Engineering β-oxidation in Yarrowia lipolytica for methyl ketone production.

Medium- and long-chain methyl ketones are fatty acid-derived compounds that can be used as biofuel blending agents, flavors and fragrances. However, their large-scale production from sustainable feedstocks is currently limited due to the lack of robust microbial biocatalysts. The oleaginous yeast Yarrowia lipolytica is a promising biorefinery platform strain for the production of methyl ketones from renewable lignocellulosic biomass due to its natively high flux towards fatty acid biosynthesis.

Age-specific ovarian cancer risks among women with a BRCA1 or BRCA2 mutation.

Objectives: For women at high risk of developing ovarian cancer, it is important to provide an accurate recommendation for the optimal age for preventive surgery in order to maximize the preventative effect while delaying symptoms associated with early surgical menopause. The goal of the current study was to estimate age-specific incidence rates of ovarian cancer among women with a BRCA1 or BRCA2 mutation.

Methods: From our international registry, we identified 5689 women with no previous diagnosis of ovarian or fallopian tube cancer or preventive oophorectomy.

Age at first full-term birth and breast cancer risk in BRCA1 and BRCA2 mutation carriers.

Purpose: In the general population, an early age at first full-term birth confers protection against the risk of developing breast cancer. The relationship between age at first birth and breast cancer risk is not clear for women with a mutation in the BRCA1 or BRCA2 gene. Thus, we undertook a case-control study of women with a BRCA1 or BRCA2 mutation to study the effects of age at first full-term birth matched for other reproductive factors.

Hormone Replacement Therapy After Oophorectomy and Breast Cancer Risk Among BRCA1 Mutation Carriers.

Importance: Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study.

Objective: To determine the association between HRT use and BRCA1-associated breast cancer.

Correction: Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers.

[This corrects the article DOI: 10.1371/journal.pone.

Author Correction to: Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease.

An Online First version of this article was made available online at http://link.springer.com/journal/40263/onlineFirst/page/1 on 12 March 2018.

Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients.

Background: The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS components and HRQoL in a representative international cohort of PD patients.

Methods: We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales.

Prospective evaluation of body size and breast cancer risk among BRCA1 and BRCA2 mutation carriers.

Background: Although evidence suggests that larger body size in early life confers lifelong protection from developing breast cancer, few studies have investigated the relationship between body size and breast cancer risk among BRCA mutation carriers. Therefore, we conducted a prospective evaluation of body size and the risk of breast cancer among BRCA mutation carriers.

Methods: Current height and body mass index (BMI) at age 18 were determined from baseline questionnaires.

Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease.

Background: Although levodopa is considered the most effective pharmacotherapy for motor symptoms of Parkinson's disease (PD), chronic use is associated with motor complications, including fluctuating response and unpredictable, involuntary movements called dyskinesia. ADS-5102 (amantadine) extended-release (ER) capsules (GOCOVRI) is a recent US FDA-approved treatment for dyskinesia in PD patients. ADS-5102 is a high-dose, ER formulation of amantadine, administered orally once daily at bedtime, that achieves high plasma drug concentrations throughout the day.

Adverse Events of Trastuzumab Emtansine (T-DM1) in the Treatment of HER2-Positive Breast Cancer Patients.

The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1).

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database.

Efficient leukocyte depletion by a novel microfluidic platform enables the molecular detection and characterization of circulating tumor cells.

RT-qPCR is a highly sensitive approach to detect rare transcripts, as derived from circulating tumor cells (CTCs) in the blood of cancer patients. However, the presence of unwanted leukocytes often leads to false positive results. Here, we evaluated whether the micro-fluidic Parsortix™ technology is appropriate to remove these leukocytes and thereby finally to improve the overall approach.

Extended-release oral capsule of carbidopa-levodopa in Parkinson disease.

Motor fluctuations complicate the treatment of patients with Parkinson's disease receiving levodopa. Extended-release carbidopa-levodopa has a pharmacokinetic profile that provides a more continuous levodopa serum concentration. Patients taking this formulation can expect longer duration of action and fewer doses per day, similar clinical improvement when compared to other levodopa formulations, and with a theoretically lower risk of developing motor fluctuations.

The association between smoking and cancer incidence in BRCA1 and BRCA2 mutation carriers.

Tobacco smoke is an established carcinogen, but the association between tobacco smoking and cancer risk in BRCA mutation carriers is not clear. The aim of this study was to evaluate prospectively the association between tobacco smoking and cancer incidence in a cohort of BRCA1 and BRCA2 mutation carriers. The study population consisted of unaffected BRCA mutation carriers.

Comparison of gaseous and particulate emissions from a pilot-scale combustor using three varieties of coal.

Gaseous and particulate emissions generated from the combustion of coal have been associated with adverse effects on human health and the environment, and have therefore been the subject of regulation by federal and state government agencies. Detailed emission characterizations are needed to better understand the impacts of pre- and post-combustion controls on a variety of coals found in the United States (U.S.

A rare case of a Wilms tumor: case report.

The nephroblastoma or Wilms tumor (WT) is the most common renal tumor in childhood, representing approximately 6-7% of all pediatric cancers, with a yearly incidence of 10 cases in one million children less than 15 years old, and continues to arouse interest by remarkable actual therapeutic successes, consecutive to the multidisciplinary approach. Its maximum incidence is around the age of 3-3.5 years old, having an equal frequency in males and females.

Two girl patients with medulloblastoma. Case reports.

Unlabelled: In childhood, the most common type of brain tumors is medulloblastoma, a highly malignant primary brain tumor that is found in the cerebellum or posterior fossa. The tumor mass increases and generates obstructive hydrocephalus. Risk factors (that might be involved in some cases) include the genetic syndrome such as type 1 neurofibromatosis, exposure to ionizing radiation and Epstein-Barr virus.

Guidance Statement On BRCA1/2 Tumor Testing in Ovarian Cancer Patients.

The approval, in 2015, of the first poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi; olaparib, Lynparza) for platinum-sensitive relapsed high-grade ovarian cancer with either germline or somatic BRCA1/2 deleterious mutations is changing the way that BRCA1/2 testing services are offered to patients with ovarian cancer. Ovarian cancer patients are now being referred for BRCA1/2 genetic testing for treatment decisions, in addition to familial risk estimation, and irrespective of a family history of breast or ovarian cancer. Furthermore, testing of tumor samples to identify the estimated 3%-9% of patients with somatic BRCA1/2 mutations who, in addition to germline carriers, could benefit from PARPi therapy is also now being considered.

Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers.

Background: Screening for ovarian cancer (OC) in women at high risk consists of a combination of carbohydrate antigen 125 (CA125) and transvaginal ultrasound, despite their low sensitivity and specificity. This could be improved by the combination of several biomarkers, which has been shown in average risk patients but has not been investigated until now in female BRCA mutation carriers.

Methods: Using a multiplex, bead-based, immunoassay system, we analyzed the concentrations of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, CA125 and human epididymis antigen 4 in 26 healthy wild type women, 26 healthy BRCA1 mutation carriers, 28 wildtype OC patients and 26 OC patients with BRCA1 mutation.

The risk of breast cancer in BRCA1 and BRCA2 mutation carriers without a first-degree relative with breast cancer.

The objective of this study was to estimate the lifetime risk of breast cancer in women with a BRCA1 or BRCA2 mutation with and without at least 1 first-degree relative with breast cancer. A total of 2835 women with a BRCA1 or BRCA2 mutation were followed. Age- and gene-specific breast cancer rates were calculated.

Identification and management of familial breast cancer in Austria.

Aim The aim of this study is to review the legal implications, the technology, the indications and the management of women with a familial background of breast and/or ovarian cancer. Methods We have reviewed the literature and national Austrian guidelines to describe the uptake of genetic counseling and the management options offered in Austria. Results Genetic testing for the BRCA1 and 2 mutations is free and readily available through a nation-wide program.

O-Acetylation is essential for functional antibody generation against Staphylococcus aureus capsular polysaccharide.

Staphylococcus aureus produces an antiphagocytic polysaccharide capsule to evade neutrophil-mediated killing. Many vaccines against encapsulated bacterial pathogens require generation of functional anti-capsular antibodies to mediate protection against infection and disease. Here it is shown that the generation of such antibody responses to S.

Gene expression information improves reliability of receptor status in breast cancer patients.

Immunohistochemical (IHC) determination of receptor status in breast cancer patients is frequently inaccurate. Since it directs the choice of systemic therapy, it is essential to increase its reliability. We increase the validity of IHC receptor expression by additionally considering gene expression (GE) measurements.

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10 with ten variants at nine new loci.