tbuckley/cabot-search huggingface dataset:
CPAP in Obstructive Sleep Apnea
Authors: Ronald D Chervin, Ilene M Rosen, Nathaniel F Watson
Journal: New England Journal of Medicine (2016)

CPAP in Obstructive Sleep ApneaTo the Editor: The results of the Sleep Apnea Cardiovascular Endpoints (SAVE) study reported by McEvoy et al. (Sept.8 issue) 1 provide the opportunity to reflect on the story of the glass that is half full.The study shows that if a person is not adherent to continuous positive airway pressure (CPAP) for a mean duration of 3.3 hours per night, he or she should not expect benefits with respect to prevention of secondary composite cardiovascular end points.Sleep apnea has major genetic determinants, so a study population involving predominantly Asian persons (64%) who are not obese (mean body-mass index [the weight in kilograms divided by the square of the height in meters], 29) and who have asymptomatic moderate-to-severe disease (apnea-hypopnea index [the number of occurrences of apnea or hypopnea per hour of sleep], 29) is a population from which extrapolations should be made carefully.There may also be a cohort effect, since a cohort with a mean age of 61 years may constitute a "survivor" population with lower event rates than those among younger cohorts.Finally, it is well known that controls in a study involving patients who are receiving standard care actually receive better care than those in observational studies.The effect size may therefore have been attenuated in the study reported by McEvoy et al.The sleep medicine community should be cautious about discarding the benefits of CPAP solely on the basis of this study.
AUTOLOGOUS STEM CELL TRANSPLANTATION with INTRAVENOUS BUSULFAN, CYCLOPHOSPHAMIDE, and ETOPOSIDE as First-LINE TREATMENT of PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA in a SINGLE CENTER.
Authors: Dok Hyun Yoon, Dae Ro Choi, Byeong Seok Sohn, Shin Kim, Dae Ho Lee, Sang-We Kim, Jung Shin Lee, Sang-Wook Lee, Jooryung Huh, Cheolwon Suh
Journal: Blood (2009)
Polish Myelodysplastic Syndromes Registry- Report of 15 Months of Activity.
Authors: Jadwiga Dwilewicz-Trojaczek, Krzysztof Madry, Beata Stella-Holowiecka, Andrzej Mital, Anna Szmigielska, Agata Obara, Anita Sikorska, Ewa Nita, Wlodzimierz Mendrek, Elzbieta Wiater, Magdalena Zalewska, Monika Biedron, Anna Jachalska, Ewa Wasilewska, Malgorzata Wojciechowska, Agnieszka Kopacz, Adam Nowicki, Agnieszka Kolkowska, Renata Guzicka-Kazimierczak, Maria Pedziwiatr, Mariola Sedzimirska, Ewa Nowak, Anna Blasiak, Ewa Baranska, Maria Soroka-Wojtaszko, Slawomir Gornik, Witold Kruger, Katarzyna Katinas, Zoriana Salamanczuk, Bozena Sokolowska, Wieslaw W. Jedrzejczak, Andrzej Deptala
Journal: Blood (2009)
Abstract 3356: Diversity of CD8+ and rgulatory T cells is inversely correlated in follicular lymphoma: A potential predictive biomarker
Authors: Justin Paul Kline, Xiao Liu, Girish Venkataraman, Jiaying Lin, Kazuma Kiyotani, Sonali M. Smith, Magdeline Montoya, Yusuke Nakamura
Journal: Cancer Research (2015)

Abstract Gene expression profiling experiments have demonstrated that the immune microenvironment in follicular lymphoma (FL) plays an important role in controlling the behavior of the disease. FL patients with tumors enriched for T cell-related transcripts have a more favorable prognosis. As T cells have been shown to mediate anti-tumor immunity in other cancers, they may also be critical in controlling the progression of FL. T cells are often identified in and around malignant follicles in FL by immunohistochemistry, but it is not known whether their presence relates to their specificity for antigens expressed by FL cells. Hypothesizing that at least a fraction of T cells in FL are truly lymphoma antigen-specific, we have begun to characterize the T cell receptor (TCR) repertoire of FL tissues using a next generation sequencing platform, and have deeply sequenced T cell receptor (TCR) cDNAs of T cell subset populations present in pretreatment FL biopsy specimens. Regulatory T cell (Treg) TCRs in FL tissues revealed a highly oligoclonal expansion, compared to those in control lymph nodes. Furthermore, an inverse correlation was observed between the diversity of Treg and CD8+ TCRs in FL specimens. Interestingly, a tumor from an FL patient, who has received no anticancer treatment for more than 10 years, was found to have missense mutations in the peptide-binding domain of both HLA class I and class II molecules, which might have presented tumor-specific antigens and enhanced host immune responses. Although further verification is required, our data suggest that the T cell repertoire is skewed and restricted in FL and support the evolving understanding of the microenvironment in this disease. Citation Format: Justin Paul Kline, Xiao Liu, Girish Venkataraman, Jiaying Lin, Kazuma Kiyotani, Sonali M. Smith, Magdeline Montoya, Yusuke Nakamura. Diversity of CD8+ and rgulatory T cells is inversely correlated in follicular lymphoma: A potential predictive biomarker. [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 3356. doi:10.1158/1538-7445.AM2015-3356
A Phase I/II trial of CD3/CD28 activated T cells in patients with chronic lymphocytic leukemia (CLL)
Authors: W. G. Wierda, T. J. Kipps, J. Castro, M. J. Keating, J. Bole, B. Anderson, J. Meyer, K. Anderson, R. J. Berenson, M. W. Frohlich
Journal: Journal of Clinical Oncology (2004)

2566 Background: T cells from CLL patients can be activated & expanded ex vivo using the Xcellerate™ Process (XP), in which peripheral blood mononuclear cells (PBMC) are incubated with anti-CD3 & anti-CD28 antibody coated magnetic beads. With this process, anergic T cells from CLL patients can be activated, leading to upregulation of important immune molecules on leukemic B cells & promotion of leukemic cell apoptosis (Bonyhadi et al., ASH 2002). This trial was initiated to evaluate the safety & efficacy of autologous Xcellerated T Cells (XCT) in CLL patients. Methods: Patients must have high risk or symptomatic/progressive intermediate risk disease & ECOG PS 0–2. PBMC are collected by leukapheresis for the XP, and patients subsequently receive a single infusion of XCT. Cohorts of 3 patients each are treated with increasing cell doses: 10 x 109, 30 x 109, and 60–100 x 109. Results: 11 of 18 patients have been treated to date, with a median f/u of 98 days (range 14–182). Baseline characteristics [median (range)] were: age 58 (39–68), years from diagnosis 3.0 (0.5–8.7), & WBC/mm3 54 (11–222). Prior treatments included fludarabine (3), non-fludarabine chemotherapy (3), experimental therapy (2) and no prior therapy (3). After the first cohort, a new bioreactor process was instituted in which T cells expanded 98 ± 31 fold, were 98.2 ± 1.3% T cells, with a CD4:CD8 ratio of 15.0 ± 28.4 (n = 9; mean ± SD). There have been no serious adverse events related to treatment to date. Following treatment, T cell counts increased. A 50% or greater reduction in lymph node area was observed in 10 patients. Median (range) spleen measurement in cm below left costal margin decreased from 4 (0–10) prior to treatment to 0 (0–4) at the time of last follow-up. Substantial decreases in peripheral leukemic cell counts have not been observed to date. Conclusions: XCT can be manufactured reproducibly in doses of up to 100 x 109 cells. Treatment leads to significant increases in T cell counts, and decreases in lymphadenopathy & splenomegaly. Repeat treatment and combination treatment with cytoreductive therapies are planned. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Xcyte Therapies, Inc. Xcyte Therapies, Inc. Xcyte Therapies, Inc. Xcyte Therapies, Inc.
Inhibitory effect of SFJP formula (SFJPF) on Gr1+ CD11b+ myeloid-derived suppressor cells (MDSCs) in the 4T1 murine mammary cancer model of depression intervened.
Authors: J. Li, Y. Zhang, L. Liang
Journal: Journal of Clinical Oncology (2011)

e13516 Background: Depression is commonly seen in women with breast cancer, which is associated with worse survival. In China, we have treated breast cancer patients with Chinese medicinal herbs for years and found it is good at resolving depression symptoms; SFJP formula (SFJPF) is one of the representative formulas. Our previous study has shown SFJPF can regulate the effect of immunosuppression of myeloid-derived suppressor cells (MDSCs) in the 4T1 Murine Mammary Cancer Model. MDSCs are a heterogeneous population of cells which have a remarkable ability to suppress T-cell responses. This study is to investigate whether depression will affect MDSCs status and the effect mechanism of Chinese medicine SFJPF. Methods: The model of depression was made through forced swimming, tail suspension, overnight food and water deprivation, heat stress, etc. The mice were divided into six groups: Depression only group (A); 4T1 tumor-bearing group (B), 4T1 tumor-bearing with depression intervened group (C); chemotherapy drug group (D); Chinese medicine SFJPF group (E); chemotherapy drug plus SFJPF group (F); and the normal mice group (G). After 28 days of treatment, the weight of the tumors and the spleens of each group mice were measured. MDSCs and its subsets, CD3+/CD8+, and the level of apoptosis of CD8+T cells in the splenocyte were assayed by flow cytometry (FCM). Results: Group C had higher weight of tumor and spleen than group B, while group A had the lowest weight of spleen. Group C mice had markedly elevated percentages and numbers of Gr1+CD11b+ MDSCs (up to 68.43% vs 5% in normal mice) in the spleen, and the lowest CD8+T cells (3.46%). There was a remarkable enhancement of CD8+T cells in group F (chemotherapy plus Chinese medicine treatment group). Meanwhile, the apoptosis rate of CD8+T cells was significantly deceased in the combined treatment group. Conclusions: Depression can suppress the immune function of normal mice and boost the development of breast cancer animal model by MDSCs expansion. Chinese medicine SFJPF combined with chemotherapy drug Gemcitabine can inhibit the effect of MDSCs immunosuppression through decreasing the apoptosis of CD8+T cells.
The Accuracy of Liver Stiffness, Spleen Diameter and Platelet Count Ratio Score (LSPS) Versus Gastroscopy to Predict the Presence of Esophageal Varices in Adult Patients With Liver Cirrhosis: A Meta-analysis
Authors: Ma. Marylaine Dujunco, Ian Homer Cua, Juliet Gopez-Cervantes
Journal: Clinical Gastroenterology and Hepatology (2016)
Implant placement post extraction in esthetic single tooth sites: when immediate, when early, when late?
Authors: Daniel Buser, Vivianne Chappuis, Urs C. Belser, Stephen Chen
Journal: Periodontology 2000 (2016)

Abstract Implant placement in post‐extraction sites of single teeth in the esthetic zone has been a topic of great interest in the field of implant dentistry since 1990. Triggered by the development of guided bone regeneration, the concept of immediate implant placement became quite popular in the 1990s. In the past 12 years, however, the dental community has begun to focus increasingly on the esthetic outcomes of post‐extraction implant placement and several studies indicated a significant risk for the development of mucosal recessions with immediate implants. Parallel with this, significant progress has been made in the understanding of tissue biology in terms of hard and soft tissue alterations post extraction, based on preclinical, clinical and radiological studies. This knowledge has helped better to understand the etiology of these esthetic complications with immediate implant placement. The present review first analyzes the various phases of the development of therapeutic strategies over the years for post‐extraction implant placement in single tooth sites in the esthetic zone. It presents the current knowledge concerning the terminology with immediate, early and late implant placement, the risk factors for the development of esthetic complications, and the selection criteria for the various treatment options. In the second part, clinical recommendations are given, since a clinician active in this field of implant therapy can use all treatment options depending on the preoperative analysis including a 3D cone beam computed tomography. The selection criteria for all four treatment options are presented and documented with typical case reports to illustrate the current treatment approaches applied in daily practice.
Abstract 209: A quantitative analysis of paclitaxel-induced mitotic catastrophe of MDA-MB-231 cells by high frequency ultrasound
Authors: Maurice M. Pasternak, Gregory J. Czarnota
Journal: Cancer Research (2015)

Abstract In recent years, high-frequency ultrasound (HFUS) has shown promise of non-invasively detecting tumor death in response to chemotherapy. However, those studies have been limited to ultrasound B-mode and immunohistochemical image comparison over extended periods of time (≥24 hours). The purpose of this study was to evaluate the relationship of quantified HFUS spectral parameters to the dynamics of tumor cell death in MDA-MB-231 cell samples exposed to paclitaxel chemotherapy. Several ultrasound parameters were investigated, including the, attenuation, spectral slope, spectral y-intercept, midband fit, estimated scatterer diameter and estimated scatterer concentration. Changes in these spectral-based parameters were evaluated in their capacity to respond to various cell death events, including mitochondrial depolarization, caspase activation, phosphatidylserine exposition, and membrane selective permeability compromise, as determined by flow cytometry analysis. Standard histology and transmission electron microscopy (TEM) permitted further investigation of possible candidates responsible for the changes detected using ultrasound. Based on TEM, negative TUNEL staining, and cell cycle analysis it was found that paclitaxel at 1mM induces mitotic catastrophe as the main cell death modality. The spectral slope correlated strongly (r2 = 0.89) with the percentage of cells arrested at the G2/M checkpoint and exhibited an opposite trend to that of systems undergoing classical apoptosis, suggesting that it may be a prime biophysical marker for differentiating modalities of tumor cell death. Midband fit increases through time suggested an increase in the concentration of acoustic scatterers. The formation of condensed chromatin condensates of a 1 micron or greater diameter in the course of paclitaxel-induced mitotic catastrophe, as revealed by TEM, were hypothesized to act as large intracellular scatterers and correlated with the increase in ultrasound midband fit. Midband fit showed the strongest correlation of all parameters (r2 = 0.99) when plotted against the percentage of the cell population expected to possess these scattering structures, establishing the first quantitative correlation of ultrasound parameters to a cell death index. These findings support that HFUS spectral parameters may be used to quantify the degree of cell death and predict the efficacy of chemotherapeutic treatment within a short post-treatment timeframe. Citation Format: Maurice M. Pasternak, Gregory J. Czarnota. A quantitative analysis of paclitaxel-induced mitotic catastrophe of MDA-MB-231 cells by high frequency ultrasound. [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 209. doi:10.1158/1538-7445.AM2015-209
Loss of Nardilysin, a Mitochondrial Co-chaperone for α-Ketoglutarate Dehydrogenase, Promotes mTORC1 Activation and Neurodegeneration
Authors: Wan Hee Yoon, Hector Sandoval, Sonal Nagarkar-Jaiswal, Manish Jaiswal, Shinya Yamamoto, Nele A. Haelterman, Nagireddy Putluri, Vasanta Putluri, Arun Sreekumar, Tulay Tos, Ayse Aksoy, Taraka Donti, Brett H. Graham, Mikiko Ohno, Eiichiro Nishi, Jill Hunter, Donna M. Muzny, Jason Carmichael, Joseph Shen, Valerie A. Arboleda, Stanley F. Nelson, Michael F. Wangler, Ender Karaca, James R. Lupski, Hugo J. Bellen
Journal: Neuron (2016)
Abstract 5543: Elucidating the cytotoxic effects of taxol,camptothecin and Lobostemon fruticosus extracts on non-small cell lung cancer
Authors: Lesetja Raymond Motadi, Lungile Ndlovu
Journal: Cancer Research (2015)

Abstract Lung cancer is reportedly the most common form of cancer worldwide, with a 13-15% occurrence of all known cancers being reported daily. Lung cancer is also the most deadly form of cancer as it has been observed to be resistant to most therapeutic treatments and it demonstrates a metastasis within lymph nodes. An alternative approach is to identify the cytotoxic effects of non-invasive medicinal plant extracts on NSCLC. Thus the aim of the study was to compare the cytotoxic effects of the invasive anti-cancer drugs, taxol and camptothecin, with less invasive plant extracts of L. fruticosus on cell line A549. Cells seem to show a degree of cell death after treatment however some degree of cells still remain viable indicating usefulness in chemotherapy. The following techniques were used, exCELLigence RTCA, Cell cycle, Annexin V apoptosis analysis and LC-MS to identify the compound. Cells treated with camptothecin, Methanol and butanol extracts indicate some degree of early apoptosis which was indicative of little to no DNA fragmentation. Cell cycle arrest was observed in both camptothecin and taxol treated cells, however there was little evidence to suggest the same for L. Fruticosus extracts as there was a high degree of cell death that was observed during the cell cycle analysis. Apoptotic genes that were found in A549 treated cells upregulated in the absence of p53. Phytochemical screening of the L. Fruticosus plant extracts indicated that the plant possesses compounds that display apoptotic activity. These findings suggest that camptothecin, taxol and extract of L. fruticosus display cytotoxic activity on A549 cells. The upregulation of genes in absence of p53 seem to suggest that treatments induce apoptosis using an alternative apoptotic pathway. Note: This abstract was not presented at the meeting. Citation Format: Lesetja Raymond Motadi, Lungile Ndlovu. Elucidating the cytotoxic effects of taxol,camptothecin and Lobostemon fruticosus extracts on non-small cell lung 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 5543. doi:10.1158/1538-7445.AM2015-5543
Efficacy of early administration of escitalopram on depressive and emotional symptoms and neurological dysfunction after stroke: a multicentre, double-blind, randomised, placebo-controlled study
Authors: Jong S Kim, Eun-Jae Lee, Dae-Il Chang, Jong-Ho Park, Seong Hwan Ahn, Jae-Kwan Cha, Ji Hoe Heo, Sung-Il Sohn, Byung-Chul Lee, Dong-Eog Kim, Hahn Young Kim, Seongheon Kim, Do-Young Kwon, Jei Kim, Woo-Keun Seo, Jun Lee, Sang-Won Park, Seong-Ho Koh, Jin Young Kim, Smi Choi-Kwon
Journal: The Lancet Psychiatry (2016)
Abstract 756: Inhibition of ABCB1 overcomes cancer stem cell-like properties and acquired resistance to MET inhibitor in non-small cell lung cancer
Authors: Teppei Sugano, Masahiro Seike, Rintaro Noro, Chie Soeno, Shinji Nakamichi, Nobuhiko Nishijima, Masaru Matsumoto, Susumu Takeuchi, Akihiko Miyanaga, Kaoru Kubota, Akihiko Gemma
Journal: Cancer Research (2015)

Abstract Non-small cell lung cancer (NSCLC) patients with EGFR mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as mechanisms of acquired resistance to EGFR-TKI. Recently, MET inhibitors have been used in NSCLC patients for clinical trials. In this study, we tried to identify the mechanisms of acquired resistant to MET inhibitor. We analyzed the antitumor effects of two MET inhibitors; PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC1 cells with MET amplification were only sensitive cells to both of MET inhibitors. We have established PHA-665752 resistant cells; namely EBC1-R cells. EBC1-R cells showed high expression levels of ATP-binding Cassette Sub-family B Member 1 (ABCB1) as wells as phosphorylation MET (p-MET). EBC1-R cells grew as cell sphere that exhibited cancer stem cell-like (CSC) properties and epithelial mesenchymal transition (EMT) feature. Two miRNAs, miR-374a and miR-138 which targeted ABCB1, were decreased in EBC1-R cells. ABCB1 inhibitor elacridar could suppress sphere numbers and EMT phenomenon and restore to the resistance to PHA-665752 in EBC1-R cells. Our study demonstrated that ABCB1 overexpression associated with CSC properties and EMT may be critical for acquire resistance for MET inhibitor. ABCB1 inhibition might be a novel therapeutic strategy for resistance to MET inhibitor in NSCLC cells. Citation Format: Teppei Sugano, Masahiro Seike, Rintaro Noro, Chie Soeno, Shinji Nakamichi, Nobuhiko Nishijima, Masaru Matsumoto, Susumu Takeuchi, Akihiko Miyanaga, Kaoru Kubota, Akihiko Gemma. Inhibition of ABCB1 overcomes cancer stem cell-like properties and acquired resistance to MET inhibitor in non-small cell lung 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 756. doi:10.1158/1538-7445.AM2015-756
Panton-Valentine Leukocidin Positive Methicillin Resistant S. Aureus Infections in Children with Cancer
Authors: Ashok Srinivasan, Steven Seifried, Jianmin Pan, Deo Kumar Srivastava, Rosalie Perkins, W Kim, Pat Flynn, Gregory Hale, Jerry Shenep, Matthew Bankowski, Randall Hayden
Journal: Blood (2008)
FDA's Approach to Regulating Biosimilars
Authors: Steven J. Lemery, M. Stacey Ricci, Patricia Keegan, Amy E. McKee, Richard Pazdur
Journal: Clinical Cancer Research (2016)

The Biologics Price Competition and Innovation (BPCI) Act, enacted as part of the Affordable Care Act, created a new licensure pathway for biological products demonstrated to be biosimilar with or interchangeable with an FDA-licensed biological product (the "reference product"). The FDA's approach to the regulation of biosimilars is based on the requirements set forth in the BPCI Act. A biosimilar product is highly similar to the reference product, notwithstanding minor differences in clinically inactive components, and there are no clinically meaningful differences between products in terms of safety, purity, and potency. The foundation of a biosimilar development program is an analytic similarity assessment that directly compares the structural/physiochemical and functional properties of the proposed biosimilar with the reference product. Data from clinical studies, which include an assessment of immunogenicity and pharmacokinetics/pharmacodynamics, are used to assess for clinically meaningful differences and not to independently establish the safety and effectiveness of the biosimilar. Like all products that the FDA regulates, the FDA requires that biosimilar products meet the agency's rigorous standards of safety and efficacy for approval. That means patients and health care professionals are able to rely upon the safety and effectiveness of biosimilar products in the same manner as for the reference product. Clin Cancer Res; 23(8); 1882-5. ©2016 AACR.
Junior doctors raise concerns about pay difference under new contract
Authors: Abi Rimmer
Journal: BMJ (2016)

Junior doctors have raised concerns about differences in pay that have arisen after the introduction of the new contract for junior doctors in England.

Since November, foundation year 1 (FY1) and FY2 doctors in England have been moving to the new contract. The contract gives a period of pay protection for doctors who were already in training programmes on 2 August 2016 and for FY1 doctors who began their training programme on 3 August 2016.

These doctors were guaranteed to receive a minimum amount of pay based on the job that they were working on the day immediately before moving to the new contract, plus the value of the GP supplement or banding supplement payable on 31 October 2015 for that job. 

Junior doctors have said that, as a result of …