tbuckley/cabot-search huggingface dataset:
K13-Propeller Mutations and Malaria Resistance
Authors: Johanna P. Daily
Journal: New England Journal of Medicine (2016)

Resistance has emerged to artemisinin, the backbone of combination therapy for the treatment of Plasmodium falciparum malaria. This week in the Journal, Ménard et al. present a global map of artemisinin genotypic resistance to inform strategies for the control and treatment of malaria.1 Artemisinin filled a critical gap created by chloroquine resistance and was designated more than a decade ago by the World Health Organization (WHO) as the drug of choice to be used in combination for malaria treatment.2 Artemisinin is the most effective drug for severe malaria.3 Furthermore, in addition to clearing the disease-causing asexual blood stages, artemisinin also . . .
Soundings: Protect and survive
Authors: Trisha Greenhalgh
Journal: BMJ (2002)

It was one of those dinner parties. At one end of the table, the men had bonded and were talking fast cars and weapons of mass destruction. At the other end, we women were politely discussing kitchen units and natural health remedies.

My opinion was being sought for a straw poll. Was I taking that new wheat-based alternative to hormone replacement therapy? I deferred, saying I didn't need any form of HRT yet. The lifestyle guru on my left corrected me: the latest research has apparently shown that the earlier everyone starts, the better. The notion that one's metabolic needs suddenly change at the climacteric is a myth scandalously perpetrated by male gynaecologists. I should start right now and take a glassful every morning, with natural yoghurt and linseed oil.

By way of apology for my wayward views, I confessed that I was a conventional doctor. A pause. Then three of them asked the same question all at once. Was I, or had I ever been, a member of any organisation that condoned the administration of the measles, mumps, and rubella (MMR) vaccines to a vulnerable infant via a common needle? I admitted that I was.

A beauty therapist proposed the hypothesis that doctors would inject anyone with anything in order to make money. Absolutely, I said, knocking back my wine and warming to my demonic role. For fifty pence, I'd pump my grandmother full of genetically modified steroids and infuse my children with bovine tuberculosis.

Nervous titters, then someone announced that it was no laughing matter. The health risks of vaccination were enormous, which was why not a single parent in her postnatal yoga class had allowed their child to have the pertussis jab, let alone the MMR. A private paediatrician in Harley Street could provide exactly the same protection at no risk through a combination of homoeopathy and Chinese herbs. The lifestyle guru nodded approvingly and lit a cigarette.

The men's conversation drifted from the other end of the table. The United Nations weapons inspectors' report was due out any day, which meant that a bioterrorist attack was probably imminent. The women fell silent. Someone wanted to know if I did any private work. I replied that we all had our price. In that case, they asked, could I get them each a smallpox jab?
Topical tofacitinib for atopic dermatitis: a phase<scp>II</scp>a randomized trial
Authors: R. Bissonnette, K.A. Papp, Y. Poulin, M. Gooderham, M. Raman, L. Mallbris, C. Wang, V. Purohit, C. Mamolo, J. Papacharalambous, W.C. Ports
Journal: British Journal of Dermatology (2016)

Despite unmet need, 15 years have passed since a topical therapy with a new mechanism of action for atopic dermatitis (AD) has been approved. Janus kinase (JAK) inhibitor treatment effect via topical application in patients with AD is unknown. Tofacitinib, a small‐molecule JAK inhibitor, was investigated for the topical treatment of AD. In this 4‐week, phase IIa, randomized, double‐blind, vehicle‐controlled study (NCT02001181), 69 adults with mild‐to‐moderate AD were randomized 1:1 to 2% tofacitinib or vehicle ointment twice daily. Percentage change from baseline (CFB) in Eczema Area and Severity Index (EASI) score at week 4 was the primary end point. Secondary efficacy end points included percentage CFB in body surface area (BSA), CFB in EASI Clinical Signs Severity Sum Score, proportion of patients with Physician's Global Assessment (PGA) response and CFB in patient‐reported pruritus. Safety, local tolerability and pharmacokinetics were monitored. The mean percentage CFB at week 4 in EASI score was significantly greater (P < 0·001) for tofacitinib (−81·7%) vs. vehicle (−29·9%). Patients treated with tofacitinib showed significant (P < 0·001) improvements vs. vehicle across all prespecified efficacy end points and for pruritus at week 4. Significant improvements in EASI, PGA and BSA were observed by week 1 and improvements in pruritus were observed by day 2. Safety/local tolerability were generally similar for both treatments, although more adverse events were observed for vehicle vs. tofacitinib. Tofacitinib ointment showed significantly greater efficacy vs. vehicle across end points, with early onset of effect and comparable safety/local tolerability to vehicle. JAK inhibition through topical delivery is potentially a promising therapeutic target for AD.
Prevention of stomatitis in patients with hormone receptor–positive advanced breast cancer treated with everolimus plus exemestane: A phase II study of a steroid-based mouthwash.
Authors: Hope S. Rugo, Mark Steven Chambers, Jennifer Keating Litton, Ingrid A. Mayer, Jaqueline Willemann Rogerio, Lisa Renee DeMars, Jose Geronimo, Ghulam Warsi, Timothy F. Meiller
Journal: Journal of Clinical Oncology (2014)

TPS661 Background: Stomatitis is a frequent adverse event associated with the oral mTOR inhibitor everolimus that can impact treatment adherence. Steroid mouthwashes, gels, or pastes used to treat recurrent aphthous stomatitis have been proposed as potential preventive therapies. This phase II, single-arm study will evaluate a steroid-based therapeutic intervention to prevent stomatitis (grade ≥2) in breast cancer patients taking everolimus + exemestane. Methods: Eligibility includes patients with HR-positive, HER2-negative advanced breast cancer, no evidence of stomatitis or other oral pathology, and a plan to start therapy with everolimus + exemestane. A baseline oral assessment will be conducted. Treatment consists of a steroid-based mouthwash (alcohol-free 0.5 mg/5 mL dexamethasone solution), swished in the mouth for a minimum of 2 minutes 4 times per day, starting on the first day of everolimus and exemestane administration. Patients will be instructed to abstain from eating or drinking for at least 1 hour after using the mouthwash. Preventive therapy will continue for 56 days, with optional continued use for an additional 56 days. The primary endpoint of this trial is the incidence of stomatitis (grade ≥2) at 56 days, defined as meeting at least 1 of the following criteria: ≤50 on Normalcy of Diet Scale to assess oral intake and a rating of 7 on two consecutive days or a rating of 8, 9, or 10 on any one day using a visual analog scale to assess oral pain. Secondary endpoints include average number of times per day the mouthwash regimen was performed and time to resolution of stomatitis (grade ≥2). Assuming a 13% absolute reduction in the rate of grade ≥2 stomatitis from the historical control rate of 33% and 1-sided type 1 error = 0.05 and power = 80%, 73 evaluable patients are required. To account for an estimated 25% of the total patient population being nonevaluable, 97 patients will be enrolled. Support: Novartis Pharmaceuticals Corporation. Clinical trial information: NCT02069093.
CBM-16TUMOR-EDUCATED PLATELET-BASED LIQUID BIOPSIES IN GLIOBLASTOMA PATIENTS
Authors: Nik Sol, Myron Best, Pepijn Schellen, Francois Rustenburg, Sjors in 't Veld, Edward Post, Heleen Verschueren, Jonas Nilsson, Davis Noske, Bauke Ylstra, Henk Verheuk, Bakhos Tannous, Pieter Wesseling, Jaap Reijneveld, Thomas Wurdinger
Journal: Neuro-Oncology (2015)

INTRODUCTION: Blood-based liquid biopsies are a potential approach for leveraging clinical cancer diagnostics and patients' treatment. However, so far, diagnostic, prognostic, predictive, and monitoring biomarkers for patients with diffuse glioma are only limitedly available, and require further validation. Tumor-educated blood platelets (TEPs) sequester several biomolecules, including EGFRvIII mRNA, during tumor growth, thereby altering their RNA profile. Therefore, we reasoned that TEPs may serve as an potential biosource for blood-based biomarkers. METHODS: Blood platelets of patients with glioblastoma and healthy individuals were isolated and subjected to total RNA isolation. Platelet mRNA was amplified using full-length SMARTer mRNA amplification, and processed for sequencing on the Illumina platform. Raw sequencing data was aligned and summarized to the human reference genome using STAR and HTseq, and subjected to differential expression analyses, hierarchical clustering and support vector machine (SVM) classification. RESULTS: We characterized the platelet RNA of 39 glioblastoma patients, and 52 healthy individuals by high-throughput RNA-sequencing. Glioblastoma patient-derived TEPs contained 457 RNAs (FDR < 0.001) that were differentially expressed as compared to healthy individuals. Gene ontology showed that these RNAs are implicated in several biological processes such as RNA translation, immune response, and DNA repair. Using SVM classification we readily separated both groups from each other (accuracy: 94%, AUC: 0.982). CONCLUSIONS AND FUTURE EXPERIMENTS: Our results suggest that TEPs harbour potential as a diagnostic biosource. To further evaluate the biomarker potential, follow-up studies using additional samples, including samples of lower grade glioma and brain metastases patients are under way. Furthermore, we have initiated the collection of clinical follow-up platelet samples to identify the potential of TEPs as disease monitoring biomarkers in glioma patients. Eventually, we believe TEPs have the potential to guide clinical decision making in every day practice.
Case 41-1969
Authors: Raymond D. Adams, William C. Schoene, Benjamin Castleman
Journal: New England Journal of Medicine (1969)

Presentation of Case First admission. A sixty-two-year-old woman was admitted to the hospital because of headaches and depression.She had been depressed since the death of her husband three years previously. For many years she had been treated for hypertension; one month before admission reserpine therapy was started. Subsequently, nasal congestion and headaches developed, and she became more depressed. The reserpine was discontinued after two weeks. Dull, severe headaches in the vertex and depression persisted. There was no vertigo, visual change, hearing loss or weight change.The patient was an alert and Cooperative right-handed woman who appeared well. The eyes, . . .
A roadmap for MERS-CoV research and product development: report from a World Health Organization consultation
Authors: Kayvon Modjarrad, Vasee S Moorthy, Peter Ben Embarek, Maria Van Kerkhove, Jerome Kim, Marie-Paule Kieny
Journal: Nature Medicine (2016)

As part of the World Health Organization (WHO) R&D Blueprint initiative, leading stakeholders on Middle East respiratory syndrome coronavirus (MERS-CoV) convened to agree on strategic public-health goals and global priority research activities that are needed to combat MERS-CoV.
Abstract 1183: Metabolic characterization of follicular lymphoma transformation
Authors: Brad Poore, Ana Ortega-Molina, Christopher Nguyen, Liang Zhao, Anne Blackwell, Thomas Hartung, Hans-Guido Wendel, Anne Le
Journal: Cancer Research (2015)

Abstract Follicular lymphoma (FL), a form of non-Hodgkin lymphoma, is the second most common form of B-cell lymphoma and remains incurable in the majority of cases despite recent advances in therapy. Following an indolent phase, 50% of patients suffer disease transformation to an aggressive form of lymphoma (transformed FL; tFL). This dramatic switch in disease behavior typically culminates in rapid deterioration and patient demise. Accordingly, much effort has been focused on understanding the genetics of transformation and has resulted in the identification of key genetic lesions (e.g. MYC activation, loss of p53, cell cycle controls, activation of NFKB (TNFAIp3/A20)). However, exactly how tumor metabolism, which is altered by these genetic lesions, contributes to disease aggressiveness is not known and therefore the metabolic changes that occur upon FL transformation are poorly understood. We have developed a murine model of FL transformation that recapitulates key genetic and pathological aspects of human FL (Oricchio et al, 2011). This model allows us to study the genetics and metabolism of FL transformation. Specifically, we will systematically define the metabolic profiles of genetically defined murine lymphomas that represent different stages of transformation and cross-compare metabolic changes to primary patient samples. This ensures focus on clinically relevant changes and provides metabolic annotation of distinct tumor genotypes. This study builds on the complementary strengths of the Le lab (Johns Hopkins) in cancer metabolism and the Wendel lab (MSKCC) in modeling FL genetics. Our study shows that MYC transformed FL exhibits a distinct metabolic profile as compared to indolent follicular lymphoma or normal spleen. The most altered pathways examined thus far are glycolysis and amino acid metabolism. We believe that the transformed lymphoma is more reliant upon glycolysis and may be exhibiting aerobic glycolysis, also known as the Warburg Effect. This is substantiated from previous experiments in which a Burkitt lymphoma line, also overexpressing MYC, was found to have altered glycolytic intermediates levels. We next plan to examine the metabolic profile of other transformed follicular lymphoma models of known genetic backgrounds. We will also cross validate the transformed mouse models with follicular lymphoma patient samples of known genetic backgrounds to identify potential metabolic markers. Citation Format: Brad Poore, Ana Ortega-Molina, Christopher Nguyen, Liang Zhao, Anne Blackwell, Thomas Hartung, Hans-Guido Wendel, Anne Le. Metabolic characterization of follicular lymphoma transformation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1183. doi:10.1158/1538-7445.AM2015-1183
神経制御 : 交感神経と迷走神経制御 (特集 最新の急性心不全治療 : 急性期から慢性期への移行を踏まえて) -- (血圧および循環血液量の制御システムとその制御機構の障害)
Authors: 拓弥 岸
Journal: Circulation (2014)
Blue remembered hills
Authors: Fiona Godlee
Journal: BMJ (2016)

We’ve heard a lot about intergenerational strife since the United Kingdom voted to leave the European Union in last month’s referendum. Younger voters, who overwhelmingly voted to remain, feel betrayed. Older voters, with less of a lifetime to lose, are accused of harbouring unrealistic nostalgia for a Britain that never existed. Something similar afflicts the dispute over the junior doctor contract, which reached another milestone this week as juniors voted to reject the latest offer (doi:10.1136/bmj.i3749). Although many senior colleagues are vocal in their support, mutterings from …
P-236 Screening practices of Australians at population and familial risk following the partial roll-out of the National Bowel Cancer Screening Program, 2009-2012
Authors: L. Flander, M. Jenkins, K. Win Aung, A. Boussioutas, J. Hopper, G. Giles, I. Winship, F. Macrae, D. Ait Ouakrim
Journal: Annals of Oncology (2016)
Clinical chemosensitization by misonidazole and related compounds: a critical evaluation.
Authors: R T Mulcahy, D L Trump
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.4.569 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3357002 Clinical chemosensitization by misonidazole and related compounds: a critical evaluation. R T MulcahyxR T MulcahySearch for articles by this author , D L TrumpxD L TrumpSearch for articles by this author Show More University of Wisconsin Clinical Cancer Center, Madison. https://doi.org/10.1200/JCO.1988.6.4.569 First Page PDF © 1988 by American Society of Clinical Oncology
PTCT-03RELAPSE MEDULLOBLASTOMA IN INFANT: COMPLETE RESPONSE WITH TEMOZOLOMIDE AND IRINOTECAN
Authors: Sébastien Perreault
Journal: Neuro-Oncology (2015)

Infants with relapse medulloblastoma (MB) usually have a dismal prognosis with an overall survival of less than 25%. Currently, there is no standard therapy established for recurrent MB. The combination of temozolomide and irinotecan has been investigated with variable results with a response rate approaching 30%. We report a 30 months old infant with prolonged and drastic response to this chemotherapy combination. This young infant presented at 9 months old with a two weeks history of bulging fontanelle and VI nerve palsy. Brain MRI showed a fourth ventricular mass with hydrocephalus. There was no evidence of metastatic dissemination. She underwent a complete resection. Pathology was compatible with a non-WNT, non-SHH classic MB. Cerebrospinal fluid was negative. Due to her age, she initially received two cycles of chemotherapy including cisplatin, cyclophosphamide, vincristine and high-dose of IV methotrexate. Unfortunately, she progressed locally and received local radiotherapy to 54 Gy. MRI conducted after radiotherapy showed a complete response of the targeted lesion but new leptomeningeal lumbar dissemination. She then received temozolomide (150 mg/m2 PO for 5 days) with irinotecan (50 mg/m2 IV for 5 days) for 12 cycles. She had a complete radiographic response and chemotherapy was withheld. However, on surveillance MRI two months later, she was found to have recurrent leptomeningeal disease involving lumbar spine. Temozolomide and irinotecan was restarted and a significant radiographic response was observed. We achieved a complete radiographic response in an infant with relapse MB whereas her tumor was resistant to conventional chemotherapy. Subtypes of medulloblastoma appear to respond drastically to temozolomide and irinotecan and this regimen offers an interesting option. However, the addition of other treatments modalities is essential to achieve a prolonged survival. The ongoing Children Oncology Group trial will likely assess the efficacy of this regimen with and without bevacizumab.
Twentieth-century psychiatry: a view from the sea
Authors: L L Havens
Journal: American Journal of Psychiatry (1981)

The author presents a broad view of the principal forces at work in twentieth-century psychiatry. He describes the approach of the various psychiatries--psychoanalytic, biological, behaviorist, social, interpersonal, and existential--to the diagnostic enterprise and the therapeutic enterprise. He finds twentieth-century diagnosis dominated by objective-descriptive psychiatry and therapy by the extraordinary growth of psychotherapy in the industrial nations. The newer psychotherapeutic methods have made the first systematic additions since Freud to our understanding of the ways in which personal change occurs.
A phase II study of two dose levels of ofatumumab induction followed by maintenance therapy in symptomatic, previously untreated chronic lymphocytic leukemia
Authors: Ian W. Flinn, Amy S. Ruppert, William Harwin, David Waterhouse, Steven Papish, Jeffrey A. Jones, John Hainsworth, John C. Byrd
Journal: American Journal of Hematology (2016)

Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib, availability of nonchemotherapy based therapies is desired. Given the 58% response rate (1996 NCI‐WG criteria) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab, we initiated a phase II trial examining response, safety, and progression‐free survival (PFS) of ofatumumab as front‐line monotherapy. Patients enrolled included untreated, symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy. Two cohorts were enrolled sequentially examining either 1 g (33 patients) or 2 g (44 patients) weekly for 8 weeks followed by maintenance dosing every 2 months for a total of 24 months. Patients receiving 1 g were older than those receiving 2 g, but there were no significant differences in other clinical characteristics. The best overall response rates in the 1 and 2 g patient cohorts were 72 and 89% (1996 NCI‐WG criteria), respectively (54 and 68%, respectively, using 2008 IWCLL criteria). All but two responses were partial. The 24‐month estimated PFS rates were 46 and 78%, respectively. Response and PFS was lower in del(17p) and del(11q) CLL patients. Differences in PFS between dose cohorts were statistically significant and remained so when adjusting for age or high‐risk cytogenetics. Toxicity of this treatment was mild with only six patients not completing therapy due to toxicity. Ofatumumab induction followed by maintenance therapy in untreated CLL represents a well‐tolerated and active regimen, particularly with the 2 g of ofatumumab. Am. J. Hematol. 91:1020–1025, 2016. © 2016 Wiley Periodicals, Inc.
Low Circulating Mannan-Binding Leptin Levels Correlate with Increased Number of Febrile Episodes in Myeloma Patients Who Undergo High Dose Melphalan with Autologous Hematopoietic Stem Cell Transplantation and Do Not Receive Antibiotic Prophylaxis
Authors: Evangelos Eleutherakis-Papaiakovou, Evangelos Terpos, Dimitrios Christoulas, Magdalini Migkou, Efstathios Kastritis, Maria Gkotzamanidou, Nikitas Nikitas, Efstathios Manios, Meletios Athanasios Dimopoulos, Christos Papadimitriou
Journal: Blood (2011)
Cdx4 Upregulates Hox Gene Expression and Generates Acute Myeloid Leukemia Alone and in Cooperation with Meis1a in a Murine Model.
Authors: Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Dohner, Patricia Ernst, Alan J. Davidson, George Q. Daley, Leonard I. Zon, D. Gary Gilliland, Brian J. Huntly
Journal: Blood (2006)
Aberrant Repertoire and Deficient Proliferation of TCR γδ T Cells in Myelodysplastic Syndromes (MDS).
Authors: Jean-Jacques Kiladjian, Géraldine Visentin, Emilie Viey, Sameh Ayari, Jean-Henri Bourhis, Salem Chouaib, Pierre Fenaux, Anne Caignard
Journal: Blood (2006)
Social ecological complexity and resilience processes
Authors: Michael Ungar
Journal: Behavioral and Brain Sciences (2015)

Abstract A social ecological model of resilience avoids the reductionism of simple explanations of the complex and multisystemic processes associated with well-being in contexts of adversity. There is evidence that when stressors are abnormally high, environmental factors account for more of an individual's resilience than do individual traits or cognitions. In this commentary, a social ecological model of resilience is discussed.
Thyrotropin-releasing hormone in schizophrenia
Authors: K L Davis, L E Hossister, P A Berger
Journal: American Journal of Psychiatry (1975)

Oral administration of thyrotropin-releasing hormone (TRH) caused deterioration in the clinical status of seven out of nine schizophrenic men. This change was particularly apparent in the four patients diagnosed as paranoid schizophrenics. Such changes might be expected from a drug with properties similar to amphetamine.