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Genetic factors and management strategies in aortic health: a literature review of inherited aortopathy.

Inherited aortopathies, including Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, are genetic disorders characterized by structural abnormalities of the aorta that predispose individuals to life-threatening complications like aneurysms and dissections. These conditions result from mutations in genes essential for maintaining aortic wall integrity, such as FBN1, TGFBR1, and COL3A1, affecting extracellular matrix components and the transforming growth factor-beta (TGF-β) pathway. Marfan syndrome has a prevalence of approximately 1 in 5000, while Loeys-Dietz syndrome and vascul

Comprehensive Review of Prevention and Management Strategies for Medication-related Osteonecrosis of the Jaw (MRONJ).

PURPOSE: To assess and classify the strategies employed in various dental specialities for the prevention and management of medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: A comprehensive literature review was conducted, acquiring studies sourced from Google Scholar and PubMed. The emphasis was on studies published in recent years, focusing on successful MRONJ prevention techniques across various dental specialties. RESULTS: Four types of prevention were identified. Primary prevention strategies include optimizing oral hygiene, managing dental caries, and extracti

Integrative Transcriptomic and Machine-Learning Analysis Reveals Immune-Inflammatory and Stress-Response Alterations in MRONJ.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive and antiangiogenic therapies, yet its molecular mechanisms remain poorly defined. The present study employed an analysis of microarray data (GSE7116) from peripheral blood mononuclear cells of patients with multiple myeloma, myeloma patients with MRONJ, and healthy controls. Differentially expressed genes were identified using the limma package, followed by functional enrichment analysis, weighted gene co-expression network analysis, and LASSO regression and CytoHubba network ranking. The predicti

Preclinical evaluation of the novel, orally bioavailable Selective Inhibitor of Nuclear Export (SINE) KPT-335 in spontaneous canine cancer: results of a phase I study.

BackgroundThe purpose of this study was to evaluate the activity of Selective Inhibitors of Nuclear Export (SINE) compounds that inhibit the function of the nuclear export protein Exportin 1 (XPO1/CRM1) against canine tumor cell lines and perform a Phase I clinical trial of KPT-335 in dogs with spontaneous cancer to provide a preliminary assessment of biologic activity and tolerability.Methods and findingsCanine tumor cell lines derived from non-Hodgkin lymphoma (NHL), mast cell tumor, melanoma and osteosarcoma exhibited growth inhibition and apoptosis in response to nanomolar concentrations o

Chronic Liver Disease Associated Cholangiocarcinoma: Genomic Insights and Precision Therapeutic Strategies.

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy arising from the biliary epithelium, with an increasing incidence and poor prognosis worldwide. Recent advances in next-generation sequencing have revealed a variety of genomic alterations-such as FGFR2 fusions, IDH1 mutations, and ERBB2 amplification-that may serve as therapeutic targets. However, the influence of underlying etiologic factors, including chronic liver and biliary diseases, on the molecular landscape of CCA remains unclear. Objective: This review aimed to synthesize the current knowledge on the genomic an

Daratumumab monotherapy in refractory warm autoimmune hemolytic anemia and cold agglutinin disease.

AbstractAutoimmune hemolytic anemia (AIHA) is a rare autoantibody-mediated disease. For steroid and/or rituximab-refractory AIHA, there is no consensus on optimal treatment. Daratumumab, a monoclonal antibody targeting CD38, could be beneficial by suppression of CD38+ plasma cells and thus autoantibody secretion. In addition, because CD38 is also expressed by activated T cells, daratumumab may also act via immunomodulatory effects. We evaluated the efficacy and safety of daratumumab monotherapy in an international retrospective study including 19 adult patients with heavily pretreated refracto

Sclerostin Alters Tumor Cell Characteristics of Oral Squamous Cell Carcinoma and May Be a Key Player in Local Bone Invasion.

Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and bone metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by quantitative real-time polymerase chain reaction (qRT-PCR), and the effect of recombinant human (rh)-sclerostin tr

The reporting quality and transparency of orthopaedic studies using Bayesian analysis requires improvement: A systematic review.

BackgroundBayesian methods are being used more frequently in orthopaedics. To advance the use and transparent reporting of Bayesian studies, reporting guidelines have been recommended. There is currently little known about the use or applications of Bayesian analysis in orthopedics including adherence to recommended reporting guidelines. The objective is to investigate the reporting of Bayesian analysis in orthopedic surgery studies; specifically, to evaluate if these papers adhere to reporting guidelines.MethodsWe searched PUBMED to December 2nd, 2020. Two reviewers independently identified s

When Cancer Is the Self: An Interpretive Description of the Experience of Identity by Hematology Cancer Patients.

BackgroundThe term "cancer" is imbued with identity signals that trigger certain assumed sociocultural responses. Clinical practice with hematological cancer patients suggests the experience of these patients may be different than that of solid tumor cancer patients.ObjectiveWe sought to explore the research question: How are identity experiences described and elucidated by adult hematological cancer patients?MethodsThis qualitative study was guided by interpretive description as the methodological framework.ResultsPreexisting identity labels and assumptions assigned to the overarching "cancer

Patient-specific risk factors for adverse outcomes following geriatric proximal femur fractures.

BACKGROUND: Proximal femur fractures (PFFs) occur frequently among geriatric patients due to diverse risk factors, such as a lower bone mineral density and the increased risk of falls. METHODS: In this review, we focus on recent literature of patient-specific risk factors and their impact on common complications and outcome parameters in patients with PFF. RESULTS: Patient- and treatment related factors have a significant impact on outcome and are associated with an increased risk of mortality, impairments in functional rehabilitation and complicative courses. CONCLUSION: Geriatric patients

Exploring the Emerging Association Between Immune Checkpoint Inhibitors and Thrombosis.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their association with thrombosis presents significant clinical challenges. Patients with cancer already exhibit elevated risks for venous thromboembolism and arterial thrombosis, with treatment modalities like chemotherapy further exacerbating this risk. Emerging evidence suggests that ICIs contribute to thrombotic events through multifactorial mechanisms, including immune dysregulation, T cell activation, endothelial dysfunction, elevated tissue factor expression, and impaired fibrinolysis. Additional risk factors

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Fit theory: A cancer experience grounded theory emerging from semi-structured interviews with cancer patients and informal caregivers in Manitoba Canada during the COVID-19 pandemic.

BackgroundIt is not clear how changes to healthcare delivery related to the COVID-19 pandemic, including virtual care and social distancing restrictions, have impacted the experience of living with cancer. This study aimed to discover a theory capable of describing the cancer experience, how the pandemic impacted it, and for guiding predictions about how to improve it.MethodsBetween October 2020 and July 2021 digitally recorded semi-structured one-on-one interviews were conducted virtually with adult cancer patients and informal caregivers in Manitoba, Canada. Transcriptions and field notes fr

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project.

The Chimeric Antigen Receptor (CAR) T Cell Safety Database Project explored the use of cross-study safety data to identify risk factors associated with severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) after CAR T cell administration. Sponsors voluntarily submitted data for 1,926 subjects from 17 phases 1 and 2 studies (six acute lymphocytic leukemia [ALL], five non-Hodgkin's lymphoma [NHL], and six multiple myeloma [MM] studies). Subjects with ALL had a higher risk for developing sCRS and sNTX compared with subjects with NHL or MM. Subjects who received CAR T c

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… Multivariate models such as logistic regression, decision trees, and random forests were developed to identify which combination of factors show a strong association with the occurrence of sCRS or sNTX. …

Recent trends in specialty pharma business model.

The recent rise of specialty pharma is attributed to its flexible, versatile, and open business model while the traditional big pharma is facing a challenging time with patent cliff, generic threat, and low research and development (R&D) productivity. These multinational pharmaceutical companies, facing a difficult time, have been systematically externalizing R&D and some even establish their own corporate venture capital so as to diversify with more shots on goal, with the hope of achieving a higher success rate in their compound pipeline. Biologics and clinical Phase II proof-of-concept (POC

Artificial inteligence and datasets for leukemia diagnosis: A scoping review of machine lerning and deep learning approaches.

Leukemia is the cancerous disease of the blood and the bone marrow that causes excessive proliferation of abnormal white blood cells, if detected too late, it can lead to potentially fatal consequences. Peripheral blood smear examinations and bone marrow biopsy are example of conventional diagnostic techniques that are invasive, time-consuming and subject to human variability. Recent advances in artificial intelligence (AI) particularly in the areas of Machine Learning (ML) and Deep Learning (DL)offer encouraging answers by making it possible to detect and classify leukemia using automated, ef

Small compound 6-O-angeloylplenolin induces mitotic arrest and exhibits therapeutic potentials in multiple myeloma.

BackgroundMultiple myeloma (MM) is a disease of cell cycle dysregulation while cell cycle modulation can be a target for MM therapy. In this study we investigated the effects and mechanisms of action of a sesquiterpene lactone 6-O-angeloylplenolin (6-OAP) on MM cells.Methodology/principal findingsMM cells were exposed to 6-OAP and cell cycle distribution were analyzed. The role for cyclin B1 to play in 6-OAP-caused mitotic arrest was tested by specific siRNA analyses in U266 cells. MM.1S cells co-incubated with interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or bone marrow stromal

Application of Artificial Intelligence Methods for Imaging of Spinal Metastasis.

Spinal metastasis is the most common malignant disease of the spine. Recently, major advances in machine learning and artificial intelligence technology have led to their increased use in oncological imaging. The purpose of this study is to review and summarise the present evidence for artificial intelligence applications in the detection, classification and management of spinal metastasis, along with their potential integration into clinical practice. A systematic, detailed search of the main electronic medical databases was undertaken in concordance with the PRISMA guidelines. A total of 30

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… Machine learning methods including random decision forest, an ensemble learning method for classifying data using decision trees, can then be performed to validate and further evaluate the classification accuracy of the set of predictors [ 61 ]. …

Contemporary Perspectives on Chronic Renal Disorders.

The prevalence of renal diseases and its associated burden on healthcare have tremendously risen in the past few years. From simple markers assessing kidney function, current renal research delves into understanding the diseases at the cellular and molecular levels and not just at treating, but at improving quality of life, arresting progression and providing personalized diagnostics and therapy. This narrative review highlights the improvements in diagnostic applications of kidney disease and briefly discusses a few notable biomarkers emphasizing the high throughput omics technologies, as wel

Effectiveness and safety of COVID-19 vaccines in patients with oncological diseases: State-of-the-art.

Although the coronavirus disease 2019 (COVID-19) pandemic was declared to be no longer "a public health emergency of international concern" with its wide range of clinical manifestations and late complications, severe acute respiratory syndrome coronavirus 2 infection proved to be a serious threat, especially to the elderly and patients with comorbidities. Patients with oncologic diseases are vulnerable to severe infection and death. Indeed, patients with oncohematological diseases have a higher risk of severe COVID-19 and impaired post-vaccination immunity. Unfortunately, cancer patients are