Procollagen-lysine 2-oxoglutarate 5-dioxygenases are responsible for 5R-hydroxylysine modification of therapeutic T-cell bispecific monoclonal antibodies produced by Chinese hamster ovary cells.

We present a detailed mass spectrometric analysis of three 2 + 1 T-cell bispecific monoclonal antibodies (TCB mAbs), where an unexpected +15.9950 Da mass shift in tryptic peptides was observed. This modification was attributed to the occurrence of 5R-hydroxylysine (Hyl) using a hybrid LC-MS/MS molecular characterization and CRISPR/Cas9 gene deletion approach.

Effects of inhaled beclometasone dipropionate/formoterol fumarate/glycopyrronium vs. beclometasone dipropionate/formoterol fumarate and placebo on lung hyperinflation and exercise endurance in chronic obstructive pulmonary disease: a randomised controlled trial.

Background: The single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) is available for maintenance therapy of chronic obstructive pulmonary disease (COPD). Cardinal features of COPD are lung hyperinflation and reduced exercise capacity. TRIFORCE aimed to evaluate the effect of BDP/FF/G on lung hyperinflation and exercise capacity in patients with COPD.

COPD Exacerbations Before and During COVID-19 in France, Germany, Italy, the UK and the US.

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) were reported less frequently during the COVID-19 pandemic. We report real-world data on COPD exacerbation rates before and during this pandemic.

Methods: Exacerbation patterns were analysed using electronic medical records or claims data of patients with COPD before (2017-2019) and during the COVID-19 pandemic (2020 through early 2022) in France, Germany, Italy, the United Kingdom and the United States.

Preservation of von Willebrand Factor Activity With the ModulHeart Device.

von Willebrand Factor (VWF) destruction is common with current heart pumps. This study evaluates VWF activity with ModulHeart, a novel device using 3 micropumps in parallel. In model 1, ModulHeart was compared with Impella devices in vitro.

Allogeneic bone marrow transplantation for patients with treatment-refractory Crohn's Disease.

Background & Aims: Durable remissions of Crohn's Disease (CD) have followed myeloablative conditioning therapy and allogeneic marrow transplantation. For patients with treatment-refractory disease, we used reduced-intensity conditioning to minimize toxicity, marrow from donors with low Polygenic Risk Scores for CD as cell sources, and protracted immune suppression to lower the risk of graft-versus-host disease (GVHD). Our aim was to achieve durable CD remissions while minimizing transplant-related complications.

Successful Autologous Hematopoietic Stem Cell Transplant in Glycine Receptor Antibody-Positive Stiff Person Syndrome: A Case Report.

Background And Objectives: To describe a case of glycine receptor (GlyR) antibody-positive stiff person syndrome (SPS) treated with autologous hematopoietic stem cell transplant (aHSCT).

Methods: This was a multicenter collaboration for the treatment of a single patient who underwent aHSCT as part of a clinical trial (NCT00716066). To objectively assess the response to transplantation, several clinical outcome measures were evaluated pretransplant and up to 18 months post-transplant, including modified Rankin Score (mRS), stiffness index, Hauser Ambulation Score (HAS), hypersensitivity index, timed 25-foot walk, and Montreal Cognitive Assessment.

The Patent and Literature Antibody Database (PLAbDab): an evolving reference set of functionally diverse, literature-annotated antibody sequences and structures.

Antibodies are key proteins of the adaptive immune system, and there exists a large body of academic literature and patents dedicated to their study and concomitant conversion into therapeutics, diagnostics, or reagents. These documents often contain extensive functional characterisations of the sets of antibodies they describe. However, leveraging these heterogeneous reports, for example to offer insights into the properties of query antibodies of interest, is currently challenging as there is no central repository through which this wide corpus can be mined by sequence or structure.

PEP-Patch: Electrostatics in Protein-Protein Recognition, Specificity, and Antibody Developability.

The electrostatic properties of proteins arise from the number and distribution of polar and charged residues. Electrostatic interactions in proteins play a critical role in numerous processes such as molecular recognition, protein solubility, viscosity, and antibody developability. Thus, characterizing and quantifying electrostatic properties of a protein are prerequisites for understanding these processes.

Improved computational epitope profiling using structural models identifies a broader diversity of antibodies that bind to the same epitope.

The function of an antibody is intrinsically linked to the epitope it engages. Clonal clustering methods, based on sequence identity, are commonly used to group antibodies that will bind to the same epitope. However, such methods neglect the fact that antibodies with highly diverse sequences can exhibit similar binding site geometries and engage common epitopes.

Organ blood flow assessment with the ModulHeart cardiorenal support device.

Background: ModulHeart (Puzzle Medical Devices Inc) is a novel percutaneous flow entrainment pump anchored in the descending aorta. The current study evaluates the hemodynamic effect of ModulHeart support and its impact on cerebral, myocardial, and renal blood flow.

Methods: ModulHeart was implanted in the descending aorta of four healthy calves.

Targeted chain-exchange-mediated reconstitution of a split type-I cytokine for conditional immunotherapy.

Antibody-cytokine fusions targeted against tumor-associated antigens (TAAs) are promising cancer immunotherapy agents, with many such molecules currently undergoing clinical trials. However, due to the limited number of tumor-specific targets, on-target off-tumor effects can lead to systemic toxicity. Additionally, targeted cytokines can be scavenged by cytokine receptors on peripheral cells, decreasing tumor penetration.

Mid-term clinical and echocardiographic results of the INSPIRIS RESILIA aortic valve: a retrospective comparison to the Magna Ease.

Objectives: The INSPIRIS aortic valve combines the RESILIA proprietary tissue preservation process and an expandable stent frame to benefit future transcatheter valve-in-valve procedures. As the INSPIRIS valve became commercially available in 2017, mid-term outcome reports are scarce. We aimed to evaluate mid-term safety and echocardiographic performance of the INSPIRIS valve in comparison to its predecessor, the Carpentier Edwards Perimount Magna Ease (ME).

Are Short Duration Naps Better than Long Duration Naps for Mitigating Sleep Inertia? Brief Report of a Randomized Crossover Trial of Simulated Night Shift Work.

Objective: We sought to test the effects of different duration naps on post-nap cognitive performance during simulated night shifts.

Methods: We used a randomized laboratory-based crossover trial design with simulated 12-hr night shifts and each participant completing three conditions of 72 hrs each (Clinicaltrials.gov; registration # NCT04469803).

ImmuneBuilder: Deep-Learning models for predicting the structures of immune proteins.

Immune receptor proteins play a key role in the immune system and have shown great promise as biotherapeutics. The structure of these proteins is critical for understanding their antigen binding properties. Here, we present ImmuneBuilder, a set of deep learning models trained to accurately predict the structure of antibodies (ABodyBuilder2), nanobodies (NanoBodyBuilder2) and T-Cell receptors (TCRBuilder2).

Comparison of the Asthma Control Questionnaire and patient diaries in uncontrolled asthma.

https://bit.ly/3TIYClX.

Assessment of Large Animal Vascular Dimensions for Intra-Aortic Device Research and Development: A Systematic Review.

Animal studies are often required to evaluate new cardiovascular medical devices before they reach the market. Moreover, first-generation novel devices including aortic endovascular prostheses and circulatory support devices are often larger than later iterations or tested in a limited range of sizes. One of the challenges in evaluating these devices is finding a model that is both accessible and anatomically similar to humans, as there is a paucity of data on vascular dimensions in large animals.

Trends and Opportunities in Organic Synthesis: Global State of Research Metrics and Advances in Precision, Efficiency, and Green Chemistry.

Organic synthesis continues to drive a broad range of research advances in chemistry and related sciences. Another clear trend in organic synthesis research is the increasing desire to target improvements in the quality of life of humankind, new materials, and product specificity. Here, a landscape view of organic synthesis research is provided by analysis of the CAS Content Collection.