Characteristics of after-discharges following compound muscle action potential or F-wave in primary peripheral nerve hyperexcitability syndrome.

INTRODUCTION/AIMS: F-wave testing frequently reveals after-discharges of varied morphologies in patients with primary peripheral nerve hyperexcitability syndrome (PNHS), although reports are scant. This study aimed to explore the morphological characteristics of the after-discharges during F-wave tests in PNHS, and to assess the association between after-discharges and the disease classification. METHODS: We conducted a retrospective analysis of patients diagnosed with PNHS between 2014 and 2022. The morphological characteristic and duration of after-discharges during F-wave tests were analyzed. After-discharges in the Morvan syndrome group were compared with those in non-Morvan group, and between groups with positive or negative voltage-gated potassium channel (VGKC) complex antibodies. RESULTS: Twenty-nine patients were included in the study, of which 25 exhibited after-discharges. All after-discharges in Morvan patients occurred following compound muscle action potential (CMAP). In non-Morvan patients, after-discharges occurred following F-wave (32%) and CMAP (47%). The durations of after-discharges following CMAP were significantly prolonged in Morvan (54.2 ± 18.8 ms) compared to non-Morvan patients (34.5 ± 15.0 ms). The majority of antibody-positive patients (18/20) exhibited after-discharges following CMAP, whereas 67% of antibody-negative patients (6/9) showed after-discharges following F-wave. DISCUSSION: The varying presentations of after-discharges, including their location (after CMAP or F-wave) and the duration of after-discharge can assist in clinically classifying PNHS.

Automated diffusion-weighted image analysis along the perivascular space index reveals glymphatic dysfunction in association with brain parenchymal lesions.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

Clinical and genetic characteristics of 1672 cases of amyotrophic lateral sclerosis in China: a single-center retrospective study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. In recent years, continuous discoveries of new ALS-causing genes have enhanced the understanding of the genotype-phenotype relationship in ALS, aiding in disease progression prediction and providing a more comprehensive basis for genetic diagnosis. METHODS: A total of 1672 ALS patients who visited the Neurology Department of Peking Union Medical College Hospital between January 2014 and December 2022 and met the revised El Escorial diagnostic criteria were included. Clinical data were collected, whole exome sequencing and dynamic mutation screening of the C9ORF72 gene were performed, and the clinical phenotypes and genotypes of the patients were analyzed. RESULTS: The average age of onset for the 1672 ALS patients was 52.6 ± 11.2 years (range 17-85 years), with a median disease duration of 14 months at the time of visit (interquartile range 9-24 months, range 2-204 months). The male to female ratio was 833:839. The patients included 297 (17.8%) with bulbar onset, 198 (11.8%) with flail arm/leg syndrome, 89 (5.3%) with familial ALS, and 52 (3.1%) with concomitant frontotemporal dementia (FTD). Pathogenic variants associated with ALS were detected in 175 patients (10.5% of the cohort), with the most common mutations being SOD1, FUS, and ANXA11. Among patients with familial ALS, 56.2% (50/89) had genetic mutations, compared to 7.9% (125/1583) in sporadic ALS cases. From the perspective of phenotype-genotype correlation, (1) In ALS-FTD patients, the most common genetic mutations were ANXA11 and C9ORF72 repeat expansions. Patients with flail arm/leg syndrome more frequently carried mutations in SOD1, ANXA11, and hnRNPA1; (2) Despite genetic heterogeneity, it was observed that mutations in FUS and NEK1 were more common in males, and patients with FUS mutations had a younger age of onset; mutations in SOD1 and SQSTM1 were more likely to present with lower limb onset. CONCLUSION: This study provides comprehensive data on the genetic characteristics of ALS patients in China through large-scale clinical data and genetic analysis of 1672 cases. Differences in age of onset, onset site, and clinical phenotype among ALS patients with different genotypes can help clinicians better predict disease progression and provide a basis for precise diagnosis and individualized treatment.

Long-term follow-up of relapse and remission of CIDP in a Chinese cohort.

Objective: We aim to describe the long-term outcome of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) after immune treatment in a Chinese cohort. Methods: Between March 2015 and March 2023, 89 patients fulfilling the criteria for CIDP were followed up for a median of 22 months after treatment. Nine had positive antibodies against nodal-paranodal cell-adhesion molecules. Patients were treated according to clinical requirements with prednisone, intravenous immunoglobulin (IVIg) and/or immunosuppressant. Results: A total of 78/89 patients had decreased inflammatory neuropathy cause and treatment (INCAT) scores at the last follow-up. For CIDP patients treated with steroids, 35 were stable without relapse after cessation or with a small maintenance dose; 2 relapsed at a high dose (20 mg/day); 15 relapsed at a low dosage (<20 mg/day) and 11 did not respond. The INCAT before treatment was significantly lower in those without relapse (median INCAT 2 vs 3, p=0.030). IVIg was effective in 37/52 CIDP patients. 28 CIDP patients and 4 autoimmune nodopathy patients were treated with immunosuppressants. The average INCAT was 3.3±1.9 before and 1.9±1.3 after immunosuppressant treatment (p=0.001) in CIDP. Conclusion: The long-term prognosis of CIDP patients was generally favourable. Nearly half of our patients treated with steroid were stable without relapse after cessation or with a small maintenance dose. The risk of relapse was higher in those with high INCAT. We recommend slowly tapering prednisone based on clinical judgement.

Leaders of Peer Groups in Chinese Early Adolescents: The Roles of Social, Academic, and Psychological Characteristics in Group Leadership.

Leadership in peer groups is an important issue in adolescent socioemotional development, yet it has received limited attention in research. This one-year longitudinal study examined peer group leadership and the roles of social, academic, and psychological characteristics in the dynamics of group leadership. Participants included 1061 Chinese students (initial mean age =11.17 years; SD = 6.98 months; 49.4% female). Data were collected from peer assessments, teacher ratings, and self-reports. The longitudinal social network analysis (SIENA) indicated that peer group leadership was fluid with leadership status evolving over time across groups in a hierarchical manner. Adolescents displaying higher social competence and aggression and lower shyness were more likely to become group leaders. Academic performance and loneliness were not significantly associated with the dynamics of peer group leadership. The results help understand peer group leadership and contributions of social behaviors to the attainment of leadership status in peer groups in early adolescence.

Dynamic Mechanism of Cerebral Venous Disruption: Longitudinal Evidence From a Community-Based Cohort.

BACKGROUND: This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. METHODS AND RESULTS: This is a longitudinal analysis of the population-based Shunyi cohort study. Baseline DMVs numbers were identified on susceptibility-weighted imaging. We assessed vertex-wise cortex maps and diffusion maps at both baseline and follow-up using FSL software and the longitudinal FreeSurfer analysis suite. We performed statistical analysis of global measurements and voxel/vertex-wise analysis to explore the relationship between DMVs number and brain structural measurements. A total of 977 participants were included in the baseline, of whom 544 completed the follow-up magnetic resonance imaging (age 54.97±7.83 years, 32% men, mean interval 5.56±0.47 years). A lower number of DMVs was associated with a faster disruption of white matter microstructural integrity, presented by increased mean diffusivity and radial diffusion (ß=0.0001 and SE=0.0001 for both, P=0.04 and 0.03, respectively), in extensive deep white matter (threshold-free cluster enhancement P<0.05, adjusted for age and sex). Of particular interest, we found a bidirectional trend association between DMVs number and change in brain volumes. Specifically, participants with mild DMVs disruption showed greater cortical enlargement, whereas those with severe disruption exhibited more significant brain atrophy, primarily involving clusters in the frontal and parietal lobes (multiple comparison corrected P<0.05, adjusted for age, sex, and total intracranial volume). CONCLUSIONS: Our findings posed the dynamic pattern of brain parenchymal lesions related to DMVs injury, shedding light on the interactions and chronological roles of various pathological mechanisms.

Genotype-phenotype association and functional analysis of hnRNPA1 mutations in amyotrophic lateral sclerosis.

BACKGROUND: Pathogenic variants in hnRNPA1 have been reported in amyotrophic lateral sclerosis (ALS) patients. However, studies on hnRNPA1 mutant spectrum and pathogenicity of variants were rare. METHODS: We performed whole exome sequencing of ALS-associated genes and subsequent verification of rare variants in hnRNPA1 in our ALS patients. The hnRNPA1 mutations reported in literature were reviewed and combined with our results to determine the genotype-phenotype relationship. Functional analysis of the novel variant p.G195A was performed in vitro by transfection of mutant hnRNPA1 into 293T cell. RESULTS: Among 207 ALS patients recruited, 3 rare hnRNPA1 variants were identified (mutant frequency 1.45%), including two recurrent mutations (p.P340S and p.G283R), and a novel rare variant p.G195A. In combination with previous reports, there are 27 ALS patients with 15 hnRNPA1 mutations identified. Disease onset age was 47.90 ± 1.52 years with predominant limb onset. The p.P340S mutation caused flail arm syndrome (FAS) in two independent families with extended life expectancy. The newly identified p.G195A mutation, lying at the start of the PrLD ("prion-like" domain)/LCD (low-complexity domain), causes local structural changes in 3D protein prediction. Upon sodium arsenite exposure, mutant hnRNPA1 retained in the nucleus but deficit of cytoplasmic G3BP1-positive stress granule clearance was observed. This is different from the p.P340S mutation which caused both cytoplasmic translocation and stress granule formation. No cytoplasmic TDP-43 translocation was observed. CONCLUSION: Mutations in hnRNPA1 are overall minor in ALS patients. The p.P340S mutation is associated with manifestation of FAS. Mutations in LCD of hnRNPA1 cause stress granule misprocessing.

vEpiNet: A multimodal interictal epileptiform discharge detection method based on video and electroencephalogram data.

To enhance deep learning-based automated interictal epileptiform discharge (IED) detection, this study proposes a multimodal method, vEpiNet, that leverages video and electroencephalogram (EEG) data. Datasets comprise 24 931 IED (from 484 patients) and 166 094 non-IED 4-second video-EEG segments. The video data is processed by the proposed patient detection method, with frame difference and Simple Keypoints (SKPS) capturing patients' movements. EEG data is processed with EfficientNetV2. The video and EEG features are fused via a multilayer perceptron. We developed a comparative model, termed nEpiNet, to test the effectiveness of the video feature in vEpiNet. The 10-fold cross-validation was used for testing. The 10-fold cross-validation showed high areas under the receiver operating characteristic curve (AUROC) in both models, with a slightly superior AUROC (0.9902) in vEpiNet compared to nEpiNet (0.9878). Moreover, to test the model performance in real-world scenarios, we set a prospective test dataset, containing 215 h of raw video-EEG data from 50 patients. The result shows that the vEpiNet achieves an area under the precision-recall curve (AUPRC) of 0.8623, surpassing nEpiNet's 0.8316. Incorporating video data raises precision from 70% (95% CI, 69.8%-70.2%) to 76.6% (95% CI, 74.9%-78.2%) at 80% sensitivity and reduces false positives by nearly a third, with vEpiNet processing one-hour video-EEG data in 5.7 min on average. Our findings indicate that video data can significantly improve the performance and precision of IED detection, especially in prospective real clinic testing. It suggests that vEpiNet is a clinically viable and effective tool for IED analysis in real-world applications.

Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurogenerative disorder with uncertain origins. Emerging evidence implicates N6-methyladenosine (m6A) modification in ALS pathogenesis. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and liquid chromatography-mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis, respectively, in patients with ALS (n = 16) and controls (n = 6). The single-cell transcriptomic dataset (GSE174332) of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes. Analysis of peripheral immune cells revealed extensive RNA hypermethylation, highlighting candidate genes with differential m6A modification and expression, including C-X3-C motif chemokine receptor 1 (CX3CR1). In RAW264.7 macrophages, disrupted CX3CR1 signaling affected chemotaxis, potentially influencing immune cell migration in ALS. Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS. Cell type-specific expression variations of these genes in the central nervous system (CNS), particularly microglia, were observed. Intercellular communication between neurons and glial cells was selectively altered in ALS CNS. This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.

BACKGROUND: It is uncertain whether rare NOTCH3 variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare NOTCH3 variants with prevalent and incident stroke and dementia, as well as cognitive function changes. METHODS AND RESULTS: In the prospective community-based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow-up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare NOTCH3 variants were defined as variants with minor allele frequency <1%. A total of 137 rare NOTCH3 carriers were enrolled in the baseline study. At baseline, rare NOTCH3 variant carriers had higher rates of stroke (8.8% versus 5.6%) and dementia (2.9% versus 0.8%) compared with noncarriers. After adjustment for associated risk factors, the epidermal growth factor-like repeats (EGFr)-involving rare NOTCH3 variants were associated with a higher risk of prevalent stroke (odds ratio [OR], 2.697 [95% CI, 1.266-5.745]; P=0.040) and dementia (OR, 8.498 [95% CI, 1.727-41.812]; P=0.032). After 5 years of follow-up, we did not find that the rare NOTCH3 variants increased the risk of incident stroke and dementia. There was no statistical difference in the change in longitudinal cognitive scale scores. CONCLUSIONS: Rare NOTCH3 EGFr-involving variants are genetic risk factors for stroke and dementia in the general Chinese population.

The development of self- and group orientations among Chinese young adolescents: Implications for social and behavioral adjustment.

Self- and group orientations represent distinct ways of perceiving the relations between the world and the self and are relevant to adolescents' development. Most of the existing studies in this area are cross-sectional, providing little information about how self- and group orientations develop. This 3-year longitudinal study examined the developmental patterns of self- and group orientations and their relations with adjustment among Chinese adolescents. The participants included 1,257 students (648 boys, initial Mage = 13.37 years, SD = 0.63 years). Data on self- and group orientations and social and behavioral adjustment were obtained from multiple sources, including self-reports, peer nominations, and teacher ratings. The results showed that self-orientation increased, and group orientation decreased during early adolescence. Moreover, an increase (slope) in self-orientation was positively associated with subsequent assertive behavior, whereas a slower decrease in group orientation was positively associated with subsequent prosocial behavior and peer preference. The initial level (intercept) of self-orientation was positively associated with later externalizing problems, and the initial level of group orientation was negatively associated with later internalizing problems. The intercepts of self- and group orientations were higher for boys than girls. No significant gender differences were found in the slopes of self- and group orientations or in the associations of intercepts and slopes with adjustment outcomes. The results indicated different developmental patterns of self- and group orientations and their different implications for adjustment in Chinese adolescents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Affinity for solitude in Chinese children and adolescents: Relations with social, school, and psychological adjustment.

This study examined relations of affinity for solitude with social-behavioral, academic, and psychological adjustment in Chinese children and adolescents. The participants included 3,417 students (1,714 boys) in fourth, sixth, and eighth grades (Mages = 10, 12, and 14 years, respectively) in China. Data on affinity for solitude were collected from students' self-reports and data on adjustment were collected from multiple sources. The results showed that whereas affinity for solitude was negatively associated with social competence and academic achievement and positively associated with behavioral problems in Grade 4, the associations were weaker or nonsignificant in Grade 6. Moreover, affinity for solitude was positively associated with academic achievement and negatively associated with behavioral problems in Grade 8. Affinity for solitude was negatively associated with psychological adjustment in general, but the associations were weaker in higher grades. The results indicate that the functional meaning of affinity for solitude may differ across developmental periods. Parents, teachers, and professionals should be aware of the different implications of affinity for solitude in childhood and adolescence and use different strategies to support children and adolescents who display affinity for solitude. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Facilitative effect of awe on cooperation: The role of the small-self and self-other inclusion.

Awe has been theorized as a kind of self-transcendence emotion that has an important impact on individual social behavior. Based on the self-transcendence of awe, this study examined how awe can increase small-self and self-other inclusion to facilitate cooperation among individuals across three studies (N = 1162). First, the relationship between awe, cooperative propensity, and the mediating role of small-self and self-other inclusion in the relationship was examined using questionnaires on trait levels (Study 1). Second, awe emotions were induced from the state level through behavioral experiments to verify the facilitative effect on cooperative behavior in multiple rounds of public goods dilemma (Study 2). Third, by adding the induction of negative awe to discuss the impact of different valence of awe on cooperative behavior, the mediating role of small-self and self-other inclusion was supported (Study 3). Results show that awe has a facilitative effect on cooperation, which provides strong evidence for the positive social function of self-transcendent emotional awe.

GRN mutation spectrum and genotype-phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort.

BACKGROUND: METHODS: The GRN mutations, especially of the loss of function type, are causative of frontotemporal dementia (FTD). However, several GRN variants can be found in other neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease. So far, there have been over 300 GRN mutations reported globally. However, the genetic spectrum and phenotypic characteristics have not been fully elucidated in Chinese population.The participants were from the dementia cohort of Peking Union Medical College Hospital (n=1945). They received history inquiry, cognitive evaluation, brain imaging and exome sequencing. The dementia subjects carrying the rare variants of the GRN were included in this study. Those with the pathogenic or likely pathogenic variants of other dementia-related genes were excluded. RESULTS: 14 subjects carried the rare variants of GRN. They were clinically diagnosed with behavioural variant of FTD (n=2), non-fluent/agrammatic variant primary progressive aphasia (PPA, n=3), semantic variant PPA (n=1), AD (n=6) and mixed dementia (n=2). 13 rare variants of GRN were found, including 6 novel variants (W49X, S226G, M152I, A91E, G79E and A303S). The most prevalent symptom was amnesia (85.7%, 12/14), followed by psychiatric and behavioural disorder (78.6%, 11/14). In terms of lobar atrophy, temporal atrophy/hypometabolism was the most common (85.7%, 12/14), followed by parietal atrophy/hypometabolism (78.6%, 11/14). CONCLUSION: The novel GRN variants identified in this study contribute to enrich the GRN mutation repertoire. There is phenotypic similarity and diversity among Chinese patients with the GRN mutations.

Neuromuscular ultrasound in combination with nerve conduction studies helps identify inflammatory motor neuropathies from lower motor neuron syndromes.

BACKGROUND AND PURPOSE: Identifying patients with inflammatory motor neuropathies (IMNs) is warranted since effective treatments are available and the prognosis of these patients differs from that of amyotrophic lateral sclerosis patients. METHODS: Between January 2019 and May 2022, 102 consecutive treatment-naïve lower motor neuron syndrome (LMNS) patients were recruited; these patients were suspected of having multifocal motor neuropathy, pure motor chronic inflammatory demyelinating polyneuropathy or amyotrophic lateral sclerosis with initial lower motor neuron presentation. Neuromuscular ultrasound (US) and nerve conduction studies (NCSs) were conducted at baseline. Relevant diagnostic investigations were performed if clinically warranted. The proposed US evidence of IMN was as follows: (i) nerve enlargement at ≥1 of the predetermined sites or (ii) absence of high intensity fasciculations in predefined muscle groups. Final diagnoses were made by experienced physicians after a prolonged follow-up period (≥12 months). IMN patients were defined as LMNS patients who experienced convincing improvements in response to immunotherapies. IMN patients without electrodiagnostic demyelinating features were diagnosed with treatment-responsive LMNS (TR-LMNS). RESULTS: In total, 16 patients were classified as IMN, including nine chronic inflammatory demyelinating polyneuropathy/multifocal motor neuropathy patients and seven TR-LMNS patients. Six TR-LMNS patients were identified by neuromuscular US. The sensitivity and specificity of NCSs, nerve US and muscle US were 56.3% and 100%, 43.8% and 90.7% and 68.8% and 97.7%, respectively. When these three modalities were combined, the sensitivity and specificity were 93.8% and 88.4%, respectively. CONCLUSION: Neuromuscular US studies are supplementary modalities to NCSs, and the combined use of these techniques might improve the identification of IMNs in LMNS patients.

The distribution pattern of nerve enlargement in clinical subtypes of chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: We aim to investigate nerve enlargement patterns and their correlation with clinical subtypes and treatment response using nerve ultrasound in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Between March 2015 and December 2021, 135 CIDP patients were recruited. Nerve ultrasound and electrophysiological studies were performed on the median and ulnar nerves. The responses to intravenous immunoglobulin (IVIg) or prednisone were evaluated with the disability score. RESULTS: There were 99 typical CIDP cases, 10 Lewis-Sumner syndrome (LSS) cases, 15 distal acquired demyelinating symmetric neuropathy (DADS) cases, nine pure motor CIDP cases, and two pure sensory CIDP cases. Sixty (61%) typical CIDP and seven (78%) pure motor CIDP patients had moderately increased or normal cross-sectional area (CSA), and 10 (67%) DADS and seven (70%) LSS patients had significantly increased CSA. The peripheral nerve showed a diffuse enlargement pattern in 46 (51%) typical CIDP, five (50%) LSS, three (25%) DADS, and three (33%) pure motor CIDP patients and a proximal regional enlargement pattern in 11 (12%) typical CIDP, one (10%) LSS, six (50%) DADS, and four (44%) pure motor CIDP patients. Patients with diffusely moderate enlargement patterns and those with proximal regional enlargement showed a higher response rate to glucocorticoids than to IVIg. CONCLUSIONS: Various distribution patterns of nerve enlargement existed in CIDP. Although almost all patterns could be detected in each CIDP subtype, diffusely moderate enlargement was more common in typical CIDP and LSS, while proximal regional enlargement was more common in DADS and pure motor CIDP. Different enlargement patterns might indicate different treatment responses.

Empathy and cooperation vary with gender in Chinese junior high school adolescents.

Previous research on the relationship between empathy and subcategories of prosocial behavior, specifically cooperation, has shown inconsistent findings. It has also paid limited attention to gender differences in the impact of empathy. Therefore, this study examined the relationship between empathy and cooperation in Chinese junior high school adolescents, and the gender differences, through three studies. In Study 1, 448 eighth-grade adolescents (age = 12-15 years, 55.1% males) completed the Interpersonal Reactivity Index and Cooperative Propensity Rating Scale; the results showed that adolescent empathy was positively associated with cooperative propensity, and this association was significantly higher for males than for females. Study 2 used longitudinal data from 246 eighth-grade adolescents (age = 12-15 years, 54.5% males) to further support the positive association between empathy and cooperation propensity and the gender differences found in Study 1. Study 3 employed the public goods dilemma to examine the effects of empathic states on the cooperative behavior of 157 eighth-grade adolescents (age = 13-16 years, 48% males) by evoking empathy. Using different research methods, this study revealed a facilitative relationship between empathy and cooperation and demonstrated that empathy was more predictive of cooperation among male than among female adolescents.

Incidence of amyotrophic lateral sclerosis-associated genetic variants: a clinic-based study.

OBJECTIVE: This study is to determine the incidence of genetic forms of amyotrophic lateral sclerosis (ALS) in clinic-based population. METHODS: Next-generation sequencing (NGS) of whole exome sequencing (WES) was conducted among a total of 374 patients with definite or probable ALS to identify ALS-associated genes based on ALSoD database ( https://alsod.ac.uk ) [2023-07-01]. RESULTS: Variants of ALS-associated genes were detected in 54.01% (202/374) ALS patients, among which 8.29% (31/374) were pathogenic/likely pathogenic (P/LP). The detection rates of P/LP variants were significantly higher in familial ALS than sporadic ALS (42.31% vs 5.75%, p < 0.001), while VUS mutations were more commonly detected in sporadic ALS (23.07% vs 47.13%, p = 0.018). There is no significant difference in detection rate between patients with and without early onset (8.93% vs 7.77%), rapid progression (9.30% vs 8.91%), cognitive decline (15.00% vs 7.93%), and cerebellar ataxia (20.00% vs 8.15%) (p > 0.05). CONCLUSION: Over half of our ALS patients carried variants of ALS-related genes, most of which were variants of uncertain significance (VUS). Family history of ALS could work as strong evidence for carrying P/LP variants regarding ALS. There was no additionally suggestive effect of indicators including early onset, progression rate, cognitive decline, or cerebellar ataxia on the recommendation of genetic testing in clinical practice.

The prognostic value of systematic genetic screening in amyotrophic lateral sclerosis patients.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with complex genetic architecture. Emerging evidence has indicated comorbidity between ALS and autoimmune conditions, suggesting a potential shared genetic basis. The objective of this study is to assess the prognostic value of systematic screening for rare deleterious mutations in genes associated with ALS and aberrant inflammatory responses. METHODS: A discovery cohort of 494 patients and a validation cohort of 69 patients were analyzed in this study, with population-matched healthy subjects (n = 4961) served as controls. Whole exome sequencing (WES) was performed to identify rare deleterious variants in 50 ALS genes and 1177 genes associated with abnormal inflammatory responses. Genotype-phenotype correlation was assessed, and an integrative prognostic model incorporating genetic and clinical factors was constructed. RESULTS: In the discovery cohort, 8.1% of patients carried confirmed ALS variants, and an additional 15.2% of patients carried novel ALS variants. Gene burden analysis revealed 303 immune-implicated genes with enriched rare variants, and 13.4% of patients harbored rare deleterious variants in these genes. Patients with ALS variants exhibited a more rapid disease progression (HR 2.87 [95% CI 2.03-4.07], p < 0.0001), while no significant effect was observed for immune-implicated variants. The nomogram model incorporating genetic and clinical information demonstrated improved accuracy in predicting disease outcomes (C-index, 0.749). CONCLUSION: Our findings enhance the comprehension of the genetic basis of ALS within the Chinese population. It also appears that rare deleterious mutations occurring in immune-implicated genes exert minimal influence on the clinical trajectories of ALS patients.