Explore the vast range of titles available.

To describe our experience with a large cohort (411 patients from 288 families) of various forms of skeletal dysplasia who were molecularly characterized. Detailed phenotyping and next-generation sequencing (panel and exome). Our analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello–Carey syndrome–like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average. By expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions.

The purposes of this study were to report clinical features of the developmental anomaly of ossification type bipartite or tripartite patella using a large series and to propose a new classification for the developmental anomaly of ossification type bipartite or tripartite patella. The first author prospectively examined 111 patients with symptomatic or asymptomatic bipartite (131 knees) or tripartite (8 knees) patellae. Eighty-six (77%) were male and 25 (23%) were female. Forty-three patients (39%) showed right knee involvement and 40 (36%) showed left, while 28 (25%) showed involvement in both knees. Forty-six bipartite and 4 tripartite patellae (36%) were symptomatic and 85 bipartite and 4 tripartite patellae (64%) were asymptomatic at initial examination. The median age at onset of pain of symptomatic patients (50 knees) was 15.6 ± 8.1 years (range, 10–51 years). The most common symptom was pain at the separated fragments during or after strenuous activity in all 50 knees. Physical examination revealed localized tenderness over the separated fragments in all 50 knees. Bipartite or tripartite patellae were classified by evaluating location and number of fragments. One hundred fifteen knees (83%) were classified as supero-lateral bipartite type, 16 (12%) were lateral bipartite type, 6 (4%) were supero-lateral and lateral tripartite type, and 2 (1%) were supero-lateral tripartite type. For the developmental anomaly of ossification type bipartite or tripartite patella, a classification based on both location and number of fragments is simple and easy to understand and applicable to all types of bipartite or tripartite patella.

Purposes Poland’s syndrome (PS) is a rare congenital malformation, which combines anomalies of the chest and the homolateral upper limb. The purposes of the paper are to study the chest musculoskeletal malformations of the syndrome and propose a classification for the thoracic anomalies through our experience and taking into account the literature. Methods We reviewed ten patients diagnosed with PS. All of them suffered from anomalies of the thorax and the ipsilateral upper extremity. We proceeded to scan the thorax with 3-D CT for better imaging of the structures and examination of the variations. Results All patients were young to middle aged: seven women and three men. Both sides of the body were affected to the same extent. Six patients presented with total absence of the pectoralis muscles and variable anomalies of the thoracic skeletal structures. Hypoplasia of the minor pectoralis and retraction of the ribs were observed in two patients, while the two other patients presented with major and minor pectoralis absence as well, except for the clavicular head. Conclusions There are many variations of PS with regard to the chest that can be best detected with 3-D CT imaging, which should be used whenever it is available. We propose a simple classification of the musculoskeletal anomalies of the chest in Poland’s syndrome that would be a useful tool for the clinicians and especially plastic surgeons to make an easy diagnosis. In combination with 3-D CT imaging, surgeons will be able to achieve the best treatment for each patient.

Considerable confusion is encountered in the literature relating classification respectively surgical repair of the anterior chest wall deformities in view of the asymmetric types which are arbitrarily ranged in one of the two main groups (impressions, protrusions). Out of 420 operations 89 (21%) were performed for pure protrusion, and 64 (15%) for mixed deformities, with asymmetric impression and protrusion present at the same time. Mixed deformities were limited to the parasternal area in 10 and extended to the entire anterior chest wall in 54 cases. Surgery was undertaken for both protrusion and mixed deformities beyond 10 years of age in 9.8%, while for a typical funnel chest deformity in 31% (p<0.001). Correction has been achieved performing double subperichondral excisions of the distorted cartilages and - if necessary - subperiosteal wedge incision of the bony segments, completed by a T shape wedge sternal incision. In order to preserve the repaired position a stainless steel stabiliser was introduced for one year behind the sternum and the entire mobilised wall area. This method was used hitherto in 60 patients with mixed, respectively severe funnel chest deformities without any complication. The \"pectus index\" calculated according to the equation A/Bx100, in which A is the internal sterno-vertebral distance and B is the transverse diameter of the chest at the level of the diaphragms in cm (normal values: 35%-45%) was followed for 7.6+/-4.5 years in 63 patients. The preoperative 53+/-7.6% decreased to 44.2+/-6.3% (p<0.05).

Sifrim–Hitz–Weiss syndrome (SIHIWES) is a recently described multisystemic neurodevelopmental disorder caused by de novo variants inCHD4. In this study, we investigated the clinical spectrum of the disorder, genotype–phenotype correlations, and the effect of different missense variants on CHD4 function. We collected clinical and molecular data from 32 individuals with mostly de novo variants in CHD4, identified through next-generation sequencing. We performed adenosine triphosphate (ATP) hydrolysis and nucleosome remodeling assays on variants from five different CHD4 domains. The majority of participants had global developmental delay, mild to moderate intellectual disability, brain anomalies, congenital heart defects, and dysmorphic features. Macrocephaly was a frequent but not universal finding. Additional common abnormalities included hypogonadism in males, skeletal and limb anomalies, hearing impairment, and ophthalmic abnormalities. The majority of variants were nontruncating and affected the SNF2-like region of the protein. We did not identify genotype–phenotype correlations based on the type or location of variants. Alterations in ATP hydrolysis and chromatin remodeling activities were observed in variants from different domains. The CHD4-related syndrome is a multisystemic neurodevelopmental disorder. Missense substitutions in different protein domains alter CHD4 function in a variant-specific manner, but result in a similar phenotype in humans.

Background The anteroposterior view of the lumbar plain radiograph (AP-LPR) was chosen as the original and first radiographic tool to determine and classify lumbosacral transitional vertebra with morphological abnormality (MA-LSTV) according to the Castellvi classification. However, recent studies found that AP-LPR might not be sufficient to detect or classify MA-LSTV correctly. The present study aims to verify the reliability of AP-LPR on detecting and classifying MA-LSTV types, taking coronal reconstructed CT images (CT-CRIs) as the gold criteria. Methods Patients with suspected MA-LSTVs determined by AP-LPR were initially enrolled. Among them, those who received CT-CRIs were formally enrolled to verify the sensitivity of AP-LPR on detecting and classifying MA-LSTV types according to the Castellvi classification principle. Results A total of 298 cases were initially enrolled as suspected MA-LSTV, among which 91 cases who received CT-CRIs were enrolled into the final study group. All suspected MA-LSTVs were verified to be real MA-LSTVs by CT-CRIs. However, 35.2% of the suspected MA-LSTV types judged by AP-LPR were not consistent with the final types judged by CT-CRIs. Two suspected type IIIa and 20 suspected type IIIb MA-LSTVs were verified to be true, while 9 of 39 suspected type IIa, 9 and 3 of 17 suspected type IIb, and 11 of 13 suspected type IV MA-LSTVs were verified to truly be type IIIa, IIIb, IV and IIIb MA-LSTVs by CT-CRIs, respectively. Incomplete joint-like structure (JLS) or bony union structure (BUS) and remnants of sclerotic band (RSB) between the transverse process (TP) and sacrum were considered to be the main reasons for misclassification. Conclusion Although AP-LPR could correctly detect MA-LSTV, it could not give accurate type classification. CT-CRIs could provide detailed information between the TP and sacrum area and could be taken as the gold standard to detect and classify MA-LSTV.

This paper introduces a solution to address the intricacy of the model employed in the deep learning-based diagnosis of musculoskeletal abnormalities and the limitations observed in the performance of a single deep learning network model. The proposed approach involves the integration of an improved EfficientNet-B2 model with MobileNetV2, resulting in the creation of FusionNet. First, EfficientNet-B2 is combined with coordinate attention (CA) to obtain CA-EfficientNet-B2. Furthermore, aiming to minimize the model parameter count, we further enhanced the mobile inverted residual bottleneck convolution module (MBConv) employed for feature extraction in EfficientNet-B2, resulting in the development of CA-MBC-EfficientNet-B2. Next, the features extracted from CA-MBC-EfficientNet-B2 and MobileNetV2 are fused. Finally, the final diagnosis of musculoskeletal abnormalities was performed by using fully connected layers. The experimental results demonstrate that, first, compared to EfficientNet-B2, CA-MBC-EfficientNet-B2 not only significantly improves the diagnostic performance of musculoskeletal abnormalities, it also reduces the parameter count and storage space by 17%. Moreover, as compared to other models, FusionNet demonstrates remarkable performance in the area of anomaly diagnosis, particularly on the elbow dataset, achieving a precision of 92.93%, an AUC of 93.89% and an accuracy of 87.10%.

This study proposes a novel multi-network architecture consisting of a multi-scale convolution neural network (MSCNN) with fully connected graph convolution network (GCN), named MSCNN-GCN, for the detection of musculoskeletal abnormalities via musculoskeletal radiographs. To obtain both detailed and contextual information for a better description of the characteristics of the radiographs, the designed MSCNN contains three subnetwork sequences (three different scales). It maintains high resolution in each sub-network, while fusing features with different resolutions. A GCN structure was employed to demonstrate global structure information of the images. Furthermore, both the outputs of MSCNN and GCN were fused through the concat of the two feature vectors from them, thus making the novel framework more discriminative. The effectiveness of this model was verified by comparing the performance of radiologists and three popular CNN models (DenseNet169, CapsNet, and MSCNN) with three evaluation metrics (Accuracy, F1 score, and Kappa score) using the MURA dataset (a large dataset of bone X-rays). Experimental results showed that the proposed framework not only reached the highest accuracy, but also demonstrated top scores on both F1 metric and kappa metric. This indicates that the proposed model achieves high accuracy and strong robustness in musculoskeletal radiographs, which presents strong potential for a feasible scheme with intelligent medical cases.

Musculoskeletal disorders cause pain, disability, and financial burdens, with rising prevalence. Virtual reality (VR) offers immersive, digital rehabilitation potential, improving motor functions and pain management. To evaluate the impact of VR on the rehabilitation of musculoskeletal disorders and to assess the consistency of evidence provided by existing systematic reviews and meta-analyses, this study focuses on musculoskeletal disorders, which encompass conditions affecting the locomotor system, such as arthritis, joint deformities, and injuries. VR therapy leverages immersive digital environments to enhance rehabilitation through digital exercises and simulations. The PubMed or MEDLINE, Embase, and Cochrane Library databases were systematically searched for relevant papers published up to April 2024. Literature screening, quality assessment, and data extraction were conducted according to predefined inclusion and exclusion criteria. The methodological quality of the included meta-analyses was evaluated using the Measurement Tool to Assess Systematic Reviews 2. The Grading of Recommendations Assessment, Development, and Evaluation system was used to classify the evidence level for each outcome as high, moderate, low, or very low. Additionally, the evidence was categorized into 5 levels based on classification criteria: I (convincing), II (highly suggestive), III (suggestive), IV (weak), and nonsignificant. This umbrella review synthesized data from 14 meta-analyses published between 2019 and 2024, involving a total of 13,184 patients. In total, 7 meta-analyses received high Measurement Tool to Assess Systematic Reviews 2 ratings, 7 were rated moderate, and the remainder were rated low. VR demonstrated promising results in musculoskeletal rehabilitation, significantly reducing knee pain (mean difference [MD] -1.38, 95% CI -2.32 to -0.44; P=.004; I =94%) and improving balance. For patients with fibromyalgia syndrome, VR effectively reduced pain (standardized mean difference [SMD] -0.45, 95% CI -0.70 to -0.20; P<.001), fatigue (SMD -0.58, 95% CI -1.01 to -0.14; P=.01), anxiety (SMD -0.50, 95% CI -0.908 to -0.029; P=.04), and depression (SMD -0.62, 95% CI -0.76 to -0.15; P=.003) while also enhancing quality of life. In individuals with back pain, VR alleviated pain-related fears (MD -5.46, 95% CI -9.40 to -1.52; P=.007; I =90%) and reduced pain intensity (MD -1.43, 95% CI -1.86 to -1.00; P<.001; I =95%). After arthroplasty, VR improved knee functionality (MD 8.30, 95% CI 6.92-9.67; P<.001; I =24%) and decreased anxiety (MD -3.95, 95% CI -7.76 to -0.13; P=.04; I =0%). VR demonstrates significant potential in the rehabilitation of various musculoskeletal conditions. It effectively alleviates pain, enhances psychological well-being, and facilitates the recovery of motor function in patients. PROSPERO CRD42024538469; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024538469.

Background Scales are mineralised exoskeletal structures that are part of the dermal skeleton. Scales have been mostly lost during evolution of terrestrial vertebrates whilst bony fish have retained a mineralised dermal skeleton in the form of fin rays and scales. Each scale is a mineralised collagen plate that is decorated with both matrix-building and resorbing cells. When removed, an ontogenetic scale is quickly replaced following differentiation of the scale pocket-lining cells that regenerate a scale. Processes promoting de novo matrix formation and mineralisation initiated during scale regeneration are poorly understood. Therefore, we performed transcriptomic analysis to determine gene networks and their pathways involved in dermal scale regeneration. Results We defined the transcriptomic profiles of ontogenetic and regenerating scales of zebrafish and identified 604 differentially expressed genes (DEGs). These were enriched for extracellular matrix, ossification, and cell adhesion pathways, but not in enamel or dentin formation processes indicating that scales are reminiscent to bone. Hypergeometric tests involving monogenetic skeletal disorders showed that DEGs were strongly enriched for human orthologues that are mutated in low bone mass and abnormal bone mineralisation diseases ( P < 2× 10 −3 ). The DEGs were also enriched for human orthologues associated with polygenetic skeletal traits, including height ( P < 6× 10 −4 ), and estimated bone mineral density (eBMD, P < 2× 10 −5 ). Zebrafish mutants of two human orthologues that were robustly associated with height ( COL11A2 , P =6× 10 −24 ) or eBMD ( SPP1 , P =6× 10 −20 ) showed both exo- and endo- skeletal abnormalities as predicted by our genetic association analyses; col11a2 Y228X/Y228X mutants showed exoskeletal and endoskeletal features consistent with abnormal growth, whereas spp1 P160X/P160X mutants predominantly showed mineralisation defects. Conclusion We show that scales have a strong osteogenic expression profile comparable to other elements of the dermal skeleton, enriched in genes that favour collagen matrix growth. Despite the many differences between scale and endoskeletal developmental processes, we also show that zebrafish scales express an evolutionarily conserved sub-population of genes that are relevant to human skeletal disease.