Evaluating synergistic effects of metformin and simvastatin on ovarian cancer cells.

Background: Ovarian Cancer (OC) stands as the most lethal gynecological malignancy, presenting an urgent clinical challenge in the quest to improve response rates. One approach to address this challenge is through drug repurposing, exemplified by the investigation of metabolic-modulating drugs such as Metformin (MTF) and Simvastatin (SIM). This study aims to explore the molecular mechanisms contributing to the potential synergistic anti-cancer effects between MTF and SIM on ovarian cancer cells.

The role of noise in denoising models for anomaly detection in medical images.

Pathological brain lesions exhibit diverse appearance in brain images, in terms of intensity, texture, shape, size, and location. Comprehensive sets of data and annotations are difficult to acquire. Therefore, unsupervised anomaly detection approaches have been proposed using only normal data for training, with the aim of detecting outlier anomalous voxels at test time.

Novel potent azetidine-based compounds irreversibly inhibit Stat3 activation and induce antitumor response against human breast tumor growth in vivo.

Signal transducer and activator of transcription (Stat)3 is a valid anticancer therapeutic target. We have discovered a highly potent chemotype that amplifies the Stat3-inhibitory activity of lead compounds to levels previously unseen. The azetidine-based compounds, including H172 (9f) and H182, irreversibly bind to Stat3 and selectively inhibit Stat3 activity (IC 0.

You do it to yourself: Attentional capture by threat-signaling stimuli persists even when entirely counterproductive.

Recent research has demonstrated a counterproductive attentional bias toward threat-related stimuli: under conditions in which fixating on a color distractor stimulus sometimes resulted in an immediate shock, participants were nevertheless more likely to look at this threat-related distractor than a neutral distractor matched for physical salience. However, participants in that prior research may not have realized that their own actions caused delivery of aversive outcomes, such that monitoring for the threat-related distractor may not have been counterproductive from participants' perspective. In Experiment 1 of the current study, we demonstrate that the attentional bias to the threat-related distractor persists (and indeed, becomes stronger) when participants are made explicitly aware that looking at this stimulus is the sole cause of aversive events, which are otherwise avoidable.

Regional disparities in access to assisted reproductive technology: assessment of patient satisfaction when employing modern technology to close the gap.

Purpose: Geographic disparities for assisted reproductive technology (ART) continue to exist. Travel cost and time off work may create additional barriers for patients living remotely. Implementing telehealth can alleviate these barriers by reducing office visits.

Discovery of Novel Azetidine Amides as Potent Small-Molecule STAT3 Inhibitors.

We optimized our previously reported proline-based STAT3 inhibitors into an exciting new series of ()-azetidine-2-carboxamide analogues that have sub-micromolar potencies. , and have STAT3-inhibitory potencies (IC) of 0.55, 0.

Geographic and Socioeconomic Factors on Survival in Esthesioneuroblastoma.

Objectives: Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy with little known regarding how regional and socioeconomic differences in the United States alter disease survival. The aim of this study is to explore the geographic difference in clinical features, socioeconomic factors, and survival outcomes of ENB patients.

Methods: ENB cases were extracted from the Surveillance, Epidemiology, and End Results registry from 1975-2016.

HER3-targeted protein chimera forms endosomolytic capsomeres and self-assembles into stealth nucleocapsids for systemic tumor homing of RNA interference in vivo.

RNA interference represents a potent intervention for cancer treatment but requires a robust delivery agent for transporting gene-modulating molecules, such as small interfering RNAs (siRNAs). Although numerous molecular approaches for siRNA delivery are adequate in vitro, delivery to therapeutic targets in vivo is limited by payload integrity, cell targeting, efficient cell uptake, and membrane penetration. We constructed nonviral biomaterials to transport small nucleic acids to cell targets, including tumor cells, on the basis of the self-assembling and cell-penetrating activities of the adenovirus capsid penton base.

Chiral Graphs: Reduced Representations of Ligand Scaffolds for Stereoselective Biomolecular Recognition, Drug Design, and Enhanced Exploration of Chemical Structure Space.

Rational structure-based drug design relies on a detailed, atomic-level understanding of protein-ligand interactions. The chiral nature of drug binding sites in proteins has led to the discovery of predominantly chiral drugs. A mechanistic understanding of stereoselectivity (which governs how one stereoisomer of a drug might bind stronger than the others to a protein) depends on the topology of stereocenters in the chiral molecule.

Manually-parcellated gyral data accounting for all known anatomical variability.

Morphometric brain changes occur throughout the lifetime and are often investigated to understand healthy ageing and disease, to identify novel biomarkers, and to classify patient groups. Yet, to accurately characterise such changes, an accurate parcellation of the brain must be achieved. Here, we present a manually-parcellated dataset of the superior frontal, the supramarginal, and the cingulate gyri of 10 healthy middle-aged subjects along with a fully detailed protocol based on two anatomical atlases.

A controlled comparison of thickness, volume and surface areas from multiple cortical parcellation packages.

Background: Cortical parcellation is an essential neuroimaging tool for identifying and characterizing morphometric and connectivity brain changes occurring with age and disease. A variety of software packages have been developed for parcellating the brain's cortical surface into a variable number of regions but interpackage differences can undermine reproducibility. Using a ground truth dataset (Edinburgh_NIH10), we investigated such differences for grey matter thickness (GM), grey matter volume (GM) and white matter surface area (WM) for the superior frontal gyrus (SFG), supramarginal gyrus (SMG), and cingulate gyrus (CG) from 4 parcellation protocols as implemented in the FreeSurfer, BrainSuite, and BrainGyrusMapping (BGM) software packages.

Hypothalamic-Pituitary-Ovarian Axis Disorders Impacting Female Fertility.

The hypothalamic-pituitary-ovarian (HPO) axis is a tightly regulated system controlling female reproduction. HPO axis dysfunction leading to ovulation disorders can be classified into three categories defined by the World Health Organization (WHO). Group I ovulation disorders involve hypothalamic failure characterized as hypogonadotropic hypogonadism.

Clinical Report of Probable Catastrophic Antiphospholipid Syndrome in Pregnancy.

Background: Catastrophic APS (CAPS) is a rare but life-threatening form of APS defined as multiorgan thrombosis affecting a minimum of three organs with confirmation by histopathology of small vessel occlusions in at least one organ or tissue. The development of CAPS in pregnancy poses many diagnostic challenges as a result of its broad range of clinical presentations and its overlap with other obstetric complications and microangiopathic diseases. Because of the high associated mortality rate, prompt recognition and treatment are paramount.

Ectopic Breast Tissue of the Vulva in a Postmenopausal Woman.

Ectopic breast tissue is a rare condition caused by remnants of the mammary ridges that fail to involute during embryologic development. To date, only 39 cases have been reported in the literature worldwide. Here, we report the 40th case of a 69-year-old G3P2 postmenopausal Caucasian woman who presented with complaint of vulvar swelling.

Chronic Pelvic Pain and Infertility Resulting from Unrecognized Retained Laminaria.

Background: In 2013, the abortion rate in the United States was found to be 200 abortions per 1,000 live births. Of these, the CDC estimates that nearly 49% were performed using unsafe measures. Even when these procedures are safely performed, patients are at risk for immediate or delayed complications.

Dimercapto-1-propanesulfonic acid (DMPS) induces metaphase II mouse oocyte deterioration.

In light of the recent lead contamination of the water in Flint, Michigan and its potential adverse outcomes, much research and media attention has turned towards the safety profile of commonly used chelators. Dimercapto-1-propanesulfonic acid (DMPS) typically used in the treatment of lead, mercury and arsenic poisoning also displays a high affinity towards transition metals such as zinc and copper, essential for biological functioning. It is given in series of dosages (0.

Recurrence of Chronic Myeloid Leukemia during Pregnancy Subsequently Achieving Complete Medical Remission.

The treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) in reproductive-aged women poses major dilemmas concerning its associated teratogenicity as observed in many animal studies. Much controversy exists regarding continuation versus discontinuation of its use in pregnancy with some studies suggesting safety of TKIs before and during pregnancy and others reporting toxicity and adverse outcomes. TKIs have become a well-established treatment option for CML, significantly improving prognosis, and yet have been reported to be fetotoxic.

Isolation and Characterization of Mesenchymal Stromal Cells from Human Umbilical Cord and Fetal Placenta.

The human umbilical cord (UC) and placenta are non-invasive, primitive and abundant sources of mesenchymal stromal cells (MSCs) that have increasingly gained attention because they do not pose any ethical or moral concerns. Current methods to isolate MSCs from UC yield low amounts of cells with variable proliferation potentials. Since UC is an anatomically-complex organ, differences in MSC properties may be due to the differences in the anatomical regions of their isolation.

Failure of the vascular hypothesis of multiple sclerosis in a rat model of chronic cerebrospinal venous insufficiency.

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A critical analysis of neuroanatomical software protocols reveals clinically relevant differences in parcellation schemes.

A high replicability in region-of-interest (ROI) morphometric or ROI-based connectivity analyses is essential for such methods to provide biomarkers of good health or disease. In this article, we focus on package design, and more specifically on cortical parcellation protocols, for novel insight into their contribution to inter-package differences. A critical analysis of cortical parcellation protocols from FreeSurfer, BrainSuite, BrainVISA and BrainGyrusMapping revealed major limitations.

Imaging signatures of meningioma and low-grade glioma: a diffusion tensor, magnetization transfer and quantitative longitudinal relaxation time MRI study.

Differentiation of cerebral tumor pathology currently relies on interpretation of conventional structural MRI and in some cases histology. However, more advanced MRI methods may provide further insight into the organization of cerebral tumors and have the potential to aid diagnosis. The objective of this study was to use multimodal quantitative MRI to measure the imaging signatures of meningioma and low-grade glioma (LGG).

Permutation and parametric tests for effect sizes in voxel-based morphometry of gray matter volume in brain structural MRI.

Permutation testing has been widely implemented in voxel-based morphometry (VBM) tools. However, this type of non-parametric inference has yet to be thoroughly compared with traditional parametric inference in VBM studies of brain structure. Here we compare both types of inference and investigate what influence the number of permutations in permutation testing has on results in an exemplar study of how gray matter proportion changes with age in a group of working age adults.