Navigating the landscape of personalized oncology: overcoming challenges and expanding horizons with computational modeling.

Objectives: We discuss challenges using computational modeling approaches for personalized prediction in clinical practice to predict treatment response for rare diseases treated by novel therapies using clinical oncology as an example context. Several challenges are discussed, including data scarcity, data sparsity, and difficulties in establishing interdisciplinary teams. Machine learning (ML), mechanistic modeling (MM), and hybrid modeling (HM) are discussed in the context of these challenges.

Heterogeneity of Lung Phagocytes and Clearance of Apoptotic Cells in Lung Injury and Repair.

Poor repair following lung injury is a significant cause of morbidity and mortality. Clearance of apoptotic cells, termed efferocytosis, has emerged as a key process that can influence repair outcomes and facilitate successful repair. Although prior literature has focused on efferocytosis by macrophages, evidence is emerging that nonprofessional phagocytes, including fibroblasts and epithelial cells, may play critical roles in efferocytosis during tissue repair.

Caffeine impairs red blood cell storage quality by dual inhibition of ADORA2b signaling and G6PD activity.

Caffeine is the most widely consumed psychoactive substance globally, yet its peripheral physiological effects remain incompletely understood. Leveraging comprehensive data from 13,091 blood donors in the REDS RBC-Omics study, we identify caffeine as a significant modulator of red blood cell (RBC) storage quality and transfusion outcomes. Elevated caffeine levels were reproducible across multiple donations from 643 recalled donors, selected based on their extremes in hemolytic propensity.

Cardiorespiratory Fitness, Physical Activity, Sedentary Behavior, and Diabetes Risk Among Breast Cancer Survivors Treated with Endocrine Therapies.

Endocrine therapies for breast cancer (BC) (i.e., selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AI)) lower the risk for cancer recurrence but are linked to an increased risk of type 2 diabetes (T2D).

Power and sample size for reversible linear mixed models with clustering and longitudinality: GLIMMPSE Version 3.

GLIMMPSE Version 3 is a free, web-based, open-source software tool, which calculates power and sample size for general linear mixed models with Gaussian errors. The software permits power calculations for clinical trials, randomized experiments, and observational studies with clustering, repeated measures, and both, and almost any testable hypothesis. The software has been supported by five United States National Institutes of Health (NIH) grants, is used for more than 14,000 power or sample size calculations per year, has been cited in almost 500 peer-reviewed manuscripts, and used to design more than 200 million dollars in NIH-funded studies.

IL15/IL15Ra complex induces an anti-tumor immune response following radiation therapy only in the absence of Tregs and fails to expand progenitor TCF1+ CD8 T cells.

In this work, we show that the combination of radiation therapy (RT) and an IL15/IL15Rα fusion complex (denoted IL15c) fails to confer anti-tumor efficacy; however, a CD8-driven anti-tumor immune response can be elicited with the concurrent administration of an aCD25 Treg-depleting antibody. Using IL15-/- and Rag1-/- knockout mouse models, we show that the response to RT + IL15c + aCD25 is dependent on both IL15 and CTLs. Furthermore, despite an equivalent survival benefit following treatment with RT + IL15c + aCD25 and combination RT and PD1-IL2v, a novel immunocytokine with PD-1 and IL2Rbg binding domains, CTL immunophenotyping and phospho-proteomic analysis of intracellular metabolites showed a significant upregulation of activation and functionality in CD8 T cells in the RT + PD1-IL2v regimen.

Displacement-encoded MRI reveals biomechanical stiffening in rheumatoid arthritis wrists: a case control study.

Identifying and diagnosing early-stage rheumatoid arthritis (RA) has remained an unmet challenge in medicine and a roadblock to identifying treatments at time points when disease-modifying therapies may be most effective. Recent studies have demonstrated that imaging the response of cartilage under mechanical loading, as well as alterations in matrix macro- and micro-molecule composition, could serve as potential biomarkers to identify tissue degeneration. Therefore, the objective of this paper was to identify RA-related cartilage degeneration in human wrists using novel MRI techniques.

Team science training for clinical and translational Scientists: An assessment of effectiveness.

Introduction: Effective interdisciplinary collaboration is essential for addressing complex clinical and translational research challenges. This paper presents and evaluates a structured team science training program developed by the Colorado Clinical and Translational Sciences Institute (CCTSI), while also introducing and validating a novel assessment tool used to measure changes in key teaming competencies.

Methods: We evaluated the effectiveness of this program between 2020 and 2022 using pre- and post-program surveys ( = 221).

Crush syndrome diagnosis and management in resource-constrained settings: A Delphi study.

Background: Crush syndrome is an important source of morbidity and mortality in resource-constrained settings including earthquake disaster zones, austere military environments, and countries where motor vehicle collisions and interpersonal violence are prevalent. In South Africa and other countries with high rates of community violence, patients develop crush due to a unique form of trauma called community assault, where individuals suspected of wrongdoing are assaulted by multiple persons as a form of mob justice. The purpose of this study is to generate consensus about crush syndrome definitions and endpoints to inform the development of scoring systems appropriate for community assault and usable in resource-limited settings.

Exploring Dropbox image downloads to iPhone via safari: File system versus camera roll validation study.

This study evaluated the forensic integrity of digital images transferred from Dropbox to iPhones via Safari, a practical scenario for evidence collection when specialized tools are unavailable. Using a quantitative, quasi-experimental design, we analyzed 60 images across three iPhones (running iOS 14.2 and 14.

Increased Exercise Tolerance in G6PD African Variant Mice Driven by Metabolic Adaptations and Erythrophagocytosis.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymatic disorder, affects over 500 million people worldwide and is often linked to exercise intolerance due to oxidative stress, but its true impact on physical performance remains unclear. This study aimed to evaluate the physiological and metabolic effects of G6PD deficiency on endurance capacity. Using humanized mice carrying the African G6PD variant [V68M; N126D] (hG6PD), we show that despite reduced pentose phosphate pathway activity, these mice exhibit a 10.

The person-centered hypothesis framework: Advancing clinical reasoning in musculoskeletal pain management.

Introduction: The Person-Centered Hypothesis (PCH) framework is a structured clinical reasoning model designed to enhance "in action" reasoning in person-centered care (PCC). The PCH integrates elements of the biopsychosocial model, pain phenotyping, and contextual factors, addressing gaps in real-time clinical decision-making.

Purpose: To describe the proposed PCH framework that synthesizes four domains: dominant pain phenotype(s), relevant clinical patterns, regional and co-existing contributors, and psychosocial and lifestyle influencing factors.

Fertility Desires and Contraceptive Transition.

Fertility desires are fundamental to understanding contraceptive use, yet the relationship between the two remains unclear and is the subject of much debate in demography. To understand the macro-level relationship between fertility desires and contraceptive transition in low- and middle-income countries, we introduce a conceptual model that articulates the micro-level processes through which a desire to avoid childbearing translates into contraceptive use and reasons for their frequent misalignment. The model calls for a more nuanced understanding of fertility desires, differentiates between the acceptability and accessibility of contraception, and highlights the multilevel forces that shape the costs of fertility regulation.

Developing sex-accurate cell culture environments.

The extracellular matrix remains under-recognized as a sex-dependent entity. Designing culture environments that account for sex as a biological variable requires considering not only cellular sex, but also the usage of sex-specific scaffolds to create a holistically sex-accurate platform.

Development of a Novel, Low-Power, Ultrasound Algorithm for the Detection of Pneumothorax Using a Large Animal Model.

Introduction: Tension pneumothorax is the third leading cause of potentially survivable death in the prehospital, combat setting. Identification of the presence of a pneumothorax before tension physiology develops remains challenging in this setting. We conducted an early developmental pilot study to determine if unprocessed raw radio frequency (RF) data from a single-crystal ultrasound array could fill this gap.

Relationship Dynamics and Young Women's Contraceptive Use.

Introduction: Research from sub-Saharan Africa has shown that women's relationships and partners influence their contraceptive use. Most relevant studies focus on relationship status with few considering how the quality of a relationship might influence women's use of contraceptives. This study is the first to examine how both positive and negative relationship dynamics are associated with young women's modern contraceptive use among those who want to postpone pregnancy for at least two years or stop childbearing altogether.

8-Oxo-7,8-dihydropurines as Building Blocks to Enhance the Selectivity of an RNA Aptamer for Aminoglycosides.

The use of nucleic acids as potential therapeutic tools, sensors, or biomaterials, among other applications, has dramatically increased. Among these, RNA aptamers are of interest due to an innate high specificity toward their cognate targets, which include small molecules, proteins, ions, or cells. In this work, we took advantage of the ability that 8-oxo-7,8-dihydroguanine (8-oxoG) has to participate in unique H-bonding interactions, and probed its use to increase/control the selectivity/affinity of aptamers of RNA and DNA.

A Linguistic Appreciation for the Art of Nursing.

This paper examines the art of nursing through linguistic appreciation interpreted from Paley's method of concept analysis and is situated within Carper's fundamental ways of knowing. Examining the theoretical framework for the art of nursing, a historical exploration for disciplinary dialogue, analyzing and interpreting existing art of nursing literature, and identifying prominent attributes embrace multiple conceptions. Five constitutive meanings develop the art of nursing as: a craft, an aesthetic, nursing science, transpersonal caring, and multiple ways of knowing.

Plasma lipid levels predict chemotherapy response and survival in acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by a low five-year survival rate. Despite having many clinical metrics to assess patient prognosis, there remain opportunities to improve risk stratification. We hypothesized that an underexplored resource to examine AML patient prognosis is the plasma metabolome.

CICADA: An automated and flexible tool for comprehensive fMRI noise reduction.

Independent component analysis (ICA) denoising methods can be highly effective for reducing functional magnetic resonance imaging (fMRI) noise. ICA denoising method success heavily depends, however, on the accurate classification of fMRI data ICs as either neural signal or noise. While manual IC classification ("manual ICA denoising") is a current gold-standard, it requires extensive time and training.

From metabolomics to transfusion-associated immunomodulation.

Purpose Of Review: This review summarizes recent advances in metabolomics that have enhanced our understanding of transfusion-related immunomodulation (TRIM), highlighting how biochemical changes in stored blood products - with a focus on packed red blood cells - affect recipient immune responses.

Recent Findings: Metabolomics has revealed critical biochemical shifts - termed storage lesions - in blood products, notably accumulation of oxidized lipids, extracellular vesicles, and hemolysis-derived molecules, such as free heme and iron. These metabolites influence recipient immunity by triggering both inflammatory and immunosuppressive pathways, mediated through mechanisms involving redox imbalance, inflammasome activation, and modulation of immune cell metabolism.

Effects of Inhaled Tobacco and Cannabis Co-Use on Respiratory Health and Tobacco Cessation. An Official American Thoracic Society Research Statement.

Background: Tobacco and cannabis are among the most widely used substances globally, and rates of co-use are on the rise. Understanding the impact of inhaled tobacco-cannabis co-use on health outcomes and tobacco cessation is critical for guiding patients and clinicians.

Objectives: To summarize the existing evidence, identify knowledge gaps, and prioritize research questions related to effects of inhaled tobacco-cannabis co-use on tobacco cessation and lung health.

Frailty, Pitavastatin, and Major Adverse Cardiovascular Events Among People With HIV.

Background: People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular diseases (ASCVDs) and geriatric syndromes, including frailty. REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) demonstrated a 36% reduction in major adverse cardiovascular events (MACE) with pitavastatin vs placebo but the role of statins for ASCVD prevention among frail PWH is not known.

Objectives: The purpose of this study was to evaluate whether frailty is associated with MACE and whether pitavastatin prevents MACE regardless of frailty.