bluuebunny/crossref_metadata_2025 huggingface dataset:
Population‐based case‐control study: chemoprotection of colorectal cancer with non‐aspirin nonsteroidal anti‐inflammatory drugs and other drugs for pain control
Authors: Rodríguez‐Miguel Antonio , García‐Rodríguez Luis A. , Gil Miguel , Barreira‐Hernández Diana , Rodríguez‐Martín Sara , de Abajo Francisco J.
Published: July 2019

Background

Inflammation and overexpression of cyclooxygenase‐2 (COX‐2) have been described to play a key role in the progression from nonpathologic intestinal mucosa to colorectal cancer (CRC).

Aims

To assess the chemoprotective effect of non‐aspirin nonsteroidal anti‐inflammatory drugs (NA‐NSAIDs) under different patterns of use in a Mediterranean population and to explore the potential effect of symptomatic slow‐acting drugs for osteoarthritis (SYSADOAs; chondroitin sulfate and glucosamine) and metamizole (or dipyrone), also reported to influence COX‐2 activity.

Methods

We performed a case‐control study nested in a cohort extracted from the primary care database, BIFAP. From 2001 to 2014, we included 15 491 incident cases and 60 000 random controls. To estimate the association between the drugs of interest and CRC, we built logistic regression models to compute the adjusted‐odds ratios (AOR) and 95% confidence intervals (CI).

Results

NA‐NSAIDs use was associated with a reduced risk of CRC (AOR = 0.67; 95% CI: 0.63‐0.71) and increased linearly with duration of treatment (p for trend <0.001). The effect diminished upon discontinuation but persisted statistically significant up to 1 year. All individual NA‐NSAIDs examined showed a decreased risk. The concomitant use of proton‐pump inhibitors (PPI) had no impact on the protective effect of NA‐NSAIDs; AORPPI + NSAID = 0.64; 0.58‐0.71. SYSADOA use was associated with a reduced risk (0.79; 0.69‐0.90) but disappeared after the exclusion of NSAID users during the previous 1 or 3 years (0.85; 0.70‐1.04 and 1.00; 0.76‐1.31 respectively). Metamizole did not show a chemoprotective effect.

Conclusions

NA‐NSAID use is associated with a duration‐dependent risk reduction of CRC not shared by SYSADOAs or metamizole.
Therapeutic drug monitoring of infliximab in spondyloarthritis. A review of the literature
Authors: Fobelo Lozano María José , Serrano Giménez Reyes , Sánchez Fidalgo Susana
Published: July 2019

Available evidence indicates that a therapeutic drug monitoring strategy leads to major cost savings related to the anti‐tumour necrosis factor‐α therapy in both inflammatory bowel disease and rheumatoid arthritis (RA) patients, with no negative impact on efficacy. However, although the systematic use of therapeutic drug monitoring could potentially be beneficial and economically acceptable to drug dose optimization, it is not justifiable for all drugs. Infliximab (IFX) is a chimeric monoclonal immunoglobulin G1 targeting tumour necrosis factor. It has been approved for the treatment of immuno‐inflammatory diseases, including RA, ankylosing spondylitis, psoriatic arthritis, Crohn's disease and ulcerative colitis. IFX's pharmacokinetics is highly variable and influences clinical response in chronic inflammatory diseases. Clinical response increases with IFX trough concentrations in RA, ankylosing spondylitis, inflammatory bowel disease and psoriatic patients. Target concentrations predictive of good clinical response were proposed in RA, Crohn's disease and ulcerative colitis. The purpose of this article is to review the current literature surrounding IFX serum concentrations and their related parameters with disease activity in patients with spondyloarthritis. Gathering information about the efficacy of IFX in patients with spondyloarthritis and relating IFX serum concentrations to disease activity were the main goals of this study.
Single‐port robot‐assisted laparoscopic radical prostatectomy: initial experience and technique with the da Vinci®SP platform
Authors: Dobbs Ryan W. , Halgrimson Whitney R. , Madueke Ikenna , Vigneswaran Hari T. , Wilson Jessica O. , Crivellaro Simone
Published: July 2019

Objectives

To assess the safety and feasibility of the da Vinci® SP (Intuitive Surgical, Sunnyvale, CA, USA) robotic platform for a consecutive series of patients who underwent single‐port robot‐assisted laparoscopic radical prostatectomy (SP‐RALP).

Patients and Methods

In all, 10 consecutive patients with biopsy confirmed prostate cancer underwent SP‐RALP at our institution. Pre‐, peri‐, and postoperative data were prospectively collected for key outcomes including: estimated blood loss (EBL), operative time, postoperative pain requirements, duration of hospital stay, and complications.

Results

The patients were aged 52–77 years with a body mass index of 24.4–36.7 kg/m2. Prostate volumes ranged from 26 to 136 mL, with a mean (sd) PSA (prostate specific antigen) level of 11.0 (10.6) ng/mL. Lymph node dissection was performed in four patients and nerve sparing in five. No intraoperative complications occurred, and no patients required conversion to an open approach. Total EBL was 20–150 mL, with a median (interquartile range [IQR]) console time of 189 (171–207) min and operative time of 234 (216–247) min. No patients were readmitted or required intervention. Urethral catheters were removed at a median (IQR) of 10 (8–11) days after surgery.

Conclusion

SP‐RALP appears to be a safe and feasible approach to performing robotic radical prostatectomy. Long‐term follow‐up will be necessary to assess initial oncological and functional results.
Shallow‐water deltaic clinoforms and process regime
Authors: Plink‐Björklund Piret
Published: July 2019

Utilizing two outcrop data sets with dip direction exposures of shallow‐water (tens of meters) deltaic clinoforms, this paper quantifies sedimentary facies proportions and clinoform lengths and gradients, and links process regimes to delta clinoform dimensions. Both data sets are from foreland basins, the Cretaceous Chimney Rock Sandstone of the Rock Springs Formation from the US Western Interior, and the Eocene Brogniartfjellet Clinoform Complex 8 of the Battfjellet Formation from the Central Basin of Spitsbergen. Sedimentary facies indicate presence of both river‐ and wave‐dominated clinothems in each data set. Facies characteristics and distribution implies that river‐dominated clinothem progradation was primarily driven by deposition from weak hyperpycnal flow turbidity currents across the clinoforms, and minor slumps. Wave‐dominated clinothems were constructed by wave processes rather than alongshore currents, and are also progradational subaerial clinoforms, with one exception, where the formation of a compound subaqueous clinoform set indicates erosion and sediment bypass above the wave base. Sediment distribution and lithological heterogeneity in the river‐dominated clinothems is controlled by individual hyperpycnal flow events or mouth‐bar collapse events, and thus by self‐organization and minimal reworking that results in a heterogeneity that is difficult to predict (high entropy). The efficient reworking of river‐derived sediments in wave‐dominated clinothems results in predictable lithological sediment partitioning (low entropy). Clinoform dimension analyses show that although of similar sediment caliber, river‐dominated clinoforms in both data sets are on average 3–4 times steeper and 3–4 times shorter than the wave‐dominated clinoforms, with mean gradients of ca 4 degrees and ca 1 degree, respectively, and mean lengths of 150–230 m and 640–760 m. These results require corroboration from additional data sets, but do suggest that river‐ and wave‐dominated delta clinoforms are likely to have distinct downdip extents (lengths) and gradients for given clinoform heights. Clinoform shape can thus be a method for differentiating ancient river‐ vs. wave‐dominated deltaic clinoforms, in addition to their sedimentary facies, biogenic features and sandstone maturity, and helpful when incorporated into reservoir models.
Similar effectiveness of R‐CHOP‐14 and ‐21 in diffuse large B‐cell lymphoma—data from the prospective German Tumour Registry Lymphatic Neoplasms
Authors: Knauf Wolfgang , Abenhardt Wolfgang , Mohm Johannes , Rauh Jacqueline , Harde Johanna , Kaiser‐Osterhues Anja , Jänicke Martina , Marschner Norbert ,   the TLN‐Group (Tumour Registry Lymphatic Neoplasms)
Published: July 2019

Objectives

R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard therapy for patients with previously untreated diffuse large B‐cell lymphomas (DLBCL). Dose‐dense two‐weekly ‘R‐CHOP‐14’ was not superior over three‐weekly ‘R‐CHOP‐21’ in randomised clinical trials (RCTs). We present real‐world data on effectiveness of R‐CHOP‐14 and R‐CHOP‐21 in patients with DLBCL treated in German routine practice.

Methods

We identified 582 patients with DLBCL treated with R‐CHOP‐14 or R‐CHOP‐21 in 92 sites from the prospective clinical cohort study Tumour Registry Lymphatic Neoplasms. Patients’ schedules were classified by (a) length of the initial first cycle and (b) length of cycles 1‐4.

Results

About 55% of patients received R‐CHOP‐21, 45% R‐CHOP‐14, in median 6 cycles. 51% and 55% of patients, respectively, were able to continue their initial R‐CHOP‐14 and R‐CHOP‐21 schedule. While most characteristics between the patient cohorts were similar, patients receiving R‐CHOP‐21 presented slightly more often with tumour stage I and lower IPI risk. 3‐year overall survival of patients with R‐CHOP‐14 and R‐CHOP‐21 did not differ: 84% vs 84% (first cycle), 87% vs 89% (cycles 1‐4).

Conclusions

Patients with DLBCL in Germany are slightly more likely to receive R‐CHOP‐21 than R‐CHOP‐14. Both schedules are similarly effective in routine practice confirming the results from RCTs.
Soil type and land use effects on tensorial properties of saturated hydraulic conductivity in northern Germany
Authors: Horn Rainer , Mordhorst Anneka , Fleige Heiner , Zimmermann Iris , Burbaum Bernd , Filipinski Marek , Cordsen Eckhard
Published: July 2019

Long‐term soil management can produce anisotropic impacts on soil structure, resulting in differences in horizontal and vertical hydraulic conductivity. As limited data exist on these impacts, this study provides a broad‐scale assessment across 764 soil profiles under arable and grassland use in northern Germany (Federal State: Schleswig‐Holstein). The soils were sampled in the four geological regions: Weichselian glacial region, the sandy outwash region (Lower “Geest”), the Saalian glacial region (Higher “Geest”) and the marshland with alluvial deposits. Saturated hydraulic conductivity (Ks, either in a horizontal (Ks_h) or vertical direction (Ks_v)) and the pore‐size distribution were determined on undisturbed soil samples (100 cm3), whereas the grain size distribution was analysed on disturbed samples from the major soil horizons. This research work presents Ks_h and Ks_v values for representative soil types of the four geological regions down to a depth of 60 cm. Irrespective of the parent material in the four geological regions, arable soils showed a pronounced anisotropy of Ks in the horizontal direction. However, Ks_h and Ks_v also showed a high variability across the geological regions from approximately 1 to 800 cm d−1, whereas the ratio of Ks_h to Ks_v ranged from 0.1 to 500. In the marshland (dominated by Gleysols), the direction‐dependent values were superimposed by sedimentation processes of the marine material and/or structural development processes such as vertical shrinkage or bioturbation processes. Under grassland, the topsoils primarily indicated horizontally anisotropic flow conditions. In the “Geest” area with a high share of dairy farming, both top‐ and subsoils displayed the highest horizontal anisotropy values, indicating the stress‐induced formation of a platy structure caused by trampling, grass harvesting or slurry application with heavy machinery. Soil type (e.g., Stagnic Luvisols, Stagnosols or Anthrosols) and horizon‐dependent horizontal anisotropy were also more pronounced in arable than in grassland subsoils.

Highlights

Hydraulic conductivity in arable subsoils shows mostly horizontal behaviour.

Hydraulic conductivity in grassland topsoils shows mostly horizontal behaviour.

The anisotropic degree and its direction depend on land use type and clay content of the soils.
Structural and biochemical consequences of pyridoxine‐dependent epilepsy mutations that target the aldehyde binding site of aldehyde dehydrogenase ALDH7A1
Authors: Laciak Adrian R. , Korasick David A. , Wyatt Jesse W. , Gates Kent S. , Tanner John J.
Published: July 2019

In humans, certain mutations in the gene encoding aldehyde dehydrogenase 7A1 are associated with pyridoxine‐dependent epilepsy (PDE). Understanding the impact of PDE‐causing mutations on the structure and activity of ALDH7A1 could allow for the prediction of symptom‐severity and aid the development of patient‐specific medical treatments. Herein, we investigate the biochemical and structural consequences of PDE missense mutations targeting residues in the aldehyde substrate binding site: N167S, P169S, A171V, G174V, and W175G. All but G174V could be purified for biochemical and X‐ray crystallographic analysis. W175G has a relatively mild kinetic defect, exhibiting a fivefold decrease in kcat with no change in Km. P169S and N167S have moderate defects, characterized by catalytic efficiencies of 20‐ and 100‐times lower than wild‐type, respectively. A171V has a profound functional defect, with catalytic efficiency 2000‐times lower than wild‐type. The crystal structures of the variants are the first for any PDE‐associated mutant of ALDH7A1. The structures show that missense mutations that decrease the steric bulk of the side chain tend to create a cavity in the active site. The protein responds by relaxing into the vacant space, and this structural perturbation appears to cause misalignment of the aldehyde substrate in W175G and N167S. The P169S structure is nearly identical to that of the wild‐type enzyme; however, analysis of B‐factors suggests the catalytic defect may result from altered protein dynamics. The A171V structure suggests that the potential for steric clash with Val171 prevents Glu121 from ion pairing with the amino group of the aldehyde substrate.

Enzymes

Aldehyde dehydrogenase 7A1 (EC1.2.1.31).

Databases

Coordinates have been deposited in the Protein Data Bank under the following accession codes: 6O4B, 6O4C, 6O4D, 6O4E, 6O4F, 6O4G, 6O4H.
Cold spot microrefugia hold the key to survival for Brazil's Critically Endangered Araucaria tree
Authors: Wilson Oliver J. , Walters Richard J. , Mayle Francis E. , Lingner Débora V. , Vibrans Alexander C.
Published: July 2019

Brazil's Araucaria tree (Araucaria angustifolia) is an iconic living fossil and a defining element of the Atlantic Forest global biodiversity hotspot. But despite more than two millennia as a cultural icon in southern Brazil, Araucaria is on the brink of extinction, having lost 97% of its extent to 20th‐century logging. Although logging is now illegal, 21st‐century climate change constitutes a new—but so far unevaluated—threat to Araucaria's future survival. We use a robust ensemble modelling approach, using recently developed climate data, high‐resolution topography and fine‐scale vegetation maps, to predict the species' response to climate change and its implications for conservation on meso‐ and microclimate scales. We show that climate‐only models predict the total disappearance of Araucaria's most suitable habitat by 2070, but incorporating topographic effects allows potential highland microrefugia to be identified. The legacy of 20th‐century destruction is evident—more than a third of these likely holdouts have already lost their natural vegetation—and 21st‐century climate change will leave just 3.5% of remnant forest and 28.4% of highland grasslands suitable for Araucaria. Existing protected areas cover only 2.5% of the surviving microrefugia for this culturally important species, and none occur in any designated indigenous territory. Our results suggest that anthropogenic climate change is likely to commit Araucaria to a second consecutive century of significant losses, but targeted interventions could help ensure its survival in the wild.
Deep soil inventories reveal that impacts of cover crops and compost on soil carbon sequestration differ in surface and subsurface soils
Authors: Tautges Nicole E. , Chiartas Jessica L. , Gaudin Amélie C. M. , O'Geen Anthony T. , Herrera Israel , Scow Kate M.
Published: July 2019

Increasing soil organic carbon (SOC) via organic inputs is a key strategy for increasing long‐term soil C storage and improving the climate change mitigation and adaptation potential of agricultural systems. A long‐term trial in California's Mediterranean climate revealed impacts of management on SOC in maize‐tomato and wheat–fallow cropping systems. SOC was measured at the initiation of the experiment and at year 19, at five depth increments down to 2 m, taking into account changes in bulk density. Across the entire 2 m profile, SOC in the wheat–fallow systems did not change with the addition of N fertilizer, winter cover crops (WCC), or irrigation alone and decreased by 5.6% with no inputs. There was some evidence of soil C gains at depth with both N fertilizer and irrigation, though high variation precluded detection of significant changes. In maize‒tomato rotations, SOC increased by 12.6% (21.8 Mg C/ha) with both WCC and composted poultry manure inputs, across the 2 m profile. The addition of WCC to a conventionally managed system increased SOC stocks by 3.5% (1.44 Mg C/ha) in the 0–30 cm layer, but decreased by 10.8% (14.86 Mg C/ha) in the 30–200 cm layer, resulting in overall losses of 13.4 Mg C/ha. If we only measured soil C in the top 30 cm, we would have assumed an increase in total soil C increased with WCC alone, whereas in reality significant losses in SOC occurred when considering the 2 m soil profile. Ignoring the subsoil carbon dynamics in deeper layers of soil fails to recognize potential opportunities for soil C sequestration, and may lead to false conclusions about the impact of management practices on C sequestration.
A review and meta‐analysis of intraspecific differences in phenotypic plasticity: Implications to forecast plant responses to climate change
Authors: Matesanz Silvia , Ramírez‐Valiente José Alberto
Published: July 2019

Aim

Many studies use differences among plant populations to infer future plant responses, but these predictions will provide meaningful insights only if patterns of plasticity among populations are similar (i.e., in the absence of population‐by‐environment interaction, P × E). In this study, we tested whether P × E is considered in climate change studies. Specifically, we evaluated whether population differentiation varies across environments and whether P × E is determined by aspects of the study system and experimental design.

Location

Global.

Methods

We conducted a literature search in the Thomson Reuters Web of Science database to identify studies assessing population differentiation in a climate change context. We quantified the occurrence of P × E and performed a meta‐analysis to calculate the percentage of traits showing P × E in the study cases.

Results

We identified 309 study cases (from 237 published articles) assessing population differentiation in 172 plant species, of which 64% included more than one test environment and tested P × E. In 77% of these studies, P × E was significant for at least one functional trait. The overall proportion of traits showing P × E was 33.4% (95% confidence interval 27.7–39.3). These results were generally consistent across life‐forms, ecoregions and type of experiment. Furthermore, population differentiation varied across test environments in 76% of cases. The overall proportion of traits showing environment‐dependent population differentiation was 53.7% (95% confidence interval 37.9–69.3).

Conclusions

Our findings revealed that differences in phenotypic plasticity among populations are common but are usually neglected in order to forecast population responses to climate change. Future studies should assess population differentiation in many test environments (accounting for P × E) that realistically reflect future environmental conditions, assessing climate change drivers that are rarely considered (e.g., multifactor experiments incorporating higher CO2 levels). Our review also revealed the predominant focus of population studies on trees from temperate climates, identifying underexplored life‐forms (shrubs, annuals), phylogenetic groups (ferns, ancient gymnosperms) and ecoregions (tropical, arctic) that should receive more attention in future.
Development of vitamin E‐enriched functional foods: stability of tocotrienols in food systems
Authors: Pandya Janam K. , DeBonee Maryssa , Corradini Maria G. , Camire Mary Ellen , McClements David Julian , Kinchla Amanda J.
Published: July 2019

Tocotrienols are members of the vitamin E family that provide many nutritional benefits. Developing tocotrienol‐fortified functional foods introduces vitamin E into consumers diets without changing their food habits. The purpose of this study was to compare the stability of tocotrienols in bulk form and six food matrices at a fixed dose (40 mg kg−1) under accelerated and conventional storage conditions. The delta‐ and gamma‐tocotrienol content was measured using HPLC, and the sensory attributes were evaluated using triangle and hedonic tests. Tocotrienol in bulk powder was less stable under stressed conditions than in bulk oil, with the powders having approximately 40% and 80% reduction in δ‐ and γ‐ after storage and bulk oil with no significant degradation. HPLC analysis demonstrated that tocotrienol content remained unchanged in dry mix lemonade, yogurt, raw and UHT milk, and margarine over time; however, complete degradation of γ‐ and partial degradation (up to 50%) of δ‐tocotrienol was observed in bread during ambient and stressed storage conditions. A significant decrease in the δ‐tocotrienol relative concentration was also observed in HTST processed milk samples. Tocotrienol addition was not perceived, and no significant difference in the product attributes and overall liking was reported in the discrimination sensory testing.
Effect of dry fractionated hybrid protein ingredients on the structural, textural, thermal and sensory properties of gluten‐free oat and faba pasta
Authors: Duta Denisa E. , Culetu Alina , Sozer Nesli
Published: July 2019

Protein‐enriched gluten‐free pasta was prepared from oat starch‐rich endosperm (SRE), which was substituted with different proportions of oat protein concentrate (OPC) and/or faba protein concentrate (FPC) fractions in order to obtain a similar protein content (18% and 35%). Accordingly, the health claims ‘source of protein’ and ‘high protein’ were achieved. Pasta with OPC and FPC had lower optimal cooking time (8 and 6.3 min), cooking loss (6% and 10.2% dm) and water absorption (152% and 147%) than control SRE pasta (9.3 min; 12.3% dm and 185%). Addition of protein concentrates produced an increase in hardness and chewiness of spaghetti. The glycaemic index of pasta was lowered by the addition of protein ingredients, the lowest value being achieved with FPC. In vitro protein digestibility of pasta increased up to 3.5% for OPC and up to 7.1% in case of FPC addition. The most protein‐digestible pasta was that with FPC addition to reach 35% protein content.
Genetic reprogramming for NK cell cancer immunotherapy with CRISPR/Cas9
Authors: Afolabi Lukman O. , Adeshakin Adeleye O. , Sani Musbahu M. , Bi Jiacheng , Wan Xiaochun
Published: July 2019

Natural killer cells are potent cytotoxic lymphocytes specialized in recognizing and eliminating transformed cells, and in orchestrating adaptive anti‐tumour immunity. However, NK cells are usually functionally exhausted in the tumour microenvironment. Strategies such as checkpoint blockades are under investigation to overcome NK cell exhaustion in order to boost anti‐tumour immunity. The discovery and development of the CRISPR/Cas9 technology offer a flexible and efficient gene‐editing capability in modulating various pathways that mediate NK cell exhaustion, and in arming NK cells with novel chimeric antigen receptors to specifically target tumour cells. Despite the high efficiency in its gene‐editing capability, difficulty in the delivery of the CRISPR/Cas9 system remains a major bottleneck for its therapeutic applications, particularly for NK cells. The current review discusses feasible approaches to deliver the CRISPR/Cas9 systems, as well as potential strategies in gene‐editing for NK cell immunotherapy for cancers.
Research Review: Psychological and psychosocial treatments for children and young people with post‐traumatic stress disorder: a network meta‐analysis
Authors: Mavranezouli Ifigeneia , Megnin‐Viggars Odette , Daly Caitlin , Dias Sofia , Stockton Sarah , Meiser‐Stedman Richard , Trickey David , Pilling Stephen
Published: July 2019

Background

Post‐traumatic stress disorder (PTSD) is a potentially chronic and disabling disorder that affects a significant minority of youth exposed to trauma. Previous studies have concluded that trauma‐focused cognitive behavioural therapy (TF‐CBT) is an effective treatment for PTSD in youth, but the relative strengths of different psychological therapies are poorly understood.

Methods

We undertook a systematic review and network meta‐analyses of psychological and psychosocial interventions for children and young people with PTSD. Outcomes included PTSD symptom change scores post‐treatment and at 1–4‐month follow‐up, and remission post‐treatment.

Results

We included 32 trials of 17 interventions and 2,260 participants. Overall, the evidence was of moderate‐to‐low quality. No inconsistency was detected between direct and indirect evidence. Individual forms of TF‐CBT showed consistently large effects in reducing PTSD symptoms post‐treatment compared with waitlist. The order of interventions by descending magnitude of effect versus waitlist was as follows: cognitive therapy for PTSD (SMD −2.94, 95%CrI −3.94 to −1.95), combined somatic/cognitive therapies, child–parent psychotherapy, combined TF‐CBT/parent training, meditation, narrative exposure, exposure/prolonged exposure, play therapy, Cohen TF‐CBT/cognitive processing therapy (CPT), eye movement desensitisation and reprocessing (EMDR), parent training, group TF‐CBT, supportive counselling and family therapy (SMD −0.37, 95%CrI −1.60 to 0.84). Results for parent training, supportive counselling and family therapy were inconclusive. Cohen TF‐CBT/CPT, group TF‐CBT and supportive counselling had the largest evidence base. Results regarding changes in PTSD symptoms at follow‐up and remission post‐treatment were uncertain due to limited evidence.

Conclusions

Trauma‐focused cognitive behavioural therapy, in particular individual forms, appears to be most effective in the management of PTSD in youth. EMDR is effective but to a lesser extent. Supportive counselling does not appear to be effective. Results suggest a large positive effect for emotional freedom technique, child–parent psychotherapy, combined TF‐CBT/parent training, and meditation, but further research is needed to confirm these findings as they were based on very limited evidence.
Immune landscape of hepatocellular carcinoma microenvironment: Implications for prognosis and therapeutic applications
Authors: Cariani Elisabetta , Missale Gabriele
Published: July 2019

The development of immunotherapy for solid tumours has boosted interest in the contexture of tumour immune microenvironment (TIME). Several lines of evidence indicate that the interplay between tumour cells and TIME components is a key factor for the evolution of hepatocellular carcinoma (HCC) and for the likelihood of response to immunotherapeutics. The availability of high‐resolution methods will be instrumental for a better definition of the complexity and diversity of TIME with the aim of predicting disease outcome, treatment response and possibly new therapeutic targets. Here, we review current knowledge about the immunological mechanisms involved in shaping the clinical course of HCC. Effector cells, regulatory cells and soluble mediators are discussed for their role defining TIME and as targets for immune modulation, together with possible immune signatures for optimization of immunotherapeutic strategies.
Why nurses should be Marxists
Authors: Porter Sam
Published: July 2019

The argument that nurses should be Marxists is made by looking at the primary areas of nursing activity in turn, giving an example of how capitalist economic relations negatively impact upon that activity, and providing a Marxist explanation of the reasons why it has that impact. In relation to the nursing activity of health promotion, it is argued that capitalism's generation of social inequality undermines the health of the population. In relation to curative activities, the focus is on how capitalism's reckless pursuit of profit has subverted the sustainability of bactericidal interventions. The argument in relation to comforting and assistive care is that the ownership and control of health services by capitalist corporations undermines therapeutic relationships. Finally, in relation to supportive care, it is contended that capitalism's requirement for a disciplined workforce can compromise healthcare professionals’ support of employees. It is concluded that if nurses aspire to have some control over their activities, then it is a good idea for them to avail of Marxism's capacity to identify the socio‐economic mechanisms by which capitalism affects nursing care.
Effect of apple cultivars and storage periods on the virulence of Neofabraea spp.
Authors: Di Francesco A. , Cameldi I. , Neri F. , Barbanti L. , Folchi A. , Spadoni A. , Baraldi E.
Published: July 2019

Bull’s eye rot is a typical quiescent postharvest apple disease in major fruit‐growing areas. The susceptibility of different apple cultivars to Neofabraea spp. (N. vagabunda and N. malicorticis) was assessed, with Granny Smith showing the most resistance and Cripps Pink the most susceptibility. To assess the factors involved in conidial germination, Neofabraea spp. were grown on crude protein extracts (CPEs) collected from apple fruits at different storage periods. Fungal germ tube growth rate and pathogenic enzyme (cellulase and xylanase) activity were assessed. Results showed that CPEs collected after 2 and 4 months of storage progressively stimulated conidial germination and germ tube elongation, while a lesser effect was observed from CPEs after 1 month of storage. Xylanase proved to be the main degrading enzyme secreted by all the isolates, while cellulase was produced only by N. vagabunda isolates. Overall, the isolate ID02 was the most virulent, based on more rapid germ tube elongation and greater activity of the lytic enzymes.
Los contornos flexibles del principio del debido proceso en las sanciones disciplinarias
Authors: Ramírez Torrado María Lourdes , Hernández Meza Nelson
Published: July 2019

La inexistencia de un estatuto general disciplinario que determine el contenido y los límites del debido proceso disciplinario, y el hecho de que las normas sectoriales guarden silencio sobre el alcance de este principio han permitido que los órganos de cierre constitucional y contencioso administrativo sean los que resuelvan en cada caso los interrogantes planteados en su aplicación. A todas luces, esta situación genera incertidumbre para el sujeto disciplinado por la ausencia de claridad en torno a esta garantía. Por ello, el objetivo de este documento es determinar y analizar cuál es el alcance que ha tenido este principio en temas disciplinarios, a partir de las sentencias de los tribunales de cierre que han dado forma al postulado en cuestión. Se ha encontrado que, si bien la doctrina jurisprudencial, en principio, es protectora del debido proceso, las garantías que lo rodean tienen, en ocasiones, un alcance discutible, pues a pesar de proteger, sin dudas, un núcleo duro del postulado, en otros aspectos no resultan ser tan garantistas.
Gadamer y la hermenéutica jurídica: ¿un insumo útil?
Authors: Pérez Lasserre Diego
Published: July 2019

Este trabajo tiene por finalidad analizar el pensamiento hermenéutico-jurídico gadameriano con la finalidad de justificar que las presuntas insuficiencias de su pensamiento no responden a carencias del mismo, sino a la óptica desde la cual este autor se aproxima al problema de la interpretación jurídica.
Performance Modeling and Analysis of a Single-Shaft Closed-Cycle Gas Turbine Using Different Operational Control Strategy
Authors: Osigwe Emmanuel O. , Gad-Briggs Arnold , Igbong Dodeye , Nikolaidis Theoklis , Pilidis Pericles
Published: July 2019

In the last few years, one considerable factor for the viability and interest in the closed-cycle gas turbine (GT) systems for nuclear or conventional power plant application is its potential to maintain high cycle performance at varying operating conditions. However, for this potential to be realized, more competitive analysis and understanding of its control strategy are importantly required. In this paper, the iterative procedure for three independent control strategies of a 40 MW single-shaft intercooled-recuperated closed-cycle GT incorporated to a generation IV nuclear reactor is been analyzed and their performance at various operating conditions compared. The rationale behind this analysis was to explore different control strategies and to identify potential limitations using each independent control. The inventory control strategy offered a more viable option for high efficiency at changes in ambient and part-load operations, however, operational limitations in terms of size and pressure of inventory tank, rotational speed for which the centrifugal forces acting on the blade tips could become too high, hence would affect the mechanical integrity and compressor performance. The bypass control responds rapidly to load rejection in the event of loss of grid power. And more interestingly, the results showed the need for a mixed or combined control instead of a single independent technique, which is limited in practice due to operational limits.
Review of Morphing Laminated Composites
Authors: Chillara V. S. C. , Dapino M. J.
Published: July 2019

Morphing structures, defined as body panels that are capable of a drastic autonomous shape transformation, have gained importance in the aerospace, automotive, and soft robotics industries since they address the need to switch between shapes for optimal performance over the range of operation. Laminated composites are attractive for morphing because multiple laminae, each serving a specific function, can be combined to address multiple functional requirements such as shape transformation, structural integrity, safety, aerodynamic performance, and minimal actuation energy. This paper presents a review of laminated composite designs for morphing structures. The trends in morphing composites research are outlined and the literature on laminated composites is categorized based on deformation modes and multifunctional approaches. Materials commonly used in morphing structures are classified based on their properties. Composite designs for various morphing modes such as stretching, flexure, and folding are summarized and their performance is compared. Based on the literature, the laminae in an n-layered composite are classified based on function into three types: constraining, adaptive, and prestressed. A general analytical modeling framework is presented for composites comprising the three types of functional laminae. Modeling developments for each morphing mode and for actuation using smart material-based active layers are discussed. Results, presented for each deformation mode, indicate that the analytical modeling can not only provide insight into the structure's mechanics but also serve as a guide for geometric design and material selection.
Comparison of DNA Methylation in Vibrio vulnificus Cells Grown in Human Serum with Those Grown in Seawater
Authors: Conrad James W. , Harwood Valerie J.
Published: July 2019

The chromosomal methylation statuses of the highly virulent
Vibrio vulnificus
strain CMCP6 grown in human serum and in seawater are compared here. Growth in seawater resulted in ∼4 times as much methylation as that in human serum, primarily N
4
-methylcytosines.
Draft Genome Sequence of Methylocystis heyeri H2
T
, a Methanotroph with Habitat-Specific Adaptations, Isolated from a Peatland Ecosystem
Authors: Oshkin Igor Y. , Miroshnikov Kirill K. , Dedysh Svetlana N.
Published: July 2019

Methylocystis heyeri
H2
T
is an aerobic facultative methanotroph which was isolated from an acidic
Sphagnum
peat bog lake and is a common inhabitant of peatland ecosystems. This bacterium possesses two particulate methane monooxygenases with low and high affinity to methane and a number of genomic adaptations to acidic conditions.
Draft Genome Sequence of a Bioflocculant-Producing Bacterium, Citrobacter freundii IFO 13545
Authors: Baranwal Priyanka , Kimura Kazuyuki , Mayilraj Shanmugam , Negoro Seiji , Takeo Masahiro
Published: July 2019

Here, we report the 5.2-Mb genome sequence of a bioflocculant-producing bacterial strain,
Citrobacter freundii
IFO 13545, which consists of 5,209,670 bp with a G+C content of 51.5% and 4,853 predicted coding sequences (CDSs). The genes related to the biosynthetic pathway of the bioflocculant were localized on the genome map.
Complete Genome Sequence of the Novel Klebsiella pneumoniae Phage Marfa
Authors: Harb Laith , Boeckman Justin , Newkirk Heather , Liu Mei , Gill Jason J. , Ramsey Jolene
Published: July 2019

Here, we describe the complete genome sequence of the T4-like
Klebsiella pneumoniae
myophage Marfa. In its 168,532-bp genome, Marfa has 289 genes, for which 122 gene functions were predicted. Many similar proteins are shared between Marfa and phage T4, as well as its closest phage relatives.
Differences in access to Emergency Paediatric Intensive Care and care during Transport (DEPICT): study protocol for a mixed methods study
Authors: Ramnarayan Padmanabhan , Evans Ruth , Draper Elizabeth S , Seaton Sarah E , Wray Jo , Morris Stephen , Pagel Christina
Published: July 2019

Introduction

Following centralisation of UK paediatric intensive care, specialist retrieval teams were established who travel to general hospitals to stabilise and transport sick children to regional paediatric intensive care units (PICUs). There is national variation among these PICU retrieval teams (PICRTs) in terms of how quickly they reach the patient’s bedside and in the care provided during transport. The impact of these variations on clinical outcomes and the experience of stakeholders (patients, families and healthcare staff) is however unknown. The primary objective of this study is to address this evidence gap.

Methods and analysis

This mixed-methods project involves the following: (1) retrospective analysis of linked data from routine clinical audits (2014–2016) to assess the impact of service variations on 30-day mortality and other secondary clinical outcomes; (2) a prospective questionnaire study conducted at 24 PICUs and 9 associated PICRTs in England and Wales over a 12-month period in 2018 to collect experience data from parents of transported children as well as qualitative analysis of in-depth interviews with a purposive sample of patients, parents and staff to assess the impact of service variations on patient/family experience; (3) health economic evaluation analysing transport service costs (and other associated costs) against lives saved and longer term measurements of quality of life at 12 months in transported children and (4) mathematical modelling evaluating the costs and potential impact of different service configurations. A final work stream involves a series of stakeholder workshops to synthesise study findings and generate recommendations.

Ethics and dissemination

The study has been reviewed and approved by the Health Research Authority, ref: 2 18 569. Study results will be actively disseminated through peer-reviewed journals, conference presentations, social media, print and broadcast media, the internet and stakeholder workshops.
Neonatal outcomes of very low birthweight infants born to mothers with hyperglycaemia in pregnancy: a retrospective cohort study in Japan
Authors: Hitaka Daisuke , Morisaki Naho , Miyazono Yayoi , Piedvache Aurelie , Nagafuji Motomichi , Takeuchi Syusuke , Kajikawa Daigo , Kanai Yu , Saito Makoto , Takada Hidetoshi
Published: July 2019

Objective

To examine the mortality and morbidities of very low birthweight (VLBW, <1500 g) infants of mothers with hyperglycaemia in pregnancy.

Design and setting

We conducted a retrospective cohort study using data from the Neonatal Research Network of Japan, a nationwide registry of VLBW infants (2003–2012).

Patients

We studied 29 626 infants born at 23 to 32 weeks without major congenital anomalies, of which 682 (2.3%) infants were from pregnancies affected by maternal hyperglycaemia.

Main outcome measures

The primary outcome was hospital mortality. Secondary outcomes were neonatal morbidities and their anthropometric values. Associations between maternal hyperglycaemia and each outcome were observed for the overall period, and statistical tests for interaction were conducted to assess whether they differed before or after the adoption of the International Association of Diabetes in Pregnancy Study Group (IADPSG) guidelines in 2010 for the diagnosis of gestational diabetes mellitus.

Results

Overall, hospital mortality (4.1% vs 5.2%), composite outcomes of mortality and severe morbidity (54.2% vs 60%), and anthropometric values were not significantly different between infants of mothers with or without hyperglycaemia in pregnancy. However, the incidence of respiratory distress syndrome (RDS) in VLBW infants from mothers with hyperglycaemia was significantly higher than those from mothers without it only before (relative risk (RR) 1.09, 95% CI 1.00 to 1.19) and not after (RR 0.97, 95% CI 0.83 to 1.11) the adoption of the IADPSG guidelines.

Conclusion

VLBW infants born to mothers with hyperglycaemia in pregnancy do not seem to be at higher risk of mortality and morbidities, except for RDS only before the adoption of the IADPSG guidelines.
Parity and dietary energy allowance during gestation influence piglet energy status and serum insulin-like growth factor 1 at birth
Authors: Miller E.G. , Huber L. , Levesque C.L. , de Lange C.F.M.
Published: July 2019

Over- or under-supplying energy by 15% to gestating sows had minimum consequences for piglet chemical body composition or energy storage (liver and muscle glycogen) at birth, when estimated amino acid requirements were met. Providing gestating sows with energy 15% below versus 15% above requirements increased piglet serum insulin-like growth factor 1 (IGF-1) concentrations at birth (P < 0.05). Piglets from first versus second parity sows had lower serum IGF-1 but greater liver glycogen and body fat. Precisely matching the estimated energy and nutrient requirements throughout gestation and across parities likely improves piglet quality; over-supplying energy appears most detrimental for piglet IGF-1 serum concentrations at birth.
Effects of mechanical site preparation and slash removal on long-term productivity of conifer plantations in Sweden
Authors: Hjelm Karin , Nilsson Urban , Johansson Ulf , Nordin Per
Published: July 2019

Mechanical site preparation is commonly used to increase survival and early growth of newly planted seedlings. Ideally, any early positive effects of site preparation should persist for a long time, but concerns have been raised as to whether intensive site preparation might have a negative effect on the long-term productivity of a stand. The present study was therefore designed to investigate the long-term effects of different site-preparation methods on productivity and determine any possible interactions with tree species and site fertility. In the 1980s, a randomized block experiment was established at sites throughout Sweden. Four site-preparation methods of various intensities were performed on different sites: (i) an untreated control, (ii) disc trenching, (iii) mounding, and (iv) ploughing. As a complementary treatment, slash was either retained or removed from some plots. Depending on soil moisture class, geographical position, and site index, Norway spruce (Picea abies (L.) Karst.), Scots pine (Pinus sylvestris L.), or lodgepole pine (Pinus contorta Douglas ex Loudon) were planted in pure stands. Growth variables such as height and diameter were measured during the first years after establishment. After about 30 years, these variables were remeasured at the level of individual trees. Overall, an increased production of the planted trees after site preparation was found. Neither intensive site preparation (such as ploughing) nor slash removal had any negative effect on the long-term productivity of these experimental stands.
Velocity–temperature correlations in high-temperature supersonic turbulent channel flows for two gas models
Authors: Zhang Junming , Chen Xiaoping , Li Yi
Published: July 2019

Velocity–temperature correlations in a high-temperature supersonic turbulent channel flows, including thermally perfect gas (TPG) and calorically perfect gas (CPG), are investigated based on the direct numerical simulation database [Chen et al., J. Turbul. 19 (2018) 365] to study the gas model effects. The results show that in fully developed turbulent channel flow, the Reynolds analogy factor remains close to 1.2 for both gas models. The “recovery enthalpy” is better than Walz’s equation to connect the mean stream-wise velocity with mean static temperature because it is independent with gas models. The modified strong Reynolds analogy for TPG is more accurate scaling than that for CPG, and the turbulent Prandtl number is insensitive to gas models. In addition, the influence of gas model on the probability density functions of stream-wise velocity and static temperature concentrate on the corresponding right tails.
Isolation, characterization, and antioxidative activity of a dioxobilin-type phylloxanthobilin from savoy cabbage
Authors: Karg Cornelia A. , Schilling Charlotte M. , Allmendinger Lars , Moser Simone
Published: July 2019

The degradation of the green pigment chlorophyll in plants is known to yield phyllobilins as highly abundant linear tetrapyrroles. Recently, a split path of the degradation pathway has been discovered, leading to so-called dioxobilin-type (or type-II) phyllobilins. The first characterized type-II phyllobilin was colorless featuring four deconjugated pyrrole units. Similar to the type-I branch, for which yellow oxidation products of the colorless phyllobilins – the type-I phylloxanthobilins – are known, a type-II phylloxanthobilin has recently been characterized from senescent leaves of grapevine. Type-I phylloxanthobilins appear to be actively produced in the plant, are known to possess interesting chemical properties, and were shown to act as potent antioxidants that can protect cells from oxidative stress. Here we report the isolation and structural characterization of a type-II phylloxanthobilin from de-greened leaves of savoy cabbage, which turned out to be structurally closely related to bilirubin. Bilirubin is known to possess high antioxidative activity; in addition, savoy cabbage is considered to promote health benefits due to its high content in antioxidants. We therefore investigated the in vitro antioxidative potential of the newly identified type-II phylloxanthobilin using two different approaches, both of which revealed an even higher antioxidative activity for the type-II phylloxanthobilin from savoy cabbage compared to bilirubin.