CoREST Complex Inhibition Alters RNA Splicing to Promote Neoantigen Expression and Enhance Tumor Immunity.

Unlabelled: Epigenetic complexes tightly regulate gene expression and colocalize with RNA splicing machinery; however, the consequences of these interactions are uncertain. Here, we identify unique interactions of the CoREST repressor complex with RNA splicing factors and their functional consequences in tumorigenesis. Using mass spectrometry, in vivo binding assays, and cryo-EM we find that CoREST complex-splicing factor interactions are direct and perturbed by the CoREST complex inhibitor, corin, leading to extensive changes in RNA splicing in melanoma and other malignancies.

Regional variations in psoriatic arthritis: Insights from a nationwide multicenter analysis in Türkiye.

Objectives: The study aimed to investigate and compare clinical features, disease activity, and the overall disease burden among psoriatic arthritis (PsA) patients across seven distinct geographic regions in Türkiye.

Patients And Methods: A multicenter cross-sectional study involving 1,134 PsA patients from 25 referral centers across seven regions was conducted. Demographic and clinical characteristics, comorbidities, joint involvement, extra-articular manifestations, and disease activity measures were evaluated across regions.

First Reported Case of Anaphylaxis to Nebulized Tranexamic Acid in a Pediatric Patient: A Rare but Critical Event.

Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss due to certain medical conditions. It has a low side effect profile and is safe to administer in most instances. Anaphylaxis cases due to intravenous TXA have been reported in the literature.

Design of Cytotoxic T Cell Epitopes by Machine Learning of Human Degrons.

Antigen processing is critical for therapeutic vaccines to generate epitopes for priming cytotoxic T cell responses against cancer and pathogens, but insufficient processing often limits the quantity of epitopes released. We address this challenge using machine learning to ascribe a proteasomal degradation score to epitope sequences. Epitopes with varying scores were translocated into cells using nontoxic anthrax proteins.

Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination.

Multivalent presentation of ligands often enhances receptor activation and downstream signalling. DNA origami offers a precise nanoscale spacing of ligands, a potentially useful feature for therapeutic nanoparticles. Here we use a square-block DNA origami platform to explore the importance of the spacing of CpG oligonucleotides.

CKLF instigates a "cold" microenvironment to promote MYCN-mediated tumor aggressiveness.

Solid tumors, especially those with aberrant MYCN activation, often harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance. Despite this knowledge, there are no effective strategies to tackle this problem. We found that chemokine-like factor () is highly expressed by various solid tumor cells and transcriptionally up-regulated by MYCN.

Effect of Robotic Rehabilitation on Hand Functions and Quality of Life in Children With Cerebral Palsy: A Prospective Randomized Controlled Study.

Objective: This study aimed to examine the impact of robotic hand rehabilitation on hand function and quality of life in children with cerebral palsy.

Design: Children with cerebral palsy aged 7-16 yrs were divided into robotic rehabilitation ( n = 9) or conventional rehabilitation ( n = 10) groups for hand rehabilitation of 30 sessions. The primary outcomes were the Fugl-Meyer Assessment for Upper Extremity and Box and Block Test.

Radiological and Clinical Outcomes of Pediatric Patients With a Supracondylar Humerus Fracture Surgically Treated With Closed Reduction and Percutaneous Pinning.

Objectives: It was aimed to evaluate the clinical and radiological results of patients operated on with closed reduction and pinning due to pediatric supracondylar humerus fractures.

Materials And Methods: The radiological and clinical results of 100 patients operated on with closed reduction and percutaneous pinning for pediatric supracondylar humerus fractures in the Department of Orthopedics and Traumatology were examined between January 2015 and February 2022. Clinical results were evaluated by performing cosmetic and functional scores defined by Flynn.

Dictionary of immune responses to cytokines at single-cell resolution.

Cytokines mediate cell-cell communication in the immune system and represent important therapeutic targets. A myriad of studies have highlighted their central role in immune function, yet we lack a global view of the cellular responses of each immune cell type to each cytokine. To address this gap, we created the Immune Dictionary, a compendium of single-cell transcriptomic profiles of more than 17 immune cell types in response to each of 86 cytokines (>1,400 cytokine-cell type combinations) in mouse lymph nodes in vivo.

Integrated Immunopeptidomic and Proteomic Analysis of COVID-19 lung biopsies.

Introduction: Severe respiratory illness is the most prominent manifestation of patients infected with SARS-CoV-2, and yet the molecular mechanisms underlying severe lung disease in COVID-19 affected patients still require elucidation. Human leukocyte antigen class I (HLA-I) expression is crucial for antigen presentation and the host's response to SARS-CoV-2.

Methods: To gain insights into the immune response and molecular pathways involved in severe lung disease, we performed immunopeptidomic and proteomic analyses of lung tissues recovered at four COVID-19 autopsy and six non-COVID-19 transplants.

Differentiation of BCMA-specific induced pluripotent stem cells into rejuvenated CD8αβ+ T cells targeting multiple myeloma.

A major hurdle in adoptive T-cell therapy is cell exhaustion and failure to maintain antitumor responses. Here, we introduce an induced pluripotent stem cell (iPSC) strategy for reprogramming and revitalizing precursor exhausted B-cell maturation antigen (BCMA)-specific T cells to effectively target multiple myeloma (MM). Heteroclitic BCMA72-80 (YLMFLLRKI)-specific CD8+ memory cytotoxic T lymphocytes (CTL) were epigenetically reprogrammed to a pluripotent state, developed into hematopoietic progenitor cells (CD34+ CD43+/CD14- CD235a-), differentiated into the T-cell lineage and evaluated for their polyfunctional activities against MM.

Novel barium-doped-baghdadite incorporated PHBV-PCL composite fibrous scaffolds for bone tissue engineering.

Bioceramic/polymer composites have dragged a lot of attention for treating hard tissue damage in recent years. In this study, we synthesized barium-doped baghdadite (Ba-BAG), as a novel bioceramic, and later developed fibrous composite poly (hydroxybutyrate) co (hydroxyvalerate)- polycaprolactone (PHBV-PCL) scaffolds containing different amounts of baghdadite (BAG) and Ba-BAG, intended to be used in bone regeneration. Our results demonstrated that BAG and Ba-doped BAG powders were synthesized successfully using the sol-gel method and their microstructural, physicochemical, and cytotoxical properties results were evaluated.

The BRD4-NUT Fusion Alone Drives Malignant Transformation of NUT Carcinoma.

Unlabelled: NUT carcinoma (NC) is an aggressive squamous carcinoma defined by the BRD4-NUT fusion oncoprotein. Routinely effective systemic treatments are unavailable for most NC patients. The lack of an adequate animal model precludes identifying and leveraging cell-extrinsic factors therapeutically in NC.

Diagnostic delay in psoriatic arthritis: insights from a nationwide multicenter study.

This study aimed to investigate the duration of diagnostic delay in patients with psoriatic arthritis (PsA) and identify potential contributing factors using a comprehensive, population-based approach. Data were obtained from the Turkish League Against Rheumatism (TLAR)-Network, involving patients who met the CASPAR criteria. Diagnostic delay was defined as time interval from symptom onset to PsA diagnosis, categorized as ≤ 2 years and > 2 years.

Design of Cytotoxic T Cell Epitopes by Machine Learning of Human Degrons.

Antigen processing is critical for producing epitope peptides that are presented by HLA molecules for T cell recognition. Therapeutic vaccines aim to harness these epitopes for priming cytotoxic T cell responses against cancer and pathogens, but insufficient processing often reduces vaccine efficacy through limiting the quantity of epitopes released. Here, we set out to improve antigen processing by harnessing protein degradation signals called degrons from the ubiquitin-proteasome system.

The effect of pharmacological treatment in combination with vitamin K on healing in an experimental rat model of osteoporosis.

Objectives: This study aims to compare the effects of teriparatide, zoledronic acid, and their combination therapy with vitamin K on osteoporotic rats.

Materials And Methods: We divided a total of 50 female Sprague-Dawley rats into five groups: A (the control group), B and D (the teriparatide group), and C and E (the zoledronic acid group). Following ovariectomy and subcutaneous heparin administration at a dose of 2 IU/kg for four weeks, osteoporosis was created.

ALK peptide vaccination restores the immunogenicity of ALK-rearranged non-small cell lung cancer.

Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is treated with ALK tyrosine kinase inhibitors (TKIs), but the lack of activity of immune checkpoint inhibitors (ICIs) is poorly understood. Here, we identified immunogenic ALK peptides to show that ICIs induced rejection of ALK tumors in the flank but not in the lung. A single-peptide vaccination restored priming of ALK-specific CD8 T cells, eradicated lung tumors in combination with ALK TKIs and prevented metastatic dissemination of tumors to the brain.

Beyond expectations: disease duration and psychological burden in psoriatic arthritis.

This study aims to investigate the relationship between disease duration and psychological burden in PsA and to identify the risk factors associated with psychological distress. Patients with PsA who met CASPAR classification criteria enrolled by Turkish League Against Rheumatism (TLAR)-Network. Patients were categorized into three groups based on disease duration: early stage (< 5 years), middle stage (≥ 5, < 10 years), and late stage (≥ 10 years).

Protocol for Classification Single-Cell PBMC Types from Pathological Samples Using Supervised Machine Learning.

Peripheral blood mononuclear cells (PBMC) are mixed subpopulations of blood cells composed of five cell types. PBMC are widely used in the study of the immune system, infectious diseases, cancer, and vaccine development. Single-cell transcriptomics (SCT) allows the labeling of cell types by gene expression patterns from biological samples.

Lynch syndrome cancer vaccines: A roadmap for the development of precision immunoprevention strategies.

Hereditary cancer syndromes (HCS) account for 5~10% of all cancer diagnosis. Lynch syndrome (LS) is one of the most common HCS, caused by germline mutations in the DNA mismatch repair (MMR) genes. Even with prospective cancer surveillance, LS is associated with up to 50% lifetime risk of colorectal, endometrial, and other cancers.

Nanogel-based coating as an alternative strategy for biofilm control in drinking water distribution systems.

Biofilm formation and detachment in drinking water distribution systems (DWDS) can lead to several operational issues. Here, an alternative biofilm control strategy of limiting bacterial adhesion by application of a poly(-isopropylmethacrylamide)-based nanogel coating on DWDS pipe walls was investigated. The nanogel coatings were successfully deposited on surfaces of four polymeric pipe materials commonly applied in DWDS construction.

Cytogenetic profile of adult AML patients in Turkey: a single center study with comprehensive comparison with literature.

Background: Cytogenetic findings are important prognostic factors in acute myeloid leukemia. Large systematic data about chromosomal characteristics of Turkish AML patients have not been reported to date.

Objectives: The karyotypic profiles of 157 adult AML patients were evaluated retrospectively and compared with other reports from different populations.