Ryanodine receptor 1 (RYR1) gene mutations are associated with central core disease (CCD), multiminicore disease (MmD) and malignant hyperthermia (MH), and have been reported to be responsible for 47-67% of patients with CCD and rare cases with MmD. However, to date, the true frequency and distribution of the mutations along the RYR1 gene have not been determined yet, since mutation screening has been limited to three 'hot spots', with particular attention to the C-terminal region. In this study, 27 unrelated Japanese CCD patients were included. Clinical histories and muscle biopsies were carefully reviewed. We sequenced all the 106 exons encoding RYR1 with their flanking exon-intron boundaries, and identified 20 novel and 3 previously reported heterozygous missense mutations in 25 of the 27 CCD patients (93%), which is a much higher mutation detection rate than that perceived previously. Among them, six were located outside the known 'hot spots'. Sixteen of 27 (59%) CCD patients had mutations in the C-terminal 'hot spot'. Three CCD patients had a probable autosomal recessive disease with two heterozygous mutations. Patients with C-terminal mutations had earlier onset and rather consistent muscle pathology characterized by the presence of distinct cores in almost all type 1 fibres, interstitial fibrosis and type 2 fibre deficiency. In contrast, patients with mutations outside the C-terminal region had milder clinical phenotype and harbour more atypical cores in their muscle fibres. We also sequenced two genes encoding RYR1-associated proteins as candidate causative genes for CCD: the 12 kD FK506-binding protein (FKBP12) and the alpha1 subunit of L-type voltage-dependent calcium channel or dihydropyridine receptor (CACNA1S). However, no mutation was found, suggesting that these genes may not, or only rarely, be responsible for CCD. Our results indicate that CCD may be caused by RYR1 mutations in the majority of patients.

The mutational spectrum and primary clinical features of patients with CADASIL from mainland China are similar to those in Caucasians. However, migraine with aura and abnormal white matter in the temporal pole are less common than among Caucasians, while brainstem involvement is more common than among Caucasians.

BackgroundEpidemiological data on the prevalence of headache in nursing staff in Mainland China are lacking. We therefore performed a study to assess the prevalence of headache, and factors associated with headaches, in nursing staff in three hospitals in North China.MethodsStratified random cluster sampling was used to select 1102 nurses from various departments in three hospitals. A structured questionnaire was used to collect epidemiological data, headache characteristics and associated factors.ResultsThe response rate was 93.0%. Among nursing staff, the 1-year prevalence of primary headache disorders was 45.3%, of migraine 14.8% (migraine with aura 3.4%, migraine without aura 11.4%), of tension-type headache (TTH) 26.2%, of chronic daily headache (CDH) 2.7%. Multivariate analysis showed that seniority (≥5 years) was a risk factor for migraine (OR 2.280), obesity (BMI ≥ 25) was a risk factor for TTH and CDH (OR 1.684 and 3.184), and age (≥40 years) was a risk factor for CDH (OR 8.455). Nurses working in internal medicine were more likely to suffer CDH than those in other departments. Working a greater number of night shifts was also associated with increased prevalence of headache.ConclusionThe prevalence of primary headache disorders in nurses is higher than that in the general population in China, and occupational factors may play an important role. Therefore, the prevalence of headache in nurses should be a focus of attention, and coping strategies should be provided. Such measures could contribute to improving patient care.

With the explosive growth of online information, recommender systems play a key role to alleviate such information overload. Due to the important application value of recommender system, there have always been emerging works in this field. In recent years, graph neural network (GNN) techniques have gained considerable interests which can naturally integrate node information and topological structure. Owing to the outperformance of GNN in learning on graph data, GNN methods have been widely applied in many fields. In recommender systems, the main challenge is to learn the efficient user/item embeddings from their interactions and side information if available. Since most of the information essentially has graph structure and GNNs have superiority in representation learning, the field of utilizing graph neural network in recommender systems is flourishing. This article aims to provide a comprehensive review of recent research efforts on graph neural network based recommender systems. Specifically, we provide a taxonomy of graph neural network based recommendation models and state new perspectives pertaining to the development of this field.

Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) in 40% of patients is associated with mutations in the C-terminal domain of RYR1, suggesting that CNMDU1 is allelic to central core disease at least in some patients.

BackgroundThe plaques at the dorsal or lateral wall of basilar artery (BA) are associated with pontine infarcts. We sought to explore the correlations between vertebrobasilar artery geometry and BA plaque locations.MethodsWe retrospectively analyzed the imaging and clinical data of 84 patients with BA atherosclerosis. On three-dimensional time-of-flight images, a side to side diameter difference of bilateral vertebral artery (VA) and BA bending were assessed. The vertebrobasilar artery geometry was qualitatively classified into four basic configurations: Walking, Tuning Fork, Dominant-Lambda, and Hypoplasia-Lambda. On high-resolution magnetic resonance imaging, the plaques were categorized based on the involvement of the ventral, dorsal, or lateral sides of BA wall. The relationships between vertebrobasilar artery geometry parameters and plaque locations were analyzed.ResultsLeft VA dominance was identified in 28(33%) patients, and right VA dominance in 22(26%) patients. BA bending were detected in 49 patients. There were no significant correlations between the diameter difference/ratio of VA diameters and plaque locations, or between BA bending and plaque locations. BA plaques were evenly distributed in the vertebrobasilar arteries with Tuning Fork and Dominant-Lambda configurations. In Hypoplasia-Lambda group, however, plaques were more frequently located at the dorsal wall (58.57%) than at the ventral (14.43%) and lateral wall (26.71%; P = 0.001). In Walking group, the plaques more likely occurred at the lateral (49.79%) and dorsal (35.07%) wall than at the ventral wall (14.86%, P = 0.02).ConclusionsThe geometric configurations of vertebrobasilar artery strongly influence the BA plaque locations. Further prospective studies are warranted to testify whether Hypoplasia-Lambda and Walking configurations are independent risk factors for pontine infarcts.Electronic supplementary materialThe online version of this article (10.1186/s12883-018-1084-6) contains supplementary material, which is available to authorized users.

BackgroundThe underlying pathophysiology of BA distribution is unclear and intriguing. Using high-resolution magnetic resonance imaging (HR-MRI), we sought to explore the plaque distribution of low-grade basilar artery (BA) atherosclerosis and its clinical relevance.MethodsWe retrospectively analyzed the imaging and clinical data of 61 patients with low-grade atherosclerotic BA stenosis (<50%). On HR-MRI, the plaques were categorized based on the involvement of the ventral, dorsal, or lateral sides of BA wall. A culprit plaque was defined if it was on the same slice or neighboring slices of symptomatic pontine infarcts and played a probable causal role (dorsal plaques with median pontine infarcts or lateral plaques with ipsilateral pontine infarcts). The relationships between plaque distribution and clinical presentations were analyzed.ResultsTwenty-five symptomatic and thirty-six asymptomatic BAs with 752 HR-MRI image slices were studied. The average length of BA atherosclerosis plaques was 12.16 ± 5.61mm (10.30 ± 6.44mm in symptomatic and 13.46 ± 7.03mm in asymptomatic patients, p = 0.079). The plaque distribution was similar at ventral (29.0%), dorsal (37.6%) and lateral walls (33.1%). The BA plaques in symptomatic patients were more frequently located at the dorsal (42.5%) and lateral (41.2%) walls than at the ventral walls (16.1%; P < 0.05). Compared with symptomatic patients, asymptomatic patients more likely had their plaques distributed at the ventral walls (P = 0.022). Culprit plaques were observed in 85.0% (17/20) pontine infarcts in symptomatic patients and only 14.3% (2/14) silent pontine infarcts in asymptomatic patients (p < 0.001).ConclusionsLow-grade BA atherosclerosis has a long distribution and evenly involves ventral, dorsal and lateral walls. The plaques at dorsal and lateral walls are associated with symptomatic pontine infarcts but not with silent infarcts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0785-y) contains supplementary material, which is available to authorized users.

Background Malignant hyperthermia (MH) is a disorder of calcium homeostasis in skeletal muscle triggered by volatile anesthetics or succinylcholine in susceptible persons. More than 100 mutations in the ryanodine receptor type 1 gene (RYR1) have been associated with MH susceptibility, central core disease, or both. RYR1 mutations may account for up to 70% of MH-susceptible cases. The authors aimed to determine the frequency and distribution of RYR1 mutations in the Japanese MH-susceptible population. Methods The authors selected 58 unrelated Japanese diagnosed as MH-susceptible for having an enhanced Ca-induced Ca release rate from the sarcoplasmic reticulum on chemically skinned muscle fibers. They sequenced the entire RYR1 coding region from genomic DNA. Muscle pathology was also characterized. Results Seven previously reported and 26 unknown RYR1 potentially pathogenic sequence variations were identified in 33 patients (56.9%). Of these patients, 48% had cores on muscle biopsy. The mutation detection rate was higher in patients with clear enhancement of Ca-induced Ca release rate (72.4%), whereas all patients with central core disease had RYR1 mutations. Six patients harbored potentially causative compound heterozygous sequence variations. Conclusions Distribution and frequency of RYR1 mutations differed markedly from those of the North American and European MH-susceptible population. Comprehensive screening of the RYR1 gene is recommended for molecular investigations in MH-susceptible individuals, because many mutations are located outside the "hot spots." Based on the observed occurrence of compound heterozygous state, the prevalence of a possibly predisposing phenotype in the Japanese population might be as high as 1 in 2,000 people.