From Death to Life/Back to the Future: Detailed Premorbid Clinical and Family History Can Save Lives and Address the Final Diagnosis in Sudden Unexplained Deaths With Negative Autopsy.

Sudden cardiac death is a sudden, unexpected death developed by one of the many different causes of cardiac arrest that occur within 1 hour of the onset of new symptoms. Sudden unexplained death (SUD) comprises a normal heart at postmortem examination and negative toxicological analysis. SUD often arises from cardiac genetic disease, particularly channelopathies.

An alternatively spliced PD-L1 isoform PD-L1∆3, and PD-L2 expression in breast cancers: implications for eligibility scoring and immunotherapy response.

Targeting PD-1/PD-L1 has shown substantial therapeutic response and unprecedented long-term durable responses in the clinic. However, several challenges persist, encompassing the prediction of treatment effectiveness and patient responses, the emergence of treatment resistance, and the necessity for additional biomarkers. Consequently, we comprehensively explored the often-overlooked isoforms of crucial immunotherapy players, leveraging transcriptomic analysis, structural modeling, and immunohistochemistry (IHC) data.

Magnetic resonance spectroscopic correlates of progression free and overall survival in "glioblastoma, IDH-wildtype, WHO grade-4".

Background: The 2021 World Health Organization (WHO) Central Nervous System (CNS) Tumor Classification has suggested that isocitrate dehydrogenase wildtype (IDH-wt) WHO grade-2/3 astrocytomas with molecular features of glioblastoma should be designated as "Glioblastoma, IDH-wildtype, WHO grade-4." This study analyzed the metabolic correlates of progression free and overall survival in "Glioblastoma, IDH-wildtype, WHO grade-4" patients using short echo time single voxel H-MRS.

Methods: Fifty-seven adult patients with hemispheric glioma fulfilling the 2021 WHO CNS Tumor Classification criteria for "Glioblastoma, IDH-wildtype, WHO grade-4" at presurgery time point were included.

Sequential filtering for clinically relevant variants as a method for clinical interpretation of whole exome sequencing findings in glioma.

Background: In the clinical setting, workflows for analyzing individual genomics data should be both comprehensive and convenient for clinical interpretation. In an effort for comprehensiveness and practicality, we attempted to create a clinical individual whole exome sequencing (WES) analysis workflow, allowing identification of genomic alterations and presentation of neurooncologically-relevant findings.

Methods: The analysis workflow detects germline and somatic variants and presents: (1) germline variants, (2) somatic short variants, (3) tumor mutational burden (TMB), (4) microsatellite instability (MSI), (5) somatic copy number alterations (SCNA), (6) SCNA burden, (7) loss of heterozygosity, (8) genes with double-hit, (9) mutational signatures, and (10) pathway enrichment analyses.

Mutations and Copy Number Alterations in Wild-Type Glioblastomas Are Shaped by Different Oncogenic Mechanisms.

Little is known about the mutational processes that shape the genetic landscape of gliomas. Numerous mutational processes leave marks on the genome in the form of mutations, copy number alterations, rearrangements or their combinations. To explore gliomagenesis, we hypothesized that gliomas with different underlying oncogenic mechanisms would have differences in the burden of various forms of these genomic alterations.

Analyses of Copy Number Variations in Myxopapillary Ependymomas of Cauda Equina.

Aim: To identify the copy number variations that are specific to myxopapillary ependymomas (MPEs) of the cauda equina.

Material And Methods: The patient cohort included five patients who underwent resection of histologically confirmed MPEs. Tumor samples collected during surgery and stored in liquid nitrogen as well as corresponding blood samples collected were analyzed.

Toward Epigenetic Drug Design for Thyroid Cancer: The Promise of PF-03814735, an Aurora Kinase Inhibitor.

Thyroid cancer (TC) is a very common malignancy worldwide. Chief among the innovative molecular drug targets for TC are epigenetic modifications. Increased telomerase activity in cancer cells makes telomerase a novel target for epigenetic anticancer drug innovation.

A novel homozygous nonsense mutation in CAST associated with PLACK syndrome.

Peeling skin syndrome is a heterogeneous group of rare disorders. Peeling skin, leukonychia, acral punctate keratoses, cheilitis and knuckle pads (PLACK syndrome, OMIM616295) is a newly described form of PSS with an autosomal recessive mode of inheritance. We report a 5.

Whole exome sequencing-based analysis to identify DNA damage repair deficiency as a major contributor to gliomagenesis in adult diffuse gliomas.

Objective: Processes that cause or contribute to cancer, such as aging, exposure to carcinogens, or DNA damage repair deficiency (DDRd), create predictable and traceable nucleotide alterations in one's genetic code (termed "mutational signatures"). Large studies have previously identified various such mutational signatures across cancers that can be attributed to the specific causative processes. To gain further insight into the processes in glioma development, the authors analyzed mutational signatures in adult diffuse gliomas (DGs).

Use of telomerase promoter mutations to mark specific molecular subsets with reciprocal clinical behavior in IDH mutant and IDH wild-type diffuse gliomas.

OBJECTIVE Recent studies have established that hemispheric diffuse gliomas may be grouped into subsets on the basis of molecular markers; these subsets are loosely correlated with the histopathological diagnosis but are strong predictors of clinical tumor behavior. Based on an analysis of molecular and clinical parameters, the authors hypothesized that mutations of the telomerase promoter (TERTp-mut) mark separate oncogenic programs among isocitrate dehydrogenase 1 and/or 2 (IDH) mutant (IDH-mut) and IDH wild-type (IDH-wt) diffuse gliomas independent of histopathology or WHO grade. METHODS Four molecular subsets of the combined statuses of IDH and TERT-promoter mutations (double mutant, IDH only, TERT only, and double negative) were defined.

Role of FLT3 in the proliferation and aggressiveness of hepatocellular carcinoma.

Background/aim: Previously we showed that Fms-like tyrosine kinase (FLT3) changes its cellular localization upon partial hepatectomy, suggesting a role in liver regeneration. FLT3 was also shown to play an important function in cellular proliferation and activation of PI3K and Ras. Thus, we aimed to investigate the role of FLT3 in hepatocellular tumorigenesis utilizing in vitro and in vivo models.

IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation.

The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown.

A case of pulmonary alveolar microlithiasis associated with a homozygous 195 kb deletion encompassing the entire SLC34A2 gene.

With around 500 cases published worldwide, pulmonary alveolar microlithiasis is a rare disorder with an autosomal recessive pattern of inheritance. We show for the first time that homozygous deletions encompassing the entire SCL34A2 can be associated with this rare genetic pulmonary disease.

Association of Pre-miRNA-499 rs3746444 and Pre-miRNA-146a rs2910164 Polymorphisms and Susceptibility to Behcet's Disease.

MiRNAs and NFKB1 are well-known immune response and inflammation regulators. MiRNA gene polymorphisms may affect miRNA biogenesis and function and, may thus, lead to changes in the expression of hundreds of genes such as NFKB1. The aim of this study was to investigate the association of Behcet's disease (BD) with NFKB1 rs28362491, pre-miRNA-146a rs2910164, and pre-miRNA-499 rs3746444 polymorphisms, as well as the analysis of their single and combined effects on its susceptibility in a Turkish population.

Chromosome 22q12.1 microdeletions: confirmation of the MN1 gene as a candidate gene for cleft palate.

We report on seven novel patients with a submicroscopic 22q12 deletion. The common phenotype constitutes a contiguous gene deletion syndrome on chromosome 22q12.1q12.

PTPRD is homozygously deleted and epigenetically downregulated in human hepatocellular carcinomas.

PTPRD (protein tyrosine phosphatase, receptor type, D) is a tumor suppressor gene, frequently inactivated through deletions or epigenetic mechanisms in several cancers with importance for global health. In this study, we provide new and functionally integrated evidence on genetic and epigenetic alterations of PTPRD gene in hepatocellular carcinomas (HCCs). Importantly, HCC is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide.

ALCAM is indirectly modulated by miR-125b in MCF7 cells.

MicroRNA (miRNA) deregulation is associated with various cancers. Among an expanding list of cancer-related miRNAs, deregulation of miR-125b has been well documented in many cancers including breast. Based on current knowledge, miR-125b is considered to be a tumor suppressor in breast cancers.

Association of NFKB1 and NFKBIA polymorphisms in relation to susceptibility of Behçet's disease.

Behçet's disease (BD) is a chronic inflammatory autoimmune disease. Although raised levels of proinflammatory cytokines in BD have been reported, the pathogenesis is still unknown. The aim of this study was to investigate the association of NFKB1 and NFKBIA polymorphisms and their single and combined analysis effects on susceptibility of BD in Turkish population.

Serum bone markers levels and bone mineral density in familial mediterranean Fever.

[Purpose] The aim of this study was to measure bone mineral density, serum and urinary bone turnover parameters, and to evaluate the influence of demographic and genetic factors on these parameters in FMF patients. [Subjects and Methods] Twenty-seven attack-free patients who were diagnosed with FMF (in accordance with Tel Hashomer criteria) were recruited at outpatient rheumatology clinics. We investigated whether there were any differences between the FMF patients and a control group in terms of lumbar and femur bone mineral density (BMD), standard deviation scores (Z scores and T scores) and bone markers.

Translating biotechnology to knowledge-based innovation, peace, and development? Deploy a Science Peace Corps--an open letter to world leaders.

Scholarship knows no geographical boundaries. This science diplomacy and biotechnology journalism article introduces an original concept and policy petition to innovate the global translational science, a Science Peace Corps. Service at the new Corps could entail volunteer work for a minimum of 6 weeks, and up to a maximum of 2 years, for translational research in any region of the world to build capacity manifestly for development and peace, instead of the narrow bench-to-bedside model of life science translation.

Injectable tissue-engineered cartilage using commercially available fibrin glue.

Objectives/hypothesis: To achieve injectable tissue-engineered cartilage using a commercially available fibrin sealant, and to determine the most suitable fibrin glue concentration, cartilage source, and cultured chondrocyte concentration.

Study Design: Animal research.

Methods: A total of 28 immunocompetent New Zealand white rabbits were divided into four groups.

Muscle hemangiomatosis presenting as a severe feature in a patient with the pten mutation: expanding the phenotype of vascular malformations in bannayan-riley-ruvalcaba syndrome.

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare autosomal, dominantly-inherited, hamartoma syndrome with distinct phenotypic features. Mutations in the PTEN gene have been identified in PTEN hamartoma tumor syndromes. Our aim was to determine the correlation of phenotype-genotype relationships in a BRRS case.

SIP1 is downregulated in hepatocellular carcinoma by promoter hypermethylation.

Background: Smad interacting protein-1 is a transcription factor that is implicated in transforming growth factor-β/bone morphogenetic protein signaling and a repressor of E-cadherin and human telomerase reverse transcriptase. It is also involved in epithelial-mesenchymal transition and tumorigenesis. However, genetic and epigenetic alterations of SIP1 have not been fully elucidated in cancers.

Mdm2 Snp309 G allele displays high frequency and inverse correlation with somatic P53 mutations in hepatocellular carcinoma.

Loss of function of the p53 protein, which may occur through a range of molecular events, is critical in hepatocellular carcinoma (HCC) evolution. MDM2, an oncogene, acts as a major regulator of the p53 protein. A polymorphism in the MDM2 promoter, SNP309 (T/G), has been shown to alter protein expression and may thus play a role in carcinogenesis.

An investigation of microRNAs mapping to breast cancer related genomic gain and loss regions.

Various regions of amplification or loss are observed in breast tumors as a manifestation of genomic instability. To date, numerous oncogenes or tumor suppressors on some of these regions have been characterized. An increasing body of evidence suggests that such regions also harbor microRNA genes with crucial regulatory roles in cellular processes and disease mechanisms, including cancer.