Engineered ipilimumab variants that bind human and mouse CTLA-4.

Testing of candidate monoclonal antibody therapeutics in preclinical models is an essential step in drug development. Identification of antibody therapeutic candidates that bind their human targets and cross-react to mouse orthologs is often challenging, especially for targets with low sequence homology. In such cases, surrogate antibodies that bind mouse orthologs must be used.

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.

Nth Slice Eraser: An Automated Algorithm to Ease Editing Workflow of Organ Contours Generated by Artificial Intelligence.

The time-consuming process of manual contouring of healthy tissue and organs in radiation therapy has prompted the development of computational systems to aid and automate this process, such as artificial intelligence (AI) segmentation and interpolation algorithms. These algorithms are useful in saving time, however, they are not always accurate. Fixing such inaccuracies by editing contours is a manual, time-consuming process as no 'undo' feature currently exists in the most commonly used treatment planning system (TPS).

Does Playing Mahjong Benefit Older Individuals? A Scoping Review.

Playing mahjong is a popular intellectual and social leisure activity in Asian countries. It is culturally believed that this activity is beneficial to cognitive and psychological functioning in older adults. However, empirical evidence of the benefits of playing mahjong is scant and scattered across the Western and Asian literature.

Understanding the Changes in Brain Activation When Viewing Products with Differences in Attractiveness.

Product design and attractiveness are pivotal factors that determine people's positive reactions when viewing a product and may eventually affect their purchasing choices. Comprehending how people assess product design is crucial. Various studies have explored the link between product attractiveness and consumer behavior, but these were predominantly behavioral studies that offered limited insight into the neural processes underlying perceptions of product attractiveness.

Feasibility of Biology-guided Radiotherapy (BgRT) Targeting Fluorodeoxyglucose (FDG) avid liver metastases.

Introduction: Biology-guided radiotherapy (BgRT) is a novel radiation delivery approach utilizing fluorodeoxyglucose (FDG) activity on positron emission tomography (PET) imaging performed in real-time to track and direct RT. Our institution recently acquired the RefleXion X1 BgRT system and sought to assess the feasibility of targeting metastatic sites in various organs, including the liver. However, in order for BgRT to function appropriate, adequate contrast in FDG activity between the tumor and the background tissue, referred to as the normalized SUV (NSUV), is necessary for optimal functioning of BgRT.

Childhood trauma, resilience, psychopathology and social functioning in schizophrenia: A network analysis.

The affective pathway to psychosis implicates affective symptoms and neuroticism as mediating steps between childhood trauma and symptoms of schizophrenia. Prior research seldom examined the interplay between childhood trauma, resilience, personality, social functioning and symptoms in schizophrenia patients. This study recruited 290 schizophrenia patients, and constructed a regularized partial correlation network of childhood trauma, resilience, big-five personality traits, symptoms and social functioning.

CC chemokine receptor 2 is allosterically modulated by sodium ions and amiloride derivatives through a distinct sodium ion binding site.

CC chemokine receptor 2 and CCL2 are highly involved in cancer growth and metastasis, and immune escape. Raised sodium ion concentrations in solid tumours have also been correlated to metastasis and immune modulation. Sodium ions can modulate class A G protein-coupled receptors through the sodium ion binding site characterized by a highly conserved aspartic acid residue (D), also present in CCR2.

Methodological approaches to studying phase separation and HIV-1 replication: Current and future perspectives.

This article reviews tried-and-tested methodologies that have been employed in the first studies on phase separating properties of structural, RNA-binding and catalytic proteins of HIV-1. These are described here to stimulate interest for any who may want to initiate similar studies on virus-mediated liquid-liquid phase separation. Such studies serve to better understand the life cycle and pathogenesis of viruses and open the door to new therapeutics.

Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy.

Photoactivated chemotherapy agents form a new branch of physically targeted anticancer agents with potentially lower systemic side effects for patients. On the other hand, limited information exists on the intracellular interactions between the photoreleased metal cage and the photoreleased anticancer inhibitor. In this work, we report a new biological study of the known photoactivated compound in the glioblastoma cancer cell line, U87MG.

Extended observation of reduced methamphetamine use with combined naltrexone plus bupropion in the ADAPT-2 trial.

Background And Aims: A 12-week placebo-controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT-2) trial evaluated the effects of extended-release injectable naltrexone plus extended-release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo.

Design: This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT-2 network trial.

Incidence and Presenting Characteristics of Angiosarcoma in the US, 2001-2020.

Importance: Angiosarcoma is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed.

Objective: To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US.

Correction: Hamilton et al. Receptors for Insulin-Like Growth Factor-2 and Androgens as Therapeutic Targets in Triple-Negative Breast Cancer. 2017, , 2305.

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Clinical Outcomes of 111 Patients with Early Onset Idiopathic Scoliosis (EOIS) Receiving Brace Treatment: A Longitudinal Retrospective Cohort Study.

: Bracing is one of the first-line treatment for early-onset idiopathic scoliosis (EOIS) to control curves from progression. This study aimed to explore the determinants that govern bracing effectiveness in EOIS. : One hundred and eleven patients with EOIS (mean age of 8.

Association between fear of falling and falls following acute and chronic stroke: a systematic review with meta-analysis.

Objectives: To examine the association between falls and fear of falling in people with stroke and to evaluate the differences between patients with acute stroke and those with chronic stroke with regard to any such association.

Methods: Articles were searched in Medline, CINAHL, AMED, Embase, PsycINFO, Cochrane Library of Reviews and PEDro from inception until March 2023. Experimental, observational or explorative studies investigating the association between fear of falling and falls in people with stroke were included.

Construction of Nonnatural Cysteine-Cross-Linked Phage Libraries.

Phage display is a powerful technique for rapid construction and screening of peptide libraries with over 10 sequence diversity. The M13 bacteriophage genome can be edited to incorporate randomized amino acids, which will be displayed on its minor coat protein (pIII). To enable screening of nonnatural cyclic peptides on phage, the minor coat protein can be modified with a chemical cross-linker.

Association of Parental Status and Gender With Burden of Multidisciplinary Tumor Boards Among Oncology Physicians.

Importance: Tumor boards are integral to the care of patients with cancer. However, data investigating the burden of tumor boards on physicians are limited.

Objective: To investigate what physician-related and tumor board-related factors are associated with higher tumor board burden among oncology physicians.

Secondary Breast Angiosarcoma After a Primary Diagnosis of Breast Cancer: A Retrospective Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database.

Objectives: Angiosarcoma is a rare complication of breast-conserving therapy. This study evaluated the change in incidence between 1992 and 2016 of secondary breast angiosarcoma (SBA) in patients with a history of breast cancer and the impact of management strategies for the original breast carcinoma on angiosarcoma treatment.

Methods: Breast cancer and angiosarcoma cases were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database.

Associations of Multiparametric Breast MRI Features, Tumor-Infiltrating Lymphocytes, and Immune Gene Signature Scores Following a Single Dose of Trastuzumab in HER2-Positive Early-Stage Breast Cancer.

Dynamic biomarkers that permit the real-time monitoring of the tumor microenvironment response to therapy are an unmet need in breast cancer. Breast magnetic resonance imaging (MRI) has demonstrated value as a predictor of pathologic complete response and may reflect immune cell changes in the tumor microenvironment. The purpose of this pilot study was to investigate the value of breast MRI features as early markers of treatment-induced immune response.

Diazaborine-Mediated Bicyclization of Native Peptides with Inducible Reversibility.

Multicyclic peptides are appealing candidates for peptide-based drug discovery. While various methods are developed for peptide cyclization, few allow multicyclization of native peptides. Herein we report a novel cross-linker DCA-RMR1, which elicits facile bicyclization of native peptides via N-terminus Cys-Cys cross-linking.