Deep learning-based design and experimental validation of a medicine-like human antibody library.

Antibody generation requires the use of one or more time-consuming methods, namely animal immunization, and in vitro display technologies. However, the recent availability of large amounts of antibody sequence and structural data in the public domain along with the advent of generative deep learning algorithms raises the possibility of computationally generating novel antibody sequences with desirable developability attributes. Here, we describe a deep learning model for computationally generating libraries of highly human antibody variable regions whose intrinsic physicochemical properties resemble those of the variable regions of the marketed antibody-based biotherapeutics (medicine-likeness).

Randomized phase II study of bevacizumab with weekly anetumab ravtansine or weekly paclitaxel in platinum-resistant/refractory high grade ovarian cancer (NCI trial).

Purpose: Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC).

Transcriptional Integration of Meiotic Prophase I Progression and Early Oocyte Differentiation.

Female reproductive senescence results from the regulated depletion of a finite pool of oocytes called the ovarian reserve. This pool of oocytes is initially established during fetal development, but the oocytes that comprise it must remain quiescent for decades until they are activated during maturation in adulthood. In order for developmentally competent oocytes to populate the ovarian reserve they must successfully initiate both meiosis and oogenesis.

Deconditioning in quiescent Crohn's Disease patients with heightened fatigue perception.

Background & Objective: IBD fatigue aetiology is poorly understood. This study quantified body composition and physical function alongside proton magnetic resonance imaging (1H MRI) and spectroscopy (31P MRS) measures of organ structure and function in quiescent Crohn's Disease patients (CD) and healthy volunteers (HV), to identify a physiological basis for IBD fatigue.

Methods: Body composition was determined using DEXA and 1H MRI.

Gene signatures derived from transcriptomic-causal networks stratify colorectal cancer patients for effective targeted therapy.

Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.

Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes.