tbuckley/cabot-search huggingface dataset:
Utility of Routine Post-Therapy Surveillance Imaging in Diffuse Large B-Cell Lymphoma
Authors: Carrie A. Thompson, Herve Ghesquieres, Matthew J. Maurer, James R. Cerhan, Pierre Biron, Stephen M. Ansell, Catherine Chassagne-Clément, David J. Inwards, Thérèse Gargi, Patrick B. Johnston, Emmanuelle Nicolas-Virelizier, William R. Macon, Marie Peix, Ivana N. Micallef, Catherine Sebban, Grzegorz S. Nowakowski, Luis F. Porrata, George J. Weiner, Thomas E. Witzig, Thomas M. Habermann, Brian K. Link
Journal: Journal of Clinical Oncology (2014)

Purpose We examined the utility of post-therapy surveillance imaging in a large, prospectively enrolled cohort of patients with diffuse large B-cell lymphoma (DLBCL) from the United States and confirmed our results in an independent cohort of patients from France. Methods Patients with newly diagnosed DLBCL and treated with anthracycline-based immunochemotherapy were identified from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence and the Léon Bérard Cancer Center, Lyon, France. In those with relapse, details at relapse and outcomes were abstracted from records. Results 680 individuals with DLBCL were identified from the MER, 552 (81%) of whom achieved remission after induction. 112 of the 552 patients (20%) suffered a relapse. The majority (64%) of relapses were identified before a scheduled follow-up visit. Surveillance imaging detected DLBCL relapse before clinical manifestations in nine out of 552 patients (1.6%) observed after therapy. In the Lyon cohort, imaging identified asymptomatic DLBCL relapse in four out of 222 patients (1.8%). There was no difference in survival after DLBCL relapse in patients detected at scheduled follow-up versus before scheduled follow-up in both the MER (P = .56) and Lyon cohorts (P = .25). Conclusion The majority of DLBCL relapses are detected outside of planned follow-up, with no difference in outcome in patients with DLBCL detected at a scheduled visit compared with patients with relapse detected outside of planned follow-up. These data do not support the use of routine surveillance imaging for follow-up of DLBCL.
Hyperparathyroidism and portacaval shunt: A syndrome or a coincidence?
Authors: Ernest Urban, Vincent J. Dindzans, David H. Van Thiel
Journal: Hepatology (1989)

This is a report of six patients with cirrhosis of the liver in whom primary hyperparathyroidism occurred due to a solitary parathyroid adenoma 3 months to 9 years after undergoing emergency portacaval shunt for hemorrhage from esophageal varices. The presenting symptoms in all six patients were weakness and bone pain. Three patients had a bone fracture after insignificant trauma, one and probably two passed kidney stones, and a duodenal ulcer developed in two. Bone x-ray films showed generalized osteoporosis in all patients. Renal function and arterial blood pH were within normal limits in every patient. The diagnosis of primary hyperparathyroidism in each patient was based on repeated demonstrations of hypercalcemia, hypophosphatemia, and markedly elevated serum immunoreactive parathyroid hormone concentrations. In all six patients, removal of the parathyroid adenoma resulted in disappearance of symptoms; normalization of serum calcium, phosphorus, and immunoreactive parathyroid hormone levels; and, in four of the six, improvement in radiographic evidence of osteoporosis during follow-up of from 1 to 6 years. The association of cirrhosis, portacaval shunt, and primary hyperparathyroidism has not been documented previously. Our six patients with primary hyperparathyroidism constitute 3.4 percent of 174 survivors of emergency portacaval shunt in a series of 264 unselected, consecutive patients with cirrhosis and bleeding esophageal varices. Hepatic osteodystrophy is known to have occurred in only 11 of these 174 survivors. Primary hyperparathyroidism may be a more common cause of hepatic osteodystrophy than has been previously recognized, and should be considered in patients with cirrhosis in whom weakness, bone pain, and bone demineralization develop, particularly if they have a portacaval anastomosis.
A Step toward an Optimized Rifampin Dose Completed
Authors: Martin J. Boeree, Andreas H. Diacon, Rodney Dawson, Kim Narunsky, Jeannine du Bois, Amour Venter, Patrick P. J. Phillips, Stephen H. Gillespie, Timothy D. McHugh, Michael Hoelscher, Norbert Heinrich, Sunita Rehal, Dick van Soolingen, Jakko van Ingen, Cecile Magis-Escurra, David Burger, Georgette Plemper van Balen, Rob E. Aarnoutse
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
The Presence of Lys27 Instead of Asn27 in Human Phospholamban Promotes Sarcoplasmic Reticulum Ca <sup>2+</sup> -ATPase Superinhibition and Cardiac Remodeling
Authors: Wen Zhao, Qunying Yuan, Jiang Qian, Jason R. Waggoner, Anand Pathak, Guoxiang Chu, Bryan Mitton, Xiaoyin Sun, Jay Jin, Julian C. Braz, Harvey S. Hahn, Yehia Marreez, Faisal Syed, Piero Pollesello, Arto Annila, Hong-Sheng Wang, Jo El J. Schultz, Jeffery D. Molkentin, Stephen B. Liggett, Gerald W. Dorn, Evangelia G. Kranias
Journal: Circulation (2006)

Background— Phospholamban (PLN) is an inhibitor of the Ca 2+ affinity of sarcoplasmic reticulum (SR) Ca 2+ -ATPase (SERCA2). The amino acid sequence of PLN is highly conserved, and although all species contain asparagine (Asn), human PLN is unique in containing lysine (Lys) at amino acid 27. Methods and Results— Human PLN was introduced in the null background. Expression of human PLN, at similar levels to mouse wild-type PLN, resulted in significant decreases in the affinity of SERCA2 for Ca 2+ , attributed to unique spatial conformation of this PLN form and increases in its monomeric active unit compared with mouse PLN. The increased inhibition by human PLN was associated with attenuated cardiac contractility in the intact-animal, organ, and cardiomyocyte levels and with depressed calcium kinetics. These inhibitory effects could not be fully reversed even on maximal isoproterenol stimulation. There were no alterations in the expression levels of SERCA2, calsequestrin, ryanodine receptor, and FKBP12, although the sodium/calcium exchanger and the L-type Ca 2+ channel expression levels were upregulated. The depressed function resulted in increased heart/body weight ratios and phosphorylation levels of Akt, p38, and Erk1/2. Conclusions— Human PLN may play a more inhibitory role than that of other species in Ca 2+ cycling. Expression of human PLN in the mouse is compensated by alterations in Ca 2+ -handling proteins and cardiac remodeling in an effort to normalize cardiac contractility. Thus, the unique amino acid sequence of human PLN may be critical in maintaining a high cardiac reserve, which is of paramount importance in the regulation of human cardiac function.
D<scp>IET AND</scp>N<scp>UTRITION IN</scp>P<scp>OOR AND</scp>M<scp>INORITY</scp>C<scp>OMMUNITIES IN</scp>T<scp>HE</scp>U<scp>NITED</scp>S<scp>TATES</scp>100 Y<scp>EARS</scp>A<scp>GO</scp>
Authors: Robert Dirks
Journal: Annual Review of Nutrition (2003)

▪ Abstract Atwater and his colleagues began studying food consumption in the closing years of the nineteenth century and from the very start devoted much effort to collecting data from poor and minority households. This paper reviews some of the fruits of these labors, particularly from the standpoint of what they contribute toward a better historical understanding of American food habits and nutrition. It surveys dietary data from African American, Appalachian white, Mexican American, native-born poor, and immigrant households. These data shed light on several areas of historical concern, including rural versus urban nutrition, seasonal hunger, class disparities, and food-habit change. I suggest the economically and culturally diverse sample of dietary patterns that comes to us as a legacy of the Atwater era sets the stage for a history of American food habits considerably more sophisticated than has been realized to date.
Reply to A. Surbone et al
Authors: James Spicer, Henrik Moller, Sophie Papa
Journal: Journal of Clinical Oncology (2013)

We read with interest the letter by Surbone and Kagawa-Singer entitled, “Culture Matters As Well.” We share their enthusiasm for the promotion of “nondiscriminatory referring clinician practices,” as well as greater exploration of the impact of anthropology and ethnography on patients’ decisions regarding cancer care and clinical trial involvement. However, we have no evidence in the early-phase setting that these factors are more important than, for example, objective measures of fitness and comorbidities. Improving cancer clinical trial access for all patients requires greater understanding of the social, cultural, physical, and emotional barriers that patients face. We are reminded by Unger et al not to overlook the importance of aspects of trial design and possible toxicity in patients’ decisions to participate. They demonstrated that choosing not to participate in a clinical trial was more likely to be motivated by such clinical considerations than by cost or convenience. Now that we have demonstrated a disparity in referrals for earlyphase trials between the least and most affluent patients in our catchment area, we are motivated to explore causality. At present, we can only speculate on the relative importance of factors such as culture, comorbidity, and referrer bias. James Spicer King’s College London; and Guy’s & St Thomas’ National Health Service Foundation Trust, London, United Kingdom
Reactive Immunization Suppresses Advanced Glycation and Mitigates Diabetic Nephropathy
Authors: Tatiana Shcheglova, Sudesh Makker, Alfonso Tramontano
Journal: Journal of the American Society of Nephrology (2009)

Agents that inhibit glycation end products by reducing the carbonyl load from glycation and glycoxidation are an emerging pharmacologic approach to treat complications of diabetes. We previously demonstrated that antibodies generated to the glycoprotein keyhole limpet hemocyanin (KLH) can cross-link with reactive carbonyl residues on protein conjugates. Here, we immunized streptozotocin-induced diabetic rats with KLH to assess the capacity of the elicited antibodies to intercept carbonyl residues on glycated proteins and to mitigate glycation-related pathology. Compared with diabetic rats immunized with adjuvant alone, KLH-immunized diabetic rats had decreased levels of glycated peptides in sera and demonstrated a reduction in albuminuria, proteinuria, deposition of glycation end products in the kidney, and histologic damage. In vitro, low molecular weight glycated peptides from rat serum reacted with anti-KLH antibodies at a faster rate than normal IgG and selectively modified the lambda chains. The reaction products contained peptide sequences from type I collagen alpha chain, albumin, and LDL receptor-related protein. These adduction reactions were inhibited by free KLH and by reduction of glycated peptides with borohydride. In summary, these results suggest that inherent reactivity of Ig light chains provides a natural mechanism for the removal of cytotoxic glycation products. This reactivity can be augmented by glycoprotein-specific reactive immunization, a potential biopharmaceutical approach to glycation-related pathology.
Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma
Authors: Matthias Lechner, Tim Fenton, James West, Gareth Wilson, Andrew Feber, Stephen Henderson, Christina Thirlwell, Harpreet K Dibra, Amrita Jay, Lee Butcher, Ankur R Chakravarthy, Fiona Gratrix, Nirali Patel, Francis Vaz, Paul O'Flynn, Nicholas Kalavrezos, Andrew E Teschendorff, Chris Boshoff, Stephan Beck
Journal: Genome Medicine (2013)

Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) represents a distinct clinical and epidemiological condition compared with HPV-negative (HPV-) HNSCC. To test the possible involvement of epigenetic modulation by HPV in HNSCC, we conducted a genome-wide DNA-methylation analysis.Using laser-capture microdissection of 42 formalin-fixed paraffin wax-embedded (FFPE) HNSCCs, we generated DNA-methylation profiles of 18 HPV+ and 14 HPV- samples, using Infinium 450 k BeadArray technology. Methylation data were validated in two sets of independent HPV+/HPV- HNSCC samples (fresh-frozen samples and cell lines) using two independent methods (Infinium 450 k and whole-genome methylated DNA immunoprecipitation sequencing (MeDIP-seq)). For the functional analysis, an HPV- HNSCC cell line was transduced with lentiviral constructs containing the two HPV oncogenes (E6 and E7), and effects on methylation were assayed using the Infinium 450 k technology.Unsupervised clustering over the methylation variable positions (MVPs) with greatest variation showed that samples segregated in accordance with HPV status, but also that HPV+ tumors are heterogeneous. MVPs were significantly enriched at transcriptional start sites, leading to the identification of a candidate CpG island methylator phenotype in a sub-group of the HPV+ tumors. Supervised analysis identified a strong preponderance (87%) of MVPs towards hypermethylation in HPV+ HNSCC. Meta-analysis of our HNSCC and publicly available methylation data in cervical and lung cancers confirmed the observed DNA-methylation signature to be HPV-specific and tissue-independent. Grouping of MVPs into functionally more significant differentially methylated regions identified 43 hypermethylated promoter DMRs, including for three cadherins of the Polycomb group target genes. Integration with independent expression data showed strong negative correlation, especially for the cadherin gene-family members. Combinatorial ectopic expression of the two HPV oncogenes (E6 and E7) in an HPV- HNSCC cell line partially phenocopied the hypermethylation signature seen in HPV+ HNSCC tumors, and established E6 as the main viral effector gene.Our data establish that archival FFPE tissue is very suitable for this type of methylome analysis, and suggest that HPV modulates the HNSCC epigenome through hypermethylation of Polycomb repressive complex 2 target genes such as cadherins, which are implicated in tumor progression and metastasis.
Amplified in breast cancer 1 enhances human cholangiocarcinoma growth and chemoresistance by simultaneous activation of Akt and Nrf2 pathways
Authors: Qiang Chen, Wenjiao Li, Yunyan Wan, Xiaochun Xia, Qiao Wu, Yanling Chen, Zhide Lai, Chundong Yu, Wengang Li
Journal: Hepatology (2011)

Transcriptional coactivator amplified in breast cancer 1 (AIB1) plays important roles in the progression of several cancers such as prostate cancer, breast cancer, and hepatocellular carcinoma. However, its role in cholangiocarcinoma (CCA), a chemoresistant bile duct carcinoma with a poor prognosis, remains unclear. In this study we found that AIB1 protein was frequently overexpressed in human CCA specimens and CCA cell lines. Down-regulation of AIB1 induced the G2/M arrest and decreased the expression of mitosis-promoting factors including Cyclin A, Cyclin B, and Cdk1 through suppressing the Akt pathway, which resulted in inhibiting CCA cell proliferation. In addition, AIB1 enhanced the chemoresistance of CCA cells at least in part through up-regulating the expression of antiapoptotic protein Bcl-2. AIB1 regulated the expression of Bcl-2 in CCA cells through activating the Akt pathway as well as suppressing intracellular reactive oxygen species (ROS). AIB1 suppressed ROS by up-regulating antioxidants such as glutathione synthetase and glutathione peroxidase, which are targets of the NF-E2-related factor 2 (Nrf2), a critical transcription factor that regulates antioxidants, detoxification enzymes, and drug efflux proteins. AIB1 also increased the expression of another two Nrf2 targets, ABCC2 and ABCG2, to enhance drug efflux. AIB1 served as an essential coactivator for Nrf2 activation by physically interacting with Nrf2 to enhance its transcriptional activity. Conclusion: AIB1 plays an important role in proliferation and chemoresistance of CCA through simultaneous activation of Akt and Nrf2 pathways, suggesting that AIB1 is a potential molecular target for CCA treatment.
Epidemiology of tuberculosis in big cities of the European Union and European Economic Area countries
Authors: G de Vries, R W Aldridge, J A Caylà, W.  H. Haas, A Sandgren, N A van Hest, I Abubakar, Collective the Tuberculosis in European Union Big Cities Working Group
Journal: Eurosurveillance (2014)

This cross-sectional survey aimed to examine the epidemiology of tuberculosis (TB) in European Union (EU) and European Economic Area (EEA) cities with populations greater than 500,000. National TB programme managers were asked to provide data on big city population size, total number of notified TB cases in big cities and national notification rate for 2009. A rate ratio was calculated using the big city TB notification rate as a numerator and country TB notification rate, excluding big city TB cases and population, as a denominator. Twenty of the 30 EU/EEA countries had at least one big city. Pooled rate ratios were 2.5, 1.0, and 0.7 in low-, intermediate- and high-incidence countries respectively. In 15 big cities, all in low-incidence countries, rate ratios were twice the national notification rate. These data illustrate the TB epidemiology transition, a situation whereby TB disease concentrates in big cities as national incidence falls, most likely as a result of the higher concentration of risk groups found there. This situation requires targeted interventions and we recommend that big city TB data, including information about patients' risk factors, are collected and analysed systematically, and that successful interventions are shared.
Decreased Incidence of Hepatocellular Carcinoma in Hepatitis B Vaccinees: A 20-Year Follow-up Study
Authors: Mei-Hwei Chang, San-Lin You, Chien-Jen Chen, Chun-Jen Liu, Chuan-Mo Lee, Shi-Ming Lin, Heng-Cheng Chu, Tzee-Chung Wu, Sheng-Shun Yang, Hsu-Sung Kuo, Ding-Shinn Chen
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundHepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma. This population-based study aimed to investigate whether prevention of hepatocellular carcinoma by the universal Taiwanese HBV vaccine program, launched in July 1984, has extended beyond childhood and to identify the predictors of hepatocellular carcinoma for vaccinated birth cohorts.
Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03
Authors: G. D'Addario, D. Rauch, R. Stupp, M. Pless, R. Stahel, N. Mach, L. Jost, L. Widmer, C. Tapia, M. Bihl, M. Mayer, K. Ribi, S. Lerch, L. Bubendorf, D.C. Betticher
Journal: Annals of Oncology (2007)
Muscle dysfunction and exercise limitation in adolescent idiopathic scoliosis
Authors: J. Martínez-Llorens, M. Ramírez, M.J. Colomina, J. Bagó, A. Molina, E. Cáceres, J. Gea
Journal: European Respiratory Journal (2009)

Adolescent idiopathic scoliosis (AIS) can lead to ventilatory restriction, respiratory muscle weakness and exercise limitation. However, both the causes and the extent of muscle dysfunction remain unclear. The aim of our study is to describe muscle weakness and its relationship to lung function and tolerance to exercise in AIS patients. Lung and muscle function, together with exercise capacity, were assessed in 60 patients with pronounced spinal deformity (&gt;40°) and in 25 healthy volunteers. Patients with AIS had only mild to moderate abnormal ventilatory patterns, the most frequent of which were restrictive abnormalities. The function of respiratory and limb muscles and exercise capacity were below normal limits in AIS patients, and were significantly lower than in controls. Exercise capacity was found to correlate with the function of inspiratory, expiratory, upper limb and lower limb muscles which, in addition, were reciprocally interrelated. Multivariate analysis showed that lower limb muscle function is the main contributor to exercise intolerance. There appeared to be no connection between spinal deformity and lung function, muscle function or exercise capacity. We conclude that AIS patients show generalised muscle dysfunction which contributes to the reduction in their exercise capacity, even in the absence of severe ventilatory impairment.
Relationship Between C-Reactive Protein and Glucose Levels in Community-Dwelling Subjects Without Diabetes
Authors: Yasufumi Doi, Yutaka Kiyohara, Michiaki Kubo, Yumihiro Tanizaki, Ken Okubo, Toshiharu Ninomiya, Masanori Iwase, Mitsuo Iida
Journal: Diabetes Care (2005)

C-reactive protein (CRP), a marker of systemic inflammation, is emerging as an independent risk factor for cardiovascular disease (1,2). It has also been reported that serum CRP levels are elevated in patients with impaired glucose tolerance (IGT) (3) or diabetes (4). A few prospective studies have shown that increased CRP levels are an independent risk factor for future diabetes (5,6). Although these findings indicate that CRP levels in peripheral blood are closely associated with glucose levels, it remains unclear whether a relationship exists between CRP levels and plasma glucose levels in the pre-diabetic range. The purpose of the present study was to investigate the relationship between CRP concentrations and pre-diabetic plasma glucose levels in a general Japanese population.

A population-based prospective study of cardiovascular disease has been underway since 1961 in the town of Hisayama, Kyushu Island, Japan. In 1988, as a part of the study, a cross-sectional diabetes survey of Hisayama residents was conducted (7). Of all 3,227 residents aged 40–79 years in the town registry, 2,587 (80.2%) consented to take part in a comprehensive assessment, including a fasting 75-g oral glucose tolerance test. After excluding 82 nonfasting participants, 15 of whom failed to complete the oral glucose tolerance test, 302 with diabetes based on the American Diabetes Association …
Detection of Human Papillomavirus-16 in Fine-Needle Aspirates to Determine Tumor Origin in Patients with Metastatic Squamous Cell Carcinoma of the Head and Neck
Authors: Shahnaz Begum, Maura L. Gillison, Theresa L. Nicol, William H. Westra
Journal: Clinical Cancer Research (2007)

Patients with head and neck squamous cell carcinoma (HNSCC) often clinically present with metastases to regional lymph nodes. Fine-needle aspiration of neck masses is routinely used to establish the presence of metastatic carcinoma and in turn to initiate a subsequent workup to determine the site of tumor origin. Human papillomavirus (HPV) 16 is an important etiologic agent for HNSCCs that arise from the oropharynx but less so for tumors from non-oropharyngeal sites. HPV16 detection thus provides a strategy for localizing an important subset of HNSCCs, but this approach has not been applied to fine-needle aspiration specimens.We did in situ hybridization for HPV16 on 77 consecutive aspirated neck masses diagnosed as metastatic squamous cell carcinoma. P16 immunohistochemistry was also done because p16 overexpression may serve as a surrogate marker of HPV-associated HNSCC.HPV16 was detected in 13 of the 77 (17%) aspirates. By site of origin, HPV16 was detected in 10 of 19 metastases from the oropharynx but in none of 46 metastases from other sites (53% versus 0%; P < 0.0001). HPV16 was not detected in 2 branchial cleft cysts misdiagnosed as metastatic squamous cell carcinoma, but it was detected in 3 of 10 metastases from occult primary tumors. P16 expression was associated with the presence of HPV16: 12 of 13 HPV16-positive metastases exhibited p16 expression, whereas only 4 of 62 HPV16-negative metastases were p16 positive (92% versus 6%; P < 0.0001). P16 expression also correlated with site of tumor origin: 13 of 19 oropharyngeal metastases were p16 positive, whereas only 1 of 46 non-oropharyngeal metastases was p16 positive (68% versus 2%; P < 0.0001).HPV16 status can be determined in tumor cells aspirated from the necks of patients with metastatic HNSCC. Its presence is a reliable indicator of origin from the oropharynx.