A novel hyperparameter search approach for accuracy and simplicity in disease prediction risk scoring.

Objective: Develop a novel technique to identify an optimal number of regression units corresponding to a single risk point, while creating risk scoring systems from logistic regression-based disease predictive models. The optimal value of this hyperparameter balances simplicity and accuracy, yielding risk scores of small scale and high accuracy for patient risk stratification.

Materials And Methods: The proposed technique applies an adapted line search across all potential hyperparameter values.

Practice of Vietnamese tertiary learners' intercultural competence: An influential factor affecting entrepreneurial capabilities.

Intercultural competence (IC) is believed to enhance new graduates' entrepreneurial capabilities and employability in this 21st century. This quantitative study investigates learners' perceived levels of IC, regarding its four components: knowledge, attitudes, skills, and awareness [1,2]. An online survey comprising 40 items adapted from Baroudi's questionnaire [3] based on Byram's conceptual framework of IC [1,2] was administered to learners at a recently established state university in the Mekong Delta of Vietnam.

Overview of approaches to estimate real-world disease progression in lung cancer.

Background: Randomized clinical trials of novel treatments for solid tumors normally measure disease progression using the Response Evaluation Criteria in Solid Tumors. However, novel, scalable approaches to estimate disease progression using real-world data are needed to advance cancer outcomes research. The purpose of this narrative review is to summarize examples from the existing literature on approaches to estimate real-world disease progression and their relative strengths and limitations, using lung cancer as a case study.

Discovery of Potent and Orally Bioavailable Pyridine N-Oxide-Based Factor XIa Inhibitors through Exploiting Nonclassical Interactions.

Activated factor XI (FXIa) inhibitors are promising novel anticoagulants with low bleeding risk compared with current anticoagulants. The discovery of potent FXIa inhibitors with good oral bioavailability has been challenging. Herein, we describe our discovery effort, utilizing nonclassical interactions to improve potency, cellular permeability, and oral bioavailability by enhancing the binding while reducing polar atoms.

PHILM2Web: A high-throughput database of macromolecular host-pathogen interactions on the Web.

During infection, the pathogen's entry into the host organism, breaching the host immune defense, spread and multiplication are frequently mediated by multiple interactions between the host and pathogen proteins. Systematic studying of host-pathogen interactions (HPIs) is a challenging task for both experimental and computational approaches and is critically dependent on the previously obtained knowledge about these interactions found in the biomedical literature. While several HPI databases exist that manually filter HPI protein-protein interactions from the generic databases and curated experimental interactomic studies, no comprehensive database on HPIs obtained from the biomedical literature is currently available.

Complete resection for a giant recurrent biliary cystadenoma: A surgical case report and review of literature.

Background: Biliary cystadenoma is a rare cystic neoplasm of the liver. The clinical signs and symptoms are nonspecific, and treatment strategy is variable.

Case Presentation: In this study, we presented a case of a 32-year-old female with multilocular biliary cystadenoma.

Copper-Catalyzed Synthesis of 5-Carboxyl-4-perfluoroalkyl Triazoles.

A facile, scalable synthesis of previously inaccessible trifluoromethyl and perfluoroalkyl triazoles is disclosed. Mediated by copper, this catalytic protocol enables access to 4-perfluoroalkyl triazoles from commodity chemicals. A catalytic Cu(II) system wherein copper serves two roles (generation of -tosyl-2-vinyldiazenes and N-N bond formation) allows for rapid assembly of 5-carboxyl-4-perfluoroalkyl-triazoles from -tosylhydrazide and perfluoroalkyl acetoacetates.

A comprehensive study of mobility functioning information in clinical notes: Entity hierarchy, corpus annotation, and sequence labeling.

Background: Secondary use of Electronic Health Records (EHRs) has mostly focused on health conditions (diseases and drugs). Function is an important health indicator in addition to morbidity and mortality. Nevertheless, function has been overlooked in accessing patients' health status.

Anterior Segment Dysgenesis With Accessory Iris Membranes in an Infant With Otopalatodigital Spectrum Disorder and Mutation in the FLNA Gene.

A 4-month-old male infant with frontometaphyseal dysplasia and de novo FLNA gene mutation died of complications of disease. Post-mortem examination revealed accessory iris membranes. This is the first report in the literature of accessory iris membranes in a confirmed case of FLNA mutation and phenotypic anomalies consistent with frontometaphyseal dysplasia.

A lattice model for active-passive pedestrian dynamics: a quest for drafting effects.

We study the pedestrian escape from an obscure room using a lattice gas model with two species of particles. One species, called passive, performs a symmetric random walk on the lattice, whereas the second species, called active, is subject to a drift guiding the particles towards the exit. The drift mimics the awareness of some pedestrians of the geometry of the room and of the location of the exit.

Broadening horizons: the case for capturing function and the role of health informatics in its use.

Background: Human activity and the interaction between health conditions and activity is a critical part of understanding the overall function of individuals. The World Health Organization's International Classification of Functioning, Disability and Health (ICF) models function as all aspects of an individual's interaction with the world, including organismal concepts such as individual body structures, functions, and pathologies, as well as the outcomes of the individual's interaction with their environment, referred to as activity and participation. Function, particularly activity and participation outcomes, is an important indicator of health at both the level of an individual and the population level, as it is highly correlated with quality of life and a critical component of identifying resource needs.

Sensorimotor Cortical Oscillations during Movement Preparation in 16p11.2 Deletion Carriers.

Sensorimotor deficits are prevalent in many neurodevelopmental disorders like autism, including one of its common genetic etiologies, a 600 kb reciprocal deletion/duplication at 16p11.2. We have previously shown that copy number variations of 16p11.

Brain MR Imaging Findings and Associated Outcomes in Carriers of the Reciprocal Copy Number Variation at 16p11.2.

Purpose To identify developmental neuroradiologic findings in a large cohort of carriers who have deletion and duplication at 16p11.2 (one of the most common genetic causes of autism spectrum disorder [ASD]) and assess how these features are associated with behavioral and cognitive outcomes. Materials and Methods Seventy-nine carriers of a deletion at 16p11.

Reciprocal white matter alterations due to 16p11.2 chromosomal deletions versus duplications.

Copy number variants at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, and speech and language disorders. A gene dosage dependence has been suggested, with 16p11.

White Matter Changes of Neurite Density and Fiber Orientation Dispersion during Human Brain Maturation.

Diffusion tensor imaging (DTI) studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features of white and gray matter. Neurite orientation dispersion and density imaging (NODDI) is a recently proposed multi-compartment biophysical model of brain microstructure that can estimate non-collinear properties of white matter, such as neurite orientation dispersion index (ODI) and neurite density index (NDI).

Nicotine receptor subtype-specific effects on auditory evoked oscillations and potentials.

Background: Individuals with schizophrenia show increased smoking rates which may be due to a beneficial effect of nicotine on cognition and information processing. Decreased amplitude of the P50 and N100 auditory event-related potentials (ERPs) is observed in patients. Both measures show normalization following administration of nicotine.

GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction.

Reduced N-methyl-D-aspartate-receptor (NMDAR) signaling has been associated with schizophrenia, autism and intellectual disability. NMDAR-hypofunction is thought to contribute to social, cognitive and gamma (30-80 Hz) oscillatory abnormalities, phenotypes common to these disorders. However, circuit-level mechanisms underlying such deficits remain unclear.

Literature mining of host-pathogen interactions: comparing feature-based supervised learning and language-based approaches.

Motivation: In an infectious disease, the pathogen's strategy to enter the host organism and breach its immune defenses often involves interactions between the host and pathogen proteins. Currently, the experimental data on host-pathogen interactions (HPIs) are scattered across multiple databases, which are often specialized to target a specific disease or host organism. An accurate and efficient method for the automated extraction of HPIs from biomedical literature is crucial for creating a unified repository of HPI data.

Optimization of a novel kinase inhibitor scaffold for the dual inhibition of JAK2 and FAK kinases.

The elaboration of a novel scaffold for the inhibition of JAK2 and FAK kinases was targeted in order to provide a dual inhibitor that could target divergent pathways for tumor cell progression.

Strategies to mitigate the bioactivation of 2-anilino-7-aryl-pyrrolo[2,1-f][1,2,4]triazines: identification of orally bioavailable, efficacious ALK inhibitors.

Chemical strategies to mitigate cytochrome P450-mediated bioactivation of novel 2,7-disubstituted pyrrolo[2,1-f][1,2,4]triazine ALK inhibitors are described along with synthesis and biological activity. Piperidine-derived analogues showing minimal microsomal reactive metabolite formation were discovered. Potent, selective, and metabolically stable ALK inhibitors from this class were identified, and an orally bioavailable compound (32) with antitumor efficacy in ALK-driven xenografts in mouse models was extensively characterized.

2,7-Pyrrolo[2,1-f][1,2,4]triazines as JAK2 inhibitors: modification of target structure to minimize reactive metabolite formation.

The JAK2/STAT pathway has important roles in hematopoiesis. With the discovery of the JAK2 V617F mutation and its presence in many patients with myeloproliferative neoplasms, research in the JAK2 inhibitor arena has dramatically increased. We report a novel series of potent JAK2 inhibitors containing a 2,7-pyrrolotriazine core.

2,7-disubstituted-pyrrolo[2,1-f][1,2,4]triazines: new variant of an old template and application to the discovery of anaplastic lymphoma kinase (ALK) inhibitors with in vivo antitumor activity.

A novel 2,7-disubstituted-pyrrolo[2,1-f][1,2,4]triazine scaffold has been designed as a new kinase inhibitor platform mimicking the bioactive conformation of the well-known diaminopyrimidine motif. The design, synthesis, and validation of this new pyrrolo[2,1-f][1,2,4]triazine scaffold will be described for inhibitors of anaplastic lymphoma kinase (ALK). Importantly, incorporation of appropriate potency and selectivity determinants has led to the discovery of several advanced leads that were orally efficacious in animal models of anaplastic large cell lymphoma (ALCL).

Discovery and process synthesis of novel 2,7-pyrrolo[2,1-f][1,2,4]triazines.

The synthesis of a new kinase inhibitor template 2-anilino-7-aryl-pyrrolo[2,1-f][1,2,4]triazine is described which includes a late stage orthogonally reactive key intermediate amenable to rapid diversification as well an optimized in situ triflate displacement to install the C2-aniline. Furthermore, an efficient scalable process approach will be highlighted which begins with tert-butyl carbazate to provide the key N-N bond and generates the pyrrolotriazine core through a stable bromoaldehyde intermediate followed by condensation with ammonium carbonate.

7-fluoroindazoles as potent and selective inhibitors of factor Xa.

We have developed a novel series of potent and selective factor Xa inhibitors that employ a key 7-fluoroindazolyl moiety. The 7-fluoro group on the indazole scaffold replaces the carbonyl group of an amide that is found in previously reported factor Xa inhibitors. The structure of a factor Xa cocrystal containing 7-fluoroindazole 51a showed the 7-fluoro atom hydrogen-bonding with the N-H of Gly216 (2.

Acidic fibroblast growth factor in synovial cells.

Objective: To characterize the production and regulation of acidic fibroblast growth factor (aFGF) in type B (fibroblast-like) synoviocytes cultured from both inflammatory and noninflammatory synovial lesions.

Methods: Immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction were used to examine the expression of aFGF by synovial cells in vitro. Incorporation of 3H-thymidine by NIH3T3 cells in the presence or absence of neutralizing antibody to aFGF was used to measure bioactive aFGF levels in culture media.