Final results of the real-life observational VICTOR-6 study on metronomic chemotherapy in elderly metastatic breast cancer (MBC) patients.

Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.

A Whole-Genome Sequencing Study Implicates GRAMD1B in Multiple Sclerosis Susceptibility.

While the role of common genetic variants in multiple sclerosis (MS) has been elucidated in large genome-wide association studies, the contribution of rare variants to the disease remains unclear. Herein, a whole-genome sequencing study in four affected and four healthy relatives of a consanguineous Italian family identified a novel missense c.1801T > C (p.

Metastatic mucinous ovarian carcinoma simulating lung primary: an integrated diagnostic lesson.

We herein document a rare instance of primary mucinous ovarian carcinoma metastatic to the left lung, whose deceptive secondary derivation was already envisaged according to the spectacular thromboembolism involving small pulmonary vessels, thereby realizing a centrifugal and centripetal metastatizing loop. This presentation was indicative of dismal prognosis. A multimodal biomarker key approach is herein emphasized, which included close clinico-pathologic data integration.

Metronomic chemotherapy (mCHT) in metastatic triple-negative breast cancer (TNBC) patients: results of the VICTOR-6 study.

Purpose: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting.

Targeted whole exome sequencing and Drosophila modelling to unveil the molecular basis of primary ovarian insufficiency.

Study Question: Can a targeted whole exome sequencing (WES) on a cohort of women showing a primary ovarian insufficiency (POI) phenotype at a young age, combined with a study of copy number variations, identify variants in candidate genes confirming their deleterious effect on ovarian function?

Summary Answer: This integrated approach has proved effective in identifying novel candidate genes unveiling mechanisms involved in POI pathogenesis.

What Is Known Already: POI, a condition occurring in 1% of women under 40 years of age, affects women's fertility leading to a premature loss of ovarian reserve. The genetic causes of POI are highly heterogeneous and several determinants contributing to its prominent oligogenic inheritance pattern still need to be elucidated.

Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color.

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified.

Assembly of High-Spin [Fe] Clusters by Ligand-Based Multielectron Reduction.

The hexanuclear [NaFe(tris-cyclo-salophen)(THF)], , and the trinuclear [NaFe(tris-cyclo-salophen)(py)], , Fe(II) clusters can be easily assembled in one step from the ligand-based reduction of the [Fe(salophen)(THF)] complex. These complexes consist of triangular cores where three Fe(II) ions are held together, within range of bonding interaction, by the hexa-amide, hexaphenolate macrocyclic ligand . The ligand is perfectly suited for binding three Fe(II) centers at short distances, allowing for strong magnetic coupling between the Fe(II) centers.

Big Data in Medicine, the Present and Hopefully the Future.

The emergence of data coming from different venues, as several "omic" approaches, is providing already compelling evidence that the smart use of this information could provide invaluable information to prevent, diagnose and treat human diseases. However, the most daunting challenges remain ahead, as the explosive accumulation of data from additional perspectives, including social graphs, biosensors, and imaging, promise to deliver crucial information that could be exploited for the improvement of the entire human race, both in developed, and developing countries, optimizing health expenses and reaching also the less fortunate sections of the societies. And yet, formidable challenges remain, that pertain for the most part to the collection of the data, their organization, and most relevantly their integration.

A bird's-eye view of Italian genomic variation through whole-genome sequencing.

The genomic variation of the Italian peninsula populations is currently under characterised: the only Italian whole-genome reference is represented by the Tuscans from the 1000 Genome Project. To address this issue, we sequenced a total of 947 Italian samples from three different geographical areas. First, we defined a new Italian Genome Reference Panel (IGRP1.

Associations of autozygosity with a broad range of human phenotypes.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy.

Metronomic chemotherapy for advanced breast cancer patients in the real world practice: Final results of the VICTOR-6 study.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected.

A catalog of genetic loci associated with kidney function from analyses of a million individuals.

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178).

CS Reductive Coupling to Acetylenedithiolate by a Dinuclear Ytterbium(II) Complex.

The activation of CS is of interest in a broad range of fields and, more particularly, in the context of creating new C-C bonds. The reaction of the dinuclear ytterbium(II) complex [Yb L ], 1, [L=(OtBu) SiO ] with carbon disulfide led to the isolation of unprecedented reduction products. In particular, the crystallographic characterization of complex [Yb L (μ-C S )], 2, provided the first example of an acetylenedithiolate ligand formed from metal reduction of CS .

Carbon dioxide reduction by dinuclear Yb(ii) and Sm(ii) complexes supported by siloxide ligands.

Two dinuclear homoleptic complexes of lanthanides(ii) supported by the polydentate tris(tertbutoxy) siloxide ligand ([Yb2L4], 1-Yb and [Sm2L4], 1-Sm, (L = (OtBu)3SiO-)) were synthesized in 70-80% yield and 1-Sm was crystallographically characterized. 1-Yb and 1-Sm are stable in solution at -40 °C but cleave the DME C-O bond over time at room temperature affording the crystal of [Yb2L4(μ-OMe)2(DME)2], 2. The 1-Yb and 1-Sm complexes effect the reduction of CO2 under ambient conditions leading to carbonate and oxalate formation.

High-resolution array-CGH analysis on 46,XX patients affected by early onset primary ovarian insufficiency discloses new genes involved in ovarian function.

Study Question: Can high resolution array-CGH analysis on a cohort of women showing a primary ovarian insufficiency (POI) phenotype in young age identify copy number variants (CNVs) with a deleterious effect on ovarian function?

Summary Answer: This approach has proved effective to clarify the role of CNVs in POI pathogenesis and to better unveil both novel candidate genes and pathogenic mechanisms.

What Is Known Already: POI describes the progression toward the cessation of ovarian function before the age of 40 years. Genetic causes are highly heterogeneous and despite several genes being associated with ovarian failure, most of genetic basis of POI still needs to be elucidated.

Promoting Emotional Well-Being in Older Breast Cancer Patients: Results From an eHealth Intervention.

Breast cancer is the most common cancer in women worldwide, with increases in diagnoses at all ages. Due to several age-related factors, older breast cancer patients show particular difficulties in adjusting to breast cancer and its related treatments. One consistent indicator of vulnerability to long-term complications is emotional distress occurring within 3 months of diagnosis.

Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.