Genetic Association of Juvenile Idiopathic Arthritis With Adult Rheumatic Disease.

Importance: Patients with juvenile idiopathic arthritis (JIA) may develop adult rheumatic diseases later in life, and prolonged or recurrent disease activity is often associated with substantial disability; therefore, it is important to identify patients with JIA at high risk of developing adult rheumatic diseases and provide specialized attention and preventive care to them.

Objective: To elucidate the full extent of the genetic association of JIA with adult rheumatic diseases, to improve treatment strategies and patient outcomes for patients at high risk of developing long-term rheumatic diseases.

Design, Setting, And Participants: In this genetic association study of 4 disease genome-wide association study (GWAS) cohorts from 2013 to 2024 (JIA, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], and systemic sclerosis [SSc]), patients in the JIA cohort were recruited from the US, Australia, and Norway (with a UK cohort included in the meta-analyzed cohort), while patients in the other 3 cohorts were recruited from US and Western European countries.

Parallel Analyses by Mass Spectrometry (MS) and Reverse Phase Protein Array (RPPA) Reveal Complementary Proteomic Profiles in Triple-Negative Breast Cancer (TNBC) Patient Tissues and Cell Cultures.

High-plex proteomic technologies have made substantial contributions to mechanism studies and biomarker discovery in complex diseases, particularly cancer. Despite technological advancements, inherent limitations in individual proteomic approaches persist, impeding the achievement of comprehensive quantitative insights into the proteome. In this study, we employed two widely used proteomic technologies, mass spectrometry (MS) and reverse phase protein array (RPPA) to analyze identical samples, aiming to systematically assess the outcomes and performance of the different technologies.

[Clinical Characteristics and Survival Analysis of Single Center Adult Chronic Myeloid Leukemia in Chronic Phase].

Objective: To investigate the clinical characteristics and prognosis of single center adult chronic myeloid leukemia in chronic phase (CML-CP).

Methods: Clinical data of 41 adult CML-CP patients in Department of Hematology, Shanghai Fengxian District Central Hospital from January 2015 to May 2021 were retrospectively analyzed. The clinical characteristics and prognosis of patients between <60 years group and ≥60 years group were compared.

Shared molecular mechanisms and transdiagnostic potential of neurodevelopmental disorders and immune disorders.

The co-occurrence and familial clustering of neurodevelopmental disorders and immune disorders suggest shared genetic risk factors. Based on genome-wide association summary statistics from five neurodevelopmental disorders and four immune disorders, we conducted genome-wide, local genetic correlation and polygenic overlap analysis. We further performed a cross-trait GWAS meta-analysis.

Revealing novel genomic insights and therapeutic targets for juvenile idiopathic arthritis through omics.

Background: The genetic architecture of JIA remains only partially comprehended. There is a clear imperative for continued endeavours to uncover insights into the underlying causes of JIA.

Methods: This study encompassed a comprehensive spectrum of endeavours, including conducting a JIA genome-wide association study (GWAS) meta-analysis that incorporated data from 4550 JIA cases and 18 446 controls.

Target genes regulated by CLEC16A intronic region associated with common variable immunodeficiency.

Background: CLEC16A intron 19 has been identified as a candidate locus for common variable immunodeficiency (CVID).

Objectives: This study sought to elucidate the molecular mechanism by which variants at the CLEC16A intronic locus may contribute to the pathogenesis of CVID.

Methods: The investigators performed fine-mapping of the CLEC16A locus in a CVID cohort, then deleted the candidate functional SNP in T-cell lines by the CRISPR-Cas9 technique and conducted RNA-sequencing to identify target gene(s).

[The role of apolipoprotein C3 in the regulation of nonalcoholic fatty liver disease, glucose and lipid metabolism, and islet β cell function].

As a member of the apolipoprotein C (ApoC) family with a relatively high content, ApoC3 plays a major role in the regulation of triglyceride metabolism, and plays an important role in the occurrence and development of cardiovascular diseases, glucose and lipid metabolism disorders. Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of a large amount of fat in the liver in the absence of a history of chronic alcohol consumption or other damage to the liver. A large number of previous studies have shown that there is a correlation between the gene polymorphism and high expression of ApoC3 and NAFLD.

Deciphering the immune modulation through deep transcriptomic profiling and therapeutic implications of DNA damage repair pattern in hepatocellular carcinoma.

Aims: DNA damage repair (DDR) plays a pivotal role in hepatocellular carcinoma (HCC), driving oncogenesis, progression, and therapeutic response. However, the mechanisms of DDR mediated immune cells and immuno-modulatory pathways in HCC are yet ill-defined.

Methods: Our study introduces an innovative deep machine learning framework for precise DDR assessment, utilizing single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data.

High-plex spatial transcriptomic profiling reveals distinct immune components and the HLA class I/DNMT3A/CD8 modulatory axis in mismatch repair-deficient endometrial cancer.

Purpose: Tumors bearing mismatch repair deficiency (MMRd) are characterized by a high load of neoantigens and are believed to trigger immunogenic reactions upon immune checkpoint blockade treatment such as anti-PD-1/PD-L1 therapy. However, the mechanisms are still ill-defined, as multiple cancers with MMRd exhibit variable responses to immune checkpoint inhibitors (ICIs). In endometrial cancer (EC), a distinct tumor microenvironment (TME) exists that may correspond to treatment-related efficacies.

[Analysis of the causes of soft tissue complications after volar locking plate for the treatment of dorsal displaced distal radius fractures].

Objective: To investigate the causes of soft tissue complications in patients with dorsal displacement distal radius fractures (DRF) after volar locking plate surgery.

Methods: From July 2016 to May 2021, 112 patients with dorsal displacement DRF were treated with volar locking plate surgery, including 45 males and 67 females. The average age was (46.

A Holocene lacustrine record of variations in chemical weathering intensity in the Mu Us Desert, China.

The Mu Us Desert is an ideal location to study environmental changes during the Late Quaternary, because of its unique characteristics. The Abaoyan (ABY) profile, a typical aeolian-lacustrine profile located at the eastern edge of the desert, was investigated in this study. A basic chronological framework was established based on a combination of radiocarbon dating by accelerator mass spectrometry and in situ sedimentary phase identification.

Persistent and enhanced carbon sequestration capacity of alpine grasslands on Earth's Third Pole.

The carbon sequestration capacity of alpine grasslands, composed of alpine meadows and steppes, in the Tibetan Plateau has an essential role in regulating the regional carbon cycle. However, inadequate understanding of its spatiotemporal dynamics and regulatory mechanisms restricts our ability to determine potential climate change impacts. We assessed the spatial and temporal patterns and mechanisms of the net ecosystem exchange (NEE) of carbon dioxide in the Tibetan Plateau.

High-Plex Spatial Profiling of RNA and Protein Using Digital Spatial Profiler.

The rapid emergence of spatial multi-omics technologies in recent years has revolutionized biomedical research. Among these, the Digital Spatial Profiler (DSP, commercialized by nanoString) has become one of the dominant technologies in spatial transcriptomics and proteomics and has assisted in deconvoluting complex biological questions. Based on our practical experience in the past 3 years with DSP, we share here a detailed hands-on protocol and key handling notes that will allow the broader community to optimize their work procedure.

Detecting the steerability through an optimized steering criterion in two-photon systems.

The steerability of a quantum state can be detected by steering inequalities. The linear steering inequalities show that more steerable states can be discovered with the increase of measurements. In order to detect more steerable states in two-photon systems, we first theoretically derive an optimized steering criterion based on infinity measurements for an arbitrary two-qubit state.

Identification of copy number variants contributing to hallux valgus.

Hallux valgus is a common form of foot deformity, and genetic factors contribute substantially to the pathogenesis of hallux valgus deformity. We conducted a genetic study on the structural variants underlying familial hallux valgus using whole exome sequencing approach. Twenty individuals from five hallux valgus families and two sporadic cases were included in this study.

Altered Functional Connectivity Strength in Distinct Brain Networks of Children With Early-Onset Schizophrenia.

Background: Schizophrenia is regarded as a brain network or connectome disorder that is associated with neurodevelopment. Children with early-onset schizophrenia (EOS) provide an opportunity to evaluate the neuropathology of schizophrenia at a very early stage without potential confounding factors. But dysfunction in brain networks of schizophrenia is inconsistent.

A reverse phase protein array based phospho-antibody characterization approach and its applicability for clinical derived tissue specimens.

Systematic quantification of phosphoprotein within cell signaling networks in solid tissues remains challenging and precise quantification in large scale samples has great potential for biomarker identification and validation. We developed a reverse phase protein array (RPPA) based phosphor-antibody characterization approach by taking advantage of the lysis buffer compatible with alkaline phosphatase (AP) treatment that differs from the conventional RPPA antibody validation procedure and applied it onto fresh frozen (FF) and formalin-fixed and paraffin-embedded tissue (FFPE) to test its applicability. By screening 106 phospho-antibodies using RPPA, we demonstrated that AP treatment could serve as an independent factor to be adopted for rapid phospho-antibody selection.

Altered functional association and couplings: Effective diagnostic neuromarkers for Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disorder causing dementia in the elderly population. Functional disconnection of brain is considered to be the main cause of AD. In this study, we applied a newly developed association (Asso) mapping approach to directly quantify the functional disconnections and to explore the diagnostic effects for AD with resting-state functional magnetic resonance imaging data from 36 AD patients and 42 age-, gender-, and education-matched healthy controls (HC).

Neural signatures of default mode network in major depression disorder after electroconvulsive therapy.

Functional abnormalities of default mode network (DMN) have been well documented in major depressive disorder (MDD). However, the association of DMN functional reorganization with antidepressant treatment and gene expression is unclear. Moreover, whether the functional interactions of DMN could predict treatment efficacy is also unknown.

[Correlation between Expression of CD47 Molecule in Patients with Newly Diagnosed Adult Acute Myeloid Leukemia and Clinical Prognosis].

Objective: To investigate the expression of CD47 molecules in patients with newly diagnosis of adult acute myeloid leukemia (AML) and its correlation with clinical prognosis.

Methods: 20 patients with acute myeloid leukemia diagnosed in Shanghai Fengxian District Central hospital from April 2020 to October 2021 and 5 cases with non malignant hematological diseases in the control group were collected, and the expression of CD47 in single nuclear cells of bone marrow and peripheral blood was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). Combined with the blood image, bone marrow smears, flow cytometry, chromosome and gene detection, ECOG score, etc.

Cases report: MRI findings of asymptomatically familial subependymal heterotopia with filamin A gene abnormality.

Subependymal heterotopia (SEH) is a rare neuronal migration disorder consisting of gray matter nodules along the lateral ventricular walls and is often associated with other brain malformations. Despite most SEH cases showing epilepsy during their lifetimes, very few patients with asymptomatically familial SEH tend to cause misdiagnosis or missed diagnosis. We present four familial SEH cases without any positive symptoms and medical history, including two fetuses, who were diagnosed by MRI and confirmed by genetic testing with mutation of filamin A.