High sensitivity of host Helios/Neuropilin-1 Treg to pretransplant conditioning hampers development of OX40/integrin-β7 regulatory cells in acute gastrointestinal GvHD.

This study sought to compare the behavior of Treg subsets displaying different coexpression patterns of Neuropilin-1 (Nrp1) and Helios, under the influence of gut stress unrelated to hematopoietic stem cell transplantation, pretransplantation conditioning, and posttransplant gastrointestinal acute graft versus host disease (GI-aGvHD). Host CD4/CD25/Foxp3 Treg cells, identified by flow cytometry, were isolated from various tissues of mice affected by these stressors. Expression of CD25, CTLA-4, CD39, OX40, integrin-β7, LAG3, TGFβ/LAP, granzyme-A, -B, and interleukin-10 was compared in four Treg subsets displaying Helios or Nrp1 only, both or none.

Genome sequencing-based discovery of a novel deep intronic APC pathogenic variant causing exonization.

Familial adenomatous polyposis (FAP) is a hereditary cancer syndrome that occurs as a result of germline mutations in the APC gene. Despite a clear clinical diagnosis of FAP, a certain proportion of the APC variants are not readily detectable through conventional genotyping routines. We accomplished genome sequencing in duo of the disease-affected proband and non-affected sibling followed by in silico predictions and a series of RNA-based assays clarifying variant functionality.

Aspirin Mediates Its Antitumoral Effect Through Inhibiting PTTG1 in Pituitary Adenoma.

Context: DNA demethylation and inhibitory effects of aspirin on pituitary cell proliferation have been demonstrated.

Objective: Our aim was to clarify the molecular mechanisms behind the aspirin-related effects in pituitary cells.

Methods: DNA methylome and whole transcriptome profile were investigated in RC-4B/C and GH3 pituitary cell lines upon aspirin treatment.

Mechanisms behind context-dependent role of glucocorticoids in breast cancer progression.

Glucocorticoids (GCs), mostly dexamethasone (dex), are routinely administered as adjuvant therapy to manage side effects in breast cancer. However, recently, it has been revealed that dex triggers different effects and correlates with opposite outcomes depending on the breast cancer molecular subtype. This has raised new concerns regarding the generalized use of GC and suggested that the context-dependent effects of GCs can be taken into potential consideration during treatment design.

Circulating Noncoding RNAs in Pituitary Neuroendocrine Tumors-Two Sides of the Same Coin.

Pituitary neuroendocrine tumors (PitNET) are common intracranial neoplasms. While in case of hormone secreting tumors pituitary hormone measurements can be used for monitoring the disease, in non-functional tumors there is a need to discover non-invasive biomarkers. Non-coding RNAs (ncRNAs) are popular biomarker candidates due to their stability and tissue specificity.

Case Report: A Novel Pathomechanism in PEComa by the Loss of Heterozygosity of .

Since the introduction of next-generation sequencing, the frequency of germline pathogenic variants and the number of cases with unusual clinical presentations have been increasing. This has led to the expansion of the classical Li-Fraumeni syndrome concept to a wider cancer predisposition syndrome designated as the Li-Fraumeni spectrum. Here, we present a case with a malignant, metastatic perivascular epithelioid cell tumor (PEComa) of the thigh muscle and a sinonasal carcinoma harboring a novel germline splice mutation (NM_000546.

Decreased Plasma Level of Cytokeratin 20 (KRT20) Is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement.

Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and prognostic value of plasma cytokeratin-15 (KRT15) cytokeratin-20 (KRT20), and occludin (OCLN) were evaluated in a discovery and a validation cohort using ELISA in comparison with elafin (PI3) and regenerating family member 3 alpha (REG3A), two established markers of skin- and gut aGvHD.

Prevalence and potential relevance of hyperuricemia in pediatric kidney transplant recipients-a CERTAIN registry analysis.

Background: Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients.

Reclassification of Five BRCA1/2 Variants with Unknown Significance Using Complex Functional Study.

Purpose: While BRCA1/2 genes are commonly investigated, variants of unknown significance (VUS) and variants with potential splice effect are still being detected and they represent a substantial challenge in genetic counseling and therapy.

Materials And Methods: Out of genetically tested 3,568 hereditary breast and ovarian cancer probands five, functionally not investigated variants with potential splice-modifying effect were subjected to functional characterization. Transcript-level analysis on peripheral blood-derived RNA of the carriers was performed to test aberrant splicing.

Essential Role of the 14q32 Encoded miRNAs in Endocrine Tumors.

Background: The 14q32 cluster is among the largest polycistronic miRNA clusters. miRNAs encoded here have been implicated in tumorigenesis of multiple organs including endocrine glands.

Methods: Critical review of miRNA studies performed in endocrine tumors have been performed.

Trimetazidine Use in Parkinson's Disease: Is It a Resolved Problem?

Trimetazidine (TMZ), an antianginal drug, can worsen the symptoms of movement disorders, therefore, the European Medicines Agency (EMA) recommended avoiding the use of this drug in Parkinson's disease (PD). We investigated the impact of this recommendation on the observed trend of TMZ use in PD in Hungary from 2010 to 2016 by conducting a nationwide, retrospective study of health administrative data of human subjects. Interrupted time series analyses were performed to explore changes in user trends after the EMA recommendations.

The effects of bisphosphonate and radiation therapy in bone-metastatic lung adenocarcinoma: the impact of KRAS mutation.

Background: KRAS mutation is the most common genetic alteration in lung adenocarcinoma (LADC) in Western countries and is associated with worse outcome in bone-metastatic cases. Yet, to date, no effective treatment guidelines were developed for these patients. Accordingly, our aim was to investigate the impact of KRAS mutation on bisphosphonate (BTx) and radiation therapy (RTx) in bone-metastatic LADC patients.

Application of Multilayer Evidence for Annotation of C-Terminal Variants.

The clinical relevance of the C-terminal stop codon variants is controversial. The pathogenic role of the germline c.9976A>T and c.

Molecular genetic testing strategies used in diagnostic flow for hereditary endocrine tumour syndromes.

Introduction: Although current guidelines prefer the use of targeted testing or small-scale gene panels for identification of genetic susceptibility of hereditary endocrine tumour syndromes, next generation sequencing based strategies have been widely introduced into every day clinical practice. The application of next generation sequencing allows rapid testing of multiple genes in a cost effective manner. Increasing knowledge about these techniques and the demand from health care providers and society, shift the molecular genetic testing towards using high-throughput approaches.

Cyclooxygenase-2 Modulates Glycosaminoglycan Production in the Skin During Salt Overload.

Sodium (Na) can accumulate in the skin tissue, sequestered by negatively charged glycosaminoglycans (GAGs). During dietary salt overload, the amount and charge density of dermal GAG molecules - e.g.

Analysis of 14 drugs in dried blood microsamples in a single workflow using whole blood and serum calibrators.

Multiplexed, high-throughput analysis facilitates therapeutic drug monitoring. 14 drugs with various physico-chemical properties were quantitated in dried blood microsamples. Analytes were extracted employing eight solvent compositions and seven extraction methods.

Comments on: A functional polymorphism rs10830963 in melatonin receptor 1B associated with the risk of gestational diabetes mellitus.

We have read with great interest the accepted manuscript of the meta-analysis performed by Huang, et al. titled "A functional polymorphism rs10830963 in melatonin receptor 1B associated with the risk of gestational diabetes mellitus" published online in the 2019 December 6 issue of Bioscience Reports (https://doi.org/10.

Species-Specific Glucose-6-Phosphatase Activity in the Small Intestine-Studies in Three Different Mammalian Models.

Besides the liver, which has always been considered the major source of endogenous glucose production in all post-absorptive situations, kidneys and intestines can also produce glucose in blood, particularly during fasting and under protein feeding. However, observations gained in different experimental animals have given ambiguous results concerning the presence of the glucose-6-phosphatase system in the small intestine. The aim of this study was to better define the species-related differences of this putative gluconeogenic organ in glucose homeostasis.

KRAS Mutations Predict Response and Outcome in Advanced Lung Adenocarcinoma Patients Receiving First-Line Bevacizumab and Platinum-Based Chemotherapy.

Bevacizumab, combined with platinum-based chemotherapy, has been widely used in the treatment of advanced-stage lung adenocarcinoma (LADC). Although KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation is the most common genetic alteration in human LADC and its role in promoting angiogenesis has been well established, its prognostic and predictive role in the above setting remains unclear. The association between KRAS exon 2 mutational status and clinicopathological variables including progression-free survival and overall survival (PFS and OS, respectively) was retrospectively analyzed in 501 Caucasian stage IIIB-IV LADC patients receiving first-line platinum-based chemotherapy (CHT) with or without bevacizumab (BEV).

Cardiometabolic correlates of sleep-disordered breathing in renal transplant children.

Sleep-disordered breathing, a prevalent condition among adult renal transplant (RTx) recipients, has become an established independent risk factor of MetS, and furthermore, it might contribute to increased CV risk. Despite the proven correlations in adults, there is a lack of evidence for its significance in the pediatric RTx population. In this study, we aimed at assessing the prevalence and the clinical correlates of SDB in RTx children.

PD-L1 Expression of Lung Cancer Cells, Unlike Infiltrating Immune Cells, Is Stable and Unaffected by Therapy During Brain Metastasis.

Background: Approximately 50% of brain metastases originate from non-small-cell lung cancer. The median survival of patients with brain metastases is 1 month without treatment. Novel immunotherapeutic strategies, such as those targeting the programmed death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) axis, are promising in patients with advanced systemic disease but are often preferentially administered to patients with tumors showing PD-L1 positivity.

True MEN1 or phenocopy? Evidence for geno-phenotypic correlations in MEN1 syndrome.

Purpose: Multiple endocrine neoplasia type 1 is a rare tumor syndrome caused by germline mutations of MEN1 gene. Phenotype varies widely, and no definitive correlation with the genotype has been observed. Mutation-negative patients with MEN1-associated tumors represent phenocopies.