Medium-Sized Rotator Cuff Tears Repaired With Transosseous-Equivalent Technique Plus Bone Marrow Stimulation Yielded Similar Short-Term Outcomes Regardless of Whether Complete or Incomplete Footprint Coverage Was Achieved.

Purpose: To compare clinical outcomes and retear rates of medium-sized rotator cuff tears repaired with incomplete footprint coverage using the transosseous-equivalent technique versus those with complete footprint coverage plus bone marrow stimulation.

Methods: The retrospective study, conducted from March 2019 to December 2021, included consecutive patients with medium-sized (1-3 cm) posterosuperior rotator cuff tears repaired using the transosseous-equivalent technique and bone marrow stimulation, with a minimum follow-up of 2 years. Patients were divided into 2 groups based on the degree of footprint coverage achieved: group C (complete coverage) and group I (incomplete coverage).

Advancing understanding of human variability through toxicokinetic modeling, in vitro-in vivo extrapolation, and new approach methodologies.

The merging of physiology and toxicokinetics, or pharmacokinetics, with computational modeling to characterize dosimetry has led to major advances for both the chemical and pharmaceutical research arenas. Driven by the mutual need to estimate internal exposures where in vivo data generation was simply not possible, the application of toxicokinetic modeling has grown exponentially in the past 30 years. In toxicology the need has been the derivation of quantitative estimates of toxicokinetic and toxicodynamic variability to evaluate the suitability of the tenfold uncertainty factor employed in risk assessment decision-making.

Integrated Deep Learning Model for the Detection, Segmentation, and Morphologic Analysis of Intracranial Aneurysms Using CT Angiography.

Purpose To develop a deep learning model for the morphologic measurement of unruptured intracranial aneurysms (UIAs) based on CT angiography (CTA) data and validate its performance using a multicenter dataset. Materials and Methods In this retrospective study, patients with CTA examinations, including those with and without UIAs, in a tertiary referral hospital from February 2018 to February 2021 were included as the training dataset. Patients with UIAs who underwent CTA at multiple centers between April 2021 and December 2022 were included as the multicenter external testing set.

An improved approach to generate IL-15/TGFβR2 iPSC-derived natural killer cells using TALEN.

We present a TALEN-based workflow to generate and maintain dual-edited (IL-15/TGFβR2) iPSCs that produce enhanced iPSC-derived natural killer (iNK) cells for cancer immunotherapy. It involves using a cell lineage promoter for knocking in (KI) gene(s) to minimize the potential effects of expression of any exogenous genes on iPSCs. As a proof-of-principle, we KI IL-15 under the endogenous B2M promoter and show that it results in high expression of the sIL-15 in iNK cells but minimal expression in iPSCs.

Three-Dimensional Quantitative Analysis of Internal Limiting Membrane Peeling Related Structural Changes in Retinal Detachment Repair.

Purpose: To assess macular microstructural changes associated with internal limiting membrane peeling (ILMP) using 3-dimensional optical coherence tomography (3D-OCT) in primary macula-off rhegmatogenous retinal detachment (RRD) repairs with vitrectomy and silicone oil (SO) tamponade.

Design: Retrospective, consecutive, interventional case series.

Methods: Setting: Institutional practice.

Optimization of Phenolic-Enriched Extracts from Olive Leaves via Ball Milling-Assisted Extraction Using Response Surface Methodology.

This study aims to extract phenolic-enriched compounds, specifically oleuropein, luteoloside, and hydroxytyrosol, from olive leaves using ball milling-assisted extraction (BMAE). Response surface methodology (RSM) and the Box-Behnken design (BBD) were used to evaluate the effects of the temperature, solvent-to-solid ratio, and milling speed on extraction recovery. The contents of the extract were determined by ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) and converted to recoveries to evaluate the extraction efficiency.

Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.

While significant advances have been made in understanding renal pathophysiology, less is known about the role of glycosphingolipid (GSL) metabolism in driving organ dysfunction. Here, we used a small molecule inhibitor of glucosylceramide synthase to modulate GSL levels in three mouse models of distinct renal pathologies: Alport syndrome (Col4a3 KO), polycystic kidney disease (Nek8), and steroid-resistant nephrotic syndrome (Nphs2 cKO). At the tissue level, we identified a core immune-enriched transcriptional signature that was shared across models and enriched in human polycystic kidney disease.

Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia.

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges.

Phage display-derived alpaca nanobodies as potential therapeutics for snake envenomation.

, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated venom.

Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia.

Background: This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia.

Methods: Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention.

Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

Background: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects.

Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma.

Background: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.

Methods: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent.

Effectiveness of Huddles in Improving the Patient Safety Attitudes Among Clinical Team Members.

Background And Objectives: Huddles among members of interdisciplinary medical teams involve short stand-up sessions and allow team members to focus on existing or emerging patient safety issues, thereby facilitating team communication. Hospital managers are able to recognize the current situation of the organization through patient safety attitudes, strengthen team members' awareness of patient safety, and improve the quality of health care. The purpose of this study was to determine the effects of huddles on improving team members' attitudes toward patient safety.

WISE: whole-scenario embryo identification using self-supervised learning encoder in IVF.

Purpose: To study the effectiveness of whole-scenario embryo identification using a self-supervised learning encoder (WISE) in in vitro fertilization (IVF) on time-lapse, cross-device, and cryo-thawed scenarios.

Methods: WISE was based on the vision transformer (ViT) architecture and masked autoencoders (MAE), a self-supervised learning (SSL) method. To train WISE, we prepared three datasets including the SSL pre-training dataset, the time-lapse identification dataset, and the cross-device identification dataset.

Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease Based on an Ancestrally Diverse Genome-Wide Association Study and Population-Specific Optimization.

Background: Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (CHD; PRS) for 5 genetic ancestry groups.

Methods: We derived ancestry-specific and multi-ancestry PRS based on pruning and thresholding (PRS) and ancestry-based continuous shrinkage priors (PRS) applied to summary statistics from the largest multi-ancestry genome-wide association study meta-analysis for CHD to date, including 1.