tbuckley/cabot-search huggingface dataset:
Decreased survival, chronic inflammation and tumor susceptibility of irradiated DR5-null mice
Authors: Niklas K. Finnberg, Elizabeth Matthew, Eric Bernhard, Andres Klein-Szanto, Wafik S. El-Deiry
Journal: Cancer Research (2006)

779   The long-term tissue response following ionizing irradiation (IR) involves molecular events in different cell types that regulate tissue homeostasis that has implications for inflammation, tissue damage and cancer. We have previously shown that loss of DR5/Killer/MK, the receptor to the cytokine Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL) in mice confers resistance to acute cell death inflicted by IR in several lymphoid and also to some extent in non-lymphoid organs (Finnberg N et al. Mol. Cell. Biol. 25:2000-2013, 2005). In the present study we explored the long-term effects (17 months) of IR in mice treated with a single sub-lethal dose of whole-body irradiation (4 Gy) at the age of 4-5 weeks. Wild-type (wt, N = 11) mice, mice heterozygous for the DR5 receptor (DR5, N = 10) and mice completely lacking the DR5-receptor (DR5-/-, N = 21) were subjected to irradiation. Increased lethality was observed in the DR5-/- group at 8 months following IR. Necropsy showed “tissue damage” (i.e., infiltrating lymphocytes, fibrosis and distorted tissue architecture) in the lungs (consistent with bronchopneumonia), small intestine and the colon of moribund DR5-/- mice. Immunohistochemistry identified infiltrating lymphocytes as CD3-positive, deposition of fibronectin and increased numbers of TUNEL-positive epithelial cells in damaged tissue. A limited number of tumors were detected in the lungs and the lymphoid tissues of DR5-/- mice and DR5 mice (but not wt mice) that survived 17 months. We propose a model wherein DR5 functions as a negative regulator of late tissue-damage involving inflammation and fibrosis following IR primarily in the lungs. In addition, TRAIL might be useful in modulating the tissue toxicity following anti-cancer therapy. Thus DR5 appears to suppress chronic inflammation and cancer following exposure to IR.
NCCN Roundtable:Value-Based Decision-Making at the Bedside
Authors: Peter B. Bach, Stephen B. Edge, Linda House, Jennifer Malin, James L. Mohler, Clifford Goodman
Journal: Journal of the National Comprehensive Cancer Network (2015)

As part of the NCCN 20th Annual Conference: Advancing the Standard of Cancer Care, a distinguished and diverse group of experts on value-based decision-making in oncology discussed guidelines and pathways and how their use has impacted bedside evidence-based decision-making for both physicians and patients. Moderated by Clifford Goodman, PhD, the roundtable also reflected on the criteria used to assess shared decision-making and the relationship between outcomes and cost when determining value.
Studies in Acute Cholecystitis
Authors: Frederick P. Ross, J. Englebert Dunphy
Journal: New England Journal of Medicine (1950)

Cholecystotomy has become an unwanted stepchild in the family of surgical procedures. Its presence as a recognized operation is admitted, but its legitimacy is suspect. In the standard textbooks of surgical methods1 2 3 the technic is but sketchily outlined, and then as a procedure carried out under general anesthesia with a full gall-bladder incision. The operation is usually mentioned as a means of escaping from a technically difficult situation by a relatively simple procedure. It has its proponents,4 5 6 but it is often regarded as an operation suitable for the timorous or inexperienced but rarely carried out by the skillful surgeon.It . . .
Amelioration of Proximal Renal Tubular Dysfunction in Type I Glycogen Storage Disease with Dietary Therapy
Authors: Yuan-Tsong Chen, Jon I. Scheinman, Hae K. Park, Rosalind A. Coleman, Charles R. Roe
Journal: New England Journal of Medicine (1990)

IN Type I glycogen storage disease, glycogen accumulates in the liver, kidney, and intestine because of deficient glucose-6-phosphatase activity (Type Ia) or deficient glucose-6-phosphate transloca...
Acute Dystonic Reactions to “Street Xanax”
Authors: Robert G. Hendrickson, Anthony P. Morocco, Michael I. Greenberg
Journal: New England Journal of Medicine (2002)

To the Editor: Acute dystonic reactions have been reported after the ingestion of numerous medications that alter dopaminergic tone in the basal ganglia or antagonize dopamine D2 receptors. At the emergency department of an urban community hospital, we have recently treated six patients presenting with acute dystonia. All patients reported the ingestion of what street sellers had assured them was Xanax (alprazolam). In five of these patients, the ingested drug was actually proved to be haloperidol. Three teenage boys presented to the emergency department with symptoms consistent with torticollis, oculogyric crisis, and opisthotonos. Each reported the ingestion of “one or . . .
A phase III double blinded, placebo controlled, randomized trial of gabapentin in patients with chemotherapy-induced peripheral neuropathy: A North Central Cancer Treatment Group study
Authors: G. Y. Wong, J. C. Michalak, J. A. Sloan, J. A. Mailliard, D. A. Nikcevich, P. J. Novotny, D. O. Warner, L. Kutteh, S. R. Dakhil, C. L. Loprinzi
Journal: Journal of Clinical Oncology (2005)

8001 Background: The purpose of this study was to determine if gabapentin, an anti-convulsant used for neuropathic pain, is effective in improving pain and symptoms due to chemotherapy-induced peripheral neuropathy. Methods: 115 patients with chemotherapy-induced peripheral neuropathy (for ≥1 month, with average pain rating of ≥4/10 or ECOG sensory neuropathy ≥1/3) were randomized in this double-blind, placebo-controlled trial to either: 1) gabapentin (target dose=900 mg TID) for 6 weeks then cross-over to placebo for 6 weeks (n=57) or 2) treatment in the reverse order (n=58). A 2-week washout occurred between cross over treatments. The co-primary endpoints were the average daily pain numerical analogue intensity rating (0=no pain to 10=worst pain imaginable) and the ECOG toxicity rating for sensory neuropathy (0=none to 3=severe). The study was designed for 100 total patients, providing 80% power to detect an average pain score difference of 0.58 standard deviations (a moderate effect size) using a two-sided t-test with 0.05 Type I error rate. Results: Gabapentin did not significantly improve the co-primary endpoints of pain intensity (-0.5 versus -1.0 change from baseline to week 6 for patients on gabapentin and placebo respectively, p=0.18) or the ECOG toxicity rating for sensory neuropathy (-0.2 versus -0.1 for gabapentin and placebo respectively, p=0.38). Patients on gabapentin reported significantly more nystagmus (p=0.009) and dizziness (p=0.02). Conclusion: Gabapentin did not significantly improve the primary endpoints of pain intensity or sensory neuropathy due to chemotherapy-induced peripheral neuropathy in this study. No significant financial relationships to disclose.
Hemophilia A and Concurrent Factor VII Deficiency
Authors: Lamont W. Gaston, Bernard F. Mach, William S. Beck
Journal: New England Journal of Medicine (1961)

THE number of adequately documented cases of congenital deficiency of two clotting factors is small; the association of antihemophilic factor and factor VII deficiency is particularly rare. Constandoulakis1 reported a family in which 2 males with hemophilia had mildly abnormal one-stage prothrombin times that could be corrected by normal plasma, but not by aluminum hydroxide adsorbed plasma or serum deficient in factor VII that was not specifically stated to be congenitally deficient. Owren factor VII complex assays were 40 and 50 per cent of normal in the 2 patients. Deficiency of antihemophilic factor was diagnosed by the thromboplastin-generation test. Prothrombin . . .
Male-to-Male Sexual Transmission of Zika Virus — Texas, January 2016
Authors: D. Trew Deckard, Wendy M. Chung, John T. Brooks, Jessica C. Smith, Senait Woldai, Morgan Hennessey, Natalie Kwit, Paul Mead
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Zika virus infection has been linked to increased risk for Guillain-Barré syndrome and adverse fetal outcomes, including congenital microcephaly. In January 2016, after notification from a local health care provider, an investigation by Dallas County Health and Human Services (DCHHS) identified a case of sexual transmission of Zika virus between a man with recent travel to an area of active Zika virus transmission (patient A) and his nontraveling male partner (patient B). At this time, there had been one prior case report of sexual transmission of Zika virus. The present case report indicates Zika virus can be transmitted through anal sex, as well as vaginal sex. Identification and investigation of cases of sexual transmission of Zika virus in nonendemic areas present valuable opportunities to inform recommendations to prevent sexual transmission of Zika virus.
Australasian College of Sport and Exercise Physicians
Authors: Adam Castricum, Michael Jamieson, Hamish Osborne, Paul Blackman
Journal: British Journal of Sports Medicine (2016)

The Board of the Australasian College of Sports Physicians is proud to announce that a special resolution was passed at the Annual General Meeting on 14 February 2016 to change the name of the College to the Australasian College of Sport and Exercise Physicians (ACSEP).

Since its humble beginnings in 1985, from a small group of 19 passionate like-minded individuals, as the Australian College of Sports Physicians, the College has always been progressive in its thinking. In 1991, the College awarded its first Fellowships. In 1992, the College began training its own registrars in private practice, a pioneering training model which continues to this day. In 1993, our New Zealand colleagues joined the College, with the name changing to Australasian College of Sports Physicians in 2005.

Importantly, the College gained specialty recognition in New Zealand in 1998 and then finally in Australia in …
S28 Effect of sleep apnoea on post-operative outcomes in cardiac surgery
Authors: M Mason, J Hernández-Sánchez, D Horton, A Clutterbuck-James, I Smith
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Obstructive sleep apnoea (OSA) is common and can be associated with adverse health outcomes. There are conflicting data for the impact of undiagnosed OSA on the outcome of surgical procedures but at least some results suggest an association with worse outcomes. EuroSCORE risk model was developed to calculate the risk of mortality after cardiac surgery. We evaluated the prevalence and impact of undiagnosed sleep apnoea (SA) on postoperative outcomes in cardiac surgery. <h3>Methods</h3> Patients undergoing coronary artery bypass grafting with or without cardiac valve surgery were screened for the presence of SA, prior to surgery, with the STOPBANG questionnaire and overnight oximetry. SA was defined as a 4% oxygen desaturation index (ODI) of ≥5/hr. A Weibull model was used to analyse lengths of stay (LoS) in intensive care unit (ICU). Complications in ICU were dichotomised and analysed with binary logistic regressions. Parsimonious models were obtained using a combination of step-wise regression and manually removing predictors that did not reach the 5% significance level. <h3>Results</h3> 122 subjects were included in final analysis of which 57 (47%) had a new diagnosis of SA. Of those, 45 (79%) had mild SA and 12 (21%) had moderate/severe SA. There was no simple relationship between OSA as measured by ODI and LoS in ICU. The most significant predictor for ICU LoS was developing complications at ICU (p &lt; 0.001). The independent predictors associated with increasing likelihood of developing major organ complications following cardiac surgery were EuroSCORE, ODI and intravenous opioid analgesia (IOA). When patients with mild and moderate SA received IOA, predicted probability of complications rose 2.4 and 1.4 times respectively (Figure 1). <h3>Conclusion</h3> We found a high prevalence of undiagnosed sleep apnoea in our cohort. EuroSCORE, SA and the administration of intravenous morphine were found to be independent risk factors for developing post-operative complications. This risk has increased when patients with SA received intravenous morphine.
Effect of Statin Treatment on Modifying Plaque Composition
Authors: Seung-Jung Park, Soo-Jin Kang, Jung-Min Ahn, Mineok Chang, Sung-Cheol Yun, Jae Hyung Roh, Pil Hyung Lee, Hyun Woo Park, Sung-Han Yoon, Duk-Woo Park, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Gary S. Mintz, Ki Hoon Han, Seong-Wook Park
Journal: Journal of the American College of Cardiology (2016)
MPTH-25AN 18-GENE EXPRESSION SIGNATURE PREDICTS RECURRENCE-FREE SURVIVAL IN MENINGIOMA
Authors: Adriana Olar, Lindsey Goodman, Khalida Wani, Nicholas Boehling, Franco DeMonte, Kenneth Aldape, Erik Sulman
Journal: Neuro-Oncology (2015)

Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. While WHO grade correlates with recurrence to a degree, there is substantial within-grade variation of recurrence risk and current risk stratification does not accurately predict which patients are likely to benefit from adjuvant radiation therapy. We hypothesized that recurrent tumors have unique gene expression profiles (GEP) that could be used to better stratify patients for radiation therapy. We optimized a recurrence predictor using a training/validation approach and a support vector machine classification method with radial-basis smoothing kernel. Three publicly available Affymetrix gene expression datasets ({type:entrez-geo,attrs:{text:GSE9438,term_id:9438}}GSE9438, {type:entrez-geo,attrs:{text:GSE16581,term_id:16581}}GSE16581, {type:entrez-geo,attrs:{text:GSE43290,term_id:43290}}GSE43290) combining 127 newly diagnosed meningioma samples served as the training set. Unsupervised variable selection was used to identify an 18-gene GEP model (18-GEP) that separated recurrences with a negligible root mean square error of 0.17. The characteristics of the training dataset were as follows: WHO grade [I-92(73%), II-32(25%), III-2(2%)]; median follow-up = 5.53 years (range:0.05-25.42); recurrences = 18. This model was tested on 62 cases from our institution [validation dataset (VD)] with similar demographics, but enriched for cases with either long clinical follow-up or known recurrence. When applied to the VD, the 18-GEP separated recurrences with a misclassification error rate of 0.25 (log-rank p = 0.0003). 18-GEP was significantly predictive of tumor recurrence, independently [p = 0.0007, HR = 7.91, 95%CI = 2.35-35.78)] and was predictive after adjustment for WHO grade, mitotic index, and Simpson grade [p = 0.047, HR = 4.73, 95%CI = (1.02-26.55)]. The expression signature included genes encoding proteins involved in normal embryonic development, cell proliferation, tumor growth and invasion (FGF9, SEMA3C, EDNRA), angiogenesis (angiopoietin-2), cell cycle regulation (CDKN1A), membrane signaling (tetraspanin-7, caveolin-2), WNT-pathway inhibitors (DKK3), complement system (C1QA) and neurotransmitter regulation (SLC1A3, Secretogranin-II). In conclusion, our gene expression classifier accurately stratifies patients with meningioma by recurrence risk and has the potential to guide therapy.
MTR-15A PRONEURAL SIGNATURE PROFILE PREDICTS RESISTANCE TO BEVACIZUMAB THERAPY IN GLIOBLASTOMA
Authors: Norihiko Saito, Kazuya Aoki, Nozomi Hirai, Satoshi Fujita, Yu Hiramoto, Haruo Nakayama, Morito Hayashi, Keisuke Ito, Hitoshi Kimura, Takatoshi Sakurai, Satoshi Iwabuchi
Journal: Neuro-Oncology (2015)

Glioblastoma, the most common adult glioma, has a dismal prognosis. Treatment with bevacizumab has not significantly prolonged overall survival. Glioblastoma resistance to angiogenesis inhibitors is attributed to interacting mechanisms. We thus began a comprehensive effort to detect expression signatures associated with therapeutic response, which might facilitate prospective selection of patients who are likely to respond to therapy. The Notch signaling pathway is an evolutionarily conserved pathway that is important in multiple cellular and developmental processes, including cell fate decision, differentiation, proliferation, survival, angiogenesis, and migration. Analysis of The Cancer Genome Atlas expression dataset identified a group of tumors with a proneural signature showing high Notch pathway activation. In this study, we compared CD133, Notch, and VEGF expressions in histological sections of primary and recurrent glioblastomas after radiotherapy and chemotherapy. Tumor samples were collected from 27 patients at the time of tumor recurrence, and immunohistochemical techniques were used to compare expression of CD133, Notch-1, and VEGF. Expressions of CD133-, Notch-1–, and VEGF-positive glioma cells were higher in recurrent glioblastomas after radiotherapy and chemotherapy. To determine the clinical importance of Notch-1 expression in glioblastoma, we analyzed 15 patients who had received bevacizumab therapy before undergoing a second surgery at recurrence. Overall survival was significantly longer in Notch-1–negative patients (8.8 months) than in Notch-1–positive patients (6.8 months). Our results show that proneural glioblastoma with high Notch pathway activation is associated with resistance to bevacizumab therapy.
Antibody Response in Serum and Nasopharynx after Naturally Acquired and Vaccine-Induced Infection with Rubella Virus
Authors: Pearay L. Ogra, Donald Kerr-Grant, Gabriel Umana, Judith Dzierba, David Weintraub
Journal: New England Journal of Medicine (1971)

Antibody response to rubella virus was studied in serum and nasopharyngeal secretions after natural infection, intranasal inoculation with RA-27/3 rubella vaccine and subcutaneous administration of HPV-77 DK/12 rubella-virus vaccine. Serum antibody responses after natural infection or immunization were similar and characterized by the sequential appearance of γM, γG and occasionally γA antibody. Secretory antibody response after natural infection or intranasal immunization was characterized by regular appearance of nasopharyngeal γntibody. Little or no nasopharyngeal response was observed after subcutaneous immunization with HPV-77 vaccine. These data may explain the poor nasopharyngeal immunity to reinfection with wild rubella virus in subjects previously immunized with parenterally administered rubella-virus vaccine.
Relevance of HL-A Antigens to Acute Humoral Rejection of Multiple Renal Allotransplants
Authors: James C. Pierce, George W. Cobb, David M. Hume
Journal: New England Journal of Medicine (1971)

Acute humoral (hyperacute) rejection occurred in 3.3 per cent of 153 first renal allotransplants and in 35 per cent of 31 second, third and fourth transplants. To test whether or not immunization by previous transplants to HL-A antigens distributed at two subloci could account for this striking increase in the frequency of immunization, the Immunization Index was calculated for donor recipient combinations of various relatedness, races and numbers of transplants. The figure of 11 cases of acute humoral rejections in 31 multiple transplants correlated well with 12.2 cases predicted by the model, and there was similar close agreement for several subgroups. Immunization to the HL-A system of histocompatibility antigens is probably sufficient to account for the percentage of acute humoral rejections observed in recipients of multiple renal allotransplants without the involvement of a third HL-A sublocus or other histocompatibility loci.
Surgery of the Thyroid Gland
Authors: Frank H. Lahey
Journal: New England Journal of Medicine (1947)

I HAVE selected the subject "Surgery of the Thyroid Gland" because the Lahey Clinic and I have literally grown up almost from the beginning of the developments in this field and have had a hand in bringing about some of them, because this experience represents almost as large an acquaintance with the subject as exists in the world today and has therefore made available to us a considerable knowledge of the unusual thyroid states with which men not dealing with these conditions daily are often not familiar, because it is particularly appropriate to present a review of this special experience . . .
P241 The feasibility and validity of objective cough monitoring in children using an adult cough detection system
Authors: D Deblej Elghamoudi, H Sumner, K McGuiness, J Smith, CS Murray
Journal: Thorax (2015)

<h3>Background</h3> In young children the evaluation of symptoms is almost wholly reliant upon parental reporting. Cough is extremely common in childhood and a tool to objectively measure cough frequency would be clinically beneficial. To date paediatric cough monitoring systems have relied on manual cough counting which is time consuming and costly. The VitaloJAK™ (Vitalograph, UK) is a custom built 24 hr semi-automated cough monitoring device that has been used successfully to quantify cough in adults. Using the VitaloJAK™ we tested the feasibility of 24 hr cough recordings in children and tested existing compression software for cough quantification. <h3>Methods</h3> Children (age 2–14 years) with acute or chronic cough were asked to wear VitaloJAK™ cough monitor for a maximum of 24 h. Feedback about the device was obtained from the child/carer were appropriate. All recordings were manually counted and also processed through the compression software. <h3>Results</h3> 40 children (21 male; mean age 8 yrs) wore the monitor for a median of 22.25 h (0.38 – 24 hrs). Children who wore the monitor as out-patients with chronic cough generally wore the monitor for longer (median 23.07 hrs) than those who were in-patients with acute symptoms (median 12.59 hrs; p = 0.06). Twenty-nine children (73%) wore the monitor for &gt;12 h and 22 for &gt;22 hrs including during the night. Eighteen (45%) children reported the monitor was heavy/bulky and eleven (28%) said at times it restricted some normal daily tasks (bending/stooping/using the toilet). Neither length of time the monitor was worn for, nor complaints about the size or restricting nature of the monitor, were age dependent. No serious adverse events were reported. One recording was excluded due to technical problems. Recordings demonstrated wide variability in frequency from 2 to 2712 coughs per recording (median 72). Following compression a median of 98.5% (85.7–100) of coughs were retained. <h3>Conclusions</h3> VitaloJAK™ semi-automated cough monitor can be used in children to accurately measure cough frequency. As with many medical interventions, it was not tolerated by all children for long periods, however the majority of children were able to wear it for &gt;12 h.