functional impairment. The lack of significance for DLB in multivariable regression could be due to small sample size because the correlation magnitude is similar to that in AD., Competing Interests: I. Rampalli, V.N. Pavlik, and J. Bishop report no disclosures relevant to the manuscript. An immediate family member of M.M. Yu has received personal compensation for serving as an employee of CVS/Aetna. The institution of M.M. Yu has received research support from Alzheimer's Association. The institution of M.M. Yu has received research support from Biogen. The institution of M.M. Yu has received research support from Eisai. M.M. Yu has a noncompensated relationship as a Steering Board member with Epic Systems that is relevant to AAN interests or activities. C.Y.R. Lin has received an honorarium from Medscape by serving as the Editor of Medscape Neurology Decision Point Alzheimer's disease section. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.TAKE-HOME POINTS→ In profound stage of dementia, the level of cognitive function is still associated with functional impairment. This information is useful for clinicians to make appropriate plans by monitoring the cognitive decline.→ In Alzheimer disease, the association was primarily identified in female patients who are younger than 75 years with higher education levels.→ Among all cognitive functions of dementia with Lewy bodies, reduced attention is the domain that most affects the patient's functional impairment., (© 2024 American Academy of Neurology.)

The aim of this article is to describe sustained myopic eye growth's effect on astrocyte cellular distribution and its association with inner retinal layer thicknesses. Astrocyte density and distribution, retinal nerve fiber layer (RNFL), ganglion cell layer, and inner plexiform layer (IPL) thicknesses were assessed using immunochemistry and spectral-domain optical coherence tomography on seventeen common marmoset retinas ( Callithrix jacchus ): six induced with myopia from 2 to 6 months of age (6-month-old myopes), three induced with myopia from 2 to 12 months of age (12-month-old myopes), five age-matched 6-month-old controls, and three age-matched 12-month-old controls. Untreated marmoset eyes grew normally, and both RNFL and IPL thicknesses did not change with age, with astrocyte numbers correlating to RNFL and IPL thicknesses in both control age groups. Myopic marmosets did not follow this trend and, instead, exhibited decreased astrocyte density, increased GFAP+ spatial coverage, and thinner RNFL and IPL, all of which worsened over time. Myopic changes in astrocyte density, GFAP+ spatial coverage and inner retinal layer thicknesses suggest astrocyte template reorganization during myopia development and progression which increased over time. Whether or not these changes are constructive or destructive to the retina still remains to be assessed.

Purpose of Review: Spinocerebellar ataxias (SCAs) are autosomal dominant degenerative syndromes that present with ataxia and brain stem abnormalities. This review describes the cognitive and behavioral symptoms of SCAs in the context of recent knowledge of the role of the cerebellum in higher intellectual function., Recent Findings: Recent studies suggest that patients with spinocerebellar ataxia can display cognitive deficits even early in the disease. These have been given the term cerebellar cognitive affective syndrome (CCAS). CCAS can be tracked using newly developed rating scales. In addition, patients with spinocerebellar ataxia also display impulsive and compulsive behavior, depression, anxiety, fatigue, and sleep disturbances. This review stresses the importance of recognizing non-motor symptoms in SCAs. There is a pressing need for novel therapeutic interventions to address these symptoms given their deleterious impact on patients' quality of life., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Phantom limb pain (PLP) frequently affects individuals with limb amputations. When PLP evolves into its chronic phase, known as chronic PLP, traditional therapies often fall short in providing sufficient relief. The optimal intervention for chronic PLP remains unclear., Objective: The objectives of this network meta-analysis (NMA) were to examine the efficacy of different treatments on pain intensity for patients with chronic PLP., Evidence Review: We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and CINAHL EBSCO, focusing on randomized controlled trials (RCTs) that evaluated interventions such as neuromodulation, neural block, pharmacological methods, and alternative treatments. An NMA was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was pain score improvement, and the secondary outcomes were adverse events., Findings: The NMA, incorporating 12 RCTs, indicated that neuromodulation, specifically repetitive transcranial magnetic stimulation, provided the most substantial pain improvement when compared with placebo/sham groups (mean difference=-2.9 points, 95% CI=-4.62 to -1.18; quality of evidence (QoE): moderate). Pharmacological intervention using morphine was associated with a significant increase in adverse event rate (OR=6.04, 95% CI=2.26 to 16.12; QoE: low)., Conclusions: The NMA suggests that neuromodulation using repetitive transcranial magnetic stimulation may be associated with significantly larger pain improvement for chronic PLP. However, the paucity of studies, varying patient characteristics across each trial, and absence of long-term results underscore the necessity for more comprehensive, large-scale RCTs., Prospero Registration Number: CRD42023455949., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Purpose: The choroid is critical for the regulation of eye growth and is involved in the pathogenesis of myopia-associated ocular complications. This study explores the relationship among choroidal biometry, photoreceptor activity, and myopic growth in marmosets (Callithrix jacchus) with lens-induced myopia., Methods: A total of 34 common marmosets aged 92 to 273 days old were included in this study. Axial myopia was induced in 17 marmosets using negative soft contact lenses and 17 marmosets served as untreated controls. Cycloplegic refraction (RE) and vitreous chamber depth (VCD) were measured using autorefraction and A-scan ultrasonography, respectively. Choroidal scans were obtained using spectral-domain optical coherence tomography and binarized to calculate subfoveal choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), and LA/SA. To assess photoreceptor activity, the a-wave of the full-field electroretinogram was measured. Regression models were used to investigate the relationship between outcome measures., Results: Eyes induced with axial myopia (RE = -7.14 ± 4.03 diopters [D], VCD = 6.86 ± 0.39 mm) showed significant reductions (4.92-21.24%) in all choroidal parameters (ChT, TCA, LA, SA, CVI, and LA/SA) compared to controls (RE = -1.25 ± 0.60 D, VCD = 6.58 ± 0.26 mm, all P < 0.05), which changed as a function of refraction and vitreous elongation, and were associated with a decrease in the a-wave amplitude. Further, multiple regression showed that a combination of ChT and CVI could well predict RE and VCD., Conclusions: This study reports the existence of significant alterations in choroidal morphology in non-human primate eyes induced with myopia. The changes in choroidal anatomy were associated with reduced light-adapted a-wave amplitude. These findings may represent early markers for reduced visual performance and chorioretinal complications known to occur in eyes with large degrees of myopia.

Background: Metabolic syndrome (MetS) is a prevalent health condition in Taiwan that places individuals at higher risk of cardiovascular disease, diabetes, and stroke. Therefore, the identification of risk factors associated with MetS is crucial. The aim of this study was to investigate the association of uric acid and MetS in a Taiwanese community with a middle-aged and elderly population., Methods: This cross-sectional study enrolled residents aged 50-90 years living in one community. All of the subjects received a standardized personal interview, including a structured questionnaire, anthropometric measurements, and blood samples were collected for laboratory testing. MetS was defined as excess waist circumference, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Multiple logistic regression models were used to evaluate uric acid tertiles associated with MetS., Results: A total of 400 subjects were enrolled in the analysis. The overall prevalence of MetS was 35.8%. The prevalence of MetS increased gradually with increasing serum uric acid levels ( p value < 0.001). A significant association between uric acid and cardiometabolic risk factors was confirmed, with a Pearson's correlation coefficient for waist circumference of 0.30 ( p < 0.001), a coefficient for systolic blood pressure of 0.13 ( p = 0.01), a coefficient for triglycerides of 0.33 ( p < 0.001), and a coefficient for high-density lipoprotein of -0.30 ( p < 0.001). The adjusted odds ratio (OR) of the high uric acid tertile level for MetS was 2.48 (95% CI = 1.31-4.71, p = 0.01). The area under the ROC curve (AUC) for uric acid in predicting MetS was 0.621 ( p < 0.001)., Conclusions: The prevalence of MetS in our study population is high. High serum uric acid levels are independently associated with the presence of MetS among the middle-aged and elderly Taiwanese population.

The role of the cerebellum in amnestic mild cognitive impairment (aMCI), typically a prodromal stage of Alzheimer's disease, is not fully understood. We studied the lobule-specific cerebello-cerebral connectivity in 15 cognitively normal and 16 aMCI using resting-state functional MRI. Our analysis revealed weaker connectivity between the cognitive cerebellar lobules and parietal lobe in aMCI. However, stronger connectivity was observed in the cognitive cerebellar lobules with certain brain regions, including the precuneus cortex, posterior cingulate gyrus, and caudate nucleus in participants with worse cognition. Leveraging these measurable changes in cerebello-parietal functional networks in aMCI could offer avenues for future therapeutic interventions.

Background & Aims: A long immune-tolerant (IT) phase lasting for decades and delayed HBeAg seroconversion (HBe-SC) in patients with chronic hepatitis B (CHB) increase the risk of liver diseases. Early entry into the immune-active (IA) phase and HBe-SC confers a favorable clinical outcome with an unknown mechanism. We aimed to identify factor(s) triggering IA entry and HBe-SC in the natural history of CHB., Methods: To study the relevance of gut microbiota evolution in the risk of CHB activity, fecal samples were collected from CHB patients (n = 102) in different disease phases. A hepatitis B virus (HBV)-hydrodynamic injection (HDI) mouse model was therefore established in several mouse strains and germ-free mice, and multiplatform metabolomic and bacteriologic assays were performed., Results: Ruminococcus gnavus was the most abundant species in CHB patients in the IT phase, whereas Akkermansia muciniphila was predominantly enriched in IA patients and associated with alanine aminotransferase flares, HBeAg loss, and early HBe-SC. HBV-HDI mouse models recapitulated this human finding. Increased cholesterol-to-bile acids (BAs) metabolism was found in IT patients because R gnavus encodes bile salt hydrolase to deconjugate primary BAs and augment BAs total pool for facilitating HBV persistence and prolonging the IT course. A muciniphila counteracted this activity through the direct removal of cholesterol. The secretome metabolites of A muciniphila, which contained small molecules structurally similar to apigenin, lovastatin, ribavirin, etc., inhibited the growth and the function of R gnavus to allow HBV elimination., Conclusions: R gnavus and A muciniphila play opposite roles in HBV infection. A muciniphila metabolites, which benefit the elimination of HBV, may contribute to future anti-HBV strategies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the classification, diagnosis and treatment status of patients with pulmonary hypertension (PH) in Yunnan province. Methods: This was a retrospective study. Hospitalized patients with PH at Yan'an Affiliated Hospital of Kunming Medical University from January 2012 to December 2019 were enrolled. The clinical data of enrolled patients, including demographic data, comorbidities, targeted drug therapy, echocardiography and right heart catheterization results, were obtained through the electronic medical record system. The composition ratio of PH, diagnosis and treatment were analyzed. Results: A total of 13 590 patients with PH were enrolled, accounting for 3.09% (13 590/440 056) of the total number of hospitalizations during the same period. The composition of PH was predominantly pulmonary arterial hypertension (PAH) (55.50% (7 542/13 590)), followed by pulmonary hypertension (PH) caused by left heart disease (24.16% (3 284/13 590)). Among them, PAH could be subdivided into four types: idiopathic pulmonary arterial hypertension (IPAH), PAH associated with connective tissue disease, PAH associated with portal hypertension, and PAH associated with congenital heart disease (CHD-PAH), with CHD-PAH as the predominating type (98.09% (7 398/7 542). Patients with PAH were predominantly adolescents. In hospitalized patients with PH, from 2012 to 2019, the proportion of children and adolescents showed a decreasing trend from year to year, and the proportion of middle-aged and older adults showed a significant increasing trend, and the proportion of female patients showed a gradual decreasing trend, and the proportion of patients with comorbid hypertension, diabetes mellitus, coronary artery disease, arrhythmia, and pneumonia showed an increasing trend. A total of 1 034 patients (7.61% (1 034/13 590)) underwent right heart catheterization. The concordance rate between echocardiographic and right heart catheterization findings was (86.98% (875/1 006)). A total of 2 574 (18.94%) of PH patients were treated with PAH targeted drugs, of which 58.16% (1 497/2 574) were treated with monotherapy. Among the PH patients treated with PAH targeted drugs, the majority of patients were PAH patients (86.44% (2 225/2 574)), and 83.53% (2 150/2 574) patients treated with PAH targeted drugs were CHD-PAH. Conclusions: Hospitalized PH patients in our center between 2012 and 2019 are predominantly CHD-PAH, and the proportion of patients receiving right heart catheterization and targeted drug therapy is relatively low. The percentage of middle-aged and elderly PH patients shows an increasing trend from year to year, as well as the percentage of those with concomitant comorbidities.

(1) Background: Many studies have revealed a relationship between serum 25-hydroxy vitamin D and physical activity. This study aimed to investigate the relationship between self-reported sitting time and serum 25-hydroxy vitamin D levels in middle-aged and elderly adults in Taiwan. (2) Methods: A total of 396 people were enrolled in our study during a community health examination in Taiwan in 2019. We grouped participants from low to high according to their tertile of serum 25-hydroxy vitamin D levels, using the following categories: deficiency, insufficiency, and sufficiency. Parameters including self-reported sitting time were analyzed between each group. Pearson correlation coefficients were calculated to explore the relationships of serum 25-hydroxy vitamin D levels with age-adjusted risk factors. A scatter plot demonstrated the relationship between serum 25-hydroxy vitamin D levels and self-reported sitting time. The association between serum 25-hydroxy vitamin D levels and self-reported sitting time was assessed by multivariate linear regression with adjustment for age, sex, waist circumference, low-density lipoprotein, triglycerides, and smoking and drinking status. (3) Results: We analyzed the data from 396 participants. A total of 41.4% of participants were male, and the average age of all participants was 64.91 (±8.80) years. The participants in the high serum 25-hydroxy vitamin D group were more likely to have shorter self-reported sitting time. Serum 25-hydroxy vitamin D was negatively correlated (Pearson's r) with self-reported sitting time, even after adjustment for age. According to the results of multivariate linear regression, vitamin D levels showed a negative association with self-reported sitting time (β = -0.131, p = 0.006) after adjustment for age, sex, waist circumference, low-density lipoprotein, triglycerides, and smoking and drinking status. (4) Conclusions: According to our research, self-reported sitting time was inversely correlated with serum 25-hydroxy vitamin D in middle-aged and elderly people in Taiwan. Meanwhile, longer self-reported sitting time can be an independent risk factor for lower serum 25-hydroxy vitamin D levels.

Background: Spinal cord stimulation (SCS) is an important pain treatment modality. This study hypothesized that a novel pulsed ultrahigh-frequency spinal cord stimulation (pUHF-SCS) could safely and effectively inhibit spared nerve injury-induced neuropathic pain in rats., Methods: Epidural pUHF-SCS (± 3V, 2-Hz pulses comprising 500-kHz biphasic sinewaves) was implanted at the thoracic vertebrae (T9 to T11). Local field brain potentials after hind paw stimulation were recorded. Analgesia was evaluated by von Frey-evoked allodynia and acetone-induced cold allodynia., Results: The mechanical withdrawal threshold of the injured paw was 0.91 ± 0.28 g lower than that of the sham surgery (24.9 ± 1.2 g). Applying 5-, 10-, or 20-min pUHF-SCS five times every 2 days significantly increased the paw withdrawal threshold to 13.3 ± 6.5, 18.5 ± 3.6, and 21.0 ± 2.8 g at 5 h post-SCS, respectively (P = 0.0002, < 0.0001, and < 0.0001; n = 6 per group) and to 6.1 ± 2.5, 8.2 ± 2.7, and 14.3 ± 5.9 g on the second day, respectively (P = 0.123, 0.013, and < 0.0001). Acetone-induced paw response numbers decreased from pre-SCS (41 ± 12) to 24 ± 12 and 28 ± 10 (P = 0.006 and 0.027; n = 9) at 1 and 5 h after three rounds of 20-min pUHF-SCS, respectively. The areas under the curve from the C component of the evoked potentials at the left primary somatosensory and anterior cingulate cortices were significantly decreased from pre-SCS (101.3 ± 58.3 and 86.9 ± 25.5, respectively) to 39.7 ± 40.3 and 36.3 ± 20.7 (P = 0.021, and 0.003; n = 5) at 60 min post-SCS, respectively. The intensity thresholds for pUHF-SCS to induce brain and sciatic nerve activations were much higher than the therapeutic intensities and thresholds of conventional low-frequency SCS., Conclusions: Pulsed ultrahigh-frequency spinal cord stimulation inhibited neuropathic pain-related behavior and paw stimulation evoked brain activation through mechanisms distinct from low-frequency SCS., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Background: Epidural analgesia is a common technique for managing perioperative and obstetric pain. Patients with cancer who cannot tolerate opioids or not responding to conventional treatment may benefit from epidural analgesia. Therefore, this systematic review aimed to analyze the efficacy and safety of epidural analgesia in patients with intractable cancer pain., Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify studies on patients with cancer who received epidural analgesia. We assessed the quality of all included studies using the risk-of-bias tool or Newcastle-Ottawa scale. The primary outcome was pain relief after epidural analgesia, and the secondary outcome was quality of life, analgesic consumption, and adverse events. The studies were grouped based on the medications used for epidural analgesia. A descriptive synthesis was performed following the Synthesis Without Meta-analysis reporting guideline., Results: Our systematic review included nine randomized controlled trials (n = 340) and 15 observational studies (n = 926). Two randomized controlled trials suggested that epidural opioids were not superior to systemic opioids in relieving pain. Epidural opioids combined with local anesthetics or adjuvants, including calcitonin, clonidine, ketamine, neostigmine, methadone, and dexamethasone, offered better analgesic effects. No significant difference in pain relief between an intermittent bolus and a continuous infusion of epidural morphine was observed. Epidural opioids had more analgesic effects on nociceptive pain than neuropathic pain. The methods used to evaluate the quality of life and the corresponding results were heterogeneous among studies. Six observational studies demonstrated that some patients could have decreased opioid consumption after epidural analgesia. Adverse events, including complications and drug-related side effects, were reported in 23 studies. Five serious complications, such as epidural abscess and hematoma, required surgical management. The heterogeneity and methodological limitations of the studies hindered meta-analysis and evidence-level determination., Conclusion: Coadministration of epidural opioids, local anesthetics, and adjuvants may provide better pain relief for intractable cancer pain. However, we must assess the patients to ensure that the benefits outweigh the risks before epidural analgesia. Therefore, further high-quality studies are required., (© 2023 World Institute of Pain.)

Introduction: Alveolar epithelial regeneration depends on the activity of resident quiescent progenitor cells. Alveolar epithelial type II (AT2) cells are known as the alveolar epithelial progenitor cells. They exit quiescent state, proliferate rapidly in response to injury and differentiate into alveolar epithelial type I (AT1) cells to regenerate the damaged alveolar epithelium. Although AT2 cell plasticity has been a very intense field of research, the role of CD8 T cell response and their released cytokine IFN-γ, in regulating AT2 cell plasticity and alveolar epithelial repair and regeneration after injury remains largely unknown., Methods: We used flow cytometry to quantify the amount of CD8 T cells in mouse lungs after bacterial pneumonia caused by Streptococcus pneumoniae . To determine whether CD8 T cells and their released cytokine IFN-γ are necessary for AT2 cell activity during alveolar epithelial regeneration, we performed loss of function studies using anti-CD8 or anti-IFN-γ monoclonal antibody (mAb) treatment in vivo . We assessed the effects of CD8 T cells and cytokine IFN-γ on AT2 cell differentiation capacity using the AT2- CD8 T cell co-culture system in vitro ., Results: We detected a transient wave of accumulation of CD8 T cells in mouse lungs, which coincided with the burst of AT2 cell proliferation during alveolar epithelial repair and regeneration in mice following bacterial pneumonia caused by Streptococcus pneumoniae . Depletion of CD8 T cells or neutralization of cytokine IFN-γ using anti-CD8 or anti-IFN-γ monoclonal antibody significantly reduced AT2 cell proliferation and differentiation into AT1 cells in mice after bacterial pneumonia. Furthermore, co-culture of CD8 T cells or cytokine IFN-γ with AT2 cells promoted AT2-to-AT1 cell differentiation in both murine and human systems. Conversely, blockade of IFN-γ signaling abrogated the increase in AT2-to-AT1 cell differentiation in the AT2- CD8 T cell co-culture system., Discussion: Our data demonstrate that CD8 T-cell response and cytokine IFN-γ are necessary for promoting AT2 cell activity during alveolar epithelial repair and regeneration after acute lung injury caused by bacterial pneumonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Ali, Pantuck, Yang, Lin, Bahmed, Kosmider and Tian.)

Challenges associated with drug-releasing stents used in percutaneous transluminal coronary angioplasty (PTCA) encompass allergic reactions, prolonged endothelial dysfunction, and delayed stent clotting. Although absorbable stents made from magnesium alloys seem promising, fast in vivo degradation and poor biocompatibility remain major challenges. In this study, zirconia (ZrO 2 ) layers were used as the foundational coat, while calcium phosphate (CaP) served as the surface layer on unalloyed magnesium specimens. Consequently, the corrosion current density was decreased to 3.86, from 13.3 μA/cm 2 . Moreover, a heparin-controlled release mechanism was created by co-depositing CaP, gelatin (Gel), and heparin (Hep) on the specimens coated with CaP/ZrO 2 , thereby boosting magnesium's blood compatibility and prolonging the heparin-releasing time. Techniques like X-ray diffractometry (XRD), focused ion beam (FIB) system, toluidine blue testing, UV-visible spectrometry, field emission scanning electron microscopy (FESEM), and surrogate tests for endothelial cell viability were employed to examine the heparin-infused coatings. The drug content rose to 484.19 ± 19.26 μg/cm 2 in multi-layered coatings (CaP-Gel-Hep/CaP-Hep/CaP/ZrO 2 ) from 243.56 ± 55.18 μg/cm 2 in a single layer (CaP-Hep), with the controlled release spanning beyond 28 days. Also, cellular viability assessments indicated enhanced biocompatibility of the coated samples relative to those without coatings. This suggests the potential of magnesium samples after coating ZrO 2 and CaP with Gel as candidates for porous biodegradable stents or even scaffolds in biomedical applications.

This study intends to assess the analgesic effects, physical facilitation, and safety of willow bark use in patients with arthritis. Our study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for relative randomized controlled trials (RCTs) describing the efficacy or adverse events of willow bark in patients with arthritis until 12 April 2023. We used Cochrane ROB 2.0 and the Grading of Recommendations, Assessment, Development, and Evaluations system to evaluate the quality of studies and evidence. The meta-analysis was carried out by the fix-effects model. This study included five studies with six RCTs consisting of 329 patients with arthritis. The results showed significant differences in pain relief and improvement in physical status for patients with arthritis between willow bark treatment and placebo groups, and no significant differences in the risk of all adverse events in patients with arthritis between willow bark treatment and placebo. Owing to the potential bias, the certainty and evidence of our findings are still inadequate. Therefore, further RCTs are needed to confirm our results.

Objective : The aim of this study was to determine whether modern congruent tibial inserts are associated with superior outcomes in total knee arthroplasty (TKA). Background : Ultracongruent fixed-bearing (UCFB) and medial congruent fixed-bearing (MCFB) inserts have been known to be effective in total knee arthroplasty with patient satisfaction. Nonetheless, no supporting evidence to date exists to rank the clinical outcomes of these various congruent inserts in TKA compared with other important considerations in TKA including cruciate-retaining fixed-bearing (CRFB) and posterior-stabilized fixed-bearing (PSFB) inserts. Methods : We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and Scopus up to 15 May 2022. We selected studies involving an active comparison of UCFB or MCFB in TKAs. We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs) and compared different congruent inserts. We ranked the clinical outcomes by SUCRA score with the estimate of the best treatment probability. Our primary outcomes were revision rates and radiolucent lines. Secondary outcomes were functional scores, including the range of motion (ROM), the Knee Society Score (KSS), the Oxford Knee Score (OKS), and WOMAC. Results : Eighteen RCTs with 1793 participants were analyzed. Our NMA ranked MCFB, CRFB, and UCFB with the lowest revision rates. CRFB and UCFB had the fewest radiolucent lines. UCFB had overall the best ROM. UCFB and MCFB had the best OKS score overall. Conclusions : The ranking probability for better clinical outcomes in congruent inserts demonstrated the superiority of congruent tibial inserts, including UCFB and MCFB. UCFB may be associated with better ROM and postoperative functional outcomes. However, integrating future RCTs for high-level evidence is necessary to confirm these findings.

Background: The management of knee osteoarthritis involves various treatment strategies. It is important to explore alternative therapies that are both safe and effective. Collagen peptides have emerged as a potential intervention for knee osteoarthritis. This study aims to evaluate the analgesic effects and safety of collagen peptide in patients diagnosed with knee osteoarthritis., Methods: We conducted a systematic literature search following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases including PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published up to 27 May 2023 that focused on the analgesic outcomes and adverse events associated with collagen peptides or hydrolyzed collagen in patients with osteoarthritis. We assessed the quality of the included studies and the strength of evidence using the Cochrane ROB 2.0 tool and Grading of Recommendations, Assessment, Development, and Evaluations., Results: Four trials involving 507 patients with knee osteoarthritis were included and analyzed using the random-effects model. All these trials were considered to have a high risk of bias. Our results revealed a significant difference in pain relief between the collagen peptide group and the placebo group in patients with knee osteoarthritis (standardized mean difference: - 0.58; 95% CI - 0.98, - 0.18, p = 0.004; I2: 68%; quality of evidence: moderate). However, there was no significant difference in the risk of adverse events between collagen peptide and placebo (odds ratio: 1.66; 95% CI 0.99, 2.78, p = 0.05; I2: 0%; quality of evidence: very low)., Conclusions: Our findings demonstrate significant pain relief in patients with knee osteoarthritis who received collagen peptides compared to those who received placebo. In addition, the risk of adverse events did not differ significantly between the collagen peptide group and the placebo group. However, due to potential biases and limitations, well-designed randomized controlled trials are needed to validate and confirm these findings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Due to the change in the structure of the proximal femur and acetabulum in patients with developmental dysplasia of the hip, total hip arthroplasty (THA) was difficult to perform for surgeons. To elevate the acetabular coverage rate, we developed a technique in the use of a patient-specific instrumentation (PSI) graft in patients with developmental dysplasia of hip (DDH) undergoing surgery. This study aims to evaluate the peri-operative outcomes of THA with PSI graft in patients with DDH. This study recruited 6 patients suffering from Crowe I DDH with secondary Grade IV osteoarthritis. All the patients underwent THA with PSI graft performed by a well-experienced surgeon. Perioperative outcomes included surgical procedures, blood loss during operation, the volume of blood transfusion, length of hospitalization, complications, and the mean difference in hemoglobin levels before and after surgery. All the outcomes analyzed were assessed by mean and standard deviation. The average duration of the surgical procedure was found to be 221.17 min, with an SD of 19.65 min. The mean blood loss during the operation was 733.33 mL, with an SD of 355.90 mL. The mean length of hospital stay was calculated to be 6 days, with an SD of 0.89 days. Furthermore, the mean difference between the pre- and postoperative hemoglobin levels was 2.15, with an SD of 0.99. A total of three patients received 2 units of leukocyte-poor red blood cells (LPR) as an accepted blood transfusion. There were no reported complications observed during the admission and one month after the operation. This study reported the peri-operative outcomes in the patients with DDH who underwent THA with PSI graft. We found that THA with PSI graft would provide a safe procedure without significant complications. We assumed that the PSI graft in THA may increase the coverage rate of the acetabulum, which may increase the graft union rates. Further cohort studies and randomized controlled trials were needed to confirm our findings.

The retinal vasculature supplies oxygen and nutrition to the cells and is crucial for an adequate retinal function. In myopia, excessive eye growth is associated with various anatomical changes that can lead to myopia-related complications. However, how myopia-induced ocular growth affects the integrity of the aged retinal microvasculature at the cellular level is not well understood. Here, we studied how aging interacts with myopia-induced alteration of the retinal microvasculature in fourteen marmoset retinas ( Callithrix jacchus ). String vessel and capillary branchpoint were imaged and quantified in all four capillary plexi of the retinal vasculature. As marmosets with lens-induced myopia aged, they developed increasing numbers of string vessels in all four vascular plexi, with increased vessel branchpoints in the parafoveal and peripapillary retina and decreased vessel branchpoints in the peripheral retina. These myopia-induced changes to the retinal microvasculature suggest an adaptive reorganization of the retinal microvascular cellular structure template with aging and during myopia development and progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Toychiev, Ablordeppey, Basciano, Srinivas and Benavente-Perez.)

Objectives: The aim of this study was to develop a deep-learning pipeline for the measurement of pericardial effusion (PE) based on raw echocardiography clips, as current methods for PE measurement can be operator-dependent and present challenges in certain situations., Methods: The proposed pipeline consisted of three distinct steps: moving window view selection (MWVS), automated segmentation, and width calculation from a segmented mask. The MWVS model utilized the ResNet architecture to classify each frame of the extracted raw echocardiography files into selected view types. The automated segmentation step then generated a mask for the PE area from the extracted echocardiography clip, and a computer vision technique was used to calculate the largest width of the PE from the segmented mask. The pipeline was applied to a total of 995 echocardiographic examinations., Results: The proposed deep-learning pipeline exhibited high performance, as evidenced by intraclass correlation coefficient (ICC) values of 0.867 for internal validation and 0.801 for external validation. The pipeline demonstrated a high level of accuracy in detecting PE, with an area under the receiving operating characteristic curve (AUC) of 0.926 (95% CI: 0.902-0.951) for internal validation and 0.842 (95% CI: 0.794-0.889) for external validation., Conclusion: The machine-learning pipeline developed in this study can automatically calculate the width of PE from raw ultrasound clips. The novel concepts of moving window view selection for image quality control and computer vision techniques for maximal PE width calculation seem useful in the field of ultrasound. This pipeline could potentially provide a standardized and objective approach to the measurement of PE, reducing operator-dependency and improving accuracy., Competing Interests: C-HH was employed by Skysource Technologies Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Cheng, Wu, Chen, Hung, Chen, Lin and Chiu.)

In the present study, Fe 1.1 (Cr x Mn 1-x ) 1.9 O 4 nanoparticles (0 ≤ x ≤ 0.5) were successfully synthesized by a combustion method, and the influence of Cr substitution on the structural and magnetic properties of the obtained nanoparticles was studied by various methods. The structural analysis revealed that the sample with x = 0 has a tetragonal structure, while all Cr-doped samples crystallize into a cubic structure. Additionally, the results of TEM show that doping with chromium leads to an increase in particle size. The magnetic hysteresis loops demonstrate the behavior typical for soft magnetic materials with low coercivity and remanence magnetization. The magnetic measurements revealed that the saturation magnetization of the obtained nanoparticles demonstrates a decreasing trend with increasing Cr content. The influence of chromium doping on the observation change in saturation magnetization is discussed. Based on the results of temperature-dependent magnetization measurements, it was found that the temperature of a magnetic transition in synthesized nanoparticles depends on Cr content.

Background: Posterior tibial plateau fractures can lead to significant posttraumatic instability if not treated properly. It remains unclear which surgical approach achieves better patient outcomes. The objective of this systematic review and meta-analysis was to assess postoperative outcomes in patients undergoing anterior, posterior, or combined approach for posterior tibial plateau fractures., Methods: The PubMed, Embase, Web of Science, The Cochrane Library, and Scopus were searched for studies published before October 26, 2022, comparing anterior, posterior, or combined approaches for posterior tibial plateau fractures. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Outcomes included complications, infections, range of motion (ROM), operation time, union rates, and functional scores. Significance was set at p < 0.05. Meta-analysis was conducted with STATA software., Results: In total, 29 studies with a total of 747 patients were included for quantitative and qualitative analysis. Compared with other approaches, the posterior approach for posterior tibial plateau fractures was associated with a better ROM and shorter operative time. The complication rates, infection rates, union time, and hospital for special surgery (HSS) scores were not significantly different between surgical approaches., Conclusions: The posterior approach for posterior tibial plateau fractures offers advantages such as improved ROM and shorter operative time. However, there are concerns regarding prone positioning in patients with medical or pulmonary comorbidities and indications in polytrauma cases. Further prospective studies are needed to determine the optimal approach for these fractures., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/A969)., (Copyright © 2023 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Water reuse from wastewater sources still remain some critical safety concerns associated with treacherous contaminants like pathogenic viruses. In this study, viral diversities in campus wastewater (CWW) and its reclaimed water (RCW) recycled for toilet flushing and garden irrigation of a university dormitory were assessed using metagenomic sequencing for acquisition of more background data. Results suggested majority (>80%) of gene sequences within assembled contigs predicted by open reading frame (ORF) finder were no-hit yet believed to be novel/unrevealed viral genomic information whereas hits matched bacteriophages (i.e., mainly Myoviridae, Podoviridae, and Siphoviridae families) were predominant in both CWW and RCW samples. Moreover, few pathogenic viruses (<1%) related to infections of human skin (e.g., Molluscum contagiosum virus, MCV), digestion system (e.g., hepatitis C virus, HCV), and gastrointestinal tract (e.g., human norovirus, HuNoV) were also noticed raising safety concerns about application of reclaimed waters. Low-affinity interactions of particular viral exterior proteins (e.g., envelope glycoproteins or spike proteins) for disinfectant ligand (e.g., chlorite) elucidated treatment limitations of current sewage processing systems even with membrane bioreactor and disinfectant contactor. Revolutionary disinfection approaches together with routine monitoring and new regulations are prerequisite to secure pathogen-correlated water quality for safer reuse of reclaimed waters., 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. Published by Elsevier Ltd.)

Introduction: Association between sugammadex and risk of postoperative nausea and vomiting remains unclear., Evidence Acquisition: We performed meta-analysis of randomized controlled trials with trial sequential analysis to compare sugammadex with neostigmine in adults receiving elective surgery under general anesthesia with postoperative extubation. Databases of MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to April 15, 2022. Primary outcome was risk of postoperative nausea and vomiting after patients received sugammadex or neostigmine. Secondary outcomes were incidences of sugammadex-related complications., Evidence Synthesis: Meta-analysis of 40 trials with 5455 patients showed an overall lower risk of postoperative nausea and vomiting in the sugammadex group than in the neostigmine group (risk ratio: 0.85, 95% CI [0.76-0.94], heterogeneity I2=4%, P=0.002). Subgroup analyses demonstrated a lower risk of postoperative nausea and vomiting associated with sugammadex than with neostigmine: 1) in the postanesthesia care unit (risk ratio: 0.77, 95% CI [0.66-0.90], I2=8%, P=0.001) but not in wards; 2) under volatile anesthetics but not total intravenous anesthesia; 3) regardless of the administration of prophylactic antiemetics; and 4) when sugammadex was administered at 2 mg/kg but not 4 mg/kg. No major complications such as cardiac arrest or refractory bradycardia were noted and every patient achieved adequate neuromuscular recovery before extubation in all of the included trials. The overall quality of evidence was moderate., Conclusions: Sugammadex was associated with a lower risk of postoperative nausea and vomiting compared with neostigmine immediately after surgery, especially for patients receiving volatile anesthetics regardless of the use of prophylactic antiemetics.

Leydig cell tumor is the most frequent non-germ cell tumors of testis. The biggest challenge of using radiotherapy to treat testicular cancer is in effectively killing cancer cells and maintaining reproductive function after treatment. Our recently published article showed that cordycepin could enhance radiosensitivity to induce mouse Leydig tumor cell apoptosis by inducing cell cycle arrest, caspase pathway and endoplasmic reticulum (ER) stress. In the present study, the potency and mechanism of a previous combination treatment protocol on reactive oxygen species (ROS) induction and DNA damage were further investigated. Our results reveal that 25 μM cordycepin plus 4 Gy radiation leads to ROS accumulation accompanied by a decrease in heme oxygenase (HO)-1 protein expression in MA-10 mouse Leydig tumor cells. Subsequently, pronounced DNA damage with phosphorylated H2A histone family member X (γ-H2AX) increase and activation of DNA damage-related signaling pathways including double and single stranded break-induced ataxia telangiectasia mutated (ATM)/checkpoint kinase (Chk)2 and ataxia telangiectasia mutated and Rad3 related (ATR)/Chk1 signaling axes were identified. p53-dependent pathway was then initiated ultimately leading to cell death. Preincubated with free radical scavenger, N-acetylcysteine (NAC), down-regulated γ-H2AX expression in treated cells and partially reduced cell death, indicating that ROS overproduction is involved in combination treatment-induced DNA damage. Furthermore, the combination treatment effectively inhibited tumor growth as reflected in the reduction of tumor volume, size and weight, and high expression level of γ-H2AX in tumor tissue in vivo , suggesting that the combination treatment inhibited tumor growth via causing DNA damage in MA-10 cells. In summary, these results expound that the combination treatment of cordycepin and radiation induces MA-10 mouse Leydig tumor cell death through ROS accumulation and DNA damage. This finding can serve as a reference guideline for future clinical therapy of testicular cancer and provide potential targets for anti-cancer drug design., Competing Interests: None., (AJCR Copyright © 2023.)

Several risk factors are related to glycemic control in patients with type 2 diabetes mellitus (T2DM), including demographics, medical conditions, negative emotions, lipid profiles, and heart rate variability (HRV; to present cardiac autonomic activity). The interactions between these risk factors remain unclear. This study aimed to use machine learning methods of artificial intelligence to explore the relationships between various risk factors and glycemic control in T2DM patients. The study utilized a database from Lin et al. (2022) that included 647 T2DM patients. Regression tree analysis was conducted to identify the interactions among risk factors that contribute to glycated hemoglobin (HbA1c) values, and various machine learning methods were compared for their accuracy in classifying T2DM patients. The results of the regression tree analysis revealed that high depression scores may be a risk factor in one subgroup but not in others. When comparing different machine learning classification methods, the random forest algorithm emerged as the best-performing method with a small set of features. Specifically, the random forest algorithm achieved 84% accuracy, 95% area under the curve (AUC), 77% sensitivity, and 91% specificity. Using machine learning methods can provide significant value in accurately classifying patients with T2DM when considering depression as a risk factor.