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.

Circulating immune biomarkers correlating with response in patients with metastatic renal cell carcinoma on immunotherapy.

As multiple front-line immune checkpoint inhibitor (ICI)-based combinations are approved for metastatic renal cell carcinoma, biomarkers predicting for ICI responses are needed past clinical prognostication scores and transcriptome gene expression profiling. Circulating markers represent opportunities to assess baseline and dynamic changes in immune cell frequency and cytokine levels while on treatment. We conducted an exploratory prospective correlative study of 33 patients with metastatic clear cell renal cell carcinoma undergoing treatment with ICIs and correlated changes in circulating immune cell subsets and cytokines with clinical responses to treatment.

Ultra-sensitive, tumor-informed ctDNA profiling in pembrolizumab-treated esophagogastric cancer patients predicts clinical responses.

To explore whether ultra-sensitive circulating tumor DNA (ctDNA) profiling enables early prediction of treatment response and early detection of disease progression, we applied NeXT Personal, an ultra-sensitive bespoke tumor-informed liquid biopsy platform, to profile tumor samples from the KeyLargo study, a phase II trial in which metastatic esophagogastric cancer (mEGC) patients received capecitabine, oxaliplatin, and pembrolizumab. All 25 patients evaluated were ctDNA-positive at baseline. Minimal residual disease (MRD) events varied from 406,067 down to 1.

Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial.

GT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a "3 + 3" schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103.

Craniosynostosis surgery practice patterns in the United States: what are we doing and how are we doing it?

Objective: The surgical management of craniosynostosis varies without consensus on technique or standard outcomes reporting. The authors of this study aimed to investigate current surgical management of craniosynostosis in the United States.

Methods: Two hundred seventy-five surgeons actively treating craniosynostosis in the United States were surveyed.

Effect of medium-chain triglycerides and whey protein isolate preloads on glycaemia in type 2 diabetes: a randomized crossover study.

Background: Small nutritional preloads can reduce postprandial glucose excursions in individuals with and without metabolic syndrome or type 2 diabetes (T2D). However, most studies have focused on preloads administered before single meals and have predominantly used protein-based preloads.

Objectives: To investigate the effects of sequential consumption of medium-chain triglycerides (MCT) and whey protein isolate (WPI) preloads before breakfast, lunch, and dinner on postprandial, diurnal, and 24-h glycaemia in individuals with T2D.

Exploring How the Kidney BEAM Physical Activity Digital Health Intervention Improved Mental Health-Related Quality of Life for People Living With Kidney Disease.

Introduction: The Kidney BEAM randomized controlled trial reported clinically meaningful and statistically significant improvements in mental health-related quality of life (HRQoL), physical function (sit-to-stand-60, but not the physical component of HRQoL) and patient activation after a 12-week physical activity digital health intervention (DHI). This study explores factors that contributed to the effectiveness of Kidney BEAM through mixed methods analyses.

Methods: Quantitative data analysis was obtained from the recently published primary manuscript.

Impact of stopping burosumab treatment at the end of skeletal growth in adolescents with X-linked hypophosphatemia (XLH).

Many adolescents with X-linked hypophosphatemia (XLH) currently have to stop treatment with burosumab at the end of skeletal growth. We describe the experience of a cohort of adolescents with XLH before, during, and after stopping burosumab (median treatment duration 37.5 months).

Subscapular Tunneling to Increase the Reach of Latissimus Dorsi Myocutaneous Flap: A Case Report.

The latissimus dorsi muscle or myocutaneous flap (LDMF) has long been a mainstay in the plastic surgeon's armamentarium, serving as a versatile and reliable tool for reconstructive procedures. Tunneling the LDMF through the subscapular route increases the reach to cover defects as far as nape of the neck. In this article, we report a case of LDMF routed through a subscapular route to cover impending hardware exposure at the nape region.

Kidney Beam-A Cost-Effective Digital Intervention to Improve Mental Health.

Introduction: There is inequity in the provision of physical rehabilitation services for people living with chronic kidney disease (CKD). The Kidney BEAM trial evaluated the clinical value and cost effectiveness of a physical activity digital health intervention (DHI) in CKD.

Methods: In a single-blind, 11 center, randomized controlled trial, 340 adult participants with CKD were randomly assigned to either the Kidney BEAM physical activity DHI or a waitlist control.

Rocatinlimab Improves Patient-Reported Outcomes in Adults with Moderate-to-Severe Atopic Dermatitis: Results from a Double-Blind Placebo-Controlled Phase 2b Study.

Introduction: In adults with moderate-to-severe atopic dermatitis (AD), rocatinlimab demonstrated significant and progressive improvement in clinical measures of disease severity compared with placebo. This post hoc analysis of a phase 2b study was undertaken to understand the disease burden and to assess the impact of rocatinlimab on patient-reported outcomes (PROs).

Methods: This analysis used baseline data from a multicenter, randomized, double-blind study of adults with moderate-to-severe AD, who completed a Worst Pruritus numerical rating scale (NRS), Sleep Disturbance NRS, and the Dermatology Life Quality Index (DLQI).

Experiences of Midwestern obstetric clinicians during the Coronavirus disease 2019 pandemic.

Background: The Coronavirus disease 2019 (COVID-19) pandemic led to healthcare system changes aimed at minimizing disease transmission that impacted experiences with obstetric healthcare.

Objective: To explore experiences of clinicians providing obstetric care during the COVID-19 pandemic.

Study Design: Qualitative, in-depth, semi-structured interviews were conducted with five nurse practitioners and 16 obstetrical physicians providing a mix of outpatient and inpatient obstetric care during the COVID-19 pandemic in a mid-sized, Midwestern city in the United States.

Characterization of the Biological Variability of the Angiome Biomarkers over Time in Healthy Participants.

Background: Biomarker analyses are an integral part of cancer research. Despite the intense efforts to identify and characterize biomarkers in patients with cancer, little is known regarding the natural variation of biomarkers in healthy populations. Here we conducted a clinical study to evaluate the natural variability of biomarkers over time in healthy participants.

Systematic literature review of the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures in adults.

This systematic literature review (SLR) assessed the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures (PGTCS) in adults to evaluate these domains in both populations and identify evidence gaps to inform future research. A search was conducted on December 7, 2022, using MEDLINE and Embase to identify studies published from 2012 onwards reporting humanistic burden (patient-reported or caregiver-reported outcomes or utilities, qualitative evaluations), economic burden (productivity loss, caregiver and societal costs of epilepsy), and sleep-related outcomes. Of the 2830 citations identified, 136 were included.

Can we really distinguish 'responders' from 'non-responders' to myopia control interventions?

Purpose: It is common to hear talk of 'responders' and 'non-responders' with respect to myopia control interventions. We consider the reality of distinguishing these sub-groups using data from the first year of the Low-concentration Atropine for Myopia Progression (LAMP) study.

Methods: The first year of the LAMP study was a robustly designed, placebo-controlled trial of three different low concentrations of atropine using a large sample size (N > 100 randomised to each group).

Spectroscopy in Nanoscopic Cavities: Models and Recent Experiments.

The ability of nanophotonic cavities to confine and store light to nanoscale dimensions has important implications for enhancing molecular, excitonic, phononic, and plasmonic optical responses. Spectroscopic signatures of processes that are ordinarily exceedingly weak such as pure absorption and Raman scattering have been brought to the single-particle limit of detection, while new emergent polaritonic states of optical matter have been realized through coupling material and photonic cavity degrees of freedom across a wide range of experimentally accessible interaction strengths. In this review, we discuss both optical and electron beam spectroscopies of cavity-coupled material systems in weak, strong, and ultrastrong coupling regimes, providing a theoretical basis for understanding the physics inherent to each while highlighting recent experimental advances and exciting future directions.