tbuckley/cabot-search huggingface dataset:
Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference‡
Authors: Markus Cornberg, Anna Suk-Fong Lok, Norah A. Terrault, Fabien Zoulim, Thomas Berg, Maurizia R. Brunetto, Stephanie Buchholz, Maria Buti, Henry L.Y. Chan, Kyong-Mi Chang, Maura Dandri, Geoffrey Dusheiko, Jordan J. Feld, Carlo Ferrari, Marc Ghany, Harry L.A. Janssen, Patrick Kennedy, Pietro Lampertico, Jake Liang, Stephen Locarnini, Mala K. Maini, Poonam Mishra, George Papatheodoridis, Jörg Petersen, Silke Schlottmann, Su Wang, Heiner Wedemeyer
Journal: Journal of Hepatology (2019)
Nicotinic Acid Tolerance Test
Authors: A. Erdei
Journal: BMJ (1947)

in this country were to use the vole vaccine.He gave me the impression that he believed it would eventually supersede B.C.G.I think there is good evidence for the belief that both methods of inoculation (a) are harmless to humans, (b) increase resistance to tuberculosis, (c) are of value only in tuberculin-negative
The solute carrier transporters and the brain: Physiological and pharmacological implications
Authors: Chengliang Hu, Lei Tao, Xizhi Cao, Ligong Chen
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Solute carriers (SLCs) are the largest family of transmembrane transporters that determine the exchange of various substances, including nutrients, ions, metabolites, and drugs across biological membranes. To date, the presence of about 287 SLC genes have been identified in the brain, among which mutations or the resultant dysfunctions of 71 SLC genes have been reported to be correlated with human brain disorders. Although increasing interest in SLCs have focused on drug development, SLCs are currently still under-explored as drug targets, especially in the brain. We summarize the main substrates and functions of SLCs that are expressed in the brain, with an emphasis on selected SLCs that are important physiologically, pathologically, and pharmacologically in the blood-brain barrier, astrocytes, and neurons. Evidence suggests that a fraction of SLCs are regulated along with the occurrences of brain disorders, among which epilepsy, neurodegenerative diseases, and autism are representative. Given the review of SLCs involved in the onset and procession of brain disorders, we hope these SLCs will be screened as promising drug targets to improve drug delivery to the brain.
TMIC-12. TUMOR EDGE-DESTINED CELLS IN GBM CELLS IN A CELL-INTRINSIC MECHANISM
Authors: Daisuke Yamashita, Mutsuko Minata, Hai Yu, Soujun Zhang, Chaoxi Li, Victoria Flanary, Sadashib Ghosh, Yeri Lee, Heejin Cho, Davide Botta, Xiaoxian Guo, Saya Ozaki, Shinobu Yamaguchi, Svetlana Komarova, Soniya Bastola, David Crossman, Louis Nabors, James Markert, Zhenglong Gu, Jeffrey Skolnick, Nicola Zamboni, Frances Lund, Do-Hyun Nam, Ichiro Nakano
Journal: Neuro-Oncology (2019)

Abstract The highly infiltrative nature of glioblastoma (GBM) underscores limited response to current therapies and subsequent unfavorable clinical outcome. Despite the gross total resection of tumors located in the enhancing lesions, GBMs inevitably recur from the areas adjacent to the resection cavity that retains tumor cells with tumor-initiating capacity with therapy resistant nature (glioma-initiating cells: GICs). Here, we identified, in clinical GBM tumors, two mutually-exclusive glioma-initiating cell subpopulations in two different regions of GBM tumors, core- and edge-located glioma-initiating cells that co-exist in single tumors (Minata et al. Cell Reports. 2019). Following this observation, we further established patient-derived GBM clones from both tumor core and edge tissues, termed core-GICs and edge-GICs, and uncovered their distinct molecular signatures. Unexpectedly, we found that these two distinct GIC subpopulations retain the spatial identity, meaning that the core GICs locate themselves in the injected site, whereas the edge GICs initiated to form edge-like lesions, when xenografted into mouse brains. Through OMICs analyses, we identified CD38 as a key molecule to determine the edge phenotype both in vitro and in vivo. Collectively, our findings indicate, for the first time, that GBM cells are heterogeneous to be composed of tumor cells destined to be located in distinct regions of the tumors in a molecularly-defined manner.
Haematemesis and melaena.
Authors: D J Allison
Journal: BMJ (1977)

weekly intervals, and reinforced the importance of treatment.The tablets were dispensed in a tin which contained 12 tablets more than required for each two weeks.A treatment period was designated as compliant if 80 % or more of the tablets had been removed.All tablet counts were made at the end of the trial.No patient defaulted from attendance and all the tablet containers were returned as requested.The tables show the number of times the 800% value was achieved.Adherence to therapy was marginally better with atenolol and with once-daily treatment, but the differences were not statistically significant by the X2 test.No patient consistently failed to comply but only one complied throughout all periods of the trial.Side effects to atenolol were inconspicuous and were not associated with periods of drug-defaulting.Despite our attempts we failed to reach our goal for con- sistent tablet-taking one-third of the time.Tablet counts are indeed likely to lead to an overestimate of compliance.
CBMT-18. THE ROLE OF BIOMARKER CANDIDATE GELSOLIN AND ITS MICRORNAS IN GLIOBLASTOMA
Authors: Mitsutoshi Nakada, Jiakang Zhang, Taskuya Furuta, Shabierjiang Jiapaer, Sho Tamai, Hemragul Sabit, Yasuo Uchida, Sumio Ohtsuki, Tetsuya Terasaki
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Among potential glioblastoma (GBM) blood biomarkers that we identified recently, we focused on gelsolin (GSN), a key regulator of actin filament disassembly. GSN was significantly lower in the blood of patients with GBM than in that of healthy controls. In this study, we analyzed the function of GSN and identified microRNAs (miRs) involved in GSN expression in GBM. METHODS QRT-PCR and western blot were introduced to evaluate the expression level of GSN in normal brain and GBM tissue. The localization of GSN was examined by immunohistochemistry and immunocytochemistry using human samples. The association between the expression level of GSN and progression free survival (PFS) /overall survival (OS) in GBM was assessed by Kaplan-Meier analysis. The function of GSN and its signal transduction in glioma cell lines were analyzed using small interfering RNA (siRNA) knockdown of GSN. Additionally, miRs controlling GSN expression were retrieved from databases of miRs, and miRs related to GSN expression were identified in GBM tissues. RESULTS The expression level of GSN was significantly lower in GBM tissues compared to normal brains. Normal astrocytes mainly expressed GSN. High expressor of GSN showed longer PFS and OS than low expressor. Proliferation and invasion in glioma cell lines were significantly promoted by siRNA for GSN accompanied with the activation of glycogen synthase kinase 3β. In GBM tissues, the expression levels of GSN and miR-654-5p, 450b-5p showed an inverse correlation. The inhibitor for miR-654-5p and miR-450b-5p accelerated GSN expression resulting reduction of proliferation. CONCLUSION GSN plays a role as suppressor of proliferation and invasion in GBM. miR-654-5p and miR-450b-5p which control GSN expression can be targets against GBM.
INNV-13. A NOVEL TELEGRAM CHAT APPLICATION BASED BOT (FLORENCEBOT) FOR BRAIN TUMOUR AFFECTED PATIENTS
Authors: Abhishek Puri, Kyle Sandeman
Journal: Neuro-Oncology (2019)

Abstract The discoverability of reliable information online is difficult. As the network grows exponentially, unregulated content has the potential to cause harm. Telegram is a popular mainstream chat application. It allows automated software called bots that interact passively with an individual. Florence bot is unique in this space for the patient support; for those affected by brain tumours. It has been developed in PHP and hosted privately by the developer. Florence links to physician generated content (hosted externally on a blogging website) such as introduction, signs and symptoms of brain tumours and various treatment options along with their side effects. The content generates “web view” in Telegram itself, preserving written and multimedia formats. It ensures minimal overheads on the bot, making it responsive. It links to brain tumour channel (automated streamed information working as a public broadcast) and physician-administered support group. A physician designed bot is preferable to a third party mobile application to ensure the accurateness of information. No user-related information is available to bot developers as it does not have tracking and advertising elements; hence safeguards users privacy. It is more accessible and cheaper to deploy than a mobile application as it uses an instant messaging app as its container, which works across computing platforms. Florence bot is expected to bridge the gap for reliable information and real-time support independent of geographical limitations.
Treatment of Diabetes Mellitus
Authors: T. Inman
Journal: BMJ (1858)

we exclude that insight of the understanding which is called intuition, because it is a part of its own innate energy which depends neither on memory nor the senses, though called into activity through their exercise.There can be no difficulty, then, in admitting that the disease under consideration exists in the only otlher set of faculties remaining; that its exciting cause is disease of the material organ in which they inhere; and that its proximate cause is a perversion of the logical understanding, and through it a perversion also o' the feelings and the will.Insanity, then, may be defined as-a dangerous mis- conception of one's personal relations, either persistent or with lucid intervals, and with or without illusions of the senses.It will give more completeness to this sketch if I add, that a true conception of the understanding is an idea or belief in confo;mity with the nature of things, and that the class of mis- conceptions may be tabulated as under:-KISCONCEPTION.1.In matters common to all men: Error and Ignorance.2. Peculiarities gradually acquired from circumstances: Eccentricity.3. Peculiarities suddenly or recently coming on from dis- ease: some forms of Monomania. 4. In which liberty is dangerous to the Individual and to Society: Insanity.a. From destruction of all mental power-De- mentia.b& From general weakness of mental power
HM43239, a Novel Potent Small Molecule FLT3 Inhibitor, in Acute Myeloid Leukemia (AML) with FMS-like Tyrosine Kinase 3 (FLT3) Mutations: Phase 1 /2 Study
Authors: Naval G. Daver, Kyoo Hyung Lee, Sung-Soo Yoon, Chul Won Jung, Hyun Jeong Kang, Sooa Jung, Sujin Seo, Jiyeon Yoon, Hyunjin Kim, Young Su Noh, Yoonha Seo, Hyeyoung Kwon, Oakpil Han, Seungjae Baek, Kyounghee Seo, Kwee Hyun Suh
Journal: Blood (2019)
Final Analysis at 5 Years Follow up of Patients with MPN-Associated Splanchnic Vein Thrombosis Treated with Ruxolitinib in a Phase 2 Study
Authors: Chiara Paoli, Paola Guglielmelli, Francesco Mannelli, Lara Mannelli, Vittorio Rosti, Maria Chiara Finazzi, Elisa Rumi, Marco Ruggeri, Alessandro Pancrazzi, Carmela Mannarelli, Guido Finazzi, Maria Luisa Ferrari, Laura Lissandrini, Duccio Fantoni, Giovanni Barosi, Mario Cazzola, Tiziano Barbui, Alessandro M. Vannucchi
Journal: Blood (2019)
Silent NK/T Cell Reactions Against Dasatinib during Sustained Deep Molecular Response before Discontinuation Are Associated with Longer Treatment-Free Remission: A Multicenter, Single-Arm, Phase 2 Study
Authors: Takashi Kumagai, Chiaki Nakaseko, Kaichi Nishiwaki, Chikashi Yoshida, Kazuteru Ohashi, Naoki Takezako, Hina Takano, Yasuji Kouzai, Tadashi Murase, Kosei Matsue, Satoshi Morita, Junichi Sakamoto,, Hisashi Wakita, Hisashi Sakamaki, Koiti Inokuchi
Journal: Blood (2019)
Thiotepa in the Conditioning Regimen Decreases Rejection after HLA Identical Allogeneic Marrow Transplantation in Children with Beta Thalassemia Major Aged Less Then 4 Years
Authors: Paola Polchi, Javid Gaziev, Guido Lucarelli, Pietro Sodani, Cecilia Alfieri, Gioia De Angelis, Cristiano Gallucci, Antonella Isgro, Marco Marziali, Andrea Roveda, Katia Paciaroni
Journal: Blood (2008)
Targeting Prostate Cancer for Gene Therapy Utilizing Lentivirus and Oncolytic VSV Virus
Authors: Maryam Moussavi
Journal: Cancer Research (2009)

Abstract : Prostate cancer is the most commonly diagnosed non-skin carcinoma, and one of the leading causes of cancerrelated deaths in North American men. Presently there are no curative therapies available for advanced metastatic prostate cancer. Oncolytic viral therapy provides an opportunity to efficiently kill primary and metastatic cancer cells while sparing normal cells. Vesicular Stomatitis Virus (VSV) is an oncolytic virus which is able to replicate in cells with a defective interferon (INF) response. Here, we examined the effect of a mutated VSV (AV3), which expresses luciferase and has an enhanced INF-sensitivity, on the viability of prostate tumours that develop in prostate-specific PTEN null transgenic mice. Prostates of PTEN knockout and control mice were injected with 5x108 pfu/ml of VSV(AV3) and monitored for luminescence over a 96h time period using the IVIS-Xenogen machine to track the virus distribution. Plaque analyses for live virus n tissues extracted at various time points revealed that VSV(AV3)predominantly replicated in the prostates of transgenic PTEN knockout mice. Additionally, using TUNNEL staining of paraffin embedded tissues, we demonstrated that VSV(AV3) is capable of selectively infecting and killing malignant prostate cells while sparing normal cells. This cancer-specific cell death was not due to infiltration of neutrophils into the prostate tumours of PTEN null mice's has been reported for other tumour mode. However, there was an increase in macrophage and Blymphocyte infiltration into the prostates of PTEN null mice compared to control mice. In conclusion, VSV(AV3) is able to replicate and selectively kill the prostate cancer cells that develop in the PTEN null mouse and hence prove clinically useful for treating locally advanced prostate cancer while sparing normal prostate tissue.
RARE-19. ASSOCIATION BETWEEN METHOTREXATE TOXICITY AND GENETIC VARIANTS OF METHIONINE AND FOLATE METABOLISM RELATED GENES IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA PATIENTS
Authors: Ka-wai Ho, Synphen Wu, Raymond Baser, Irene Orlow, Denise Correa
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Methotrexate (MTX) is the backbone of therapy for primary central nervous system lymphoma (PCNSL). There have been conflicting results over whether polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and transcobalamin 2 (TCN2) genes modulate MTX-associated toxicity. METHODS This is a retrospective study involving patients who underwent MTX-based chemotherapy for PCNSL and were genotyped for polymorphisms in the MTHFR (Ala222Val, C &gt;T; Glu429Ala, A &gt;C) and TCN (Arg259Pro, C &gt;T) genes as part of a separate study investigating the association of genetic risk factors for treatment-related cognitive dysfunction. Renal, hepatic, and bone marrow toxicities were graded according to CTCAEv5.0, and only toxicities grade 3 or higher were considered clinically significant. MRIs of the brain during and after MTX treatment were rated for white matter changes (WMC) and cortical atrophy (CA). Genotypes were cross-tabulated with toxicities and worsening of WMC and CA. Associations were tested using Fisher’s exact tests. RESULTS We identified 35 PCNSL patients treated with MTX and had available genotyping data. 18 patients (51%) carried one or more MTHFR-T (c.222 Val) alleles, 16 patients (46%) had one or more MTHFR- C (c.429 Ala) alleles, and 30 patients (86%) had one or more TCN-G (c. 259 Pro) alleles. Bivariate analysis revealed that the MTHFR-T (c.222Val) allele was associated with increased hepatotoxicity (p=0.03). None of the polymorphisms tested were associated with renal or bone marrow toxicity. Though changes in CA were observed, the association of polymorphisms with WMC or CA did not reach statistical significance, potentially confounded by small sample size and limited sensitivity of rating scales. CONCLUSION These preliminary observations suggest that the Val on codon 222 of the MTHFR gene might be involved in the modulation of toxicity, however a larger study is required to assess whether variants involved in methionine metabolism may influence MTX-associated hepatotoxicity in PCNSL patients.
Reiter's Disease
Authors: P N Bardhan
Journal: BMJ (1947)

was this March, when a friend staying with her had a relapse in her home.I I hope that this case will help further in stressing the fact that primary malaria can be a factor in diagnosis in this country at the present time, where malarial carriers are more numerous and the Anopheles maculipennis known to be present.-Iam, etc.
BCL-2 Is Expressed in Advanced Mastocytosis and Midaustorin Induces Venetoclax Sensitivity of Mast Leukemia Cell Lines
Authors: Danielle Canioni, Josquin Moraly, Ludovic Lhermitte, Laura Polivka, Mélanie Féroul, Julien Rossignol, Laurent Frenzel, Michel Arock, Patrice Dubreuil, Leila maouche-Chretien, Olivier Hermine
Journal: Blood (2019)
Discontinuation Patterns in Patients Receiving Novel Oral Agents for Chronic Lymphocytic Leukemia in the Veterans Health Administration
Authors: Hsu-Chih Chien, Vikas Patil, Kelli M Rasmussen, Christina Yong, Juliana M L Biondo, Mary Halloran, Sheila Shapouri, Mei Wu, Zachary R Burningham, Brian C Sauer, Ahmad S Halwani
Journal: Blood (2019)
Umbilicated papules on the face
Authors: Yue-Tong Qian, Dong-Lai Ma
Journal: BMJ (2019)

A 5 year old boy presented with a three month history of multiple mildly pruritic, dome shaped, skin coloured, shiny, centrally umbilicated papules (average diameter 1-5 mm) on his face and neck. His medical history included atopic dermatitis, for which he had been treated with topical hydrocortisone, without improvement. The papules were distributed mostly on the perioral and perinasal areas (fig 1) and neck. He had no lesions elsewhere on his body. Ocular examination and laboratory investigations were normal, and he tested negative for HIV. Biopsy of a lesion was sent for histopathological examination (fig 2). …
Segmental Aspiration Pneumonia and Bronchiectasis
Authors: K. D. F. Morle, P. W. Robertson
Journal: BMJ (1953)

NODOSABr_____r two years' history of nasal obstruction, ultimately developing ulcerating lesions of the nose and trachea, and died after one year's illness; at necropsy an acute necrotizing arteritis was found in many organs.We feel that these two cases are perhaps examples of nasal granuloma with periarteritis, as described here.We have been able to examine slides of nasal lesions and post-mortem specimens of four cases of classical malignant granuloma of the nose.No evidence of periarteritis nodosa was seen, and the local lesion was a chronic non-specific inflammation.Therefore we have no evidence to enable us to decide whether the classical destructive "malignant granuloma of the nose" is another manifestation of the condition previously discussed or something entirely different. SummaryTwo cases are described in which periarteritis nodosa was preceded by an ulcerating granuloma of the nasal mucosa.Seven similar cases, and possibly two others, have been collected from the literature.The significance of the nasal lesions is discussed and the possible connexion pointed out between this condi- tion and the so-called "malignant granuloma of the nose.
The Impact of Pre-Diagnosis Tobacco Use in Mantle Cell Lymphoma
Authors: Jason Romancik, Jeffrey M. Switchenko, Krithika Shanmugasundaram, Subir Goyal, Oscar Calzada, Michael C. Churnetski, Bhaskar Kolla, Veronika Bachanova, James N. Gerson, Stefan K. Barta, Max J. Gordon, Alexey Danilov, Natalie S Grover, Stephanie Mathews, Madelyn Burkhart, Reem Karmali, Yazeed Sawalha, Brian T. Hill, Nilanjan Ghosh, Steven I Park, Narendranath Epperla, David A. Bond, Talha Badar, Kristie A. Blum, Mehdi Hamadani, Timothy S. Fenske, Mary-Kate Malecek, Brad S. Kahl, Peter Martin, Jin Guo, Christopher R. Flowers, Jonathon B. Cohen
Journal: Blood (2019)
Pioglitazone Did Not Affect PPAR-Γ, STAT5, HIF2α and CITED2 Gene Expression in Chronic Myeloid Leukemia Patients with Deep Molecular Response
Authors: Ana Beatriz Pascoal Lopes, Eliana C Miranda, Valquíria Mariane Oliveira Póvoa, Bruna Rocha Vergílio, Graziele Cristina Pavan Furlin, Marcia Torresan Delamain, Gislaine Borba Duarte, Carmino Antonio Souza, Erich V De Paula, Katia B Pagnano
Journal: Blood (2019)
Use of Antagonists in Drug-Induced Coma
Authors: Jerome T. Fishgold
Journal: JAMA (1963)

<h3>To the Editor:</h3> —I wish to take violent exception to the bold-face initial conclusion that was reached in the article "The Use of Antagonists in Drug-Induced Coma," by Adriani and Arens, in the March 10 issue ofThe Journal(<b>179:</b>752-758). It was stated that: "Her recovery was clearly due to the use of a respirator and administration of picrotoxin." The conclusion that the patient recovered because of the administration of picrotoxin is not borne out in a closer reading of the case report. The patient was not in very bad shape when therapy with picrotoxin was begun. She was not in shock and she<i>was</i>breathing. From the description of the patient, I believe that the use of analeptics was unwarranted at this stage of the game. Administration of picrotoxin was begun, and then the patient was "hooked." When an attempt was made to stop the picrotoxin, the patient
Polatuzumab Vedotin, an Antibody-Drug Conjugate Targeting CD79b, Is a Highly Active Agent Against Burkitt Lymphoma and Primary Mediastinal B-Cell Lymphoma
Authors: Anthony N. Audino, Matthew J. Barth, Aradhana Tiwari, Dina Edani, Janet Ayello, Lauren Harrison, Erin Morris, Jessica C. Hochberg, Stanton Goldman, Christian Klein, Mitchell S Cairo
Journal: Blood (2019)
Evaluation of the Human Factor IX Gene Therapy Vector TAK-748 in Hemophilia: Results from Non-Clinical Studies in Factor IX Knockout Mice and Rhesus Monkeys
Authors: Markus Weiller, Helen Wang, Sogué Coulibaly, Maria Schuster, Hanspeter Rottensteiner, Kefeng Sun, Marinee K Chuah, Thierry Vandendriessche, Friedrich Scheiflinger, Werner Höllriegl
Journal: Blood (2019)