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Age is a major risk factor for severe coronavirus disease 2019 (COVID-19), yet the mechanisms behind this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host immune response in the blood and the upper airway, as well as the nasal microbiome in a prospective, multicenter cohort of 1031 vaccine-naïve patients hospitalized for COVID-19 between 18 and 96 years old. We performed mass cytometry, serum protein profiling, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays, and blood and nasal transcriptomics...

Predictions under interventions are estimates of what a person's risk of an outcome would be if they were to follow a particular treatment strategy, given their individual characteristics. Such predictions can give important input to medical decision-making. However, evaluating the predictive performance of interventional predictions is challenging. Standard ways of evaluating predictive performance do not apply when using observational data, because prediction under interventions involves obtaining predictions of the outcome under conditions that are different from those that are observed for a subset of individuals in the validation dataset...

PURPOSE: Although ongoing studies are assessing the efficacy of new systemic therapies for patients with triple negative breast cancer (TNBC), the overwhelming majority have excluded patients with brain metastases (BM). Therefore, we aim to characterize systemic therapies and outcomes in a cohort of patients with TNBC and BM managed with stereotactic radiosurgery (SRS) and delineate predictors of increased survival. METHODS: We used our prospective patient registry to evaluate data from 2012 to 2023...

In multiple myeloma (MM), B cell maturation antigen (BCMA)-directed CAR T cells have emerged as a novel therapy with potential for long-term disease control. Anti-BCMA CAR T cells with a CD8-based transmembrane (TM) and CD137 (41BB) as intracellular costimulatory domain are in routine clinical use. As the CAR construct architecture can differentially impact performance and efficacy, the optimal construction of a BCMA-targeting CAR remains to be elucidated. Here, we hypothesized that varying the constituents of the CAR structure known to impact performance could shed light on how to improve established anti-BCMA CAR constructs...

BACKGROUND AND PURPOSE: Efficient abstract scoring for congress presentation is important. Given the emergence of new study methodologies, a scoring system that accommodates all study designs is warranted. We aimed to assess the equivalence of a simplified, 2-question abstract grading system with a more complex currently used system in assessing abstracts submitted for orthopedic scientific meetings in a serial randomized study. METHODS: Dutch Orthopedic Association Scientific Committee (DOASC) members were randomized to grade abstracts using either the current grading system, which includes up to 7 scoring categories, or the new grading system, which consists of only 2 questions...

No abstract text is available yet for this article.

BACKGROUND: Collaborations between patient organisations (POs) and the pharmaceutical industry can help identify and address the unmet needs of people living with a disease. In Alzheimer's disease (AD), the scale and complexity of the current unmet needs call for a broad and cross-sectoral collaboration, including people living with Alzheimer's (PLWA), their care partners and the wider research community. OBJECTIVE: This study aimed to describe learnings from the Finding Alzheimer's Solutions Together (F...

BACKGROUND: Irish farmers are adversely affected by noncommunicable diseases. Although there has been an increase in farmer health promotion activities in Ireland, farmers views on lifestyle programs are currently unknown. OBJECTIVES: To qualitatively analyze the impact of the previously mentioned 6-week physical activity and health education intervention on farmer health and to investigate how best to support this cohort moving forward. METHODS: A qualitative study was conducted online (two interviews, three focus groups) with fourteen Irish farmers (53...

INTRODUCTION: People living with HIV receiving (PLWH) statin therapy have shown improved lipid profiles. However, they are not free from side effects, thereby requiring strict monitoring of the therapy. The meta-analysis aims to analyze the effect of statins in PLWH, and critically appraise the effectiveness of statin therapy in PLWH. METHODS: The PubMed, Scopus, and Web of Science servers were used to conduct a systematic search in compliance with the PRISMA guidelines...

BACKGROUND: Research on the lived experience of dementia is burgeoning across the social and health sciences. Yet, very little is still known about the experience of dementia for many tribes and ethnoreligious groups, as most studies are conducted in Western countries. OBJECTIVE: The aim is to advance the understanding of the role of faith and prayer in the lives of people with dementia in Nigeria through a lens of everyday citizenship. METHOD: Interviews were conducted with 17 older people with dementia in a low-income, Yoruba-speaking community in Southwestern Nigeria...

As we celebrate International Women's Day 2024 with the theme "Inspire Inclusion", the women of the ACS Medicinal Chemistry Division (MEDI) want to foster a sense of belonging, relevance, and empowerment by sharing uplifting stories of what inspired them to become medicinal chemists. In this editorial, we are featuring female medicinal chemistry scientists to provide role models, encouragement, and inspiration to others. We asked women medicinal chemists to contribute a brief paragraph about what inspired them to become medicinal chemists or what inspires them today as medicinal chemists...

RATIONALE & OBJECTIVE: Kidney function can be adversely affected by significant tricuspid regurgitation (TR) owing to effects on cardiac output and systemic venous congestion. However, the impact of significant TR on short- and long-term kidney function following a kidney transplant remains uncertain. STUDY DESIGN: Retrospective observational cohort. SETTING & PARTICIPANTS: Kidney transplant recipients from a single center between 2016 and 2019...

No abstract text is available yet for this article.

OBJECTIVE: To develop a consensus guideline to meet nutritional challenges faced by infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: The CDH Focus Group utilized a modified Delphi method to develop these clinical consensus guidelines (CCG). Topic leaders drafted recommendations after literature review and group discussion. Each recommendation was sent to focus group members via a REDCap survey tool, and members scored on a Likert scale of 0-100...

The alternative splicing of PML precursor mRNA gives rise to various PML isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers. PML depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER+ breast cancer, in a mouse model...

Constitutional loss of SMAD4 function results in Juvenile Polyposis-Hereditary Haemorrhagic Telangiectasia Overlap Syndrome (JP-HHT). A retrospective multi-centre case-note review identified 28 patients with a pathogenic SMAD4 variant from 13 families across all Scottish Clinical Genetics Centres. This provided a complete clinical picture of the Scottish JP-HHT cohort. Colonic polyps were identified in 87% (23/28) and gastric polyps in 67% (12/18) of screened patients. Complication rates were high: 43% (10/23) of patients with polyps required a colectomy and 42% (5/12) required a gastrectomy...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

PURPOSE: Personalized medicine poses great opportunities and challenges. While therapeutic landscape markedly expands, descriptions about status, clinical implementation and real-world benefits of precision oncology and molecular tumor boards (MTB) remain sparse, particularly in the field of genitourinary (GU) cancer. Hence, this study characterized urological MTB cases to better understand the potential role of MTB in uro-oncology. METHODS: We analyzed patients with complete data sets being reviewed at an MTB from January 2019 to October 2022, focusing on results of molecular analysis and treatment recommendations...

INTRODUCTION: Opioids are commonly used for perioperative analgesia, yet children still suffer high rates of severe post-surgical pain and opioid-related adverse effects. Persistent and severe acute surgical pain greatly increases the child's chances of chronic surgical pain, long-term opioid use, and opioid use disorder. AREAS COVERED: Enhanced recovery after surgery (ERAS) protocols, are often inadequate in treating a child's severe surgical pain. Research suggests that 'older' and longer-acting opioids such as methadone are providing better methods to treat acute post-surgical pain...