tbuckley/cabot-search huggingface dataset:
GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma.
Authors: Laurie Helen Sehn, Neil Sun Chua, Jiri Mayer, Gregory Scott Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Hale Fowler, Vincent Delwail, Oliver W. Press, Gilles A. Salles, John G. Gribben, Anne Lennard, Pieternella J. Lugtenburg, Natalie Franklin, Elisabeth Wassner Fritsch, Guenter Fingerle-Rowson, Bruce D. Cheson
Journal: Journal of Clinical Oncology (2015)

LBA8502 Background: Treatments are limited and outcomes poor in rituximab-refractory (Rit-Ref) iNHL. Bendamustine (B) has a 9 mo median PFS and 10 mo response duration in ph II trials. Obinutuzumab (GA101/Gazyva [G]) is a glycoengineered type II aCD20 mAb with activity and acceptable safety in Rit-Ref NHL. Methods: GADOLIN (NCT01059630) is a ph III open label study in pts with CD20+ Rit-Ref iNHL. In the B arm, pts received B 120 mg/m 2 (d1+2, c1–6) alone; GB arm pts received B 90 mg/m 2 (d1+2, c1–6) with G 1000 mg (d1, 8, 15 c1, d1 c2–6) for up to six 28d cycles. Non-PD GB pts then received G monotherapy every 2 mo for up to 2 yrs. Primary endpoint was PFS assessed by an independent radiology facility (IRF), with 80% power to detect 43% improvement in median PFS. Results: In the protocol specified interim analysis, 396 pts were randomized to receive B (n = 202 [198 treated]) or GB (n = 194). The IDMC recommended to unblind the study as the primary endpoint had been reached (4 Feb 2015). Baseline characteristics were balanced between arms. Median age was 63 yrs and pts had a median of 2 prior therapies. Median observation time was 20 mo (B) and 22 mo (GB). IRF-assessed median PFS was 14.9 mo (B) and not reached (NR) for GB (HR 0.55, 95% CI 0.4–0.74; p = 0.00011). Median investigator-assessed PFS was 14 mo for B and 29 mo for GB (HR 0.52, 95% CI 0.39–0.70; p &lt; 0.0001). There were no significant differences in IRF-assessed ORR (63.0% B vs 69.1% GB) or CR (12.2% B vs 11.2% GB) at end of induction, in IRF-assessed best overall response up to 12 mo from start of treatment (76.6% B vs 78.6% GB), or in preliminary OS (median OS NR in either arm). In the treatment period, there were fewer Grade ≥ 3 adverse events with B than GB (62.1% B vs 68% GB), notably neutropenia (26.3% B vs 33.0% GB) and infusion-related reactions (3.5% B vs 8.8% GB), but more Grade ≥ 3 thrombocytopenia (16.2% B vs 10.8% GB), anemia (10.1% B vs 7.7% GB) and pneumonia (5.6% B vs 2.6% GB). Conclusions: G combined with B (90 mg/m 2 ) followed by G maintenance significantly improved PFS vs B alone (120 mg/m 2 ) in Rit-Ref iNHL. The clinically meaningful PFS improvement with GB is the first randomized evidence of benefit for a novel aCD20 mAb in Rit-Ref iNHL. Clinical trial information: NCT01059630.
Middle lobe pulmonary torsion after recurrent pleural effusions in a cirrhotic patient
Authors: Gilberto Szarf, Caroline Fontes R Dario, Rodrigo Caruso Chate, Elaine Yanata, Eduardo Werebe, Marcelo Buarque Gusmao Funari
Journal: Thorax (2015)

A 57-year-old man was admitted with acute chest pain and shortness of breath. He had cirrhosis secondary to hepatitis C infection and had undergone multiple thoracocentesis in the last months for recurrent pleural effusions. Chest X-ray showed increased density in the right lung base and chest CT showed a right pleural effusion, partial atelectasis of the right lower lobe, middle lobe bronchovascular structures twisted on themselves with a swirling appearance, obliteration of the proximal middle lobe artery, narrowing of the accompanying bronchus and ground-glass opacities in this same lobe (figure 1). Symptoms persisted over the next week and …
The preparticipation physical examination for athletics: a systematic review of current recommendations
Authors: Peter J Carek, Arch Mainous
Journal: BMJ (2003)

Abstract  OBJECTIVE: To examine the medical literature regarding the effectiveness of the preparticipation physical examination (PPE) in satisfying the basic requirements for medical screening.  DESIGN: Medline database (1966 to August 2002) search using the terms “preparticipation physical examination” and “physical examination.”  MAIN OUTCOME MEASURE: The United States Preventive Services Task Force (USPSTF) description of an effective screening test was used to determine whether the studies available provide evidence that the PPE satisfies the basic requirements for medical screening.  RESULTS: 176 articles were identified. The articles did not specify the presence of a randomized control group, nor did they describe subjects who were inappropriately cleared or restricted. Therefore, false-positive and false-negative rates were not presented. As the accuracy of the screening test was not demonstrated, the PPE failed to satisfy one of the major requirements for an effective screening test.  CONCLUSION: The PPE for athletes does not satisfy the basic requirements for medical screening as described by the USPSTF.
Late-breaking abstract: Critical role of proton-sensing OGR1 in dendritic cells in development of asthma
Authors: Haruka Aoki, Takeshi Hisada, Chihiro Mogi, Masakiyo Yatomi, Hiroaki Tsurumaki, Yosuke Kamide, Akihiro Ono, Yasuhiko Koga, Kunio Dobashi, Tamotsu Ishizuka, Masanobu Yamada, Fumikazu Okajima
Journal: European Respiratory Journal (2014)

Background: Ovarian cancer G protein-coupled receptor 1 (OGR1) stimulation by extracellular protons causes the activation of G proteins and subsequent cellular functions. However, the physiological and pathophysiological roles of OGR1 in airway responses remain largely unknown.

Objective: We examined whether OGR1 is involved in the asthmatic inflammatory responses.

Methods: Mice deficient in OGR1 were sensitized and challenged with ovalbumin (OVA) to measure airway inflammation and hyperresponsiveness. To examine the involvement of dendritic cells (DCs) in the airway responses, OVA-pulsed bone marrow-derived DCs were intratracheally transferred. Functional OGR1 expression and its activities in relation to migration in DCs were examined in vitro .

Results: OGR1-deficient mice are resistant to the cardinal features of asthma, including airway eosinophilia, bronchial hyperresponsiveness, and goblet cell metaplasia, in association with a remarkable inhibition of TH2 cytokine production, in an OVA-induced asthma model. Intratracheal transfer of OVA-primed bone marrow-derived DCs from OGR1-deficient mice to wild-type (WT) mice developed lower airway hyperresponsiveness and eosinophilia after OVA inhalation compared with the transfer of those from WT mice. The presence of functional OGR1 in DCs was confirmed by the expression of OGR1 mRNA and OGR1-dependent Ca2+ response. Migration of OVA-sensitized DCs was attenuated by OGR1 deficiency in an in vitro Transwell assay and an in vivo footpad assay.

Conclusion: OGR1 in DCs is critical for TH2 phenotype modulation and subsequent induction of airway inflammation and hyperresponsiveness.
Umeclidinium/vilanterol (UMEC/VI) once daily (OD) vs fluticasone/salmeterol combination (FSC) twice daily (BD) in patients with moderate-to-severe COPD and infrequent COPD exacerbations
Authors: D. Singh, S. Worsley, C.-Q. Zhu, L. Hardaker, A. Church
Journal: European Respiratory Journal (2014)

Background: UMEC (a LAMA) plus VI (a LABA) is a new combination bronchodilator maintenance treatment for COPD. FSC is indicated as a maintenance therapy for COPD.

Objective: To compare the efficacy and safety of UMEC/VI inhalation powder with FSC in pts with moderate-to-severe COPD and infrequent COPD exacerbations (none in previous year).

Methods: A 12-week, multicentre, double-blind, parallel-group, double-dummy study. Pts (n=716) were randomised 1:1 to UMEC/VI 62.5/25mcg OD (via ELLIPTA™ device) or FSC 500/50µg BD (via DISKUS device™). Endpoints included: LS mean Δ from baseline (BL) in weighted mean (wm) FEV1 over 0–24h post-dose at Day 84 (primary); trough FEV1 at Day 84 (secondary); symptoms. Safety included AEs and vital signs.

Results: UMEC/VI statistically significantly improved all lung function measures, including peak, onset and duration of effect vs FSC. Improvements with UMEC/VI vs FSC were 80mL (95%CI: 46,113) for 0–24h wmFEV1 and 90mL (55,125) for trough FEV1 (both p 1 unit) and quality of life (Δ from BL in SGRQ Total score >4 unit decrease) over 12 weeks. AEs (UMEC/VI, FSC): on-treatment (28%,29%); drug-related (2%,4%); on-treatment SAEs (2%,<1%). Vitals signs: little Δ from BL with UMEC/VI or FSC. Deaths: 1 (UMEC/VI group; not drug related).

Conclusions: UMEC/VI 62.5/25mcg OD over 12 weeks led to significant, sustained and clinically meaningful improvements in lung function vs FSC 500/50mcg BD in these pts. No new safety findings were reported.

Funding: GSK (DB2116134;[NCT01822899][1]).

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01822899&atom=%2Ferj%2F44%2FSuppl_58%2FP290.atom
Effect of pulmonary rehabilitation on systemic inflammatory markers, muscle cross section area and functional parameters in interstitial lung disease
Authors: Balakrishnan Menon, Vishal Bansal, Brijesh Prajapat
Journal: European Respiratory Journal (2012)

Introduction: 

Interstitial Lung Diseases (ILD) are chronic debilitating diseases with severe exercise limitation. We studied the effect of pulmonary rehabilitation (PR) on systemic inflammatory markers, muscle cross sectional area and other functional parameters in patients of ILD.

Aims and Objectives: 

To evaluate the levels of C-Reactive Protein (CRP), Matrix Metalloproteinase 9 (MMP9), Tissue Inhibitor of Metalloprotinase (TIMP), 6 minute walk distance (6MWD), Mid thigh Cross Sectional Area on CT (MTCSACT) and Carbon Monoxide Diffusion Capacity (DLCO) before and after PR in patients of ILD.

Methods: 

Fourteen patients of ILD were evaluated at baseline and after 4 weeks of standard therapy. Supervised PR along with standard medications was then given for further 8 weeks.

Results: 

Mean values of CRP changed from 5.76±5.11 to 2.18±1.02 mg/L after rehabilitation [p=0.02]. MMP9 was 838.07±252.37 before and 547.93±168.57 ng/ml after PR [p=0.05]. Mean values of TIMP changed from 182.07±105.07 to 660.43±354.85 ng/ml after PR [p=0.04].

The Mean values of 6MWD changed from 379.43±47.94 to 493.78±47.47 m after PR [p=0.001]. Levels of DLCO changed from 6.23±2.45 to 13.87±3.85 ml/min/mmHg after PR [p=0.05]. Mean values of MTCSACT changed from 8026.07±1141.96 to 10182.00±1752.10 mm2 after PR [p=0.02]

Significant correlation was obtained between MMP9 and MTCSACT [r=0.702, p=0.005] and between 6MWD and DLCO [r=0.764, p=0.001].

Conclusion: 

Pulmonary rehabilitation causes significant improvement in systemic inflammatory markers, muscle cross sectional area and functional parameters in ILD patients along with significant improvement in gas exchange.
Distinguished Prognosis of Hepatocellular Carcinoma With or Without Cirrhosis: A Long-term Follow-up Analysis
Authors: S.L. Yang, L.P. Liu, Y.F. Sun, X.R. Yang, J. Fan, J.W. Ren, G.G. Chen, P.B.S. Lai
Journal: Clinical Gastroenterology and Hepatology (2015)
Analysis of immunoglobulin heavy chain V-D-J and D-J junctional diversity in human fetal B cells
Authors: Kylie M. Drake, Ian M. Morison
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1537 

During normal B-cell development the immunoglobulin heavy chain gene rearranges, by first joining a D to a J segment on both alleles, followed by a V to D-J rearrangement on one allele. A key feature of early human fetal lymphoid development is the absence of random nucleotides between the rearranged V, D and J segments. The addition of N nucleotides at these junctions requires the enzyme terminal deoxynucleotidyl transferase (TdT). TdT is not expressed during early fetal lymphopoiesis but has been observed by the end of the first trimester but data are sparse. The absence of N nucleotides in the majority of childhood ALLs suggests an early fetal origin. By defining the window-in-time during which TdT-negative B cell development occurs, we will be able to refine the timing of the origin of the B cells that give rise to ALL. Therefore we have analysed the V-DJ and D-J rearrangements in liver from normal human fetuses aged from 6 and 13 weeks gestation. Sequences were analysed by comparison to the Immunogenetics (IMGT/V-quest) and V-base databases to determine the presence or absence of N nucleotides. From this data we were able to elucidate the timing of the switch from a TdT-negative to a TdT-positive B-cell. In addition, TdT expression was confirmed by performing immunohistochemistry in the same fetal liver samples.
My Last Post
Authors: George P. Canellos
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.10.2585 Journal of Clinical Oncology - published online before print September 21, 2016 My Last Post George P. CanellosxGeorge P. CanellosSearch for articles by this author https://doi.org/10.1200/JCO.2001.19.10.2585 Full Text PDF Figures and Tables "My Last Post." Journal of Clinical Oncology, 19(10), pp. 2585–2586© 2001 by American Society of Clinical Oncology
Keeping Children’s Attention
Authors: Jenny S. Radesky, Dimitri A. Christakis
Journal: JAMA Pediatrics (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Pericoital application of tenofovir gel reduced risk for herpes simplex virus type 2 in HIV-negative women
Authors: Jihoon Baang
Journal: Annals of Internal Medicine (2015)

Source Citation Abdool Karim SS, Abdool Karim Q, Kharsany AB, et al; CAPRISA 004 Trial Group. Tenofovir gel for the prevention of herpes simplex virus type 2 infection. N Engl J Med. 2015;373:530-9. 26244306
Enactive neuroscience, the direct perception hypothesis, and the socially extended mind
Authors: Tom Froese
Journal: Behavioral and Brain Sciences (2015)

Abstract Pessoa's The Cognitive-Emotional Brain (2013) is an integrative approach to neuroscience that complements other developments in cognitive science, especially enactivism. Both accept complexity as essential to mind; both tightly integrate perception, cognition, and emotion, which enactivism unifies in its foundational concept of sense-making; and both emphasize that the spatial extension of mental processes is not reducible to specific brain regions and neuroanatomical connectivity. An enactive neuroscience is emerging.
Discovery and development of MP529, a new effective and selective inhibitor of Aurora A kinase.
Authors: Adrianne Clifford, Cory Grand, Hariprasad Vankayalapati, Xiaohui Liu, Xinyu Zhang, Jeremy Lamb, David Bearss
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3261 

Genetic instability can lead to tumorigenesis, creating the need for cells to develop mechanisms and checkpoints to ensure faithful replication and division of genetic material. These mechanisms and checkpoints remain intact in normal cells, but are often disrupted or lost in cancer cells. Aurora kinases have mitotic regulatory functions and are important proteins in the maintenance of genetic stability, especially during mitosis. Aurora A localizes to the centrosomes during mitosis and is required for spindle assembly; atypical amounts of Aurora A in cells cause abnormal spindle formation and disruption of the spindle-assembly checkpoint. Overexpression of Aurora has been observed in several types of human cancers including breast, colorectal, prostate, ovarian, and pancreas. Aurora A represents a logical target because of its implication in tumorigenesis and, being a kinase, lends itself to small molecule inhibition. We have developed new small molecule inhibitors, the MP529 series, which demonstrate both activity and specificity for Aurora A kinase. These compounds were developed using our proprietary CLIMB drug discovery process which involves physical screening of much fewer compounds than traditional methods, (less than one hundred versus several million), and produces superior results. The crystal structure of Aurora A kinase was used as a substrate for docking to generate a subset of leads from our large virtual library of compounds; this subset of leads was selected based on calculated binding energies. The lead compounds were then subjected to a number of in silico physiochemical and ADMET prediction algorithms to determine which were most likely to be “drug-like”. This computational screen produced a group of candidates of the substituted (4-p-tolylsulfamoyl-phenyl) amide class, the MP529 series. These compounds demonstrate nanomolar activity against Aurora-A kinase in biochemical enzyme based assays, while exhibiting little to no activity versus Aurora B. In cell based assays the MP529 series induced phenotypes indicative of Aurora A inhibition, and these compounds have been extended into in vivo studies. This series of compounds has been evaluated in in vivo xenograft models and shows efficacy while maintaining desirable pharmacokinetic properties and a large therapeutic window. The MP529 series is a unique set of compounds that demonstrate improved activity and selectivity for the Aurora A target, and is currently undergoing late-stage preclinical development.
Surgical treatment of primary lung cancer in patients less than 40 years of age.
Authors: T Shimono, T Hayashi, M Kimura, I Yada, S Namikawa, H Yuasa, M Kusagawa
Journal: Journal of Clinical Oncology (1994)

PURPOSE AND METHODS The major purpose of this study was to determine whether the survival rate in young lung cancer patients after surgical treatment differs from that in older patients. An analysis was performed for all patients with bronchogenic carcinoma who underwent surgery at Mie University Hospital from 1965 to 1990. RESULTS Of 803 patients, 24 (2.99%) were 33 to 39 years old. At the time of surgery, the disease was diagnosed as stage I in seven patients (29%), stage II in four (17%), stage IIIa in seven (29%), stage IIIb in two (8%), and stage IV in four (17%), while 46.3% of the patients older than 40 years of age had either stage IIIa, IIIb, or IV disease. All of the 24 patients less than 40 years of age underwent thoracotomy: curative resection in 14 cases, palliative resection in sex, and probe-thoracotomy in four. The 5-year survival rate for all stages of disease was 31.4% in these 24 patients, and 41.9% in 603 patients greater than 40 years of age. The 5-year survival rate for stage I disease was 35.7% in the seven younger patients and 78.0% in the 207 older patients; for stage II, it was 25.5% in the four younger patients and 40.6% in the 98 older patients; for stage III, it was 33.3% in the nine younger patients and 15.6% in the 250 older patients; and for stage IV, it was 25% in the four younger patients and 6.6% in the 48 older patients. There were no significant differences in survival rate between the two age groups for all patients or for those with each stage of disease. CONCLUSION Although younger patients tended to have more advanced disease, long-term survival in these patients did not differ from that of older patients.
New insights into the risk of breast cancer in childhood cancer survivors treated with chest radiation: A report from the Childhood Cancer Survivor Study (CCSS) and the Women's Environmental Cancer and Radiation Epidemiology(WECARE) Study.
Authors: Chaya S. Moskowitz, Joanne F. Chou, Suzanne L. Wolden, Jonine L. Bernstein, Jyoti Malhotra, Danielle Novetsky Friedman, Nidha Z. Mubdi, Tara O. Henderson, Wendy M. Leisenring, Marilyn Stovall, Sue Hammond, John D. Boice, Melissa M. Hudson, Lisa Diller, Smita Bhatia, Joseph Philip Neglia, Colin B. Begg, Leslie L. Robison, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2012)

CRA9513 Background: The risk of breast cancer (BC) by age 50 among women treated for childhood cancer with chest radiation therapy (RT) and how this risk compares with that of BRCA1 and BRCA2 (BRCA1/2) mutation carriers is unknown. Methods: We evaluated the risk of BC in a cohort of 1268 female 5-yr childhood cancer survivors treated with chest RT and estimated the cumulative incidence of BC non-parametrically treating death as a competing risk. The cumulative incidence of BC in BRCA1/2 mutation carriers was estimated with the kin-cohort method using data from 4570 female first-degree relatives of women diagnosed with unilateral BC (probands) participating in the WECARE Study. Absolute Excess Risks (AERs) were estimated using population-based data from the SEER program. Results: With a median follow-up of 26 yrs (range 5-39) for the CCSS cohort, 175 women were diagnosed with BC at a median age of 38 yrs (range 24-53) and a median latency of 23 yrs (range 7-38); the overall cumulative incidence of BC by age 50 was 24% (95% confidence interval [CI] 20-28%) and among Hodgkin lymphoma survivors was 30% (95% CI 25-35%). In comparison, among first-degree relatives of WECARE Study probands 324 were diagnosed with BC (median age at diagnosis, 55 yrs (range 26-90)). The estimated cumulative incidence by age 50 was 31% (95% CI 16-47%) and 10% (95% CI 2-23%) in carriers of BRCA1 and BRCA2 mutations, respectively. The population cumulative incidence of BC is 4% by age 50. Among the childhood cancer survivors, AERs for BCs diagnosed per 10,000 person-years of observation were respectively 34 (95% CI 18-52), 27 (95% CI 11-45), and 95 (95% CI 78-112) among women treated with 10-19 Gy (23%), 20-29 Gy (17%), and 30+ Gy (56%) of chest RT. Conclusions: Women treated for childhood cancer with chest RT have a substantial risk of BC comparable to BRCA1/2 mutation carriers and considerably greater than that of the general population. Women treated with 10-19 Gy RT had an increased excess risk warranting consideration of breast cancer surveillance strategies similar to the current recommendations for women treated with &gt; 20 Gy.