bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractEnzymes 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

AbstractIsolated 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

AbstractThe 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

AbstractAimsTo 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.MethodsIn 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.ResultsParticipants 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.ConclusionInclusion 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

AbstractThe 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

AbstractClimate 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.
Adverse Childhood Experiences (ACEs) and Headaches Among Children: A Cross‐Sectional Analysis
Authors: Mansuri Fahad , Nash Michelle Crozier , Bakour Chighaf , Kip Kevin 
Published: February 2020

ObjectivesThis cross‐sectional study examined the association between adverse childhood experiences (ACEs) and history of frequent headaches (including migraine) among children 3‐17 years old using data from the 2016 and 2017 U.S. National Survey of Children’s Health (NSCH).BackgroundACEs include abuse (physical, emotional, or sexual), parental divorce, death, mental illness, or addiction, and are linked to higher morbidity and mortality in adulthood. A relationship between ACEs and headaches exists among adults, but studies examining the relationship among children are lacking. To our knowledge, no studies have examined the link among children using NSCH data.MethodsThe NSCH is a nationally representative survey of U.S. children’s physical and emotional well‐being aimed at understanding their health needs. Parental‐reported information was collected on child history of headaches and 9 ACEs for the selected child. The survey collected information on 71,881 children in 2016 and 2017 out of which 61,565 were eligible for the study (age ≥3 years and not missing data on history headaches). Children with missing values for headache, ACEs, or covariates (n = 58,958) were excluded from the final analysis. We used multivariable logistic regression with survey weighting and adjusted for demographics and comorbidities (anxiety, depression, epilepsy, and brain injury) to examine the association between ACEs and headaches overall and stratified by gender. We further assessed the independent relationship between each ACE and headaches.ResultsIn the current study, out of 61,656 children, 26,884 (48.6%) experienced at least 1 ACE and 3426 (6.5%) experienced 4+ ACEs. Overall, compared with children with no ACEs, the adjusted odds of headache were 1.34 times higher among children with 1 reported ACE (95% CI: 1.07, 1.68), 2.15 times higher among children with 2 ACEs (95% CI: 1.66, 2.80), 1.89 times higher among children with 3 ACEs (95% CI: 1.40, 2.53), and 3.40 times higher among children with 4+ ACEs (95% CI: 2.61, 4.43). Females with 3 and 4+ ACEs were somewhat more likely to report headaches compared to males with the same number of ACEs. Individually, no ACE was independently associated with history of headaches except for difficulty due to family’s income (aOR = 2.46, 95% CI: 1.98, 3.06).ConclusionExperiencing one or more ACEs vs none was associated with higher risk of headaches in children, and difficulty due to family’s income was the only ACE independently associated with headaches. Our findings support results of other studies on ACEs and headache in young adults and suggest that adverse ACE‐related health outcomes begin earlier than previously recognized. Additionally, struggling due to low income may represent a constellation of chronic stressors that independently contribute to poor health outcomes in childhood as compared to other individual ACEs. Future research should examine the importance of specific ACE clusters and stressors during childhood.
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

AimSarcopenia 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.MethodsPatients (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.ResultsCorrelation 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.ConclusionsCBMMs 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

AimsMetanephric 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 resultsWe 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.ConclusionsAlthough 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.
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

SummaryUnder 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

AbstractClinical 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

AbstractThe 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.