tbuckley/cabot-search huggingface dataset:
Intakes of Red Meat, Processed Meat, and Meat Mutagens Increase Lung Cancer Risk
Authors: Tram Kim Lam, Amanda J. Cross, Dario Consonni, Giorgia Randi, Vincenzo Bagnardi, Pier Alberto Bertazzi, Neil E. Caporaso, Rashmi Sinha, Amy F. Subar, Maria Teresa Landi
Journal: Cancer Research (2009)

Red and processed meat intake may increase lung cancer risk. However, the epidemiologic evidence is inconsistent and few studies have evaluated the role of meat mutagens formed during high cooking temperatures. We investigated the association of red meat, processed meat, and meat mutagen intake with lung cancer risk in Environment And Genetics in Lung cancer Etiology, a population-based case-control study. Primary lung cancer cases (n = 2,101) were recruited from 13 hospitals within the Lombardy region of Italy examining approximately 80% of the cases from the area. Noncancer population controls (n = 2,120), matched to cases on gender, residence, and age, were randomly selected from the same catchment area. Diet was assessed in 1,903 cases and 2,073 controls and used in conjunction with a meat mutagen database to estimate intake of heterocyclic amines (HCA) and benzo(a)pyrene (BaP). Multivariable odds ratios (OR) and 95% confidence intervals (95% CI) for sex-specific tertiles of intake were calculated using unconditional logistic regression. Red and processed meat were positively associated with lung cancer risk (highest-versus-lowest tertile: OR, 1.8; 95% CI, 1.5-2.2; P trend < 0.001 and OR, 1.7; 95% CI, 1.4-2.1; P trend < 0.001, respectively); the risks were strongest among never smokers (OR, 2.4; 95% CI, 1.4-4.0; P trend = 0.001 and OR, 2.5; 95% CI, 1.5-4.2; P trend = 0.001, respectively). HCAs and BaP were significantly associated with increased risk of lung cancer. When separated by histology, significant positive associations for both meat groups were restricted to adenocarcinoma and squamous cell carcinoma but not small cell carcinoma of the lung. In summary, red meat, processed meat, and meat mutagens were independently associated with increased risk of lung cancer.
Early and late outcome after single step dilatational tracheostomy versus the guide wire dilating forceps technique: a prospective randomized clinical trial
Authors: Bernard G. Fikkers, Marieke Staatsen, Frank J. A. van den Hoogen, Johannes G. van der Hoeven
Journal: Intensive Care Medicine (2011)

Percutaneous tracheostomy is frequently performed in long-term ventilated patients in the intensive care unit (ICU). Unfortunately, despite many years of experience, the optimal technique is still unknown, especially considering the occurrence of late complications. The purpose of this study was to determine which of the two most frequently used percutaneous tracheostomy techniques performs best with the emphasis on late complications. This prospective randomized trial involved 120 patients, comparing two techniques of percutaneous tracheostomy, the guide wire dilating forceps (GWDF) and the single step dilatational tracheostomy (SSDT) technique. Sixty patients in each group underwent a percutaneous tracheostomy and were followed for up to 3 months after decannulation. The majority of complications in both groups were minor (58.3% in the GWDF group and 61.7% in the SSDT group). We found a trend towards more major perioperative complications in the GWDF group versus the SSDT group, 10.0 versus 1.7% (p = 0.06). One patient in the SSDT group developed a significant tracheal stenosis. However, this may also have been related to prolonged translaryngeal intubation. Results of magnetic resonance imaging (MRI) investigations showed only minor tracheal changes. Only 37.5% of patients in the GWDF group and 31.8% in the SSDT group had no complaints after their percutaneous tracheostomy. Compared with the GWDF, the SSDT shows a trend toward less major perioperative complications with a comparable long-term outcome.
Glioblastoma and Other Malignant Gliomas
Authors: Antonio Omuro
Journal: JAMA (2013)

<h3>Importance</h3> Glioblastomas and malignant gliomas are the most common primary malignant brain tumors, with an annual incidence of 5.26 per 100 000 population or 17 000 new diagnoses per year. These tumors are typically associated with a dismal prognosis and poor quality of life. <h3>Objective</h3> To review the clinical management of malignant gliomas, including genetic and environmental risk factors such as cell phones, diagnostic pitfalls, symptom management, specific antitumor therapy, and common complications. <h3>Evidence Review</h3> Search of PubMed references from January 2000 to May 2013 using the terms<i>glioblastoma</i>,<i>glioma</i>,<i>malignant glioma</i>,<i>anaplastic astrocytoma</i>,<i>anaplastic oligodendroglioma</i>,<i>anaplastic oligoastrocytoma</i>, and<i>brain neoplasm</i>. Articles were also identified through searches of the authors' own files. Evidence was graded using the American Heart Association classification system. <h3>Findings</h3> Only radiation exposure and certain genetic syndromes are well-defined risk factors for malignant glioma. The treatment of newly diagnosed glioblastoma is based on radiotherapy combined with temozolomide. This approach doubles the 2-year survival rate to 27%, but overall prognosis remains poor. Bevacizumab is an emerging treatment alternative that deserves further study. Grade III tumors have been less well studied, and clinical trials to establish standards of care are ongoing. Patients with malignant gliomas experience frequent clinical complications, including thromboembolic events, seizures, fluctuations in neurologic symptoms, and adverse effects from corticosteroids and chemotherapies that require proper management and prophylaxis. <h3>Conclusions and Relevance</h3> Glioblastoma remains a difficult cancer to treat, although therapeutic options have been improving. Optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment.
Studies on the Mechanism of Reduced Urinary Osmolality after Exposure of the Renal Papilla
Authors: Elaine L. Chuang, H. John Reineck, Richard W. Osgood, Robert T. Kunau, Jay H. Stein
Journal: Journal of Clinical Investigation (1978)

Studies were performed in Munich-Wistar rats to determine whether changes in papillary plasma flow might be responsible for the concentrating defect which occurs after exposure of the extrarenal papilla. Papillary plasma flow was measured by 125I-albumin accumulation. Initial studies in hydropenic animals revealed that papillary plasma flow was 40% higher in the kidney with the exposured papilla, 41 vs. 29 ml/min per 100 g of papilla (P < 0.001). This increase in papillary plasma flow was detectable 15 or 45 min after removing the ureter. Because it was unclear whether the rise in papillary plasma flow was a cause or the result of the fall in urine osmolality, similar studies were performed in animals undergoing a water diuresis. In this setting, papillary plasma flow still increased on the exposed side compared to the control side, 81 vs. 60 ml/min per 100 g, despite similarly low urine osmolalities of 155 and 174 mosmol/kg, respectively. This finding is compatible with the possibility that papillary exposure per se causes an increase in papillary plasma flow and that this hemodynamic alteration may lead to a reduction in urinary osmolality secondary to washout of the medullary interstitium. A final group of hydropenic rats was given either indomethacin or meclofenamate before removing the ureter. In these studies, there was no difference in either the papillary plasma flow or the urine osmolality between control and exposed kidneys. It is therefore suggested that opening the ureter induces an increase in papillary plasma flow by some mechanism which may involve an alteration in prostaglandin synthesis.
The Human Microbiome: From Symbiosis to Pathogenesis
Authors: Emiley A. Eloe-Fadrosh, David A. Rasko
Journal: Annual Review of Medicine (2013)

The human microbiota is a complex assemblage of the microbes inhabiting many sites in the human body. Recent advances in technology have enabled deep sequencing and analysis of the members and structures of these communities. Two sites, the vagina and gastrointestinal tract, are highlighted to exemplify how technological advances have enhanced our knowledge of the host–microbiota system. These examples represent low- and high-complexity communities, respectively. In each example, certain community structures are identified that can be extrapolated to larger collections representing multiple individuals and potential disease or health states. One common feature is the unexpected diversity of the microbiota at any of these locations, which poses a challenge for relating the microbiota to health and disease. However, we anticipate microbiota compositional measurements could become standard clinical practice in the future and may become diagnostic for certain diseases or increased susceptibility to certain disorders. The microbiota of a number of disease states are currently being examined to identify potential correlations. In line with these predictions, it is possible that existing conditions may be resolved by altering the microbiota in a positive way.
Early detection of pneumonia as a risk factor for mortality in burned patients in Menoufiya University Hospital
Authors: Rana El-Helbawy, Mohamed Megahed, Ayman Omar, Hala Elmeselhy, Rabab Abd El-Halim
Journal: European Respiratory Journal (2013)

Background  Pneumonia is common among critically ill burned patients. It is a major cause of morbidity and mortality in burn victims. Prediction of mortality in severely burned patient remains unreliable.  Objective:  The aim of this research is to study the incidence, early diagnosis and management of nosocomial pneumonia and to discuss the relationship between pneumonia and death in burn patients.  Methods  This study was carried out on 80 burn patients (35 males and 45 females) admitted to Menoufiya University Hospital Burn Center and Chest Department (Egypt) from September 2011 to Mars 2012.  Results  Our study found an overall burn patient mortality rate of 26.25 %( 21/80). The incidence of pneumonia was 15% (12/80). The mortality rate among patients of pneumonia was 50% (6/12) compared with 22 %( 15/68) for those without pneumonia. The pneumonia was two times higher in the subset of patients with inhalation injury compared with group of patients without inhalation injury (P Conclusions  Pneumonia was an important factor for predicting burn patient mortality. Early detection and management of pneumonia are absolutely essential.
Evaluation of WHO criteria for identifying patients with severe acute respiratory syndrome out of hospital: prospective observational study
Authors: T. H Rainer
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b> To determine the clinical and radiological features of severe acute respiratory syndrome (SARS) and to evaluate the accuracy of the World Health Organization9s guidelines on defining cases of SARS. <b>Design</b> Prospective observational study. <b>Setting</b> A newly set up SARS screening clinic in the emergency department of a university hospital in Hong Kong9s New Territories. <b>Participants</b> 556 hospital staff, patients, and relatives who attended the screening clinic and who had had contact with someone with SARS. <b>Main outcome measure</b> Number of confirmed cases of SARS. <b>Results</b> Of the 556 people, 141 were admitted to hospital, and 97 had confirmed SARS. Fever, chills, malaise, myalgia, rigor, loss of appetite, vomiting, diarrhoea, and neck pain but not respiratory tract symptoms were significantly more common among the 97 patients than among the other patients. The overall accuracy of the WHO guidelines for identifying suspected SARS was 83% and their negative predictive value was 86% (95% confidence interval 83% to 89%). They had a sensitivity of 26% (17% to 36%) and a specificity of 96% (93% to 97%). <b>Conclusions</b> Current WHO guidelines for diagnosing suspected SARS may not be sufficiently sensitive in assessing patients before admission to hospital. Daily follow up, evaluation of non-respiratory, systemic symptoms, and chest radiography would be better screening tools.
Nuclear versus Cytoplasmic Localization of Filamin A in Prostate Cancer: Immunohistochemical Correlation with Metastases
Authors: Roble G. Bedolla, Yu Wang, Alfredo Asuncion, Karim Chamie, Salma Siddiqui, Maria M. Mudryj, Thomas J. Prihoda, Javed Siddiqui, Arul M. Chinnaiyan, Rohit Mehra, Ralph W. de Vere White, Paramita M. Ghosh
Journal: Clinical Cancer Research (2009)

Abstract Purpose: We previously showed that nuclear localization of the actin-binding protein, filamin A (FlnA), corresponded to hormone-dependence in prostate cancer. Intact FlnA (280 kDa, cytoplasmic) cleaved to a 90 kDa fragment which translocated to the nucleus in hormone-naïve cells, whereas in hormone-refractory cells, FlnA was phosphorylated, preventing its cleavage and nuclear translocation. We have examined whether FlnA localization determines a propensity to metastasis in advanced androgen-independent prostate cancer. Experimental Design: We examined, by immunohistochemistry, FlnA localization in paraffin-embedded human prostate tissue representing different stages of progression. Results were correlated with in vitro studies in a cell model of prostate cancer. Results: Nuclear FlnA was significantly higher in benign prostate (0.6612 ± 0.5888), prostatic intraepithelial neoplasia (PIN; 0.6024 ± 0.4620), and clinically localized cancers (0.69134 ± 0.5686) compared with metastatic prostate cancers (0.3719 ± 0.4992, P = 0.0007). Cytoplasmic FlnA increased from benign prostate (0.0833 ± 0.2677), PIN (0.1409 ± 0.2293), localized cancers (0.3008 ± 0.3762, P = 0.0150), to metastases (0.7632 ± 0.4414, P &amp;lt; 0.00001). Logistic regression of metastatic versus nonmetastatic tissue yielded the area under the receiver operating curve as 0.67 for nuclear-FlnA, 0.79 for cytoplasmic-FlnA, and 0.82 for both, indicating that metastasis correlates with cytoplasmic to nuclear translocation. In vitro studies showed that cytoplasmic localization of FlnA induced cell invasion whereas nuclear translocation of the protein inhibited it. FlnA dephosphorylation with the protein kinase A inhibitor H-89 facilitated FlnA nuclear translocation, resulting in decreased invasiveness and AR transcriptional activity, and induced sensitivity to androgen withdrawal in hormone-refractory cells. Conclusions: The data presented in this study indicate that in prostate cancer, metastasis correlates with cytoplasmic localization of FlnA and may be prevented by cleavage and subsequent nuclear translocation of this protein.
A New Locus for Familial FSGS on Chromosome 2P
Authors: Rasheed Gbadegesin, Peter Lavin, Louis Janssens, Bartlomiej Bartkowiak, Alison Homstad, Guanghong Wu, Brandy Bowling, Jason Eckel, Chris Potocky, Diana Abbott, Peter Conlon, William K. Scott, David Howell, Elizabeth Hauser, Michelle P. Winn
Journal: Journal of the American Society of Nephrology (2010)

FSGS is a clinicopathologic entity characterized by nephrotic syndrome and progression to ESRD. Although the pathogenesis is unknown, the podocyte seems to play a central role in this disorder. Here, we present six kindreds with hereditary FSGS that did not associate with mutations in known causal genes, and we report a new locus for the disease on chromosome 2p15 in one kindred. We performed genome-wide linkage analysis and refined the linkage area with microsatellite markers and haplotype analysis to define the minimal candidate region. Genome-wide linkage analysis yielded a maximum two-point logarithm of odds (LOD) score of 3.6 for the six families on chromosome 2p. One family contributed the largest proportion of the additive score (LOD 2.02) at this locus. Multipoint parametric LOD score calculation in this family yielded a significant LOD score of 3.1 at markers D2S393 and D2S337, and fine mapping of this region with microsatellite markers defined a minimal candidate region of 0.9 Mb with observed recombinations at markers D2S2332 and RS1919481. We excluded the remaining five families from linkage to this region by haplotype analysis. These data support a new gene locus for familial FSGS on chromosome 2p15. Identification of the mutated gene at this locus may provide further insight into the disease mechanisms of FSGS.
Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk
Authors: Alexander Thompson
Journal: JAMA (2008)

The importance of the cholesteryl ester transfer protein (CETP) pathway in coronary disease is uncertain. Study of CETP genotypes can help better understand the relevance of this pathway to lipid metabolism and disease risk.To assess associations of CETP genotypes with CETP phenotypes, lipid levels, and coronary risk.Studies published between January 1970 and January 2008 were identified through computer-based and manual searches using MEDLINE, EMBASE, BIOSIS, Science Citation Index, and the Chinese National Knowledge Infrastructure Database. Previously unreported studies were sought through correspondence with investigators.Relevant studies related principally to 3 common (TaqIB [rs708272], I405V [rs5882], and -629C>A [rs1800775]) and 3 uncommon (D442G [rs2303790], -631C>A [rs1800776], and R451Q [rs1800777]) CETP polymorphisms.Information on CETP genotypes, CETP phenotypes, lipid levels, coronary disease, and study characteristics was abstracted from publications, supplied by investigators, or both.Ninety-two studies had data on CETP phenotypes, lipid levels, or both in 113,833 healthy participants, and 46 studies had data on 27,196 coronary cases and 55,338 controls. For each A allele inherited, individuals with the TaqIB polymorphism had lower mean CETP mass (-9.7%; 95% confidence interval [CI], -11.7% to -7.8%), lower mean CETP activity (-8.6%; 95% CI, -13.0% to -4.1%), higher mean high-density lipoprotein cholesterol (HDL-C) concentrations (4.5%; 95% CI, 3.8%-5.2%), and higher mean apolipoprotein A-I concentrations (2.4%; 95% CI, 1.6%-3.2%). The pattern of findings was very similar with the I405V and -629C>A polymorphisms. The combined per-allele odds ratios (ORs) for coronary disease were 0.95 (95% CI, 0.92-0.99) for TaqIB, 0.94 (95% CI, 0.89-1.00) for I405V, and 0.95 (95% CI, 0.91-1.00) for -629C>A.Three CETP genotypes that are associated with moderate inhibition of CETP activity (and, therefore, modestly higher HDL-C levels) show weakly inverse associations with coronary risk. The ORs for coronary disease were compatible with the expected reductions in risk for equivalent increases in HDL-C concentration in available prospective studies.
Pulmonary surfactant maintains patency of conducting airways in the rat.
Authors: G Enhorning, L C Duffy, R C Welliver
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The hypothesis was tested that after extrusion of the liquid columns that often block the lumen of conducting airways, the latter will remain open because of well-functioning pulmonary surfactant preventing the liquid columns from returning. The extirpated lungs of 22 Wistar rats were studied. Via a tracheal tube a very fine catheter (PE 10) was inserted and advanced until it pierced the pleura. It was extracted until only 2 mm remained in the lung parenchyma. A pressure transducer measured the resistance that met a steady flow of air through the series of tubes: the PE 10 tube, the conducting airway of the lung, and the tracheal tube. The airway resistance was studied for 240 s after three airway flushings, two with saline solution and one with calf lung surfactant extract (CLSE), 3 mg/ml. The pressure recording showed that a low pressure, indicating airway patency, occurred for only 31 +/- 8 s (mean +/- SEM) after the first saline flush, and for 26 +/- 8 s after the second. After the CLSE flush the airway remained open for 174 +/- 12 s, which indicated a significantly reduced resistance (p < 0.0001). The results imply that well-functioning pulmonary surfactant is required for a low airway resistance.
Association of extent and infection of pancreatic necrosis with organ failure and death in acute necrotizing pancreatitis
Authors: Pramod Kumar Garg, Kaushal Madan, Girish Kumar Pande, Sudeep Khanna, Garipati Sathyanarayan, Narendra Prasad Bohidar, Rakesh Kumar Tandon
Journal: Clinical Gastroenterology and Hepatology (2005)
The status of LTP as a mechanism of memory formation in the mammalian brain
Authors: Tracey J. Shors, Louis D. Matzel
Journal: Behavioral and Brain Sciences (2000)

Long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy that many consider the best candidate currently available for a neural mechanism of memory formation and/or storage in the mammalian brain. In our target article, LTP: What's learning got to do with it?, we concluded that there was insufficient data to warrant such a conclusion. In their commentaries, Jeffery and Zhadin raise a number of important issues that we did not raise, both for and against the hypothesis. Although we agree with a number of these issues, we maintain that there remains insufficient evidence that LTP is a memory mechanism.
Evolution of DNA Methylation Is Linked to Genetic Aberrations in Chronic Lymphocytic Leukemia
Authors: Christopher C. Oakes, Rainer Claus, Lei Gu, Yassen Assenov, Jennifer Hüllein, Manuela Zucknick, Matthias Bieg, David Brocks, Olga Bogatyrova, Christopher R. Schmidt, Laura Rassenti, Thomas J. Kipps, Daniel Mertens, Peter Lichter, Hartmut Döhner, Stephan Stilgenbauer, John C. Byrd, Thorsten Zenz, Christoph Plass
Journal: Cancer Discovery (2013)

Although clonal selection by genetic driver aberrations in cancer is well documented, the ability of epigenetic alterations to promote tumor evolution is undefined. We used 450k arrays and next-generation sequencing to evaluate intratumor heterogeneity and evolution of DNA methylation and genetic aberrations in chronic lymphocytic leukemia (CLL). CLL cases exhibit vast interpatient differences in intratumor methylation heterogeneity, with genetically clonal cases maintaining low methylation heterogeneity and up to 10% of total CpGs in a monoallelically methylated state. Increasing methylation heterogeneity correlates with advanced genetic subclonal complexity. Selection of novel DNA methylation patterns is observed only in cases that undergo genetic evolution, and independent genetic evolution is uncommon and is restricted to low-risk alterations. These results reveal that although evolution of DNA methylation occurs in high-risk, clinically progressive cases, positive selection of novel methylation patterns entails coevolution of genetic alteration(s) in CLL.