tbuckley/cabot-search huggingface dataset:
Contrasting Expression Patterns of Histone mRNA and microRNA 760 in Patients with Gastric Cancer
Authors: Takeshi Iwaya, Takeo Fukagawa, Yutaka Suzuki, Yusuke Takahashi, Genta Sawada, Masahisa Ishibashi, Junji Kurashige, Tomoya Sudo, Fumiaki Tanaka, Kohei Shibata, Fumitaka Endo, Hirokatsu Katagiri, Kaoru Ishida, Kohei Kume, Satoshi Nishizuka, Hisae Iinuma, Go Wakabayashi, Masaki Mori, Mitsuru Sasako, Koshi Mimori
Journal: Clinical Cancer Research (2013)

Recent studies revealed that both disseminated tumor cells and noncancerous cells contributed to cancer progression cooperatively in the bone marrow. Here, RNA-seq analysis of bone marrow from gastric cancer patients was performed to identify prognostic markers for gastric cancer.Bone marrow samples from eight gastric cancer patients (stages I and IV: n = 4 each) were used for RNA-seq analysis. Results were validated through quantitative real-time PCR (qRT-PCR) analysis of HIST1H3D expression in 175 bone marrow, 92 peripheral blood, and 115 primary tumor samples from gastric cancer patients. miR-760 expression was assayed using qRT-PCR in 105 bone marrow and 96 primary tumor samples. Luciferase reporter assays were performed to confirm whether histone mRNAs were direct targets of miR-760. miR-760 expression was also evaluated in noncancerous cells from gastric cancer patients.RNA-seq analysis of bone marrow samples from gastric cancer patients revealed higher expression of multiple histone mRNAs in stage IV patients. HIST1H3D expression in the bone marrow, peripheral blood, and primary tumor of stage IV patients was higher than that in stage I patients (P = 0.0284, 0.0243, and 0.0006, respectively). In contrast, miR-760 was downregulated in the bone marrow and primary tumor of stage IV patients compared with stage I patients (P = 0.0094 and 0.0018, respectively). Histone mRNA and miR-760 interacted directly. Furthermore, miR-760 was downregulated in noncancerous mucosa in stage IV gastric cancer patients.Histone mRNA was upregulated, whereas miR-760 was downregulated in the bone marrow and primary tumor of advanced gastric cancer patients, suggesting that the histone mRNA/miR-760 axis had a crucial role in the development of gastric cancer.
Colon Cancer Cells Escape 5FU Chemotherapy-Induced Cell Death by Entering Stemness and Quiescence Associated with the c-Yes/YAP Axis
Authors: Yasmine Touil, Wassila Igoudjil, Matthieu Corvaisier, Anne-Frédérique Dessein, Jérôme Vandomme, Didier Monté, Laurence Stechly, Nicolas Skrypek, Carole Langlois, Georges Grard, Guillaume Millet, Emmanuelle Leteurtre, Patrick Dumont, Stéphanie Truant, François-René Pruvot, Mohamed Hebbar, Fan Fan, Lee M. Ellis, Pierre Formstecher, Isabelle Van Seuningen, Christian Gespach, Renata Polakowska, Guillemette Huet
Journal: Clinical Cancer Research (2013)

Metastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of patients with colon cancer with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery.We show that a clonal 5F31 cell population, resistant to 1 μmol/L 5FU, express a typical cancer stem cell-like phenotype and enter into a reversible quiescent G0 state upon reexposure to higher 5FU concentrations. These quiescent cells overexpressed the tyrosine kinase c-Yes that became activated and membrane-associated upon 5FU exposure. This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes-associated protein) molecular complex and depleted nuclear YAP levels. Consistently, YES1 silencing decreased nuclear YAP accumulation and induced cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. Moreover, the YES1 and YAP transcript levels positively correlated with colon cancer relapse and shorter patient survival (P < 0.05 and P < 0.025, respectively).We identified c-Yes and YAP as potential molecular targets to eradicate quiescent cancer cells and dormant micrometastases during 5FU chemotherapy and resistance and as predictive survival markers for colon cancer.
Urinary Plasmin Inhibits TRPV5 in Nephrotic-Range Proteinuria
Authors: Kukiat Tudpor, Sergio Laínez, Arjan J. Kwakernaak, Nadezda V. Kovalevskaya, Sjoerd Verkaart, Siebe van Genesen, Annemiete van der Kemp, Gerjan Navis, René J.M. Bindels, Joost G.J. Hoenderop
Journal: Journal of the American Society of Nephrology (2012)

Urinary proteins that leak through the abnormal glomerulus in nephrotic syndrome may affect tubular transport by interacting with membrane transporters on the luminal side of tubular epithelial cells. Patients with nephrotic syndrome can develop nephrocalcinosis, which animal models suggest may develop from impaired transcellular Ca2+ reabsorption via TRPV5 in the distal convoluted tubule (DCT). In nephrotic-range proteinuria, filtered plasminogen reaches the luminal side of DCT, where it is cleaved into active plasmin by urokinase. In this study, we found that plasmin purified from the urine of patients with nephrotic-range proteinuria inhibits Ca2+ uptake in TRPV5-expressing human embryonic kidney 293 cells through the activation of protease-activated receptor-1 (PAR-1). Preincubation with a plasmin inhibitor, a PAR-1 antagonist, or a protein kinase C (PKC) inhibitor abolished the effect of plasmin on TRPV5. In addition, ablation of the PKC phosphorylation site S144 rendered TRPV5 resistant to the action of plasmin. Patch-clamp experiments showed that a decreased TRPV5 pore size and a reduced open probability accompany the plasmin-mediated reduction in Ca2+ uptake. Furthermore, high-resolution nuclear magnetic resonance spectroscopy demonstrated specific interactions between calmodulin and residues 133–154 of the N-terminus of TRPV5 for both wild-type and phosphorylated (S144pS) peptides. In summary, PAR-1 activation by plasmin induces PKC-mediated phosphorylation of TRPV5, thereby altering calmodulin-TRPV5 binding, resulting in decreased channel activity. These results indicate that urinary plasmin could contribute to the downstream effects of proteinuria on the tubulointerstitium by negatively modulating TRPV5.
Immunogenicity and crossreactivity of specificity-associated markers on alloreactive T cells. Confirmation based on the model of tolerance abolition by adoptive transfer.
Authors: H Kimura, W K Silvers, D B Wilson
Journal: The Journal of Experimental Medicine (1986)

Syngeneic or parental strain T cells adoptively transferred into hybrid rats tolerant of third party alloantigens (L/DA tolerant of BN), in numbers insufficient to abolish tolerance, induce instead an active resistance to tolerance abolition with larger, usually effective dosages of donor cells. Of particular interest is the finding that immunization with T cells from one parental strain donor (e.g., DA) inhibited the tolerance-abolishing alloreactivity (anti-BN) of subsequently transferred T cells from the same (DA) and the other (L) parental strain donor. We conclude that anti-MHC receptors on T cells from different genetic backgrounds reactive to the same third party alloantigens share the same conserved immunogenic specificity-associated markers (SAM). The nonpolymorphism of anti-MHC receptors shown here in the transplantation tolerance model is a confirmation of the same conclusion drawn from earlier studies with the GVHD-resistance model, and it therefore suggests that these two models of T cell MHC interactions involve very similar mechanisms of T cell idiotypic regulation.
The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke
Authors: Long-Jun Wu, Gongxiong Wu, M Reza Akhavan Sharif, Amanda Baker, Yonghui Jia, Frederic H Fahey, Hongbo R Luo, Edward P Feener, David E Clapham
Journal: Nature Neuroscience (2012)
American Society of Clinical Oncology/National Comprehensive Cancer Network Quality Measures
Authors: Christopher E. Desch, Kristen K. McNiff, Eric C. Schneider, Deborah Schrag, Joan McClure, Eva Lepisto, Molla S. Donaldson, Katherine L. Kahn, Jane C. Weeks, Clifford Y. Ko, Andrew K. Stewart, Stephen B. Edge
Journal: Journal of Clinical Oncology (2008)

Purpose The National Cancer Policy Board recommended the creation of quality measures and a national reporting system in 1999. Representatives from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) collaborated to create metrics suitable for national performance measurement. Methods Content and methodology experts nominated by ASCO and NCCN met to select and refine metrics for breast, colon, and rectal cancer based on National Initiative for Cancer Care Quality and NCCN measures and NCCN and ASCO guidelines. Measures were selected based on their impact on disease free and overall survival, the degree to which opportunities for improvement exist, and the feasibility of data collection. Results Three breast cancer measures and four colorectal cancer measures were chosen. Measures for breast cancer included adjuvant hormone therapy for hormone receptor–positive tumors, chemotherapy for hormone receptor–negative cancer, and radiation after lumpectomy. Colorectal measures included adjuvant radiation and chemotherapy for rectal cancer, and adjuvant chemotherapy for colon cancer. All but one were recommended as accountability measures and one for quality improvement (removal and examination of 12 or more lymph nodes in colon cancer). Specifications were developed for each measure using tumor registries as the data source. Conclusion ASCO/NCCN measures can be implemented by health systems, provider groups or payors for improvement or accountability using local tumor registries to furnish data on staging and treatment.
Molecular epidemiology of clinical Acinetobacter baumannii and Acinetobacter genomic species 13TU isolates using a multilocus sequencing typing scheme
Authors: H. Wisplinghoff, C. Hippler, S.G. Bartual, C. Haefs, D. Stefanik, P.G. Higgins, H. Seifert
Journal: Clinical Microbiology and Infection (2008)
Concurrent processing of saccades
Authors: Robert M. McPeek, Edward L. Keller, Ken Nakayama
Journal: Behavioral and Brain Sciences (1999)

We summarize several experiments indicating that the saccadic system is capable of simultaneously programming two movements toward different goals. This concurrent processing of saccades can lead to the execution of two saccades separated by an extremely short intersaccadic interval. This supports the idea of target competition proposed in Findlay &amp; Walker's article, but suggests a greater degree of parallel processing. We provide evidence that concurrent processing of two saccades is not limited to higher-level planning subsystems; rather, it also involves both regions close enough to the motor output that it can systematically affect saccade trajectory.
Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma
Authors: Stephen J. Schuster, Sattva S. Neelapu, Barry L. Gause, John E. Janik, Franco M. Muggia, Jon P. Gockerman, Jane N. Winter, Christopher R. Flowers, Daniel A. Nikcevich, Eduardo M. Sotomayor, Dean S. McGaughey, Elaine S. Jaffe, Elise A. Chong, Craig W. Reynolds, Donald A. Berry, Carlos F. Santos, Mihaela A. Popa, Amy M. McCord, Larry W. Kwak
Journal: Journal of Clinical Oncology (2011)

Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) -specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial.Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control.Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients.Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.
A clinical prediction rule for identifying patients with patellofemoral pain who are likely to benefit from foot orthoses: a preliminary determination
Authors: Bill Vicenzino, Natalie Collins, Joshua Cleland, Thomas McPoil
Journal: British Journal of Sports Medicine (2008)

To develop a clinical prediction rule to identify patients with patellofemoral pain (PFP) who are more likely to benefit from foot orthoses.Posthoc analysis of one treatment arm of a randomised clinical trial.Single-centre trial in a community setting in Brisbane, Australia.42 participants (mean age 27.9 years) with a clinical diagnosis of PFP (median duration 36 months).Foot orthoses fitted by a physiotherapist.Five-point global improvement scale at 12-week follow-up, dichotomised with marked improvement equalling success.Potential predictor variables identified by univariate analyses were age, height, pain severity, anterior knee pain scale score, functional index questionnaire score, foot morphometry (arch height ratio, mid-foot width difference from non-weight bearing to weight bearing) and overall orthoses comfort. Parsimonious fitting of these variables to a model that explained success with orthoses identified the following: age (>25 years), height (<165 cm), worst pain visual analogue scale (<53.25 mm) and a difference in mid-foot width from non-weight bearing to weight bearing (>10.96 mm). The pretest success rate of 40% increased to 86% if the patient exhibited three of these variables (positive likelihood ratio 8.8; 95% CI 1.2 to 66.9).Post-hoc analysis identified age, height, pain severity and mid-foot morphometry as possible predictors of successful treatment of PFP with foot orthoses, thereby providing practitioners with information for prescribing foot orthoses in PFP and stimulating further research.
Interferon-lambda genotype and low serum low-density lipoprotein cholesterol levels in patients with chronic hepatitis C infection
Authors: Josephine H. Li, Xiang Qian Lao, Hans L. Tillmann, Jennifer Rowell, Keyur Patel, Alexander Thompson, Sunil Suchindran, Andrew J. Muir, John R. Guyton, Stephen D. Gardner, John G. McHutchison, Jeanette J. McCarthy
Journal: Hepatology (2010)

Recently, genetic polymorphisms occurring in the interferon (IFN)-lambda gene region were associated with response to IFN-based treatment of hepatitis C infection. Both infection with the hepatitis C virus and IFN therapy are associated with decreased serum cholesterol and high cholesterol has been associated with increased likelihood to respond to IFN. We sought to determine if the IFN-lambda gene variant was also associated with serum lipid levels in chronic hepatitis C patients. We compared genotypes of the rs12979860 polymorphism, located proximal to the IL28 gene, with serum lipid and apolipoprotein levels in 746 subjects with chronic hepatitis C virus infection, not currently undergoing treatment, using multivariable analysis of variance. Levels of total cholesterol ( P = 6.0 × 10−4), apolipoprotein B ( P = 1.3 × 10−6) and low-density lipoprotein (LDL) cholesterol ( P = 8.9 × 10−10) were significantly higher in subjects carrying the rs12979860 CC responder genotype compared with those with the CT or TT genotype. Levels of triglycerides ( P = 0.03), apolipoprotein A-I ( P = 0.06), and apolipoprotein E ( P = 0.01) were slightly lower in the rs12979860 CC genotype group, whereas levels of high-density lipoprotein cholesterol ( P = 0.78) and apolipoprotein C-III ( P = 0.74) did not vary by rs12979860 genotype. Conclusion: Our results suggest that low levels of LDL cholesterol in chronic hepatitis C patients may be a marker of host endogenous IFN response to hepatitis C and that subjects with the rs12979860 CC responder genotype may have a lower endogenous IFN response to the virus. Hepatology 2010
Survival in epithelial ovarian cancer: a multivariate analysis incorporating BRCA mutation status and platinum sensitivity
Authors: D.J. Gallagher, J.A. Konner, K.M. Bell-McGuinn, J. Bhatia, P. Sabbatini, C.A. Aghajanian, K. Offit, R.R. Barakat, D.R. Spriggs, N.D. Kauff
Journal: Annals of Oncology (2010)
Noninvasive ventilation in chronic ventilatory failure due to chronic obstructive pulmonary disease
Authors: M.W. Elliott
Journal: European Respiratory Journal (2002)

Noninvasive ventilation (NIV) has been one of the major advances in respiratory medicine in the last decade. In particular, it has found widespread application in the management of patients with chronic obstructive pulmonary disease (COPD). There is a robust evidence base for its use in acute exacerbations of COPD, but the evidence that it is effective in chronic COPD is much less strong. Despite this, COPD is one of the most common reasons for long-term home mechanical ventilation.

Early experience was with negative pressure devices, usually used for short periods in hospital 1–4. Studies were uncontrolled and with small numbers of patients, but did suggest possible benefits. The use of negative pressure devices at home and during sleep in patients with COPD has been largely unsuccessful 3, 5. In two controlled trials, patients were generally unable to sleep during negative pressure ventilation, and most either failed to complete the protocol because of lack of improvement or discomfort associated with the use of the equipment 5, or did not wish to continue treatment after the study was completed 3. Negative pressure devices are cumbersome and relatively inefficient, particularly when the impedance to inflation is high, and may not be able to provide adequate ventilation during sleep. They predispose to the development or accentuation of upper airway collapse 6, and this may be a particular problem during sleep in the obese patient with COPD.

In most studies of negative pressure ventilation in COPD, the primary focus of therapy was to rest respiratory muscles, which were thought to be in a state of chronic fatigue. Unfortunately, in the absence of any reliable test of respiratory muscle fatigue this approach remains speculative. In an attempt to definitively answer whether respiratory muscle fatigue exists in stable chronic …
The Incidence and Characteristics of Patients with Conversion Reactions: I. A General Hospital Consultation Service Sample
Authors: F. PATRICK MCKEGNEY
Journal: American Journal of Psychiatry (1967)

The brief survey data presented above should demonstrate that conversion, or hysteria, still exists in a significant proportion of patients seen in a general hospital psychiatric practice. The critical incidence study would, of course, involve a prospective, case-finding approach rather than relying upon identification through consultation request, since the conversion mechanism, like tuberculosis and syphilis, is a "great imitator." In addition, the frequent coexistence of conversion reaction with demonstrable organic disease mitigates against early recognition by physicians of the psychological disturbance. There does seem to be some reciprocal relationship between depression and conversion reaction which is not completely accounted for by diagnostic distortion. Conversion reactions are found in men at a frequency about half that in women. Finally, patients recognized as having conversion symptoms are referred for outpatient psychotherapy much more often than are patients with other psychiatric diagnoses. However, a follow-up study is necessary to determine what percentage of these patients with physical symptomatology, frequently reinforced by medical or surgical diagnostic and therapeutic procedures, actually carry out recommendations for psychiatric treatment. This brief survey of a large sample of patients seen in psychiatric consultation should provide a basis of comparison and suggestions for further investigations and should emphasize the need for close evaluation of psychological factors in all medical and surgical patients.
Understanding the challenges of service change – learning from acute pain services in the UK
Authors: AE Powell, HTO Davies, J Bannister, WA Macrae
Journal: Journal of the Royal Society of Medicine (2009)

To explore organizational difficulties faced when implementing national policy recommendations in local contexts.Qualitative case study involving semi-structured interviews with health professionals and managers working in and around acute pain services.Three UK acute hospital organizations.Identification of the content, context and process factors impacting on the implementation of the national policy recommendations on acute pain services; insights into and deeper understanding of the generic obstacles to change facing service improvements.The process of implementing policy recommendations and improving services in each of the three organizations was undermined by multiple factors relating to: doubts and disagreements about the nature of the change; challenging local organizational contexts; and the beliefs, attitudes and responses of health professionals and managers. The impact of these factors was compounded by the interaction between them.Local implementation of national policies aimed at service improvement can be undermined by multiple interacting factors. Particularly important are the pre-existing local organizational contexts and histories, and the deeply-ingrained attitudes, beliefs and assumptions of diverse staff groups. Without close attention to all of these underlying issues and how they interact in individual organizations against the background of local and national contexts, more resources or further structural change are unlikely to deliver the intended improvements in patient care.
Topical Tazarotene Chemoprevention Reduces Basal Cell Carcinoma Number and Size in <b> <i>Ptch1</i> </b>+/− Mice Exposed to Ultraviolet or Ionizing Radiation
Authors: Po-Lin So, Kenneth Lee, Jennifer Hebert, Patricia Walker, Ying Lu, Jimmy Hwang, Levy Kopelovich, Mohammed Athar, David Bickers, Michelle Aszterbaum, Ervin H. Epstein
Journal: Cancer Research (2004)

Abstract Oral retinoids can reduce basal cell carcinoma (BCC) incidence in genetically susceptible patients, and one topical retinoid, tazarotene, has been reported to cure some sporadic BCCs. Therefore, we have tested whether this agent would affect BCCs in Ptch1+/− mice in a controlled chemoprevention trial. We found that topical tazarotene dramatically inhibits the formation of BCCs induced with either UV or ionizing radiation. The ability of tazarotene to inhibit BCC formation in this mouse model provides encouragement for the use of tazarotene in skin cancer chemoprevention trials in humans.