AI identifies potent inducers of breast cancer stem cell differentiation based on adversarial learning from gene expression data.

Cancer stem cells (CSCs) are a subpopulation of cancer cells within tumors that exhibit stem-like properties and represent a potentially effective therapeutic target toward long-term remission by means of differentiation induction. By leveraging an artificial intelligence approach solely based on transcriptomics data, this study scored a large library of small molecules based on their predicted ability to induce differentiation in stem-like cells. In particular, a deep neural network model was trained using publicly available single-cell RNA-Seq data obtained from untreated human-induced pluripotent stem cells at various differentiation stages and subsequently utilized to screen drug-induced gene expression profiles from the Library of Integrated Network-based Cellular Signatures (LINCS) database.

PATZ1 in Non-Small Cell Lung Cancer: A New Biomarker That Negatively Correlates with PD-L1 Expression and Suppresses the Malignant Phenotype.

Non-small cell lung cancer (NSCLC), the leading cause of cancer death worldwide, is still an unmet medical problem due to the lack of both effective therapies against advanced stages and markers to allow a diagnosis of the disease at early stages before its progression. Immunotherapy targeting the PD-1/PD-L1 checkpoint is promising for many cancers, including NSCLC, but its success depends on the tumor expression of PD-L1. PATZ1 is an emerging cancer-related transcriptional regulator and diagnostic/prognostic biomarker in different malignant tumors, but its role in lung cancer is still obscure.

Comparison between an Emerging Point-of-Care Tool for TSH Evaluation and a Centralized Laboratory-Based Method in a Cohort of Patients from Southern Italy.

Endocrine and metabolic disorders are a common condition in Europe and worldwide, and, among these, thyroid dysfunction still remains a problem. The measurement of thyroid stimulating hormone (TSH) levels represents the first-line assay for the assessment of thyroid function. In the present study, we compared serum concentrations of TSH, measured using a commercially available point-of-care test (POCT) method (FastPack IP) and an established "conventional" laboratory-based method (Beckmann Access 2) in a cohort of patients from Foggia in Southern Italy.

A randomised, single-blind, placebo-controlled, dose-finding safety and tolerability study of the anti-CD3 monoclonal antibody otelixizumab in new-onset type 1 diabetes.

Aims/hypothesis: Numerous clinical studies have investigated the anti-CD3ɛ monoclonal antibody otelixizumab in individuals with type 1 diabetes, but limited progress has been made in identifying the optimal clinical dose with acceptable tolerability and safety. The aim of this study was to evaluate the association between dose-response, safety and tolerability, beta cell function preservation and the immunological effects of otelixizumab in new-onset type 1 diabetes.

Methods: In this randomised, single-blind, placebo-controlled, 24 month study, conducted in five centres in Belgium via the Belgian Diabetes Registry, participants (16-27 years old, <32 days from diagnosis of type 1 diabetes) were scheduled to receive placebo or otelixizumab in one of four dose cohorts (cumulative i.

Differential insulin response to oral glucose tolerance test (OGTT) in overweight/obese polycystic ovary syndrome patients undergoing to myo-inositol (MYO), alpha lipoic acid (ALA), or combination of both.

Polycystic ovary syndrome is characterized by several endocrine impairments, insulin resistance and hyperinsulinemia. We aimed to evaluate the effects of myo-inositol (MYO), alpha-lipoic acid (ALA) and a combination of both. Setting: retrospective study.

Hormonal contraception in women with endometriosis: a systematic review.

Objective: A systematic review was carried out of studies of women with endometriosis, to examine the evidence for efficacy of the use of hormonal contraception to improve disease-related pain and decrease postoperative risk of disease recurrence.

Methods: A search of the Medline/PubMed and Embase databases was performed to identify all published English language studies on hormonal contraceptive therapies (combined hormonal contraceptives [CHCs], combined oral contraceptives [COCs], progestin-only pills [POPs] and progestin-only contraceptives [POCs]) in women with a validated endometriosis diagnosis, in comparison with placebo, comparator therapies or other hormonal therapies. Main outcome measures were endometriosis-related pain (dysmenorrhoea, pelvic pain and dyspareunia), quality of life (QoL) and postoperative rate of disease recurrence during treatment.

Target engagement and cellular fate of otelixizumab: a repeat dose escalation study of an anti-CD3ε mAb in new-onset type 1 diabetes mellitus patients.

Aims: This paper describes the pharmacological findings from a study where otelixizumab, an anti-CD3ɛ mAb, was dosed in new onset Type 1 diabetes mellitus (NOT1DM) patients. This is the first time that the full dose-response of an anti-CD3ɛ mAb has been investigated in the clinic. The data have been validated using a previously developed pharmacokinetic/pharmacodynamic (PK/PD) model of otelixizumab to simulate the interplay between drug administration, CD3ɛ target engagement and downmodulation.

Association between pelvic organ prolapse and climacteric symptoms in postmenopausal women.

Objective: To evaluate whether climacteric symptoms are related to pelvic organ prolapse (POP) in postmenopausal women.

Study Design: A cross-sectional investigation was performed on 1382 postmenopausal women attending an outpatient service for menopause at a university hospital.

Main Outcome Measures: Data regarding climacteric symptoms, as captured by the Greene Climacteric Scale, and objective POP were retrieved from an electronic database.

Assessment of plasma acylcarnitines before and after weight loss in obese subjects.

Acylcarnitines, fatty acid oxidation (FAO) intermediates, have been implicated in diet-induced insulin resistance and type 2 diabetes mellitus, as increased levels are found in obese insulin resistant humans. Moreover plasma acylcarnitines have been associated with clinical parameters related to glucose metabolism, such as fasting glucose levels and HbA1c. We hypothesized that plasma acylcarnitines would correlate with energy expenditure, insulin sensitivity and other clinical parameters before and during a weight loss intervention.

Metabolic impact of combined hormonal contraceptives containing estradiol.

Introduction: Is the replacement of ethinyl-estradiol (EE) with estradiol (E2) in combined hormonal contraceptives (CHCs) associated with fewer metabolic effects, leading to a further improvement on safety of hormonal contraceptives?

Areas Covered: This is a narrative review paper including all available data on the metabolic impact of CHCs containing E2 published in English up to December 2015. Modification of a metabolic variable of interest during the first months of treatment was considered as an outcome.

Expert Opinion: E2 was extensively used in oral contraceptives associated to nomegestrol acetate (NOMAc) in a monophasic 24 + 4 or its ester E2 valerate to dienogest (DNG) in a quadriphasic 26 + 2 regimen.

Body composition and resting metabolic rate of perimenopausal women using continuous progestogen contraception.

Objective: The effect on body composition and in particular on fat mass (FM) of 12 months' use of a desogestrel (DSG)-only contraceptive pill or the levonorgestrel-releasing intrauterine system (LNG-IUS) was evaluated in women in the perimenopause.

Methods: An observational study comprised 102 perimenopausal women: 42 received a 75 μg DSG pill, 34 received the 52 mg LNG-IUS, and 26 received no treatment. Body composition, body weight and resting metabolic rate (RMR) were evaluated at baseline and again after 12 months.

Effect of oral contraceptives containing estradiol and nomegestrol acetate or ethinyl-estradiol and chlormadinone acetate on primary dysmenorrhea.

Objective: To study the three cycles effect on primary dysmenorrhea of the monophasic 24/4 estradiol/nomegestrol acetate (E2/NOMAC) and of the 21/7 ethinyl-estradiol/chlormadinone acetate (EE/CMA) oral contraceptive. The tolerability and the effect of both preparations on metabolism and health-related quality of life were also evaluated.

Design: Prospective observational cohort study.

GSK256073 acutely regulates NEFA levels via HCA2 agonism but does not achieve durable glycaemic control in type 2 diabetes. A randomised trial.

This study investigated safety and efficacy of GSK256073, an in vitro potent, selective GPR109A agonist, for treatment of subjects with type 2 diabetes mellitus (Type 2 DM) poorly controlled with metformin alone. Patients with Type 2 DM (n=94) were enroled into this randomised, double-blind (sponsor unblinded), placebo-controlled, parallel group trial. Participants received placebo for two weeks before being randomised (2:2:2:2:1:1) to receive doses of GSK256073 5mg twice-daily (BID), 10mg once-daily (QD), 25mg BID, 50mg QD or placebo BID or QD in addition to their current metformin treatment.

Pelvic pain and quality of life of women with endometriosis during quadriphasic estradiol valerate/dienogest oral contraceptive: a patient-preference prospective 24-week pilot study.

Objective: The progestin dienogest (DNG) given alone effectively reduces pelvic pain of women with endometriosis. It is not clear whether the same occurs when DNG is associated with estradiol (E2).

Design: Patient preference prospective observational study.

Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus.

Unlabelled: Metformin, a biguanide derivate, has pleiotropic effects beyond glucose reduction, including improvement of lipid profiles and lowering microvascular and macrovascular complications associated with type 2 diabetes mellitus (T2DM). These effects have been ascribed to adenosine monophosphate-activated protein kinase (AMPK) activation in the liver and skeletal muscle. However, metformin effects are not attenuated when AMPK is knocked out and intravenous metformin is less effective than oral medication, raising the possibility of important gut pharmacology.

Prospective measurement of blood pressure and heart rate over 24 h in women using combined oral contraceptives with estradiol.

Objective: Combined oral contraceptives (COCs) containing ethinyl-estradiol are known to increase blood pressure (BP). We evaluated whether COCs containing estradiol (E2) influence 24-h ambulatory BP and heart rate (HR) in normotensive and normal-weight women.

Study Design: Twenty-four-hour BP and HR were measured every 30 min with an ambulatory BP device in 18 normotensive healthy non-smoking women prior to (Days 3-6 of menstrual cycle) and after 6 months of use (Days 20-24 of cycle 6) of a COC containing either a quadriphasic combination of E2 valerate plus dienogest (n=11) or a monophasic association of micronized E2 plus nomegestrol acetate (n=7).

Neuroendocrine and sympathetic responses to an orexin receptor antagonist, SB-649868, and alprazolam following insulin-induced hypoglycemia in humans.

Rationale: The orexin-hypocretin system is important for translating peripheral metabolic signals and central neuronal inputs to a diverse range of behaviors, from feeding, motivation and arousal, to sleep and wakefulness. Orexin signaling is thus an exciting potential therapeutic target for disorders of sleep, feeding, addiction, and stress.

Objectives/methods: Here, we investigated the low dose pharmacology of orexin receptor antagonist, SB-649868, on neuroendocrine, sympathetic nervous system, and behavioral responses to insulin-induced hypoglycemic stress, in 24 healthy male subjects (aged 18-45 years; BMI 19.

Exploring glycosuria as a mechanism for weight and fat mass reduction. A pilot study with remogliflozin etabonate and sergliflozin etabonate in healthy obese subjects.

Inhibitors of sodium-dependent glucose co-transporter 2 (SGLT2) increase glucose excretion in the urine and improve blood glucose in Type 2 diabetes mellitus. Glycosuria provides an energy and osmotic drain that could alter body composition. We therefore conducted a pilot study comparing the effects on body composition of two SGLT2 inhibitors, remogliflozin etabonate (RE) 250 mg TID ( = 9) and sergliflozin etabonate (SE) (1000 mg TID) ( = 9), with placebo ( = 12) in obese non-diabetic subjects.

Modification of 24-h ambulatory blood pressure and heart rate during contraception with the vaginal ring: a prospective study.

Background: Hypertension is recognized as a major risk factor for coronary, cerebral and renal vascular disease. Hormonal methods of contraception may increase the risk for cardiovascular events. We evaluated whether the combined hormonal contraceptive vaginal ring that releases 15-mcg ethinylestradiol and 120 mcg of etonogestrel each day influences 24-h ambulatory blood pressure.

Undifferentiated pleomorphic sarcoma with osteoclast-like giant cells of the female breast.

The authors describe a case of undifferentiated pleomorphic sarcoma of the breast occurring in a 50-year-old woman who presented with a palpable mass in her right breast. She first noticed the mass one month previously. Core needle biopsy showed connective tissue including epithelioid and spindle cells.

Combined oral contraceptive containing drospirenone does not modify 24-h ambulatory blood pressure but increases heart rate in healthy young women: prospective study.

Background: Hypertension is a primary cardiovascular risk factor. Oral contraceptives (OCs) may increase blood pressure and cardiovascular events. We evaluated whether an OC containing ethynylestradiol (EE) in association with the spironolactone-derived progestin drospirenone (DRSP) influences 24-h ambulatory blood pressure of normotensive women.

Neural and behavioral effects of a novel mu opioid receptor antagonist in binge-eating obese people.

Background: Binge eating is associated with obesity and has been conceptualized as "food addiction." However, this view has received only inconsistent support in humans, and limited evidence relates key neurocircuitry to the disorder. Moreover, relatively few studies have used pharmacologic functional magnetic resonance imaging to probe the underlying basis of altered eating behaviors.

Borderline ovarian tumors: features and controversial aspects.

Objective: To investigate features and controversial aspects of the borderline ovarian tumor (BOT), a neoplasm with favorable prognosis representing 10-15% of epithelial ovarian tumors.

Study Design: : We retrospectively studied all patients treated at our institution from 2000 to 2010 taking into account the age, the stage, the type of surgery, the tumor size, the symptoms, the pre- and post-intervention tumor marker levels (CA125, CA19.9, CA15.

The relationship between fat mass, eating behaviour and obesity-related psychological traits in overweight and obese individuals.

Behavioural and psychological factors related to eating have been associated with obesity, although their relationship to anthropometric measures, more specifically fat mass, has not been fully examined. This study examined the relationship between fat mass (n=98; 75M, 23 F) and behavioural measures of eating and obesity related psychological traits (n=337; 226M, 111 F) in overweight and obese individuals (Mean BMI 30.5±4.

Effects of mu opioid receptor antagonism on cognition in obese binge-eating individuals.

Rationale: Translational research implicates the mu opioid neurochemical system in hedonic processing, but its role in dissociable high-level cognitive functions is not well understood. Binge-eating represents a useful model of 'behavioural addiction' for exploring this issue.

Objective: The aim of this study was to objectively assess the cognitive effects of a mu opioid receptor antagonist in obese individuals with binge-eating symptoms.