Rare variant association analyses reveal the significant contribution of carbohydrate metabolic disturbance in severe adolescent idiopathic scoliosis.

Background: Adolescent idiopathic scoliosis (AIS), the predominant genetic-influenced scoliosis, results in spinal deformities without vertebral malformations. However, the molecular aetiology of AIS remains unclear.

Methods: Using genome/exome sequencing, we studied 368 patients with severe AIS (Cobb angle >40°) and 3794 controls from a Han Chinese cohort.

Core planar cell polarity genes and in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear.

SIGMA leverages protein structural information to predict the pathogenicity of missense variants.

Leveraging protein structural information to evaluate pathogenicity has been hindered by the scarcity of experimentally determined 3D protein. With the aid of AlphaFold2 predictions, we developed the structure-informed genetic missense mutation assessor (SIGMA) to predict missense variant pathogenicity. In comparison with existing predictors across labeled variant datasets and experimental datasets, SIGMA demonstrates superior performance in predicting missense variant pathogenicity (AUC = 0.

Impaired glycine neurotransmission causes adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting millions of adolescents worldwide, but it lacks a defined theory of etiopathogenesis. Because of this, treatment of AIS is limited to bracing and/or invasive surgery after onset. Preonset diagnosis or preventive treatment remains unavailable.

Exploring the association between congenital vertebral malformations and neural tube defects.

Congenital vertebral malformations (CVMs) and neural tube defects (NTDs) are common birth defects affecting the spine and nervous system, respectively, due to defects in somitogenesis and neurulation. Somitogenesis and neurulation rely on factors secreted from neighbouring tissues and the integrity of the axial structure. Crucial signalling pathways like Wnt, Notch and planar cell polarity regulate somitogenesis and neurulation with significant crosstalk.

Retrospective Analysis of Associated Anomalies in 636 Patients with Operatively Treated Congenital Scoliosis.

Background: Congenital scoliosis is frequently associated with anomalies in multiple organ systems. However, the prevalence and distribution of associated anomalies remain unclear, and there is a large amount of variation in data among different studies.

Methods: Six hundred and thirty-six Chinese patients who had undergone scoliosis correction surgery at Peking Union Medical College Hospital from January 2012 to July 2019 were recruited, as a part of the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study.

Artificially Intelligent Three-Dimensionally-Printed Patient-Specific Instrument Improves Total Hip Arthroplasty Accuracy.

Background: Patient-specific instrumentation (PSI) has the potential to improve the accuracy of implant positioning in total hip arthroplasty (THA). This prospective clinical study aimed to develop artificial intelligence to increase PSI production efficiency and assess accuracy, clinical outcomes, and learning curves.

Methods: A convolutional neural network was applied to automatically process computer tomography images.

Functional characteristics of a broad spectrum of TBX6 variants in Mayer-Rokitansky-Küster-Hauser syndrome.

Purpose: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus, cervix, and the upper part of the vagina in females. Whole-gene deletion and loss-of-function variants in TBX6 have been identified in association with MRKHS. We aimed to expand the spectrum of TBX6 variants in MRKHS and explore the biological effect of the variant alleles.

Does Abnormal Preoperative Coagulation Status Lead to More Perioperative Blood Loss in Spinal Deformity Correction Surgery?

This study aims to analyze the potential association between the preoperative coagulation status and perioperative blood loss in spinal deformity correction surgery. The preoperative coagulation status and estimated blood loss (EBL) during operation, postoperative wound drainage, and allogeneic transfusion during and after operation were recorded and analyzed. Among the 164 patients, 26 had a longer prothrombin time (PT), 13 had a lower fibrinogen level, 55 had a longer activated partial thromboplastin time (APTT), and 2 had a longer thrombin time (TT), and the platelet count (PLT) was all normal or higher than the normal level.

Exosomes derived from magnetically actuated bone mesenchymal stem cells promote tendon-bone healing through the miR-21-5p/SMAD7 pathway.

Graft healing after anterior cruciate ligament reconstruction (ACLR) involves slow biological processes, and various types of biological modulations have been explored to promote tendon-to-bone integration. Exosomes have been extensively studied as a promising new cell-free strategy for tissue regeneration, but few studies have reported their potential in tendon-to-bone healing. In this study, a novel type of exosome derived from magnetically actuated (iron oxide nanoparticles (IONPs) combined with a magnetic field) bone mesenchymal stem cells (BMSCs) (IONP-Exos) was developed, and the primary purpose of this study was to determine whether IONP-Exos exert more significant effects on tendon-to-bone healing than normal BMSC-derived exosomes (BMSC-Exos).

Validation of CT-Based Three-Dimensional Preoperative Planning in Comparison with Acetate Templating for Primary Total Hip Arthroplasty.

Objective: This study aims to compare the accuracy of CT-based preoperative planning with that of acetate templating in predicting implant size, neck length, and neck cut length, and to evaluate the reproducibility of the two methods.

Methods: This prospective study was conducted between August 2020 and March 2021. Patients who underwent elective primary total hip arthroplasty by a single surgeon were assessed for eligibility.

Development and Validation of an Artificial Intelligence Preoperative Planning System for Total Hip Arthroplasty.

Background: Accurate preoperative planning is essential for successful total hip arthroplasty (THA). However, the requirements of time, manpower, and complex workflow for accurate planning have limited its application. This study aims to develop a comprehensive artificial intelligent preoperative planning system for THA (AIHIP) and validate its accuracy in clinical performance.

Identification of Novel Variants in a Cohort of Congenital Contractural Arachnodactyly.

Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant disorder of connective tissue characterized by crumpled ears, arachnodactyly, camptodactyly, large joint contracture, and kyphoscoliosis. The nature course of CCA has not been well-described. We aim to decipher the genetic and phenotypic spectrum of CCA.

Delineation of dual molecular diagnosis in patients with skeletal deformity.

Background: Skeletal deformity is characterized by an abnormal anatomical structure of bone and cartilage. In our previous studies, we have found that a substantial proportion of patients with skeletal deformity could be explained by monogenic disorders. More recently, complex phenotypes caused by more than one genetic defect (i.

PhenoApt leverages clinical expertise to prioritize candidate genes via machine learning.

In recent years, exome sequencing (ES) has shown great utility in the diagnoses of Mendelian disorders. However, after rigorous filtering, a typical ES analysis still involves the interpretation of hundreds of variants, which greatly hinders the rapid identification of causative genes. Since the interpretations of ES data require comprehensive clinical analyses, taking clinical expertise into consideration can speed the molecular diagnoses of Mendelian disorders.

Survey of the demand for care services for older people and the training needs of their care workers: a cross-sectional study in Northeast China.

Background: The older population is increasingly utilizing professional healthcare services, while the requirements for caregivers are becoming more demanding. Therefore, it is important to be mindful not only of the service needs of older people but also to consider the training needs of their care workers. The present study aimed to investigate the care service needs for older people and the training needs of their care workers.

A genotype-first analysis in a cohort of Mullerian anomaly.

Müllerian anomaly (M.A.) is a group of congenital anatomic abnormalities caused by aberrations of the development process of the Müllerian duct.

Measuring Balance Abilities of Transtibial Amputees Using Multiattribute Utility Theory.

Background: Berg Balance Scale (BBS) can be considered the standard for assessment of functional balance but has a noted ceiling effect in active transtibial amputees (TTAs). Development of ceiling-free measures based on quantitative measurement techniques that is suitable for patients in any experience levels, yet sensitive enough to capture improvements in any stage of prosthetic rehabilitation, is needed. Does a scoring scheme based on Multiattribute Utility (MAU) theory assess balance abilities of multileveled TTAs comparable to BBS?

Methods: A case-control study including 28 participants (8 novice TTAs, 10 experienced TTAs, and 10 healthy controls) was conducted.

Aberrant interaction between mutated ADAMTSL2 and LTBP4 is associated with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a complex spinal deformity with a prevalence of 1%-3%. Genetic factors have been associated with the etiology of AIS. However, previous studies mainly focused on common single nucleotide polymorphisms which confer modest disease risk.

De novo variants in H3-3A and H3-3B are associated with neurodevelopmental delay, dysmorphic features, and structural brain abnormalities.

The histone H3 variant H3.3, encoded by two genes H3-3A and H3-3B, can replace canonical isoforms H3.1 and H3.

The Mutational Landscape of in Congenital Scoliosis and Adolescent Idiopathic Scoliosis.

Depletion of is associated with both congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS) in zebrafish models. However, only one human variant of has been reported previously in a patient with AIS. In this study, we systemically investigated the variant landscape of in 583 patients with CS and 302 patients with AIS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study.