tbuckley/cabot-search huggingface dataset:
VEGFr inhibitor YN968D1 xenograft dose response studies against human colon cancer Ls174t and HT29
Authors: Ling-Hua Zhang, Ling Lu, Lei Wu, Keith Dredge, J Blake Bartlett, Peter H. Schafer, George Muller, Angus Dalgleish
Journal: Cancer Research (2006)

1761  Inhibition of angiogenesis is currently perceived as one of the promising strategies in the cancer therapy. Thalidomide (Thalomid®) and its Immunomodulatory Drug (IMiD®) analogs have entered into clinical trials for the treatment of various types of cancers. Lenalidomide (Revlimid®, CC-5013) is currently being assessed in oncology clinical trials worldwide. In this study we have compared the anti-angiogenic mechanisms of thalidomide and lenalidomide in a variety of experimental systems representing distinct events of the angiogenic process. Endothelial cell (EC) proliferation is stimulated by growth factors. Neither thalidomide nor lenalidomide have an appreciable inhibitory effect on growth factor-induced proliferation of human umbilical vein endothelial cells (HUVEC). In both the HUVEC and B16-F10 mouse melanoma tube formation assays, lenalidomide appears to be at least 10-fold more potent than thalidomide, the latter indicating that effects extend to vessels lined by tumor cells. However, in endothelial cell migration assays, thalidomide is more active than lenalidomide; in both the HUVEC and B16-F10 monolayer scratch migration assays, thalidomide is clearly more potent than lenalidomide in preventing the migration of cells into the wounded/scratched region. In assays of HUVEC migration towards specific angiogenic factors, such as VEGF, bFGF, and TNF-α, thalidomide is also more potent than lenalidomide. Interestingly, assays where the whole physiological process of angiogenesis can be studied show differential sensitivities. Lenalidomide is more potent in the rat aorta assay, whereas thalidomide is more potent in the human umbilical explant assay. Mechanistic studies on signal transduction events triggered by VEGF show that both thalidomide and lenalidomide partially inhibit Akt phosphorylation in VEGF-induced HUVEC. Furthermore, inhibitory effects on the phosphorylation of Gab1, a scaffolding protein upstream of Akt activation, have been observed. In summary, our data indicate that both thalidomide and lenalidomide interfere with key events in the angiogenic process and that they can be differentiated qualitatively depending on which component part is studied.
Interdisciplinary palliative care communication for quality palliative care: Outcomes of a statewide train-the-trainer course.
Authors: Betty R. Ferrell, Haley Buller, Wendy Anderson, Judith A. Paice, Doranne Donesky
Journal: Journal of Clinical Oncology (2018)

83 Background: Expert communication skills are essential for the delivery of effective palliative care across the domains of care. However, few healthcare providers receive formal communication training. The purpose of this presentation is to describe a train-the-trainer course for interprofessional hospital-based palliative care teams to prepare them to teach other healthcare professionals palliative care communication skills. Methods: This project was organized by the eight domains of the National Consensus Project (NCP) guidelines for quality palliative care and provided communication skills training for California-based teams. Funded by the Archstone Foundation, this 2-day train-the-trainer course included skill-building exercises and interactive discussions to assist participants in integrating communication skills-building into their clinical settings. Using a goal-directed method of teaching, the faculty assisted teams in developing three institutional goals for providing palliative care communication training to other healthcare professionals. Evaluation of the course included immediate post-course evaluation and follow-up evaluation at 6 and 9 months. Results: The first statewide interprofessional communication training took place in January 2018 with 26 palliative care teams consisting of primarily nurses, followed by social workers, chaplains and physicians. The 46 course participants’ post-course evaluations demonstrated high satisfaction with the course. On a scale of 1 to 5 (1 = lowest), the course met participants’ expectations and objectives (4.8). The teams’ pre-course goals focused on: 1) staff education, training and mentorship, and 2) institution-wide system changes involving communication with palliative care. Conclusions: A 6 and 9 month follow-up will evaluate team progress on institutional goals (e.g. status and implementation) and provide an update on the additional healthcare professionals trained by course participants and changes implemented within their health system.
Older patients with IBD might have higher risk of Parkinson’s disease
Authors: Qian-Yi Wan, Rui Zhao, Xiao-Ting Wu
Journal: Gut (2018)

We read with interest the study by Villumsen et al 1 which reported that patients with IBD had a 22% increased risk of Parkinson’s disease (PD) compared with non-IBD individuals. The study supported the theory that intestinal environment could influence the function of central nervous system which was also called the gut–brain axis. Recently, a meta-analysis by Zhu et al 2 suggested that the overall risk of PD in patients with IBD was significantly higher than controls (OR 1.41; 95% CI 1.19 to 1.66). However, only four studies were included in the meta-analysis. We also noticed a case–control study by Camacho-Soto et al 3 reporting that the risk of PD was inversely associated with IBD (OR 0.85; 95% CI 0.80 to 0.91), which was not …
The European Respiratory Society's 10 Principles for Lung Health
Authors: Ildikó Horváth, Maeve Barry, Guy Brusselle, Otto Chris Burghuber, Andrew Bush, Carlos Robalo Cordeiro, Mina Gaga, Christina Gratziou, Isabel Saraiva, Daiana Stolz, Thierry Troosters, Tobias Welte, Giovanni Battista Migliori, Guy Joos
Journal: European Respiratory Journal (2018)

<b>With the ERS 10 Principles for Lung Health, @ERSTalk proposes a call to action to improve respiratory health and invites all stakeholders (politicians, policy makers, patients and the public) to support it</b>http://ow.ly/9dW730mkhZu
Multidrug resistance (MDR) in AML: Predicting P-glycoprotein (Pgp) function by direct measurement of drug efflux is more effective than use of surrogate efflux indicators
Authors: MyDoanh Chau, Ante Lundberg, Maria Baer, Harry Erba, Robert Capizzi, Alfred Ajami
Journal: Cancer Research (2008)

3238  Assessment of Pgp function in leukemic blasts provides useful prognostic information regarding rates and treatment response and may be used for therapy selection in acute myeloid leukemia (AML) patients. Traditional assessment of Pgp function has utilized fluorescent indicators, such as DiOC2(3)or rhodamine 123 (Rh123), as surrogates for drug uptake and efflux. The objectives of this study were 1) to compare the performance of these two commonly used probes and representative therapeutic drugs in bidirectional in vitro permeability models, and 2) to validate the methodology for measuring Pgp+ status in patient cells when exposed to actual drugs susceptible to MDR [eg, daunorubicin (DNR), epirubicin (EPI), etoposide (VP-16), idarubicin (IDA), and mitoxantrone (MIT)] versus the surrogate probes and amonafide, a topoisomerase II inhibitor, which is not an MDR substrate (O’Loughlin et al. Blood 2007). Pgp-mediated differential transport was assessed in Caco-2 cells (Pgplow) or MDR1-MDCK (Pgphigh) monolayer cells as a bidirectional efflux/influx ratio (BD) calculated from separate apical-to-basolateral (A-B) and basolateral-to-apical (B-A) drug permeability measurements or as a monodirectional efflux/influx ratio (MD) based on the change in B-A permeability, both performed before and after co-administration of cyclosporin A (CSA), an inhibitor of Pgp. Our results indicated a significant correlation between BD and MD. The two methods afforded the same rank order in extent of efflux for the cohort of test compounds in both Pgplow and Pgphigh. The net efflux of amonafide was
Exercise counseling in integrative cancer care: Effects on patient self-reported symptoms and quality of life.
Authors: Gabriel Lopez, Carol A Eddy, Wenli Liu, Yisheng Li, Minxing Chen, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2018)

227 Background: Exercise has shown benefits for cancer prevention and contributes to improved treatment-related outcomes. We reviewed characteristics of cancer patients referred for physical therapist-led exercise counseling at a comprehensive cancer center and its effects on self-reported symptoms and quality of life. Methods: Patients presenting for outpatient exercise counseling from February 2016 to May 2017 completed the Edmonton Symptom Assessment Scale (ESAS; 0-10 scale, 10 most severe) pre/post-encounter and PROMIS10 global health assessment pre-encounter. ESAS individual items and subscales of Physical Distress (PHS), Psychological Distress (PSS), and Global Distress (GDS) were analyzed. We used paired t-tests to compare: (1) ESAS symptoms before and after each encounter and (2) ESAS and PROMIS10 scores at baseline and first follow-up. Results: Of 350 participants, most were female (77.7%), white (66.3%), and had breast (43%) cancer; 31% had at least one follow-up visit with the physical therapist. Symptom scores at baseline (frequency; mean) included poor sleep (68.2%; 3.5), poor well-being (67.4%; 3.2), and fatigue (64.7%; 3.1). Examination of pre- to post-exercise counseling outcomes revealed statistically, and clinically significant improvement in GDS (-3.32, SD 6.52, p&lt;0.001). On follow-up, statistically and clinically significant improvements were observed for ESAS measures of fatigue (-1.22, p=0.01), GDS (-4.81, p=0.01), and PHS (-3.1, p=0.03) and PROMIS10 global health, mental health, and physical health scores (all p’s&lt;0.05). Conclusions: Patients presenting for exercise counseling had a low to moderate symptom burden and experienced significant improvement in global distress after one encounter. Longitudinal evaluation revealed improvement in global health and fatigue. Additional research is needed to learn more about patient selection and timing of exercise counseling interventions.
A comparison of DNA repair activity in several lymphocyte preparations
Authors: Myron D. Gross, Bharat Thyagarajan, Poonguzhali Kailash, Jennifer Hayes, Waseem Khaliq, Kristin Anderson, Gregory Veltri, David R. Jacobs
Journal: Cancer Research (2005)

4056  DNA repair activity has been measured in circulating lymphocytes and may be a risk factor for several cancers. The measurements of DNA repair activity in lymphocytes have utilized several lymphocyte preparations without consideration of whether differences exist between these preparations. In this study, we have measured one pathway of DNA repair activity, nucleotide excision repair activity (NER), in four lymphocyte preparations including fresh cells (without culturing), cryopreserved cells (frozen as whole blood in dimethyl sulfoxide and grown in culture), immortalized cells (transformed with the Ebstein Barr Virus and cultured), and cultured cells (fresh cells grown in culture). Single blood draws were obtained from each individual in two groups of five healthy subjects. Cultured and immortalized cells were prepared from each blood sample from the first group. In the second group, fresh, cryopreserved and immortalized cells were prepared from each blood sample. DNA repair activity was measured in each cell preparation with an alkaline unwinding flow cytometric assay that was adapted for measurement of NER activity by using UV-C radiation as a DNA damaging agent. Intra-individual variability in DNA repair activity by this assay had a coefficient of variation of 13% as determined in separate studies. Despite a highly reliable assay, the mean DNA repair activity varied across cell preparations and only moderate correlations were found between the DNA repair activities of some preparations. The mean DNA repair activity (area under curve ± SD) was 364±103 and 144±25 in culture and immortalized cells from group 1 (p
Emerging Role of Combination Immunotherapy in the First-line Treatment of Advanced Renal Cell Carcinoma
Authors: Saby George, Brian I. Rini, Hans J. Hammers
Journal: JAMA Oncology (2018)

<h3>Importance</h3> Novel immunotherapies, notably the immune checkpoint inhibitors, have been shown to be efficacious in patients with advanced renal cell carcinoma, but innate or adaptive resistance is observed with single-agent immunotherapy. New combination treatment strategies are needed that can improve efficacy in a broader patient population, without exacerbating the toxic effects. <h3>Observations</h3> Numerous late-phase trials are ongoing to investigate (1) dual immune checkpoint inhibition or (2) combined inhibition of immune checkpoints and vascular endothelial growth factor. Initial results from studies of the nivolumab plus ipilimumab and atezolizumab plus bevacizumab combinations have demonstrated efficacy compared with sunitinib malate in treatment-naïve patients with advanced renal cell carcinoma; moreover, the safety profile of these combinations compare favorably with sunitinib. Nevertheless, immune checkpoint inhibition is associated with unique immune-related adverse events, and practicing physicians must be educated on how to best identify and manage these events. <h3>Conclusions and Relevance</h3> Evidence suggests that immunotherapy-based combination regimens will be an important addition to the treatment of advanced renal cell carcinoma in both the first- and later-line setting; however, clinical study data and clinical practice experience indicate that optimizing the management of the associated immune-related adverse events is essential to maximizing the advantages of these therapies.
Dynamic Magnetic Nanomixers for Improved Microarray Assays by Eliminating Diffusion Limitation
Authors: Qirong Xiong, An Eng Lim, Yun Lim, Yee Cheong Lam, Hongwei Duan
Journal: Advanced Healthcare Materials (2018)

Microarrays are widely used in high-throughput analysis of DNA, protein, and small molecules. However, the majority of microarray assays need improved assay speed and sensitivity due to the slow molecular diffusion from bulk solutions to probe surfaces. Here, a new class of magnetic nanomixers in DNA and protein microarray assays is reported to eliminate the diffusion constraint through dynamic mixing. It is demonstrated that the dynamic nanomixers can improve the assay kinetics at least by a factor of 4 and 2 for DNA and protein microarray assays, respectively. By using the dynamic nanomixers, the sensitivities of detecting Escherichia coli O157:H7 DNA and prostate specific antigen increase by more than four-fold. The dynamic mixing also greatly reduces the spot-to-spot variation to below 10% across a broad concentration range, providing more accurate assay results. In comparison with existing methods, this magnetic nanomixer-based approach offers rapid turnaround, improved sensitivity, good accuracy, low cost, simple operation, and excellent compatibility with commercial microarrays.
Differential T cell responses against DosR-associated antigen Rv2028c in BCG-vaccinated populations with tuberculosis infection
Authors: Hui-Min Zhao, Rui Du, Chun-Ling Li, Ping Ji, Hai-cong Li, Kang Wu, Zhidong Hu, Shui-Hua Lu, Douglas B. Lowrie, Xiao-Yong Fan
Journal: Journal of Infection (2018)
A Mixed Variant of Castleman Disease Detected by Somatostatin Receptor Scintigraphy with 99mTc-HYNIC-TOC and 18F-FDG PET/CT
Authors: Qingqing Pan, Xin Zhang, Yaping Luo, Yanru Ma, Fang Li
Journal: Clinical Nuclear Medicine (2018)

A 50-year-old woman was found with a hypervascular abdominal mass in the right lower quadrant in contrast-enhanced CT. Somatostatin receptor scintigraphy with Tc-HYNIC-TOC showed positivity of the abdominal mass and detected additional lesion with moderate increased radioactivity in the right axilla. In F-FDG PET/CT, both of the lesions were FDG-avid. A hypermetabolic node in the right supraclavicular fossa was also noted. The histopathological examination of the abdominal mass after surgical resection revealed Castleman disease, a mixed hyaline vascular and plasma cell variant. The right axillary and supraclavicular lesions were considered involvement of Castleman disease.
Adult Hyalomma marginatum tick positive for Rickettsia aeschlimannii in Austria, October 2018
Authors: Georg Gerhard Duscher, Adnan Hodžić, Peter Hufnagl, Walpurga Wille-Piazzai, Anna-Magarita Schötta, Mateusz Andrzej Markowicz, Agustín Estrada-Peña, Gerold Stanek, Franz Allerberger
Journal: Eurosurveillance (2018)

We report on a non-indigenous adult Hyalomma marginatum tick in Austria carrying the human pathogenic Rickettsia aeschlimannii; presumably introduced as a nymph via migratory birds and completed the moulting within the same year. It was negative for Crimean-Congo haemorrhagic fever virus, but the finding of R. aeschlimannii represents a potential threat for humans due to its zoonotic character. Awareness of invasive tick species and carried pathogens should be improved in central and northern Europe.
Safety and efficacy at 240 weeks of different raltegravir formulations in children with HIV-1: a phase 1/2 open label, non-randomised, multicentre trial
Authors: Sharon Nachman, Carmelita Alvero, Hedy Teppler, Brenda Homony, Anthony J Rodgers, Bobbie L Graham, Terence Fenton, Lisa M Frenkel, Renee S Browning, Rohan Hazra, Andrew A Wiznia, Edward Acosta, Steve Douglas, Carrie Fry, Samantha Kuryla, Lynette Perdue, Pearl Samson, Steven Spector, MariPat Toye, Nancy Tustin, Scott Watson, Carol Worrell, Nan Zheng
Journal: The Lancet HIV (2018)
Clinical significance of PD-1/PD-Ls gene amplification and overexpression in patients with hepatocellular carcinoma
Authors: Li-Jie Ma, Fei-Ling Feng, Liang-Qing Dong, Zhao Zhang, Meng Duan, Long-Zi Liu, Jie-Yi Shi, Liu-Xiao Yang, Zhi-Chao Wang, Shu Zhang, Zhen-Bin Ding, Ai-Wu Ke, Ya Cao, Xiao-Ming Zhang, Jian Zhou, Jia Fan, Xiao-Ying Wang, Qiang Gao
Journal: Theranostics (2018)

Background: The remarkable clinical activity of PD-1 antibody in advanced hepatocellular carcinoma (HCC) highlights the importance of PD-1/PD-L1-mediated immune escape as therapeutic target in HCC. However, the frequency and prognostic significance of PD-Ls genetic alterations in HCC remain unknown. Methods: Fluorescence in situ hybridization were used to determine PD-Ls genetic alterations, and qPCR data coupled with immunofluorescence were used to measure the mRNA and protein levels of PD-Ls. Clinical relevance and prognostic value of 9p24.1 genetic alterations were investigated on tissue microarray containing three independent cohorts of 578 HCC patients. The results were further validated in an independent cohort of 442 HCC patients from The Cancer Genome Atlas (TCGA) database. Results: In total, 7.1%-15.0% for amplification and 15.8%-31.3% for polysomy of 9p24.1 were revealed in three cohorts of HCC patients, similar to the objective response rate of PD-1 antibody in HCC. Patients with 9p24.1 genetic alterations significantly and independently correlated with unfavorable outcomes than those without. FISH and qPCR data coupled with immunofluorescence revealed that genetic alterations of 9p24.1 robustly contributed to PD-L1 and PD-L2 upregulation. In addition, increased expression of PD-L1 instead of PD-L2 also predicted poor survival by multivariate analyses. Meanwhile, high infiltration of PD-1+ immune cells also indicated dismal survival in HCC. Conclusions: Amplification or higher expression of PD-L1 significantly and independently correlated with unfavorable survival in HCC patients, authenticating the PD-1/PD-L1 axis as rational immunotherapeutic targets for HCC.
Real-World Database Examining the Association Between Avascular Necrosis of the Femoral Head and Diabetes in Taiwan
Authors: Shih-Wei Lai, Cheng-Li Lin, Kuan-Fu Liao
Journal: Diabetes Care (2018)

No study has been conducted to evaluate the association between avascular necrosis of the femoral head and diabetes. This study's aim was to assess this issue in Taiwan.A population-based cohort study was performed to analyze the database of Taiwan's National Health Insurance Program. There were 27,869 subjects aged 20-84 years with newly diagnosed diabetes from 2000 to 2012 as the group with diabetes. The group without diabetes included 111,476 sex- and age-matched subjects without diabetes. The incidence of avascular necrosis of the femoral head at the end of 2013 was measured. A multivariable Cox proportional hazards regression model was used to measure the hazard ratio (HR) and 95% CI for avascular necrosis of the femoral head associated with diabetes.The overall incidence of avascular necrosis of the femoral head was 1.37-fold higher in the group with diabetes than in the group without diabetes (6.53 vs. 4.76 per 1,000 person-years [95% CI 1.31-1.43]). After adjusting for confounders, the HR of avascular necrosis of the femoral head was 1.16 (95% CI 1.11-1.21) for the subjects with diabetes compared with the subjects without diabetes.Patients with diabetes have a 1.16-fold increased risk for developing avascular necrosis of the femoral head.
Abstract P377: Insulin Resistance is Associated With Carotid Intima-media Thickness in Non-diabetic Subjects: the ELSA-Brasil Cohort Baseline
Authors: Itamar S Santos, Márcio S Bittencourt, Alessandra C Goulart, Maria I Schmidt, Maria F Diniz, Paulo A Lotufo, Isabela M Bensenor
Journal: Circulation (2017)

Background: Epidemiological studies have analyzed the association between carotid intima-media thickness (CIMT) and insulin resistance, glucose levels or glycated hemoglobin with mixed results. Objective: To evaluate the association between CIMT and homeostasis model assessment - insulin resistance (HOMA-IR), fasting and post-load plasma glucose and glycated hemoglobin in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline. Methods: We included 8,028 participants (aged 35-74 years) without diabetes or overt cardiovascular disease who had complete CIMT data at baseline. We built crude and adjusted linear and binary logistic models to evaluate the association between CIMT and (a) HOMA-IR; (b) fasting plasma glucose; (c) post-load plasma glucose; and (d) glycated hemoglobin. We also built post-hoc models, stratified by sex. Results: In the fully-adjusted linear models, only the association between CIMT (in mm) and HOMA-IR remained significant (table). Consistent with these results, only the association between the highest age- sex- and race-specific CIMT quartile and HOMA-IR was significant in the adjusted model (odds ratio [OR]: 1.10; 95% CI: 1.04 - 1.17). The association between HOMA-IR and the highest CIMT quartile remained significant in sex-specific analyses (OR: 1.10; 95% CI: 1.02 - 1.20 for men and OR: 1.10; 95% CI: 1.02 - 1.20 for women). We did not find an independent association between CIMT and glucose or glycated hemoglobin levels. Conclusion: We found a direct, independent association between HOMA-IR and CIMT in a large sample of non-diabetic men and women. Mechanisms unrelated to glucose homeostasis, as a direct effect of insulin on atherosclerosis or medial hypertrophy, may be involved in this association.
OP0204 Dominant b cell receptor clones in peripheral blood predict onset of arthritis in individuals at risk for rheumatoid arthritis – a validation cohort
Authors: A. Musters, M.H. van Beers-Tas, M.E. Doorenspleet, P.L. Klarenbeek, B.D. van Schaik, A.H. van Kampen, F. Baas, D. van Schaardenburg, N. de Vries
Journal: Annals of the Rheumatic Diseases (2018)

improved well-being scores, normalised median ESR-and CRP-levels.Inactive disease was reached by 3 patients at 1 year.Conclusions: MSC infusions in refractory JIA patients are safe, although in sJIA stopping the 'failing' biologic treatment carries a risk of a MAS flare since the drug might still suppress the systemic features.Furthermore, intravenous administration of MSC might be efficacious even in multiple biological-failing JIA patients with damage.