tbuckley/cabot-search huggingface dataset:
Defining Disease Severity in Inflammatory Bowel Diseases: Current and Future Directions
Authors: Laurent Peyrin-Biroulet, Julián Panés, William J. Sandborn, Séverine Vermeire, Silvio Danese, Brian G. Feagan, Jean-Frédéric Colombel, Stephen B. Hanauer, Beth Rycroft
Journal: Clinical Gastroenterology and Hepatology (2015)

Although most treatment algorithms in inflammatory bowel disease (IBD) begin with classifying patients according to disease severity, no formal validated or consensus definitions of mild, moderate, or severe IBD currently exist. There are 3 main domains relevant to the evaluation of disease severity in IBD: impact of the disease on the patient, disease burden, and disease course. These measures are not mutually exclusive and the correlations and interactions between them are not necessarily proportionate. A comprehensive literature search was performed regarding current definitions of disease severity in both Crohn's disease and ulcerative colitis, and the ability to categorize disease severity in a particular patient. Although numerous assessment tools for symptoms, quality of life, patient-reported outcomes, fatigue, endoscopy, cross-sectional imaging, and histology (in ulcerative colitis) were identified, few have validated thresholds for categorizing disease activity or severity. Moving forward, we propose a preliminary set of criteria that could be used to classify IBD disease severity. These are grouped by the 3 domains of disease severity: impact of the disease on the patient (clinical symptoms, quality of life, fatigue, and disability); measurable inflammatory burden (C-reactive protein, mucosal lesions, upper gastrointestinal involvement, and disease extent), and disease course (including structural damage, history/extension of intestinal resection, perianal disease, number of flares, and extraintestinal manifestations). We further suggest that a disease severity classification should be developed and validated by an international group to develop a pragmatic means of identifying patients with severe disease. This is increasingly important to guide current therapeutic strategies for IBD and to develop treatment algorithms for clinical practice.
The worldwide spread of ciprofloxacin-resistant Shigella sonnei among HIV-infected men who have sex with men, Taiwan
Authors: C.-S. Chiou, H. Izumiya, M. Kawamura, Y.-S. Liao, Y.-S. Su, H.-H. Wu, W.-C. Chen, Y.-C. Lo
Journal: Clinical Microbiology and Infection (2016)
Diabetes and the Association of Postoperative Hyperglycemia With Clinical and Economic Outcomes in Cardiac Surgery
Authors: Giampaolo Greco, Bart S. Ferket, David A. D’Alessandro, Wei Shi, Keith A. Horvath, Alexander Rosen, Stacey Welsh, Emilia Bagiella, Alexis E. Neill, Deborah L. Williams, Ann Greenberg, Jeffrey N. Browndyke, A. Marc Gillinov, Mary Lou Mayer, Jessica Keim-Malpass, Lopa S. Gupta, Samuel F. Hohmann, Annetine C. Gelijns, Patrick T. O'Gara, Alan J. Moskowitz
Journal: Diabetes Care (2016)

OBJECTIVE The management of postoperative hyperglycemia is controversial and generally does not take into account pre-existing diabetes. We analyzed clinical and economic outcomes associated with postoperative hyperglycemia in cardiac surgery patients, stratifying by diabetes status. RESEARCH DESIGN AND METHODS Multicenter cohort study in 4,316 cardiac surgery patients operated on in 2010. Glucose was measured at 6-h intervals for 48 h postoperatively. Outcomes included cost, hospital length of stay (LOS), cardiac and respiratory complications, major infections, and death. Associations between maximum glucose levels and outcomes were assessed with multivariable regression and recycled prediction analyses. RESULTS In patients without diabetes, increasing glucose levels were associated with a gradual worsening of outcomes. In these patients, hyperglycemia (≥180 mg/dL) was associated with an additional cost of $3,192 (95% CI 1,972 to 4,456), an additional hospital LOS of 0.8 days (0.4 to 1.3), an increase in infections of 1.6% (0.5 to 2.8), and an increase in respiratory complications of 2.6% (0.0 to 5.3). However, among patients with insulin-treated diabetes, optimal outcomes were associated with glucose levels considered to be hyperglycemic (180 to 240 mg/dL). This level of hyperglycemia was associated with cost reductions of $6,225 (−12,886 to −222), hospital LOS reductions of 1.6 days (−3.7 to 0.4), infection reductions of 4.1% (−9.1 to 0.0), and reductions in respiratory complication of 12.5% (−22.4 to −3.0). In patients with non–insulin-treated diabetes, outcomes did not differ significantly when hyperglycemia was present. CONCLUSIONS Glucose levels &amp;lt;180 mg/dL are associated with better outcomes in most patients, but worse outcomes in patients with diabetes with a history of prior insulin use. These findings support further investigation of a stratified approach to the management of patients with stress-induced postoperative hyperglycemia based on prior diabetes status.
Topical corticosteroid has no influence on inflammation or efficacy after ingenol mebutate treatment of grade I to III actinic keratoses (AK): A randomized clinical trial
Authors: Andrés Már Erlendsson, Katrine Elisabeth Karmisholt, Christina Skovbølling Haak, Ida-Marie Stender, Merete Haedersdal
Journal: Journal of the American Academy of Dermatology (2016)
Generation and utilization of polyfunctional anti-tumor CD4+ T cells
Authors: Gang Zhou, Zhi-Chun Ding
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts There is accumulating evidence that polyfunctional T cells, effector T cells capable of simultaneously producing multiple pro-inflammatory cytokines, are more efficacious in controlling infection and cancer. However, how polyfunctional CD4+ effector cells are induced is not
More use should be made of specialist nurses
Authors: I. Kunkler, A. Tierney, N. Jodrell, J. Forbes
Journal: BMJ (1996)

Routine follow up ofbreast cancer in primary care Follow up by non-specialists should not be encouraged EDITOR,-While I welcome new initiatives in the management of breast cancer, I believe that the study by Eva Grunfeld and colleagues must be interpreted with caution.'The authors report no delay in the diagnosis of recurrent breast cancer or reduction in the quality of life of patients randomised to follow up by their general practitioner, but their conclusions must be questioned.The data on recurrence are based on a short follow up (18 months) and small numbers (10 women followed up by their general practitioner, 16 followed up in hospital), and the comparisons of quality of life are flawed.Women randomised to follow up by their general practitioner knew that they were under special surveillance, which is different from being "discharged" from hospital.A third of women declined to enter the trial even under these circumstances.Guidelines drawn up by the breast surgeons' group of the British Association of Surgical Oncology recommend that a breast clinic sees a minimum of 50 cancers a year, rising to 100-150 to be cost effective,2 and this view is endorsed by the senate of the royal surgical colleges.Grunfeld and colleagues' study seems to lend support to
Immune Tolerance for Autoimmune Disease and Cell Transplantation
Authors: Xunrong Luo, Stephen D. Miller, Lonnie D. Shea
Journal: Annual Review of Biomedical Engineering (2016)

The undesired destruction of healthy cells, either endogenous or transplanted, by the immune system results in the loss of tissue function or limits strategies to restore tissue function. Current therapies typically involve nonspecific immunosuppression that may prevent the appropriate response to an antigen, thereby decreasing humoral immunity and increasing the risks of patient susceptibility to opportunistic infections, viral reactivation, and neoplasia. The induction of antigen-specific immunological tolerance to block undesired immune responses to self- or allogeneic antigens, while maintaining the integrity of the remaining immune system, has the potential to transform the current treatment of autoimmune disease and serve as a key enabling technology for therapies based on cell transplantation.
TGFβ and activin A control regulatory T cells in irradiated tumors
Authors: Claire Vanpouille-Box, Silvia Formenti, Sandra Demaria
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Transforming Growth Factor-beta (TGFβ) and activin A (actA) are members of the TGFβ superfamily and display overlapping biological activities, including the ability to promote the conversion of conventional CD4 T cells to regulatory T cells (Tregs). We have recently shown that
Effect of process parameters on the recrystallization and size control of puerarin using the supercritical fluid antisolvent process
Authors: Ying Li, Yibin Yu, Hanbing Wang, Fengguang Zhao
Journal: Asian Journal of Pharmaceutical Sciences (2016)

The purpose of this study was to investigate the influence of the supercritical CO2 processing on the particle size and morphology of puerarin crystals. The process parameters included solvents, temperature, pressures, antisolvent times, addition volumes, antisolvent addition rates and solute concentrations. After being processed, the dramatic reduction of the dimensions and the change of the crystal shape were noticed. Decreasing the antisolvent addition rate, increasing the temperature and the addition volume below 50 ml led to a decrease in size. The new crystal of puerarin generated at the optimal conditions was 30.34 µm. The solvent of methanol and the concentration of 60 mg/ml were found to determine the type and degree of crystallinity of particles. These results showed that this process has the potential to produce a drug recrystallization product with newly generated crystal forms and the size of drug particles could be controlled through the tuning of various experimental conditions.
Minds, brains, and programs
Authors: John R. Searle
Journal: Behavioral and Brain Sciences (1980)

Abstract This article can be viewed as an attempt to explore the consequences of two propositions. (1) Intentionality in human beings (and animals) is a product of causal features of the brain. I assume this is an empirical fact about the actual causal relations between mental processes and brains. It says simply that certain brain processes are sufficient for intentionality. (2) Instantiating a computer program is never by itself a sufficient condition of intentionality. The main argument of this paper is directed at establishing this claim. The form of the argument is to show how a human agent could instantiate the program and still not have the relevant intentionality. These two propositions have the following consequences: (3) The explanation of how the brain produces intentionality cannot be that it does it by instantiating a computer program. This is a strict logical consequence of 1 and 2. (4) Any mechanism capable of producing intentionality must have causal powers equal to those of the brain. This is meant to be a trivial consequence of 1. (5) Any attempt literally to create intentionality artificially (strong AI) could not succeed just by designing programs but would have to duplicate the causal powers of the human brain. This follows from 2 and 4. “Could a machine think?” On the argument advanced here only a machine could think, and only very special kinds of machines, namely brains and machines with internal causal powers equivalent to those of brains. And that is why strong AI has little to tell us about thinking, since it is not about machines but about programs, and no program by itself is sufficient for thinking.
The 2015 World Health Organization Classification of Lung Tumors
Authors: William D. Travis, Elisabeth Brambilla, Andrew G. Nicholson, Yasushi Yatabe, John H.M. Austin, Mary Beth Beasley, Lucian. R. Chirieac, Sanja Dacic, Edwina Duhig, Douglas B. Flieder, Kim Geisinger, Fred R. Hirsch, Yuichi Ishikawa, Keith M. Kerr, Masayuki Noguchi, Giuseppe Pelosi, Charles A. Powell, Ming Sound Tsao, Ignacio Wistuba
Journal: Journal of Thoracic Oncology (2015)
Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial
Authors: Kazumasa Fujitani, Han-Kwang Yang, Junki Mizusawa, Young-Woo Kim, Masanori Terashima, Sang-Uk Han, Yoshiaki Iwasaki, Woo Jin Hyung, Akinori Takagane, Do Joong Park, Takaki Yoshikawa, Seokyung Hahn, Kenichi Nakamura, Cho Hyun Park, Yukinori Kurokawa, Yung-Jue Bang, Byung Joo Park, Mitsuru Sasako, Toshimasa Tsujinaka
Journal: The Lancet Oncology (2016)
Maraviroc contributes to the restoration of the homeostasis of regulatory T-cell subsets in antiretroviral-naive HIV-infected subjects
Authors: M.M. Pozo-Balado, I. Rosado-Sánchez, G. Méndez-Lagares, M.M. Rodríguez-Méndez, E. Ruiz-Mateos, M.R. Benhnia, M.A. Muñoz-Fernández, M. Leal, Y.M. Pacheco
Journal: Clinical Microbiology and Infection (2016)
Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial
Authors: Nadia Harbeck, Chiun-Sheng Huang, Sara Hurvitz, Dah-Cherng Yeh, Zhimin Shao, Seock-Ah Im, Kyung Hae Jung, Kunwei Shen, Jungsil Ro, Jacek Jassem, Qingyuan Zhang, Young-Hyuck Im, Marek Wojtukiewicz, Qiang Sun, Shin-Cheh Chen, Rainer-Georg Goeldner, Martina Uttenreuther-Fischer, Binghe Xu, Martine Piccart-Gebhart
Journal: The Lancet Oncology (2016)
Clinical scale labeling of T cell immunotherapy for MRI cell tracking
Authors: Brooke M Helfer, William Shingleton, Shannon Eaker, Charles O'Hanlon, Eric Ahrens
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Leukocyte immunotherapies have made a great progress and hold much promise in the treatment of cancer. Specifically, in the case of B cell malignancies (such as Acute Lymphoblastic Leukemia, or ALL), CAR (chimeric antigen receptor) and TCR (T cell receptor) cell therapies have
Association of Shiny White Blotches and Strands With Nonpigmented Basal Cell Carcinoma
Authors: Cristián Navarrete-Dechent, Shirin Bajaj, Michael A. Marchetti, Harold Rabinovitz, Stephen W. Dusza, Ashfaq A. Marghoob
Journal: JAMA Dermatology (2016)

Basal cell carcinoma (BCC) is the most common type of skin cancer and is usually nonpigmented. Shiny white structures (SWSs) are frequently present in BCC.To determine the diagnostic accuracy of various morphologies of SWSs for diagnosis of nonpigmented BCC.Nonpigmented skin tumors, determined clinically and dermoscopically, were identified from a database of lesions consecutively biopsied over a 3-year period (January 2, 2009, to December 31, 2012) from a single dermatology practice. Data analysis was conducted from October 9, 2014, to November 15, 2015. Investigators blinded to histopathologic diagnosis evaluated the polarized dermoscopic images for the presence of SWSs, which were categorized as blotches, strands, short white lines, and rosettes. Measures of diagnostic accuracy for BCC were estimated. Participants included 2375 patients from a dermatologic clinic in Plantation, Florida. Review of the medical records identified 2891 biopsied skin lesions; 457 of these were nonpigmented neoplasms.Diagnosis of BCC with dermoscopy compared with all other diagnoses combined was the primary outcome; the secondary outcome was diagnosis of BCC compared with amelanotic melanoma. We calculated diagnostic accuracy measured as odds ratios (ORs), sensitivity, and specificity of shiny white blotches and/or strands for the diagnosis of BCC.Of the 457 nonpigmented neoplasms evaluated, 287 (62.8%) were BCCs, 106 (23.2%) were squamous cell carcinoma, 39 (8.5%) were lichen planus-like keratosis, 21 (4.6%) were melanomas, and 4 (0.9%) were nevi. The prevalence of SWSs was 49.0% (n = 224). In multivariate analysis (reported as OR [95% CI]) controlling for age, sex, and anatomical location, the presence of any SWS was associated with a diagnosis of BCC (2.3 [1.5-3.6]; P < .001). Blotches (6.3 [3.6-10.9]; P < .001), strands (4.9 [2.9-8.4]; P < .001), and blotches and strands together (6.1 [3.3-11.3]; P < .001) were positively associated with BCC. Shiny white blotches and strands together had a diagnostic sensitivity of 30% and specificity of 91%.The combined presence of shiny white blotches and strands is associated with high diagnostic specificity for nonpigmented BCC.
Il-6 is non-essential to murine CD19 CAR efficacy, but can mediate acute GVHD following allogeneic BMT with CAR T cell infusion
Authors: Elad Jacoby, Haiying Qin, James Kochenderfer, Yinmeng Yang, Chris Chien, Terry Fry
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Chimeric-antigen-receptor (CAR) T cells targeting CD19 show dramatic remissions in refractory or relapsed acute lymphoblastic leukemia. Interleukin-6 (IL-6) has been associated with severe cytokine release syndrome (CRS) following CAR T cell treatment, leading to significant
Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma.
Authors: R Pazdur, E Diaz-Canton, W P Ballard, J E Bradof, S Graham, S G Arbuck, J L Abbruzzese, R Winn
Journal: Journal of Clinical Oncology (1997)

The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, was selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents. We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma.Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days). Patients were assessed for response after two courses.Seventeen patients with metastatic colorectal cancer were entered onto this trial. No complete or partial responses were noted. Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute granulocyte count (AGC) was 1,500/microL. The median number of courses given was two and the median time to disease progression was 8 weeks.At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer. 9-AC infusion schedules of longer duration are currently being investigated in this disease.
P0973 : Quercetin ameliorates MCD-induced non-alcoholic fatty liver disease in mice by modulating inflammatory, oxidative/nitrosative stress and lipid metabolism-related gene deregulation via the PI3K/AKT pathway
Authors: S. Pisonero-Vaquero, Á. Martínez-Ferreras, M.V. García-Mediavilla, S. Martínez-Flórez, A. Fernández, M. Benet, J.L. Olcoz, R. Jover, J. González-Gallego, S. Sánchez-Campos
Journal: Journal of Hepatology (2015)
Abstract P1-12-14: Retinoic acid sensitizes triple-negative breast cancer cells to tamoxifen treatment
Authors: Krysta M Coyle, Cheryl A Dean, Diana B Jo, Margaret Thomas, Mohammad Sultan, Paola Marcato
Journal: Cancer Research (2015)

Abstract Tamoxifen, an estrogen receptor (ER) antagonist, is often used as an adjuvant endocrine therapy in the successful treatment of ER+ breast tumors. Tumors that lack ER, progesterone receptor (PR) and HER2 expression (i.e. triple-negative breast cancers) cannot be treated with adjuvant endocrine therapies, like tamoxifen, and are often more aggressive. Inducing ER expression is a potential strategy for sensitization of triple-negative breast cancers to adjuvant endocrine therapies. Given recent evidence suggesting cross-talk between the retinoic acid (RA) and estrogen signaling pathways, we investigated if RA induces expression of ER in triple-negative breast cancer cells. We hypothesize that this would lead to sensitization of the cells to tamoxifen treatment. Quantitative PCR of mRNA isolated from triple-negative MDA-MB-231 cells treated with RA and estradiol had increased ER transcript levels. Furthermore, treatment with estradiol and RA synergistically induced increased expression of RA-inducible genes. In cell proliferation studies, neither RA nor estradiol treatment alone significantly altered the growth of MDA-MB-231 cells; however, when treated with both estradiol and RA together, the growth of the cells increased significantly. This suggests that the RA-mediated increase in ER expression sensitizes MDA-MB-231 cells to estradiol-induced cell growth. Next, we investigated whether the increased ER expression sensitized MDA-MB-231 cells to tamoxifen treatment. Tamoxifen did not decrease the growth of MDA-MB-231 cells; however, when applied in combination with both estradiol and RA, tamoxifen significantly reduced MDA-MB-231 proliferation. Furthermore, tamoxifen treatment reduced the synergistic effects of estradiol/RA on RA-inducible gene expression. Together, these results suggest that the use of RA in combination with tamoxifen warrants further investigation as a potential treatment for triple-negative breast cancers. The success of the combination treatment of tamoxifen and RA in the reduction of triple-negative breast cancer cell tumor xenografts will provide further justification for this strategy in the treatment of triple-negative breast cancers. Citation Format: Krysta M Coyle, Cheryl A Dean, Diana B Jo, Margaret Thomas, Mohammad Sultan, Paola Marcato. Retinoic acid sensitizes triple-negative breast cancer cells to tamoxifen treatment [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-14.
A hybrid mobile approach for population-wide HIV testing in rural east Africa: an observational study
Authors: Gabriel Chamie, Tamara D Clark, Jane Kabami, Kevin Kadede, Emmanuel Ssemmondo, Rachel Steinfeld, Geoff Lavoy, Dalsone Kwarisiima, Norton Sang, Vivek Jain, Harsha Thirumurthy, Teri Liegler, Laura B Balzer, Maya L Petersen, Craig R Cohen, Elizabeth A Bukusi, Moses R Kamya, Diane V Havlir, Edwin D Charlebois
Journal: The Lancet HIV (2016)
A career in public health
Authors: James Sidebotham, Anjum Memon
Journal: BMJ (2014)

Public health is an often unseen and misunderstood   field of medicine that many medical students and junior doctors will be little exposed to as a specialty or a career option. Challenges such as tackling smoking, alcohol misuse, obesity, and infectious diseases are just a small part of the vast amount of work that goes on. The 2012 Health and Social Care Act, which brought about large scale change to the structure of health services in England, moved responsibility for public health from the NHS to local authorities. As a result, the specialty, which has never been prominent in the undergraduate medical curriculum, has become even more hidden. This article aims to explain the career opportunities available in public health—an exciting and influential specialty whose importance has been highlighted by the current Ebola virus epidemic.