Toward precision medicine: End-to-end design and construction of integrated microneedle-based theranostic systems.

With the growing demand for precision medicine and advancements in microneedle technology, microneedle-based drug delivery systems have evolved into integrated theranostic platforms. However, the development of these systems is currently limited by the absence of clear conclusions and standardized construction strategies. The end-to-end concept offers an innovative approach to theranostic systems by creating a seamless process that integrates target sampling, sensing, analysis, and on-demand drug delivery.

Healthcare Utilization and Chronic Disease Management for Non-Medicaid-Eligible Patients in a City-Wide Safety-Net Healthcare Access Program.

Background: In 2019, New York City (NYC) launched NYC Care (NYCC), a healthcare access program through NYC Health + Hospitals (H + H) for individuals who are ineligible for federally funded health insurance programs or cannot purchase insurance through the State Marketplace, predominantly undocumented individuals.

Objective: To examine the sociodemographic characteristics, healthcare use patterns, and chronic disease quality measures for diabetes mellitus (DM) and hypertension among NYCC patients compared with Medicaid patients seen at NYC H + H.

Design: Observational study.

DDR2 signaling and mechanosensing orchestrate neuroblastoma cell fate through different transcriptome mechanisms.

The extracellular matrix (ECM) regulates carcinogenesis by interacting with cancer cells via cell surface receptors. Discoidin Domain Receptor 2 (DDR2) is a collagen-activated receptor implicated in cell survival, growth, and differentiation. Dysregulated DDR2 expression has been identified in various cancer types, making it as a promising therapeutic target.

Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory.

P21-activated kinase 3 (PAK3) gene mutations are linked to several neurodevelopmental disorders, but the underlying mechanisms remain unclear. In this study, we used a tetracycline-inducible system to control the expression of a mutant PAK3 (mPAK3) protein in immediate early gene, namely cFos, positive cells to disrupt PAK signaling, specifically in cells activated by social interaction in transgenic mice. We show that the expression of mPAK3-GFP proteins was in cFos-expressing excitatory and inhibitory neurons in various brain regions, such as the cortex and hippocampus, commonly activated during learning and memory.

Effect of vimentin on cell migration in collagen-coated microchannels: A mimetic physiological confined environment.

Cancer cell migration through tissue pores and tracks into the bloodstream is a critical biological step for cancer metastasis. Although studies have shown that expression of vimentin can induce invasive cell lines, its role in cell cytoskeleton reorganization and cell motility under physical confinement remains unknown. Here, a microfluidic device with cell culture chamber and collagen-coated microchannels was developed as an model for physiological confinement environments.

End-to-end application of model-informed drug development for ertugliflozin, a novel sodium-glucose cotransporter 2 inhibitor.

Model-informed drug development (MIDD) is critical in all stages of the drug-development process and almost all regulatory submissions for new agents incorporate some form of modeling and simulation. This review describes the MIDD approaches used in the end-to-end development of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor approved for the treatment of adults with type 2 diabetes mellitus. Approaches included (1) quantitative systems pharmacology modeling to predict dose-response relationships, (2) dose-response modeling and model-based meta-analysis for dose selection and efficacy comparisons, (3) population pharmacokinetics (PKs) modeling to characterize PKs and quantify population variability in PK parameters, (4) regression modeling to evaluate ertugliflozin dose-proportionality and the impact of uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A9 genotype on ertugliflozin PKs, and (5) physiologically-based PK modeling to assess the risk of UGT-mediated drug-drug interactions.

Meta-Analysis of Noncompartmental Pharmacokinetic Parameters of Ertugliflozin to Evaluate Dose Proportionality and UGT1A9 Polymorphism Effect on Exposure.

Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, is primarily metabolized via glucuronidation by the uridine 5'-diphospho-glucuronosyltransferase (UGT) isoform UGT1A9. This noncompartmental meta-analysis of ertugliflozin pharmacokinetics evaluated the relationship between ertugliflozin exposure and dose, and the effect of UGT1A9 genotype on ertugliflozin exposure. Pharmacokinetic data from 25 phase 1 studies were pooled.

Advancing Biosensors with Machine Learning.

Chemometrics play a critical role in biosensors-based detection, analysis, and diagnosis. Nowadays, as a branch of artificial intelligence (AI), machine learning (ML) have achieved impressive advances. However, novel advanced ML methods, especially deep learning, which is famous for image analysis, facial recognition, and speech recognition, has remained relatively elusive to the biosensor community.

Bioequivalence of Metformin in Ertugliflozin/Metformin Fixed-Dose Combination Tablets to Canadian-Sourced Metformin Coadministered With Ertugliflozin Under Fasted and Fed States.

A fixed-dose combination (FDC) product of a selective sodium-glucose cotransporter 2 inhibitor ertugliflozin and immediate-release metformin is approved for type 2 diabetes mellitus in the United States, European Union countries, Canada, and other countries. Two studies were conducted to assess the bioequivalence of metformin in the ertugliflozin/metformin FDC tablets to the corresponding doses of Canadian-sourced metformin (Glucophage) coadministered with ertugliflozin. Both studies were phase 1 randomized, open-label, 2-period, single-dose crossover studies (n = 32) in which healthy subjects received an ertugliflozin/metformin FDC tablet (2.

Batch fabrication of electrochemical sensors on a glycol-modified polyethylene terephthalate-based microfluidic device.

Developing low-cost methods for the fabrication of electrochemical microfluidic devices is urgently needed for transferring such devices from fundamental research to daily-life technology. Herein, glycol-modified polyethylene terephthalate (PETG)-based microfluidic devices with embedded channels and gold film electrode (GFE) are developed by a one-step, low-cost, straightforward, and mass-producible method, and are sealed by a reversible hydrophilic tape-based mechanism. Easily accessible poly (methyl methacrylate) (PMMA), polyethylene terephthalate (polyester, PET), and PETG are explored as substrate options for fabricating electrochemical sensors.

Neuroligin 2 regulates absence seizures and behavioral arrests through GABAergic transmission within the thalamocortical circuitry.

Epilepsy and autism spectrum disorders (ASD) are two distinct brain disorders but have a high rate of co-occurrence, suggesting shared pathogenic mechanisms. Neuroligins are cell adhesion molecules important in synaptic function and ASD, but their role in epilepsy remains unknown. In this study, we show that Neuroligin 2 (NLG2) knockout mice exhibit abnormal spike and wave discharges (SWDs) and behavioral arrests characteristic of absence seizures.

Diagnostic methods and potential portable biosensors for coronavirus disease 2019.

Timely detection and diagnosis are urgently needed to guide epidemiological measures, infection control, antiviral treatment, and vaccine research. In this review, biomarkers/indicators for diagnosis of coronavirus disease 2019 (COVID-19) or detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the environment are summarized and discussed. It is concluded that the detection methods targeting antibodies are not suitable for screening of early and asymptomatic cases since most patients had an antibody response at about 10 days after onset of symptoms.

Coexisting attractors in the context of cross-scale population dynamics: measles in London as a case study.

Patterns of measles infection in large urban populations have long been considered the paradigm of synchronized nonlinear dynamics. Indeed, recurrent epidemics appear approximately mass-action despite underlying heterogeneity. However, using a subset of rich, newly digitized mortality data (1897-1906), we challenge that proposition.

Molecularly Imprinted Polymers and Surface Imprinted Polymers Based Electrochemical Biosensor for Infectious Diseases.

Owing to their merits of simple, fast, sensitive, and low cost, electrochemical biosensors have been widely used for the diagnosis of infectious diseases. As a critical element, the receptor determines the selectivity, stability, and accuracy of the electrochemical biosensors. Molecularly imprinted polymers (MIPs) and surface imprinted polymers (SIPs) have great potential to be robust artificial receptors.

Bioequivalence of Ertugliflozin/Sitagliptin Fixed-Dose Combination Tablets and Coadministration of Respective Strengths of Individual Components.

A fixed-dose combination (FDC) tablet of ertugliflozin, a selective inhibitor of sodium-glucose cotransporter 2, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, was developed for the treatment of patients with type 2 diabetes mellitus. Four studies were conducted under fasted conditions to demonstrate bioequivalence of ertugliflozin/sitagliptin FDC tablets and individual components at respective strengths when coadministered in healthy subjects. All studies had open-label, randomized, 2-period, 2-sequence, single-dose crossover designs.

Bioequivalence of Ertugliflozin/Metformin Fixed-Dose Combination Tablets and Coadministration of Respective Strengths of Individual Components.

A fixed-dose combination (FDC) of ertugliflozin, a selective sodium-glucose cotransporter 2 inhibitor, and immediate-release metformin is approved for the treatment of type 2 diabetes mellitus in the United States and European Union. Four open-label, randomized, 2-period, single-dose, crossover studies were conducted under fasted conditions in healthy subjects to demonstrate bioequivalence of the ertugliflozin/metformin FDC tablets and coadministration of the individual components at respective strengths. In each study, 32 or 34 subjects received an ertugliflozin/metformin FDC tablet (2.

A PK/PD study comparing twice-daily to once-daily dosing regimens of ertugliflozin in healthy subjects .

Objective: Ertugliflozin is approved in the US and European Union as a stand-alone product for adults with type 2 diabetes mellitus as once daily (QD) dosing. The approved fixed-dose combination (FDC) of ertugliflozin and immediate-release metformin is dosed twice daily (BID). This study assessed steady-state pharmacokinetics (PK; area under the concentration-time curve over 24 hours (AUC)) and pharmacodynamics (PD; urinary glucose excretion over 24 hours (UGE)) for ertugliflozin 5 and 15 mg total daily doses administered BID or QD.

Effect of Food on the Pharmacokinetics of Ertugliflozin and Its Fixed-Dose Combinations Ertugliflozin/Sitagliptin and Ertugliflozin/Metformin.

Ertugliflozin, an inhibitor of sodium-glucose cotransporter 2, is approved in the United States and European Union for the treatment of type 2 diabetes in adults, both as monotherapy and as part of fixed-dose combination (FDC) therapies with either sitagliptin or immediate-release metformin. The effect of a standard, high-fat breakfast on the pharmacokinetics of the highest strengths of ertugliflozin monotherapy (15 mg), ertugliflozin/sitagliptin FDC (15-/100-mg), and ertugliflozin/metformin FDC (7.5-/1000-mg) tablets was evaluated.

Pharmacokinetics of Single-dose Ertugliflozin in Patients With Hepatic Impairment.

Purpose: Ertugliflozin, an oral, highly selective inhibitor of the sodium-glucose cotransporter 2, is approved in the United States and the European Union for the treatment of adults with type 2 diabetes mellitus. Hepatic impairment may affect, to varying degrees, the absorption, metabolism, and excretion of drugs and may be associated with a lower plasma protein binding compared with that in healthy individuals. This study was conducted to assess the effect of hepatic impairment on the pharmacokinetic (PK), safety, and tolerability profiles of ertugliflozin after administration of a single, 15-mg oral dose.

Assessment of the Drug Interaction Potential of Ertugliflozin With Sitagliptin, Metformin, Glimepiride, or Simvastatin in Healthy Subjects.

Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of adults with type 2 diabetes mellitus, is expected to be coadministered with sitagliptin, metformin, glimepiride, and/or simvastatin. Four separate open-label, randomized, single-dose, crossover studies were conducted in healthy adults to assess the potential pharmacokinetic interactions between ertugliflozin 15 mg and sitagliptin 100 mg (n = 12), metformin 1000 mg (n = 18), glimepiride 1 mg (n = 18), or simvastatin 40 mg (n = 18). Noncompartmental pharmacokinetic parameters derived from plasma concentration-time data were analyzed using mixed-effects models to assess interactions.

Novel Application of the Two-Period Microtracer Approach to Determine Absolute Oral Bioavailability and Fraction Absorbed of Ertugliflozin.

Ertugliflozin, a sodium glucose cotransporter-2 inhibitor, is approved in the United States for treatment of type 2 diabetes mellitus. A novel two-period study design with C microtracer dosing in each period was used to determine absolute oral bioavailability (F) and fraction absorbed (F ) of ertugliflozin. Eight healthy adult men received 100-μg i.

Recent advances in spectroelectrochemistry.

The integration of two quite different techniques, conventional electrochemistry and spectroscopy, into spectroelectrochemistry (SEC) provides a complete description of chemically driven electron transfer processes and redox events for different kinds of molecules and nanoparticles. SEC possesses interdisciplinary advantages and can further expand the scopes in the fields of analysis and other applications, emphasizing the hot issues of analytical chemistry, materials science, biophysics, chemical biology, and so on. Considering the past and future development of SEC, a review on the recent progress of SEC is presented and selected examples involving surface-enhanced Raman scattering (SERS), ultraviolet-visible (UV-Vis), near-infrared (NIR), Fourier transform infrared (FTIR), fluorescence, as well as other SEC are summarized to fully demonstrate these techniques.