bluuebunny/crossref_metadata_2025_split huggingface dataset:
A quasi-digital approach to peptide sequencing using tandem nanopores with endo- and exo-peptidases
Authors: Sampath G. 
Published: April 2015

AbstractA method of sequencing peptides using tandem cells (RSC Adv., 2015,5, 167-171;RSC Adv., 2015,5, 30694-30700) and peptidases is considered. A double tandem cell (two tandem cells in tandem) has three nanopores in series, an amino-acid-specific endopeptidase attached downstream of the first pore, and an exopeptidase attached downstream of the second pore. The endopeptidase cleaves a peptide threaded through the first pore into fragments that are well separated in time. Fragments pass through the second pore and are each cleaved by the exopeptidase into a series of single residues; the latter pass through the third pore and cause separate current blockades that can be counted. This leads to an ordered list of integers corresponding to the number of residues in each fragment. With 20 cells, one per amino acid type, and 20 peptide copies, the resulting 20 lists of integers are used by a simple algorithm to assemble the sequence. This is a quasi-digital process that uses the lengths of subsequences to sequence the peptide, it differs from conventional analog methods which seek to identify monomers in a polymer via differences in blockade levels, residence times, or transverse currents. Several implementation issues are discussed. In particular the problem of fast analyte translocation, widely considered intransigent, may be resolved through the use of a sufficiently long (40-60 nm) third pore. This translates to a required bandwidth of 1-2 MHz, which is within the range of currently available CMOS circuits.
SCT promoter methylation is a highly discriminative biomarker for lung and many other cancers
Authors: Sathe Adwait , Zhang Yu-An , Ma Xiaotu , Ray Pradipta , Cadinu Daniela , Wang Yi-Wei , Yao Xiao , Liu Xiaoyun , Tang Hao , Wang Yunfei , Huang Ying , Liu Changning , Gu Jin , Akerman Martin , Mo Yifan , Cheng Chao , Xuan Zhenyu , Chen Lei , Xiao Guanghua , Xie Yang , Girard Luc , Wang Hongyang , Lam Stephen , Wistuba Ignacio I , Zhang Li , Gazdar Adi F , Zhang Michael Q 
Published: April 2015

AbstractAberrant DNA methylation has long been implicated in cancers. In this work we present a highly discriminative DNA methylation biomarker for non-small cell lung cancers and fourteen other cancers. Based on 69 NSCLC cell lines and 257 cancer-free lung tissues we identified a CpG island in SCT gene promoter which was verified by qMSP experiment in 15 NSCLC cell lines and 3 immortalized human respiratory epithelium cells. In addition, we found that SCT promoter was methylated in 23 cancer cell lines involving >10 cancer types profiled by ENCODE. We found that SCT promoter is hyper-methylated in primary tumors from TCGA lung cancer cohort. Additionally, we found that SCT promoter is methylated at high frequencies in fifteen malignancies and is not methylated in ∼1000 non-cancerous tissues across >30 organ types. Our study indicates that SCT promoter methylation is a highly discriminative biomarker for lung and many other cancers.
Medical constructions of long‐term exhaustion, past and present
Authors: Lian Olaug S. , Bondevik Hilde 
Published: April 2015

AbstractCulture and history affect the ways in which medical knowledge is shaped, sustained and changed. The less knowledge we have, the larger the space for the cultural imprint becomes. Based on these assumptions, we ask: how have medical constructions of long‐term exhaustion changed over time, and how are changing constructions related to societal change? To discuss these questions we conducted a comparative study of medical texts from two historical periods: 1860–1930 and 1970–2013. Our data are limited to two diagnoses: neurasthenia and encephalomyelitis. After comparing the two periods by identifying diverging and converging aspects, we interpreted observed continuities and interruptions in relation to historical developments. We found that in the medical literature, long‐term exhaustion became transformed from a somatic ailment bred by modern civilisation to a self‐inflicted psychiatric ailment. At the same time, it changed from being a male‐connoted high‐status condition to a female‐connoted low‐status condition. We interpret these changes as contingent upon culturally available modes of interpretations. Medical knowledge thereby becomes infused with cultural norms and values which give them a distinct cultural bias. The historical controversies surrounding this medically contested condition neatly display the socially contingent factors that govern the social construction of medical knowledge.
The risk experience: the social effects of health screening and the emergence of a proto‐illness
Authors: Gillespie Chris 
Published: April 2015

AbstractThose who undergo health screening often experience physical and emotional effects as a result of the screening process. However, the effects of health screening go beyond these physical and mental complications, often having profound social effects for those who are screened. This study explores the social implications of health screening for people who undergo it and are designated as being at risk for potential disease. Through a qualitative analysis of the experiences of individuals with elevated cholesterol levels and men with elevated prostate‐specific antigen (PSA) levels, this research offers a description of the experience of being at risk, identifying three primary components: increased medical contact, a restructuring of everyday routines and altered social relationships. Whereas the at‐risk health status engendered by current clinical approaches to screening and surveillance has been characterised as proto‐disease, this study develops a companion definition of proto‐illness to characterise the social experience of life with an identified health risk. Those who are at risk act in ways that are similar to those who are ill. The concept of proto‐illness implies that the experience of risk is parallel to the experience of illness and contributes to the sociology of medical screening by establishing a much needed bridge between the two experiences.
Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock
Authors: Dahl R. M. , Grønlykke L. , Haase N. , Holst L. B. , Perner A. , Wetterslev J. , Rasmussen B. S. , Meyhoff C. S. ,   the 6S‐Trial and TRISS Trial investigators
Published: April 2015

BackgroundSupplemental oxygen therapy is used for intensive care (ICU) patients with severe sepsis, but with no general guidelines and few safety data. The aim of this observational study was to describe the variability in oxygen administration as well as the association between partial pressure of arterial oxygen (PaO2) and mortality.MethodsWe extracted data from two Scandinavian clinical trials of ICU patients with severe sepsis or septic shock. We calculated average PaO2 and fraction of inspired oxygen (FiO2) from trial inclusion and the following 5 days, and assessed the association between PaO2 and 90‐day mortality.ResultsThe median PaO2 was 9.8 kPa [5–95% range 6.4–19.9] and FiO2 was 0.51 [5–95% range 0.27–1.00], respectively. Eight hundred and five of 1,770 patients (45%) died. The relative risk of mortality was 1.43 [95% CI: 1.19–1.65] in patients with average PaO2 < 8 kPa and 1.29 [95% CI: 0.84–1.68] in patients with average PaO2 ≥ 16 kPa, as compared to patients with average PaO2 10–12 kPa. The relative risk of mortality was 1.38 [95% CI: 1.17–1.58] in patients with an average FiO2 0.60–0.80 and 2.10 [95% CI: 1.88–2.23] in patients with an average FiO2 ≥ 0.80 as compared to patients with an average FiO2 ≤ 0.40.ConclusionAdministration of oxygen in patients with severe sepsis resulted in a wide range of PaO2. Significantly higher mortality was observed in patients with an average PaO2 < 8 kPa and FiO2 ≥ 0.60. The results do not imply causation and the associations between average PaO2 and adverse outcomes have to be assessed further.
Peripherally applied opioids for postoperative pain: evidence of an analgesic effect? A systematic review and meta‐analysis
Authors: Nielsen B. N. , Henneberg S. W. , Schmiegelow K. , Friis S. M. , Rømsing J. 
Published: April 2015

BackgroundOpioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain.MethodsWe searched PubMed (1966 to June 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity scores, consumption of supplemental analgesics and time to first analgesic were included. Trials with sample sizes of fewer than 10 patients per treatment group or trials with opioids administered intra‐articularly or as peripheral nerve blocks were excluded.ResultsData from 26 studies, including 1531 patients and 13 different surgical interventions were included. Clinical heterogeneity of the studies was substantial. Meta‐analysis indicated statistically significant, but not clinically relevant, reductions in VAS score at 6–8 h (mean difference −4 mm, 95% CI: −6 to −2) and 12 h postoperatively (mean difference −5 mm, 95% CI: −7 to −3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41–265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved postoperative analgesia.ConclusionEvidence of a clinically relevant analgesic effect of peripherally applied opioids for acute postoperative pain is lacking. The analgesic effect of peripherally applied opioids may depend on the presence of preoperative inflammation.
DNA methylation and healthy human aging
Authors: Jones Meaghan J. , Goodman Sarah J. , Kobor Michael S. 
Published: April 2015

SummaryThe process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next‐generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site‐specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age‐related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining ‘epigenetic age’ for human health and outline some important caveats to existing and future studies.
Oral candidal carriage in asymptomatic patients
Authors: Mun MSS , Yap T , Alnuaimi AD , Adams GG , McCullough MJ 
Published: April 2015

AbstractBackgroundInterest in the association between oral cancer risk and Candida‐associated promotion of mucosal dysplasia continues. However, little is known of the presence and amount of oral yeast in the mouths of healthy patients without mucosal lesions. The purpose of this prospective cross‐sectional clinical study was to ascertain the prevalence and degree of carriage of Candida in the oral cavities of a non‐cancer population, with reference to a range of parameters affecting the oral environment.MethodsOral rinse samples were collected from a sample of 203 patients attending the Royal Dental Hospital of Melbourne and analysed for the presence and degree of colonization of yeast species that were phenotypically identified as albicans and non‐albicans species.ResultsOral yeast carriage was found in 98/203 patients (48.3%), and of these, 83 (84.7%) patients carried C. albicans. There was no statistical difference in carriage when comparing gender, age, or presence of a removable prosthesis.ConclusionsBoth smoking and the presence of active carious lesions were found to be positively correlated with the carriage of oral Candida. Individuals who are current smokers are nearly seven times more likely to have oral Candida, and participants with high candidal colonization are more likely to be current smokers. Participants with active carious lesions were also more likely to carry oral Candida.
Pregnancies in women with childhood vesicoureteral reflux
Authors: Roihuvuo‐Leskinen Hanna‐Mari , Vainio Merja I. , Niskanen Kaija M. , Lahdes‐Vasama Tuija T. 
Published: April 2015

AbstractObjectiveThe frequency of pregnancy complications together with renal scarring and voiding dysfunction‐related risk factors were investigated in a cohort of women with a history of childhood vesicoureteral reflux (VUR).DesignA retrospective cross‐sectional cohort study.PopulationEighty‐seven primi‐ or multiparous middle‐aged women diagnosed with primary non‐obstructive VUR in childhood.MethodsPregnancy outcome was assessed from case records and from patient interviews. Urine flow tests for voiding patterns, renal ultrasound for detecting scars, and blood samples for renal function were investigated. The median follow‐up time was 38 years.Main outcome measuresPrevalence of pregnancy complications in women with childhood VUR in relation to renal scars and voiding abnormalities.ResultsMaternal complications were seen in 64% of the women and fetal complications in 13%. The women with renal scars (48/87) more often had hypertension (33%), proteinuria (40%) and urinary tract infections (42%) during pregnancy than women without scarring. The frequency of fetal complications was not increased by renal scarring or proteinuria during pregnancy. Urinary tract infections during pregnancy (33% of the women) and voiding abnormalities (18%) did not increase the frequency of fetal or maternal complications. The women with fetal complications were more predisposed to frequent urinary tract infections during adult life (55%) than were those without fetal complications (24%) (p = 0.04).ConclusionsThe maternal complication rates in women with childhood VUR were increased only by renal scarring. Frequent urinary tract infections during adulthood seemed to predict an elevated risk of fetal complications.
Acceptance and Commitment Therapy and nicotine patch for smokers with bipolar disorder: preliminary evaluation of in‐person and telephone‐delivered treatment
Authors: Heffner Jaimee L , McClure Jennifer B , Mull Kristin E , Anthenelli Robert M , Bricker Jonathan B 
Published: April 2015

ObjectivesPeople with bipolar disorder are two to three times more likely to smoke and 50% less likely to quit than the general population. New treatments are needed to improve smoking cessation outcomes in this group. The study aim was to develop and pilot test a novel cessation intervention for smokers with bipolar disorder using Acceptance and Commitment Therapy (ACT) combined with nicotine patches.MethodsThe ten‐session ACT intervention was initially evaluated as in‐person, individual counseling (n = 10), then as telephone‐delivered counseling (n = 6). Participants were adult smokers with no more than mild current symptoms of bipolar disorder.ResultsFor the in‐person protocol, end‐of‐treatment outcomes were: 80% retention, 40% of participants with carbon monoxide (CO)‐verified seven‐day point prevalence abstinence (PPA), 90% satisfied with treatment, 8.3 of ten sessions attended, and 54% increase in acceptance of cravings to smoke (i.e., ACT's theory‐based change process) from baseline. The seven‐day PPA at one‐month follow‐up was 30%. For the telephone protocol, end‐of‐treatment outcomes were: 67% retention, 33% reporting seven‐day PPA, 100% satisfied with treatment, 6.7 of ten treatment calls completed, and 55% increase in acceptance from baseline. At one‐month follow‐up, seven‐day PPA was 17%. The proportion of treatment completers who used at least 80% of the nicotine patches was 62.5% for the in‐person protocol and 0% for the telephone protocol.ConclusionsBoth in‐person and telephone‐delivered ACT were feasible. Despite low adherence to nicotine patches, the intervention showed preliminary evidence of facilitating quitting and impacting ACT's change mechanism. A randomized, controlled trial of this targeted ACT intervention is now needed.
Intravenous carbamazepine as short‐term replacement therapy for oral carbamazepine in adults with epilepsy: Pooled tolerability results from two open‐label trials
Authors: Lee Deborah , Kalu Uwa , Halford Jonathan J. , Biton Victor , Cloyd James , Klein Pavel , Bekersky Ihor , Peng Guangbin , Dheerendra Suresh , Tolbert Dwain 
Published: April 2015

SummaryObjectiveTo report tolerability findings and maintenance of seizure control from a pooled analysis of phase I open‐label trial OV‐1015 (NCT01079351) and phase III study 13181A (NCT01128959).MethodsPatients receiving a stable oral dosage of carbamazepine were switched to an intravenous (IV) carbamazepine formulation solubilized in a cyclodextrin matrix (at a 70% dosage conversion) for either a 15‐ or a 30‐min infusion every 6 h for up to 7 days and then switched back. A subset of patients who tolerated 15‐min infusions also received 2‐ to 5‐min (rapid) infusions. Assessments included physical and laboratory evaluations, electrocardiography (ECG) studies, as well as adverse event (AE) monitoring for tolerability. Convulsion/seizure AE terms and data from seizure diaries were used as proxies for the assessment of consistency of seizure control between formulations.ResultsOf the 203 patients exposed to IV carbamazepine (30 min, n = 43; 15 min, n = 160), 113 received 149 rapid infusions. During infusion, the most commonly reported AEs (≥5%) were dizziness (19%), somnolence (6%), headache (6%), and blurred vision (5%). IV carbamazepine was not associated with clinically relevant cardiac AEs. The tolerability profile appeared similar between patients who received <1,600 mg/day (n = 174) and ≥1,600 mg/day (n = 29) carbamazepine. Cyclodextrin exposure was not associated with clinically relevant changes in AEs or renal biomarkers. Seizure control was maintained as patients transitioned between oral and IV carbamazepine.SignificanceIV carbamazepine administered as multiple 30‐ or 15‐min infusions every 6 h, and as a single rapid infusion, was well tolerated as a short‐term replacement in adults with epilepsy receiving stable dosages of oral carbamazepine. Infusion site reactions, which were generally mild, were the only unique AEs identified; seizure control was generally unchanged when patients were switching between formulations.
Inter‐domain electron transfer in cellobiose dehydrogenase: modulation by pH and divalent cations
Authors: Kracher Daniel , Zahma Kawah , Schulz Christopher , Sygmund Christoph , Gorton Lo , Ludwig Roland 
Published: April 2015

The flavocytochrome cellobiose dehydrogenase (CDH) is secreted by wood‐decomposing fungi, and is the only known extracellular enzyme with the characteristics of an electron transfer protein. Its proposed function is reduction of lytic polysaccharide mono‐oxygenase for subsequent cellulose depolymerization. Electrons are transferred from FADH2 in the catalytic flavodehydrogenase domain of CDH to haem b in a mobile cytochrome domain, which acts as a mediator and transfers electrons towards the active site of lytic polysaccharide mono‐oxygenase to activate oxygen. This vital role of the cytochrome domain is little understood, e.g. why do CDHs exhibit different pH optima and rates for inter‐domain electron transfer (IET)? This study uses kinetic techniques and docking to assess the interaction of both domains and the resulting IET with regard to pH and ions. The results show that the reported elimination of IET at neutral or alkaline pH is caused by electrostatic repulsion, which prevents adoption of the closed conformation of CDH. Divalent alkali earth metal cations are shown to exert a bridging effect between the domains at concentrations of > 3 mm, thereby neutralizing electrostatic repulsion and increasing IET rates. The necessary high ion concentration, together with the docking results, show that this effect is not caused by specific cation binding sites, but by various clusters of Asp, Glu, Asn, Gln and the haem b propionate group at the domain interface. The results show that a closed conformation of both CDH domains is necessary for IET, but the closed conformation also increases the FAD reduction rate by an electron pulling effect.
Snaps and mends: DNA breaks and chromosomal translocations
Authors: Javadekar Saniya M. , Raghavan Sathees C. 
Published: April 2015

Integrity in entirety is the preferred state of any organism. The temporal and spatial integrity of the genome ensures continued survival of a cell. DNA breakage is the first step towards creation of chromosomal translocations. In this review, we highlight the factors contributing towards the breakage of chromosomal DNA. It has been well‐established that the structure and sequence of DNA play a critical role in selective fragility of the genome. Several non‐B‐DNA structures such as Z‐DNA, cruciform DNA, G‐quadruplexes, R loops and triplexes have been implicated in generation of genomic fragility leading to translocations. Similarly, specific sequences targeted by proteins such as Recombination Activating Genes and Activation Induced Cytidine Deaminase are involved in translocations. Processes that ensure the integrity of the genome through repair may lead to persistence of breakage and eventually translocations if their actions are anomalous. An insufficient supply of nucleotides and chromatin architecture may also play a critical role. This review focuses on a range of events with the potential to threaten the genomic integrity of a cell, leading to cancer.