Genetic characteristics of 23 Y-chromosomal STRs in the Kinh population in Northern Vietnam.

We collected and analysed the genetic characteristics of 23 Y-STR data of 200 unrelated Kinh individuals living in the North of Vietnam. Haplotype frequencies and forensic parameters were calculated, showing high discrimination value. Population comparison analysis was performed to determine the genetic relationship with neighbouring ethnicities, in particular with Thai and Han populations.

The Immune Contexture Associates with the Genomic Landscape in Lung Adenomatous Premalignancy.

Epithelial cells in the field of lung injury can give rise to distinct premalignant lesions that may bear unique genetic aberrations. A subset of these lesions may escape immune surveillance and progress to invasive cancer; however, the mutational landscape that may predict progression has not been determined. Knowledge of premalignant lesion composition and the associated microenvironment is critical for understanding tumorigenesis and the development of effective preventive and interception strategies.

Characterization of a carbapenem- and colistin-resistant carrying Tn in genomic context.

We report a clinical strain of , PIMB10EC27, isolated in Vietnam in 2010 that was resistant to 21 of 26 tested antibiotics, including carbapenems (MICs >64 µg/mL) and colistin (MIC >128 µg/mL). The complete genome of strain PIMB10EC27 was sequenced by PacBio RSII and the Illumina Miseq system. Whole-genome analysis revealed that PIMB10EC27 contains a chromosome of the ST513 group (PIMBEC27, length 5,272,177 bp) and two plasmids, pEC27-1 of the IncX3 group (length 62,470 bp) and pEC27-2 of the IncHI1 group (length 84,602 bp).

The microdosimetric extension in TOPAS: development and comparison with published data.

Microdosimetric energy depositions have been suggested as a key variable for the modeling of the relative biological effectiveness (RBE) in proton and ion radiation therapy. However, microdosimetry has been underutilized in radiation therapy. Recent advances in detector technology allow the design of new mico- and nano-dosimeters.

First Detection of Chronic Wasting Disease in a Wild Red Deer () in Europe.

Chronic wasting disease (CWD) is a fatal contagious prion disease naturally occurring in cervids in North America. In 2016, CWD was detected in wild reindeer () and moose () in Norway. Here, we report the first known naturally infected wild Norwegian red deer ().

Engineering Na1.7 Inhibitory JzTx-V Peptides with a Potency and Basicity Profile Suitable for Antibody Conjugation To Enhance Pharmacokinetics.

Drug discovery research on new pain targets with human genetic validation, including the voltage-gated sodium channel Na1.7, is being pursued to address the unmet medical need with respect to chronic pain and the rising opioid epidemic. As part of early research efforts on this front, we have previously developed Na1.

Double Robust Efficient Estimators of Longitudinal Treatment Effects: Comparative Performance in Simulations and a Case Study.

A number of sophisticated estimators of longitudinal effects have been proposed for estimating the intervention-specific mean outcome. However, there is a relative paucity of research comparing these methods directly to one another. In this study, we compare various approaches to estimating a causal effect in a longitudinal treatment setting using both simulated data and data measured from a human immunodeficiency virus cohort.

INVESTIGATING VARIABLE RBE IN A 12C MINIBEAM FIELD WITH MICRODOSIMETRY AND GEANT4.

An experimental and simulation-based study was performed on a 12C ion minibeam radiation therapy (MBRT) field produced with a clinical broad beam and a brass multi-slit collimator (MSC). Silicon-on-insulator (SOI) microdosimeters developed at the Centre for Medical Radiation Physics (CMRP) with micron sized sensitive volumes were used to measure the microdosimetric spectra at varying positions throughout the MBRT field and the corresponding dose-mean lineal energies and RBE for 10% cell survival (RBE10) were calculated using the modified Microdosimetric Kinetic Model (MKM). An increase in the average RBE10 of ∼30% and 10% was observed in the plateau region compared to broad beam for experimental and simulation values, respectively.

Time-of-flight spectrometry of ultra-short, polyenergetic proton bunches.

A common approach for spectrum determination of polyenergetic proton bunches from laser-ion acceleration experiments is based on the time-of-flight (TOF) method. However, spectra obtained using this method are typically given in relative units or are estimated based on some prior assumptions on the energy distribution of the accelerated ions. In this work, we present a new approach using the TOF method that allows for an absolute energy spectrum reconstruction from a current signal acquired with a sub-nanosecond fast and 10 m thin silicon detector.

The Combination of Metformin and Valproic Acid Has a Greater Anti-tumoral Effect on Prostate Cancer Growth than Either Drug Alone.

Background/aim: The hypoglycemic drug metformin (MET) and the anti-epileptic drug valproic acid (VPA) have individually shown anti-tumor effects in prostate cancer in vitro. The present study intended to investigate the efficacy of the combination of MET and VPA in prostate cancer treatment in a pre-clinical xenograft model.

Materials And Methods: Prostate cancer cell lines (LNCaP and PC-3) were inoculated under the skin of BALB/c nude mice.

Novel Type of Chronic Wasting Disease Detected in Moose (Alces alces), Norway.

Chronic wasting disease (CWD) persists in cervid populations of North America and in 2016 was detected for the first time in Europe in a wild reindeer in Norway. We report the detection of CWD in 3 moose (Alces alces) in Norway, identified through a large scale surveillance program. The cases occurred in 13-14-year-old female moose, and we detected an abnormal form of prion protein (PrP) in the brain but not in lymphoid tissues.

Pogostemins A-C, three new cytotoxic meroterpenoids from Pogostemon auricularius.

Pogostemins A-C (1-3), three new meroterpenoids with pyrone-sesquiterpenoid hybrid skeletons, were isolated from the aerial parts of Pogostemon auricularius. Their chemical structures were elucidated by 1D- and 2D-NMR and HRESIMS analyses. Compound 1 showed significant cytotoxicities against the human colon adenocarcinoma SW-480, epidermoid carcinoma KB, gastric cancer AGS, hepatoma cancer Hep-G2, and lung cancer LU-1 cell lines with IC values of 7.

Understanding the Binding Mechanism of Amyloid-β Inhibitors from Molecular Simulations.

In recent years, Aβ aggregation prevention, one of the most concerned strategies in drug development has been carefully assessed to treat Alzheimer's disease. Aβ peptides can transform structurally from random coil monomer into β-stranded protofibril via multiple oligomeric states. Among the various Aβ species, the identification of binding targets has been challenging due to the heterogeneity and metastable nature.

pH-Driven Mechanistic Switching from Electron Transfer to Energy Transfer between [Ru(bpy)] and Ferrocene Derivatives.

The metal-to-ligand charge transfer excited states of [Ru(bpy)] (bpy = 2,2'-bipyridine) may be deactivated via energy transfer or electron transfer with ferrocene derivatives in aqueous conditions. Stern-Volmer quenching analysis revealed that the rate constant for [Ru(bpy)] excited-state quenching depends on solution pH when a ferrocenyl-amidinium derivative (Fc-am) containing a proton-responsive functionality tethered to the ferrocene center was present. By contrast, the rate constant with which the [Ru(bpy)] excited state is quenched by an analogous ferrocene derivative (ferrocenyl-trimethylammonium, Fc-mam) that lacks a protonic group does not depend on pH.

Sex-related disparities in obstructive coronary artery disease, percutaneous coronary intervention, and mortality in adults with cardiac arrest.

Objectives: Despite numerous advances in the delivery of resuscitative care, cardiac arrest (CA) continues to be associated with high morbidity and mortality. We sought to examine the association between sex and presence of obstructive coronary artery disease (CAD), percutaneous coronary intervention (PCI), and mortality in adults with CA.

Methods: The study population included 208 consecutive patients hospitalized with CA who underwent resuscitation and subsequent coronary angiogram at an academic tertiary medical center.

Combination Therapies Using Metformin and/or Valproic Acid in Prostate Cancer: Possible Mechanistic Interactions.

Prostate cancer (PCa) is the most frequent cancer in men. The evolution from local PCa to castration-resistant PCa, an end-stage of disease, is often associated with changes in genes such as p53, androgen receptor, PTEN, and ETS gene fusion products. Evidence is accumulating that repurposing of metformin (MET) and valproic acid (VPA) either when used alone, or in combination, with another therapy, could potentially play a role in slowing down PCa progression.

Binding Modes of a Glycopeptidomimetic Molecule on Aβ Protofibrils: Implication for Its Inhibition Mechanism.

We recently reported that a glycopeptidomimetic molecule significantly delays the fibrillization process of Aβ peptide involved in Alzheimer's disease. However, the binding mode of this compound, named 3β, was not determined at the atomic scale, hindering our understanding of its mechanism of action and impeding structure-based design of new inhibitors. In the present study, we performed molecular docking calculations and molecular dynamics simulations to investigate the most probable structures of 3β complexed with Aβ protofibrils.

ProfPPIdb: Pairs of physical protein-protein interactions predicted for entire proteomes.

Motivation: Protein-protein interactions (PPIs) play a key role in many cellular processes. Most annotations of PPIs mix experimental and computational data. The mix optimizes coverage, but obfuscates the annotation origin.

Chronic low dose ethanol induces an aggressive metastatic phenotype in TRAMP mice, which is counteracted by parthenolide.

Despite advances in prostate cancer therapy, dissemination and growth of metastases results in shortened survival. Here we examined the potential anti-cancer effect of the NF-κB inhibitor parthenolide (PTL) and its water soluble analogue dimethylaminoparthenolide (DMAPT) on tumour progression and metastasis in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model of prostate cancer. Six-week-old male TRAMP mice received PTL (40 mg/kg in 10% ethanol/saline), DMAPT (100 mg/kg in sterile water), or vehicle controls by oral gavage thrice weekly until palpable tumour formation.

Reciprocal Regulation of DUSP9 and DUSP16 Expression by HIF1 Controls ERK and p38 MAP Kinase Activity and Mediates Chemotherapy-Induced Breast Cancer Stem Cell Enrichment.

Triple-negative breast cancer (TNBC) has a poor prognosis due to its aggressive characteristics and lack of targeted therapies. Cytotoxic chemotherapy may reduce tumor bulk, but leaves residual disease due to the persistence of chemotherapy-resistant breast cancer stem cells (BCSC), which are critical for tumor recurrence and metastasis. Here, we demonstrate that hypoxia-inducible factor (HIF)-1-dependent regulation of mitogen-activated protein kinase (MAPK) signaling pathways contributes to chemotherapy-induced BCSC enrichment.

The relative biological effectiveness for carbon, nitrogen, and oxygen ion beams using passive and scanning techniques evaluated with fully 3D silicon microdosimeters.

Background: The aim of this study was to measure the microdosimetric distributions of a carbon pencil beam scanning (PBS) and passive scattering system as well as to evaluate the relative biological effectiveness (RBE) of different ions, namely C, N, and O, using a silicon-on-insulator (SOI) microdosimeter with well-defined 3D-sensitive volumes (SV). Geant4 simulations were performed with the same experimental setup and results were compared to the experimental results for benchmarking.

Method: Two different silicon microdosimeters with rectangular parallelepiped and cylindrical shaped SVs, both 10 μm in thickness were used in this study.

Silencing the Snail-Dependent RNA Splice Regulator ESRP1 Drives Malignant Transformation of Human Pulmonary Epithelial Cells.

Epithelial-to-mesenchymal transition (EMT) is organized in cancer cells by a set of key transcription factors, but the significance of this process is still debated, including in non-small cell lung cancer (NSCLC). Here, we report increased expression of the EMT-inducing transcription factor Snail in premalignant pulmonary lesions, relative to histologically normal pulmonary epithelium. In immortalized human pulmonary epithelial cells and isogenic derivatives, we documented Snail-dependent anchorage-independent growth and primary tumor growth and metastatic behavior Snail-mediated transformation relied upon silencing of the tumor-suppressive RNA splicing regulatory protein ESRP1.

Prolonged Duration of Therapy Is Associated With Improved Survival in Patients Treated for Relapsed/Refractory Multiple Myeloma in Routine Clinical Care in the United States.

Background: In clinical trials, an extended therapy duration has been associated with better outcomes in patients with newly diagnosed multiple myeloma (NDMM). However, data on how the therapy duration affects the outcomes for patients with relapsed/refractory multiple myeloma (RRMM) are limited. We conducted a large, retrospective study in the United States to evaluate the effect of the duration of second-line therapy on overall survival.