Quantitative systems toxicology modeling in pharmaceutical research and development: An industry-wide survey and selected case study examples.

Quantitative systems toxicology (QST) models are increasingly being applied for predicting and understanding toxicity liabilities in pharmaceutical research and development. A European Federation of Pharmaceutical Industries and Associations (EFPIA)-wide survey was completed by 15 companies. The results provide insights into the current use of QST models across the industry.

Transition to Adulthood through Coaching and Empowerment in Rheumatology (TRACER): A feasibility study protocol.

The transition from pediatric to adult care for patients with chronic disease is a vulnerable period, with risks of disengagement from care and subsequent complications of inadequately managed disease. This period comes at a time when there are many other transitions occurring in the young person's life, including changes to vocation, social supports, and to their physiology. The aim of the TRACER study is to assess the feasibility of conducting a multi-center, randomized-controlled trial of a virtual Transition Coach Intervention in youth transferring from pediatric to adult rheumatology care.

Endeavours made by trade associations, pharmaceutical companies and regulators in the replacement, reduction and refinement of animal experimentation in safety testing of pharmaceuticals.

Following the European Commission decision to develop a roadmap to phase out animal testing and the signing of the US Modernisation Act, there is additional pressure on regulators and the pharmaceutical industry to abandon animal experimentation in safety testing. Often, endeavours already made by governments, regulators, trade associations, and industry to replace, reduce and refine animal experimentation (3Rs) are unnoticed. Herein, we review such endeavours to promote wider application and acceptance of 3Rs.

The TRUST Study-TRansition US Together: Evaluating the Impact of a Parent- and Adolescent-Centered Transition Toolkit on Transition Readiness in Patients with Juvenile Idiopathic Arthritis and Childhood-Onset Systemic Lupus Erythematosus.

Objective: Adolescents with chronic rheumatic disease must increasingly take on more responsibility for disease management from parents as they transition from pediatric to adult care. Yet, there are limited resources to inform and support parents about transition. Here, we evaluate the impact of a Transition Toolkit, geared towards parents and adolescents, on transition readiness, and explore the potential impact of parent-adolescent communication.

Mimicking opioid analgesia in cortical pain circuits.

The anterior cingulate cortex plays a pivotal role in the cognitive and affective aspects of pain perception. Both endogenous and exogenous opioid signaling within the cingulate mitigate cortical nociception, reducing pain unpleasantness. However, the specific functional and molecular identities of cells mediating opioid analgesia in the cingulate remain elusive.

Axial Spondyloarthritis: Does Magnetic Resonance Imaging Classification Improve Report Interpretation.

Objective: The interpretation of magnetic resonance imaging (MRI) reports is crucial for the diagnosis of axial spondyloarthritis, but the subjective nature of narrative reports can lead to varying interpretations. This study presents a validation of a novel MRI reporting system for the sacroiliac joint in clinical practice.

Methods: A historical review was conducted on 130 consecutive patients referred by 2 rheumatologists for initial MRI assessment of possible axial spondyloarthritis.

The Strength Characteristics of Elite and Subelite Female Gaelic Football Players.

Hughes, W, Healy, R, Lyons, M, Higginbotham, C, Lane, A, and Beattie, K. The strength characteristics of elite and subelite female Gaelic football players. J Strength Cond Res 38(6): 1072-1081, 2024-There is currently an underrepresentation of sports science research focused on the female athlete, specifically in the context of Gaelic football.

Clinical Characteristics of Adolescents With Juvenile Idiopathic Arthritis Transitioning to Adult Rheumatology Care in Canada: Results From the CAPRI Registry.

Objective: Using Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) juvenile idiopathic arthritis (JIA) registry data, we describe (1) clinical characteristics of patients with JIA transitioning to adult care, (2) prevalence of disease-related damage and complications, and (3) changes in disease activity during the final year prior to transfer.

Methods: Registry participants who turned 17 years between February 2017 and November 2021 were included. Clinical characteristics and patient-reported outcomes (PROs) at the last recorded pediatric rheumatology visit, and changes observed in the year prior to that visit were analyzed.

A dynamic model of the intestinal epithelium integrates multiple sources of preclinical data and enables clinical translation of drug-induced toxicity.

We have built a quantitative systems toxicology modeling framework focused on the early prediction of oncotherapeutic-induced clinical intestinal adverse effects. The model describes stem and progenitor cell dynamics in the small intestinal epithelium and integrates heterogeneous epithelial-related processes, such as transcriptional profiles, citrulline kinetics, and probability of diarrhea. We fitted a mouse-specific version of the model to quantify doxorubicin and 5-fluorouracil (5-FU)-induced toxicity, which included pharmacokinetics and 5-FU metabolism and assumed that both drugs led to cell cycle arrest and apoptosis in stem cells and proliferative progenitors.

First Dark Matter Search Results from the LUX-ZEPLIN (LZ) Experiment.

The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t.

Mind the Gap: A Longitudinal Analysis of the Experiences of Adolescents and Parents in a Rheumatology Transition Clinic.

Background: The transition from pediatric to adult care is a critical time when adolescent patients and their families face many challenges. This period can be associated with an increase in disease-related morbidity and mortality. The aim of our study is to identify gaps in transition-related care to help guide areas for improvement.

A survey of Canadian adult rheumatologists' knowledge, comfort level, and barriers in assessing psychosocial needs of young adults with rheumatic diseases.

To assess adult rheumatologists' comfort level, current practices, and barriers to provision of optimal care in supporting young adults with pediatric-onset rheumatic conditions in Canada. Survey questions were informed by literature review, a needs assessment, and using milestones listed by the Royal College of Physicians and Surgeons of Canada for the entrustable professional activities (EPAs) applicable to care for rheumatology patients transitioning to adult practice. The electronic survey was distributed to adult rheumatology members of the Canadian Rheumatology Association over 4 months.

The Natural Stilbenoid (-)-Hopeaphenol Inhibits HIV Transcription by Targeting Both PKC and NF-κB Signaling and Cyclin-Dependent Kinase 9.

Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to harbor replication-competent and transcriptionally active virus in infected cells, which in turn can lead to ongoing viral antigen production, chronic inflammation, and increased risk of age-related comorbidities. To identify new agents that may inhibit postintegration HIV beyond cART, we screened a library of 512 pure compounds derived from natural products and identified (-)-hopeaphenol as an inhibitor of HIV postintegration transcription at low to submicromolar concentrations without cytotoxicity. Using a combination of global RNA sequencing, plasmid-based reporter assays, and enzyme activity studies, we document that hopeaphenol inhibits protein kinase C (PKC)- and downstream NF-κB-dependent HIV transcription as well as a subset of PKC-dependent T-cell activation markers, including interleukin-2 (IL-2) cytokine and CD25 and HLA-DRB1 RNA production.

The Effect of Different Strength Training Modalities on Sprint Performance in Female Team-Sport Athletes: A Systematic Review and Meta-Analysis.

Background: There has been a rise in the participation, professionalism, and profile of female sports in recent years. Sprinting ability is an important quality for successful athletic performance in many female team sports. However, much of the research to date on improving sprint performance in team sports is derived from studies with male participants.

Effect of pregnancy on scleroderma progression.

Objective: To explore the trajectory of scleroderma disease activity in women who experienced a pregnancy after systemic sclerosis diagnosis compared to nulliparous women.

Methods: We analyzed data from the Canadian Scleroderma Research Group registry by identifying nulliparous women and women with ⩾1 pregnancy after systemic sclerosis diagnosis. Patient characteristics were compared between groups at registry entry.

Prediction of inotropic effect based on calcium transients in human iPSC-derived cardiomyocytes and machine learning.

Functional changes to cardiomyocytes are undesirable during drug discovery and identifying the inotropic effects of compounds is hence necessary to decrease the risk of cardiovascular adverse effects in the clinic. Recently, approaches leveraging calcium transients in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been developed to detect contractility changes, induced by a variety of mechanisms early during drug discovery projects. Although these approaches have been able to provide some predictive ability, we hypothesised that using additional waveform parameters could offer improved insights, as well as predictivity.

Evaluation of an infrared thermography camera for measuring body temperature in dairy calves.

The objective of this diagnostic accuracy study was to validate an infrared thermography (IRT) camera and its software (FLIR One, FLIR, Global) for accuracy and precision for ocular temperature readings to serve as a proxy for rectal temperature in commercially housed calves. A total of 318 male Holstein calves were enrolled into this study from the day of arrival to a calf rearing facility until 14 d later. Researchers took an ocular temperature reading using an IRT camera, and a rectal temperature on each calf each day in the morning.

Descriptive analysis of the changes in Johne's disease management practices on Ontario dairy farms through repeat risk assessment.

Johne's disease (JD) control is often based on the culling of positive animals and the adoption of management practices that minimize exposure of calves to the pathogen Mycobacterium avium ssp. paratuberculosis (MAP). From 2010 to 2013, Ontario, Canada, instituted a voluntary Johne's control program consisting of whole-herd testing and a Risk Assessment and Management Plan (RAMP).

Navel healing in male and female Holstein calves over the first 14 days of life: A longitudinal cohort study.

The objectives of this study were (1) to describe navel healing in male and female neonatal Holstein calves over a 14-d observation period, and (2) to determine the associations of dam parity, calving factors, and calf factors with navel measurements and time to healing. A total of 68 Holstein calves (43 female and 25 male) were enrolled. Navel healing outcomes (cessation of navel discharge, navel cord remnant drying, navel cord remnant drop-off) and navel stump measurement outcomes (proximal diameter, distal diameter, length) were recorded every 24 ± 1 h for a 14-d observation period.

The Role of Strength on Punch Impact Force in Boxing.

Beattie, K and Ruddock, AD. The role of strength on punch impact force in boxing. J Strength Cond Res 36(10): 2957-2969, 2022-The ability to punch with a high impact force is beneficial to boxers as there is an increased likelihood of success.

TBX2 acts as a potent transcriptional silencer of tumour suppressor genes through interaction with the CoREST complex to sustain the proliferation of breast cancers.

Chromosome 17q23 amplification occurs in 20% of primary breast tumours and is associated with poor outcome. The TBX2 gene is located on 17q23 and is often over-expressed in this breast tumour subset. TBX2 is an anti-senescence gene, promoting cell growth and survival through repression of Tumour Suppressor Genes (TSGs), such as NDRG1 and CST6.

Self-Reported Transition Readiness of Adolescent Patients with Rheumatic Disease: Do the Parents Agree?

Our objective was to compare transition readiness assessment scores from adolescents with rheumatic disease with their parents and analyze their level of agreement. We found that adolescents and parents generally agree on the level of the transition readiness; however, there is occasional disagreement in specific domains.