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Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.

The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We posit that a priority is to develop pan-family drug cocktails to enhance potency, limit toxicity, and avoid drug resistance. We urge cocktail development for all viruses with pandemic potential both in the short term (<1 to 2 years) and longer term wi

A Pilot Randomized Controlled Trial and Multi-Omics Analysis of Electrolysed Alkaline Water: Impacts on Gut Microbiota and Metabolic Signatures in Hyperuricemia.

Background/Objectives: Hyperuricemia (HUA) is the second most common metabolic disease in China (24.5% in males, 3.6% in females), which can induce multiple complications such as gout and diabetes. Existing urate-lowering drugs have significant hepatorenal toxicity, necessitating safe lifestyle interventions. Electrolyzed alkaline water (EAW) as daily drinking water has shown preliminary effectiveness, but it lacks randomized controlled evidence and mechanistic studies at the microbiome-metabolome interface. Methods: We conducted a 12-week randomized controlled trial in 40 adults aged 18-65 ye

What is an "early palliative care" intervention? A scoping review of controlled studies in oncology.

IntroductionEarly palliative care (EPC) has been advocated to improve cancer patients' health. However, EPC differs with regard to its elements and target groups. It is not known which parts of EPC contribute to effectiveness for which patient group. This scoping review provides a structured analysis of EPC interventions and outcome measures.DesignWe searched EMBASE, MEDLINE, CINAHL, and CENTRAL up to February 2022. We included randomized controlled trials (RCT), nonrandomized trials, cohort studies (CS), and controlled before-after studies of EPC in adult patients in English, Dutch, and Germa

Теоретический опыт в множестве склерозов: функциональные неврологические симптомы, недовольство изображением тела и расстройство пищевой практики. Обзор описательной части.

Множественный склероз (MS) — хроническое заболевание центральной нервной системы, связанное с целым рядом физических, когнитивных и психологических трудностей. Помимо классических неврологических симптомов, нарушения физического опыта, включая функциональные неврологические симптомы, соматизацию, расстройства, связанные с изображением тела, и расстройство питания, представляют собой недооцененный, но клинически значимый аспект болезни. В настоящем докладе обобщаются данные, полученные от взрослого и педиатрического населения, с уделением особого внимания частому соучастию этих нарушений в рабо

Role of B-Cell in the Pathogenesis of Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare multisystem autoimmune disease, characterized by fibrosis, vasculopathy, and autoimmunity. Recent advances have highlighted the significant implications of B-cells in SSc. B-cells are present in affected organs, their subpopulations are disrupted, and they display an activated phenotype, and the regulatory capacities of B-cells are impaired, as illustrated by the decrease in the IL-10+ producing B-cell subpopulation or the inhibitory membrane co-receptor density. Recent multi-omics evidence highlights the role of B-cells mainly in the early stage of SSc and p

Simultaneous Inhibition of Mcl-1 and Bcl-2 Induces Synergistic Cell Death in Hepatocellular Carcinoma.

Despite the recent approval of new therapies, the prognosis for patients with hepatocellular carcinoma (HCC) remains poor. There is a clinical need for new highly effective therapeutic options. Here, we present a combined application of BH3-mimetics as a potential new treatment option for HCC. BH3-mimetics inhibit anti-apoptotic proteins of the BCL-2 family and, thus, trigger the intrinsic apoptosis pathway. Anti-apoptotic BCL-2 proteins such as Bcl-2 and Mcl-1 are frequently overexpressed in HCC. Therefore, we analyzed the efficacy of the two BH3-mimetics ABT-199 (Bcl-2 inhibitor) and MIK665

Identifying and handling unbalanced baseline characteristics in a non-randomized, controlled, multicenter social care nurse intervention study for patients in advanced stages of cancer.

PurposeGiven the psychosocial burdens patients in advanced stages of cancer face, innovative care concepts are needed. At the same time, such vulnerable patient groups are difficult to reach for participation in intervention studies and randomized patient inclusion may not be feasible. This article aims to identify systematic biases respectively selection effects occurring during the recruitment phase and to discuss their potential causes based on a non-randomized, multicenter intervention study with patients in advanced stages of cancer.MethodsPatients diagnosed with at least one of 16 predef

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

Activated Ras as a Therapeutic Target: Constraints on Directly Targeting Ras Isoforms and Wild-Type versus Mutated Proteins.

The ability to selectively and directly target activated Ras would provide immense utility for treatment of the numerous cancers that are driven by oncogenic Ras mutations. Patients with disorders driven by overactivated wild-type Ras proteins, such as type 1 neurofibromatosis, might also benefit from progress made in that context. Activated Ras is an extremely challenging direct drug target due to the inherent difficulties in disrupting the protein:protein interactions that underlie its activation and function. Major investments have been made to target Ras through indirect routes. Inhibition

Complication avoidance, rehabilitation, pain therapy and palliative care for patients with metastatic spine tumors: WFNS spine committee recommendations.

ObjectiveThis review aims to formulate the most current, evidence-based recommendations regarding complication avoidance, rehabilitation, pain therapy and palliative care for patients with metastatic spine tumors.MethodsA systematic literature search in PubMed and MEDLINE, and was performed from 2013 to 2023 using the search terms "complications" + "spine metastases", "spine metastases" + + "rehabilitation", "spine metastases" + "pain therapy" + "palliative care". Screening criteria resulted in 35, 15 and 56 studies respectively that were analyzed. Using the Delphi method and two rounds of vot

Bortezomib-induced gastrointestinal dysfunction, peripheral neuropathy and neuroimmune signalling are influenced by the gut microbiota in mice.

BACKGROUND: Peripheral neuropathy and gastrointestinal dysfunction are frequent, debilitating side effects of the neurotoxic myeloma drug bortezomib that reduce quality of life and adherence to optimal therapy. Therapeutic strategies to manage these complications are limited. Here, we have developed a mouse model of bortezomib side effects to investigate the role of the gut microbiota in their development. METHODS: C57BL/6 specific pathogen-free (SPF), germ-free (GF) and ex-GF mice (colonised with healthy gut microbiota via faecal microbiota transplantation [FMT]) were treated with bortezomib

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

Мультиэнштейная геномная ассоциация и мультиомикальный анализ позволяют выявить специфичные особенности многоклерозной генетики.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы, характеризующееся обезвоживанием, распространяющимся в пространстве и во времени. Здесь мы провели исследование ассоциации генома (GWAS) с использованием 688 Количество дел, связанных с НР и 205,199 :: контроль со стороны японского населения и выявление важных связей в основном сложном регионе, связанном с гистокомпьютерностью, и в 11q24 году вариант риска, учитывающий специфику населения. С помощью межнаселенных метаанализов GWAS с использованием всего 29,374 случаи и случаи 1,843,563 контроля с 4

Exploring neutrophil extracellular traps: mechanisms of immune regulation and future therapeutic potential.

Neutrophil extracellular traps (NETs) are complex, web-like structures consisting of DNA intertwined with antimicrobial proteins, which neutrophils release upon immune activation. These structures play a crucial role in pathogen elimination, particularly in infectious diseases. However, their involvement in various pathological conditions is multifaceted and context-dependent, while NETs contribute to host defense against infections, they can also exacerbate sterile inflammation, autoimmune disorders, and tumor progression. This review provides a comprehensive analysis of the molecular mechani

Scoping Review and Meta-Analysis Suggests that Cannabis Use May Reduce Cancer Risk in the United States.

Introduction:Cannabis smoke contains carcinogens similar to tobacco, in addition to compounds with antitumor activity. Cannabis use reduces the risk of obesity and cannabinoids inhibit chronic inflammation, known causes of cancer. The net effect of Cannabis use on cancer risk is not known. Objective: To examine the association between Cannabis use and cancer risk in the United States. Methods: Identify and analyze published data on cancer risk in Cannabis users. Results: A total of 55 data points, consisting of risk ratios of cancer in Cannabis users and nonusers, were identified from 34 studi

A Literature Review on the Impact of the Gut Microbiome on Cancer Treatment Efficacy, Disease Evolution and Toxicity: The Implications for Hematological Malignancies.

The gut microbiome plays a crucial role in modulating the efficacy and toxicity of cancer therapies, particularly in hematological malignancies. This review examines the dynamic interplay between gut microbiota and cancer treatments, such as chemotherapy, immunotherapy, and hematopoietic stem cell transplantation (HSCT). Disruptions in the gut microbiome, known as dysbiosis, are associated with adverse effects like gastrointestinal toxicity, neutropenia and cardiotoxicity during chemotherapy. Conversely, the supplementation of probiotics has shown potential in mitigating these side effects by

Proceedings of the International Cancer Imaging Society Meeting and 21st Annual Teaching Course : Boston, MA, USA. 12-14 September 2022

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Morphine-3-glucuronide upregulates PD-L1 expression via TLR4 and promotes the immune escape of non-small cell lung cancer.

ObjectivePatients with cancer pain are highly dependent on morphine analgesia, but studies have shown a negative correlation between morphine demand and patient outcomes. The long-term use of morphine may result in abnormally elevated serum morphine-3-glucuronide (M3G) levels. Hence, the effects of M3G on tumor progression are worth studying.MethodsThe effects of M3G on PD-L1 expressions in human non-small cell lung cancer (NSCLC) cell lines were first evaluated. Activation of TLR4 downstream pathways after M3G treatment was then determined by Western blot. The effects of M3G on human cytotoxi

Multiple myeloma care, treatment patterns, and treatment durations in academic and community care settings.

AIM: Evaluate multiple myeloma (MM) treatment patterns, healthcare utilization (HCRU), and costs from academic and community settings. METHODS: This observational study linked US MM insurance claims (1 April 2017-30 June 2022) with provider affiliations to evaluate patient characteristics and treatment durations across patient cohorts defined by care setting of treatment (academic only, community only, mixed [both]), as well as treatment patterns, HCRU, and costs of care (e.g. treatment, office visits, hospitalization) in each setting. RESULTS: 3778 patients were included. By cohort (n = 530

The role of VWF/FVIII in thrombosis and cancer progression in multiple myeloma and other hematological malignancies.

Cancer associated thrombosis (CAT) is associated with significant morbidity and mortality, highlighting an unmet clinical need to improve understanding of the pathophysiology of CAT. Multiple myeloma (MM) is associated with one of the highest rates of thrombosis despite widespread use of thromboprophylactic agents. The pathophysiology of thrombosis in MM is multifactorial and patients with MM appear to display a hypercoagulable phenotype with potential contributory factors including raised von Willebrand factor (VWF) levels, activated protein C resistance, impaired fibrinolysis, and abnormal t

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… Under normal conditions, APC functions to proteolytically inactivate both factor Va and factor VIIIa, limiting coagulation activity and thrombin generation. …