Pivotal trial characteristics and types of endpoints used to support Food and Drug Administration rare disease drug approvals between 2013 and 2022.

Background/aims: Rare disease drug development faces unique challenges, such as genotypic and phenotypic heterogeneity within small patient populations and a lack of established outcome measures for conditions without previously successful drug development programs. These challenges complicate the process of selecting the appropriate trial endpoints and conducting clinical trials in rare diseases. In this descriptive study, we examined novel drug approvals for non-oncologic rare diseases by the U.

Systematic review of MRI safety literature in relation to radiofrequency thermal injury prevention.

Introduction: Magnetic resonance imaging (MRI) is a rapidly evolving modality, generally considered safe due to lack of ionising radiation. While MRI technology and techniques are improving, many of the safety concerns remain the same as when first established. Patient thermal injuries are the most frequently reported adverse event, accounting for 59% of MRI incidents to the Food and Drug Administration (FDA).

Genetic Transformation of Cryptococcus Species with Agrobacterium Transfer DNA.

Transformation of foreign DNA into Cryptococcus species is a powerful tool for exploring gene functions in these human pathogens. Agrobacterium tumefaciens-mediated transformation (AtMT) has been used for the stable introduction of exogenous DNA into Cryptococcus for over two decades, being particularly impactful for insertional mutagenesis screens to discover new genes involved in fungal biology. A detailed protocol to conduct this transformation method is provided in the chapter.

Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty.

The genetic material encoded on X and Y chromosomes provides the foundation by which biological sex differences are established. Epigenetic regulators expressed on these sex chromosomes, including Kdm6a (Utx), Kdm5c, and Ddx3x have far-reaching impacts on transcriptional control of phenotypic sex differences. Although the functionality of UTY (Kdm6c, the Y-linked homologue of UTX), has been supported by more recent studies, its role in developmental sex differences is not understood.

Impact of Race and Area Deprivation on Triple-Negative Metastatic Breast Cancer Outcomes.

Objectives: To describe area deprivation, anxiety, depression, relative dose intensity of first-line metastatic breast cancer (MBC) treatment, and survival in Black and White women who had died from triple-negative MBC, including interaction analysis.

Sample & Setting: This cohort study drew from a database of women who had died from MBC (N = 53).

Methods & Variables: Descriptive statistics, independent t tests, analysis of variance, and Mann-Whitney U tests were used, and effect sizes were calculated.

Toward Autism-Friendly Magnetic Resonance Imaging: Exploring Autistic Individuals' Experiences of Magnetic Resonance Imaging Scans in the United Kingdom, a Cross-Sectional Survey.

Background: Autistic individuals might undergo a magnetic resonance imaging (MRI) examination for clinical concerns or research. Increased sensory stimulation, lack of appropriate environmental adjustments, or lack of streamlined communication in the MRI suite may pose challenges to autistic patients and render MRI scans inaccessible. This study aimed at (i) exploring the MRI scan experiences of autistic adults in the United Kingdom; (ii) identifying barriers and enablers toward successful and safe MRI examinations; (iii) assessing autistic individuals' satisfaction with MRI service; and (iv) informing future recommendations for practice improvement.

Participation of HIV-1 infected treatment-naive females in clinical trials and sex differences in efficacy and safety outcomes.

Objectives: To examine female participation and the observed efficacy and safety by sex from phase 3 HIV-1 trials submitted to the United States Food and Drug Administration (FDA) to support approval or a major labeling change.

Design: Our analyses were based on phase 3 trials in HIV-1 infected treatment-naive adults submitted to FDA since 2010.

Methods: We evaluated enrollment of treatment-naive females in 18 clinical trials for HIV-1.

Progress and opportunities for women in clinical trials: A look at recent data and initiatives from the U.S. FDA.

Recruiting and retaining diverse populations in clinical research is critically important. Over the years, we have seen improvements in the representation of women in clinical trials submitted in FDA marketing applications, and we are encouraged by the potential for new strategies to further their representation.

A systematic review of person-centred adjustments to facilitate magnetic resonance imaging for autistic patients without the use of sedation or anaesthesia.

Autistic patients often undergo magnetic resonance imaging examinations. Within this environment, it is usual to feel anxious and overwhelmed by noises, lights or other people. The narrow scanners, the loud noises and the long examination time can easily cause panic attacks.

Discovery of florylpicoxamid, a mimic of a macrocyclic natural product.

Natural products have routinely been used both as sources of and inspiration for new crop protection active ingredients. The natural product UK-2A has potent anti-fungal activity but lacks key attributes for field translation. Post-fermentation conversion of UK-2A to fenpicoxamid resulted in an active ingredient with a new target site of action for cereal and banana pathogens.

Ejaculate Allocation and Sperm Characteristics Differ among Alternative Male Types in a Species of Fish with Cooperation and Competition among Unrelated Males.

Sexual selection arising from sperm competition has driven the evolution of immense variation in ejaculate allocation and sperm characteristics not only among species, but also among males within a species. One question that has received little attention is how cooperation among males affects these patterns. Here we ask how male alternative reproductive types differ in testes size, ejaculate production, and sperm morphology in the ocellated wrasse, a marine fish in which unrelated males cooperate and compete during reproduction.

Autism-friendly MRI: Improving radiography practice in the UK, a survey of radiographer practitioners.

Introduction: Autistic individuals undergoing magnetic resonance imaging (MRI) examinations may face significant challenges, mainly due to sensory overload and MRI environment-related limitations. This study aimed to explore radiographers' perspectives and experiences regarding MRI scanning of autistic individuals.

Methods: Data collection was achieved using a specifically designed mixed methods questionnaire on Qualtrics.

A Case of Medullary Infarct Causing Central Alveolar Hypoventilation.

Central alveolar hypoventilation (CAH) is a rarely encountered pathology characterized by decreased ventilation due to the loss of autonomic control. Most cases present at birth, as it can be a rare genetic disorder, but we aim to show that it can occur as an acquired condition too. We present a case of a 65-year-old man who developed CAH as a sequela of an ischemic stroke and discuss possible pathophysiology.

Heterogeneity in treatment effects across diverse populations.

Differences in patient characteristics, including age, sex, and race influence the safety and effectiveness of drugs, biologic products, and medical devices. Here we provide a summary of the topics discussed during the opening panel at the 2018 Johns Hopkins Center for Excellence in Regulatory Science and Innovation symposium on Assessing and Communicating Heterogeneity of Treatment Effects for Patient Subpopulations: Challenges and Opportunities. The goal of this session was to provide a brief overview of FDA-regulated therapeutics, including drugs, biologics and medical devices, and some of the major sources of heterogeneity of treatment effects (HTE) related to patient demographics, such as age, sex and race.

Neurocysticercosis Presenting With a New-Onset Seizure: A Case Report.

Neurocysticercosis (NCC) is a common infection that is found worldwide but is often neglected in the United States (US). This case report aims to illustrate the presentation of the disease, provide information on this globally prevalent pathogen, and shed light on the diagnostic workup and treatment of the infection. We discuss the case of a 31-year-old male patient of Central American origin presenting with a new-onset seizure.

The Quality of End-of-Life Care for Women Deceased From Metastatic Breast Cancer.

Metastatic breast cancer (MBC) carries unique disease burdens with potential for poor-quality end-of-life (EOL) care. It is the purpose of this article to explore the association of poor-quality EOL care indicators according to key tumor, demographic, social, and clinical factors. End-of-life quality indicators were based on Emanuel and Emanuel's good death model in conjunction with Earle et al (2003).

Brain and placental transcriptional responses as a readout of maternal and paternal preconception stress are fetal sex specific.

Introduction: Despite a wealth of epidemiological evidence that cumulative parental lifetime stress experiences prior to conception are determinant of offspring developmental trajectories, there is a lack of insight on how these previous stress experiences are stored and communicated intergenerationally. Preconception experiences may impact offspring development through alterations in transcriptional regulation of the placenta, a major determinant of offspring growth and sex-specific developmental outcomes. We evaluated the lasting influence of maternal and paternal preconception stress (PCS) on the mid-gestation placenta and fetal brain, utilizing their transcriptomes as proximate readouts of intergenerational impact.

Protocol for Symptom Experience, Management, Outcomes, and Adherence in Women Receiving Breast Cancer Chemotherapy.

Background: The 5-year survival for Black women with breast cancer in the United States is lower than White women for stage-matched disease. Our past and ongoing work and that of others suggest that symptom incidence, cancer-related distress, and ineffective communication contribute to racial disparity in dose reduction and early therapy termination. Although race is perhaps the most studied social determinant of health, it is clear that race alone does not account for all disparities.

Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment.

Extracellular vesicles (EVs) are a unique mode of intercellular communication capable of incredible specificity in transmitting signals involved in cellular function, including germ cell maturation. Spermatogenesis occurs in the testes, behind a protective barrier to ensure safeguarding of germline DNA from environmental insults. Following DNA compaction, further sperm maturation occurs in the epididymis.

The new age of insecticide discovery-the crop protection industry and the impact of natural products.

Improvements in food production and disease vector control, to feed and protect an expanding global population, require new options and approaches for insect control. A changing and an increasingly stringent regulatory landscape, shifts in pest spectrum due to changes in agronomic practices, and insect resistance to existing insecticides, all contribute to the challenges of, and need for, developing new insect control agents. The nature of insecticides emanating from discovery R&D-based companies in the European Union, Japan, and the United States have evolved from a concentration on a few classes of insecticides and modes of action (MoA), to a far more diversified collection of insecticidal molecules that embody many new, or under-utilized MoAs.

Sedation practices in pediatric patients with acute lymphoblastic leukemia.

Background: The 5-year survival for pediatric acute lymphoblastic leukemia (ALL) is greater than 90%. One late effect of pediatric ALL associated with numerous long-term difficulties is neurocognitive deficits. The experience at our institution, as well as conversations with oncologists at other institutions, suggests an increase in the use of sedation during lumbar punctures (LPs) for treatment of pediatric ALL.

A preliminary ergonomic analysis of the MRI work system environment: Implications and recommendations for safety and design.

Introduction: The MRI work system environment in acute hospitals poses a significant risk of harm to patients, healthcare practitioners and others, but knowledge of hazards and potential design improvements are limited as safety research is lacking. The aim of this exploratory study was to understand how the discipline of Human Factors and Ergonomics (HFE) can support the understanding and improvement of safety and performance of MRI working environments.

Methods: A multi-method study of two MRI units in Scottish acute hospital settings based on Human Factors and Ergonomics (HFE) principles was undertaken in May 2016.

Symptom Experience, Management, and Outcomes According to Race and Social Determinants Including Genomics, Epigenomics, and Metabolomics (SEMOARS + GEM): an Explanatory Model for Breast Cancer Treatment Disparity.

Even after controlling for stage, comorbidity, age, and insurance status, black women with breast cancer (BC) in the USA have the lowest 5-year survival as compared with all other races for stage-matched disease. One potential cause of this survival difference is the disparity in cancer treatment, evident in many population clinical trials. Specifically, during BC chemotherapy, black women receive less relative dose intensity with more dose reductions and early chemotherapy cessation compared with white women.

The Impact of Age and Adjuvant Chemotherapy Modifications on Survival Among Black Women With Breast Cancer.

Background: Black women receive less relative dose intensity with more dose reductions and early chemotherapy cessation compared with White women. Adding further risk, older patients with breast cancer are most at risk for treatment modifications; however, it is unclear if this remains true for Black patients. Furthermore, the clinical implications of treatment modifications and delays on survival is uncertain, particularly in Black patients.