tbuckley/cabot-search huggingface dataset:
Institutional review of pelvic lymphoma: A 24-year experience
Authors: E. S. Ratner, D. M. O’Malley, J. McAlpine, B. Litkouhi, M. Kelly, T. J. Rutherford, M. Azodi, O. O. Fadare, D. L. Cooper, P. E. Schwartz
Journal: Journal of Clinical Oncology (2005)

6702 Background: The manifestation of lymphoma as a pelvic mass is rare with most previous literature reporting a poor prognosis. Our objective is to report our experience with this rare gynecologic malignancy. Methods: Retrospective review was performed on patients (pts) diagnosed with lymphoma of the gynecologic organs between 1980 and 2004. Medical records, diagnostic imaging and pathology reports were reviewed. Histologic classification was based on the Working Formulation and staging on the Ann Arbor system. Results: 19 pts with diagnosis of pelvic lymphoma (PL) were identified. 18 of these presented as primary lymphomas of gynecologic organs. Location of pelvic mass included ovarian (11), uterine (2), vaginal (2), uterine and ovarian (1), vaginal and cervical (1). The median age at presentation was 53 yrs (19–87). Eleven percent presented as stage I, 5% stage II, 5% stage III, and 79% stage IV. Presentations included abdominal and pelvic discomfort and bloating (32%), abnormal vaginal bleeding (11%), fever/night sweats (11%). 7 pts were asymptomatic (37%). 6 cases were identified as incidental findings (3 cases were identified during workup for concomitant endometrial cancer). PL phenotype was B cell (100%) with diffuse cell (64%) and follicular/mixed (11%) as most common histologic subsets. Combination chemotherapy was administered to 17 pts, with additional radiation therapy in 2 and stem cell treatment in 2. Four pts were diagnosed within the last 6 months and are alive and undergoing treatment. In the remaining 15 pts, median follow-up time was 36 months (m) (6–247). Overall median survival in this group was 36 m (6–247), 11 are alive with no evidence of disease (NED). Three of the primary pelvic lymphomas have recurred (one brain, one bone, and one lung/bone). All three patients are deceased; their median survival from initial diagnosis was 17 m (9–47) and 6 m (2–6) from recurrence. The one patient with known lymphoma and an ovarian recurrence is alive with NED 48 m after diagnosis. Conclusion: We present one of the largest single institution experiences with PL. While previous studies have reported a poor outcome, we demonstrate a more favorable prognosis. With appropriate diagnosis PL can be managed successfully with histologic specific chemotherapy. No significant financial relationships to disclose.
PRAME as an Independent Biomarker for Metastasis in Uveal Melanoma
Authors: Matthew G. Field, Christina L. Decatur, Stefan Kurtenbach, Gülçin Gezgin, Pieter A. van der Velden, Martine J. Jager, Kaleigh N. Kozak, J. William Harbour
Journal: Clinical Cancer Research (2016)

Uveal melanoma (UM) can be classified by gene expression profiling (GEP) into Class 1 (low metastatic risk) and Class 2 (high metastatic risk), the latter being strongly associated with mutational inactivation of the tumor suppressor BAP1. Nevertheless, a small percentage of Class 1 tumors give rise to metastatic disease. The purpose of this study was to identify biomarkers of metastasis in Class 1 tumors.A total of 389 consecutive patients with UM were assigned to Class 1 or Class 2 using a prospectively validated 12-gene prognostic classifier. Selected tumors were further analyzed using global GEP and single nucleotide polymorphism microarrays. PRAME (preferentially expressed antigen in melanoma) mRNA expression was analyzed in 64 Class 1 tumors by qPCR.Among Class 1 UMs, the most significant predictor of metastasis was PRAME mRNA expression (P = 0.0006). The 5-year actuarial rate of metastasis was 0% for Class1(PRAME-), 38% for Class1(PRAME+), and 71% for Class 2 tumors. Median metastasis-free survival for Class1(PRAME+) patients was 88 months, compared to 32 months for Class 2 patients. Findings were validated using three independent datasets, including one using disomy 3 to identify low-risk UM. Chromosome copy number changes associated with Class1(PRAME+) tumors included gain of 1q, 6p, 8q, and 9q and loss of 6q and 11q. PRAME expression was associated with larger tumor diameter (P = 0.05) and SF3B1 mutations (P = 0.003).PRAME is an independent prognostic biomarker in UM, which identifies increased metastatic risk in patients with Class 1 or disomy 3 tumors. This finding may further enhance the accuracy of prognostic testing and precision medicine for UM.
Dependence of Chromosome Pulverization in Virus-Fused Cells on Events in the G2 Period&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Sei-ichi Matsui, Herbert Weinfeld, Avery A. Sandberg
Journal: JNCI Journal of the National Cancer Institute (1971)

The synthesis of a factor, PF, necessary for chromosome pulverization in Sendai virus-induced fused cells was studied in a Chinese hamster cell line (Don). Puromycin (PM), cycloheximide (CHE), and actinomycin D (AMD) were used to block protein and RNA synthesis, especially in the G2 period, including the time during which PF synthesis is expected to take place. Terminal points of action of the drugs on protein and RNA synthesis required for G2-metaphase transition were first determined, and those used for the Don cells were 125 ± 10 and 65 ± 5 minutes before the onset of meta phase, respectively. Substantial numbers of metaphase cells produced in the presence of either PM or CHE for 65 minutes before fusion failed to induce pulverization when made to coexist with interphase nuclei in multinucleate cells, as a result of subsequent cell fusion by Sendai virus. Cells produced in the presence of AMD for 125 minutes could still induce pulverization in multinucleate cells. These findings indicate that PF formation is related to protein synthesis in late G2, and that if RNA is necessary for PF formation, its synthesis probably takes place before G2. Detailed analysis of pulverization frequency as a function of time of exposure to inhibitors, before fusion, revealed that synthesis of PF takes place from 15–45 minutes before the onset of metaphase. Furthermore, PF synthesis in G2 is independent of virus-dependent metabolic events related to protein synthesis. PF may not be necessary for G2-metaphase transition and its exact role in normal cell physiology remains unknown.
Leveraging RB status to define therapy for castrate-resistant prostate cancer.
Authors: Renee de Leeuw, Clay de Comstock, Daniela de Pollutri, Matthew Joseph Schiewer, Stephen J Ciment, Tanmayi de Mankame, William Ostrander, Robert Benjamin Den, William Kevin Kelly, Leonard G. Gomella, Adam Dicker, Maha Hussain, Karen E. Knudsen
Journal: Journal of Clinical Oncology (2014)

96 Background: Loss of retinoblastoma (RB) tumor suppressor is overrepresented in castrate-resistant prostate cancer (CRPC) compared to primary PCa. We previously showed using analyses of human tissue and in vitro and in vivo modeling that RB constrains androgen receptor (AR) function, and that loss of RB is sufficient promote resistance to castration and AR antagonists. Thus, novel strategies are needed to treat RB-deficient tumor. By contrast, in tumors retaining RB, suppressing enhancing RB activity would be of therapeutic advantage, and may be accomplished through next-generation Cdk4/6 inhibitors. Methods: Stable isogenic pairs of prostate cancer cell lines either retaining RB or RB depleted (by shRNA) were assessed in vitro and in xenografts for response to Cdk4/6 kinase inhibitors or the cabazitaxel. In addition, using an ex vivo explant assay, fresh tumor tissue samples from radical prostatectomy were exposed to the Cdk4/6 inhibitor or cabazitaxel for up to 7 days, and evaluated by IHC for Ki67, Caspase-3, and AR. Results: Cdk4/6 inhibition blocks tumor cell proliferation dependent on RB status. This was further confirmed ex vivo, as evidenced by a marked reduction in Ki67 staining in Cdk4/6 inhibitor treated explant tissue from two prostate cancer patients. Conversely, in vitro studies revealed a modest sensitization of RB-depleted tumors to cabazitaxel that was dramatically enhanced in vivo and after castration. Cabazitaxel, like docetaxel, targets the cell architecture and induces cell death, but also induces a distinct gene expression profile that may partially explain efficacy in docetaxel-resistant tumors. Neither taxane showed affects on AR nuclear localization using in vivoor explant studies. Conclusions: These results strongly support our hypothesis that RB status can be used as a metric to define therapeutic response to cabazitaxel, as such that loss of RB function induces sensitization taxanes, whereas RB proficient tumors give an enhanced response to Cdk4/6 kinase inhibitors.
Proactive tobacco treatment offering free nicotine replacement therapy and telephone counselling for socioeconomically disadvantaged smokers: a randomised clinical trial
Authors: Steven S Fu, Michelle van Ryn, David Nelson, Diana J Burgess, Janet L Thomas, Jessie Saul, Barbara Clothier, John A Nyman, Patrick Hammett, Anne M Joseph
Journal: Thorax (2016)

<h3>Background</h3> Evidenced-based tobacco cessation treatments are underused, especially by socioeconomically disadvantaged smokers. This contributes to widening socioeconomic disparities in tobacco-related morbidity and mortality. <h3>Methods</h3> The Offering Proactive Treatment Intervention trial tested the effects of a proactive outreach tobacco treatment intervention on population-level smoking abstinence and tobacco treatment use among a population-based sample of socioeconomically disadvantaged smokers. Current smokers (n=2406), regardless of interest in quitting, who were enrolled in the Minnesota Health Care Programs, the state9s publicly funded healthcare programmes for low-income populations, were randomly assigned to proactive outreach or usual care. The intervention comprised proactive outreach (tailored mailings and telephone calls) and free cessation treatment (nicotine replacement therapy and intensive, telephone counselling). Usual care comprised access to a primary care physician, insurance coverage of Food and Drug Administration-approved smoking cessation medications, and the state9s telephone quitline. The primary outcome was self-reported 6-month prolonged smoking abstinence at 1 year and was assessed by follow-up survey. <h3>Findings</h3> The proactive intervention group had a higher prolonged abstinence rate at 1 year than usual care (16.5% vs 12.1%, OR 1.47, 95% CI 1.12 to 1.93). The effect of the proactive intervention on prolonged abstinence persisted in selection models accounting for non-response. In analysis of secondary outcomes, use of evidence-based tobacco cessation treatments were significantly greater among proactive outreach participants compared with usual care, particularly combination counselling and medications (17.4% vs 3.6%, OR 5.69, 95% CI 3.85 to 8.40). <h3>Interpretation</h3> Population-based proactive tobacco treatment increases engagement in evidence-based treatment and is effective in long-term smoking cessation among socioeconomically disadvantaged smokers. Findings suggest that dissemination of population-based proactive treatment approaches is an effective strategy to reduce the prevalence of smoking and socioeconomic disparities in tobacco use. <h3>Trial registration number</h3> NCT01123967.
Idelalisib-related pneumonitis
Authors: Eglantine Haustraete, Julie Obert, Samia Diab, Sarah Abbes, Jean-Marc Zini, Sandrine Valade, Nathalie Lerolle, Nicolas Albin, Bertrand Arnulf, Jean-David Bouaziz, Claire Hussenet, Abdellatif Tazi, Anne Bergeron
Journal: European Respiratory Journal (2016)

Idelalisib (Zydelig; Gilead Sciences Inc., Foster City, CA, USA) has recently been approved in combination with rituximab for the treatment of refractory chronic lymphocytic leukaemia (CLL) in patients who have received at least one prior therapy, as a first-line treatment in the presence of a 17p deletion or TP53 mutation in patients unsuitable for chemoimmunotherapy, or as a monotherapy in follicular lymphoma refractory to two prior lines of treatment. Idelalisib specifically inhibits phosphatidylinositol 3-kinase δ (PI3Kδ), which is part of the B-cell receptor signalling pathway, the activity of which is increased in B-cell malignancies, and which promotes cellular proliferation and survival [1–4]. Here, we report on five patients who were diagnosed with pneumonitis related to idelalisib treatment. Lung physicians and haematologists should be aware of the possibility of idelalisib-related lung manifestations <http://ow.ly/XmjGm>
WITHDRAWN: Rod shaped nanocrystals exhibit superior in vitro dissolution and in vivo bioavailability over spherical like nanocrystals: A case study of lovastatin
Authors: Mengran Guo, Qiang Fu, Mo Li
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
P43 Adhesion of human bone marrow-derived mesenchymal stem cells to liver sinusoidal endothelium is both CD29 and CD44 dependant, whilst initial tethering of MSCs to endothelium involves CD29 but not CD44
Authors: V Aldridge, A Garg, J Youster, P Newsome
Journal: Gut (2010)

Introduction  Whilst MSCs have been postulated to have a range of functions within the liver little is known about the factors regulating their migration, adhesion and localisation within liver tissue. Modulation of this process may have important therapeutic implications.  Aim  To define the adhesion molecule profile on hMSCs and the molecular regulation of their interaction with liver sinusoidal endothelium.  Method  Adhesion molecule expression of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) was comprehensively profiled by flow cytometry before and after TNFα stimulation. Static adhesion assays were performed to assess binding to hBM-MSCs (±adhesion molecule blockade) to both extra-cellular matrix (ECM) proteins and sections of liver tissue. This was further assessed in flow assays over ECM and liver sinusoidal endothelial cells. MSC migration towards chemokine ligands was studied in Boyden assays.  Results  hBM-MSCs expressed known markers (CD90/CD44/CD105) and demonstrated tri-lineage differentiation. Profiling of the adhesion molecules expressed by hBM-MSCs using flow cytometry found that they express high levels of integrin subunits (CD29 (β1), CD49c (α3), CD49d (α4)) and chemokine receptors CCR4 and CCR5. Furthermore, TNF stimulation increased expression of chemokine receptors including CCR4 and CCR5 by approximately 20%. In static binding asays, MSCs bound to immobilised ligands such as VCAM-1 and fibronectin, whose expression is increased in injured liver. In static liver tissue binding assays CD29 and CD44 blockade reduced binding to the liver sinusoids (30.9%±9 and 31%±7, respectively, both p  Conclusion  Binding of hBM-MSCs to liver sinusoidal endothelium occurs via tethering and firm adhesion without prior rolling. Tethering is mediated by CD29, whilst firm adhesion of hBM-MSCs to LSEC involves CD29 and CD44 interactions. The ability of MSCs to migrate in response to CCR4 and CXCR4 ligands, along with studies showing upregulation of these ligands in injured liver tissue suggests that these receptors may be involved in controlling MSC migration to and/or within injured liver.
Cameron had no formal correspondence with Keogh before promising a seven day NHS
Authors: Abi Rimmer
Journal: BMJ (2015)

No formal correspondence took place between Prime Minister David Cameron and the medical director of NHS England on the definition of seven day services before Cameron announced his plan to create “a truly seven day NHS,” an investigation by BMJ Careers has found.

The BMA said that the lack of any formal correspondence on a definition of seven day services was “astounding.”

The Department of Health had previously refused a freedom of information (FOI) request from BMJ Careers to see correspondence between itself and the prime minister discussing the definition of seven day services.1 This time, BMJ Careers approached NHS England using FOI legislation to request copies of any correspondence between the Prime Minister’s Office and Bruce Keogh, NHS England’s medical director, from April 2013 (when NHS England was created) to 30 July 2015 regarding what constitutes seven day services …
Electrical Chips for Biological Point-of-Care Detection
Authors: Bobby Reddy, Eric Salm, Rashid Bashir
Journal: Annual Review of Biomedical Engineering (2016)

As the future of health care diagnostics moves toward more portable and personalized techniques, there is immense potential to harness the power of electrical signals for biological sensing and diagnostic applications at the point of care. Electrical biochips can be used to both manipulate and sense biological entities, as they can have several inherent advantages, including on-chip sample preparation, label-free detection, reduced cost and complexity, decreased sample volumes, increased portability, and large-scale multiplexing. The advantages of fully integrated electrical biochip platforms are particularly attractive for point-of-care systems. This review summarizes these electrical lab-on-a-chip technologies and highlights opportunities to accelerate the transition from academic publications to commercial success.
Effect of immunosuppressive therapy on interferon γ release assay for latent tuberculosis screening in patients with autoimmune diseases: a systematic review and meta-analysis
Authors: Sunny H Wong, Qinyan Gao, Kelvin K F Tsoi, William K K Wu, Lai-shan Tam, Nelson Lee, Francis K L Chan, Justin C Y Wu, Joseph J Y Sung, Siew C Ng
Journal: Thorax (2015)

Objective Interferon γ release assay (IGRA) is commonly used to diagnose latent TB infection (LTBI). Immunosuppressive therapy may affect its performance but data are conflicting. We aimed to determine the effect of immunosuppressive therapy on the performance of IGRA in patients with autoimmune diseases. Methods We searched PubMed, MEDLINE, EMBASE and the Cochrane Library up to December 2014. We included studies that reported the IGRA results in patients with autoimmune disease with or without immunosuppressive therapy. The pooled effect of immunosuppressive therapy on IGRA was estimated using a Peto fixed-effects model. Results We included 17 studies with 3197 participants in the meta-analysis. Among the subjects, 71.5% were taking immunosuppressive therapy and 56.7% had received Bacillus Calmette–Guérin vaccination. Compared with patients not on immunosuppressants, patients receiving immunosuppressive therapy were less likely to have a positive IGRA result (OR 0.66, 95% CI 0.53 to 0.83, I 2 =23%), especially patients receiving anti-tumour necrosis factor (anti-TNF) treatment (OR 0.50, 95% CI 0.29 to 0.88). The use of immunosuppressive therapy was also associated with a lower rate of positive tuberculin skin test result (OR 0.51, 95% CI 0.42 to 0.61). Conclusions Our meta-analysis showed that IGRA results are negatively affected by immunosuppressive therapy. IGRA alone may not be sufficiently sensitive to diagnose LTBI in patients on immunosuppressive therapy. Patients should preferably be screened for LTBI before initiation of immunosuppressive therapy, especially before anti-TNF therapy.
Treatment of Presbyopia in Emmetropes Using a Shape-Changing Corneal Inlay
Authors: Jeffrey Whitman, Paul J. Dougherty, Gregory D. Parkhurst, John Olkowski, Stephen G. Slade, John Hovanesian, Ralph Chu, Jon Dishler, Dan B. Tran, Robert Lehmann, Harvey Carter, Roger F. Steinert, Douglas D. Koch
Journal: Ophthalmology (2016)
VAB-6 and cisplatin-cyclophosphamide combinations in the treatment of metastatic seminoma patients: The U.S.S.R. experience
Authors: S A Tjulandin, A V Khlebnov, R J Nasirova, Z P Mikhina, G V Molchanov, V N Sholokhov, V A Sokolov, N A Vetrova, A M Garin
Journal: Annals of Oncology (1991)
A Genetic Mechanism for Convergent Skin Lightening during Recent Human Evolution
Authors: Zhaohui Yang, Hua Zhong, Jing Chen, Xiaoming Zhang, Hui Zhang, Xin Luo, Shuhua Xu, Hua Chen, Dongsheng Lu, Yinglun Han, Jinkun Li, Lijie Fu, Xuebin Qi, Yi Peng, Kun Xiang, Qiang Lin, Yan Guo, Ming Li, Xiangyu Cao, Yanfeng Zhang, Shiyu Liao, Yingmei Peng, Lin Zhang, Xiaosen Guo, Shanshan Dong, Fan Liang, Jun Wang, Andrew Willden, Hong Seang Aun, Bun Serey, Tuot Sovannary, Long Bunnath, Ham Samnom, Graeme Mardon, Qingwei Li, Anming Meng, Hong Shi, Bing Su
Journal: Molecular Biology and Evolution (2016)

Skin lightening among Eurasians is thought to have been a convergence occurring independently in Europe and East Asia as an adaptation to high latitude environments. Among Europeans, several genes responsible for such lightening have been found, but the information available for East Asians is much more limited. Here, a genome-wide comparison between dark-skinned Africans and Austro-Asiatic speaking aborigines and light-skinned northern Han Chinese identified the pigmentation gene OCA2, showing unusually deep allelic divergence between these groups. An amino acid substitution (His615Arg) of OCA2 prevalent in most East Asian populations-but absent in Africans and Europeans-was significantly associated with skin lightening among northern Han Chinese. Further transgenic and targeted gene modification analyses of zebrafish and mouse both exhibited the phenotypic effect of the OCA2 variant manifesting decreased melanin production. These results indicate that OCA2 plays an important role in the convergent skin lightening of East Asians during recent human evolution.
Thrombotic thrombocytopenic purpura associated with ticlopidine therapy.
Authors: S F Leavey, J Weinberg
Journal: Journal of the American Society of Nephrology (1997)

A patient who developed thrombotic microangiopathy while on ticlopidine therapy is reported. Thrombotic microangiopathy resolved with discontinuation of the drug and treatment with plasma exchange and has not recurred during 10 months of follow-up. The emerging data on the risk of developing thrombotic microangiopathy while on Ticlopidine and the possible mechanisms underlying this association are reviewed. The need for careful monitoring of the platelet count and hematocrit in addition to the white cell count during the first 3 months of therapy with this drug is emphasized. It is important that nephrologists, who are frequently called upon to diagnose thrombotic microangiopathy, be aware of its association with ticlopidine. Other drug-induced syndromes of thrombotic microangiography are also considered and compared, with respect to possible mechanisms of disease in each case.
Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration
Authors: Gavin M. Douglas, Michael D. Wilson, Alan M. Moses
Journal: Molecular Biology and Evolution (2016)

Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations. In contrast, degeneration of pseudogene transcriptional regulation is not well understood. Here, we test two predictions of regulatory degeneration along a pseudogenized lineage: 1) Decreased transcription factor (TF) binding and 2) accelerated evolution in putative cis-regulatory regions. We find evidence for decreased TF binding levels nearby two primate pseudogenes compared with functional liver genes. However, the majority of TF-bound sequences nearby pseudogenes do not show evidence for lineage-specific accelerated rates of evolution. We conclude that decreases in TF binding level could be a marker for regulatory degeneration, while sequence degeneration in primate cis-regulatory modules may be obscured by background rates of TF binding site turnover.