Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and confers a poor prognosis. Beyond standard systemic therapy with multikinase inhibitors, recent studies demonstrate the potential for robust and durable responses from immune checkpoint inhibition in subsets of HCC patients across disease etiologies. The majority of HCC arises in the context of chronic inflammation and from within a fibrotic liver, with many cases associated with hepatitis virus infections, toxins, and fatty liver disease. Many patients also have concomitant cirrhosis which is associated with both local and systemic immune deficiency. Furthermore, the liver is an immunologic organ in itself, which may enhance or suppress the immune response to cancer arising within it. Here, we explore the immunobiology of the liver from its native state to chronic inflammation, fibrosis, cirrhosis and then to cancer, and summarize how this unique microenvironment may affect the response to immunotherapy

Stemming the Global Trade in Falsified and Substandard Medicines

Drug safety and quality is an essential assumption of clinical medicine, but there is growing concern that this assumption is not always correct. Poor manufacturing and deliberate fraud occasionally compromises the drug supply in the United States, and the problem is far more common and serious in low- and middle-income countries with weak drug regulatory systems. An Institute of Medicine consensus committee report identified the causes and possible solutions to the problem of falsified and substandard drugs around the world. The vocabulary people use to discuss the problem is itself a concern. The word counterfeit is often used innocuously to describe any drug that is not what it seems, but some NGOs and emerging manufacturing nations object to this term. These groups see hostility to generic pharmaceuticals in a discussion of counterfeit medicines. These groups see hostility to generic pharmaceuticals in a discussion of counterfeit medicines. Precisely speaking, a counterfeit drug infringes on a registered trademark, and trademark infringement in not necessarily a problem of public health consequence. Instead of talking broadly about counterfeit drugs, the WHO and other stakeholders should consider two main categories of drug quality problems. Falsified medicines misrepresent the product’s identity or source or both. Substandard drugs fail to meet the national specifications given in an accepted pharmacopeia or the manufacturer’s dossier. In practice, there is often considerable overlap between categories. There is considerable uncertainty about the size of the falsified and substandard drug market. Improved pharmacovigilance, especially in developing countries, give a better picture of the scope of the problem. In the United States, tighter regulatory controls on the wholesale market and a mandatory drug tracking system would improve drug safety. In developing countries, development finance organizations should invest in small- and medium-sized pharmaceutical manufacturers, and governments should use tools such as franchising, accreditation, low-interest loans, and task shifting to encourage private sector investment in drug retail. Finally, the WHO should work with stakeholders such as the UNODC and the WCO to develop an international code of practice on falsified and substandard drugs

Neglected Dimensions of Global Security: The Global Health Risk Framework Commission

The world has experienced global health crises ranging from novel influenzas (H5N1 and H1N1) and coronaviruses (SARS and MERS) to the Ebola and Zika viruses. In each case, governments and international organizations seemed unable to react quickly and decisively. Health crises have unmasked critical vulnerabilities— weak health systems, failures of leadership, and political overreaction and underreaction. The Global Health Risk Framework Commission, for which the National Academy of Medicine served as the secretariat, recently set out a comprehensive strategy to safeguard human and economic security from pandemic threats

PhyreStorm: A Web Server for Fast Structural Searches Against the PDB

AbstractThe identification of structurally similar proteins can provide a range of biological insights, and accordingly, the alignment of a query protein to a database of experimentally determined protein structures is a technique commonly used in the fields of structural and evolutionary biology. The PhyreStorm Web server has been designed to provide comprehensive, up-to-date and rapid structural comparisons against the Protein Data Bank (PDB) combined with a rich and intuitive user interface. It is intended that this facility will enable biologists inexpert in bioinformatics access to a powerful tool for exploring protein structure relationships beyond what can be achieved by sequence analysis alone. By partitioning the PDB into similar structures, PhyreStorm is able to quickly discard the majority of structures that cannot possibly align well to a query protein, reducing the number of alignments required by an order of magnitude. PhyreStorm is capable of finding 93±2% of all highly similar (TM-score>0.7) structures in the PDB for each query structure, usually in less than 60s. PhyreStorm is available at http://www.sbg.bio.ic.ac.uk/phyrestorm/

NIDDK’s Short-Term Research Experience for Underrepresented Persons (STEP-UP) Program

This abstract provides an overview to this issue

Remote Sensing of Parasitic Nematodes in Plants

A method and apparatus for remote sensing of parasitic nematodes in plants, now undergoing development, is based on measurement of visible and infrared spectral reflectances of fields where the plants are growing. Initial development efforts have been concentrated on detecting reniform nematodes (Rotylenchulus reniformis) in cotton plants, because of the economic importance of cotton crops. The apparatus includes a hand-held spectroradiometer. The readings taken by the radiometer are processed to extract spectral reflectances at sixteen wavelengths between 451 and 949 nm that, taken together, have been found to be indicative of the presence of Rotylenchulus reniformis. The intensities of the spectral reflectances are used to estimate the population density of the nematodes in an area from which readings were taken

Changes in the TRMM Version 7 Space/Time Averaged Level 3 Data Products Based on GPROF TMI Swath-Based Precipitation Retrievals

TRMM has three level 3 (space/time averaged) data products that aggregate level 2 TRMM Microwave Imager (TMI) GPROF precipitation retrievals. These three products are TRMM 3A12, which is a monthly accumulation of 2A12 the GPROF swath retrieval product; TRMM 3B31, which is a monthly accumulation of 2A12 and 2B31 the combined retrieval product that uses both Precipitation Radar (PR) and TMI data; and 3G68 and its variants, which provide hourly retrievals for TMI, PR and combined. The 3G68 products are packaged as daily files but provide hourly information at 0.5 deg x 0.5 deg resolution globally, 0.25 deg x 0.25 deg globally, or 0.1 deg x 0.1 deg over Africa, Australia and South America. This paper will present early information of the changes in the v7 TMI GPROF level 2 retrievals that have an impact on the level 3 accumulations. This paper provides an analysis of the effect the 2A12 GPROF changes have on 3G68 products. In addition, it provides a comparison between the TRMM level 3 products that use the TMI GPROF swath retrievals