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Increase in Nuclear Cell-Free DNA is Associated with Major Adverse Events in Adult and Pediatric Heart Transplant Recipients.

Clin Transplant 2021 Oct 14:e14509. Epub 2021 Oct 14.

Division of Pediatric Cardiothoracic Surgery, Department of Surgery, Medical College of Wisconsin, Herma Heart Institute, Children's Wisconsin, Milwaukee, WI, United States.

Background: Cell-free DNA is an emerging biomarker. While donor fraction may detect graft events in heart transplant recipients, the prognostic value of total nuclear cell-free DNA (ncfDNA) itself is largely unexplored.

Objective: Explore the relationship between ncfDNA and clinical events in heart transplant recipients. Read More

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October 2021

Definitive screening accelerates Taxol biosynthetic pathway optimization and scale up in Saccharomyces cerevisiae cell factories.

Biotechnol J 2021 Oct 14:e2100414. Epub 2021 Oct 14.

Institute for Bioengineering, School of Engineering, University of Edinburgh, Edinburgh, UK.

Background: Recent technological advancements in synthetic and systems biology have enabled the construction of microbial cell factories expressing diverse heterologous pathways in unprecedentedly short time scales. However, the translation of such laboratory scale breakthroughs to industrial bioprocesses remains a major bottleneck.

Methods And Major Results: In this study, an accelerated bioprocess development approach was employed to optimize the biosynthetic pathway of the blockbuster chemotherapy drug, Taxol. Read More

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October 2021

Unfolding the potential of anti-programmed cell death protein 1 blockade in Hodgkin lymphoma - combination and personalisation?

Br J Haematol 2021 Oct 14. Epub 2021 Oct 14.

Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Cologne, Germany.

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October 2021

T-cell immune response after mRNA SARS-CoV-2 vaccines is frequently detected also in the absence of seroconversion in patients with lymphoid malignancies.

Br J Haematol 2021 Oct 14. Epub 2021 Oct 14.

School of Medicine, University of Milano, Italy.

Patients affected by lymphoid malignancies (LM) are frequently immune-compromised, suffering increased mortality from COVID-19. This prospective study evaluated serological and T-cell responses after complete mRNA vaccination in 263 patients affected by chronic lymphocytic leukaemia, B- and T-cell lymphomas and multiple myeloma. Results were compared with those of 167 healthy subjects matched for age and sex. Read More

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October 2021

Effectiveness of Chest CT in Children: CT Findings in Relation to the Clinical Question.

Rofo 2021 Oct 14. Epub 2021 Oct 14.

Diagnostic and Interventional Radiology, Universitätsklinikum Tübingen, Tübingen, Germany.

Purpose:  To estimate the effectiveness and efficiency of chest CT in children based on the suspected diagnosis in relation to the number of positive, negative, and inconclusive CT results.

Materials And Methods:  In this monocentric retrospective study at a university hospital with a division of pediatric radiology, 2019 chest CT examinations (973 patients; median age: 10.5 years; range: 2 days to 17. Read More

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October 2021

Pulmonary Imaging of Immunocompromised Patients during Hematopoietic Stem Cell Transplantation using Non-Contrast-Enhanced Three-Dimensional Ultrashort Echo Time (3D-UTE) MRI.

Rofo 2021 Oct 14. Epub 2021 Oct 14.

Department of Diagnostic and Interventional Radiology, University Hospital of Würzburg, Germany.

Purpose:  To evaluate the feasibility of non-contrast-enhanced three-dimensional ultrashort echo time (3D-UTE) MRI for pulmonary imaging in immunocompromised patients during hematopoietic stem cell transplantation (HSCT).

Methods:  MRI was performed using a stack-of-spirals 3D-UTE sequence (slice thickness: 2.34mm; matrix: 256 × 256; acquisition time: 12. Read More

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October 2021

Phase 2 multicenter trial of ofatumumab and prednisone as initial therapy of chronic graft-vs-host disease.

Blood Adv 2021 Oct 14. Epub 2021 Oct 14.

H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States.

Standard initial therapy of chronic graft vs. host disease (cGVHD) with glucocorticoids results in suboptimal and transient responses in a significant number of patients. Safety and feasibility of anti-CD20 directed B-cell therapy with ofatumumab (1000 mg IV on days 0 and 14) and prednisone (1 mg/kg/day) was previously established in our phase I trial (n=12). Read More

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October 2021

Multiple Myeloma Cells Depend on the DDI2/NRF1-mediated Proteasome Stress Response for Survival.

Blood Adv 2021 Oct 14. Epub 2021 Oct 14.

Harvard Medical School, United States.

Multiple myeloma (MM) cells suffer from baseline proteotoxicity due to an imbalance between the load of misfolded proteins awaiting proteolysis and the capacity of the ubiquitin-proteasome system to degrade them. This intrinsic vulnerability is at the base of MM sensitivity to agents that perturb proteostasis such as proteasome inhibitors (PIs), the mainstay of modern-day myeloma therapy. De-novo and acquired PI resistance are important clinical limitations, adversely affecting prognosis. Read More

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October 2021

A clinical, histopathological, and molecular study of two cases of VEXAS syndrome without a definitive myeloid neoplasm.

Blood Adv 2021 Oct 14. Epub 2021 Oct 14.

Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States.

VEXAS (vacuoles, E1 enzyme, X- linked, autoinflammatory, somatic) syndrome is caused by somatic mutations in UBA1 and is identified using a genotype-driven method. This condition connects unrelated men with adult-onset inflammatory syndromes in association with hematologic manifestations of peripheral cytopenia and bone marrow myeloid dysplasia. While bone marrow vacuolization restricted to myeloid and erythroid precursors has been identified in VEXAS patients, the detailed clinical and histopathological features of peripheral blood and bone marrows remain unclear. Read More

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October 2021

INCB84344-201: Ponatinib and steroids in frontline therapy of unfit patients with Ph+ acute lymphoblastic leukemia.

Blood Adv 2021 Oct 14. Epub 2021 Oct 14.

Incyte Corporation, Wilmington, Delaware, United States.

Tyrosine kinase inhibitors have improved survival for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, prognosis for old or unfit patients remains poor. In the INCB84344-201 (formerly GIMEMA LAL 1811) prospective, multicenter, phase 2 trial, we tested the efficacy and safety of ponatinib plus prednisone in newly diagnosed patients with Ph+ ALL aged ≥60 years, or unfit for intensive chemotherapy and stem cell transplantation. Read More

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October 2021

Worse outcome and distinct mutational pattern in follicular lymphoma with anti-HBc positivity.

Blood Adv 2021 Oct 14. Epub 2021 Oct 14.

Group of Applied Clinical Research in Hematology, Cancer Research Program-IMIM (Hospital del Mar Medical Research Institute) Barcelona, Spain.

Epidemiological studies have demonstrated the association between hepatitis B virus (HBV) infection and B-cell non-Hodgkin lymphomas (NHL), mainly for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). We studied a cohort of 121 FL patients for HBV infection status, clinical features and gene mutational profile. Anti-HBc was detectable in sixteen patients (13. Read More

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October 2021

Mega-dose 90Y-Ibritumomab tiuxetan prior to allogeneic transplantation is effective for aggressive large B-cell lymphoma.

Blood Adv 2021 Oct 14. Epub 2021 Oct 14.

Fred Hutchinson Cancer Research Center, United States.

Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative for relapsed or refractory B-cell lymphomas (BCL), though outcomes are worse in aggressive disease and most patients will still experience relapse. Radioimmunotherapy (RIT) using 90Y-Ibritumomab tiuxetan can induce disease control across lymphoma subtypes in a dose-dependent fashion. We hypothesized that mega-doses of 90Y-Ibritumomab tiuxetan with reduced-intensity conditioning (RIC) could safely produce deeper remissions in aggressive BCL further maintained with the immunologic effect of allo-HCT. Read More

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October 2021

Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model.

Blood Adv 2021 Oct 14. Epub 2021 Oct 14.

Hannover Medical School, Hannover, Germany.

Primary or secondary immunodeficiencies are characterized by disruption of the cellular and humoral immunity. Respiratory infections are a major cause of morbidity and mortality among immunodeficient or immunocompromised patients with Staphylococcus aureus being a common offending organism. We here propose an adoptive macrophage transfer approach aiming to enhance impaired pulmonary immunity against S. Read More

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October 2021

Cisplatin-Based versus Carboplatin-Based Chemotherapy for Extra-Pulmonary Neuroendocrine Carcinomas; A Real-World Study.

Neuroendocrinology 2021 Oct 14. Epub 2021 Oct 14.

Objective: To assess the survival differences between cisplatin/etoposide versus carboplatin/etoposide chemotherapy regimens in the management of extra-pulmonary neuroendocrine carcinomas (NECs).

Methods: Administrative cancer care databases in the province of Alberta, Canada were reviewed, and patients with extra-pulmonary NECs (including those with small cell and large cell neuroendocrine carcinomas) who were treated with either cisplatin/ etoposide or carboplatin/ etoposide, 2004-2019, were reviewed. Kaplan-Meier survival estimates were used to compare the survival outcomes according to the type of platinum agent, and multivariable Cox regression analysis was used to assess the impact of the type of platinum agent on overall survival outcomes. Read More

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October 2021

The Role of Streptococcal Cell-Envelope Proteases in Bacterial Evasion of the Innate Immune System.

J Innate Immun 2021 Oct 14:1-20. Epub 2021 Oct 14.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Bacteria possess the ability to evolve varied and ingenious strategies to outwit the host immune system, instigating an evolutionary arms race. Proteases are amongst the many weapons employed by bacteria, which specifically cleave and neutralize key signalling molecules required for a coordinated immune response. In this article, we focus on a family of S8 subtilisin-like serine proteases expressed as cell-envelope proteases (CEPs) by group A and group B streptococci. Read More

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October 2021

Small Airway Susceptibility to Chemical and Particle Injury.

Respiration 2021 Oct 14:1-13. Epub 2021 Oct 14.

Toxicology Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Didcot, United Kingdom.

Small airways (SA) in humans are commonly defined as those conducting airways <2 mm in diameter. They are susceptible to particle- and chemical-induced injury and play a major role in the development of airway disease such as COPD and asthma. Susceptibility to injury can be attributed in part to structural features including airflow dynamics and tissue architecture, but recent evidence may indicate a more prominent role for cellular composition in directing toxicological responses. Read More

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October 2021

Ataxia Telangiectasia and Rad3-Related Activation by DNA Damage Mitigates Maladaptive Repair after Acute Kidney Injury.

Nephron 2021 Oct 14:1-4. Epub 2021 Oct 14.

Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

DNA damage is an important consequence of injury to the proximal tubule. The proximal tubule cell responds to this damage by mounting a DNA damage response (DDR). Two protein kinases, ataxia-telangiectasia mutated (ATM) or ataxia telangiectasia and Rad3-related (ATR), play an important role in this DDR. Read More

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October 2021

Circ_ROBO2/miR-149 Axis Promotes the Proliferation and Migration of Human Aortic Smooth Muscle Cells by Activating NF-κB Signaling.

Cytogenet Genome Res 2021 Oct 14:1-11. Epub 2021 Oct 14.

Department of Cardiovascular Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China.

Atherosclerosis is the leading global cause of mortality. The occurrence of coronary artery disease (CAD) is regulated by a diversity of pathways, including circRNAs. However, the potential mechanisms of circRNAs in CAD remain unclear. Read More

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October 2021

Effect of the Fungal Immunomodulatory Protein FIP-fve in the Neutrophilic Asthma Animal Model.

Int Arch Allergy Immunol 2021 Oct 14:1-12. Epub 2021 Oct 14.

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Background: Asthma animal models provide valuable information about the pathogenesis and the treatment of asthma. An ovalbumin (OVA)/complete Freund's adjuvant (CFA)-sensitized model was developed to induce neutrophil-dominant asthma and to investigate whether fungal immunomodulatory peptide-fve (FIP-fve) could improve asthma features in the OVA/CFA-sensitized model.

Methods: We used female BALB/c mice and sensitized them intraperitoneally with OVA/CFA on days 1, 2, and 3. Read More

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October 2021

Telomerase-Positive Somatic Tissues of Honeybee Queens (Apis mellifera) Display No DNA Replication.

Cytogenet Genome Res 2021 Oct 14:1-6. Epub 2021 Oct 14.

Institute of Entomology, Biology Centre of the Czech Academy of Sciences, České Budějovice, Czechia.

Telomere biology is closely linked to the process of aging. The restoration of telomere length by maintaining telome-rase activity in certain cell types of human adults allows for the proliferative capacity of the cells and preserves the regeneration potential of the tissue. The absence of telome-rase, that leads to telomere attrition and irreversible cell cycle arrest in most somatic cells, acts as a protective mechanism against uncontrolled cancer growth. Read More

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October 2021

A new colorimetric assay for sensitive detection of glucose-6-phosphate dehydrogenase deficiency based on silver nanoparticles.

Nanotechnology 2021 Oct 14. Epub 2021 Oct 14.

Tarbiat Modares University, Amirabad, Tehran, Tehran, +981234, Iran (the Islamic Republic of).

Glucose-6-phosphate dehydrogenase (G6PD) is the principal enzyme in the pentose phosphate pathway (PPP) that plays a fundamental role in the production of nicotinamide adenine dinucleotide phosphate (NADPH), which is very important in preventing the oxidation of cells, especially red blood cells (RBC). This enzyme deficiency was associated with many disorders, the most common of which were hemolysis episodes. In the last decade, nanoparticles have been used to design optical and electronic sensors due to their unique properties. Read More

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October 2021

Emerging targets for anticancer vaccination: PD-1.

ESMO Open 2021 Oct 11;6(5):100278. Epub 2021 Oct 11.

Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. Electronic address:

Among the mechanisms by which tumor cells escape the immune surveillance, one is the interaction between programmed cell death protein 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1). Inhibition of the PD-1/PD-L1 pathway with monoclonal antibodies as immune checkpoint inhibitors targeting PD-1 or its ligand, PD-L1, represents a milestone in cancer therapy. The application of these antibodies, however, suffers from drawbacks including failure to show a response or benefit in a majority of patients following monotherapy or combination therapy, their frequent administration, and cost intensiveness. Read More

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October 2021

Foresight regarding drug candidates acting on the succinate-GPR91 signalling pathway for non-alcoholic steatohepatitis (NASH) treatment.

Biomed Pharmacother 2021 Oct 12;144:112298. Epub 2021 Oct 12.

Hydrogen Medicine Center of Taishan Academy of Medical Sciences, Taian City Central Hospital, Taian 271000, PR China. Electronic address:

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is a liver manifestation of metabolic syndrome, with a histological spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH can evolve into progressive liver fibrosis and eventually lead to liver cirrhosis. The pathological mechanism of NASH is multifactorial, involving a series of metabolic disorders and changes that trigger low-level inflammation in the liver and other organs. Read More

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October 2021

Bisdemethoxycurcumin alleviates vandetanib-induced cutaneous toxicity in vivo and in vitro through autophagy activation.

Biomed Pharmacother 2021 Oct 12;144:112297. Epub 2021 Oct 12.

Center for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, PR China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China. Electronic address:

High incidence of cutaneous toxicity ranging from 29.2% to 71.2% has been reported during clinical use of vandetanib, which is a multi-target kinase inhibitor indicated for the treatment of unresectable medullary thyroid carcinoma. Read More

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October 2021

Next-gen therapeutics to spare and expand beta-cell mass.

Curr Opin Pharmacol 2021 Oct 11;61:77-82. Epub 2021 Oct 11.

Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy; International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Università di Milano, Milan, Italy; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

The most effective and physiological way to treat hyperglycemia is to restore beta-cell function and to rescue production of endogenous insulin. Increasing evidence suggests that both type 1 and type 2 diabetes are characterized by a significant defect in beta-cell mass, leading to the manifestation of the disease. Novel alternative approaches are needed to spare and expand beta-cell mass in patients with diabetes. Read More

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October 2021

Influence of amphotericin B on the DPPC/DOPC/sterols mixed monolayer in the presence of calcium ions.

Biophys Chem 2021 Sep 29;279:106695. Epub 2021 Sep 29.

Shaanxi Engineering Research Center of Controllable Neutron Source, School of Science, Xijing University, Xi'an 710123, China.

Amphotericin B, an acquainted antifungal drug, has reattracted the attention of most scholars due to its one important advantage of making the fungus less resistant. Amphotericin B's antifungal properties are derived from its ability to interact with ergosterols on the fungal cells' membrane to form pores. However, the cholesterol in the human cell membranes is similar in structure to ergosterol, which cause the drug to produce certain toxicity and make the clinical use of amphotericin B limited. Read More

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September 2021

Atractylenolide inhibits apoptosis and oxidative stress of HTR-8/SVneo cells by activating MAPK/ERK signalling in preeclampsia.

Phytomedicine 2021 Sep 26;93:153773. Epub 2021 Sep 26.

Chinese Medicine College, Shandong University of Traditional Chinese Medicine, Shandong, Jinan 250355, China. Electronic address:

Background: Preeclampsia (PE) is a severe hypertension-related disorder occurring during pregnancy that leads to significant mortality and morbidity in both the foetus and mother. Atractylenolide (ATL), a traditional Chinese natural agent isolated from the herb Atractylodes macrocephala, exhibits a series of pharmacological activities, including anti-oxidative stress and anti-inflammatory effects.

Purpose: The impacts of ATL on apoptosis and oxidative stress in HTR-8/SVneo cells during PE development was investigated. Read More

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September 2021

Compound Kushen Injection intervenes metabolic reprogramming and epithelial-mesenchymal transition of HCC via regulating β-catenin/c-Myc signaling.

Phytomedicine 2021 Sep 27;93:153781. Epub 2021 Sep 27.

Modern Research Center for Traditional Chinese Medicine, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China; Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Taiyuan, China. Electronic address:

Background: Hepatocellular carcinoma (HCC) is one of the most extensive and most deadly cancers worldwide. The invasion and metastasis characteristics of HCC dramatically affect the prognosis and survival of HCC patients. Compound Kushen Injection (CKI) is a GMP produced, proverbially applied traditional Chinese medicine formula in China to treat cancer-associated pains, and used as an adjunctive therapy for HCC. Read More

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September 2021

In vitro anti-motile effects of Rhoifolin, a flavonoid extracted from Callicarpa nudiflora on breast cancer cells via downregulating Podocalyxin-Ezrin interaction during Epithelial Mesenchymal Transition.

Phytomedicine 2021 Jan 28;93:153486. Epub 2021 Jan 28.

School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China. Electronic address:

Background: Callicarpa nudiflora (C. nudiflora), which is a medical herb in genus of Callicarpa, widely grows in the southern part of China. Several investigations had shown that this herb exerts anti-tumor effects. Read More

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January 2021

Generation of induced pluripotent stem cell lines from peripheral blood mononuclear cells of three drug resistant and three drug responsive epilepsy patients.

Stem Cell Res 2021 Oct 9;56:102564. Epub 2021 Oct 9.

The University of Queensland, UQ Centre for Clinical Research, Herston, Brisbane, QLD 4029, Australia; Department of Neurology, Royal Brisbane and Women's Hospital, Herston, Brisbane, QLD 4029, Australia.

Epilepsy is a common neurological disorder characterized by seizures. Unfortunately, 30-40% of all epilepsy patients are resistant to at least two or more anti-seizure medications. Attempts to treat these patients and prevent further seizures necessitates multiple drug trials for the patient. Read More

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October 2021