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Improving Evidence-Based Practice through Preregistration of Applied Research: Barriers and Recommendations
Account Res. 2021 Aug 16. doi: 10.1080/08989621.2021.1969233. Online ahead of print.ABSTRACTPreregistration is the practice of publicly publishing plans on central components of the research process before access to, or collection, of data. Within the context of the replication crisis, open science practices like preregistration have been pivotal in facilitating greater transparency in research. However, such practices have been applied nearly exclusively to basic academic research, with rare consideration of the relevance to applied and consultancy-based research. This is particularly problematic as such research is typic...
Source: Accountability in Research - August 16, 2021 Category: Medical Ethics Authors: Thomas Rhys Evans Peter Branney Andrew Clements Ella Hatton Source Type: research
What We Learned in 25 Years of Interactive Molecular Design Sessions
ChemMedChem. 2021 Aug 10. doi: 10.1002/cmdc.202100351. Online ahead of print.ABSTRACTWe retrace Prof. François Diederich's consultancy work for Roche and its impact over the years he worked with us. François Diederich uniquely shaped our approach to molecular design, and interactions with him and his research group at ETH Zurich have created deep insights into molecular recognition. Herein we share how his style and approach continue to inspire us.PMID:34374230 | DOI:10.1002/cmdc.202100351
Source: ChemMedChem - August 10, 2021 Category: Chemistry Authors: Bernd Kuhn Wolfgang Haap Ulrike Obst-Sander Christian Kramer Martin Stahl Source Type: research
Individual planning starts at school. Tools and practices promoting autonomy and supporting transition to work for adolescents with autism spectrum disorder
Ann Ist Super Sanita. 2020 Apr-Jun;56(2):222-229. doi: 10.4415/ANN_20_02_12.ABSTRACTThere is an increasing need for effective services and strategies to favor the transition from school to post-school/working experience for individuals with disabilities and specifically with autism spectrum disorder (ASD). Post-school options are still limited, and most adults with ASD struggle in finding adequate and stable job opportunities. This work analyzes the increasing number of laws issued in Italy in the last decades in order to improve social and working inclusion. The central role of the individual educational planning (IEP) as...
Source: Annali dell'Istituto Superiore di Sanita - June 23, 2020 Category: International Medicine & Public Health Authors: Fiorenzo Laghi Barbara Trimarco Source Type: research
159PPrognostic immunoprofiling of muscle invasive bladder cancer (MIBC) patients in a multicentre setting
ConclusionsOur multicentre and multi-assay study suggests that the density of CD8 positive cells in the tumour core is a robust prognostic factor in MIBC. Further investigation of PD-L1 and CD3 cell density is warranted.Legal entity responsible for the studyDefiniens AG; The Walter and Eliza Hall Institute of Medical Research; University of St Andrews.FundingDefiniens AG.DisclosureK. Nekolla: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. N. Brieu: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. C.G. Gavriel: Research grant / Funding (self...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
389TiPPRECYCLE: Impact of CANKADO-based eHealth-support on quality of life in metastatic breast cancer patients treated with palbociclib and endocrine therapy
AbstractBackgroundEfficacy and quality of life (QoL) are key factors when selecting therapies for metastatic breast cancer (MBC) patients. The addition of targeted oral agents such as CDK4/6 inhibitors to endocrine therapy is the new standard for HR+ HER2- MBC and substantially prolongs progression-free survival. However more complex oral medication in oncology might require substantial improvement of patient management. Despite several advantages of oral treatments, patients become increasingly self-responsible and physician-patient contact is reduced. Adherence, maintaining patients ’ satisfaction and early detection m...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
CD55 and CD59 Can Limit the Anti-Tumor Efficacy of Daratumumab in Natural Killer/T-Cell Lymphoma
In this report we show that subsequent testing in an NKTL mouse xenograft model confirms the potency of Daratumumab in vivo as evidenced by the inhibition in tumour progression and prolongation of mouse survival. When treatment was continued over a month, some tumors began to rapidly enlarge ('Resistant') while the rest remained similar or smaller ('Sensitive') than the tumour volume at the initiation of Daratumumab treatment. An mRNA analysis comparing 'Resistant' and 'Sensitive' tumors showed that while both tumours bore similar levels of CD38 expression, resistant tumours displayed an upregulation of complement inhibito...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mustafa, N., Nee, A. H. F., Chooi, J. Y., Toh, S. H. M., Hee, Y. T., Selvarajan, V., Zhou, L., Yang, J., Chng, W. J. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Poster I Source Type: research
Recurrent Mutations in EGR2 Direct Specific Epigenetic Reconfiguration in Chronic Lymphocytic Leukemia
Epigenetic alterations are universal in cancer and are important in establishing the malignant phenotype. Dissection of the factors that shape the tumor-specific epigenome may reveal insight into key aspects of tumorigenesis and therapeutic resistance. In chronic lymphocytic leukemia (CLL), we have previously found that broad changes in epigenetic patterns co-occur with the evolution of genetic alterations. We have also uncovered that aberrant patterning of DNA methylation in CLL involves excessive activity of a defined group of transcription factors (TFs), including the early growth response (EGR) TF family. Recent work h...
Source: Blood - November 21, 2018 Category: Hematology Authors: Weigel, C., Assenov, Y., Imbusch, C., Wang, Q., Beekman, R., Giacopelli, B., Wu, Y.-z., Brocks, D., Dieter, W., Odilia, P., Schmezer, P., Brors, B., Mertens, D., Rippe, K., Rassenti, L. Z., Kipps, T. J., Woyach, J. A., Blachly, J. S., Campo, E., Zenz, T., Tags: 602. Disordered Gene Expression in Hematologic Malignancy, including Disordered Epigenetic Regulation: Epigenetic Modification Source Type: research
Hypofibrinogenemia and Disseminated Intravascular Coagulation Rarely Complicate Treatment-Naive Acute Lymphoblastic Leukemia
Discussion: Our study demonstrated that HF and DIC in treatment-naive ALL are uncommon. The rare incidence of DIC in our population is consistent with prior studies in adult ALL (Sarris et al., Blood, 1992). Our findings are also similar to those reported in patients with non-APL acute myeloid leukemia (Weltermann et al., Leukemia, 1998). In contrast, most patients with APL exhibit HF (Lou et al., Leuk Res, 2016). Proposed mechanisms of coagulopathy in APL include primary activation of fibrinolysis, as well as expression of tissue factor and cancer procoagulant by the malignant promyelocytes themselves; these mechanisms ap...
Source: Blood - November 21, 2018 Category: Hematology Authors: Gaulin, C., Chan, A., Geyer, M. B., Park, J. H., Mantha, S., Tallman, M. S. Tags: 322. Disorders of Coagulation or Fibrinolysis: Poster I Source Type: research
Genome Wide Association Analyses Identify Pleiotropic Variants Associated with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Susceptibility
The first two authors and last two authors contributed equally.Genome-wide association studies (GWAS) have identified risk loci for Acute Lymphoblastic Leukemia (ALL), Chronic Lymphoblastic Leukemia (CLL) and Non-Hodgkin Lymphoma, however an Acute Myeloid Leukemia (AML) GWAS has not been published to date. We performed a GWAS to identify AML and Myelodysplastic Syndrome (MDS) risk loci using a nested case-control study design in the DISCOVeRY-BMT cohorts which includes almost 2000 AML and MDS patients as cases and 2813 unrelated donors as controls.Genotyping was performed using the Illumina Human OmniExpress BeadChip and i...
Source: Blood - November 21, 2018 Category: Hematology Authors: Wang, J., Clay-Gilmour, A. I., Karaesmen, E., Rizvi, A., Zhu, Q., Yan, L., Preus, L., Liu, S., Stram, D., Pooler, L., Cheng, X., Haiman, C., Van Den Berg, D., Webb, A., Brock, G., Griffiths, E. A., Spellman, S. R., Pasquini, M. C., McCarthy, P. L., Allan, Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research
MDM2 and Aurora Kinase a Contribute to SETD2 Loss of Function in Advanced Systemic Mastocytosis: Implications for Pathogenesis and Treatment
The SETD2 gene encodes the only methyltransferase responsible for histone H3 lysine 36 trimethylation (H3K36Me3) in humans. H3K36me3 play a key role in preserving the fidelity of transcription elongation and splicing. In addition, SETD2/H3K36me3 have more recently been implicated in the maintenance of genomic integrity by regulating homologous recombination (HR) repair, Mismatch Repair (MMR) mitotic spindle assembly and chromosome segregation. SETD2 deletions and/or inactivating mutations occur in many solid tumors and have recently been found also in acute leukemias. We have reported that the HMC-1.1 and -1.2 mast cell le...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mancini, M., Monaldi, C., De Santis, S., Papayannidis, C., Rondoni, M., Bavaro, L., Martelli, M., Maria Chiara, A., Curti, A., Ficarra, E., Paciello, G., Fontana, M. C., Zanotti, R., Bonifacio, M., Scaffidi, L., Pagano, L., Criscuolo, M., Albano, F., Cice Tags: 635. Myeloproliferative Syndromes: Basic Science: Poster I Source Type: research
Targeting Oncoprotein Translation with Rocaglates in MYC-Driven Lymphoma
Background: c-MYC (MYC) is commonly dysregulated in aggressive B cell lymphomas. MYC associated lymphoma, especially Double Hit lymphoma (DHL) and Double-Expression Lymphoma (DEL) which are characterized by MYC and BCL2 dual overexpression usually present with the inferior outcome as rapid disease progression and poor response to standard chemotherapy regimen. Nevertheless, MYC is considered as an "undruggable" target and targeting strategies such as suppressing MYC transcription by bromodomain (BRD)-4 inhibitors have been widely investigated in both preclinical models and clinical trials. However, increasing evidence has ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, X., Bi, C., Lu, T., Yue, T., Zhang, W., Zhang, X., Cheng, W., Tian, T., Lunning, M. A., Vose, J. M., Pelletier, J., Porco, J. A., Tao, J., Fu, K. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Specific Pathway Inhibitors Source Type: research
Musashi 2 Is Overexpressed in Poor Outcome CLL Patients and Their Proliferative Fraction and Silencing This Gene Induces Apoptosis and Increases Cell Adhesion and Movement
The growth of CLL cells stems from a small fraction of dividing CD5+B cells. The size and rate of growth of this proliferative fraction (PF) correlates directly with poor outcome prognostic markers and inversely with time-to-first-treatment. Furthermore, since dividing cells upregulate DNA mutators (AID and APOBEC), the PF can acquire new DNA abnormalities that can lead to more lethal disease. Hence, cells of the PF are important targets for therapy.By gene expression profile analysis, we found that Musashi 2 (MSI2) is highly expressed in the PF (CXCR4DimCD5Bright) compared with the resting fraction (RF) that expresses the...
Source: Blood - November 21, 2018 Category: Hematology Authors: Palacios, F., Yan, X.-J., Ferrer, G., Barrientos, J. C., Kolitz, J. E., Allen, S. L., Kanti R., R., Chiorazzi, N. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster I Source Type: research
Concomitant Targeting of FLT3 and BTK with CG'806 Overcomes FLT3-Inhibitor Resistance through Inhibition of Autophagy
Fms-like tyrosine kinase 3 (FLT3)-targeted therapy represents an important paradigm in the management of patients with highly aggressive FLT3 mutated acute myeloid leukemia (AML). However, clinical efficacy is usually transient and followed by emergence of resistance to FLT3-inhibitors (Borthakur et al., 2011; Cortes et al., 2013; Zhang et al., 2008). Such resistance often results from acquired mutations of TKD, which are frequently identified in D835, Y842 and F691 residues (Smith et al., 2015; Smith et al., 2012; Zhang et al., 2014). It was reported that the FLT3-ITD-targeting drug sorafenib can induce autophagy in human...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, W., Yu, G., Zhang, H., Ly, C., Yuan, B., Ruvolo, V., Piya, S., Bhattacharya, S., Zhang, Q., Borthakur, G., Battula, V. L., Konopleva, M. Y., Rice, W. G., Andreeff, M. Tags: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster II Source Type: research
Cirmtuzumab Inhibits Non-Canonical Wnt Signaling without Enhancing Canonical Wnt/{beta}-Catenin Signaling in Chronic Lymphocytic Leukemia
In this study, we examined whether genetic silencing of ROR1 or inhibition of ROR1-signaling also could influence canonical Wnt signaling. To inhibit ROR1 signaling we used the humanized anti-ROR1 mAb cirmtuzumab, which is being evaluated in patients with CLL (Choi MY, et al, Cell Stem Cell, 22:951, 2018). Surprisingly, we found that CRISPR/Cas9 deletion of ROR1 in 293T cells also could enhance the capacity of Wnt3a to activate canonical Wnt-signaling, albeit to a lesser extent than CRISPR/Cas9 deletion of ROR2; conversely, re-introduction of ROR1 into ROR1-deleted 293T cells suppressed Wnt3a-induced activation of canonica...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, H., Zhang, S., Ghia, E. M., Choi, M. Y., Zhang, J., Chen, L., Widhopf II, G. F., Rassenti, L. Z., Kipps, T. J. Tags: 605. Molecular Pharmacology, Drug Resistance-Lymphoid and Other Diseases: Poster II Source Type: research
