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DEAD-box RNA helicase 3 (DDX3) and its homologs play a vital role in translation initiation by unwinding secondary structures of selected mRNAs. The human DDX3 gene is located on the sex chromosomes, so there are DDX3X and DDX3Y. DDX3X is ubiquitously expressed in almost all tissues and critical for embryonic development, whereas DDX3Y is only expressed in the testis and essential for male fertility. Drosophila belle (bel) is the single ortholog of DDX3, and mutations in bel cause male and female infertility. Using Drosophila bel mutants and Ddx3x conditional knockout (cKO) mice, we confirmed the pivotal role of DDX3 in female fertility and ovarian development. Drosophila bel mutants exhibited female infertility and immature egg chambers. Consistently, oocyte-specific Ddx3x knockout in mice resulted in female infertility and impaired oogenesis. We further found that immature egg chambers in Drosophila bel mutants and impaired follicular development in oocyte-specific Ddx3x cKO mice were caused by excessive apoptosis. We also identified a set of DDX3 target genes involved in oocyte meiosis and maturation and demonstrated that DDX3 is involved in their translation in human cells. Our results suggest that DDX3 is critical for female fertility via translational control in oogenesis., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval All animal studies were carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the NIH. The experimental procedures using mice were reviewed and approved by the Institutional Animal Care and Use Committee at Chang Gung University, Taiwan (IACUC:CGU110-208)., (© 2024. The Author(s).)

Background: Systemic Janus kinase inhibitors (JAKi) and dupilumab both have emerged as promising therapeutics for atopic dermatitis (AD). Dupilumab has a favorable safety profile, but oral JAKi therapy has been established in other diseases that carry potential comorbid susceptibilities that influence safety., Objective: We sought to provide real-world evidence of the comparative safety of oral JAKi versus dupilumab in patients with AD., Methods: The study used observational data from multiple healthcare organizations in the US. Patients with AD treated with either oral JAKi (upadacitinib, abrocitinib, and baricitinib) or dupilumab were enrolled. The 2 treatment groups were propensity score matched 1:1 on the basis of demographics, comorbidities, and prior medications. Safety outcomes within 2 years after the initiation of medications were measured by hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: A total of 14,716 patients were included, with 942 patients treated with oral JAKi and 13,774 with dupilumab. The 2 treatment groups respectively included 938 patients after matching. Treatment with oral JAKi was not associated with increased risks of mortality, malignancies, major adverse cardiovascular events, venous thromboembolism, renal events, or serious gastrointestinal events. However, patients receiving oral JAKi showed significantly higher risks of skin and subcutaneous tissue infection (HR = 1.35, 95% CI = 1.07-1.69), herpes infection (herpes simplex, HR = 1.64, 95% CI = 1.03-2.61; herpes zoster, HR = 2.51, 95% CI = 1.14-5.52), acne (HR = 2.09, 95% CI = 1.54-2.84), cytopenia (anemia, HR = 1.83, 95% CI = 1.39-2.41; neutropenia, HR = 4.02, 95% CI = 1.91-8.47; thrombocytopenia, HR = 1.76, 95% CI = 1.08-2.89), and hyperlipidemia (HR = 1.45, 95% CI = 1.09-1.92); the risk of ophthalmic complications was higher in those receiving dupilumab (HR = 1.49, 95% CI = 1.03-2.17)., Conclusion: Oral JAKi did not exhibit concerning safety issues in treating patients with AD but increased the risk of infections and abnormalities in laboratory findings. Long-term follow-up data are required to validate these results., Competing Interests: Disclosure statement M.O. was supported by grants NIH/NIAID R01 AI142872, R01 AI172938, and R21 AI151591. W.P. was supported by grant NIH/NIAID K24 AI106822. Disclosure of potential conflict of interest: E. B. Hawryluk is on the advisory board of Apogee; consults for Skin Analytics; and receives royalties from UpToDate as an author and reviewer. L. C. Schneider is an investigator for Regeneron and DBV Technologies; and is on the advisory boards of Sanofi, Triveni Bio, DBV, Alladapt Immunotherapeutics, BioThea Pharmaceuticals, Ukko, Leo Pharmaceuticals, DAIT/NIAID, and the National Eczema Association. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

A healthy lifespan relies on independent living, in which active skeletal muscle is a critical element. The cost of not recognizing and acting earlier on unhealthy or aging muscle could be detrimental, since muscular weakness is inversely associated with all-cause mortality. Sarcopenia is characterized by a decline in skeletal muscle mass and strength and is associated with aging. Exercise is the only effective therapy to delay sarcopenia development and improve muscle health in older adults. Although numerous interventions have been proposed to reduce sarcopenia, none has yet succeeded in clinical trials. This review evaluates the biological gap between recent clinical trials targeting sarcopenia and the preclinical studies on which they are based, and suggests an alternative approach to bridge the discrepancy., Competing Interests: Declaration of interests The author declares no competing interests., (Copyright © 2024 The Author. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

The recent unprecedented progress in ageing research and drug discovery brings together fundamental research and clinical applications to advance the goal of promoting healthy longevity in the human population. We, from the gathering at the Aging Research and Drug Discovery Meeting in 2023, summarised the latest developments in healthspan biotechnology, with a particular emphasis on artificial intelligence (AI), biomarkers and clocks, geroscience, and clinical trials and interventions for healthy longevity. Moreover, we provide an overview of academic research and the biotech industry focused on targeting ageing as the root of age-related diseases to combat multimorbidity and extend healthspan. We propose that the integration of generative AI, cutting-edge biological technology, and longevity medicine is essential for extending the productive and healthy human lifespan.

Vinca alkaloids, a class of tubulin-binding agent, are widely used in treating cancer, yet the emerging resistance compromises their efficacy. Hepatoma up-regulated protein (HURP), a microtubule-associated protein displaying heightened expression across various cancer types, reduces cancer cells' sensitivity to vinca-alkaloid drugs upon overexpression. However, the molecular basis behind this drug resistance remains unknown. Here we discover a tubulin-binding domain within HURP, and establish its role in regulating microtubule growth. Cryo-EM analysis reveals interactions between HURP's tubulin-binding domain and the vinca domain on β-tubulin -- the site targeted by vinca alkaloid drugs. Importantly, HURP competes directly with vinorelbine, a vinca alkaloid-based chemotherapeutic agent, countering microtubule growth defects caused by vinorelbine both in vitro and in vivo. Our findings elucidate a mechanism driving drug resistance in HURP-overexpressing cancer cells and emphasize HURP tubulin-binding domain's role in mitotic spindle assembly. This underscores its potential as a therapeutic target to improve cancer treatment., (© 2024. The Author(s).)

This cross-sectional study examined sleep disturbance associations between parents and their school-age children with overweight and obesity. A 7-day wrist-worn actigraph recording was performed on 246 children aged 6-9 years with overweight and obesity recruited from 10 public elementary schools in Taipei, Taiwan. Children's sleep disturbance was assessed using the Children's Sleep Habits Questionnaire. Parental subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index, with parental depressive symptoms measured using the Epidemiologic Studies-Depression Scale. General linear models were used to examine sleep disturbance associations within parent-child dyads. The results showed that 208 (84.6%) children had a clinically significant sleep disturbance score, and 123 (50%) parents had poor sleep quality. Higher children's sleep disturbance scores significantly predicted poorer parental sleep quality (b = 0.11, p < 0.001). Poorer parental sleep quality was associated with more severe sleep disturbances in children (b = 0.46, p < 0.001). This association was independent of children's actigraphic sleep (all p > 0.05) and was not attenuated by adjustment for parental depressive symptoms (b = 0.14, p < 0.001). Findings from our study suggest that sleep disturbances occur in both parents and their school-age children with overweight and obesity, with a significant bidirectional association between the two. Nurses and healthcare professionals should proactively assess and screen for sleep disturbances in parent-child dyads of children with overweight and obesity. Future studies should develop family-based sleep interventions and evaluate their effects on the sleep, health, and well-being of children with overweight and obesity and their parents., (© 2024 Wiley Periodicals LLC.)

Background: Dupilumab is the first and only biologic agent approved for the treatment of atopic dermatitis (AD) in pediatric patients aged from 6 months to 17 years. The study aimed to evaluate the impact of dupilumab on the occurrence of comorbidities in pediatric patients with AD., Methods: In this population-based cohort study, we utilized electronic health records from multiple healthcare organizations across the United States. Pediatric patients (<18 years of age) with a diagnosis of AD initiating dupilumab were propensity-score matched 1:1 to those initiating other systemic agents (azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, or systemic corticosteroids). The primary outcomes were new-onset comorbidities emerging during the study period measured by the risk ratio (RR) and its confidence interval (CI). Subgroup analyses were stratified by age (0-5 years, 6-11 years, and 12-17 years), sex, and race., Results: A total of 3575 pediatric patients with AD treated with dupilumab were matched to 3575 patients treated with other systemic agents. The dupilumab cohort was associated with a lowered risk of new-onset atopic comorbidities (including asthma [RR, 0.72; 95% CI, 0.59-0.89] and allergic rhinitis [RR, 0.62; 95% CI, 0.52-0.74]), infections (e.g., skin and soft tissue infection [RR, 0.70; 95% CI, 0.63-0.76] and respiratory tract infection [RR = 0.56; 95% CI, 0.51-0.61]), psychiatric disorders (e.g., mood disorder [RR, 0.52; 95% CI, 0.39-0.70] and anxiety [RR, 0.57; 95% CI, 0.46-0.70], sleep disturbance [RR, 0.60; 95% CI, 0.47-0.77]), neurologic and developmental disorders (e.g., attention deficit hyperactivity disorder [RR, 0.54; 95% CI, 0.38-0.75]). Furthermore, the positive effects are found to be more pronounced in younger children (aged 0-5 years) with AD., Conclusions: Treatment with dupilumab compared to systemic agents resulted in reductions in AD-related comorbidities in pediatric patients., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case-control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies., Methods: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000-2012. The case group comprised patients with severe sepsis after their first psychiatric admission ( n  = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic-severe sepsis associations., Results: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin-angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk., Conclusion: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients., 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.

Atemoya ( Annona cherimola × Annona squamosa ) is a specialty crop in Taiwan. Thermal treatment induces bitterness, complicating seasonal production adjustments and surplus reduction. In this research, sensory-guided separation, metabolomics, and orthogonal partial least squares discrimination analysis (OPLS-DA) are used for identifying the bitterness in atemoya which originates from catechins, epicatechin trimers, and proanthocyanidins. Different thermal treatments (65 °C, 75 °C, and 85 °C) revealed that the glucose and fructose contents in atemoya significantly decreased, while total phenols, flavonoids, and tannins significantly increased. The concentration of 5-hydroxymethylfurfural (5-HMF) increased from 23.16 ng/g in untreated samples to 400.71 ng/g (AP-65), 1208.59 ng/g (AP-75), and 2838.51 ng/g (AP-85). However, these levels are below the 5-HMF bitterness threshold of 3780 ng/g. Combining mass spectrometry analysis with sensory evaluation, OPLS-DA revealed that atemoya treated at 65 °C, 75 °C, and 85 °C exhibited significant bitterness, with the main bitter components being proanthocyanidin dimers and trimers., Competing Interests: None., (© 2024 The Authors.)

Introduction: Spontaneous bacterial peritonitis (SBP) bacteriology has changed over time. Reappraisal of primary SBP prophylaxis showed an increased rate of resistance in patients on primary prophylaxis with resultant discontinuation of this prophylaxis throughout the Veterans Affairs (VA). We aimed to re-evaluate the risk-benefit ratio of secondary SBP prophylaxis (SecSBPPr)., Methods: Using validated International Classification of Diseases-9/10 codes, we used the VA Corporate Data Warehouse and the Non-VA National TriNetX database to identify patients in 2 different large US systems who survived their first SBP diagnosis (with chart review from 2 VA centers) between 2009 and 2019. We evaluated the prevalence of SecSBPPr and compared outcomes between those who started on SecSBPPr vs not., Results: We identified 4,673 veterans who survived their index SBP episode; 54.3% of whom were prescribed SecSBPPr. Multivariable analysis showed higher SBP recurrence risk in those on vs off SecSBPPr (hazards ratio 1.63 [1.40-1.91], P < 0.001). This was accompanied by higher fluoroquinolone resistance odds in SecSBPPr patients (odds ratio = 4.32 [1.36-15.83], P = 0.03). In TriNetX, we identified 6,708 patients who survived their index SBP episode; 48.6% were on SecSBPPr. Multivariable analysis similarly showed SecSBPPr increased SBP recurrence risk (hazards ratio 1.68 [1.33-1.80], P < 0.001). Both data sets showed higher SBP recurrence trends over time in SecSBPPr patients. Results remained consistent at 6-month and 2-year timepoints., Discussion: In 2 national data sets of >11,000 patients with SBP, we found that SecSBPPr was prescribed in roughly half of patients. When initiated, SecSBPPr, compared with no prophylaxis after SBP, increased the risk of SBP recurrence in multivariable analysis by 63%-68%, and this trend worsened over time. SecSBPPr should be reconsidered in cirrhosis., (Copyright © 2024 by The American College of Gastroenterology.)

Abstract: It is well known that oligodendrocyte-associated Nogo-A protein is an important regulator of axonal outgrowth and an important inhibitor of functional recovery and anatomical plasticity after central nervous system (CNS) injury. Abundant studies of oligodendrocyte-associated Nogo-A function in the uninjured rodent have suggested a role in neuronal development and synaptic function. On the other hand, the roles of neuron-associated (i.e., neuronal) Nogo-A have not been fully investigated. We have previously shown that neuronal Nogo-A influence dendritic spine density and morphology in pyramidal neurons of the intact neocortex. To further examine the role of neuronal Nogo-A in this synaptic population, we designed an RNAi directed against Nogo-A, delivered to the developing rat sensorimotor cortex using a neurotropic viral vector adeno-associated virus (AAV) 2/8. We examined the transduced neocortex for molecules important for synaptic plasticity, including N-Methyl-D-Aspartate (NMDA) receptor subunits GRIN2A; glutamate receptor subunit epsilon-1 (NR2A), and GRIN2B; glutamate receptor subunit epsilon-2 (NR2B), as well as postsynaptic density-95 (PSD-95). Furthermore, we also determined the density of excitatory synapses by examining the presynaptic protein vesicular glutamate transporter 1 (vGLut1) as a marker for potential excitatory synapses. Our results showed that neuronal Nogo-A knockdown in postnatal pyramidal neurons of the sensorimotor cortex led to a significant decrease in NMDA receptor subunits NR2A and NR2B messenger RNA when examined as adults. However, there was no difference in PSD-95 expression in comparison to controls. In addition, the decrease in the number of vGlut1(+) puncta on branches of apical dendrites of pyramidal neurons indicated the loss of synapses that have a strong influence on direct current entering the dendrite. Taken together, these results indicate that neuronal Nogo-A may regulate synaptic plasticity by modulating the components of excitatory synapses. This finding represents a novel role in excitatory synaptic formation for neuronal Nogo-A in developing neurons of the uninjured CNS., (Copyright © 2024 Copyright: © 2024 Journal of Physiological Investigation.)

Background: Limited research has delved into the effects of work characteristics on premenstrual symptoms (PMS) in women, which can influence work performance and overlook potential hazards for women in their work environments. This study aimed to investigate the impact of shift work and working in a clean room on premenstrual symptoms, menstrual status, and menstrual pain among employed females in an electronics manufacturer., Methods: A retrospective cohort study was conducted on menstruating female employees between August and December 2014, aged 18-55, who received regular employee health checks. Questionnaires were designed to collect information on demographics, personal lifestyle, menstrual status, menstrual pain scores, and self-reported premenstrual symptoms., Results: Among 7,193 participants, 18.6% reported moderate to severe menstrual pain affecting their work. Female workers who reported shift work showed an increased prevalence of moderate to severe premenstrual symptoms, including fatigue (RR = 1.20), somatic discomforts (RR = 1.04), diarrhea (RR = 1.04), and tension (RR = 1.05). Additionally, shift work was associated with an elevated risk of experiencing a moderate or significant impact of menstrual pain on work (RR = 1.03), menstrual irregularity (RR = 1.30), and high menstrual pain (RR = 1.23). Working in a clean room was associated with an increased risk of high menstrual pain (RR = 1.13). Subjects working shifts in a clean room had the highest pain scores compared to the other groups., Conclusion: This study underscores the association of work-related factors on PMS in female employees. Our findings contribute to a better understanding of premenstrual symptoms in female workers with different work characteristics, emphasizing the potential hazards of work-related factors on female employees., Competing Interests: The authors have no proprietary interest in any aspect of the study., (© 2024 Occupational Safety and Health Research Institute. Published by Elsevier B.V. on behalf of Institute, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency.)

Background and Purpose: Radiomics offers little explainability. This study aims to develop a radiomics model (Rad-Score) using diffusion-weighted imaging (DWI) to predict high-risk patients for nodal metastasis or recurrence in endometrial cancer (EC) and corroborate with choline metabolism., Materials and Methods: From August 2015 to July 2018, 356 EC patients were enrolled. Rad-Score was developed using LASSO regression in a training cohort (n = 287) and validated in an independent test cohort (n = 69). MR spectroscopy (MRS) was also used in 230 patients. Nuclear MRS measured choline metabolites in 70 tissue samples. The performance was compared against European Society for Medical Oncology (ESMO) risk groups. A P < .05 denoted statistical significance., Results: Rad-Score achieved 71.1% accuracy in the training and 71.0% in the testing cohorts. Incorporating clinical parameters of age, tumor type, size, and grade, Rad-Signature reached accuracies of 73.2% in training and 75.4% in testing cohorts, closely matching the performance to the post-operatively based ESMO's 70.7% and 78.3%. Rad-Score was significantly associated with increased total choline levels on MRS (P = .034) and tissue levels (P = .019)., Conclusions: Development of a preoperative radiomics risk score, comparable to ESMO clinical standard and associated with altered choline metabolism, shows translational relevance for radiomics in high-risk EC patients., Trial Registration: This study was registered in ClinicalTrials.gov on 2015-08-01 with Identifier NCT02528864., (© 2024. The Author(s).)

This article describes the application of transition theory to assist a family with an infant with congenital complex gastroschisis. The nursing period, from March 3, 2023 to May 9, 2023, encompassed care from hospitalization to discharge. The author employed transition theory as a guide and used physical assessments, observations, and interviews for data collection as well as behavioral processes records. The primary nursing problem was identified as "preparation for family operation process enhancement/child's congenital disease and complex care needs, and the family's response to the challenges of the disease and care adaptation." The three phases of nursing care were summarized as: (1) the family adjustment to uncertainty, (2) undertaking caregiving roles and responsibilities, and (3) role development and family reconnection. The author established specific goals for each phase and provided corresponding interventions for the family. In the first phase, the author guided the family in expressing their concerns, and offered personalized health education information as well as psychological support to help them understand the progression of their child's disease and alleviate related anxiety and confusion. In the second phase, the author offered sleep guidance and customized home care schedules to support coping skill development and role functioning. In the third phase, the family was encouraged to explore the meaning of life while accompanying their child's growth in order to achieve spiritual growth and deepen the reconnection within the family. Ultimately, the family strengthened their confidence and capabilities in caregiving and embraced optimism and expectations for the future, enabling them to adapt smoothly to life after their child's return home. When families are confronted with their child's diagnosis with a congenital disease, they often find themselves in a state of self-doubt and faced with continuous challenges. Nurses may employ transition theory throughout the nursing process to better understand and address the evolving needs of both children and their families during the transition phase. Furthermore, transition theory may be applied to help nurses better assess, plan, and care for their patients, which can enhance the capabilities of families and facilitate their successful navigation through the challenging transition journey.

This randomized controlled trial was conducted to assess the effectiveness of a family-based and mobile-assisted lifestyle intervention in reducing weight gain among school-age children with overweight and obesity. A total of 164 school-age children with overweight or obesity and their parents were randomized to the treatment intervention (n = 82) or an attention-control group (n = 82). The treatment intervention included three face-to-face education sessions, augmented by monthly text messages sent to parents on their mobile devices. The primary outcome was child BMI-for-age z-score. Secondary outcomes included child BMI, percent body fat, and actigraphy-assessed sleep as well as parental sleep quality. Outcomes were assessed at baseline, 3, 6, and 12 months after the intervention, with treatment effects analyzed using general linear models for repeated measures. Our results showed that children in the treatment intervention group had significantly lower BMI-for-age z score, BMI, and percent body fat than did those in the control group, with an adjusted mean difference of 0.31 units (95% CI: -0.59 to -0.03; p = 0.03), 1.34 kg/m ² (95% CI, -2.42 to -0.26; p = 0.01), and 3.12% (95% CI, -5.93 to -0.30; p = 0.03), respectively. No treatment effects were observed for child and parental sleep. Our findings suggest that family-based and mobile-assisted lifestyle intervention results in significant and sustained benefits to enhanced weight management for school-age children with overweight and obesity. Nurses planning and delivering childhood overweight and obesity treatment interventions should consider a family-based approach with the assistance of mobile devices., (© 2024 Wiley Periodicals LLC.)

Background: Individuals with schizophrenia face high mortality risks. The effects of lipid-modifying agents on this risk remain understudied., Aim: This study was conducted to investigate the effects of lipid-modifying agents on mortality risk in people with schizophrenia., Method: This nationwide cohort study collected the data of people with schizophrenia from Taiwan's National Health Insurance Research Database for the period between 1 January 2001 and 31 December 2019. Multivariable Cox proportional hazards regression with a time-dependent model was used to estimate the hazard ratio for mortality associated with each lipid-modifying agent., Results: This study included 110 300 people with schizophrenia. Of them, 22 528 died (19 754 from natural causes and 1606 from suicide) during the study period, as confirmed using data from Taiwan's national mortality database. The use of lipid-modifying agents was associated with reduced risks of all-cause (adjusted hazard ratio [aHR]:0.37; P < 0.001) and natural (aHR:0.37; P < 0.001) mortality during a 5-year period. Among the lipid-modifying agents, statins and fibrates were associated with reduced risks of all-cause mortality (aHRs:0.37 and 0.39, respectively; P < 0.001 for both) and natural mortality (aHRs: 0.37 and 0.42, respectively; P < 0.001 for both). Notably, although our univariate analysis indicated an association between the use of lipid-modifying agents and a reduced risk of suicide mortality, the multivariate analysis revealed no significant association., Conclusions: Lipid-modifying agents, particularly statins and fibrates, reduce the risk of mortality in people with schizophrenia. Appropriate use of lipid-modifying agents may bridge the mortality gap between these individuals and the general population.

Background: Chronic fatigue syndrome (CFS) has been linked to several conditions, including infections, immune system changes, or emotional stress. Our study aimed to assess the risk of CFS after a pneumonia diagnosis using data from National Health Insurance Research Database of Taiwan., Methods: In this nested case-control study, we identified 2,000,000 adult patients from a nationwide population-based health insurance claims database spanning from January 1, 2000, to December 31, 2017. Each case diagnosed with a pathogenic infection was matched with a corresponding control using propensity scores. We excluded individuals under 20 years of age, those with a history of pathogenic infections before the index date, or those with more than one potential pathogen. To estimate hazard ratios (HR) and the adjusted hazard ratio (aHR) with their respective 95 % confidence intervals (CI), we applied univariable and multivariable Cox proportional hazard models. The multivariable analysis incorporated adjustments for age, sex, and comorbidity-related confounders., Results: The relationship between infection and the subsequent risk of CFS was assessed using Cox proportional hazards regression analysis. The incidence density rates were 6.13 and 8.70 per 1000 person-years among the non-pulmonary infection and pulmonary infection populations, respectively (adjusted hazard ratio [HR] = 1.4, 95 % confidence interval [CI] 1.32-1.5). Patients infected with Pseudomonas, Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, and influenza virus exhibited a significantly higher risk of CFS than those without these pathogens (p < 0.05). Additionally, patients with pneumonia had a significantly increased risk of thromboembolism compare with control group (p < 0.05)., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Individuals with bipolar disorder (BD) face a high risk of heart failure and left ventricular (LV) dysfunction. Despite strong evidence that high LV relative wall thickness (RWT) is a risk marker for heart failure, few studies have evaluated LV RWT and aggravating factors in individuals with BD., Methods: We recruited 104 participants (52 patients with BD and 52 age- and sex-matched mentally healthy controls) to undergo echocardiographic imaging and biochemistry, high-sensitivity C-reactive protein (hs-CRP), and blood cell count measurements. LV RWT was estimated using the following equation: (2 × LV posterior wall end-diastolic thickness)/LV end-diastolic diameter. Clinical data were obtained through interviews and chart reviews., Results: The BD group exhibited a significantly greater LV RWT (Cohen's d = 0.53, p = 0.003) and a less favorable mitral valve E/A ratio (Cohen's d = 0.54, p = 0.023) and LV global longitudinal strain (Cohen's d = 0.57, p = 0.047) than did the control group. Multiple linear regression revealed that in the BD group, serum triglyceride levels (β = 0.466, p = 0.001), platelet-to-lymphocyte ratios (β = 0.324, p = 0.022), and hs-CRP levels (β = 0.289, p = 0.043) were all significantly and positively associated with LV RWT., Limitations: This study applied a cross-sectional design, meaning that the direction of causation could not be inferred., Conclusions: Patients with BD are at a risk of heart failure, as indicated by their relatively high LV RWT. Lipid levels and systemic inflammation may explain this unfavorable association., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Metabolic-associated fatty liver disease (MAFLD) is predominantly associated with metabolic disturbances representing aberrant liver function and increased uric acid (UA) levels. Growing evidences have suggested a close relationship between metabolic disturbances and the gut microbiota. A placebo-controlled, double-blinded, randomized clinical trial was therefore conducted to explore the impacts of daily supplements with various combinations of the probiotics, Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 with a focus on liver function and serum UA levels. Test subjects with abnormal levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and UA were recruited and randomly allocated into six groups. Eighty-two participants successfully completed the 60-day intervention without any dropouts or occurrence of adverse events. The serum AST, ALT, and UA levels were significantly reduced in all treatment groups (P < 0.05). The fecal microbiota analysis revealed the intervention led to an increase in the population of commensal bacteria and a decrease in pathobiont bacteria, especially Bilophila wadsworthia. The in vitro study indicated the probiotic treatments reduced lipid accumulation and inflammatory factor expressions in HepG2 cells, and also promoted UA excretion in Caco-2 cells. The supplementation of multi-strain probiotics (TSF331, TSR332, and TSP05) together can improve liver function and UA management and may have good potential in treating asymptomatic MAFLD. Trial registration. The trial was registered in the US Library of Medicine (clinicaltrials.gov) with the number NCT06183801 on December 28, 2023., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Glac Biotech Co., Ltd. provided financial support in the form of salaries for [J.-H.L., C.-H.L., Y.-W.K., J.-F.C., S.-Y.T., C.-M.L., Y.-C.H., Y.-Y.H., K.-C.H., H.-H.H.], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Our skin provides a protective barrier that shields us from our environment. Barrier function is typically associated with the interfollicular epidermis; however, whether hair follicles influence this process remains unclear. Here, we utilize a potent genetic tool to probe barrier function by conditionally ablating a quintessential epidermal barrier gene, Abca12, which is mutated in the most severe skin barrier disease, harlequin ichthyosis. With this tool, we deduced 4 ways by which hair follicles modulate skin barrier function. First, the upper hair follicle (uHF) forms a functioning barrier. Second, barrier disruption in the uHF elicits non-cell-autonomous responses in the epidermis. Third, deleting Abca12 in the uHF impairs desquamation and blocks sebum release. Finally, barrier perturbation causes uHF cells to move into the epidermis. Neutralizing IL-17a, whose expression is enriched in the uHF, partially alleviated some disease phenotypes. Altogether, our findings implicate hair follicles as multi-faceted regulators of skin barrier function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The roles of endogenous stress hormones (norepinephrine, epinephrine, and cortisol) in cardiovascular diseases have been discussed. However, the higher versus lower level of stress hormones in relation to cardiovascular risks remained uncertain., Methods: We searched databases from their inception to 31, March 2023. We conducted a meta-analysis to estimate the effect of higher to lower level of stress hormones with random effect model. Subgroup and meta-regression analysis were done to clarify the heterogeneity., Results: In total, 33 studies involving 43641 participants were included. With regard to cardiovascular disease risks, a higher risk for individuals with higher level of all stress hormones (risk ratio (RR), 1.63; 95 % Confidence intervals (CIs): 1.36, 1.97) was noted compared with lower level of all stress hormones. The meta-regression showed that as the follow-up year increased per year, the impact of higher level of all stress hormones on the risk of cardiovascular disease declined significantly (RR, -0.09; 95 % CIs: 0.15, -0.03, p = 0.006). A significantly higher risk of cardiovascular diseases for individuals with higher level of norepinephrine (RR, 1.68; 95 % CIs: 1.37, 2.06), with higher level of epinephrine (RR, 1.58; 95 % CIs: 1.10, 2.26), and with higher level of cortisol (RR, 1.60; 95 % CIs: 1.04, 2.26) were noted compared with a lower level of each stress hormone., Conclusion: Higher levels of stress hormones were significantly associated with higher risks of cardiovascular diseases compared with lower levels of stress hormones., Competing Interests: The authors declare no potential conflicts of interest., (© 2024 The Authors.)

Peritoneal fibrosis, a common complication observed in long-term peritoneal dialysis patients, can gradually lead to ultrafiltration failure and the development of encapsulating peritoneal sclerosis. Although mechanisms of peritoneal fibrosis have been proposed, effective therapeutic options are unsatisfactory. Recently, several tyrosine kinase inhibitors have proven to be anti-fibrosis in rodent models. To assess the potential therapeutic effects of tyrosine kinase inhibitors on peritoneal fibrosis in the larger animal model, a novel porcine model of peritoneal fibrosis induced by 40 mM methylglyoxal in 2.5 % dialysate was established, and two different doses (20 mg/kg and 30 mg/kg) of sorafenib were given orally to evaluate their therapeutic efficacy in this study. Our results showed that sorafenib effectively reduced adhesions between peritoneal organs and significantly diminished the thickening of both the parietal and visceral peritoneum. Angiogenesis, vascular endothelial growth factor A production, myofibroblast infiltration, and decreased endothelial glycocalyx resulting from dialysate and methylglyoxal stimulations were also alleviated with sorafenib. However, therapeutic efficacy in ameliorating loss of mesothelial cells, restoring decreased ultrafiltration volume, and improving elevated small solutes transport rates was limited. In conclusion, this study demonstrated that sorafenib could potentially be used for peritoneal fibrosis treatment, but applying sorafenib alone might not be sufficient to fully rescue methylglyoxal-induced peritoneal defects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Quantification of metabolites concentrations in institutional unit (IU) is important for inter-subject and long-term comparisons in the applications of magnetic resonance spectroscopy (MRS). Recently, deep learning (DL) algorithms have found a variety of applications on the process of MRS data. A quantification strategy compatible to DL base MRS spectral processing method is, therefore, useful., Materials and Methods: This study aims to investigate whether metabolite concentrations quantified using a convolutional neural network (CNN) based method, coupled with a scaling procedure that normalizes spectral signals for CNN input and linear regression, can effectively reflect variations in metabolite concentrations in IU across different brain regions with varying signal-to-noise ratios (SNR) and linewidths (LW). An error index based on standard error (SE) is proposed to indicate the confidence levels associated with metabolite predictions. In vivo MRS spectra were acquired from three brain regions of 43 subjects using a 3T system., Results: The metabolite concentrations in IU of five major metabolites, quantified using CNN and LCModel, exhibit similar ranges with Pearson's correlation coefficients ranging from 0.24 to 0.78. The SE of the metabolites shows a positive correlation with Cramer-Rao lower bound (CRLB) (r=0.46) and  absolute CRLB (r=0.81), calculated by multiplying CRLBs with the quantified metabolite content., Conclusion: In conclusion, the CNN based method with the proposed scaling procedures can be employed to quantify in vivo MRS spectra and derive metabolites concentrations in IU. The SE can be used as error index, indicating predicted uncertainties for metabolites and sharing information similar to the absolute CRLB., (© 2023. The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

Background: Pediatric longitudinal melanonychia (LM) can exhibit atypical features that mimic red-flag signs for subungual melanoma in adults and lead to diagnostic uncertainty. Nail biopsy may be unnecessary if clinical inspection and dermoscopy suggest a benign nature., Methods: We searched PubMed and Embase from inception to February 2023 for studies of any design reporting either the number or proportion of clinical and dermoscopic features in at least five children (≤18 years) with LM. Non-English articles, reviews, and abstracts were excluded. We performed a systematic review and meta-analysis to collate all existing data., Results: A total of 1218 articles were screened and 24 studies with 1391 pediatric patients were included. Nevus was the most common diagnosis (86.3%). The most prevalent sites were fingernails (76.2%) and first digits (45.4%). Pooled proportions of common features were: dark-color bands (69.8%), multi-colored bands (47.6%), broad bandwidth (41.1%), pseudo-Hutchinson sign (41.0%), irregular patterns (38.1%), Hutchinson sign (23.7%), dots and globules (22.5%), nail dystrophy (18.2%), and triangular sign (10.9%). Outcomes included progression (widening or darkening, 29.9%), stability (23.3%), and spontaneous regression (narrowing or fading, 19.9%). Only eight cases of subungual melanoma in situ were reported, and no invasive melanomas were identified., Conclusion: Although atypical characteristics are common in pediatric LM, the probability of malignant transformation is exceedingly low. Appropriate evaluation and management of pediatric LM includes careful clinical and dermoscopic inspection with attention to benign features followed by long-term interval follow-up., (© 2024 Wiley Periodicals LLC.)

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO 2max ), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion ( p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage ( p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 ( p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.

Background: During the COVID-19 pandemic, visitation restrictions in line with infection control policies curtailed opportunities for family members to learn essential caregiving skills in the intensive care unit. This limitation decreased satisfaction among family members, possibly indicating their increased difficulties in care due to the lack of face-to-face guidance. Thus, increasing family member understanding of and ability to apply learning content without direct interaction presents a significant and urgent challenge. Moreover, because of lack of caregiving confidence, some family members may be reluctant to facilitate the discharge of critically ill patients, causing delays in discharge planning. These challenges underscore the obstacles faced by nursing health education during the pandemic., Purpose: This study was designed to utilize cloud technology to enhance the knowledge and skills of families caring for infants with congenital heart disease at home and to assess their satisfaction with the associated homecare learning platform., Resolution: Based on our hospital's cloud-based health education platform, a series of personalized instructional video materials was developed for families of infants with congenital heart disease. These materials cover comprehensively the entire treatment process, from diagnosis to post-discharge home care skills, for these patients. To facilitate autonomous learning, the videos in this series were made accessible to the families anytime, anywhere via personal devices such as smartphones and tablets. Concurrently, a chatbot tool was integrated to provide guidance on inpatient care for infants with congenital heart disease, including fundamental aspects of newborn care, with the aim of equipping parents and caregivers with the knowledge and skills necessary to provide basic post-discharge care. To ensure the families acquired personalized care skills, after completing the learning modules, practical bedside training sessions incorporating knowledge and skills assessments were organized for family members., Results: After project implementation, the average knowledge score for family members increased significantly from 79.1 to 100 (perfect score). The proportion of family members proficient in executing caregiving techniques autonomously also rose impressively from 30% to 95%. Furthermore, average overall satisfaction with cloud-based technology-assisted caregiving learning among the family members rose 31.4% from 3.5 to 4.6., Conclusions: This project represents a viable solution to providing clinical nursing guidance independent of the constraints of time and location, and effectively enhances homecare-skill-related learning outcomes in family members, especially with regard to caring for infants with congenital heart disease.

Aim: Clozapine is indicated as the last-line agent for the treatment of refractory schizophrenia due to its side effects. This study included an Asian schizophrenia population and investigated the effect of clozapine on the risks of all-cause, natural, and suicide mortality., Methods: This study included a large-scale schizophrenia inpatient cohort derived from the National Health Insurance Research Database from January 1, 2001, to December 31, 2019 (n = 43,025). Of them, we selected those who received clozapine (clozapine cohort, n = 5800). From those who never used clozapine, we selected two individuals for each patient in the clozapine cohort by matching by age, sex, and the year of the index date (ratio: 1:2, control cohort, n = 11,583). The clozapine and nonclozapine control cohorts together were defined as the study cohort (n = 17,383). Multivariate Cox proportional-hazards regression with a time-dependent model was performed to investigate the effect of individual antipsychotic agents on mortality., Results: All individual first-generation antipsychotics were not associated with mortality risk. However, most individual second-generation antipsychotics exerted protective effects against all-cause and natural mortality. Furthermore, only clozapine and risperidone were significantly associated with a low risk of suicide mortality. Only clozapine exhibited a dose-dependent relationship with all-cause, natural, and suicide mortality., Conclusions: This study provides robust evidence supporting the strong protective effect of clozapine on all-cause, suicide, and natural mortality risks in an Asian population. Under close monitoring, clozapine use can be advantageous in patients with schizophrenia who are at a high risk of suicide., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Poor body composition may affect health status, and better body composition is often associated with better academic performance. Nursing students face heavy academic and practical pressures, and the relationship between body composition and academic performance in this group is not fully understood., Methods: This cross-sectional observational study used de-identified student data from a university of technology in southern Taiwan to analyze the correlation between body composition characteristics and academic performance using regression models., Results: A total of 275 nursing college students were divided into four groups according to academic performance. The group with the lowest academic performance had a lower percentage of body fat (P < 0.05) but a higher percentage of muscle mass (P < 0.05) than the other three groups. Academic performance was positively correlated with percentage of body fat (R = 0.16, P < 0.01) and body age (R = 0.41, P < 0.01), but was negatively correlated with percentage of muscle mass (R = - 0.16, P < 0.01). Percentage of body fat, visceral fat area, and body age were significant discriminators of academic performance (P < 0.05)., Conclusions: The relationship between academic performance and body composition among nursing college students is not straightforward. Contrary to our initial hypothesis, students with higher academic performance tended to have a higher percentage of body fat and a lower percentage of muscle mass. Percentage of body fat, visceral fat area, and body age were significant discriminators of academic performance, indicating that body composition should be considered an important factor in nursing education and practice., (© 2024. The Author(s).)

Sleep disturbances in children with epilepsy are prevalent, and are associated with substantial adverse medical and psychosocial consequences. This study is a 5-year follow-up of a clinic-based sleep intervention study that randomized 100 toddlers and preschool-age children with epilepsy to a usual care group or a sleep intervention group. The intervention group received standard paediatric neurology care plus three education sessions during the child's routine clinic visit. The outcomes measured were: (1) child sleep by actigraphy and parental report; and (2) maternal sleep and depression. We aimed to evaluate the long-term benefits of a clinic-based sleep intervention for paediatric epilepsy. In total, 42 families (42.0%) participated. The average child's age at follow-up was 9.55 years. Thirty-eight (90.5%) children were not obtaining sufficient sleep at baseline, and 40 (95.2%) at the 5-year follow-up. The numbers of children with clinically significant sleep disturbances were 40 (95.2%) at baseline and 36 (85.7%) at the 5-year follow-up. Fourteen mothers (33.3%) had poor sleep quality and high depressive symptoms at both assessment time points. There were no differences (P > 0.05) in the child and maternal outcomes between the two trial arms. Overall, there was no evidence that a clinic-based sleep intervention that effectively improved multiple aspects of sleep in toddlers and preschool-age children with epilepsy had long-lasting beneficial effects. Our findings suggest that sleep interventions for families of children with epilepsy require ongoing reinforcement and monitoring during routine paediatric neurology care to prevent sleep problems from persisting or recurring., (© 2023 European Sleep Research Society.)

Background: Parenting self-efficacy is essential for the transition to parenthood. As digital parenting educational interventions are rapidly being developed, their effects have not been examined by pooling available randomized controlled trials (RCTs)., Objectives: To comprehensively investigate the effects of digital educational interventions on parents' self-efficacy, social support, and depressive symptoms in the first year after childbirth and identify the significant associated factors., Methods: This study searched six electronic databases for relevant RCTs examining the efficacy of digital parenting interventions from inception to September 2022. The studied outcomes included changes in parent's self-efficacy, social support, and depressive symptoms observed after participating in a digital parenting program. The random-effects model was used to pool results. Subgroup and moderator analyses were performed., Results: In total, seven RCTs enrolling 1342 participants were included. The parents who received digital parenting interventions had higher parenting self-efficacy (standardized mean difference [SMD]: 1.06, 95 % confidence interval [CI]: 0.40-1.71, p =.002) and social support (SMD: 2.72, 95 % CI: 0.38-5.07, p =.02) and decreased depressive symptoms at 3 months postpartum (SMD: -0.39, 95 % CI: -0.73 to - 0.04, p =.03). Providing the interventions for ≥ 6 weeks (SMD: 1.62, 95 % CI: 1.18-2.06, p <.001), providing in-person orientation (SMD: 1.88, 95 % CI: 1.32-2.44, p <.001), including a guided curriculum (SMD: 2.00, 95 % CI: 1.78-2.22, p <.001), and conducting interventions in Organisation for Economic Co-operation and Development countries (SMD: 1.98, 95 % CI: 1.78-2.19, p <.001) were identified as significant moderators., Conclusions: Digital parenting interventions significantly increase parenting self-efficacy and social support as well as alleviate depressive symptoms for parents during their first year after childbirth. Such interventions can be beneficial for parents who prefer online education. Future studies investigating the long-term effects of these interventions are warranted., Registration: The protocol for this systematic review and meta-analysis is registered in PROSPERO (registration number: CRD42021243641)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The fundamental mechanisms by which a diet affects susceptibility to or modifies autoimmune diseases are poorly understood. Excess dietary salt intake acts as a risk factor for autoimmune diseases; however, little information exists on the impact of salt intake on type 1 diabetes. To elucidate the potential effect of high salt intake on autoimmune diabetes, nonobese diabetic (NOD) mice were fed a high-salt diet (HSD) or a normal-salt diet (NSD) from 6 to 12 weeks of age and monitored for diabetes development. Our results revealed that the HSD accelerated diabetes progression with more severe insulitis in NOD mice in a CD4+ T-cell-autonomous manner when compared with the NSD group. Moreover, expression of IL-21 and SPAK in splenic CD4+ T cells from HSD-fed mice was significantly upregulated. Accordingly, we generated T-cell-specific SPAK knockout (CKO) NOD mice and demonstrated that SPAK deficiency in T cells significantly attenuated diabetes development in NOD mice by downregulating IL-21 expression in CD4+ T cells. Furthermore, HSD-triggered diabetes acceleration was abolished in HSD-fed SPAK CKO mice when compared with HSD-fed NOD mice, suggesting an essential role of SPAK in salt-exacerbated T-cell pathogenicity. Finally, pharmacological inhibition of SPAK activity using a specific SPAK inhibitor (closantel) in NOD mice ameliorated diabetogenesis, further illuminating the potential of a SPAK-targeting immunotherapeutic approach for autoimmune diabetes. Here, we illustrate that a substantial association between salt sensitivity and the functional impact of SPAK on T-cell pathogenicity is a central player linking high-salt-intake influences to immunopathophysiology of diabetogenesis in NOD mice., (© 2024 by the American Diabetes Association.)

Shortening the aging duration and enhancing the functional components of garlic present significant technical challenges that need to be addressed. Thus, this study aimed to evaluate the potential role of pulsed electric field (PEF) treatment, a novel nonthermal food processing method, in promoting and enhancing the functional attributes of aged garlic. Our results showed that 2-4 kV/cm PEF pretreatment increased S-allyl cysteine (SAC), total polyphenol (TPC), and flavonoid contents (TFC) compared with un-pretreated garlic during aging. The browning and texture-softening were also significantly improved during processing time, though the latter showed no significant difference from the eighth day to the end of the aging process. The principal component analysis results showed that PEF positively affects the SAC and TFC formations without adverse effects. Among the PEF pretreatments, 3 kV/cm is the most effective in enhancing functional component production compared with the other PEF pretreatments. Therefore, PEF pretreatment is a time-saving process that promotes and enhances the functionality of aged garlic.

Objective: To explore the potential predictors of people with Parkinson disease (PD) who would benefit the most from treadmill training., Design: A cohort study., Setting: Medical university rehabilitation settings., Participants: Seventy participants diagnosed of idiopathic PD., Interventions: Twelve sessions of treadmill training., Main Outcome Measures: Hierarchical logistic regression models were used to explore significant predictors of the treadmill training effect with respect to 3 health domains: Unified Parkinson's Disease Rating Scales part III (UPDRS III); gait speed; Parkinson's Disease Questionnaire-39 (PDQ-39). A receiver operating characteristic (ROC) curve analysis was conducted to identify proper cut-off points for clinical use., Results: Male sex (adjusted odds ratio [OR]: 3.73, P=.036) significantly predicted the improvement of UPDRS III. Individuals with a slower baseline gait speed (cut-off: 0.92 m/s, adjusted OR: 14.06, P<.001) and higher baseline balance confidence measured by the Activity-specific Balance Confidence scale (cut-off: 84.5 points, adjusted OR: 4.66, P=.022) have greater potential to achieve clinically relevant improvements in gait speed. A poorer baseline PDQ-39 score (cut-off: 23.1, adjusted OR: 7.47, P<.001) predicted a greater quality of life improvement after treadmill training., Conclusions: These findings provide a guideline for clinicians to easily identify suitable candidates for treadmill training. Generalization to more advanced patients with PD warrants further investigation., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

In light of industrial developments, water pollution by heavy metals as hazardous chemicals has garnered attention. Addressing the urgent need for efficient heavy metal removal from aqueous environments, this study delves into using poly-γ-glutamic acid (γ-PGA) for the bioflocculation of heavy metals. Utilizing γ-PGA variants from Bacillus subtilis with different molecular weights and salt forms (Na-bonded and Ca-bonded), the research evaluates their adsorption capacities for copper (Cu), lead (Pb), and cadmium (Cd) ions. It was found that Na-bonded γ-PGA with a high molecular weight showed the highest heavy metal adsorption (92.2-98.3%), particularly at a 0.5% concentration which exhibited the highest adsorption efficiency. Additionally, the study investigated the interaction of γ-PGA in mixed heavy metal environments, and it was discovered that Na-γ-PGA-HM at a 0.5% concentration showed a superior adsorption efficiency for Pb ions (85.4%), highlighting its selectivity as a potential effective biosorbent for wastewater treatment. This research not only enlightens the understanding of γ-PGA's role in heavy metal remediation but also underscores its potential as a biodegradable and non-toxic alternative for environmental cleanup. The findings pave the way for further exploration into the mechanisms and kinetics of γ-PGA's adsorption properties.

We propose and experimentally demonstrate for the first time up to the authors' knowledge a wide field-of-view (FOV) water-to-air optical transmission using rolling-shutter (RS) based optical camera communication (OCC). Here, we evaluate the proposed OCC system without water ripple and with different percentage increases of water ripple. Long short term memory neural network (LSTM-NN) is utilized to mitigate the wavy water turbulence induced link outage and to decode 4-level pulse-amplitude-modulation (PAM4) RS pattern by meeting the pre-forward error correction bit-error-rate (pre-FEC BER = 3.8 × 10 -3 ). We also evaluate the FOVs of the proposed water-to-air RS-based OCC system. This can be implemented by using different angular rotations of the camera. Experimental results show that the proposed OCC system can support ±70°, ± 30°, and ±30° rotations around the z-, y- and x-directions, respectively when operated at 6 kbit/s and decoded using LSTM-NN.

Aim: People with schizophrenia are at a greater risk of poor physical health than the general population. This study investigated the annual incidence of physical illnesses after a new schizophrenia diagnosis, which has rarely been investigated in the literature., Methods: The authors collected data from Taiwan's National Health Insurance Research Database from January 1, 1996, to December 31, 2013, and enrolled 1910 patients with newly diagnosed schizophrenia cases aged 10-40 years and 7640 age- and sex-matched controls from the general population. They estimated the 1-year prevalence and annual incidence rate ratio (IRR) of specified physical diseases across 3 years in the schizophrenia group compared with the controls., Results: Several physical illnesses were prevalent within 1 year of schizophrenia diagnosis. Regarding incident physical illnesses, patients had a moderate to strong risk of numerous physical illnesses (IRR > 3.0: ischemic heart disease, cerebrovascular disease, diabetes mellitus, and cancer; IRR 1.8-3.0: other forms of heart disease, vein and lymphatic diseases, pneumonia, chronic hepatic disease, and ulcer disease) within the first year after schizophrenia diagnosis. The IRRs of most physical illnesses declined over 3 years, except for that of cerebrovascular disease, which significantly increased (IRR > 3.0) over the 3 years after schizophrenia diagnosis. Cerebrovascular disease had a significant incidence risk (IRR > 3) persistently across the 3 years., Conclusion: Various comorbid physical illnesses can occur in the early stages of schizophrenia. Clinicians should consider these vulnerabilities to physical illnesses during the evaluation of patients with newly diagnosed schizophrenia by attempting to prevent, screen for, and manage them., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

One-carbon metabolism plays a crucial role in tumorigenesis as it supplies the one-carbon units necessary for nucleotide synthesis, epigenetic regulation, and redox metabolism, ensuring the rapid proliferation of cancer cells. However, their roles in prostate cancer progression remain poorly understood. In this study, we investigated the association between genetic variants in the one-carbon metabolism pathway and clinical outcomes in patients receiving androgen deprivation therapy for prostate cancer. The associations of 130 single-nucleotide polymorphisms located within 14 genes involved in the one-carbon metabolism pathway with cancer-specific survival (CSS), overall survival, and progression-free survival were assessed using Cox regression in 630 patients with prostate cancer. Subsequently, functional studies were performed using prostate cancer cell lines. After adjusting for covariates and multiple testing, MTHFD1L rs2073190 was found to be significantly associated with CSS ( P = 0.000184). Further pooled analysis of multiple datasets demonstrated that MTHFD1L was upregulated in prostate cancer and increased MTHFD1L expression was positively correlated with tumor aggressiveness and poor patient prognosis. Functionally, MTHFD1L knockdown suppressed prostate cancer cell proliferation and colony formation. RNA sequencing and pathway analysis revealed that differentially expressed genes were predominantly enriched in the cell cycle pathway. In conclusion, genetic variants in MTHFD1L of one-carbon metabolism may serve as promising predictors, and our findings offer valuable insights into the underlying genetic mechanisms of prostate cancer progression., Competing Interests: None., (AJCR Copyright © 2024.)

Mitochondrial division inhibitor 1 (Mdivi-1) is a well-known synthetic compound aimed at inhibiting dynamin-related protein 1 (Drp1) to suppress mitochondrial fission, making it a valuable tool for studying mitochondrial dynamics. However, its specific effects beyond Drp1 inhibition remain to be confirmed. In this study, we employed integrative proteomics and phosphoproteomics to delve into the molecular responses induced by Mdivi-1 in SK-N-BE(2)C cells. A total of 3070 proteins and 1945 phosphorylation sites were identified, with 880 of them represented as phosphoproteins. Among these, 266 proteins and 97 phosphorylation sites were found to be sensitive to the Mdivi-1 treatment. Functional enrichment analysis unveiled their involvement in serine biosynthesis and extrinsic apoptotic signaling pathways. Through targeted metabolomics, we observed that Mdivi-1 enhanced intracellular serine biosynthesis while reducing the production of C24:1-ceramide. Within these regulated phosphoproteins, dynamic dephosphorylation of proteasome subunit alpha type 3 serine 250 (PSMA3-S250) occurred after Mdivi-1 treatment. Further site-directed mutagenesis experiments revealed that the dephosphorylation-deficient mutant PSMA3-S250A exhibited a decreased cell survival. This research confirms that Mdivi-1's inhibition of mitochondrial division leads to various side effects, ultimately influencing cell survival, rather than solely targeting Drp1 inhibition.

Congenital melanocytic nevi (CMN) carry an increased risk of melanoma and may be disfiguring, and consensus regarding treatment recommendations is lacking. While clinical monitoring is the standard of care, many caregivers are interested in its removal to prevent psychosocial burden or to decrease risk. Although melanoma can occur regardless of CMN removal, there are a variety of treatments that may offer improved cosmesis or local symptom control, including surgical excision, laser therapy, and other superficially destructive techniques. Regardless of the selected management, these patients are monitored for ongoing melanoma risk. An extensive discussion with families regarding the risks and benefits of observation versus active intervention is essential. To facilitate these discussions, we herein summarize current CMN management strategies and considerations.

This study investigated the ERK pathway of the peripheral nervous system and discovered a gender-specific pattern of ERK activation in the dorsal root ganglion of an acid-induced chronic widespread muscular pain model. We employed a twice acid-induced chronic musculoskeletal pain model in rats to evaluate mechanical pain behavior in both male and female groups. We further conducted protein analysis of dissected dorsal root ganglions from both genders. Both male and female rats exhibited a similar pain behavior trend, with females demonstrating a lower pain threshold. Protein analysis of the dorsal root ganglion (DRG) showed a significant increase in phosphorylated ERK after the second acid injection in all groups. However, phosphorylation of ERK was observed in the dorsal root ganglion, with higher levels in the male ipsilateral group compared to the female group. Moreover, there was a no difference between the left and right sides in males, whereas the significant difference was observed in females. In conclusions, the administration of acid injections induced painful behavior in rats, and concurrent with this, a significant upregulation of pERK was observed in the dorsal root ganglia, with a greater magnitude of increase in males than females, and in the contralateral side compared to the ipsilateral side. Our findings shed light on the peripheral mechanisms underlying chronic pain disorders and offer potential avenues for therapeutic intervention., 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.

Aim: First grade is a transition from pre-school to school-age. The change in lifestyle behaviours such as sleep may have a physiological response, which contributes to the presence or absence of two highly incident diseases: dental caries or myopia. The aim of the study was to examine the association between sleep and myopia as well as sleep and dental caries in first graders., Design: It is a cross-sectional study., Methods: This was a recruitment phase of an interventional study. A total of 338 children whose caregivers completed a Children's Sleep Habits Questionnaire. Caregivers also provided information regarding myopia and caries status of children and their parents. Binary logistic regression was applied to analyse the potential risk factors., Results: Dental caries and myopia rates were 45.9% and 9.5%, respectively. After adjusting for children's gender, children's age, fathers with caries and mothers with caries, the odds ratio for dental caries in children who slept less than 9 h when compared to those who slept for nine and more hours was 1.94. Mothers with caries were 3.37 times more likely to have children with caries than mothers without caries. However, sleep was not associated with myopia in first graders., Conclusion: Sleeping less than 9 h and maternal caries were risk factors of children developing dental caries. Future sleep and myopia studies can be conducted on higher graders who may present prolonged exposure and accumulations of myopic risk factors., Implications: Screening of children with insufficient sleep is needed for nurses to enable the early identification of high-risk groups for dental caries in school settings. Family nurses are encouraged to work with family members to implement tailored sleep interventions, in order to facilitate better sleep and oral health practices in both school and home settings., Registration: This study protocol was registered on ClinicalTrials.gov (Registration number: Redacted)., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)