Project description:Dengue viruses (DENV) are by far the most important arboviral pathogens in the tropics around the world, putting at risk of infection nearly a third of the global human population. DENV are members of the genus Flavivirus in the Family Flaviviridae and comprise four antigenically distinct serotypes (DENV-1-4). Although they share almost identical epidemiological features, they are genetically distinct. Phylogenetic analyses have revealed valuable insights into the origins, epidemiology and the forces that shape DENV evolution in nature. In this review, we examine the current status of DENV evolution, including but not limited to rates of evolution, selection pressures, population sizes and evolutionary constraints, and we discuss how these factors influence transmission, pathogenesis and emergence.
Project description:The Guidelines programme of the German Society of Gynaecology and Obstetrics (DGGG) is an executive part of the DGGG Guidelines Commission. It includes in-house planning and organisation of all guidelines as well as representation outside of the DGGG. This article does not concern the development of the guidelines as much as it concerns the planning, organisation, registration, editing and publication of the guidelines in context of the DGGG Guidelines programme. It targets interested parties, especially authors and coordinators of guidelines.
Project description:I am pleased to introduce Methods and Protocols, a new multidisciplinary, peer-reviewed, open access journal devoted to providing an open forum to report on new procedural approaches and cutting-edge methodological developments.[...].
Project description:Orthotopic liver transplantation (OLT) has been effective in managing end-stage liver disease since the advent of cyclosporine immunosuppression therapy in 1980. The major limitations of OLT are organ supply, monetary cost, and the burden of lifelong immunosuppression. Hepatocyte transplantation, as a substitute for OLT, has been an exciting topic of investigation for several decades. HT is potentially minimally invasive and can serve as a vehicle for delivery of personalized medicine through autologous cell transplant after modification ex vivo. However, 3 major hurdles have prevented large-scale clinical application: (1) availability of transplantable cells; (2) safe and efficient ex vivo gene therapy methods; and (3) engraftment and repopulation efficiency. This review will discuss new sources for transplantable liver cells obtained by lineage reprogramming, clinically acceptable methods of genetic manipulation, and the development of hepatic irradiation-based preparative regimens for enhancing engraftment and repopulation of transplanted hepatocytes. We will also review the results of the first 3 patients with genetic liver disorders who underwent preparative hepatic irradiation before hepatocyte transplantation.
Project description:Chemicals are measured regularly in air, food, the environment, and the workplace. Biomonitoring of chemicals in biological fluids is a tool to determine the individual exposure. Blood protein adducts of xenobiotics are a marker of both exposure and the biologically effective dose. Urinary metabolites and blood metabolites are short term exposure markers. Stable hemoglobin adducts are exposure markers of up to 120 days. Blood protein adducts are formed with many xenobiotics at different sites of the blood proteins. Newer methods apply the techniques developed in the field of proteomics. Larger adducted peptides with 20 amino acids are used for quantitation. Unfortunately, at present the methods do not reach the limits of detection obtained with the methods looking at single amino acid adducts or at chemically cleaved adducts. Therefore, to progress in the field new approaches are needed.
Project description:Heating as a medical intervention in cancer treatment is an ancient approach, but effective deep heating techniques are lacking in modern practice. The use of electromagnetic interactions has enabled the development of more reliable local-regional hyperthermia (LRHT) techniques whole-body hyperthermia (WBH) techniques. Contrary to the relatively simple physical-physiological concepts behind hyperthermia, its development was not steady, and it has gone through periods of failures and renewals with mixed views on the benefits of heating seen in the medical community over the decades. In this review we study in detail the various techniques currently available and describe challenges and trends of oncological hyperthermia from a new perspective. Our aim is to describe what we believe to be a new and effective approach to oncologic hyperthermia, and a change in the paradigm of dosing. Physiological limits restrict the application of WBH which has moved toward the mild temperature range, targeting immune support. LRHT does not have a temperature limit in the tumor (which can be burned out in extreme conditions) but a trend has started toward milder temperatures with immune-oriented goals, developing toward immune modulation, and especially toward tumor-specific immune reactions by which LRHT seeks to target the malignancy systemically. The emerging research of bystander and abscopal effects, in both laboratory investigations and clinical applications, has been intensified. Our present review summarizes the methods and results, and discusses the trends of hyperthermia in oncology.
Project description:Machine learning has undergone a transition phase from being a pure statistical tool to being one of the main drivers of modern medicine. In gastroenterology, this technology is motivating a growing number of studies that rely on these innovative methods to deal with critical issues related to this practice. Hence, in the light of the burgeoning research on the use of machine learning in gastroenterology, a systematic review of the literature is timely. In this work, we present the results gleaned through a systematic review of prominent gastroenterology literature using machine learning techniques. Based on the analysis of 88 journal articles, we delimit the scope of application, we discuss current limitations including bias, lack of transparency, accountability, and data availability, and we put forward future avenues.
Project description:More than 30% of the world population suffers from allergy. Allergic individuals are characterized by the production of immunoglobulin E (IgE) antibodies against innocuous environmental allergens. Upon allergen recognition IgE mediates allergen-specific immediate and late-phase allergic inflammation in different organs. The identification of the disease-causing allergens by demonstrating the presence of allergen-specific IgE is the key to precision medicine in allergy because it allows tailoring different forms of prevention and treatment according to the sensitization profiles of individual allergic patients. More than 30 years ago molecular cloning started to accelerate the identification of the disease-causing allergen molecules and enabled their production as recombinant molecules. Based on recombinant allergen molecules, molecular allergy diagnosis was introduced into clinical practice and allowed dissecting the molecular sensitization profiles of allergic patients. In 2002 it was demonstrated that microarray technology allows assembling large numbers of allergen molecules on chips for the rapid serological testing of IgE sensitizations with small volumes of serum. Since then microarrayed allergens have revolutionized research and diagnosis in allergy, but several unmet needs remain. Here we show that detection of IgE- and IgG-reactivity to a panel of respiratory allergens microarrayed onto silicon elements is more sensitive than glass-based chips. We discuss the advantages of silicon-based allergen microarrays and how this technology will allow addressing hitherto unmet needs in microarray-based allergy diagnosis. Importantly, it described how the assembly of silicon microarray elements may create different microarray formats for suiting different diagnostic applications such as quick testing of single patients, medium scale testing and fully automated large scale testing.
Project description:The use of immunotherapy has revolutionized the treatment regimen of certain cancer types, but response assessment has become a difficult task with conventional methods such as CT/MRT or FDG PET-CT and the classical response criteria such as RECIST or PERCIST which have been developed for chemotherapeutic treatment. Plenty of new tracers have been published to improve the assessment of treatment response and to stratify the patient population. We gathered the information on published tracers (in total, 106 individual SPECT/PET tracers were identified) and performed a descriptor-based analysis; in this way, we classify the tracers with regard to target choice, developability (probability to progress from preclinical stage into the clinic), translatability (probability to be widely applied in the 'real world'), and (assumed) diagnostic quality. In our analysis, we show that most tracers are targeting PD-L1, PD-1, CTLA-4, and CD8 receptors by using antibodies or their fragments. Another finding is that plenty of tracers possess only minor iterations regarding chelators and nuclides instead of approaching the problem in a new innovative way. Based on the data, we suggest an orthogonal approach by targeting intracellular targets with PET-activatable small molecules that are currently underrepresented.