Mutational Landscapes of Normal Skin and Their Potential Implications in the Development of Skin Cancer: A Comprehensive Narrative Review.

Recent evidence suggests that physiologically normal skin harbors pervasive mutant clones with cancer drivers. Normal skin has the highest burden of somatic mutations due to persistent ultraviolet exposure throughout life. The mutation burden exponentially increases with age and is further modified by skin site, sun-damage history, and skin phototype.

A double CYP27A1 gene mutation in spinal cerebrotendinous xanthomatosis in a patient presenting with spastic gait: a case report.

Background: Cerebrotendinous xanthomatosis (CTX, OMIM #213700) is a rare inherited metabolic disease caused by the mutation in the CYP27A1 gene. Spinal CTX is a rare clinical subgroup of CTX which lacks typical symptoms seen in classical CTX. Here we report a spinal CTX case revealed double mutation of CYP27A1 gene.

Intratumoral IL-12 delivery via mesenchymal stem cells combined with PD-1 blockade leads to long-term antitumor immunity in a mouse glioblastoma model.

Background: Although PD-1 blockade is effective for treating several types of cancer, the efficacy of this agent in glioblastoma is largely limited. To overcome non-responders and the immunosuppressive tumor microenvironment, combinational immunotherapeutic strategies with anti-PD-1 need to be considered. Here, we developed IL-12-secreting mesenchymal stem cells (MSC_IL-12) with glioblastoma tropism and evaluated the therapeutic effects of anti-PD-1, MSC_IL-12, and their combination against glioblastoma.

The RNA ligation method using modified splint DNAs significantly improves the efficiency of circular RNA synthesis.

Circular RNA (circRNA) is a non-coding RNA with a covalently closed loop structure and usually more stable than messenger RNA (mRNA). However, coding sequences (CDSs) following an internal ribosome entry site (IRES) in circRNAs can be translated, and this property has been recently utilized to produce proteins as novel therapeutic tools. However, it is difficult to produce large proteins from circRNAs because of the low circularization efficiency of lengthy RNAs.

Striatal Hyperperfusion Observed in Dual-Phase 18F-FP-CIT PET Imaging of Hyperglycemic Chorea.

A 76-year-old woman with a history of diabetes mellitus presented with right-side dominant generalized chorea. At presentation, her blood glucose level was 500 mg/dL with an HbA1C of 11%. Because the patient had been on levodopa treatment from her primary physician, a dual-phase 18F-FP-CIT PET scan was performed.

Pearls & Oy-sters: Familial Verbal Auditory Agnosia Due to Repeat Expansion.

Chromosome 9 open reading frame 72 () gene pathogenic variants have been typically associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), but recent studies suggest their involvement in other disorders. This report describes a family with an autosomal dominant pattern of inheritance of progressive verbal auditory agnosia due to GGGGCC repeat expansion in C9orf72. A 60-year-old right-handed male truck driver presented with slowly progressive poor speech perception for 8 years, which became most troublesome when receiving verbal orders over the phone.

Single-cell RNA sequencing of a poorly metastatic melanoma cell line and its subclones with high lung and brain metastasis potential reveals gene expression signature of metastasis with prognostic implication.

The molecular mechanisms underlying melanoma metastasis remain poorly understood. In this study, we aimed to delineate the mechanisms underlying gene expression alterations during metastatic potential acquisition and characterize the metastatic subclones within primary cell lines. We performed single-cell RNA sequencing of a poorly metastatic melanoma cell line (WM239A) and its subclones with high metastatic potential to the lung (113/6-4L) and the brain (131/4-5B1 and 131/4-5B2).

Single-cell RNA sequencing reveals a pro-metastatic subpopulation and the driver transcription factor NFE2L1 in ovarian cancer cells.

Background: Although cytoreductive surgery followed by adjuvant chemotherapy is effective as a standard treatment for early-stage ovarian cancer, the majority of ovarian cancer cases are diagnosed at the advanced stages with dissemination to the peritoneal cavity, leading to a poor prognosis. Therefore, it is crucial to understand the cellular and molecular mechanisms underlying metastasis and identify novel therapeutic targets.

Objective: In this study, we aimed to elucidate the mechanisms underlying gene expression alterations during the acquisition of metastatic potential and characterize the metastatic subpopulations within ovarian cancer cells.

Targeted deep sequencing reveals genomic alterations of actinic keratosis/cutaneous squamous cell carcinoma in situ and cutaneous squamous cell carcinoma.

Actinic keratosis (AK) and cutaneous squamous cell carcinoma in situ (CIS) are two of the most common precursors of cutaneous squamous cell carcinoma (cSCC). However, the genomic landscape of AK/CIS and the drivers of cSCC progression remain to be elucidated. The aim of our study was to investigate the genomic alterations between AK/CIS and cSCC in terms of somatic mutations and copy number alterations (CNAs).

Two subtypes of cutaneous melanoma with distinct mutational signatures and clinico-genomic characteristics.

To decipher mutational signatures and their associations with biological implications in cutaneous melanomas (CMs), including those with a low ultraviolet (UV) signature. We applied non-negative matrix factorization (NMF) and unsupervised clustering to the 96-class mutational context of The Genome Atlas (TCGA) cohort ( = 466) as well as other publicly available datasets ( = 527). To explore the feasibility of mutational signature-based classification using panel sequencing data, independent panel sequencing data were analyzed.

Different Molecular Features of Epithelioid and Giant Cells in Foreign Body Reaction Identified by Single-Cell RNA Sequencing.

Although macrophage‒epithelioid cell (EPC)‒giant cell (GC) differentiation is acknowledged in foreign body reaction (FBR), the exact molecular features remain elusive. To discover the molecular profiles of EPC and GC, we analyzed mouse sponge and silk FBRs by integrating single-cell RNA sequencing and spatial sequencing, which identified seven cell types, including macrophages and fibroblasts. Macrophages comprised three subsets with a trajectory from M2-like cell to EPC to GC.

Encephalitis with status epilepticus and stroke as complications of non-severe COVID-19 in a young female patient: a case report.

Background: Neurological manifestations of COVID-19 are thought to be associated with the disease severity of COVID-19 and poor clinical outcomes. Dysregulated immune responses are considered to be mediating such complications. Our case illustrates multiple critical neurological complications simultaneously developed in a patient with non-severe COVID-19 and successful recovery with a multifaceted therapeutic approach.

Single-cell RNA sequencing reveals the existence of pro-metastatic subpopulation within a parental B16 murine melanoma cell line.

The mechanism of melanoma metastasis is poorly understood, especially at the single-cell level. To understand the evolution from primary melanoma to metastasis, we investigated single-cell transcriptome profiles of parental B16 melanoma cells (B16F0) and its highly metastatic subclone (B16F10). Genomic alterations between cells were also analyzed by whole-exome sequencing.