A cleft lip and palate gene, Irf6, is involved in osteoblast differentiation of craniofacial bone.

Background: Interferon regulatory factor 6 (IRF6) plays a critical role in embryonic tissue development, including differentiation of epithelial cells. Besides orofacial clefting due to haploinsufficiency of IRF6, recent human genetic studies indicated that mutations in IRF6 are linked to small mandible and digit abnormalities. The function of IRF6 has been well studied in oral epithelium; however, its role in craniofacial skeletal formation remains unknown.

Melasma: update on management.

Melasma is a common, acquired, chronic cutaneous pigment disorder that is often difficult to treat and has a high recurrence rate. The goal of a melasma treatment regimen is to decrease pigment production and increase elimination. Topical tyrosinase inhibitors block melanin synthesis and thereby reduce pigment production.

Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation.

Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m. Dose adjustment was defined as a reduction in standard dosing ≥20%, based on ideal, reported dosing and actual weights.

TMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated Wnt/β-catenin signalling.

Vesicular acidification and trafficking are associated with various cellular processes. However, their pathologic relevance to cancer remains elusive. We identified transmembrane protein 9 (TMEM9) as a vesicular acidification regulator.

Deregulation of CRAD-controlled cytoskeleton initiates mucinous colorectal cancer via β-catenin.

Epithelial integrity is maintained by the cytoskeleton and through cell adhesion. However, it is not yet known how a deregulated cytoskeleton is associated with cancer. We identified cancer-related regulator of actin dynamics (CRAD) as frequently mutated or transcriptionally downregulated in colorectal cancer.

Targeted Gene Sequencing in Children with Crohn's Disease and Their Parents: Implications for Missing Heritability.

Crohn's disease is a complex genetic trait characterized by chronic relapsing intestinal inflammation. Genome wide association studies (GWAS) have identified more than 170 loci associated with the disease, accounting for ∼14% of the disease variance. We hypothesized that rare genetic variation in GWAS positional candidates also contribute to disease pathogenesis.

Inflammation and fatigue in early, untreated Parkinson's Disease.

Objectives: Parkinson's disease (PD)-related fatigue is a significant clinical problem, and the pathological processes that cause fatigue remain unknown. The aim of the present study was to explore the possible association of peripheral inflammation markers and fatigue in PD.

Materials & Methods: We included 47 drug naïve, newly diagnosed PD patients with low (≤3.

Trends in Illicit Drug Use Among Smokers and Nonsmokers in the United States, 2002-2014.

Objective: Cigarette smoking has declined in the United States. Still, identifying prevalent and modifiable barriers to quitting can help inform the next steps for tobacco control. Illicit drug use, which may be increasingly common in the United States, could be one such factor.

Preclinical Data Supporting Antitumor Activity of PD-1 Blockade.

Antibodies that block the PD-1 coinhibitory receptor on T cells or its primary ligand, PD-L1, have demonstrated unprecedented efficacy across a diverse array of both solid and hematologic malignancies in the clinic. These advances were built on a foundation of murine preclinical tumor model studies, which both demonstrated the therapeutic potential of PD-1/PD-L1 antibody blockade and also provided critical insights into the cellular and molecular processes underlying their capacity to elicit immune-mediated tumor regressions. As the field of immunotherapy moves toward higher-order combinations of agents, effective utilization of murine tumor models to optimize the composition of PD-1 antibody combination therapies, as well as their dosing and scheduling, will be essential for effective clinical translation.

Ovarian and Uterine Functions in Female Survivors of Childhood Cancers.

Unlabelled: Adult survivors of childhood cancers are more prone to developing poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. Chemotherapy drugs exert cytotoxic effects systemically and therefore can damage the ovaries, leading to infertility, premature ovarian failure, and, to a lesser extent, spontaneous abortions. They have very limited or no deleterious effects on the uterus that can be recognized clinically.

Impact of Intensity-Modulated Radiotherapy on Health Care Costs of Patients With Anal Squamous Cell Carcinoma.

Purpose: Drivers of variation in the cost of care after chemoradiotherapy for the management of anal squamous cell carcinoma (SCC) have not been fully elucidated. We sought to characterize the direct and indirect impact of radiotherapy modality on health care costs among patients with anal SCC.

Patients And Methods: A retrospective cohort study was performed using the 2014 linkage of the SEER-Medicare database.

Intercellular Genetic Interaction Between Irf6 and Twist1 during Craniofacial Development.

Interferon Regulatory Factor 6 (IRF6) and TWIST1 are transcription factors necessary for craniofacial development. Human genetic studies showed that mutations in IRF6 lead to cleft lip and palate and mandibular abnormalities. In the mouse, we found that loss of Irf6 causes craniosynostosis and mandibular hypoplasia.

The somatic mutation landscape of premalignant colorectal adenoma.

Objective: There are few studies which characterised the molecular alterations in premalignant colorectal adenomas. Our major goal was to establish colorectal adenoma genome atlas and identify molecular markers of progression from colorectal adenoma to adenocarcinoma.

Design: Whole-exome sequencing and targeted sequencing were carried out in 149 adenoma samples and paired blood from patients with conventional adenoma or sessile serrated adenoma to characterise the somatic mutation landscape for premalignant colorectal lesions.

Cancer Drugs: An International Comparison of Postlicensing Price Inflation.

Purpose: The cost of cancer drugs forms a rising proportion of health care budgets worldwide. A number of studies have examined international comparisons of initial cost, but there is little work on postlicensing price increases. To examine this, we compared cancer drug prices at initial sale and subsequent price inflation in the United States and United Kingdom and also reviewed relevant price control mechanisms.

New B-cell Lymphomas in the Setting of a Previous Rare Breast Implant-Associated B-cell Lymphoma.

We present a follow-up of a patient who underwent right-sided subtotal mastectomy and placement of right-sided saline implant in 1968 for a phyllodes tumor and then in 2012 was diagnosed with a rare B-cell type lymphoma of the right breast. In 2015, she was diagnosed with diffuse large B-cell lymphoma involvement of the left breast and left leg and experienced subsequent self-regression of leg lesions without therapy.

A review of melasma treatment focusing on laser and light devices.

Melasma is a pigmentary disorder of unclear etiology with numerous treatment options and high recurrence rates. Laser and light therapies may be utilized cautiously as second- or third-line options for recalcitrant melasma, but low-energy settings are preferred due to the risk of postinflammatory hyperpigmentation and melasma stimulation. Commonly used lasers include the low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser, nonablative fractionated lasers, and intense pulsed light.

Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial.

Background: The AURELIA trial demonstrated significantly improved progression-free survival (PFS) with bevacizumab added to chemotherapy for platinum-resistant ovarian cancer (PROC).

Methods: Patients with PROC were randomised to receive investigator-selected single-agent chemotherapy alone or with bevacizumab. Post-hoc exploratory analyses assessed efficacy, safety and patient-reported outcomes according to age <65 versus ≥65years.

Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia.

Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance.

Regorafenib- associated panniculitis.

Regorafenib is a second-generation multikinase inhibitor that is approved for the treatment of metastatic colon cancer and advanced gastrointestinal stromal tumors. Hand-foot skin reaction, alopecia, and oral mucositis are well-established side effects of this medication. Herein, we discuss a 60-year-old woman who developed a lobular and septal granulomatous panniculitis after six months of therapy with regorafenib.

A Multicenter Study of Volumetric Computed Tomography for Staging Malignant Pleural Mesothelioma.

Background: Standard imaging modalities are inaccurate in staging malignant pleural mesothelioma (MPM). Single-institution studies suggest that volumetric computed tomography (CT) is more accurate but labor intensive. We established a multicenter network to test interobserver variability, accuracy (relative to pathologic stage), and the prognostic significance of semiautomated volumetric CT.