tbuckley/cabot-search huggingface dataset:
Pan Canadian Rash Trial: A Randomized Phase III Trial Evaluating the Impact of a Prophylactic Skin Treatment Regimen on Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor–Induced Skin Toxicities in Patients With Metastatic Lung Cancer
Authors: Barbara Melosky, Helen Anderson, Ronald L. Burkes, Quincy Chu, Desiree Hao, Vincent Ho, Cheryl Ho, Wendy Lam, Christopher W. Lee, Natasha B. Leighl, Nevin Murray, Sophie Sun, Robert Winston, Janessa J. Laskin
Journal: Journal of Clinical Oncology (2015)

Purpose Erlotinib is an epidermal growth factor receptor inhibitor approved for patients with advanced non–small-cell lung cancer (NSCLC) whose epidermal growth factor receptor expression status is positive or unknown. Although it is efficacious, erlotinib can cause skin toxicity. This prospective, randomized phase III trial examined the effect of prophylactic treatment of erlotinib-induced skin rash. Patients and Methods Patients receiving erlotinib in the second- or third-line setting for advanced NSCLC were randomly assigned to prophylactic minocycline (100 mg twice per day for 4 weeks), reactive treatment (after rash developed, per grade of rash), or no treatment unless severe (grade 3). Rash incidence and severity, time to maximal rash, time to resolution, and overall survival (OS) were compared among treatment groups. Results In all, 150 patients were randomly assigned, 50 to each of three treatment arms. The incidence of skin toxicity was 84% regardless of treatment arm. Prophylactic treatment with minocycline significantly lengthened the time to the most severe grade of rash. Grade 3 rash was significantly higher in the no-treatment arm. OS was not significantly different among treatment arms, but patients receiving prophylactic or reactive treatments had a longer OS (7.6 and 8 months, respectively) than those who received no rash treatment (6 months). Rash was not self-limiting. Conclusion The incidence of all grades of rash did not differ statistically among the three arms, so the trial was negative. The incidence of grade 3 skin toxicities was reduced in patients who were treated with prophylactic minocycline or reactive treatment. Efficacy was not compromised. Prophylactic minocycline and reactive treatment are both acceptable options for the necessary treatment of erlotinib-induced rash in the second- or third-line setting of metastatic NSCLC.
Radiation Therapy for Hodgkin Lymphoma—Can It Be Administered More Safely if Necessary?
Authors: David J. Straus, Oren Cahlon
Journal: JAMA Oncology (2015)

This Viewpoint discusses ways to balance the benefits and harms of radiation treatment options for patients with Hodgkin lymphoma, and proposes clinical trials to test use of residual site radiation treatment after chemotherapy vs radiating all initial site of involvement alongside chemotherapy.
Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study
Authors: Ulla Uusitalo, Xiang Liu, Jimin Yang, Carin Andrén Aronsson, Sandra Hummel, Martha Butterworth, Åke Lernmark, Marian Rewers, William Hagopian, Jin-Xiong She, Olli Simell, Jorma Toppari, Anette G. Ziegler, Beena Akolkar, Jeffrey Krischer, Jill M. Norris, Suvi M. Virtanen
Journal: JAMA Pediatrics (2015)

Probiotics have been hypothesized to affect immunologic responses to environmental exposures by supporting healthy gut microbiota and could therefore theoretically be used to prevent the development of type 1 diabetes mellitus (T1DM)-associated islet autoimmunity.
Bioavailability of Trace Mineral Elements
Authors: Richard M. Forbes, John W. Erdman
Journal: Annual Review of Nutrition (1983)

INTRODUCTION          ..            ,',',, .,' 2 1 3 CHROMIUM, ......   .,         .. ,.,',   ,'',      .,.,        214 COPPER ,.    ..  ..    .,  .. ......         ... ,.,'  .,  '  215 MANGANESE,., ..        .. ,',.,        2 1 8 SELENIUM ,.,.,.,,., ...... ..  .,, ..,    .,, .,',    2 1 8 ZINC .,,,.,,.,.,,.,,.,,., ........       .,',' 220 IRON. ,,.  . ...  '  ..  ...       ,  ., ,, .. ,' 223 CONCLUSION ... ,',    ,',,., ..  .. ,,,    ..  226
Developmental Trajectories of Impaired Community Functioning in Schizophrenia
Authors: Eva Velthorst, Abraham Reichenberg, Ori Kapra, Shira Goldberg, Menachem Fromer, Eyal Fruchter, Karen Ginat, Lieuwe de Haan, Michael Davidson, Mark Weiser
Journal: JAMA Psychiatry (2015)

Community functioning is a core component of the functional deficits in schizophrenia, yet little systematic research on the origins of these functional deficits has been performed.To examine 3 key domains of community functioning--social activity, independent behavior, and functioning in school or work--before first hospitalization for schizophrenia and to determine whether these domains are familial.In this population-based, prospective study that included a sibling-control comparison, data from the Israeli National Draft Board Registry were linked with data from the Israeli Psychiatric Hospitalization Case Registry. The merged file included data for all male adolescents who visited the draft board and were followed up for as much as 25.4 years from draft board assessment (through the end of 2010). The 3 functional domains for cases, their unaffected siblings, and controls were compared by time between assessment and time to hospitalization. Analyses were conducted from March 13, 2014, to October 19, 2014.The trajectories and familiality of 3 key components of community functioning--social activity, independent behavior, and functioning in school or work--in the years preceding hospitalization for schizophrenia.Participants included 723,316 Israeli male adolescents who underwent a mandatory behavioral assessment to determine eligibility for military service. Linkage identified 3929 individuals hospitalized for schizophrenia. Data for 338,550 sibling pairs, 1659 hospitalized with schizophrenia, were similarly ascertained. Among those with schizophrenia, impairments in social activity (effect size [d], 0.55) and functioning in school or work (d = 0.37) were recognizable up to 15 years before hospitalization. Independent behavior seemed preserved until the few years before first admission. For social activity, differences between cases and controls were progressively greater for patients admitted closer to time of testing (F = 115.33, P < .001). Unaffected siblings had small impairments compared with controls in social activity (F = 28.25, P < .001) and functioning in school or work scales (F = 14.77, P < .001). Group familial (sibling) correlations were relatively high for social activity (r = 0.40; 95% CI, 0.39-0.41) and functioning in school or work (r = 0.50; 95% CI, 0.49-0.51) but nil for independent behavior (r = 0; 95% CI, -0.01 to -0.01). Impairments in siblings had no progressive increase and were unrelated to their affected sibling's time of illness onset (time trend: social activity: F = 5.463, P = .02; independent behavior: F = 0.908, P = .34; and functioning in school or work: F = 1.386, P = .24).Various components of impaired community functioning in schizophrenia followed different developmental trajectories. Our results indicate that impairments in social activity and functioning in school or work are familial.
Senior house officer training
Authors: G A Bunch, J Bahrami, R Macdonald, N. Kapur, M. Rickenbach, J. Dunleavey, P. Little, M. Mullee, B. Ramsay
Journal: BMJ (1997)

Nicotine replacement therapy should be prescribable on NHSEditor-I welcome the publication of the open letter to the prime minister about tobacco-the most important preventable cause of death in Europe. 1 As Jo E Asvall points out in the letter, tobacco control demands the support of, and action by, the total government, not just the Department of Health.Among the actions Asvall calls for is that "support for smoking cessation is made widely available, particularly through primary health care professionals, including doctors, nurses, pharmacists, and dentists."Nicotine replacement therapy (nicotine gum, patches, nasal spray, and oral inhaler) is now fully established as an effective adjunct to such professional advice and support.Systematic review of many trials has shown a doubling of sustained smoking cessation when nicotine replacement therapy is compared with placebo. 2 The offer of nicotine patches to motivated subjects for a week in the first instance could be a useful policy. 3 But the recommendation of such therapy by health professionals and the use of such therapy by smokers are severely limited by NHS "blacklisting."I can prescribe on the NHS for alcohol problems and even obesity.I can also prescribe for tobacco addiction-but only products of unproved efficacy for this problem, such as tranquillisers and antidepressants, not one of proved effectiveness.Why not nicotine replacement therapy?So much for evidence based medicine.
Peroral endoscopic myotomy for achalasia after distal gastrectomy
Authors: Shinwa Tanaka, Fumiaki Kawara, Haruhiro Inoue, Manabu Kurosawa, Takashi Toyonaga, Takeshi Azuma
Journal: Endoscopy (2015)

Achalasia is a relatively rare esophageal motility disorder with a reported incidence of approximately 1 in 100 000 worldwide [1]. The occurrence of achalasia in patients with a distal gastrectomy is rare. We present a patient with achalasia and a distal gastrectomy who was successfully treated with peroral endoscopic myotomy (POEM).
M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment
Authors: Eva Van Overmeire, Benoît Stijlemans, Felix Heymann, Jiri Keirsse, Yannick Morias, Yvon Elkrim, Lea Brys, Chloé Abels, Qods Lahmar, Can Ergen, Lars Vereecke, Frank Tacke, Patrick De Baetselier, Jo A. Van Ginderachter, Damya Laoui
Journal: Cancer Research (2015)

Tumors contain a heterogeneous myeloid fraction comprised of discrete MHC-II(hi) and MHC-II(lo) tumor-associated macrophage (TAM) subpopulations that originate from Ly6C(hi) monocytes. However, the mechanisms regulating the abundance and phenotype of distinct TAM subsets remain unknown. Here, we investigated the role of macrophage colony-stimulating factor (M-CSF) in TAM differentiation and polarization in different mouse tumor models. We demonstrate that treatment of tumor-bearing mice with a blocking anti-M-CSFR monoclonal antibody resulted in a reduction of mature TAMs due to impaired recruitment, extravasation, proliferation, and maturation of their Ly6C(hi) monocytic precursors. M-CSFR signaling blockade shifted the MHC-II(lo)/MHC-II(hi) TAM balance in favor of the latter as observed by the preferential differentiation of Ly6C(hi) monocytes into MHC-II(hi) TAMs. In addition, the genetic and functional signatures of MHC-II(lo) TAMs were downregulated upon M-CSFR blockade, indicating that M-CSFR signaling shapes the MHC-II(lo) TAM phenotype. Conversely, granulocyte macrophage (GM)-CSFR had no effect on the mononuclear tumor infiltrate or relative abundance of TAM subsets. However, GM-CSFR signaling played an important role in fine-tuning the MHC-II(hi) phenotype. Overall, our data uncover the multifaceted and opposing roles of M-CSFR and GM-CSFR signaling in governing the phenotype of macrophage subsets in tumors, and provide new insight into the mechanism of action underlying M-CSFR blockade.
Correlation of Pharmacological Effects with Plasma Levels of Antihypertensive Drugs in Man
Authors: Zafar H. Israili
Journal: The Annual Review of Pharmacology and Toxicology (1979)

After a traumatic childhood in Europe during the Second World War, I found that scientific research in Israel was a pleasure beyond my expectations. Over the last 65 year, I have worked on the chemistry and pharmacology of natural products. During the ...Read More
Pneumococcal vaccination and childhood pneumonia in South Africa
Authors: Kim Mulholland, Cattram Nguyen
Journal: Thorax (2015)

For the past 30 years the dominant role of acute respiratory infections, especially pneumonia, as a cause of illness and death in children in the developing world has been appreciated. The strategy employed throughout the developing world to address the problem was based on the early detection and treatment of likely pneumonia cases at the community level by primary healthcare workers using a strategy developed in Papua New Guinea in the 1970s.1 The strategy relied on two physical signs—fast breathing (to identify possible pneumonia cases in need of antibiotics) and lower chest wall indrawing (to identify more severe cases in need of admission). Originally a programme, solely for the management of acute respiratory infection cases, this was integrated, in 1991, into a broader case management strategy for young children, Integrated Management of Childhood Illness (IMCI).2 IMCI has since formed the basis of child survival strategies throughout the developing world. The effectiveness of this approach is uncertain, although it is clear that child mortality has since fallen throughout most of the developing world. Studies of the aetiology of severe pneumonia have repeatedly shown the dominant bacterial causes to be Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae (usually type b or Hib), and these are generally assumed to be responsible for most deaths.

In a global public health effort that is unprecedented since the UNICEF-WHO led Universal Childhood Immunisation campaign of the 1980s, the international community is in the process of rolling out new expensive vaccines, including Hib and pneumococcal conjugate vaccines (PCVs) into the poorest countries of the world (http://www.gavi.org/support/nvs/pneumococcal/).3 This is not just the latest in a series of new vaccines to be added to national programmes. Hib and PCV introduction represent a direct attack on the leading cause of child illness and death in the world today, …
Next Generation Clinical-Stage HbF Inducers Exhibit Multiple Molecular Actions In Vitro and In Vivo and Offer Personalized Therapeutic Regimens
Authors: Betty S. Pace, Jose I Sangerman, Michael S Boosalis, Roman Wolf, Yan Dai, David H.K. Chui, Levi Makala, Biadru Li, Douglas V Faller, Susan P Perrine
Journal: Blood (2013)
Stature loss following skeletal irradiation for childhood cancer.
Authors: J H Silber, P S Littman, A T Meadows
Journal: Journal of Clinical Oncology (1990)

A model is presented to predict adult stature in children treated successfully for cancer outside the CNS. The model is based on radiation dose in Gray adjusted for location of therapy and attained stature (GALA); ideal adult stature (IAS), assuming the patient had not developed cancer, calculated by the Roche-Wainer-Thissen (RWT) method (which uses patient stature and weight before developing cancer, and parent stature data); a femur correction if both the acetabula or heads of both femurs were irradiated (FEMUR); and sex. The model was constructed using data from 49 patients with a mean time from completion of therapy to follow-up of 8.9 years (range, 3.3 to 15.4 years). Thirteen patients received no radiotherapy. All model coefficients were highly significant (P less than .001), and the model appears to be an excellent predictor of adult stature, with a multiple correlation coefficient of 0.84 (R2 = .74) between corrected adult stature (CAS) based on the most recent follow-up stature available for the patient projected to final adult stature, compared with the model's predicted adult stature (MPAS), based only on initial data at presentation and subsequent radiation treatment. Patients who did not receive radiotherapy did not have loss of stature, ie, there was no significant difference between IAS and CAS, (P less than .71; n = 13), but patients who received radiotherapy had shorter statures than would be expected from the healthy population model (P less than .0004; n = 36). The magnitude of the loss in stature appears to be well explained by the dose and location of radiation, the stature already achieved at the time of radiotherapy, along with IAS, FEMUR, and sex. We believe this model will help clinicians to predict the growth effects of radiotherapy in children with cancer not involving the CNS.
Very Low Calorie Diets in the Management of Obesity
Authors: D H Lockwood, J M Amatruda
Journal: Annual Review of Medicine (1984)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
The Leukocyte Common Antigen Family
Authors: M L Thomas
Journal: Annual Review of Immunology (1989)

The leukocyte-common antigen (L-CA) family is a group of high molecular weight glycoproteins uniquely expressed on the surface of all leukocytes and their hemopoietic progenitors ( 114). Members of this family differ by both protein sequence and carbohydrate structures and are expressed by leukocyte populations in specific patterns ( 15-27). An example of the differential expression is shown for the rat L-CA family in Figure 1 ( 19). Thymocytes express the lowest apparent molecular weight form of 1 80 kd; B lymphocytes express the highest form, 220 kd; and T lymphocytes express multiple forms. Differences also exist between T-cell subsets (Figure 1 C); CD8 T cells (Te/s) express the higher molecular weight forms more abundantly than do CD4 T cells (T H) ' The cell-type-specific patterns of expression are conserved throughout mammalian evolution ( 1, 2, 91 1, 19, 28), and there appear to be similar patterns of expression in chicken lymphocytes (29). L-CA is referred to in the literature by different names, including T200 (30), B220 for the B cell form ( 1 2) , the mouse allotypic marker Ly-5 ( 3 1 ) and more recently CD45 (32). L-CA is the most accurate descriptive name and is used for the purpose of this review. The L-CA family is a major cell surface component of lymphocytes and carries much of the carbohydrate of these cells. It has been estimated that 10% of the lymphocyte surface is occupied by one or more L-CA members (33). Because of this abundance, L-CA was easily detected on SDS-poly­ acrylamide gels of lymphocyte membranes (36-39) (Figure lA). It was also initially characterized as the major specificity of antilymphocyte sera (34) and as an allotypic marker (31 , 35). The primary protein structure has been determined from the analysis of cDNA clones, and this information,
Chemotherapy in Prevention of the Recurrence of Resectable Cancer
Authors: G Bonadonna, G Tancini, A Rossi, M Gasparini
Journal: Annual Review of Medicine (1978)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Wider political context underlying the NHS junior doctors’ dispute
Authors: David J Hunter
Journal: BMJ (2015)

Unhappy doctors are back centre stage with a vengeance

Whatever the rights and wrongs of the dispute over the junior doctor contract, the ramifications will be felt throughout the NHS for some time to come. These have their roots in a wider political context that may prove decisive in settling the longer term fate of the NHS.

This dispute has striking echoes of the deep malaise among doctors in the late 1990s and early 2000s, also a time when the NHS was under severe financial pressure and undergoing reorganisation. The then prime minister, Tony Blair, spoke of bearing “the scars on my back” from attempts to reshape public services. An editorial in The BMJ in 2001 asked why doctors were unhappy.1 It suggested the causes were multiple but highlighted one in particular: the mismatch between what doctors were trained for and what they are required to do. Trained in a particular medical specialty, doctors found …
The American Psychiatric Association Practice Guidelines for the Psychiatric Evaluation of Adults
Authors: Joel J. Silverman, Marc Galanter, Maga Jackson-Triche, Douglas G. Jacobs, James W. Lomax, Michelle B. Riba, Lowell D. Tong, Katherine E. Watkins, Laura J. Fochtmann, Richard S. Rhoads, Joel Yager
Journal: American Journal of Psychiatry (2015)
Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren's Syndrome
Authors: G. Nocturne, A. Virone, Wan‐Fai Ng, V. Le Guern, E. Hachulla, D. Cornec, C. Daien, O. Vittecoq, B. Bienvenu, C. Marcelli, D. Wendling, Z. Amoura, R. Dhote, C. Lavigne, R. Fior, J. E. Gottenberg, R. Seror, X. Mariette
Journal: Arthritis & Rheumatology (2015)

To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (SS).A multicenter case-control survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after diagnosis of primary SS and were mainly recruited through the Club Rhumatismes et Inflammation network. For each case, 2 controls (matched for disease duration and age) were randomly selected among patients with primary SS and without lymphoma. Cases and controls were compared using univariate analysis and then using multivariate analysis to identify independent predictors of lymphoma.One hundred one patients with primary SS and lymphoma were included. Eighty-seven patients were women (86.1%), and the mean ± SD age at lymphoma diagnosis was 57.4 ± 12.6 years. The most frequent histologic type was B cell non-Hodgkin's lymphoma (NHL) in 99 of 101 patients, with marginal-zone lymphoma in 76 of the 99 patients (76.8%) including 58 (58.6%) with lymphoma of the mucosa-associated lymphoid tissue type. Lymphomas were most frequently located in the salivary glands (43 patients). A specific treatment was initiated at diagnosis in 87 patients with B cell NHL, and 61 patients (61.6%) achieved complete sustained remission after the first line of treatment. In the multivariate analysis, salivary gland enlargement, the presence of rheumatoid factor (RF), low C4, cryoglobulinemia, lymphopenia, and disease activity according to the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (excluding the lymphoma domain) were found to be predictors of lymphoma. No previous treatment for primary SS was associated with any effect on lymphoma occurrence.In addition to previously known factors predictive of lymphoma occurrence, the independent roles of RF and disease activity were demonstrated in this case-control study of primary SS-associated lymphoma. Our findings highlight the roles of chronic antigenic stimulation and disease activity in the development of this severe complication.
Evidence for Expansion of Sinonasal B-Lineage Cells in Chronic Rhinosinusitis
Authors: Kathryn E. Hulse, James Norton, Robert Kern, David Conley, Rakesh Chandra, Bruce Tan, Anju Peters, Leslie C. Grammer, Kathleen E. Harris, Sudarshan Seshadri, Roderick Carter, Lydia Suh, Atsushi Kato, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2013)