tbuckley/cabot-search huggingface dataset:
Inhibition of ADAMTS13 Activity By Human Neutrophil Peptide 1 (HNP-1): Potential Link Between Inflammation, Onset of Thrombotic Thrombocytopenic Purpura, and Other Thrombosis
Authors: Jialing Bao, Khalil Bdeir, Don L. Siegel, Douglas B. Cines, X. Long Zheng
Journal: Blood (2014)
Safety and Efficacy of New Moroctocog Alfa Drug (Octofactor) in Prophylactic Treatment in Adolescent Patients with Severe and Moderate Hemophilia a
Authors: Ekaterina Shiller, Vladimir Vdovin, Victor Petrov, Pavel Svirin, Tatiana Andreeva, Inna Lavrichenko, Artem Bullikh, Igor Koltunov, Igor Davydkin, Igor Kurtov, Alexandr Shuster, Dmitry Kudlay, Sergey Lukyanov, Anton Borozinets, Eugene Nikitin, Ekaterina Klykova
Journal: Blood (2015)
Identification of Existing Drugs That Effectively Target <i>NTRK1</i> and <i>ROS1</i> Rearrangements in Lung Cancer
Authors: Curtis R. Chong, Magda Bahcall, Marzia Capelletti, Takayuki Kosaka, Dalia Ercan, Taebo Sim, Lynette M. Sholl, Mizuki Nishino, Bruce E. Johnson, Nathanael S. Gray, Pasi A. Jänne
Journal: Clinical Cancer Research (2016)

Efforts to discover drugs that overcome resistance to targeted therapies in patients with rare oncogenic alterations, such as NTRK1 and ROS1 rearrangements, are complicated by the cost and protracted timeline of drug discovery.
Heterogeneity of chronic graft-versus-host disease biomarkers: association with CXCL10 and CXCR3+ NK cells
Authors: Amina Kariminia, Shernan G. Holtan, Sabine Ivison, Jacob Rozmus, Marie-Josée Hebert, Paul J. Martin, Stephanie J. Lee, Daniel Wolff, Peter Subrt, Sayeh Abdossamadi, Susanna Sung, Jan Storek, Megan Levings, Mahmoud Aljurf, Mukta Arora, Corey Cutler, Geneviève Gallagher, John Kuruvilla, Jeff Lipton, Thomas J. Nevill, Laura F. Newell, Tony Panzarella, Joseph Pidala, Gizelle Popradi, David Szwajcer, Jason Tay, Cynthia L. Toze, Irwin Walker, Stephen Couban, Barry E. Storer, Kirk R. Schultz
Journal: Blood (2016)
AirLab: a cloud-based platform to manage and share antibody-based single-cell research
Authors: Raúl Catena, Alaz Özcan, Andrea Jacobs, Stephane Chevrier, Bernd Bodenmiller
Journal: Genome biology (2016)

Single-cell analysis technologies are essential tools in research and clinical diagnostics. These methods include flow cytometry, mass cytometry, and other microfluidics-based technologies. Most laboratories that employ these methods maintain large repositories of antibodies. These ever-growing collections of antibodies, their multiple conjugates, and the large amounts of data generated in assays using specific antibodies and conditions makes a dedicated software solution necessary. We have developed AirLab, a cloud-based tool with web and mobile interfaces, for the organization of these data. AirLab streamlines the processes of antibody purchase, organization, and storage, antibody panel creation, results logging, and antibody validation data sharing and distribution. Furthermore, AirLab enables inventory of other laboratory stocks, such as primers or clinical samples, through user-controlled customization. Thus, AirLab is a mobile-powered and flexible tool that harnesses the capabilities of mobile tools and cloud-based technology to facilitate inventory and sharing of antibody and sample collections and associated validation data.
IRB and Research Regulatory Delays Within the Military Health System: Do They Really Matter? And If So, Why and for Whom?
Authors: Michael C. Freed, Laura A. Novak, William D. S. Killgore, Sheila A. M. Rauch, Tracey P. Koehlmoos, J. P. Ginsberg, Janice L. Krupnick, Albert "Skip" Rizzo, Anne Andrews, Charles C. Engel
Journal: The American Journal of Bioethics (2016)

Institutional review board (IRB) delays may hinder the successful completion of federally funded research in the U.S. military. When this happens, time-sensitive, mission-relevant questions go unanswered. Research participants face unnecessary burdens and risks if delays squeeze recruitment timelines, resulting in inadequate sample sizes for definitive analyses. More broadly, military members are exposed to untested or undertested interventions, implemented by well-intentioned leaders who bypass the research process altogether. To illustrate, we offer two case examples. We posit that IRB delays often appear in the service of managing institutional risk, rather than protecting research participants. Regulators may see more risk associated with moving quickly than risk related to delay, choosing to err on the side of bureaucracy. The authors of this article, all of whom are military-funded researchers, government stakeholders, and/or human subject protection experts, offer feasible recommendations to improve the IRB system and, ultimately, research within military, veteran, and civilian populations.
Efficacy and safety of half-dose pegfilgrastim in cancer patients receiving cytotoxic chemotherapy.
Authors: Ryan C. Ramaekers, Jon Olsen, Angela Mae Obermiller, Melhem Salim Jabbour, Mark Tharnish, Megan Schriner, Rita Hays, Deborah Nelson, Heather Benzel, Rebecca Hadenfeldt, Courtney Fuller, Mehmet Sitki Copur
Journal: Journal of Clinical Oncology (2012)

9110 Background: Pegfilgrastim reduces neutropenia risk in patients (pts) on cytotoxic chemotherapy. A single 6 mg dose per chemotherapy cycle commonly causes bone pain and leukocytosis. While half-dose pegfilgrastim has been shown to be safe and effective in breast cancer pts, there is no data on half-dose pegfilgrastim in general oncology pts. Methods: We evaluated the efficacy and safety of half-dose pegfilgrastim in general oncology pts on cytotoxic chemotherapy at St Francis Cancer Center. Pts who received at least one dose of 6 mg pegfilgrastim and developed NCI-CTCAE grade 2 or more bone pain and/or leukocytosis (WBC&gt;10,000/ml) were given 3 mg dose pegfilgrastim on their following chemotherapy cycles. Pt demographics, type/number of chemotherapy regimens, efficacy, side effects and complications were evaluated. McNemar’s test, logistic regression analysis and ANOVA were used for statistical analysis. Results: Twenty-six pts (3 males, 23 females, all Caucasian) with median age 55 (range 34-86) received a total of eighty-three 3 mg doses of pegfilgrastim. Cancers treated were breast (N=16), colorectal (N=7), head and neck (N=1), non-Hodgkin lymphoma (N=1) and non-small cell lung cancer (N=1). Chemotherapy received was anthracycline (N=9), taxane (N=7), 5-FU/oxaliplatin (N=7), 5-FU/cisplatin (N=1), gemcitabine/oxaliplatin (N=1), pemetrexed/carboplatin (N=1). No neutropenia or chemotherapy dose modifications occurred on half-dose pegfilgrastim. In the 26 pts we report, bone pain occurred in 23 pts at 6 mg and 14 pts at 3 mg dose. Leukocytosis occurred in 23 pts at 6 mg and only 2 pts at 3 mg dose (McNemar’s test, P&lt;0.01). While older age and full-dose pegfilgrastim were predictive of bone pain, more than one line of chemotherapy and half-dose pegfilgrastim were predictive of lack of leukocytosis (logistic regression analysis/ANOVA, P&lt;0.01). Conclusions: Half-dose pegfilgrastim in general oncology pts receiving cytotoxic chemotherapy seems to be safe and effective with less bone pain and leukocytosis without resultant neutropenia or need for chemo modification. Larger prospective studies of half-dose pegfilgrastim in this setting are needed to further understand the feasibility of this approach.
Fluoride and osteoporosis.
Authors: J Franke
Journal: BMJ (1972)

After a review of the historical background and the first studies with fluoride therapy for osteoporosis the author presents his own studies of more than 100 cases of industrial fluorosis. It is followed by instructions how to perform the fluoride therapy: indications, contra-indications, dosage, controls and additional therapy. Since 1969 we treated 158 patients suffering from primary and secondary osteoporosis with 3 different sodium fluoride preparations (pure sodium fluoride powder, Ossin, Koreberon). Clinically and subjectively, 80.4% recovered or became symptom-free. In 53.8% (with Koreberon in 64%), we detected radiologically distinct reossification in the spine after 23 +/- 12 months, in a further 26.6% the reossification was questionable and only 4.4% showed further fractures. In summary, we found about 20% of fast-responders (reossification after 13.2 months, high alkaline phosphatase), 60% of responders and 20% of non-responders. The strengthening effect of the sodium fluoride therapy becomes especially evident if considering the spontaneous fracture rate. Side effects were: gastrointestinal disturbances (34%), gastric ulcers (4.4%), stress fractures (6.9%), very common arthralgies (34%), and sometimes overdosages (fluorosis). Only if therapy is controlled most intensively will the greatest effectiveness be obtained.
IMPS-39IDO1: MORE THAN JUST AN ENZYME IN MALIGNANT GLIOMA
Authors: Derek Wainwright
Journal: Neuro-Oncology (2015)

The upregulation of indoleamine 2,3 dioxygenase 1 (IDO1) in glioblastoma (GBM) is associated with significantly decreased survival in patients. Coincidently, a GL261 glioma model genetically deficient (ie. knocked down) for tumor-derived IDO1 fails to accumulate significant levels of immunosuppressive regulatory T cells (Treg; CD4+CD25+FoxP3+), which is commensurate with a substantial survival advantage. Paradoxically, mice bearing malignant glioma and administered L1-MT, an enzymatic inhibitor of IDO1, fail to demonstrate any survival advantage. To further understand the role of IDO1 in brain tumors, my laboratory recently crossed the tamoxifen-inducible model of malignant glioma [tGBM; GFAP(ERT2)Cre+/-;p53fl/fl;Rbfl/fl;pTENfl/fl] (Chow et al., 2011; Cancer Cell) with IDO1fl/fl or IDO1−/- mice to conditionally- or globally-delete IDO1, respectively. In contrast to previous findings, the loss of tumor-derived IDO1 did not increase overall survival, with a median of 153.5 ±7.0-, 136 ±4.3- and 144.5 ±5.9-days post-tamoxifen administration for tGBM-IDO1wt/wt, tGBM-IDO1fl/fl and tGBM-IDO1−/- mice, respectively (11-12 mice/group). Concordantly, Treg accumulated in the tGBM brain tumors, regardless of IDO1 status. Unexpectedly, when tGBM-WT and tGBM-IDO1−/- tumors were isolated, followed by intracranial re-implantation (ic.) into immunocompetent syngeneic hosts, mice bearing IDO1−/- glioma survived 45.4 ±4.3 days post-ic., which was significantly longer than mice bearing WT glioma at 30.4 ±2.6 days post-ic (P = 0.0069; n = 5-9/group). These data, in combination with recent work from my laboratory demonstrating that, IDO1 in glioma cells fail to metabolize tryptophan into kynurenine, led us to search for a novel and/or contextual function. Here, we present bioinformatics analysis, Western blotting of nuclear and cytoplasmic extracts, as well as immunofluorescence showing that, IDO1 is detectable in the nucleus of glioma cells, in vivo. Strikingly, Chip-Seq. analysis confirms that IDO1 binds to- and enriches-specific DNA sites. This work identifies a novel and previously unappreciated role for IDO1-mediated immune-evasion and introduces new targets for therapeutic discovery and intervention against malignant brain tumors.
The effect of front-line chemotherapy on overall survival in patients with malignant pleural mesothelioma.
Authors: Emin Tamer Elkiran, Alper Sevinc, Hakan Harputluoglu
Journal: Journal of Clinical Oncology (2013)

e18560 Background: Malignant pleural mesothelioma (MPM) is a relatively rare, but aggressive tumor that causes high mortality. The major risk factor involved in the etiology is environmental and occupational exposure to asbestos. The optimal modality of therapy is controversial. Methods: The present study retrospectively evaluated the 141 patients from the database. Results: There were 80 males and 61 females with a mean age of 56 ± 1.07 years. The median survival in patients who were administered front-line chemotherapy was 17 months (95% CI: 13.19-20.81). 106 patients were administered pemetrexed-platinum combination and 35 patients were administered gemcitabine-platinum combination as front-line chemotherapy. For the patients who received pemetrexed-platinum regimen, a median of 6 cycles of chemotherapy was administered and 50 patients (47.2%) were able to receive all 6 cycles as planned. For the patients who received gemcitabine-platinum regimen, a median of 6 cycles of chemotherapy was administered and 19 patients (54.3%) were able to receive all 6 cycles. Median survival was found 16 months in the pemetrexed-platinum regimen and 26 months in the gemcitabine- platinum regimen. There was no statistically significant difference between the patients who received pemetrexed-platinum and gemcitabine-platinum regimens in terms of the median overall survival (p = 0.15). Conclusions: Results of our study suggest that chemotherapy prolongs overall survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found to be similar.
When emotion and cognition do (not) work together: Delusions as emotional and executive dysfunctions
Authors: Valentina Petrolini
Journal: Behavioral and Brain Sciences (2015)

Abstract In this commentary, I argue that the cognitive-emotional framework put forward by Pessoa (2013) can be successfully applied to psychopathology and, in particular, to the reasoning of delusional subjects . More specifically, I show that the notion of executive competition (Ch. 7) offers a significant contribution to the idea that delusions may involve both executive and emotional dysfunctions.
Preclinical and clinical studies on afatinib in monotherapy and in combination regimens: Potential impact in colorectal cancer
Authors: I. De Pauw, A. Wouters, J. Van den Bossche, M. Peeters, P. Pauwels, V. Deschoolmeester, J.B. Vermorken, F. Lardon
Journal: Pharmacology & Therapeutics (2016)
Ipilimumab Combined with Nivolumab: A Standard of Care for the Treatment of Advanced Melanoma?
Authors: Matteo S. Carlino, Georgina V. Long
Journal: Clinical Cancer Research (2016)

Ipilimumab, an inhibitor of CTLA-4 on T cells, was the first drug to improve overall survival in patients with advanced melanoma. Subsequently, inhibitors of PD-1, including nivolumab and pembrolizumab, were shown to be superior to ipilimumab with a more favorable safety profile. The combination of ipilimumab and nivolumab is associated with a further improvement in response rate and progression-free survival; however, the combination is associated with an increased rate of immune-related toxicities. In 2015, the FDA approved the combination for the treatment of BRAF wild-type advanced melanoma. This review examines the preclinical rationale for the combination of ipilimumab and nivolumab as well as the efficacy and toxicity data from clinical trials in patients with advanced melanoma. Finally, alternative treatment options are discussed with a focus on patient selection. Clin Cancer Res; 22(16); 3992-8. ©2016 AACR.
Population pharmacokinetic (PPK) analysis for 5-FU, tegafur (FT), gimeracil (CDHP), and oteracil potassium (Oxo) in the eight clinical studies of S-1 in Western patients with advanced solid tumors.
Authors: K. Yoshida, K. Ikeda, K. Yoshisue, W. Rodriguez, G. Bodoky, V. Moiseyenko, M. Lichinitser, K. Saito, F. M. Benedetti, J. A. Ajani
Journal: Journal of Clinical Oncology (2011)

53 Background: This analysis was performed to establish the PPK model of S-1, and to identify the intrinsic or extrinsic factors that influence S-1 exposure in the Western patients with advanced solid tumor. Methods: PK data obtained in seven phase I and one phase III (FLAGS) studies were combined for PPK analysis. The total number of patients was 315, and the number of data points for FT, CDHP, 5-FU and Oxo were 2,860, 2,625, 2,492, and 2,484, respectively. The two-compartment model was used for FT, CDHP and Oxo, whereas for 5-FU, inhibitory effect of CDHP on 5-FU clearance was incorporated into a two-compartment model to describe its non-linear PK. The final models were validated by visual predictive check and bootstrapping. Results: The individual fit and the stability of four models were acceptable. The predicted daily AUCs (at steady state) were calculated to evaluate the effect of covariates. The daily AUC of 5-FU strongly correlated with oral clearance (CL/F) of CDHP, but not with that of FT. The ethnic difference in exposure to 5-FU was not apparent despite the significantly lower CL/F of FT observed in the Asian patients. Co-administration with food delayed the absorption of S-1 but exhibited no or limited effect on the AUC of FT, CDHP and 5-FU, whereas the bioavailability of Oxo decreased to approximately 30%. Renal function primarily influenced CDHP exposure and, in turn, 5-FU. The model simulation suggested that the S-1 dosages of 30, 25 and 20 mg/m 2 BID could achieve similar daily AUC of 5-FU in the Western patients with normal renal function (CLcr&gt;80 mL/min), mild (50-80 mL/min) and moderate (30-50 mL/min) renal impairment, respectively. Other factors such as age, gender, liver function, serum albumin, PS, gastric cancer, gastrectomy, combination with cisplatin and liver metastasis, had little or minimal impact on the daily AUC of 5-FU. Conclusions: This analysis suggests that the daily AUC of 5-FU after S-1 administration is primarily affected by the CDHP levels, and hence renal function remains the primary factor for 5-FU PK in patients. Other factors as well as CL/F of FT had little impact on 5-FU. [Table: see text]
TRPV4 and sensory afferent activation: role of ATP
Authors: Sara J. Bonvini, Mark A. Birrell, Megan S. Grace, Sarah A. Maher, John J. Adcock, Michael A. Wortley, Eric Dubuis, Yee-Man Ching, Anthony P. Ford, Fisnik Shala, Montserrat Miralpeix, Gema Tarrason, Jaclyn A. Smith, Maria G. Belvisi
Journal: Journal of Allergy and Clinical Immunology (2016)
Learning about teaching requires thinking about the learner
Authors: Kathleen H. Corriveau
Journal: Behavioral and Brain Sciences (2015)

Kline argues for an expanded taxonomy of teaching focusing on the adaptive behaviors needed to solve learning problems. Absent from her analysis is an explicit definition of learning, or a discussion of the iterative nature of the relationship between teaching and learning. Including the learner in the discussion may help to distinguish among the adaptive values of different teaching behaviors.
P-selectin is a nanotherapeutic delivery target in the tumor microenvironment
Authors: Yosi Shamay, Moshe Elkabets, Hongyan Li, Janki Shah, Samuel Brook, Feng Wang, Keren Adler, Emily Baut, Maurizio Scaltriti, Prakrit V. Jena, Eric E. Gardner, John T. Poirier, Charles M. Rudin, José Baselga, Adriana Haimovitz-Friedman, Daniel A. Heller
Journal: Science Translational Medicine (2016)

Disseminated tumors are poorly accessible to nanoscale drug delivery systems because of the vascular barrier, which attenuates extravasation at the tumor site. We investigated P-selectin, a molecule expressed on activated vasculature that facilitates metastasis by arresting tumor cells at the endothelium, for its potential to target metastases by arresting nanomedicines at the tumor endothelium. We found that P-selectin is expressed on cancer cells in many human tumors. To develop a targeted drug delivery platform, we used a fucosylated polysaccharide with nanomolar affinity to P-selectin. The nanoparticles targeted the tumor microenvironment to localize chemotherapeutics and a targeted MEK (mitogen-activated protein kinase kinase) inhibitor at tumor sites in both primary and metastatic models, resulting in superior antitumor efficacy. In tumors devoid of P-selectin, we found that ionizing radiation guided the nanoparticles to the disease site by inducing P-selectin expression. Radiation concomitantly produced an abscopal-like phenomenon wherein P-selectin appeared in unirradiated tumor vasculature, suggesting a potential strategy to target disparate drug classes to almost any tumor.
How does psychotherapy work? A case study in multilevel explanation
Authors: Rebecca Roache
Journal: Behavioral and Brain Sciences (2015)

Abstract Multilevel explanations abound in psychiatry. However, formulating useful such explanations is difficult or (some argue) impossible. I point to several ways in which Lane et al. successfully use multilevel explanations to advance understanding of psychotherapeutic effectiveness. I argue that the usefulness of an explanation depends largely on one's purpose, and conclude that this point has been inadequately recognised in psychiatry.
Gifts
Authors: Mary E Black
Journal: BMJ (2007)

This June, the 21 year old son of our closest family friends was stabbed to death as he slept.

The next days were a blur. Friends, neighbours, and relatives gathered around and stayed close to the family. Everyone brought gifts; the fridge was kept full, the house swept, cold water kept ready for the hot, hot days. My husband rigged sails up to shade the veranda and the visitors. Black clothes were bought, chocolate and coffee stacked high. An elderly neighbour dropped her longstanding feud over something trivial and turned to sweeping the shared yard, cutting her best roses to lay in tribute. The funeral was huge. The press kept away as the family had asked them to. As the father of the young man said, “ It took my son's death to create a perfect society”.

At times like this, everyone brings gifts—of their time, their tears, their labour, their cars for the funeral, anything at all. As doctors, nurses, health workers we have additional gifts to offer, either in our professional roles or as friends who know that little bit more about morgues, autopsies, police surgeons. We can be called upon to identify bodies when relatives cannot face it. Or to explain yet again how the deceased may have felt in those last moments. We are fortunate that we can offer these special gifts.

There is a code among the bereaved; after a loss, they seek the eyes of someone who has walked that path before. It therefore helps when strangers as well as friends can see the status of mourners. All religions mark the bereaved and accord them special status with ceremonies, mourning garb, and rituals, and civil society marks them too with notices in the press, black ties, and condolence letters. The bereaved are given dispensations from everyday life. They serve as a reminder to us of how unimportant all else is save our beliefs, our core values, love, and life itself. They allow us to pause, to drop pretences, to pray, to go home and treasure our own families, to do better in future.

How then can we be so blind in our modern, hi-tech world? What must it feel like, your emotions like a peeled egg, walking away from a deathbed in some intensive care unit through the bustling wards of a hospital, into some anonymous city street; death can be just an end point or a failed intervention and the bereaved so rarely have a special place, or a sign on them, or special ways of behaving that set them apart. By failing to honour or recognise the bereaved among us, we may miss the most important gift of any offered after a death: the great gift that the bereaved offer of themselves.
Case 21-1981
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Richard H. Egdahl, Paul E. Steele
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 28-year-old man was admitted to the hospital because of hypercalcemia.He was well until 13 months earlier, when fever developed, with a sore throat, cervical lymphadenopathy, nausea, and diarrhea. A throat culture yielded streptococci; penicillin was given for seven days, with improvement. One month later a sore throat and fever recurred. Another throat culture was negative for streptococci, but penicillin was again administered, with improvement during the next two weeks. The patient was fatigued and discontinued his customary vigorous exercise program. Five months before admission he entered another hospital after a third episode of a sore . . .