tbuckley/cabot-search huggingface dataset:
Abstract 138: Effects of Compression Rate on Coronary Perfusion Pressure and Carotid Blood Flow in a Porcine Model of Shock-Induced Pulseless Electrical Activity
Authors: Xiaobo Wu, Weilun Quan, Yinlun Weng, Wei Chen, Shijie Sun, Wanchun Tang
Journal: Circulation (2012)

Background:  The 2010 AHA guidelines recommend a chest compression (CC) depth of at least 2 inches. However, most clinical studies found an inverse association between CC depth and rate. The effect of CC rate on coronary perfusion pressure (CPP) and carotid blood flow (CBF) has not been determined. This study was to investigate hemodynamic responses to CC at different compression rate in a post- shock PEA porcine model.   Methods:  Ventricular fibrillation was electrically induced and untreated for 2 - 7 mins in 12 domestic pigs weighing 22-24kg. Post- shock PEA was induced with electric shock. Peak aortic pressures below 40 mm Hg was used to identify a qualified PEA. Once PEA was induced, animals received 30 sec PEA-triggered synchronized sternal CC using a modified Thumper device. CC depth was maintained at 2 inches. If animals were resuscitated after the study sequence PEA induction and the study sequence were repeated after 30 mins recovery.   Results:  A total of 1102 compression cycles from 29 qualified PEA events were included in the analyses. The rate of induced PEA varied from 30 to 125 bpm. When the CC rate increased from 80 to 120 bpm with fixed CC depth, CPP increased by 5.6 mmHg (32.9%) and CBF increased by 46.4 ml/min (50.2%). Both CPP and CBF were positively correlated to CC rate with correlation coefficients of 0.32 and 0.49 (p=0), respectively. Linear regression found a positive trend for both CPP and CBF with slopes over the CC rate of 0.14 and 1.16 (p=0), respectively.   Conclusions:  In this shock induced PEA porcine model, both CPP and CBF increased with CC rate. These results indicate that faster sternal CC would generate better coronary and cerebral perfusion in the range between 80 to 120 bpm.
Susceptibility to chronic mucus hypersecretion: A genome-wide association study
Authors: Akkelies Dijkstra, Joanna Smolonska, Marike Boezen, Pieter Zanen, Rob van Klaveren, Michael Owsijewitsch, Ewa Nizankowska, Ciska Wijmenga, Harry Groen, Dirkje Postma
Journal: European Respiratory Journal (2011)

Background: Patients with COPD with chronic mucus hypersecretion (CMH) have a significantly increased FEV1 decline and a higher risk of hospitalization than those without CMH. Moreover, although individuals with CMH are more likely to be ex- or current smokers, so far it is unclear why some smokers develop CMH and others do not. A plausible explanation for this phenomenon would be a genetic predisposition.

Methods: We performed a genome wide association study (GWAs) using the Nelson study (a population-based lung cancer screening study from Groningen and Utrecht, the Netherlands) including 717 subjects with and 1,795 without CMH, all ex or current heavy smokers (>20 pack years). Lung function results and information about sputum expectoration during the previous year were collected at the start of the study. To enhance power we added 590 blood bank controls. Genotyping data were analyzed using PLINK with adjustment for center (Groningen/Utrecht). We aimed to replicate the results by evaluating the top single nucleotide polymorphisms (SNPs) in 7 European cohorts contributing 487 cases and 1,118 controls.

Results: We identified 77 SNPs associated with CMH with a p-value <10-4, of which 5 SNPs had a p-value <10-5. Meta-analysis of selected top SNPs in the initial and replication cohorts identified 3 SNPs with a p-value <10-6 and 3 with a p-value <10-5. Some genes close to these SNPs have been reported to be associated with epithelial changes.

Conclusion: This study suggests that susceptibility to CMH is associated with genetic predisposition. To confirm these data replication will be extended to 3 additional cohorts.
Central venous catheters (CVC) in bone marrow transplantation and leukemia patients
Authors: B. Barman, R. Ghosh, A. Mondal, K. Saha, S. Mukhopadhyay, A. Mukhopadhyay
Journal: Journal of Clinical Oncology (2005)

8269 Background: Patients undergoing autologous and allogenic Bone Marrow Transplantation (BMT) and treatment for Acute Leukemia were evaluated to study infectious and non-infectious complications with the use of long term Central venous Catheters. Methods: The study group consists of 79 patients including children and adults with single, double and triple lumen catheters (82). The study period was between August 1998 to September 2004. The standard of care includes aseptic cleaning with spirit and povidone-iodine solution, application of povidone-iodine ointment at exit site and covering the sterile slit gauze-piece and plaster. It was changed every alternate day. Central Venous catheter lumen flushing was done with 4ml of heparinzied saline (100 units/mL) every day before changing IV tubing and bi-valve. Total 82 catheters were inserted in 79 patients. One patient required double and another required triple insertion. Results: During the period of analysis (total 8067 days, median 78.5 days), 31 episodes of infections complications were encountered; exit site - 5 (6.0%), tunnel - 1(7.5%), lumen colonization - 17(20.7%) and septicemia 8(9.7%). Infectious complication rate was 0.3 per 100 days and non-infectious complications rate was 0.07 per 100 days. 7 episodes of non infectious complications comprised dislodgment 3(3.6%), fractures 91(1.2%),block 3(3.6%). Conclusions: We found that CVC infections varies according to the number of lumen, frequency of IV tube changing, immune status, duration of catheter use, occurrence and outcome of catheter occlusion and administration of TPN. No significant financial relationships to disclose.
Adaptive and nonadaptive consequences of chemical inhibition of intercellular communication.
Authors: J E Trosko, C C Chang
Journal: Pharmacological Reviews (1984)

Intercellular communication is a fundamental process in multicellular organisms developed to orchestrate homeostatic control of mitotic and differentiation processes in pre- and postmitotic cells. Endogenous and exogenous chemicals can, via a series of mechanisms, interfere with intercellular communication between and within various tissues. The responses to the inhibition of non-gap-junctional and gap-junctional communication can be either adaptive or nonadaptive depending on the mitigating circumstances. The inhibition of gap-junctional communication appears to be one of the sequelae of a membrane-triggered response to many natural and man-made pharmacological chemicals. The biological consequences of inhibited intercellular communication might include teratogenesis (embryo or fetal toxicity), tumor promotion, reproductive toxicology, and neuroendocrine-related disorders.
P-281 The GERCOR and Köhne prognostic models in metastatic colorectal cancer (mCRC) patients treated with bevacizumab-based first-line therapy: comparison and validation of both models in a real-life setting
Authors: G. Bruixola, R. Diaz Beveridge, M. Melian, E. Reche, C. Escoín, O. Niño, C. Salvador, D. Akhoundova, E. Navarro, S. Palanca, J. Caballero, A. Giménez, A. Segura, J. Aparicio
Journal: Annals of Oncology (2015)
Role of the Chemotherapy Research Laboratory in Clinical Cancer Research&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: M J SHEAR
Journal: JNCI Journal of the National Cancer Institute (1951)

Role of the Chemotherapy Research Laboratory in Clinical Cancer Research M. J. Shear M. J. Shear Laboratory of Chemical Pharmocology, National Cancer Institute3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 3, December 1951, Pages 569–581, https://doi.org/10.1093/jnci/12.3.569 Published: 01 December 1951 Article history Received: 12 September 1951 Published: 01 December 1951
Tumor hypoxia drives immune suppression and immunotherapy resistance
Authors: Midan Ai, Pratha Budhani, Jie Sheng, Sadhana Balasubramanyam, Todd Bartkowiak, Ashvin R Jaiswal, Casey R Ager, Dhwani D Haria, Michael A Curran
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Tumor hypoxia predicts poor outcomes across all cancers and has long been recognized as a critical source of resistance to both chemotherapy and radiotherapy. Despite the success of T cell immune checkpoint blockade in treating melanoma, aggressive adenocarcinomas of the prostate
Establishing International Blood Pressure References Among Nonoverweight Children and Adolescents Aged 6 to 17 Years
Authors: Bo Xi, Xin’nan Zong, Roya Kelishadi, Young Mi Hong, Anuradha Khadilkar, Lyn M. Steffen, Tadeusz Nawarycz, Małgorzata Krzywińska-Wiewiorowska, Hajer Aounallah-Skhiri, Pascal Bovet, Arnaud Chiolero, Haiyan Pan, Mieczysław Litwin, Bee Koon Poh, Rita Y.T. Sung, Hung-Kwan So, Peter Schwandt, Gerda-Maria Haas, Hannelore K. Neuhauser, Lachezar Marinov, Sonya V. Galcheva, Mohammad Esmaeil Motlagh, Hae Soon Kim, Vaman Khadilkar, Alicja Krzyżaniak, Habiba Ben Romdhane, Ramin Heshmat, Shashi Chiplonkar, Barbara Stawińska-Witoszyńska, Jalila El Ati, Mostafa Qorbani, Neha Kajale, Pierre Traissac, Lidia Ostrowska-Nawarycz, Gelayol Ardalan, Lavanya Parthasarathy, Min Zhao, Tao Zhang
Journal: Circulation (2016)

Background— Several distributions of country-specific blood pressure (BP) percentiles by sex, age, and height for children and adolescents have been established worldwide. However, there are no globally unified BP references for defining elevated BP in children and adolescents, which limits international comparisons of the prevalence of pediatric elevated BP. We aimed to establish international BP references for children and adolescents by using 7 nationally representative data sets (China, India, Iran, Korea, Poland, Tunisia, and the United States). Methods and Results— Data on BP for 52 636 nonoverweight children and adolescents aged 6 to 19 years were obtained from 7 large nationally representative cross-sectional surveys in China, India, Iran, Korea, Poland, Tunisia, and the United States. BP values were obtained with certified mercury sphygmomanometers in all 7 countries by using standard procedures for BP measurement. Smoothed BP percentiles (50th, 90th, 95th, and 99th) by age and height were estimated by using the Generalized Additive Model for Location Scale and Shape model. BP values were similar between males and females until the age of 13 years and were higher in males than females thereafter. In comparison with the BP levels of the 90th and 95th percentiles of the US Fourth Report at median height, systolic BP of the corresponding percentiles of these international references was lower, whereas diastolic BP was similar. Conclusions— These international BP references will be a useful tool for international comparison of the prevalence of elevated BP in children and adolescents and may help to identify hypertensive youths in diverse populations.
Phase I/II Study of Sorafenib in Combination with Hepatic Arterial Infusion Chemotherapy Using Low-Dose Cisplatin and 5-Fluorouracil
Authors: Kazuomi Ueshima, Masatoshi Kudo, Masatoshi Tanaka, Takashi Kumada, Hobyung Chung, Satoru Hagiwara, Tatsuo Inoue, Norihisa Yada, Satoshi Kitai
Journal: Liver Cancer (2015)

We conducted a phase I/II study in patients with advanced hepatocellular carcinoma (HCC) to determine the recommended dose, as well as the safety and efficacy, of combination therapy of sorafenib with hepatic arterial infusion chemotherapy (HAIC) using low dose cisplatin (CDDP) and 5-fluorouracil (5FU). Cohorts consisting of 3-6 patients with HCC received an escalated dose of CDDP and 5-FU until a maximum-tolerated dose was achieved. The treatment regimen was as follows: oral administration of sorafenib (400 mg twice daily for 28 days) combined with HAIC using CDDP (14-20 mg/m&lt;sup&gt;2&lt;/sup&gt;, on days 1 and 8) and 5-FU (170-330 mg/m&lt;sup&gt;2&lt;/sup&gt;, continuously on days 1-5 and 8-12) via an implanted catheter system). Each treatment cycle consisted of 28 days and three cycles of combination therapy. At the end of the first cycle, adverse events were evaluated and future dose escalation was determined. Eighteen patients with advanced HCC were enrolled. Dose-limiting toxicity was observed in two patients from cohort 1 (erythema multiforme and grade 4 thrombocytopenia) and in one patient from cohort 2 (erythema multiforme). Seven of the 18 patients achieved a partial response, seven showed stable disease, two were diagnosed as progressive disease, and two were not assessable. The response rate was 38.9% and the disease control rate was 77.8%. The time-to-progression was 9.7 months and the 1-year survival rate was 88.2%. Oral administration of 400 mg of sorafenib twice daily, 20 mg/m&lt;sup&gt;2&lt;/sup&gt; of intra-arterial infusion of CDDP, and 5-FU at 330 mg/m&lt;sup&gt;2&lt;/sup&gt; are the recommended doses for combination therapy, which was well tolerated and efficacious. This combination therapy may be a promising treatment for patients with advanced HCC. A large prospective randomized multicenter study (ClinicalTrials.gov Identifier NCT01214343) is ongoing.
Abstract 259: National Variability in Survival Outcomes of Out-of-Hospital Cardiac Arrest: The All-Japan Utstein Registry
Authors: Kohei Hasegawa, Yusuke Tsugawa, Atsushi Hiraide, David F M Brown
Journal: Circulation (2012)

Introduction Health and policy implications of national variability in survival outcomes of out-of-hospital cardiac arrest (OHCA) remain to be determined. Hypothesis We tested the hypothesis that survival outcomes of OHCA would differ across geographic regions in Japan. Methods Analysis of a prospective nation-wide population-based dataset of the whole population across Japan involving all patients who had a non-traumatic OHCA resuscitated by emergency responders from January 2005 through December 2010. The study endpoints were 1-month survival and favorable neurological survival 1 month after an OHCA, defined as Cerebral Performance Category 1 or 2. We compared unadjusted and multivariable-adjusted rates of the outcomes among 7 geographic regions using regression model with generalized estimating equations to control for patient- and prehospital-level characteristics (Table). Results In the total catchment population of 128 million, 670 313 patients with OHCA were documented. Of 660 672 resuscitation attempts, 539 641 non-traumatic OHCA patients were eligible for analysis. The adjusted incidence of OHCA per 100 000 population ranged from 58.9 to 78.8 (median, 65.3). One-month survival ranged from 3.7% to 6.1%, with a median of 5.6%; we observed a large variation among regions in multivariable adjusted rate of 1-month survival, ranging from 3.8% to 6.5% (median, 4.7%). Similarly, neurologically favorable survival varied by region from 1.9% to 3.0%, with a median of 2.5%; adjusted rate of neurologically favorable survival ranged from 1.9% to 3.6% (median, 2.7%), with significant differences across regions (P&lt;.001). Conclusion In this nation-wide population-based study in Japan, there were significant and important regional differences in OHCA survival outcomes.
Efficacy and safety of bevacizumab (BEV)-based combination regimens in patients with metastatic colorectal cancer (mCRC): Randomized phase II study of BEV + FOLFIRI versus BEV + XELIRI (FNCLCC ACCORD 13/0503 study)
Authors: M. Ducreux, A. Adenis, J. Mendiboure, E. François, E. Boucher, B. Chauffert, M. Ychou, J. Pierga, C. Montoto-Grillot, T. Conroy
Journal: Journal of Clinical Oncology (2009)

4086 Background: The combination of BEV and chemotherapy is highly effective in patients with mCRC and improves response rate, progression-free survival and overall survival compared with chemotherapy alone. This randomized non-comparative phase II trial evaluated the efficacy and safety of BEV in combination with either XELIRI or FOLFIRI as first-line therapy for mCRC. Methods: Patients were eligible for inclusion in this study if they had histologically proven measurable mCRC, were aged 18–75 years, and had an ECOG performance status (PS) of 0–2. Patients were treated with 8 cycles of XELIRI (irinotecan 200 mg/m 2 on Day 1 and capecitabine 1000 mg/m 2 bid on Days 1–14) + BEV 7.5 mg/kg on Day 1, every 3 weeks or 12 cycles of FOLFIRI (irinotecan 200 mg/m 2 on Day 1 + 5-fluorouracil (5-FU) 400 mg/m 2 + folinic acid 400 mg/m 2 on day 1 followed by 5-FU 2400 mg/m 2 via 46-h infusion) + BEV 5 mg/kg on day 1, every 2 weeks. BEV was continued to disease progression. Patients aged ≥65 years received a lower daily dose of capecitabine (800 mg/m 2 bid). The primary endpoint was crude progression-free survival (PFS) at 6 months. Results: In total, 145 patients were entered in the study between March 2006 and January 2008; 72 patients received BEV + XELIRI and 73 patients received BEV + FOLFIRI (male 64%/48%; median age 61/61 years; 35/36% aged &gt;65 years). Preliminary results from the first 6 months of follow-up are reported here. A total of 491/783 cycles was administered, 63%/67% receiving at least the initially planned number of cycles (8 cycles for BEV + XELIRI and 12 for BEV + FOLFIRI). Main results are given in the table . Conclusions: This randomized non-comparative study has shown that BEV + XELIRI and BEV + FOLFIRI are similarly effective treatments for patients with mCRC, with manageable toxicity profiles. Results with updated follow-up will be presented at the Meeting. [Table: see text] [Table: see text]
Association of Cesarean Delivery and Formula Supplementation With the Intestinal Microbiome of 6-Week-Old Infants
Authors: Juliette C. Madan, Anne G. Hoen, Sara N. Lundgren, Shohreh F. Farzan, Kathryn L. Cottingham, Hilary G. Morrison, Mitchell L. Sogin, Hongzhe Li, Jason H. Moore, Margaret R. Karagas
Journal: JAMA Pediatrics (2016)

The intestinal microbiome plays a critical role in infant development, and delivery mode and feeding method (breast milk vs formula) are determinants of its composition. However, the importance of delivery mode beyond the first days of life is unknown, and studies of associations between infant feeding and microbiome composition have been generally limited to comparisons between exclusively breastfed and formula-fed infants, with little consideration given to combination feeding of both breast milk and formula.To examine the associations of delivery mode and feeding method with infant intestinal microbiome composition at approximately 6 weeks of life.Prospective observational study of 102 infants followed up as part of a US pregnancy cohort study.Delivery mode was abstracted from delivery medical records, and feeding method prior to the time of stool collection was ascertained through detailed questionnaires.Stool microbiome composition was characterized using next-generation sequencing of the 16S rRNA gene.There were 102 infants (mean gestational age, 39.7 weeks; range, 37.1-41.9 weeks) included in this study, of whom 70 were delivered vaginally and 32 by cesarean delivery. In the first 6 weeks of life, 70 were exclusively breastfed, 26 received combination feeding, and 6 were exclusively formula fed. We identified independent associations between microbial community composition and both delivery mode (P< .001; Q < .001) and feeding method (P = .01; Q < .001). Differences in microbial community composition between vaginally delivered infants and infants delivered by cesarean birth were equivalent to or significantly larger than those between feeding groups (P = .003). Bacterial communities associated with combination feeding were more similar to those associated with exclusive formula feeding than exclusive breastfeeding (P = .002). We identified 6 individual bacterial genera that were differentially abundant between delivery mode and feeding groups.The infant intestinal microbiome at approximately 6 weeks of age is significantly associated with both delivery mode and feeding method, and the supplementation of breast milk feeding with formula is associated with a microbiome composition that resembles that of infants who are exclusively formula fed. These results may inform feeding choices and shed light on the mechanisms behind the lifelong health consequences of delivery and infant feeding modalities.
Kinase Activity Of Pak2, An Effector Of Rac/CDC42 and Its Interaction With β-PIX Is Required For Murine Hematopoietic Stem Cell Shape, F-Actin Formation, Directional Migration In Vitro and For HSPC Homing To Bone Marrow In Vivo
Authors: Pavankumar N.G. Reddy, Jenna Wood, Chad E Harris, Ke Xu, Meaghan McGuinness, Maria Radu, Rachelle Kosoff, Jonathan Chernoff, David A. Williams
Journal: Blood (2013)
Epigenetic Regulation of the Homeobox Gene<i>MSX1</i>Associates with Platinum-Resistant Disease in High-Grade Serous Epithelial Ovarian Cancer
Authors: Nair A. Bonito, Jane Borley, Charlotte S. Wilhelm-Benartzi, Sadaf Ghaem-Maghami, Robert Brown
Journal: Clinical Cancer Research (2016)

Although high-grade serous ovarian cancer (HGSOC) is frequently chemoresponsive, a proportion of patients do not respond to platinum-based chemotherapy at presentation or have progression-free survival (PFS) of less than 6 months. Validated predictive biomarkers of lack of response would enable alternative treatment stratification for these patients and identify novel mechanisms of intrinsic resistance. Our aim was to identify DNA methylation biomarkers of poor response to chemotherapy and demonstrate involvement of the associated gene in platinum drug cell sensitivity.
MyD88/CD40-based inducible co-stimulation to improve CAR T cell therapy
Authors: Melinda Mata, Claudia Gerken, David M Spencer, Stephen Gottschalk
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Adoptive immunotherapy with genetically modified T cells holds promise in improving outcomes for cancer patients. While a broad array of genetic modification strategies are being explored, few allow for the specific manipulation of adoptively transferred T cells in vivo . One
Melanoma, Version 4.2014
Authors: Daniel G. Coit, John A. Thompson, Robert Andtbacka, Christopher J. Anker, Christopher K. Bichakjian, William E. Carson, Gregory A. Daniels, Adil Daud, Dominick DiMaio, Martin D. Fleming, Rene Gonzalez, Valerie Guild, Allan C. Halpern, F. Stephen Hodi, Mark C. Kelley, Nikhil I. Khushalani, Ragini R. Kudchadkar, Julie R. Lange, Mary C. Martini, Anthony J. Olszanski, Merrick I. Ross, April Salama, Susan M. Swetter, Kenneth K. Tanabe, Vijay Trisal, Marshall M. Urist, Nicole R. McMillian, Maria Ho
Journal: Journal of the National Comprehensive Cancer Network (2014)

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.