Translational research

In transplantation, hypothermic machine perfusion (HMP) has been shown to be superior to static cold storage (SCS) in terms of functional outcomes. Ex vivo machine perfusion offers the possibility to deliver drugs or other active substances, such as Mesenchymal Stem Cells (MSCs), directly into an organ without affecting the recipient. MSCs are multipotent, self-renewing cells with tissue-repair capacities, and their application to ameliorate ischemia- reperfusion injury (IRI) is being investigated in several preclinical and clinical studies...

Osteoporotic vertebral compression fractures (OVCFs) significantly increase morbidity and mortality, presenting a formidable challenge in healthcare. Traditional interventions such as vertebroplasty and kyphoplasty, despite their widespread use, are limited in addressing the secondary effects of vertebral fractures in adjacent areas and do not facilitate bone regeneration. This review paper explores the emerging domain of regenerative therapies, spotlighting stem cell therapy's transformative potential in OVCF treatment...

The evolution of the translation system is a fundamental issue in the quest for the origin of life. A feasible evolutionary scenario necessitates the autonomous emergence of a protoribosome capable of catalyzing the synthesis of the initial peptides. The peptidyl transferase center (PTC) region in the modern ribosomal large subunit is believed to retain a vestige of such a prebiotic non-coded protoribosome, which would have self-assembled from random RNA chains, catalyzed peptide bond formation between arbitrary amino acids, and produced short peptides...

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, which play a critical role in maintaining immune homeostasis, are crucial in pregnancy to prevent immune-mediated rejection of the foetus. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring foetal acceptance...

Systemic sclerosis (SSc) is a heterogeneous disease characterized by autoimmunity, vasculopathy, and fibrosis which affects the skin and internal organs. One key aspect of SSc vasculopathy is pulmonary arterial hypertension (SSc-PAH) which represents a leading cause of morbidity and mortality in patients with SSc. The pathogenesis of pulmonary hypertension is complex, with multiple vascular cell types, inflammation, and intracellular signaling pathways contributing to vascular pathology and remodeling. In this review, we focus on shared molecular features of pulmonary hypertension and those which make SSc-PAH a unique entity...

Non-small cell lung cancer, even when diagnosed in early stages, has been linked with poor survival rates and distant recurrence patterns. Novel therapeutic approaches harnessing the immune system have been implemented in early stages, following the designated steps of advanced NSCLC treatment strategies. Immune-checkpoint inhibitor (ICI) regimens as monotherapy, combinational, or alongside chemotherapy have been intensely investigated as adjuvant, neoadjuvant, and, more recently, perioperative therapeutic strategies, representing pivotal milestones in the evolution of early lung cancer management while holding great potential for the future...

While RNA sequencing and multi-omic approaches have significantly advanced cancer diagnosis and treatment, their limitation in preserving critical spatial information has been a notable drawback. This spatial context is essential for understanding cellular interactions and tissue dynamics. Multiplex digital spatial profiling (MDSP) technologies overcome this limitation by enabling the simultaneous analysis of transcriptome and proteome data within the intact spatial architecture of tissues. In breast cancer research, MDSP has emerged as a promising tool, revealing complex biological questions related to disease evolution, identifying biomarkers, and discovering drug targets...

Microtubule targeting agents (MTAs) are commonly prescribed to treat cancers and predominantly kill cancer cells in mitosis. Significantly, some MTA-treated cancer cells escape death in mitosis, exit mitosis and become malignant polyploid giant cancer cells (PGCC). Considering the low number of cancer cells undergoing mitosis in tumor tissues, killing them in interphase may represent a favored antitumor approach. We discovered that ST-401, a mild inhibitor of microtubule (MT) assembly, preferentially kills cancer cells in interphase as opposed to mitosis, a cell death mechanism that avoids the development of PGCC...

BACKGROUND: English is generally recognized as the international language of science and most research on evidence-based medicine is produced in English. While Bangla is the dominant language in Bangladesh, public midwifery degree programs use English as the medium of instruction (EMI). This enables faculty and student access to the latest evidence-based midwifery content, which is essential for provision of quality care later. Yet, it also poses a barrier, as limited English mastery among students and faculty limits both teaching and learning...

BACKGROUND: Lumbar puncture (LP) is an important yet difficult skill in medical practice. In recent years, the number of LPs in clinical practice has steadily decreased, which reduces residents' clinical exposure and may compromise their skills and attitude towards LP. Our study aims to assess whether the novel bioimpedance needle is of assistance to a novice provider and thus compensates for this emerging knowledge gap. METHODS: This randomized controlled study, employing a partly blinded design, involved 60 s- and third-year medical students with no prior LP experience...

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma...

BACKGROUND: Disparities in child healthcare service utilization are unacceptably high in Ethiopia. Nevertheless, little is known about underlying barriers to accessing child health services, especially among low socioeconomic subgroups and in remote areas. This study aims to identify barriers to equity in the use of child healthcare services in Ethiopia. METHODS: Data were obtained from 20 key- informant interviews (KII) and 6 focus group discussions (FGD) with mothers and care givers...

INTRODUCTION: Lung cancer is a prevalent malignancy globally, and immunotherapy has revolutionized its treatment. However, resistance to immunotherapy remains a challenge. Abnormal cholinesterase (ChE) activity and choline metabolism are associated with tumor oncogenesis, progression, and poor prognosis in multiple cancers. Yet, the precise mechanism underlying the relationship between ChE, choline metabolism and tumor immune microenvironment in lung cancer, and the response and resistance of immunotherapy still unclear...

A drug molecule is a substance that changes an organism's mental or physical state. Every approved drug has an indication, which refers to the therapeutic use of that drug for treating a particular medical condition. While the Large Language Model (LLM), a generative Artificial Intelligence (AI) technique, has recently demonstrated effectiveness in translating between molecules and their textual descriptions, there remains a gap in research regarding their application in facilitating the translation between drug molecules and indications (which describes the disease, condition or symptoms for which the drug is used), or vice versa...

Wound healing presents a complex physiological process that involves a sequence of events orchestrated by various cellular and molecular mechanisms. In recent years, there has been growing interest in leveraging nanomaterials and peptides to enhance wound healing outcomes. Nanocarriers offer unique properties such as high surface area-to-volume ratio, tunable physicochemical characteristics, and the ability to deliver therapeutic agents in a controlled manner. Similarly, peptides, with their diverse biological activities and low immunogenicity, hold great promise as therapeutics in wound healing applications...

Predicting the course of neurodegenerative disorders early has potential to greatly improve clinical management and patient outcomes. A key challenge for early prediction in real-world clinical settings is the lack of labeled data (i.e., clinical diagnosis). In contrast to supervised classification approaches that require labeled data, we propose an unsupervised multimodal trajectory modeling (MTM) approach based on a mixture of state space models that captures changes in longitudinal data (i.e., trajectories) and stratifies individuals without using clinical diagnosis for model training...

The impacts of climate change on vector-borne diseases are uneven across human populations. This pattern reflects the effect of changing environments on the biology of transmission, which is also modulated by social and other inequities. These disparities are also linked to research outcomes that could be translated into tools for transmission reduction, but are not necessarily actionable in the communities where transmission occurs. The transmission of vector-borne diseases could be averted by developing research that is both hypothesis-driven and community-serving for populations affected by climate change, where local communities interact as equal partners with scientists, developing and implementing research projects with the aim of improving community health...

BACKGROUND: Rising admission rates of Hispanic/Latinx families to the neonatal intensive care unit (NICU) have increased the number of non-English-speaking individuals who may wish to participate in research studies. However, a lack of appropriately translated research study materials may limit the opportunity for these families to be involved in research that could impact the care that infants and families receive in the NICU. PURPOSE: The primary purpose was to pilot test study materials that were transcreated from English to Spanish with the assistance of a bilingual community advisory board with Spanish-speaking parents of NICU infants...

BACKGROUND: Population physical activity promotion (PPAP) is one of the most effective noncommunicable disease prevention strategies, yet coordination is lacking around the world. Whole-of-system approaches and complex systems methods are called for to advance PPAP. This paper reports on a project which (1) used an Attributes Framework with system mapping (group model building and causal loop diagramming of feedback loops) and (2) identified potential leverage points to address the challenge of effective coordination of multisectoral PPAP in British Columbia...

BACKGROUND: Mesenchymal stem cell (MSC)-based therapies have yielded beneficial effects in a broad range of preclinical models and clinical trials for human diseases. In the context of MSC transplantation, it is widely recognized that the main mechanism for the regenerative potential of MSCs is not their differentiation, with in vivo data revealing transient and low engraftment rates. Instead, MSCs therapeutic effects are mainly attributed to its secretome, i.e., paracrine factors secreted by these cells, further offering a more attractive and innovative approach due to the effectiveness and safety of a cell-free product...