Opportunities for More Tailored Approaches to Genotoxicity Testing and Carcinogenicity Strategy for Oligonucleotide Therapeutics: Outcome of an Industry Survey.

The Oligonucleotide Nonclinical Working Group (WG) of the European Federation of Pharmaceutical Industries and Associations conducted an industry survey to understand current practices and regulatory expectations for genotoxicity and carcinogenicity assessment of oligonucleotide therapeutics (ONTs), along with historical genotoxicity testing results. The survey, involving 29 pharmaceutical and biotechnology companies, revealed a consistent absence of genotoxicity across a diverse range of oligonucleotide classes and chemistries, consistent with previous observations. Despite the lack of genotoxicity, companies continue to follow standard testing guidelines, with only limited divergence.

First-in-Human Phase 1 study of a CD16A bispecific innate cell engager, AFM24, targeting EGFR-expressing solid tumors.

Purpose: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on natural killer (NK) cells/macrophages and EGFR on tumor cells, redirecting antitumor activity towards tumors. The safety and tolerability of AFM24 was evaluated in this Phase 1/2a dose escalation/dose expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

Sedation and Ventilator Weaning Bundle and Time to Extubation in Infants With Bronchiolitis: Secondary Analysis of the Sedation AND Weaning in Children (SANDWICH) Trial.

Objective: The Sedation and Weaning in Children (SANDWICH) trial of a sedation weaning and ventilator liberation bundle had a primary outcome of time to successful extubation, and showed significant but small difference. We explored the impact of the intervention on infants with bronchiolitis.

Design: Post hoc subgroup analysis of a cluster-randomized trial, 2018 to 2019 (ISRCTN16998143).

A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator.

Background: Adiposity is an established risk factor for colorectal cancer (CRC). The pathways underlying this relationship, and specifically the role of circulating proteins, are unclear.

Methods: Utilizing two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and colocalization, based on summary data from large sex-combined and sex-specific genetic studies, we estimated the univariable associations between: (i) body mass index (BMI) and waist-hip ratio (WHR) and overall and site-specific (colon, proximal colon, distal colon, and rectal) CRC risk, (ii) BMI and WHR and circulating proteins, and (iii) adiposity-associated circulating proteins and CRC risk.

A diffusion-based super resolution model for enhancing sonar images.

Improved hardware and processing techniques such as synthetic aperture sonar have led to imaging sonar with centimeter resolution. However, practical limitations and old systems limit the resolution in modern and legacy datasets. This study proposes using single image super resolution based on a conditioned diffusion model to map between images at different resolutions.

A rhamnose-rich O-antigen of MP20 is required for symbiosis with .

a β-proteobacterium, forms a nitrogen-fixing symbiosis with many species of the large legume genus as well as with common bean ( L.). are considered to have evolved nodulation independently from the well-studied α-proteobacteria symbionts of legumes.

Exploring Context Allows Us to Better Understand Physical Activity in People with and Without Parkinson's Who Have Fallen: A Mixed Methods Study.

Falls are a frequent and serious problem for older adults, especially for those living with Parkinson's. The relationship between falls and physical activity is complex, and people often restrict activity following a fall. Exercise is an important aspect of reducing further risk of a fall and a key component of the management of Parkinson's.

Harnessing cell aggregates for enhanced adeno-associated virus manufacturing: Cultivation strategies and scale-up considerations.

The possibility to produce recombinant adeno-associated virus (rAAV) by adherent HEK293T cells was studied in a stirred tank bioreactor (STR) culture of cell aggregates. A proof-of-concept of rAAV production was successfully demonstrated in a process where single cells were first expanded, then cell aggregates were formed by dilution into a different medium 1 day before triple plasmid transfection was conducted. An alternative approach for the STR inoculation using a seed taken from a high cell density perfusion (HCDP) culture was also investigated.

A cross-sectional survey of psychiatrists' experiences of using telepsychiatry during the COVID-19 pandemic and the relationship with burnout in selected high, middle, and low-income countries.

Background: The COVID-19 pandemic necessitated substantial modifications in the delivery of patient care on a global scale. Telemedicine-based care services were implemented worldwide to maximize access to healthcare systems.

Aims: This study aimed to investigate the use of and satisfaction with telepsychiatry services implemented during the COVID-19 pandemic by psychiatrists across low, middle, and high income countries, and to assess levels of burnout among psychiatrists providing telepsychiatry services in different settings and countries.

Greenhouse Gas Emissions and Decarbonization Potential of Global Fired Clay Brick Production.

Fired clay bricks (FCBs) are a dominant building material globally due to their low cost and simplicity of production, especially in low- and middle-income countries. With a projected rising housing demand, commensurate growth in brick demand is anticipated, the production of which could result in significant greenhouse gas (GHG) emissions. Robust models are needed to estimate brick demand and emissions to systematically address decarbonization pathways.

Long-term impact of exposure to Royal Guard, a pyriproxyfen-based bed net, on pyrethroid-resistant malaria vectors from Cameroon using DNA-based metabolic resistance markers.

Background: Escalating pyrethroid resistance in malaria vectors highlights the urgency of implementing new control tools incorporating non-pyrethroid molecules. Here, using DNA-based metabolic resistance markers, we assessed the efficacy of the dual active ingredients net Royal Guard against pyrethroids-resistant malaria vectors in Cameroon, establishing its long-term impact on mosquitoes' life traits after exposure.

Results: Cone assays revealed low efficacy of Royal Guard against field Anopheles populations.

Effect of Physical Exercise on Telomere Length: Umbrella Review and Meta-Analysis.

Background: Telomere length (TL) is a marker of cellular health and aging. Physical exercise has been associated with longer telomeres and, therefore, healthier aging. However, results supporting such effects vary across studies.

Impact of Scleroderma-Associated Autoantibodies on Clinical Outcome Assessments: Post Hoc Analysis From a Randomised, Double-blind, Placebo-controlled, Phase 3 Trial of Tocilizumab in Scleroderma.

Objective: Scleroderma-associated autoantibodies (SSc-Abs) are specific in participants (pts) with systemic sclerosis and are associated with organ involvement. Our objective was to assess the influence of baseline SSc-Abs on the trajectories of the clinical outcome assessments (COAs) in a phase III randomized controlled trial.

Methods: We used data on both the groups who received placebo (Pbo) and tocilizumab from the focuSSced trial.

Lateral Atrial Expression Patterns Provide Insights into Local Transcription Disequilibrium Contributing to Disease Susceptibility.

Background: Transcriptional dysregulation, possibly affected by genetic variation, contributes to disease development. Due to dissimilarities in development, function, and remodeling during disease progression, transcriptional differences between the left atrial (LA) and right atrial (RA) may provide insight into diseases such as atrial fibrillation.

Methods: Lateral differences in atrial transcription were evaluated in CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) using a 2-stage discovery and replication design.

Structural and Functional Characterization of the Aorta in Hypertrophic Obstructive Cardiomyopathy.

Background: Changes in the phenotype and genotype in hypertrophic cardiomyopathy (HCM) are thought to involve the myocardium as well as extracardiac tissues. Here, we describe the structural and functional changes in the ascending aorta of obstructive patients with HCM.

Methods: Changes in the aortic wall were studied in a cohort of 101 consecutive patients with HCM undergoing myectomy and 9 normal controls.

Trends and Themes in the Study of Value in Orthopedic Surgery: A Systematic Review.

Background: The study of value in orthopedic surgery aims to maximize health outcomes gained per unit cost through various health economic tools but is fragmented across various subspecialties and geographies. Therefore, it is difficult to ascertain whether this research methodology is being used to its full potential across all orthopedic subspecialties and geographies.

Purpose: We sought to assess the distribution of prior health economics literature in orthopedic surgery across subspecialties and geographies.

Long-term ultrasonographic changes of the canine prostate gland after castration.

Introduction: Ultrasound imaging (US) is the method of choice to assess the canine prostate gland. Whilst recent studies have documented the role of castration in the development of prostatic neoplasia, little is known about parenchymal and perfusion features of the normal and abnormal prostate in neutered dogs. No data are available concerning prostatic changes after the first 90 days following castration.

Effect of blindfolding the lead resuscitator on frequency of closed-loop communication during veterinary cardio-pulmonary resuscitation training: a randomized, controlled pilot study.

Objective: To evaluate the effect of blindfolding the lead resuscitator during veterinary cardiopulmonary resuscitation (CPR) simulation training sessions on frequency of completed closed-loop communication statements (CLC).

Design: Ten groups of staff volunteers were recruited for a prospective, randomized, blinded, observational pilot study over a 6-month period. Additionally, two associated online questionnaires were completed by participants.

Holocord syringomyelia in 18 dogs.

Holocord syringomyelia (HSM) is characterized by a continuous spinal cord cavitation along its entire length and is currently poorly documented in dogs. This retrospective multicentric case series investigates the clinical and MRI findings in 18 dogs with HSM. The median age at presentation was 82 months (range 9-108 months) and French Bulldogs were overrepresented (50%).

Remedial, institutional or radical? Explaining community responses to violence against women in an NGO programme to prevent violence in Mumbai, India.

Despite ambitions in development and global health policy to transform communities into supportive environments for women facing risks of violence, our understanding of how to best engage communities remains incomplete. In particular, there is little evidence on the types of strategies that communities employ to address violence against women (VAW). We aimed to describe and analyse the processes involved in community responses to incidents of VAW in a non-governmental organisation (NGO) violence prevention programme in Mumbai, India.

Spirometric pattern and cardiovascular risk: a prospective study of 0.3 million Chinese never-smokers.

Background: Existing studies have not provided robust evidence about the CVD risk of non-smoking patients with restrictive spirometric pattern (RSP) or airflow obstruction (AFO), and how the risk is modified by body shape. We aimed to bridge the gap.

Methods: We used never-smokers' data from the China Kadoorie Biobank (CKB) and performed Cox models by sex (278,953 females and 50,845 males).

Bone imaging modality precision and agreement between DXA, pQCT, and HR-pQCT.

Quantifying precision error for DXA, peripheral QCT (pQCT), and HR-pQCT is crucial for monitoring longitudinal changes in body composition and musculoskeletal outcomes. Agreement and associations between bone variables assessed using pQCT and second-generation HR-pQCT are unclear. This study aimed to determine the precision of, and agreement and associations between, bone variables assessed via DXA, pQCT, and second-generation HR-pQCT.

Impact of mask wearing time on fluid consumption and physical activity during the COVID-19 pandemic.

Purpose: To examine the associations between mask-wearing on fluid consumption and physical activity behaviors during the COVID-19 pandemic.

Methods: 137 college students (female, 72.5%; age, 26 ± 9 y) completed a survey detailing their fluid intake, physical activity behaviors, and time spent wearing a mask throughout the day during the previous month in the Fall 2020 academic semester.

The burden of hepatitis E virus infection among Ghanaian pregnant women.

Introduction: Hepatitis E virus (HEV) infection poses a significant burden on pregnant women, with associated negative outcomes. Although well-described in many developed countries, the epidemiology of the disease and its impact on maternal and fetal health in Ghana is not fully understood.

Materials And Methods: A cross-sectional survey was conducted in the antenatal clinics of 10 district hospitals in five regions of Ghana.