tbuckley/cabot-search huggingface dataset:
Temperature Records and Ovarian Activity
Authors: M. Barton
Journal: BMJ (1948)

simply as Rh,rh, a name which clearly indicates positive reactions with sera anti-rh', anti-Rh,, and anti-hr', and negative reactions with anti-rh".12. No simple unified tables regarding the types and their heredity involving the other proposed systems of notations are available for use.13.The C-D-E and other-proposed notations are not mentioned in most standard laboratory texts, and are therefore unintelligible to the average reader.-I am, etc., New York.
Grades of hypothyroidism.
Authors: R L Himsworth, P M Fraser
Journal: BMJ (1973)

On Mount Kenya this year I witnessed high-altitude oedema presenting as coma.The patient, a 25-year-old European, had walked from 6,500 feet (1,980m) to 15,500 feet (4,724 m) altitude in a day and a half- he had proved to be the fittest member of the party.On the next day he developed headache and nausea, causing him to rest.He was rational till night.During that night he had loud but not alarming breathing.Next morning he was unrousable, with temperature of 38 5'C, tachycardia, tachypnoea, and frothy saliva.Cyanosis was not present at any stage of the illness.After first-aid treatment (parenteral digoxin, frusemide, chlorpromazine, and pencillin, with oxygen) he was evacuated by stretcher and helicopter.Chest x-ray showed pulmonary oedema.His fundi later showed retinal haemorrhages.C.S.F.pressure was high.After a week of treatment including positive-pressure venti- lation, diuretics, dexamethasone, and anti- biotics he recovered consciousness.A spastic quadriplegia gradually resolved, leading to complete recovery after about two months.The mechanism of the cerebral "oedema" is uncertain.It is clearly not just due to hypoxia.Cerebral arteriolar constriction (due to hypocarbia), with or without diffuse thrombosis or haemorrhage, must be a partial explanation.
MEDI2228, a Novel Bcma Antibody-PBD Conjugate, Sensitizes Human Multiple Myeloma Cells to NK Cell-Mediated Cytotoxicity and Upregulates CD38 Expression in MM Cells
Authors: Lijie Xing, Yuyin Li, Liang Lin, Tengteng Yu, Kenneth Wen, Shih-Feng Cho, Phillip A Hsieh, Krista Kinneer, Nikhil C. Munshi, Kenneth C. Anderson, Yu-Tzu Tai
Journal: Blood (2019)
INNV-41. PROSPECTIVE SELECTION OF RECURRENT GLIOBLASTOMA PATIENTS FOR TAILORED THERAPIES. RESULTS OF AN INSTITUTIONAL EXPERIENCE
Authors: Quintino Giorgio D’Alessandris, Nicola Montano, Maurizio Martini, Tonia Cenci, Rina Di Bonaventura, Martina Giordano, Valerio Caccavella, Vittorio Stumpo, Alessandra Cocomazzi, Liverana Lauretti, Eduardo Fernandez, Alessandro Olivi, Luigi Larocca, Roberto Pallini
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Failure of clinical trials with targeted therapies in glioblastoma (GBM) is probably due to the enrollment of molecularly unselected patients. In preliminary studies, we prospectively selected recurrent GBM patients on the basis of molecular pattern and administered targeted therapy accordingly. This tailored approach gave encouraging results in term of low recurrence rate (RR) and high 6-month progression free survival (PFS-6). Here, we present the long-term results of our work. METHODS On recurrent tumor samples of 34 adult patients, we assessed the expression of VEGF and PTEN through immunohistochemistry and of EGFRvIII through RT-PCR. Patients with VEGF overexpression were treated with bevacizumab (10 mg/Kg i.v. every 2 weeks in 6-week cycles). Patients with EGFRvIII expression and normal PTEN expression added erlotinib (150 mg/day orally). Patients with loss of PTEN expression, irrespective of EGFRvIII status, added sirolimus (1–10 mg/day orally). RESULTS Sixteen patients received bevacizumab alone (bev), 14 bevacizumab plus erlotinib (bev+erl) and 4 bevacizumab plus sirolimus (bev+sir). RR was 50% in the whole cohort and 37.5%, 57.1% and 75% in bev, bev+erl and bev+sir groups, respectively. PFS-6 was 55.9% in the whole cohort and 50%, 64.3% and 50% in bev, bev+erl and bev+sir groups, respectively. Our data compare favorably with those from the large EORTC 26101 trial, which showed a RR of 41.5% and a PFS-6 lower than 30%. When considering sustained response (defined as PFS ≥ 12 months), we overall observed a 20.6% rate, with the highest value in bev+erl subgroup (28.6%). Interestingly, in EORTC 26101 trial, less than 10% of patients achieved PFS ≥ 12 months. CONCLUSIONS Our results confirm that the tailored approach in recurrent GBM provides an advantage in terms of RR, PFS and, above all, of long-term responses, compared with trials without molecular selection.
Potential effect of age of BCG vaccination on global paediatric tuberculosis mortality: a modelling study
Authors: Partho Roy, Johan Vekemans, Andrew Clark, Colin Sanderson, Rebecca C Harris, Richard G White
Journal: The Lancet Global Health (2019)

BCG has been recommended at birth in countries with a high tuberculosis burden for decades, yet delayed vaccination is widespread. To support a WHO guidance review, we estimated the potential global tuberculosis mortality benefit of administering BCG on time and consequences of later administration.We estimated age-specific BCG coverage in 152 high-burden countries using data from large, nationally representative household surveys, to parameterise a static mathematical model, calibrated to global childhood tuberculosis deaths in 2016. 12 hypothetical scenarios explored the effect of BCG delivery at birth, 6 weeks, 6 months, or 9-12 months, on tuberculosis deaths per global birth cohort by age 15 years, including delivery at the time of the first diphtheria-tetanus-pertussis vaccine (DTP1) or the first measles-containing vaccine (MCV1). We assumed constant vaccine efficacy by age, but varied coverage and degree of vaccination delay, including no delay.In 152 high-burden countries, we estimated that BCG coverage in 2016 was 37% at 1 week of age, 67% at 6 weeks, and 92% at 3 years. Modelled scenarios in which 92% BCG coverage was achieved at birth reduced tuberculosis deaths in the global birth cohort by 5449 (95% uncertainty range 218-15 071) or 2·8% (0·1-7·0) by age 15 years. 100% coverage at birth reduced tuberculosis deaths by 16·5% (0·7-41·9). Later administration increased tuberculosis deaths-eg, BCG vaccination at 6 weeks, the recommended age of DTP1, increased tuberculosis deaths by 0·2% (0-0·4), even if BCG reached DTP1 coverage levels (94% at 3 years).Reducing delays and increasing coverage at birth would substantially reduce global paediatric tuberculosis mortality. Modelled scenarios whereby BCG was administered later in the infant schedule were all estimated to increase tuberculosis deaths, even with increased coverage. The WHO recommendation for BCG at birth should be maintained and emphasised.WHO.
IMMU-35. COMPLEMENT SYSTEM AND GLIOBLASTOMA: AN INTRICATE RELATIONSHIP
Authors: Sandeep Mittal, Shayak Sengupta, Sabbir Khan, Kain McGee, Kristin Alfaro-Munoz, Veerakumar Balasubramaniyan, John DeGroot
Journal: Neuro-Oncology (2019)

Abstract The complement system is a vital part of the innate immune system which plays a critical role in immune surveillance and inflammatory processes. Malignant and host cells express various complement inhibitory proteins on their surface to protect against complement mediated cytotoxicity. Imbalanced complement activation triggers inflammation and alters the tumor microenvironment. Complement activation has been shown to induce proliferation and migration of breast, ovarian and lung cancer cells. At this time, the expression and functional role of the complement cascade in glioblastoma (GBM) remain elusive. Here, we investigated the role of complement proteins and their receptor expression in human primary glioma stem-like cells (GSCs) and human GBM tissues. Western blot data demonstrated a high level of expression of central complement components and their receptors in GSCs. RT-PCR data further confirmed the high expression of complement genes which was similar or higher to normal human astrocytes (HA), a cell with high baseline expression levels of complement genes. Flow cytometry analysis revealed that almost 95% of GSCs expressed the anaphylatoxin complement receptors C3aR and C5aR on their cell surfaces which was consistent with our immunohistochemistry analysis of freshly resected GBM tissues. Furthermore, anaphylatoxin C5a exposure increased the proliferation of a subgroup of GSCs while reduced in another subset. Interestingly, C5a exposure was found to increase the expression of various pro-inflammatory markers in GSCs with reduced proliferation. Fluorescence-activated cell sorting (FACS) analysis of freshly isolated human GBM tissue revealed predominant expression of C5aR on cancer cells (CD11b-/CD45- cells) rather than on immune cells. RT-PCR analysis also demonstrated high expression levels of complement genes with concomitant decrease in complement inhibitory genes in human GBM tissue. Evaluation of the differential role of the complement system in GSCs along with their role in in vivo glioma models is ongoing.
TMOD-32. GL261 LUCIFERASE-EXPRESSING CELLS ELICIT AN ANTI-TUMOR IMMUNE RESPONSE: AN EVALUATION OF MURINE GLIOMA MODELS
Authors: Victoria Sanchez, John Lynes, Stuart Walbridge, Xiang Wang, Nancy Edwards, Anthony Nwankwo, Gifty Dominah, Arnold Obungu, Nicholas Adamstein, Pradeep Dagur, Tianxia Wu, Dragan Maric, Jeeva Munasinghe, John Heiss, Edjah K Nduom
Journal: Neuro-Oncology (2019)

Abstract Preclinical models that reliably recapitulate the immunosuppressive properties of human gliomas are essential to assess immune-based therapies. Intracranially injected GL261 cells are widely used as an immunocompetent animal model of glioma, but it is common practice to transfect these with luciferase to facilitate tumor monitoring during treatment. Our group has previously shown that the luciferase-expressing GL261 Red-FLuc cells create an inflammatory response when implanted intracranially. Now, we additionally explore the inflammatory response of GL261-Luc2 cells and demonstrate a similar host immune response occurs with this model as well. In our in vivo evaluation, C57BL/6 mice underwent stereotaxic, intracranial implantation with GL261, GL261 Red-FLuc or GL261-Luc2 cells at doses of 5x104cells/5mL or 3x105cells/5uL.MRIs were performed to monitor relative tumor growth. To assess intrinsic differences between cell lines, in vitro cytokine profiles were evaluated by proteome microarray. Kaplan-Meier survival analyses demonstrated median survival for mice implanted with GL261 cells at 5x104cells was 18 to 21 days. The GL261-Red FLuc implanted mice cells did not reach median survival at either tumor dose with greater than 60% of mice termed long-term survivors. Finally, mice injected with GL261-Luc2 cells at 3x105cells reached median survival at 23 days, but median survival was significantly prolonged for mice implanted with GL261-Luc2 at a dose of 5x104cells (37 days, with 40% becoming long-term survivors) compared to GL261 implanted mice. MRIs reveal differences in tumor growth that correspond with the differences in median survival between groups. In addition, proteomic analyses revealed significantly elevated inflammatory cytokines such as IFN-gamma, IL-7 and TNF-alpha in the supernatants of the GL261 Red-FLuc cells and GL261-Luc2 cells. Further immune characterization is ongoing. Our data suggests that GL261 Red-FLuc and GL261-Luc2 murine models elicit an anti-tumor immune response by increasing pro-inflammatory modulators which stimulate the tumoricidal function of immune cells in the tumor microenvironment.
Keratinocyte carcinoma in organ transplant recipients
Authors: S. Menzies, E. O'Leary, G. Callaghan, M. Galligan, S. Deady, B. Gadallah, P. Lenane, A. Lally, D.D. Houlihan, P.G. Morris, D.J. Sexton, P.A. McCormick, J.J. Egan, J.P. O'Neill, P.J. Conlon, F.J. Moloney
Journal: British Journal of Dermatology (2019)

Skin cancer commonly affects people who have received a solid organ transplant (heart, lung, liver and kidney). Transplant patients can get multiple skin cancers, some of which can grow very quickly. The commonest types of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Immunosuppressant medication is used to prevent rejection of the transplanted organ. This alters the body's immune system, which in turn means that transplant patients are more prone to skin cancers that can grow rapidly. Over the last 20 years, newer immunosuppressants have been introduced which are thought to lessen the risk of skin cancer. Previous studies have shown a lower risk of SCC with the newer medication, but no study to date has looked at BCC rates. This study, from Ireland, aimed to find out if the rate of skin cancer in transplant patients has reduced over the last 20 years, spanning the introduction of newer immunosuppressive medications. The National Cancer Registry of Ireland registers all skin cancers for the Republic of Ireland. The authors looked at the rate of skin cancer in people who received a solid organ transplant and compared this to the rate of skin cancer in the general population. They found that the rate of SCC and BCC in patients who received an organ transplant has significantly reduced over the last two decades. This change in risk of skin cancer coincided with changes in immunosuppressant medication, along with focused education and regular skin cancer screening for transplant recipients.
Phase II Study of Midostaurin + Chemotherapy in Pediatric Patients with Untreated, Newly Diagnosed, FLT3-Mutated Acute Myeloid Leukemia (AML)
Authors: Dirk Reinhardt, Christian Michel Zwaan, Albert Hoenekopp, Julie Niolat, Sophie Ifrah, Florence Noel-Baron, Franco Locatelli
Journal: Blood (2019)
Formulation Design, Optimization and In Vivo Evaluations of an α-Tocopherol-Containing Self-Emulsified Adjuvant System using Inactivated Influenza Vaccine
Authors: Rushit N. Lodaya, Amey P. Kanitkar, Kristian Friedrich, Dawn Henson, Ryan Yamagata, Sandra Nuti, Corey P. Mallett, Sylvie Bertholet, Mansoor M. Amiji, Derek T. O’Hagan
Journal: Journal of Controlled Release (2019)

α-Tocopherol has been used as an immune supplement in humans, as an emulsion adjuvant component in several veterinary vaccines as well as an immunomodulatory component of AS03, an emulsion adjuvant that was used in an H1N1 pandemic vaccine (Pandemrix). AS03 is manufactured using microfluidization and high-pressure homogenization. Such high energy and complex manufacturing processes make it difficult and expensive to produce emulsion adjuvants on a large scale, especially in developing countries. In this study we have explored simpler, comparatively inexpensive methods, to formulate emulsion adjuvants containing α-tocopherol, that have the potential to be made in any well-established scale-up facility. This might facilitate producing and stock-piling adjuvant doses and therefore aide in pandemic preparedness. We used design of experiment as a tool to explore incorporating α-tocopherol into self-emulsified systems containing squalene oil and polysorbate 80. We created novel self-emulsified adjuvant systems (SE-AS) and evaluated their potency in vivo in BALB/c mice with inactivated quadrivalent influenza vaccine (QIV) and tested the cellular and humoral immune responses against the four vaccine strains.
An embryonic CaVβ1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse
Authors: Massiré Traoré, Christel Gentil, Chiara Benedetto, Jean-Yves Hogrel, Pierre De la Grange, Bruno Cadot, Sofia Benkhelifa-Ziyyat, Laura Julien, Mégane Lemaitre, Arnaud Ferry, France Piétri-Rouxel, Sestina Falcone
Journal: Science Translational Medicine (2019)

CaVβ1E boosts downstream growth differentiation factor 5 signaling to counteract muscle mass loss in denervated or aged mouse muscles.
ACTR-54. VIGILANT OBSERVATION OF GLIADEL WAFER IMPLANT (VIGILANT) REGISTRY: INTERIM ANALYSIS
Authors: Kevin Lillehei, Steven Kalkanis, Linda Liau, Jeffrey Olson, Nina Paleologos, Timothy Ryken, Tania Johnson, Evan Scullin
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION The Vigilant ObservatIon of GlIadeL WAfer ImplaNT (VIGILANT) registry (NCT02684838) was initiated to evaluate the use of BCNU wafers for treatment of CNS malignancies in contemporary practice and in the new era of molecular analysis. METHODS The VIGILANT registry is an observational study. Each patient receives usual care from treating physicians in routine quarterly visits, with no registry-specific visits required. The VIGILANT registry will enroll up to 500 patients at 35 US sites. Patients must be ≥18 years of age with no medical conditions increasing risk through participation. Patient follow-up will last 3 years. RESULTS The interim analysis is ongoing, with the following preliminary data. Of the 143 patients enrolled to date (mean age 59.8 ± 13.41 years, 60.1% male, 82.5% white), BCNU wafers have been implanted for newly diagnosed glioblastoma (GBM) in 49 (34.3%); for recurrent GBM in 48 (33.6%); for brain metastases in 28 (19.6%); for anaplastic oligodendroglioma in 4 (2.8%); and for other CNS tumors in 14 (9.8%). For patients with recurrent GBM, the median time from prior to current CNS tumor diagnosis was 341.5 days (IQR 88, 890). The majority of recurrent GBM patients had previously undergone systematic chemotherapy (87.5%) and radiation therapy (70.8%); only 8 (16.7%) had previously received BCNU wafers and only 4 (8.3%) had previously undergone alternating electric-field therapy. Of patients with brain metastases, 15 (51.7%) had previously undergone stereotactic radiosurgery. Of GBM patients with baseline biomarker assessments, MGMT promoter status was methylated in 52.1% (37/71), and IDH1 mutation status was positive in 15.9% (11/69). Median survival and contemporary practice patterns will be available at the time of presentation. CONCLUSIONS In the VIGILANT registry to date, BCNU wafers have been implanted most often and with equal frequency for treatment of newly diagnosed and recurrent GBM. Preliminary safety and efficacy data are pending.
Side-effects of Tranylcypromine
Authors: P. W. Richmond, A. H. Roberts
Journal: BMJ (1963)

with the tissue-buffering mechanism for storage of catechol amines.Under these circumstances it is also likely that the tissue monoamine system is more sensi- tive to the action of ephedrine and amphetamine.It is clear that tranylcypromine should never be given either in the form of " parstelin " (tranylcypromine and trifluo- perazine) or of " parnate " (tranylcypromine) within one to two weeks of giving ephedrine or amphetamine as well.In view of the pharmacological action of the drug on so many systems it should probably not be given with anything else at all, at any rate in the present state of our knowledge.The side-effects of tranylcypromine are due to amine-oxidase inhibition, but there is comparatively little to suggest that this is true of its antidepressant action.One hopes that it will be possible to separate these effects.since the practical difficulty of ensuring that a patient will not con- sume other tablets as well as tranylcypromine makes the drug a liability in prac- tice.Although all these effects have been known since 1960 they are often still unrecognized.-Iam, etc.,
Identify AMPK-Mediated Autophagy and Oxphos As a Novel Metabolic Vulnerability for Targeted Therapy in Mantle Cell Lymphoma
Authors: Yixin Yao, Yang Liu, Hui Zhang, Angela Leeming, Joseph Mitchell McIntosh, Preetesh Jain, Liang Zhang, Krystle Nomie, Michael L. Wang
Journal: Blood (2019)
A Novel Revcar Platform for Switchable and Gated Tumor Targeting
Authors: Anja Feldmann, Anja Hoffmann, Enrico Kittel-Boselli, Ralf Bergmann, Stefanie Koristka, Nicole Berndt, Claudia Arndt, Liliana Raquel Loureiro, Nicola Mitwasi, Justyna Jureczek, Martin Bornhaeuser, Michael Bachmann
Journal: Blood (2019)
Identification of Circulating microRNA Signatures As Potential Noninvasive Biomarkers for Prediction to Response to Extracorporeal Photoapheresis in Patients with Graft Versus Host Disease
Authors: Raul Teruel Montoya, Oriana López-Godino, Nuria Garcia-Barbera, Rosa Cifuentes-Riquelme, Maria Sola, Inmaculada Heras, Cesare Perotti, Vicente Vicente Garcia, Rocio González-Conejero, Claudia Del Fante, Constantino Martínez, Maria Luisa Lozano
Journal: Blood (2019)
Effects of a Resuscitation Strategy Targeting Peripheral Perfusion Status versus Serum Lactate Levels among Patients with Septic Shock. A Bayesian Reanalysis of the ANDROMEDA-SHOCK Trial
Authors: Fernando G. Zampieri, Lucas P. Damiani, Jan Bakker, Gustavo A. Ospina-Tascón, Ricardo Castro, Alexandre B. Cavalcanti, Glenn Hernandez
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: A recent randomized controlled trial showed that a peripheral perfusion-guided resuscitation strategy was associated with lower mortality and less organ dysfunction when compared with lactate-guided resuscitation strategy in patients with septic shock, but the difference in the primary outcome, 28-day mortality, did not reach the proposed statistical significance threshold (P = 0.06). We tested different analytic methods to aid in the interpretation of these results.Objectives: To reassess the results of the ANDROMEDA-SHOCK trial using both Bayesian and frequentist frameworks.Methods: All patients recruited in ANDROMEDA-SHOCK were included. Both a post hoc Bayesian analysis and a mixed logistic regression analysis were performed. The Bayesian analysis included four different priors (optimistic, neutral, null, and pessimistic) for mortality endpoints. The probability of having a Sequential Organ Failure Assessment in the lowest quartile at 72 hours was assessed using Bayesian networks.Measurements and Main Results: In the Bayesian analysis, the posterior probability that a peripheral perfusion-targeted resuscitation strategy is superior to lactate-targeted resuscitation at 28 days was above 90% for all priors; the probability of benefit at 90 days was above 90% for all but the pessimistic prior. Using an optimistic prior, posterior median odds ratios were 0.61 (95% credible interval, 0.41-0.90) and 0.68 (95% credible interval, 0.47-1.01) for 28-day and 90-day mortality, respectively. The comparable frequentist odds ratios for 28-day and 90-day mortality were 0.61 (95% confidence interval [CI], 0.38-0.92) and 0.70 (95% CI, 0.45-1.08), respectively. The odds that that patients in the peripheral perfusion-targeted resuscitation arm had Sequential Organ Failure Assessment scores in the lower quartile at 72 hours was 1.55 (95% CI, 1.02-2.37).Conclusions: Peripheral perfusion-targeted resuscitation may result in lower mortality and faster resolution of organ dysfunction when compared with a lactate-targeted resuscitation strategy.
Stein-Leventhal Syndrome
Authors: A. Sharman
Journal: BMJ (1960)

marked photophobia.Nuchal rigidity was slight and Kernig's sign was negative.There was no muscle weakness and all reflexes were present and normal.Fundoscopic examination revealed no abnormality.Lumbar puncture produced an opalescent fluid with a high protein as shown by a strong positive Pandy's test, cell count was 320/c.mm., protein 300 mg./ 100 ml., sugar 18 mg./ 100 ml., and chlorides 630 mg./100 ml.Scanty acid/alcohol-fast bacilli were seen
Efficacy and Safety Profile of Bortezomib Based Regimens for Treatment of Newly Diagnosed Amyloidosis: A Systematic Review of Literature
Authors: Muhammad Abdullah Yousaf, Muhaddis Ejaz Ahmad, Maaz Ahmed Yusufi, Hamza Hassan, Adeela Mushtaq, Ahmad Iftikhar, Mustafa Nadeem Malik, Abdul Rafae, Zunairah Shah, Ahmed Ibrahim, Adnan Basheer, Faiz Anwer
Journal: Blood (2019)