tbuckley/cabot-search huggingface dataset:
PWE-103 Vitamin D Deficiency in Crohns Disease and Ulcerative Colitis: Abstract PWE-103 Table
Authors: M S Mohammad, J Mayberry
Journal: Gut (2013)

<h3>Introduction</h3> The role of vitamin D in inflammation and its possible cancer protective effects are now coming to the fore. Inflammatory bowel disease (IBD) provides a model where both roles can be assessed. Early studies have indicated that vitamin D deficiency is common amongst patients with this condition. Leicester in the UK has a significant population of patients from both English and South Asian backgrounds and so allows comparisons to be made between people of different ethnicities and different experiences of vitamin D deficiency. <h3>Methods</h3> Vitamin D (25 OH D) status was measured in 148 consecutive patients with IBD, who attended the gastroenterology clinics during a period of one year (Jan to Dec 2011). Vitamin D levels were graded as severe deficiency (&lt; 15 nmol/l), moderate deficiency (16–30 nmol/l), insufficiency (31–50 nmol/l ), adequate (51–75 nmol/l), and ideal (&gt; 76 nmol/l). All case notes were reviewed and data analysed using χ2 statistic. <h3>Results</h3> 148 patients had IBD, 64% were women and 36% men. 93 patients (61%) with ulcerative colitis (UC) and 55 (39%) Crohns disease (CD). Of the 93 patients with UC, 50 were English and 43 South Asian. Of the 55 patients with CD, 43 were English and 12 of South Asian background. The proportions amongst both communities and across the disease groups were not significantly different when analysed with a χ2 statistics. <h3>Conclusion</h3> Vitamin D deficiency is common in all patients with inflammatory bowel disease. It plays a vital role in bone health, immune regulation and cancer prevention in IBD. The optimal target level of 25(OH) vitamin D in IBD patients is uncertain as is the best therapeutic modality. The precise threshold for 25(OH) vitamin D level is poorly defined in the literature and so is the dosing and duration of treatment. Its frequency is almost similar in South Asian and English patients with Crohn’s disease which suggests that mal-absorption of the vitamin may play a part in the vitamin D deficiency. In contrast it is commoner in South Asian patients with ulcerative colitis than amongst English patients and this warrants further investigation. It may suggest that in the future South Asian patients will be at greater risk of colonic carcinoma as a complication of ulcerative colitis. <h3>Disclosure of Interest</h3> None Declared.
Combined Bcl-2/Mammalian Target of Rapamycin Inhibition Leads to Enhanced Radiosensitization via Induction of Apoptosis and Autophagy in Non–Small Cell Lung Tumor Xenograft Model
Authors: Kwang Woon Kim, Luigi Moretti, Lauren Rhea Mitchell, Dae Kwang Jung, Bo Lu
Journal: Clinical Cancer Research (2009)

Radiotherapy has a central role in the treatment of non-small cell lung cancer. Effectiveness of this modality, however, is often limited as resistance results from defects in cell death.We investigated whether simultaneous up-regulation of apoptosis, via Bcl-2 inhibitor ABT-737, and autophagy, via mammalian target of rapamycin inhibitor rapamycin, can be used to enhance radiosensitivity of H460 cells in vitro and growth delay in a xenograft model.In vitro studies confirmed that ABT-737 and rapamycin induce apoptosis and autophagy, respectively. ABT-737 induced cleaved caspase-3, a marker of apoptosis, and rapamycin correlated with an increase in punctate localization of green fluorescent protein-LC3, characteristic of autophagy. The combination ABT-737/rapamycin markedly enhanced sensitivity of H460 cells to radiation (dose enhancement ratio = 2.47; P = 0.002) in clonogenic assay. In addition, the combination ABT-737/rapamycin/radiation showed a dramatic tumor growth delay in a mouse xenograft model. In vivo immunohistochemistry staining showed that combination therapy yielded over a 100% increase in caspase-3 activity (apoptosis) and a 6-fold decrease in p62 protein level (indicative of autophagic flux) compared with radiation alone control group. Moreover, cell proliferation (Ki-67 staining) was reduced by 77% (P = 0.001) and vascular density (von Willebrand factor staining) by 67.5% (P = 0.09) compared with radiation alone. Additional in vitro studies in human umbilical vein endothelial cells indicated that combined therapy also significantly decreases tubule formation.These results suggest that concurrent induction of apoptosis and autophagy enhances radiation therapy both in vitro and in lung cancer xenograft models. Further investigations are warranted to assess the clinical potential of such strategy in lung cancer patients.
<i>KEAP1</i> Genetic Polymorphisms Associate with Breast Cancer Risk and Survival Outcomes
Authors: Jaana M. Hartikainen, Maria Tengström, Robert Winqvist, Arja Jukkola-Vuorinen, Katri Pylkäs, Veli-Matti Kosma, Ylermi Soini, Arto Mannermaa
Journal: Clinical Cancer Research (2015)

Defective oxidative stress response may increase cancer susceptibility. In tumors, these rescue mechanisms may cause chemo- and radioresistance impacting patient outcome. We previously showed that genetic variation in the nuclear factor erythroid 2-related factor 2 (NFE2L2) is associated with breast cancer risk and prognosis. Here we further studied this pathway by investigating Kelch-like ECH-associated protein 1 (KEAP1).Five tagging SNPs in the KEAP1 gene were genotyped in 996 breast cancer cases and 880 controls from two Finnish case-control sets. KEAP1 protein expression was studied in 373 invasive breast cancer tumors.rs34197572 genotype TT was associated with increased risk of breast cancer in the KBCP samples [P = 1.8×10(-4); OR, 7.314; confidence interval (CI), 2.185-24.478]. rs11085735 allele A was associated with lower KEAP1 protein expression (P = 0.040; OR,= 3.545) and high nuclear NRF2 expression (P = 0.009; OR, 2.445) and worse survival in all invasive cases (P = 0.023; HR, 1.634). When including treatment data, rs11085735 was associated with recurrence-free survival (RFS; P = 0.020; HR, 1.545) and breast cancer-specific survival (P = 0.016; HR, 1.683) and rs34197572 with overall survival (P = 0.045; HR, 1.304). rs11085735 associated with RFS also among tamoxifen-treated cases (P = 0.003; HR, 3.517). Among radiotherapy-treated cases, overall survival was associated with rs34197572 (P = 0.018; HR, 1.486) and rs8113472 (P = 0.025; HR, 1.455). RFS was associated with rs9676881 (P = 0.024; HR, 1.452) and rs1048290 (P = 0.020; HR, 1.468) among all invasive cases and among estrogen receptor (ER)-positive tamoxifen-treated cases (P = 0.018; HR, 2.407 and P = 0.015; HR, 2.476, respectively).The present findings suggest that the investigated SNPs have effects related to oxidative stress induced by cancer treatment, supporting involvement of the NRF2/KEAP1 pathway in breast cancer susceptibility and patient outcome.
Hypersomnia as presenting symptom of anti-Ma2-associated encephalitis: Case study
Authors: Iñigo Rojas-Marcos, Francesc Graus, Gema Sanz, Arturo Robledo, Carlos Diaz-Espejo
Journal: Neuro-Oncology (2006)

We describe a patient who presented with excessive daytime sleepiness (EDS) and was eventually diagnosed with anti-Ma2 encephalitis. Neurological examination disclosed somnolence, left palpebral ptosis, and vertical gaze paresis. A brain MRI showed high signal intensity in the hypothalamus and each hippocampus. Ma2 antibodies were found in the patient's serum, and fiberbronchoscopy disclosed a lung carcinoma. After three months of steroid treatment, the results of the patient's neurological exam became normal. We conclude that anti-Ma2 encephalitis may present with mostly isolated EDS and that it may respond to steroids despite old age and the presence of an untreated lung cancer.
Oxidative stress and antioxidants: exposure and impact on female fertility
Authors: E. H. Ruder, T. J. Hartman, J. Blumberg, M. B. Goldman
Journal: Human Reproduction Update (2008)

BACKGROUNDReproductive failure is a significant public health concern. Although relatively little is known about factors affecting fertility and early pregnancy loss, a growing body of literature suggests that environmental and lifestyle factors play an important role. There is sufficient evidence to hypothesize that diet, particularly its constituent antioxidants, and oxidative stress (OS) may influence the timing and maintenance of a viable pregnancy. We hypothesize that conditions leading to OS in the female affect time-to-pregnancy and early pregnancy loss.
Successful Treatment of Cat-scratch Disease With Ciprofloxacin
Authors: H. Preston Holley
Journal: JAMA (1991)

Cat-scratch disease is usually a benign, self-limited disease. Infection may be asymptomatic but is commonly associated with painful regional lymphadenitis. Occasionally, disease may result in systemic symptoms and dissemination. Five adult patients, aged 24 to 57 years, were diagnosed as having cat-scratch disease, based on a positive history of cat scratches followed by typical symptoms including painful regional lymphadenitis, malaise, and positive cat-scratch skin tests. Diagnostic evaluations revealed no other cause for the lymphadenitis. Three patients had not received prior treatment with antibiotics, and two patients had failed to improve on other antibiotics. All five were treated with oral ciprofloxacin, 500 mg by mouth, twice daily. All patients had dramatic improvement in symptoms within a few days and none has relapsed during follow-up. This is the first report of successful treatment of cat-scratch disease with ciprofloxacin, which appears to be an effective therapy for cat-scratch disease in adults.
Phase II Study of Neoadjuvant Chemotherapy and Radiation Therapy in the Management of High-Risk, High-Grade, Soft Tissue Sarcomas of the Extremities and Body Wall: Radiation Therapy Oncology Group Trial 9514
Authors: William G. Kraybill, Jonathon Harris, Ira J. Spiro, David S. Ettinger, Thomas F. DeLaney, Ronald H. Blum, David R. Lucas, David C. Harmon, G. Douglas Letson, Burton Eisenberg
Journal: Journal of Clinical Oncology (2006)

On the basis of a positive reported single-institution pilot study, the Radiation Therapy Oncology Group initiated phase II trial 9514 to evaluate its neoadjuvant regimen in a multi-institutional Intergroup setting.Eligibility included a high-grade soft tissue sarcoma > or = 8 cm in diameter of the extremities and body wall. Patients received three cycles of neoadjuvant chemotherapy (CT; modified mesna, doxorubicin, ifosfamide, and dacarbazine [MAID]), interdigitated preoperative radiation therapy (RT; 44 Gy administered in split courses), and three cycles of postoperative CT (modified MAID).Sixty-six patients were enrolled, of whom 64 were analyzed. Seventy-nine percent of patients completed their preoperative CT and 59% completed all planned CT. Three patients (5%) experienced fatal grade 5 toxicities (myelodysplasias, two patients; infection, one patient). Another 53 patients (83%) experienced grade 4 toxicities; 78% experienced grade 4 hematologic toxicity and 19% experienced grade 4 nonhematologic toxicity. Sixty-one patients underwent surgery. Fifty-eight of these were R0 resections, of which five were amputations. There were three R1 resections. The estimated 3-year rate for local-regional failure is 17.6% if amputation is considered a failure and 10.1% if not. Estimated 3-year rates for disease-free, distant-disease-free, and overall survival are 56.6%, 64.5%, and 75.1%, respectively.This combined-modality treatment can be delivered successfully in a multi-institutional setting. Efficacy results are consistent with previous single-institution results.
Reproducible Quantification of Cancer-Associated Proteins in Body Fluids Using Targeted Proteomics
Authors: Ruth Hüttenhain, Martin Soste, Nathalie Selevsek, Hannes Röst, Atul Sethi, Christine Carapito, Terry Farrah, Eric W. Deutsch, Ulrike Kusebauch, Robert L. Moritz, Emma Niméus-Malmström, Oliver Rinner, Ruedi Aebersold
Journal: Science Translational Medicine (2012)

A compendium of SRM assays for cancer-associated proteins provides a resource for accelerating and planning biomarker verification studies.
Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients
Authors: E Truyen
Journal: Thorax (2006)

Asthma is a chronic inflammatory disorder of the airways driven by T cell activation. Th2 cells and their cytokines are thought to play a role in the pathophysiology of allergic as well as non-allergic asthma.Airway cells were obtained by sputum induction from 15 healthy and 39 asthmatic individuals and the airway T cell cytokine profiles (interleukin (IL)-4, IL-5, IL-13, IL-10 and interferon (IFN)-gamma) at the mRNA level were studied by real time RT-PCR.Asthma patients had increased expression of IL-5 (p = 0.001) and IL-13 (p = 0.03) mRNA in sputum compared with non-asthmatic controls. IL-4 mRNA and IFN-gamma mRNA were detectable in the sputum of 44% and 21% of patients, respectively, but not in controls. Sputum IL-10 mRNA levels did not differ significantly between patients and controls. Sputum mRNA expression levels of IL-4, IL-5, and IL-13 were significantly correlated with the percentage of eosinophils and were higher in subjects with allergic asthma than in those with non-allergic asthma (p = 0.03, p = 0.02 and p = 0.0002, respectively); they did not differ between mild asthmatic subjects and those with moderate to severe asthma. In contrast, IFN-gamma mRNA expression was higher in non-allergic than in allergic patients (p = 0.04) and higher in patients with moderate to severe asthma than in those with mild asthma (p<0.01). Sputum IL-5 mRNA levels (but not the other cytokine mRNA levels) were also correlated with exhaled nitric oxide (eNO) and with bronchial hyperreactivity expressed as the histamine concentration resulting in a 20% decrease in forced expiratory volume in 1 second.Real time RT-PCR analysis of mRNA in induced sputum confirms a predominance of Th2 cytokines in both allergic and non-allergic asthma. IL-5 levels reflect eosinophil infiltration as well as eNO levels and hyperreactivity, and levels of the Th1 cytokine IFN-gamma indicate asthma severity. The technique is a promising tool for use in further studies of asthma severity and disease activity.
NADPH Oxidase p22phox and Catalase Gene Variants Are Associated with Biomarkers of Oxidative Stress and Adverse Outcomes in Acute Renal Failure
Authors: Mary C. Perianayagam, Orfeas Liangos, Alexey Y. Kolyada, Ron Wald, Robert W. MacKinnon, Lijun Li, Madhumati Rao, Vaidyanathapuram S. Balakrishnan, Joseph V. Bonventre, Brian J. Pereira, Bertrand L. Jaber
Journal: Journal of the American Society of Nephrology (2006)

Reactive oxygen species are important mediators of injury in acute renal failure (ARF). Although polymorphisms that affect key pro- and antioxidant enzymes might alter the susceptibility to oxidative stress-mediated injury, the use of genetic epidemiology for the study of oxidative stress-related genes has received little attention in ARF. The relationship of single-nucleotide polymorphisms in the coding region (C to T substitution at position +242) of the pro-oxidant enzyme NADPH oxidase p22phox subunit gene and in the promoter region (C to T substitution at position -262) of the antioxidant enzyme catalase gene to adverse clinical outcomes was evaluated prospectively in a cohort of 200 hospitalized patients with established ARF of mixed cause and severity. Genomic DNA was extracted from peripheral blood leukocytes and analyzed with a restriction fragment length polymorphism PCR method. Genotype-phenotype associations were characterized by measuring circulating nitrotyrosine and catalase activity. Observed and expected genotype frequencies were not significantly different, and overall baseline characteristics were not significantly different according to the various genotype groups. A genotype-phenotype association was demonstrable between the NADPH oxidase p22phox genotypes and plasma nitrotyrosine level (P = 0.06), as well as between the catalase genotypes and whole-blood catalase activity (P < 0.001). Compared with the NADPH oxidase p22phox CC genotype group, the T-allele group had a higher cumulative probability of remaining hospitalized (P = 0.03). Compared with the NADPH oxidase p22phox CC genotype, the T-allele carrier state was associated with 2.1-fold higher odds for dialysis requirement or hospital death (P = 0.01). This association persisted with 2.0- to 2.2-fold higher odds for this composite outcome after adjustment for race; gender; age; and the Acute Physiology and Chronic Health Evaluation II score (P = 0.03), the Multiple Organ Failure score (P = 0.01), or presence of sepsis (P = 0.02). The polymorphism in the gene that encodes the NADPH oxidase p22phox subunit at position +242 is associated with dialysis requirement or hospital death among patients with ARF. Larger studies are needed to confirm these relationships.
Tips for teaching evidence-based medicine in a clinical setting: lessons from adult learning theory. Part two
Authors: Sadia Malick, Kausik Das, Khalid S Khan
Journal: Journal of the Royal Society of Medicine (2008)

Summary Evidence-based medicine (EBM) is the clinical use of current best available evidence from relevant, valid research. Provision of evidence-based healthcare is the most ethical way to practise as it integrates up-to-date patient-oriented research into the clinical decision-making to improve patients' outcomes. This article provides tips for teachers to teach clinical trainees the final two steps of EBM: integrating evidence with clinical judgement and bringing about change.
Alterations of thoraco-abdominal volumes in patients with spinal muscle atrophy (SMA)
Authors: Antonella LoMauro, Marianna Romei, Rita Priori, Marianna Laviola, Maria Grazia D'Angelo, Andrea Aliverti
Journal: European Respiratory Journal (2013)

SMA is an autosomal recessive disease characterized by degeneration of motor neurons of spinal cord resulting in muscle wasting and weakness. Although, there is a general consensus that intercostal muscles are weakened and the diaphragm is relatively spared, particularly in SMAI and SMAII, the most severe forms of the disease, very little attention has been paid to possible alterations in the respiratory pattern in the mild SMAIII form. Thoraco-abdominal volumes were measured in 4 SMAII and 14 SMAIII patients and 18 age-matched controls during quiet breathing (QB), maximal voluntary cough (CGH) and slow vital capacity (SVC) in supine position by Opto-Electronic Plethysmography. SMAIII patients were divided into the recently proposed sub-classification 1  into SMAIIIA (wheelchair bound) and SMAIIIB (ambulant). SMAIIIB patients and controls showed a similar ability to significantly increase the percentage contribution of pulmonary rib cage (ΔV RC,P (%)) with the voluntary maneuvers. Conversely, SMAII and SMAIIIA patients were both characterized by similar reduced thoracic expansion (figure).  In conclusion, in SMAII and SMAIIIA patients intercostal muscles weakness results in a poor thoracic expansion during quiet breathing and maximal voluntary respiratory maneuvers. The sub-classification of type III is valid not only for motor ability, but also for respiratory function.   1  Mercuri et al, Lancet Neurol 2012; 11: 443–52.
Ancestral and Derived Protein Import Pathways in the Mitochondrion of Reclinomonas americana
Authors: J. Tong, P. Dolezal, J. Selkrig, S. Crawford, A. G. B. Simpson, N. Noinaj, S. K. Buchanan, K. Gabriel, T. Lithgow
Journal: Molecular Biology and Evolution (2010)

The evolution of mitochondria from ancestral bacteria required that new protein transport machinery be established. Recent controversy over the evolution of these new molecular machines hinges on the degree to which ancestral bacterial transporters contributed during the establishment of the new protein import pathway. Reclinomonas americana is a unicellular eukaryote with the most gene-rich mitochondrial genome known, and the large collection of membrane proteins encoded on the mitochondrial genome of R. americana includes a bacterial-type SecY protein transporter. Analysis of expressed sequence tags shows R. americana also has components of a mitochondrial protein translocase or "translocase in the inner mitochondrial membrane complex." Along with several other membrane proteins encoded on the mitochondrial genome Cox11, an assembly factor for cytochrome c oxidase retains sequence features suggesting that it is assembled by the SecY complex in R. americana. Despite this, protein import studies show that the RaCox11 protein is suited for import into mitochondria and functional complementation if the gene is transferred into the nucleus of yeast. Reclinomonas americana provides direct evidence that bacterial protein transport pathways were retained, alongside the evolving mitochondrial protein import machinery, shedding new light on the process of mitochondrial evolution.
Dual-Modality, Dual-Functional Nanoprobes for Cellular and Molecular Imaging
Authors: Jyothi U. Menon, Praveen K. Gulaka, Madalyn A. McKay, Sairam Geethanath, Li Liu, Vikram D. Kodibagkar
Journal: Theranostics (2012)

An emerging need for evaluation of promising cellular therapies is a non-invasive method to image the movement and health of cells following transplantation.However, the use of a single modality to serve this purpose may not be advantageous as it may convey inaccurate or insufficient information.Multi-modal imaging strategies are becoming more popular for in vivo cellular and molecular imaging because of their improved sensitivity, higher resolution and structural/functional visualization.This study aims at formulating Nile Red doped hexamethyldisiloxane (HMDSO) nanoemulsions as dual modality (Magnetic Resonance Imaging/Fluorescence), dual-functional (oximetry/detection) nanoprobes for cellular and molecular imaging.HMDSO nanoprobes were prepared using a HS15-lecithin combination as surfactant and showed an average radius of 71±39 nm by dynamic light scattering and in vitro particle stability in human plasma over 24 hrs.They were found to readily localize in the cytosol of MCF7-GFP cells within 18 minutes of incubation.As proof of principle, these nanoprobes were successfully used for fluorescence imaging and for measuring pO 2 changes in cells by magnetic resonance imaging, in vitro, thus showing potential for in vivo applications.
Plasma biomarker analysis of ovarian cancer patients undergoing immunotherapy with therapeutic cancer vaccine DPX-Survivac
Authors: Mohan Karkada, Devanand Pinto, Eve Teh, Kenneth Chisholm, Tara Quinton, Neil Berinstein, Marc Mansour
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immune based therapies for cancer are emerging as promising strategies to treat a number of malignancies. A more thorough biomarker assessment of the patients may provide insights into the variability in response to such immune therapies. In a Phase I/Ib clinical trial with the
Inhibition of hepatitis C entry: too soon to dismiss while many are still being denied treatment
Authors: Susan L Uprichard, Bruno Sainz
Journal: Gut (2014)

Recently in Gut, Xiao et al. detailed an extensive analysis of synergistic inhibition of HCV achieved in various in vitro and in vivo models systems when HCV entry inhibitors were combined with different direct acting antivirals (DAAs) and host-targeted antiviral (HTAs). 1 However, a follow-up commentary by Pawlotsky suggested that "there is no unmet clinical need" for the treatment of HCV that cannot be addressed by the HCV drugs currently approved or in late stage clinical development. 2Here we comment on the original study and subsequent commentary.