tbuckley/cabot-search huggingface dataset:
Recovery of CD8+ T-Cell Function During Systemic Chemotherapy in Advanced Ovarian Cancer
Authors: Sharon Coleman, Aled Clayton, Malcolm D. Mason, Bharat Jasani, Malcolm Adams, Zsuzsanna Tabi
Journal: Cancer Research (2005)

Abstract Immunologic approaches are emerging as new treatment options in several types of cancer. However, whereas the ability of patients to develop potent CD8+ T-cell responses is crucial for efficient antitumor responses, immunocompetence and T-cell function are not tested routinely in patients entering immunotherapy. The objective of our study was to monitor T-cell function in advanced cancer and during chemotherapy. CD8+ T-cell function of 21 patients with advanced ovarian cancer (stages III-IV) was assessed by cytokine flow cytometry following stimulation of 42 PBMC samples with a panel of synthetic viral peptides in vitro, consisting of pan-Caucasian epitopes. CD8+ T-cell responses were significantly lower in patients with high levels (&amp;gt;200 units/mL) of Ca125 (marker of tumor load and progression) than in those with low Ca125 levels (P = 0.0013). In longitudinal studies of nine patients, chemotherapy was associated with decreasing Ca125 levels in seven cases and also with improvement or maintenance of CD8+ T-cell function in seven cases. After the full course of chemotherapy, five of nine patients in remission displayed potent CD8+ T-cell responses, whereas four of nine patients in progression displayed low or decreasing T-cell responses, pointing toward a correlation between T-cell function and clinical response. Our results show for the first time that CD8+ T-cell function is not permanently suppressed in advanced cancer and successful chemotherapy is associated with improved antigen-specific T-cell reactivity. We suggest that functional assays determining T-cell immunocompetence can be valuable tools for optimizing cancer immunotherapy for improved clinical success.
Non-tuberculous mycobacteria in extra-pulmonary specimens: Role of nosocomial transmission
Authors: Imran Ahmed, Kauser Jabeen, Muhammad Irfan, Rumina Hasan
Journal: European Respiratory Journal (2014)

Background:  Non-tuberculous mycobacteria (NTM) are ubiquitous in nature and cause infections in both immuno-compromised patients and immuno-competent individuals. Healthcare associated NTM infections have been reported wordwide. Treatment of NTM infections requires determination of clinical significance, identification and susceptibility profile. From Pakistan there is lack of data on healthcare associated NTM infections. This study was performed to determine NTM isolates and their clinical significance from extra-pulmonary clinical specimens submitted at a tertiary care hospital laboratory.   Methods:  NTM isolated from 25955 clinical specimens over a period of 24 months (January 2010 to December 2011) were included. All NTM were identified using conventional tests. Clinical details were extracted from laboratory data. Drug susceptibility testing (DST) was performed by broth microdilution and interpreted according to Clinical and Laboratory Standards Institute9s document M24-A2.   Results:  A total of 12 NTM were isolated from extra-pulmonary specimens over the study period. Of these 8 were rapidly growing mycobacteria (RGM) and 4 were slow growing mycobacteria (SGM). Clinical significance could be determined in 9/12 specimens. Seven NTM isolates from 3 patients were post-surgical and likely to be healthcare associated infections.   Conclusion:  This is the first study reporting healthcare associated NTM infections from extra-pulmonary clinical specimens from Pakistan. Isolation of NTM from clinical specimens should prompt to evaluate their clinical significance. Healthcare associated NTM infections should be suspected in non-healing post-surgical wounds.
Overall Genomic Pattern Is a Predictor of Outcome in Neuroblastoma
Authors: Isabelle Janoueix-Lerosey, Gudrun Schleiermacher, Evi Michels, Véronique Mosseri, Agnès Ribeiro, Delphine Lequin, Joëlle Vermeulen, Jérôme Couturier, Michel Peuchmaur, Alexander Valent, Dominique Plantaz, Hervé Rubie, Dominique Valteau-Couanet, Caroline Thomas, Valérie Combaret, Raphaël Rousseau, Angelika Eggert, Jean Michon, Frank Speleman, Olivier Delattre
Journal: Journal of Clinical Oncology (2009)

Purpose For a comprehensive overview of the genetic alterations of neuroblastoma, their association and clinical significance, we conducted a whole-genome DNA copy number analysis. Patients and Methods A series of 493 neuroblastoma (NB) samples was investigated by array-based comparative genomic hybridization in two consecutive steps (224, then 269 patients). Results Genomic analysis identified several types of profiles. Tumors presenting exclusively whole-chromosome copy number variations were associated with excellent survival. No disease-related death was observed in this group. In contrast, tumors with any type of segmental chromosome alterations characterized patients with a high risk of relapse. Patients with both numerical and segmental abnormalities clearly shared the higher risk of relapse of segmental-only patients. In a multivariate analysis, taking into account the genomic profile, but also previously described individual genetic and clinical markers with prognostic significance, the presence of segmental alterations with (HR, 7.3; 95% CI, 3.7 to 14.5; P &lt; .001) or without MYCN amplification (HR, 4.5; 95% CI, 2.4 to 8.4; P &lt; .001) was the strongest predictor of relapse; the other significant variables were age older than 18 months (HR, 1.8; 95% CI, 1.2 to 2.8; P = .004) and stage 4 (HR, 1.8; 95% CI, 1.2 to 2.7; P = .005). Finally, within tumors showing segmental alterations, stage 4, age, MYCN amplification, 1p and 11q deletions, and 1q gain were independent predictors of decreased overall survival. Conclusion The analysis of the overall genomic pattern, which probably unravels particular genomic instability mechanisms rather than the analysis of individual markers, is essential to predict relapse in NB patients. It adds critical prognostic information to conventional markers and should be included in future treatment stratification.
The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings
Authors: G. Cavaletti, D.R. Cornblath, I.S.J. Merkies, T.J. Postma, E. Rossi, B. Frigeni, P. Alberti, J. Bruna, R. Velasco, A.A. Argyriou, H.P. Kalofonos, D. Psimaras, D. Ricard, A. Pace, E. Galiè, C. Briani, C. Dalla Torre, C.G. Faber, R.I. Lalisang, W. Boogerd, D. Brandsma, S. Koeppen, J. Hense, D. Storey, S. Kerrigan, A. Schenone, S. Fabbri, M.G. Valsecchi, A. Mazzeo, A. Pace, A. Pessino, A. Schenone, A. Toscano, A.A. Argyriou, B. Brouwer, B. Frigeni, B. Piras, C. Briani, C. Dalla Torre, C. Dominguez Gonzalez, C.G. Faber, C. Tomasello, D. Binda, D. Brandsma, D. Cortinovis, D. Psimaras, D. Ricard, D. Storey, D.R. Cornblath, E. Galiè, E. Lindeck Pozza, E. Rossi, E.K. Vanhoutte, F. Lanzani, F. Pastorelli, G. Altavilla, G. Cavaletti, G. Granata, H.P. Kalofonos, I. Ghignotti, I.S.J. Merkies, J. Bruna, J. Hense, J.J. Heimans, L. Mattavelli, L. Padua, L. Reni, M. Bakkers, M. Boogerd, M. Campagnolo, M. Cazzaniga, M. Eurelings, M. Leandri, M. Lucchetta, M. Penas Prado, M. Russo, M.G. Valsecchi, M.L. Piatti, P. Alberti, P. Bidoli, R. Grant, R. Plasmati, R. Velasco, R.I. Lalisang, R.J. Meijer, S. Fabbri, S.G. Dorsey, S. Galimberti, S. Kerrigan, S. Koeppen, T.J. Postma, W. Boogerd, W. Grisold
Journal: Annals of Oncology (2012)
Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease
Authors: Ilaria Croci, Nuala M Byrne, Stéphane Choquette, Andrew P Hills, Veronique S Chachay, Andrew D Clouston, Trisha M O'Moore-Sullivan, Graeme A Macdonald, Johannes B Prins, Ingrid J Hickman
Journal: Gut (2012)

We set ourselves very high standards at work and when there is a sense that somehow we have failed, we are left feeling disappointed and frustrated. We all set very high standards for ourselves. When those feelings are exacerbated by the embarrassment of a public dressing down, especially if there isn’t an opportunity to explain just how difficult the situation had been, we are left feeling angry and let down. Most of us learn how a bully behaves in the playground or at nursery school—and yet, when it happens as an adult at work we often fail to realise what is happening. Harassment or undermining behaviour can be more challenging to identify because it isn’t always obvious and can happen without colleagues being aware. Sometimes, it isn’t even apparent to those who experience it, until an event means the problem becomes overwhelming. In fact, many people who experience undermining at work perceive the problem as their own and this can have a far more insidious impact on well-being, professional performance and mental health.
Effects of 8 Weeks of Flexibility and Resistance Training in Older Adults With Type 2 Diabetes
Authors: Matthew T. Herriott, Sheri R. Colberg, Henri K. Parson, Tanja Nunnold, Aaron I. Vinik
Journal: Diabetes Care (2004)

Flexibility is often downplayed as unimportant to fitness. However, flexibility training is imperative to maintain full range of motion (ROM) of joints, particularly in individuals with type 2 diabetes, who may experience limited joint mobility due to glycation of joint structures (1). Maladies such as “frozen shoulder” are common complaints in type 2 diabetes (2).

Conflicting evidence exists about the effect of resistance training on flexibility. For healthy adults, such training will improve flexibility as long as exercises incorporate a full ROM, opposing muscle groups (agonist and antagonist) are trained, and flexibility exercises are done. However, combined strength and flexibility training may not be as effective as flexibility training alone for improving joint ROM in shoulder abduction (3), although strength training alone may increase it (4). Thus, the purpose of this study was to determine whether 8 weeks of combined training improves flexibility in older adults with and without type 2 diabetes.

Nine individuals with type 2 diabetes (5 men and 4 women) and 10 sedentary control subjects (6 men and 4 women) participated. The mean age for the two groups (type 2 diabetic and control subjects) was 50.6 ± 2.8 and 54.7 ± 2.8 years, respectively, and BMI was similar prior to training (32.0 ± 2.4 and 33.1 ± 1.4 kg/m …
Maintenance Phase Efficacy of Sertraline for Chronic Depression&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Martin B. Keller
Journal: JAMA (1998)

Context.—The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness.Objective.—To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression").Design.—A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996.Setting.—Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers.Intervention.—Maintenance treatment with either sertraline hydrochloride (n=77) in flexible doses up to 200 mg or placebo (n=84).Patients.—A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase.Main Outcome Measure.—Time to recurrence of major depression.Results.—Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P=.002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P=.001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P=.005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata.Conclusions.—Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients.
Persistent tactile allodynia and spinal glia activation in the K/BxN serum transfer arthritis model
Authors: C A Christianson, M Corr, G S Firestein, T L Yaksh, C I Svensson
Journal: Annals of the Rheumatic Diseases (2010)

Chronic pain is a major health problem affecting approximately 20% of the population resulting in marked reduced quality of life for the individual, as well as extensive costs for society. A large-scale survey undertaken in 15 European countries showed that 40% of the people who reported persistent pain (>6 months) had joint pain and that osteoarthritis (OA) and rheumatoid arthritis (RA) combined was the most common cause of pain (42%). 1 Preclinical studies of pain mechanisms in RA have …
Heparin increases hillock formation in mesangial cell cultures.
Authors: S H Ayo, J I Kreisberg
Journal: Journal of the American Society of Nephrology (1991)

Mesangial cells in culture develop hillocks, which are composed of aggregates of cells, necrotic cellular debris, and extracellular matrix material. The significance and mechanism of their formation are unknown. To determine whether a proliferative component is involved in hillock formation, cells were treated with heparin or irradiated to inhibit proliferation. Heparin caused a 50% inhibition of mesangial cell growth and stimulated hillock formation three-fold to fourfold. Irradiated cells developed hillocks to the same extent as did nonirradiated cells, and the addition of heparin also increased hillock formation threefold to fourfold. Dextran sulfate and chondroitin B sulfate had no effect on mesangial cell hillock formation. Mesangial cells cultured in the presence of 50 micrograms/mL of heparin were less tightly adhered than nontreated cells, as assessed by a trypsin adhesion assay (control cells, 12% detached; heparin-treated cells, 72% detached). Thus, it appears that heparin, a glycosaminoglycan with potent antimitogenic activity, stimulates mesangial cell hillock formation, possibly by decreasing cell adhesion.
RELATION OF CHROMOSOME 4 (LINKAGE GROUP VIII) TO MURINE LEUKEMIA VIRUS-ASSOCIATED ANTIGENS OF AKR MICE
Authors: H. Ikeda, E. Stockert, W. P. Rowe, E. A. Boyse, F. Lilly, H. Sato, S. Jacobs, L. J. Old
Journal: The Journal of Experimental Medicine (1973)

Genes specifying or controlling the expression of G(IX) (cell surface), GCSA (cell surface), and gs (internal viral) antigens are located in chromosome 4 (linkage group [LG] VIII) of the AKR mouse. All three antigens may exhibit mendelian inheritance, mice being antigen positive or antigen negative, but each may also appear in leukemic cells of mice whose inherited genotype was antigen negative. The G(IX)-determining gene in LG VIII of AKR mice apparently is equivalent to Gv-1, which determines expression of the same antigen in 129 strain mice, but which in the latter strain is located in LG IX. As the estimated distance of Gv-1 from H-2 in 129 mice is considerable (37 units) further tests are now indicated to assess the possibility of pseudolinkage in this case. The Fv-1 locus, also located in LG VIII, influences the mouse's titer of MuLV, and might thereby be thought to regulate the G(IX) and gs phenotypes of AKR backcross segregants. But the data indicate a discrete LG VIII locus for G(IX), since expression of this antigen is mendelian and independent of infectious virus titer. Since the G(IX) and GCSA phenotypes of AKR backcross segregants were invariably concordant, these two antigens must be specified or controlled by closely linked genes, and the latter also is presumably independent of virus titer. The question as to what extent expression of gs antigen in the segregants is secondary to virus production is undecided.
Surgical versus conservative treatment for high-risk stress fractures of the lower leg (anterior tibial cortex, navicular and fifth metatarsal base): a systematic review
Authors: Wouter H Mallee, Hanneke Weel, C Niek van Dijk, Maurits W van Tulder, Gino M Kerkhoffs, Chung-Wei Christine Lin
Journal: British Journal of Sports Medicine (2014)

Aim To compare surgical and conservative treatment for high-risk stress fractures of the anterior tibial cortex, navicular and proximal fifth metatarsal. Methods Systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, SPORTDiscus and PEDro were performed to identify relevant prospective and retrospective studies. Two reviewers independently extracted data and assessed methodological quality. Main outcomes were return to sport and complication rate. Results 18 studies were included (2 anterior tibia (N=31), 8 navicular (N=200) and 8 fifth metatarsal (N=246)). For anterior tibial fracture, no studies on initial surgery were eligible. Conservative treatment resulted in high complication rates and few cases returned to sport. For navicular fracture, a weighted mean return to sport of 22 for conservative and 16 weeks for surgical treatment was found. Six weeks of non-weightbearing cast was mostly used as conservative treatment. Surgical procedures varied widely. For the fifth metatarsal fracture, weighted mean return to sport was 19 for conservative and 14 weeks for surgical treatment. Surgery consisted of intramedullary screw fixation or tension band wiring. For conservative methods, insufficient details were reported. Overall, there was a high risk of bias; sample sizes were small and GRADE level of evidence was low. Conclusions Strong conclusions for surgical or conservative therapy for these high-risk stress fractures cannot be drawn; quality of evidence is low and subjected to a high risk of bias. However, there are unsatisfying outcomes of conservative therapy in the anterior tibia. The role of initial surgery is unknown. For the navicular, surgery provided an earlier return to sport; and when treated conservatively, weightbearing should be avoided. For the fifth metatarsal, surgery provided the best results. Treatment decision-making would greatly benefit from further prospective research. Study registration number PROSPERO database of systematic reviews: CRD42013004201.
Cardiovascular Phenotype in Turner Syndrome—Integrating Cardiology, Genetics, and Endocrinology
Authors: Kristian H. Mortensen, Niels H. Andersen, Claus H. Gravholt
Journal: Endocrine Reviews (2012)

Cardiovascular disease is emerging as a cardinal trait of Turner syndrome, being responsible for half of the 3-fold excess mortality. Turner syndrome has been proposed as an independent risk marker for cardiovascular disease that manifests as congenital heart disease, aortic dilation and dissection, valvular heart disease, hypertension, thromboembolism, myocardial infarction, and stroke. Risk stratification is unfortunately not straightforward because risk markers derived from the general population inadequately identify the subset of females with Turner syndrome who will suffer events. A high prevalence of endocrine disorders adds to the complexity, exacerbating cardiovascular prognosis. Mounting knowledge about the prevalence and interplay of cardiovascular and endocrine disease in Turner syndrome is paralleled by improved understanding of the genetics of the X-chromosome in both normal health and disease. At present in Turner syndrome, this is most advanced for the SHOX gene, which partly explains the growth deficit. This review provides an up-to-date condensation of current state-of-the-art knowledge in Turner syndrome, the main focus being cardiovascular morbidity and mortality. The aim is to provide insight into pathogenesis of Turner syndrome with perspectives to advances in the understanding of genetics of the X-chromosome. The review also incorporates important endocrine features, in order to comprehensively explain the cardiovascular phenotype and to highlight how raised attention to endocrinology and genetics is important in the identification and modification of cardiovascular risk.
Tregs and rethinking cancer immunotherapy
Authors: Tyler J. Curiel
Journal: Journal of Clinical Investigation (2007)

Tumors express antigens that should induce immune-mediated rejection, but spontaneous rejection of established tumors is rare. Recent work demonstrates that one reason for the lack of tumor rejection is that tumors actively defeat host immunity. This concept forces us to rethink current approaches to harnessing potent, specific host immunity to battle cancer, most of which are based on the paradigm that inducing more antitumor immune cells alone is therapeutic. However, as I discuss in this Personal Perspective, a newer paradigm predicts that reducing tumor-driven immune suppression will be clinically beneficial. CD4+CD25+ Tregs are one mechanism of tumor-driven immune evasion that provide prototypical targets for testing novel anticancer treatment strategies within the newer paradigm.
Validation of Steady-State Insulin Sensitivity Indices in Chronic Kidney Disease
Authors: Michael F. Crutchlow, Bruce Robinson, Binu Pappachen, Neil Wimmer, Andrew J. Cucchiara, Debbie Cohen, Raymond Townsend
Journal: Diabetes Care (2007)

Insulin resistance may contribute to cardiovascular disease and the progression of renal insufficiency in patients with chronic kidney disease (CKD). However, feasible methods for estimating insulin sensitivity in large-population CKD studies have not been validated. The purpose of this study was to attempt to validate several commonly used steady-state insulin sensitivity (SI-SS) indices in a CKD population.Twenty-seven subjects with estimated glomerular filtration rate (eGFR) ranging from 70 to <10 ml/min per 1.73 m2 (median eGFR = 48) underwent a frequently sampled intravenous glucose tolerance test (FSIVGTT) on a single occasion. Correlations were obtained between the minimal model-derived insulin sensitivity parameter from the FSIVGTT (SI-FSIVGTT) and seven SI-SS indices derived from fasting insulin and glucose data obtained just before the FSIVGTT.Each of the seven steady-state indices was significantly correlated with SI-FSIVGTT. For indices obtained using the mean of four fasting insulin and glucose values over 15 min, Pearson correlation coefficients (|r|) ranged from 0.51 to 0.87 (P < 0.01 for each). For indices using single fasting insulin and glucose values, |r| ranged from 0.51 to 0.72 (P < 0.01 for each). By both the four and one time point approaches, 1/I(0) had the highest correlation with SI-FSIVGTT. The correlation with SI-FSIVGTT did not change significantly according to eGFR level for any of the SI-SS indices.SI-SS indices are valid surrogates for SI-FSIVGTT in the CKD population. Their use will expand the range of testable hypotheses in CKD cohort studies.