tbuckley/cabot-search huggingface dataset:
Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Laurie H. Sehn, Alex F. Herrera, Christopher R. Flowers, Manali K. Kamdar, Andrew McMillan, Mark Hertzberg, Sarit Assouline, Tae Min Kim, Won Seog Kim, Muhit Ozcan, Jamie Hirata, Elicia Penuel, Joseph N. Paulson, Ji Cheng, Grace Ku, Matthew J. Matasar
Journal: Journal of Clinical Oncology (2019)

Patients with transplantation-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) fare poorly, with limited treatment options. The antibody-drug conjugate polatuzumab vedotin targets CD79b, a B-cell receptor component.Safety and efficacy of polatuzumab vedotin with bendamustine and obinutuzumab (pola-BG) was evaluated in a single-arm cohort. Polatuzumab vedotin combined with bendamustine and rituximab (pola-BR) was compared with bendamustine and rituximab (BR) in a randomly assigned cohort of patients with transplantation-ineligible R/R DLBCL (primary end point: independent review committee [IRC] assessed complete response [CR] rate at the end of treatment). Duration of response, progression-free survival (PFS), and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods.Pola-BG and pola-BR had a tolerable safety profile. The phase Ib/II pola-BG cohort (n = 27) had a CR rate of 29.6% and a median OS of 10.8 months (median follow-up, 27.0 months). In the randomly assigned cohort (n = 80; 40 per arm), pola-BR patients had a significantly higher IRC-assessed CR rate (40.0% v 17.5%; P = .026) and longer IRC-assessed PFS (median, 9.5 v 3.7 months; hazard ratio [HR], 0.36, 95% CI, 0.21 to 0.63; P < .001) and OS (median, 12.4 v 4.7 months; HR, 0.42; 95% CI, 0.24 to 0.75; P = .002; median follow-up, 22.3 months). Pola-BR patients had higher rates of grade 3-4 neutropenia (46.2% v 33.3%), anemia (28.2% v 17.9%), and thrombocytopenia (41% v 23.1%), but similar grade 3-4 infections (23.1% v 20.5%), versus the BR group. Peripheral neuropathy associated with polatuzumab vedotin (43.6% of patients) was grade 1-2 and resolved in most patients.Polatuzumab vedotin combined with BR resulted in a significantly higher CR rate and reduced the risk of death by 58% compared with BR in patients with transplantation-ineligible R/R DLBCL.
Relationship between Clinical/Hematological Response and Increase of Plamacells in the Bone Marrow of Patients with Chronic Myelogenous Leukemia Imatinib Mesylate Treatment (631).
Authors: Alessandro Poggi, Ivana Pierri, Silvia Catellani, Francesca Olcese, Antonella Marasco, Marta Zancolli, Maurizio Miglino, Nicoletta Colombo, Marco Gobbi, Maria R. Zocchi
Journal: Blood (2007)
Computationally designed antibody–drug conjugates self-assembled via affinity ligands
Authors: Nimish Gupta, Aasif Ansari, Gaurao V. Dhoke, Maheshwerreddy Chilamari, Jwala Sivaccumar, Smita Kumari, Snigdha Chatterjee, Ravinder Goyal, Pradip Kumar Dutta, Mallik Samarla, Madhumita Mukherjee, Arindam Sarkar, Swadhin K. Mandal, Vishal Rai, Goutam Biswas, Aniruddha Sengupta, Sudip Roy, Monideepa Roy, Shiladitya Sengupta
Journal: Nature Biomedical Engineering (2019)
Should medical schools relax academic admission criteria?
Authors: Drew Tarmey, Diana F Wood, Mark S Lillicrap, Holly C Canuto
Journal: BMJ (2019)

We need to recruit more medical students, and not requiring A level chemistry may help to create a more equitable and diverse medical workforce, says <b>Drew Tarmey</b>. But <b>Diana Wood</b>, <b>Mark Lillicrap</b>, and <b>Holly Canuto</b> argue that studying chemistry helps with medical study and that more evidence is needed before changing admission criteria
Role of the microRNA-7 (miR-7) in the Inhibition of Chemoresistance and Migration of Lymphoma Non-Hodgkin's through Regulation of YY1 and KLF4
Authors: Mario Morales-Martinez, Gabriel G Vega, Natividad Neri Munoz, M. J Nambo, Isabel Alvarado, Ivonne Cuadra, M. A. Duran-Padilla, Sara Huerta-Yepez, Mario I Vega
Journal: Blood (2019)
Efficacy and Safety of Ferric Carboxymaltose Injection in Reducing Anemia in Patients Receiving Chemotherapy for Non-Myeloid Malignancies: A Phase 3, Placebo-Controlled Study (IRON CLAD)
Authors: Jeffrey A. Gilreath, Tamta Makharadze, Ralph V. Boccia, Anna Krupa, David H. Henry
Journal: Blood (2019)
SP and NK1R: new targets in the treatment of chronic pruritus
Authors: S. Ständer, G. Yosipovitch
Journal: British Journal of Dermatology (2019)

Chronic itch (pruritus) can severely affect quality of life; it can be associated with several different skin diseases or systemic disease (affecting the whole body rather than just the skin). Current treatments are not always successful, and a fuller understanding of the mechanisms of itch should lead to better treatment.
Primary biliary cirrhosis.
Authors: J Neuberger, M Lombard, R Galbraith
Journal: Gut (1991)

<h3>ABSTRACT</h3> Sex differences in whole-body fat storage exist in many species. For example, <i>Drosophila</i> females store more fat than males. Yet, the mechanisms underlying this sex difference in fat storage remain incompletely understood. Here, we identify a key role for sex determination gene <i>transformer</i> (<i>tra</i>) in regulating the male-female difference in fat storage. Normally, a functional Tra protein is present only in females, where it promotes female sexual development. We show that loss of Tra in females reduced whole-body fat storage, whereas gain of Tra in males augmented fat storage. Tra’s role in promoting fat storage was largely due to its function in neurons, specifically the Adipokinetic hormone (Akh)-producing cells (APCs). Our analysis of Akh pathway regulation revealed a male bias in APC activity and Akh pathway function, where this sex-biased regulation influenced the sex difference in fat storage by limiting triglyceride accumulation in males. Importantly, Tra loss in females increased Akh pathway activity, and genetically manipulating the Akh pathway rescued Tra-dependent effects on fat storage. This identifies sex-specific regulation of Akh as one mechanism underlying the male-female difference in whole-body triglyceride levels, and provides important insight into the conserved mechanisms underlying sexual dimorphism in whole-body fat storage.
Robots and Tools for Remodeling Bone
Authors: Dave Hill, Tom Williamson, Chow Yin Lai, Martin Leary, Milan Brandt
Journal: IEEE Reviews in Biomedical Engineering (2019)

The field of robotic surgery has progressed from small teams of researchers repurposing industrial robots, to a competitive and highly innovative subsection of the medical device industry. Surgical robots allow surgeons to perform tasks with greater ease, accuracy, or safety, and fall under one of four levels of autonomy; active, semi-active, passive, and remote manipulator. The increased accuracy afforded by surgical robots has allowed for cementless hip arthroplasty, improved postoperative alignment following knee arthroplasty, and reduced duration of intraoperative fluoroscopy among other benefits. Cutting of bone has historically used tools such as hand saws and drills, with other elaborate cutting tools now used routinely to remodel bone. Improvements in cutting accuracy and additional options for safety and monitoring during surgery give robotic surgeries some advantages over conventional techniques. This article aims to provide an overview of current robots and tools with a common target tissue of bone, proposes a new process for defining the level of autonomy for a surgical robot, and examines future directions in robotic surgery.
Identification of Cell-Type-Specific Mutations in Angioimmunoblastic T-Cell Lymphoma
Authors: Tran Bich Nguyen, Mamiko Sakata-Yanagimoto, Yukitsugu Asabe, Kenichi Yoshida, Hideharu Muto, Rie Nakamoto-Matsubara, Koji Izutsu, Naoya Nakamura, Kengo Takeuchi, Seishi Ogawa, Shigeru Chiba
Journal: Blood (2014)
Detection of Extracellular Protein Kinase A (ECPKA) Autoantibody in Non-Hodgkin’s Lymphoma: Its Increased Antibody Titer Decreases with a Favorable Treatment Response.
Authors: Chul Won Choi, Hee Yun Seo, Hwa Jung Sung, Soo-Young Yoon, Seok Jin Kim, Byung Soo Kim, Jun Suk Kim, Meyoung-Kon Kim
Journal: Blood (2006)
Outcomes in Heparin-Induced Thrombocytopenia Managed with Direct Oral Anticoagulants
Authors: Nwabundo Anusim, Filip Ionescu, Anish S Konde, Vishal Jindal, Ruby Gupta, Marianne Terese Huben, Susanna Gaikazian, Ishmael Jaiyesimi
Journal: Blood (2019)
Letter to the Editor
Authors: Domenico Rubello, Milton D. Gross
Journal: Clinical Nuclear Medicine (2007)

Nuclear Medicine Service; PET Unit, Istituto Oncologico Veneto; (IOV); ‘S. Maria della Misericordia’ Rovigo Hospital; Viale Tre Martiri, 140, 45100, Rovigo, Italy; [email protected] Division of Nuclear Medicine; Department of Radiology; University of Michigan; Department of Veterans Affairs Health System; Ann Arbor, MI
CMET-16. A PHASE II TRIAL OF BEVACIZUMAB IN PATIENTS WITH RECURRENT SOLID TUMOR BRAIN METASTASES WHO HAVE PROGRESSED FOLLOWING WHOLE BRAIN RADIATION THERAPY (WBRT): FINAL RESULTS
Authors: Priya Kumthekar, Karan Dixit, Sean Grimm, Rimas Lukas, Margaret Schwartz, Irene Helenowski, Laura Sharp, Valerie Nelson, Jeffrey Raizer
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Brain metastases (BM) are the most common intracranial tumor with limited treatment options following the progression after WBRT. METHODS This open label phase 2 study for patients have progressed following WBRT enrolled participants who received bevacizumab 10 mg/kg intravenously every two weeks until CNS disease progression (one cycle=4 weeks). The primary endpoint was objective radiographic tumor response as defined by modified Response Assessment in Neuro-oncology (RANO) criteria. Secondary endpoints included safety, progression free survival (PFS), time to response, duration of response, overall survival (OS), and quality of life (QOL) as measured by FACT-G and FACT-Br. RESULTS A total of 27 patients were registered of which 24 were evaluable for ORR (3 came off study prior to first follow up MRI brain). Median age was 53 (range 27–73), median number of cycles was 5.5 (range 1–20) with a median follow up of 8.7 months (range 2.4–47.9mo). Of the 24 evaluable patients, 6 showed radiographic response (Partial response=6, stable disease=16, progressive disease=2, 81% (22/24) experienced clinical benefit). The 6 month PFS: 46% (95% CI: 25% - 67%) and median PFS was 5.3 months. Median OS was 9.5 months (95% confidence interval 6.3m – 15.0m). For the patients who completed sequential QOL assessments, there no decline in QOL seen secondary to treatment and there was a non statistically significant improvement seen in the FACT-Br questionnaire. Overall, treatment was well tolerated with 3 grade 3 adverse events seen: hypertension (n=3), headache (n=1) and thrombotic event (n=1). CONCLUSION For this pretreated BM population with historically poor clinical outcome and survival, we showed disease response with bevacizumab therapy, drug tolerability and improved survival as compared to historical controls. While larger studies are needed to confirm, bevacizumab therapy could be a viable option for solid tumor BM patients who experience progression following WBRT.
Engineering High Affinity and Cleavage Resistant CD16 to Augment ADCC of Placental Hematopoietic Stem Cells-Derived Natural Killer Cells
Authors: Xuan Guo, Srinivas Somanchi, Rohit Mathur, Shuyang He, Qian Ye, Andrea Difiglia, Salvatore Rotondo, Hemlata Rana, Weifang Ling, James Edinger, Robert Hariri, Xiaokui Zhang
Journal: Blood (2019)
Internal tandem duplication of FLT3 induces increased ROS production, DNA damage and misrepair: implications for RAC1-STAT5 function in genomic instability in myeloid malignancies
Authors: Kamal Datta, Kyu-Tae Kim, Dan Grosu, Paul Shapiro, Donald Small, Feyruz Rassool
Journal: Cancer Research (2007)

5260  Activating mutations of FMS-like tyrosine kinase 3 (FLT3) occur in about 30% of myeloid malignancies and at least for the internal tandem duplications (ITDs) of the juxtamembrane region, are an independent predictor of poor clinical outcome. Known FLT3 signaling includes activation of the RAS-MAP kinase, PI3 kinase/AKT, and STAT5 pathways with increased cellular survival. However, little is known about how FLT3/ITD in acute myeloid leukemia (AML) contributes to aggressive disease with poor prognosis. Here, we report that the aggressive nature of FLT3/ITD AML could be due to increased genomic instability that is driven by increased reactive oxygen species (ROS), DNA double-strand breaks (DSBs) and reduced repair fidelity. A murine myeloid progenitor cell line (32D) stably expressing FLT3/ITD (32D/ITD), show increased ROS, as measured by flow cytometry using the fluorescent probe H2DCFDA, compared with isogenic controls. Intriguingly, we find that STAT5 binds RAC1, an essential component of ROS-producing NADPH oxidase, and this novel finding suggests that STAT5 may have unique non-genomic functions involved in regulating RAC1 activation and ROS generation. FLT3 inhibitor, CEP-701, treated 32D/ITD cells show decreased RAC1-GTP activity as well as ROS levels. Also, FLT3 mutant cells treated with either the inhibitor of RAC1 or with siRNA to knocked-down STAT5 expression show markedly reduced ROS. Importantly, human leukemia cell lines expressing naturally occurring FLT3/ITD mutations (MOLM-14 & MV-4-11) also show significantly decreased ROS in a dose and time dependent manner, following treatment with CEP-701, confirming the mouse cell line data. Inhibition of NADPH oxidase by diphenyleneidonium also showed decreased ROS production in all cell lines tested. Blocking ROS production in FLT3/ITD cells with CEP-701 treatment also showed significant decreases in γH2AX foci formation suggesting reduced DSB. An in vitro DSB repair assay based on plasmid rejoining in nuclear extracts was used to assess DSB repair fidelity following inhibition of FLT3. Higher repair fidelity was observed following inhibition of FLT3-mediated endogenous ROS production in human AML cells. We show that constitutive activation of FLT3 signaling in AML mediates increased ROS production, DNA damage with decreased repair fidelity. Blocking of FLT3 and its downstream signaling decreased these activities that likely promote genomic instability. Our data serve as a model system to further study the role of FLT3-mediated increased ROS in propagating genomic instability and disease progression and could also lead to identification of downstream molecules for therapeutic targeting in an effort to stabilize the genome and halt disease progression in AML
Comparison of Four Different Humanized Hematopoietic Niche Xenotransplantation Methods to Engraft Myelodysplastic Syndromes (MDS)
Authors: Eva Altrock, Carla Sens-Albert, Johann-Christoph Jann, Johanna Flach, Vladimir Ryabov, Nanni Schmitt, Alexander Streuer, Qingyu Xu, Verena Nowak, Justine Danner, Julia Obländer, Nina Draeger, Iris Palme, Ahmed Jawhar, Cleo-Aron Weis, Vanessa Weyer, Florian Nolte, Georgia Metzgeroth, Alexander Marx, Christoph Groden, Wolf-Karsten Hofmann, Daniel Nowak
Journal: Blood (2019)
Trisomy 21 Driven Pro-Inflammatory Signalling in Fetal Bone Marrow May Play a Role in Perturbed B-Lymphopoiesis and Acute Lymphoblastic Leukemia of Down Syndrome
Authors: Sorcha Isabella O'Byrne, Natalina Elliott, Gemma Buck, Siobhan Rice, David O'Connor, Jana Oswald, Hannah Fuchs, Ella-Mae Labbett, Nicholas James Fordham, Anindita Roy, Irene Roberts
Journal: Blood (2019)
Evolution of Clinically Relevant Subclones during Chemotherapy Treatment of ALL As Determined By Single-Cell DNA and RNA Sequencing
Authors: Llucia Albertí Servera, Sofie Demeyer, Inge Govaerts, Olga Gielen, Heidi Segers, Anne Uyttebroeck, Nancy Boeckx, Johan A. Maertens, Kim De Keersmaecker, Jan Cools
Journal: Blood (2019)
EXTH-66. THERAPEUTIC VULNERABILITIES AND RADIOSENSITIZATION INDUCED BY IDH MUTANT DEPENDENT SUPPRESSION OF DNA DAMAGE REPAIR IN GLIOMA AND CHOLANGIOCARCINOMA
Authors: Yuxiang Wang, Aaron Wild, Timothy Chan
Journal: Neuro-Oncology (2019)

Abstract Mutations in isocitrate dehydrogenase (IDH) identified across cancer types lead to global changes to the epigenome that drive tumorigenesis. Yet, effectiveness of targeted therapies against mutant IDH remains unclear. Here we demonstrate that IDH-mutant glioma and cholangiocarcinoma patient specimens display elevated overall DNA damage responses. With tissue culture and multiple preclinical animal models of glioma and cholangiocarcinoma, we report that the reduced efficiency of DNA damage repair conferred by mutant IDH can be exploited by PARP inhibitors. Moreover, pharmacological effects of PARP inhibitors are dramatically enhanced by introducing concurrent, local ionizing radiation treatment to the animals. Thus, our study characterized the synergy of PARPi and radiation specifically towards IDH-mutant tumors, pointing out that in addition to ongoing trials using PARPi as mono agent, clinical trials that combine PARPi and radiation should be specifically considered. Furthermore, PARPi + RT may represent a readily translatable approach that is selective for tumor cells, transcends histologic origin, and has potential to improve outcomes in multiple diseases.
CMET-06. AN ANALYSIS OF RESPONSE ENDPOINTS FOR BRAIN METASTASIS PATIENTS TREATED WITH STEREOTACTIC RADIOSURGERY AND PD(L)-1 INHIBITORS
Authors: Rupesh Kotecha, Jacob Miller, Joseph Kim, Aditya Juloori, Samuel Chao, Erin Murphy, David Peereboom, Alireza Mohammadi, Gene Barnett, Michael Vogelbaum, Lilyana Angelov, John Suh, Manmeet Ahluwalia
Journal: Neuro-Oncology (2019)

Abstract PURPOSE Recent trials have evaluated the role of anti-PD(L)-1 inhibitors alone in patients with newly diagnosed brain metastasis, resulting in a suggested paradigm shift. In the absence of randomized comparisons, an evaluation of outcomes for similar patients treated with radiotherapy are needed to provide baseline comparative data. METHODS This retrospective cohort study included patients diagnosed with brain metastasis from 2010–2017 at a single tertiary care institution who received SRS and at least one anti-PD(L)-1 inhibitor. Primary endpoints included the rate of best intracranial response (either a complete [CR] or partial response [PR]), rate of intracranial benefit (percentage of patients with stable disease [SD] for at least 6 months), and overall objective response rates. RESULTS 150 patients met the eligibility criteria for this study and the median follow-up time was 10 months (Range: 1–130 months). Only a minority of patients from this cohort would have been eligible for comparative systemic therapy alone trials: 8 (CheckMate 204, CM), 8 (ABC), and 50 patients (Yale Institutional trial, YI). Best intracranial objective response rates for these trial eligible patients were 64% (CM), 64% (ABC), and 72% (YI), respectively. The 6-month rates of intracranial benefit across patients were 75% (CM), 75% (ABC), and 93% (YI), respectively. The rates of either a CR, PR, or SD across trial eligible patients were 100% (CM), 100% (ABC), and 94% (YI), respectively. More than 50% of patients experienced out-of-field progression in each of the patient subgroups. CONCLUSIONS Over a seven year period, very few patients treated with SRS and anti-PD(L)-1 inhibitor therapy in a busy academic practice would have been eligible for systemic therapy alone per trial eligibility criteria. In these highly favorable subgroups, patients experience high rates of objective response, best intracranial response, and intracranial benefit after SRS and anti-PD(L)-1 therapy, representing optimal brain metastasis management.
The Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement
Authors: David M. Kent, Jessica K. Paulus, David van Klaveren, Ralph D'Agostino, Steve Goodman, Rodney Hayward, John P.A. Ioannidis, Bray Patrick-Lake, Sally Morton, Michael Pencina, Gowri Raman, Joseph S. Ross, Harry P. Selker, Ravi Varadhan, Andrew Vickers, John B. Wong, Ewout W. Steyerberg
Journal: Annals of Internal Medicine (2019)

Heterogeneity of treatment effect (HTE) refers to the nonrandom variation in the magnitude or direction of a treatment effect across levels of a covariate, as measured on a selected scale, against a clinical outcome. In randomized controlled trials (RCTs), HTE is typically examined through a subgroup analysis that contrasts effects in groups of patients defined "1 variable at a time" (for example, male vs. female or old vs. young). The authors of this statement present guidance on an alternative approach to HTE analysis, "predictive HTE analysis." The goal of predictive HTE analysis is to provide patient-centered estimates of outcome risks with versus without the intervention, taking into account all relevant patient attributes simultaneously. The PATH (Predictive Approaches to Treatment effect Heterogeneity) Statement was developed using a multidisciplinary technical expert panel, targeted literature reviews, simulations to characterize potential problems with predictive approaches, and a deliberative process engaging the expert panel. The authors distinguish 2 categories of predictive HTE approaches: a "risk-modeling" approach, wherein a multivariable model predicts the risk for an outcome and is applied to disaggregate patients within RCTs to define risk-based variation in benefit, and an "effect-modeling" approach, wherein a model is developed on RCT data by incorporating a term for treatment assignment and interactions between treatment and baseline covariates. Both approaches can be used to predict differential absolute treatment effects, the most relevant scale for clinical decision making. The authors developed 4 sets of guidance: criteria to determine when risk-modeling approaches are likely to identify clinically important HTE, methodological aspects of risk-modeling methods, considerations for translation to clinical practice, and considerations and caveats in the use of effect-modeling approaches. The PATH Statement, together with its explanation and elaboration document, may guide future analyses and reporting of RCTs.
Increased Mean Corpuscular Volume Is an Independent Predictor for Worse Overall Survival in Patients with Newly Diagnosed Light Chain Amyloidosis
Authors: Abdullah S. Al Saleh, M Hasib Sidiqi, Eli Muchtar, Angela Dispenzieri, Francis K. Buadi, Rahma M Warsame, Martha Q. Lacy, David Dingli, Nelson Leung, Wilson I Gonsalves, Taxiarchis Kourelis, Prashant Kapoor, Ronald S. Go, Robert A. Kyle, S. Vincent Rajkumar, Morie A Gertz, Shaji K. Kumar
Journal: Blood (2019)