tbuckley/cabot-search huggingface dataset:
Cbx4 Governs HIF-1α to Potentiate Angiogenesis of Hepatocellular Carcinoma by Its SUMO E3 Ligase Activity
Authors: Jie Li, Ying Xu, Xi-Dai Long, Wei Wang, Hui-Ke Jiao, Zhu Mei, Qian-Qian Yin, Li-Na Ma, Ai-Wu Zhou, Li-Shun Wang, Ming Yao, Qiang Xia, Guo-Qiang Chen
Journal: Cancer Cell (2014)
Pressure Ulcer Risk Factors Among Hospitalized Patients With Activity Limitation
Authors: Richard M. Allman
Journal: JAMA (1995)

To identify specific demographic, medical, functional status, and nutritional characteristics that predict the development of stage 2 or greater pressure ulcers among patients whose activity is limited to bed or chair.Prospective inception cohort study.Tertiary care, urban, university teaching hospital.A total of 286 patients fulfilling the following criteria: admitted to the hospital within the previous 3 days, age 55 years or more, expected to be confined to bed or chair for at least 5 days or had a hip fracture, and without a stage 2 or greater pressure ulcer.Time to in-hospital development of a stage 2 or greater pressure ulcer.Total cumulative incidence of pressure ulcers was 12.9% (n = 37) after a median time of 9 days from admission to final skin examination. Age of 75 years or more, dry skin, nonblanchable erythema (a stage 1 pressure ulcer), previous pressure ulcer history, immobility, fecal incontinence, depleted triceps skinfold, lymphopenia (lymphocyte count < 1.50 x 10(9)/L), and decreased body weight (< 58 kg) were significantly associated with pressure ulcer development by univariate Kaplan-Meier survival analyses (P < .05 by log-rank test). Risk ratios (and 95% confidence intervals) for predictors (P < or = .05) of pressure ulcer development after multivariable Cox regression analysis included the following: nonblanchable erythema, 7.52 (1.00 to 59.12); lymphopenia, 4.86 (1.70 to 13.89); immobility, 2.36 (1.14 to 4.85); dry skin, 2.31 (1.02 to 5.21); and decreased body weight, 2.18 (1.05 to 4.52). The 3-week cumulative incidence of pressure ulcers with none, one, two, or three or more of these characteristics was 0%, 11.4%, 39.6%, and 67.9%, respectively (P < .001 by log-rank test).These results suggest that nonblanchable erythema, lymphopenia, immobility, dry skin, and decreased body weight are independent and significant risk factors for pressure ulcers in hospitalized patients whose activity is limited to bed or chair.
How Not to Search for Isochores: A Reply to Cohen et al
Authors: O. Clay
Journal: Molecular Biology and Evolution (2005)

In a recent paper in these pages, Cohen et al. search for isochores in the human genome, based on a system of attributes that they assign to isochores. The putative isochores that they find and choose for presentation are almost all below 45% GC and cover only about 41% of the genome. Closer inspection reveals that the authors' methodology systematically loses GC-rich isochores because it does not anticipate the considerable fluctuations and corresponding long-range correlations that characterize mammalian DNA and that are highest in GC-rich DNA. Thus, they over-fragment GC-rich isochores (and also many GC-poor isochores) beyond recognition.
A biomechanical review of factors affecting rowing performance
Authors: A Baudouin, D Hawkins
Journal: British Journal of Sports Medicine (2002)

This review analyses rowing by linking the biological and mechanical systems that comprise the rowing system. Blade force was found to be the only propulsive force to counter the drag forces, consisting of both air drag and hydrodynamic drag, acting on the system. Vertical oscillations of the shell are shown to have minimal impact on system dynamics. The oar acts as the link between the force generated by the rower and the blade force and transmits this force to the rowing shell through the oarlock. Blade dynamics consist of both lift and drag mechanisms. The force on the oar handle is the result of a phased muscular activation of the rower. Oar handle force and movement are affected by the joint strength and torque-velocity characteristics of the rower. Maximising sustainable power requires a matching of the rigging setup and blade design to the rower’s joint torque-velocity characteristics. Coordination and synchrony between rowers in a multiple rower shell affects overall system velocity. Force-time profiles should be better understood to identify specific components of a rower’s biomechanics that can be modified to achieve greater force generation.
Searching for Stem/Progenitor Cells in the Adult Mouse Kidney
Authors: Fangming Lin, Peter Igarashi
Journal: Journal of the American Society of Nephrology (2003)

Stem cells are generally defined as clonogenic cells that are capable of both self-renewal and multilineage differentiation ([1–3][1][⇓][2][⇓][3]). The fertilized zygote has the highest developmental potential and gives rise to the cells of the entire organism. More than 20 years ago,
ON 01910.Na Is Selectively Cytotoxic for Chronic Lymphocytic Leukemia Cells through a Dual Mechanism of Action Involving PI3K/AKT Inhibition and Induction of Oxidative Stress
Authors: Colby M. Chapman, Xiameng Sun, Mark Roschewski, Georg Aue, Mohamed Farooqui, Lawrence Stennett, Federica Gibellini, Diane Arthur, Patricia Pérez-Galán, Adrian Wiestner
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Chronic lymphocytic leukemia (CLL), a malignancy of mature B cells, is incurable with chemotherapy. Signals from the microenvironment support leukemic cell survival and proliferation and may confer chemotherapy resistance. ON 01910.Na (Rigosertib), a multikinase phosphoinositide 3-kinase (PI3K) inhibitor, is entering phase III trials for myelodysplastic syndrome. Our aim was to analyze the efficacy of ON 01910.Na against CLL cells in vitro and investigate the molecular effects of this drug on tumor biology. Experimental Design: Cytotoxicity of ON 01910.Na against CLL cells from 34 patients was determined in vitro with flow cytometry of cells stained with Annexin V and CD19. Global gene expression profiling on Affymetrix microarrays, flow cytometry, Western blotting, and cocultures with stroma cells were used to delineate ON 01910.Na mechanism of action. Results: ON 01910.Na induced apoptosis in CLL B cells without significant toxicity against T cells or normal B cells. ON 01910.Na was equally active against leukemic cells associated with a more aggressive disease course [immunoglobulin heavy-chain variable region unmutated, adverse cytogenetics] than against cells without these features. Gene expression profiling revealed two main mechanisms of action: PI3K/AKT inhibition and induction of ROS that resulted in an oxidative stress response through activating protein 1 (AP-1), c-jun-NH2-terminal kinase, and ATF3 culminating in the upregulation of NOXA. ROS scavengers and shRNA mediated knockdown of ATF3- and NOXA-protected cells from drug-induced apoptosis. ON 01910.Na also abrogated the prosurvival effect of follicular dendritic cells on CLL cells and reduced SDF-1–induced migration of leukemic cells. Conclusions: These data support the clinical development of ON 01910.Na in CLL. Clin Cancer Res; 18(7); 1979–91. ©2012 AACR.
THE INTERACTION OF MYCOPLASMAS WITH MAMMALIAN CELLS
Authors: Dorothea Zucker-Franklin, Morton Davidson, Lewis Thomas
Journal: The Journal of Experimental Medicine (1966)

The incubation of mycoplasmas with human peripheral blood buffy coats resulted in the uptake of these microorganisms by more than 50% of the mononuclear cells. Mycoplasmas adhered to the plasma membranes of all leukocytes, most of which developed long cytoplasmic processes not seen in the controls. In human and rat thoracic duct lymph, about 6% of the cells ingested the microorganisms. T(2) phage and thorotrast were taken up by a similar percentage of lymphocytes. On morphological grounds, the cells which were able to take up PPLO's or particles could not be distinguished from the cells which were incapable of this function. Following phagocytosis, neither the cell nor the microorganism showed any morphological alterations over a 3 hr period of observation. The demonstration that a small percentage of "lymphocytes" are able to phagocytose may have pathological and immunological implications.
Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D
Authors: Takehiko Nakamura, Tomomichi Ono, Koji Yoshimura, Tatsuyoshi Arao, Seiji Kondo, Masamitsu Ichihashi, Akira Matsumoto, Yoshisada Fujiwara
Journal: Journal of the American Academy of Dermatology (1991)
Primary Follicular Lymphoma of the Duodenum Is a Distinct Mucosal/Submucosal Variant of Follicular Lymphoma: A Retrospective Study of 63 Cases
Authors: Ana-Iris Schmatz, Berthold Streubel, Elisabeth Kretschmer-Chott, Andreas Püspök, Ulrich Jäger, Christine Mannhalter, Markus Tiemann, German Ott, Wolfgang Fischbach, Peter Herzog, Gerhard Seitz, Manfred Stolte, Markus Raderer, Andreas Chott
Journal: Journal of Clinical Oncology (2011)

Small series with limited follow-up have suggested primary follicular lymphoma of the duodenum (FL-D) to be an indolent disease. We report our experience on a large series of patients followed for a median time period of longer than 6 years.The study comprised 63 patients with primary FL-D defined as stage I disease. Endoscopy and detailed pathologic work-up was performed at diagnosis and at restaging to monitor the behavior of the neoplastic process.Histologically, all 63 patients had FL, low grade (1 to 2). Duodenal endosonography demonstrated lesions confined to mucosa/submucosa in 19 of 20 patients. At an overall median follow-up of 77 months (range, 12 to 177 months), only two untreated patients had developed nodal disease, the remaining 61 patients never experienced extrasmall intestinal disease and large cell transformation did not occur at all. Among 24 patients followed by watch and wait strategy, seven showed spontaneous complete regression and 17 had stable disease; radiotherapy resulted in complete regression in all 19 patients; anti-CD20 antibody monotherapy achieved complete regression in four patients and stable disease in one patient. Various chemotherapy protocols in eight patients caused complete regression in all of them, but local relapses occurred in three. No patients required surgery or died of disease.These findings characterize primary FL-D as a remarkably indolent FL variant, which, even left untreated, does not develop tumorous growth, very rarely disseminates (two of 63 patients) and does not transform to high grade disease. A watch and wait approach appears to be the most sensible strategy.
Exploration and development of practice with non invasive ventilation (NIV) to patients with chronic obstructive pulmonary disease (COPD) in exacerbation based on the patients, their relatives and healthcare professionals perspectives on treatment
Authors: Helle Marie Christensen, Ingrid Louise Titlestad, Lotte Huniche
Journal: European Respiratory Journal (2012)

Background:  Assessment of life expectancy and end stage COPD is difficult and often discussed in the clinical setting with regards to the ordination “Not-to-intubate” and “Continuation of respiratory assistance/NIV” as life sustaining treatment. There is little knowledge of how the patients experience NIV, and health care professionals express a need for developing new clinical strategies which draws on patient9s perspectives.   Aim:  To provide insight into how patients with COPD experience treatment with NIV. To develop new clinical strategies for treatment with NIV based on patients, relatives, and health care professionals perspectives.   Method:  The project is based on critical psychological practice research. A group of co-researchers convenes 10 times over the course of 12 months including the principal researcher and interdisciplinary clinicians from the Department of Respiratory Medicine. The group describes and analyzes practice of NIV treatment in the department. Clinicians contribute with experience based issues, and the researcher contributes with issues based on a combination of fieldwork and semi-structured interviews with patients and their relatives.   Results:  At present 11 patients who have been hospitalized and treated with NIV in 2011 and 3 of their relatives have been interviewed. Patient interviews revealed that all 11 patients expected and wanted to be treated with NIV if necessary in the future even though 2 patients described fear during treatment and 10 experienced more or less discomfort with the treatment.
Phase III Trial of Doxorubicin With or Without Cisplatin in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study
Authors: J. Tate Thigpen, Mark F. Brady, Howard D. Homesley, John Malfetano, Brent DuBeshter, Robert A. Burger, Shu Liao
Journal: Journal of Clinical Oncology (2004)

Purpose Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents. This trial of stage III, IV, or recurrent disease evaluated whether combining these agents increases response rate (RR) and prolongs progression-free survival (PFS) and overall survival (OS) over doxorubicin alone. Patients and Methods Of 299 patients registered, 281 (94%) were eligible. Regimens were doxorubicin 60 mg/m 2 intravenously or doxorubicin 60 mg/m 2 plus cisplatin 50 mg/m 2 every 3 weeks until disease progression, unacceptable toxicity, or a total of 500 mg/m 2 doxorubicin. Results There were 12 (8%) complete (CR) and 26 (17%) partial responses (PR) among 150 patients receiving doxorubicin versus 25 (19%) CRs and 30 (23%) PRs among patients receiving the combination. The overall response rate was higher among patients receiving the combination (42%) compared with patients receiving doxorubicin (25%; P = .004). Median PFS was 5.7 and 3.8 months, respectively, for the combination and single agent. The PFS hazard ratio was 0.736 (95% CI, 0.577 to 0.939; P = .014). Median OS was 9.0 and 9.2 months, respectively, for the combination and single agent. Overall death rates were similar in the two groups (hazard ratio, 0.928; 95% CI, 0.727 to 1.185). Nausea, vomiting, and hematologic toxicities were common. The combination produced more grade 3 to 4 leukopenia (62% v 40%), thrombocytopenia (14% v 2%), anemia (22% v 4%), and nausea/vomiting (13% v 3%). Conclusion Adding cisplatin to doxorubicin in advanced endometrial carcinoma improves RR and PFS with a negligible impact on OS and produces increased toxicity. These results have served as a building block for subsequent phase III trials in patients with disseminated and high-risk limited endometrial carcinoma.
Rehabilitation After Immobilization for Ankle Fracture
Authors: Anne M. Moseley, Paula R. Beckenkamp, Marion Haas, Robert D. Herbert, Chung-Wei Christine Lin
Journal: JAMA (2015)

<h3>Importance</h3> The benefits of rehabilitation after immobilization for ankle fracture are unclear. <h3>Objectives</h3> To determine the effectiveness of a supervised exercise program and advice (rehabilitation) compared with advice alone and to determine if effects are moderated by fracture severity or age and sex. <h3>Design, Setting, and Participants</h3> The EXACT trial was a pragmatic, randomized clinical trial conducted from December 2010 to June 2014. Patients with isolated ankle fracture presenting to fracture clinics in 7 Australian hospitals were randomized on the day of removal of immobilization. Of 571 eligible patients, 357 chose not to participate and 214 were allocated to rehabilitation (n = 106) or advice alone (n = 108), with 194 (91%) followed up at 1 month, 173 (81%) at 3 months, and 170 (79%) at 6 months. There were no withdrawals attributed to adverse effects. Recruitment terminated early on December 31, 2013 (planned enrollment, 342; actual, 214), because funding was exhausted. <h3>Interventions</h3> Supervised exercise program and advice about self-management (rehabilitation) (individually tailored, prescribed, monitored, and progressed) or advice alone, both delivered by a physical therapist. <h3>Main Outcomes and Measures</h3> Primary outcomes were activity limitation assessed using the Lower Extremity Functional Scale (score range, 0-80; higher scores indicate better activity), and quality of life assessed using the Assessment of Quality of Life (score range, 0-1; higher scores indicate better quality of life), measured at baseline and at 1, 3 (primary time point), and 6 months. <h3>Results</h3> Mean activity limitation and quality of life at baseline were 30.1 (SD, 12.5) and 0.51 (SD, 0.24), respectively, for advice and 30.2 (SD, 13.2) and 0.54 (SD, 0.24) for rehabilitation, increasing to 64.3 (SD, 13.5) and 0.85 (SD, 0.17) for advice vs 64.3 (SD, 15.1) and 0.85 (SD, 0.20) for rehabilitation at 3 months. Rehabilitation was not more effective than advice for activity limitation (mean effect at 3 months, 0.4 [95% CI, −3.3 to 4.1]) or quality of life (−0.01 [95% CI, −0.06 to 0.04]). Treatment effects were not moderated by fracture severity or age and sex. <h3>Conclusions and Relevance</h3> A supervised exercise program and advice did not confer additional benefits in activity limitation or quality of life compared with advice alone for patients with isolated and uncomplicated ankle fracture. These findings do not support the routine use of supervised exercise programs after removal of immobilization for patients with isolated and uncomplicated ankle fracture. <h3>Trial Registration</h3> anzctr.org.au Identifier:ACTRN12610000979055
Distribution of C-Peptide and Its Determinants in North American Children at Risk for Type 1 Diabetes
Authors: Ping Xu, Xiaoning Qian, Desmond A. Schatz, David Cuthbertson, Jeffrey P. Krischer
Journal: Diabetes Care (2014)

To determine basal and stimulated C-peptide percentiles in North American children and adolescents at risk for type 1 diabetes (T1D) and to examine factors associated with this distribution in the Diabetes Prevention Trial-Type 1 (DPT-1).We included 582 subjects aged 4-18 years at randomization in the DPT-1 trials. A 2-h oral glucose tolerance test (OGTT) was performed at baseline and every 6 months during the 5-year follow-up period. The percentile values of C-peptide after baseline OGTT were estimated according to age, BMI Z score (BMIZ), and/or sex categories. Conditional quantile regression was used to examine the relationship between C-peptide percentiles and various independent variables.The basal and stimulated C-peptide levels increased significantly as age and BMIZ increased (P < 0.05). Both age and BMIZ had a stronger impact on the upper quartile of C-peptide distributions than the lower quartile. Sex was only significantly associated with stimulated C-peptide. Higher stimulated C-peptide levels were generally observed in girls compared with boys at the same age and BMIZ (P < 0.05). HLA type and number of positive antibodies and antibody titers (islet cell antibody [ICA], insulin autoantibody, GAD65A, and ICA512A) were not significantly associated with C-peptide distribution after adjustment for age, BMIZ, and sex.Age-, sex-, and BMIZ-specific C-peptide percentiles can be estimated for North American children and adolescents at risk for T1D. They can be used as an assessment tool that could impact the recommendations in T1D prevention trials.
Response to neoadjuvant chemotherapy in lobular and ductal breast carcinomas: a retrospective study on 860 patients from one institution
Authors: M. Tubiana-Hulin, D. Stevens, S. Lasry, J.M. Guinebretière, L. Bouita, C. Cohen-Solal, P. Cherel, J. Rouëssé
Journal: Annals of Oncology (2006)
miR-107 promotes tumor progression by targeting the let-7 microRNA in mice and humans
Authors: Pai-Sheng Chen, Jen-Liang Su, Shih-Ting Cha, Woan-Yuh Tarn, Ming-Yang Wang, Hsing-Chih Hsu, Ming-Tsan Lin, Chia-Yu Chu, Kuo-Tai Hua, Chiung-Nien Chen, Tsang-Chih Kuo, King-Jen Chang, Michael Hsiao, Yi-Wen Chang, Jin-Shing Chen, Pan-Chyr Yang, Min-Liang Kuo
Journal: Journal of Clinical Investigation (2011)

MicroRNAs (miRNAs) influence many biological processes, including cancer. They do so by posttranscriptionally repressing target mRNAs to which they have sequence complementarity. Although it has been postulated that miRNAs can regulate other miRNAs, this has never been shown experimentally to our knowledge. Here, we demonstrate that miR-107 negatively regulates the tumor suppressor miRNA let-7 via a direct interaction. miR-107 was found to be highly expressed in malignant tissue from patients with advanced breast cancer, and its expression was inversely correlated with let-7 expression in tumors and in cancer cell lines. Ectopic expression of miR-107 in human cancer cell lines led to destabilization of mature let-7, increased expression of let-7 targets, and increased malignant phenotypes. In contrast, depletion of endogenous miR-107 dramatically increased the stability of mature let-7 and led to downregulation of let-7 targets. Accordingly, miR-107 expression increased the tumorigenic and metastatic potential of a human breast cancer cell line in mice via inhibition of let-7 and upregulation of let-7 targets. By mutating individual sites within miR-107 and let-7, we found that miR-107 directly interacts with let-7 and that the internal loop of the let-7/miR-107 duplex is critical for repression of let-7 expression. Altogether, we have identified an oncogenic role for miR-107 and provide evidence of a transregulational interaction among miRNAs in human cancer development.
In vitro and in vivo analysis of a JAK inhibitor in rheumatoid arthritis
Authors: Y Tanaka, Y Maeshima, K Yamaoka
Journal: Annals of the Rheumatic Diseases (2012)

Multiple cytokines play a pivotal role in the pathogenesis of rheumatoid arthritis (RA). The appropriate intracellular signalling pathways must be activated via cytokine receptors on the cell surface, and the tyrosine kinases transduce the first 'outside to in' signals to be phosphorylated after receptor binding to its ligand. Among them, members of the Janus kinase (JAK) family are essential for the signalling pathways of various cytokines and are implicated in the pathogenesis of RA. The in vitro, ex vivo and in vivo effects of a JAK inhibitor CP-690,550 (tofacitinib) for the treatment of RA are reported. In vitro experiments indicated that the effects of tofacitinib were mediated through suppression of interleukin 17 (IL-17) and interferon γ production and proliferation of CD4 T cells, presumably Th1 and Th17. A treatment study was conducted in the severe combined immunodeficiency (SCID)-HuRAg mice, an RA animal model using SCID mice implanted with synovium and cartilage from patients. Tofacitinib reduced serum levels of human IL-6 and IL-8 in the mice and also reduced synovial inflammation and invasion into the implanted cartilage. A phase 2 double-blind study using tofacitinib was carried out in Japanese patients with active RA and inadequate response to methotrexate (MTX). A total of 140 patients were randomised to tofacitinib 1, 3, 5, 10 mg or placebo twice daily and the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12, a primary end point, was significant for all tofacitinib treatment groups. Thus, an orally available tofacitinib in combination with MTX was efficacious and had a manageable safety profile. Tofacitinib at 5 and 10 mg twice a day appears suitable for further evaluation to optimise the treatment of RA.