tbuckley/cabot-search huggingface dataset:
Novel BCR-ABL1 Tyrosine Kinase Inhibitor (TKI) HQP1351 (Olverembatinib) Is Efficacious and Well Tolerated in Patients with T315I-Mutated Chronic Myeloid Leukemia (CML): Results of Pivotal (Phase II) Trials
Authors: Qian Jiang, Xiaojun Huang, Zi Chen, Qian Niu, Dayu Shi, Zongru Li, Yue Hou, Yu Hu, Weiming Li, Xiaoli Liu, Na Xu, Yongping Song, Yanli Zhang, Li Meng, Zhenya Hong, Bingcheng Liu, Shan Zeng, Lichuang Men, Yan Li, Suning Chen, Mengxing Xue, Huanling Zhu, He Li, Xin Du, Jin Lou, Xiaohan Zhang, Yang Liang, Yujun Dai, Ming Lu, Hengbang Wang, Jiao JI, Changai Yue, Dajun Yang, Yifan Zhai
Journal: Blood (2020)
Covid-19: Official data on England are patchy, say researchers behind new evaluation dashboard
Authors: Jacqui Wise
Journal: BMJ (2020)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Covid-19: Official data on England are patchy, say researchers behind new evaluation dashboard Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Comparison of Two Alkylating Agents Among Refractory Multiple Myeloma: Published and Our Retrospective Bendamustine Combination Experience with Melflufen As Single Agent
Authors: Ekin Kircali, Guldane Cengiz, Sevgi Çolak, Mehmet Gunduz, Pinar Ataca Atilla, Erden Atilla, Mehmet Özen, Muhit Ozcan, Meral Beksac
Journal: Blood (2020)
Combination of Homoharringtonine with Venetoclax and Azacitidine Excerts Better Treatment Response in Relapsed /Refractory Acute Myeloid Leukemia
Authors: Guopan Yu, Na Xu, Fen Huang, Zhiping Fan, Hui Liu, Pengcheng Shi, Hongsheng Zhou, Zhixiang Wang, Yu Zhang, Qifa Liu
Journal: Blood (2020)
Improved Outcome with a Pediatric-Inspired Regimen for Philadelphia-Negative Acute Lymphoblastic Leukemia in the Elderly
Authors: Francois Xavier Gros, Pierre-Yves Dumas, Edouard Forcade, Claire Calmettes, Margot Robles, Vincent Servant, Nicolas Lechevalier, Audrey Bidet, Noel Milpied, Arnaud Pigneux, Thibaut Leguay
Journal: Blood (2017)
Abstract MP125: Branched-chain Keto Acids, Not Branched-chain Amino Acids, Impairs Cardiac Insulin Sensitivity by Disrupting Insulin Signaling in the Mitochondria
Authors: Qutuba Karwi, Golam Mezbah Uddin, Cory S Wagg, Gary D Lopaschuk
Journal: Circulation Research (2020)

Alterations in branched-chain amino acids (BCAA) oxidation have been linked to the development of cardiac insulin resistance and its negative impact on cardiac function. However, it is not clear if these detrimental effects are due to the accumulation of BCAAs or branched-chain keto acids (BCKAs). It is also unknown how impaired BCAAs oxidation mediates cardiac insulin resistance. To examine this, we specifically deleted mitochondrial branched-chain aminotransferase (BCATm) in the heart to selectively increase in BCAAs and decrease in BCKAs in the heart. BCATm -/- mice had normal cardiac function compared to their wildtype littermates (WT Cre+/+ ). However, there was a significant increase in insulin-stimulated cardiac glucose oxidation rates in BCATm -/- mice, independent of any changes in glucose uptake or glycolytic rates. This enhancement in cardiac insulin sensitivity was associated with an increase in the phosphorylation of Akt and activation of pyruvate dehydrogenase (PDH), the rate-limiting enzyme of glucose oxidation. To determine the impact of reversing these events, we examined the effects of increasing cardiac BCKAs on cardiac insulin sensitivity. We perfused isolated working mice hearts with high levels of BCKAs (α;-keto-isocaproate 80 μM, α;-keto-β;-methylvalorate 100μM, α;-keto-isovalorate 70 μM), levels that can be seen during diabetes and obesity. The BCKAs completely blunted insulin-stimulated glucose oxidation rates. We also found that BCKAs abolished insulin-stimulated mitochondrial translocation of Akt, an effect which was associated with PDH deactivation. We conclude that the accumulation of BCKAs, and not BCAAs, is a major contributor to cardiac insulin resistance via abrogating mitochondrial translocation of Akt.
Abstract 437: A Novel Variant Cell Cycle Related Kinase Protect Heart Against Ischemia by Promoting Cardiomyocytes Survival
Authors: Lo Lai, Hongyu Qiu
Journal: Circulation Research (2020)

Background and objects: Our previous studies identified a novel variant of cell cycle-related kinase in heart (cardiac CCRK or cCCRK) which is different from generic CCRK found in other tissues in terms of its amino acid sequence, substrates, protein-protein interaction and tissue distribution. cCCRK has been found dramatically decreased in the failed heart tissues, while overexpress of cCCRK in cardiac myocytes in vitro protected the cells against induced cell death. Therefore, we tested the hypothesis here that cCCRK acts as a potential candidate of cell survival promotor providing cardiaoprotection in vivo upon cardiac ischemic stress. Methods and results: A cardiac specific transgenic (TG) mouse was generated with an alpha- MHC premotor in which cCCRK was overexpressed by 3.5 folds compared to wild type mice (WT). Both cCCRK TG and the litter-mated WT mice were subjected to an 45 minutes myocardial ischemia followed by an 24 hours reperfusion (IR), and the infarct size was measured by 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We found that despite the similar risk area, infarct size was significantly reduced by 50% in the TG mice verse WT mice (p&lt;0.05). The apoptosis in the adjacent area of the heart tissues measured by TUNEL was reduced by 30% in TG mice vs WT (p&lt;0.05). Mechanistically, the survival-promoting signaling pathway, including phosphorylated extracellular-signal-regulated kinase (p-ERK), phosphorylated Mitogen-activated protein kinase/ERK kinase (p-MEK), and P21, was activated in the heart tissues from TG vs WT mice (p&lt;0.05 vs WT). Overexpression of cCCRK in cardiac myocytes in vitro reduced chelerythrine-induced apoptosis reflected by a reduction of caspase 3 activity, this protection was abolished by the Inhibition of MEK with the treatment of its inhibitor U1206 vs vehicle controls (p&lt;0.05 vs vehicle). Conclusion: This study demonstrated that overexpression of a variant of CCRK in heart provides protection against ischemic stress by activating survival signaling.
Effect of Food on MDM2 Inhibitor KRT-232 Pharmacokinetics and Macrophage Inhibitory Cytokine-1 (MIC-1) Response in Healthy Volunteers
Authors: Shekman Wong, Cecile Marie Krejsa, Dana Lee, Anna Harris, Emilie Simard, Xiaohui Wang, Igor Rubets, Martine Allard, Terry Podoll, Terry O'Reilly, J. Greg Slatter
Journal: Blood (2020)
TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes
Authors: Nadine M. Tung, Mark E. Robson, Steffen Ventz, Cesar A. Santa-Maria, Rita Nanda, Paul K. Marcom, Payal D. Shah, Tarah J. Ballinger, Eddy S. Yang, Shaveta Vinayak, Michelle Melisko, Adam Brufsky, Michelle DeMeo, Colby Jenkins, Susan Domchek, Alan D’Andrea, Nancy U. Lin, Melissa E. Hughes, Lisa A. Carey, Nick Wagle, Gerburg M. Wulf, Ian E. Krop, Antonio C. Wolff, Eric P. Winer, Judy E. Garber
Journal: Journal of Clinical Oncology (2020)

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) in germline (g)BRCA1/2 mutation carriers. Olaparib Expanded, an investigator-initiated, phase II study, assessed olaparib response in patients with MBC with somatic (s)BRCA1/2 mutations or g/s mutations in homologous recombination (HR)-related genes other than BRCA1/2.Eligible patients had MBC with measurable disease and germline mutations in non-BRCA1/2 HR-related genes (cohort 1) or somatic mutations in these genes or BRCA1/2 (cohort 2). Prior PARPi, platinum-refractory disease, or progression on more than two chemotherapy regimens (metastatic setting) was not allowed. Patients received olaparib 300 mg orally twice a day until progression. A single-arm, two-stage design was used. The primary endpoint was objective response rate (ORR); the null hypothesis (≤ 5% ORR) would be rejected within each cohort if there were four or more responses in 27 patients. Secondary endpoints included clinical benefit rate and progression-free survival (PFS).Fifty-four patients enrolled. Seventy-six percent had estrogen receptor-positive HER2-negative disease. Eighty-seven percent had mutations in PALB2, sBRCA1/2, ATM, or CHEK2. In cohort 1, ORR was 33% (90% CI, 19% to 51%) and in cohort 2, 31% (90% CI, 15% to 49%). Confirmed responses were seen only with gPALB2 (ORR, 82%) and sBRCA1/2 (ORR, 50%) mutations. Median PFS was 13.3 months (90% CI, 12 months to not available/computable [NA]) for gPALB2 and 6.3 months (90% CI, 4.4 months to NA) for sBRCA1/2 mutation carriers. No responses were observed with ATM or CHEK2 mutations alone.PARP inhibition is an effective treatment for patients with MBC and gPALB2 or sBRCA1/2 mutations, significantly expanding the population of patients with breast cancer likely to benefit from PARPi beyond gBRCA1/2 mutation carriers. These results emphasize the value of molecular characterization for treatment decisions in MBC.
THU0065 Clinical significance of anti-asparaginyl trna synthetase autoantibodies
Authors: M Hirakata, A Suwa, T Nojima, M Suzuki, S Nagai, T Mimori, IN Targoff
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Autoantibodies to 5 of the aminoacyl tRNA synthetases (those for histidine, threonine, alanine, isoleucine and glycine) have been described, and each is associated with a similar syndrome of myositis (PM or DM) with interstitial lung disease (ILD), arthritis, and other features.<sup>1</sup> We have identified novel autoantibodies to asparaginyl tRNA synthetase (AsnRS),<sup>2</sup> but the clinical significance of this sixth anti-synthetase antibody has not been well-defined. <h3>Objectives</h3> The aim of the present study was to identify patients with anti-AsnRS and elucidate the clinical and immunogenetic features of this sixth anti-synthetase autoantibodies. <h3>Methods</h3> Sera from more than 2,500 patients with connective tissue disease including myositis and ILD in collaborating centres, and control sera were examined for anti-AsnRS antibodies by immunoprecipitation. Positive sera and controls were tested for the ability to inhibit AsnRS by preincubation of the enzyme source with the serum. The HLA-class II (DRB1, DQA1, DQB1, DPB1) alleles were identified from RFLP of PCR-amplified genomic DNA. The concentration of KL-6 (a new marker for ILD) in serum was determined by a specific ELISA.<sup>3</sup> <h3>Results</h3> Anti-KS antibodies were identified in the sera of 8 patients (5 Japanese, 1 U. S., 1 German, 1 Korean), by immunoprecipitation of the same distinctive set of tRNAs and protein that differed from those precipitated by the other 5 anti-synthetases, and showed specific inhibition of AsnRS activity. Two of these patients had DM, but seven of 8 (88%) had ILD. Four (50%) had arthritis, and one had Raynaud phenomenon. This anti-synthetase was very rare among myositis patients, found in &lt;0.2% of U. S. myositis patients, and 0% of Japanese myositis patients, but was found in 3% of Japanese ILD patients. Thus, most patients with anti-AsnRS antibodies had chronic ILD with or without features of connective tissue disease. Furthermore, four of 5 patients in whom KL-6 levels were measured, showed markedly elevated levels (mean level 919.8 U/ml; normal &lt; 500 U/ml). Interestingly, all four Japanese patients tested had DR 2 (DRB1*1501/1502), compared to 33% of healthy controls. <h3>Conclusion</h3> These results indicate that anti-AsnRS antibodies, like anti-PL-12 (alanyl tRNA synthetase) antibodies, have a stronger association with ILD than with myositis, and may be associated with the DR2 phenotype. <h3>References</h3> Targoff IN. Rheum Dis Clin North Am. 1994;20:857–80 Hirakata M, <i>et al</i>. J Immunol. 1999;162:2315–20 Nakajima H, <i>et al</i>. J Rheumatol. 2000;27:1164–70
Carfilzomib, Elotuzumab and Dexamethasone for Relapsed or Refractory Myeloma Patients
Authors: Raija Helena Silvennoinen, Hareth Nahi, Pekka Anttila, Perttu Koskenvesa, Juha Lievonen, Anu Marttila, Ville Varmavuo, Anu Sikiö, Marita Nurmi, Marjaana Säily, Anu Partanen, Marja Sankelo, Sini Luoma, Pentti Mäntymaa, Sorella Ilveskero, Henrik Rode Eshoj, Lene Kongsgaard Nielsen, Esa Jantunen, Caroline A Heckman
Journal: Blood (2020)
The Central Role of MAPK-ERK Signaling in IL7-Dependent and IL7-Independent Steroid Resistance Reveals a Broad Application of MEK-Inhibitors Compared to JAK1/2-Inhibition in T-ALL
Authors: Jordy C.G. Van Der Zwet, Jessica G.C.A.M. Buijs-Gladdines, Valentina Cordo', Donna Debets, Willem K. Smits, Zhongli Chen, Jelle Dylus, Guido Zaman, Maarten Altelaar, Koichi Oshima, Beat Bornhauser, Jean-Pierre Bourquin, Jan Cools, Adolfo A. Ferrando, Josef Vormoor, Rob Pieters, Britta Julia Vormoor, Jules P.P. Meijerink
Journal: Blood (2020)
Clinicopathologic Predictors of Reversibility Dialysis Dependent Acute Kidney Injury in Patients with Myeloma Cast Nephropathy
Authors: Evgeniia V. Kazarina, Irina G. Rekhtina, Ekaterina S. Stolyarevich, Alla M. Kovrigina, Valentina N. Dvirnyk, Sergei M. Kulikov, Larisa Mendeleeva, Valeriy G. Savchenko
Journal: Blood (2020)
Selection of RARA-Positive Newly Diagnosed Unfit AML Patients with Elevated RARA Gene Expression Enriches for Features Associated with Primary Resistance to Venetoclax and Clinical Response to SY-1425, a Potent and Selective RARα Agonist, Plus Azacitidine
Authors: Christopher Fiore, Michael J. Kelly, Angela Volkert, Li Zhou, Kate Madigan, Matthew Eaton, Graeme Hodgson, David A. Roth, Qing Kang-Fortner
Journal: Blood (2020)
Mutational and Copy Number Profiling of Circulating Tumor DNA in Acute Myeloid Leukemia Using Targeted Next Generation Sequencing
Authors: Ing Soo Tiong, Clarissa Wilson, Satwica Yerneni, John Markham, Karen Dun, Ashish Bajel, Ella R Thompson, David Alan Westerman, Piers Blombery
Journal: Blood (2020)
Microvascular Stasis Inhibition By Hemopexin in the Townes Mouse Model of Sickle Cell Disease
Authors: Thomas Gentinetta, Gregory M. Vercellotti, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Ping Zhang, Gregory J Kato, Nathan Brinkman, Adrian Zuercher, John D Belcher
Journal: Blood (2020)
Validation of the Bioequivalence of USP Potency Adjusted Porcine, Ovine, and Bovine Heparins
Authors: Nausheen Baig, Ahmed Kouta, Walter Jeske, Debra Hoppensteadt, Jeanine Walenga, Omer Iqbal, Fakiha Siddiqui, Mamdouh Bakhos, Jawed Fareed
Journal: Blood (2020)
Post-Transplant Lymphoproliferative Disorder after Liver Transplant: A Systematic Review
Authors: Mobeen Zaka Haider, Zarlakhta Zamani, Hafsa Shahid, Muhammad Taqi, Zahoor Ahmed, Hasan Mahmood Mirza, Aneeza Irfan, Khadija Noor Sami, Deepak Kumar, Fnu Kiran, Syed Maaz Abdullah, Faiz Anwer
Journal: Blood (2020)
Sleep and the athlete: narrative review and 2021 expert consensus recommendations
Authors: Neil P Walsh, Shona L Halson, Charli Sargent, Gregory D Roach, Mathieu Nédélec, Luke Gupta, Jonathan Leeder, Hugh H Fullagar, Aaron J Coutts, Ben J Edwards, Samuel A Pullinger, Colin M Robertson, Jatin G Burniston, Michele Lastella, Yann Le Meur, Christophe Hausswirth, Amy M Bender, Michael A Grandner, Charles H Samuels
Journal: British Journal of Sports Medicine (2020)

Elite athletes are particularly susceptible to sleep inadequacies, characterised by habitual short sleep (&lt;7 hours/night) and poor sleep quality (eg, sleep fragmentation). Athletic performance is reduced by a night or more without sleep, but the influence on performance of partial sleep restriction over 1–3 nights, a more real-world scenario, remains unclear. Studies investigating sleep in athletes often suffer from inadequate experimental control, a lack of females and questions concerning the validity of the chosen sleep assessment tools. Research only scratches the surface on how sleep influences athlete health. Studies in the wider population show that habitually sleeping &lt;7 hours/night increases susceptibility to respiratory infection. Fortunately, much is known about the salient risk factors for sleep inadequacy in athletes, enabling targeted interventions. For example, athlete sleep is influenced by sport-specific factors (relating to training, travel and competition) and non-sport factors (eg, female gender, stress and anxiety). This expert consensus culminates with a sleep toolbox for practitioners (eg, covering sleep education and screening) to mitigate these risk factors and optimise athlete sleep. A one-size-fits-all approach to athlete sleep recommendations (eg, 7–9 hours/night) is unlikely ideal for health and performance. We recommend an individualised approach that should consider the athlete’s perceived sleep needs. Research is needed into the benefits of napping and sleep extension (eg, banking sleep).
Recommended Guidelines for Reviewing, Reporting, and Conducting Research on In-Hospital Resuscitation: The In-Hospital ‘Utstein Style’
Authors: Richard O. Cummins, Douglas Chamberlain, Mary Fran Hazinski, Vinay Nadkarni, Walter Kloeck, Efraim Kramer, Lance Becker, Colin Robertson, Rudi Koster, Arno Zaritsky, Leo Bossaert, Joseph P. Ornato, Victor Callanan, Mervyn Allen, Petter Steen, Brian Connolly, Arthur Sanders, Ahamed Idris, Stuart Cobbe
Journal: Circulation (1997)
Impaired Osteoblastic Differentiation of MSCs Suppresses Normal Hematopoiesis in MDS
Authors: Yasutaka Hayashi, Kimihito Cojin Kawabata, Yosuke Tanaka, Yasufumi Uehara, Shigeru Kiryu, Yasunori Ota, Yusuke Yoshioka, Yo Mabuchi, Tatsuki Sugiyama, Keiko Mikami, Moe Tamura, Tsuyoshi Fukushima, Shuhei Asada, Reina Takeda, Yuya Kunisaki, Tomofusa Fukuyama, Susumu Goyama, Kazuaki Yokoyama, Arinobu Tojo, Yoshio Katayama, Fumio Arai, Takashi Nagasawa, Takahiro Ochiya, Daichi Inoue, Toshio Kitamura
Journal: Blood (2020)
The Role of Genetic Polymorphisms of<i>TPMT</i>and<i>NUDT15</i>Genes in Adult Patients with Ph-Negative Acute Lymphoblastic Leukemia in Russia
Authors: Ekaterina S. Kotova, Olga A. Gavrilina, Igor A Yakutik, Andrey B. Sudarikov, Elena N. Parovichnikova, Vera V. Troitskaya, Andrey N. Sokolov, Galina A. Isinova, Ksenija I. Zarubina, Valeriy G. Savchenko
Journal: Blood (2020)
Safety, Efficacy, and Patient-Reported Outcomes of Venetoclax in Combination with Azacitidine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome: A Phase 1b Study
Authors: Jacqueline S. Garcia, Andrew H. Wei, Uma Borate, Chun Yew Fong, Maria R. Baer, Florian Nolte, Joseph G. Jurcic, Meagan A. Jacoby, Wan-Jen Hong, Uwe Platzbecker, Olatoyosi Odenike, Ilona Cunningham, Ying Zhou, Bo Tong, Leah Hogdal, Rajesh Kamalakar, Jessica E. Hutti, Steve Kye, Guillermo Garcia-Manero
Journal: Blood (2020)
Diagnostic Whole Exome Sequencing for 166 Patients with Inherited Bone Marrow Failure Syndrome
Authors: Motoharu Hamada, Hideki Muramatsu, Yusuke Okuno, Ayako Yamamori, Taro Yoshida, Masayuki Imaya, Manabu Wakamatsu, Shunsuke Miwata, Kotaro Narita, Daisuke Ichikawa, Rieko Taniguchi, Atsushi Narita, Nozomu Kawashima, Eri Nishikawa, Nobuhiro Nishio, Asahito Hama, Masafumi Ito, Tomoo Ogi, Seiji Kojima, Yoshiyuki Takahashi
Journal: Blood (2020)
Comparison of Community-Level and Patient-Level Social Risk Data in a Network of Community Health Centers
Authors: Erika K. Cottrell, Michelle Hendricks, Katie Dambrun, Stuart Cowburn, Matthew Pantell, Rachel Gold, Laura M. Gottlieb
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Responding to the substantial research on the relationship between social risk factors and health, enthusiasm has grown around social risk screening in health care settings, and numerous US health systems are experimenting with social risk screening initiatives. In the absence of standard social risk screening recommendations, some health systems are exploring using publicly available community-level data to identify patients who live in the most vulnerable communities as a way to characterize patient social and economic contexts, identify patients with potential social risks, and/or to target social risk screening efforts. <h3>Objective</h3> To explore the utility of community-level data for accurately identifying patients with social risks by comparing the social deprivation index score for the census tract where a patient lives with patient-level social risk screening data. <h3>Design, Setting, and Participants</h3> Cross-sectional study using patient-level social risk screening data from the electronic health records of a national network of community health centers between June 24, 2016, and November 15, 2018, linked to geocoded community-level data from publicly available sources. Eligible patients were those with a recorded response to social risk screening questions about food, housing, and/or financial resource strain, and a valid address of sufficient quality for geocoding. <h3>Exposures</h3> Social risk screening documented in the electronic health record. <h3>Main Outcomes and Measures</h3> Community-level social risk was assessed using census tract–level social deprivation index score stratified by quartile. Patient-level social risks were identified using food insecurity, housing insecurity, and financial resource strain screening responses. <h3>Results</h3> The final study sample included 36 578 patients from 13 US states; 22 113 (60.5%) received public insurance, 21 181 (57.9%) were female, 17 578 (48.1%) were White, and 10 918 (29.8%) were Black. Although 6516 (60.0%) of those with at least 1 social risk factor were in the most deprived quartile of census tracts, patients with social risk factors lived in all census tracts. Overall, the accuracy of the community-level data for identifying patients with and without social risks was 48.0%. <h3>Conclusions and Relevance</h3> Although there is overlap, patient-level and community-level approaches for assessing patient social risks are not equivalent. Using community-level data to guide patient-level activities may mean that some patients who could benefit from targeted interventions or care adjustments would not be identified.
Efficacy of Subsequent Therapies in Multiple Myeloma Patients after Progression on a BCMA Targeting Therapy: A Single-Center Experience
Authors: Barry Paul, Myra Robinson, Kristen Cassetta, Daniel Slaughter, Jordan Robinson, Ami P Ndiaye, Manisha Bhutani, Peter M. Voorhees, Saad Z. Usmani, Shebli Atrash
Journal: Blood (2020)