Discordance between a deep learning model and clinical-grade variant pathogenicity classification in a rare disease cohort.

Genetic testing is essential for diagnosing and managing clinical conditions, particularly rare Mendelian diseases. Although efforts to identify rare phenotype-associated variants have focused on protein-truncating variants, interpreting missense variants remains challenging. Deep learning algorithms excel in various biomedical tasks, yet distinguishing pathogenic from benign missense variants remains elusive.

Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy in Parkinson's disease.

Human induced pluripotent stem cell (hiPSC)-derived midbrain dopaminergic cells (mDACs) represent a promising source for autologous cell therapy in Parkinson's disease (PD), but standardized regulatory criteria are essential for clinical translation. In this pre-clinical study, we generated multiple clinical-grade hiPSC lines from freshly biopsied fibroblasts of four sporadic PD patients using episomal reprogramming and differentiated them into mDACs using a refined 21-day protocol. Rigorous evaluations included whole-genome/exome sequencing, RNA sequencing, and in vivo studies, including a 39-week Good Laboratory Practice-compliant mouse safety study.

Comparison of Urinary Red Blood Cell Distribution (URD) and Dysmorphic Red Blood Cells for Detecting Glomerular Hematuria: A Multicenter Study.

Background: The clinical utility of urinary red blood cell (RBC) distribution (URD) remains limited. This study aimed to compare the diagnostic performance of URD and dysmorphic RBC (dRBC) in a multicenter study.

Methods: This study enrolled 703 patients who visited four tertiary medical centers in Korea.

Feasibility of an indocyanine green-hyaluronic acid mixture (LuminoMark™) for targeting suspicious axillary lymph nodes in patients with breast cancer.

Purpose: During breast cancer surgery, the use of dyes such as indigo carmine, methylene blue, or indocyanine green (ICG) for targeting axillary lymph nodes (ALNs) under ultrasound guidance can result in rapid diffusion, complicated tissue differentiation, and disruption of staining. LuminoMark™, a novel ICG-hyaluronic acid mixture, can provide real-time visualization and minimize dye spread, thereby ensuring a clear surgical field. The aim of our study was to evaluate the efficacy of LuminoMark™ for targeting ALNs in patients with breast cancer.

Preoperative and Postoperative Platelet-Lymphocyte Ratio Is a Prognostic Marker for Patients With Soft Tissue Sarcoma Treated With Curative Resection.

Background/aim: Systemic inflammation has been implicated in the development and progression of cancer. Inflammatory markers have been identified as prognostic indicators in numerous malignancies. This study explored the prognostic relevance of the initial and postoperative neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on relapse-free survival (RFS) and overall survival (OS) in patients with soft-tissue sarcoma (STS) who underwent curative resection.

Discordance between a deep learning model and clinical-grade variant pathogenicity classification in a rare disease cohort.

Genetic testing has become an essential component in the diagnosis and management of a wide range of clinical conditions, from cancer to developmental disorders, especially in rare Mendelian diseases. Efforts to identify rare phenotype-associated variants have predominantly focused on protein-truncating variants, while the interpretation of missense variants presents a considerable challenge. Deep learning algorithms excel in various applications across biomedical tasks, yet accurately distinguishing between pathogenic and benign genetic variants remains an elusive goal.

Primary Solid Pseudopapillary Tumor of the Ovary: A Case Report and Review of the Literature.

Introduction: Solid pseudopapillary neoplasms (SPNs) are rare and mainly originate from the pancreas. SPNs originating from the ovary (SPN-O) are extremely rare, and only 13 cases have been reported in the English literature since 2010.

Case: We report a 31-year-old woman with SPN-O accompanied by multiple metastases in the abdominal cavity.

Rare/Common Variants Are Associated with Inhaled Corticosteroid Response among Children with Asthma.

Inhaled corticosteroids (ICS) are efficacious in the treatment of asthma, which affects more than 300 million people in the world. While genome-wide association studies have identified genes involved in differential treatment responses to ICS in asthma, few studies have evaluated the effects of combined rare and common variants on ICS response among children with asthma. Among children with asthma treated with ICS with whole exome sequencing (WES) data in the PrecisionLink Biobank (91 White and 20 Black children), we examined the effect and contribution of rare and common variants with hospitalizations or emergency department visits.

Long non-coding RNA SOX2OT in tamoxifen-resistant breast cancer.

Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7).

Exploration of MELK as a downstream of Del-1 and druggable targets in triple-negative breast cancer.

Purpose: In our previous study, Developmental endothelial locus-1 (Del-1) was a promising predictive marker for breast cancer. However, the downstream targets of Del-1 remain unknown. Here, we sought to discover a druggable target downstream of Del-1 and investigate the mechanism by which it regulates the course of breast cancer.

Investigating the Influence of PbS Quantum Dot-Decorated TiO Photoanode Thickness on Photoelectrochemical Hydrogen Production Performance.

To maximize the photoelectrochemical (PEC) hydrogen production performance of quantum dot (QD)-decorated photoelectrodes, it is crucial to prioritize the optimization of electrode's structure, including thickness and porosity. In this study, we prepare PbS QD-decorated mesoporous TiO photoanodes for PEC hydrogen production, and systematically investigate the influence of the photoanode thickness on optical properties and PEC performances. As the thickness of photoanodes increases from 6.

Effectiveness of Carboplatin-Prescreening Intradermal Skin Tests to Reduce Unanticipated Immediate Hypersensitivity Reactions: A Comparative Study.

Background: Carboplatin administration poses a risk of immediate hypersensitivity reactions (IHRs) that tend to increase with repeated administration and are mostly IgE-mediated.

Objective: This study evaluated the usefulness of carboplatin-prescreening intradermal skin tests (IDTs).

Methods: Carboplatin-prescreening IDTs were routinely conducted in patients with a history of receiving six or more carboplatin cycles beginning in January 2021.

Centrosome clustering control in osteoclasts through CCR5-mediated signaling.

Osteoclasts uniquely resorb calcified bone matrices. To exert their function, mature osteoclasts maintain the cellular polarity and directional vesicle trafficking to and from the resorbing bone surface. However, the regulatory mechanisms and pathophysiological relevance of these processes remain largely unexplored.

Association between Neuroligin-1 polymorphism and plasma glutamine levels in individuals with autism spectrum disorder.

Background: Unravelling the relationships between candidate genes and autism spectrum disorder (ASD) phenotypes remains an outstanding challenge. Endophenotypes, defined as inheritable, measurable quantitative traits, might provide intermediary links between genetic risk factors and multifaceted ASD phenotypes. In this study, we sought to determine whether plasma metabolite levels could serve as endophenotypes in individuals with ASD and their family members.

Chylothorax associated with primary membranous nephropathy: a case report.

Background: Chylothorax is a state in which pleurisy is induced by chylomicron leakage due to lymphatic injury. Membranous nephropathy (MN) is one of the relatively common glomerular diseases that cause nephrotic syndrome in adults. Chylothorax at the onset of nephrotic syndrome is very rare in adult patients.

Treatment outcomes of advanced/metastatic extramammary Paget's disease in Korean patients: KCSG-RC20-06.

Background: Extramammary Paget's disease (EMPD) is rare. There are no standard treatments due to its rarity and few clinical trials.

Methods: The objective of this multicenter study was to investigate treatment outcomes of Korean patients with advanced/metastatic EMPD.

Implant-associated biofilm infection established in an experimental Galleria mellonella model.

The study reports in vivo biofilm infection implemented in an insect model. We mimicked implant-associated biofilm infections in Galleria mellonella larvae using toothbrush bristles and methicillin-resistant Staphylococcus aureus (MRSA). In vivo biofilm formation on bristle was achieved by sequentially injecting a bristle and MRSA into the larval hemocoel.

ADGR: Admixture-Informed Differential Gene Regulation.

The regulatory elements in proximal and distal regions of genes are involved in the regulation of gene expression. Risk alleles in intronic and intergenic regions may alter gene expression by modifying the binding affinity and stability of diverse DNA-binding proteins implicated in gene expression regulation. By focusing on the local ancestral structure of coding and regulatory regions using the paired whole-genome sequence and tissue-wide transcriptome datasets from the Genotype-Tissue Expression project, we investigated the impact of genetic variants, in aggregate, on tissue-specific gene expression regulation.

Oncologic necessity for the complete removal of residual microcalcifications after neoadjuvant chemotherapy for breast cancer.

The surgical range of breast cancer that shows pathologic complete response (pCR) without change in microcalcifications after neoadjuvant chemotherapy (NAC) is controversial. This study examined whole breast specimens to evaluate the necessity of mastectomy in those cases. The viability of cancer cells around the residual microcalcification was assessed using prospectively collected breast samples to confirm the presence or absence of cancer cells.