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Oncolytic Virus Therapy in a New Era of Immunotherapy, Enhanced by Combination with Existing Anticancer Therapies: Turn up the Heat!

Oncolytic viral therapy is a promising treatment for cancer, where 'cold' tumour cells can become 'hot' to the host immune system. However, with few FDA approved therapies, development of new strategies for more cancer types has been slow and relatively unsuccessful in recent years, Combination therapy has been successful for other types of cancer treatment, therefore, may be a viable alternative to improve the efficacy of oncolytic viral therapy which may reduce some of the adverse events of currently used monotherapies, oncolytic virus therapy and chemotherapy being mutually complimentary wi

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… Real-life use of talimogene laherparepvec (T-VEC) in melanoma patients in centers in Austria, Switzerland and Germany. J Immunother Cancer. 2021;9:e001701. doi: 10.1136/jitc-2020-001701. 25. Bach N, Winzer R, Tolosa E, Fiedler W, Brauneck F. The Clinical Significance of CD73 in Cancer. …

Boanmycin overcomes bortezomib resistance by inducing DNA damage and endoplasmic reticulum functional impairment in multiple myeloma.

BackgroundMultiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells and is currently incurable. Despite advancements in therapeutic strategies, resistance to proteasome inhibitors, particularly bortezomib (BTZ), poses a substantial challenge to disease management. This study aimed to explore the efficacy of boanmycin, a novel antitumor antibiotic, in overcoming resistance to BTZ in MM.MethodsBTZ-resistant cells were generated over a period of at least 6 months by gradually increasing the concentration of BTZ. The viability of MM cell lines

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… Absorbance readings were obtained at a wavelength of 450 nm via a Spark microplate reader (TECAN, Austria). CFSE staining assay The cells were incubated with carboxyfluorescein succinimidyl ester (CFSE) at a final concentration of 5 µM for 30 min at 37 °C in an incubator. …

FAST: быстрая, свободная, последовательная и неконтролируемая система сегментации и отслеживания олигодендроцитов.

Чтобы разработать репаративную терапию для неврологических расстройств, таких как множественный склероз (MS), нам нужно лучше понять физиологию потери и замены олигодендроцитов, клеток, которые делают миелин и являются объектом поражения в MS. В Vivo двухфотографическая флуоресцентная микроскопия позволяет непосредственно визуализировать олигодендроциты в нетронутом мозгу трансгенных моделей мыши, что позволяет глубже понять продольную динамику замены олигодендроцитов после повреждения. Однако задача отслеживания судьбы отдельных олигодендроцитов требует больших усилий для ручной аннотации и я

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… Vienna, Austria: R Foundation for Statistical Computing. Sheintuch L, Rubin A, Brande-Eilat N, Geva N, Sadeh N, Pinchasof O, Ziv Y (2017) Tracking the same neurons across multiple days in Ca2+ imaging data. …

Иммунорегулирующий амфипатический песптид, полученный из молекулы защиты фасиолы гепатики (FhHDM-1.C2), демонстрирует мощную биотерапевтическую активность в мусриновой модели множественного склероза.

Молекулярные защитные молекулы (HDM) — семейство иммунных регуляционных пептидов, которые выражаются исключительно триматодными червями. Ранее мы продемонстрировали, что в vivo FhHDM-1, архетипный член HDM, регулировала макрофагическую реакцию на подстрекательские лиганды, тем самым облегчая процесс повреждения иммунной ткани в нескольких мусриновых моделях воспалительных заболеваний. Соответственно, мы исходили из того, что понимание взаимосвязи между структурой и функцией НДМ облегчило бы идентификацию минимального биоактивного пептида, который представлял бы собой более синтезируемый, эконо

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… leukemia THP‐1 cell line (ATCC, Manassas, USA) was cultured (P2‐30) in RPMI 1640 medium with L‐glutamine (2 mM) (Gibco, ThermoFisher Scientific, UK) supplemented with 10% (v/v) heat‐inactivated FBS (Gibco, ThermoFisher Scientific, UK) and 1% (v/v) penicillin/streptomycin (PAA Laboratories GmbH, Pasching, Austria …

Trazodone in the Management of Major Depression Among Elderly Patients with Dementia: A Narrative Review and Clinical Insights.

ObjectiveMajor depressive disorder (MDD) often co-occurs with dementia and other neurological disorders, and treatment with antidepressants can improve symptoms, quality of life, and survival in these patients. This narrative review provides an expert opinion about the role and effectiveness of trazodone in the treatment of older adults with MDD and cognitive impairment due to physical illnesses, such as dementia.ResultsBecause of its mechanism of action, trazodone can treat several depression symptoms often seen in people with dementia, including insomnia, agitation, anxiety, cognitive impair

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… Effects of psychotropic medication on cognition, caregiver burden, and neuropsychiatric symptoms in alzheimer’s disease over 12 months: results from a prospective registry of dementia in Austria (PRODEM). J Alzheimers Dis . 2019;71(2):623–630. doi: 10.3233/JAD-181102 62. …

The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors.

Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of the development of virulence inhibitors, inhibition of quorum sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS-dependent gene expression. Methods: Forty-five pharmacological agents,

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… TPh), simvastatin (SA), atorvastatin (SA), 6. mucolytics and antitussives: ambroxol (TPh), acetyl-cysteine (TPh), guaifenesin (SA), 7. neuroleptic drugs: promethazine (SA), chlorpromazine (SA), thioridazine (SA), 8. antimetabolite anticancer agents: methotrexate (Ebewe Pharma, Unterach am Attersee, Austria …

CPUY201112, a novel synthetic small-molecule compound and inhibitor of heat shock protein Hsp90, induces p53-mediated apoptosis in MCF-7 cells.

Heat-shock protein 90 (Hsp90) is highly expressed in many tumor cells and is associated with the maintenance of malignant phenotypes. Targeting Hsp90 has had therapeutic success in both solid and hematological malignancies, which has inspired more studies to identify new Hsp90 inhibitors with improved clinical efficacy. Using a fragment-based approach and subsequent structural optimization guided by medicinal chemistry principles, we identified the novel compound CPUY201112 as a potent Hsp90 inhibitor. It binds to the ATP-binding pocket of Hsp90 with a kinetic dissociation (Kd) constant of 27

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… R Foundation for Statistical Computing, V., Austria. (14/08/2015). URL http://www.R-project.org/ . Samarasinghe B., Wales C. T., Taylor F. R. & Jacobs A. T. Heat shock factor 1 confers resistance to Hsp90 inhibitors through p62/SQSTM1 expression and promotion of autophagic flux. …

Clinical value and cost-effectiveness analysis of conditionally approved anticancer drugs in China from 2015 to 2023.

BackgroundThe conditional approval (CA) process in China was established in 2015 to expedite access to urgently-needed drugs, however, the clinical benefits of CA drugs and potential gaps between pre-approval and confirmatory trials remain uncertain. Herein, we aim to compare the clinical values between CA and non-CA anticancer drugs from 2015 to 2023, and to explore the relationship between clinical benefit and average daily cost of treatment of drugs.MethodsThis retrospective study analyzed anticancer drugs first approved in China [2015-2023] using data from National Medical Products Adminis

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… Figures were conducted using R (R Core Team, Vienna, Austria), version 4.1.1 (R package forestplot, version 3.1.3 and R package ggplot2, version 3.4.4). P<0.05 was considered to be statistically significant. …

Long-term follow-up of vertebral compression fractures in inpatients treated with integrative Korean medicine: An observational study.

Conservative management is the recommended first-line treatment for thoracolumbar vertebral compression fractures (VCFs), with integrative Korean medicine (IKM) being widely used for treatment in Korea. However, evidence regarding long-term treatment outcomes is lacking. We aimed to investigate the effectiveness of IKM treatment for thoracolumbar VCFs. Data from inpatients with thoracolumbar VCFs who received IKM treatment, comprising acupuncture, pharmacopuncture, electroacupuncture, Chuna manual therapy, and herbal medicine, at 4 KM hospitals from April 1, 2016 to June 30, 2022 were analyzed

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… All analyses were conducted using R 4.2.1 for Windows (R Foundation for Statistical Computing, Vienna, Austria). 3. Results 3.1. Participants From April 1, 2016, to June 30, 2022, a total of 994 patients underwent inpatient treatment for fractures at 4 KM hospitals. …

Parameters Associated With Renal Recovery and Survival in Myeloma Patients With Acute Renal Failure to Cast Nephropathy.

Acute renal failure due to cast nephropathy (CAN) is a severe complication of multiple myeloma (MM). Here, we aimed to identify parameters associated with renal outcomes and survival in newly diagnosed MM patients with CAN-related acute renal failure and to validate the IMWG criteria for renal response. CAN diagnosis was based on biopsy or clinical assessment. Of 787 registered patients, 354 met the inclusion criteria, requiring at least two therapy cycles with documented chemotherapy response, renal response, and eGFR. Baseline free light chain (FLC) levels (median 6825.65 mg/L) decreased bel

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… response | 15–29 | 30–59 Minor response | < 15 | 15–29 Non‐definable | 15–29 | 30–59 Statistical Analysis Statistical analyses were performed using SPSS software version 17.0 (IBM SPSS Statistics, IBM Corporation, Armonk, NY) and RStudio (version 4.3.3; R Foundation for Statistical Computing, Vienna, Austria …

Глобальная распространенность и факторы риска суицидальных идеи при множественном склерозе: систематический обзор и мета-анализ.

СЮ, попытки и смерть часто описываются и расследуются в связи с такими хроническими неврологическими расстройствами, как множественный склероз (MS). В ходе этого систематического обзора и метаанализа была проведена оценка глобальной распространенности СИ у пациентов с НР и продемонстрированы связанные с этим факторы риска. Это может помочь врачу сократить число попыток самоубийства и улучшить состояние здоровья населения. МЕТОДЫ: Был проведен всеобъемлющий систематический поиск на PubMed, Scopus, Embase и Web of Science с целью поиска исследований, в которых сообщалось о распространенности SI

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… Statistical Analysis The statistical analyses were performed in R version 4.2.2 (R Core Team [2021], Vienna, Austria). To estimate the overall pooled prevalence, a random effects model was used. …

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

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… All statistical analyses were performed in R (version 4.1.0, the R Foundation for Statistical Computing, Vienna, Austria), using the TwoSampleMR package. 2.6. …

Real-World Treatment Outcomes of Different Sequencing Options with Daratumumab, Lenalidomide, and Dexamethasone in Patients with Transplant-Ineligible Multiple Myeloma in Japan.

Multiple myeloma (MM) is a hematologic malignancy characterized by monoclonal proliferation of plasma cells that leads to bone disease, including lytic lesions and osteoporosis [...].

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… All other analyses were conducted using SAS version 9.4 (SAS Institute, Cary, NC, USA) and R version 4.3.1 (R Core Team, R Foundation for Statistical Computing, Vienna, Austria). 3. Results 3.1. …

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

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… Patients were included in 10 different centers in 5 countries (Austria, Italy, France, The Netherlands, and United Kingdom). Hemoglobin (Hb) response was considered none, partial (PR; Hb, 10-12 g/dL or >2 g/dL increase), or complete (CR; Hb > 12 g/dL), in the absence of recent RBC transfusion. …

Frequency of Topical Immunomodulatory and Immunosuppressive Therapies for Ocular Chronic Graft-versus-Host Disease.

Introduction: The purpose of the study was to evaluate the frequency of topical immunomodulatory and immunosuppressive therapies in patients with ocular chronic graft-versus-host disease (cGVHD) in consideration of inflammatory activity and systemic immunosuppressive therapies in a tertiary care university hospital setting. Methods: We included 95 adult patients (48 male, 47 female) with ocular chronic graft-versus-host disease (cGVHD) after alloHSCT (median age 49.5 years). Clinical ophthalmological findings and the grade of ocular cGVHD according to the NIH eye score and the German-Austrian-…

Comparative Efficacy of Talquetamab vs. Current Treatments in the LocoMMotion and MoMMent Studies in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma.

IntroductionTalquetamab, a bispecific antibody targeting GPRC5D × CD3, is approved for the treatment of patients with triple-class -exposed (TCE) relapsed/refractory multiple myeloma (RRMM) on the basis of the results from the phase I/II MonumenTAL-1 trial. The relative effectiveness of talquetamab vs. real-world physician's choice of therapy (RWPC) was assessed using adjusted comparisons.MethodsAn external control arm for MonumenTAL-1 (subcutaneously administered talquetamab 0.4 mg/kg weekly [QW] and 0.8 mg/kg every other week [Q2W]) was created from two observational real-world studies: Loco

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… Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA) and R version 3.6.1 and 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria). …

Oral foci of infection and their relationship with hospital stay after haematopoietic cell transplantation.

PurposeOral focus screening is recommended before HCT (haematopoietic cell transplantation). Acute foci are generally treated pre-HCT. However, it is unclear whether chronic foci should be treated pre-HCT. This study aimed to evaluate the association between number of foci and early post-HCT morbidity and mortality.MethodsPatients who received an oral screening pre-HCT at Radboudumc between 2013 and 2023, with a recent panoramic radiograph, were included. Foci were defined as teeth or implants with deep pockets, furcation radiolucencies, periapical radiolucencies, deep caries, partial eruption

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… Statistical analyses were performed using R (version 4.1.3; R Foundation for Statistical Computing, Vienna, Austria). Results In total, 520 patients were subjected to an oral focus screening within the inclusion period and actually received their planned autologous or allogeneic HCT. …

A systematic review and meta-analysis of carfilzomib-associated thrombocytopenia as an adverse event in patients with multiple myeloma.

BackgroundCarfilzomib is a second-generation proteasome inhibitor (PI) used for combination therapy with dexamethasone and/or lenalidomide in patients with relapsed or refractory multiple myeloma. Reports indicate that PIs have a unique toxicity profile that includes thrombocytopenia as a hematologic adverse event; however, its occurrence has not yet been quantified systematically.ObjectivesThe main objective of our systematic review and meta-analysis is to investigate the incidence of thrombocytopenia in patients with multiple myeloma after treatment with carfilzomib.DesignSelection of studie

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… Data was managed and analyzed using a MS Excel 2019 (Microsoft Corporation, Redmond, WA, USA), RevMan 5.4.1 (Cochrane, London, UK, 2020), and R Statistical Software (v4.1.2; R Core Team, R Fundation for Statistical Computing, Vienna, Austria, 2021) via “meta” R package (v5.5-0). …

Patient-reported outcomes of chimeric antigen receptor T-cell therapy in hematologic malignancies: a systematic review and meta-analysis.

Few studies evaluated patient-reported outcomes (PROs) for patients with hematologic malignancies receiving with Chimeric Antigen Receptor T (CAR-T) cell therapy. We performed a systematic review and meta-analysis to evaluate the benefits of CAR-T cell therapies focused on PROs. A systematic literature searched from PubMed, Cochrane, and the Web of Science from inception to September 2023. Study selection and data extraction were conducted independently by two reviewers based on pre-specified criteria. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) R

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… Statistical analysis The PROM outcome data were analyzed using R software and RStudio (version 2022.12.0 + 353; R Core Team, Vienna, Austria) and the Comprehensive Metaanalysis 2.0 13 . …

Rack1-mediated ferroptosis affects hindgut development in rats with anorectal malformations: Spatial transcriptome insights.

Anorectal malformation (ARM), a common congenital anomaly of the digestive tract, is a result of insufficient elongation of the urorectal septum. The cytoplasmic protein Receptor of Activated C-Kinase 1 (Rack1) is involved in embryonic neural development; however, its role in embryonic digestive tract development and ARM formation is unexplored. Our study explored the hindgut development and cell death mechanisms in ARM-affected rats using spatial transcriptome analysis. We induced ARM in rats by administering ethylenethiourea via gavage on gestational day (GD) 10. On GDs 14-16, embryos from b

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… Pathway RespOnsive GENes (PROGENy) and non‐negative matrix factorisation (NNMF) algorithms Pathway activity analysis was conducted using the ‘PROGENy’ package (version 1.12.0) in R software (version 4.0.3; R Foundation for Statistical Computing, Vienna, Austria). …