Enhancing NK cell-mediated tumor killing of B7-H6 cells with bispecific antibodies targeting allosteric sites of NKp30.

In this work, we report the discovery and engineering of allosteric variable domains of the heavy chain (VHHs) derived from camelid immunization targeting NKp30, an activating receptor on natural killer (NK) cells. The aim was to enhance NK cell-mediated killing capacities by identifying VHHs that do not compete with the natural ligand of NKp30:B7-H6, thereby maximizing the recognition of B7-H6 tumor cells. By relying on the DuoBody technology, bispecific therapeutic antibodies were engineered, creating a panel of bispecific antibodies against NKp30xEGFR (cetuximab moiety) or NKp30xHER2 (trastuzumab moiety), called natural killer cell engagers (NKCEs).

Microemulsion-Inspired Polysaccharide Nanoparticles for an Advanced Targeted Thrombolytic Treatment.

Among cardiovascular diseases, thrombotic diseases such as ischemic heart disease and acute ischemic strokes are the most lethal, responsible by themselves for a quarter of worldwide deaths. While surgical treatments exist, they may not be used in all situations, and systemic thrombolytic drug injection, such as recombinant tissue plasminogen activators (rtPA), often remains necessary, despite serious limitations including short therapeutic window, severe side effects, and failure to address the complex nature of thrombi. This prompted intense research into alternative thrombolytics or delivery methods, including nanomedicine.

Predictive analysis of economic and clinical outcomes in total knee arthroplasty: Identifying high-risk patients for increased costs and length of stay.

Purpose: The purpose of this study was to predict high-risk patients who experience significant increases in hospital charges and length of stay (LOS) following specific postoperative complications.

Methods: This study analyzed over two million patients from the Nationwide Inpatient Sample database undergoing elective total knee arthroplasty (TKA) for primary osteoarthritis. Baseline demographics, clinical characteristics and incidence of postoperative complications were examined.

Intraoperative Periprosthetic Fractures in Total Hip Arthroplasty: A 1.6-Million-Patient Analysis of Complications, Costs, and the Challenges in AI-Based Prediction.

Periprosthetic fractures following total hip arthroplasty are serious complications occurring in up to 2.4% of primary cases, contributing to significant morbidity, extended hospital stays, and elevated healthcare costs. Predicting these fractures remains a challenge despite advances in surgical techniques and prosthetic materials.

Allosteric antibodies: a novel paradigm in drug discovery.

Allostery represents a fundamental mechanism in protein regulation, enabling modulation of protein function from sites distal to the active site. While traditionally explored in the context of small molecules, allosteric modulation is gaining traction as a main mode of action in the realm of antibodies, which offer enhanced specificity and reduced toxicity. This review delves into the rapidly growing field of allosteric antibodies, highlighting recent therapeutic advancements and novel druggability avenues.

A platform for the early selection of non-competitive antibody-fragments from yeast surface display libraries.

In this work, we report the development of a platform for the early selection of non-competitive antibody-fragments against cell surface receptors that do not compete for binding of their natural ligand. For the isolation of such subtype of blocking antibody-fragments, we applied special fluorescence-activated cell sorting strategies for antibody fragments isolation from yeast surface display libraries. Given that most of the monoclonal antibodies approved on the market are blocking ligand-receptor interactions often leading to resistance and/or side effects, targeting allosteric sites represents a promising mechanism of action to open new avenues for treatment.

Two-Dimensional Mammography Imaging Techniques for Screening Women with Silicone Breast Implants: A Pilot Phantom Study.

This study aimed to evaluate the impact of three two-dimensional (2D) mammographic acquisition techniques on image quality and radiation dose in the presence of silicone breast implants (BIs). Then, we propose and validate a new International Atomic Energy Agency (IAEA) phantom to reproduce these techniques. Images were acquired on a single Hologic Selenia Dimensions unit.

Discovery of potent allosteric antibodies inhibiting EGFR.

In this work, we report the discovery of potent anti-epidermal growth factor receptor (EGFR) allosteric heavy-chain antibodies by combining camelid immunization and fluorescence-activated cell sorting (FACS). After immunization and yeast surface display library construction, allosteric clones were obtained by introducing the labeled EGF Fc fusion protein as an additional criterion for FACS. This sorting method enabled the identification of 11 heavy-chain antibodies that did not compete with the orthosteric ligand EGF for the binding to EGFR.

The schizophrenia risk gene C4 induces pathological synaptic loss by impairing AMPAR trafficking.

Neuroimmune interactions play a significant role in regulating synaptic plasticity in both the healthy and diseased brain. The complement pathway, an extracellular proteolytic cascade, exemplifies these interactions. Its activation triggers microglia-dependent synaptic elimination via the complement receptor 3 (CR3).

A Proposal for a Process from as Low as Reasonably Achievable to an Ultra-Low-Level Goal in Chest Computed Tomography.

To define and evaluate a radiation dose optimization process for chest computed tomography (CT) imaging. Data from unenhanced and enhanced chest CT acquisitions performed between June 2018 and January 2020 in adult patients were included in the study. Images were acquired on a Siemens SOMATOM Definition Edge CT.

ESR Essentials: response assessment criteria in oncologic imaging-practice recommendations by the European Society of Oncologic Imaging.

Assessing the response to oncological treatments is paramount for determining the prognosis and defining the best treatment for each patient. Several biomarkers, including imaging, can be used, but standardization is fundamental for consistency and reliability. Tumor response evaluation criteria have been defined by international groups for application in pharmaceutical clinical trials evaluating new drugs or therapeutic strategies.

Etiology, Outcomes, and Complications of Total Hip Arthroplasty in Younger Patients: A Nationwide Big Data Analysis.

This study investigates the rising trend of total hip arthroplasty (THA) in patients under 55 years old, commonly referred to as "younger" THA patients. Traditionally a procedure for older adults with osteoarthritis, THA is increasingly performed on younger patients. Using data from the Nationwide Inpatient Sample (NIS) from 2016 to 2019, we analyze the factors driving this trend, including the causes of hip issues, patient characteristics, and coexisting medical conditions.

Evaluating the factor structure and measurement invariance of the 20-item short version of the UPPS-P Impulsive Behavior Scale across multiple countries, languages, and gender identities.

The UPPS-P Impulsive Behavior Model and the various psychometric instruments developed and validated based on this model are well established in clinical and research settings. However, evidence regarding the psychometric validity, reliability, and equivalence across multiple countries of residence, languages, or gender identities, including gender-diverse individuals, is lacking to date. Using data from the International Sex Survey ( = 82,243), confirmatory factor analyses and measurement invariance analyses were performed on the preestablished five-factor structure of the 20-item short version of the UPPS-P Impulsive Behavior Scale to examine whether (a) psychometric validity and reliability and (b) psychometric equivalence hold across 34 country-of-residence-related, 22 language-related, and three gender-identity-related groups.

Enhancing fall risk assessment: instrumenting vision with deep learning during walks.

Background: Falls are common in a range of clinical cohorts, where routine risk assessment often comprises subjective visual observation only. Typically, observational assessment involves evaluation of an individual's gait during scripted walking protocols within a lab to identify deficits that potentially increase fall risk, but subtle deficits may not be (readily) observable. Therefore, objective approaches (e.

Comparative evaluation of postoperative outcomes and expenditure between robotic and conventional single-level lumbar fusion surgery: a comprehensive analysis of nationwide inpatient sample data.

Introduction: In this study, we investigate the evolution of lumbar fusion surgery with robotic assistance, specifically focusing on the impact of robotic technology on pedicle screw placement and fixation. Utilizing data from the Nationwide Inpatient Sample (NIS) covering 2016 to 2019, we conduct a comprehensive analysis of postoperative outcomes and costs for single-level lumbar fusion surgery. Traditionally, freehand techniques for pedicle screw placement posed risks, leading to the development of robotic-assisted techniques with advantages such as reduced misplacement, increased precision, smaller incisions, and decreased surgeon fatigue.