EHE cell cultures: a platform for mechanistic and therapeutic investigation.

Epithelioid hemangioendothelioma (EHE) is a difficult to treat vascular sarcoma defined by TAZ- CAMTA1 or YAP-TFE3 fusion proteins. Human cell lines needed to further understand the pathogenesis of EHE have been lacking. Herein, we describe a method to generate EHE extended primary cell cultures.

K27-linked RORγt ubiquitination by Nedd4 potentiates Th17-mediated autoimmunity.

Background: The HECT E3 ubiquitin ligase Nedd4 has been shown to positively regulate T cell responses, but its role in T helper (Th) cell differentiation and autoimmunity is unknown. Th17 cells are believed to play a pivotal role in the development and pathogenesis of autoimmune diseases. Nevertheless, the regulation of RORγt activation during Th17 cell differentiation by TCR signaling is yet to be elucidated.

PI3K regulates TAZ/YAP and mTORC1 axes that can be synergistically targeted.

Purpose: Sarcomas are a heterogeneous group of cancers with few shared therapeutic targets. PI3K signaling is activated in various subsets of sarcomas, representing a shared oncogenic signaling pathway. Oncogenic PI3K signaling has been challenging to target therapeutically.

Novel Variants of IGF2 Gene Are Linked With Neural Tube Defects-An In Silico to Clinical Approach in West Bengal, India.

Background: Neural tube defects (NTDs) are defined as an incomplete closure of the neural tube (NT), with a prevalence of 1.2 per 1000 live births around the world. Methylation of the maternally imprinted gene Insulin-like growth factor 2 (IGF2) is one of the epigenetic mechanisms that contribute significantly to the development of NTDs.

Analysis of DNMT1 gene variants in progression of neural tube defects-an in silico to in vitro approach.

Neural tube defects (NTDs) are significant congenital deformities of the central nervous system among which spina bifida is the most common form that occurs due to defect in the neurulation process of embryogenesis. NTDs are among the most common type of birth defects occurring at a range of 0.5-10 in every 1000 live births worldwide and are thought to have multifactorial etiology, including multigenetic and epigenetic notions.

Remediating textbook deficiencies by leveraging community question answers.

The paper presents a method for recommending augmentations against conceptual gaps in textbooks. Question Answer (QA) pairs from community question-answering (cQA) forums are noted to offer precise and comprehensive illustrations of concepts. Our proposed method retrieves QA pairs for a target concept to suggest two types of augmentations: basic and supplementary.

Dichotomy in Growth and Invasion from Low- to High-Grade Glioma Cellular Variants.

Glial dysfunction outraging CNS plasticity and integrity results in one of the most dangerous cancers, namely glioma, featuring little median survival period and high recurrence. The hallmark properties of proliferation, invasion and angiogenesis with the infiltrated macrophages in glioma are expected to be tightly coupled or cross-linked, but not properly related so far. The present study is aimed to find a relationship between this featured quadrangle from lower to higher grades (HG) of post-operative glioma tissues and their invading subsets.

Quantifying and visualizing site performance in clinical trials.

Background: One of the keys to running a successful clinical trial is the selection of high quality clinical sites, i.e., sites that are able to enroll patients quickly, engage them on an ongoing basis to prevent drop-out, and execute the trial in strict accordance to the clinical protocol.

Microglial Contribution to Glioma Progression: an Immunohistochemical Study in Eastern India.

Human glioma, arising from glial cells of the central nervous system, accounts for almost 30%of all brain tumours , neoplasms with a poor prognosis and high mortality rates worldwide. In the present study we assessed tissue architectural modifications associated with macrophage lineage cells, controversial major immune effector cells within the brain, in human glioma tissue samples from eastern India. Ethically cleared post-operative human glioma samples from our collaborative neurosurgery unit with respective CT/MRI and patient history were collected from the Nodal Centre of Neurosciences in Kolkata, over 9 months.

Reliability and Validity of Prototype Diagnosis for Adolescent Psychopathology.

The current study investigated the interrater reliability and validity of prototype ratings of 5 common adolescent psychiatric disorders: attention-deficit/hyperactivity disorder, conduct disorder, major depressive disorder, generalized anxiety disorder, and posttraumatic stress disorder. One hundred fifty-seven adolescent inpatient participants consented to participate in this study. We compared ratings from 2 inpatient clinicians, blinded to each other's ratings and patient measures, after their separate initial diagnostic interview to assess interrater reliability.

Formal modeling of a system of chemical reactions under uncertainty.

We describe a novel formalism representing a system of chemical reactions, with imprecise rates of reactions and concentrations of chemicals, and describe a model reduction method, pruning, based on the chemical properties. We present two algorithms, midpoint approximation and interval approximation, for construction of efficient model abstractions with uncertainty in data. We evaluate computational feasibility by posing queries in computation tree logic (CTL) on a prototype of extracellular-signal-regulated kinase (ERK) pathway.

Construct validity of the Schwartz Outcome Scale: validation using a 28-day inpatient chemical rehabilitation patient sample.

The Schwartz Outcome Scale-10 (SOS-10) is a 10-item self-report that measures quality of life and psychological well-being. It is easy to administer and score, and past research has revealed its utility, validity, and reliability with different samples (i.e.

Alzheimer's disease - not an exaggeration of healthy aging.

The world population is becoming older now. The boom of the elderly population comes from public health efforts to improve living conditions and prevent disease, and from improved medical interventions. People more than 65-year-old who are representing 12.

Quality-by-design case study: investigation of the role of poloxamer in immediate-release tablets by experimental design and multivariate data analysis.

The role of poloxamer 188, water and binder addition rate, on retarding dissolution in immediate-release tablets of a model drug from BCS class II was investigated by means of multivariate data analysis (MVDA) combined with design of experiments (DOE). While the DOE analysis yielded important clues into the cause-and-effect relationship between the responses and design factors, multivariate data analysis of the 40+ variables provided additional information on slowdown in tablet dissolution. A steep dependence of both tablet dissolution and disintegration on the poloxamer and less so on other design variables was observed.

A Quality by Design approach to investigate tablet dissolution shift upon accelerated stability by multivariate methods.

This paper presents the use of experimental design, optimization and multivariate techniques to investigate root-cause of tablet dissolution shift (slow-down) upon stability and develop control strategies for a drug product during formulation and process development. The effectiveness and usefulness of these methodologies were demonstrated through two application examples. In both applications, dissolution slow-down was observed during a 4-week accelerated stability test under 51°C/75%RH storage condition.

Genomics Portals: integrative web-platform for mining genomics data.

Background: A large amount of experimental data generated by modern high-throughput technologies is available through various public repositories. Our knowledge about molecular interaction networks, functional biological pathways and transcriptional regulatory modules is rapidly expanding, and is being organized in lists of functionally related genes. Jointly, these two sources of information hold a tremendous potential for gaining new insights into functioning of living systems.

Quality by design case study: an integrated multivariate approach to drug product and process development.

To facilitate an in-depth process understanding, and offer opportunities for developing control strategies to ensure product quality, a combination of experimental design, optimization and multivariate techniques was integrated into the process development of a drug product. A process DOE was used to evaluate effects of the design factors on manufacturability and final product CQAs, and establish design space to ensure desired CQAs. Two types of analyses were performed to extract maximal information, DOE effect & response surface analysis and multivariate analysis (PCA and PLS).

Application of robotics to steady state enzyme kinetics: analysis of tight-binding inhibitors of dipeptidyl peptidase IV.

Using available commercial robotics and instrumentation, we developed a fully automated and rigorous steady state enzyme kinetic assay for dipeptidyl peptidase IV (DPP IV; E.C. 3.