Cancer-Therapy-Induced Cardiotoxicity: Results of the Analysis of the UK Yellow Card Adverse Drug Reaction (ADR) Reporting.

Non-small cell lung cancer (NSCLC) is a predominant cause of oncological mortality in the United Kingdom. There is a diverse spectrum of therapeutic options available, such as chemotherapies, targeted therapies and immunotherapies, which have significantly advanced patient prognoses. However, despite these advancements, there is an escalating concern regarding the potential cardiotoxic effects associated with these treatments.

Left out in the cold - inequity in infectious disease control due to cold chain disparity.

Vaccines and diagnostic tools stand out as among the most influential advancements in public health, credited with averting an estimated 6 million deaths annually and substantially alleviating the burden of infectious disease. Despite this progress, the global imperative to prevent, detect, and combat infectious disease persists. Regrettably, hundreds of thousands of lives are still lost due to inadequate access to vaccines and diagnostics.

Contemporary Practice and Considerations for Real-World Data Source Identification and Feasibility Assessment.

Purpose: There has been rapid growth in the variety and number of real-world data (RWD) sources, as well as the number of regulatory documents that provide guidance for assessing the suitability of RWD sources for pharmacoepidemiology studies. This study aims to assess differences in RWD guidance and variability in current practice for identifying and assessing RWD for studies with regulatory purpose.

Methods: Key criteria for feasibility assessment were mapped against relevant regulatory guidance documents across US, EU, and Asia-Pacific regions.

Defining correlates of protection for mammalian livestock vaccines against high-priority viral diseases.

Enhancing livestock biosecurity is critical to safeguard the livelihoods of farmers, global and local economies, and food security. Vaccination is fundamental to the control and prevention of exotic and endemic high-priority infectious livestock diseases. Successful implementation of vaccination in a biosecurity plan is underpinned by a strong understanding of correlates of protection-those elements of the immune response that can reliably predict the level of protection from viral challenge.

Using Data Science Tools to Reveal and Understand Subtle Relationships of Inhibitor Structure in Frontal Ring-Opening Metathesis Polymerization.

The rate of frontal ring-opening metathesis polymerization (FROMP) using the Grubbs generation II catalyst is impacted by both the concentration and choice of monomers and inhibitors, usually organophosphorus derivatives. Herein we report a data-science-driven workflow to evaluate how these factors impact both the rate of FROMP and how long the formulation of the mixture is stable (pot life). Using this workflow, we built a classification model using a single-node decision tree to determine how a simple phosphine structural descriptor () can bin long versus short pot life.

Use of quantitative bias analysis to evaluate single-arm trials with real-world data external controls.

Purpose: Use of real-world data (RWD) for external controls added to single-arm trials (SAT) is increasingly prevalent in regulatory submissions. Due to inherent differences in the data-generating mechanisms, biases can arise. This paper aims to illustrate how to use quantitative bias analysis (QBA).

Updated core competencies in pharmacoepidemiology to inform contemporary curricula and training for academia, government, and industry.

Purpose: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions.

A human obesity-associated MC4R mutation with defective Gq/11α signaling leads to hyperphagia in mice.

Melanocortin 4 receptor (MC4R) mutations are the most common cause of human monogenic obesity and are associated with hyperphagia and increased linear growth. While MC4R is known to activate Gsα/cAMP signaling, a substantial proportion of obesity-associated MC4R mutations do not affect MC4R/Gsα signaling. To further explore the role of specific MC4R signaling pathways in the regulation of energy balance, we examined the signaling properties of one such mutant, MC4R (F51L), as well as the metabolic consequences of MC4RF51L mutation in mice.

Identification of cardiotoxicity related to non-small cell lung cancer (NSCLC) treatments: A systematic review.

In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart's function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease.

Identification of a novel role for the immunomodulator ILRUN in the development of several T cell subsets in mice.

Inflammation and lipid regulator with UBA-like and NBR1-like domains (ILRUN) is a protein-encoding gene associated with innate immune signaling, lipid metabolism and cancer. In the context of innate immunity, ILRUN inhibits IRF3-mediated transcription of antimicrobial and proinflammatory cytokines by inducing degradation of the transcriptional coactivators CBP and p300. There remains a paucity of information, however, regarding the innate immune roles of ILRUN beyond in vitro analyses.

Impact of European Union Label Changes for Fluoroquinolone-Containing Medicinal Products for Systemic and Inhalation Use: Post-Referral Prescribing Trends.

Introduction: Concerns of the persistence and severity of the adverse effects of fluoroquinolones, mainly involving the nervous system, muscles and joints, resulted in the 2018 referral procedure led by the European Medicines Agency (EMA). They advised to stop prescribing fluoroquinolones for infections of mild severity or of a presumed self-limiting course and for prevention of infections, plus to restrict prescriptions in cases of milder infections where other treatment options are available, and restrict in at-risk populations. We aimed to examine whether the impact of EMA regulatory interventions implemented throughout 2018-2019 had an impact on fluoroquinolone prescribing rates.

The Pyruvate Kinase Deficiency Global Longitudinal (Peak) Registry: rationale and study design.

Introduction: Pyruvate kinase (PK) deficiency is a rare, under-recognised, hereditary condition that leads to chronic haemolytic anaemia and potentially serious secondary complications, such as iron overload, cholecystitis, pulmonary hypertension and extramedullary haematopoiesis. It is an autosomal recessive disease caused by homozygous or compound heterozygous mutations in the gene. Due to its rarity and clinical heterogeneity, information on the natural history and long-term clinical course of PK deficiency is limited, presenting major challenges to patient management, the development of new therapies and establishing disease-specific treatment recommendations.

The impact of stress and anesthesia on animal models of infectious disease.

Stress and general anesthesia have an impact on the functional response of the organism due to the detrimental effects on cardiovascular, immunological, and metabolic function, which could limit the organism's response to an infectious event. Animal studies have formed an essential step in understanding and mitigating infectious diseases, as the complexities of physiology and immunity cannot yet be replicated . Using animals in research continues to come under increasing societal scrutiny, and it is therefore crucial that the welfare of animals used in disease research is optimized to meet both societal expectations and improve scientific outcomes.

Genomic Characterization of Salmonella enterica serovar Weltevreden Associated with Human Diarrhea.

Salmonella Weltevreden is an emerging pathogen associated with human diarrhea, and knowledge of the genomics and epidemiology of this serovar is still limited. In this study, we performed whole-genome sequencing of 96 Weltevreden isolates recovered from diarrheal patients and 62 isolates from food animals in China between 2006 and 2017. Together, with an additional 199 genome sequences of .

H7N9 bearing a mutation in the nucleoprotein leads to increased pathology in chickens.

The zoonotic H7N9 avian influenza (AI) virus first emerged in 2013 as a low pathogenic (LPAI) strain, and has repeatedly caused human infection resulting in severe respiratory illness and a mortality of ~39% (>600 deaths) across five epidemic waves. This virus has circulated in poultry with little to no discernible clinical signs, making detection and control difficult. Contrary to published data, our group has observed a subset of specific pathogen free chickens infected with the H7N9 virus succumb to disease, showing clinical signs consistent with highly pathogenic AI (HPAI).

Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in adults with non-transfusion dependent α-thalassaemia or β-thalassaemia: an open-label, multicentre, phase 2 study.

Background: Patients with non-transfusion-dependent thalassaemia (NTDT), although they do not require regular blood transfusions for survival, can still accrue a heavy burden of comorbidities. No approved disease-modifying therapies exist for these patients. We aimed to investigate the safety and efficacy of mitapivat (Agios Pharmaceuticals, Cambridge, MA, USA), a pyruvate kinase activator, in adults with non-transfusion-dependent (NTD) α-thalassaemia or NTD β-thalassaemia.

"They're just, like, there": A constructivist grounded theory study of student experiences with school resource officers.

School-based policing has become common practice, but there is limited qualitative research examining what meanings students make of police presence in their schools. This study sought to understand how students construct narratives of police presence in their schools based on their experiences with school resource officers (SROs). Drawing on constructivist grounded theory methodology with a sample of 17 students, this study found that students are continuously integrating multiple conflicting narratives about SROs: students experience SROs as an established yet ambiguous presence, which produces mixed feelings of reassurance, wariness, and intimidation.

A Landscape Analysis of Post-Marketing Studies Registered in the EU PAS Register and ClinicalTrials.gov Focusing on Pregnancy Outcomes or Breastfeeding Effects: A Contribution from the ConcePTION Project.

Introduction: A large proportion of medicine product labels lack information on safety in pregnancy and breastfeeding. To address this gap, pharmaceutical companies are requested to develop post-approval studies regarding the use of drugs by pregnant and breastfeeding women.

Objective: Our study aims to review key features of observational studies in pregnancy and breastfeeding and their impact on the respective medicine product labels.