tbuckley/cabot-search huggingface dataset:
Real-time health monitoring through urine metabolomics
Authors: Ian J. Miller, Sean R. Peters, Katherine A. Overmyer, Brett R. Paulson, Michael S. Westphall, Joshua J. Coon
Journal: npj Digital Medicine (2019)

Current healthcare practices are reactive and based on limited physiological information collected months or years apart. By enabling patients and healthy consumers access to continuous measurements of health, wearable devices and digital medicine stand to realize highly personalized and preventative care. However, most current digital technologies provide information on a limited set of physiological traits, such as heart rate and step count, which alone offer little insight into the etiology of most diseases. Here we propose to integrate data from biohealth smartphone applications with continuous metabolic phenotypes derived from urine metabolites. This combination of molecular phenotypes with quantitative measurements of lifestyle reflect the biological consequences of human behavior in real time. We present data from an observational study involving two healthy subjects and discuss the challenges, opportunities, and implications of integrating this new layer of physiological information into digital medicine. Though our dataset is limited to two subjects, our analysis (also available through an interactive web-based visualization tool) provides an initial framework to monitor lifestyle factors, such as nutrition, drug metabolism, exercise, and sleep using urine metabolites.
Investigation of Allocar TTM Targeting CD70 As a Potential Therapy for an Array of Hematological Malignancies
Authors: Siler Panowski, Surabhi Srinivasan, Thomas Van Blarcom, Cesar Sommer, Hsin-Yuan Cheng, Thomas Pertel, Marianne A Santaguida, Roman Galetto, Alan Dunlop, Reuben Benjamin, Barbra Sasu
Journal: Blood (2019)
Optimal - a Study of Bortezomib, Bendamustine and Dexamethasone (BBD) Vs Thalidomide, Bendamustine and Dexamethasone (BTD) in Patients with Renal Failure Defined As an Egfr below 30 Mls/Min
Authors: Karthik Ramasamy, Mark T Drayson, Gulnaz Iqbal, Victoria Stalker, Salma Akhtar, Janet Dunn, Stephen Schey
Journal: Blood (2019)
Exploitation of CD133 for the Targeted Imaging of Lethal Prostate Cancer
Authors: Paige M. Glumac, Joseph P. Gallant, Mariya Shapovalova, Yingming Li, Paari Murugan, Shilpa Gupta, Ilsa M. Coleman, Peter S. Nelson, Scott M. Dehm, Aaron M. LeBeau
Journal: Clinical Cancer Research (2019)

Aggressive variant prostate cancer (AVPC) is a nonandrogen receptor-driven form of disease that arises in men in whom standard-of-care therapies have failed. Therapeutic options for AVPC are limited, and the development of novel therapeutics is significantly hindered by the inability to accurately quantify patient response to therapy by imaging. Imaging modalities that accurately and sensitively detect the bone and visceral metastases associated with AVPC do not exist.This study investigated the transmembrane protein CD133 as a targetable cell surface antigen in AVPC. We evaluated the expression of CD133 by microarray and IHC analysis. The imaging potential of the CD133-targeted IgG (HA10 IgG) was evaluated in preclinical prostate cancer models using two different imaging modalities: near-infrared and PET imaging.Evaluation of the patient data demonstrated that CD133 is overexpressed in a specific phenotype of AVPC that is androgen receptor indifferent and neuroendocrine differentiated. In addition, HA10 IgG was selective for CD133-expressing tumors in all preclinical imaging studies. PET imaging with [89Zr]Zr-HA10 IgG revealed a mean %ID/g of 24.30 ± 3.19 in CD133-positive metastatic lesions as compared with 11.82 ± 0.57 in CD133-negative lesions after 72 hours (P = 0.0069). Ex vivo biodistribution showed similar trends as signals were increased by nearly 3-fold in CD133-positive tumors (P < 0.0001).To our knowledge, this is the first study to define CD133 as a targetable marker of AVPC. Similarly, we have developed a novel imaging agent, which is selective for CD133-expressing tumors, resulting in a noninvasive PET imaging approach to more effectively detect and monitor AVPC.
Glycolysis Restoration Attenuates Damaged Bone Marrow Endothelial Cells
Authors: Zhong-Shi Lyu, Wei-Li Yao, Qi Wen, Hong-Yan Zhao, Fei-Fei Tang, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Hsiang-Ying Lee, Xiao-Jun Huang, Yuan Kong
Journal: Blood (2019)
Dose-Adjusted EPOCH and Rituximab (DA-EPOCH-R) Treatment in Dual Expressor Diffuse Large B-Cell and Double/Triple Hit Lymphomas: TP53 Mutations Influence on Clinical Outcome
Authors: Anna Dodero, Anna Guidetti, Fabrizio Marino, Cristiana Carniti, Stefania Banfi, Alessandra Tucci, Monica Balzarotti, Antonello Domenico Cabras, Valentina Monti, Liliana Franca Devizzi, Lucia Farina, Maria Chiara Di Chio, Giuseppe Rossi, Carmelo Carlo-Stella, Paolo Corradini
Journal: Blood (2019)
GENE-46. XAF1 DRIVES DIFFERENTIAL PLASTICITY TOWARDS ADAPTIVE RESISTANCE BETWEEN MGMT-HYPERMETHYLATED AND MGMT-HYPOMETHYLATED GLIOBLASTOMA
Authors: Qiong Wu, Anders Berglund, Dapeng Wang, Solmaz Sahebjam, Robert MacAulay, James Mulé, Arnold Etame
Journal: Neuro-Oncology (2019)

Abstract Although, the epigenetic regulation of O6-alkylguanine DNA alkyltransferase (MGMT) in GBM is an established surrogate of intrinsic resistance to temozolomide (TMZ), the evolution of GBM habitats towards adaptive resistance to TMZ relative to MGMT promoter methylation status remains unclear. We report a novel epigenetic regulation of plasticity towards adaptive resistance in GBM. Using an adaptive TMZ resistance model of MGMT-hypermethylated and MGMT-hypomethylated GBM cellular habitats, a counter-intuitive inverse correlation was noted between intrinsic MGMT-dependent TMZ resistance versus plasticity towards adaptive TMZ resistance. Upon TMZ challenge, GBM cellular habitats with lower intrinsic resistance demonstrated significant genetic perturbations and aggressive phenotypic alterations compared to GBM habitats with higher intrinsic resistance. A resulting gene signature associated with plasticity for adaptive resistance from our model significantly correlated with GBM survival in the TCGA dataset. XAF-1 emerged as a key gene whose epigenetic regulation mediated differential plasticity towards adaptive resistance to TMZ in GBM habitats. Genetic silencing of XAF-1 significantly compromised plasticity towards adaptive resistance. XAF1 expression was found to highly correlate with promoter methylation status, and negatively correlate with long-term survival in GBM patient survival. Our studies have shed some light with respect to the plasticity of GBM habitats towards adaptive resistance evolution to TMZ relative to MGMT promoter methylation status. Particularly, a novel and translational role for XAF1 in GBM has been uncovered.
CMET-14. BRAIN METASTASES: A NEW PATHOPHYSIOLOGY, A NEW TREATMENT PARADIGM, AND, PERHAPS, A NEW PROGNOSIS
Authors: Richard Dowd, Tao Ouyang, Krishnamoorthy Thamburaj, Dawit Aregawi, Howard Safran, Brad Zacharia, Michael Glantz
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Brain metastases are widely held to reach the CNS through the blood stream. We provide evidence that the initial site of most CNS metastases is the CSF, with subsequent invasion of brain parenchyma. We also model the therapeutic implications of this novel hypothesis. METHODS Two neuro-radiologists independently assessed whether brain metastases were contiguous with CSF spaces in 200 consecutive patients using pre-treatment MRI. CSF was examined for malignant cells in 66 newly diagnosed, previously untreated patients. We contoured normal brain MRIs of 3 patients to calculate the percentage of brain within 5 mm of a CSF space. We queried an international neoplastic meningitis database to document response of brain metastases to intra-CSF chemotherapy. RESULTS Mean age was 64.2. One hundred patients were male; 143 had lung cancer, 15 melanoma, 12 gastrointestinal, 11 breast, 9 renal, 7 bladder. Mean number of metastases was 4.63. Eighty-five percent of metastases touched a CSF space. In 67% of patients, all metastases touched a CSF space. Neither histology, number or size of metastases, nor patient age predicted contiguity with CSF spaces. In our consecutive subset of patients, 44% (10/23) with one, 46% (5/11) with two, 63% (5/8) with three, and 71% (17/24) with &gt;3 metastases had malignant cells in the CSF (R2=0.93, p=0.037). Five of 7 patients with both brain and CSF metastases receiving only IT chemotherapy experienced a substantial reduction in the size of at least some metastases. Up to 75% of the brain parenchyma lies within 5 mm of CSF spaces. CONCLUSIONS Our data suggest that brain metastases may access the CNS through the CSF rather than the bloodstream. IT chemotherapy may treat brain metastases. We suggest that the CSF should be monitored in all patients with, or at risk for, brain metastases. True cures may require treatment of the CSF space.
Integrated Genomic, Functional and Prognostic Characterization of Atypical Chronic Myeloid Leukemia (aCML) in a Cohort of 43 Patients
Authors: Diletta Fontana, Daniele Ramazzotti, Andrea Aroldi, Antonio Niro, Luca Massimino, Delphine Rea, Fabio Stagno, Bruno Martino, Leonardo Campiotti, Giovanni Caocci, Elena Maria Elli, Monica Fumagalli, Fabio Ciceri, Rocco Piazza, Carlo Gambacorti-Passerini
Journal: Blood (2019)
Adoptively Transferred Donor-Derived Cytokine Induced Memory-like NK Cells Persist and Induce Remission in Pediatric Patient with Relapsed Acute Myeloid Leukemia after Hematopoietic Cell Transplantation
Authors: Jeffrey J. Bednarski, Clare Zimmerman, Amanda F Cashen, Sweta Desai, Mark Foster, Tim Schappe, Ethan McClain, Michelle Becker-Hapak, Melissa M Berrien-Elliott, Todd A Fehniger
Journal: Blood (2019)
Healthcare Resource Utilization and Costs in Patients with Relapsed and Refractory Diffuse Large B-Cell Lymphoma: A U.S. Real-World Observational Study
Authors: Xiaoqin Yang, François Laliberté, Guillaume Germain, Monika Raut, Mei Sheng Duh, Shuvayu S Sen, Dominique Lejeune, Kaushal D Desai, Philippe Armand
Journal: Blood (2019)
Availability of experimental therapy outside of randomized clinical trials in oncology
Authors: E. P. Hamilton, G. H. Lyman, S. Kim, J. Peppercorn
Journal: Journal of Clinical Oncology (2009)

6539 Background: Investigational cancer therapies may be available outside of trials, or “off protocol” (OPRx), with implications for patient safety, trial accrual, and access to care. Previous studies suggest OPRx is prevalent in oncology, but there is little consensus on when it should or should not be considered. We evaluated the scope and impact of OPRx through assessment of availability of the experimental arms of recent randomized trials (RCT), and evaluation of study outcomes and accrual. Methods: We conducted a Medline search to identify all English language phase III RCT of medical interventions in oncology over a 2-year period ending April 17, 2008. We determined availability of experimental interventions based on FDA approval for any indication. We limited assessment of accrual (time to trial completion, patients/month) to studies with US sites. Significance of results was assessed by Fisher's exact test and unpaired t-test. Results: We identified 172 eligible RCT. The majority of RCT (108, 63%) evaluated drugs that were available OPRx at trial initiation, while an additional 19 (11%) trial drugs became available during the trial. 64 (55%) were available due to FDA approval for the same cancer in a different setting, 40 (35%) for a different cancer, and 12 (10%) for a non-cancer indication. 25% of trials were conducted at only US sites, 15% included US and international sites, and 60% were international only. Trials in which OPRx was available had slower time to completion compared to trials in which OPRx was unavailable (48 vs. 26 months, p = 0.04) and a trend towards slower accrual (14.0 vs. 40.7 patients/month, p = 0.06). For the majority of RCT (66%), there was at least one grade 3/4 toxicity that was greater in the experimental arm, for 47% the experimental interventions proved superior for 1 major outcome, and 27% demonstrated improvement in overall survival. These outcomes did not vary based on availability OPRx. Conclusions: The majority of recent oncology trials involve experimental regimens that are available outside of a trial. The safety and efficacy of novel interventions must be determined by trials but availability of OPRX may impact accrual. Guidelines are needed for OPRx in oncology. No significant financial relationships to disclose.
Targeting mTOR in Head and Neck Cancer—Letter
Authors: Liam Masterson, Matt Lechner, Terry M. Jones
Journal: Clinical Cancer Research (2019)

Statement of Relevance: mTOR signal inhibition in HPV-associated oropharyngeal carcinoma requires further investigation before large scale clinical projects are commenced.We read with interest the article by Day and colleagues (1), which reports a phase I clinical trial assessing the effect of mTOR signal inhibition with rapamycin in head and neck squamous cell carcinoma (HNSCC) in the neoadjuvant setting. The article achieved its goals to evaluate the mTOR pathway as a therapeutic target, assess clinical safety, and define the antitumor activity of rapamycin.The study concluded that cancers with upregulated mTOR signaling, such as HNSCC, may be vulnerable to rapamycin treatment. After a short period of treatment (∼21 days), 5 of 16 patients treated by the mTOR inhibitor (rapamycin) had a partial or complete response using RECIST criteria. Eight of the 16 patients were defined as p16+ oropharyngeal carcinomas. Analysis of tumor samples revealed inhibition of mTOR signaling, with decreased phosphorylation of the downstream metabolites (e.g., AKTS473 and pS6) in >90% of patients. Treatment was well tolerated with no grade 4 or unexpected toxicities. No significant immune suppression was observed.We congratulate the study authors for translating recent large scale genomic research findings from The Cancer Genome Atlas (TCGA; ref. 2) into clinical practice. The TCGA study (279 patients) indicated a significant diversity of genetic alterations, however, a handful of signal pathways were upregulated including the CDKN2A, TP53, NOTCH1, FAT1, and CASP8 tumor suppressor genes, and PI3K pathway oncogenes.Although, the TCGA study clearly indicates the PI3K pathway to be a targetable pathway in HNSCC, we would suggest caution with regards to human papillomavirus (HPV)-associated oropharyngeal carcinoma—of the 279 patients included in the study only 36 were defined as HPV+ and even a smaller proportion were from the oropharynx.Further deep sequencing genomic studies are in progress that may help to refine the various targetable pathways in HNSCC. These include the UK-based 100K genome atlas (ref. 3; 393 patients with HNSCC now recruited), the Australian Genomics Health Alliance (4), and the European Union Digital Single Market (5)See the Response, p. 6555No potential conflicts of interest were disclosed.
ピタバスタチンは高コレステロール血症の患者における血清LOX‐1リガンド濃度とMTI‐MMP発現を低下させるが,エイコサペンタエン酸は作用を示さない
Authors: Uzui Hiroyasu, Hayashi Hideki, Nakae Izuru, Matsumoto Tetsuya, Uenishi Hiroaki, Hayasaki Hisae, Asaji Takayoshi, Matsui Shinobu, Miwa Kunihisa, Lee Jong-Dae, Sawamura Tatsuya, Fujita Masatoshi
Journal: Circulation (2013)
Effects of Ramadan Fasting in Patients with Chronic Myeloid Leukemia in Chronic Phase
Authors: Mohamed A Yassin, Rola S Ghasoub, Mahmood B Aldapt, Mohammad Abdul-Jaber Abdulla, Prem Chandra, Hawraa M Shwaylia, Abdulqadir Jeprel Nashwan, Nancy Kassem, Susanna Jane Akiki
Journal: Blood (2019)
The Novel Role That Nrf2 Plays in Erythropoiesis during Aging
Authors: Serge Cedrick Toya Mbiandjeu, Alessandro Mattè, Enrica Federti, Massimiliano Perduca, Immacolata Andolfo, Achille Iolascon, Maria Teresa Valenti, Arianna Pisani, Luca Dalle Carbonare, Pietro Pucci, Angela Amoresano, Mohandas Narla, Lucia De Franceschi
Journal: Blood (2019)
Treatment of Elderly Patients with Acute Promyelocytic Leukemia: A Real Life Experience of the "Rete Ematologica Lombarda"
Authors: Valentina Mancini, Erika Borlenghi, Livia Leuzzi, Claudia Basilico, Massimo Bernardi, Patrizia Zappasodi, Monica Fumagalli, Elisabetta Todisco, Chiara Cattaneo, Federico Lussana, Giambattista Bertani, Erika Ravelli, Nicola Fracchiolla, Mauro Turrini, Giuseppe Rossi, Silvia Cantoni, Roberto Cairoli
Journal: Blood (2019)
TMOD-21. TARGETING ANAPLASTIC MENINGIOMA WITH PANOBINOSTAT IN PATIENT-DERIVED ORTHOTOPIC XENOGRAFT (PDOX) MODELS DERIVED FROM A MATCHING PAIR OF PRIMARY AND RECURRENT TUMORS
Authors: Huiyuan Zhang, Lin Qi, Yuchen Du, Frank Braun, Mari Kogiso, Lei Huang, Tiemo Klisch, Yanling Zhao, Lei Guo, Can Li, Sibo Zhao, Holly B Lindsay, Sarah Injac, Patricia Baxter, Jack Su, Clifford Stephan, Charles Keller, Jianhua Yang, Xiao-Nan Li, Akash Patel
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Meningioma is the most common brain tumor in adults. Despite the overall benign nature of meningioma, skull base tumors can be difficult to completely resect while others exhibit progression and aggressive profiles. The lack of clinically relevant animal models is blocking the development of novel therapies. MATERIAL AND METHODS Twelve surgical specimens (1 × 105) from 11 adult meningioma patients were implanted into the frontal cranial-base of the brain of SCID mice. Mice were then followed and assessed for tumor formation. Tumor growth was confirmed by small animal MRI. Pathologic features of the PDOX models and the matched patient tumors were compared with standard H&amp;E and immunohistochemical staining. RNAseq was performed to examine the molecular fidelity of PDOX tumors and to identify new therapeutic targets. A panel of 60 clinically-relevant drugs was developed for screening drug sensitivity. In vivo examination of therapeutic efficacy of Panobinostat was performed in two models by treating preformed PDOX tumors with i.p. injection (10 mg/kg), 5 days on, 5 days off for 2 cycles. RESULTS Intracranial xenograft formation was confirmed in two samples derived from the same patient, the first an atypical meningioma (K029MEN-P) and the second, which progressed to anaplastic meningioma at recurrence (K029MEN-R). MRI scanning revealed that the PDOX tumors grew from the skull base. These patient tumor cells can be cryopreserved for long-term maintenance of tumorigenicity. The xenograft tumors replicated histopathological features of parental tumors. Overall gene expression profiles of PDOX were similar to the original patient tumors. Using MEN primary culture cells, we screened 60 drugs and identified 12 (20%) active compounds. Panobinostat also significantly prolonged survival of mice bearing orthotopic meningiomas. CONCLUSION A set of meningioma PDOX models derived from primary and recurrent tumor was established. Our data further demonstrate that panobinostat exerts potent antitumor activity against high-grade meningioma.
Promising Prognostic Values of Sequential Gene Expression Profiling in Multiple Myeloma Patients Undergoing Various Systemic Therapy
Authors: Yazan Migdady, Taiga Nishihori, Rachid Baz, Ram Thapa, Youngchul Kim, Dung-Tsa Chen, Ryan K Van Laar, Richard A Bender, Siegel M Erin, Vonetta Williams, Michelle Fouriner, Melissa Alsina, Kenneth H. Shain
Journal: Blood (2016)
Clonal B-Cell Lymphocytosis with Mariginal-Zone Features: Comparison with Overt Splenic Marginal-Zone Lymphomas in 77 Patients from a Monocentric Series
Authors: Michele Merli, Benedetta Bianchi, Lorenza Bertù, Andrea Ferrario, Barbara Mora, Silvia Uccella, Daniela Furlan, Maria Grazia Tibiletti, Simona Cattaneo, Fausto Sessa, Francesco Passamonti
Journal: Blood (2019)
Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline
Authors: Payam Nahid, Sundari R. Mase, Giovanni Battista Migliori, Giovanni Sotgiu, Graham H. Bothamley, Jan L. Brozek, Adithya Cattamanchi, J. Peter Cegielski, Lisa Chen, Charles L. Daley, Tracy L. Dalton, Raquel Duarte, Federica Fregonese, C. Robert Horsburgh, Faiz Ahmad Khan, Fayez Kheir, Zhiyi Lan, Alfred Lardizabal, Michael Lauzardo, Joan M. Mangan, Suzanne M. Marks, Lindsay McKenna, Dick Menzies, Carole D. Mitnick, Diana M. Nilsen, Farah Parvez, Charles A. Peloquin, Ann Raftery, H. Simon Schaaf, Neha S. Shah, Jeffrey R. Starke, John W. Wilson, Jonathan M. Wortham, Terence Chorba, Barbara Seaworth
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Section:ChooseTop of pageAbstract <<ContentsOverviewIntroductionGood Practices for Treati...Treatment of MDR-TB, Numb...Drugs and Drug ClassesBuilding a Treatment Regi...Role of Therapeutic Drug ...Shorter-Course, Standardi...Role of Surgery in MDR-TBTreatment of Isoniazid-Re...Treatment of MDR-TB in Sp...Treatment of Contacts Exp...Summary of Key Difference...ReferencesCITING ARTICLES
Maintenance Decitabine (DAC) Improves Disease-Free (DFS) and Overall Survival (OS) after Intensive Therapy for Acute Myeloid Leukemia (AML) in Older Adults, Particularly in FLT3-ITD-Negative Patients: ECOG-ACRIN (E-A) E2906 Randomized Study
Authors: James M. Foran, Zhuoxin Sun, David F. Claxton, Hillard M Lazarus, Daniel A. Arber, Jacob M. Rowe, Elisabeth Paietta, Janis Racevskis, Jessica K. Altman, Selina M. Luger, Aref Al-Kali, Hong Zheng, Keith W. Pratz, Edward R. Broun, Bayard L Powell, Kristen Marie O'Dwyer, John E. Godwin, Yishai Ofran, Mark Litzow, Martin S. Tallman
Journal: Blood (2019)
Analysis of Mutational Landscape in Systemic Anaplastic Large Cell Lymphoma Identifies Novel Prognostic Markers
Authors: Cosimo Lobello, Boris Tichý, Vojtěch Bystrý, Lenka Radova, Daniel Filip, Marek Mraz, Ivonne Aidee Montes Mojarro, Falko Fend, Nina Prokoph, Hugo Larose, Suzanne Turner, Huan-Chang Liang, Olaf Merkel, Kateřina Kamarádová, David Belada, Geeta G Sharma, Luca Mologni, Carlo Gambacorti-Passerini, Andrea Janikova, Sarka Pospisilova
Journal: Blood (2019)
Correction: Cytosolic PCNA interacts with p47phox and controls NADPH oxidase NOX2 activation in neutrophils
Authors: Delphine Ohayon, Alessia De Chiara, Pham My-Chan Dang, Nathalie Thieblemont, Simon Chatfield, Viviana Marzaioli, Sabrina Sofia Burgener, Julie Mocek, Céline Candalh, Coralie Pintard, Pascale Tacnet-Delorme, Gilles Renault, Isabelle Lagoutte, Maryline Favier, Francine Walker, Margarita Hurtado-Nedelec, Dominique Desplancq, Etienne Weiss, Charaf Benarafa, Dominique Housset, Jean-Claude Marie, Philippe Frachet, Jamel El-Benna, Véronique Witko-Sarsat
Journal: The Journal of Experimental Medicine (2019)
Long-Term Clinical Outcomes of Lentiglobin Gene Therapy for Transfusion-Dependent β-Thalassemia in the Northstar (HGB-204) Study
Authors: Janet L. Kwiatkowski, Alexis A. Thompson, John E.J. Rasko, Suradej Hongeng, Gary J. Schiller, Usanarat Anurathapan, Marina Cavazzana, P. Joy Ho, Manfred Schmidt, Morris Kletzel, Elliott P. Vichinsky, Briana Deary, Ying Chen, Alexandria Petrusich, Mark C. Walters
Journal: Blood (2019)