tbuckley/cabot-search huggingface dataset:
<i>Notes from the Field:</i> Chlorination Strategies for Drinking Water During a Cholera Epidemic — Tanzania, 2016
Authors: Alice Wang, Colleen Hardy, Anangu Rajasingham, Andrea Martinsen, Lindsay Templin, Stanislaus Kamwaga, Kiwe Sebunya, Brenda Jhuthi, Michael Habtu, Stephen Kiberiti, Khalid Massa, Rob Quick, Jane Mulungu, Rachel Eidex, Thomas Handzel
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Since August 2015, the Ministry of Health, Community Development, Gender, Elderly and Children (MoHCDGEC) of Tanzania has been leading the response to a widespread cholera outbreak. As of June 9, 2016, cholera had affected 23 of 25 regions in Tanzania, with 21,750 cumulative cases and 341 deaths reported (Ally Nyanga, MoHCDGEC Emergency Operations Center, personal communication, June 2016). Approximately one fourth of all cases occurred in the Dar es Salaam region on the east coast. Regions surrounding Lake Victoria, in the north, also reported high case counts, including Mwanza with 9% (Ally Nyanga, MoHCDGEC Emergency Operations Center, personal communication, June 2016). Since the start of the outbreak, MoHCDGEC and the Ministry of Water (MOW) have collaborated with the Tanzania Red Cross Society, United Nations Children's Fund (UNICEF), World Health Organization (WHO), and CDC to enhance the water, sanitation, and hygiene (WASH) response to prevent the further spread of cholera.
Experience with a 22 molecular marker predesigned tissue microarray in the preoperative setting of breast cancer treated with FEC-docetaxel, comparing complete responders with incomplete responders, and incomplete responders before and after treatment
Authors: J. Gasent Blesa, V. Alberola Candel, L. Sanchez Verde, M. Rodríguez Pinilla, E. Adrover Cebrián, M. Piris Pinilla
Journal: Journal of Clinical Oncology (2008)

22151 Background: Studies with Tissue Microarray (TMA) technology in the preoperative setting of breast cancer have been done using thousands of genes, searching for the most relevant genes associated with complete pathologic response (pCR). We pre-designed a TMA with a short panel of genes and tested in 21 patients treated with FEC-Docetaxel preoperative chemotherapy. Panel genes: p53, NFkB, p16, p27, Cyclin E, Ki-67, VEGFR3 PDGFR, AKT/PKB, ER, PR, C-ERBb2, mTOR, Topo II, MAPK, C-MYC, ECadherin, BRCA1, MLH1, MSH2, CHK1, CHK2 p53. Methods: Median age: 54 Histologies: Ductal 19, Lobular 2.Pre-chemotherapy UICC stages: IIA 8, IIB 3, IIA 7, IIIB 2, IIIC 1. Grade: I 4, II 6, III 11. Total administered Cycles: 115, 18 patients completed 8 planned cycles 8 patients shown pCR (38.1%); 7 patients partial response (33.2%) 4 patients stability (19%), and progression in 2 patients (9.5%). Results: Grade was correlated with E-Cadherin (p=0,016), PDGFR (p=0,026), CHK2 (p=0.054), p53 (p=0.055). T was correlated with mTOR (p=0.026), E-Cadherin (p=0.042), p53 (p=0.053). Nodal infiltration was correlated with Ki-67 (p=0.019), and PDGFR (p=0.049). Stage was correlated with C-MYC (p=0.032). Ki-67 was associated with complete pathologic response (pCR) (p=0.019). Positivity for BRCA1, CHK2, and ERK-P, and negativity for MSH2, were close to signigicance. In patients without pCR, we found increase in the expression for BRCA1, MSH2, ERK, VEFGR3 and mTOR, to be the most relevant. Conclusion: We correlated clinic-pathological data with our TMA, and new relevant associations are described. Ki-67 was significantly associated with pCR, and near significance in some other markers. Variations in the level of expression of: BRCA1, MSH2, ERK, VEGFR, were associated with persistence of disease. Some of our associations lack statistical significance due to the small sample, but may be relevant in view of their correlation with previous clinical experience. To our knowledge, this is the first time that this strategy has been used. We have shown its feasibility, and we are working now to expand this technique. No significant financial relationships to disclose.
Emerging Frontiers of Neuroengineering: A Network Science of Brain Connectivity
Authors: Danielle S. Bassett, Ankit N. Khambhati, Scott T. Grafton
Journal: Annual Review of Biomedical Engineering (2017)

Neuroengineering is faced with unique challenges in repairing or replacing complex neural systems that are composed of many interacting parts. These interactions form intricate patterns over large spatiotemporal scales and produce emergent behaviors that are difficult to predict from individual elements. Network science provides a particularly appropriate framework in which to study and intervene in such systems by treating neural elements (cells, volumes) as nodes in a graph and neural interactions (synapses, white matter tracts) as edges in that graph. Here, we review the emerging discipline of network neuroscience, which uses and develops tools from graph theory to better understand and manipulate neural systems from micro- to macroscales. We present examples of how human brain imaging data are being modeled with network analysis and underscore potential pitfalls. We then highlight current computational and theoretical frontiers and emphasize their utility in informing diagnosis and monitoring, brain-machine interfaces, and brain stimulation. A flexible and rapidly evolving enterprise, network neuroscience provides a set of powerful approaches and fundamental insights that are critical for the neuroengineer's tool kit.
Phase I study of bortezomib and <sup>153</sup>Sm-lexidronam combination for refractory and relapsed multiple myeloma
Authors: H. S. Yeh, R. A. Swift, D. Ferretti, R. A. Mapes, W. F. Goeckeler, J. R. Berenson
Journal: Journal of Clinical Oncology (2006)

7614 Background: Multiple myeloma (MM) is a highly radiosensitive B-cell malignancy and radiation therapy has been an effective treatment for these patients. Recent preclinical studies have demonstrated that the bone-seeking radionuclide, Samarium Sm 153 lexidronam (Sam) in combination with the proteasome inhibitor, bortezomib (Vel), can synergistically inhibit proliferation of myeloma cell lines in vitro and reduce MM growth in mice bearing human MM without significant myelotoxicity. These results provide the basis for a new therapeutic approach of combining Vel and Sam to overcome resistance and to minimize nontumor tissue toxicity among refractory and relapsed MM patients. Methods: The primary objective of this Phase I study is to determine the response rate and tolerability of Vel + Sam combination in patients with relapsed or refractory MM. Patients will be enrolled on this Phase I dose-escalation trial which involves six cohorts. Previous treatment with Vel is permissible. Dose escalation in parallel arms is as follows: A complete treatment cycle is 8 weeks. Vel is given on days 1, 4, 8 and 11 followed by a 45-day rest period. Sam is administered on day 4. The cycle is repeated on Day 57 if disease is stable or improved and platelets and neutrophils recover to at least grade 1 toxicity. DLT is defined as cycle 1 grade 4 hematologic or grade ≥3 non-hematologic toxicity. Results: Cohorts 1 and 4 have been enrolled (3 patients per cohort). One cycle of treatment has been completed thus far. No significant toxicity has been observed except a transient fever in one patient. There have been no dose limiting toxicities to date. The first six patients will be evaluated for response within the next two weeks. Conclusions: The trial will continue to enroll patients in cohorts 2 and 5. Updated results from the trial will be presented at the meeting. [Table: see text] [Table: see text]
Discovery of recurrent <i>KIF5B-RET</i> fusions and other targetable alterations from clinical NSCLC specimens.
Authors: Marzia Capelletti, Doron Lipson, Geoff Otto, Roman Yelensky, Dalia Ercan, Jhingook Kim, Hidefumi Sasaki, Hyeong Ryul Kim, Seung-Il Park, Jeffrey S. Ross, Philip Stephens, Maureen T. Cronin, Pasi Antero Janne
Journal: Journal of Clinical Oncology (2012)

7510 Background: Many NSCLCs have driving oncogenic alterations including in EGFR, KRAS, ERBB2, BRAF, ALK and ROS1. Clinically effective drugs are approved for EGFR and ALK and clinical trials are underway for other genomic targets. Thus having a means of identifying genomic alterations in routine formalin fixed paraffin embedded (FFPE) clinical specimens is critical. Methods: We sequenced 24 FFPE NSCLC specimens with a next generation sequencing (NGS) assay that captures and sequences 2574 coding exons of 145 cancer relevant genes plus 37 introns from 14 genes often rearranged in cancer. Tumors from 643 additional patients were genotyped for KIF5B-RET. Results: We identified 50 alterations in 21 genes with at least one in 83% (20/24) of tumors (range 1-7). In 72% (36/50) of NSCLCs, at least one alteration was associated with a current clinical treatment or targeted therapy trial, including mutations in KRAS, BRAF, EGFR, MDM2, CDKN2A, CCNE1, CDK4, NF1 and PIK3CA. We also found an 11,294,741 bp pericentric inversion on chromosome 10 generating a novel gene fusion joining exons 1-15 of KIF5B to exons 12-20 of RET (K15:R12) in a Caucasian never smoker. This fusion gene contains the kinesin motor and coiled-coil domains of KIF5B and the entire RET tyrosine kinase domain. In 643 additional tumors we identified 11 fusion positive patients who were all wild type for known oncogenes (frequency of 6.3% (10/159)). Four unique KIF5B-RET variants were found: 8 K15:R12, 3 K16:R12, 1 K22:R12 and 1 K15:R11. We introduced K15:R12 into Ba/F3 cells and observed IL-3 independent growth consistent with oncogenic transformation. KIF5B-RET Ba/F3 cells were sensitive to sunitinib, sorafenib and vandetinib, multi-targeted kinase inhibitors that inhibit RET, but not gefitinib, an EGFR kinase inhibitor. Sunitinib, but not gefitinib, inhibited RET phosphorylation in these cells. Conclusions: We identified both known and novel genomic alterations from NSCLC FFPE specimens using a single test. Our findings suggest that RET inhibitors should be tested in prospective clinical trials in NSCLC patients bearing KIF5B-RET rearrangements and that NGS is a feasible approach to stratifying patients for treatment based on their genomic profiles.
Open heart surgery devices may be contaminated, US health officials warn
Authors: Michael McCarthy
Journal: BMJ (2016)

US health officials have warned healthcare providers and patients of the potential risk of infection from contaminated devices commonly used in open heart surgery.1 The devices, Stockert 3T heater-coolers, made by LivaNova (formerly Sorin Group Deutschland GmbH), have been used in both Europe and North America.

The warning was issued after investigators found that the devices, which provide temperature controlled water to heart-lung machines during open heart surgery, had been contaminated by the bacterium Mycobacterium …
PML/RARα Mediates Resistance to Apoptosis and Down-Regulation of the NF-κB Pathway in Acute Promyelocytic Leukemia.
Authors: Zaida Garcia-Casado, Jose Cervera, Juan C. Pajuelo, Ana Valencia, Carlos Garcia, Guillermo Martin, Pascual Bolufer, Eva Barragan, Sandra Ballester, Juan S. Oltra, Nerea Martinez, Maria L. Marty, Miguel A. Piris, Miguel A. Sanz
Journal: Blood (2004)
Flavopiridol Is An Effective Therapy to Bridge Patients with Chronic Lymphocytic Leukemia (CLL) to Reduced-Intensity Conditioning Allogeneic Stem Cell Transplant
Authors: Samantha M. Jaglowski, Joseph M. Flynn, Jeffrey A. Jones, Thomas S. Lin, Beth Fischer, Diane Scholl, Patrick Elder, Steven M. Devine, Michael R. Grever, John C. Byrd, Leslie Andritsos
Journal: Blood (2010)
Intra-Clonal Diversity Identified by CD19-Mediated Signaling Correlates with Disease Progression In Chronic Lymphocytic Leukemia (CLL)
Authors: Yair Herishanu, Sigi Kay, Nili Dezorella, Inbal Hazan-Hallevi, Svetlana Trestman, Chava Perry, Varda Deutsch Deutsch, Aaron Polliack, Elizabeth Naparstek, Ben-Zion Katz
Journal: Blood (2010)
The Significance of Elevated Beta 2-Microglobulin (b2-m) in B-CLL: Evidence of in Vitro b2-m Secretion Following Activation of B-CLL Cells.
Authors: Alain Berrebi, Lev Shvidel, Fabian David Arditti, Lucette Bassous, Michal Haran, Mordechai Shtalrid
Journal: Blood (2009)
Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma
Authors: Zijun Y. Xu-Monette, Ling Li, John C. Byrd, Kausar J. Jabbar, Ganiraju C. Manyam, Charlotte Maria de Winde, Michiel van den Brand, Alexandar Tzankov, Carlo Visco, Jing Wang, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W. L. Choi, Jooryung Huh, Maurilio Ponzoni, Andrés J. M. Ferreri, Michael B. Møller, Ben M. Parsons, Jane N. Winter, Michael Wang, Frederick B. Hagemeister, Miguel A. Piris, J. Han van Krieken, L. Jeffrey Medeiros, Yong Li, Annemiek B. van Spriel, Ken H. Young
Journal: Blood (2016)
Surface Expression of TGFβ Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer
Authors: Alessandra Metelli, Bill X. Wu, Caroline W. Fugle, Saleh Rachidi, Shaoli Sun, Yongliang Zhang, Jennifer Wu, Stephen Tomlinson, Philip H. Howe, Yi Yang, Elizabeth Garrett-Mayer, Bei Liu, Zihai Li
Journal: Cancer Research (2016)

GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly. In genetic studies in normal mammary gland epithelial and carcinoma cells, GARP expression increased TGFβ bioactivity and promoted malignant transformation in immunodeficient mice. In breast carcinoma-bearing mice that were immunocompetent, GARP overexpression promoted Foxp3+ Treg activity, which in turn contributed to enhancing cancer progression and metastasis. Notably, administration of a GARP-specific mAb limited metastasis in an orthotopic model of human breast cancer. Overall, these results define the oncogenic effects of the GARP-TGFβ axis in the tumor microenvironment and suggest mechanisms that might be exploited for diagnostic and therapeutic purposes. Cancer Res; 76(24); 7106-17. ©2016 AACR.
Efficient in vitro expression of the human reverse transcriptase (hTERT) but impaired maturation in dendritic cells of lung cancer patients
Authors: B. Gahn, A. Brill, I. Bolz, W. Klapper, N. Schub, A. Heiser, M. Gramatzki, M. Kneba
Journal: Journal of Clinical Oncology (2007)

13518 An innovative treatment strategy for patients with lung cancer is the targeting of tumor associated antigens with cellular effector cells. The telomerase catalytic subunit (hTERT) is an attractive target for cytotoxic T cells that is highly expressed in both NSCLC and SCLC cells. The aim of the study was the expression of hTERT in dendritic cells (DC) that are the most powerful antigen presenting cells for the induction of cellular immune responses. We used electrotransfection of DC with hTERT mRNA that enables an HLA independent whole antigen approach potentially targeting a wide range of hTERT epitopes. Immature DC were prepared from peripheral blood monocytes in serum-free growth medium, GM-CSF and IL-4. Subsequently the DC were electroporated with mRNA and matured in a cytokine cocktail consisting of IL-1 beta, IL-6, TNF-alpha and PGE2. Verification of hTERT mRNA transfection efficiency was performed by analyzing the induction of telomerase activity with the TRAP assay, the efficiency of GFP electrotransfection was determined by FACS. To optimize mRNA electrotransfection conditions the DCs of 3 healthy individuals were transfected with green fluorescent protein (GFP) mRNA. The percentage of electrotransfected DC was in between 18–89% (mean 46%). Subsequently we electrotransfected DCs in 3 lung cancer patients (1 SCLC, 2 NSCLC). In 1 patient GFP mRNA transfection resulted in 62% GFP positive DC. In the 2 other patients the telomerase activity in the DC 24 hrs after hTERT electrotransfection was equivalent to HL60 cells that biologically express high levels of hTERT. Importantly the DC of one patient did not mature after electrotransfection and incubation in the maturation cocktail. The same was true in another patient, in whom an electrotransfection was not done. In both patients the DC were expressing high levels of HLA-DR and no lineage markers, but CD83 as an indicator of maturation was found in only 1% and 9% respectively. Also the costimulatory molecules CD80 and CD86 were expressed at low levels only. These data show that strong hTERT expression can be achieved in DCs of lung cancer patients using mRNA electrotransfection but demontrate the need for other more potent maturation stimuli. No significant financial relationships to disclose.
The Glass Watchers
Authors: Stewart F. Babbott
Journal: Annals of Internal Medicine (2016)

On Being a Doctor18 October 2016The Glass WatchersStewart F. Babbott, MDStewart F. Babbott, MDFrom University of Virginia Health System, Charlottesville, Virginia.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-2539 Audio Reading - “The Glass Watchers” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "The Glass Watchers," by S.F. Babbott. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Glass-paned buildings are majestic monuments to vision and engineering. But design and technology aren't perfect, and glass, on occasion, cracks and falls. Recall Boston's John Hancock Tower in 1973, a prominent structure out of whose lofty supports 500-pound panes of glass succumbed to gravity and crashed to the streets below. Shards scattered and nerves frayed. While engineers studied the potential causes, builders installed plywood in place of the missing panes. The public was transfixed. And the glass watchers began their vigil.Hired to observe the building from a safe distance, the binoculared sentinels waited, watched, and warned. Each pane's construction ... Author, Article, and Disclosure InformationAffiliations: From University of Virginia Health System, Charlottesville, Virginia.Corresponding Author: Stewart F. Babbott, MD, University of Virginia Health System, Department of Medicine, Division of General, Geriatric, Palliative and Hospital Medicine, 81 Hospital Drive, PO Box 800901, Charlottesville, VA 22908; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “The Glass Watchers” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "The Glass Watchers," by S.F. Babbott. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 18 October 2016Volume 165, Issue 8Page: 597-598KeywordsEngineersFallsForecastingHospital medicineMedical educationNervesPatientsSuicideTemperatureVision ePublished: 18 October 2016 Issue Published: 18 October 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Tinzaparin prophylaxis against thromboembolic complications in brain tumor patients
Authors: J. J. Vredenburgh, C. Bohlin, D. A. Reardon, A. Desjardins, J. Quinn, J. Rich, S. Sathornsumetee, L. B. Marks, A. H. Friedman, H. S. Friedman
Journal: Journal of Clinical Oncology (2006)

1539 Background: Thromboembolic complications are common in brain tumor patients, contribute to the morbidity and mortality and complicate treatment. Twenty to 40% of brain tumor patients develop a deep venous thrombosis and/or pulmonary embolus during their course. Thromboembolic complications are the second leading cause of death in brain tumor patients. One of the low molecular weight heparins, tinzaparin, has increased factor Xa activity as opposed to thrombin inhibition, which may improve the therapeutic:toxicity ratio. Methods: We report a phase II trial of prophylactic tinzaparin for newly diagnosed brain tumor patients. Twenty-seven of the planned 40 patients have been accrued. Patients received daily tinzaparin at a fixed dose of 4500 IU subcutaneously beginning a minimum of 48 hours post-operatively and a maximum of 4 weeks post-operatively. Patients were scheduled to receive tinzaparin for 12 months. During chemotherapy cycles, the blood counts were monitored weekly. If the platelet count was &lt;50,000, the tinzaparin was held until the platelets were &gt;100,000. Results: One of the patients developed a grade 3 CNS hemorrhage, necessitating cessation of the tinzaparin, there have been no grade 4 or 5 CNS hemorrhages or treatment associated mortality. Also, there have been no ≥ grade 2 systemic hemorrhages. One patient developed a deep venous thrombosis while taking tinzaparin, and three patients developed thromboembolic complications while off tinzaparin secondary to thrombocytopenia. One patient was taken off study for increased liver function tests, possibly secondary to tinzaparin. The patients have taken the tinzaparin for 4–52 weeks, with a median of 18 weeks. Conclusions: Tinzaparin at a fixed prophylactic dose is safe and may decrease the incidence of thromboembolic complications in brain tumor patients. If the completed phase II study yields similar results, a phase III trial is warranted. No significant financial relationships to disclose.
Ruxolitinib Mediated Paradox JAK2 Hyperphosphorylation Is Due To The Protection Of Activation Loop Phosphotyrosines From Phosphatases
Authors: Sivahari P. Gorantla, Kolluri Suresh Babu, Anna Lena Illert, Nikolas von Bubnoff, Christian Peschel, Justus Duyster
Journal: Blood (2013)
Characterization of a Microchip Flow-Chamber System for the Analysis of Platelet Thrombus Formation Using Whole Blood Samples - Studies On Healthy Subjects
Authors: Yusuke Yamaguchi, Takanori Moriki, Atsuko Igari, Yumiko Matsubara, Tomoko Ohnishi, Kazuya Hosokawa, Mitsuru Murata
Journal: Blood (2012)
Clinical and Radiographic Evaluation of Spleen Size during Peripheral Blood Progenitor Cell (PBPC) Mobilization by Filgrastim: Results of an Open-Label Trial in Normal Donors.
Authors: Patrick J. Stiff, William Bensinger, Muneer H. Abidi, Roger Gingrich, Andrew S. Artz, Wade Lovelace, Matthew Guo, Lyndah Dreiling
Journal: Blood (2007)
The Role of a Dynamic Craniospinal Compliance in NPH—A Review and Future Challenges
Authors: Christine Goffin, Steffen Leonhardt, Klaus Radermacher
Journal: IEEE Reviews in Biomedical Engineering (2016)

Despite the normal mean intracranial pressure in normal pressure hydrocephalus, the cerebral ventricles enlarge. Many hypotheses exist as to why, and these have lately been investigated in simulation. These can be grouped into one of two categories: 1) Tissue damage is caused by a transmantle pressure gradient widening the ventricles mechanically. 2) The overall cerebrospinal fluid dynamics are disturbed resulting from various pathologies. This paper reviews the literature regarding the computational simulation models investigating the development of enlarging ventricles in connection with the onset of hydrocephalus. The models are categorized by the underlying hypothesis and their results are contrasted with clinical findings in the field. Finally, open questions are identified for future modeling approaches.
PD-1 Blockade with Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Safety, Efficacy, and Biomarker Assessment
Authors: Philippe Armand, Margaret A. Shipp, Vincent Ribrag, Jean-Marie Michot, Pier Luigi Zinzani, Martin Gutierrez, Ellen Snyder, Alejandro D. Ricart, Arun Balakumaran, Craig H. Moskowitz
Journal: Blood (2015)