A Population Pharmacokinetic Analysis to Evaluate the Impact of Renal Impairment on the Pharmacokinetics of Iberdomide.

Iberdomide, a novel potent cereblon E3 ligase modulator, is under investigation for multiple myeloma. This study assessed how renal impairment (RI) affects iberdomide pharmacokinetics (PK). Twenty-six subjects with varying renal function, including those with severe renal impairment and those requiring intermittent hemodialysis (IHD), received a single oral 1 mg dose of iberdomide.

Bioimpedance Measurements of Fibrotic and Acutely Injured Lung Tissues.

In injured and diseased tissues, changes in molecular and cellular compositions, as well as tissue architecture, lead to alterations in both physiological and physical characteristics. Notably, the electrical properties of tissues, which can be characterized as bioelectrical impedance (bioimpedance), are closely linked to the health and pathological conditions of the tissues. This highlights the significant role of quantitatively characterizing these electrical properties in improving the accuracy and speed of diagnosis and prognosis.

Enhancing brain tumor surgery precision with multimodal connectome imaging: Structural and functional connectivity in language-dominant areas.

Objectives: Language is a critical aspect of human cognition and function, and its preservation is a priority for neurosurgical interventions in the left frontal operculum. However, identification of language areas can be inconsistent, even with electrical mapping. The use of multimodal structural and functional neuroimaging in conjunction with intraoperative neuromonitoring may augment cortical language area identification to guide the resection of left frontal opercular lesions.

Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.

How can we make sound replication decisions?

Replication and the reported crises impacting many fields of research have become a focal point for the sciences. This has led to reforms in publishing, methodological design and reporting, and increased numbers of experimental replications coordinated across many laboratories. While replication is rightly considered an indispensable tool of science, financial resources and researchers' time are quite limited.

Automating the practice of science: Opportunities, challenges, and implications.

Automation transformed various aspects of our human civilization, revolutionizing industries and streamlining processes. In the domain of scientific inquiry, automated approaches emerged as powerful tools, holding promise for accelerating discovery, enhancing reproducibility, and overcoming the traditional impediments to scientific progress. This article evaluates the scope of automation within scientific practice and assesses recent approaches.

Is Ockham's razor losing its edge? New perspectives on the principle of model parsimony.

The preference for simple explanations, known as the parsimony principle, has long guided the development of scientific theories, hypotheses, and models. Yet recent years have seen a number of successes in employing highly complex models for scientific inquiry (e.g.

How should the advancement of large language models affect the practice of science?

Large language models (LLMs) are being increasingly incorporated into scientific workflows. However, we have yet to fully grasp the implications of this integration. How should the advancement of large language models affect the practice of science? For this opinion piece, we have invited four diverse groups of scientists to reflect on this query, sharing their perspectives and engaging in debate.

Immune checkpoint inhibitors in pediatric patients with melanoma: a systematic literature review.

This study summarized the existing evidence on the outcomes and safety of anti-PD-1s, anti-PD-L1s and anti-CTLA-4s in pediatric patients with melanoma. MEDLINE and Embase were searched from database inception to 01-12-2023. Of 1537 records identified, 27 studies (k) of 64 patients were included.

Tissue Selective Ultrasonic Debridement with Cryopreserved Human Skin Allograft to Heal a Chronic Wound: A Case Report.

Tissue selective ultrasonic debridement is a new method of debriding chronic wounds that prepares the wound for advanced tissue application. This article presents the case of an 89-year-old woman with a chronic nonhealing wound to her lateral distal leg. The wound had a significant amount of biofilm and fibrous slough.

Heel Offloading Posterior Splint for Treatment of Heel Ulcerations.

Total contact casting is the gold standard for plantar foot ulcers but has been questioned in heel pressure ulcers. Current offloading of heel ulcers is typically removable offloading boots. We describe using a modified posterior splint to offload heel ulcers in nonweightbearing patients.

Anxiety and Depression Affect Sleep Quality: A Preliminary Investigation in Crowdsourced Samples of Autistic and Non-Autistic Adults.

We aimed to compare sleep problems in autistic and non-autistic adults with co-occurring depression and anxiety. The primary research question was whether autism status influences sleep quality, after accounting for the effects of depression and anxiety. We hypothesized that autistic adults would report higher levels of depression, anxiety, and sleep problems compared to non-autistic adults, after controlling for these covariates.

The Johns Hopkins Hope at Hopkins Clinic: supporting the comprehensive needs of individuals with metastatic breast cancer.

Purpose: Individuals with metastatic breast cancer (MBC) may live with their disease for many years. We initiated the Johns Hopkins Hope at Hopkins Clinic to assess the needs and optimize the care of these patients.

Patients And Methods: Patients with MBC who agreed to participate in the Clinic in addition to usual care completed patient-reported outcome (PRO) surveys.

Mindful self-compassion for lung cancer (MSC-LC): Incorporating perspectives of lung cancer patients, clinicians, and researchers to create an adapted intervention to reduce lung cancer stigma.

Background: Stigma is a pervasive and distressing problem experienced frequently by lung cancer patients, and there is a lack of psychosocial interventions that target the reduction of lung cancer stigma. Mindful self-compassion (MSC) is an empirically supported intervention demonstrated to increase self-compassion and reduce feelings of shame and distress in non-cancer populations. However, there are several anticipated challenges for delivering MSC to lung cancer patients, and modifications may be needed to improve acceptability, appropriateness, and feasibility.

Temporal Microenvironment Mapping (μMap) of Intracellular Trafficking Pathways of Cell-Penetrating Peptides Across the Blood-Brain Barrier.

Peptides play critical roles in cellular functions such as signaling and immune regulation, and peptide-based biotherapeutics show great promise for treating various diseases. Among these, cell-penetrating peptides (CPPs) are particularly valuable for drug delivery due to their ability to cross cell membranes. However, the mechanisms underlying CPP-mediated transport, especially across the blood-brain barrier (BBB), remain poorly understood.

A rare case of pontine tegmental cap dysplasia.

Pontine Tegmental Cap Dysplasia (PTCD) is a rare hindbrain malformation characterized by cranial nerve dysfunction, cerebellar abnormalities, and developmental delays of varying severity. This case report presents a 12-month-old female with significant developmental delays, hypotonia, and cranial nerve abnormalities. The findings underscore the critical role of radiology and neuroimaging in diagnosing and managing PTCD.

Nicotinamide mononucleotide restores impaired metabolism, endothelial cell proliferation and angiogenesis in old sedentary male mice.

Aging is accompanied by a decline in neovascularization potential and increased susceptibility to ischemic injury. Here, we confirm the age-related impaired neovascularization following ischemic leg injury and impaired angiogenesis. The age-related deficits in angiogenesis arose primarily from diminished EC proliferation capacity, but not migration or VEGF sensitivity.

A novel machine learning based framework for developing composite digital biomarkers of disease progression.

Background: Current methods of measuring disease progression of neurodegenerative disorders, including Parkinson's disease (PD), largely rely on composite clinical rating scales, which are prone to subjective biases and lack the sensitivity to detect progression signals in a timely manner. Digital health technology (DHT)-derived measures offer potential solutions to provide objective, precise, and sensitive measures that address these limitations. However, the complexity of DHT datasets and the potential to derive numerous digital features that were not previously possible to measure pose challenges, including in selection of the most important digital features and construction of composite digital biomarkers.

AI-assisted exposure-response data analysis: Quantifying heterogeneous causal effects of exposures on survival times.

AI-assisted data analysis can help risk analysts better understand exposure-response relationships by making it relatively easy to apply advanced statistical and machine learning methods, check their assumptions, and interpret their results. This paper demonstrates the potential of large language models (LLMs), such as ChatGPT, to facilitate statistical analyses, including survival data analyses, for health risk assessments. Through AI-guided analyses using relatively recent and advanced methods such as Individual Conditional Expectation (ICE) plots using Random Survival Forests and Heterogeneous Treatment Effects (HTEs) estimated using Causal Survival Forests, population-level exposure-response functions can be disaggregated into individual-level exposure-response functions.

Serum metabolomic signatures of patients with rare neurogenetic diseases: an insight into potential biomarkers and treatment targets.

Introduction: To further advance our understanding of Muscular Dystrophies (MDs) and Spinocerebellar Ataxias (SCAs), it is necessary to identify the biological patterns associated with disease pathology. Although progress has been made in the fields of genetics and transcriptomics, there is a need for proteomics and metabolomics studies. The present study aimed to be the first to document serum metabolic signatures of MDs (DMD, BMD, and LGMD 2A) SCAs (SCA 1-3), from a South Asian perspective.

A variational graph-partitioning approach to modeling protein liquid-liquid phase separation.

Graph neural networks (GNNs) have emerged as powerful tools for representation learning. Their efficacy depends on their having an optimal underlying graph. In many cases, the most relevant information comes from specific subgraphs.

Strategies in Management of Pulmonary Embolism With Acute Ischemic Stroke: A Systematic Review.

Pulmonary embolism (PE) and acute ischemic stroke (AIS) are serious conditions with high morbidity and mortality. In the USA, PE causes around 100,000 deaths annually, with higher incidence in males. AIS following PE occurs in 1-10% of cases and is a leading cause of death within 2 - 4 weeks post-stroke.