tbuckley/cabot-search huggingface dataset:
Phase I trial of gefitinib (ZD1839) in combination with concurrent carboplatin, paclitaxel and radiation therapy in patients with stage III non-small cell lung cancer
Authors: D. Rischin, B. Burmeister, P. Mitchell, M. Boyer, M. Macmanus, E. Walpole, M. Feigen, M. M. Tin, D. Ball
Journal: Journal of Clinical Oncology (2004)

7077 Background: Gefitinib (‘Iressa’, ZD1839) enhances tumor radioresponsiveness in preclinical studies, and is approved as monotherapy in non-small-cell lung cancer (NSCLC). The aim was to establish the recommended doses of gefitinib, carboplatin, and paclitaxel given concurrently with radical radiation therapy (RT) in patients (pts) with stage III NSCLC. Methods: Pts with histologic diagnosis of NSCLC, stage III disease (no pleural effusion or cervical lymphadenopathy), ECOG PS 0/1, weight loss ≤10%, and no prior RT for NSCLC were eligible. Pts received RT (60 Gy/30 fx/6 weeks) to the primary site and involved regional nodes. Concurrent oral gefitinib 250 mg/day and carboplatin AUC 2, weekly were administered with RT on dose level 1, and weekly paclitaxel was added at 25, 35, and 45 mg/m2 at dose levels 2, 3, and 4, respectively. The first 6 pts continued gefitinib after chemoRT; however, the protocol was amended to cease gefitinib at the end of chemoRT, following reports of interstitial lung disease elsewhere. Results: A total of 15 pts have been enrolled in this study from 4 institutions: median age (range), 65 (50–76) years; M/F, 11/4; stage IIIA/IIIB, 9/6; squamous-cell/large-cell/adenocarcinoma, 8/5/2. Dose escalation up to dose level 4 has been completed without any dose limiting toxicities, and additional pts are currently being treated on an expanded cohort to confirm the safety of this dose level and to obtain further efficacy data. Treatment was well tolerated: esophagitis (grade 2, n=2; grade 3, n=2); pneumonitis (grade 2, n=5; 4 of which occurred in pts who continued gefitinib after chemoRT); diarrhea (grade 2, n=1; grade 3, n=1). The PET complete response (CR) rate in 11 evaluable pts was 55%. The CT CR rate was 27% and partial response rate was 64%, for an overall response rate of 91%. Conclusions: This regimen of concurrent gefitinib, radical RT (60 Gy) and full dose weekly carboplatin and paclitaxel was generally well tolerated. Preliminary efficacy data are encouraging and updated survival and toxicity data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca
The effect of pulmonary rehabilitation on the sit-to-stand test in COPD
Authors: Mehul Patel, Jane Canavan, Amy Clark, Karen Ingram, Ria Fowler, Michael Polkey, Wiliam Man
Journal: European Respiratory Journal (2011)

Background:  The sit-to-stand (STS) test is a component of the Short Physical Performance Battery (SPPB), it measures the fastest time to stand from a seated position 5 times with folded arms. We hypothesised the STS may be a useful outcome measure in COPD and that it would improve after an 8-week outpatient pulmonary rehabilitation (PR) program.   Methods:  In 83 COPD patients (43M: 40F) referred to PR, the following were measured before and after PR: STS, incremental shuttle walk (ISW), MRC Dyspnoea score (MRC) and St George9s Respiratory Questionnaire (SGRQ). Modified BODE (ISW as the exercise component) and ADO scores were calculated as composite mortality indices. Spearman9s rank correlation was used to assess the relationship between STS and baseline characteristics and Wilcoxon signed rank test to assess the effect of PR on STS. We estimated minimal clinically important difference (MCID) using an anchor based approach against a 5-point Likert scale and the MCID of ISW.   Results:  18 patients were unable to complete STS either pre- or post-PR. 6 were unable to perform STS pre-PR but improved sufficiently to do so after PR. STS at baseline correlated significantly with ISW (r=-0.53), MRC (r=0.35), modified BODE (r=0.26) and ADO (r=0.35), but not with age, FEV 1 %predicted, BMI or SGRQ. In 65 patients with full pre- and post-PR data, median STS time improved from 13.8s to 12.0s following PR (p   Conclusions:  Not all COPD patients referred to PR can complete a STS. The STS is sensitive to change following PR. The MCID for the STS is probably a decrease of greater than 2 seconds.
Abstract #4456: Interaction between APC and heat-shock proteins: A potential therapeutic target
Authors: Maged Zeineldin, Kristi Neufeld
Journal: Cancer Research (2009)

Mutation of the Adenomatous polyposis coli gene (APC) is an early step in the progression of about 80% of all colorectal cancers. The product of the APC gene, APC, is a large protein implicated in many cellular functions including cellular proliferation, migration, adhesion, and chromosome segregation. Most APC mutations result in truncation of the C-terminal half of the APC protein. Heat-shock proteins are multifunctional proteins that assist client protein folding, protect proteins from aggregation, participate in translocation of some proteins to their subcellular locations and are involved in signaling pathways. Heat-shock protein 90 (HSP90) inhibitors have been tested as potential cancer therapeutic agents. HSP70 has been shown to interact with the N-terminal portion of APC. We show evidence that HSP90 inhibitor stabilizes both full-length and truncated APC. In addition, we have evidence suggesting that this APC stabilization requires HSP70 induction. Using the HSP90 inhibitor, Geldanamycin, and an inducer of HSP70/90, we have been examining the potential therapeutic implications of APC interaction with heat-shock proteins both in-vitro, using cell cultures and in-vivo, using mouse models with mutant APC.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4456.
Anti-human heat shock protein 60 antibodies and longitudinal change in percent emphysema and lung function: The MESA lung study
Authors: Carrie P. Aaron, Eric A. Hoffman, Russel Tracy, Joseph Schwartz, Karen Hinckley Stukovsky, Lewis J. Smith, Kathleen M. Donohue, R. Graham Barr
Journal: European Respiratory Journal (2013)

Rationale Heat shock proteins (HSP) are chaperone molecules that stabilize cell proteins and increase in cell stress. The role of HSP60 antibodies (ab) in the progression of emphysema and airflow obstruction is unclear. We hypothesized that HSP60-ab levels would be associated with longitudinal increase in percent emphysema and decline in lung function.  Methods The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants 45-84 yrs old without clinical cardiovascular disease. Baseline serum HSP60-abs were measured by ELISA, %emphysema was measured on lung fields of cardiac CTs 2-3 times over a median of 4 yrs and spirometry was performed twice over 5 yrs. Mixed effect models adjusted for age, sex, race/ethnicity, height, weight, education, packyrs and cigarettes/day plus, for %emphysema models, CT scanner model and mAs.  Results In 998 participants with HSP60-abs (age 59.4±9.8 yrs, 43% male, 54% ever smokers) the mean log-HSP60-ab was 9.6±0.9 ng/ml and the mean increase in %emphysema was 0.27%/yr (P  Conclusions In preliminary analyses, higher levels of HSP60-abs were associated with accelerated increase in percent emphysema among smokers and a faster decline in FVC in all participants in a population-based study.  Funding NIH R01 HL77612, RC1 HL100543, R01-HL093081, N01-HC-95159 to N01-HC-95169, UL1-T40.
The importance of stabilizing PaCO2 during long-term non-invasive ventilation in patients with COPD
Authors: Tomomasa Tsuboi, Toru Oga, Kensuke Sumi, Kazuko Machida, Motoharu Ohi, Kazuo Chin
Journal: European Respiratory Journal (2014)

Background: In subjects with COPD, the importance of changes in PaCO 2  during long-term non-invasive ventilation (NIV) on continuation remains uncertain. We intended to elucidate whether stabilizing PaCO 2  during NPPV had an advantageous prognostic effect.  Methods: Data from 54 subjects with COPD and who received long-term NIV were studied retrospectively. The annual change in PaCO 2  during NPPV was determined using a simple linear regression method for each subject who had at least two six-month intervals of PaCO 2  data. Annual changes in PaCO 2  during long-term NIV and probable confounders were analysed with discontinuation of long-term NIV as the principal consequence.  Results: Thirty seven subjects who had more than two six-month intervals of PaCO 2  data were involved in this study. PaCO 2  during long-term NIV increased slightly in 19 subjects (group 1; less than 2 mmHg/y), and increased greatly in 18 subjects (group 2; more than 2 mmHg/y). In multivariate modality model, lesser annual changes in PaCO 2  (P = 0.009) and lesser PaCO 2  six months after the start of long-term NIV (P = 0.03) were associated with a significantly higher probability of continuing NPPV. The two- and five-year probabilities of continuing NIV for group-1 were 89% and 66%, respectively, while those for group-2 were 78% and 32%, respectively.  Conclusion: A decrease in not only the PaCO 2  six months after the start of long-term NIV but the annual change of PaCO 2  during long-term NIV was shown to be a significantly prognostic variable.
Press: Popularising hospital performance data
Authors: P. Anderson
Journal: BMJ (1999)

The publication last week of the first set of performance tables for hospitals in England provoked a storm of comparisons between hospitals by the media. England's Department of Health is keen,however, to stress that comparative death rate data should not be used to “name and shame” particular hospitals. Within two hours of the department's press conference last Wednesday, BBC television reported live from a ward at St George's Hospital, London, pointing out that it seemed to have the worst death rate after non-emergency surgery of any teaching hospital in the country. By 6 pm, the BBC's online news service had pinpointed St George's Hospital, Salford Royal Hospitals NHS Trust, and North Devon NHS Healthcare Trust—all apparently having high death rates compared with their counterparts.

Thursday's national newspapers continued the exercise. The Times , Independent , Daily Telegraph , and Guardian published excerpts from tables listing different hospitals' performance, and interviewed representatives of those hospitals that seemed to have the worst performance. Among the tabloid newspapers, the Daily Mail dedicated two pages …
Human Trafficking of Children and Adolescents
Authors: Abigail English
Journal: JAMA Pediatrics (2015)

Human trafficking has severe adverse effects on the health, development, well-being, and human rights of vulnerable young people globally and in the United States. Awareness of human trafficking—once hidden in the shadows—is growing. Although precise estimates are not available of how many children and adolescents are affected, there is little doubt that young people everywhere have experienced physical and sexual violence from being trafficked and millions worldwide are at risk. Despite the increased awareness, significant gaps remain in evidence-based knowledge about the causes, consequences, and responses; the gaps are particularly noteworthy with respect to the health implications of human trafficking and the appropriate role of health care professionals. Language: en
2p15-p16.1 microdeletions encompassing and proximal to BCL11A are associated with elevated HbF in addition to neurologic impairment
Authors: Alister P. W. Funnell, Paolo Prontera, Valentina Ottaviani, Maria Piccione, Antonino Giambona, Aurelio Maggio, Fiorella Ciaffoni, Sandra Stehling-Sun, Manuela Marra, Francesca Masiello, Lilian Varricchio, John A. Stamatoyannopoulos, Anna R. Migliaccio, Thalia Papayannopoulou
Journal: Blood (2015)
Plasma protein biomarkers enhance the clinical prediction of kidney injury recovery in patients undergoing liver transplantation
Authors: Josh Levitsky, Talia B. Baker, Chunfa Jie, Shubhada Ahya, Murray Levin, John Friedewald, Patrice Al‐Saden, Daniel R. Salomon, Michael M. Abecassis
Journal: Hepatology (2014)

Biomarkers predictive of recovery from acute kidney injury (AKI) after liver transplantation (LT) could enhance decision algorithms regarding the need for liver-kidney transplantation or renal sparing regimens. Multianalyte plasma/urine kidney injury protein panels were performed immediately before and 1 month post-LT in an initial test group divided by reversible pre-LT AKI (rAKI = post-LT renal recovery) versus no AKI (nAKI). This was followed by a larger validation set that included an additional group: irreversible pre-LT AKI (iAKI = no post-LT renal recovery). In the test group (n = 16), six pre-LT plasma (not urine) kidney injury proteins (osteopontin [OPN], neutrophil gelatinase-associated lipocalin, cystatin C, trefoil factor 3, tissue inhibitor of metalloproteinase [TIMP]-1, and β-2-microglobulin) were higher in rAKI versus nAKI (P < 0.05) and returned to normal values with renal recovery post-LT. In the validation set (n = 46), a number of proteins were significantly higher in both rAKI and iAKI versus nAKI. However, only pre-LT plasma OPN (P = 0.009) and TIMP-1 (P = 0.019) levels were significantly higher in rAKI versus iAKI. Logistic regression modeling was used to correlate the probability of post-LT rAKI, factoring in both pre-LT protein markers and clinical variables. A combined model including elevated OPN and TIMP-1 levels, age <57, and absence of diabetes had the highest area under the curve of 0.82, compared to protein-only and clinical variable-only models.These data suggest that plasma protein profiles might improve the prediction of pre-LT kidney injury recovery after LT. However, multicenter, prospective studies are needed to validate these findings and ultimately test the value of such protein panels in perioperative management and decision making.
Akt-dependent inhibition of glycogen synthase kinase 3-beta regulates viability and function of vascular endothelium in response to radiation
Authors: Eugenia M. Yazlovitskaya, Jiahua Tan, Dennis E. Hallahan
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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The vascular endothelium plays a critical role in the response of tumors and normal tissues to ionizing radiation. One of the main signal transduction pathways induced by radiation in endothelial cells is PI3K/Akt pathway. Since this pathway leads to the cell survival and promotes development of tumor vasculature, its inhibition enhances the cytotoxic effect of radiation in tumor vascular endothelium resulting in improved tumor control. Therefore, understanding of detailed molecular mechanism of radiation-induced activation of PI3K/Akt pathway in vascular endothelium is necessary for development of new radiosensitizing agents. Previously we have shown that phosphorylation of Akt at Ser473 in endothelium was increased within minutes of irradiation and that Akt-mediated signaling abrogated radiation-induced apoptosis. In this study we investigated radiation effect on Akt down-stream target, glycogen synthase kinase 3-beta (GSK3β). It was established that Akt negatively regulates pro-apoptotic function of GSK3β by phosphorylating GSK3β at Ser9. GSK3β was phosphorylated at Ser9 within minutes of exposure to ionizing radiation. This phosphorylation was diminished by overexpression of the nonfunctional double mutant Akt (T308A, S473A). Radiation treatment caused GSK3β translocation from membrane (active kinase) to cytoplasm (inhibited kinase). In the irradiated endothelial cells, overexpression of the nonfunctional mutant Akt or constitutively active mutant GSK3β (S9A) eliminated resistance to apoptosis leading to increased cell death, while addition of GSK3β antagonists or overexpression of mutant kinase dead GSK3β abrogated this effect. Overexpression of the nonfunctional mutant Akt demonstrated that radiation-induced Akt activation was responsible for endothelial cell migration and capillary tubule formation. In mouse angiogenesis models, microvascular response to ionizing radiation was enhanced by Akt inhibition and capillary-like tubule formation was aborted by GSK3β inhibitors. In summary, our results suggest that Akt signaling through its down-stream target GSK3β contributes to endothelial cell survival and capillary formation following ionizing radiation exposure. Therefore, GSK3β signaling pathway could present new molecular targets for the augmentation of cancer radiotherapy.
Abstract 12613: Comparison of the Predictive Utility of Atrial, N-Terminal Pro-Atrial, and N-Terminal Pro-B-Type Natriuretic Peptides for Death and Cardiovascular Events: Superiority of N-Terminal Pro-B-Type Natriuretic Peptide
Authors: Paul McKie, Alessandro Cataliotti, S J Sangaralingham, Tomoko Ichiki, Margaret Redfield, Horng Chen, Richard Rodeheffer, John Burnett
Journal: Circulation (2010)

Background: BNP and especially NT-proBNP have prognostic value for death and cardiovascular (CV) morbidity. ANP, like BNP, is a hormone released in response to myocardial stimuli. Few studies evalu...
Integrated Medical-Behavioral Care Compared With Usual Primary Care for Child and Adolescent Behavioral Health
Authors: Joan Rosenbaum Asarnow, Michelle Rozenman, Jessica Wiblin, Lonnie Zeltzer
Journal: JAMA Pediatrics (2015)

<h3>Importance</h3> Recent health care legislation and shifting health care financing strategies are transforming health and behavioral health care in the United States and incentivizing integrated medical-behavioral health care as a strategy for improving access to high-quality care for behavioral health conditions, enhancing patient outcomes, and containing costs. <h3>Objective</h3> To conduct a systematic meta-analysis of randomized clinical trials to evaluate whether integrated medical-behavioral health care for children and adolescents leads to improved behavioral health outcomes compared with usual primary care. <h3>Data Sources</h3> Search of the PubMed, MEDLINE, PsycINFO, and Cochrane Library databases from January 1, 1960, through December 31, 2014, yielded 6792 studies, of which 31 studies with 35 intervention-control comparisons and 13 129 participants met the study eligibility criteria. <h3>Study Selection</h3> We included randomized clinical trials that evaluated integrated behavioral health and primary medical care in children and adolescents compared with usual care in primary care settings that met prespecified methodologic quality criteria. <h3>Data Extraction and Synthesis</h3> Two independent reviewers screened citations and extracted data, with raw data used when possible. Magnitude and direction of effect sizes were calculated. <h3>Main Outcomes and Measures</h3> Meta-analysis with a random effects model were conducted to examine an overall effect across all trials, and within intervention and prevention trials. Subsequent moderator analyses for intervention trials explored the relative effects of integrated care type on behavioral health outcomes. <h3>Results</h3> Meta-analysis with a random-effects model indicated a significant advantage for integrated care interventions relative to usual care on behavioral health outcomes (<i>d</i> = 0.32; 95% CI, 0.21-0.44;<i>P</i> &lt; .001). Moderator analyses indicated larger effects for treatment trials that targeted diagnoses and/or elevated symptoms (<i>d</i> = 0.42; 95% CI, 0.29-0.55;<i>P</i> &lt; .001) relative to prevention trials (<i>d</i> = 0.07; 95% CI, −0.13 to 0.28;<i>P</i> = .49). The probability was 66% that a randomly selected youth would have a better outcome after receiving integrated medical-behavioral treatment than a randomly selected youth after receiving usual care. The strongest effects were seen for treatment interventions that targeted mental health problems and those that used collaborative care models. <h3>Conclusions and Relevance</h3> Our results, demonstrating the benefits of integrated medical-behavioral primary care for improving youth behavioral health outcomes, enhance confidence that the increased incentives for integrated health and behavioral health care in the US health care system will yield improvements in the health of children and adolescents.
Retinal Nerve Fiber Layer Imaging with Spectral-Domain Optical Coherence Tomography
Authors: Christopher K.S. Leung, Shi Lam, Robert N. Weinreb, Shu Liu, Cong Ye, Lan Liu, Jing He, Gilda W.K. Lai, Taiping Li, Dennis S.C. Lam
Journal: Ophthalmology (2010)
Changes in Cytokines and Aggrecan ARGS Neoepitope in Synovial Fluid and Serum and in C‐Terminal Crosslinking Telopeptide of Type II Collagen and N‐Terminal Crosslinking Telopeptide of Type I Collagen in Urine Over Five Years After Anterior Cruciate Ligament Rupture: An Exploratory Analysis in the Knee Anterior Cruciate Ligament, Nonsurgical Versus Surgical Treatment Trial
Authors: André Struglics, Staffan Larsson, Nobuyuki Kumahashi, Richard Frobell, L. Stefan Lohmander
Journal: Arthritis & Rheumatology (2015)

Objective To prospectively monitor levels of proinflammatory cytokines and aggrecan ARGS neoepitope in synovial fluid and serum as well as levels of C‐terminal crosslinking telopeptide of type II collagen (CTX‐II) and N‐terminal crosslinking telopeptide of type I collagen (NTX‐I) in urine after acute anterior cruciate ligament (ACL) rupture. Methods Synovial fluid, serum, and urine were collected from 121 adults on 6 occasions over 5 years after acute ACL injury. Reference samples were obtained from subjects without knee injury. Concentrations of interleukin‐6 (IL‐6), IL‐8, IL‐10, interferon‐γ (IFNγ), tumor necrosis factor (TNF), aggrecan ARGS neoepitope, CTX‐II, and NTX‐I were measured by enzyme‐linked immunosorbent assay. Results Shortly after ACL injury, cytokine concentrations in synovial fluid were elevated 6‐fold (TNF) to 1,050‐fold (IL‐6) compared to reference levels, while concentrations of aggrecan ARGS neoepitope in synovial fluid and serum and CTX‐II in urine were elevated 1.4‐fold to 8‐fold. Thereafter, concentrations of cytokines and aggrecan ARGS neoepitope in synovial fluid decreased with different half‐lives (in years: IL‐6 0.9, IL‐8 2.2, IL‐10 2.3, IFNγ 3.1, TNF 3.6, aggrecan ARGS neoepitope 4.0). After 5 years, the TNF concentration in synovial fluid remained higher than the reference level. There was a correlation between the concentrations of aggrecan ARGS neoepitope in synovial fluid and serum (r s = 0.36). Concentrations of aggrecan ARGS neoepitope in synovial fluid and of CTX‐II and NTX‐I in urine were correlated with concentrations of cytokines in synovial fluid (r s = 0.41–0.49 and r s = 0.21–0.31, respectively). Conclusion Acute ACL injury induced highly increased levels of inflammatory cytokines in the joint, and these were associated with proteolysis of aggrecan and type II collagen. Cytokine levels remained increased up to 5 years after injury, indicative of extended local inflammation in the joint.
Enhanced epidemiological surveillance of influenza A(H1N1)v in Italy
Authors: C Rizzo, S Declich, A Bella, M G Caporali, S Lana, M G Pompa, L Vellucci, S Salmaso
Journal: Eurosurveillance (2009)

As of 7 July 2009, a total of 158 laboratory-confirmed cases of influenza A(H1N1)v were reported in Italy, from half of the 21 Italian regions. To date all cases have had symptoms consistent with seasonal influenza and no severe or fatal cases have been reported. An active surveillance of cases has been set up in Italy in order to undertake appropriate measures to slow down the spread of the new virus. This report describes the routine and enhanced surveillance currently ongoing in Italy.