Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Future challenges for UK regulation of brain organoid research.

One of this century's most dramatic scientific developments is the reprogramming of stem cells in order to create organoids, that is, self-organizing 3D models that mimic the structure and function of human organs. This article considers whether brain organoids in particular might raise any new questions for law, now or in the near future. If complex human brain organoids were to become capable of consciousness or sentience, the current regulation of human tissue research, which protects the interests of tissue donors, might need to be supplemented in order to protect the interests of the tissue itself.

A systematic review of parent-child communication in pediatric asthma.

Objective: Parent-child communication is integral to pediatric asthma management. This review evaluates parent-child communication among youth with asthma and their caregivers. It aims to characterize the type of communication according to a unifying framework (Murphy, L.

Nickel-Catalyzed O-Arylation of N-Protected Amino Alcohols with (Hetero)aryl Chlorides.

The aryloxyamine motif is a prominent pharmacophore in drug design and development. While these biologically relevant structures could in principle be sustainably assembled from the base metal-catalyzed O-arylation of inexpensive and abundant amino alcohols with (hetero)aryl chlorides, reports of such challenging C-O bond formations with useful scope are lacking. In response, we report herein the hitherto unknown Ni-catalyzed C-O cross-coupling of N-protected amino alcohols (primary, secondary, and tertiary) with (hetero)aryl chlorides.

Rapamycin improves satellite cells' autophagy and muscle regeneration during hypercapnia.

Both CO2 retention, or hypercapnia, and skeletal muscle dysfunction predict higher mortality in critically ill patients. Mechanistically, muscle injury and reduced myogenesis contribute to critical illness myopathy, and while hypercapnia causes muscle wasting, no research has been conducted on hypercapnia-driven dysfunctional myogenesis in vivo. Autophagy flux regulates myogenesis by supporting skeletal muscle stem cell - satellite cell - activation, and previous data suggest that hypercapnia inhibits autophagy.

Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals.

The origins of sex differences in human disease are elusive, in part because of difficulties in separating the effects of sex hormones and sex chromosomes. To separate these variables, we examined gene expression in four groups of trans- or cisgender individuals: XX individuals treated with exogenous testosterone (n=21), XY treated with exogenous estradiol (n=13), untreated XX (n=20), and untreated XY (n=15). We performed single-cell RNA-sequencing of 358,426 peripheral blood mononuclear cells.

Succinate dehydrogenase-complex II regulates skeletal muscle cellular respiration and contractility but not muscle mass in genetically induced pulmonary emphysema.

Reduced skeletal muscle mass and oxidative capacity coexist in patients with pulmonary emphysema and are independently associated with higher mortality. If reduced cellular respiration contributes to muscle atrophy in that setting remains unknown. Using a mouse with genetically induced pulmonary emphysema that recapitulates muscle dysfunction, we found that reduced activity of succinate dehydrogenase (SDH) is a hallmark of its myopathic changes.

Regulating embryo models in the UK.

One of this century's most dramatic scientific developments is the reprogramming of stem cells in order to create self-organizing embryo-like entities, known as stem cell based embryo models (SCBEMs). The science is moving very quickly, but if, as increasingly appears to be the case, scientists are capable of creating entities that are effectively indistinguishable from sperm and egg derived embryos, important legal questions arise. In countries like the UK, where a strict regulatory regime applies to research on embryos, should this be extended to SCBEM research, or would a different regulatory response be appropriate? Drawing on the 1984 Warnock Report, the Human Fertilisation and Embryology Act 1990 and the latest guidelines from the International Society for Stem Cell Research, this article considers principles for the regulation of the creation and use of SCBEMs.

Habitat and Respiratory Strategy Effects on Hypoxia Performance in Anuran Tadpoles.

A critical component of animal conservation in a changing world is an understanding of the physiological resilience of animals to different conditions. In many aquatic animals, hypoxia (low environmental oxygen levels) is a regular occurrence, but the likelihood and severity of hypoxia vary across habitats. Fast-flowing, stream-like habitats are never hypoxic, so long as flow is maintained.

Medicine in the marketplace: clinician and patient views on commercial influences on assisted reproductive technology.

Research Question: What are the views and experiences of patient and expert stakeholders on the positive and negative impacts of commercial influences on the provision of assisted reproductive technology (ART) services, and what are their suggestions for governance reforms?

Design: Semi-structured interviews were conducted with 31 ART industry experts from across Australia and New Zealand and 25 patients undergoing ART from metropolitan and regional Australia, between September 2020 and September 2021. Data were analysed using thematic analysis.

Results: Expert and patient participants considered that commercial forces influence the provision of ART in a number of positive ways - increasing sustainability, ensuring consistency in standards and providing patients with greater choice.

Key Considerations for the Treatment of Advanced Breast Cancer in Older Adults: An Expert Consensus of the Canadian Treatment Landscape.

The prevalence of breast cancer amongst older adults in Canada is increasing. This patient population faces unique challenges in the management of breast cancer, as older adults often have distinct biological, psychosocial, and treatment-related considerations. This paper presents an expert consensus of the Canadian treatment landscape, focusing on key considerations for optimizing selection of systemic therapy for advanced breast cancer in older adults.

How do universities support communication skills for clinical placements with culturally and linguistically diverse students? A scoping review.

Aim: The aim of this scoping review was to examine and synthesise contemporary research on clinical communication interventions for tertiary students from a culturally and linguistically diverse background enrolled in a health professional qualification.

Background: Clinical communication competence is essential to high quality healthcare and thus is a critical component of all health professional education. The rise in tertiary students from non-English speaking backgrounds in Australia and many other countries has escalated concern over the communication skills required for success in clinical placements and future practice as a health professional.

Current Challenges and Disparities in the Delivery of Equitable Breast Cancer Care in Canada.

Recent exciting advances in the diagnosis and management of breast cancer have improved outcomes for Canadians diagnosed and living with breast cancer. However, the reach of this progress has been uneven; disparities in accessing care across Canada are increasingly being recognized and are at risk of broadening. Members of racial minority groups, economically disadvantaged individuals, or those who live in rural or remote communities have consistently been shown to experience greater challenges in accessing 'state of the art' cancer care.

Human embryo models: the importance of national policy and governance review.

Integrated and non-integrated stem cell-based embryo models are becoming widely adopted tools in biomedical research with distinct advantages over animal models for studying human development. Although SCB-EMs have tremendous benefits for research, they raise a number of social, ethical and legal questions that affect future research and widespread adoption in industry and clinical settings. The 2021 International Society for Stem Cell Research Guidelines for Stem Cell Research and Clinical Translation provide helpful guidance on many of these issues but do not have force in domestic law.

Sequencing of Endocrine and Targeted Therapies in Hormone-Sensitive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.

Journal of Clinical OncologyOptimizing the selection and sequencing of endocrine and targeted therapies for hormone-sensitive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer is a rapidly evolving field owing in large part to an increasing pace of drug development coupled with a greater understanding of the genomic drivers of breast cancer. The recently published results from the MAINTAIN clinical trial begin to answer an important question in this patient population-can the well-established benefit with first-line cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors be stretched further by continuing this drug class beyond progression and selecting an alternate endocrine therapy partner? We present a case of a patient with hormone-sensitive HER2 low metastatic breast cancer who underwent circulating tumor DNA next-generation sequencing to better inform her treatment options after progression on first-line therapy with a CDK 4/6 inhibitor and aromatase inhibitor. Our clinical approach in this patient population prioritizes the identification of actionable mutations with high-quality evidence for efficacy on the basis of clinical trials post-CDK 4/6 inhibitors, while balancing comorbidities and patient priorities for care.

Assessing the language of 2 year-olds: From theory to practice.

Early screening for language problems is a priority given the importance of language for success in school and interpersonal relationships. The paucity of reliable behavioral instruments for this age group prompted the development of a new touchscreen language screener for 2-year-olds that relies on language comprehension. Developmental literature guided selection of age-appropriate markers of language disorder risk that are culturally and dialectally neutral and could be reliably assessed.

A Psychosocial Care Model for Families Affected by Congenital Heart Disease.

Objectives: To develop a model of family-based psychosocial care for congenital heart disease (CHD).

Design: Qualitative study using crowdsourced data collected from parents of young children with CHD who received care across 42 hospitals.

Setting: Yammer, a social networking platform used to facilitate online crowdsourcing and qualitative data collection.

Feasibility of Virtually Delivering Functional Fitness Assessments and a Fitness Training Program in Community-Dwelling Older Adults.

The COVID-19 pandemic limited older adults' access to preventative and diagnostic services and negatively affected accessibility to age-appropriate exercise programs. The purpose of this study was to assess the feasibility of conducting guided virtual functional fitness assessments before and after participation in an 8-week virtual, live fitness program (Vivo) designed for older adults. It was hypothesized there would be no significant difference between in-person and virtual functional fitness assessments and function would improve following the program.

Is the use of IVF add-on treatments driven by patients or clinics? Findings from a UK patient survey.

There are conflicting narratives over what drives demand for add-ons. We undertook an online survey of IVF patients to determine whether patients perceive that use of IVF add-ons is driven by patients or practitioners. People who underwent IVF in the UK in the previous five years were recruited via social media Survey questions focussed on the roles of clinician offer and patient request, including who first suggested use of add-ons in IVF consultations, where patients first heard about them, and which information sources they trusted.

Lack of correlation between growth rate and sequence type among Cronobacter sakazakii.

Species identification and growth rates for a collection of Cronobacter strains from clinical and non-clinical sources have been previously reported. However, advancements in DNA sequencing-based identification methods now allow for more accurate identification. Here we report the sequence types (STs) for 24 strains of Cronobacter sakazakii and examine any possible correlation between sequence type and growth rate, which could influence risk through greater pathogen multiplication and reach of infectious doses during time between formula preparation and feeding.