tbuckley/cabot-search huggingface dataset:
2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung
Authors: Brian L. Graham, Vito Brusasco, Felip Burgos, Brendan G. Cooper, Robert Jensen, Adrian Kendrick, Neil R. MacIntyre, Bruce R. Thompson, Jack Wanger
Journal: European Respiratory Journal (2017)

This document provides an update to the European Respiratory Society (ERS)/American Thoracic Society (ATS) technical standards for single-breath carbon monoxide uptake in the lung that was last updated in 2005. Although both DLCO (diffusing capacity) and TLCO (transfer factor) are valid terms to describe the uptake of carbon monoxide in the lung, the term DLCO is used in this document. A joint taskforce appointed by the ERS and ATS reviewed the recent literature on the measurement of DLCO and surveyed the current technical capabilities of instrumentation being manufactured around the world. The recommendations in this document represent the consensus of the taskforce members in regard to the evidence available for various aspects of DLCO measurement. Furthermore, it reflects the expert opinion of the taskforce members on areas in which peer-reviewed evidence was either not available or was incomplete. The major changes in these technical standards relate to DLCO measurement with systems using rapidly responding gas analysers for carbon monoxide and the tracer gas, which are now the most common type of DLCO instrumentation being manufactured. Technical improvements and the increased capability afforded by these new systems permit enhanced measurement of DLCO and the opportunity to include other optional measures of lung function.
Cover Image: Detection of hair follicle-associated Merkel cell polyomavirus in an immunocompromised host with follicular spicules and alopecia
Authors: K. Nemeth, A. Gorog, E. Mezey, D. Pinter, E. Kuroli, J. Harsing, L. Kovacs, M. Fischer, P. Rady, P. Sillo, S. Tyring, S. Karpati
Journal: British Journal of Dermatology (2016)
Immunogenicity of Influenza Vaccination in Patients with Non-Hodgkin Lymphoma: Final Report after Two Epidemic Seasons.
Authors: Piotr Centkowski, Lidia B. Brydak, Magdalena Machala, Ewa Kalinka, Maria Blasinska-Morawiec, Irena Federowicz, Jan Walewski, Joanna Wegrzyn, Dariusz Wolowiec, Ewa Maranda, Joanna Sawczuk-Chabin, Przemyslaw Bilinski, Krzysztof Warzocha
Journal: Blood (2006)
Abstract 302: High throughput drug screening with engineered tumor spheroids
Authors: Stephanie Lemmo, Ehsan Aefi, Gary Luker, Hossein Tavana
Journal: Cancer Research (2015)

Abstract Physiologically relevant, in vitro cell-based models are important tools to identify effective anticancer drugs. Three-dimensional (3D) clusters of cancer cells, called tumor spheroids, mimic key characteristics of avascular tumors such as diffusion limitations and hypoxia, and hence serve as a relevant model for compound screening. Nevertheless, current spheroid formation techniques face difficulties to generate large number of uniform sized spheroids, conveniently maintain them in culture and biochemically analyze them using commercially available tools. To address this need, we developed a robotic, high throughput technology for three-dimensional culture of cancer cells that is simple to implement, produces consistent size spheroids in standard microwell plates, and allows convenient robotic media exchange and drug addition, and analysis of cellular responses using microplate readers. The technology is based on the use of an aqueous two-phase system. Cancer cells confined in a drop of the denser aqueous phase are robotically dispensed into a microwell containing the immersion aqueous phase. Cells remain within the drop at the bottom of the microwell and form a viable spheroid. We demonstrate the robust performance of this technology by evaluating the effect of two clinically used drugs against biologically aggressive skin cancer and triple negative breast cancer (TNBC) cells. Skin cancer spheroids treated with paclitaxel and cisplatin show dose-dependent decrease in cell viability, but with a greater resistance compared to the monolayer culture (2D) of cells (paclitaxel: LD50,3D = 178.5 nM, LD50,2D = 22.1 nM and cisplatin: LD50,3D = 131.7 μM and LD50,2D = 29.2 μM. TNBC cell monolayer and spheroids treated with cisplatin displayed a similar LD50 value of ∼13.1 μM. However, unlike the monolayer culture of TNBC cells that showed a dose-response to paclitaxel with LD50,2D = 8.0 nM, TNBC spheroids showed resistance to this drug, even at micromolar-scale concentrations, and maintained a high viability. In conclusion, our tumor spheroid technology enables quick and efficient generation of relevant tumor models in standard microplates to conveniently treat with chemical compounds and analyze. This technology allows investigating the efficacy of drug compounds against cancer cells and reveals cellular responses not captured with widely-used monolayer cultures. The ease of conducting and analyzing high throughput experiments will substantially reduce labor and cost, and expedite discovery of effective anti-cancer compounds with a physiologic tumor model. Citation Format: Stephanie Lemmo, Ehsan Aefi, Gary Luker, Hossein Tavana. High throughput drug screening with engineered tumor spheroids. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 302. doi:10.1158/1538-7445.AM2015-302
NIMG-42LOWER BRAIN NETWORK EFFICIENCY IN IDH1 WILD TYPE (IDH-WT) MALIGNANT ASTROCYTOMA COMPARED TO IDH1 MUTANT (IDH1-M)
Authors: Shelli Kesler, Kyle Noll, Daniel Cahill, Ganesh Rao, Jeffrey Wefel
Journal: Neuro-Oncology (2015)

We previously demonstrated that patients with IDH1-WT compared to IDH1-M malignant astrocytoma exhibited worse cognitive function. We hypothesized that this is due to greater lesion momentum that may preclude compensatory brain reorganization. Therefore, in the present study, we examined the structural  of patients with IDH1-M and -WT tumors to determine if brain network organization differed between these patient groups. Volumetric, T1 MRI scans were evaluated retrospectively from 15 IDH1-M and 15 IDH1-WT. There were no differences between groups in terms of age, sex or education. Groups did not differ in tumor laterality but IDH1-M demonstrated less incidence of glioblastoma (p = .025), more frequent temporal lobe tumor location (p = .036) and moderately larger tumor volumes (p = .10). Discrete cortical and subcortical gray matter volumes were extracted from the MRI for each subject and cross-correlated across subjects to create an association matrix for each group. Matrices were corrected for tumor volume and histology. Graph theory was applied to these matrices to construct a large-scale structural brain network, or connectome for each group. We then measured the  global efficiency (Geff) for each group. Geff is a measure of network organization pertaining to integration and information flow. Nonparametric permutation analysis indicated that Geff was significantly lower in the IDH1-WT group (Geff = .41) compared to IDH1-M (Geff = .59, p = .001). IDH1-WT also demonstrated less network hubs than IDH1-M suggesting disconnection of critical brain regions. In summary, brain network integration, efficiency and connectivity are lower in IDH1-WT tumor compared to IDH1-M. This finding was independent of tumor volume and histology. This may reflect the slower growth of the IDH1-M tumor, which may allow the brain time to adapt to the tumor's presence and reorganize critical neurocircuitry.
An Apicomplexan Actin-Binding Protein Serves as a Connector and Lipid Sensor to Coordinate Motility and Invasion
Authors: Damien Jacot, Nicolò Tosetti, Isa Pires, Jessica Stock, Arnault Graindorge, Yu-Fu Hung, Huijong Han, Rita Tewari, Inari Kursula, Dominique Soldati-Favre
Journal: Cell Host & Microbe (2016)
Personalized Prescription Feedback Using Routinely Collected Data to Reduce Antibiotic Use in Primary Care
Authors: Lars G. Hemkens, Ramon Saccilotto, Selene Leon Reyes, Dominik Glinz, Thomas Zumbrunn, Oliver Grolimund, Viktoria Gloy, Heike Raatz, Andreas Widmer, Andreas Zeller, Heiner C. Bucher
Journal: JAMA Internal Medicine (2016)

Feedback interventions using routinely collected health data might reduce antibiotic use nationwide without requiring the substantial resources and structural efforts of other antibiotic stewardship programs.To determine if quarterly antibiotic prescription feedback over 2 years reduces antibiotic use when implemented in a complex health care system.Pragmatic randomized trial using routinely collected claims data on 2900 primary care physicians with the highest antibiotic prescription rates in Switzerland.Physicians were randomized to quarterly updated personalized antibiotic prescription feedback over 2 years (n = 1450) or usual care (n = 1450). Feedback was provided both by mail and online from October 2013 to October 2015 and was supported by an initial 1-time provision of evidence-based guidelines.The primary outcome was the prescribed defined daily doses (DDD) of any antibiotic to any patient per 100 consultations in the first year analyzed by intention-to-treat. We further analyzed prescriptions of specific antibiotics, age groups, and sex for the first and second year to investigate persistency of effects over time.The 2900 physicians had 10 660 124 consultations over 2 years of follow-up, prescribed 1 175 780 packages of antibiotics with 10 290 182 DDD. Physicians receiving feedback prescribed the same amount of antibiotics to all patients in the first year (between-group difference, 0.81%; 95% CI, -2.56% to 4.30%; P = .64) and second year (between-group difference, -1.73%; 95% CI, -5.07% to 1.72%; P = .32) compared with the control group. Prescribing to children aged 6 to 18 years was -8.61% lower in the feedback than in the control group in the first year (95% CI, -14.87% to -1.90%; P = .01). This difference diminished in the second year (between-group difference, -4.10%; 95% CI, -10.78% to 3.07%; P = .25). Physicians receiving feedback prescribed fewer antibiotics to adults aged 19 to 65 years in the second year (between-group difference, -4.59%; 95% CI, -7.91% to -1.16%; P < .01). Prescribing to other patient groups or of specific antibiotic types was not significantly different between groups.This nationwide antibiotic stewardship program with routine feedback on antibiotic prescribing was not associated with a change of antibiotic use. In older children, adolescents, and younger adults less antibiotics were prescribed, but not consistently over the entire intervention period.clinicaltrials.gov Identifier: NCT01773824.
Nox2 siRNA Transfection Down Regulates VEGF Induced-Angiogenesis on Endothelial Progenitor Cells Which Are Derived From HCB
Authors: Eun-Sun Yoo, Yeung-Chul Mun, Eun Mi Nam, Kyoung Eun Lee, Jung Won Huh, Soon Nam Lee, Jung Yeon Cho, Jee Young Ahn, Solip Lee, Chu-Myong Seong
Journal: Blood (2010)
Usefulness of Peripheral Blood Circulating DNAs As an Alternative to DNA From Bone Marrow Cells to Detect CpG Global Methylation Status and Genetic Mutations in Patients with Myelodysplastic Syndromes
Authors: Chisako Iriyama, Akihiro Tomita, Hideaki Hoshino, Mizuho Shirahata, Yoko Hibi, Kiyofumi Yamada, Hitoshi Kiyoi, Tomoki Naoe
Journal: Blood (2012)
Molecular and Pharmacologic Suppression of MAPK Activity Rescues Differentiation of BCR/ABL+ Myeloid Progenitors by Releasing C/EBPa from the Inhibitory Effect of hnRNP E2.
Authors: Ji-Suk Chang, Ramasamy Santhanam, Edward Briercheck, Anna Eiring, Rossana Trotta, Mario Notari, Denis-Claude Roy, Michael A. Caligiuri, Danilo Perrotti
Journal: Blood (2006)
OP19DEVELOPING STRATIFIED SERUM SPECTROSCOPIC DIAGNOSTICS FOR BRAIN TUMOURS: FINDING THE FEATURES
Authors: James R. Hands, Graeme Clemens, Robert W. Lea, Katherine M. Ashton, Timothy P. Dawson, Michael D. Jenkinson, Andrew Brodbelt, Charles Davis, Ryan Stables, Matthew J. Baker
Journal: Neuro-Oncology (2015)

INTRODUCTION: The ability to diagnose brain cancer rapidly from serum samples is of great interest; such a diagnosis would allow for rapid testing and decreased time to results providing a responsive diagnostic environment. Infrared (IR) is an excellent method for the analysis of a wide range of materials. Our previous research has demonstrated the ability of IR to discriminate high grade and low-grade brain cancer and normal serum to sensitivities and specificities on average of 93.75 and 96.53 % respectively. This paper reports the analysis of 433 patients, feature extraction to discover the salient spectral markers and the development of a discrete frequency collection methodology to provide rapid diagnosis (e.g. 16 patients in ∼2 minutes). METHOD: A volume of 1 µl of serum was analysed in triplicate. This dataset was then analysed using pattern recognition algorithms and feature extraction for the following strata 1) Cancer vs Non-cancer, 2) Metastatic Brain Cancer vs Brain Cancer vs Non-Cancer, 3) Organ of tumour origin, 4) Brain tumour severity and 5) Subtype of Brain Cancer. Following this a discrete frequency approach was developed to provide rapid serum spectroscopic diagnosis. RESULTS: Using a 433 patient dataset (3897 spectra) we achieve optimum sensitivities and specificities of between 80.0 and 100 % for all strata and identify the biochemical components, responsible for the discrimination. In addition a discrete frequency approach was shown to be robust and reproducible. CONCLUSION: Infrared technology has been demonstrated to be appropriate for the clinical environment, capable of diagnosing to high sensitivity andspecificity and with the advent of discrete frequency IR applicable over clinically relevant times.
A Subcutaneously Administered Investigational RNAi Therapeutic (ALN-CC5) Targeting Complement C5 for Treatment of PNH and Complement-Mediated Diseases: Interim Phase 1 Study Results
Authors: Anita Hill, Jorg Taubel, Jim Bush, Anna Borodovsky, Noriyuki Kawahata, Helen Mclean, Christine Powell, Prasoon Chaturvedi, Garvin Warner, Pushkal Garg, Benny Sorensen
Journal: Blood (2015)
NPM Mutations and Not FLT3 Mutations Are a Potential Marker for Monitoring Minimal Residual Disease in Acute Myeloid Leukemia.
Authors: Michela Palmisano, Tiziana Grafone, Emanuela Ottaviani, Nicoletta Testoni, Stefania Paolini, Cristina Papayannidis, Michela Rondoni, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2006)
Use of radiation therapy after breast-conserving surgery among Medicaid recipients with early-stage breast cancer.
Authors: S. B. Wheeler, Y. Wu, A. Meyer, W. R. Carpenter, L. C. Richardson, J. L. Smith, M. A. Lewis, B. Weiner
Journal: Journal of Clinical Oncology (2011)

6097 Background: We sought to identify factors associated with overall receipt and timing of initiation of radiation therapy (RT) following breast conserving surgery (BCS) in a low income population with early stage breast cancer (BrCa). Methods: North Carolina (NC) Central Cancer Registry data were systematically linked with Medicaid claims to conduct a retrospective analysis of care received by low income women diagnosed with stage I-II BrCa in 2003-2007. Analytic files were limited to cases continuously enrolled in Medicaid 1 month pre- and 12 months post-diagnosis, ages 18-64, with no history of cancer. Women who received mastectomy subsequent to BCS and before RT were excluded. We used chi-squared tests and Kaplan-Meier curves to explore bivariate relationships and employed multivariate logistic and Cox hazards models to explore factors associated with overall receipt and timing of RT initiation post-BCS. We were particularly interested in receipt of RT within 1 year of diagnosis, the time interval specified in relevant BrCa quality metrics. Results: In total, 126 women met all inclusion criteria and had complete claims, of whom 48% were white, 45% were black, and 7% were classified as other race. Overall, 81% of patients received RT post-BCS; median time to RT initiation was 170 days. In multivariate logistic regressions, having received chemotherapy prior to RT was highly associated with initiating RT within 1 year (OR: 3.92 [1.28, 12.06]), and higher comorbidity burden was associated with significantly lower likelihood of RT within 1 year (OR: 0.37 [0.15-0.92]). In multivariate hazards models stratified by chemotherapy use, higher comorbidity burden was associated with delayed RT initiation (HR: 0.67 [0.42-1.07]). We observed no racial variation in crude or multivariate models. Conclusions: We found significant improvement in overall receipt of guideline-recommended RT post-BCS in this Medicaid population, compared to earlier studies in the 1990s indicating that one-third of low income BrCa patients do not receive RT post-BCS. Prior receipt of chemotherapy and comorbidity burden were important predictors of overall receipt and timeliness of RT.
Rituximab and High-Dose Methylprednisolone for the Initial Treatment of Chronic Lymphocytic Leukemia Is Associated with Promising Clinical Activity and Minimal Hematologic Toxicity
Authors: Aanelle F James, Januario E. Castro, Jose David Sandoval-Sus, Sonia Jain, Janet Bole, Laura Rassenti, Thomas J. Kipps
Journal: Blood (2008)
Abstract 1337: Up-regulation of mannose 6-phosphate receptor induced by BRAF inhibitor PLX4720 is linked to phosphatidylserine externalization and shows positive effects for combination therapies
Authors: Sergio Lavilla-Alonso, Rolf Brekken, Dmitry Gabrilovich
Journal: Cancer Research (2015)

Abstract New therapies of metastatic melanoma, including BRAF inhibitors, check-point blockade or adoptive T-cell transfer, hold high promise. However, their efficacy remains unsatisfactory. Combination of different modalities offers an opportunity to enhance their effect. We studied mannose 6-phosphate receptor (MPR) previously implicated in synergistic effect of cancer chemotherapy and immunotherapy. Approximately 50% of human melanomas bear the activating mutation V600E in BRAF that can be selectively targeted with BRAF inhibitor PLX4720. We have observed that in vitro treatment of human V600E-positive melanoma cells 451Lu and WM983B leads to a dose-dependent up-regulation of mannose 6-phosphate receptor (MPR) in the cell surface. An increase in cell surface MPR, enhanced recombinant Granzyme B uptake, a requirements for effective combination with immunotherapy. This effect of PLX4720 on MPR expression was reproduced in a mouse model featuring xenograft 451Lu-derived subcutaneous tumors. This effect was limited only to sensitive cell lines, disappearing completely after resistance had been induced by extended treatment with growing doses of the drug. We have previously determined that autophagy has a key role in MPR up-regulation after chemotherapy or radiation therapy. However, in the case of PLX4720, autophagy occurs 1-2 days after the start of the treatment while membrane MPR was up-regulated not early than 3-4 and 10-14 days after the start of the treatment in 451Lu and WM983B cells respectively. In addition, autophagy was present independently of whether the cells were resistant to PLX4720 or not. These data indicate that autophagy was probably not responsible in PLX4720 inducible up-regulation of MPR. We observed a parallel changes in MPR up-regulation and phosphatidylserine (PS) externalization in live melanoma cells. PS and MPR co-localized on cell surface after the treatment with PLX4720. Co-incubation of PLX4720 with PS-specific antibody resulted in an ablation of the subsequent membrane MPR up-regulation. These observations help to explain the synergism between immunotherapy and targeted therapy of melanoma and to design clinical trials. Citation Format: Sergio Lavilla-Alonso, Rolf Brekken, Dmitry Gabrilovich. Up-regulation of mannose 6-phosphate receptor induced by BRAF inhibitor PLX4720 is linked to phosphatidylserine externalization and shows positive effects for combination therapies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1337. doi:10.1158/1538-7445.AM2015-1337
Dear John Hunter
Authors: Christina Messiou, Daniel Vanel, Rob Pollock, Martyn Cooke, Eleanor Moskovic, Cate Savidge, Laurence King, Anisha Patel, Robin L Jones
Journal: BMJ (2016)

Dear Mr John Hunter,

Thank you very much for the thorough history of your patient, who presented with a mass in the thigh. We have now had the opportunity to review the case notes and specimens at the Sarcoma Unit at the Royal Marsden Hospital. We apologise for the breach of requirements on waiting times for cancer treatment, but your patient’s presentation in 1786 predated our founding in 1851.

#### John Hunter (1728-93)

John Hunter was one of the most distinguished surgeons of his day. He worked at St George’s Hospital in his later career and was appointed as surgeon to King George III. He is said to have died after an argument over the admission of medical students. The specimens and notes reviewed in this article are kept within the Hunterian museum at The Royal College of Surgeons.

For our records we quote the following extract from your original notes:

> “A man came into St George’s Hospital, November 1786, with a hard swelling of the lower part of the thigh. It appeared to be a thickening of the bone. It was increasing very rapidly, and at this time so large as to interfere with the motion of the joint, so as to render the leg useless. The tumour was hard as bone.
> 
> The man had been in perfect health in this part, till about 5 months before, and then began to feel shooting or darting pains in that part of the thigh. The part began evidently to enlarge, although at first very slowly; but in the …
Abstract 5296: FOXP1 expression is associated with tumor progression and poor prognosis in cervical cancer
Authors: Hanbyoul Cho, Woo Kyeom Yang, Sol Kim, Ha-Yeon Shin, Eun Ju Lee, Jae-Hoon Kim
Journal: Cancer Research (2015)

Abstract Background: The forkhead box protein 1 (FOXP1) is considered as both a tumor suppressor candidate and a potential oncogene. Here, we investigated FOXP1 expression in cervical cancer, and the clinical significance of FOXP1 and it's mechanism of action in cervical cancer. Methods: To investigate the potential correlation between FOXP1 and various clinicopathologic parameters, we assessed the expression of FOXP1 in archival tumor tissue specimens from 158 patients with cervical cancer and 280 with cervical intraepithelial neoplasia as well as 378 matched nonadjacent normal tissues by immunohistochemical (IHC) staining. Subsequently, we studied the FOXP1's functional role by small interfering RNA (siRNA) approaches. Results: IHC staining demonstrated that FOXP1 expression increased during the normal to tumor transition of cervical carcinoma (P&amp;lt;0.001), and this increased expression was significantly associated with tumor stage (P = 0.009) and tumor grade (P&amp;lt;0.001). In multivariate analysis, FOXP1+ (P = 0.031) and tumor stage (P = 0.032) were independent prognostic factors for overall survival. FOXP1 knockdown by siRNA decreased cell proliferation, migration, and tumorigenesis in HeLa and CaSki cells. Conclusions: Taken together, our data indicate that FOXP1 has a crucial role in cervical cancer progression, and its overexpression is associated with poor prognosis, supporting that FOXP1 may be used as a promising novel target for therapeutic interventions. Citation Format: Hanbyoul Cho, Woo Kyeom Yang, Sol Kim, Ha-Yeon Shin, Eun Ju Lee, Jae-Hoon Kim. FOXP1 expression is associated with tumor progression and poor prognosis in cervical cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5296. doi:10.1158/1538-7445.AM2015-5296