tbuckley/cabot-search huggingface dataset:
Diagnostic role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in benign disease: Experience from a UK tertiary referral centre
Authors: Dinesh Shrikrishna, Andrew R L Medford
Journal: European Respiratory Journal (2014)

Introduction: Endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) is a well recognised, minimally invasive, diagnostic and staging tool for patients with malignancy. However, increasingly this technique is also being utilised in the diagnosis of benign disease (Gupta D. et al. Chest 2014; epub Jan 30).

Aims: To evaluate the diagnostic efficacy of EBUS-TBNA in patients with suspected benign mediastinal disease in a UK tertiary referral centre.

Methods: We retrospectively analysed data on patients undergoing EBUS-TBNA for suspected benign disease from Feb 2010 to Dec 2013. The sensitivity, negative predictive value (NPV) and accuracy of EBUS-TBNA for the diagnosis of sarcoidosis and tuberculosis (TB) was then determined.

Results: We studied 106 patients with suspected benign mediastinal disease (mean (SD), age 49(15) years, 60% male). Of those, 84 patients had an EBUS-TBNA to investigate for sarcoidosis and 19 patients for TB. The remaining 3 cases were performed for benign cysts. In patients suspected to have sarcoidosis, EBUS-TBNA had a sensitivity of 96.0%, an NPV of 75.0%, a diagnostic accuracy of 96.4% and a prevalence of 70.8%. Of the 3 false negatives for sarcoidosis, 2 were diagnosed by mediastinoscopy and 1 by transbronchial biopsy. In those patients with a suspected diagnosis of TB, EBUS-TBNA had a sensitivity of 92.3%, an NPV of 85.7%, an accuracy of 94.7% and a prevalence of 12.2%. The one false negative for TB was identified on broncho-alveolar lavage.

Conclusion: This UK tertiary centre data suggests that EBUS-TBNA provides a valuable diagnostic tool for patients with benign disease.
Ras/Raf-1/MAPK Pathway Mediates Response to Tamoxifen but not Chemotherapy in Breast Cancer Patients
Authors: Liane M. McGlynn, Tove Kirkegaard, Joanne Edwards, Sian Tovey, David Cameron, Chris Twelves, John M.S. Bartlett, Timothy G. Cooke
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The expression and activation of the Ras/Raf-1/mitogen-activated protein kinase (MAPK) pathway plays an important role in the development and progression of cancer, and may influence response to treatments such as tamoxifen and chemotherapy. In this study we investigated whether the expression and activation of the key components of this pathway influenced clinical outcome, to test the hypothesis that activation of the MAPK pathway drives resistance to tamoxifen and chemotherapy in women with breast cancer. Experimental Design: Breast tumors from patients at the Glasgow Royal Infirmary and others treated within the BR9601 trial were analyzed for expression of the three Ras isoforms, total Raf-1, active and inactive forms of Raf-1 [pRaf(ser338) and pRaf(ser259), respectively], MAPK, and phospho-MAPK using an immunohistochemical approach. Analyses were done with respect to disease free-survival and overall survival. Results: Expression and activation of the Ras pathway was associated with loss of benefit from treatment with tamoxifen but not chemotherapy. Overexpression of pRaf(ser338) was associated with shortened disease-free and overall survival time in univariate analyses. Multivariate analysis suggested pRaf(ser338) was independent of known prognostic markers in predicting outcome following tamoxifen treatment (P = 0.03). Conclusion: This study suggests that activation of the Ras pathway predicts for poor outcome on tamoxifen but not chemotherapy, and identifies pRaf(ser338) as a potential marker of resistance to estrogen receptor–targeted therapy. In addition, it suggests that expression of pRaf(ser338) could identify patients for whom tamoxifen alone is insufficient adjuvant systemic therapy, but for whom the addition of chemotherapy may be of benefit.
Prevalence and Clinical Implications of Epstein–Barr Virus Infection in <i>De Novo</i> Diffuse Large B-Cell Lymphoma in Western Countries
Authors: Chi Young Ok, Ling Li, Zijun Y. Xu-Monette, Carlo Visco, Alexander Tzankov, Ganiraju C. Manyam, Santiago Montes-Moreno, Karen Dybaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Jiayu Chen, Kristy L. Richards, Eric D. Hsi, William W. L. Choi, J. Han van Krieken, Jooryung Huh, Weiyun Ai, Maurilio Ponzoni, Andrés J.M. Ferreri, John P. Farnen, Michael B. Møller, Carlo E. Bueso-Ramos, Roberto N. Miranda, Jane N. Winter, Miguel A. Piris, L. Jeffrey Medeiros, Ken H. Young
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Epstein–Barr virus–positive (EBV+) diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East-Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV+ DLBCL, independent of age, treated with rituximab combined with CHOP (R-CHOP) in developed Western countries. Experimental design: A large cohort (n = 732) of patients with DLBCL treated with R-CHOP chemotherapy is included from the multicenter consortium. This study group has been studied for expression of different biomarkers by immunohistochemistry, genetic abnormalities by FISH and mutation analysis, genomic information by gene expression profiling (GEP), and gene set enrichment analysis (GSEA). Results: Twenty-eight patients (4.0%) were positive for EBV with a median age of 60.5 years. No clinical characteristics distinguished patients with EBV+ DLBCL from patients with EBV-negative (EBV−) DLBCL. Genetic aberrations were rarely seen. NF-κB p50, phosphorylated STAT-3, and CD30 were more commonly expressed in EBV+ DLBCLs (P &amp;lt; 0.05). Significant differences in survival were not observed in patients with EBV+ DLBCL versus EBV− DLBCL. However, CD30 expression combined with EBV conferred an inferior outcome. GEP showed a unique expression signature in EBV+ DLBCL. GSEA revealed enhanced activity of the NF-κB and JAK/STAT pathways independent of molecular subtype. Conclusions: The clinical characteristics of patients with EBV+ versus EBV− DLBCL are similar and EBV infection does not predict a worse outcome. EBV+ DLBCL, however, has a unique genetic signature. CD30 expression is more common in EBV+ DLBCL and, consistent CD30 and EBV is associated with an adverse outcome. Clin Cancer Res; 20(9); 2338–49. ©2014 AACR.
Splenomegaly in Bacillary Dysentery
Authors: R. P. Warin, R. S. Alexander
Journal: BMJ (1945)

failure may also have aggravated the general condition and increased the size of the liver from acute passive congestion.No doubt the var-ious effusions and petechial haemorrhages were direct consequences of hepatic failure.In view of the extensive necrosis it is perhaps surprising that jaundice was completely absent.Either the liver destruc- tion was too rapid or this was really an example of extreme fatty degeneration of the organ following an acute infection -bronchopneumonia in this instance, as was stated in the his- tory.The latter explanation, however, was not supported by the histological findings, but certainly the possibility of a ful- minating virus hepatitis cannot be completely excluded.Lastly. of drugs sulohathiazole alone was given, to a total of 8 g. two weeks before death.Fatal cases of hepatitis are known to have followed sulphonamide therapy, and symptoms have niot always declared themselves until after the final with- drawal of the drug.Of all possible causes, this does seem the most feasible; but, unfortunately, the available evidence is inconclusive.
Premature immune senescence during HIV-1 vertical infection relates with response to influenza vaccination
Authors: Alberto Cagigi, Stefano Rinaldi, Angela Di Martino, Emma Concetta Manno, Paola Zangari, Angela Aquilani, Nicola Cotugno, Luciana Nicolosi, Alberto Villani, Stefania Bernardi, Isabella Donatelli, Savita Pahwa, Paolo Rossi, Paolo Palma
Journal: Journal of Allergy and Clinical Immunology (2013)
125 years after Robert Koch's discovery of the tubercle bacillus: the new XDR-TB threat. Is “science” enough to tackle the epidemic?
Authors: G. B. Migliori, R. Loddenkemper, F. Blasi, M. C. Raviglione
Journal: European Respiratory Journal (2007)

March 24, 2007 will mark the 125th anniversary of Robert Koch's discovery of the tuberculosis (TB) bacillus (figs 1⇓ and 2⇓). This anniversary comes after a year of major achievements for the international TB community.



Fig. 1— 
Robert Koch (1843–1910), who discovered Mycobacterium tuberculosis in 1882. Nobel Laureate Physiology or Medicine, 1905.





Fig. 2— 
The title page of Robert Koch's original article published in Berliner Klinische Wochenschrift on April 10, 1882 1. This journal is no longer in existence. Provided courtesy of H.L. Rieder (Tuberculosis Division, International Union Against Tuberculosis and Lung Disease, Paris, France).



Firstly, in 2006, the new Stop TB Strategy was launched by the World Health Organization (WHO), following intensive exploration and discussion with TB control programme managers in high burden countries and partner organisations, including technical agencies and donors 2. The DOTS strategy (consisting of five key elements: government commitment, diagnosis through microscopy, standardised and supervised treatment, uninterrupted drug supply, and regular programme monitoring), which greatly contributed to the improvement of global TB control over the last 10 yrs 3, was revisited to pursue DOTS expansion while making explicit six additional components that must be implemented to reach the 2015 Millennium Development Goals (MDGs) relevant to TB control. Thus, the new Stop TB Strategy consists of: 1) the pursuit of high-quality DOTS expansion and enhancement; 2) addressing TB/HIV, multidrug-resistant (MDR)-TB and other challenges; 3) contribution to the strengthening of health systems; 4) engaging all care providers; 5) the empowerment of people and communities with TB; and 6) enabling and promoting research. The MDGs relevant to TB aim at combating HIV, malaria and other diseases. Its target 8 consists of halting TB by 2015 and beginning to reverse the incidence of disease; indicator 23 addresses TB prevalence and mortality; and indicator 24 is the proportion of cases detected …
Effects of warm-up and precooling on endurance performance in the heat
Authors: Sandra Ückert, Winfried Joch
Journal: British Journal of Sports Medicine (2007)

Objective: To examine the effects of different thermoregulatory preparation procedures (warm-up (WU), precooling (PC), control (C)) on endurance performance in the heat. Methods: 20 male subjects completed three treadmill runs to exhaustion (5 days apart). In each session, all subjects performed an incremental running test after WU (20 min at 70% maximum heart rate (HR)), after PC (wearing a cooling vest (0°C–5°C) for 20 min at rest) or without particular preparation (C). After a 5-min break, the exercise protocol commenced at a workload of 9 km/h and was increased by 1 km/h every 5 min until the point of volitional fatigue. Running performance, HR, blood lactate concentration, tympanic temperature and skin temperature were measured in each trial. Results: In the PC condition, the running performance (32.5 (5.1) min; mean (SD)) was significantly (p&lt;0.05) higher than in WU (26.9 (4.6) min) and in C conditions (30.3 (4.3) min). During the first 30 min of testing, HR, tympanic temperature and skin temperature were significantly (p&lt;0.05) lower after PC than after WU. There were no significant differences in lactate concentration; however, there was a trend to lower values after WU. Conclusions: The use of an ice-cooling vest for 20 min before exercising improved running performance, whereas the 20 min WU procedure had a distinctly detrimental effect. Cooling procedures including additional parts of the body such as the head and the neck might further enhance the effectiveness of PC measures.
Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo
Authors: Xuyu Zhou, Samantha L Bailey-Bucktrout, Lukas T Jeker, Cristina Penaranda, Marc Martínez-Llordella, Meredith Ashby, Maki Nakayama, Wendy Rosenthal, Jeffrey A Bluestone
Journal: Nature Immunology (2009)
Stress fractures of the femoral shaft in women’s college lacrosse: a report of seven cases and a review of the literature
Authors: L Kang, D Belcher, M J Hulstyn
Journal: British Journal of Sports Medicine (2005)

Background: Stress fractures do not often occur in the shaft of the femur. They are more common in the femoral neck, the tibial shaft, the metatarsals, and other bones of the foot. In female athletes, stress fractures classically afflict the distance runner, the ballerina, the gymnast, and the figure skater. Objectives: To describe the clinical presentation, diagnosis, treatment, and outcome of seven college female lacrosse players with femoral shaft stress fractures, and review the literature. Results: The unusual results of this study support the principle that clinical suspicion should be high when treating any female athlete regardless of the sport. In this case series, an abrupt change in the quality of the running surface during the competitive training season was the only underlying common thread among the athletes. Conclusion: The findings suggest that risk factors for the female athlete are variable and are no longer limited to the undernourished or overtrained.
Effective Use of Subcutaneous Immune Globulin (SCIG) for an Infant with X-linked Agammaglobulinemia (X-LA)
Authors: C.M. Duff, E. Faulkner, Z. Schirm, J. Lang, C.A. Rodriguez, J.W. Sleasman
Journal: Journal of Allergy and Clinical Immunology (2009)
Ubiquitin-Proteasome System Stress Sensitizes Ovarian Cancer to Proteasome Inhibitor–Induced Apoptosis
Authors: Martina Bazzaro, Michael K. Lee, Alessia Zoso, Wanda L.H. Stirling, Antonio Santillan, Ie-Ming Shih, Richard B.S. Roden
Journal: Cancer Research (2006)

Abstract The ubiquitin-proteasome system (UPS) mediates targeted protein degradation. Notably, the UPS determines levels of key checkpoint proteins controlling apoptosis and proliferation by controlling protein half-life. Herein, we show that ovarian carcinoma manifests an overstressed UPS by comparison with normal tissues by accumulation of ubiquitinated proteins despite elevated proteasome levels. Elevated levels of total ubiquitinated proteins and 19S and 20S proteasome subunits are evident in both low-grade and high-grade ovarian carcinoma tissues relative to benign ovarian tumors and in ovarian carcinoma cell lines relative to immortalized surface epithelium. We find that ovarian carcinoma cell lines exhibit greater sensitivity to apoptosis in response to proteasome inhibitors than immortalized ovarian surface epithelial cells. This sensitivity correlates with increased cellular proliferation rate and UPS stress rather than absolute proteasome levels. Proteasomal inhibition in vitro induces cell cycle arrest and the accumulation of p21 and p27 and triggers apoptosis via activation of caspase-3. Furthermore, treatment with the licensed proteasome inhibitor PS-341 slows the growth of ES-2 ovarian carcinoma xenograft in immunodeficient mice. In sum, elevated proliferation and metabolic rate resulting from malignant transformation of the epithelium stresses the UPS and renders ovarian carcinoma more sensitive to apoptosis in response to proteasomal inhibition. (Cancer Res 2006; 66(7): 3754-63)
Influence of Elevated Cardiometabolic Risk Factor Levels on Treatment Changes in Type 2 Diabetes
Authors: Jaco Voorham, Flora M. Haaijer-Ruskamp, Ronald P. Stolk, Bruce H.R. Wolffenbuttel, Petra Denig
Journal: Diabetes Care (2008)

Undertreatment of risk factors in patients with type 2 diabetes is common. We assessed the influence of elevated levels of blood pressure, total cholesterol, and A1C on decisions of Dutch general practitioners to change drug treatment in a cohort of 3,029 patients during a 1-year period. Respectively, 58, 71, and 21% of patients remained untreated despite poor blood pressure, lipid levels, and glycemic control. Of poorly controlled but already drug-treated patients, 52% did not receive intensification for antihypertensive medication, 81% not for lipid-lowering medication, and 43% not for glucose-lowering medication. We observed a significantly lower treatment intervention rate in moderately than in poorly controlled patients for blood pressure. This was not seen for decisions on cholesterol or A1C results. The low overall action rates observed for blood pressure and especially lipid management cannot sufficiently be explained by the use of treatment thresholds higher than those indicated by guidelines.
Size matching in lung transplantation using predicted total lung capacity
Authors: J.P. Ouwens, T.W. van der Mark, W. van der Bij, A. Geertsma, W.J. de Boer, G.H. Koëter
Journal: European Respiratory Journal (2002)

Height is used in allocation of donor lungs as an indirect estimate of thoracic size. Total lung capacity (TLC), determined by both height and sex, could be a more accurate functional estimation of thoracic size. Size-matching criteria based on height versus predicted TLC was retrospectively evaluated, and, furthermore, whether a TLC mismatch was related to clinical and functional complications. The ratio of donor and recipient height, as well as the ratio of predicted TLC in donors and recipients, were calculated in 80 patients after bilateral lung transplantation. Complications evaluated included persistent atelectasis, persistent pneumothorax and increased number of days in intensive care, occurrence of bronchiolitis obliterans syndrome and limitation of exercise capacity. Median height donor/recipient ratio was 1.01 (0.93–1.12). Median predicted TLC donor/recipient ratio was 1.01 (with a clearly broader range 0.72–1.41). Neither sex mismatch nor TLC mismatch were related to clinical or functional complications. Allocation of donor lungs based upon height alone leads to a substantial mismatch in total lung capacity caused by sex mismatch. The absence of complications suggests that a greater height donor/recipient discrepancy can be accepted for allocation than previously assumed.
Expression of KIR2DL1 on the entire NK cell population: a possible novel immunodeficiency syndrome
Authors: Roi Gazit, Ben-Zion Garty, Yehudith Monselise, Vered Hoffer, Yaron Finkelstein, Gal Markel, Gil Katz, Jacob Hanna, Hagit Achdout, Raizy Gruda, Tsufit Gonen-Gross, Ofer Mandelboim
Journal: Blood (2004)
Lubricin Restoration in a Mouse Model of Congenital Deficiency
Authors: Adele Hill, Kimberly A. Waller, Yajun Cui, Justin M. Allen, Patrick Smits, Ling X. Zhang, Ugur M. Ayturk, Steven Hann, Samantha G. Lessard, David Zurakowski, Matthew L. Warman, Gregory D. Jay
Journal: Arthritis & Rheumatology (2015)

Congenital deficiency of the principal boundary lubricant in cartilage (i.e., lubricin, encoded by the gene PRG4) increases joint friction and causes progressive joint failure. This study was undertaken to determine whether restoring lubricin expression in a mouse model would prevent, delay, or reverse the disease process caused by congenital deficiency. Using genetically engineered lubricin-deficient mice, we restored gene function before conception or at ages 3 weeks, 2 months, or 6 months after birth. The effect of restoring gene function (i.e., expression of lubricin) on the tibiofemoral patellar joints of mice was evaluated histologically and by ex vivo biomechanical testing. Restoring gene function in mice prior to conception prevented joint disease. In 3-week-old mice, restoring gene function improved, but did not normalize, histologic features of the articular cartilage and whole-joint friction. In addition, cyclic loading of the joints produced fewer activated caspase 3-containing chondrocytes when lubricin expression was restored, as compared to that in littermate mice whose gene function was not restored (nonrestored controls). Restoration of lubricin expression in 2-month-old or 6-month-old mice had no beneficial effect on histopathologic cartilage damage, extent of whole-joint friction, or activation of caspase 3 when compared to nonrestored controls. When boundary lubrication is congenitally deficient and cartilage becomes damaged, the window of opportunity for restoring lubrication and slowing disease progression is limited.
Mutational Signatures Indicative of Environmental Stress in Bacteria
Authors: Ram Maharjan, Thomas Ferenci
Journal: Molecular Biology and Evolution (2014)

Evolutionary innovations are dependent on mutations.Mutation rates are increased by adverse conditions in the laboratory, but there is no evidence that stressful environments that do not directly impact on DNA leave a mutational imprint on extant genomes.Mutational spectra in the laboratory are normally determined with unstressed cells but are unavailable with stressed bacteria.To by-pass problems with viability, selection effects, and growth rate differences due to stressful environments, in this study we used a set of genetically engineered strains to identify the mutational spectrum associated with nutritional stress.The strain set members each had a fixed level of the master regulator protein, RpoS, which controls the general stress response of Escherichia coli.By assessing mutations in cycA gene from 485 cycloserine resistant mutants collected from as many independent cultures with three distinct perceived stress (RpoS) levels, we were able establish a dose-dependent relationship between stress and mutational spectra.The altered mutational patterns included base pair substitutions, single base pair indels, longer indels, and transpositions of different insertion sequences.The mutational spectrum of low-RpoS cells closely matches the genome-wide spectrum previously generated in laboratory environments, while the spectra of high RpoS, high perceived stress cells more closely matches spectra found in comparisons of extant genomes.Our results offer an explanation of the uneven mutational profiles such as the transition-transversion biases observed in extant genomes and provide a framework for assessing the contribution of stressinduced mutagenesis to evolutionary transitions and the mutational emergence of antibiotic resistance and disease states.
The Effect of Race on Invasive Staging and Surgery in Non–Small-Cell Lung Cancer
Authors: Christopher S. Lathan, Bridget A. Neville, Craig C. Earle
Journal: Journal of Clinical Oncology (2005)

Black patients with early-stage non-small-cell lung cancer (NSCLC) have worse overall survival than white patients. Decreased likelihood of resection has been implicated. To isolate the effect of decision making from access to care, we used receipt of surgical staging as a proxy for access and willingness to undergo invasive procedures, and examined treatments and outcomes by race.We examined registry and claims data of Medicare-eligible patients with nonmetastatic NSCLC in areas monitored by the Surveillance, Epidemiology, and End Results program from 1991 to 2001. Patients who obtained invasive staging, defined as bronchoscopy, mediastinoscopy, or thoracoscopy, were included. Logistic regression and Cox modeling calculated the odds of having staging and surgery, and survival outcomes.A total of 14,224 patients underwent staging, and 6,972 had surgery for lung cancer. Black patients were less likely to undergo staging (odds ratio [OR] = 0.75; 95% CI, 0.67 to 0.83), and once staged, were still less likely to have surgery than whites (OR = 0.55; 95% CI, 0.47 to 0.64). Survival for blacks and whites was equivalent after resection (hazard ratio = 1.02; P = .06). Staged black patients were less likely to receive a recommendation for surgery when it was not clearly contraindicated (67.0% v 71.4%; P < .05), and were more likely to decline surgery (3.4% v 2.0%; P < .05).Black patients obtain surgery for lung cancer less often than whites, even after access to care has been demonstrated. They are more likely not to have surgery recommended, and more likely to refuse surgery. Additional research should focus on the physician-patient encounter as a potential source of racial disparities.