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Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art

Care of cancer patients at the end of life in a German university hospital: A retrospective observational study from 2014.

BackgroundCancer care including aggressive treatment procedures during the last phase of life in patients with incurable cancer has increasingly come under scrutiny, while integrating specialist palliative care at an early stage is regarded as indication for high quality end-of-life patient care.AimTo describe the demographic and clinical characteristics and the medical care provided at the end of life of cancer patients who died in a German university hospital.MethodsRetrospective cross-sectional study on the basis of anonymized hospital data for cancer patients who died in the Munich Univers

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… The term “palliative care” is often misunderstood as terminal care only [ 64 ]. Some physicians also believe that merely mentioning the term “palliative medicine” will deprive the patient of any hope and that the term is associated with the stigma of death. …

Nerve Growth Factor and Autoimmune Diseases.

NGF plays a crucial immunomodulatory role and increased levels are found in numerous tissues during autoimmune states. NGF directly modulates innate and adaptive immune responses of B and T cells and causes the release of neuropeptides and neurotransmitters controlling the immune system activation in inflamed tissues. Evidence suggests that NGF is involved in the pathogenesis of numerous immune diseases including autoimmune thyroiditis, chronic arthritis, multiple sclerosis, systemic lupus erythematosus, mastocytosis, and chronic granulomatous disease. Furthermore, as NGF levels have been link

Cultural adaptation and validation of the Sinhala version of the spiritual needs assessment for patients (S-SNAP) questionnaire.

BackgroundSpiritual support for patients and caregivers of critically ill patients is associated with improved quality of life. This aspect, however, is not incorporated into the current care pathways in Sri Lanka. The Spiritual Needs Assessment for Patients (SNAP) questionnaire, comprised of 3 domains: psychosocial, spiritual and religious, gives a platform for clinicians to assess the spiritual needs of those patients. This study presents the results of validation of the Sinhala version of the SNAP (S-SNAP) questionnaire.MethodsThe SNAP was translated from English to Sinhala using the standa

Изучение многочисленных патобиологии миэломы и сигнатур иммунных клеток: свидетельства из двунаправленного генетического анализа.

По-прежнему не до конца изучена причинно-следственная связь между сигнатурой иммунных клеток и патологией множественной миэломы (ММ). Цель этого исследования заключалась в изучении двусторонних причинно-следственных связей между 731 :: распространение характеристик иммунных клеток и риск MM с использованием two- выборка, двунаправленный подход к менделизации на случайной основе (MR). Two- анализы МВ были проведены с использованием обобщенных статистических данных общегеномического исследования (GWAS) 731 Фенотипы иммунных клеток и наборы данных MM GWAS. Для оценки надежности и надежности резул

Expert consensus on the clinical application of antibody-drug conjugates in the treatment of malignant tumors (2021 edition).

Antibody-drug conjugates (ADCs) are targeted biological agents composed of a cytotoxic drug linked to a monoclonal antibody through a linker. The monoclonal antibody targets tumor cells and transports small-molecule cytotoxic drugs for specific delivery and minimal off-target side effects. It is necessary for clinicians to understand the molecular characteristics and mechanisms of ADCs. Patients' survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions. This consensus provides a systematic review of commercially available ADCs a

Design characteristics, risk of bias, and reporting of randomised controlled trials supporting approvals of cancer drugs by European Medicines Agency, 2014-16: cross sectional analysis.

ObjectiveTo examine the design characteristics, risk of bias, and reporting adequacy of pivotal randomised controlled trials of cancer drugs approved by the European Medicines Agency (EMA).DesignCross sectional analysis.SettingEuropean regulatory documents, clinical trial registry records, protocols, journal publications, and supplementary appendices.Eligibility criteriaPivotal randomised controlled trials of new cancer drugs approved by the EMA between 2014 and 2016.Main outcome measuresStudy design characteristics (randomisation, comparators, and endpoints); risk of bias using the revised Co

Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.

The ubiquitin-proteasome system (UPS) is a critical regulator of cellular protein levels and activity. It is, therefore, not surprising that its dysregulation is implicated in numerous human diseases, including many types of cancer. Moreover, since cancer cells exhibit increased rates of protein turnover, their heightened dependence on the UPS makes it an attractive target for inhibition via targeted therapeutics. Indeed, the clinical application of proteasome inhibitors in treatment of multiple myeloma has been very successful, stimulating the development of small-molecule inhibitors targetin

Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer's, Parkinson's, and Huntington's Diseases and Amyotrophic Lateral Sclerosis.

Neurodegenerative diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to experience exponential growth thanks to numerous advancements in technology, shifts in the understanding of the disease as a phenomenon, and the change in the perspective regarding gene editing and the advantages of this action. The aim of this paper is to analyze the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Hunti

Simultaneous occurrence of two B-cell malignancies: A case report.

The present study describes the case of a 75-year-old male with coexisting multiple myeloma and diffuse large B-cell lymphoma. Although the two malignancies are mature B-cell neoplasms, their clinical manifestations are very different and the clinical approaches used to treat these two types of tumor vary. The patient in the present case was diagnosed with the simultaneous existence of two different B-cell tumors and was successfully treated using the DCEP regimen. The simultaneous presentation of two mature B-cell neoplasms, types of hematological malignancy, is very rare, thus the present ca

Psychometric Assessment of SpiDiscI: Spiritual Distress Scale for Palliative Care Patients in India.

ObjectivesSpirituality has an impact on the quality of life of palliative care patients and it influences the way in which they experience their disease. Spiritual distress is a common issue among palliative care patients in India that is best assessed through a tool specifically designed for them. This study presents the findings of a psychometric assessment of SpiDiscI: a 16-item spiritual distress scale for Hindi speaking palliative care patients in India.Materials and methodsThis study used a non-experimental cross-sectional sample survey design. 400 cancer patients undergoing pain treatme

Harnessing live vectors for cancer vaccines: Advancing therapeutic immunotherapy.

Cancer vaccines represent a promising approach within immunotherapies. These vaccines are tailored to target tumor-specific antigens, thereby offering a precision approach to cancer treatment. The key principles in developing therapeutic cancer vaccines include identifying appropriate vaccine targets and selecting effective vaccine delivery platforms. These delivery platforms are diverse and have evolved to enhance the immune response. This review explores live cancer vaccines and the biological entities involved. Live cancer vaccines leverage the use of various biological entities to stimulat

A phase I dose-escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mTORC1/mTORC2 kinase inhibitor CC-223 in patients with advanced solid tumors or multiple myeloma.

BackgroundThe mammalian target of rapamycin (mTOR) pathway is essential for tumor development, yet mTOR inhibitors have yielded modest results. This phase 1 study investigated the mTORC1/mTORC2 inhibitor CC-223 in patients with advanced cancer.MethodsPatients with advanced solid tumors or multiple myeloma received an initial dose of 7.5-60 mg of CC-223, followed by oral daily dosing in 28-day cycles until disease progression. The primary objective was to determine the safety, tolerability, nontolerated dosage, maximum tolerated dosage (MTD), and preliminary pharmacokinetic profile. Secondary o

Myeloma bone disease.

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BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medica

Prevention of cancer-therapy related cardiac dysfunction.

PURPOSE OF REVIEW: Introduction of modern cancer therapies has led to increased survival of affected patients. With this advantage, the incidence of cancer therapy-related cardiac dysfunction (CTRCD) has increased and reasonable prevention strategies become necessary. This review outlines the major approaches to limit development and progression of CTRCD. RECENT FINDINGS: A broad range of cancer therapies can provoke CTRCD ranging from mild asymptomatic forms to severe heart failure. Profound cardiological assessment of cardiovascular comorbidities before initiation of cancer therapy allows i

Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia.

Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylation is mediated by DNA methyltransferases (DNMTs) consisting of DNMT1, DNMT3A, and DNMT3B. DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML. The clinical response predictive roles of DNMTs in clinical trials utilising hy

Bronchiolitis Obliterans Syndrome Following High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation in a Pediatric Patient With Neuroblastoma.

Bronchiolitis obliterans syndrome (BOS) is a chronic obstructive pulmonary disorder most often recognized as a pulmonary manifestation of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (HSCT). Its occurrence following autologous HSCT (auto-HSCT) is exceedingly rare, and its clinical features and prognosis remain poorly defined. We report the case of a five-year-old girl with neuroblastoma who developed BOS after high-dose chemotherapy with thiotepa and melphalan followed by auto-HSCT. Respiratory symptoms, including dyspnea, wheeze, and oxygen desatu

Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment.

Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard "one size fits all"

Нейростероиды и неврологические расстройства.

Нейростероиды играют важную роль в качестве эндогенных нейромодуляторов, которые производятся на местном уровне в центральной нервной системе и быстро изменяют взрываемость нейронов и активацию микроглиальных клеток и астроцитов. Здесь мы рассматриваем механизмы синтеза, метаболизма и действия нейростероидов в центральной нервной системе. Нейростероиды могут играть различные роли в центральной нервной системе в физиологических условиях, связывая их с мембранными ионными каналами и рецепторами, такими, как рецепторы гамма-аминобутирной кислоты типа А, рецепторы Nметил-D-асортатных рецепторов, к