tbuckley/cabot-search huggingface dataset:
P0514 : The correlation between 25-hydroxyvitamin D level and liver fibrosis assessed by transient elastography in patients with compensated chronic liver disease
Authors: Y.S. Kim, S.G. Kim, B.J. Ko, S.W. Jeong, J.Y. Jang, Y.D. Kim, G.J. Cheon, H.S. Kim, B.S. Kim, S.M. Kim
Journal: Journal of Hepatology (2015)
Mechanisms of Muscle Wasting — The Role of the Ubiquitin–Proteasome Pathway
Authors: William E. Mitch, Alfred L. Goldberg
Journal: New England Journal of Medicine (1996)

All proteins in mammalian cells are continually being degraded and replaced. In the cytosol, nucleus, and organelles, individual proteins are degraded at widely differing rates; some cytosolic enzymes have half-lives as short as 10 minutes, whereas others last for days. The average rate of protein turnover also varies among tissues; the majority of proteins in rat hepatocytes are replaced every few days, whereas those in muscle or brain cells are replaced every one to two weeks. The amount of intracellular protein turned over each day is quite large. In a normal 70-kg adult, about 280 g of protein is synthesized . . .
Case 9-2008
Authors: Thomas B. Dodson, Noopur S. Raje, Paul A. Caruso, Andrew E. Rosenberg
Journal: New England Journal of Medicine (2008)

A 65-year-old woman was seen in the oral surgery clinic because of a nonhealing ulcer of the mandible at the site of a tooth that had been extracted 3 years earlier. The patient had multiple myeloma and had been treated with intravenous bisphosphonates for 6 years. Examination disclosed red, raised soft tissue in the right mandible, with mucosal ulceration and exposed bone. A diagnostic procedure was performed.
Prognostic significance of plasma Epstein-Barr virus (EBV) DNA level in patients with locally advanced head and neck carcinoma treated with concurrent cisplatin and concomitant boost radiotherapy (CBRT)
Authors: K. H. Yu, A. K. Chan, G. M. Tse, M. K. Kam, E. P. Hui, A. D. King, A. C. Vlantis, K. T. Wong, D. Y. Lo, A. T. Chan
Journal: Journal of Clinical Oncology (2006)

20003 Background: EBV DNA is detectable in the plasma in most patients (Pts) with lymphoepithelial carcinoma (LECA) and in some Pts with squamous cell carcinoma (SCC) of the HN. We investigated the prognostic significance of plasma EBV DNA level in a prospective phase II trial of concurrent cisplatin and CBRT for locally advanced HN carcinomas. Methods: Eligibility criteria included newly-diagnosed SCC or LECA of non-nasopharyngeal HN sites; stage III or IV disease; ECOG performance status ≤ 1; and age ≤ 70 years. Plasma EBV DNA levels were measured by real-time quantitative polymerase chain reaction (PCR) before treatment and at 6 weeks post-treatment. Pre-treatment gross tumor volume (GTV) was measured on CT, and invasion of bone and cartilage was assessed on CT and MRI. Cisplatin 40–50 mg/m 2 was given on days 1, 8, 15 and 22 of CBRT. Radiotherapy consisted of 54 Gy/30 fractions/6 weeks and a concomitant boost (18 Gy/12 fractions) in the last 12 treatment days. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Survival curves were compared by the log-rank test and multivariate analysis was performed with Cox regression. Results: Between March 2001 and January 2005, 46 Pts were recruited (36 with SCC and 10 with LECA). Thirty-four Pts had stage III and 12 had stage IV disease. Pre-treatment plasma EBV DNA level was &gt; 0 copy/ml in all Pts with LECA (range, 37 - 211737 copies/ml) and in 8 Pts with SCC (range, 10 - 48734 copies/ml). Ten Pts had plasma EBV DNA level &gt; 0 copy/ml at 6 weeks post-treatment. With a median follow-up of 1.6 years, the 1-year OS rate was 87.7 % and 1-year PFS rate was 68.3%. On multivariate analysis, plasma EBV DNA &gt; 0 copy/ml at 6 weeks post-treatment was the only independent predictive factor of decreased OS [hazard ratio (HR) 3.59, p = 0.04] for the entire group. In the subgroup of Pts with SCC, pre-treatment EBV DNA &gt; 0 copy/ml was the only independent predictive factor of decreased locoregional PFS (HR 7.08, p = 0.03). Conclusions: Plasma EBV DNA level is a prognostic factor in Pts with locally advanced HN SCC and LECA. Further studies are warranted to confirm the finding and to elucidate its biological basis. No significant financial relationships to disclose.
Congenital Syphilis in Massachusetts
Authors: Nicholas J. Fiumara
Journal: New England Journal of Medicine (1951)

PHYSICIANS are in agreement that congenital syphilis is preventable. Modern medicine has provided the medical profession with epidemiologic, diagnostic and therapeutic weapons so that congenital syphilis need not occur. Hence, the key to the solution of the problem of congenital syphilis is the prevention and control of syphilis in pregnancy.Today, penicillin offers the most effective antibiotic yet discovered for the treatment of syphilis. It is the drug of choice in syphilotherapy because of its ease of administration, its safety and the brief period of time required to complete treatment. Its efficacy is equal if not superior to that of . . .
Callander's Surgical Anatomy.
Journal: Annals of Internal Medicine (1952)

90Reviews making statements about some population of children, presumably those living in the north-east of Scotland.However, since no indication is given of the sampling methods used, these measurements do not enable any statements to be made about the character- istics of any population.It is a great pity that these Tables are open to so many grounds of criticism but it is most essential that future workers should realize their shortcomings.Before starting on their measurements, students new to this field would be wise to take advantage of the advice of the Committee on Growth and Form set up by the Medical Research Council.
Vitamin A and Birth Defects — Continuing Caution is Needed
Authors: Godfrey P. Oakley, J. David Erickson
Journal: New England Journal of Medicine (1995)

Vitamins are essential to good health, yet the consumption of excessive amounts of some vitamins, particularly A and D, can lead to toxicity. In this issue of the Journal, Rothman et al.1 add to a body of evidence suggesting that the consumption of too much vitamin A by pregnant women may cause birth defects. On the other hand, the Public Health Service recommends that all women capable of becoming pregnant should consume 0.4 mg of folic acid daily to prevent the serious and common birth defects spina bifida and anencephaly.24 It is important for women and their physicians not . . .
Psychiatric developments: a new journal
Authors: S B Guze, M Roth
Journal: American Journal of Psychiatry (1984)

SIR: Oxford University Press has recently decided to publish a new journal under our editorship, called Psychiatnc Developments. It will be a quarterly publication devoted to advances and prospects in psychiatric research and psychiatnic practice. The journal will be international in its coverage and interdisciplinary in its content. It will primarily provide authoritative, critical reviews of the latest developments in the clinical, epidemiological, and neurobiological areas of psychiatry. It is intended to disseminate information and significant analyses widely and to foster professional communication among researchers and clinicians around the world in a variety of fields. Any such new effort requires a word of justification at a time of literary abundance in the fields of psychiatry and neuroscience. We would argue that this very abundance of new information and insight itself justifies the synthesis attempted in the pages of our slender quarterly. There is a danger of information overload, of retreat into fragmentation and safe intellectual seclusion. This has to be countered by a systematic attempt to synthesize and select. The formulation of a coherent picture often demands fresh ideas or insights, and this activity lies at the heart of scientific enterprise. Out of such formulations come the sharply pointed questions that are capable of advancing knowledge. Today more than ever the panorama is wide in its sweep, stretching from the molecular biology of genes, through the neurobiology and pharmacology of neuronal networks, to the psychological factors in early development that contribute to shape mental life, and finally to man in his familial and social setting. With all this, the central problems posed by mental disorder remain unanswered. It has seemed to us that one contribution toward accelerating progress could come from improvement in the reciprocal flow of information between those mainly concerned with scientific work and whose lives are largely devoted to the care of patients. The last half century has shown that effective communication between basic scientists and practicing clinicians is the life blood that sustains the highest levels of both clinical practice and creative inquiry. We hope Psychiatric Developments will contribute to such communication. Communications concerning editorial matters may be directed to either of the editors; information about subscriptions and related matters may be directed to Oxford University Press, 200 Madison Ave., New York, NY 10016.
EPID-01CHICKEN POX AND GLIOMA RISK: PRELIMINARY RESULTS FROM THE GLIOGENE INTERNATIONAL CASE-CONTROL STUDY
Authors: E. Susan Amirian, Michael Scheurer, Georgina Armstrong, Renke Zhou, Ching Lau, Elizabeth Claus, Jill Barnholtz-Sloan, Dora Il'yasova, Joellen Schildkraut, Francis Ali-Osman, Siegal Sadetzki, Christoffer Johansen, Richard Houlston, Robert Jenkins, Daniel Lachance, Sara Olson, Jonine Bernstein, Ryan Merrell, Margaret Wrensch, Faith Davis, Rose Lai, Sanjay Shete, Christopher I. Amos, Beatrice S. Melin, Melissa Bondy
Journal: Neuro-Oncology (2015)

The role of viral infections in gliomagenesis has long been in question. Varicella zoster virus (VZV) is a neurotropic alpha-herpesvirus that causes chicken pox among initial infection and shingles upon re-activation later in life. VZV infection has been associated with lower glioma risk in some studies, but several gaps in knowledge remain. Using data from our large consortium, the Glioma International Case-Control Study (GICC), we examined the association between history of chicken pox and glioma risk, overall, by tumor subtype, and by age at glioma diagnosis. Data on 4545 glioma cases and 4173 controls from 14 different sites across five countries was combined using maximum likelihood estimation/restricted maximum likelihood meta-analysis methods. Reporting a positive history of chicken pox was associated with a 21% lower glioma risk, compared to having a negative history of chicken pox (95% CI: 0.65-0.96). When stratified by glioma subtype, a significant protective effect was observed among glioblastoma (GBM) cases (meta-OR: 0.72; 95% CI: 0.55-0.95), but not among the non-GBM group (meta-OR: 0.89; 95% CI: 0.70-1.13). Our findings corroborate previous reports on the protective effect of chicken pox on glioma risk in one of the largest study populations available on this rare and highly fatal disease.
Timing of the loss of Pten protein determines disease severity in a mouse model of myeloid malignancy
Authors: Y. Lucy Liu, Yan Yan, Cody Webster, Lijian Shao, Shelly Y. Lensing, Hongyu Ni, Wei Feng, Natalia Colorado, Rupak Pathak, Zhifu Xiang, Martin Hauer-Jensen, Shaoguang Li, Daohong Zhou, Peter D. Emanuel
Journal: Blood (2016)
Dupilumab Suppresses Fractional Exhaled Nitric Oxide (FeNO) and Biomarkers of Type 2 Inflammation in Adult Patients with Persistent Uncontrolled Asthma Despite Use of Medium-to-High Dose Inhaled Corticosteroids Plus Long-Acting Beta-Agonists (ICS/LABAs)
Authors: Brian N. Swanson, Ariel Teper, Jennifer D. Hamilton, Bingzhi Zhang, Heribert Staudinger, Nian Tian, Ying Wang, Jeffrey E. Ming, Neil M.H. Graham, Gianluca Pirozzi
Journal: Journal of Allergy and Clinical Immunology (2016)
PWE-367 Are we seeing less colorectal cancers in clinic and as emergency admissions as a result of the uk colorectal cancer screening programme?
Authors: R Fernandes, A Venkatasubramaniam, K Chandrakumaran, S Arnold
Journal: Gut (2015)

Introduction The UK Cancer Reform Strategy in 2007 recommended The NHS Bowel Screening Programme be extended to incorporate those up to 75 years, on a background of screened 60–69 year olds. Flexible sigmoidoscopy to those aged 55 years is now being rolled out, with a view to extending this screening throughout the UK by 2016. It is postulated that as the screening programme develops, fewer patients will present as symptomatic cancers as acute admissions or referrals. Method Our institution is a renowned colorectal hospital, with a large tertiary referral base. A retrospective analysis of all cases of colorectal malignancy since the advent of screening in 2008 was collated through an established patient database. Patient age, mode of presentation and tumour status at time of diagnosis were evaluated, along with post-operative histology. The data was grouped per age and into bi-annual groups: 2008–2009, 2010–2011, 2012–2013. Results There were 487 patients who had a diagnosis of colorectal malignancy inclusive of tertiary referrals and were aged >60 years. From these patients, 395 arose from referrals and acute admissions and 92 arose directly via the screening programme. There were no statistical differences in age, gender or Dukes Stage between each group either overall or between each bi-annual group. However, it is evident that in each sequential bi-annual year the proportion of patients diagnosed through screening rises; 17%, 18% and 22%. Conclusion Our results failed to demonstrate that following the introduction of the screening programme there was a reduction in patients presenting as emergencies or through the outpatient clinic with symptoms from their colorectal malignancy. However, it did demonstrate that the proportion of patients diagnosed through screening is progressively rising. Disclosure of interest None Declared.
Benzodiazepines: behavioral and neurochemical mechanisms
Authors: L Stein, J D Belluzzi, C D Wise
Journal: American Journal of Psychiatry (1977)

The therapeutic effects of benzodiazepines in psychoneurosis may depend in part on their ability to release or disinhibit a patient's anxiety-suppressed gratification-seeking behavior. Benzodiazepines may disinhibit behavior by reducing the activity of serotonin (and possibly acetylcholine) neurons in the brain's "punishment" system. Reduction of serotonin transmission may be due to a facilitation of gamma-aminobutyric acid (GABA)-mediated presynaptic inhibition at the serotonin nerve terminal.
Does This Patient Have Infectious Mononucleosis?
Authors: Mark H. Ebell, Marlene Call, JoAnna Shinholser, Jack Gardner
Journal: JAMA (2016)

Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis.To systematically review the literature regarding the value of the clinical examination and white blood cell count for the diagnosis of mononucleosis.The databases of PubMed (from 1966-2016) and EMBASE (from 1947-2015) were searched and a total of 670 articles and abstracts were reviewed for eligibility.Eleven studies were included that reported data sufficient to calculate sensitivity, specificity, or both for clinical examination findings and white blood cell count parameters compared with a valid reference standard.Data were abstracted from each article by at least 2 reviewers, with discrepancies reconciled by consensus. Clinical findings evaluated in only 1 study are reported with sensitivity, specificity, likelihood ratio (LR), and 95% confidence interval, which were calculated from the available data. Findings evaluated in only 2 studies were summarized with their range, findings evaluated in 3 studies were summarized with a univariate random-effects summary, and findings evaluated in 4 or more studies were summarized with a bivariate random-effects meta-analysis.Sensitivity, specificity, and LRs for the diagnosis of mononucleosis.Mononucleosis is most commonly present among patients aged 5 to 25 years (especially those aged 16-20 years, among whom approximately 1 in 13 patients presenting with sore throat has mononucleosis). The likelihood of mononucleosis is reduced with the absence of any lymphadenopathy (summary sensitivity, 0.91; positive LR range, 0.23-0.44), whereas the likelihood increases with the presence of posterior cervical adenopathy (summary specificity, 0.87; positive LR, 3.1 [95% CI, 1.6-5.9]), inguinal or axillary adenopathy (specificity range, 0.82-0.91; positive LR range, 3.0-3.1), palatine petechiae (specificity, 0.95; positive LR, 5.3 [95% CI, 2.1-13]), and splenomegaly (specificity range, 0.71-0.99; positive LR range, 1.9-6.6). Symptoms are of limited value for the diagnosis of mononucleosis; sore throat and fatigue are sensitive (range, 0.81-0.83) but nonspecific. The presence of atypical lymphocytosis significantly increases the likelihood of mononucleosis (summary LR, 11.4 [95% CI, 2.7-35] for atypical lymphocytes ≥10%, 26 [95% CI, 9.6-68] for those with 20%, and 50 [95% CI, 38-64] for those with 40%). The combination of a patient having greater than 50% lymphocytes and greater than 10% atypical lymphocytes also is useful (specificity, 0.99; positive LR, 54 [95% CI, 8.4-189]).In adolescent and adult patients presenting with sore throat, the presence of posterior cervical, inguinal or axillary adenopathy, palatine petechiae, splenomegaly, or atypical lymphocytosis is associated with an increased likelihood of mononucleosis.
Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032.
Authors: Scott Joseph Antonia, Johanna C. Bendell, Matthew Hiram Taylor, Emiliano Calvo, Dirk Jaeger, Filippo G. De Braud, Patrick Alexander Ott, M. Catherine Pietanza, Leora Horn, Dung T. Le, Michael Morse, Jose A. Lopez-Martin, Paolo Antonio Ascierto, Olaf Christensen, Joseph Grosso, Jason S. Simon, Chen-Sheng Lin, Joseph Paul Eder
Journal: Journal of Clinical Oncology (2015)

7503 Background: Patients (pts) with SCLC respond to initial platinum (PLT) based chemotherapy (CT), but rapidly progress. Combined blockade of PD-1 and CTLA-4 immune checkpoint pathways has anti-tumor activity with a manageable safety profile. Nivolumab (NIVO) is a fully human IgG4 PD-1 immune checkpoint inhibitor approved in the US & Japan. Interim safety and efficacy of NIVO +\- ipilimumab (IPI), a CTLA-4 checkpoint inhibitor, in pretreated SCLC pts are reported. Methods: Pts who were PLT sensitive or refractory and had progressive disease were enrolled regardless of tumor PD-L1 status or number of prior CT regimens. This open-label study randomized pts to NIVO 3 mg/kg IV Q2W or NIVO+IPI (1 + 1 mg/kg, 1 + 3 mg/kg or 3 + 1 mg/kg) IV Q3W for 4 cycles followed by NIVO 3 mg/kg Q2W. Primary objective was overall response rate (ORR). Other objectives were safety, PFS, OS and biomarker analysis. Results: Seventy-five pts were enrolled (NIVO, n = 40; NIVO+IPI, n = 35); 59% had ≥ 2 prior regimens. Drug-related adverse events (DrAEs) in ≥ 10% were fatigue (18%), diarrhea (13%), nausea (10%), and decreased appetite (10%) with NIVO; and fatigue (29%), diarrhea (17%), pruritus (14%), nausea, endocrine disorders and rash (11% each) with NIVO+IPI. Gr 3/4 DrAE in ≥ 5% included diarrhea and rash (6% each; NIVO+IPI). Drug-related pneumonitis occurred in 2 pts (1 per arm). One pt experienced a drug-related SAE of myasthenia gravis on study which was fatal. Of 40 evaluable NIVO pts, partial response (PR) was seen in 6, 15% (duration of ongoing responses [DOR] 80-251+ days); stable disease (SD) in 9, 22.5%; and progressive disease (PD) in 25, 62.5%. In 20 evaluable NIVO+IPI pts, 1 had complete response (CR), 5% (DOR 322+ days); 4 had a PR, 20% (DOR 41-83+ days); 6 had SD, 30%, and 9 had PD, 45%. In the NIVO+IPI arm, 12 pts had not reached first tumor assessment and 3 were not evaluable. Nine pts (23%) continue treatment with NIVO and 19 (54%) with NIVO+IPI. Conclusions: In this PD-L1 unselected SCLC population with progression post-PLT, NIVO alone or combined with IPI was tolerable. ORR was 15% (NIVO) and 25% (NIVO+IPI) for evaluable pts; durable responses were noted. Updated safety, clinical activity and biomarker analysis will be presented. Clinical trial information: NCT1928394.
Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial
Authors: Timothy M Nywening, Andrea Wang-Gillam, Dominic E Sanford, Brian A Belt, Roheena Z Panni, Brian M Cusworth, Adetunji T Toriola, Rebecca K Nieman, Lori A Worley, Motoyo Yano, Kathryn J Fowler, A Craig Lockhart, Rama Suresh, Benjamin R Tan, Kian-Huat Lim, Ryan C Fields, Steven M Strasberg, William G Hawkins, David G DeNardo, S Peter Goedegebuure, David C Linehan
Journal: The Lancet Oncology (2016)
CHOP-R + bortezomib as initial therapy for diffuse large B-cell lymphoma (DLBCL)
Authors: J. P. Leonard, R. R. Furman, Y. K. Cheung, J. M. Vose, P. W. Glynn, J. Ruan, P. Martin, R. Niesvizky, A. LaCasce, A. Chadburn, M. Coleman
Journal: Journal of Clinical Oncology (2007)

8031 Background: Bortezomib is a proteasome inhibitor with anti-tumor activity in B cell malignancies. These effects, which may relate to NF-kappaB associated pathways, could sensitize tumor cells to standard chemotherapy-based regimens and enhance efficacy. We report findings of a phase I/II trial of dose-escalated bortezomib + standard CHOP-rituximab in DLBCL patients (accrual of the MCL cohort of this study remains ongoing). Methods: Patients with previously untreated DLBCL (n=40) received CHOP-21 + rituximab (375 mg/m 2 each cycle) plus bortezomib at 0.7 mg/m 2 (Arm 0, n=4), 1.0 mg/m 2 (Arm 1, n=8) or 1.3 mg/m 2 (Arm 2, n=28 including phase I and all phase II) on days 1 and 4 of each cycle Results: Median age (n=40) was 58 years (range 21–86), thirty-five subjects (88%) had stage III/IV disease at study entry, and 29 (73%) had elevated serum lactate dehydrogenase (LDH). Patients generally had unfavorable baseline international prognostic index (IPI) scores of 2 in 16 subjects (40%) and 3–5 in 19 subjects (48%). Median follow-up is 21 months (range 9 - 35 months). Treatment was generally well tolerated. Peripheral neuropathy occurred in 22 subjects (55%), with 45% grade 1, 5% grade 2 and 5% grade 3. Grade 4 hematologic toxicity included thrombocytopenia (15%) and leukopenia (15%). Four subjects (3 over age 75 and all with high risk IPI) died prior to first response assessment. Intent to treat (ITT) overall response rate (n=40) is 90% with 68% CR/CRu. For the evaluable subset (n=36), ORR was 100% with CR/CRu 75%. Kaplan-Meier estimate (n=40) of 2-year progression-free survival is 72%. Of all 19 enrolled (ITT) patients in the high-intermediate or high-risk IPI groups, 14 (74%) were alive without progression at last assessment. Correlation of outcome with cell of origin type (activated B cell vs germinal center) is ongoing. Conclusions: Bortezomib can be administered with acceptable toxicity in conjunction with CHOP-R chemotherapy. Efficacy findings with this combination regimen in newly-diagnosed DLBCL are encouraging and warrant further study. No significant financial relationships to disclose.
Voice Trial-Results from a Multicenter Phase Ii Study of Assessment of Clinical Efficacy and Safety in Capecitabine Plus Intermittent Oxaliplatin Together with Bevacizumab As the First-Line Therapy for the Patients with Advanced Colorectal Cancer
Authors: C. Kosugi, K. Koda, T. Denda, K. Ishibashi, H. Ishida, K. Seike, H. Sakata, S. Yanagisawa, T. Natsume, W. Takayama, N. Koike, H. Matsubara, K. Tanaka, M. Yamazaki, K. Shuto, M. Suzuki, K. Matsuo, M. Mori, A. Hirano
Journal: Annals of Oncology (2014)