Exploring the factor structure of a Chinese version of the CORE-OM: insights from network approach and bifactor modeling.

OBJECTIVE: The Clinical Outcomes in Routine Evaluation (CORE-OM) is a measure of clinical outcomes that has been widely used in mental health research. Nevertheless, the exploration of the factor structure of the CORE-OM yields diverse results. This study aims to explore the factor structure with an innovative method known as exploratory graph analysis (EGA) and supplemented with bifactor modeling. METHOD: A Chinese version of the CORE-OM was administrated to a total of 1361 clinical college students. We first examined the factor structure of the CORE-OM using EGA, and then compared the model derived by EGA with other models using CFA to find the most reasonable model. RESULTS: The result of EGA indicated a four-factor model of CORE-OM. The CFA further suggested a bifactor model with a four-factor structure combined with a general factor. The bifactor modeling suggested a significant proportion of shared variance among the variables was attributed to the general factor. The four-factor bifactor model exhibited a satisfactory fit to the data. CONCLUSION: The results confirm the robustness and parsimonious nature of a four-factor bifactor model for the Chinese version of CORE-OM. It is suitable for measuring intrapersonal psychological distress, positive emotions, interpersonal problems, and risk-related issues among the Chinese population.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Effects of nutritional indices and inflammatory parameters on patients received immunotherapy for non-small cell lung cancer.

OBJECTIVE: This research explored the relationship between a patient's nutritional state and inflammatory markers and the prognosis of their non-small cell lung cancer (NSCLC) treatment while receiving a combination of chemotherapy and immunotherapy. METHOD: This retrospective and single-center analysis included NSCLC patients who received a combination of chemotherapy and immunotherapy at the Department of Oncology at Shanghai Lung Hospital. Patients were categorized based on malnutrition, sarcopenia, sarcopenic obesity, and advanced-lung-cancer-inflammation-index (ALI) scores after collecting nutritional and inflammatory indices. Kaplan-Meier and the Cox models were utilized to analyze survival. RESULTS: There was a significant correlation between malnutrition, sarcopenia, sarcopenic obesity, and low ALI scores with lower overall survival (OS) and progression-free survival (PFS) (p < 0.05). Low ALI score and malnutrition were independent factors influencing patient survival in terms of both OS and PFS (p < 0.01). CONCLUSION: The nutritional and inflammatory indices of immunotherapy-treated NSCLC patients substantially affect their prognosis. Assessing these variables could aid in optimizing treatment strategies and improving patient outcomes. Additional research is required to comprehend the intricate relationship between nutrition, inflammation, and cancer progression and to develop individualized therapies.

CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy.

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with leukoencephalopathy. However, since only three patients from a single family were reported, it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/NUTM2B-AS1. Here, using repeat-primed-polymerase chain reaction and long-read sequencing, we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1, typically presenting with oculopharyngodistal myopathy. The CGG repeat expansions range from 161 to 669 repeat units. Most of the patients present with ptosis, restricted eye movements, dysphagia, dysarthria, and diffuse limb muscle weakness. Only one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance imaging. Muscle biopsies from three patients show a myopathic pattern and rimmed vacuoles. Analyses of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity, suggesting that RNA toxicity and mitochondrial dysfunction may contribute to pathogenesis. Our study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

Adaptation and validation of the Abrams geriatric self-neglect assessment scale among older Chinese people admitted to the hospital.

OBJECTIVES: Elder self-neglect is a global public health problem, and older people admitted to the hospital may have a higher risk of self-neglect due to their deteriorating health conditions. This study aimed to translate, adapt and validate the Abrams geriatric self-neglect assessment scale (AGSS) among older Chinese people admitted to the hospital. METHODS: Data were derived from a cross-sectional survey of a convenience sample of 452 older people admitted to a general hospital. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine the structural validity of the AGSS. Content validity, criterion validity, internal consistency reliability, and test-retest reliability were also conducted to assess the psychometric properties of the scale. RESULTS: EFA yielded a 6-item one-factor model, which was supported by CFA and explained 44.74% of the total variance. The internal consistency was acceptable (Cronbach α = 0.740), and the test-retest reliability with a 14-day interval was good (intraclass correlation coefficient, ICC = 0.966). Significantly positive correlations with the caregiver-rated elder self-neglect assessment scale (r = 0.648) supported the concurrent validity of the scale. Significant differences in scores between respondents with different ages, marital statuses, educational levels and numbers of chronic diseases demonstrated the discriminative validity. CONCLUSION: The Chinese version of the AGSS is an easy-to-use, reliable and valid measure with satisfactory psychometric properties. Future studies should recruit a more representative sample of older people in China to verify the applicability of the scale. IMPLICATIONS FOR PRACTICE: The Chinese version of the AGSS enables clinical staff to accurately screen for and assess elder self-neglect upon hospital admission, which can inform the development of specific interventions and assignment of additional guardianship to those at risk of elder self-neglect.

Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease.

OBJECTIVE: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. METHODS: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays. RESULTS: Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation. INTERPRETATION: Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2023;93:244-256.

Self-neglect among older adults admitted to a Chinese comprehensive hospital in the COVID-19 pandemic era: a cross-sectional study.

This study aims to explore the prevalence of self-neglect and associated factors among older adults admitted to the hospital in the COVID-19 pandemic context. The cross-sectional study conducted at a Chinese comprehensive hospital between January and April 2021, 452 older adults were recruited to complete the Abrams Geriatric Self-Neglect Scale, Social Support Rate Scale, FRAIL scale, Barthel index, Patient Health Questionnaire-9, and 10-item Connor-Davidson Resilience Scale. Multivariate logistic regression was used to explore the factors associated with elder self-neglect. The results showed that the prevalence of self-neglect among our sample was 30.3%. Factors that were associated with the risk of elder self-neglect included male, having multiple children (≥4), receiving infrequent visits from children, frailty, and depression. There is a need to screen for self-neglect among older adults admitted to the hospital in the COVID-19 pandemic context. Tailored interventions are warranted to improve the quality of life of older adults.

Peak expiratory flow is a reliably household pulmonary function parameter correlates with disease severity and survival of patients with amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease; most ALS patients die within 3 to 5 years after symptom onset, usually as a consequence of respiratory failure. In the present study, we aim to screen the survival-related pulmonary function parameters, and to explore the predictive value of peak expiratory flow (PEF) in disease severity and prognosis in patients with ALS. METHODS: The discovery cohort included 202 ALS patients, and the demographic and clinical characteristics of eligible patients were collected and pulmonary function tests were performed using MS-PFT spirometer. In the validation cohort, 62 newly diagnosed ALS patients performed the pulmonary function test by MS-PFT spirometer and household peak flow meter (KOKA) simultaneously. RESULTS: Among 12 pulmonary function parameters, FVC, FEV1, PEF, MEF75%, and MVV were identified to be independent predictive factors for survival. PEF was highly correlated with FVC (r = 0.797), MVV (r = 0.877), FEV1 (r = 0.847), and MEF75% (r = 0.963). Besides, the values of PEF were positively associated with disease severity (ALSFRS-R score, rs = 0.539, P < 0.0001), and negatively associated with progression rate (ΔALSFRS-R, rs = -0.316, P < 0.0001). Finally, we also confirmed that the values of KOKA-measured PEF were highly correlated with the ones measured using MS-PFT spirometer (r = 0.9644, p < 0.0001). CONCLUSIONS: Our work emphasizes the critical role of PFTs in predicting prognosis of ALS patients. PEF is an easily available pulmonary function index, which is also a promising indicator in predicting disease severity and survival for ALS patients.

Effects of Short-Term Unsupervised Exercise, Based on Smart Bracelet Monitoring, on Body Composition in Patients Recovering from Breast Cancer.

OBJECTIVE: We aimed to investigate the effects of exercise, monitored and managed using smart bracelets, on body composition, and quality of life in breast cancer survivors. METHODS: A before-and-after study was conducted in 109 patients who were in the recovery phase of breast cancer and attended the Breast Surgery Department of the Cancer Hospital of Fudan University up to December 2017. Patients were advised to adhere to at least 150 minutes of moderate-intensity exercise per week, and a smart bracelet was issued to each participant to record their daily exercise data for 3 months. Bioelectrical impedance analysis was used to observe the effects of short-term unsupervised exercise intervention on body composition in patients recovering from breast cancer. Patients completed the Functional Assessment of Cancer Therapy-Breast to assess health-related quality of life. RESULTS: Weight, body mass index (BMI), body fat mass (BFM), fat mass index (FMI), percent body fat (PBF), arm circumference (AC), arm muscle circumference (AMC), and visceral fat area (VFA) were lower than baseline after exercising for 3 months based on data from the wearable devices (P < .05). The only significant improvement was found in the "additional concerns about breast cancer" category among the quality-of-life assessments (P < .05). The average walking time was negatively associated with BFM, PBF, and FMI, while the average calorie consumption due to running was positively associated with fat free mass (FFM). CONCLUSION: In this study, we demonstrated that short-term exercise may be beneficial for postoperative breast cancer survivors. A wearable device could help patients track physical data easily and promote a healthier and more positive life.

Family Resilience, Parenting Styles and Psychosocial Adjustment of Children With Chronic Illness: A Cross-Sectional Study.

Objectives: To evaluate the level of parent-reported family resilience, parenting styles and psychosocial adjustment of children with chronic illness and to identify the relationships between family resilience, parenting styles and psychosocial adjustment in families with children with chronic illness. Methods: A cross-sectional study was conducted between June 2019 and August 2019. A total of 236 parents of children with chronic illness and 98 parents with healthy children were recruited from general hospitals by convenience sampling. A parent completed the Chinese Family Resilience Assessment Scale, the Parenting Rearing Patterns Questionnaire and the Strengths and Difficulties Questionnaire. Family resilience, parenting styles, and psychosocial adjustment of children with chronic illness were compared with those of healthy children. Structural Equation Modeling (SEM) was performed to explore the mediation effect of parenting styles between family resilience and psychosocial adjustment among children with chronic illness. Results: Parents of children with chronic illness reported lower level of family resilience and authoritative parenting, but more peer relationship problems compared to parents of healthy children. SEM showed that authoritative parenting fully mediated the relationship between family resilience and psychosocial adjustment of children with chronic illness. Conclusion: Childhood chronic illness reduces family resilience, authoritative parenting and children's psychosocial adjustment, but authoritative parenting mediated these effects, so authoritative parenting may be important for family resilience in families of children with chronic illness. Pediatric clinicians and nurses should provide family-centered interventions, as well as parenting training, to improve children's psychosocial outcomes.

Serum Uric Acid Levels Predict Mortality Risk in Male Amyotrophic Lateral Sclerosis Patients.

Objective: To explore the associations between serum uric acid levels with survival in male and female ALS patients. Methods: A longitudinal cohort study was carried out including 313 sporadic and 16 familial ALS patients with repeated serum uric acid measurements. Multivariate Cox regression models were used to evaluate the survival-related factors. Results: There were 207 male and 122 female, and the mean age of onset was 55.7 ± 11.2 years old. The male patients had significantly higher baseline uric acid levels than that in female patients (342.4 ± 91.4 vs. 279.3 ± 71.4 µmol/L; p < 0.0001). The uric acid levels were inversely associated with the decline rate of ALSFRS-R per month (ΔALSFRS-R). After multivariate Cox regression analysis, a survival advantage was found in male, but not female, with higher serum uric acid levels. In males, a shorter diagnostic delay (≤10 m), lower BMI at baseline (≤18.70 kg/m2), faster disease progression (ΔALSFRS-R > 0.63), and lower baseline uric acid levels (≤292 µmol/L, HR: 1.936; 95% CI: 1.334-2.810) were associated with a shorter survival. During follow-up, the serum uric acid levels were not significantly altered over time. Conclusion: There is an inverse correlation between baseline serum uric acid levels and risk of death, prominently in male ALS patients.

Decreased serum creatinine levels predict short survival in amyotrophic lateral sclerosis.

OBJECTIVE: To explore the associations between serum creatinine and creatine kinase (CK) levels with survival in male and female ALS patients. METHODS: A prospective cohort study was carried out including 346 ALS patients with repeated serum creatinine and CK measurements. Kaplan Meier analysis and multivariable Cox regression were used to perform survival analysis. RESULTS: There were 218 male and 128 female patients, and the males had significantly higher baseline serum creatinine and CK levels than females. After multivariable Cox regression analysis, lower baseline serum creatinine levels were associated with a short survival in both male (≤61 µmol/L, HR: 1.629; 95%CI: 1.168-2.273) and female ALS patients (≤52 µmol/L, HR: 1.677; 95%CI: 1.042-2.699), whereas, the serum CK levels were not correlated with survival. Besides, creatinine levels were positively associated with ALSFRS-R scores, and inversely with the decline rate of ALSFRS-R per month. During follow-up, serum creatinine levels tended to be decreased along with the disease progression, and the higher decline rate of creatinine per month (>1.5) showed significantly shorter survival, compared to the lower group (≤1.5) (30.0 months vs. 65.0 months, Chi square = 28.25, P < 0.0001). INTERPRETATION: Serum creatinine could be a reliable and easily accessible prognostic chemical marker for ALS, and decreased baseline creatinine levels could predict a poor prognosis and a short survival in both male and female ALS patients.

Evaluation of SORD mutations as a novel cause of Charcot-Marie-Tooth disease.

Biallelic mutations in the sorbitol dehydrogenase (SORD) encoding gene were recently identified as a common genetic cause in autosomal-recessive CMT patients. Here, we investigated the clinical, genetic, and electrophysiological characteristics of three CMT patients with biallelic SORD mutations from a Chinese cohort. Two patients harbored c.757delG (p.A253Qfs*27) homozygous mutations, and one patient carried both c.757delG (p.A253Qfs*27) and c.625C>T (p.R209X) compound heterozygous mutations. Interestingly, the two patients homozygous for the c.757delG mutation exhibited positive responses for pinprick test. In conclusion, we confirmed SORD mutations as causative for CMT and further expanded the mutational and phenotypic spectrum of SORD-related CMT.

Relationship of childhood trauma, psychological resilience, and family resilience among undergraduate nursing students: A cross-sectional study.

PURPOSE: To analyze how family resilience mediates the relationship between childhood trauma and psychological resilience in undergraduate nursing students. DESIGN AND METHODS: A cross-sectional survey design was used to investigate 698 nursing undergraduate students (mean age: 18.77 ± 0.86 years) using the Childhood Trauma Questionnaire, Family Resilience Assessment Scale, and Connor-Davidson Resilience Scale. The mediating effect of family resilience was estimated using structural equation modeling and the bootstrap method. FINDINGS: Both childhood trauma and family resilience were associated with psychological resilience. Family resilience showed a partial mediating effect between childhood trauma and psychological resilience, accounting for 21.5% of the total effect. PRACTICE IMPLICATION: Our findings may help inform family interventions to improve the psychological resilience of nursing students, especially for those with childhood trauma experience.

Median Nerve-Neurophysiological Index Correlates With the Survival of Patients With Amyotrophic Lateral Sclerosis.

Objective: This study aims to explore the association between median nerve-neurophysiological index (NI) and survival of patients with amyotrophic lateral sclerosis (ALS). Methods: A retrospective case series with a prospective follow-up study was performed in 238 patients with ALS. Their clinical profiles and NI were recorded. Kaplan-Meier curves and Cox regression were adopted to perform survival analysis. Results: The median survival time of all ALS cases was 33.0 months. Multivariate analysis showed that older age of onset, shorter diagnostic delay, higher ΔALSFRS-R, and faster progression {NI ≤ 2.15; hazard ratio [HR] = 1.543 [95% confidence interval (CI), 1.136-2.094]} were associated with short survival. NI was correlated with ALSFRS-R at baseline (r s = 0.3153; p < 0.0001) and ALSFRS-R at different time points of follow-up (r s = 0.5127; p < 0.0001). The higher NI slope of decline (> 0.25) showed shorter survival compared with the lower group (≤ 0.25; 34.0 vs. 52.0 months; p = 0.0003). A predictive model was constructed based on the age of onset, diagnostic delay, median nerve NI, and ΔALSFRS-R. The higher predictive score (> 14) showed significantly shorter survival compared with the lower group (≤ 14; HR = 3.907, 95% CI, 2.857-5.342). Conclusion: Median nerve NI and its slope of decline were predictive of survival of ALS.

Whole exome sequencing reveals a broader variant spectrum of Charcot-Marie-Tooth disease type 2.

Charcot-Marie-Tooth disease type 2 (CMT2) is a clinically and genetically heterogeneous inherited neuropathy. Although new causative and disease-associated genes have been identified for CMT2 in recent years, molecular diagnoses are still lacking for a majority of patients. We here studied a cohort of 35 CMT2 patients of Chinese descent, using whole exome sequencing to investigate gene mutations and then explored relationships among genotypes, clinical features, and mitochondrial DNA levels in blood as assessed by droplet digital PCR. We identified pathogenic variants in 57% of CMT2 patients. The most common genetic causes in the cohort were MFN2 mutations. Two patients with typical CMT phenotype and neuromyotonia were detected to harbor compound heterozygous variations in the HINT1 gene. In conclusion, our work supports that the molecular diagnostic rate of CMT2 patients can be increased via whole exome sequencing, and our data suggest that assessment of possible HINT1 mutations should be undertaken for CMT2 patients with neuromyotonia.

Dosage effect of multiple genes accounts for multisystem disorder of myotonic dystrophy type 1.

Multisystem manifestations in myotonic dystrophy type 1 (DM1) may be due to dosage reduction in multiple genes induced by aberrant expansion of CTG repeats in DMPK, including DMPK, its neighboring genes (SIX5 or DMWD) and downstream MBNL1. However, direct evidence is lacking. Here, we develop a new strategy to generate mice carrying multigene heterozygous mutations to mimic dosage reduction in one step by injection of haploid embryonic stem cells with mutant Dmpk, Six5 and Mbnl1 into oocytes. The triple heterozygous mutant mice exhibit adult-onset DM1 phenotypes. With the additional mutation in Dmwd, the quadruple heterozygous mutant mice recapitulate many major manifestations in congenital DM1. Moreover, muscle stem cells in both models display reduced stemness, providing a unique model for screening small molecules for treatment of DM1. Our results suggest that the complex symptoms of DM1 result from the reduced dosage of multiple genes.

ATP1A1 mutations cause intermediate Charcot-Marie-Tooth disease.

Intermediate Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited neuropathies characterized by progressive muscle weakness and atrophy of the distal extremities, distal sensory loss. There were still a large proportion of causative genes for intermediate CMT failed to be identified. Here, using whole-exome sequencing technique, we identified two novel missense mutations in ATP1A1 gene, c.620C>T (p.S207F) and c.2629G>A (p.G877S), in two Chinese CMT families. Further functional analysis revealed that these mutations led to the loss function of the ATP1A1 protein. The two mutations did not affect the levels of messenger RNA but possessed a damaging effect on ATP1A1 protein expression and they downregulated the protein levels of ATP1A1 by promoting its proteasome degradation. Taken together, we confirmed ATP1A1 as a novel causative gene for intermediate CMT.

Correction: 3-deazaneplanocin A protects against cisplatin-induced renal tubular cell apoptosis and acute kidney injury by restoration of E-cadherin expression.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.