tbuckley/cabot-search huggingface dataset:
The combined human sperm proteome: cellular pathways and implications for basic and clinical science
Authors: Alexandra Amaral, Judit Castillo, João Ramalho-Santos, Rafael Oliva
Journal: Human Reproduction Update (2013)

The human sperm cell is very well suited for proteomic studies, as it is accessible, can be easily purified and is believed to be transcriptionally and translationally silent. The recent use of advanced proteomic approaches is clearly challenging the understanding of sperm biology. The aims of this review are to discuss the various human sperm proteomic studies, to create a compiled list of all the sperm proteins described to date and to re-assess the potential functional implications. A search of the scientific literature available in the PubMed/Medline database at 31 December 2012 was conducted for studies on human sperm proteomics. The complete list of proteins obtained was carefully analysed using different bioinformatics tools, including Reactome, a knowledgebase of biological pathways. A total of 30 studies were identified. The proteomics studies have resulted in the identification of 6198 different proteins, an important proportion of which (around 30%) are known to be expressed in the testis. The proteins were assigned to various functional pathways, including metabolism, apoptosis, cell cycle, meiosis and membrane trafficking, among others. Unexpectedly, the sperm cell also contains a range of proteins involved in RNA metabolism and translational regulation, as well as proteins usually located in organelles believed to be absent in sperm, such as cytoplasmatic ribosomes and peroxisomes. Additionally, some proteins whose levels seem to be altered in low-quality sperm might have clinical relevance. The analysis of the most complete sperm proteome available to date indicates the presence of several cellular protein pathways previously ignored in the male gamete. Confirming the activity of each of these pathways and understanding their biological significance will certainly boost the knowledge of human sperm and male fertility and infertility in the next years.
Infiltrative patterns of glioblastoma spread detected via diffusion MRI after treatment with cediranib
Authors: Elizabeth R. Gerstner, Poe-Jou Chen, Patrick Y. Wen, Rakesh K. Jain, Tracy T. Batchelor, Gregory Sorensen
Journal: Neuro-Oncology (2010)

To evaluate the role of apparent diffusion coefficient (ADC) imaging in assessing tumor cell infiltration after treatment with the antivascular endothelial growth factor (anti-VEGF) agent, cediranib, we prospectively analyzed diffusion MRI scans from 30 patients participating in a Phase II trial of cediranib for recurrent glioblastoma. A patient-specific threshold was selected below which ADC values were determined to be abnormally low and suggestive of tumor. We determined the percent of low ADC in the FLAIR hyperintensity surrounding the enhancing tumor and then visualized the location of these low ADC voxels. The percent volume of the FLAIR hyperintensity comprised by low ADC increased significantly from baseline (2.3%) to day 28 (2.9%), day 56 (5.0%), and day 112 (6.3%) of treatment with cediranib suggesting increasing infiltrative tumor in some patients. Visualization of the location of the low ADC voxels suggested regions of tumor growth that were not visible on contrast-enhanced MRI. ADC maps can be used to suggest regions of infiltrative tumor cells with anti-VEGF therapy and should be validated in future studies.
Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis
Authors: A Kling, M Seddighzadeh, L Arlestig, L Alfredsson, S Rantapaa-Dahlqvist, L Padyukov
Journal: Annals of the Rheumatic Diseases (2007)

To analyse the association between the genetic polymorphisms within the HTR2A gene for the serotonin receptor and rheumatoid arthritis (RA).HTR2A gene polymorphisms were analysed in patients with RA and controls from two study populations using PCR based restriction endonuclease mapping or TaqMan allelic discrimination with more than 4000 individuals included in the current study.At the discovery stage we detected significant differences in frequency of rs6313 (T102C polymorphism) between the patients with RA and controls (p = 0.006). Following validation with an extended set of single nucleotide polymorphisms (SNPs) and number of DNA samples, a trend in associations in allelic model for SNPs rs6314, rs1328674, rs6313 and rs6311 (p = 0.006, 0.002, 0.006, 0.009) was seen, although it was lost after correction for multi-comparison for all but rs1328674 (empirical p value = 0.021). However, haplotype frequency analysis based on these four SNPs showed significantly low representation of TCTT combination in patients with RA in comparison with controls (3.6% and 5.6%, p<0.001 on chi(2) test, empirical p = 0.004 after 100 000 permutations) and a significantly higher frequency of CTCC combination in patients with RA in comparison with controls (3.6% and 2.2%, p = 0.002 on chi(2) test, empirical p = 0.022 after 100 000 permutations).In our study, genetic polymorphisms at the HTR2A gene are associated with susceptibility for RA, suggesting possible links between the serotonergic system and development of the disease.
Chronic Kidney Disease in Long-Term Survivors of Hematopoietic Cell Transplantation
Authors: Sangeeta Hingorani
Journal: Journal of the American Society of Nephrology (2006)

High-dose myeloablative hematopoietic cell transplantation is becoming an increasingly common treatment modality for a variety of diseases. Patient survival may be limited by substantial treatment-related toxicities, including chronic kidney disease (CKD). Although the majority of CKD after transplantation is idiopathic, thrombotic microangiopathic syndromes and nephrotic syndrome have been described. Epidemiology, pathogenesis, and potential treatment options for the various clinical syndromes that are associated with CKD in hematopoietic cell transplantation patients is reviewed. As the indications for and the numbers of transplants that are performed worldwide increases, so will the burden of CKD. The nephrologists and oncologists will have to work together to identify patients who are at risk for CKD early to prevent its development and progression to end-stage kidney disease.
Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis
Authors: D. Gupta, R. Agarwal, A. N. Aggarwal, S. K. Jindal
Journal: European Respiratory Journal (2007)

The aetiology of sarcoidosis is currently unknown. Due to the clinical and histological similarities between sarcoidosis and tuberculosis, the role of mycobacteria has been repeatedly investigated as an aetiological agent for sarcoidosis. The current meta-analysis aimed to evaluate the available molecular evidence on the possible role of mycobacteria in the development of sarcoidosis. The MEDLINE, EMBASE, CINAHL, DARE and CENTRAL databases were searched for relevant studies published from 1980 to 2006, and studies evaluating the presence of mycobacteria using molecular techniques in biological samples of patients with sarcoidosis were included in the current analysis. The 95% confidence intervals (CI) were calculated for the expected proportion (of individual studies); the data was then pooled to obtain a summary success rate with 95% CI. The odds ratio (95% CI) was also calculated in order to assess the presence of mycobacteria in samples of patients with sarcoidosis versus those from nonsarcoidosis control samples. The database search yielded 31 studies. All studies used polymerase chain reaction for nucleic acid amplification followed by identification of nucleic acid sequences specific for different types of mycobacteria. Overall, 231 out of the 874 patients were positive for mycobacteria with a positive signal rate of 26.4 (23.6–29.5%), and the odds of finding mycobacteria in samples of patients with sarcoidosis versus controls were 9.67 (4.56–20.5%) using the random effects model and 19.49 (11.21–35.54%) using the exact method. There was methodological and statistical heterogeneity and evidence of publication bias. The results of the current study illustrate a demonstrable mycobacterial presence in sarcoidosis lesions suggesting an association between mycobacteria and some cases of sarcoidosis. To avoid methodological diversity, larger multicentre trials with a central laboratory for sample testing should be designed.
Engineering Myocardial Tissue
Authors: Thomas Eschenhagen, Wolfram H. Zimmermann
Journal: Circulation Research (2005)

To create an artificial heart is one of the most ambitious dreams of the young field of tissue engineering, a dream that, when publicly announced in 1999 (LIFE initiative around M. Sefton), provoked as much compassion as scepticism in the scientific and lay press. Today, it is fair to state that the field is still far away from having built the "bioartificial heart." Nevertheless, substantial progress has been made over the past 10 years, and a realistic perspective exists to create 3-dimensional heart muscle equivalents that may not only serve as experimental models but could also be useful for cardiac regeneration.
Detection of Pulmonary Emboli With <sup>99m</sup>Tc-Labeled Anti–D-dimer (DI-80B3)Fab′ Fragments (ThromboView)
Authors: Timothy A. Morris, Michael Gerometta, Roger D. Yusen, Richard H. White, James D. Douketis, Scott Kaatz, Richard C. Smart, David Macfarlane, Jeffrey S. Ginsberg
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

We report a new method to diagnose acute pulmonary embolism (PE) by single photon emission computerized tomography (SPECT) after administration of (99m)Tc-labeled anti-D-dimer (DI-80B3) monoclonal antibody Fab' fragments. This novel technique provides an additional approach to diagnosing PE in patients for whom other methods are nondiagnostic or contraindicated.We performed a prospective, multicenter study to investigate the sensitivity and specificity of (99m)Tc-DI-80B3/SPECT in patients with suspected acute PE.Subjects with a moderate to high clinical probability of PE or a positive D-dimer test underwent a PE-protocol contrast-enhanced multidetector thoracic computed tomography (CT) scan as well as (99m)Tc-DI-80B3/SPECT (0.5 mg (99m)Tc-DI-80B3 intravenously followed by a thoracic SPECT 2.5 h later). Separate and independent adjudication committees, blinded to clinical data and other test results, interpreted the (99m)Tc-DI-80B3/SPECT scans (PE detected as foci of abnormally increased (99m)Tc uptake) and the thoracic CT scans using Prospective Investigation of Pulmonary Embolism Diagnosis II criteria.Of the 52 patients who were enrolled and completed both tests, 42 had both evaluable SPECT scans and thoracic CT scans. Using the criterion standard (thoracic CT scan) there were 21 patients with PE and 21 without. (99m)Tc-DI-80B3/SPECT had a sensitivity of 76.2% (95% confidence interval, 52.8-91.8%) and a specificity of 90.5% (95% confidence interval, 69.8-98.8%). Treatment-related serious adverse events did not occur.(99m)Tc-DI-80B3/SPECT was sensitive and specific for acute PE in subjects with moderate to high clinical probability of PE or a positive D-dimer test. (99m)Tc-DI-80B3/SPECT demonstrated an acceptable safety profile and avoids exposure to contrast.
Long-term cosmetic changes after breast-conserving treatment of patients with stage I–II breast cancer and included in the EORTC ‘boost versus no boost’ trial
Authors: J.M. Immink, H. Putter, H. Bartelink, J.S. Cardoso, M.J. Cardoso, M.H.V. van der Hulst-Vijgen, E.M. Noordijk, P.M. Poortmans, C.C. Rodenhuis, H. Struikmans
Journal: Annals of Oncology (2012)
Prostate Brachytherapy and Second Primary Cancer Risk: A Competitive Risk Analysis
Authors: Karel A. Hinnen, Michael Schaapveld, Marco van Vulpen, Jan. J. Battermann, Henk van der Poel, Inge M. van Oort, Joep G.H. van Roermund, Evelyn M. Monninkhof
Journal: Journal of Clinical Oncology (2011)

To assess the risk of second primary cancer (SPC) after [(125)I]iodine prostate cancer brachytherapy compared with prostatectomy and the general population.In a cohort consisting of 1,888 patients with prostate cancer who received monotherapy with brachytherapy (n = 1,187; 63%) or prostatectomy (n = 701; 37%), SPC incidences were retrieved by linkage with the Dutch Cancer Registry. Standardized incidence rates (SIRs) and absolute excess risks (AERs) were calculated for comparison.A total of 223 patients were diagnosed with SPC, 136 (11%) after brachytherapy and 87 (12%) after prostatectomy, with a median follow-up of 7.5 years. The SIR for all malignancies, bladder cancer, and rectal cancer were 0.94 (95% CI, 0.78 to 1.12), 1.69 (95% CI, 0.98 to 2.70), and 0.90 (95% CI, 0.41 to 1.72) for brachytherapy and 1.04 (95% CI, 0.83 to 2.28), 1.82 (95% CI, 0.87 to 3.35), and 1.50 (95% CI, 0.68 to 2.85) for prostatectomy, respectively. Bladder SPC risk was significantly increased after brachytherapy for patients age 60 years or younger (SIR, 5.84; 95% CI, 2.14 to 12.71; AER, 24.03) and in the first 4 years of follow-up (SIR, 2.14; 95% CI, 1.03 to 3.94; AER, 12.24). Adjusted for age, the hazard ratio (brachytherapy v prostatectomy) for all SPCs combined was 0.87 (95% CI, 0.64 to 1.18).Overall, we found no difference in SPC incidence between patients with prostate cancer treated with prostatectomy or brachytherapy. Furthermore, no increased tumor incidence was found compared with the general population. We observed a higher than expected incidence of bladder SPC after brachytherapy in the first 4 years of follow-up, probably resulting from lead time or screening bias. Because of power limitations, a small increased SPC risk cannot be formally excluded.
High-sensitivity C-reactive protein is associated with hippocampus volume in nondementia patients with type 2 diabetes mellitus
Authors: Futoshi Anan, Takayuki Masaki, Tsuyoshi Shimomura, Minoru Fujiki, Yoshikazu Umeno, Nobuoki Eshima, Tetsunori Saikawa, Hironobu Yoshimatsu
Journal: Metabolism (2010)
P96 Haplotype variability in Pseudomonas aeruginosa (Psa) strains in the adult CF population
Authors: A. Ashish, J. Fothergill, E. Mowat, J. Greenwood, C. Winstanley, M. Walshaw
Journal: Thorax (2010)

<h3>Introduction</h3> Morphological type variation in Psa is thought to aid its survival in hostile environments, including the CF lung. Previous studies using PGFE have shown wide heterogeneity in LES strain, despite this, little is known about their phenotypic diversity (haplotypes). To look at this further, we compared the haplotypes of the most successful and prevalent UK transmissible Psa (the Liverpool epidemic strain, LES) with those of sporadic strains and assessed their response to antibiotic pressure. <h3>Methods</h3> Sputum from two groups of adult CF patients chronically infected (for at least 4 years) with sporadic single Psa strains or LES was analysed at the beginning and end of an intravenous antibiotic-treated exacerbation, where every patient had subjective and spirometric improvement, and also for LES patients over a period of time (at least 4 months) when they were in a stable state. From each sample, 40 single Psa colonies were selected (with every morphological type proportionately represented), and colony morphology, susceptibility to six antibiotics (ciprofloxacin, ceftazidime, colomycin, meropenem, tobramycin, piperacillin/tazobactam), hypermutability (rate of spontaneous mutation to rifampicin resistance) and auxotrophy (ability to grow on glucose M9 media) determined. Each Psa colony could potentially exhibit any of nine combinations: antibiotic susceptibility patterns, auxotrophy, hypermutability, and six colony morphologies. The resulting haplotypes were compared for LES and unique strains using ‘e-burst’ software. <h3>Results</h3> Overall, 151 unique haplotypes were defined (96 LES, 75 sporadic, 20 shared), with LES demonstrating the greater number (X<sup>2</sup>=4.67, p&lt;0.03). Following antibiotic pressure, there was an alteration in haplotypes which was similar in both groups (LES 54%, sporadic 64%, p=0.28): but during the stable state LES demonstrated a significantly greater change in haplotypes (89%, p=0.004). <h3>Conclusion</h3> A change in haplotypes occurs in all CF Psa strains during treatment for clinical exacerbations, presumably as a defence mechanism against the challenge of hostile antibiotic therapy. However, the enhanced haplotype variability of transmissible strains with time when there is no antibiotic pressure may be a strategy that confers a survival advantage compared to sporadic strains: studies are under way to explore this further.
Severe obstructive sleep apnoea secondary to pressure garments used in the treatment of hypertrophic burn scars
Authors: M. Hubbard, I.B. Masters, G.r Williams, A.b Chang
Journal: European Respiratory Journal (2000)

Obstructive sleep apnoea (OSA) secondary to pressure garments used to treat hypertrophic scarring of burns has never been reported. The present study describes two children who presented with OSA following introduction of such garments for management of hypertrophic scars following severe facial and upper body burns. Complex sleep polysomnography confirmed severe OSA with desaturations sufficient to result in physiological dysfunction that significantly improved on removal of the garments. As there is little evidence to suggest that the use of such garments alters the end result, the potentially serious side effect of obstructive sleep apnoea should be considered before their use is advised.
Detection of Epstein-Barr Virus in Invasive Breast Cancers
Authors: M. Bonnet, J.-M. Guinebretiere, E. Kremmer, V. Grunewald, E. Benhamou, G. Contesso, I. Joab
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Epstein-Barr virus (EBV) may be a cofactor in the development of different malignancies, including several types of carcinomas. In this study, we investigated the presence of EBV in human breast cancers. METHODS: We used tissues from 100 consecutive primary invasive breast carcinomas, as well as 30 healthy tissues adjacent to a subset of the tumors. DNA was amplified by use of the polymerase chain reaction (PCR), with the primers covering three different regions of the EBV genome. Southern blot analysis was performed by use of a labeled EBV Bam HI W restriction fragment as the probe. Infected cells were identified by means of immunohistochemical staining, using monoclonal antibodies directed against the EBV nuclear protein EBNA-1. RESULTS: We were able to detect the EBV genome by PCR in 51% of the tumors, whereas, in 90% of the cases studied, the virus was not detected in healthy tissue adjacent to the tumor ( P <.001). The presence of the EBV genome in breast tumors was confirmed by Southern blot analysis. The observed EBNA-1 expression was restricted to a fraction (5%-30%) of tumor epithelial cells. Moreover, no immunohistochemical staining was observed in tumors that were negative for EBV by PCR. EBV was detected more frequently in breast tumors that were hormone-receptor negative ( P = .01) and those of high histologic grade ( P = .03). EBV detection in primary tumors varied by nodal status ( P = .01), largely because of the difference between subjects with more than three lymph nodes versus less than or equal to three lymph nodes involved (72% versus 44%). CONCLUSIONS: Our results demonstrated the presence of the EBV genome in a large subset of breast cancers. The virus was restricted to tumor cells and was more frequently associated with the most aggressive tumors. EBV may be a cofactor in the development of some breast cancers.
Osteoprotegerin and Mortality in Type 2 Diabetic Patients
Authors: Henrik Reinhard, Maria Lajer, Mari-Anne Gall, Lise Tarnow, Hans-Henrik Parving, Lars M. Rasmussen, Peter Rossing
Journal: Diabetes Care (2010)

OBJECTIVE Plasma osteoprotegerin (OPG) is an emerging strong and independent predictor of cardiovascular disease (CVD) in high-risk populations. OPG is a bone-related glycopeptide produced by vascular smooth muscle cells, and increased plasma OPG levels may reflect arterial vascular damage. We aimed to investigate the prognostic value of OPG in relation to all-cause and cardiovascular mortality in a cohort of type 2 diabetic patients. RESEARCH DESIGN AND METHODS In a prospective observational follow-up study, 283 type 2 diabetic patients (172 men; aged 53.9 ± 8.8 years) were followed for a median of 16.8 years (range 0.2–23.0). Baseline plasma OPG concentrations were determined by immunoassay. RESULTS During follow-up, 193 (68%) patients died. High versus low levels of OPG predicted all-cause mortality (covariate-adjusted for urinary albumin excretion rate [UAER], estimated glomerular filtration rate, and conventional risk factors); hazard ratio (HR) 1.81 [95% CI 1.21–2.69]. The all-cause predictive effect of OPG was independent of NH2-terminal pro-brain natriuretic peptide (NT-proBNP) and was also useful within groups divided according to level of UAER. In total, 103 (73%) patients died because of CVD. High and medium versus low levels of OPG predicted cardiovascular mortality (unadjusted HR 1.86 [95% CI 1.07–3.23] and 3.51 [2.10–5.85], respectively). However, after adjustment for the covariates, HRs were no longer significant. CONCLUSIONS Elevated plasma OPG is a strong predictor of all-cause mortality in type 2 diabetic patients. The effect of OPG on all-cause mortality was independent of conventional cardiovascular risk factors, UAER, and NT-proBNP levels.
Participation of Physicians in Capital Punishment
Authors: R D Truog, T A Brennan
Journal: New England Journal of Medicine (1993)

Despite objections by many professional organizations,18 the participation of physicians and nurses in capital punishment continues and is likely to become more common in the years ahead911. This participation raises important questions about the ethical standards of the medical profession and how they should be enforced. The majority of Americans favor capital punishment,12 and many physicians believe that medical participation in executions is not only ethical but a civic duty13,14. Simply requiring that physicians not be forced to participate against their conscience would not put an end to medical involvement in capital punishment. Should medical . . .
Venous thromboembolic disease and bronchial cancer
Authors: N. Dermech, S. Souilah, Z. Ellalia, A. Fissah, S. Taright, R. Amrane
Journal: European Respiratory Journal (2012)

Venous thromboembolic disease (VTED), defined by the occurrence of a deep thrombosis and/or lung embolism. It is a frequent complication of cancer, particularly during chemotherapy. On average, it occurs with 15 to 20% of the patients, and is one of the main causes of death (one hospitalized cancer patient out of seven).  We have retrospectively evaluated the occurrence of VTED in 139 bronchial cancer patients treated at the pneumology service of CHU Bab El Oued over a twelve-month duration. The incidence was of 8.6% (twelve cases out of 139), 50% of the VTED were present at the time of diagnosis and 50% appeared during the three following months. Among the twelve VTED diagnosed cases (three women and nine men), we found a predominance of the adenocarcinoma type (41.66%). All cases were stage III and IV and had received chemotherapy, with complementary surgical treatment for two patients. The twelve VTED cases had received an anticoagulant treatment with six deaths occurring after six months of treatment, three recoveries and three patients still under anticoagulants.  In conclusion: bronchial cancer predisposes the occurrence of a venous thromboembolic event which, once associated to neoplasia, is a factor of high mortality risk. VTED is more frequent with advanced stages bronchial cancer patients, in adenocarcinoma and with patients under chemotherapy. Response to anticoagulant treatment is uncertain and death can occur after stopping the treatment, which justifies discussing the continuance of anticoagulants, and sometimes even their prescription as preventive treatment.