bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycosyltransferases promote development and prevent promiscuous cell aggregation in the choanoflagellate S. rosetta
Authors: Wetzel Laura A. , Levin Tera C. , Hulett Ryan E. , Chan Daniel , King Grant A. , Aldayafleh Reef , Booth David S. , Sigg Monika Abedin , King Nicole
Published: August 2018

The mechanisms underlying multicellular development in the animal stem lineage may be reconstructed through the study of choanoflagellates, the closest living relatives of animals. To determine the genetic underpinnings of multicellularity in the emerging model choanoflagellate S. rosetta, we performed a screen for mutants with defects in multicellular rosette development. In two of the mutants, Jumble and Couscous, single cells failed to develop into orderly rosettes but instead aggregated promiscuously into amorphous clumps of cells. Both mutants mapped to lesions in genes encoding glycosyltransferases and the mutations perturbed glycosylation patterns in the extracellular matrix (ECM). In animals, glycosyltransferases transfer activated sugars to donor molecules and thereby sculpt the polysaccharide-rich ECM, regulate integrin and cadherin activity, and, when disrupted, contribute to tumorigenesis. The finding that glycosyltransferases promote proper rosette development and prevent cell aggregation in S. rosetta suggests a pre-metazoan role for glycosyltransferases in regulating development and preventing abnormal tumor-like multicellularity.

IMPACT STATEMENT

A genetic screen reveals that glycosyltransferases are required for proper rosette development and the prevention of cell clumping in one of the closest living relatives of animals, the choanoflagellate S. rosetta.
TheAcinetobacter baumanniiMla system and glycerophospholipid transport to the outer membrane
Authors: Kamischke Cassandra , Fan Junping , Bergeron Julien , Kulasekara Hemantha D. , Dalebroux Zachary D. , Burrell Anika , Kollman Justin M. , Miller Samuel I.
Published: August 2018

The outer membrane (OM) of Gram-negative bacteria serves as a selective permeability barrier that allows entry of essential nutrients while excluding toxic compounds, including antibiotics. The OM is asymmetric and contains an outer leaflet of lipopolysaccharides (LPS) or lipooligosaccharides (LOS) and an inner leaflet of glycerophospholipids (GPL). We screenedAcinetobacter baumanniitransposon mutants and identified a number of mutants with OM defects, including an ABC transporter system homologous to the Mla system inE. coli. We further show that this opportunistic, antibiotic-resistant pathogen uses this multicomponent protein complex and ATP hydrolysis at the inner membrane to promote GPL export to the OM. The broad conservation of the Mla system in Gram-negative bacteria suggests the system may play a conserved role in OM biogenesis. The importance of the Mla system toAcinetobacter baumanniiOM integrity and antibiotic sensitivity suggests that its components may serve as new antimicrobial therapeutic targets.
Copy Number Variation in Gluthatione S-Transferase Variants using Multiplex Ligation-Dependent Probe Amplification in a Health Population in Goiânia – Go
Authors: Pereira Lucas Carlos Gomes , Bérgamo Nádia Aparecida , Bicudo Lucilene Arilho , Tacon Jalsi Arruda , Gamba Bruno Faulin , Silveira-Lacerda Elisangela de Paula
Published: August 2018

Genetic polymorphisms in glutathione S-transferases (GSTs) genes might influence the detoxification activities of the enzymes predisposing individuals to a lot of diseases. Owing to the presence of these genetic variants, inter-individual and ethnic differences in GSTs detoxification capacity have been observed in various populations. Therefore, the present study was performed to determine GST variants in 100 healthy individuals from Goiânia – GO with a new methodology. GSTM1, GSTT1 and GSTP1 variants were analyzed by a MPLA (Multiplex Ligation by Probe Amplification) approach. The results obtained for the GSTM1 gene in exon 3 we found 43 deletions and 24 duplications, for exon 5 we found 45 deletions and 11 duplications, for the GSTT1 gene in exon 1 we found 14 deletions, and 18 duplications, for exon 5 we found 23 deletions and 28 duplications. For the GSTP1 gene in exon 3, we found only 1 deletion and for exon 4 we do not found any alteration. These findings in healthy population, give us such more information for the future epidemiological and clinical studies. Using to examine the effect of these combinations in drugs metabolism and cancer predisposition, further largest group would be needed, since their frequencies are quite low. To our of GSTs variations, this is the first study with this methodology indicating the frequencies of genetic variants of GST superfamily in a health population in a Goiânia population, and this study gives us new possibilities and data for new research using this same methodology.
Mating system ofUstilago esculentaand its polymorphism
Authors: Liang Syun-Wun , Huang Yen-Hua , Chiu Jian-Ying , Tseng Hsin-Wan , Haung Jin-Hsing , Shen Wei-Chiang
Published: August 2018

Zizania latifoliaTurcz., which is mainly distributed in Asia, has had a long cultivation history as a cereal and vegetable crop. On infection with the smut fungusUstilago esculenta, Z. latifoliabecomes an edible vegetable, water bamboo. Two main cultivars, with a green shell and red shell, are cultivated for commercial production in Taiwan. Previous studies indicated that cultivars ofZ. latifoliamay be related to infection withU. esculentaisolates. However, related research is limited. The infection process of the corn smut fungusUstilago maydisis coupled with sexual development and under control of the mating type locus. Thus, we aimed to use knowledge ofU. maydisto reveal the mating system ofU. esculenta. We collected water bamboo and isolated 145U. esculentastrains from Taiwan’s major production areas. By using PCR and idiomorph screening among meiotic offspring and field isolates, we identified three idiomorphs of the mating type locus and found no sequence recombination between them. Whole-genome sequencing (Illumina and Pacbio) suggested that the mating system ofU. esculentawas bipolar. Mating type locus 1 (MAT-1) was 555,862 bp, and contained 44% repeated sequences. Sequence comparison revealed thatU. esculenta MAT-1shared better conservation with the sex chromosome ofU. maydisthanU. hordei. These results can be utilized to further explore the genomic diversity ofU. esculentaisolates and their application for water bamboo breeding.
Mycobacteria-specific CD4+IFN-γ+ cell expresses naïve-surface markers and confers superior protection against tuberculosis infection compared to central and effector memory CD4+ T cell subsets
Authors: Yuan Jinyun , Tenant Janice , Pacatte Thomas , Eickhoff Christopher , Blazevic Azra , Hoft Daniel F. , Chatterjee Soumya
Published: August 2018

Failure of the most recent tuberculosis (TB) vaccine trial to boost BCG mediated anti-TB immunity despite highly durable Th1-specific central (TCM) and effector (TEM) memory cell responses, highlights the importance of identifying optimal T cell targets for protective vaccines. Here we describe a novel, Mycobacterium tuberculosis (Mtb)-specific IFN-γ+CD4+ T cell population expressing surface markers characteristic of naïve T cells (TNLM), that were induced in both human (CD45RA+CCR7+CD27+CD95-) and murine (CD62L+CD44-Sca-1+CD122-) systems in response to mycobacteria. In BCG vaccinated subjects and those with latent TB infection, TNLM cells, compared to bonafide naïve CD4+ T cells were identified by absence of CD95 expression and had increased expression CCR7 and CD27, the activation markers T-bet, CD69 and PD-1 and the survival marker CD74. Increased TNLM frequencies were noted in the lung and spleen of wild type C57BL6 mice at 2 weeks after infection with Mtb, and progressively decreased at later time points, a pattern not seen in TNF-α+CD4+ T cells expressing naïve cell surface markers. Importantly, adoptive transfer of highly purified TNLM from vaccinated ESAT-61-20-specific TCR transgenic mice conferred superior protection against Mtb infection in Rag-/- mice when compared with total meory populations (central and effector memory cells). Thus, TNLM cells may represent a memory T cell population that if optimally targeted may significantly improve future TB vaccine responses.
Time-resolved mapping of genetic interactions to model rewiring of signaling pathways
Authors: Heigwer Florian , Scheeder Christian , Miersch Thilo , Schmitt Barbara , Blass Claudia , Pour-Jamnani Mischan Vali , Boutros Michael
Published: August 2018

Context-dependent changes in genetic vulnerabilities are important to understand the wiring of cellular pathways and variations in different environmental conditions. However, methodological frameworks to investigate the plasticity of genetic networks over time or in response to external stresses are lacking. To analyze the plasticity of genetic interactions, we performed an arrayed combinatorial RNAi screen inDrosophilacells at multiple time points and after pharmacological inhibition of Ras signaling activity. Using an image-based morphology assay to capture a broad range of phenotypes, we assessed the effect of 12768 pairwise RNAi perturbations in six different conditions. We found that genetic interactions form in different trajectories and developed an algorithm, termed MODIFI, to analyze how genetic interactions rewire over time. Using this framework, we identified more statistically significant interactions compared to endpoints assays and further observed several examples of context-dependent crosstalk between signaling pathways such as an interaction between Ras and Rel which is dependent on MEK activity.
De Novo Mutational Signature Discovery in Tumor Genomes using SparseSignatures
Authors: Lal Avantika , Liu Keli , Tibshirani Robert , Sidow Arend , Ramazzotti Daniele
Published: August 2018

Cancer is the result of mutagenic processes that can be inferred from tumor genomes by analyzing rate spectra of point mutations, or “mutational signatures”. Here we present SparseSignatures, a novel framework to extract signatures from somatic point mutation data. Our approach incorporates a user-specified background signature, employs regularization to reduce noise in non-background signatures, uses cross-validation to identify the number of signatures, and is scalable to large datasets. We show that SparseSignatures outperforms current state-of-the-art methods on simulated data using a variety of standard metrics. We then apply SparseSignatures to whole genome sequences of pancreatic and breast tumors, discovering well-differentiated signatures that are linked to known mutagenic mechanisms and are strongly associated with patient clinical features.

Authors Summary

Cancer is a genetic disease, occurring as a result of mutagenic processes causing DNA somatic mutations in genes controlling cellular growth and division. These somatic mutations arise from processes such as defective DNA repair and environmental mutagens, which massively increase the rate of somatic variants. As a result, due to the specificity of molecular lesions caused by such processes, and the specific repair mechanisms deployed by the cell to mitigate the damage, mutagenic processes generate characteristic point mutation rate spectra which are called mutational signatures. These signatures can indicate which mutagenic processes are active in a tumor, reveal biological differences between cancer subtypes, and may be useful markers for therapeutic response. Here, we develop SparseSignatures, a novel framework for mutational signature discovery capable of both identifying the active signatures in a dataset of point mutations and calculating their exposure values, i.e., the number of mutations originating from each signature in each patient. We show that our approach outperforms current state-of-the-art methods on simulated data using a variety of standard metrics and then apply SparseSignatures to whole genome sequences of pancreatic and breast tumors, discovering well-differentiated signatures that are linked to known mutagenic mechanisms.
Pervasive Transcription Fine-tunes Replication Origin Activity
Authors: Candelli Tito , Gros Julien , Libri Domenico
Published: August 2018

RNA polymerase (RNAPII) transcription occurs pervasively, which raises the important question of its functional impact on other DNA-associated processes, including replication. In budding yeast, replication originates from Autonomously Replicating Sequences (ARSs), generally located in intergenic regions. The influence of transcription on ARSs function has been studied for decades, but these earlier studies have necessarily neglected the role of non-annotated transcription. We studied the relationships between pervasive transcription and replication origin activity using high-resolution transcription maps. We show that ARSs alter the pervasive transcription landscape by pausing and terminating neighboring RNAPII transcription, thus limiting the occurrence of pervasive transcription within origins. We provide evidence that quasi-symmetrical binding of the ORC complex to ARS borders is responsible for pausing/termination. We also show that low, physiological levels of pervasive transcription impact the function of replication origins. Overall, our results have important implications for understanding the impact of genomic location on origin function.
Pathway-specific asymmetries between ON and OFF visual signals
Authors: Ravi Sneha , Ahn Daniel , Greschner Martin , Chichilnisky E.J , Field Greg D.
Published: August 2018

Visual processing is largely organized into ON and OFF pathways that signal stimulus increments and decrements, respectively. These pathways exhibit natural pairings based on morphological and physiological similarities, such as ON and OFF alpha ganglion cells in the mammalian retina. Several studies have noted asymmetries in the properties of ON and OFF pathways. For example, the spatial receptive fields (RFs) of OFF alpha cells are systematically smaller than ON alpha cells. Analysis of natural scenes suggests these asymmetries are optimal for visual encoding. To test the generality of ON-OFF asymmetries, we measured the spatiotemporal RF properties of multiple RGC types in rat retina. Through a quantitative and serial classification, we identified three functional pairs of ON and OFF RGCs. We analyzed the structure of their RFs and compared spatial integration, temporal integration, and gain across ON and OFF pairs. Similar to previous results from cat and primate, RGC types with larger spatial RFs exhibited briefer temporal integration and higher gain. However, each pair of ON and OFF RGC types exhibited distinct asymmetric relationships between receptive field properties, some of which were opposite to previous reports. These results reveal the functional organization of six RGC types in the rodent retina and indicate that ON-OFF asymmetries are pathway specific.

Significance Statement

Circuits that process sensory input frequently process increments separately from decrements, so called ‘ON’ and ‘OFF’ responses. Theoretical studies indicate this separation, and associated asymmetries in ON and OFF pathways, may be beneficial for encoding natural stimuli. However, the generality of ON and OFF pathway asymmetries has not been tested. Here we compare the functional properties of three distinct pairs of ON and OFF pathways in the rodent retina and show their asymmetries are pathway specific. These results provide a new view on the partitioning of vision across diverse ON and OFF signaling pathways
Motor Learning Without Moving: Proprioceptive and Predictive Hand Localization After Passive Visuoproprioceptive Discrepancy Training
Authors: Mostafa Ahmed A. , ’t Hart Bernard Marius , Henriques Denise Y.P.
Published: August 2018

An accurate estimate of limb position is necessary for movement planning, before and after motor learning. Where we localize our unseen hand after a reach depends on felt hand position, or proprioception, but in studies and theories on motor adaptation this is quite often neglected in favour of predicted sensory consequences based on efference copies of motor commands. Both sources of information should contribute, so here we set out to further investigate how much of hand localization depends on proprioception and how much on predicted sensory consequences. We use a training paradigm combining robot controlled hand movements with rotated visual feedback that eliminates the possibility to update predicted sensory consequences (‘exposure training’), but still recalibrates proprioception, as well as a classic training paradigm with self-generated movements in another set of participants. After each kind of training we measure participants’ hand location estimates based on both efference-based predictions and afferent proprioceptive signals with self-generated hand movements (‘active localization’) as well as based on proprioception only with robot-generated movements (‘passive localization’). In the exposure training group, we find indistinguishable shifts in passive and active hand localization, but after classic training, active localization shifts more than passive, indicating a contribution from updated predicted sensory consequences. Both changes in open-loop reaches and hand localization are only slightly smaller after exposure training as compared to after classic training, confirming that proprioception plays a large role in estimating limb position and in planning movements, even after adaptation. (data: https://doi.org/10.17605/osf.io/zfdth, preprint: https://doi.org/10.1101/384941)
Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold
Authors: Sun Mingxuan , Biggs Ronald , Hornick Jessica , Marko John F.
Published: August 2018

During cell division, chromosomes must be folded into their compact mitotic form to ensure their segregation. This process is thought to be largely controlled by the action of condensin SMC protein complexes on chromatin fibers. However, how condensins organize metaphase chromosomes is not understood. We have combined micromanipulation of single human mitotic chromosomes, sub-nanonewton force measurement, siRNA interference of condensin subunit expression, and fluorescence microscopy, to analyze the role of condensin in large-scale chromosome organization. Condensin depletion leads to a dramatic (~10 fold) reduction in chromosome elastic stiffness relative to the native, non-depleted case. We also find that prolonged metaphase stalling of cells leads to overloading of chromosomes with condensin, with abnormally high chromosome stiffness. These results demonstrate that condensin is a main element controlling the stiffness of mitotic chromosomes. Isolated, slightly stretched chromosomes display a discontinuous condensing staining pattern, suggesting that condensins organize mitotic chromosomes by forming isolated compaction centers that do not form a continuous scaffold.
Brain peak width of skeletonised mean diffusivity (PSMD), processing speed, and other cognitive domains
Authors: Deary Ian J. , Ritchie Stuart J. , Maniega Susana Muñoz , Cox Simon R. , Hernández Maria C. Valdés , Starr John M. , Wardlaw Joanna M. , Bastin Mark E.
Published: August 2018

It is suggested that the brain’s peak width of skeletonised water mean diffusivity (PSMD) is a neuro-biomarker of processing speed, a crucial contributor to cognitive ageing. We tested whether PSMD is more strongly correlated with processing speed than with other cognitive domains, and more strongly than other structural brain MRI indices. Participants were 731 Lothian Birth Cohort 1936 members, mean age 73 years (SD=0.7); analytical sample was 656-680. Cognitive domains tested were: processing speed (5 tests), visuospatial (3), memory (3), and verbal (3). Brain-imaging variables included PSMD, white matter diffusion parameters and hyperintensity volumes, grey and white matter volumes, and perivascular spaces. PSMD was significantly associated with all processing speed tests; absolute standardised beta values were 0.11 to 0.23 (mean = 0.17). Other structural brain-imaging variables correlated as or more strongly. PSMD was significantly associated with processing speed (−0.27), visuospatial (−0.23), memory (−0.17), and general cognitive ability (−0.25). PSMD correlated with processing speed: but not more strongly than with other cognitive domains; and not more strongly than other brain-imaging measures.
Effects of the maternal factor Zelda on zygotic enhancer activity in theDrosophilaembryo
Authors: Li Xiao-Yong , Eisen Michael B.
Published: August 2018

The maternal factor Zelda is broadly bound to zygotic enhancers during early fly embryogenesis, and has been shown to be important for the expression of a large number of genes. However, its function remains poorly understood. Here, we carried out detailed analysis of the functional role of Zelda on the activities of a group of enhancers that drive patterned gene expression along the anterior -posterior axis. We found that among these enhancers, only one lost its activity entirely when all its Zelda bind sites were mutated. For all others, mutations of all of their Zelda binding sites only had limited effect, which varied temporally and spatially. These results suggest that Zld may exert a quantitative effect on a broad range of enhancers, which presumably is critical to generate highly diverse spatial and temporal expression patterns for different genes in the developmental gene network in fly embryo. Lastly, we found that the observed effect of Zelda site mutations was much stronger when a mutant enhancer was tested using a BAC based reporter construct than a simple reporter construct, suggesting that the effect of Zld is dependent on chromatin environment.
MyoviridaePhagePDXKills EnteroaggregativeEscherichia coliwithout Human Microbiome Dysbiosis
Authors: Cepko Leah C. S. , Garling Eliotte E. , Dinsdale Madeline J. , Scott William P. , Bandy Loralee , Nice Tim , Faber-Hammond Joshua , Mellies Jay L.
Published: August 2018

Purpose

To identify therapeutic a bacteriophage that kills diarrheagenic enteroaggregativeEscherichia coli(EAEC) while leaving the human microbiome intact.

Methodology

Phages from wastewater in Portland, OR, were screened for bacteriolytic activity using an overlay assay, and isolated in a sequential procedure to enrich for the recognition of core bacterial antigens. Electron microscopy and genome sequencing were performed to classify the isolated phage, and the host range was determined by spot tests and plaque assays. One-step growth curves and time-kill assays were conducted to characterize the life cycle of the phage, and to interrogate the multiplicity of infection (MOI) necessary for killing. A mouse model of infection was used to determine whether the phage could be used therapeutically against EAECin vivo. Anaerobic culture in the presence of human fecal bacteria determined whether the phage could kill EAECin vitro, and to assess whether the microbiome had been altered.

Results

The isolated phage, termedEscherichia virus PDX, is a member of the strictly lyticMyoviridaefamily of viruses. PhagePDXkilled EAEC isolate EN1E-0227, a case-associated isolate from a child in rural Tennessee, in a dose-dependent manner, and also formed plaques on case-associated clinical EAEC isolates from Columbian children suffering from diarrhea. A single dose ofPDX, at a MOI of 100, one day post infection, reduced the population of recovered EAEC isolate EN1E-0227 bacteria in fecal pellets in a mouse model of colonization, over a five-day period. PhagePDXalso killed EAEC EN1E-0227 when cultured anaerobicallyin vitroin the presence of human fecal bacteria. While the addition of EAEC EN1E-0227 reduced the α-diversity of the human microbiota, that of the cultures with either feces alone, feces with EAEC andPDX, or with just thePDXphage were not different statistically, as measured by Chao1 and Shannon diversity indices. Additionally, β-diversity and differential abundance analyses show that conditions withPDXadded were not different from feces alone, but all groups were significantly different from feces + EAEC.

Conclusions

The strictly bacteriolytic,Myoviridae Escherichia virus PDXkilled EAEC isolate EN1E-0227 bacteria bothin vivoandin vitro, while simultaneously not altering the diversity of normal human microbiota in anaerobic culture. Thus, thePDXphage could be part of an effective therapeutic intervention for children in developing countries who suffer from acute, or persistent EAEC-mediated diarrhea, and to help reduce the serious effects of environmental enteropathy. Because the emerging pathogen EAEC is now the second leading cause of traveler’s diarrhea,PDXcould also provide therapeutic relief for these individuals, particularly in light of the growing crisis of antibiotic resistances.
Hessian single molecule localization microscopy using sCMOS camera
Authors: Xue Fudong , He Wenting , Xu Fan , Zhang Mingshu , Chen Liangyi , Xu Pingyong
Published: August 2018

Single-molecule localization microscopy (SMLM) has the highest spatial resolution among the existing super-resolution (SR) imaging techniques, but its temporal resolution needs further improvement. An sCMOS camera can effectively increase the imaging rate due to its large field of view and fast imaging speed. Using an sCMOS camera for SMLM imaging can significantly improve the imaging time resolution, but the unique single pixel-dependent readout noise of sCMOS cameras severely limits their application in SMLM imaging. This paper develops a Hessian-based SMLM (Hessian-SMLM) method that can correct the variance, gain and offset of a single pixel of a camera and effectively eliminate the pixel-dependent readout noise of sCMOS cameras, especially when the signal-to-noise ratio is low. Using Hessian SMLM to image mEos3.2-labeled actin was able to significantly reduce the artifacts due to camera noise.
Exogenous DCPTA ameliorates the soil drought effect on nitrogen metabolism in maize during the pre-female inflorescence emergence stage
Authors: Xie Tenglong , Gu Wanrong , Liguo Zhang , Li Congfeng , Li Wenhua , Wei Shi
Published: August 2018

2-(3,4-Dichlorophenoxy) triethylamine (DCPTA) regulates many aspects of plant development; however, its effects on soil drought tolerance are unknown. We pre-treated maize (Zea mays L.) by foliar application of DCPTA and subsequently exposed the plants to soil drought and rewatering conditions during the pre-female inflorescence emergence stage. Exogenous DCPTA significantly alleviated drought-induced decreases in maize yield, shoot and root relative growth rate (RGR), leaf relative water content (RLWC), net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (Tr), nitrate (NO3−), nitrite (NO2−), and soluble protein contents, and nitrate reductase (NR), nitrite reductase (NiR), isocitrate dehydrogenase (ICDH), alanine aminotransferase (AlaAT) and aspartate aminotransferase (AspAT) activities; increases in the intercellular CO2 concentration (Ci), the ammonium (NH4+) and free amino acid contents, and the glutamate dehydrogenase (GDH) and protease activities. Simultaneously, exogenous DCPTA improved the spatial and temporal distribution of roots and increased the root hydraulic conductivity (Lp), flow rate of root-bleeding sap and NO3− delivery rates. Moreover, Exogenous DCPTA protected the chloroplast structure from drought injury. Taken together, our results suggest that exogenous DCPTA mitigates the repressive effects of drought on N metabolism and subsequently enhances drought tolerance during the pre-female inflorescence emergence stage of maize.

Highlights

This is the first article that explores the effects of DCPTA on nitrogen metabolism and the first article that explores the effects of DCPTA on crops under soil drought conditions.
Actinic keratosis – review for clinical practice
Authors: de Oliveira Erika C. V. , da Motta Valéria R. V. , Pantoja Paola C. , Ilha Carolina S. de O. , Magalhães Renata F. , Galadari Hassan , Leonardi Gislaine R.
Published: August 2018

Actinic keratosis (AK) is a lesion that arises as a result of excessive exposure to solar radiation and appearing predominantly on Fitzpatrick phototype I and II skin. Given that some AKs evolve into squamous cell carcinoma, these lesions are considered premalignant in nature, occurring mostly in elderly men and immunosuppressed individuals chronically exposed to ultraviolet (UV) radiation. There are several mechanisms for the formation of AKs; among them are oxidative stress, immunosuppression, inflammation, altered proliferation and dysregulation of cell growth, impaired apoptosis, mutagenesis, and human papillomavirus (HPV). Through the understanding of these mechanisms, several treatments have emerged. Among the options for AK treatment, the most commonly used include 5‐fluorouracil (5‐FU), cryotherapy, diclofenac, photodynamic therapy (PDT), imiquimod (IQ), retinoids, and ingenol mebutate (IM). There have been recent advances in the treatment options that have seen the emergent use of newer agents such as resiquimod, betulinic acid, piroxicam, and dobesilate. The combination between therapies has presented relevant results with intention to reduce duration of therapy and side effects. All AK cases must be treated because of their propensity to transform into malignancy and further complicate treatment. In addition to medical or surgical care, education about sun exposure prevention remains the best and most cost‐effective method for AK prevention. The objective of this article is to conduct a literature review of the clinical presentation of AK including advances in treatment options available.
Risk factors for early and late procedure‐related adverse events in percutaneous endoscopic gastrostomy: A single center, retrospective study
Authors: Peveling‐Oberhag Jan , Osman Imad , Walter Dirk , Filmann Natalie , Stratmann Katharina , Hausmann Johannes , Knop Viola , Waidmann Oliver , Vermehren Johannes , Herrmann Eva , Zeuzem Stefan , Friedrich‐Rust Mireen , Blumenstein Irina , Albert Jörg G
Published: August 2018

Background

Percutaneous endoscopic gastrostomy (PEG) provides the most common method to ensure enteral nutrition for various indications. However, PEG placement may be associated with relevant procedure‐related morbidity and mortality. We aimed to identify clinical parameters predicting an increased risk of PEG‐related adverse events.

Methods

A retrospective analysis was performed for all patients who had undergone PEG placement in our center between August 2010 and January 2014. PEG‐related adverse events and risk factors were evaluated through review of endoscopic reports and medical charts. All patients were followed until death or study closure (median follow‐up 30 months, range 12–48).

Results

A total of 576 patients (417 male, mean age 56) were included. Indication for PEG insertion was preemptive or therapeutic in underlying oncological disease (n = 410), neurological diseases (n = 114), or others (n = 151). The pull method was used in 501 patients (87%). Overall, 56 (59%) and 39 (41%) patients had early (< 30 days) and late (> 30 days) adverse events of which 11.8% and 4.7% were classified as minor and major, respectively. Multivariate analysis showed that a high number of comorbidities, an oncological indication, and, as a statistical trend, high body mass index were associated with early adverse events. The use of the push method for insertion of PEG was associated with increased late adverse events, which mainly consisted of tube dislocations.

Conclusions

Clinical parameters that may easily be accessed correlate to an unfavorable outcome of a PEG procedure. This should raise the endoscopist's awareness for patients at high risk for adverse events.
MiR‐302 enhances the viability and stemness of male germline stem cells
Authors: Zhu Haijing , Zheng Liming , Wang Long , Tang Furong , Hua Jinlian
Published: August 2018

Contents

MicroRNAs were reported to be able to regulate mGSCs’ self‐renewal through post‐transcriptional inhibition of gene expression. miR‐302 worked as one important microRNA family existed mainly in human ESCs, and its role in mGSCs has not been reported yet. To elucidate the role of miR‐302 in dairy goat mGSCs, the expression profile of miR‐302 was explored through qPCR and FISH. Furthermore, to detect the function of miR‐302, the expression vector containing miR‐302 was transfected into mGSCs, and then, the cell cycle, the cell apoptosis and the genes associated with mGSCs’ self‐renewal and differentiation were examined. The results showed that miR‐302 expressed in testis moderately and located on the basement of seminiferous tubes which shared the same location as mGSCs. Transfection of the vector containing miR‐302 fragment into the immortalized mGSCs obviously enhanced the cell proliferation ability and the attachment ability, also, promoted the expression level of CD49f and OCT4. Also, miR‐302 reduced the cell apoptosis and downregulated the expression of P21. miR‐302 sustained mGSCs’ proliferation in vitro.
Reconceptualizing Physical Education Curricula to Meet the Needs of All Students
Authors: Solmon Melinda A.
Published: August 2018

The traditional sport-based multiactivity approach that continues to dominate secondary physical education curricula is problematic on a number of levels. It is often not perceived as making a valuable contribution to the educational process by school administrators or as culturally relevant and interesting to many students. This paper highlights Catherine Ennis’s work related to the shortcomings of this model and the need to move toward a more educational focus. Initially, Ennis described the curricular strife that developed as teachers clung to this approach in the face of a changing educational landscape. Her work evolved to include students’ perspectives, and her writings gave voice to their disengagement and discontent. She continued her extensive writings related to this topic across her career, exploring alternatives and offering solutions to reconceptualize physical education programs to maximize their contribution to the school curriculum and to meet the needs of all students.
Effects of mindfulness-based interventions on alexithymia: a systematic review
Authors: Norman Hilary , Marzano Lisa , Coulson Mark , Oskis Andrea
Published: August 2018

Question

Alexithymia has been found to be modifiable through treatment, with associated clinical benefits. Recent studies have begun to test the potential of mindfulness-based interventions to reduce alexithymia, using skills-based, group training to improve non-judgemental, present-moment awareness. The objective of this review therefore was to conduct a systematic synthesis to assess the current state of knowledge about the effect of mindfulness-based interventions on alexithymia to inform clinical practice.

Study selection and analysis

We carried out a systematic review of the literature and found four randomised controlled trials of the effect of mindfulness-based interventions on alexithymia, with a combined total of 460 participants.

Findings

A random-effects meta-analysis, combining study endpoint data, showed a statistically significant effect of mindfulness-based treatment on alexithymia (Toronto Alexithymia Scale) compared with the control group (mean difference=−5.28, 95% CI −9.28 to −1.28, p=0.010). Subgroup analysis was conducted to investigate sources of heterogeneity (I2=52%). Heterogeneity was reduced when the meta-analysis was restricted to interventions of a similar duration (3 months or less).

Conclusions

Findings from our study should be replicated in further research with larger samples; however, the results indicate that mindfulness-based interventions may be an effective treatment in reducing alexithymia.
Results of the British Society of Gastroenterology supporting women in gastroenterology mentoring scheme pilot
Authors: Smith Katherine H , Hallett Rachel Justine , Wilkinson-Smith Victoria , Neild Penny Jane , Brooks Alenka J , Lockett Melanie Jane , Thomas-Gibson Siwan , Eaden Jayne Alison , Edwards Cathryn
Published: August 2018

Introduction

Mentorship has long been recognised as beneficial in the business world and has more recently been endorsed by medical and academic professional bodies. Recruitment of women into gastroenterology and leadership roles has traditionally been difficult. The Supporting Women in Gastroenterology network developed this pilot scheme for female gastroenterologists 5 years either side of the Completion Certificate of Specialist Training (CCST) to examine the role that mentorship could play in improving this discrepancy.

Method

Female gastroenterology trainees and consultant gastroenterologists within 5 years either side of CCST were invited to participate as mentees. Consultant gastroenterologists of both genders were invited to become mentors. 35 pairs of mentor:mentees were matched and completed the scheme over 1 year. Training was provided.

Results

The majority of the mentees found the sessions useful (82%) and enjoyable (77%), with the benefit of having time and space to discuss professional or personal challenges with a gastroenterologist who is not a colleague. In the longitudinal study of job satisfaction, work engagement, burnout, resilience, self-efficacy, self-compassion and work-life balance, burnout scale showed a small but non significant improvement over the year (probably an effect of small sample size). Personal accomplishment improved significantly. The main challenges were geography, available time to meet and pair matching. The majority of mentors surveyed found the scheme effective, satisfying, mutually beneficial (70%) and enjoyable (78%).

Conclusion

Mentorship is shown to be beneficial despite the challenges and is likely to improve the recruitment and retention of women into gastroenterology and leadership roles, but is likely to benefit gastroenterologists of both genders.
Five-year outcomes of transcatheter reduction of significant mitral regurgitation in high-surgical-risk patients
Authors: Kar Saibal , Feldman Ted , Qasim Atif , Trento Alfredo , Kapadia Samir , Pedersen Wesley , Lim D Scott , Kipperman Robert , Smalling Richard W , Bajwa Tanvir , Hermann Howard C , Hermiller James B , Lasala John M , Reisman Mark , Glower Donald , Mauri Laura , Whitlow Patrick
Published: August 2018

Objectives

This study evaluates the 5-year clinical outcomes of transcatheter mitral valve (MV) repair with the MitraClip device in patients at high risk for MV surgery treated in the Endovascular Valve Edge-to-Edge Repair (EVEREST) II High Risk Study (HRS).

Methods

Patients with mitral regurgitation (MR) 3+ or 4+ and predicted surgical mortality risk ≥12% or surgeon assessment based on prespecified high-risk factors were enrolled. Patients prospectively consented to 5 years of follow-up.

Results

At 5 years, clinical follow-up was achieved in 90% of 78 enrolled patients. The rate of postprocedural adverse events declined from 30 days to 1 year follow-up and was stable thereafter through 5 years. Two patients (2.6%) developed mitral stenosis (MS). Two patients underwent MV surgery, including one due to MS. A total of 42 deaths were reported through 5 years. Effectiveness measures at 5 years showed reductions in MR severity to ≤2+ in 75% of patients (p=0.0107), left ventricular (LV) end-diastolic volume (−38.2 mL; 95% CI −55.0 to –21.4; p<0.0001) and LV end-systolic volume (−14.6 mL; 95% CI −27.7 to −1.5; p=0.0303) compared with baseline. The New York Heart Association (NYHA) functional class improved from baseline to 5 years (p<0.005), and septal-lateral annular dimensions remained stable with no indication of mitral annular dilation through 5 years.

Conclusions

The EVEREST II HRS demonstrated long-term safety and efficacy of MitraClip in high-surgical-risk patients through 5 years. The observed mortality was most likely a consequence of the advanced age and comorbidity profile of the enrolled patients, while improvements in NYHA class in surviving patients were durable through long-term follow-up.

Trial registration number

NCT01940120.
Baseline and longitudinal change in blood pressure and mortality in a Chinese cohort
Authors: Wang Jian-Bing , Huang Qiu-Chi , Hu Shu-Chang , Zheng Pei-Wen , Shen Peng , Li Die , Lu Huai-Chu , Gao Xiang , Lin Hong-Bo , Chen Kun
Published: August 2018

Background

A J-curve association has been demonstrated for blood pressure (BP) and all-cause mortality, but data on longitudinal change of BP and mortality in Chinese population are limited.

Methods

We performed a retrospective cohort study to examine the association between BP (at baseline and longitudinal change) and risk of mortality in Yinzhou District, Ningbo, China, based on the Yinzhou Health Information System. At baseline, a total of 181 352 subjects aged over 18 years with at least one BP examination record were recruited through the Yinzhou Health Information System. The final analysis was restricted to 168 061 participants after exclusion of outliers of BP.

Results

A U-shaped association was observed for BP at baseline and risk of total and cardiovascular mortality. When compared with normotensive participants, patients with hypotension (HRs=1.51, 95% CI 1.21 to 1.88) and stage 3 hypertension (1.28, 95% CI 1.09 to 1.50) had an increased risk of all-cause mortality. Relative to stable BP of normotension, having a rise in BP from normotension to hypertension or from prehypertension to hypertension both conferred an increased risk of total and cardiovascular mortality (total: 1.39 (95% 1.10 to 1.75) and 1.40 (95% 1.15 to 1.69); cardiovascular: 2.22 (95% CI 1.35 to 3.65) and 1.89 (95% CI 1.20 to 2.96), respectively).

Conclusions

Our findings emphasise that hypotension and stage 3 hypertension were associated with an increased risk of all-cause mortality. Longitudinal change from normotensive or prehypertensive levels to 140/90 mm Hg or higher could increase the risk of total and cardiovascular mortality.
Randomised controlled trial of escitalopram for cervical dystonia with dystonic jerks/tremor
Authors: Zoons Evelien , Booij Jan , Delnooz Catherine C S , Dijk Joke M , Dreissen Yasmine E M , Koelman Johannes H T M , van der Salm Sandra M A , Skorvanek Matej , Smit Marenka , Aramideh Majid , Bienfait Henriette , Boon Agnita J W , Brans Jeroen W M , Hoogerwaard Edo , Hovestadt Ad , Kamphuis Daan J , Munts Alexander G , Speelman Johannes D , Tijssen Marina A J
Published: August 2018

Objective

Trials for additional or alternative treatments for cervical dystonia (CD) are scarce since the introduction of botulinum neurotoxin (BoNT). We performed the first trial to investigate whether dystonic jerks/tremor in patients with CD respond to the selective serotonin reuptake inhibitor (SSRI) escitalopram.

Methods

In a randomised, double-blind, crossover trial, patients with CD received escitalopram and placebo for 6 weeks. Treatment with BoNT was continued, and scores on rating scales regarding dystonia, psychiatric symptoms and quality of life (QoL) were compared. Primary endpoint was the proportion of patients that improved at least one point on the Clinical Global Impression Scale for jerks/tremor scored by independent physicians with experience in movement disorders.

Results

Fifty-threepatients were included. In the escitalopram period, 14/49 patients (29%) improved on severity of jerks/tremor versus 11/48 patients (23%) in the placebo period (P=0.77). There were no significant differences between baseline and after treatment with escitalopram or placebo on severity of dystonia or jerks/tremor. Psychiatric symptoms and QoL improved significantly in both periods compared with baseline. There were no significant differences between treatment with escitalopram and placebo for dystonia, psychiatric or QoL rating scales. During treatment with escitalopram, patients experienced slightly more adverse events, but no serious adverse events occurred.

Conclusion

In this innovative trial, no add-on effect of escitalopram for treatment of CD with jerks was found on motor or psychiatric symptoms. However, we also did not find a reason to withhold patients treatment with SSRIs for depression and anxiety, which are common in dystonia.

Trial registration number

NTR2178.
A clinical comparison of Atlas and LVIS Jr stent-assisted aneurysm coiling
Authors: Gross Bradley A , Ares William J , Ducruet Andrew F , Jadhav Ashutosh P , Jovin Tudor G , Jankowitz Brian Thomas
Published: August 2018

Background

Case series have described the safety and efficacy of LVIS Jr and Atlas stent-assisted aneurysm coiling, but their comparative clinical performance has not yet been formally studied.

Objective

To clinically compare LVIS Jr and Atlas stents, emphasizing comparative rates of technical success and complications.

Methods

Our institutional endovascular database was queried for aneurysms treated by stent-assisted coiling with either the LVIS Jr or Atlas stents. Demographic data, aneurysm information, treatment technique, periprocedural and device-related complications, and initial and follow-up angiographic results were evaluated.

Results

Thirty-seven patients underwent Atlas stent placement and 27 patients underwent LVIS Jr stent placement for aneurysm coiling. There was no significant difference in aneurysm location, size, coiling technique, and coil packing density between the two cohorts. The rate of initial Raymond 1 occlusion was significantly greater in the Atlas cohort (57% vs 41%, P=0.03). The rate of postoperative ischemic complications, both clinically apparent and as defined on postoperative MRI diffusion-weighted imaging, did not significantly differ between the two groups. Follow-up DSA demonstrated a significantly greater rate of Raymond 1 or 2 occlusion for the Atlas cohort (100% vs 81%, P=0.04), and a significantly lower rate of in-stent stenosis (0% vs 19%, P=0.04).

Conclusion

This institutional analysis demonstrates greater obliteration rates and lower in-stent stenosis rates for aneurysms treated via Atlas stent-assisted coiling as compared with those treated via LVIS Jr stent-assisted coiling.
Clinicopathological case: progressive somnolence and dementia in an accountant: when the shine rubs off the gold standard
Authors: Soane Tim , Schott Jonathan M , Stone Jon , Smith Colin , Pal Suvankar , Davenport Richard J
Published: August 2018

A 63-year-old accountant developed progressive somnolence, cognitive decline, gait disturbance and cerebellar dysfunction with autonomic features. This report documents the clinicopathological conference at the 39th Edinburgh Advanced Neurology Course 2017.