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1.
Matthew F. Buas Haiwei Gu Danijel Djukovic Jiangjiang Zhu Lynn Onstad Brian J. Reid Daniel Raftery Thomas L. Vaughan 《Metabolomics : Official journal of the Metabolomic Society》2017,13(3):23
Introduction/objectives
Incidence of esophageal adenocarcinoma (EA), an often fatal cancer, has increased sharply over recent decades. Several important risk factors (reflux, obesity, smoking) have been identified for EA and its precursor, Barrett’s esophagus (BE), but a key challenge remains in identifying individuals at highest risk, since most with reflux do not develop BE, and most with BE do not progress to cancer. Metabolomics represents an emerging approach for identifying novel biomarkers associated with cancer development.Methods
We used targeted liquid chromatography-mass spectrometry (LC-MS) to profile 57 metabolites in 322 serum specimens derived from individuals with gastroesophageal reflux disease (GERD), BE, high-grade dysplasia (HGD), or EA, drawn from two well-annotated epidemiologic parent studies.Results
Multiple metabolites differed significantly (P?<?0.05) between BE versus GERD (n?=?9), and between HGD/EA versus BE (n?=?4). Several top candidates (FDR q?≤?0.15), including urate, homocysteine, and 3-nitrotyrosine, are linked to inflammatory processes, which may contribute to BE/EA pathogenesis. Multivariate modeling achieved moderate discrimination between HGD/EA and BE (AUC?=?0.75), with less pronounced separation for BE versus GERD (AUC?=?0.64).Conclusion
Serum metabolite differences can be detected between individuals with GERD versus BE, and between those with BE versus HGD/EA, and may help differentiate patients at different stages of progression to EA.2.
Benjamin H Natelson Roxann Intriligator Neil S Cherniack Helena K Chandler Julian M Stewart 《Dynamic medicine : DM》2007,6(1):2
Context
Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance.Objective
To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls.Design
Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.Setting
Referral practice and research center.Participants
60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test.Main outcome measures
Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.Results
CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.Conclusion
A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.3.
Seyed Mehdi Sajjadi Abbas Khosravi Jalil Pakravesh Zahra-soheila Soheili Shahram Samiei Saeed Mohammadi Mohammad Ali Jalali far 《生物学前沿》2016,11(6):471-475
BACKGROUND
Recurrent pregnancy loss (RPL) is a heterogeneous condition and thrombophilias have been considered as a probable cause.OBJECTIVE
The aim of this study was to investigate the prevalence of the coagulation factor XIII Val34Leu polymorphism among women with unexplained RPL.METHODS
A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Val34Leu polymorphism among the cases and controls was investigated using PCR-RFLP method.RESULTS
Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls (P<0.05): 33.5% vs. 15%, and 9.2% vs. 2%, respectively.CONCLUSION
These results indicate a significant association between FXIII Val34Leu polymorphism and unexplained RPL in the Iranian patient.4.
Background
Soluble receptor for advanced glycation end-products (sRAGE) and advanced glycation end-products (AGE) have been associated with risks of cardiovascular disease. Because sRAGE is regarded as a scavenger to AGE, we hypothesized that the ratio of AGE to sRAGE (AGE/sRAGE) is associated with albuminuria in hypertensive patients.Methods
In this cross-sectional study, a total of 104 patients with essential hypertension were recruited. Hypertension was defined as a systolic blood pressure?≥?140 mmHg, a diastolic blood pressure?≥?90 mmHg, or use of antihypertensive treatment. Albuminuria was defined as albumin excretion rate ≧ 20 μg/min. Multivariate logistic regression analyses were performed to evaluate the association between AGE/sRAGE and albuminuria.Results
Among the 104 patients, 30 (28.8%) patients had albuminuria and 74 (71.2%) patients did not. Patients with albuminuria had higher AGE (2.15 vs. 1.71 μg/mL), lower sRAGE (424.5 vs. 492.5 pg/ml) and higher AGE/sRAGE (3.79 vs. 3.29 μg/pg) than those without albuminuria. Multivariate logistic regression model revealed that AGE/sRAGE (OR?=?1.131, 95% CI?=?1.001–1.278, P?=?0.048) was independently associated with albuminuria. There was no significant relationship between AGE and sRAGE alone with albuminuria.Conclusion
This study suggests that the ratio of AGE to sRAGE may be a surrogate biomarker for microvascular injury. Further prospective studies of the prognostic value of the ratio in relation to microvasular injury are needed.5.
Zichen?Yang Jian?Sun Xiaofeng?Yang Zhiyuan?Zhang Bangwei?Lou Jian?Xiong Hermann?J?Schluesener Zhiren?Zhang
Background
Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies and is characterized by inflammation and demyelination in the peripheral nervous system. Fascin is an evolutionarily highly conserved cytoskeletal protein of 55 kDa containing two actin binding domains that cross-link filamentous actin to hexagonal bundles.Methods
Here we have studied by immunohistochemistry the spatiotemporal accumulation of Fascin?+?cells in sciatic nerves of EAN rats.Results
A robust accumulation of Fascin?+?cell was observed in the peripheral nervous system of EAN which was correlated with the severity of neurological signs in EAN.Conclusion
Our results suggest a pathological role of Fascin in EAN.Virtual slides
The virtual slides for this article can be found here: http://www.diagnosticphatology.diagnomx.eu/vs/67345934511148116.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.7.
Rachel A. Spicer Christoph Steinbeck 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):16
Introduction
Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.Objectives
(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.Methods
A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.Results
Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.Conclusion
Further efforts are required to improve data sharing in metabolomics.8.
Etrusca Brogi Elena Bignami Anna Sidoti Mohammed Shawar Luna Gargani Luigi Vetrugno Giovanni Volpicelli Francesco Forfori 《Cardiovascular ultrasound》2017,15(1):23
Background
Lung ultrasound can be used as an alternative to chest radiography (CXR) for the diagnosis and follow-up of various lung diseases in the intensive care unit (ICU). Our aim was to evaluate the influence that introducing a routine daily use of lung ultrasound in critically ill patients may have on the number of CXRs and as a consequence, on medical costs and radiation exposure.Methods
Data were collected by conducting a retrospective evaluation of the medical records of adult patients who needed thoracic imaging and were admitted to our academic polyvalent ICU. We compared the number of CXRs and relative costs before and after the introduction of lung ultrasound in our ICU.Results
A total of 4134 medical records were collected from January 2010 to December 2014. We divided our population into two groups, before (Group A, 1869 patients) and after (Group B, 2265 patients) the introduction of a routine use of LUS in July 2012. Group A performed a higher number of CXRs compared to Group B (1810 vs 961, P = 0.012), at an average of 0.97 vs 0.42 exams per patient. The estimated reduction of costs between Groups A and B obtained after the introduction of LUS, was 57%. No statistically significant difference between the outcome parameters of the two groups was observed.Conclusions
Lung ultrasound was effective in reducing the number of CXRs and relative medical costs and radiation exposure in ICU, without affecting patient outcome.9.
JB Parentes-Vieira PV Lopes-Costa CG Pires AR dos Santos JD Pereira-Filho BB da Silva 《International Seminars in Surgical Oncology : ISSO》2007,4(1):22
Background
The objective of this study was to evaluate angiogenesis according to CD34 antigen expression in estrogen receptor (ER)-positive and negative breast carcinomas.Methods
This study comprised 64 cases of infiltrating ductal carcinoma in postmenopausal women divided into two groups: Group A: ER-positive, n = 35; and Group B: ER-negative, n = 29. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. Microvessel count was carried out in 10 fields per slide using a 40× objective lens (magnification 400×). Statistical analysis of the data was performed using Student's t-test (p < 0.05).Results
The mean number of vessels stained with the anti-CD34 antibody in the estrogen receptor-positive and negative tumors was 23.51 ± 1.15 and 40.24 ± 0.42, respectively. The number of microvessels was significantly greater in the estrogen receptor-negative tumors (p < 0.001).Conclusion
ER-negative tumors have significantly greater CD34 antigen expression compared to ER-positive tumors.10.
Nadine Strehmel David Strunk Veronika Strehmel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):135
Introduction
Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.Objectives
To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.Methods
The extracted compounds were analyzed by LC/MS and GC/MS.Results
The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.Conclusion
From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.11.
Ying Wang Brian D. Carter Susan M. Gapstur Marjorie L. McCullough Mia M. Gaudet Victoria L. Stevens 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):129
Introduction
Processing delays after blood collection is a common pre-analytical condition in large epidemiologic studies. It is critical to evaluate the suitability of blood samples with processing delays for metabolomics analysis as it is a potential source of variation that could attenuate associations between metabolites and disease outcomes.Objectives
We aimed to evaluate the reproducibility of metabolites over extended processing delays up to 48 h. We also aimed to test the reproducibility of the metabolomics platform.Methods
Blood samples were collected from 18 healthy volunteers. Blood was stored in the refrigerator and processed for plasma at 0, 15, 30, and 48 h after collection. Plasma samples were metabolically profiled using an untargeted, ultrahigh performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) platform. Reproducibility of 1012 metabolites over processing delays and reproducibility of the platform were determined by intraclass correlation coefficients (ICCs) with variance components estimated from mixed-effects models.Results
The majority of metabolites (approximately 70% of 1012) were highly reproducible (ICCs?≥?0.75) over 15-, 30- or 48-h processing delays. Nucleotides, energy-related metabolites, peptides, and carbohydrates were most affected by processing delays. The platform was highly reproducible with a median technical ICC of 0.84 (interquartile range 0.68–0.93).Conclusion
Most metabolites measured by the UPLC–MS/MS platform show acceptable reproducibility up to 48-h processing delays. Metabolites of certain pathways need to be interpreted cautiously in relation to outcomes in epidemiologic studies with prolonged processing delays.12.
Background
Fevers of unknown origin constitute a substantial disease burden in Southeast Asia. In majority of the cases, the cause of acute febrile illness is not identified.Methods
We used MassTag PCR, a multiplex assay platform, to test for the presence of 15 viral respiratory agents from 85 patients with unexplained respiratory illness representing six disease clusters that occurred in Cambodia between 2009 and 2012.Results
We detected a virus in 37 (44%) of the cases. Human rhinovirus, the virus detected most frequently, was found in both children and adults. The viruses most frequently detected in children and adults, respectively, were respiratory syncytial virus and enterovirus 68. Sequence analysis indicated that two distinct clades of enterovirus 68 were circulating during this time period.Conclusions
This is the first report of enterovirus 68 in Cambodia and contributes to the appreciation of this virus as an important respiratory pathogen.13.
Ferran Casbas Pinto Srinivarao Ravipati David A. Barrett T. Charles Hodgman 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):81
Introduction
It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.Objectives
This work simplifies this process.Methods
A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.Results
The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.Conclusion
This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.14.
Background
Currently, information on factors associated with anxiety in family caregivers of children with chronic diseases is unavailable, indicating a significant gap in the literature. Therefore, this study aims to identify the psychosocial and sociodemographic variables associated with anxiety in family caregivers of children with chronic diseases.Methods
In 2018, a nonprobability sample of 446 family caregivers was recruited at the National Institute of Health in Mexico City. The participants completed a sociodemographic variable questionnaire, clinical questions, and 18 psychosocial assessment scales, including a scale to assess family caregiver anxiety.Results
Family caregiver anxiety was correlated with almost all psychosocial variables and one out of three clinical variables but with none of the sociodemographic variables. Furthermore, a multiple linear regression model with five psychosocial variables was established to predict family caregiver anxiety.Conclusions
Some psychosocial variables have effects on caregiver anxiety that are relevant for interventions. Clinical interventions should be implemented based on the psychosocial variables associated with family caregiver anxiety.15.
Introduction
Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.Objectives
Assessment of the quality of raw data processing in untargeted metabolomics.Methods
Five published untargeted metabolomics studies, were reanalyzed.Results
Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.Conclusion
Incomplete raw data processing shows unexplored potential of current and legacy data.16.
Background
In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.Methods
The physical basis of these intuitive maps is clarified by means of analytically solvable problems.Results
Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.Conclusion
Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.17.
Jack W. KentJr 《BMC genetics》2016,17(Z2):S5
Background
New technologies for acquisition of genomic data, while offering unprecedented opportunities for genetic discovery, also impose severe burdens of interpretation andpenalties for multiple testing.Methods
The Pathway-based Analyses Group of the Genetic Analysis Workshop 19 (GAW19) sought reduction of multiple-testing burden through various approaches to aggregation of highdimensional data in pathways informed by prior biological knowledge.Results
Experimental methods testedincluded the use of "synthetic pathways" (random sets of genes) to estimate power and false-positive error rate of methods applied to simulated data; data reduction via independent components analysis, single-nucleotide polymorphism (SNP)-SNP interaction, and use of gene sets to estimate genetic similarity; and general assessment of the efficacy of prior biological knowledge to reduce the dimensionality of complex genomic data.Conclusions
The work of this group explored several promising approaches to managing high-dimensional data, with the caveat that these methods are necessarily constrained by the quality of external bioinformatic annotation.18.
Alexis Catala Rachel Culp-Hill Travis Nemkov Angelo D’Alessandro 《Metabolomics : Official journal of the Metabolomic Society》2018,14(7):100
Introduction
Mass spectrometry and computational biology have advanced significantly in the past ten years, bringing the field of metabolomics a step closer to personalized medicine applications. Despite these analytical advancements, collection of blood samples for routine clinical analysis is still performed through traditional blood draws.Objective
TAP capillary blood collection has been recently introduced for the rapid, painless draw of small volumes of blood (~?100 μL), though little is known about the comparability of metabolic phenotypes of blood drawn via traditional venipuncture and TAP devices.Methods
UHPLC-MS-targeted metabolomics analyses were performed on blood drawn traditionally or through TAP devices from 5 healthy volunteers. Absolute quantitation of 45 clinically-relevant metabolites was calculated against stable heavy isotope-labeled internal standards.Results
Ranges for 39 out of 45 quantified metabolites overlapped between drawing methods. Pyruvate and succinate were over threefold higher in the TAP samples than in traditional blood draws. No significant changes were observed for other carboxylates, glucose or lactate. TAP samples were characterized by increases in reduced glutathione and decreases in urate and cystine, markers of oxidation of purines and cysteine—overall suggesting decreased oxidation during draws. The absolute levels of bile acids and acyl-carnitines, as well as almost all amino acids, perfectly correlated among groups (Spearman r?≥?0.95).Conclusion
Though further more extensive studies will be mandatory, this pilot suggests that TAP-derived blood may be a logistically-friendly source of blood for large scale metabolomics studies—especially those addressing amino acids, glycemia and lactatemia as well as bile acids, acyl-carnitine levels.19.
Alexander Kogan Eilon Ram Shany Levin Enrique Z. Fisman Alexander Tenenbaum Ehud Raanani Leonid Sternik 《Cardiovascular diabetology》2018,17(1):151
Background
Type 2 diabetes mellitus (DM) is a frequent co-morbidity among patients undergoing coronary artery bypass grafting (CABG) surgery. The aim of this study was to evaluate the impact of DM on the early- and long-term outcomes of patients who underwent isolated CABG.Methods
We performed an observational cohort study in a large tertiary medical center over a period of 11 years. All data from patients who had undergone isolated CABG surgery between 2004 and 2014 were obtained from our departmental database. The study population included 2766 patients who were divided into two groups: Group I (1553 non-diabetic patients), and Group II (1213 patients suffering from type 2 DM). Group II patients were then divided into two subgroups: subgroup IIA (981 patients treated with oral antihyperglycemic medications) and subgroup IIB (232 insulin-treated patients with or without additional oral antihyperglycemic drugs). In-hospital, 1-, 3-, 5- and 10-year mortality outcome variables were evaluated. Mean follow-up was 97?±?41 months.Results
In-hospital mortality was similar between Group I and Group II patients (1.87% vs. 2.31%, p?=?0.422) and between the subgroups IIA and IIB (2.14% vs. 3.02%, p?=?0.464). Long-term mortality (1, 3, 5 and 10 years) was higher in Group II (DM type 2) compared with Group I (non-diabetic patients) (5.3% vs. 3.6%, p?=?0.038; 9.3% vs. 5.6%, p?<?0.001; 15.3% vs. 9.3%, p?<?0.001 and 47.3% vs. 29.6% p?<?0.001). Kaplan–Meier analysis demonstrated that all-cause mortality was higher in Group II compared with Group I (p?<?0.001) and in subgroup IIB compared with subgroup IIA (p?=?0.001). Multivariable analysis showed that DM increased the mortality hazard by twofold, and among diabetic patients, insulin treatment increased the mortality hazard by twofold.Conclusions
Diabetic and non-diabetic patients have similar in-hospital mortality rates. Survival rates of diabetic patients start to deteriorate 3 year after surgery. Type 2 DM is an independent predictor for long-term mortality after isolated CABG surgery. Mortality is even higher when the diabetes treatment strategy included insulin.20.
Sonia Liggi Christine Hinz Zoe Hall Maria Laura Santoru Simone Poddighe John Fjeldsted Luigi Atzori Julian L. Griffin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):52