bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune epigenetic age in pregnancy and 1 year after birth: Associations with weight change
Authors: Ross Kharah M. , Carroll Judith , Horvath Steve , Hobel Calvin J. , Coussons‐Read Mary E. , Dunkel Schetter Christine
Published: February 2020

Problem

Epigenetic age indices are markers of biological aging determined from DNA methylation patterns. Accelerated epigenetic age predicts morbidity and mortality. Women tend to demonstrate slower blood epigenetic aging compared to men, possibly due to female‐specific hormones and reproductive milestones. Pregnancy and the post‐partum period are critical reproductive periods that have not been studied yet with respect to epigenetic aging. The purpose of this paper was to examine whether pregnancy itself and an important pregnancy‐related variable, changes in body mass index (BMI) between pregnancy and the post‐partum period, are associated with epigenetic aging.

Method of Study

A pilot sample of 35 women was recruited as part of the Healthy Babies Before Birth (HB3) project. Whole blood samples were collected at mid‐pregnancy and 1 year post‐partum. DNA methylation at both time points was assayed using Infinium 450K and EPIC chips. Epigenetic age indices were calculated using an online calculator.

Results

Paired‐sample t‐tests were used to test differences in epigenetic age indices from pregnancy to 1 year after birth. Over this critical time span, women became younger with respect to phenotypic epigenetic age, GrimAge, DNAm PAI‐1, and epigenetic age indices linked to aging‐related shifts in immune cell populations, known as extrinsic epigenetic age. Post‐partum BMI retention, but not prenatal BMI increases, predicted accelerated epigenetic aging.

Conclusion

Women appear to become younger from pregnancy to the post‐partum period based on specific epigenetic age indices. Further, BMI at 1 year after birth that reflects weight retention predicted greater epigenetic aging during this period.
Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines ‐ recommendations on the use of biologicals in severe asthma
Authors: Agache Ioana , Rocha Claudio , Beltran Jessica , Song Yang , Posso Margarita , Solà Ivan , Alonso‐Coello Pablo , Akdis Cezmi , Akdis Mubeccel , Canonica Giorgio W. , Casale Thomas , Chivato Tomas , Corren Jonathan , Del Giacco Stefano , Eiwegger Thomas , Firinu Davide , Gern James E. , Hamelmann Eckard , Hanania Nicola , Mäkelä Mika , Martín Irene Hernández , Nair Parameswaran , O'Mahony Liam , Papadopoulos Nikolaos G. , Papi Alberto , Park Hae‐Sim , Pérez de Llano Luis , Quirce Santiago , Sastre Joaquin , Shamji Mohamed , Schwarze Jurgen , Canelo‐Aybar Carlos , Palomares Oscar , Jutel Marek
Published: February 2020

Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews assessed the efficacy and safety of benralizumab, dupilumab and omalizumab (alphabetical order) vs standard of care for patients with uncontrolled severe allergic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma‐related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. All three biologicals reduced with high certainty the annualized asthma exacerbation rate: benralizumab incidence rate ratios (IRR) 0.63 (95% CI 0.50 − 0.81); dupilumab IRR 0.58 (95%CI 0.47 − 0.73); and omalizumab IRR 0.56 (95%CI 0.42 − 0.73). Benralizumab and dupilumab improved asthma control with high certainty and omalizumab with moderate certainty; however, none reached the minimal important difference (MID). Both benralizumab and omalizumab improved QoL with high certainty, but only omalizumab reached the MID. Omalizumab enabled ICS dose reduction with high certainty. Benralizumab and omalizumab showed an increase in drug‐related adverse events (AEs) with low to moderate certainty. All three biologicals had moderate certainty for an ICER/QALY value above the willingness to pay threshold. There was high certainty that in children 6‐12 years old omalizumab decreased the annualized exacerbation rate [IRR 0.57 (95%CI 0.45‐0.72)], improved QoL [relative risk 1.43 (95%CI 1.12 −1.83)], reduced ICS [mean difference (MD) −0.45 (95% CI −0.58 to −0.32)] and rescue medication use [ MD −0.41 (95%CI −0.66 to −0.15)].
A prospective study of perinatal and metabolic risk factors for early childhood caries
Authors: Boustedt Katarina , Roswall Josefine , Kjellberg Emma , Twetman Svante , Dahlgren Jovanna
Published: February 2020

Aim

To study the relationship between early childhood caries and perinatal and metabolic risk factors in a cohort of preschool children.

Methods

The study population consisted of 208 children followed from birth to 6.5 years. We extracted the perinatal factors from medical records and questionnaires and assessed the occurrence of caries at the age of 5 years. Indicators of the metabolic syndrome (waist circumference, blood pressure, fasting insulin, glucose and dyslipidaemia) were recorded at 6.5 years of age.

Results

Infants born moderately to late preterm and infants born small for gestational age were more likely to have early childhood caries at 5 years of age (relative risk 4.2 and 2.3, respectively; P < .05). The presence of metabolic risk factors according to the IDEFICS monitoring levels did not differ between children with or without caries but a statistically significant correlation was found between the fasting glucose values and the number of decayed or filled teeth (r = 0.18; P < .05).

Conclusion

Being born preterm or small for gestational age increased the risk of early childhood caries. Preschool children with caries had higher fasting glucose levels but no other signs of the metabolic syndrome.
School bonding and ethos in trajectories of offending: Results from the Belfast Youth Development Study
Authors: Higgins Kathryn , Perra Oliver , Jordan Julie‐Ann , O'Neill Tara , McCann Mark
Published: February 2020

Background

Aspects of the school environment, such as school attachment levels, are linked to adolescent offending. Previous research has not clarified whether a school‐ or individual‐level intervention approach to improving pupil school attachment and commitment is most likely to reduce adolescent offending.

Aim

The present study assessed the impact of individual‐ and school‐level variables on offending behaviour from ages 14–16 years.

Sample

The participants were 4,049 young people from 42 mainstream schools who took part in the Belfast Youth Development Study.

Method

Multilevel modelling was used to examine the relative influence of individual‐ and school‐level variables on offending behaviour in adolescence.

Results

Pupils who had high levels of school commitment and attachment and were involved in fewer fights at age 13 reported lower levels of offending at age 14 years. Differences between schools accounted for 7% of the variation in offending. Lower individual‐level commitment was associated with higher initial levels of offending at age 14 if the school‐level ethos was of higher commitment. Lack of safety at the school level appeared to be detrimental for young people not exposed to socio‐economic deprivation.

Conclusions

Individual‐level targeted interventions are likely to be a more cost‐effective approach of reducing offending behaviour in adolescence. Additional, albeit smaller, reductions in offending levels could be achieved through school‐level interventions in some school types (e.g., deprived areas).
The antiarrhythmic compound efsevin directly modulates voltage‐dependent anion channel 2 by binding to its inner wall and enhancing mitochondrial Ca2+ uptake
Authors: Wilting Fabiola , Kopp Robin , Gurnev Philip A. , Schedel Anna , Dupper Nathan J. , Kwon Ohyun , Nicke Annette , Gudermann Thomas , Schredelseker Johann
Published: February 2020

Background and Purpose

The synthetic compound efsevin was recently identified to suppress arrhythmogenesis in models of cardiac arrhythmia, making it a promising candidate for antiarrhythmic therapy. Its activity was shown to be dependent on the voltage‐dependent anion channel 2 (VDAC2) in the outer mitochondrial membrane. Here, we investigated the molecular mechanism of the efsevin–VDAC2 interaction.

Experimental Approach

To evaluate the functional interaction of efsevin and VDAC2, we measured currents through recombinant VDAC2 in planar lipid bilayers. Using molecular ligand‐protein docking and mutational analysis, we identified the efsevin binding site on VDAC2. Finally, physiological consequences of the efsevin‐induced modulation of VDAC2 were analysed in HL‐1 cardiomyocytes.

Key Results

In lipid bilayers, efsevin reduced VDAC2 conductance and shifted the channel's open probability towards less anion‐selective closed states. Efsevin binds to a binding pocket formed by the inner channel wall and the pore‐lining N‐terminal α‐helix. Exchange of amino acids N207, K236 and N238 within this pocket for alanines abolished the channel's efsevin‐responsiveness. Upon heterologous expression in HL‐1 cardiomyocytes, both channels, wild‐type VDAC2 and the efsevin‐insensitive VDAC2AAA restored mitochondrial Ca2+ uptake, but only wild‐type VDAC2 was sensitive to efsevin.

Conclusion and Implications

In summary, our data indicate a direct interaction of efsevin with VDAC2 inside the channel pore that leads to modified gating and results in enhanced SR‐mitochondria Ca2+ transfer. This study sheds new light on the function of VDAC2 and provides a basis for structure‐aided chemical optimization of efsevin.
Overview of treatment approaches to osteoporosis
Authors: Langdahl Bente L.
Published: February 2020

Efficient therapies are available for the treatment of osteoporosis. Anti‐resorptive therapies, including bisphosphonates and denosumab, increase bone mineral density (BMD) and reduce the risk of fractures by 20–70%. Bone‐forming or dual‐action treatments stimulate bone formation and increase BMD more than the anti‐resorptive therapies. Two studies have demonstrated that these treatments are superior to anti‐resorptives in preventing fractures in patients with severe osteoporosis. Bone‐forming or dual‐action treatments should be followed by anti‐resorptive treatment to maintain the fracture risk reduction. The BMD gains seen with bone‐forming and dual‐action treatments are greater in treatment‐naïve patients compared to patients pretreated with anti‐resorptive treatments. However, the antifracture efficacy seems to be preserved. Treatment failure will often lead to switch of treatment from orally to parentally administrated anti‐resorptives treatment or from anti‐resorptive to bone‐forming or dual‐action treatment. Osteoporosis is a chronic condition and therefore needs a long‐term management plan with a personalized approach to treatment.

LINKED ARTICLES

This article is part of a themed issue on The molecular pharmacology of bone and cancer‐related bone diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc
Upregulation of ZNF148 in SDHB‐deficient gastrointestinal stromal tumor potentiates Forkhead box M1‐mediated transcription and promotes tumor cell invasion
Authors: Gao Xiaodong , Ma Chunmin , Sun Xiangwei , Zhao Qin , Fang Yong , Jiang Yuhui , Shen Kuntang , Shen Xian
Published: February 2020

Succinate dehydrogenase (SDH) deficiency is associated with gastrointestinal stromal tumor (GIST) oncogenesis, but the underlying molecular mechanism remains to be further investigated. Here, we show that succinate accumulation induced by SDHB loss of function increased the expression of zinc finger protein 148 (ZNF148, also named ZBP‐89) in GIST cells. Meanwhile, ZNF148 is found to be phosphorylated by ERK at Ser306, and this phosphorylation results in ZNF148 binding to Forkhead box M1 (FOXM1). Through the complex formation at the promoter, ZNF148 facilitates Histone H3 acetylation and FOXM1‐mediated Snail transcription, which eventually promotes cell invasion and tumor growth. The clinical analysis indicates that SDHB deficiency is associated with elevated ZNF148 levels, and ZNF148‐S306 phosphorylation level displays a positive correlation with poor prognosis in GIST patients. These findings illustrate an unidentified molecular mechanism underlying FOXM1‐regulated gene transcription related to GIST cell invasion, which highlights the physiological effects of SDHB deficiency on the invasiveness of GIST.
Expression, mutation, and methylation of cereblon‐pathway genes at pre‐ and post‐lenalidomide treatment in multiple myeloma
Authors: Tachita Takuto , Kinoshita Shiori , Ri Masaki , Aoki Sho , Asano Arisa , Kanamori Takashi , Yoshida Takashi , Totani Haruhito , Ito Asahi , Kusumoto Shigeru , Komatsu Hirokazu , Yamagata Kazufumi , Kubo Kohmei , Tohkin Masahiro , Fukuda Shinsaku , Iida Shinsuke
Published: February 2020

Cereblon (CRBN) is a target for immunomodulatory drugs. This study investigated the prognostic value of the expression of CRBN‐pathway genes on the clinical relevance of lenalidomide (Len) treatment and evaluated the levels of CRBN‐binding proteins and mutations in these genes after Len treatment. Forty‐eight primary multiple myeloma cells were collected prior to treatment with Len and dexamethasone (Ld) and 25 paired samples were obtained post‐Ld therapy. These tumor cells were used to determine the expression and mutated forms of the CRBN‐pathway genes. Following normalization with CRBN levels, there was a significantly reduced IKZF1/CRBN ratio in samples that responded poorly to Ld therapy. Moreover, patients with low ratios of IKZF1/CRBN showed a significantly shorter progression‐free survival (PFS) and overall survival (OS) than those with higher ratios. However, patients with high ratios of KPNA2/CRBN showed a significantly shorter PFS and OS than patients with lower ratios. Of the 25 paired samples analyzed, most samples showed a reduction in the expression of CRBN and an increase in IKZF1 gene expression. No mutations were observed in CRBN, IKZF1, or CUL4A genes in the post‐Ld samples. In conclusion, a decreased expression of IKZF1 and increased expression of KPNA2 compared to that of CRBN mRNA predicts poor outcomes of Ld therapy.
Novel Abs targeting the N‐terminus of fibroblast growth factor 19 inhibit hepatocellular carcinoma growth without bile‐acid‐related side‐effects
Authors: Liu Huisi , Zheng Sanduo , Hou Xinfeng , Liu Ximing , Du Kaixin , Lv Xueyuan , Li Yulu , Yang Fang , Li Wenhui , Sui Jianhua
Published: February 2020

Hepatocellular carcinoma (HCC) is a common and particularly fatal form of cancer for which very few drugs are effective. The fibroblast growth factor 19 (FGF19) has been viewed as a driver of HCC development and a potential Ab target for developing novel HCC therapy. However, a previously developed anti‐FGF19 Ab disrupted FGF19’s normal regulatory function and caused severe bile‐acid‐related side‐effects despite of having potent antitumor effects in preclinical models. Here, we developed novel human Abs (G1A8 and HS29) that specifically target the N‐terminus of FGF19. Both Abs inhibited FGF19‐induced HCC cell proliferation in vitro and significantly suppressed HCC tumor growth in mouse models. Importantly, no bile‐acid‐related side effects were observed in preclinical cynomolgus monkeys. Fundamentally, our study demonstrates that it is possible to target FGF19 for anti‐HCC therapies without adversely affecting its normal bile acid regulatory function, and highlights the exciting promise of G1A8 or HS29 as potential therapy for HCC.
Inhibition of human CYP1 enzymes by a classical inhibitor α‐naphthoflavone and a novel inhibitor N‐(3, 5‐dichlorophenyl)cyclopropanecarboxamide: An in vitro and in silico study
Authors: Juvonen Risto Olavi , Jokinen Elmeri Matias , Javaid Adeel , Lehtonen Marko , Raunio Hannu , Pentikäinen Olli Taneli
Published: February 2020

Enzymes in the cytochrome P450 family 1 (CYP1) catalyze metabolic activation of procarcinogens and deactivation of certain anticancer drugs. Inhibition of these enzymes is a potential approach for cancer chemoprevention and treatment of CYP1‐mediated drug resistance. We characterized inhibition of human CYP1A1, CYP1A2, and CYP1B1 enzymes by the novel inhibitor N‐(3,5‐dichlorophenyl)cyclopropanecarboxamide (DCPCC) and α‐naphthoflavone (ANF). Depending on substrate, IC50 values of DCPCC for CYP1A1 or CYP1B1 were 10–95 times higher than for CYP1A2. IC50 of DCPCC for CYP1A2 was 100‐fold lower than for enzymes in CYP2 and CYP3 families. DCPCC IC50 values were 10–680 times higher than the ones of ANF. DCPCC was a mixed‐type inhibitor of CYP1A2. ANF was a competitive tight‐binding inhibitor of CYP1A1, CYP1A2, and CYP1B1. CYP1A1 oxidized DCPCC more rapidly than CYP1A2 or CYP1B1 to the same metabolite. Molecular dynamics simulations and binding free energy calculations explained the differences of binding of DCPCC and ANF to the active sites of all three CYP1 enzymes. We conclude that DCPCC is a more selective inhibitor for CYP1A2 than ANF. DCPCC is a candidate structure to modulate CYP1A2‐mediated metabolism of procarcinogens and anticancer drugs.
Functional analysis of SEMA3A variants identified in Chinese patients with isolated hypogonadotropic hypogonadism
Authors: Dai Wenting , Li Jia‐Da , Zhao Yaguang , Wu Jiayu , Jiang Fang , Chen Dan‐Na , Zheng Ruizhi , Men Meichao
Published: February 2020

Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder characterized by impaired sexual development and infertility, caused by the deficiency of hypothalamic gonadotropin‐releasing hormone neurons. IHH is named Kallmann's syndrome (KS) or normosmic IHH (nIHH) when associated with a defective or normal sense of smell. Variants in SEMA3A have been recently identified in patients with KS. In this study, we screened SEMA3A variants in a cohort of Chinese patients with IHH by whole exome sequencing. Three novel heterozygous SEMA3A variants (R197Q, R617Q and V458I) were identified in two nIHH and one KS patients, respectively. Functional studies indicated that R197Q and R617Q variants were ineffective in activating the phosphorylation of FAK (focal adhesion kinase) in GN11 cells, despite normal production and secretion in HEK293T cells. The V458I SEMA3A had defect in secretion as it was not detected in the conditioned medium from HEK293T cells. Compared with wild type SEMA3A protein, all three SEMA3A mutant proteins were ineffective in inducing the migration of GN11 cells. Our study further showed the contribution of SEMA3A loss‐of‐function variants to the pathogenesis of IHH.
Orthographic consistency influences morphological processing in reading aloud: Evidence from a cross‐linguistic study
Authors: Mousikou Petroula , Beyersmann Elisabeth , Ktori Maria , Javourey‐Drevet Ludivine , Crepaldi Davide , Ziegler Johannes C. , Grainger Jonathan , Schroeder Sascha
Published: February 2020

The present study investigated whether morphological processing in reading is influenced by the orthographic consistency of a language or its morphological complexity. Developing readers in Grade 3 and skilled adult readers participated in a reading aloud task in four alphabetic orthographies (English, French, German, Italian), which differ in terms of both orthographic consistency and morphological complexity. English is the least consistent, in terms of its spelling‐to‐sound relationships, as well as the most morphologically sparse, compared to the other three. Two opposing hypotheses were formulated. If orthographic consistency modulated the use of morphology in reading, readers of English should show more robust morphological processing than readers of the other three languages, because morphological units increase the reliability of spelling‐to‐sound mappings in the English language. In contrast, if the use of morphology in reading depended on the morphological complexity of a language, readers of French, German, and Italian should process morphological units in printed letter strings more efficiently than readers of English. Both developing and skilled readers of English showed greater morphological processing than readers of the other three languages. These results support the idea that the orthographic consistency of a language, rather than its morphological complexity, influences the extent to which morphology is used during reading. We explain our findings within the remit of extant theories of reading acquisition and outline their theoretical and educational implications.
The combination of insulin resistance and visceral adipose tissue estimation improves the performance of metabolic syndrome as a predictor of type 2 diabetes
Authors: Antonio‐Villa N. E. , Bello‐Chavolla O. Y , Vargas‐Vázquez A. , Mehta R. , Aguilar‐Salinas C. A. ,   for the Metabolic Syndrome Study Group
Published: February 2020

Aims

To assess the performance of metabolic syndrome as a predictor of type 2 diabetes in a model that also includes both a measure of insulin resistance and a metabolic score for visceral fat, and to propose a novel metabolic syndrome definition.

Methods

In a prospective Metabolic Syndrome Cohort (n=6143), we evaluated improvements in type 2 diabetes risk prediction using International Diabetes Federation‐defined and Adult Treatment Panel III‐defined metabolic syndrome, after inclusion in the model of updated homeostatic model assessment of insulin resistance and a metabolic score for visceral fat. We also developed a modified metabolic syndrome construct, 'MS‐METS', which used the metabolic score for visceral fat instead of waist circumference to evaluate improved predictive performance for risk of developing type 2 diabetes.

Results

Participants who had metabolic syndrome as defined by both the Adult Treatment Panel III and the International Diabetes Federation criteria had a higher risk of type 2 diabetes compared to participants who did not meet these criteria. Addition of updated homeostatic model assessment of insulin resistance and metabolic score for visceral fat to both metabolic syndrome definitions increased predictive performance for type 2 diabetes risk. Homeostatic model assessment of insulin resistance was the only additional predictor of type 2 diabetes in participants without metabolic syndrome. Conversely, in participants with metabolic syndrome, the use of the metabolic score for visceral fat was the stronger added predictor for type 2 diabetes. When evaluating participants using the MS‐METS definition we observed the largest improvement in predictive ability for type 2 diabetes risk and a significant reduction in risk overestimation compared to evaluation using metabolic syndrome defined according to the International Diabetes Federation and Adult Treatment Panel III criteria alone.

Conclusion

Inclusion of updated homeostatic model assessment of insulin resistance and metabolic score for visceral fat increases performance of metabolic syndrome in prediction of type 2 diabetes. Assessment of insulin resistance could be more useful than conventional metabolic syndrome and assessment of visceral adipose tissue could be more useful in people with metabolic syndrome. Metabolic syndrome as defined using our modified MS‐METS construct improved the accuracy of type 2 diabetes prediction.
Validating generality of recently developed critical plane model for fatigue life assessments using multiaxial test database on seventeen different materials
Authors: Arora Punit , Gupta Suneel K. , Samal Mahendra K. , Chattopadhyay Jayanta
Published: February 2020

The present studies are aimed at validation of a newly developed critical plane model with respect to large variety of engineering materials used for different applications. This newly developed model has been recently reported by present authors. To strengthen general applicability of this model, multiaxial test database consisting of a wide variety of multiaxial loading paths have been considered. The strain paths include pure axial, pure torsion, in‐phase axial‐torsion, out‐of‐phase axial‐torsion with phase shift angles varying from 30° to 180° having sine/trapezoidal/triangular strain waveforms, with/without mean axial/shear strains and asynchronous axial‐torsion strain paths of different frequency ratios etc.

The materials covered in present study are mainly categorized as ferrous and nonferrous alloys. In ferrous alloy category, material grades from plain carbon steel (mild steel, 16MnR, SA333 Gr. 6, E235 and E355), low‐alloy steel (1Cr‐Mo‐V and S460 N) and austenitic stainless steel (SS304, SS316L and SS347) have been considered. In nonferrous alloy category, aluminium alloys (2024T3‐Al, 7075T651‐Al, and PA38‐T6‐Al), titanium (pure titanium and TC4 alloy), cobalt base super‐alloy (Haynes 188), and nickel alloy (Inconel‐718) have been considered.

The predicted and test fatigue lives are found in good agreement for all these materials and complex multiaxial loading paths.
Asynchronous range shifts drive alpine plant–pollinator interactions and reduce plant fitness
Authors: Richman Sarah K. , Levine Jonathan M. , Stefan Laura , Johnson Christopher A.
Published: February 2020

Climate change is driving species' range shifts, which are in turn disrupting species interactions due to species‐specific differences in their abilities to migrate in response to climate. We evaluated the consequences of asynchronous range shifts in an alpine plant–pollinator community by transplanting replicated alpine meadow turfs downslope along an elevational gradient thereby introducing them to warmer climates and novel plant and pollinator communities. We asked how these novel plant–pollinator interactions affect plant reproduction. We found that pollinator communities differed substantially across the elevation/temperature gradient, suggesting that these plants will likely interact with different pollinator communities with warming climate. Contrary to the expectation that floral visitation would increase monotonically with warmer temperatures at lower elevations, visitation rate to the transplanted communities peaked under intermediate warming at midelevation sites. In contrast, visitation rate generally increased with temperature for the local, lower elevation plant communities surrounding the experimental alpine turfs. For two of three focal plant species in the transplanted high‐elevation community, reproduction declined at warmer sites. For these species, reproduction appears to be dependent on pollinator identity such that reduced reproduction may be attributable to decreased visitation from key pollinator species, such as bumble bees, at warmer sites. Reproduction in the third focal species appears to be primarily driven by overall pollinator visitation rate, regardless of pollinator identity. Taken together, the results suggest climate warming can indirectly affect plant reproduction via changes in plant–pollinator interactions. More broadly, the experiment provides a case study for predicting the outcome of novel species interactions formed under changing climates.
Calculated body muscle mass as a useful screening marker for low skeletal muscle mass and sarcopenia in chronic liver disease
Authors: Ichikawa Tatsuki , Miyaaki Hisamitsu , Miuma Satoshi , Motoyoshi Yasuhide , Yamashima Mio , Yamamichi Shinobu , Koike Makiko , Honda Tetsurou , Yajima Hiroyuki , Uehara Ryouhei , Miyazaki Osamu , Hino Naoyuki , Hirata Ryousuke , Taura Naota , Nakao Kazuhiko
Published: February 2020

Aim

Sarcopenia is a harmful condition in patients with chronic liver disease. However, the evaluation of body muscle mass requires expensive instrumentation. The sarcopenia index (SI): (creatinine / cystatin C × 100) has been reported to correlate with muscle volume. A calculated body muscle mass (CBMM) using creatinine, cystatin C, and bodyweight also correlates with muscle mass. We evaluated the applicability of using SIs and CBMMs as screening methods for sarcopenia.

Methods

Patients (n = 303) with liver damage were evaluated for creatinine, cystatin C, and grip strength (GS). All patients were evaluated using cross‐sectional computed tomography images of the third lumbar vertebrae to determine their skeletal muscle (SM) mass. CBMMs and SIs were compared with SMs, GSs, and sarcopenia.

Results

Correlation coefficients (R) between SMI (SM / height2 [m2]) and CBMM, and between GS and CBMM were 0.643 and 0.723, respectively. Factors contributing to low GSs; low SM indices; and sarcopenia were age and SM; sex, age, GS, SI, and CBMM indices; and sex, bodyweight, and CBMM, respectively, in the multivariate logistic analyses. Receiver operating characteristic curve analysis between sarcopenia and CBMM showed an area under the receiver operating characteristic curve of 0.78504 in women and 0.86067 in men. Cut‐off CBMM values for sarcopenia were 27.903 (sensitivity 0.73958) in women and 39.731 (sensitivity 0.7941) in men.

Conclusions

CBMMs and SIs are simple and minimally invasive screening methods in which low levels are indicative of sarcopenia in patients with liver disease.
Molecular characterisation of metanephric adenomas beyond BRAF: genetic evidence for potential malignant evolution
Authors: Chan Emily , Stohr Bradley A , Croom Nicole A , Cho Soo‐Jin , Garg Karuna , Troxell Megan L , Higgins John P , Bean Gregory R
Published: February 2020

Aims

Metanephric adenomas (MAs) are conventionally regarded as rare renal tumours with indolent behaviour; limited case reports have described MAs with aggressive features. Conventional MAs harbour hotspot BRAF V600E mutations. A BRAF V600E senescence pathway, mediated by cyclin‐dependent kinase inhibitor 2A (CDKN2A)/p16, has been proposed to confer MA benignity. Aside from BRAF, the molecular landscape in both conventional MAs and those with aggressive features has not been fully characterised. The aim of this study was to molecularly profile a series of MAs to investigate the correlation between genomic findings and clinical outcome.

Methods and results

We retrospectively examined the histomorphology and patient outcomes of 11 conventional MAs and one MA with aggressive features. Each was subjected to capture‐based next‐generation DNA sequencing of 479 cancer‐related genes and immunohistochemical profiling. All tumours were positive for WT1 immunostaining and BRAF V600E mutation. One conventional MA contained an additional somatic BRCA2 pathogenic mutation. The MA with aggressive features had a biphasic appearance: one component was epithelial, with areas morphologically consistent with conventional MA; the second component was sarcomatous, with areas of solid and angiosarcomatous growth. Differential profiling of the two populations revealed identical BRAF, EIF1AX and TERT promoter hotspot mutations in the epithelial and sarcomatous components. Deep deletion of CDKN2A and MYC amplification were identified only in the sarcomatous component.

Conclusions

Although the vast majority of MAs show indolent behaviour, rare pathogenic alterations can occur in conventional MAs in addition to BRAF. Molecular profiling of a case with aggressive clinical and pathological features shows genetic evidence for malignant evolution in MAs.
The relationship between trainers’ media‐didactical competence and media‐didactical self‐efficacy, attitudes and use of digital media in training
Authors: Bonnes Caroline , Leiser Carmen , Schmidt‐Hertha Bernhard , Rott Karin Julia , Hochholdinger Sabine
Published: February 2020

The ongoing digitalization in the training sector produces new demands on the media‐didactical competence of trainers. We conducted an online survey of 279 trainers in Germany to investigate the relationships among media‐didactical competence, media‐didactical self‐efficacy, attitudes toward the use of digital media and the actual use of digital media in training. Furthermore, we compared trainers who attended a course on digital media with trainers who did not attend such a course. The analysis of the theoretically expected correlations between the variables resulted in not all hypotheses being accepted. The analysis of the group differences showed that the trainers who attended a course on digital media had higher media‐didactical competence and media‐didactical self‐efficacy scores and used digital media more often in training. There was no significant difference in negative attitudes. The implications for the promotion of the media‐didactical competence of trainers are discussed.
Histone hyperacetylation mediates enhanced IL‐1β production in LPS/IFN‐γ‐stimulated macrophages
Authors: Dong Zhen , Li Ruoshui , Xu Lei , Xin Kaiyue , Xu Yamei , Shi Haiming , Sun Aijun , Ge Junbo
Published: February 2020

Under the condition of lipopolysaccharide (LPS)/interferon (IFN)‐γ activation, macrophage metabolism is converted from oxidative phosphorylation to glycolysis. In the present work, we analysed whether glycolysis could affect interleukin (IL)‐1β expression through altering histone acetylation levels in mouse bone marrow‐derived macrophages. Immunocytochemistry and Western blot analysis are used to characterize histone acetylation in macrophages stimulated by LPS/IFN‐γ. Real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay were used to determine IL‐1β production. The metabolism of macrophages was monitored in real‐time by the Seahorse test. Our results showed that glycolytic metabolism could enhance histone acetylation and promote IL‐1β production in LPS/IFN‐γ‐activated macrophages. Moreover, increased production of IL‐1β by glycolysis was mediated through enhanced H3K9 acetylation. Importantly, it was found that a high dose of histone deacetylase inhibitor could also significantly increase the expression of IL‐1β in the absence of glycolytic metabolism. In conclusion, this study demonstrates that glycolytic metabolism could regulate IL‐1β expression by increasing histone acetylation levels in LPS/IFN‐γ‐stimulated macrophages.
‘Why didn't you just give them PRN?’: A qualitative study investigating the factors influencing implementation of sensory modulation approaches in inpatient mental health units
Authors: Wright Lisa , Bennett Sally , Meredith Pamela
Published: February 2020

Clinical guidelines and policies worldwide call for sensory modulation approaches to be incorporated into inpatient mental health care to assist in eliminating the use of restrictive practices. Although increasing evidence shows that these approaches reduce patient distress and the need for seclusion and restraint, sensory modulation approaches have been challenging to implement in many psychiatric units. Implementation strategies can effectively support inclusion of new approaches by addressing potential barriers to change and supporting likely enabling factors. This study aimed to gain a better understanding of the barriers and enablers influencing implementation of sensory modulation approaches in psychiatric inpatient units in one health region in Australia. A qualitative descriptive study design was used, with three focus groups and a total of 15 participants from nursing and allied health disciplines answering questions about the use of sensory modulation approaches. Framework analysis using the Theoretical Domains Framework and thematic analysis was used to analyse data. Overall, participants were positive about the use of sensory modulation approaches, particularly for reducing distress. Four domains (Social Influences; Belief about Consequences; Professional Role and Identify; and Environmental Context and Resources) were identified as the most salient. The key influencing factors were support from peers; beliefs about risks; belief it was part of their role; and availability of resources and materials. Numerous challenges and opportunities related to implementing sensory modulation approaches in mental health inpatient units, identified in this study, provide insights to support effective implementation of these approaches, underpinning more person‐centred, trauma‐informed, and recovery‐orientated care.
An evaluation of a psychoeducation programme for emotion identification and expression in individuals diagnosed with schizophrenia
Authors: Aşık Elif , Ünsal Gül
Published: February 2020

The inability of individuals diagnosed with schizophrenia to recognize facial expressions is an important issue that has an impact on social functioning. This study was conducted to determine the effects of a psychoeducation programme for emotion identification and expression in those diagnosed with schizophrenia on their ability to identify and discriminate between emotions and social functionality. This quasi‐experimental study (pretest–post‐test, with control group) comprised an intervention (21) and a control (21) group conducted with individuals diagnosed with schizophrenia. A 10‐week psychoeducation programme was offered to the intervention group. Measuring instruments were administered to the groups before the intervention, after the intervention, and 3 months after that. The measuring instruments consisted of a personal information form, the Facial Emotion Identification Test, Facial Emotion Discrimination Test, and Personal and Social Performance Scale. The data were analysed using the ‘two‐way repeated measures analysis of variance’. The TREND method was used for reporting. In the first measurements taken after the psychoeducation programme, a significant difference was found between the two groups in terms of their ‘Facial Emotion Identification Test’ and ‘Personal and Social Performance Scale’ mean scores. In the measurements taken 3 months after the psychoeducation programme, this difference had disappeared. The psychoeducation programme is an effective programme that makes recognition of facially expressed emotions possible and increases the social functioning of patients.
Influenza Classification Suite: An automated Galaxy workflow for rapid influenza sequence analysis
Authors: Eisler Diane , Fornika Dan , Tindale Lauren C. , Chan Tracy , Sabaiduc Suzana , Hickman Rebecca , Chambers Catharine , Krajden Mel , Skowronski Danuta M. , Jassem Agatha , Hsiao William
Published: February 2020

Influenza viruses continually evolve to evade population immunity, and the different lineages are assigned into clades based on shared mutations. We have developed a publicly available computational workflow, the Influenza Classification Suite, for rapid clade mapping of sequenced influenza viruses. This suite provides a user‐friendly workflow implemented in Galaxy to automate clade calling and antigenic site extraction. Workflow input includes clade definition and amino acid index array files, which can be customized to identify any clades of interest. The Influenza Classification Suite provides rapid, high‐resolution understanding of circulating influenza strain evolution to inform influenza vaccine effectiveness and the need for potential vaccine reformulation.
Deep sternal wound infection following cardiac surgery: A comparison of the monolateral with the bilateral pectoralis major flaps
Authors: Lo Torto Federico , Turriziani Gianmarco , Donato Casella , Marcasciano Marco , Redi Ugo , Greco Manfredi , Miraldi Fabio , Ribuffo Diego
Published: February 2020

Deep sternal wound infections are a serious complication following sternotomy for cardiothoracic surgery. “Conventional” treatment provides debridement and secondary closure or closed catheter irrigation. The combination of the Negative Pressure Therapy with flap coverages is an accepted technique and one or both Pectoralis Major muscles could be chosen. A multistep protocol was adopted. One hundred and sixty seven patients were treated with the combination of Negative Pressure Therapy with the Pectoralis Major muscle flap: 86 monolateral flap and 81 bilateral flap reconstruction. The main complications (hematoma, seroma, dehiscence, and re‐infection), the need for re‐intervention, mortality rates, Intensive Care Unit, and hospitalisation time were assessed. The mono‐pectoralis group had fewer complications and need for revision, with a shorter hospital stay. A statistically significant difference emerged for the hematoma rate (P = .0079). Monolateral flap should to be preferred because with the same coverage effectiveness, it guarantees the saving of controlateral muscle with its functionality and the possibility of its use in case of failure. Furthermore, as the technique is less invasive, it can be reserved for more fragile patients.
Simulating functional diversity of European natural forests along climatic gradients
Authors: Thonicke Kirsten , Billing Maik , von Bloh Werner , Sakschewski Boris , Niinemets Ülo , Peñuelas Josep , Cornelissen J. Hans C. , Onoda Yusuke , van Bodegom Peter , Schaepman Michael E. , Schneider Fabian D. , Walz Ariane
Published: February 2020

Aim

We analyse how functional diversity (FD) varies across European natural forests to understand the effects of environmental and competitive filtering on plant trait distribution.

Location

Forest ecosystems in Europe from 11°W to 36°E and 29.5°N to 62°N.

Taxon

Pinaceae, Fagaceae and Betulaceae, Oleaceae, Tiliaceae, Aceraceae, Leguminosae (unspecific).

Methods

We adopted the existing Dynamic Global Vegetation Model Lund‐Potsdam‐Jena managed Land of flexible individual traits (LPJmL‐FIT) for Europe by eliminating both bioclimatic limits of plant functional types (PFTs) and replacing prescribed values of functional traits for PFTs with emergent values under influence of environmental filtering and competition. We quantified functional richness (FR), functional divergence (FDv) and functional evenness (FE) in representative selected sites and at Pan‐European scale resulting from simulated functional and structural trait combinations of individual trees. While FR quantifies the amount of occupied trait space, FDv and FE describe the distribution and abundance of trait combinations, respectively, in a multidimensional trait space.

Results

Lund‐Potsdam‐Jena managed Land of flexible individual traits reproduces spatial PFTs and local trait distributions and agrees well with observed productivity, biomass and tree height of European natural forests. The observed site‐specific trait distributions and spatial gradients of traits of the leaf‐ and stem‐resource economics spectra coincide with environmental filtering and the competition for light and water in environments with strong abiotic stress. Where deciduous and needle‐leaved trees co‐occur, for example, in boreal and mountainous forests, the potential niche space is wide (high FR), and extreme ends in the niche space are occupied (high FDv). We find high FDv in Mediterranean forests where drought increasingly limits tree growth, thus niche differentiation becomes more important. FDv decreases in temperate forests where a cold climate increasingly limits growth efficiency of broad‐leaved summer green trees, thus reducing the importance of competitive exclusion. Highest FE was simulated in wet Atlantic and southern Europe which indicated relatively even niche occupation and thus high resource‐use efficiency.

Main Conclusions

We find FD resulting from both environmental and competitive filtering. Pan‐European FR, FDv and FE demonstrate the influence of climate gradients and intra‐ and inter‐PFT competition. The indices underline a generally high FD of natural forests in Europe. Co‐existence of functionally diverse trees across PFTs emerges from alternative (life‐history) strategies, disturbance and tree demography.
Activation of autophagy inhibits nucleotide‐binding oligomerization domain‐like receptor protein 3 inflammasome activation and attenuates myocardial ischemia‐reperfusion injury in diabetic rats
Authors: Zhang Dengwen , He Yi , Ye Xiaodong , Cai Yin , Xu Jindong , Zhang Liangqing , Li Mingyi , Liu Hao , Wang Sheng , Xia Zhengyuan
Published: February 2020

Aims/Introduction

Diabetic hearts are more vulnerable to ischemia‐reperfusion injury (I/RI). The activation of nucleotide‐binding oligomerization domain‐like receptor protein 3 (NLRP3) inflammasome can mediate the inflammatory process, and hence might contribute to myocardial I/RI. Activation of autophagy can eliminate excess reactive oxygen species and alleviate myocardial I/RI in diabetes. The present study aimed to investigate whether the activation of autophagy can alleviate diabetic myocardial I/RI through inhibition of NLRP3 inflammasome activation.

Materials and Methods

A dose of 65 mg/kg streptozotocin was given by tail vein injection to establish a type 1 diabetes model in the rats. The left anterior descending coronary artery was ligated for 30 min followed by reperfusion for 2 h to establish a myocardial I/RI model. H9C2 cardiomyocytes were exposed to high glucose (33 mmol/L) and subjected to hypoxia–reoxygenation (6 h hypoxia followed by 4 h reoxygenation).

Results

The diabetic rats showed significant inhibition of cardiac autophagy (decreased LC3‐II/I and increased p62) that was concomitant with increased activation of NLRP3 inflammasome (increased NLRP3, apoptosis‐related spots protein cleaved caspase‐1, interleukin‐18, interleukin‐1β) and more severe myocardial I/RI (elevated creatine kinase myocardial band, lactate dehydrogenase and larger infarct size). However, administration of rapamycin, an inhibitor of the autophagy, to activate autophagy resulted in the inhibition of NLRP3 inflammasome, and finally alleviated myocardial I/RI. In vitro, high glucose inhibited autophagy, while activating NLRP3 inflammasome in H9C2 cardiomyocytes and aggravating hypoxia–reoxygenation injury, but rapamycin reversed these adverse effects of high glucose.

Conclusion

Activation of autophagy can suppress the formation of NLRP3 inflammasome, which in turn attenuates myocardial ischemia‐reperfusion injury in diabetic rats.
Apparently contradictory routes in the expansion of two fish species in the Eastern Atlantic
Authors: Bañón Rafael , de Carlos Alejandro , Alonso‐Fernández Alexandre , Ramos Fernando , Baldó Francisco
Published: February 2020

One specimen of the boreal Clupea harengus (Clupeidae) was caught southerly, in the Gulf of Cádiz (southern Spain), whereas a specimen of the subtropical Epinephelus aeneus (Serranidae) was caught northerly, in Galician waters (north‐west of Spain). These catches represent a new southernmost record in the eastern Atlantic for C. harengus and the second northernmost for E. aeneus. The co‐occurrence of warm and cold affinity fishes in temperate latitudes is unusual, but the existence of anomalies in the temperature of the Atlantic waters could be behind these findings.