Furo[2,3-d]pyrimidines as Mackinazolinone/Isaindigotone Analogs: Synthesis, Modification, Antitumor Activity, and Molecular Docking Study.

The chemical transformation of the tricyclic furo[2,3-d]pyrimidines was performed under isosteric and scaffold-hopping strategies focusing on the synthesis of its arylidene and imine-containing derivatives. Naturally-occurring alkaloids mackinazolinone and isaindigotone were as templates of target heterocycles. Synthesized compounds evaluated for their antitumor activity on human cancer cervical HeLa, breast MCF-7, and colon HT-29 cell lines.

Design, combinatorial synthesis and cytotoxic activity of 2-substituted furo[2,3-d]pyrimidinone and pyrrolo[2,3-d]pyrimidinone library.

A facile protocol was developed for the combinatorial synthesis of furo[2,3-d]pyrimidinone and pyrrolo[2,3-d]pyrimidinone library via a one-pot condensation, from 2-amino furans/pyrroles. Herein reported process required a similar reaction condition, providing mild access to two diverse series of natural product-like heterocycles. Both furo[2,3-d]pyrimidinones and pyrrolo[2,3-d]pyrimidinones were evaluated in vitro against a panel of human cancer cell lines including against human cancer HeLa (cervical), MCF-7 (breast) and HT-29 (colon) cell lines.

Using Artificial Intelligence With Natural Language Processing to Combine Electronic Health Record's Structured and Free Text Data to Identify Nonvalvular Atrial Fibrillation to Decrease Strokes and Death: Evaluation and Case-Control Study.

Background: Nonvalvular atrial fibrillation (NVAF) affects almost 6 million Americans and is a major contributor to stroke but is significantly undiagnosed and undertreated despite explicit guidelines for oral anticoagulation.

Objective: The aim of this study is to investigate whether the use of semisupervised natural language processing (NLP) of electronic health record's (EHR) free-text information combined with structured EHR data improves NVAF discovery and treatment and perhaps offers a method to prevent thousands of deaths and save billions of dollars.

Methods: We abstracted 96,681 participants from the University of Buffalo faculty practice's EHR.

One-Pot Green Synthesis of Acridine Alkaloid Derivatives and Screening of in vitro Anti-cancer Activity Against Cdc25b and SHP1.

Aim: To develop anti-cancer active pharmaceutical intermediates.

Background: Acridone derivatives possess a wide range of pharmacological activities: 1) they intercalate DNA and 2) form a covalent bond with DNA.

Objective: To screen in vitro anti-cancer activity against Cdc25b and SHP1 of new acridone derivatives and preliminary study on the structure-activity relationship.

Clinical Data Warehouse Query and Learning Tool Using a Human-Centered Participatory Design Process.

BMI Investigator (BMII) is an interactive web-based tool with a learning knowledge base, which provides a way for researchers to query structured, unstructured, genomic and image data contained in a data warehouse. We demonstrate how development of an efficient, usable, and learnable web interface for a diverse group of research stakeholders benefits from an iterative human-centered participatory design process utilizing a team of clinicians, students, programmers, and informatics experts.

Barriers, Facilitators, and Solutions to Optimal Patient Portal and Personal Health Record Use: A Systematic Review of the Literature.

Patient portal and personal health record adoption and usage rates have been suboptimal. A systematic review of the literature was performed to capture all published studies that specifically addressed barriers, facilitators, and solutions to optimal patient portal and personal health record enrollment and use. Consistent themes emerged from the review.

Secondary Use of EHR: Interpreting Clinician Inter-Rater Reliability Through Qualitative Assessment.

In a retrospective secondary-use EHR study identifying a cohort of Non-Valvular Atrial Fibrillation (NVAF) patients, chart abstraction was done by two sets of clinicians to create a gold standard for risk measures CHA2DS2-VASc and HAS-BLED. Inter-rater reliability between each set of clinicians for NVAF and the outcomes of interest were variable, ranging from extremely low agreement to high agreement. To assess the chart abstraction process, a focus group and a survey was conducted.

Invasive Aspergillus Laryngotracheobronchitis in an Adult with Primary CNS Lymphoma.

Invasive aspergillosis can be difficult to diagnose, and early recognition and initiation of therapy is imperative for improving patient outcomes. A case of invasive Aspergillus laryngotracheobronchitis is presented here with a review of the relevant literature. A 58-year-old male undergoing treatment for CNS lymphoma presented with neutropenic sepsis and acute respiratory distress requiring intubation.

Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate.

TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo.

Systems genetics analysis of mouse chondrocyte differentiation.

One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks.

Smad signaling in skeletal development and regeneration.

Smad proteins are intracellular molecules that mediate the canonical signaling cascade of TGFbeta superfamily growth factors. The TGFbeta superfamily comprises two groups of growth factors, BMPs and TGFbetas. Both groups can be further divided into several sub-groups based on sequence homologies and functional similarities.

BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation.

Bone morphogenetic protein (BMP) signaling is required for endochondral bone formation. However, whether or not the effects of BMPs are mediated via canonical Smad pathways or through noncanonical pathways is unknown. In this study we have determined the role of receptor Smads 1, 5 and 8 in chondrogenesis.

Conditional Kif3a ablation causes abnormal hedgehog signaling topography, growth plate dysfunction, and excessive bone and cartilage formation during mouse skeletogenesis.

The motor protein Kif3a and primary cilia regulate important developmental processes, but their roles in skeletogenesis remain ill-defined. Here we created mice deficient in Kif3a in cartilage and focused on the cranial base and synchondroses. Kif3a deficiency caused cranial base growth retardation and dysmorphogenesis, which were evident in neonatal animals by anatomical and micro-computed tomography (microCT) inspection.

Development of the post-natal growth plate requires intraflagellar transport proteins.

In the post-natal growth plate, chondrocytes are arranged in columns parallel to the long axis of the bone. Chondrocytes divide perpendicular to this axis and then move into position one on top of another in a process called "rotation" that maintains columnar organization. Primary cilia are non-motile microtubule base appendages extending from the surface of almost all vertebrate cells.

Intraflagellar transport is essential for endochondral bone formation.

While cilia are present on most cells in the mammalian body, their functional importance has only recently been discovered. Cilia formation requires intraflagellar transport (IFT), and mutations disrupting the IFT process result in loss of cilia and mid-gestation lethality with developmental defects that include polydactyly and abnormal neural tube patterning. The early lethality in IFT mutants has hindered research efforts to study the role of this organelle at later developmental stages.

A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells.

Mesenchymal stem cells have the potential to differentiate into various cell lineages, including adipocytes and osteoblasts. The induction of adipocyte differentiation by glucocorticoids (GCs) not only causes the accumulation of fat cells in bone marrow, but also depletes the supply of osteoblasts for new bone formation, thus leading to osteoporosis. We have shown that a GC-induced leucine-zipper protein (GILZ) antagonizes adipocyte differentiation.