Pharmacologic Inhibitor of DNA-PK, M3814, Potentiates Radiotherapy and Regresses Human Tumors in Mouse Models.

Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions in DNA are the most deleterious form of damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component of nonhomologous end joining (NHEJ), one of the two major pathways for DSB repair.

Ex situ management as insurance against extinction of mammalian megafauna in an uncertain world.

The persistence of endangered species may depend on the fate of a very small number of individual animals. In situ conservation alone may sometimes be insufficient. In these instances, the International Union for Conservation of Nature provides guidelines for ex situ conservation and the Convention on Biological Diversity (CBD) indicates how ex situ management can support the CBD's objectives by providing insurance policies for species.

Hepatitis E Is a Rare Finding in Liver Transplant Patients With Chronic Elevated Liver Enzymes and Biopsy-Proven Acute Rejection.

Background: In past decades, liver transplant (LT) patients were not routinely screened for hepatitis E virus (HEV) infection, and thus it might have been misdiagnosed as an acute rejection episode. Our aim was to analyze a real-world cohort of LT patients who presented with at least 1 episode of biopsy-proven acute rejection (BPAR) and suffered from persistent elevated transaminases, to evaluate the frequency of HEV infection misdiagnosed as a rejection episode.

Methods: Data from 306 patients transplanted between 1997 and 2017, including 565 liver biopsies, were analyzed.

Inkjet-Printing of Nanoparticle Gold and Silver Ink on Cyclic Olefin Copolymer for DNA-Sensing Applications.

Inkjet technology as a maskless, direct-writing technology offers the potential for structured deposition of functional materials for the realization of electrodes for, e.g., sensing applications.

DNA-PK Inhibitor, M3814, as a New Combination Partner of Mylotarg in the Treatment of Acute Myeloid Leukemia.

Despite significant advances in the treatment of acute myeloid leukemia (AML) the long-term prognosis remains relatively poor and there is an urgent need for improved therapies with increased potency and tumor selectivity. Mylotarg is the first AML-targeting drug from a new generation of antibody drug conjugate (ADC) therapies aiming at the acute leukemia cell compartment with increased specificity. This agent targets leukemia cells for apoptosis with a cytotoxic payload, calicheamicin, carried by a CD33-specific antibody.

Mass-producible micro-optical elements by injection compression molding and focused ion beam structured titanium molding tools.

We demonstrate mass production compatible fabrication of polymer-based micro Fresnel lenses by injection compression molding. The extremely robust titanium-molding tool is structured with high precision by focused ion beam milling. In order to achieve optimal shape accuracy in the titanium we use an iterative design optimization.

Nucleic acid-cleaving catalytic DNA for sensing and therapeutics.

DNAzymes with nucleic acid-cleaving catalytic activity are increasing in versatility through concerted efforts to discover new sequences with unique functions, and they are generating excitement in the sensing community as cheap, stable, amplifiable detection elements. This review provides a comprehensive list and detailed descriptions of the DNAzymes identified to date, classified by their associated small molecule or ion needed for catalysis; of note, this classification clarifies conserved regions of various DNAzymes that are not obvious in the literature. Furthermore, we detail the breadth of functionality of these DNA sequences as well as the range of reaction conditions under which they are useful.

Exploratory analysis of front-line therapies in REVEL: a randomised phase 3 study of ramucirumab plus docetaxel versus docetaxel for the treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy.

Introduction: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease. Front-line therapy may affect responses to subsequent treatment regimens, thus influencing second-line therapy decision making. In the randomised phase 3 REVEL study, second-line ramucirumab plus docetaxel (ram+doc) versus docetaxel (doc) improved survival of patients with metastatic NSCLC.

Better Health Choices: Feasability and preliminary effectiveness of a peer delivered healthy lifestyle intervention in a community mental health setting.

Background: To reduce smoking and improve other health behaviours of people living with severe mental illness, healthy lifestyle interventions have been recommended. One approach to improving the availability of these types of interventions is to utilise the mental health peer workforce. The current study aimed to evaluate the feasibility of peer-workers facilitating a telephone delivered healthy lifestyle intervention within community based mental health settings.

Clinical application of genomic high-throughput data: Infrastructural, ethical, legal and psychosocial aspects.

Genomic high-throughput technologies (GHTT) such as next-generation sequencing represent a fast and cost-effective tool toward a more comprehensive understanding of the molecular background of complex diseases. However, technological advances contrast with insufficient application in clinical practice. Thus, patients, physicians, and other professionals are faced with tough challenges that forestall the efficient and effective implementation.

HCMV Infection in a Mesenchymal Stem Cell Niche: Differential Impact on the Development of NK Cells versus ILC3.

Human cytomegalovirus (HCMV) is highly prevalent in most populations worldwide and has a major influence on shaping the human immune system. Natural killer (NK) cells are important antiviral effectors that adapt to HCMV infection by expansion of virus-specific effector/memory cells. The impact of HCMV infection on the development of NK cells and innate lymphoid cells (ILC) in general is less well understood.

Treatment of signs and symptoms of the common cold using EPs 7630 - results of a meta-analysis.

The efficacy of preparation EPs 7630 in the common cold (CC) was assessed by performing meta-analyses of randomized, double-blind, placebo-controlled trials. Mean differences (MD) and risk ratios (RR) with their 95% confidence intervals (CI) were computed. Five trials with a total of 833 patients were included.

Effect of glucose and insulin supplementation on the isolation of primary human hepatocytes.

Primary human hepatocytes (PHHs) remain the gold standard for investigations of xenobiotic metabolism and hepatotoxicity. However, scarcity of liver tissue and novel developments in liver surgery has limited the availability and quality of tissue samples. In particular, warm ischemia shifts the intracellular metabolism from aerobic to anaerobic conditions, which increases glycogenolysis, glucose depletion and energy deficiency.

Consequences Matter: Compassion in Conservation Means Caring for Individuals, Populations and Species.

Human activity affecting the welfare of wild vertebrates, widely accepted to be sentient, and therefore deserving of moral concern, is widespread. A variety of motives lead to the killing of individual wild animals. These include to provide food, to protect stock and other human interests, and also for sport.

File audit to assess sustained fidelity to a recovery and wellbeing oriented mental health service model: an Australian case study.

Background: Over the past decade there has been increasing attention to implementing recovery-oriented approaches within mental health service practice and enhancing fidelity to such approaches. However, as is often the case with evidence-based practices, less attention has been paid to the sustainability of recovery-oriented approaches over time. This study sought to investigate whether fidelity to a recovery-oriented practice framework - the Collaborative Recovery Model could be sustained over time.

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial.

Background: Ramucirumab-an IgG1 vascular endothelial growth factor receptor 2 antagonist-plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial.

Methods: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy.

Uncoupling protein 1 and the capacity for nonshivering thermogenesis are components of the glucose homeostatic system.

Uncoupling protein 1 (Ucp1) provides nonshivering thermogenesis (NST) fueled by the dissipation of energy from macronutrients in brown and brite adipocytes. The availability of thermogenic fuels is facilitated by the uptake of extracellular glucose. This conjunction renders thermogenic adipocytes in brown and white adipose tissue (WAT) a potential target against obesity and glucose intolerance.

Use of Propofol Plus Dexmedetomidine in Patients Experiencing Severe Alcohol Withdrawal in the Intensive Care Unit.

Alcohol abuse and alcohol withdrawal syndrome are major problems in the United States. This retrospective chart review assessed efficacy and safety of propofol plus dexmedetomidine used in combination as adjunctive therapy to benzodiazepines compared with either agent used alone in the treatment of severe alcohol withdrawal. Patients admitted to the intensive care unit and experiencing severe alcohol withdrawal between September 1, 2015 and September 30, 2018 were assessed for eligibility.

3,4-Dimethoxychalcone induces autophagy through activation of the transcription factors TFE3 and TFEB.

Caloric restriction mimetics (CRMs) are natural or synthetic compounds that mimic the health-promoting and longevity-extending effects of caloric restriction. CRMs provoke the deacetylation of cellular proteins coupled to an increase in autophagic flux in the absence of toxicity. Here, we report the identification of a novel candidate CRM, namely 3,4-dimethoxychalcone (3,4-DC), among a library of polyphenols.

Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Dual blockade of the EGFR and VEGF pathways in EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) is supported by preclinical and clinical data, yet the approach is not widely implemented. RELAY assessed erlotinib, an EGFR tyrosine kinase inhibitor (TKI) standard of care, plus ramucirumab, a human IgG1 VEGFR2 antagonist, or placebo in patients with untreated EGFR-mutated metastatic NSCLC.

Methods: This is a worldwide, double-blind, phase 3 trial done in 100 hospitals, clinics, and medical centres in 13 countries.

On the impact of service-oriented patterns on software evolvability: a controlled experiment and metric-based analysis.

Background: Design patterns are supposed to improve various quality attributes of software systems. However, there is controversial quantitative evidence of this impact. Especially for younger paradigms such as service- and Microservice-based systems, there is a lack of empirical studies.

Last neurologic event is associated with risk of in-hospital stroke or death after carotid endarterectomy or carotid artery stenting: Secondary data analysis of the German statutory quality assurance database.

Objective: We sought to analyze the association between last neurologic event and the risk of stroke or death among patients treated with carotid endarterectomy (CEA) or carotid artery stenting (CAS) under routine conditions in Germany.

Methods: Secondary data analysis was performed based on the German statutory quality assurance database for carotid procedures. A total of 144,347 patients treated by CEA and 14,794 patients treated by CAS were included in the analysis.

Quantifying the damage caused by fruit bats to backyard lychee trees in Mauritius and evaluating the benefits of protective netting.

The Mauritius fruit bat (Pteropus niger) has been the subject of repeated culling campaigns, apparently in response to pressure from the fruit-growing industry concerned over damage to commercially valuable orchard crops such as lychees. More than 31,000 fruit-bearing lychee trees also exist in private backyards, making this an issue pertinent to a wide cross-section of the Mauritian general public and not just those involved in commercial fruit production. The level of damage caused by bats to fruit crops is often debated and the low number of robust damage assessment studies hampers mitigation efforts.