A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T proliferation and anti-tumor immunity in mice.

Current antibody-based immunotherapy depends on tumor antigen shedding for proper T cell priming. Here we select a novel human CD40 agonistic drug candidate and generate a bispecific antibody, herein named BiA9*2_HF, that allows for rapid antibody-peptide conjugate formation. The format is designed to facilitate peptide antigen delivery to CD40 expressing cells combined with simultaneous CD40 agonistic activity.

Management of Adult Patients with Newly Diagnosed or Relapsed Primary Immune Thrombocytopenia in Eastern Austria.

Background:  Treatment sequence in primary immune thrombocytopenia (ITP) is based on national and international recommendations, treatment availability, and physician expertise.

Aim:  This article aimed to provide real-world data on treatment sequence and responses to first- and second-line treatments in newly diagnosed and relapsed adult ITP patients.

Methods:  We analyzed a cohort of 46 adult ITP patients from the Vienna ITP Biobank, who started first-line therapy within 1 week before their first study visit between February 2016 and March 2023.

Optimizing Anti-Myelin-Associated Glycoprotein and IgM-Gammopathy Testing for Neuropathy Treatment Evaluation.

Background And Objectives: Patients with typical anti-myelin-associated glycoprotein (anti-MAG) neuropathy have IgM-gammopathy, mimic distal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and are treatment resistant. Anti-MAG patients go unrecognized when IgM-gammopathy is undetected or with atypical phenotypes. We investigated an optimal anti-MAG titration cutoff for excluding CIDP and the impact of IgM-gammopathy detection on neuropathy treatment evaluation without anti-MAG antibodies.

Harnessing plant biosynthesis for the development of next-generation therapeutics.

Genomics-based predictions indicate that plants harbor the ability to make a vast array of as yet undiscovered chemistry. Recent advances open up the potential to harness this capability at unprecedented scale for the discovery and development of new therapeutics.

Disease Characteristics and Outcomes of 493 Young Myeloma Patients Treated With Modern Therapies: A Canadian Myeloma Research Group Database Study.

Background: Young patients ≤ 50 years old with multiple myeloma (MM) account for about 10% of cases and are underrepresented in the literature.

Methods: We explored disease characteristics, treatments, and outcomes following modern therapies of young MM patients using the Canadian Myeloma Research Group (CMRG) database. We included 493 patients ≤ 50 years old diagnosed with MM or plasma cell leukemia without concurrent amyloidosis or POEMS syndrome from January 1, 2010, to July 1, 2022.

Rapid mechanical phenotyping of breast cancer cells based on stochastic intracellular fluctuations.

Predicting the phenotypic impact of genetic variants and treatments is crucial in cancer genetics and precision oncology. Here, we have developed a noise decorrelation method that enables quantitative phase imaging (QPI) with the capability for label-free noninvasive mapping of intracellular dry mass fluctuations within the millisecond-to-second timescale regime, previously inaccessible due to temporal phase noise. Applied to breast cancer cells, this method revealed regions driven by thermal forces and regions of intense activity fueled by ATP hydrolysis.

The Difference in Achilles Tendon Loading within Immobilizing Boots Based on Ankle Angle, Boot Type, and Walking Speed.

Background: Achilles tendon rupture is an increasingly common injury treated with progressive rehabilitation in an immobilizing boot. However, it is poorly understood how ankle angle, boot type, and walking speed affect Achilles tendon loading.

Hypothesis: These different parameters would affect Achilles tendon loading in terms of (from greatest to least) ankle angle constraint, immobilization style, boot construction, and walking speed.

Career Sustainability: Perspectives From Early, Mid and Late Academic Career Radiologists.

Three radiologists representing unique career stages and paths have reflected on tips for achieving personal and career satisfaction that are relevant to their respective stage. Using published resources to lend support to these tips, this review article concludes by offering tangible tools that academic radiology departments can utilize to help customize faculty development to their staff at the various career stages.

Effects of Losartan and Fisetin on Microfracture-Mediated Cartilage Repair of Ankle Cartilage in a Rabbit Model.

Background: Microfracture is one surgical treatment strategy for osteochondral lesions of the talus (OLTs) but results in fibrocartilage repair tissue, which has inferior mechanical properties to native hyaline cartilage. Biological regulation of microfracture has been suggested to improve the quality of cartilage repair in patients.

Purpose: To determine if administration of losartan, fisetin, or losartan and fisetin combined can enhance microfracture-mediated cartilage repair of OLTs in a rabbit model.

Leveraging Continuous Glucose Monitoring Data as an Additional Source for Glucagon Prescription Behavior.

Objective: Hypoglycemia can be life-threatening for patients with diabetes. We aimed to 1) evaluate percentage of glucagon prescription in patients with hypoglycemia on continuous glucose monitoring (CGM) reports, and 2) determine incident glucagon prescription after an educational letter delivered to the providers.

Research Design And Methods: The study had 2 components - retrospective chart review and a quality improvement (QI) component.

Depolymerizing F-actin accelerates the exit from pluripotency to enhance stem cell-derived islet differentiation.

Improving generation of insulin-producing islets from human pluripotent stem cells (hPSCs) would enhance their clinical relevance for treating diabetes. Here, we demonstrate that cytoskeletal state at the onset of differentiation is critical for definitive endoderm formation. Depolymerizing F-actin with latrunculin A (latA) during the first 24 hours of differentiation facilitates rapid exit from pluripotency and alters Activin/Nodal, BMP, JNK-JUN, and WNT pathway signaling dynamics during definitive endoderm formation.

ACSS2 regulates ferroptosis in an E2F1-dependent manner in breast cancer brain metastatic cells.

Brain metastasis diagnosis in breast cancer patients is considered an end-stage event. The median survival after diagnosis is measured in months, thus there is an urgent need to develop novel treatment strategies. Breast cancers that metastasize to the brain must adapt to the unique brain environment and are highly dependent on acetate metabolism for growth and survival.

2024 AAHA Community Care Guidelines for Small Animal Practice.

Community care is a creative way of thinking about health care that mobilizes resources within a community and consists of four core principles: recognition of the urgency of access-to-care for the veterinary profession, collaboration within community networks, family-centered health care, and redefining the gold standard of care. The AAHA Community Care Guidelines for Small Animal Practice offer strategies to help busy veterinary practitioners increase access to care within their practice and community by optimizing collaborative networks. While these guidelines do not claim to provide exhaustive solutions to access-to-care issues, they propose a starting point from which private practices can explore and implement workable solutions for their community and their practice.

The Pharmacogenomics Global Research Network Implementation Working Group: global collaboration to advance pharmacogenetic implementation.

Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual's genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice.

Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise.

In the Greenlandic Inuit population, 4% are homozygous carriers of a genetic nonsense TBC1D4 p.Arg684Ter variant leading to loss of the muscle-specific isoform of TBC1D4 and an approximately tenfold increased risk of type 2 diabetes. Here we show the metabolic consequences of this variant in four female and four male homozygous carriers and matched controls.

Finesse in Primary Open Rhinoplasty.

Rhinoplasty remains one of the most technically demanding operations in plastic surgery, and it continues to be one of the top 5 aesthetic surgical procedures performed. The focus of this article is open rhinoplasty, the central focus of the practice of the senior author (R.J.

Validation of Noninvasive Derivation of the Central Aortic Pressure Waveform from Fingertip Photoplethysmography Using a Novel Selective Transfer Function Method.

Introduction: Central aortic pressure waveform analyses can provide clinically relevant information beyond conventional brachial blood pressure (BP) assessment. This waveform can be reproduced noninvasively through application of a generalized transfer function (GTF) on a peripheral waveform, as conventionally performed by applanation tonometry. Photoplethysmography (PPG) is an alternate approach; however, differences in measurement site and modality demand the use of a transfer function (TF) specific for those differences.