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Identification of small molecules uncoupling the Notch::Jagged interaction through an integrated high-throughput screening.

Notch signaling plays an important role in several cellular functions including growth, differentiation, cell fate determination and stemness. Increased Notch activity has been linked to several types of cancers. Activation of Notch signaling is triggered by the interaction of Notch receptors (Notch1-4) with 5 different ligands (Jagged1-2 and Dll1-3-4) expressed on the neighbouring cells. Currently, indirect approaches to inhibit Notch signalling are based on the inhibition of the key step of Notch activation catalyzed by the γ-Secretase and thereby affect several different γ-Secretase substra

Atezolizumab alleviates the immunosuppression induced by PD‑L1‑positive neutrophils and improves the survival of mice during sepsis.

BACKGROUND: Until recently, tumors of the clivus and the anterior region of the posterior cranial fossa were considered extremely difficult to access and often inoperable using standard transcranial approaches. With the introduction into the neurosurgical practice of minimally invasive methods utilizing endoscopic techniques, it became possible to effectively remove hard-to-reach tumors, including central tumors of the anterior region of the posterior cranial fossa. METHODS: From 2008 to the present time, the inpatient institution has operated on 140 patients with various tumors of the base o

A brief clinical genetics review: stepwise diagnostic processes of a monogenic disorder-hypertriglyceridemia.

The completion of the Human Genome Project and tremendous advances in automated high-throughput genetic analysis technologies have enabled explosive progress in the field of genetics, which resulted in countless discoveries of novel genes and pathways. Many phenotype- or disease-associated single nucleotide polymorphisms (SNPs) with a high statistical significance have been identified through numerous genome-wide association studies (GWAS), and various polygenic risk scoring (PRS) schemes have been proposed to identify individuals with a high risk for a certain trait or disorder. Meanwhile, me

The needs of cancer patients during the COVID-19 pandemic-psychosocial, ethical and spiritual aspects-systematic review.

The COVID-19 pandemic resulted in unprecedented changes in the functioning of the health care system, which were connected with the occurrence of new challenges for both the health care system's employees and for the patients. The purpose of the present article is to analyze the needs of persons with oncological diseases. Taking into account the multiple aspects of the term health, psychological, social, and existential needs of the patients were analyzed. This article is directed mainly at persons who remain in a direct therapeutic relation with a patient. It is to facilitate recognizing the

Gene and Cell Therapy for Sarcomas: A Review.

Background: The heterogeneity of sarcomas and resulting distinct sub-type specific characteristics, their high recurrence rates, and tendency for distant metastasis, continue to present significant challenges to providing optimal treatments. Objective: To provide a comprehensive review of current literature and clinical trials in gene and cell therapies for sarcomas. Methods: A comprehensive literature search was conducted utilizing the following databases: PubMed, Medline, Google Scholar and clinicaltrials.gov. Search terms included "gene therapy", "cell therapy", "NK cell therapy, "CAR-T the

CAR T cells for pediatric CNS tumors: Clinical experience and reverse translational opportunities.

Central nervous system (CNS) tumors are one of the leading causes of cancer-related mortality in children and young adults. Despite decades of research, effective treatments for these tumors are still lacking and new therapeutic options are urgently needed. While chimeric antigen receptor (CAR) T cell therapies have revolutionized the treatment of hematologic malignancies, these cellular therapies are only beginning to show evidence of activity in CNS tumors. In this review, we will discuss current CAR T cell clinical trials with a focus on trials in the pediatric CNS tumor space. In addition,

Global burden and regional inequalities of cancer in older adults from 1990 to 2021 and its projection until 2050.

BackgroundGlobal ageing will further exacerbate the cancer burden, and the intersection of cancer and ageing represents an emerging and significant global public health challenge.MethodsBased on the Global Burden of Disease 2021 (GBD 2021) data, we utilized the estimated annual percentage change and Joinpoint regression model to examine the temporal trends in the global cancer burden among elderly population from 1990 to 2021. Pearson's rank correlation analysis was conducted to assess the relationship between disease burden and the socio-demographic index (SDI). Furthermore, an autoregressive

On CAR-Ts, decentralized in-house models, and the hospital exception. Routes for sustainable access to innovative therapies.

Chimeric Antigen Receptor T cells, or CAR-Ts, are a novel class of gene and cell 'one-shot' therapies based upon collecting, reprogramming, and using patients' own immune cells to treat their cancer. The article discusses the status, prospects, and some relevant legal issues of this frontier of personalized medicine. In particular, it explores the legitimacy of 'in-house' CAR-Ts, ie treatments manufactured and delivered to patients within the same clinical center by relying upon automated cell processing systems, a decentralized model which is very different from the one currently adopted for

Машинное обучение для прогнозирования заболеваний с высоким коэффициентом риска у пациентов с раком.

ЦЕЛЬ: Инфекционные осложнения у больных раком способствуют госпитализации, нарушению лечения и смертности. Цель этого исследования заключалась в разработке моделей машинного обучения (ML) для стратификации рисков, связанных с госпитализацией (ИРХ) больных раком. МЕТОДЫ: Взрослые пациенты, у которых диагностировали и лечили лимфому, множественную миелому (ММ), хроническую лимфоцитическую лейкемию (КЛЛ), цветную или лёгкую раку. 2013 в адрес 2023 В него были включены страны Северной Дании. Были использованы данные национальных реестров раковых заболеваний и данных о состоянии здоровья пациентов.

Improved functional assessment in cancer patients using home-based digital technologies.

Accurate assessment of performance status (PS) in oncology care is crucial for improving clinical decisions, therapy selection and anticipated risks of treatment toxicity. While physical function is traditionally assessed in the clinic, in-clinic instruments do not capture the full spectrum of daily functioning. Digital health technologies (DHTs) can address this limitation by passively monitoring patients in their daily environment. Our study showed at-home physical activity and gait metrics from DHTs were associated with self-reported PS in participants with cancer, and these metrics had gre

Development of an Electronic Medical Record-Based Score for Heart Failure Prediction in Cancer Survivors.

BackgroundAwareness of heart failure (HF) as a long-term complication of cancer has led to an interest in HF surveillance among survivors. However, existing HF risk scores are not tailored for survivors and not designed for the use in electronic medical records (EMRs) or administrative data sets where clinical data such as blood pressure and pathology results are often unavailable.ObjectivesThe objective of the study is to develop a cancer-specific incident HF risk score suitable for screening in EMR or administrative data sets.MethodsThe cancer-specific HF prediction from EMRs in survivor hea

Биомаркеры по исследованиям в области клинической медицины: исследование литературы в базе данных PubMed и критическая оценка.

Биомаркер, короткая форма "биологического маркера", появилась в научной литературе в 1940-х годах. С тех пор было предложено множество различных определений, однако общеприменимое объяснение термина " биомаркер " в науке является чрезвычайно сложным. Слово "биомаркер" встречается в 1.3 million статьи в научной базе данных PubMed , которая в настоящее время включает более 39 million Ссылки на биомедицинскую литературу. Биомаркеры тесно связаны со здоровьем и болезнями человека. В настоящей статье делается попытка подойти к многогранному термину "биомаркет" и оценить его с клинической

45th International Symposium on Intensive Care & Emergency Medicine.

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Half a century of healing: celebrating the 50th anniversary of EBMT.

EBMT is a non-profit organization with a clear mission: "to save the lives of patients with blood cancers and other life-threatening diseases by advancing the fields of blood and marrow transplantation and cell therapy worldwide through science, education and advocacy". In 1974, EBMT was established by European physicians in St. Moritz to share bone marrow transplantation (BMT) experiences and foster collaboration. Founding members included Jon Van Rood, Bruno Speck, and Eliane Gluckman. By 1989, the group expanded significantly, emphasizing mutual trust and collaboration. EBMT played a crucia

Результаты среди пациентов MM, получающих раннее вмешательство в процесс развития MRD после автономной трансплантации стволовых клеток.

Для оценки реакции нескольких пациентов, страдающих миеломой (ММ), на лечение необходимо проводить обследование на наличие минимальных остаточных заболеваний (МСД). Многие пациенты, прежде чем удовлетворять критериям клинического или биохимического прогресса (PD), сталкиваются с MRD (MRD-P), в связи с чем возникают вопросы о сроках лечения. В этом ретроспективном исследовании было исследовано воздействие раннего вмешательства (РВ) на прогнозы 42 вновь диагностированные пациенты MM, разработавшие MRD-P после первоначального лечения аутологической трансплантации стволовых клеток. В группе EI (n

Impact of Kidney Failure Risk Prediction Clinical Decision Support on Monitoring and Referral in Primary Care Management of CKD: A Randomized Pragmatic Clinical Trial.

Rationale & objectiveTo design and implement clinical decision support incorporating a validated risk prediction estimate of kidney failure in primary care clinics and to evaluate the impact on stage-appropriate monitoring and referral.Study designBlock-randomized, pragmatic clinical trial.Setting & participantsTen primary care clinics in the greater Boston area. Patients with stage 3-5 chronic kidney disease (CKD) were included. Patients were randomized within each primary care physician panel through a block randomization approach. The trial occurred between December 4, 2015, and December 3,

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… Multicomponent interventions should be studied within an Implementation Science framework to determine which components are consistently deployed and which components have the most impact. …

Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision.

Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and

Implementing Telemedicine in Clinical Practice in the First Digital Hematology Unit: Feasibility Study.

BackgroundCurrently, there are no telemedicine models that fully integrate all areas of hematology into daily practice.ObjectiveThe objectives of this feasibility study were to assess the practicality of implementing telemedicine into our clinical practice in the first Digital Hematology Unit and propose an innovative integrative design for clinical practice.MethodsWe designed the Digital Hematology Unit, which is a specific physical space dedicated to carrying out telemedicine and monitoring patients in a holistic way. Also, a satisfaction questionnaire was performed and health care indicator

EU Regulatory Pathways for ATMPs: Standard, Accelerated and Adaptive Pathways to Marketing Authorisation.

Advanced therapy medicinal products (ATMPs) require evaluation by the European Medicines Agency's Committee for Advanced Therapies prior to being placed on the European market, subject to a Marketing Authorisation granted by the European Commission. In common with other medicinal products, various regulatory pathways are available for taking ATMPs through clinical trials to market authorisation, and the regulatory pathway taken will depend on a product's characteristics and the target patient population. With the industry poised to deliver more late-stage clinical and commercial ATMPs for seri

Expected benefits and concerns regarding virtual reality in caring for terminally ill cancer patients - a qualitative interview study.

BackgroundMany palliative cancer patients require inpatient hospital treatment for medical reasons, which contrasts their frequent desire to be at home. Virtual reality (VR) could be a way of bringing the home environment closer to them. First observations have shown benefits from VR for inpatients in palliative care. The aim of this qualitative, descriptive study was to explore the expectations of in-patients suffering from incurable cancer and their relatives about VR, in particular individualized VR images of the patients' own home.MethodsSemi-structured interviews with inpatients suffering