tbuckley/cabot-search huggingface dataset:
A Calculating Device to Predict Individualized Outcomes in Adrenocortical Carcinoma
Authors: Nancy D. Perrier
Journal: JAMA Surgery (2015)

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E1308: Reduced-dose IMRT in human papilloma virus (HPV)-associated resectable oropharyngeal squamous carcinomas (OPSCC) after clinical complete response (cCR) to induction chemotherapy (IC).
Authors: Anthony Cmelak, Shuli Li, Shanthi Marur, Weiqiang Zhao, William H. Westra, Christine H. Chung, Maura L. Gillison, Jill Gilbert, Julie E. Bauman, Lynne I. Wagner, Robert L. Ferris, David R. Trevarthen, A. Dimitrios Colevas, Balkrishna N. Jahagirdar, Barbara Burtness
Journal: Journal of Clinical Oncology (2014)

LBA6006 Background: HPV+ patients (pts) in E2399 obtained a 2-yr 95% survival and 86% PFS after IC and 70Gy chemoradiation. We hypothesized reduced-dose IMRT (54Gy, 23% reduction) in HPV+ OPSCC pts could maintain high LR control and 85% 2-yr PFS in pts with cCR to IC. Methods: Pts with resectable stage III/IVa,b HPV+ OPSCC received IC q3 weeks x 3 with paclitaxel 90mg/m2 days (D) 1,8,15, cisplatin 75mg/m2 D1, and standard cetuximab (Cetux) weekly schedule. IC response determined IMRT dose independently at primary and involved nodes: IMRT 54Gy/27 if cCR vs. 69.3Gy/33 if &lt;cCR. Cetux was continued during IMRT. Primary endpoint was 2-yr PFS. Results: 90 pts were enrolled (80 analyzable). Med FU is 23.3 months (mo). Tumor and Nodal stage: T4-10%, T3-17%, T2-50%, and T1-23%; N0,1-16%, N2a,b-54%, N2c-31%. Med age 57yrs. 46% never smoked and 84% not current smokers. IC and C-IMRT was well tolerated: 96% received all 3-cycles of IC. 71% had cCR. 62 pts (78%) received reduced-dose Cetux-IMRT. For all reduced IMRT pts, 23mo PFS is 84%, primary site LC 94%, nodal control 95%, and distant 92%. Post-treatment neck dissection was positive for tumor in 4/8 reduced dose IMRT pts compared to 1/3 pts treated with std dose. One late grade 3 toxicity occurred in 1 reduced-dose pt: hypomagnesemia at 30mo. Conclusions: IC + reduced-dose Cetux-IMRT produced high tumor control rates. Late toxicities were minimal. Low dose pts achieved 84% PFS at 23mo and 95% 2-yr survival. Pts with &lt;10yrs smoking, T1-3 and N0-2b disease achieved 96% PFS. Further studies of reduced-dose IMRT in chemoresponsive HPV+ pts are warranted. Clinical trial information: NCT01084083. [Table: see text]
Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3
Authors: Chiharu Kawamura, Masahiro Kizaki, Kenji Yamato, Hideo Uchida, Yumi Fukuchi, Yutaka Hattori, Takeyoshi Koseki, Tatsuji Nishihara, Yasuo Ikeda
Journal: Blood (2000)
Risk factors for Group B Streptococcus colonisation and disease in Gambian women and their infants
Authors: K. Le Doare, S. Jarju, S. Darboe, F. Warburton, A. Gorringe, P.T. Heath, B. Kampmann
Journal: Journal of Infection (2016)

ObjectivesTo determine risk factors for GBS colonisation in Gambian mothers and in their infants from birth to day 60–89 of age.MethodsSwabs and breastmilk from mothers/infant pairs were collected and cultured on selective agar. Negative samples were analysed for GBS DNA via real-time PCR. Positive isolates were serotyped using multiplex PCR and gel-agarose electrophoresis.ResultsSeven hundred and fifty women/infant pairs were recruited. 253 women (33.7%) were GBS-colonised at delivery. The predominant serotypes were: V (55%), II (16%), III (10%), Ia (8%) and Ib (8%). 186 infants were colonised (24.8%) at birth, 181 (24.1%) at 6 days and 96 at day 60–89 (14%). Infants born before 34 weeks of gestation and to women with rectovaginal and breastmilk colonisation at delivery had increased odds of GBS colonisation at birth. Season of birth was associated with increased odds of persistent infant GBS colonisation (dry season vs. wet season AOR 2.9; 95% CI 1.6–5.2).ConclusionGBS colonisation is common in Gambian women at delivery and in their infants to day 60−89 and is dominated by serotype V. In addition to maternal colonisation, breastmilk and season of birth are important risk factors for infant GBS colonisation.
Correlation of KRAS status with clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) treated first-line with FOLFOX6 + cetuximab (FX+C) or FOLFIRI + cetuximab (FF+C): The CECOG/CORE1.2.001 trial
Authors: I. Koza, F. Wrba, D. Vrbanec, J. Ocvirk, T. E. Ciuleanu, S. Beslija, D. Papamichael, D. Messinger, C. C. Zielinski, T. Brodowicz
Journal: Journal of Clinical Oncology (2009)

4055 Background: Previous retrospective analyses of KRAS mutation status from the randomized CECOG/CORE 1.2.001 phase II trial has shown that treatment with cetuximab plus standard chemotherapy (CT) in pts with KRAS wild-type (wt) tumors leads to significantly better progression-free survival (PFS) and overall survival (OS) compared with KRAS mutant (mt) tumors. Methods: CECOG investigators performed a post-study survival update, re-assessing the impact of KRAS status and other possible predictive factors for OS using multivariable Cox proportional hazard methods. Results: KRAS-evaluable tissue was available from 117 (77%) of 151 pts in the ITT population. KRAS wt status was detected in 53% (n=62) of tumors (34/57 and 28/60 in the FX+C and FF+C arm, respectively). After a median follow up of 29 months (mo), OS in pts with KRAS wt tumors was significantly improved compared to pts with KRAS mt tumors (median 20.8 vs 15.9 mo; hazard ratio (HR)=1.62; p=0.0296). OS analysis by treatment arm revealed a statistically significant difference in favor of pts with KRAS wt tumors in the FX+C arm (median 22.5 vs 15.2; HR=2.06; p=0.0201) and no significant differences in the FF+C arm. Exploratory multivariable Cox proportional hazard analysis showed that as well as KRAS wt status (vs KRAS mt), an acne-like rash of grade 2/3 (vs grade 0/1) in the first 6 weeks and no prior treatment (vs prior neo-/adjuvant treatment) were the strongest independent predictors for prolonged survival (each p&lt;0.005). Conclusions: This analysis confirmed the results of previous studies: treatment with cetuximab plus standard CT in pts with KRAS wt tumors leads to significantly better OS compared to pts with KRAS mt tumors. The early occurrence of a cetuximab-related grade 2/3 acne-like rash seems to be an independent predictor for prolonged survival in addition to KRAS status. The relevance of the lower predictive value of KRAS status noted for OS in the FF+C arm pts vs the significant effect in the FX+C arm is undetermined due to the low sample size of the subgroup analyses. [Table: see text]
Early diagnosis of childhood tuberculosis
Authors: M. Desai, D. Spencer
Journal: BMJ (1996)

in those dying of cardiac causes compared with those who survived (0.11 (0.07) and 0.05 (0.02) ms"2 respectively, P<0.001).However, heart rates were similar in the two groups (66 (12) beats/minute in survivors and 66 (13) beats/ minute in those who died).Although there are methodological problems with qualitative measurement of QTc dispersion, previous work has shown that variation in interlead measurements far outweigh inaccuracies introduced by any other factor, including interobserver and intraobserver variation.2In our study the intraobserver and interobserver vari- ability expressed in absolute values was of the order of 1 1 ms"2 and 16 ms"/2 respectively, suggesting that the differences in QTc dispersion between patient groups cannot be explained by variability in measurement.In fact, we reported coefficients of variation on page 875 of our article.The study by Agha W Haider and Saba Naz showing reduced QTc dispersion in patients with preinfarction angina warrants further investigation.Although preinfarction angina might confer some early benefit in hospital, it tends to be associated with more recurrent ischaemia and a worse longer term outcome.3A recent study showing increased QT dispersion in diabetic patients with autonomic dysfunction4 suggests that measurement of QT dispersion in this group of patients may be a cheap and valuable tool for detecting patients at increased risk of sudden cardiac death, as suggested by Gyorgy Jermendy.
Impact on therapeutic index of a chronomodulated infusion at conventional doses of oxaliplatin (OHP), 5-fluorouracil (5-FU) and folinic acid (AF) in not previously treated metastatic colorectal cancer patients: A multicentric observational study
Authors: M. Pirovano, A. Zambelli, F. Gherardi, S. Masseroni, A. Nasisi, L. Paraboni, G. Martignoni, M. Meregalli, C. S. Huscer, D. Tabiadon
Journal: Journal of Clinical Oncology (2007)

14572 Background: FOLFOX4 schedule represents the standard treatment for metastatic colorectal cancer in EU, but is characterized by relevant adverse effects like G3–4 neutropenia in 42 % of patients (data from MOSAIC study). Adjustment of chemotherapy delivery schedule to the circadian timing system allows a significative improvement of tolerability. Objective of this multicentric observational study is the evaluation of therapeutic index of a OHP and 5-FU + AF based schedule at the same doses of FOLFOX 4, but administered according to a chronomodulated schedule (FLOX-1). Methods: From November 2005 to December 2006, we treated 41 metastatic colorectal cancer patients (19 male and 22 female, average age 65) with OHP 85 mg/m 2 /d1q14 sinusoidal 12 hour infusion with flow rate peak at 04.00 PM; 5-FU 1000 mg and AF 100 mg/m 2 /d1–2q14 sinusoidal 12 hour infusion with flow rate peak at 04.00 AM: a total of 258 cycles (5.5 average for patient) were administered using Melodie infusional programmable system (138 cycles) and CIP preprogrammed disposable system (128 cycles), all in homecare regimen. These data confirm a significative tolerability improvement of OHP, 5-FU and AF schedule when infused according to a chronomulated infusion prophile in metastatic colorectal cancer patients. Results: Overall average dose intensity was 39.1 mg/m 2 /w for OHP and 907.5 mg/m 2 /w for 5-FU respectively. No G3-G4 haematological, hepatic and neurological toxicity were observed. ORR (CR+PR) was 41%. No patient has been treated with G-CSF. Conclusions: These data confirm a significative tolerability improvement of OHP, 5-FU and AF schedule when infused according to a chronomulated infusion prophile in metastatic colorectal cancer patients. No significant financial relationships to disclose.
P0187 : A Randomized controlled trial comparing the alfapump© with paracentesis in patients with refractory ascites: Clinical and pathophysiological effects on cardiac, haemodynamic, inflammatory, renal and nutritional parameters
Authors: D. Adebayo, A. Mohammed, S. Arora, F. De Chiara, C. Trepte, S. Whitaker, V. Mishra, D. Cohen, D. Sharma, M. Malago, R. Jalan
Journal: Journal of Hepatology (2015)
Case Control Cohort Study of Cancer Rates in Synchronous Primary Sclerosing Cholangitis and Inflammatory Bowel Disease Versus Patients With Inflammatory Bowel Disease Alone
Authors: K. Liu, R. Wang, V. Kariyawasam, P. Lunney, M. Wells, S. Strasser, G. McCaughan, C. Corte, R.W.L. Leong
Journal: Clinical Gastroenterology and Hepatology (2015)
The impact of malignant pleural effusion – A retrospective review
Authors: Richard Budd, Nanu Acharya, Muhammad Malik
Journal: European Respiratory Journal (2011)

Barnsley Hospital (BH) serves a population of 220,000 people. The respiratory specialists have noticed a high burden of care associated with the management of pleural disease. An average United Kingdom (UK) district general hospital would expect to diagnose and treat approximately 250 new cases of malignant pleural effusion (MPE) per year [1]. Projected figures suggest an increase of 100,000 cancer diagnoses per year within the UK of which 15% will have an associated MPE [1]. One NHS bed day costs £225 [2] and with this in mind we considered the workload and financial resources required to manage these cases.   Method:  We retrospectively analysed data over an 18-month period, searching clinical coding archives using the keyword “pleural effusion”. Cases with a malignancy coded under the heading “primary diagnosis”, “diagnosis 1” or “diagnosis 2” were identified as having a MPE. These cases were reviewed to assess total number of inpatient days, number of patient episodes and length of stay (LOS).   Results:  Number of patient episodes for pleural effusion of any cause = 1195  Number of patient episodes for MPE = 226 (including recurrent admissions)  Number of MPE secondary to lung cancer = 90 (39.8%)  Average LOS for MPE = 7.3 days   Conclusion:  The burden of MPE management at BH is significant, considering that in this 18 month period 1650 inpatient days were utilised.  By highlighting the financial impact of this data there has been a successful bid by the lead lung cancer specialist for funding of a medical thoracoscopy service in BH. A recent audit of the medical thoracoscopy service has confirmed a reduction in LOS and recurrent admissions.   Reference:   1British Thoracic Society Pleural Disease Guidelines 2010.  2http://www.institute.nhs.uk/.
Both knowledge and compassion are needed
Authors: S. Browne
Journal: BMJ (1994)

EDITOR,—Kenneth Calman calls for a full debate on the purpose of medicine and its basic values and a continuing review of medical education, emphasising diagnosis and high ethical standards.1 Western medicine, classed as a caring profession from the fourth century to the present day, owes a great debt to the Christian faith and individual Christians for its caring tradition and its progress.2

Dr Thomas Sydenham (1624-89) has …
Clinical characteristics, treatment and outcomes of MRSA bacteraemia in the elderly
Authors: Guillermo Cuervo, Oriol Gasch, Evelyn Shaw, Mariana Camoez, María Ángeles Domínguez, Belén Padilla, Vicente Pintado, Benito Almirante, José A. Lepe, Francisco López-Medrano, Enrique Ruiz de Gopegui, José A. Martínez, José Miguel Montejo, Elena Perez-Nadales, Ana Arnáiz, Miguel Ángel Goenaga, Natividad Benito, Juan Pablo Horcajada, Jesús Rodríguez-Baño, Miquel Pujol, A. Jover, F. Barcenilla, M. Garcia, M. Pujol, O. Gasch, M.A. Domínguez, M. Camoez, C. Dueñas, E. Ojeda, J.A. Martinez, F. Marco, F. Chaves, M. Lagarde, F. López-Medrano, J.M. Montejo, E. Bereciartua, J.L. Hernández, M.A. Von Wichmann, M.A. Goenaga, J.M. García-Arenzana, B. Padilla, C. Padilla, E. Cercenado, G. García-Pardo, J. Tapiol, J.P. Horcajada, M. Montero, M. Salvado, A. Arnáiz, C. Fernandez, E. Calbo, M. Xercavins, A. Granados, D. Fontanals, V. Pintado, E. Loza, J. Torre-Cisneros, R. Lara, F. Rodríguez-López, M. Rodríguez, C. Natera, I. Gracia-Ahufinger, J.R. Blanco, I. Olarte, N. Benito, B. Mirelis, J. Murillas, E. Ruiz de Gopegui, E. Espejo, M.A. Morera, J. Rodríguez-Baño, L.E. López-Cortés, A. Pascual, C. Martín, J.A. Lepe, J. Molina, R. Sordé, B. Almirante, N. Larrosa
Journal: Journal of Infection (2015)
Differences in lateral hemispheric asymmetries of glucose utilization between early- and late-onset Alzheimer-type dementia
Authors: E Koss, R P Friedland, B A Ober, W J Jagust
Journal: American Journal of Psychiatry (1985)

Positron emission tomography with [18F]fluorodeoxyglucose revealed greater right than left hemispheric impairment of cortical glucose metabolism in patients with probable Alzheimer's disease who were younger than 65 but not in those over 65. This asymmetry was related to poor visuospatial performance.
Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel–Lindau Gene Mutation Status
Authors: Yosra Messai, Sophie Gad, Muhammad Zaeem Noman, Gwenael Le Teuff, Sophie Couve, Bassam Janji, Solenne Florence Kammerer, Nathalie Rioux-Leclerc, Meriem Hasmim, Sophie Ferlicot, Véronique Baud, Arnaud Mejean, David Robert Mole, Stéphane Richard, Alexander M.M. Eggermont, Laurence Albiges, Fathia Mami-Chouaib, Bernard Escudier, Salem Chouaib
Journal: European Urology (2015)
Forward-Viewing Colonoscopy Versus Full-Spectrum Endoscopy (Fuse) for Dysplasia Detection With and Without Chromoendoscopy In Inflammatory Bowel Diseases: A Prospective, Randomized-order, Crossover Tandem Surveillance Colonoscopy Study
Authors: M. Ooi, J. Panetta, M. Zhu, C. Corte, R.W.L. Leong
Journal: Clinical Gastroenterology and Hepatology (2015)
EBV-miR-BHRF1-2 targets PRDM1/Blimp1: potential role in EBV lymphomagenesis
Authors: J Ma, K Nie, D Redmond, Y Liu, O Elemento, D M Knowles, W Tam
Journal: Leukemia (2015)

PRDM1/Blimp1, a master regulator of B-cell terminal differentiation, has been identified as a tumor suppressor gene in aggressive lymphomas, including diffuse large B-cell lymphoma (DLBCL). It has been shown in DLBCL and Hodgkin lymphoma that PRDM1 is downregulated by cellular microRNAs. In this study, we identify the Epstein–Barr virus (EBV) microRNA (miRNA), EBV-miR-BHRF1-2, as a viral miRNA regulator of PRDM1. EBV-miR-BHRF1-2 repressed luciferase reporter activity by specific interaction with the seed region within the PRDM1 3’ untranslated region. EBV-miR-BHRF1-2 inhibition upregulated PRDM1 protein expression in lymphoblastoid cell lines (LCL), supporting a role of miR-BHRF1-2 in PRDM1 downregulation in vivo. Discordance of PRDM1 messenger RNA and protein expressions is associated with high EBV-miR-BHRF1-2 levels in LCLs and primary post-transplant EBV-positive DLBCL. Enforced expression of PRDM1-induced apoptosis and cell cycle arrest in LCL cells. Inhibition of EBV-miR-BHRF1-2 negatively regulates cell cycle and decreases expression of SCARNA20, a small nucleolar RNA that is also downregulated by PRDM1 overexpression. The interaction between EBV-miR-BHRF1-2 and PRDM1 may be one of the mechanisms by which EBV-miR-BHRF1-2 promotes EBV lymphomagenesis. Our results support the potential of EBV-miR-BHRF1-2 as a therapeutic target in EBV-associated lymphoma.
Lincrna Hotset Regulates Hox Gene Transcription and Promotes Early Hematopoietic Fates
Authors: Changwang Deng, Ying Li, Besabeh Tusi, Wei Jian, Bhavita Patel, Yangqiu Li, Jorg Bungert, Lei Zhou, Yi Qiu, Suming Huang
Journal: Blood (2014)
Real-time microscopy of interactions between alveolar macrophages and the alveolar epithelium in situ
Authors: Kristin Westphalen, Jahar Bhattacharya
Journal: European Respiratory Journal (2014)

Background: Alveolar macrophages (AMs) are the first line of defense in the lung. The mechanisms of how alveolar macrophages interact with the alveolar epithelium to modulate lung inflammation are not well defined. Methods: To visualize AMs in situ , we expressed Enhanced Yellow Fluorescent Protein in CD11c+ AMs (AMYFP). We isolated and blood-perfused lungs of AMYFP mice at constant pulmonary artery, left atrial and alveolar pressures of 10, 3 and 5 cmH2O, respectively. We imaged the lungs by confocal microscopy. We micropunctured single alveoli and microinfused dyes and reagents. To define the role of gap junctional channels (GJCs) in lung injury, we crossed AMYFP mice with Cx43floxed/floxed mice (AMYFPCx43-/-). We treated mice with intra-nasal instillations of 1 mg/kg LPS 24 h before we excised the lungs. Results: Calcium uncaging experiments in wild type mice revealed that 38±10% of all AMs formed functional GJCs with the alveolar epithelium. As compared to wild type mice, AM-specific knockout of Cx43 in AMCx43-/- mice resulted in a 2-fold higher neutrophil recruitment to the lung 24 h after LPS and reduced survival after 25 mg/kg LPS (P<0.05). Cytokines of macrophages origin (MIP-1alpha) but also cytokines that were predominantly of epithelial origin (CXCL1 and 5) were increased in the bronchoalveolar lavage, suggesting that AM-epithelial communication may serve as a feedback loop to regulate lung inflammation. Conclusions: For the first time, we report that AMs form GJCs with the alveolar epithelium. The interaction between AMs and the epithelium through GJCs was crucial in that knockout of GJCs in AMs aggravated lung injury (HL78645, HL64896).
Biopersistence of nanoparticle in inhalation and intratracheal instillation studies for hazard assessment
Authors: Takako Oyabu, Yasuo Morimoto, Byeong-Woo Lee, Takami Okada, Hiroto Izumi, Taisuke Tomonaga, Yukiko Yoshiura, Manabu Shimada, Masaru Kubo, Toshihiko Myojo
Journal: European Respiratory Journal (2014)

For assessing the inhalation toxicity of nanoparticles, we performed an inhalation study and an intratracheal instillation study of the same material, nickel oxide nanoparticle, at almost the same dose to rat lung and compared the results of the two methods.

In inhalation study, male Fisher 344 rats were exposed to NiO nanoparticles at 0, 1.65±0.20 and 0.32±0.07 mg/m3 for 4 weeks. In instillation study, 0, 0.2, 1 mg of NiO nanoparticle suspended in 0.4 ml distilled water were intratracheally instilled into male Fisher 344 rat's lung. In the recovery period after the inhalation and the instillation, each 10 rats of each group were dissected at from 3 days to 12 months and NiO amounts in 5 lungs each were determined by ICP-AES after acid digestion.

The NiO amounts at 3 days after the inhalation were 40±2.4 μg in low concentration exposure and 132±9.9 μg in high concentration exposure, respectively. And those at 3 days after the instillation were 136±6.5 μg in 0.2 mg and 738±50 μg in 1.0 mg, respectively. The amounts of NiO in lung at 3 days after the high inhalation exposure and those after 0.2 mg instillation were almost the same.

Biological half times of NiO until 6 months were 3.7 months in low and 4.5 months in high inhalation exposure and 4.9 months in 0.2 mg and 9.5 months in 1.0 mg, respectively.

Our results suggested that both inhalation study and instillation study show the similar biopersistence at almost the same lung dose. Further researches are continued.

This work is on the research program of “Development of innovative methodology for safety assessment of industrial nanomaterials supported by Ministry of Economy, Trade and Industry (METI) of Japan.