HiMAL: Multimodal Hierarchical Multi-task Auxiliary Learning framework for predicting Alzheimer's disease progression.

Objective: We aimed to develop and validate a novel multimodal framework erarchical ulti-task uxiliary earning ( framework, for predicting cognitive composite functions as auxiliary tasks that estimate the longitudinal risk of transition from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD).

Materials And Methods: HiMAL utilized multimodal longitudinal visit data including imaging features, cognitive assessment scores, and clinical variables from MCI patients in the Alzheimer's Disease Neuroimaging Initiative dataset, to predict at each visit if an MCI patient will progress to AD within the next 6 months. Performance of HiMAL was compared with state-of-the-art single-task and multitask baselines using area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics.

OpenSep: a generalizable open source pipeline for SOFA score calculation and Sepsis-3 classification.

EHR-based sepsis research often uses heterogeneous definitions of sepsis leading to poor generalizability and difficulty in comparing studies to each other. We have developed OpenSep, an open-source pipeline for sepsis phenotyping according to the Sepsis-3 definition, as well as determination of time of sepsis onset and SOFA scores. The Minimal Sepsis Data Model was developed alongside the pipeline to enable the execution of the pipeline to diverse sources of electronic health record data.

Sepsis Prediction for the General Ward Setting.

Objective: To develop and evaluate a sepsis prediction model for the general ward setting and extend the evaluation through a novel pseudo-prospective trial design.

Design: Retrospective analysis of data extracted from electronic health records (EHR).

Setting: Single, tertiary-care academic medical center in St.

Respiratory support status from EHR data for adult population: classification, heuristics, and usage in predictive modeling.

Objective: Respiratory support status is critical in understanding patient status, but electronic health record data are often scattered, incomplete, and contradictory. Further, there has been limited work on standardizing representations for respiratory support. The objective of this work was to (1) propose a practical terminology system for respiratory support methods; (2) develop (meta-)heuristics for constructing respiratory support episodes; and (3) evaluate the utility of respiratory support information for mortality prediction.

Comparison of early warning scores for sepsis early identification and prediction in the general ward setting.

The objective of this study was to directly compare the ability of commonly used early warning scores (EWS) for early identification and prediction of sepsis in the general ward setting. For general ward patients at a large, academic medical center between early-2012 and mid-2018, common EWS and patient acuity scoring systems were calculated from electronic health records (EHR) data for patients that both met and did not meet Sepsis-3 criteria. For identification of sepsis at index time, National Early Warning Score 2 (NEWS 2) had the highest performance (area under the receiver operating characteristic curve: 0.

A Pragmatic Machine Learning Model To Predict Carbapenem Resistance.

Infection caused by carbapenem-resistant (CR) organisms is a rising problem in the United States. While the risk factors for antibiotic resistance are well known, there remains a large need for the early identification of antibiotic-resistant infections. Using machine learning (ML), we sought to develop a prediction model for carbapenem resistance.

Spot the difference: comparing results of analyses from real patient data and synthetic derivatives.

Background: Synthetic data may provide a solution to researchers who wish to generate and share data in support of precision healthcare. Recent advances in data synthesis enable the creation and analysis of synthetic derivatives as if they were the original data; this process has significant advantages over data deidentification.

Objectives: To assess a big-data platform with data-synthesizing capabilities (MDClone Ltd.

Comparison of Sepsis Definitions as Automated Criteria.

Objectives: Assess the impact of heterogeneity among established sepsis criteria (Sepsis-1, Sepsis-3, Centers for Disease Control and Prevention Adult Sepsis Event, and Centers for Medicare and Medicaid severe sepsis core measure 1) through the comparison of corresponding sepsis cohorts.

Design: Retrospective analysis of data extracted from electronic health record.

Setting: Single, tertiary-care center in St.

The Clinical Course of Coronavirus Disease 2019 in a US Hospital System: A Multistate Analysis.

There are limited data on longitudinal outcomes for coronavirus disease 2019 (COVID-19) hospitalizations that account for transitions between clinical states over time. Using electronic health record data from a hospital network in the St. Louis, Missouri, region, we performed multistate analyses to examine longitudinal transitions and outcomes among hospitalized adults with laboratory-confirmed COVID-19 with respect to 15 mutually exclusive clinical states.

Acid Resistance of Glass Ionomer Cement Restorative Materials.

In view of the need for aesthetics, restorations of teeth will typically be completed using tooth colored restorative materials. With the advent of biomimetic restorative materials, such as glass ionomer cements (GIC), much greater emphasis is now being placed on how well such materials can resist the challenge of acids that are present in foods and drinks, or gastric contents that are regurgitated. This laboratory study compared the dissolution and behavior of five GIC materials (GC Fuji VII, GC Fuji Bulk, GC Fuji IX Fast, Fuji IX Extra and GC Equia Forte Fil) when exposed to three acids (citric acid, phosphoric acid and lactic acid), versus ultrapure deionized water, which was used as a control.

Small Molecule Inhibition of CPS1 Activity through an Allosteric Pocket.

Carbamoyl phosphate synthetase 1 (CPS1) catalyzes the first step in the ammonia-detoxifying urea cycle, converting ammonia to carbamoyl phosphate under physiologic conditions. In cancer, CPS1 overexpression supports pyrimidine synthesis to promote tumor growth in some cancer types, while in others CPS1 activity prevents the buildup of toxic levels of intratumoral ammonia to allow for sustained tumor growth. Targeted CPS1 inhibitors may, therefore, provide a therapeutic benefit for cancer patients with tumors overexpressing CPS1.

Novel Visualization of Infections in Intensive Care Units.

Background: Accurate and timely surveillance and diagnosis of healthcare-facility onset infection (HO-CDI) is vital to controlling infections within the hospital, but there are limited tools to assist with timely outbreak investigations.

Objectives: To integrate spatiotemporal factors with HO-CDI cases and develop a map-based dashboard to support infection preventionists (IPs) in performing surveillance and outbreak investigations for HO-CDI.

Methods: Clinical laboratory results and Admit-Transfer-Discharge data for admitted patients over two years were extracted from the Information Warehouse of a large academic medical center and processed according to Center for Disease Control (CDC) National Healthcare Safety Network (NHSN) definitions to classify infection (CDI) cases by onset date.

Deconvolution of images from 3D printed cells in layers on a chip.

Layer-by-layer cell printing is useful in mimicking layered tissue structures inside the human body and has great potential for being a promising tool in the field of tissue engineering, regenerative medicine, and drug discovery. However, imaging human cells cultured in multiple hydrogel layers in 3D-printed tissue constructs is challenging as the cells are not in a single focal plane. Although confocal microscopy could be a potential solution for this issue, it compromises the throughput which is a key factor in rapidly screening drug efficacy and toxicity in pharmaceutical industries.

Physical-Performance Outcomes and Biomechanical Correlates from the 32-Week Yoga Empowers Seniors Study.

. Yoga Empowers Seniors Study (YESS) quantified physical demands associated with yoga performance using biomechanical methods. This study evaluated the efficacy of the program on physical function outcomes.

Connexin Controls Cell-Cycle Exit and Cell Differentiation by Directly Promoting Cytosolic Localization and Degradation of E3 Ligase Skp2.

Connexins and connexin channels play important roles in cell growth/differentiation and tumorigenesis. Here, we identified a relationship between a connexin molecule and a critical cell-cycle regulator. Our data show that connexin (Cx) 50 regulated lens cell-cycle progression and differentiation by modulating expression of cyclin-dependent kinase inhibitor p27/p57 and E3 ubiquitin ligase Skp2.

The association between unilateral heel-rise performance with static and dynamic balance in community dwelling older adults.

As a measure of both strength and muscle endurance of the plantar flexors, the unilateral heel rise (UHR) test has been suggested as a method to evaluate balance capabilities in older adults. Thus, the purpose of this study was to examine the association between UHR performance with biomechanical measures of balance in seniors. Twenty-two older adults completed two testing sessions.

Physical demand profiles of hatha yoga postures performed by older adults.

Understanding the physical demands placed upon the musculoskeletal system by individual postures may allow experienced instructors and therapists to develop safe and effective yoga programs which reduce undesirable side effects. Thus, we used biomechanical methods to quantify the lower extremity joint angles, joint moments of force, and muscle activities of 21 Hatha yoga postures, commonly used in senior yoga programs. Twenty older adults, 70.

The biomechanical demands of standing yoga poses in seniors: The Yoga empowers seniors study (YESS).

Background: The number of older adults participating in yoga has increased dramatically in recent years; yet, the physical demands associated with yoga performance have not been reported. The primary aim of the Yoga Empowers Seniors Study (YESS) was to use biomechanical methods to quantify the physical demands associated with the performance of 7 commonly-practiced standing yoga poses in older adults.

Methods: 20 ambulatory older adults (70.

The physical demands of the tree (vriksasana) and one-leg balance (utthita hasta padangusthasana) poses performed by seniors: a biomechanical examination.

Yoga is considered especially suitable for seniors because poses can be modified to accommodate practitioners' capabilities and limitations. In this study, biomechanical assessments on healthy seniors (n = 20; 70.1 ± 3.

Yoga Empowers Seniors Study (YESS): Design and Asana Series.

The practice of yoga asanas (postures) may be an optimal method of preserving or enhancing physical function in older men and women. However, the physical demands, efficacy and safety of an asana practice for seniors have not been well studied. The Yoga Empowers Seniors Study (YESS) is an intervention development study that created two senior-adapted series of asanas targeted for an ambulatory older population.

Orally bioavailable imidazoazepanes as calcitonin gene-related peptide (CGRP) receptor antagonists: discovery of MK-2918.

In our ongoing efforts to develop CGRP receptor antagonists for the treatment of migraine, we aimed to improve upon telecagepant by targeting a compound with a lower projected clinical dose. Imidazoazepanes were identified as potent caprolactam replacements and SAR of the imidazole yielded the tertiary methyl ether as an optimal substituent for potency and hERG selectivity. Combination with the azabenzoxazinone spiropiperidine ultimately led to preclinical candidate 30 (MK-2918).

Transcriptional regulation in yeast during diauxic shift and stationary phase.

The preferred source of carbon and energy for yeast cells is glucose. When yeast cells are grown in liquid cultures, they metabolize glucose predominantly by glycolysis, releasing ethanol in the medium. When glucose becomes limiting, the cells enter diauxic shift characterized by decreased growth rate and by switching metabolism from glycolysis to aerobic utilization of ethanol.

Amino acid residue Val362 plays a critical role in maintaining the structure of C terminus of connexin 50 and in lens epithelial-fiber differentiation.

We have previously shown that connexin (Cx) 50, unlike the other two lens connexins, Cx43 and Cx46, promotes chicken lens epithelial-fiber differentiation in a channel-independent manner. Here, we show that deletion of the PEST motif at the C terminus (CT) domain of Cx50 attenuates the stimulatory effect of Cx50 on lens fiber differentiation. Valine 362, a residue located within the PEST domain, is functionally involved.

Optimization of azepanone calcitonin gene-related peptide (CGRP) receptor antagonists: development of novel spiropiperidines.

Several novel spiropiperidine-based CGRP receptor antagonists have been developed that maintain good potency and have reduced potential for metabolism.