Integrating Model-Informed Drug Development With AI: A Synergistic Approach to Accelerating Pharmaceutical Innovation.

The pharmaceutical industry constantly strives to improve drug development processes to reduce costs, increase efficiencies, and enhance therapeutic outcomes for patients. Model-Informed Drug Development (MIDD) uses mathematical models to simulate intricate processes involved in drug absorption, distribution, metabolism, and excretion, as well as pharmacokinetics and pharmacodynamics. Artificial intelligence (AI), encompassing techniques such as machine learning, deep learning, and Generative AI, offers powerful tools and algorithms to efficiently identify meaningful patterns, correlations, and drug-target interactions from big data, enabling more accurate predictions and novel hypothesis generation.

Resazurin dye is an in vivo sensor of kidney tubular function.

Glomerular filtration rate (GFR) is the main functional index of kidney health and disease. Currently, no methods are available to directly measure tubular mass and function. Here, we report a serendipitous finding that the in vitro cell viability dye resazurin can be used in mice as an exogenous sensor of tubular function.

Ketogenic Diet Reduces Age-Induced Chronic Neuroinflammation in Mice.

The ketone body beta-hydroxybutyrate (BHB) is an acidic energy metabolite that is synthesized during periods of fasting or exercise. Our previous study demonstrated that an every other week cyclic ketogenic diet (Cyclic KD), which induces blood BHB levels similar to those observed during fasting, reduces midlife mortality and improves memory in aging mice. In addition to its canonical role as an energy metabolite, BHB regulates gene expression and inflammatory activation through non-energetic signaling pathways.

Priming and task-specific training for arm weakness post stroke: A randomized controlled trial.

Objective: The objective of this work was to evaluate if task-specific training (TST) preceded by bilateral upper limb motor priming (BUMP) reduces upper limb impairment more than TST preceded by control priming ([CP], sham electrical stimulation) in people with chronic stroke.

Methods: In this single-blind, randomized controlled trial, 76 adults with moderate to severe upper limb hemiparesis ≥6 months post-stroke were stratified by baseline impairment and randomized to receive either BUMP or CP prior to receiving the same TST protocol. Participants completed 30 h of treatment in 15 days over 6 weeks.

Hypoxia favors tumor growth in colorectal cancer in an integrin αDβ1/hemoglobin δ-dependent manner.

Low oxygen tension (PO), characterizes the tissue environment of tumors. The colorectal tumor line Colo205, grown under reduced oxygen tension expresses a novel αDβ1 integrin, which forms a cell surface complex with hemoglobin δ. This resulted in high local affinity for oxygen, which increased cell adhesion as compared with cells grown under normal oxygen tension.

β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.

Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). We identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility. βHB primarily provides ATP substrate during periods of reduced glucose availability, and regulates other cellular processes through protein interactions.

Families on the Space-Time Continuum: Conceptualizing and Measuring Temporal and Spatial Dimensions.

The "space-time continuum" is a theoretical framework in physics that removes the distinction between time and space and, instead, treats them as part of a seamless continuum. In this paper, I use it as the basis for a new approach to understanding the opportunities and challenges for low-income families through a focus on two key dimensions of family life: time and space. The spatial element refers to the physical proximity of family members and the temporal pertains to the duration of time in which family members maintain particular arrangements in response to economic shocks, health challenges and new opportunities for social mobility.

Leaf architecture and functional traits for 122 species at the University of California Botanical Garden at Berkeley.

The dataset contains leaf venation architecture and functional traits for a phylogenetically diverse set of 122 plant species (including ferns, basal angiosperms, monocots, basal eudicots, asterids, and rosids) collected from the living collections of the University of California Botanical Garden at Berkeley (37.87° N, 122.23° W; CA, USA) from February to September 2021.

Blood flow modulation to improve motor and neurophysiological outcomes in individuals with stroke: a scoping review.

Ischemic Conditioning (IC) is a procedure involving brief periods of occlusion followed by reperfusion in stationary limbs. Blood Flow Restriction with Exercise (BFR-E) is a technique comprising blood flow restriction during aerobic or resistance exercise. Both IC and BFR-E are Blood Flow Modulation (BFM) strategies that have shown promise across various health domains and are clinically relevant for stroke rehabilitation.

Employment, income, and sleep in South Africa: An actor-partner interdependence model approach.

Objective: We analyze the relationship between employment status, income, and sleep in South Africa to address two research questions: (1) How does employment status influence the sleep quantity of the individual and their partner? (2) How does income impact the sleep quantity of the individual and their partner?

Method: Using data from 1600 Black African couples in the South African Time Use Study, we employ the Actor-Partner Interdependence Model to investigate the relationship between employment status, income, and sleep in couples. We categorize nighttime sleep into three categories: recommended sleep (7-9 hours), short sleep (<7 hours), and long sleep (>9 hours).

Results: Employed individuals were more likely to get the recommended amount of sleep and less likely to experience long sleep.

Integrative genomic analysis of the lung tissue microenvironment in SARS-CoV-2 and NL63 patients.

The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus has affected over 700 million people, and caused over 7 million deaths throughout the world as of April 2024, and continues to affect people through seasonal waves. While over 675 million people have recovered from this disease globally, the lingering effects of the disease are still under study. Long term effects of SARS-CoV-2 infection, known as 'long COVID,' include a wide range of symptoms including fatigue, chest pain, cellular damage, along with a strong innate immune response characterized by inflammatory cytokine production.

Leaf venation network architecture coordinates functional trade-offs across vein spatial scales: evidence for multiple alternative designs.

Variation in leaf venation network architecture may reflect trade-offs among multiple functions including efficiency, resilience, support, cost, and resistance to drought and herbivory. However, our knowledge about architecture-function trade-offs is mostly based on studies examining a small number of functional axes, so we still lack a more integrative picture of multidimensional trade-offs. Here, we measured architecture and functional traits on 122 ferns and angiosperms species to describe how trade-offs vary across phylogenetic groups and vein spatial scales (small, medium, and large vein width) and determine whether architecture traits at each scale have independent or integrated effects on each function.

Safety & efficacy of a robotic hip exoskeleton on outpatient stroke rehabilitation.

Objective: The objective of this study was to analyze the safety and efficacy of using a robotic hip exoskeleton designed by Samsung Electronics Co., Ltd., Korea, called the Gait Enhancing and Motivating System-Hip (GEMS-H), in assistance mode only with the poststroke population in an outpatient-rehabilitation setting.

Rewriting the textbook for pharma: how to adapt and thrive in a digital, personalized and collaborative world.

The pharmaceutical industry is undergoing a sweeping transformation, driven by technological innovations, demographic shifts, regulatory changes and consumer expectations. For adaptive players in pharma to excel in this rapidly changing landscape, which will be markedly different from today by 2030 and beyond, they will require a different set of skills, capabilities and mindsets, as well as a willingness to collaborate and co-create value with multiple stakeholders. The industry needs to rewrite the textbook for pharma by embracing and implementing four key dimensions of change: digitalization, personalization, collaboration and innovation.

Deletion of NuRD component in nephron progenitor cells causes developmentally programmed FSGS.

Low nephron endowment at birth is a risk factor for chronic kidney disease. The prevalence of this condition is increasing due to higher survival rates of preterm infants and children with multi- organ birth defect syndromes that affect the kidney and urinary tract. We created a mouse model of congenital low nephron number due to deletion of in nephron progenitor cells.

Using large language models for safety-related table summarization in clinical study reports.

Objectives: The generation of structured documents for clinical trials is a promising application of large language models (LLMs). We share opportunities, insights, and challenges from a competitive challenge that used LLMs for automating clinical trial documentation.

Materials And Methods: As part of a challenge initiated by Pfizer (organizer), several teams (participant) created a pilot for generating summaries of safety tables for clinical study reports (CSRs).

The Association of Interlimb Coordination and Temporal Symmetry With Walking Function and Motor Impairment After Stroke.

Objective: Interlimb coordination during walking is impaired after stroke, with unknown effects on walking function. This cross-sectional study determined associations of interlimb coordination and temporal symmetry with walking function and motor impairment.

Design: During walking, participants wore wireless sensors to detect heel strikes.

Effects of Performance-Based Financing on Availability, Quality, and Use of Family Planning Services in the Democratic Republic of Congo: An Impact Evaluation.

Access to high-quality family planning services remains limited in many low- and middle-income countries, resulting in a high burden of unintended pregnancies and adverse health outcomes. We used data from a large randomized controlled trial in the Democratic Republic of Congo to test whether performance-based financing (PBF) can increase the availability, quality, and use of family planning services. Starting at the end of 2016, 30 health zones were randomly assigned to a PBF program, in which health facilities received financing conditional on the quantity and quality of offered services.

Impact of radiation dose distribution on nutritional supplementation needs in head and neck cancer radiotherapy: a voxel-based machine learning approach.

Objectives: To investigate the relationship between nutritional supplementation and radiation dose to the pharyngeal constrictor muscles and larynx for head and neck (HN) cancer patients undergoing radiotherapy.

Methods: We retrospectively analyzed radiotherapy (RT) dose for 231 HN cancer patients, focusing on the pharyngeal constrictors and larynx. We defined nutritional supplementation as feeding tube utilization or >10% weight loss from baseline within 90 days after radiotherapy completion.