tbuckley/cabot-search huggingface dataset:
A retrospective study analyzing activity of ofatumumab in blastic variant mantle cell lymphoma.
Authors: Vikas Ghai, Kamal Sharma, Zainul Hasanali, Sara Shimko, August Stuart, Jason Liao, Elliot E Epner
Journal: Journal of Clinical Oncology (2012)

e18500 Background: The blastic variant (BV) form of mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin's lymphoma (NHL) for which no standard of care exists. Ofatumumab is a CD20-directed monoclonal antibody (mAb) FDA approved for the treatment of patients with CLL. We retrospectively studied relapsed BV of MCL in patients treated with regimens containing ofatumumab and previous or concurrent epigenetic therapy (cladribine (2-CdaA) and vorinostat). Methods: BV was confirmed by histopathological patterns, ki-67 proliferation index, immunophenotyping, and t(11;14) by FISH and/or cyclin D1 overexpression. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression free survival and complete response. Correlative studies to support the hypothesis that epigenetic modulation of multiple genes in multiple pathways can potentiate the activity of mAbs were performed. Results: Ofatumumab administered to 5 Stage IV BV of MCL patients (Table). 3/5 patients had a radiological complete response, lasting 21.1, 13.4 and 12 months, The other 2 patients had partial response and are on the maintenance. Observed PFS in this cohort is a median 13 months (2.7-20.7). Correlative studies following epigenetic therapy found upregulation of the following genes by RT-PCR: NOXA1 (3/5 patients), CEBP1 (2/5) and EZH2 (2/5). Conclusions: Epigenetic drugs can augment the activity of mAbs. In this case, a more potent mAb improves response in MCL. Correlative studies to support the hypothesis that epigenetic modulation of multiple genes in multiple pathways can potentiate activity of mAbs. The combination of 2-CdA and vorinostat synergistically activates genes silenced by histone deacetylation, histone methylation and DNA methylation and enhances the activity of the mAb ofatumumab. [Table: see text]
JAK2 V617F Mutation in Essential Thrombocythemia: Clinical Associations and Long-Term Prognostic Relevance.
Authors: Alexandra P. Wolanskyj, Terra L. Lasho, Susan M. Schwager, Rebecca F. McClure, Martha Wadleigh, Stephanie J. Lee, D. Gary Gilliland, Ayalew Tefferi
Journal: Blood (2005)
Combining the Allosteric ABL1 Inhibitor Asciminib (ABL001) with Ponatinib Suppresses Emergence of and Restores Efficacy Against Highly Resistant BCR-ABL1 Compound Mutants
Authors: Christopher A. Eide, Matthew S. Zabriskie, Samantha L. Savage, Orlando Antelope, Nadeem A. Vellore, Hein Than, Anna Reister Schultz, Phillip M. Clair, Amber D. Bowler, Anthony D. Pomicter, Dongqing Yan, Anna V. Senina, Qiang Wang, Todd W. Kelley, Philippe Szankasi, Michael C. Heinrich, Jeffrey W. Tyner, Delphine Rea, Jean-Michel Cayuela, Dong-Wook Kim, Cristina E. Tognon, Thomas O'Hare, Brian J. Druker, Michael W. Deininger
Journal: Blood (2019)
Efficacy of the Enquiring About Tolerance (EAT) study among infants at high risk of developing food allergy
Authors: Michael R. Perkin, Kirsty Logan, Henry T. Bahnson, Tom Marrs, Suzana Radulovic, Joanna Craven, Carsten Flohr, E.N. Mills, Serge A. Versteeg, Ronald van Ree, Gideon Lack, Louise Young, Victoria Offord, Mary DeSousa, Jason Cullen, Katherine Taylor, Anna Tseng, Bunmi Raji, Sarah Byrom, Gillian Regis, Charlie Bigwood, Charlotte Stedman, Sharon Tonner, Emily Banks, Yasmin Kahnum, Rachel Babic, Ben Stockwell, Erin Thompson, Lorna Wheatley, Devi Patkunam, Kerry Richards, Ewa Pietraszewicz, Alick Stephens, Asha Sudra, Victor Turcanu
Journal: Journal of Allergy and Clinical Immunology (2019)

The Enquiring About Tolerance (EAT) study was a randomized trial of the early introduction of allergenic solids into the infant diet from 3 months of age. The intervention effect did not reach statistical significance in the intention-to-treat analysis of the primary outcome.We sought to determine whether infants at high risk of developing a food allergy benefited from early introduction.A secondary intention-to-treat analysis was performed of 3 groups: nonwhite infants; infants with visible eczema at enrollment, with severity determined by SCORAD; and infants with enrollment food sensitization (specific IgE ≥0.1 kU/L).Among infants with sensitization to 1 or more foods at enrollment (≥0.1 kU/L), early introduction group (EIG) infants developed significantly less food allergy to 1 or more foods than standard introduction group (SIG) infants (SIG, 34.2%; EIG, 19.2%; P = .03), and among infants with sensitization to egg at enrollment, EIG infants developed less egg allergy (SIG, 48.6%; EIG, 20.0%; P = .01). Similarly, among infants with moderate SCORAD (15-<40) at enrollment, EIG infants developed significantly less food allergy to 1 or more foods (SIG, 46.7%; EIG, 22.6%; P = .048) and less egg allergy (SIG, 43.3%; EIG, 16.1%; P = .02).Early introduction was effective in preventing the development of food allergy in specific groups of infants at high risk of developing food allergy: those sensitized to egg or to any food at enrollment and those with eczema of increasing severity at enrollment. This efficacy occurred despite low adherence to the early introduction regimen. This has significant implications for the new national infant feeding recommendations that are emerging around the world.
ERS and tobacco harm reduction
Authors: Charlotta Pisinger, Elif Dagli, Filippos T. Filippidis, Linnea Hedman, Christer Janson, Stelios Loukides, Sofia Ravara, Isabel Saraiva, Jørgen Vestbo
Journal: European Respiratory Journal (2019)

<b>ERS supports the World Health Organization9s Framework Convention on Tobacco Control, which also provides regulation to novel products, and cannot recommend tobacco harm reduction as a population-based strategy</b>http://bit.ly/2rxTZ5b
Apomorphine sublingual film for off episodes in Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 study
Authors: C Warren Olanow, Stewart A Factor, Alberto J Espay, Robert A Hauser, Holly A Shill, Stuart Isaacson, Rajesh Pahwa, Mika Leinonen, Parul Bhargava, Ken Sciarappa, Bradford Navia, David Blum, xx xx
Journal: The Lancet Neurology (2019)
Association of Receipt of a Housing Voucher With Subsequent Hospital Utilization and Spending
Authors: Craig Evan Pollack, Amanda L. Blackford, Shawn Du, Stefanie Deluca, Rachel L. J. Thornton, Bradley Herring
Journal: JAMA (2019)

<h3>Importance</h3> Although neighborhoods are thought to be an important health determinant, evidence for the relationship between neighborhood poverty and health care use is limited, as prior studies have largely used observational data without an experimental design. <h3>Objective</h3> To examine whether housing policies that reduce exposure to high-poverty neighborhoods were associated with differences in long-term hospital use among adults and children. <h3>Design, Setting, and Participants</h3> Exploratory analysis of the Moving to Opportunity for Fair Housing Demonstration Program, a randomized social experiment conducted in 5 US cities. From 1994 to 1998, 4604 families in public housing were randomized to 1 of 3 groups: a control condition, a traditional Section 8 voucher toward rental costs in the private market, or a voucher that could only be used in low-poverty neighborhoods. Participants were linked to all-payer hospital discharge data (1995 through 2014 or 2015) and Medicaid data (1999 through 2009). The final follow-up date ranged from 11 to 21 years after randomization. <h3>Exposures</h3> Receipt of a traditional or low-poverty voucher vs control group. <h3>Main Outcomes and Measures</h3> Rates of hospitalizations and hospital days, and hospital spending. <h3>Results</h3> Among 4602 eligible individuals randomized as adults, 4072 (88.5%) were linked to health data (mean age, 33 years [SD, 9.0 years]; 98% female; median follow-up, 11 years). There were no significant differences in primary outcomes among adults randomized to receive a voucher compared with the control group (unadjusted hospitalization rate, 14.0 vs 14.7 per 100 person-years, adjusted incidence rate ratio [IRR], 0.95 [95% CI, 0.84-1.08;<i>P</i> = .45]; hospital days, 62.8 vs 67.0 per 100 person-years; IRR, 0.93 [95% CI, 0.77-1.13;<i>P</i> = .46]; yearly spending, $2075 vs $1977; adjusted difference, −$129 [95% CI, −$497 to $239;<i>P</i> = .49]). Among 11 290 eligible individuals randomized as children, 9118 (80.8%) were linked to health data (mean age, 8 years [SD, 4.6 years]; 49% female; median follow-up, 11 years). Receipt of a housing voucher during childhood was significantly associated with lower hospitalization rates (6.3 vs 7.3 per 100 person-years; IRR, 0.85 [95% CI, 0.73-0.99;<i>P</i> = .03]) and yearly inpatient spending ($633 vs $785; adjusted difference, −$143 [95% CI, −$256 to −$31;<i>P</i> = .01]) and no significant difference in hospital days (25.7 vs 28.8 per 100 person-years; IRR, 0.92 [95% CI, 0.77-1.11;<i>P</i> = .41]). <h3>Conclusions and Relevance</h3> In this exploratory analysis of a randomized housing voucher intervention, adults who received a housing voucher did not experience significant differences in hospital use or spending. Receipt of a voucher during childhood was significantly associated with lower rates of hospitalization and less inpatient spending during long-term follow-up.
Skeletal Muscle Mass Influences Tolerability and Prognosis in Hepatocellular Carcinoma Patients Treated with Lenvatinib
Authors: Haruki Uojima, Makoto Chuma, Yoshiaki Tanaka, Hisashi Hidaka, Takahide Nakazawa, Shogo Iwabuchi, Satoshi Kobayashi, Nobuhiro Hattori, Katsuaki Ogushi, Manabu Morimoto, Tatehiro Kagawa, Katsuaki Tanaka, Makoto Kako, Wasaburo Koizumi
Journal: Liver Cancer (2019)

Background: Low skeletal muscle mass is significantly associated with severe adverse events (AEs) from chemotherapy, and low tolerability leads to decreased survival. We aimed to investigate whether body skeletal muscle mass is correlated with tolerability and prognosis in patients with hepatocellular carcinoma (HCC) treated with lenvatinib. Methods: This multicenter, retrospective study was conducted at five locations in Japan. We included 100 patients with HCC treated with lenvatinib. Skeletal muscle mass was measured by computed tomography and normalized for height in m2 as skeletal muscle index (SMI). The assessment criteria for low SMI were taken from the sarcopenia criteria of the Japan Society of Hepatology. We investigated the influence of low SMI on drug withdrawal due to severe AEs in the first 2 months and on time to treatment failure (TTF) and overall survival (OS). Results: The numbers of high- and low-SMI patients were 41 and 59, respectively. Those with severe AEs leading to withdraw in the high- and low-SMI groups were 7 and 23, respectively. The low-SMI group had a higher withdrawal rate than the high-SMI group (p = 0.042). The median TTF in the low- and high-SMI groups was 139 and 230 days, respectively. The median OS in the low- and high-SMI groups was 264 and 353 days, respectively. Patients in the low-SMI group experienced significantly worse OS and TTF than those in the high-SMI group (log-rank test for trend: TTF, p = 0.010; OS, p = 0.021). Conclusion: Decreased skeletal muscle mass is associated with the occurrence of severe AEs and worse TTF and OS. Skeletal muscle mass can be used as a predictive marker for tolerability and prognosis to lenvatinib in patients with HCC.
μ Opioid Receptor Stimulates a Growth Promoting and Pro-Angiogenic Tumor Microenvironment by Transactivating VEGF Receptor-2/Flk-1.
Authors: Elliot J. Stephenson, Humberto J. Martinez-Suarez, Mariya Farooqui, Debabrata Mukhopadhyay, Deborah A. Hughes, Priyabrata Mukherjee, Kalpna Gupta
Journal: Blood (2005)
Diabetes Digital App Technology: Benefits, Challenges, and Recommendations. A Consensus Report by the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) Diabetes Technology Working Group
Authors: G. Alexander Fleming, John R. Petrie, Richard M. Bergenstal, Reinhard W. Holl, Anne L. Peters, Lutz Heinemann
Journal: Diabetes Care (2019)

Digital health technology, especially digital and health applications ("apps"), have been developing rapidly to help people manage their diabetes. Numerous health-related apps provided on smartphones and other wireless devices are available to support people with diabetes who need to adopt either lifestyle interventions or medication adjustments in response to glucose-monitoring data. However, regulations and guidelines have not caught up with the burgeoning field to standardize how mobile health apps are reviewed and monitored for patient safety and clinical validity. The available evidence on the safety and effectiveness of mobile health apps, especially for diabetes, remains limited. The European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have therefore conducted a joint review of the current landscape of available diabetes digital health technology (only stand-alone diabetes apps, as opposed to those that are integral to a regulated medical device, such as insulin pumps, continuous glucose monitoring systems, and automated insulin delivery systems) and practices of regulatory authorities and organizations. We found that, across the U.S. and Europe, mobile apps intended to manage health and wellness are largely unregulated unless they meet the definition of medical devices for therapeutic and/or diagnostic purposes. International organizations, including the International Medical Device Regulators Forum and the World Health Organization, have made strides in classifying different types of digital health technology and integrating digital health technology into the field of medical devices. As the diabetes digital health field continues to develop and become more fully integrated into everyday life, we wish to ensure that it is based on the best evidence for safety and efficacy. As a result, we bring to light several issues that the diabetes community, including regulatory authorities, policy makers, professional organizations, researchers, people with diabetes, and health care professionals, needs to address to ensure that diabetes health technology can meet its full potential. These issues range from inadequate evidence on app accuracy and clinical validity to lack of training provision, poor interoperability and standardization, and insufficient data security. We conclude with a series of recommended actions to resolve some of these shortcomings.
Association of genetic polymorphisms in the folate pathway with efficacy and toxicity of methotrexate in pediatric osteosarcoma.
Authors: Jeong A Park, Hyoung Jin Kang, Ho Joon Im, Hee Young Shin, Hyo Seop Ahn
Journal: Journal of Clinical Oncology (2013)

10051 Background: Osteosarcoma is the most common childhood malignant bone tumor. Methotrexate (MTX), one of the main drugs used for osteosarcoma, is a representative folic acid antagonist. Genetic polymorphisms in folate pathway genes are expected to influence the response and toxicity of high-dose MTX therapy. However, there are scarce data available regarding associations between genetic polymorphisms and pediatric osteosarcoma. This study evaluated the effect of common genetic polymorphisms in the folate metabolic pathway on overall survival, event-free survival and histological response to neoadjuvant chemotherapy including high-dose MTX. In addition, whether these genetic polymorphisms affect the concentrations of MTX and toxicity after high-dose MTX therapy for osteosarcoma was investigated. Methods: Blood and tissue samples from 48 osteosarcoma patients who had completed chemotherapy were obtained, and the following polymorphisms were analyzed; RFC1 80G&gt;A, DHFR 829C&gt;T, MTHFR 677C&gt;T, MTHFR 1298A&gt;C, AMPD1 34C&gt;T, ATIC 347C&gt;G, and ITPA 94C&gt;A. Associations between candidate polymorphisms and survival, histological response (tumor necrosis rate) and MTX level and toxicity after high-dose MTX therapy were analyzed. Results: Event-free survival significantly decreased in DHFR 829 CC homozygote (P=0.045). Variant carriers of MTHFR 677C&gt;T had tendency towards poor histological response (P=0.078). MTX concentration was significantly associated with RFC1 80G&gt;A polymorphism (P=0.027). Liver toxicity after high-dose MTX was associated with ATIC 347C&gt;G (P=0.043) and tended to increase in carriers of MTHFR 677C&gt;T (P=0.069). Severe stomatitis was associated with RFC1 80G&gt;A (P=0.012). Conclusions: This study has demonstrated that several genetic polymorphisms in folate pathway can significantly influence therapeutic response, clinical outcome and MTX level and toxicity after high-dose MTX therapy in osteosarcoma patients. If these associations are independently validated, these variants could be used as genetic predictors of clinical outcome in the treatment of patients with osteosarcoma, aiding the development of tailored therapeutic approaches.
Comparative Analysis of Alpha-Beta T-Cell and B-Cell Depleted (abTCD) HLA-Haploidentical Hematopoietic Stem Cell Transplantation (haplo-HSCT) Versus Abtcd Haplo-HSCT with T-Cell Add-Back of Rivogenlecleucel Cell [Donor T Cells Transduced with the Inducible Caspase 9 (iC9) Gene Safety Switch] in Children with High-Risk Acute Leukemia (AL) in Remission
Authors: Annalisa Ruggeri, Pietro Merli, Mattia Algeri, Marco Zecca, Franca Fagioli, Giuseppina Li Pira, Valentina Bertaina, Arcangelo Prete, Mauro Montanari, Francesca Del Bufalo, Luciana Vinti, Daria Pagliara, Melissa Aldinger, Kai Chan, Paul Woodard, Federica Galaverna, Franco Locatelli
Journal: Blood (2019)
Rituximab in Relapsed Lymphocyte Predominant Hodgkin’s Disease (LPHD). Long-Term Results of a Phase-II Study from the German Hodgkin Lymphoma Study Group (GHSG).
Authors: Holger Schulz, Sven Trelle, Marcel Reiser, Marcus Sieber, Volker Diehl, Andreas Engert
Journal: Blood (2005)
Deubiquitinase USP28 inhibits ubiquitin ligase KLHL2-mediated uridine-cytidine kinase 1 degradation and confers sensitivity to 5'-azacytidine-resistant human leukemia cells
Authors: Heng Zhang, He Huang, Xing Feng, Huiwen Song, Zhiyong Zhang, Aizong Shen, Xingfeng Qiu
Journal: Theranostics (2019)

Resistance to the chemotherapeutic drug 5'-azacytidine (5'-AZA) is a major obstacle in the treatment of patients with acute myeloid leukemia (AML). The uridine-cytidine kinase 1 (UCK1) has an established role in activating 5'-AZA and its protein level is significantly downregulated in patients resistant to the drug. However, the underlying molecular mechanism for the reduced UCK1 expression remains to be elucidated. Methods: Using mass spectrometry and molecular biochemistry analyses, we identified specific enzymes mediating UCK1 degradation. Human AML cell lines and murine AML model were used to characterize the effects of these enzymes on 5'-AZA resistance. Results: We demonstrated that the ubiquitin E3 ligase KLHL2 interacted with UCK1 and mediated its polyubiquitination at the K81 residue and degradation. We showed that deubiquitinase USP28 antagonized KLHL2-mediated polyubiquitylation of UCK1. We also provided evidence that ATM-mediated phosphorylation of USP28 resulted in its disassociation from KLHL2 and UCK1 destabilization. Conversely, UCK1 phosphorylation by 5'-AZA-activated ATM enhanced the KLHL2-UCK1 complex formation. Importantly, silencing KLHL2 or USP28 overexpression not only inhibited AML cell proliferation but also sensitized AML cells to 5'-AZA-induced apoptosis in vitro and in vivo. These results were no longer observed in USP28-deficient cells. Conclusions: Our study revealed a novel mechanism by which the KLHL2/USP28/ATM axis mediates resistance of AML cells to 5'-AZA by regulating UCK1 ubiquitination and phosphorylation. These results have direct clinical implications and provide a rationale for the combination drug treatment of AML patients.
Preliminary Results from a Phase I Study of Revlimid® (Lenalidomide) in Combination with Vidaza® (Azacitidine) in Patients with Advanced Myelodysplastic Syndromes (MDS).
Authors: Mikkael A. Sekeres, Alan List, David Cuthbertson, Ronald Paquette, Thomas Loughran, Jaroslaw P. Maciejewski
Journal: Blood (2007)
IgA—about the unexpected
Authors: Andrew J. Macpherson, Stephanie C. Ganal-Vonarburg
Journal: The Journal of Experimental Medicine (2018)

In this issue of JEM, Nakajima et al. (https://doi.org/10.1084/jem.20180427) demonstrate that glycan-dependent, epitope-independent IgA coating of intestinal bacteria alters bacterial gene expression and metabolism. This conferred coated bacteria with fitness within the mucus niche and contributed to intestinal homeostasis through cross-phylum interactions.
High Dose (HD-AraC) vs Standard Dose Cytosine Arabinoside (SD-AraC) during Induction in Acute Myelogenous Leukemia (AML): Impact on Stem Cell Mobilization after Consolidation and on Autologous Transplantation (Second Report of the EORTC-Leukemia Group (LG) - GIMEMA AML-12 Trial.
Authors: Roelof Willemze, Stefan Suciu, Franco Mandelli, T.M. de Witte, Boris Labar, Jean-Pierre Marie, Giovanna Meloni, Martin Mistrik, Vincenzo Liso, Meral Beksac, Francesco Fabbiano, Antonio Peta, Xavier Thomas, Dominique Bron, Georges Fillet, Petra Muus, Aurora Theys, Paola Fazi, Liliana Baila, Marco Vignetti, Sergio Amadori
Journal: Blood (2006)
Chikungunya virus replication in skeletal muscle cells is required for disease development
Authors: Anthony J. Lentscher, Mary K. McCarthy, Nicholas A. May, Bennett J. Davenport, Stephanie A. Montgomery, Krishnan Raghunathan, Nicole McAllister, Laurie A. Silva, Thomas E. Morrison, Terence S. Dermody
Journal: Journal of Clinical Investigation (2019)

Chikungunya virus (CHIKV) is an arbovirus capable of causing a severe and often debilitating rheumatic syndrome in humans. CHIKV replicates in a wide variety of cell types in mammals, which has made attributing pathologic outcomes to replication at specific sites difficult. To assess the contribution of CHIKV replication in skeletal muscle cells to pathogenesis, we engineered a CHIKV strain exhibiting restricted replication in these cells via incorporation of target sequences for skeletal muscle cell-specific miR-206. This virus, which we term SKE, displayed diminished replication in skeletal muscle cells in a mouse model of CHIKV disease. Mice infected with SKE developed less severe disease signs, including diminished swelling in the inoculated foot and less necrosis and inflammation in the interosseous muscles. SKE infection was associated with diminished infiltration of T cells into the interosseous muscle as well as decreased production of Il1b, Il6, Ip10, and Tnfa transcripts. Importantly, blockade of the IL-6 receptor led to diminished swelling of a control CHIKV strain capable of replication in skeletal muscle, reducing swelling to levels observed in mice infected with SKE. These data implicate replication in skeletal muscle cells and release of IL-6 as important mediators of CHIKV disease.
医生们对循证医学术语的知识：全科医生可能不懂专门术语，但可利用知识
Authors: 乌正赉
Journal: BMJ (2002)

英国医学杂志 (ＢＭＪ 2 0 0 2 ;3 2 4:95 0 )发表了一篇关于澳大利亚全科医生自我评价循证医学技能的报告1。报告结果不容乐观。根据 5 0名澳大利亚全科医生对循证医学常用的7条术语的理解划分等级 ,理解程度包括从“对我来说理解这些术语没有什么用处” ,到“我知道这条术语 ,并能给其他人作解释”。平均只有 2 2 %的人认为他们知道每条术语 ,并可以向他人作解释。更有甚者 ,在后面的结构式访谈中 ,只有一名全科医生能对其中的任何一条术语作出完全满意的解释 ,且许多解释中有不少错误理解。该研究论文的著者们认为 ,全科医生必须懂得这些术语以实施循证医学。但是怎样才能做到这点 ,尚少
Evidence That Human NKT Cells Enhance Haemopoiesis through Recognition of CD1d Expressed in Haemopoietic Stem Cells with Long Term Clonogenic Capacity.
Authors: Ioannis Kotsianidis, Scott Patterson, Marianna Politou, Antonio Almeida, Despoina Pantelidou, Costas Tsatalas, George Bourikas, Irene Roberts, Anastasios Karadimitris
Journal: Blood (2004)