In Vitro-In Vivo Correlation Of Amorphous Solid Dispersion Enabled Itraconazole Tablets.

Purpose: There are scarce reports on in vitro-in vivo correlation (IVIVC) model development of immediate-release (IR) formulations, and few investigations of the impacts of formulation and process of spray-dried solid dispersions (SDD)-based tablets on human pharmacokinetics (PK), despite commercial product successes. The goal of this study was to investigate the formulation and process factors that impact bioavailability enhancement of IR itraconazole SDD tablets; and to develop an FDA level A IVIVC that would predict in vivo PK performance from in vitro dissolution testing.

Methods: A direct, differential-equation-based IVIVC model approach was employed, using an oral solution for post-dissolution disposition and Fast-, Medium-, and Slow-release tablets.

A patient first perspective of sleep disturbance across therapeutic areas: a systematic literature review of qualitative studies.

Background: Sleep, a vital pillar of health, impacts daily functioning and overall quality of life. Despite extensive research on sleep disturbances within specific therapeutic areas (TAs), there's limited understanding of how these disturbances affect patients across multiple TAs. This systematic literature review adopts a patient-centered approach to explore the meaningful aspects of health and concepts of interest relating to sleep and sleep disturbances across a variety of TAs, utilizing qualitative research to bridge the gap between patient experiences and clinical measures.

PD-1 transcriptomic landscape across cancers and implications for immune checkpoint blockade outcome.

Programmed cell death protein 1 (PD-1) is a critical immune checkpoint receptor and a target for cancer immune checkpoint inhibitors (ICI). We investigated PD-1 transcript expression across cancer types and its correlations to clinical outcomes. Using a reference population, PD-1 expression was calculated as percentiles in 489 of 514 patients (31 cancer types) with advanced/metastatic disease.

Lactobacillus acidophilus (strain Scav) Postbiotic Metabolites Reduce Infection and Modulate Inflammation in an in vivo model of Pseudomonas aeruginosa wound infection.

Aims: This study assessed the antibacterial, anti-biofilm, and immunomodulatory activity of Lactobacillus acidophilus (strain Scav) postbiotic (LaP) in a mouse model of Pseudomonas aeruginosa wound infection and evaluated the bioactive components of the LaP.

Methods And Results: LaP was tested for P. aeruginosa clearance and immunomodulatory activity during wound infection.

Automated versus Manual Femoral Component Rotation Planning in Robotic-Assisted and Conventional Total Knee Arthroplasty: A Retrospective Comparison.

Background: The purpose of this study was to determine if using automated femoral rotation planning in robotic-assisted total knee arthroplasty (RA-TKA) was associated with differences in functional outcomes compared to patients who underwent manually set femoral rotation in RA-TKA or conventional TKA (C-TKA).

Methods: This was a retrospective, multi-center study of patients who underwent TKA utilizing conventional methods with femoral component rotation set to three degrees externally (C-TKA) [n = 108 knees], RA-TKA with automated femoral rotation planning intrinsic to the system (A-RA-TKA) [n = 111], and RA-TKA with femoral rotation manually set by the surgeon (M-RA-TKA) [n = 152], at least one year before follow-up. Outcome measures included the range of motion (ROM), Knee Injury and Osteoarthritis Joint Replacement (KOOS-JR), and Forgotten Joint Score (FJS).

Relations of temporoparietal connectivity with neighborhood social fragmentation in youth at clinical high-risk for psychosis.

Temporoparietal brain areas comprise a candidate set of regions for interrogating the brain functional correlates of socioenvironmental factors in people at clinical high-risk for psychosis (CHR-P). Temporal lobe abnormalities have been shown to be common among people with schizophrenia spectrum conditions. Further, temporoparietal brain regions are implicated in tasks relevant to psychosocial outcomes, including coherent autobiographical memory recall and multimodal integration.

Real-World Treatment Patterns and Outcomes in Patients With Bacillus Calmette-Guérin-Unresponsive High-Risk Non-Muscle-Invasive Bladder Cancer: A Multicountry Medical Chart Review.

Introduction: Treatment patterns for patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) who are ineligible for or decline radical cystectomy (RC) are inconsistently reported. We retrospectively described demographic, clinical, and treatment characteristics for these patients and assessed their clinical outcomes.

Patients And Methods: Medical charts of patients with BCG-unresponsive high-risk NMIBC (carcinoma in situ [cohort A] or T1/high-grade Ta [cohort B]) who were ineligible for or declined RC documented between January 1, 2011, and December 31, 2018, at 15 academic centers were reviewed.

Cryo-ET reveals the in situ architecture of the polar tube invasion apparatus from microsporidian parasites.

Microsporidia are divergent fungal pathogens that employ a unique harpoon-like apparatus called the polar tube (PT) to invade host cells. The long PT is fired out of the microsporidian spore over the course of just a few hundred milliseconds. Once fired, the PT is thought to pierce the plasma membrane of a target cell and act as a conduit for the transfer of the parasite into the host cell, which initiates infection.

The decade-long growth of government-authored news media in China under Xi Jinping.

Autocratic governments around the world use clandestine propaganda campaigns to influence the media. We document a decade-long trend in China toward the planting of government-authored articles in party and commercial newspapers. To examine this phenomenon, we develop an approach to identifying scripted propaganda-the coerced reprinting of lightly adapted government-authored articles in newspapers-that leverages the footprints left by the government when making media interventions.

"Kids and Girls": Parents convey a male default in child-directed speech.

Adults tend to view men (more so than women) as default , with numerous real-world consequences for gender equity. In the United States, the tendency to center men in concepts of develops across middle childhood, yet the specific mechanisms that contribute to it remain unknown. Here, we investigate one subtle but potentially powerful social mechanism: the category labels that parents use to describe boys/men and girls/women in conversations with their children.

Noninvasive identification of metabolic dysfunction-associated steatohepatitis (INFORM MASH): a retrospective cohort and disease modeling study.

Background: Using common clinical parameters, we aimed to noninvasively identify and predict metabolic dysfunction - associated steatohepatitis (MASH)/MASH with clinically significant fibrosis.

Research Design And Methods: Patients aged ≥ 18 with electronic health record (EHR) documented liver function tests and liver biopsies between 2016-2021 were retrospectively identified from the Geisinger Health System Research Liver Registry. MASH cases were confirmed using the nonalcoholic fatty liver disease (NAFLD) activity score.

MRI-based Deep Learning Algorithm for Assisting Clinically Significant Prostate Cancer Detection: A Bicenter Prospective Study.

Background Although artificial intelligence is actively being developed for prostate MRI, few studies have prospectively validated these tools. Purpose To compare the diagnostic performance of a commercial deep learning algorithm (DLA) and radiologists' clinical reports for cancer detection in participants from two hospitals using histopathologic findings from biopsy specimens as the reference standard. Materials and Methods This prospective bicenter study enrolled participants suspected of having prostate cancer (PCa) who were scheduled for biopsy based on clinical information, including prostate MRI, from December 2022 to July 2023.

Impact of Condoliase on Health-Related Quality of Life in Participants with Radicular Leg Pain Associated with Lumbar Disc Herniation: Results From a United States Phase 3 Clinical Trial.

Study Design: An exploratory analysis of a randomized, double-blind, sham-controlled, phase 3 study.

Objective: To evaluate the impact of SI-6603 (condoliase) on health-related quality of life (HRQoL)-related outcomes in patients with lumbar disc herniation (LDH)-associated radicular leg pain from the Discovery 6603 study (NCT03607838).

Summary Of Background Data: Condoliase is a novel chemonucleolytic agent that selectively degrades chondroitin sulfate in the nucleus pulposus.

LNS8801: An enantiomerically pure agonist of the G protein-coupled estrogen receptor suitable for clinical development.

Estrogen effects in tissue are mediated in part through activation of the surface estrogen receptor GPER, a broadly expressed G protein-coupled receptor that impacts a wide range of normal and pathologic processes, including metabolism, vascular health, inflammation, and cancer. A commonly used synthetic and specific GPER agonist, named G-1, antagonizes tumors by promoting cellular differentiation and enhancing tumor immunogenicity. G-1 is a racemic compound, and since its discovery, the question of whether both enantiomers display agonist activity or the agonist activity resides primarily in a single enantiomer has never been fully resolved.

Macitentan for Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Pulmonary Vascular Disease: Results of the SERENADE Randomized Clinical Trial and Open-Label Extension Study.

Background: Despite favorable hemodynamic and neurohormonal effects, endothelin receptor antagonists have not improved outcomes in patients with heart failure (HF), possibly because they cause fluid retention.

Methods: In this randomized, double-blind, multicenter trial (SERENADE [Macitentan in Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease]), we evaluated the effects of an endothelin receptor antagonist, macitentan, in patients with HF, left ventricular ejection fraction ≥40%, and pulmonary vascular disease. After a 4-week placebo run-in (to ensure clinical stability), followed by a 5-week single-blind macitentan run-in, patients who did not exhibit fluid retention were randomized to macitentan or placebo.

Comparative Analysis of Artificial Intelligence Platforms in Generating Post-Operative Instructions for Rhinologic Surgery.

Recently, artificial intelligence (AI) platforms such as ChatGPT and Google Gemini have progressed at a rapid pace. To allow for optimal medical outcomes and patient safety, it is crucial that patients have clearly written post-operative instructions. Patients are increasingly turning to AI platforms for medical information.

What role for real-world evidence in market access of biosimilars?

Experience with the use of biosimilars in real-life practice provides an excellent opportunity to collect real-world evidence aimed at addressing residual uncertainties about biosimilars. Hence, this aims to explore the role of real-world evidence on biosimilars by showcasing how real-world evidence studies have contributed to addressing key questions affecting biosimilar market access. We find that the comparable efficacy and safety of a biosimilar and the reference product is corroborated by real-world evidence.

Impact of Concomitant Tonsillectomy on the Management and Outcomes of Pediatric Adenoidectomy.

Adenoidectomy is a common otolaryngologic procedure that may be performed with concomitant tonsillectomy (T&A). This study investigates differences between pediatric inpatients undergoing adenoidectomy alone and T&A. The 2016 Kid's Inpatient Database was used to identify pediatric patients undergoing adenoidectomy (ICD-10: 0CTQXZZ) with and without tonsillectomy (ICD-10: 0CTP, 0CBP).

Self-reported history of head injury is associated with cognitive impulsivity on a delay discounting task.

Background: Head injuries are a major health care concern that can produce many long lasting cognitive, mental, and physical problems. An emerging literature indicates increased impulsivity in patients with a history of traumatic brain injury (TBI). In a recent study, Veterans with clinically-assessed history of mild TBI had increased cognitive, but not motor, impulsivity.

Atrial Fibrillation (AF) and Heart Failure With Preserved Ejection Fraction (HFpEF): Advances and Challenges.

This state-of-the-art review is based on the Philippe Coumel Lecture in 2024 (Figure 1). It highlights the confluence of two major cardiovascular epidemics, atrial fibrillation and heart failure, with preserved ejection fraction. In these conditions, advances in electrophysiology and heart failure physiology are intertwined and are integrated in this review.

Trajectories of pharmacological therapies for treatment-resistant depression: a longitudinal study.

Background: Treatment-resistant depression (TRD) in major depressive disorder (MDD) is defined as the failure of two or more antidepressants. Few studies have characterized the natural history and treatment patterns of these patients. This study aims to identify the natural history of disease and treatment trajectories for patients with TRD.