tbuckley/cabot-search huggingface dataset:
Brain Structure and Function Differences in Monozygotic Twins: Possible Effects of Breast Cancer Chemotherapy
Authors: Robert J. Ferguson, Brenna C. McDonald, Andrew J. Saykin, Tim A. Ahles
Journal: Journal of Clinical Oncology (2007)

Adjuvant chemotherapy has been associated with mild cognitive decline among a subset of breast cancer survivors. Late cognitive effects after chemotherapy can have a deleterious impact on survivor quality of life and functional health; however, the etiology of chemotherapy-related cognitive dysfunction remains unknown.We present a case of monozygotic twins who are discordant for breast cancer and chemotherapy exposure (ie, one twin contracted breast cancer and underwent chemotherapy, and the other had no breast cancer). As part of a larger study, each was evaluated with standardized, self-report measures of cognitive function, standard neuropsychological tests, and structural and functional magnetic resonance imaging (MRI).Results indicated small differences in neuropsychological test performance but striking contrasts in self-reported cognitive complaints and structural and functional MRI images. Specifically, the twin who underwent chemotherapy had substantially more subjective cognitive complaints, more white matter hyperintensities on MRI, and an expanded spatial extent of brain activation during working memory processing than her nonaffected twin.This case illustrates possible physiologic mechanisms that could produce long-term cognitive complaints among chemotherapy recipients and help formulate hypotheses for further empirical study in the area of chemotherapy-associated cognitive dysfunction.
MinK-Related Peptide 1 Associates With Kv4.2 and Modulates Its Gating Function
Authors: Mei Zhang, Min Jiang, Gea-Ny Tseng
Journal: Circulation Research (2001)

Abstract —Inherited mutations and a polymorphism in minK-related peptide 1 (MiRP1) have been linked to congenital or acquired long-QT syndrome, pointing to the importance of MiRP1 in maintaining the cardiac electrical stability. We tested whether MiRP1 could affect the function of Kv4.x (x=2 and 3), the major pore-forming (α) subunits of transient outward ( I to ) channels in the heart. We used the Xenopus oocyte expression system to examine the effects of MiRP1 on Kv4.x channel gating kinetics and current amplitude and correlated these effects with MiRP1 expression level. MiRP1 slowed the rates of Kv4.2 activation and inactivation and shifted the voltage dependence of channel gating in the positive direction. These effects had a similar “dose” dependence: they plateaued at a cRNA ratio (MiRP1:Kv4.2) of 13:1, with half-maximum effects at estimated cRNA ratios of 2 to 4. On the other hand, MiRP1 had no significant effects on Kv4.2 current amplitude in the same range of expression level. When expressed at a comparable low level, MiRP1 had similar (although smaller) effects on Kv4.3 but could not modulate Kv1.4 (another α subunit of I to channels in the heart). Kv4.2 could be coimmunoprecipitated with epitope-tagged MiRP1, indicating that the 2 could form a stable complex. Our data suggest that MiRP1 may serve as a regulatory (β) subunit of I to channels in the heart. This is supported by the observation that MiRP1 induced an “overshoot” of Kv4.2 current amplitude during channel recovery from inactivation, similar to the overshoot of I to described for human epicardial myocytes.
Triglycerides and total serum cholesterol in rotator cuff tears: do they matter?
Authors: U G Longo, F Franceschi, F Spiezia, F Forriol, N Maffulli, V Denaro
Journal: British Journal of Sports Medicine (2009)

In this study, the serum triglycerides and total serum cholesterol levels in patients with rotator cuff tear were determined.Frequency-matched case-control study. Setting University teaching hospital.240 individuals who were operated on at our institution were included in the study. 120 patients (45 men and 75 women; mean age 64.86 years, range 40 to 83 years) who underwent arthroscopic repair of a rotator cuff tear were included in group 1. 120 patients (45 men and 75 women; mean age 63.91 years, range 38 to 78 years) who underwent arthroscopic meniscectomy for a meniscal tear and had no evidence of shoulder pathology were included in group 2 (control group). These patients were frequency-matched by age (within 3 years) and sex with patients of group 1.Measurement of serum triglyceride and total cholesterol concentrations.When comparing the two groups, there was no difference either in serum triglyceride concentration or total serum cholesterol concentration.There appears to be no association between serum triglyceride concentration and total serum cholesterol concentration in rotator cuff tears.
Serum Protein MALDI Profiling to Distinguish Upper Aerodigestive Tract Cancer Patients From Control Subjects
Authors: D. Sidransky
Journal: JNCI Journal of the National Cancer Institute (2003)

There are no reliable blood markers for the early detection and monitoring of aerodigestive tract tumors. Recent studies have suggested that serum protein patterns may be able to distinguish cancer patients from control subjects.We used matrix-assisted laser desorption and ionization (MALDI) mass spectroscopy to obtain serum protein patterns from patients with head and neck cancer (n = 99) or lung cancer (n = 92) and from control subjects (n = 143) at risk for the development of these cancers. From the mass spectra, we predicted the cancer status of patients using a simple classification procedure based on a t test feature selection and linear discriminant analysis (LDA). We cross-validated the data with 200 random data simulations to establish a range of the LDA tuning parameter, which was used to construct receiver operating characteristic (ROC) curves.Average total protein levels were higher in case patients than in control subjects, although the differences were not statistically significant. Ten individual m/z peaks, from 5 to 111 kd, appeared frequently in head and neck cancer patients but not in control subjects. Using the 45 top predictors, selected by spectral mass and LDA, we observed that ROC curves differed from those expected under the null hypothesis, suggesting that spectral profiles from the sera of patients with head and neck cancer statistically significantly differed from the sera of control subjects. The model developed on head and neck cancer patients could also be used to identify patients with lung cancer.The pattern of protein spectra in total serum reliably distinguished cancer case patients from control subjects. Incorporation of MALDI assays into prospective longitudinal trials to assess the true predictive values of protein spectra in cancer detection is needed.
Double-Blind, Randomized Controlled Trial on the Effect of Leukocyte-Depleted Erythrocyte Transfusions in Cardiac Valve Surgery
Authors: Y.M. Bilgin, L.M.G. van de Watering, L. Eijsman, M.I.M. Versteegh, R. Brand, M.H.J. van Oers, A. Brand
Journal: Circulation (2004)

Background— Leukocytes in allogeneic blood transfusions are believed to be the cause of immunomodulatory events. A few trials on leukocyte removal from transfusions in cardiac surgery have been conducted, and they showed inconclusive results. We found in a previous study a decrease in mortality rates and number of infections in a subgroup of more heavily transfused patients. Methods and Results— Patients (n=496) undergoing valve surgery (with or without CABG) were randomly assigned in a double-blind fashion to receive standard buffy coat–depleted (PC) or prestorage, by filtration, leukocyte-depleted erythrocytes (LD). The primary end point was mortality at 90 days, and secondary end points were in-hospital mortality, multiple organ dysfunction syndrome, infections, intensive care unit stay, and hospital stay. The difference in mortality at 90 days was not significant (PC 12.7% versus LD 8.4%; odds ratio [OR], 1.52; 95% confidence interval [CI], 0.84 to 2.73). The in-hospital mortality rate was almost twice as high in the PC group (10.1% versus 5.5% in the LD group; OR, 1.99; 95% CI, 0.99 to 4.00). The incidence of multiple organ dysfunction syndrome in both groups was similar, although more patients with multiple organ dysfunction syndrome died in the PC group. LD was associated with a significantly reduced infection rate (PC 31.6% versus LD 21.6%; OR, 1.64; 95% CI, 1.08 to 2.49). In both groups, intensive care unit stay and hospital stay were similar, and postoperative complications increased with the number of transfused units. Conclusions— Mortality at 90 days was not significantly different; however, a beneficial effect of LD in valve surgery was found for the secondary end points of in-hospital mortality and infections.
Safety of Yttrium-90 Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed Low-Grade, Follicular, or Transformed Non-Hodgkin’s Lymphoma
Authors: Thomas E. Witzig, Christine A. White, Leo I. Gordon, Gregory A. Wiseman, Christos Emmanouilides, James L. Murray, John Lister, Pratik S. Multani
Journal: Journal of Clinical Oncology (2003)

Radioimmunotherapy (RIT) with yttrium-90 ((90)Y)-labeled anti-CD20 antibody ((90)Y ibritumomab tiuxetan; Zevalin, IDEC Pharmaceuticals Corporation, San Diego, CA) has a high rate of tumor response in patients with relapsed or refractory, low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL). This study presents the safety data from 349 patients in five studies of outpatient treatment with (90)Y ibritumomab tiuxetan.Patients received rituximab 250 mg/m(2) on days 1 and 8, and either 0.4 mCi/kg (15 MBq/kg) or 0.3 mCi/kg (11 MBq/kg) of (90)Y ibritumomab tiuxetan on day 8 (maximum dose, 32 mCi). Patients were observed for up to 4 years after therapy or until progressive disease.Infusion-related toxicities were typically grade 1 or 2 and were associated with rituximab. No significant organ toxicity was noted. Toxicity was primarily hematologic, with nadir counts occurring at 7 to 9 weeks and lasting approximately 1 to 4 weeks depending on the method of calculation. After the 0.4-mCi/kg dose, grade 4 neutropenia, thrombocytopenia, and anemia occurred in 30%, 10%, and 3% of patients, respectively, and after the 0.3-mCi/kg dose, these grade 4 toxicities occurred in 35%, 14%, and 8% of patients, respectively. The risk of hematologic toxicity increased with degree of baseline bone marrow involvement with NHL. Seven percent of patients were hospitalized with infection (3% with neutropenia) and 2% had grade 3 or 4 bleeding events. Myelodysplasia or acute myelogenous leukemia was reported in five patients (1%) 8 to 34 months after treatment.Single-dose (90)Y ibritumomab tiuxetan RIT has an acceptable safety profile in relapsed NHL patients with less than 25% lymphoma marrow involvement, adequate marrow reserve, platelets greater than 100,000 cells/ micro L, and neutrophils greater than 1,500 cells/ micro L.
The Revised CONSORT Statement for Reporting Randomized Trials: Explanation and Elaboration
Authors: Douglas G. Altman
Journal: Annals of Internal Medicine (2001)

Overwhelming evidence now indicates that the quality of reporting of randomized, controlled trials (RCTs) is less than optimal. Recent methodologic analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which boast the elimination of systematic error as their primary hallmark. Systematic error in RCTs reflects poor science, and poor science threatens proper ethical standards. A group of scientists and editors developed the CONSORT (Con solidated S tandards o f R eporting T rials) statement to improve the quality of reporting of RCTs. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have adopted the CONSORT statement. The CONSORT statement facilitates critical appraisal and interpretation of RCTs by providing guidance to authors about how to improve the reporting of their trials. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the CONSORT statement. The meaning and rationale for each checklist item are presented. For most items, at least one published example of good reporting and, where possible, references to relevant empirical studies are provided. Several examples of flow diagrams are included. The CONSORT statement, this explanatory and elaboration document, and the associated Web site ( http://www.consort-statement.org ) should be helpful resources to improve reporting of randomized trials. Throughout the text, terms marked with an asterisk are defined at end of text.
Appropriate Use of Screening and Diagnostic Tests to Foster High-Value, Cost-Conscious Care
Authors: Amir Qaseem, Patrick Alguire, Paul Dallas, Lawrence E. Feinberg, Faith T. Fitzgerald, Carrie Horwitch, Linda Humphrey, Richard LeBlond, Darilyn Moyer, Jeffrey G. Wiese, Steven Weinberger
Journal: Annals of Internal Medicine (2012)

Reader Survey: Which testing scenarios are low value? Unsustainable rising health care costs in the United States have made reducing costs while maintaining high-quality health care a national priority. The overuse of some screening and diagnostic tests is an important component of unnecessary health care costs. More judicious use of such tests will improve quality and reflect responsible awareness of costs. Efforts to control expenditures should focus not only on benefits, harms, and costs but on the value of diagnostic tests—meaning an assessment of whether a test provides health benefits that are worth its costs or harms. To begin to identify ways that practicing clinicians can contribute to the delivery of high-value, cost-conscious health care, the American College of Physicians convened a workgroup of physicians to identify, using a consensus-based process, common clinical situations in which screening and diagnostic tests are used in ways that do not reflect high-value care. The intent of this exercise is to promote thoughtful discussions about these tests and other health care interventions to promote high-value, cost-conscious care.
Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation
Authors: Alexander Pedroza-Gonzalez, Kangling Xu, Te-Chia Wu, Caroline Aspord, Sasha Tindle, Florentina Marches, Michael Gallegos, Elizabeth C. Burton, Daniel Savino, Toshiyuki Hori, Yuetsu Tanaka, Sandra Zurawski, Gerard Zurawski, Laura Bover, Yong-Jun Liu, Jacques Banchereau, A. Karolina Palucka
Journal: The Journal of Experimental Medicine (2011)

The human breast tumor microenvironment can display features of T helper type 2 (Th2) inflammation, and Th2 inflammation can promote tumor development. However, the molecular and cellular mechanisms contributing to Th2 inflammation in breast tumors remain unclear. Here, we show that human breast cancer cells produce thymic stromal lymphopoietin (TSLP). Breast tumor supernatants, in a TSLP-dependent manner, induce expression of OX40L on dendritic cells (DCs). OX40L+ DCs are found in primary breast tumor infiltrates. OX40L+ DCs drive development of inflammatory Th2 cells producing interleukin-13 and tumor necrosis factor in vitro. Antibodies neutralizing TSLP or OX40L inhibit breast tumor growth and interleukin-13 production in a xenograft model. Thus, breast cancer cell–derived TSLP contributes to the inflammatory Th2 microenvironment conducive to breast tumor development by inducing OX40L expression on DCs.
Female genital mutilation: the role of health professionals in prevention, assessment, and management
Authors: J. Simpson, K. Robinson, S. M. Creighton, D. Hodes
Journal: BMJ (2012)

#### Summary points Female genital mutilation (FGM), also known as female circumcision or cutting, is thought to affect 100-140 million women worldwide.1 It describes a range of procedures, often involving partial or total excision of the external female genitalia, that are carried out for non-medical reasons (box 1; figs 1-4⇓ ⇓ ⇓ ⇓).2 FGM breaches international human rights law, in particular the United Nations Convention on the Rights of the Child,3 and has been criminalised in much of the world, including many African countries in which it is traditionally practised. The United Kingdom is one of several Western countries that have enacted specific legislation in response to international migration (box 2).4 #### Box 1 Classification of female genital mutilation5
Stanniocalcin-1 Inhibits Renal Ischemia/Reperfusion Injury via an AMP-Activated Protein Kinase-Dependent Pathway
Authors: Jenny Szu-Chin Pan, Luping Huang, Tatiana Belousova, Lianghao Lu, Yongjie Yang, Roger Reddel, Andy Chang, Huiming Ju, Gabriel DiMattia, Qiang Tong, David Sheikh-Hamad
Journal: Journal of the American Society of Nephrology (2014)

AKI is associated with increased morbidity, mortality, and cost of care, and therapeutic options remain limited. Reactive oxygen species are critical for the genesis of ischemic AKI. Stanniocalcin-1 (STC1) suppresses superoxide generation through induction of uncoupling proteins (UCPs), and transgenic overexpression of STC1 inhibits reactive oxygen species and protects from ischemia/reperfusion (I/R) kidney injury. Our observations revealed high AMP-activated protein kinase (AMPK) activity in STC1 transgenic kidneys relative to wild-type (WT) kidneys; thus, we hypothesized that STC1 protects from I/R kidney injury through activation of AMPK. Baseline activity of AMPK in the kidney correlated with the expression of STCs, such that the highest activity was observed in STC1 transgenic mice followed (in decreasing order) by WT, STC1 knockout, and STC1/STC2 double-knockout mice. I/R in WT kidneys increased AMPK activity and the expression of STC1, UCP2, and sirtuin 3. Inhibition of AMPK by administration of compound C before I/R abolished the activation of AMPK, diminished the expression of UCP2 and sirtuin 3, and aggravated kidney injury but did not affect STC1 expression. Treatment of cultured HEK cells with recombinant STC1 activated AMPK and increased the expression of UCP2 and sirtuin 3, and concomitant treatment with compound C abolished these responses. STC1 knockout mice displayed high susceptibility to I/R, whereas pretreatment of STC1 transgenic mice with compound C restored the susceptibility to I/R kidney injury. These data suggest that STC1 is important for activation of AMPK in the kidney, which mediates STC1-induced expression of UCP2 and sirtuin 3 and protection from I/R.
Insulin-Mediated Acceleration of Breast Cancer Development and Progression in a Nonobese Model of Type 2 Diabetes
Authors: Ruslan Novosyadlyy, Danielle E. Lann, Archana Vijayakumar, Anne Rowzee, Deborah A. Lazzarino, Yvonne Fierz, Joan M. Carboni, Marco M. Gottardis, Patricia A. Pennisi, Alfredo A. Molinolo, Naamit Kurshan, Wilson Mejia, Stefania Santopietro, Shoshana Yakar, Teresa L. Wood, Derek LeRoith
Journal: Cancer Research (2010)

Abstract Epidemiologic studies suggest that type 2 diabetes (T2D) increases breast cancer risk and mortality, but there is limited experimental evidence supporting this association. Moreover, there has not been any definition of a pathophysiological pathway that diabetes may use to promote tumorigenesis. In the present study, we used the MKR mouse model of T2D to investigate molecular mechanisms that link T2D to breast cancer development and progression. MKR mice harbor a transgene encoding a dominant-negative, kinase-dead human insulin-like growth factor-I receptor (IGF-IR) that is expressed exclusively in skeletal muscle, where it acts to inactivate endogenous insulin receptor (IR) and IGF-IR. Although lean female MKR mice are insulin resistant and glucose intolerant, displaying accelerated mammary gland development and enhanced phosphorylation of IR/IGF-IR and Akt in mammary tissue, in the context of three different mouse models of breast cancer, these metabolic abnormalities were found to accelerate the development of hyperplastic precancerous lesions. Normal or malignant mammary tissue isolated from these mice exhibited increased phosphorylation of IR/IGF-IR and Akt, whereas extracellular signal-regulated kinase 1/2 phosphorylation was largely unaffected. Tumor-promoting effects of T2D in the models were reversed by pharmacological blockade of IR/IGF-IR signaling by the small-molecule tyrosine kinase inhibitor BMS-536924. Our findings offer compelling experimental evidence that T2D accelerates mammary gland development and carcinogenesis,and that the IR and/or the IGF-IR are major mediators of these effects. Cancer Res; 70(2); 741–51
Cyclophosphamide, Vincristine, Methotrexate with Leucovorin Rescue, and Cytarabine (COMLA) Combination Sequential Chemotherapy for Advanced Diffuse Histiocytic Lymphoma
Authors: DONALD L. SWEET
Journal: Annals of Internal Medicine (1980)

A program of combination sequential chemotherapy using cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) was administered to 42 previously untreated patients with advanced diffuse histiocytic lymphoma. Twenty-three patients achieved a complete remission as determined by strict clinical restaging criteria. The observed median duration of survival for the complete responders is longer than 33 months. Eight patients achieved a partial response, with a median survival longer than 21 months. Eleven patients showed no response, with a median survival of 5 months. Toxicity was acceptable. None of the responders have shown central nervous system relapse. There was no difference in response rates between patients with stage III or IV lymphoma or between asymptomatic or symptomatic patients. The COMLA program produces a high rate of complete and durable remissions and should be considered as an initial form of management of patients with advanced diffuse histiocytic lymphoma.
Chylothorax secondary to obstruction of the superior vena cava: a complication of the LeVeen shunt.
Authors: W H Warren, J S Altman, S A Gregory
Journal: Thorax (1990)

A case of thrombosis of the superior vena cava was complicated by bilateral chylothoraces and a widened mediastinum. Removal of a clotted LeVeen shunt led to prompt resolution of the obstruction and chylothoraces.