tbuckley/cabot-search huggingface dataset:
Report on the Treatment of Hodgkin Lymphoma with ABVD Chemotherapy at Two Rural District Hospitals in Rwanda
Authors: Cyprien Shyirambere, Rebecca Deboer, Yvan Butera, Caitlin Driscoll, Jean Bosco Bigirimana, Francois Regis Uwizeye, Temidayo Fadelu, Paul H Park, Alan Paciorek, Leslie E. Lehmann, Lawrence N. Shulman
Journal: Blood (2019)
The Dual PI3K-δ/γ Inhibitor Duvelisib in Combination with the Bcl-2 Inhibitor Venetoclax Shows Promising Responses in Richter Syndrome-PDX Models
Authors: Andrea Iannello, Francesca Arruga, Nicoletta Vitale, Elisa Marchi, Richard R. Furman, John N. Allan, Silvia Coma, Jonathan A. Pachter, Silvia Deaglio, Tiziana Vaisitti
Journal: Blood (2019)
Activation of β-Catenin Cooperates with Loss of Pten to Drive AR-Independent Castration-Resistant Prostate Cancer
Authors: Rachana Patel, Elspeth A. Brzezinska, Peter Repiscak, Imran Ahmad, Ernest Mui, Meiling Gao, Arnaud Blomme, Victoria Harle, Ee Hong Tan, Gaurav Malviya, Agata Mrowinska, Carolyn J. Loveridge, Linda K. Rushworth, Joanne Edwards, Chara Ntala, Colin Nixon, Ann Hedley, Gillian Mackay, Saverio Tardito, Owen J. Sansom, Hing Y. Leung
Journal: Cancer Research (2019)

Abstract Inhibition of the androgen receptor (AR) is the main strategy to treat advanced prostate cancers. AR-independent treatment-resistant prostate cancer is a major unresolved clinical problem. Patients with prostate cancer with alterations in canonical WNT pathway genes, which lead to β-catenin activation, are refractory to AR-targeted therapies. Here, using clinically relevant murine prostate cancer models, we investigated the significance of β-catenin activation in prostate cancer progression and treatment resistance. β-Catenin activation, independent of the cell of origin, cooperated with Pten loss to drive AR-independent castration-resistant prostate cancer. Prostate tumors with β-catenin activation relied on the noncanonical WNT ligand WNT5a for sustained growth. WNT5a repressed AR expression and maintained the expression of c-Myc, an oncogenic effector of β-catenin activation, by mediating nuclear localization of NFκBp65 and β-catenin. Overall, WNT/β-catenin and AR signaling are reciprocally inhibited. Therefore, inhibiting WNT/β-catenin signaling by limiting WNT secretion in concert with AR inhibition may be useful for treating prostate cancers with alterations in WNT pathway genes. Significance: Targeting of both AR and WNT/β-catenin signaling may be required to treat prostate cancers that exhibit alterations of the WNT pathway.
Post-pill amenorrhoea.
Authors: R P Shearman
Journal: BMJ (1977)

The writer has always used a 12-month period before diagnosing secondary amenorrhea whereas a previously published article used a 4-month period. The spontaneous cure rate of amenorrhea of this short duration is relatively high. The writer has never claimed a causal relationship between oral contraceptives and secondary amenorrhea, but there is a high index of suspicion. Full investigation should be made, mainly to exclude pituitary tumor. In a recent series of patients with galactorrhea and amenorrhea, 20 of 25 with proved pituitary adenomas gave a history of oral contraceptive use. Clomiphene-responsive amenorrhea patients represent a heterogeneous group of disparate causes of anovulation and should not be grouped together. After 12 months or more of amenorrhea, patients followed-up for 18 months to 11 years still had a 30% persistence of the condition.
The Canadian Tyrosine Kinase Inhibitor Discontinuation Trial with Imatinib Discontinuation As a First Attempt and with Dasatinib Discontinuation As a Second Attempt of Treatment-Free Remission: Results of 4 Years of Follow-up
Authors: Dennis Dong Hwan Kim, Isabelle Bence-Bruckler, Lambert Busque, Donna L. Forrest, Lynn Savoie, Mary-Margaret Keating, Robert Delage, Anargyros Xenocostas, Elena Liew, Pierre Laneuville, Kristjan Paulson, Jeffrey H. Lipton, Suzanne Kamel-Reid, Brian Leber
Journal: Blood (2019)
TMIC-07. SYMBIOTIC MACROPHAGE-GLIOMA CELL INTERACTIONS REVEAL SYNTHETIC LETHALITY IN PTEN NULL GLIOMA
Authors: Peiwen Chen, Ronald DePinho, Wang Alan
Journal: Neuro-Oncology (2019)

Abstract Heterotypic interactions across diverse cell types of the tumor microenvironment (TME) can enable tumor progression and offer points for potential therapeutic intervention. Employing Glioblastoma Multiforme (GBM) as a model system, we sought to (i) understand the nature of specific oncogenic signals in glioma cells that affects immune cells, and (ii) identify immune cell factors which may support glioma growth and survival. Combined profiling and functional studies of glioma cells established that PTEN deficiency, a signature GBM alteration, specifically tracks with an immune profile dominated by tumor-associated macrophages (TAMs, a key type of immune cells in GBM which can constitute up to half of the tumor mass) via upregulation of lysyl oxidase (LOX). Mechanistically, the PTEN-SRC/AKT axis regulates YAP1, which directly upregulates LOX expression and secretion in glioma cells via binding to the LOX promoter. The secreted LOX from glioma cells functions as a potent macrophage chemoattractant to promote macrophage recruitment via activation of the beta1 integrin-PYK2 pathway in macrophages. Consequently, these infiltrating macrophages secrete SPP1 (secreted phosphoprotein 1) which sustains glioma cell survival and stimulates angiogenesis. In human and mouse PTEN-null GBM models, but not PTEN-intact GBM models, LOX inhibition markedly inhibits tumor growth and extends the survival of tumor-bearing mice by decreasing macrophage infiltration, impairing SPP1 expression and attenuating angiogenesis. In silico analysis of human GBM shows that increased YAP1-LOX and b1 integrin-SPP1 signaling positively correlates with higher macrophage density and lower overall survival. Together, the symbiotic glioma (PTEN-YAP1-LOX) and macrophage (beta1 integrin-PYK2-SPP1) interactions provide novel therapeutic targets for this intractable disease.
Personalized Ubiquitination Signatures for Predicting Response to Proteasome Inhibitor-Based Therapy of MM Patients
Authors: Haim Tsubery, Lerman Gali, Kronenfeld Gali, Itamar Sela, Yifat Merbl, Ayelet Itzhaki-Alfia, Svetlana Trestman, Yael C Cohen, Irit Avivi
Journal: Blood (2019)
2019 American Heart Association Focused Update on Advanced Cardiovascular Life Support: Use of Advanced Airways, Vasopressors, and Extracorporeal Cardiopulmonary Resuscitation During Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Authors: Ashish R. Panchal, Katherine M. Berg, Karen G. Hirsch, Peter J. Kudenchuk, Marina Del Rios, José G. Cabañas, Mark S. Link, Michael C. Kurz, Paul S. Chan, Peter T. Morley, Mary Fran Hazinski, Michael W. Donnino
Journal: Circulation (2019)

The fundamentals of cardiac resuscitation include the immediate provision of high-quality cardiopulmonary resuscitation combined with rapid defibrillation (as appropriate). These mainstays of therapy set the groundwork for other possible interventions such as medications, advanced airways, extracorporeal cardiopulmonary resuscitation, and post-cardiac arrest care, including targeted temperature management, cardiorespiratory support, and percutaneous coronary intervention. Since 2015, an increased number of studies have been published evaluating some of these interventions, requiring a reassessment of their use and impact on survival from cardiac arrest. This 2019 focused update to the American Heart Association advanced cardiovascular life support guidelines summarizes the most recent published evidence for and recommendations on the use of advanced airways, vasopressors, and extracorporeal cardiopulmonary resuscitation during cardiac arrest. It includes revised recommendations for all 3 areas, including the choice of advanced airway devices and strategies during cardiac arrest (eg, bag-mask ventilation, supraglottic airway, or endotracheal intubation), the training and retraining required, the administration of standard-dose epinephrine, and the decisions involved in the application of extracorporeal cardiopulmonary resuscitation and its potential impact on cardiac arrest survival.
The Lazy Eye
Authors: T. K. Lyle
Journal: BMJ (1947)

<h3>Objectives</h3> Bariatric surgery is the most clinically effective treatment for people with severe and complex obesity, however, the psychosocial outcomes are less clear. Follow-up care after bariatric surgery is known to be important, but limited guidance exists on what this should entail, particularly related to psychological and social well-being. Patients’ perspectives are valuable to inform the design of follow-up care. This study investigated patients’ experiences of life after bariatric surgery including important aspects of follow-up care, in the long term. <h3>Design</h3> A qualitative study using semistructured individual interviews. A constant comparative approach was used to code data and identify themes and overarching concepts. <h3>Setting</h3> Bariatric surgery units of two publicly funded hospitals in the South of England. <h3>Participants</h3> Seventeen adults (10 women) who underwent a primary operation for obesity (mean time since surgery 3.11 years, range 4 months to 9 years), including Roux-en-Y gastric bypass, adjustable gastric band and sleeve gastrectomy, agreed to participate in the interviews. <h3>Results</h3> Experiences of adapting to life following surgery were characterised by the concepts of ‘normality’ and ‘ambivalence’, while experiences of ‘abandonment’ and ‘isolation’ dominated participants’ experiences of follow-up care. Patients highlighted the need for more flexible, longer-term follow-up care that addresses social and psychological difficulties postsurgery and integrates peer support. <h3>Conclusions</h3> This research highlights unmet patient need for more accessible and holistic follow-up care that addresses the long-term multidimensional impact of bariatric surgery. Future research should investigate effective and acceptable follow-up care packages for patients undergoing bariatric surgery.
Hypercoagulability Biomarkers in a New Score Linked to Treatment Resistance for Multiple Myeloma Patients. the Roadmap-MM Study
Authors: Loula Papageorgiou, Despina Fotiou, Patrick Van Dreden, Laurent Garderet, Meletios A. Dimopoulos, Ismail Elalamy, Mohamad Mohty, Grigoris Gerotziafas
Journal: Blood (2019)
Clinical and Functional Studies Reveal That TP73 Isoforms Levels Are Associated with Prognosis and RA-Resistance in Acute Promyelocytic Leukemia
Authors: César Alexander Ortiz Rojas, Diego A Pereira-Martins, Isabel Weinhäuser, Luciana Yamamoto Almeida, Thiago Mantello Bianco, Lorena Lobo Figueiredo-Pontes, Luisa C A Koury, Raul Antônio Morais Melo, Rosane Bittencourt, Katia B Pagnano, Ricardo Pasquini, Elenaide C. Nunes, Evandro Maranhão Fagundes, Ana Beatriz F. Gloria, Fabio R. Kerbauy, Armand Keating, Martin S. Tallman, Raul Ribeiro, Richard Dillon, Arnold Ganser, Bob Löwenberg, Peter Valk, Miguel A. Sanz, Nancy Berliner, Eduardo M Rego
Journal: Blood (2019)
Trans-Synaptic Signaling through the Glutamate Receptor Delta-1 Mediates Inhibitory Synapse Formation in Cortical Pyramidal Neurons
Authors: Matteo Fossati, Nora Assendorp, Olivier Gemin, Sabrina Colasse, Florent Dingli, Guillaume Arras, Damarys Loew, Cécile Charrier
Journal: Neuron (2019)

Fine orchestration of excitatory and inhibitory synaptic development is required for normal brain function, and alterations may cause neurodevelopmental disorders. Using sparse molecular manipulations in intact brain circuits, we show that the glutamate receptor delta-1 (GluD1), a member of ionotropic glutamate receptors (iGluRs), is a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. GluD1 is selectively required for the formation of inhibitory synapses and regulates GABAergic synaptic transmission accordingly. At inhibitory synapses, GluD1 interacts with cerebellin-4, an extracellular scaffolding protein secreted by somatostatin-expressing interneurons, which bridges postsynaptic GluD1 and presynaptic neurexins. When binding to its agonist glycine or D-serine, GluD1 elicits non-ionotropic postsynaptic signaling involving the guanine nucleotide exchange factor ARHGEF12 and the regulatory subunit of protein phosphatase 1 PPP1R12A. Thus, GluD1 defines a trans-synaptic interaction regulating postsynaptic signaling pathways for the proper establishment of cortical inhibitory connectivity and challenges the dichotomy between iGluRs and inhibitory synaptic molecules.
Genome-Wide CRISPR Library Screening Identifies CDK6 As Genetic Vulnerability in Adult T-Cell Leukemia/Lymphoma
Authors: Takashi Ishio, Joji Shimono, Sarvesh Kumar, Yuquan Lin, Emmanuel Bachy, Michael N. Petrus, Yandan Yang, Michiyuki Maeda, Hideki Goto, Satoshi Hashino, Takanori Teshima, Thomas A. Waldmann, Louis Staudt, Masao Nakagawa
Journal: Blood (2019)
Renal Pelvis Urothelial Carcinoma With Bowel Metastases
Authors: Alex Cheen Hoe Khoo, Weng Heng Tang
Journal: Clinical Nuclear Medicine (2019)

Abstract Urothelial carcinoma is the fourth most common genitourinary tumor with the majority of the tumor involving the urinary bladder. Only 5% involves the renal pelvis and ureter. Metastatic urothelial carcinoma of the renal pelvis frequently involves the lymph nodes, lung, liver, bone, and peritoneum. We share rare interesting 18 F-FDG PET/CT images of a 60-year-old man with metastatic urothelial carcinoma of the renal pelvis to the bowel.
CBMT-31. HDAC INHIBITION DIMINISHES THE GROWTH OF ENDOGENOUS IDH MUTANT GLIOMAS
Authors: Lubayna Elahi, Matthew Garrett, Lea Guo, Michael Condro, Riki Kawaguchi, Shwetal Mehta, Albert Lai, Whitney Pope, Harley Kornblum
Journal: Neuro-Oncology (2019)

Abstract Histone deacetylase inhibitors (HDACi’s) have emerged as a promising class of drugs for treatment of malignancies such as glioblastoma (GBM). Several studies have demonstrated the anti-tumor property of HDACi’s against GBM in both in vitro and in vivo experiments. Nonetheless, in clinical trials, HDACi only marginally increased overall survival of patients with GBM. The mixed results of trials with HDACi’s in glioma have prompted us to hypothesize that improved selection of patients by tumor characteristics could enhance the efficacy of therapy. We specifically tested the effects of valproic acid (VPA), a HDACi and an antiepileptic drug against IDH mutant gliomas. We have previously demonstrated that our IDH mutant glioma cell lines have gene expression and methylation patterns highly similar to IDH mutant tumors in situ. Mutant IDH1 alters the epigenetic landscape of gliomas leading to the hypermethylation phenotype and transcriptional repression of genes. This repression of genes may contribute to tumorigenesis and progression of IDH mutant gliomas. We found that VPA inhibits the growth of patient-derived IDH1 mutant glioma lines. In addition, RNA sequencing analysis of vehicle and VPA-treated IDH1 mutant glioma cells showed de-repression of several genes previously shown to be downregulated in IDH1 mutant glioma cell lines. We also treated cells with another HDACi LBH589 and found that both VPA and LBH589 upregulates similar gene sets suggesting that HDAC inhibition promotes de-repression of previously repressed genes. Ongoing studies are aimed at determining the molecular mechanism by which VPA regulates the growth of IDH1 mutant tumors.
Infographic running myth: static stretching reduces injury risk in runners
Authors: James L N Alexander, Christian J Barton, Richard W Willy
Journal: British Journal of Sports Medicine (2019)

It is a commonly held belief that static stretching plays an important role in improving running performance and decreasing injury risk.1 As such static stretching, undertaken as part of a ‘warm-up’ prior to running, at the end of a run or as part of a strength training programme, is a common practice among runners of all levels. Static stretching involves lengthening a muscle to the point at which a gentle tension is felt and remaining in this position, typically for a minimum of 30 seconds per stretch.2 

Current research evidence definitively reports that this belief is, in fact, incorrect (figure 1).3 4 



Figure 1 
Infographic



Running places significantly high loads through the joints and soft tissues of the body. As a result, runners are at a …
The herbal dietary supplement Gamma-Linolenic Acid (GLA; 18:3n-6) inhibits the promoter activity of the Her-2/neu (erbB-2) oncogene through the PEA3 Ets transcription factor: A novel mode for sensitization of Her-2/neu-overexpressing breast cancer cells to trastuzumab (Herceptin™)
Authors: Javier A. Menendez, Luciano Vellon, Ramon Colomer, Ruth Lupu
Journal: Cancer Research (2005)

3393  The ω-6 polyunsaturated fatty acid gamma-linolenic acid (GLA; 18:3n-6) has raised interest as novel anti-cancer agent as it exerts selective cytotoxic and anti-proliferative effects on human cancer cells without affecting normal cells or creating harmful systemic side effects. We previously reported that exogenous supplementation with GLA synergistically sensitizes cultured breast cancer cells to anti-mitotic drugs such as paclitaxel, vinorelbine, and docetaxel. This GLA-induced sensitization was also synergistic with the antiestrogens tamoxifen and faslodex. Since the overexpression of Her-2/neu oncogene has been associated to chemotherapy and antiestrogen resistance in breast carcinomas, we hypothesized that GLA-related anti-tumoral actions may involve regulation of Her-2/neu-driven cellular signaling. To study this issue we used BT-474 and SK-Br3 breast cancer cells, which naturally exhibit amplification of the Her-2/neu oncogene. Flow cytometric and immunoblotting analyses demonstrated a dramatic reduction of Her-2/neu protein expression following treatment with GLA. Interestingly, a significant accumulation of the DNA-binding protein PEA3, a member of the Ets transcription factor family that specifically targets a DNA sequence on the Her-2/neu promoter and down-regulates its activity, was observed in GLA-treated cells. Moreover, when a luciferase reporter gene driven by the Her-2/neu promoter was transiently into BT-474 and SK-Br3 breast cancer cells, GLA exposure was found to dramatically repress the promoter activity of Her-2/neu gene. Remarkably, a Her-2/neu promoter bearing a mutated PEA3 binding sequence was not subject to negative regulation by GLA, thus demonstrating that the intact PEA3 binding site on the Her-2/neu promoter is required for the GLA-mediated transcriptional repression of Her-2/neu oncogene in breast cancer cells. The concurrent exposure to GLA and sub-optimal concentrations of trastuzumab synergistically down-regulated Her-2/neu expression, while the nature of the cytotoxic interactions between GLA and trastuzumab revealed a strong synergism as assessed by MTT-based cell viability and anchorage-independent soft-agar colony formation assays. GLA co-exposure synergistically enhanced trastuzumab efficacy towards Her-2/neu overexpressors by promoting DNA fragmentation-associated with apoptotic cell death, as confirmed by TUNEL assays. These findings demonstrate that GLA, a naturally occurring anti-tumor agent, transcriptionally represses Her-2/neu gene expression, which, in turn, interacts synergistically with anti-Her-2/neu immunotherapy by promoting apoptotic cell death of breast cancer cells with Her-2/neu oncogene amplification.
Phase 2 Study of Frontline Brentuximab Vedotin Plus Nivolumab in Patients with Hodgkin Lymphoma Aged ≥60 Years
Authors: Christopher A. Yasenchak, Rodolfo Bordoni, Victor Yazbeck, Dipti Patel-Donnelly, Thomas Anderson, Timothy Larson, Trevor Newhook, Matthew Mei, Linda Ho, Jonathan W. Friedberg
Journal: Blood (2019)
Integrated Single Cell Transcriptomics Defines an Engineered Niche Supporting Hematopoietic Stem Cell Development Ex Vivo
Authors: Brandon Hadland, Barbara Varnum-Finney, Stacey Dozono, Tessa Dignum, Cynthia Nourigat-Mckay, Dana Jackson, Shahin Rafii, Cole Trapnell, Irwin D. Bernstein
Journal: Blood (2019)
The Clinical Application of Oncomine Myeloid Next Generation Sequencing (NGS): Comparison of Cytogenetics and NGS in Patients with Suspected Myelodysplastic Syndrome
Authors: Eri Kawata, Anargyros Xenocostas, Cyrus C. Hsia, Uday Deotare, Lalit Saini, Ping Yang, Michael Levy, Hanxin Lin, Bekim Sadikovic, Ian Chin-Yee
Journal: Blood (2019)
Downregulation of PHGDH expression and hepatic serine level contribute to the development of fatty liver disease
Authors: Woo-Cheol Sim, Wonseok Lee, Hyungtai Sim, Kang-Yo Lee, Seung-Hwan Jung, You-Jin Choi, Hyun Young Kim, Keon Wook Kang, Ji-Yoon Lee, Young Jae Choi, Sang Kyum Kim, Dae Won Jun, Won Kim, Byung-Hoon Lee
Journal: Metabolism (2019)
SURG-29. LASER INTERSTITIAL THERMAL THERAPY COMPARED TO CRANIOTOMY FOR TREATMENT OF RECURRENT GLIOBLASTOMA
Authors: Ali Palejwala, Kyle O’connor, Chad Glenn, Michael Sughrue
Journal: Neuro-Oncology (2019)

Abstract There have been publications that propose the use of laser interstitial thermal therapy (LITT) as a viable alternative to craniotomy for the treatment of glioblastoma (GBM). The aim of this study was to retrospectively compare outcomes after LITT versus craniotomy for patients with recurrent GBM. To adequately match the cohorts, we included only pre-treatment tumor volumes of under 15 cc. We retrospectively collected data on all patients presenting with recurrent GBM, with a recurrence volume under 15 cc. These patients were either treated with LITT or craniotomy by the senior author. Data included demographics, tumor location and volume, tumor markers, perioperative complications, re-initiation of adjuvant chemotherapy, and long-term follow up data. We performed 23 LITT treatments and 34 craniotomies for recurrent GBM in patients that met selection criteria. There was no significant difference in the patients’ age, tumor volume (6.38 for craniotomy versus 5.765 cc for LITT), location, and post-procedure KPS. Patients that underwent LITT had significantly reduced inpatient stays in comparison to craniotomy (1.7 versus 4.2 days). They also had less perioperative complications (13.0% versus 32.3% for craniotomy). It was found that 28 out of the 34 patients that underwent craniotomy were able to undergo adjuvant therapy; in comparison, 15 out of the 23 patients who underwent LITT had undergone adjuvant therapy. Of these patient’s that underwent adjuvant therapy, 87% of patients were able to receive bevacizumab or a clinical trial versus 42% after craniotomy. Progression-free survival (PFS) and overall survival (OS) after procedure were similar for LITT versus craniotomy, respectively: % PFS-survival at 6 months = 23.5% versus 21.7%. Overall survival did not significantly differ at 9 months versus 9.9 months respectively. LITT appears to be safe and may be as efficacious as craniotomy in achieving progression free survival for small to moderate volume recurrent GBM.
Tumor-Specific Cell-Free DNA (cfDNA) in the Cerebrospinal Fluid (CSF) Detects Cytologically Occult Central Nervous System (CNS) Involvement in Aggressive Lymphomas
Authors: Adam J Olszewski, Anna D Chorzalska, Diana O Treaba, John L Reagan, Pamela C Egan, Habibe Kurt, James Butera, William Rafelson, Alexander C Mohler, Thomas A Ollila, Rabin Niroula, Jordan Robison, Chelsea D Mullins, Patrycja M Dubielecka
Journal: Blood (2019)