Pharmacologic Management of Heart Failure with Preserved Ejection Fraction (HFpEF) in Older Adults.

There are several pharmacologic agents that have been touted as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF). However, it is important to recognize that older adults with HFpEF also contend with an increased risk for adverse effects from medications due to age-related changes in pharmacokinetics and pharmacodynamics of medications, as well as the concurrence of geriatric conditions such as polypharmacy and frailty. With this review, we discuss the underlying evidence for the benefits of various treatments in HFpEF and incorporate key considerations for older adults, a subpopulation that may be at higher risk for adverse drug events.

Utility of Parent and Teacher Behavior Ratings for Self-Regulatory Outcomes of Preschool Children: A Multi-Study Examination.

Despite frequent reliance on teacher and parent ratings of children's behavior for multi-informant assessment, agreement between teachers' and parents' ratings is low. This study examined the predictive utility of teacher and parent ratings for children's self-regulatory outcomes (i.e.

Light buckets and laser beams: mechanisms and applications of photobiomodulation (PBM) therapy.

Photobiomodulation (PBM) therapy, a non-thermal light therapy using nonionizing light sources, has shown therapeutic potential across diverse biological processes, including aging and age-associated diseases. In 2023, scientists from the National Institute on Aging (NIA) Intramural and Extramural programs convened a workshop on the topic of PBM to discuss various proposed mechanisms of PBM action, including the stimulation of mitochondrial cytochrome C oxidase, modulation of cell membrane transporters and receptors, and the activation of transforming growth factor-β1. They also reviewed potential therapeutic applications of PBM across a range of conditions, including cardiovascular disease, retinal disease, Parkinson's disease, and cognitive impairment.

Cohort study on the Effect of various nicotine consumption modalities on Mohs surgery complications.

Knowledge on the effect of different nicotine consumption modalities on dermatologic surgical outcomes is limited, with conflicting conclusions. Cigarette smoking is known to adversely affect outcomes, but the impact of other nicotine consumption modalities like cigars, smokeless tobacco, and nicotine replacement therapy (NRT) is less understood. Our objective was to evaluate the impact of various nicotine consumption modalities on complication rates after Mohs micrographic surgery (MMS).

Nanoscale Viscometry Reveals an Inherent Mucus Defect in Cystic Fibrosis.

The abnormally viscous and thick mucus is a hallmark of cystic fibrosis (CF). How the mutated CF gene causes abnormal mucus remains an unanswered question of paramount interest. Mucus is produced by the hydration of gel-forming mucin macromolecules that are stored in intracellular granules prior to release.

Impact of Recent Translational and Therapeutic Developments on Clinical Course of BCR::ABL1-Positive and -Negative Myeloproliferative Neoplasms.

Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues.

New onset refractory status epilepticus: Long-term outcomes beyond seizures.

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.

Supporting students with complex communication needs: special education teachers' reflections on their training.

Special education teachers support students with complex communication needs across the day. Yet, evidence suggests that these professionals are entering the field without being fully prepared to support these students by having the knowledge and skill to implement augmentative and alternative communication practices. The lack of preparedness from these professionals creates barriers for students with complex communication needs, their families, and other team members.

Response to neoadjuvant chemotherapy leads to better survival outcomes in upper tract urothelial carcinoma.

Objectives: To evaluate the benefit of neoadjuvant chemotherapy (NAC) for patients with high-risk upper tract urothelial carcinoma (UTUC) using a large, well-curated multi-institutional database.

Patients And Methods: This study was a multi-institutional retrospective analysis conducted by the UTUC Collaborative Network (UCAN), combining data from 2276 patients with UTUC who underwent radical nephroureterectomy at seven high-volume tertiary care centres in the United States. The UCAN data were analysed to evaluate the impact of response to NAC on survival outcomes in patients with UTUC.

Impacts of Ethical Dilemmas and Moral Distress in Pediatric Hematology Oncology Nurses.

Purpose: To assess the level of moral distress (MD) and perceptions of ethical climate among pediatric hematology/oncology (PHO) nurses and to identify bioethics topics where increased education was desired.

Methods: In this cross-sectional study, we administered the 26-item Swedish Moral Distress Scale-Revised (sMDS-R), specifically revised and validated for pediatric oncology, in conjunction with the Clinical Ethics Needs Assessment Survey (CENAS). Electronic surveys were sent to inpatient and outpatient PHO nurses.

Nursing knowledge in cardio-oncology: results of an international learning needs-assessment survey.

Background: With early detection and improvements in systemic and local therapies, millions of people are surviving cancer, but for some at a high cost. In some cancer types, cardiovascular disease now competes with recurrent cancer as the cause of death. Traditional care models, in which the cardiologist or oncologist assess patients individually, do not address complex cancer and cardiovascular needs.

Enhancer regulatory networks globally connect non-coding breast cancer loci to cancer genes.

Background: Genetic studies have associated thousands of enhancers with breast cancer (BC). However, the vast majority have not been functionally characterized. Thus, it remains unclear how BC-associated enhancers contribute to cancer.

Evaluation of macular retinal oximetry across different levels of diabetic retinopathy: a cross sectional study.

Background: This study evaluates retinal oxygen saturation and vessel density within the macula and correlates these measures in controls and subjects with type 2 diabetes (DM) with (DMR) and without (DMnR) retinopathy. Changes in retinal oxygen saturation have not been evaluated regionally in diabetic patients.

Methods: Data from seventy subjects (28 controls, 26 DMnR, and 16 DMR were analyzed.

Knowledge, attitude and practices regarding vitamin D among adults in Ghana: a cross-sectional study.

Background: Vitamin D deficiency is a major public health concern, affecting approximately half of the world's population, partly due to limited public knowledge about vitamin D sources. However, there is lack of data on awareness, knowledge, attitudes, and practices regarding vitamin D in high-risk countries like Ghana. We investigated vitamin D awareness, knowledge and its associated factors in the Ghanaian population.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Comparison of failure rates between full-barium and striped barium distal shunt catheters: a matched case-control study.

Purpose: We hypothesize that distal shunt catheters fully impregnated with barium are more prone to failure compared to distal catheters with only a barium stripe. We sought to evaluate this distinction using a matched case-control study.

Methods: Patient records over an 8-year period were queried for distal shunt revisions for fracture or disconnection (cases).

Survey and perspective on verification, validation, and uncertainty quantification of digital twins for precision medicine.

Digital twins in precision medicine provide tailored health recommendations by simulating patient-specific trajectories and interventions. We examine the critical role of Verification, Validation, and Uncertainty Quantification (VVUQ) for digital twins in ensuring safety and efficacy, with examples in cardiology and oncology. We highlight challenges and opportunities for developing personalized trial methodologies, validation metrics, and standardizing VVUQ processes.

Defective homologous recombination and genomic instability predict increased responsiveness to carbon ion radiotherapy in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is notably resistant to conventional chemotherapy and radiation treatment. However, clinical trials indicate that carbon ion radiotherapy (CIRT) with concurrent gemcitabine is effective for unresectable locally advanced PDAC. This study aimed to identify patient characteristics predictive of CIRT response.

Spin transport properties in a topological insulator sandwiched between two-dimensional magnetic layers.

Non-trivial band topology along with magnetism leads to different novel quantum phases. When time-reversal symmetry is broken in three-dimensional topological insulators (TIs) through, e.g.

SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs.

SAMHD1 is a dNTPase that impedes replication of HIV-1 in myeloid cells and resting T lymphocytes. Here we elucidate the substrate activation mechanism of SAMHD1, which involves dNTP binding at allosteric sites and transient tetramerization. Our findings reveal that tetramerization alone is insufficient to promote dNTP hydrolysis; instead, the activation mechanism requires an inactive tetrameric intermediate with partially occupied allosteric sites.

Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

Soil Nitrogen Supply Exerts Largest Influence on Leaf Nitrogen in Environments with the Greatest Leaf Nitrogen Demand.

Accurately representing the relationships between nitrogen supply and photosynthesis is crucial for reliably predicting carbon-nitrogen cycle coupling in Earth System Models (ESMs). Most ESMs assume positive correlations amongst soil nitrogen supply, leaf nitrogen content, and photosynthetic capacity. However, leaf photosynthetic nitrogen demand may influence the leaf nitrogen response to soil nitrogen supply; thus, responses to nitrogen supply are expected to be the largest in environments where demand is the greatest.