bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Synthetic Challenge of Thioglycolurils
Authors: Singh Mandeep , Parvari Galit , Botoshansky Mark , Keinan Ehud , Reany Ofer 
Published: January 2014

AbstractThe very high stability of cucurbiturils under harsh acidic conditions and their reported prolific chemistry over more than three decades pose a question: why has no thiocucurbituril been reported to date? Furthermore, although glycoluril is a highly stable, easily accessible precursor of all cucurbiturils, its sulfur analog represents a yet unmet synthetic challenge. The reaction between glyoxal and thiourea was found to stop at the level of dihydroxyimidazolidine‐2‐thione, which is quite unstable under various acidic conditions. In an attempt to answer these questions, several stable analogs of thioglycoluril, that is, monothioglycoluril, ditolylthioglycoluril, and its diether derivative were prepared and characterized in the hope that they could be employed as building blocks for the synthesis of thiocucurbiturils. Several side products were also obtained that highlight the complex reactivity of thiourea in these reactions. The crystal structures of the above‐mentioned thioglycolurils are dominated by networks of hydrogen‐bonding interactions. Attempts to co‐oligomerize these compounds with formaldehyde clearly suggest that it is impossible to synthesize thiocucurbiturils by the methods commonly used for the preparation of cucurbiturils. Given that thiocucurbiturils are expected to be stable molecules, alternative synthetic strategies that are different from the thermodynamically controlled approaches must be designed.
Assessment of Mutational Load in Biopsy Tissue Provides Additional Information About Genomic Instability to Histological Classifications of Barrett's Esophagus
Authors: Khara Harshit S. , Jackson Sara A. , Nair Saraswathi , Deftereos Georgios , Patel Shweta , Silverman Jan F. , Ellsworth Eric , Sumner Cameron , Corcoran Brendan , Smith Dennis M. , Finkelstein Sydney , Gross Seth A. 
Published: January 2014

Abstract
Purpose
Progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is associated with accumulated genomic instability. Current risk stratification of BE for EAC relies on histological classification and grade of dysplasia. However, histology alone cannot assess the risk of patients with inconsistent or non-dysplastic BE histology. We, therefore, examined the presence and extent of genomic instability in advanced and less advanced BE histology using mutational load (ML).

Methods
ML summarized the presence and clonality of loss of heterozygosity (LOH) mutations and the emergence of new alleles, manifested as microsatellite instability (MSI) mutations, in ten genomic loci around tumor suppressor genes associated with EAC. The ML of 877 microdissected targets from BE biopsies was correlated to their histology. Histological targets were categorized into three levels: no ML, low ML, and high ML.

Results
Increasing ML correlated with increasingly severe histology. By contrast, proportions of targets that lacked mutations decreased with increasingly severe histology. A portion of targets with non-dysplastic and low-grade histology shared a similar ML as those with higher risk and EAC disease. The addition of MSI characterization to ML helped to differentiate the ML between advanced and less advanced histology.

Conclusions
Given that EAC is associated with accumulated genomic instability, high ML in less severe histology may identify BE disease at greater risk of progression to EAC. ML may help to better manage BE in early histological stages and when histology alone provides insufficient information.
Coupling of the Okuda–Dawson model with a shear current-driven wave and the associated instability
Authors: MASOOD W. , SALEEM H. 
Published: January 2014

AbstractIt is pointed out that the Okuda–Dawson mode can couple with the newly proposed current-driven wave. It is also shown that the Shukla–Varma mode can couple with these waves if the density inhomogeneity is taken into account in a plasma containing stationary dust particles. A comparison of several low-frequency electrostatic waves and instabilities driven by shear current and shear plasma flow in an electron–ion plasma with and without stationary dust is also presented.
Emerging paradigms in anti-infective drug design
Authors: BARRETT MICHAEL P. , CROFT SIMON L. 
Published: January 2014

ABSTRACTThe need for new drugs to treat microbial infections is pressing. The great progress made in the middle part of the twentieth Century was followed by a period of relative inactivity as the medical needs relating to infectious disease in the wealthier nations receded. Growing realisation that anti-infectives are needed in many parts of the world, to treat neglected diseases as well as to combat the burgeoning risk of resistance to existing drugs, has galvanised a new wave of research into anti-microbial drugs. The transfer of knowledge from the Pharmaceutical industry relating to the importance of understanding how to target drugs successfully within the body, and improved understanding of how pathogens interact with their hosts, is driving a series of new paradigms in anti-infective drug design. Here we provide an overview of those processes as an introduction to a series of articles from experts in this area that emerged from a meeting entitled “Emerging Paradigms in Anti-Infective Drug Design” held in London on the 17th and 18th September 2012. The symposium was organised jointly by British Society for Parasitology (BSP) and the Biological & Medicinal Chemistry sector of the Royal Society of Chemistry (RSC) and held at the London School of Hygiene & Tropical Medicine. The symposium set out to cover all aspects of the identification of new therapeutic modalities for the treatment of neglected and tropical diseases. We aimed to bring together leading scientists from all the disciplines working in this field and cover the pharmacology, medicinal chemistry and drug delivery of potential new medicines. Sessions were held on: “Target diseases and targets for drugs”, “Target based medicinal chemistry”, “Bioavailability and chemistry”, “Targeting intracellular microbes”, “Alternative approaches and models”, and “New anti-infectives – how do we get there?”This symposium was organised by Simon Croft (LSHTM) and Mike Barrett (University of Glasgow) for the BSP, and David Alker (David Alker Associates) and Andrew Stachulski (University of Liverpool) for the Biological & Medicinal Chemistry sector of the RSC.
Lineage-specific expansions of TET/JBP genes and a new class of DNA transposons shape fungal genomic and epigenetic landscapes
Authors: Iyer Lakshminarayan M. , Zhang Dapeng , de Souza Robson F. , Pukkila Patricia J. , Rao Anjana , Aravind L. 
Published: January 2014

Significance
5-Methylcytosine in DNA of eukaryotes, such as humans, is an important epigenetic mark. The recently characterized TET/JBP enzymes generate oxidized derivatives of methylcytosine, such as hydroxy-, formyl-, and carboxymethylcytosine in mammals, which serve as further epigenetic marks or intermediates for demethylation. Unlike animals, which contain one to three TET genes, fungi, such as mushrooms and rusts, display lineage-specific expansions with numerous TET/JBP genes, which are often associated with a unique class of transposable elements. We present evidence that expansion and turnover of these elements and associated TET/JBP genes play important roles in genomic organization, epigenetics, and speciation of fungal lineages, especially basidiomycetes (mushrooms, rusts, and smuts). Domesticated versions of these transposons might also participate in genome rearrangements or repair in humans.
D-Tailor: automated analysis and design of DNA sequences
Authors: Guimaraes Joao C. , Rocha Miguel , Arkin Adam P. , Cambray Guillaume 
Published: January 2014

Abstract
Motivation: Current advances in DNA synthesis, cloning and sequencing technologies afford high-throughput implementation of artificial sequences into living cells. However, flexible computational tools for multi-objective sequence design are lacking, limiting the potential of these technologies.
Results: We developed DNA-Tailor (D-Tailor), a fully extendable software framework, for property-based design of synthetic DNA sequences. D-Tailor permits the seamless integration of multiple sequence analysis tools into a generic Monte Carlo simulation that evolves sequences toward any combination of rationally defined properties. As proof of principle, we show that D-Tailor is capable of designing sequence libraries comprising all possible combinations among three different sequence properties influencing translation efficiency in Escherichia coli. The capacity to design artificial sequences that systematically sample any given parameter space should support the implementation of more rigorous experimental designs.
Availability: Source code is available for download at https://sourceforge.net/projects/dtailor/
Contact: aparkin@lbl.gov or cambray.guillaume@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online (D-Tailor Tutorial).
Outcome Characteristics of Multiple-Valve Surgery
Authors: Vassileva Christina M. , Li Shuang , Thourani Vinod H. , Suri Rakesh M. , Williams Matthew L. , Lee Richard , Rankin J. Scott 
Published: January 2014

Objective Multiple-valve (MUV) procedures currently exhibit higher operative mortality than do single-valve procedures, but a paucity of scientific information exists to explain the observation. This topic was examined using The Society of Thoracic Surgeons Database. Methods All patients in the The Society of Thoracic Surgeons data set undergoing valve surgery (except pulmonary valve and aortic root operations) from 1993 through 2007 were identified (N = 623,039). Baseline characteristics and postoperative outcomes were contrasted between all seven combinations of single-valve and MUV procedures involving aortic, mitral, and tricuspid valves. Seven independent logistic regression analyses were performed, based on the seven procedures, and multivariable risk factors for mortality were compared, with emphasis on single-valve versus MUV procedures. Results Baseline characteristics for MUV procedures (n = 67,926) shared many similarities to those for single-valve procedures (n = 555,113), including age, ejection fraction, and comorbidities. Preoperative renal failure, New York Heart Association class III to IV, nonelective presentation, and reoperation were slightly more common in MUV subsets, and coronary bypass was less frequent. Operative mortality was almost double for MUV as compared with single-valve procedures (10.7% vs 5.7%, P = 0.0001). Categorical predictors with the largest odds ratios for mortality were emergency status, renal failure, and second reoperation. However, predictors for mortality were generally consistent in order and magnitude between the single-valve and MUV subgroups. Conclusions Despite similarities in preoperative profiles of the patients undergoing single-valve and MUV procedures, mortality for MUV surgery remains considerably higher. Determinants of operative mortality and morbidity differ little across the procedural groups, and these findings serve as a benchmark for future studies, as well as suggest a continued search for explanations of poorer MUV outcomes.
Is the one‐step nucleic acid amplification assay better for intra‐operative assessment of breast sentinel nodes?
Authors: Bettington Mark , Lakhani Sunil R. , Ung Owen A. 
Published: January 2014

AbstractBackgroundIntra‐operative assessment of sentinel lymph nodes in breast cancer offers the opportunity to prevent two‐stage surgical procedures. At our institution we employ touch imprint cytology (TIC), which lacks sensitivity. In this study we compare the one‐step nucleic acid amplification (OSNA) assay to TIC.MethodsImprints were taken from 63 lymph nodes from 35 patients. The lymph nodes were sectioned at 2‐mm intervals and alternate slices submitted for either histology or OSNA assay, with histology as the reference standard.ResultsSeven patients were histologically positive. Nine and five patients were positive by OSNA and TIC, respectively. Sensitivity, specificity, positive and negative predictive value for the OSNA assay were 85.7%, 85.7%, 63.6% and 96.6% and for TIC were 70.0%, 96.6%, 87.5% and 90.3%.ConclusionIn this study OSNA had a higher sensitivity than TIC. Fewer patients assessed by the OSNA assay would have required a two‐stage procedure. The OSNA assay appears to be a highly cost‐effective method for providing rapid and reliable intra‐operative assessment of sentinel lymph nodes.
CD38 and E2F transcription factor 2 have uniquely increased expression in rheumatoid arthritis synovial tissues
Authors: Chang X , Yue L , Liu W , Wang Y , Wang L , Xu B , Wang Y , Pan J , Yan X 
Published: January 2014

SummaryThe purpose of the current study was to find novel rheumatoid arthritis (RA)-specific gene expression by simultaneously comparing the expression profiles of the synovial tissues from patients with RA, osteoarthritis (OA) and ankylosing spondylitis (AS). The Illumina Human HT-12 v4 Expression BeadChip was used to investigate the global gene expression profiles in synovial tissues from RA (n = 12), OA (n = 14) and AS (n = 7) patients. By comparing the profiles in synovial tissues from RA, OA and AS, we identified the CD38, ankyrin repeat domain 38 (ANKRD38), E2F transcription factor 2 (E2F2), craniofacial development protein 1 (CFDP1), cluster of differentiation (CD)7, interferon-stimulated exonuclease gene 20 kDa (ISG20) and interleukin-2 receptor gamma (IL)-2RG genes as differentially expressed gene expression in RA synovial tissues. The increased expression of CD38, E2F2 and IL-2RG, as revealed using real-time polymerase chain reaction (PCR) with synovial tissues from RA (n = 30), OA (n = 26) and AS patients (n = 20), was in agreement with the microarray data. Immunohistochemistry revealed significant CD38 expression and E2F2 in synovial membranes from RA patients (n = 5). The CD38+ cells had high a percentage in the RA patients' blood (n = 103) and in the CD3+ and CD56+ subsets. The CD38+ cell percentage was correlated significantly with RF level (P = 0·026) in RA patients. The IL-1α and IL-β levels were depressed significantly in the culture medium of RA synovial fibroblast cells (n = 5) following treatment with siRNAs targeting the E2F2 or CD38 genes. This study suggests that the uniquely increased expression of CD38 and E2F2 in RA synovial tissues contribute to the immunoactivation of the disease.
Adverse effects and safety profile of perampanel: A review of pooled data
Authors: Rugg‐Gunn Fergus 
Published: January 2014

SummaryQuality of life is directly related to the number and severity of adverse effects, and a successful antiepileptic medication must demonstrate a good balance between efficacy and tolerability. Perampanel is a newly licensed antiepileptic medication for the adjunctive treatment of patients (age 12 and older) with partial epilepsy with or without secondary generalization. Safety endpoints in the three phase III trials (304, 305, and 306) included treatment‐emergent adverse events (TEAEs), vital signs, clinical laboratory parameters, and electrocardiography studies (ECGs). The most common adverse drug reactions in patients receiving perampanel were dizziness, somnolence, fatigue, irritability, nausea, and falls. Of particular concern to patients are cognitive and psychiatric side effects. Overall, depression and aggression were reported more frequently in patients taking perampanel, particularly at higher doses, than in patients taking placebo. TEAEs necessitated the withdrawal of perampanel in 99 patients (9.5%) and placebo in 21 patients (4.8%). Typically this was due to dizziness, convulsion, and somnolence. There were no clinically important changes or treatment group differences in vital signs, ECG measures, or biochemical or hematologic parameters. Weight increase of greater than 7% was seen in 14.6% of perampanel‐treated patients versus 7.1% of placebo‐treated patients. Overall, perampanel appears to be associated with a relatively low incidence of serious adverse effects, particularly at low doses, and the majority of TEAEs were mild or moderate in intensity. The incidence of predictable side effects, such as somnolence and dizziness, is seen more frequently at higher doses. Of importance is the greater rate of psychiatric side effects in patients treated with perampanel, principally, irritability and aggression, than with placebo. However, the rate of serious psychiatric TEAEs was low.
Quality of life by proxy and mortality in institutionalized older adults with dementia
Authors: González‐Vélez Abel E , Forjaz María Joao , Giraldez‐García Carolina , Martín‐García Salomé , Martínez‐Martín Pablo ,   Spanish Research Group on Quality of Life and Ageing
Published: January 2014

AimThis study aimed at analyzing the effect of quality of life (QoL) on mortality in older adults with dementia living in long‐term care facilities.MethodsA prospective observational cohort study was carried out on 412 residents aged older than 60 years, diagnosed with dementia according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Besides assessment of QoL (EQ‐5D index by proxy) and perceived health status (EQ‐VAS), baseline measurements included severity of dementia (Clinical Dementia Rating Scale [CDR]), comorbidity (number of self‐reported chronic conditions), disability evaluation (Barthel Index), cognitive state (Mini Examen Cognoscitivo, a validated and modified Spanish version of the Mini‐Mental State Examination) and depression (Cornell Depression Scale for Dementia). Sociodemographic and clinical variables were analyzed as potential effect modifiers and confounders in the relationship between QoL and mortality using a multivariate logistic regression analysis.ResultsAfter an 18‐month follow up, 138 residents had died. Adjusting for CDR and Barthel Index, the odds of mortality were multiplied by 0.25 (95% CI 0.09–0.70) and 0.79 (95% CI 0.26–2.42) for every unit of change in the EQ‐5D index in the residents with Cornell score <6 and ≥6, respectively.ConclusionThe present study suggests that the effect of QoL on mortality in institutionalized adults with dementia should take into account the presence or absence of depression. In addition, residents with a greater disability and more advanced dementia should be a target for interventions in rehabilitation care. Geriatr Gerontol Int 2015; 15: 38–44.
A Pitfall on Postoperative Radiographs in Dogs After Tibial Plateau Leveling Osteotomy
Authors: Olive Julien , Thiery Mélaine , Chailleux Nadège , Blond Laurent 
Published: January 2014

ObjectiveTo identify the cause of an occasional radiolucent line in the tibia on postoperative radiographs after tibial plateau leveling osteotomy (TPLO) in dogs.Study DesignRetrospective case series and ex vivo experiment.Sample PopulationDogs (n = 80; 87 stifles) with cranial cruciate ligament (CCL) rupture that had TPLO; and 4 canine tibia specimens.MethodsMedical records (2007–2010) and radiographs of dogs that had TPLO were reviewed and examined for presence of a radiolucent line on postoperative radiographs. The TPLO procedure was reproduced ex vivo to determine the origin of this line by use of metallic wires to identify bone contours.ResultsA curvilinear radiolucent line was visible in 14 (16%) tibias and was 5.4 times more likely to be visible with lateral misalignment of the tibial diaphysis relative to the plateau and 2.6 times more likely visible on caudocranial radiographs with the stifle in outward rotation. Fracture complication rate was higher in dogs with this radiolucent line (P = .02) and with lateral misalignment of the tibial diaphysis relative to the plateau (risk ratio, 3.8). The line could be reproduced ex vivo and caused by superimposition of the craniomedial border of osteotomy with the tibial plateau.ConclusionsThe radiolucent line was a spurious fracture line created by the medial margin of the tibial osteotomy and confounding factors such as tibial misalignment may explain the apparently associated higher complication rate.
Oceanic currents, not land masses, maintain the genetic structure of the mangrove Rhizophora mucronata Lam. (Rhizophoraceae) in Southeast Asia
Authors: Wee Alison K. S. , Takayama Koji , Asakawa Takeshi , Thompson Bijoy , Onrizal  , Sungkaew Sarawood , Tung Nguyen Xuan , Nazre M. , Soe Khin Khin , Tan Hugh T. W. , Watano Yasuyuki , Baba Shigeyuki , Kajita Tadashi , Webb Edward L. 
Published: January 2014

AbstractAimMangroves are intertidal plants with sea‐dispersed propagules, hence their population structure can offer valuable insights into the biogeographical processes driving population subdivision in coastal species. In this study, we used molecular markers and ocean circulation simulations to examine the effects of ocean currents and land masses on the genetic structure of the major mangrove species Rhizophora mucronata.LocationSoutheast Asia.MethodsWe assessed the genetic structure of 13 R. mucronata populations from continental Southeast Asia and Sumatra using 10 microsatellite loci. We first examined the relative effects of geographical distance and land mass (the Malay Peninsula) in shaping the genetic structure of R. mucronata in Southeast Asia. We then characterized the genetic structure of R. mucronata and compared it to the simulated ocean circulation patterns within our study region.ResultsDespite the low genetic diversity, significant genetic structuring was detected across R. mucronata populations. Contrary to observations on other mangrove species, genetic differentiation in R. mucronata was not found across the coasts of the Malay Peninsula, nor was it correlated with geographical distance. Instead, the most distinct genetic discontinuity was found at the boundary between the Andaman Sea and the Malacca Strait, and this can be explained by the prevailing ocean currents in this region.Main conclusionsOur study presents novel evidence that the genetic structure of R. mucronata is maintained by ocean current‐facilitated propagule dispersal.
The small‐island effect: empty islands, temporal variability and the importance of species composition
Authors: Morrison Lloyd W. 
Published: January 2014

AbstractAimTo evaluate the evidence for a small‐island effect (SIE) on insular floras, considering the effects of including islands without the species of interest, temporal variability and species composition.LocationSmall islands in the Andros, Exuma Cays and Abaco archipelagos of the Bahamas.MethodsAn information‐theoretic multimodel inference approach was used, comparing the fit of a linear model versus two breakpoint models to species–area data. Corrected Akaike's information criterion (AICc) scores were compared to determine the model(s) with the most support.ResultsStrong evidence for an SIE was found in the Andros and Exuma Cays archipelagos. At Andros, an SIE was always apparent, regardless of whether islands with no species were included or which time period was considered. In the Exuma Cays, the inclusion of islands with no species changed the inference of the existence of an SIE in one comparison, and the shape of the SIE (i.e. the best‐fitting model) in two comparisons. Data from the Exuma Cays indicated that the existence of an SIE, as well as the shape of the SIE, may vary over time. Evidence for an SIE for the Abaco archipelago was equivocal, although fewer data were available.Main conclusionsEven though it has been suggested that the exclusion of islands with no species may result in the erroneous detection of an SIE, the inclusion of islands with no species had little effect on the evidence for an SIE in this system. The finding that evidence for, and the shape of, the SIE can change over time suggests caution in interpreting SIE studies for systems that are not in equilibrium. Patterns of species composition as a function of island size support the hypothesis that disturbance events shape the habitat found on these islands, which limits the species pool that can survive on the smaller islands, resulting in an SIE.