tbuckley/cabot-search huggingface dataset:
Insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), and mammographic breast density
Authors: C. Diorio, M. Pollak, C. Byrne, B. Mâsse, G. Côté, N. Hébert-Croteau, M. Yaffe, S. Bérubé, C. Morin, J. Brisson
Journal: Journal of Clinical Oncology (2004)

9501 Background: A few small studies have suggested that higher IGF-I and lower IGFBP-3 may be associated with increased premenopausal mammographic breast density, one of the strongest known breast cancer risk factors. This large cross-sectional study was designed specifically to evaluate the associations of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 molar ratio with breast density. Methods: For this study, 784 premenopausal and 791 postmenopausal healthy women were recruited during screening mammography examinations. Using a computer-assisted method, a single observer assessed mammographic breast density with high reproducibility (intraclass correlation coefficient = 0.98). Blood samples collected at the time of the mammography allowed measurement of plasma IGF-I and IGFBP-3 levels by ELISA methods (coefficients of variation below 10% and 13%, respectively). Spearman's partial correlation coefficients (r) were used to evaluate the associations while adjusting for confounding factors including age, body mass index and IGF-I or IGFBP-3 when applicable. Results: Among premenopausal women, breast density is positively associated with IGF-I and IGF-I/IGFBP-3 ratio (r = 0.084, p = 0.019 and r = 0.070, p = 0.051, respectively) and negatively associated with IGFBP-3 (r = −0.123, p = 0.0005). No significant correlations were observed among postmenopausal women. Correlations among postmenopausal women (p-values) for IGF-I, IGFBP-3 and their ratio were 0.038 (0.282), −0.019 (0.593) and 0.035 (0.332), respectively. Conclusions: To date, this is the largest study of the relation of IGF to breast density. IGF-I and the IGF-I/IGFBP-3 ratio were correlated with mammographic breast density among premenopausal women supporting the view that the IGF axis plays a role in the development of some breast cancers among premenopausal women by its influence on breast density. No significant financial relationships to disclose.
Focus on harm reduction in fight against HIV, says report
Authors: Sophie Cousins
Journal: BMJ (2016)

New HIV infections among people who inject drugs could be virtually eliminated by 2030 if a small percentage of global drug control spending is redirected towards harm reduction programmes, a new report has said.

The report, The Case for a Harm Reduction Decade: Progress, Potential and Paradigm Shifts ,1 by UK based non-governmental organisation Harm Reduction International (HRI), found that redirecting 7.5% of the money spent on the “war on drugs” could reduce HIV related deaths by 94%.

The modelling by David Wilson, head of infectious disease modelling at the Centre for Population Health at the Burnet Institute in Melbourne, found that even if 2.5% …
Posters_Wednesday_14 October 2009
Journal: Intensive Care Medicine (2009)

In adult cardiac surgery, the predictive value for AKI of neutrophil gelatinase-associated lipocalin (NGAL) appears to have wide variability.The choice of definition of acute kidney injury (AKI) might, at least in part, account for such variability.OBJECTIVES.In this investigation, we assessed the impact of the definition of AKI on the performance of plasma NGAL as renal biomarker in adult patients after cardiac surgery. METHODS.In a prospective study of 100 adult cardiac surgery patients, we assessed the value of postoperative plasma NGAL in predicting AKI according to the degree of severity used for its definition.RESULTS.The predictive value of plasma NGAL varied according to the AKI definition used and was higher for more severe AKI (increase in creatinine [50%: mean AUC-ROC 0.79 ± 0.01) compared to less severe AKI ([25%: mean AUC-ROC 0.65 ± 0.02); p = 0.001.The discriminatory ability of NGAL for AKI also increased with increasing RIFLE classes (AUC-ROC R: 0.72, I: 0.79, F: 0.80) or AKIN stages (AUC-ROC 1: 0.75, 2: 0.78, 3: 0.81); p = 0.015.It was highest for the prediction of renal replacement therapy (AUC-ROC: 0.83). CONCLUSIONS.In adult cardiac surgery patients, the predictive value of NGAL increases with grade of AKI.This observation needs to be taken into account when interpreting any future studies of this biomarker.
Pemetrexed (Pem) and Cisplatin (Cis) with Concurrent Thoracic Radiation After Pem + Cis Induction in Patients (Pts) with Unresectable Locally Advanced (La) Nonsquamous Non-Small Cell Lung Cancer (Ns-Nsclc): Results in Different Age Groups (≤70 Yrs, &gt;70 Yrs)
Authors: P. Garrido Lopez, S. Novello, W. Engel-Riedel, M. Serke, P. Giraud, C.M. Visseren-Grul, S. Ameryckx, V. Soldatenkova, N. Chouaki
Journal: Annals of Oncology (2014)
Fertility outcomes in asthma: a clinical study of 245 women with unexplained infertility
Authors: Elisabeth Juul Gade, Simon Francis Thomsen, Svend Lindenberg, Vibeke Backer
Journal: European Respiratory Journal (2016)

Evidence is increasing of an association between asthma and aspects of female reproduction. However, current knowledge is limited and furthermore relies on questionnaire studies or small populations. In a prospective observational cohort study to investigate whether time to pregnancy, the number of fertility treatments, and the number of successful pregnancies differ significantly between women with unexplained infertility with and without asthma. 245 women with unexplained infertility (aged 23–45 years) underwent questionnaires and asthma and allergy testing while undergoing fertility treatment. 96 women entering the study had either a former doctor's diagnosis of asthma or were diagnosed with asthma when included. After inclusion they were followed for a minimum of 12 months in fertility treatment, until they had a successful pregnancy, stopped treatment, or the observation ended. The likelihood of achieving pregnancy was lower in women with asthma compared with those without asthma: median total time to pregnancy was 32.3 months in non-asthmatic women versus 55.6 months in those with asthma, hazard ratio 0.50 (95% confidence interval 0.34–0.74) p&lt;0.001. Women with asthma had fewer successful pregnancies during fertility treatment, 39.6 versus 60.4% (p=0.002). Increasing age was of negative importance for expected time to pregnancy, especially among asthmatic women (interaction between age and asthma on time to pregnancy, p=0.001). Female asthmatics had a longer time to pregnancy and less often became pregnant than non-asthmatic women. Increasing age reduced the chances of conceiving especially among asthmatic women. The causal relationship between asthma and subfertility remains unclear.
Phase II trial of combined modality therapy (cmt) with myeloid growth factors in patients with locally advanced non-small cell lung cancer (NSCLC)
Authors: R. Lilenbaum, M. Samuels, M. Taffaro-Neskey, M. Cusnir, J. Pizzolato, A. Blaustein
Journal: Journal of Clinical Oncology (2008)

7567 Background: Myelosuppression is a frequent toxicity of CMT, leading to clinical complications and dose reductions, which may compromise outcome in a potentially curative setting. A randomized trial in LD-SCLC (JCO 1995), which tested CMT with or without GM- CSF, showed increased toxicities in the GM-CSF arm and set the standard of care to this date. Due to recent improvements in thoracic radiotherapy and supportive care, we sought to reevaluate the addition of myeloid growth factors to CMT. Methods: Pts with stage IIIA/B NSCLC, PS 0–1, and FEV1 ≥ 1.5, received cisplatin 75mg/m2 d1 + etoposide 80mg/m2 d1–3 q. 3 wks for 2 cycles concurrent with TRT to 61Gy, using 3-D technique. Filgrastim 5mcg/kg/day was administered for 10 days beginning d4 of each chemotherapy cycle. Pts with CR/PR/SD received docetaxel 75mg/m2 q. 21 days for 3 cycles with pegfilgrastim 6mg on d2. The primary endpoint was a 50% reduction in the incidence of Gr 3/4 neutropenia from the 74% noted in the SWOG 9504 trial. Results: 20 out of 28 required pts have been enrolled. Results are available for 18 pts. Median age 66.3 (50–77); 75% male; IIIA/B: 13/7; Gr3–4 neutropenia was 27.7% and 5.5% respectively. There were no episodes of FN. Gr 4 thrombocytopenia was 22.2% with a platelet range of 9–24K and 1 pt requiring 1 transfusion. Gr3 esophagitis and pneumonitis were 11.1% and 5.5%, with no Gr 4. No pts died of treatment-related toxicities. Dose reductions/omissions/delays occurred in only 5% of patients during CMT. Response after CMT (17pts): 58.8%; after consolidation (16pts): 68.7% (including 31% CR). Median survival: 18.1 mo and 1-y survival: 70.5%. Conclusions: In contrast to the current standard of care, this pilot experience suggests that the addition of filgrastim to thoracic chemoradiotherapy is safe and effective. The rate of Gr ¾ toxicities, including FN rates, compares favorably to previous trials utilizing a similar regimen. Dose intensity is maintained in both the CMT and consolidation phases. This strategy has been incorporated into a LD-SCLC trial (RTOG 0623). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen
Role of Cadmium and Folate Levels in Risks of Allergic and Respiratory Diseases of Early Childhood: The Mothers and Children's Environmental Health Study
Authors: Ja Hyeong Kim, Eun-Hee Ha, Hye sook Park, Mina Ha, Yun-Chul Hong, Jin-A. Jung, Yangho Kim
Journal: Journal of Allergy and Clinical Immunology (2016)
Changes in TfR1 Expression and Trafficking Correlate with Erythroid Effectiveness in β-Thalassemic Mice
Authors: Huihui Li, Lionel Blanc, Tenzin Choesang, Huiyong Chen, Maria Feola, Weili Bao, Petra Pham, Antonia Follenzi, Guiyuan Li, Yelena Ginzburg
Journal: Blood (2014)
Clinical Response of Carcinomas Harboring the BRD4–NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628
Authors: Anastasios Stathis, Emanuele Zucca, Mohamed Bekradda, Carlos Gomez-Roca, Jean-Pierre Delord, Thibault de La Motte Rouge, Emmanuelle Uro-Coste, Filippo de Braud, Giuseppe Pelosi, Christopher A. French
Journal: Cancer Discovery (2016)

The antineoplastic, prodifferentiative effects of bromodomain and extra-terminal (BET) bromodomain (BRD) inhibitors were initially discovered in NUT midline carcinoma (NMC), an aggressive subtype of squamous cancer driven by the BRD4-NUT fusion oncoprotein. BRD4-NUT blocks differentiation and maintains tumor growth through a potent chromatin-modifying mechanism. OTX015/MK-8628, a novel oral BET inhibitor, targets BRD2/3/4/T with preclinical activity in NMC and several other tumor types and is currently in clinical development. Antitumor activity was evaluated in four patients with advanced-stage NMC with confirmed BRD4-NUT fusions who were treated with 80 mg OTX015/MK-8628 once daily in a compassionate-use context. Two patients responded rapidly with tumor regression and symptomatic relief, and a third had meaningful disease stabilization with a minor metabolic response. The main side effects were mild to moderate gastrointestinal toxicity and fatigue, and reversible grade 3 thrombocytopenia. This is the first proof-of-concept evidence of clinical activity of a BRD inhibitor in targeting BRD4-NUT.We present the first clinical proof-of-concept that targeting BRD4-NUT with a BET inhibitor results in impressive and rapid antitumor activity in NMC. It offers strong potential for future clinical application in this rare patient population as either a single agent or in combination with other agents. Cancer Discov; 6(5); 492-500. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 461.
Dose-Incidence Variations of Reticulum Cell Sarcoma in Mice With Irradiated Bone Marrow
Authors: V Covelli, E Ballardin, V Di Majo, B Bassani, P Metalli
Journal: JNCI Journal of the National Cancer Institute (1978)

The average final incidence of reticulum cell sarcoma (RCS) in untreated control (C57BL/Cnefemale X C3H/Cnemale)F1 male mice was 57% and was not significantly changed by single acute whole-body doses of X-rays up to 400 rads. Higher doses sharply decreased this incidence to very low levels. In a syngeneic chimera system, however, irradiation (400 rads) of bone marrow prior to transplantation significantly increased the frequency and rate of RCS relative to transplantation of unirradiated marrow. An endogenous repopulating system was tested; marrow was irradiated in situ by a limb-shielding technique. The results indicated a biphasic dose-incidence curve with a peak at 500 rads. The rising part of the curve was in agreement with and extended the conclusion from the exogenous system, whereas the descending portion at higher doses paralleled the trend observed in the whole-body X-irradiated animals. Finally, the irradiation of two hind legs resulted in a higher frequency of RCS than did irradiation of only one leg at the same dose levels.
Mammary Tumorigenesis in Chemical Carcinogen-Treated Mice. VII. Prolactin and Progesterone Levels in BALB/c Mice2
Authors: Daniel Medina, S. B. O' Bryan, M. R. Warner, Y. N. Sinha, W. P. VanderLaan, S. McCormack, P. Hahn
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Mammary Tumorigenesis in Chemical Carcinogen-Treated Mice. VII. Prolactin and Progesterone Levels in BALB/c Mice Get access Daniel Medina, Daniel Medina Search for other works by this author on: Oxford Academic PubMed Google Scholar S. B. O' Bryan, S. B. O' Bryan Search for other works by this author on: Oxford Academic PubMed Google Scholar M. R. Warner, M. R. Warner Search for other works by this author on: Oxford Academic PubMed Google Scholar Y. N. Sinha, Y. N. Sinha Search for other works by this author on: Oxford Academic PubMed Google Scholar W. P. VanderLaan, W. P. VanderLaan Search for other works by this author on: Oxford Academic PubMed Google Scholar S. McCormack, S. McCormack Search for other works by this author on: Oxford Academic PubMed Google Scholar P. Hahn P. Hahn Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 1, July 1977, Pages 213–219, https://doi.org/10.1093/jnci/59.1.213 Published: 01 July 1977 Article history Received: 08 November 1976 Accepted: 06 January 1977 Published: 01 July 1977
Immunotherapy Experiments With a Methylcholanthrene-Induced Guinea Pig Liposarcoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Frederick R. Eilber, E. Carmack Holmes, Donald L. Morton
Journal: JNCI Journal of the National Cancer Institute (1971)

Intradermal immunization of syngeneic guinea pigs with a methylcholanthrene-induced liposarcoma effectively prevented the growth of an intramuscular tumor challenge when immunization was initiated at the same time as, or up to 10 days after, challenge. The most effective immunogens for intradermal immunization were viable cells from grafts of the transplanted tumor, but irradiated tumor cells and tumor cells grown in tissue culture were also effective.
Profile of illness in Syrian refugees: A GeoSentinel analysis, 2013 to 2015
Authors: Frank P. Mockenhaupt, Kira A. Barbre, Mogens Jensenius, Carsten S. Larsen, Elizabeth D. Barnett, William Stauffer, Camilla Rothe, Hilmir Asgeirsson, Davidson H. Hamer, Douglas H. Esposito, Philippe Gautret, Patricia Schlagenhauf
Journal: Eurosurveillance (2016)

Screening of 488 Syrian unaccompanied minor refugees (< 18 years-old) in Berlin showed low prevalence of intestinal parasites (Giardia, 7%), positive schistosomiasis serology (1.4%) and absence of hepatitis B. Among 44 ill adult Syrian refugees examined at GeoSentinel clinics worldwide, cutaneous leishmaniasis affected one in three patients; other noteworthy infections were active tuberculosis (11%) and chronic hepatitis B or C (9%). These data can contribute to evidence-based guidelines for infectious disease screening of Syrian refugees.
Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study
Authors: Howard L. Kaufman, Thomas Amatruda, Tony Reid, Rene Gonzalez, John Glaspy, Eric Whitman, Kevin Harrington, John Nemunaitis, Andrew Zloza, Michael Wolf, Neil N. Senzer
Journal: Journal for ImmunoTherapy of Cancer (2016)

We previously reported that talimogene laherparepvec, an oncolytic herpes virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), resulted in an objective response rate of 26 % in patients with advanced melanoma in a phase II clinical trial. The response of individual lesions, however, was not reported. Since talimogene laherparepvec is thought to mediate anti-tumor activity through both direct tumor cytolysis and induction of systemic tumor-specific immunity, we sought to determine the independent response rate in virus-injected and non-injected lesions.Fifty patients with stage IIIC or IV melanoma were treated with talimogene laherparepvec in a multi-institutional single-arm open-label phase II clinical trial. In this study patients were treated until a complete response was achieved, all accessible tumors disappeared, clinically significant disease progression, or unacceptable toxicity. This report is a post hoc analysis of the systemic effects of talimogene laherparepvec in injected lesions and two types of uninjected lesions-non-visceral lesions and visceral lesions.Eleven of 23 patients (47.8 %) had a ≥ 30 % reduction in the total burden of uninjected non-visceral lesions, and 2 of 12 patients (16.7 %) had a ≥ 30 % reduction in the total burden of visceral lesions. Among 128 evaluable lesions directly injected with talimogene laherparepvec, 86 (67.2 %) decreased in size by ≥ 30 % and 59 (46.1 %) completely resolved. Of 146 uninjected non-visceral lesions, 60 (41.1 %) decreased in size by ≥ 30 %, the majority of which (44 [30.1 %]) completely resolved. Of 32 visceral lesions, 4 (12.5 %) decreased in size by ≥ 30 %, and 3 (9.4 %) completely resolved. The median time to lesion response was shortest for lesions that were directly injected (18.4 weeks), followed by uninjected non-visceral lesions (23.1 weeks) and visceral lesions (51.3 weeks), consistent with initiation of a delayed regional and systemic anti-tumor immune response to talimogene laherparepvec.These results support a regional and systemic effect of talimogene laherparepvec immunotherapy in patients with advanced melanoma.
Spine Radiosurgery in the Management of Renal Cell Carcinoma Metastases
Authors: Neil K. Taunk, Daniel E. Spratt, Mark Bilsky, Yoshiya Yamada
Journal: Journal of the National Comprehensive Cancer Network (2015)

Renal cell carcinoma (RCC) presents an interesting challenge in radiation oncology. Improved systemic therapy has significantly prolonged survival. Modern imaging has allowed practitioners to effectively identify patients with oligometastatic disease. Conventionally fractionated radiation therapy is a first-line treatment option for palliation of bone metastases, including the spine, but has limited efficacy and durability. Conventional treatment may not be sufficient in metastatic RCC because of the disease's relative radioresistance. Improved technology, including custom immobilization and on-board treatment imaging, has allowed ultra-high-dose radiation therapy, or stereotactic radiosurgery (SRS), to effectively treat metastatic disease in the spine. Safety and efficacy have already been established for intracranial disease and data are emerging for extracranial metastasis. Spine SRS offers local control rates and durable pain improvement in up to 90% of patients. Many series have already reported its effectiveness, and prospective multi-institutional trials are underway. Spine SRS should be strongly considered in select patients with refractory or oligometastatic disease.
Analysis of a single institution series of 155 patients treated with adjuvant trastuzumab
Authors: C. Farrell, A. M. Wardley, H. Mitchell, A. McGurk, V. Lau, B. Magee, J. Loncaster, A. Stewart, G. Wilson, P. Burt
Journal: Journal of Clinical Oncology (2008)

11504 Background: Following interim results of the HERA study (2005) trastuzumab (T) was introduced as standard clinical practice three weekly for 18 cycles postchemotherapy (CT). Cardiac dysfunction (CD) was monitored by MUGA every 3 months. Methods: Single institution series of patients treated with T from Sept-Dec 2006. Patients with baseline LVEF (BL) < 55% had echo/cardiology assessment before T. A proforma was used prospectively for data collection; SPSS used for data entry/analysis. Results: 155 patients were treated with T, including 13 (8.4%) over 65 years. However, there was no significant difference (NS) between age and CD, nor cycles of T administered. 154 patients had CT with anthracycline, but CT type was NS. 107 (69%) had radiotherapy. BL ranged from 47–80%. 148 (95.5%) had a normal BL, 2 had BL <50% and 5 BL 50–54%. All 7 with abnormal BL had further CD during T, although 5 (71.4%) recovered and completed T, compared with 124 (83.8%) with normal BL completed T and 19 (12.8%) with CD. There was a significant difference (SD) in BL and development of CD (p<0.001), but NS in BL and completion of T (p=0.602). 129 (83.2%) completed T, but it was suspended in 38 (24.5%): 7 developed MBC, 5 unable to tolerate T and 26 (16.8%) had CD. Of the 26 with CD, 12 (46.2%) completed T and 6 (23.1%) resumed then had further CD. 19 (73%) with CD had normal BL, but 9 (5.8%) normal LVEF at 12 months, compared with 96 (74.4%) with no CD. NS between CD and survival. The time from CT to T ranged from 3–84 weeks, median14.5 weeks. 62 (41.1%) started T ≤ 12 weeks from CT, but this was NS on BL/ final LVEF, CD or completing T. However, there was a SD in MBC/death if this time lag was >12 weeks (p=0.048). Following T, 7 patients (4.5%) have died and 3 (1.9%) have MBC, however 145 (93.5%) are alive without recurrence. Conclusions: Cardiac monitoring is crucial during T, and caution needed if BL is abnormal, since this may predict further CD during T. Although 26/155 developed CD, the majority improved their LVEF on stopping T and 12/26 went on to complete T despite CD. Age alone was not associated with CD and completion of T, which is reassuring in an ageing population. The disparity in time lag from CT to T occurred due to initial implementation in UK. There was a significant increase in MBC/death if T started >12 wks after CT, which has implications for practice. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Roche Roche
Should caffeine abuse, dependence, or withdrawal be added to DSM-IV and ICD-10?
Authors: J R Hughes, A H Oliveto, J E Helzer, S T Higgins, W K Bickel
Journal: American Journal of Psychiatry (1992)

The authors reviewed basic science and clinical data on caffeine abuse, dependence, and withdrawal in order to make a conclusion about whether these disorders exist and should be included in DSM-IV and ICD-10.Studies were located through computerized searches, reference sections of published articles, and written requests.The studies show that abstinence from caffeine induces a withdrawal syndrome of headache, fatigue, and drowsiness which begins within 12-24 hours and lasts about 1 week. The syndrome can be severe and appears to be one reason for continued use of coffee. The prevalence of this caffeine withdrawal syndrome is unknown. Use of caffeine may aggravate some common behavioral and medical disorders. In double-blind tests, a subset of coffee and soda drinkers reliably self-administered caffeinated beverages in preference to uncaffeinated beverages. Clinical indicators of dependence, such as difficulty stopping use of caffeine and use despite harm, have not been documented.Caffeine withdrawal but not caffeine abuse or dependence should be included as a diagnosis in DSM-IV and ICD-10. Future research should focus on whether some caffeine users exhibit clinical indicators of drug dependence.