Induction of Transient Virus Replication Facilitates Antigen-Independent Isolation of SIV-Specific Monoclonal Antibodies.

Structural characterization of the HIV-1 Envelope (Env) glycoprotein has facilitated the development of Env probes to isolate HIV-specific monoclonal antibodies (mAbs). However, preclinical studies have largely evaluated these virus-specific mAbs against chimeric viruses, which do not naturally infect non-human primates, in contrast to the unconstrained simian immunodeficiency virus (SIV)mac239 clone. Given the paucity of native-like reagents for the isolation of SIV-specific B cells, we examined a method to isolate SIVmac239-specific mAbs without using Env probes.

Predictors of urinary and blood Metal(loid) concentrations among pregnant women in Northern Puerto Rico.

Given the potential adverse health effects related to toxic trace metal exposure and insufficient or excessive levels of essential trace metals in pregnant women and their fetuses, the present study characterizes biomarkers of metal and metalloid exposure at repeated time points during pregnancy among women in Puerto Rico. We recruited 1040 pregnant women from prenatal clinics and collected urine, blood, and questionnaire data on demographics, product use, food consumption, and water usage at up to three visits. All samples were analyzed for 16 metal(loid)s: arsenic (As), barium (Ba), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), cesium (Cs), copper (Cu), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), titanium (Ti), uranium (U), vanadium (V), and zinc (Zn).

Onset and tempo of sexual maturation is differentially associated with gestational phthalate exposure between boys and girls in a Mexico City birth cohort.

Phthalates are endocrine disrupting compounds commonly found in consumer products, exposure to which may influence reproductive maturation. Effects from exposure in utero on the onset and progression of sexual development are understudied. We examined longitudinal associations between gestational phthalate exposure and sexual maturation at two points in adolescence (8-14, 9-18 years).

Randomized, double-blind, placebo-controlled phase II study of istiratumab (MM-141) plus nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine in front-line metastatic pancreatic cancer (CARRIE).

Background: Preclinical data suggest that dual blockade of the insulin-like growth factor-1 receptor (IGF-1R) and HER3 pathways has superior activity to IGF-1R blockade alone in pancreatic ductal adenocarcinoma (PDAC). We tested whether istiratumab, an IGF-1R- and ErbB3-bispecific antibody, can enhance the efficacy of standard of care (SOC) chemotherapy in patients with metastatic PDAC selected for high IGF-1 serum levels.

Patients And Methods: CARRIE was an international, randomized, double-blind, placebo-controlled phase II study for patients with previously untreated metastatic PDAC.

Health-care investments for the urban populations, Bangladesh and India.

Objective: To estimate the costs and mortality reductions of a package of essential health interventions for urban populations in Bangladesh and India.

Methods: We used population data from the countries' censuses and United Nations Population Division. For causes of mortality in India, we used the Indian Million Death Study.

MRI Tumor Regression Grade and Circulating Tumor DNA as Complementary Tools to Assess Response and Guide Therapy Adaptation in Rectal Cancer.

Purpose: Response to preoperative chemo-radiotherapy (CRT) varies. We assessed whether circulating tumor DNA (ctDNA) might be an early indicator of tumor response or progression to guide therapy adaptation in rectal cancer.

Experimental Design: A total of 243 serial plasma samples were analyzed from 47 patients with localized rectal cancer undergoing CRT.

Elevated glucose acts directly on osteocytes to increase sclerostin expression in diabetes.

Bone quality in diabetic patients is compromised, leading to weaker bones and increased fracture risk. However, the mechanism by which this occurs in diabetic bone remains to be fully elucidated. We hypothesized that elevated glucose and glucose variation would affect the function of osteocytes, essential regulators of bone homeostasis and quality.

Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment.

Background: Patient derived organoids (PDOs) can be established from colorectal cancers (CRCs) as in vitro models to interrogate cancer biology and its clinical relevance. We applied mass spectrometry (MS) immunopeptidomics to investigate neoantigen presentation and whether this can be augmented through interferon gamma (IFNγ) or MEK-inhibitor treatment.

Methods: Four microsatellite stable PDOs from chemotherapy refractory and one from a treatment naïve CRC were expanded to replicates with 100 million cells each, and HLA class I and class II peptide ligands were analyzed by MS.

Impact of Hurricanes Irma and Maria on Puerto Rico Maternal and Child Health Research Programs.

Puerto Rico was hit by two major hurricanes in September 2017 causing great devastation, losing over 90% of the power grid, wireless communication and access to potable water, and destroying many homes. Our research programs: Puerto Rico Testsite for Exploring Contamination Threats (PROTECT), Center for Research on Early Childhood Exposure and Development in Puerto Rico (CRECE), Zika in Infants and Pregnancy (ZIP), and Environmental Influences on Child Health Outcomes (ECHO) are ongoing observational cohort studies that have been investigating environmental risk factors for perinatal health outcomes among Puerto Rican mothers and infants. Our projects paused operations for about two weeks, to begin recovery process and become a source of assistance, retaining 95% of study participants across all research programs.

An exploratory analysis of urinary organophosphate ester metabolites and oxidative stress among pregnant women in Puerto Rico.

Background: Organophosphate esters (OPEs) are used as flame retardants and plasticizers. Oxidative stress, the imbalance of reactive oxygen species and antioxidants, measured prenatally has been associated with adverse birth outcomes including preeclampsia and preterm birth. We are the first study to investigate the relationship between OPEs and oxidative stress among pregnant women.

Mechanisms of Racial Health Disparities: Evidence on Coping and Cortisol from MIDUS II.

Objective: Blunted patterns of daily cortisol, an indicator of hypothalamic-pituitary-adrenal (HPA) axis stress response system dysregulation, are implicated in poor health outcomes and racial health disparities. It is unknown how coping-an important, but understudied, component of the stress-health disparities relationship-relates to these biological mechanisms of health.

Methods: This study investigated relationships, including racial differences, between 12 coping strategies and early-day cortisol changes (diurnal cortisol slopes from peak to before lunch) among 700 35-85-year-old Black and White male participants in the National Survey of Midlife Development in the United States (MIDUS) II.

A Sexually Dimorphic Role for STAT3 in Sonic Hedgehog Medulloblastoma.

Medulloblastoma is the most common malignant brain tumor in children and represents 20% of all pediatric central nervous system neoplasms. While advances in surgery, radiation and chemotherapy have improved overall survival, the lifelong sequelae of these treatments represent a major health care burden and have led to ongoing efforts to find effective targeted treatments. There is a well-recognized male bias in medulloblastoma diagnosis, although the mechanism remains unknown.

Targeting EGFR pathway in metastatic colorectal cancer- tumour heterogeniety and convergent evolution.

Despite significant progress in management of metastatic colorectal cancer (mCRC) pertaining to better screening procedures and amelioration of the therapeutic armamentarium with targeted therapies, prognosis remains poor. Targeting epidermal growth factor receptor (EGFR) has been of particular interest owing to favourable efficacy benefits demonstrated by monoclonal antibodies (cetuximab and panitumumab) in various clinical settings and development of predictive biomarkers informing treatment decisions respectively. In spite of optimal patient selection based on RAS mutation status, primary and secondary resistance to monoclonal antibodies is higher than desired.

Renal epithelial cells retain primary cilia during human acute renal allograft rejection injury.

Objectives: Primary cilia are sensory organelles which co-ordinate several developmental/repair pathways including hedgehog signalling. Studies of human renal allografts suffering acute tubular necrosis have shown that length of primary cilia borne by epithelial cells doubles throughout the nephron and collecting duct, and then normalises as renal function returns. Conversely the loss of primary cilia has been reported in chronic allograft rejection and linked to defective hedgehog signalling.

Occupational Exposure to the Ugandan Research Strain (MR766) of Zika Virus.

A laboratory worker suffered an accidental needle-stick resulting in an exposure to the Ugandan strain (MR766) of Zika virus, which has rarely been studied in humans. We report the clinical presentation and outcomes, molecular and serological diagnostic results, and antibody response.

A Recombinant Rhesus Monkey Rhadinovirus Deleted of Glycoprotein L Establishes Persistent Infection of Rhesus Macaques and Elicits Conventional T Cell Responses.

A replication-competent, recombinant strain of rhesus monkey rhadinovirus (RRV) expressing the Gag protein of SIVmac239 was constructed in the context of a glycoprotein L (gL) deletion mutation. Deletion of gL detargets the virus from Eph family receptors. The ability of this gL-minus Gag recombinant RRV to infect, persist, and elicit immune responses was evaluated after intravenous inoculation of two RRV-naive rhesus monkeys.

Outcomes of Patients with Early Onset Colorectal Cancer Treated in a UK Specialist Cancer Center.

The incidence of early onset colorectal cancer (EOCRC) is rapidly increasing, but there remains paucity of outcome data for young CRC patients. We reviewed the characteristics and outcomes of 241 adults, age <50, who were diagnosed with EOCRC between January 2009 and December 2014. Median age was 42, 56% were male, and 7% had hereditary etiology.

Clonal diversity of MYC amplification evaluated by fluorescent in situ hybridisation and digital droplet polymerase chain reaction in oesophagogastric cancer: Results from a prospective clinical trial screening programme.

Introduction: The MYC proto-oncogene is among the most commonly dysregulated genes in human cancers. We report screening data from the iMYC trial, an ongoing phase II study assessing ibrutinib monotherapy in advanced pretreated MYC- and/or HER2-amplified oesophagogastric cancer, representing the first attempt to prospectively identify MYC amplifications in this tumour type for the purposes of therapeutic targeting.

Methods: Screening utilising a fluorescent in situ hybridisation (FISH) assay for assessment of tumour MYC amplification has been instituted.

The association of urinary organophosphate ester metabolites and self-reported personal care and household product use among pregnant women in Puerto Rico.

Background: Organophosphate esters (OPEs) are widely detected among U.S. pregnant women.

Trends and presentation patterns of acute rheumatic fever hospitalisations in the United States.

Objective: Rheumatic fever, an immune sequela of untreated streptococcal infections, is an important contributor to global cardiovascular disease. The goal of this study was to describe trends, characteristics, and cost burden of children discharged from hospitals with a diagnosis of RF from 2000 to 2012 within the United States.

Methods: Using the Kids' Inpatient Database, we examined characteristics of children discharged from hospitals with the diagnosis of rheumatic fever over time including: overall hospitalisation rates, age, gender, race/ethnicity, regional differences, payer type, length of stay, and charges.

Influence of sex on chemotherapy efficacy and toxicity in oesophagogastric cancer: A pooled analysis of four randomised trials.

Background: Sex contributes to interpatient variability of chemotherapy metabolism and dose response, potentially influencing both efficacy and toxicity; however, comparative data on its effect on oesophagogastric cancer are lacking.

Patients And Methods: Data for patients with advanced oesophagogastric cancer randomised to comparable first-line chemotherapy regimens within four United Kingdom prospective trials were pooled, and key demographic and outcome measures were compared between males and females.

Results: A total of 1654 patients were included: 1328 (80.