tbuckley/cabot-search huggingface dataset:
S87 Are oral steroids effective in treating the symptoms of acute lower respiratory tract infection in non-asthmatic adults? The Oral Steroids for Acute Cough (OSAC) placebo-controlled randomised trial
Authors: AD Hay, HE Downing, ST Brookes, G Young, A Harnden, SP Hollinghurst, D Kendrick, P Little, MT May, MV Moore, E Orton, K Wang, MJ Thompson
Journal: Thorax (2015)

<h3>Background</h3> The majority of UK adults experience at least one lower respiratory tract infection (LRTI, or acute bronchitis) a year. Despite an absence of evidence in this patient group, some GPs prescribe inhaled or oral corticosteroids. OSAC sought to demonstrate 'proof of concept' symptomatic effectiveness of a moderate dose of oral corticosteroid for adults without asthma or COPD with acute LRTI. <h3>Methods</h3> OSAC was a double blind, placebo controlled RCT set in GP practices in England, powered to investigate if oral prednisolone reduces the duration of moderately bad or worse cough and/or the severity of its associated symptoms, when compared to placebo, by at least 20%. Adults (≥18 years) with acute (≤28 days) cough, for whom same-day antibiotics were not clinically indicated, and without asthma or COPD, received 40 mg oral prednisolone or matched placebo for 5 days. Symptom diaries, completed for up to 28 days, measured two primary outcomes: the duration of moderately bad or worse cough; and the average severity of all symptoms on days 2 to 4 on a scale of 0–6. We sought to demonstrate a minimum clinically important reduction of 20% in each outcome. <h3>Results</h3> 398 participants were randomised to either prednisolone or placebo tablets (198 and 200 respectively) from 54 UK primary care sites. Attrition was lower than expected, giving over 85% power for the two primary outcomes. Data were analysed on an intention-to-treat basis. The median duration of moderately bad or worse cough was 5 days in both groups (IQRs 2–8 and 3–8 for prednisolone and placebo respectively). Adjusting for trial centre and baseline characteristics, this gave a hazard ratio of 1.11 (95% CI 0.89 to 1.39, p = 0.35). Symptom severity was lower in the prednisolone group (mean 1.99 vs 2.16), adjusted difference -0.090 (-0.212 to 0.003, p = 0.152). <h3>Conclusions</h3> We found no evidence that a moderately high dose of oral corticosteroid reduced either duration of moderately bad (or worse) cough, or symptom severity at days 2 to 4 in adults without asthma or COPD with LRTI not requiring immediate antibiotic treatment. Lower dose oral or high dose inhaled corticosteroids are also unlikely to be beneficial.
Abstract 11515: Does Prolonged Dual Antiplatelet Therapy Increase Mortality After Drug-Eluting Stent Implantation?
Authors: John A Bittl, Usman Baber, Steven M Bradley
Journal: Circulation (2015)

Introduction: The Dual Antiplatelet Therapy (DAPT) trial found a borderline increase in the rate of all-cause mortality in patients treated with 30 compared with 12 months of DAPT (2.0% vs. 1.5%, HR 1.36, 95% CI 1.00-1.85, P = 0.05). Hypothesis: A finding of borderline significance in a mega-trial may reflect the play of chance. Methods: We used a Bayesian conjugate-normal approach (Figure A) to update the mortality results from the DAPT trial with an empiric prior probability distribution based on results in 9 smaller randomized controlled trials (RCTs). Results: The empiric prior (blue), which suggests that the odds of mortality in the 9 smaller RCTs could be 6% lower or as much as 40% higher after prolonged than after short DAPT, overlaps with the likelihood (red) from the DAPT trial itself. Bayesian inference (black) affirms a significant increase in mortality with prolonged DAPT (posterior mean odds ratio [OR] 1.21, 95% Bayesian confidence interval [BCI] 1.02-1.44). Sensitivity analysis, which weighs the number of effective events by the proportion of patients with acute coronary syndromes, produces a nearly identical point estimate (OR 1.23, 95% BCI 0.96-1.58). Conclusions: Our analysis provides credible evidence that 30 months of DAPT is associated with higher mortality rates than is 12 months of therapy. The mortality increase in the DAPT trial is predictable from prior RCTs and not likely to be a chance finding.
Smartphone-Based Fluorescent Diagnostic System for Highly Pathogenic H5N1 Viruses
Authors: Seon-Ju Yeo, Kyunghan Choi, Bui Thi Cuc, Nguyen Ngoc Hong, Duong Tuan Bao, Nguyen Minh Ngoc, Mai Quynh Le, Nguyen Le Khanh Hang, Nguyen Co Thach, Shyam Kumar Mallik, Hak Sung Kim, Chom-Kyu Chong, Hak Soo Choi, Haan Woo Sung, Kyoungsik Yu, Hyun Park
Journal: Theranostics (2015)

Field diagnostic tools for avian influenza (AI) are indispensable for the prevention and controlled management of highly pathogenic AI-related diseases.More accurate, faster and networked on-site monitoring is demanded to detect such AI viruses with high sensitivity as well as to maintain up-to-date information about their geographical transmission.In this work, we assessed the clinical and field-level performance of a smartphone-based fluorescent diagnostic device with an efficient reflective light collection module using a coumarin-derived dendrimer-based fluorescent lateral flow immunoassay.By application of an optimized bioconjugate, a smartphone-based diagnostic device had a two-fold higher detectability as compared to that of the table-top fluorescence strip reader for three different AI subtypes (H5N3, H7N1, and H9N2).Additionally, in a clinical study of H5N1-confirmed patients, the smartphone-based diagnostic device showed a sensitivity of 96.55% (28/29) [95% confidence interval (CI): 82.24 to 99.91] and a specificity of 98.55% (68/69) (95% CI: 92.19 to 99.96).The measurement results from the distributed individual smartphones were wirelessly transmitted via short messaging service and collected by a centralized database system for further information processing and data mining.Smartphone-based diagnosis provided highly sensitive measurement results for H5N1 detection within 15 minutes.Because of its high sensitivity, portability and automatic reporting feature, the proposed device will enable agile identification of patients and efficient control of AI dissemination.
Abstract 052: Genome-wide Methylation Study of Body Mass Index (BMI) in African American Adults: Preliminary Data from the ARIC Study
Authors: Ellen W Demerath, Weihua Guan, James S Pankow, Megan L Grove, Kari E North, Myriam Fornage, Jan Bressler, Thomas H Mosley, Eric A Boerwinkle
Journal: Circulation (2013)

Background and Objective: DNA methylation patterns are influenced by environmental factors, alter gene expression, and can point to genomic regions affected by behavioral and lifestyle factors, such as obesity. However, analytic strategies for high dimensional methylation data are still evolving. Here we present preliminary analyses examining cross-sectional associations between DNA methylation level and BMI in African-American adults enrolled in the Atherosclerosis Risk in Communities (ARIC) study. Methods: BMI was measured at the same study visit as the DNA sample used for analysis. We used the Illumina Infinium HumanMethylation450 BeadChip to measure average methylation levels (beta values) in bisulfite-converted peripheral blood DNA obtained from participants from the Jackson, MS and Forsyth County, NC field centers. After excluding outlier samples and CpG sites using quality control filters, a model adjusting BMI (continuous) for batch (plate) and a model additionally adjusting for a small set of potential confounders (age, sex, center, smoking) were tested, with average beta value as the dependent variable. Robust standard errors were used for statistical testing and Bonferroni-corrected p value for significance was p&lt;1 x 10 -7 . Results: A total of 2,873 individuals and 473,788 CpG sites entered the analysis. In the minimally-adjusted analysis, there were over 300 regions distributed across all 22 autosomes with at least one significant association between BMI and CpG methylation. Adjusting for confounders sharply reduced the evidence for association to a total of approximately 20 regions on 11 autosomes. Conclusion: Use of the 450K methylation BeadChip in large epidemiologic cohorts has potential to help identify genes that are transcriptionally altered by common behavioral factors such as obesity, leading to improved understanding of related diseases. However, whereas genetic associations with disease are generally unconfounded by demographic and other covariate factors, methylation associations can be strongly affected by selection of covariates as well as other analytic choices.
Cortisol Secretion and Metabolism in Anorexia Nervosa
Authors: Robert M. Boyar, Leon D. Hellman, Howard Roffwarg, Jack Katz, Barnett Zumoff, John O'Connor, H. Leon Bradlow, David K. Fukushima
Journal: New England Journal of Medicine (1977)

We studied cortisol secretion and metabolism in 10 women with anorexia nervosa. The 24-hour mean plasma cortisol concentration was 8.9 mug per deciliter (controls, 4.9) (P less than 0.01). Secretory patterns showed normal circadian rhythms. Cortisol half-life was prolonged from 60 to 78 minutes (P less than 0.01), and metabolic clearance rate was decreased from 359 to 177 liters per day (P less than 0.001). Cortisol production was normal (19.4 mg per day). Urinary cortisol was slightly elevated in two of five patients. These findings, as well as the increased tetrahydrocortisol/tetrahydrocortisone ratio (1.2 vs 0.65, P less than 0.01), also appear in hypothyroid patients. Thyroid-function studies showed normal total and free thyroxine and thyrotropin, but low plasma tri-iodothyronine levels (52.7+/-13.2 vs. 137.8+/-24.1 ng per deciliter in the controls, P less than 0.001). In five additional patients with anorexia nervosa studied before and after short-term tri-iodothyronine administration, metabolic abnormalities decreased as plasma tri-iodothyronine levels rose to or above normal.
ATPS-09A MITOCHONDRIAL METABOLISM INHIBITOR RADIO-SENSITIZES GLIOBLASTOMA TUMOURS IN MICE
Authors: Sylvia Chung, Stephanie Decollogne, Wendy Ha, Pierre Dilda, Philip Hogg, Kerrie McDonald
Journal: Neuro-Oncology (2015)

PENAO (4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid) is a mitochondrial metabolism inhibitor that is currently in Phase I clinical testing in patients with solid tumors refractory to standard therapy. PENAO is a cysteine mimetic trivalent arsenical that enters cells via an organic ion transporter and accumulates in the mitochondrial matrix where the arsenical moiety cross-links Cys160 and Cys257 on the matrix face of adenine nucleotide translocase (ANT), which inactivates the transporter. ANT inactivation leads to partial uncoupling of oxidative phosphorylation, increase in superoxide production, proliferation arrest and ultimately apoptosis of the cell. PENAO only reacts with ANT when cells are proliferating as Cys160 and Cys257 appear to be disulfide bonded in growth quiescent cells, and so unreactive towards PENAO. PENAO inhibited the proliferation of a panel of 13 glioblastoma cells, including cells from both primary and recurrent tumors, with IC50 values ranging from 0.3-4.5 µM. The IC50 values for proliferation arrest of normal lung fibroblasts and astrocytes are 9 µM and 7 µM, respectively, indicating selectivity for glioblastoma cells. Administration of PENAO (3 mg/kg/day) to mice bearing subcutaneous glioblastoma xenografts resulted in significant inhibition of tumor growth (7 partial and 3 complete responses). Ki67 and TUNEL staining of tumor sections showed that PENAO induced tumor cell growth arrest and death, respectively. Pharmacokinetic analysis demonstrated that PENAO readily crossed the blood-brain-barrier and accumulated specifically in tumor tissue. There were also no signs or symptoms of treatment toxicity. As PENAO induces superoxide production in glioblastoma cells, we hypothesized that PENAO in combination with radiation would synergise. Combining 2 Gy/day radiation (20 Gy total) with intraperitoneal administration of 20 mg/kg/day PENAO, resulted in significant improvement in median survival in an orthotopic glioblastoma murine model. These in-vitro and in-vivo results show that PENAO is a potential new therapeutic for glioblastoma, alone or in combination with radiation therapy
The evidence base for orthopaedics and sports medicine: scandalously poor in parts
Authors: L Stefan Lohmander, Ewa M Roos
Journal: British Journal of Sports Medicine (2016)

Medicine rests on an uneven evidence base.Some interventions are supported by large multicenter randomised controlled trials that have a low risk of bias and are powered for hard endpoints-a high level of evidence.Others depend on retrospective observational data that provide a lower level of evidence.Yet others were theorised and considered biologically or mechanistically plausible and are heirlooms of eminence based medicine.
Acquired Cytomegalovirus Infection
Authors: James B. Hanshaw, Robert F. Betts, Gilbert Simon, Ragna C. Boynton
Journal: New England Journal of Medicine (1965)

SINCE the isolation of the first strains of cytomegalovirus1 2 3 their role as pathogens for the fetus has been well documented.4,5 Infection in utero is characterized by generalized disease, which may resemble congenital toxoplasmosis, neonatal hepatitis or sepsis. It is manifested by jaundice, with elevation of the direct bilirubin, a petechial rash, hepatosplenomegaly, microcephaly and psychomotor retardation. This condition (congenital cytomegalic inclusion disease) represents one of the few examples of vertical transmission of an infectious disease in man. Infants affected excrete virus in the urine for months and years after birth4 5 6 —a circumstance unusual in human biology. Because acquired infections . . .
S56 Moving lentiviral-based gene therapy into a first-in-man CF trial
Authors: U Griesenbach, EWFW Alton, JM Beekman, AC Boyd, M Chan, JC Davies, LA Davies, HE Davidson, JF Dekkers, S Gea-Sorli, DR Gill, M Hasegawa, T Higgins, L Hyndman, G McLachlan, M Inoue, SC Hyde, C Moran, C Meng, MC Paul-Smith, IA Pringle, KM Pytel, A Rodriguez-Martinez, BJ Stevenson, S Tsugumine
Journal: Thorax (2015)

<h3></h3> The UK CF Gene Therapy Consortium has developed a pipeline of vectors to deliver CFTR into the airway epithelium. The first of these (plasmid/liposome complexes) recently completed a Phase IIb trial. Anticipating that increased efficiency of gene transfer will be required, we have developed an F/HN-pseudotyped lentivirus which is ~2 logs more efficient in lung gene transfer than non-viral vectors, a single administration lasts for the lifetime of a mouse, and can be repeatedly administered. This vector is targeted for a first-in-man study in 2016, and in preparation for this we have assessed (1) selection of the most efficient promoter/enhancer for lung gene transfer, (2) assessment of toxicity “benchmarked” against the leading non-viral formulation including mapping of integration sites, (3) determination of transduction efficiency which will be used to inform dose-ranging in the trial and characterisation of the cell types transduced by the vector, (4) understanding the impact of pre-existing and acquired anti-viral immunity on transduction efficiency and toxicity, (5) confirmation of CFTR expression and function in relevant models and (6) comparison of vector stability in a jet and single-pass mesh nebuliser. Data will be presented for each of these components, which we believe support progression into human studies. Trial design as well as a regulatory-compliant toxicology study will also be discussed.
New York–Presbyterian and GE
Authors: Herbert Pardes
Journal: New England Journal of Medicine (2005)

To the Editor: In his Perspective article, Dr. Garber (Oct. 14 issue)1 appropriately alerts us to the potential for conflicts of interest when an academic medical center forms a relationship with a business company. New York–Presbyterian Hospital is very sensitive to this possibility. At the same time, academic medical centers, facing formidable challenges to bring down the costs of care without affecting quality or access, would do well to embrace best business practices and new technology, regardless of where those ideas originate. Our collaboration with GE Medical Systems is based on having access to business skills and cutting-edge equipment that, . . .
ATCT-26TUMOR TREATING FIELDS-MEDIATED GENE EXPRESSION IN PATIENTS WITH GBM
Authors: Niv Pencovich, Oz Haim, Ester Feldmesser, Andrew Kanner, Zvi Ram
Journal: Neuro-Oncology (2015)

Tumor Treating Fields (TTFields) is a novel therapeutic modality approved for the treatment of recurrent glioblastoma (GBM) and has recently been shown in a large pivotal study to be very effective in newly-diagnosed GBM. The alternating electric fields interfere with microtubule assembly in the mitotic spindle, causes dielectrophoretic movement of intracellular organelles during phases of cell division, and lead to disruption of chromosome segregation and subsequent cell death. Nevertheless, the TTFields-mediated gene expression in GBM is yet unknown. Here we used RNA-sequencing to evaluate the alterations in the genome-wide expression pattern of GBM tumors resected from patients following TTFields treatment (n = 6), compared to tumors from patients treated with chemotherapy only (n = 6). Overall, 281 and 154 genes were up-regulated and down-regulated, respectively, following TTFields treatment compared to chemotherapy only (Over 2-fold change, P < 0.05). This gene set included numerous factors that were previously shown to play a role in GBM progression. Gene set enrichment analysis revealed that the genes that were affected by TTFields were highly enriched in key functions related to tumor progression, including epithelial to mesenchymal transition (EMT), cell cycle, and more. These data suggest that apart from its physical effects during cell cycle, TTFields therapy results in de-regulation of GBM gene expression. Moreover, TTFields-affected gene-set may offer new potential candidates for novel targeted GBM therapies.
Case 1-1995
Authors: J. LoCicero, E.J. Mark
Journal: New England Journal of Medicine (1995)

Presentation of CaseAn 80-year-old man was admitted to the hospital because of an enlarging lung tumor of long duration, recurrent bouts of postobstructive pneumonia, and recent respiratory distress.There was a history of a slowly growing mass in the left main bronchus that had first been noted on radiographs of the chest obtained 22 years earlier. The patient refused to undergo a thoracotomy, and the findings at bronchoscopic examination were considered to be consistent with a carcinoid tumor; no biopsy specimen was obtained. During the ensuing 15 years there were no symptoms referable to the mass.Seven years before . . .
Chemotherapy of Acute Leukemia in Childhood
Authors: D. J. Fernbach, K. M. Griffith, M. E. Haggard, T. M. Holcomb, W. W. Surow, T. J. Vietti, J. Windmiller
Journal: New England Journal of Medicine (1966)

THE Pediatric Division of the Southwest Cancer Chemotherapy Study Group has reported on the effectiveness of cyclophosphamide (Cytoxan) in inducing remissions in children with advanced acute leukemia.1 , 2 These preliminary results were particularly encouraging because cyclophosphamide, an alkylating agent of the mustard group, was found to act independently of other antileukemic drugs: steroids; 6-mercaptopurine (Purinethol, a purine antagonist); and methotrexate (a folic acid antagonist). It is also assumed to act with no crossresistance to vincristine (a periwinkle alkaloid). Subsequently, 137 patients with untreated acute leukemia were admitted to a Cooperative study to determine the effectiveness of cyclophosphamide at the beginning of . . .
Human Papillomavirus Infection as a Risk Factor for Squamous-Cell Carcinoma of the Head and Neck
Authors: Jon Mork, A. Kathrine Lie, Eystein Glattre, Sarah Clark, Göran Hallmans, Egil Jellum, Pentti Koskela, Bjørn Møller, Eero Pukkala, John T. Schiller, Zhaohui Wang, Linda Youngman, Matti Lehtinen, Joakim Dillner
Journal: New England Journal of Medicine (2001)

Oncogenic human papillomaviruses (HPVs), especially HPV type 16 (HPV-16), cause anogenital epithelial cancers and are suspected of causing epithelial cancers of the head and neck.
The Sooner the Better
Authors: Thomas P. Duffy
Journal: New England Journal of Medicine (1993)

A 19-year-old female college student who had just returned from a vacation at a resort in Mexico was admitted to the hospital with a three-day history of fever, muscle and joint pains, and a generalized rash.My first concern would be to establish the circumstances surrounding the patient's trip to Mexico. The explanation for her illness may be an exposure unique to the location of her journey or, conversely, a commonplace disorder such as a sexually transmitted disease or an allergic reaction to a medication. The chronology of the illness and its medical treatment, if any, and the . . .
Brief Communication: Effect of Protease Inhibitors on Focus Formation by Murine Sarcoma Virus 2
Authors: Yasuhito Yuasa, Hiroto Shimojo, Takaaki Aoyagi, Hamao Umezawa
Journal: JNCI Journal of the National Cancer Institute (1975)

The effect of six protease inhibitors, isolated from various species of actinomycetes, on focus formation by murine sarcoma virus was examined. Pepstatin was the only inhibitor. The treatment of cells with pepstatin at various times possibly retards the early stage of infection with murine sarcoma virus.
The Relation of Hydrocortisone Injections to Cleft Palate in Mice
Authors: Theodore H. Ingalls, Francis J. Curley
Journal: New England Journal of Medicine (1957)

THIS account reports the results of experiments in which pregnant mice of unpedigreed ancestry were injected on a single day of gestation with hydrocortisone acetate for the purpose of studying factors causing cleft palate in unborn embryos. The point of departure was a series of experiments by Fraser, Fainstat and their colleagues1 , 2 demonstrating that four daily injections of 2.5 mg. of cortisone acetate into pregnant mice of two highly inbred strains beginning on the eleventh day of pregnancy regularly induced cleft palates in the progeny from one strain, but did so in only 17 per cent of progeny from another . . .
Single oral dose pharmacokinetics (PK) and safety of 2-methoxyestradiol (2ME2) in patients with solid tumors
Authors: N. J. Lakhani, A. Sparreboom, J. Venitz, W. Dahut, W. D. Figg
Journal: Journal of Clinical Oncology (2005)

2071 Background: 2ME2 is an endogenous metabolite of estrogen and possesses potent antiangiogenic and pro-apoptotic activities. The objectives of this Phase I study were to characterize the toxicity profile and PK of 2ME2, and to determine the maximum tolerated dose (MTD). Methods: Twenty patients with solid tumors were given a single oral dose of 2ME2, 3 each at dose level (DL) 1 (400 mg/day) and DL 2 (800 mg/day), 6 at DL 3 (1600 mg/day), 5 at DL 4 (2200 mg/day) and 3 at DL 5 (3000 mg/day), for characterization of PK; followed by twice-daily oral dosing (400 mg/q12 h to 3000 mg/q12 h) in a dose escalation scheme. Blood samples were drawn before and 0.5, 1.5, 2, 3, 4, 5, 6, 9, 12, 24, 38 and 50 hours after the first dose of 2ME2. A novel LC/MS/MS method was developed and validated to determine 2ME2 in plasma with lower limit of quantitation of 1 ng/mL. Results: 2ME2 was well tolerated, and MTD was not reached at completion of DL 5. One patient had grade 4 angioedema 38 days into 2ME2 treatment at DL 3. 2ME2 was undetectable in plasma of 2 patients each at DL 1 and 2, and 1 patient each at DL 3, 4 and 5. For those patients with quantifiable concentrations, noncompartmental PK parameters are summarized in the table below. Conclusions: Oral 2ME2 is very well tolerated. Interindividual PK variability of 2ME2 is high, but the drug appears to be absorbed rapidly. Overall, circulating concentrations are very low, presumably due to dissolution rate-limited absorption and extensive first-pass elimination. No significant financial relationships to disclose.