bluuebunny/crossref_metadata_2025 huggingface dataset:
A 12-month follow-up of a transdiagnostic indicated prevention of internalizing symptoms in school-aged children: the results from the EMOTION study
Authors: Loevaas M. E. S. , Lydersen S. , Sund A. M. , Neumer S-P. , Martinsen K. D. , Holen S. , Patras J. , Adolfsen F. , Rasmussen L-M. P. , Reinfjell T.
Published: April 2020

Background

Anxious and depressive symptoms in youth are highly prevalent, are often comorbid and have a high rate of relapse. Preventive interventions are promising, but follow-up results are lacking. The transdiagnostic EMOTION program is an indicated preventive cognitive behavioral therapy (CBT) intervention targeting children aged 8–12 years.

Methods

The present study investigates the 12 months follow-up effects of the EMOTION intervention in a cluster randomized controlled trial (RCT) with 795 children that included both child self-reports and parental reports.

Results

Mixed model analyses showed a larger decrease of symptoms in the intervention group than in the control group for child self-reported anxious symptoms (The Multidimensional Anxiety Scale for Children (MASC) difference 4.56, CI 1.83 to 7.29, p = .001). Parental reports for both anxious (MASC difference 2.50, CI .26 to 4.74, p = .029) and depressive (The Mood and Feelings Questionnaire-short form (SMFQ) difference 1.55, CI .83 to 2.26, p ≤ .001) symptoms in children also showed a reduction. No statistically significant difference was found for child self-reported depressive symptoms (SMFQ difference .69, CI − .22 to 1.60, p = .139).

Conclusion

The transdiagnostic EMOTION program has shown the potential for long-term reductions in symptoms of both anxiety and depression in school-aged children. However, results regarding depressive symptoms must be considered preliminary as only parental report indicated effect.

Trial registration The regional ethics committee (REC) of Norway approved the study. Registration number: 2013/1909; Project title: Coping Kids: a randomized controlled study of a new indicated preventive intervention for children with symptoms of anxiety and depression. ClinicalTrials.gov Identifier; NCT02340637.
Apolipoprotein-mediated regulation of lipid metabolism induces distinctive effects in different types of breast cancer cells
Authors: Ben Hassen Céline , Gutierrez-Pajares Jorge L. , Guimaraes Cyrille , Guibon Roseline , Pinault Michelle , Fromont Gaëlle , Frank Philippe G.
Published: April 2020

Background

The highest incidence of breast cancer is in the Western world. Several aspects of the Western lifestyle are known risk factors for breast cancer. In particular, previous studies have shown that cholesterol levels can play an important role in the regulation of tumor progression.

Methods

In the present study, we modulated cholesterol metabolism in the human breast cancer cell lines MCF-7 and MDA-MB-231 using a genetic approach. Apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE) were expressed in these cell lines to modulate cholesterol metabolism. The effects of these apolipoproteins on cancer cell properties were examined.

Results

Our results show that both apolipoproteins can regulate cholesterol metabolism and can control the epithelial-to-mesenchymal transition process. However, these effects were different depending on the cell type. We show that expressing apoA-I or apoE stimulates proliferation, migration, and tumor growth of MCF-7 cells. However, apoA-I or apoE reduces proliferation and migration of MDA-MB-231 cells.

Conclusions

These data suggest that modulating sterol metabolism may be most effective at limiting tumor progression in models of triple-negative cancers.
Design and rationale of a randomized control trial testing the effectiveness of combined therapy with STAtin plus FENOfibrate and statin alone in non-diabetic, combined dyslipidemia patients with non-intervened intermediate coronary artery disease - STAFENO study
Authors: Kwon Taek-Geun , Jang Albert Youngwoo , Kim Sang Wook , Hong Young Joon , Bae Jang-Ho , Lee Sung Yun , Kim Sang-Hyun , Han Seung Hwan
Published: April 2020

Background

Despite the chronicled success of low-density lipoprotein cholesterol (LDLc)-lowering statin therapy, substantial residual cardiovascular (CV) disease risk remains a problem worldwide, highlighting the need to for combination therapies targeting non-LDLc factors, such as with fenofibrate.

Methods/design

The STAFENO trial is a prospective, randomized, open-label, multi-center trial to compare the effect of statin plus fenofibrate with statin alone on the reduction and stabilization of plaque in non-diabetic, combined dyslipidemia patients with non-intervened, intermediate coronary artery disease (CAD) using virtual histology-intravascular ultrasound at 12 months. A total of 106 eligible patients are planned to be randomized to receive either a combination therapy (rosuvastatin 10 mg plus fenofibrate 160 mg/day) or monotherapy (rosuvastatin 10 mg/day) for 12 months. The primary endpoint of this study is the percentage change in the necrotic core volume. Secondary endpoints include changes in tissue characteristics and 1-year major CV events, including all-cause mortality, CV mortality, nonfatal myocardial infarction, stroke, and revascularization of the intervened and non-intervened lesions.

Discussion

The STAFENO trial will address whether combination treatment of statin and fenofibrate has an additive beneficial effect compared to statin alone on the reduction and stabilization of plaque and CV events in non-diabetic, combined dyslipidemia patients with non-intervened intermediate CAD.

Trial registration

ClinicalTrials.gov, NCT02232360. Registered 9 February 2014.

https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0004ULE&selectaction=Edit&uid=U00023SZ&ts=2&cx=juppd2
Distribution and pyrethroid resistance status of Aedes aegypti and Aedes albopictus populations and possible phylogenetic reasons for the recent invasion of Aedes aegypti in Nepal
Authors: Kawada Hitoshi , Futami Kyoko , Higa Yukiko , Rai Ganesh , Suzuki Takashi , Rai Shiba Kumar
Published: April 2020

Background

When the first systematic list of mosquitoes in Nepal was reported in 1990, there was no description ofAedes aegypti(L.), whileAedes albopictus(Skuse) has been included in theStegomyiasubgroup since the 1950s. The first record ofAe. aegyptiin Nepal was reported in 2009, suggesting some coincidence between the invasion of this species and the first record of dengue fever in Nepal in 2006.

Results

We performed a field survey of the distribution and insecticide susceptibility ofAe. aegyptiandAe. albopictusin Nepal in 2017 and 2018. Mosquito larvae were collected from used tires located along the streets of Kathmandu, Bharatpur and Pokhara, and a simplified bioassay was used to assess the susceptibility of the larvae to pyrethroid insecticides usingd-allethrin. The presence or absence of point mutations in the voltage-gated sodium channel was also detected by direct sequencing. V1016G was detected at a high frequency and a strong correlation was observed between the frequencies of V1016G and susceptibility indices inAe. aegyptipopulations. F1534C was also detected at a relatively low frequency. InAe. albopictuspopulations, susceptibilities tod-allethrin were high and no point mutations were detected. Analysis of the cytochromecoxidase subunit 1 (cox1) gene was performed for assessing genetic diversity and the existence of two strains were identified inAe. aegyptipopulations. One consisted of 9 globally-distributed haplotypes while the other was derived from an African haplotype.

Conclusions

The high pyrethroid resistance, high V1016G frequency, and relatively low quantity of insecticides used to control dengue vectors in Nepal may have resulted in only weak selection pressure favoring insecticide resistance and could support the hypothesis that this species has recently been introduced from neighboring Asian countries where pyrethroid resistance is relatively widespread.
ATAC-seq normalization method can significantly affect differential accessibility analysis and interpretation
Authors: Reske Jake J. , Wilson Mike R. , Chandler Ronald L.
Published: April 2020

Background

Chromatin dysregulation is associated with developmental disorders and cancer. Numerous methods for measuring genome-wide chromatin accessibility have been developed in the genomic era to interrogate the function of chromatin regulators. A recent technique which has gained widespread use due to speed and low input requirements with native chromatin is the Assay for Transposase-Accessible Chromatin, or ATAC-seq. Biologists have since used this method to compare chromatin accessibility between two cellular conditions. However, approaches for calculating differential accessibility can yield conflicting results, and little emphasis is placed on choice of normalization method during differential ATAC-seq analysis, especially when global chromatin alterations might be expected.

Results

Using an in vivo ATAC-seq data set generated in our recent report, we observed differences in chromatin accessibility patterns depending on the data normalization method used to calculate differential accessibility. This observation was further verified on published ATAC-seq data from yeast. We propose a generalized workflow for differential accessibility analysis using ATAC-seq data. We further show this workflow identifies sites of differential chromatin accessibility that correlate with gene expression and is sensitive to differential analysis using negative controls.

Conclusions

We argue that researchers should systematically compare multiple normalization methods before continuing with differential accessibility analysis. ATAC-seq users should be aware of the interpretations of potential bias within experimental data and the assumptions of the normalization method implemented.
Epigenetic prediction of complex traits and mortality in a cohort of individuals with oropharyngeal cancer
Authors: Langdon Ryan J. , Beynon Rhona A. , Ingarfield Kate , Marioni Riccardo E. , McCartney Daniel L. , Martin Richard M. , Ness Andy R. , Pawlita Michael , Waterboer Tim , Relton Caroline , Thomas Steven J. , Richmond Rebecca C.
Published: April 2020

Background

DNA methylation (DNAm) variation is an established predictor for several traits. In the context of oropharyngeal cancer (OPC), where 5-year survival is ~ 65%, DNA methylation may act as a prognostic biomarker. We examined the accuracy of DNA methylation biomarkers of 4 complex exposure traits (alcohol consumption, body mass index [BMI], educational attainment and smoking status) in predicting all-cause mortality in people with OPC.

Results

DNAm predictors of alcohol consumption, BMI, educational attainment and smoking status were applied to 364 individuals with OPC in the Head and Neck 5000 cohort (HN5000; 19.6% of total OPC cases in the study), followed up for median 3.9 years; inter-quartile range (IQR) 3.3 to 5.2 years (time-to-event—death or censor). The proportion of phenotypic variance explained in each trait was as follows: 16.5% for alcohol consumption, 22.7% for BMI, 0.4% for educational attainment and 51.1% for smoking. We then assessed the relationship between each DNAm predictor and all-cause mortality using Cox proportional-hazard regression analysis. DNAm prediction of smoking was most consistently associated with mortality risk (hazard ratio [HR], 1.38 per standard deviation (SD) increase in smoking DNAm score; 95% confidence interval [CI] 1.04 to 1.83;P0.025, in a model adjusted for demographic, lifestyle, health and biological variables). Finally, we examined the accuracy of each DNAm predictor of mortality. DNAm predictors explained similar levels of variance in mortality to self-reported phenotypes. Receiver operator characteristic (ROC) curves for the DNAm predictors showed a moderate discrimination of alcohol consumption (area under the curve [AUC] 0.63), BMI (AUC 0.61) and smoking (AUC 0.70) when predicting mortality. The DNAm predictor for education showed poor discrimination (AUC 0.57).Ztests comparing AUCs between self-reported phenotype ROC curves and DNAm score ROC curves did not show evidence for difference between the two (alcohol consumptionP0.41, BMIP0.62, educational attainmentP0.49, smokingP0.19).

Conclusions

In the context of a clinical cohort of individuals with OPC, DNAm predictors for smoking, alcohol consumption, educational attainment and BMI exhibit similar predictive values for all-cause mortality compared to self-reported data. These findings may have translational utility in prognostic model development, particularly where phenotypic data are not available.
Vitamin C improves the therapeutic potential of human amniotic epithelial cells in premature ovarian insufficiency disease
Authors: Hou Shunyu , Ding Chenyue , Shen Han , Qian Chunfeng , Zou Qinyan , Lu Jiafeng , Huang Boxian , Tan Jichun , Li Hong
Published: April 2020

Background

Human amniotic epithelial cell (hAEC) transplantation holds great promise in treating premature ovarian insufficiency (POI). However, some deficient biological characteristics of hAECs restrict their application.

Methods

Vitamin C (VC) was added to the culture media of hAECs for 2 weeks. Then, the proliferative ability, migration ability, pluripotency, and self-renewal of VC-treated hAECs (VC-hAECs) were determined. Next, hAECs and VC-hAECs were transplanted into the ovaries of cyclophosphamide (CTX)-induced POI model mice. The ovarian function of POI mice was evaluated after transplantation by counting follicle numbers and measuring the blood levels of AMH, E2, and FSH. The rescue effects of VC-hAECs and hAECs were unveiled by coculturing with CTX-damaged human ovarian granulosa cells (hGCs) and analyzing relative marker expression. Additionally, ovarian marker expression and transplant survival were detected in POI mice after transplantation to verify the beneficial effect of VC-hAECs. The cytokine profiles of VC-hAECs and hAECs were revealed by performing a cytokine array and an ELISA to show their paracrine function.

Results

Our results indicated that VC promoted the proliferation, migration, pluripotency, and self-renewal of hAECs in vitro. The most effective concentration of VC was 50 μg/ml. After transplantation into the POI mouse model, VC-hAECs reversed ovarian function more powerfully than hAECs. Human granulosa cell marker expression in CTX-damaged hGCs was increased after coculture with VC-hAECs compared with hAECs. In the ovaries of the POI mice, ovarian marker expression was greater after VC-hAEC transplantation than after hAEC transplantation. VC-hAECs showed higher transplant survival than hAECs. Furthermore, VC-hAECs secreted more growth factors than hAECs.

Conclusion

Treatment with VC promoted the proliferation, migration, self-renewal, and paracrine functions of hAECs. Additionally, VC elevated the therapeutic potential of hAECs in treating POI.
Runx1t1 promotes the neuronal differentiation in rat hippocampus
Authors: Zou Linqing , Li Haoming , Han Xiao , Qin Jianbing , Song Guoqi
Published: April 2020

Background

Runt-related transcription factor 1 translocated to 1 (Runx1t1) is one of the members of the myeloid translocation gene family. Our previous work showed that Runx1t1 induced the neuronal differentiation of radial glia cells in vitro.

Methods

To better uncover the role of Runx1t1 in hippocampal neurogenesis, in this study, we further explore its localization and function during the hippocampal neurogenesis.

Results

Our results showed that insufficient expression of Runx1t1 reduced the neuronal differentiation, and overexpression of Runx1t1 promoted the neuronal differentiation in vitro. We also found that Runx1t1 localized in neurons but not astrocytes both in vivo and in vitro. Furthermore, we found that Runx1t1 overexpression elevated the number of newborn neurons in the hippocampal dentate gyrus.

Conclusions

Taken together, our results further proved that Runx1t1 could be worked as a regulator in the process of hippocampal neurogenesis.
Bedside prediction of intradialytic hemodynamic instability in critically ill patients: the SOCRATE study
Authors: Bigé Naïke , Lavillegrand Jean-Rémi , Dang Julien , Attias Philippe , Deryckere Stéphanie , Joffre Jérémie , Dubée Vincent , Preda Gabriel , Dumas Guillaume , Hariri Geoffroy , Pichereau Claire , Baudel Jean-Luc , Guidet Bertrand , Maury Eric , Boelle Pierre-Yves , Ait-Oufella Hafid
Published: April 2020

Background

Despite improvements in intermittent hemodialysis management, intradialytic hemodynamic instability (IHI) remains a common issue that could account for increased mortality and delayed renal recovery. However, predictive factors of IHI remain poorly explored. The objective of this study was to evaluate the relationship between baseline macrohemodynamic, tissue hypoperfusion parameters and IHI occurrence.

Methods

Prospective observational study conducted in a 18-bed medical ICU of a tertiary teaching hospital. Cardiovascular SOFA score, index capillary refill time (CRT) and lactate level were measured just before (T0) consecutive intermittent hemodialysis sessions performed for AKI. The occurrence of IHI requiring a therapeutic intervention was recorded.

Results

Two hundred eleven sessions, corresponding to 72 (34%) first sessions and 139 (66%) later sessions, were included. As IHI mostly occurred during first sessions (43% vs 12%, P < 0.0001), following analyses were performed on the 72 first sessions. At T0, cardiovascular SOFA score ≥1 (87% vs 51%, P = 0.0021) was more frequent before IHI sessions, as well as index CRT ≥ 3 s (55% vs 15%, P = 0.0004), and hyperlactatemia > 2 mmol/L (68% vs 29%, P = 0.0018). Moreover, the occurrence of IHI increased with the number of macrohemodynamic and tissue perfusion impaired parameters, named SOCRATE score (cardiovascular SOFA, index CRT and lactATE): 10% (95% CI [3%, 30%]), 33% (95% CI [15%, 58%]), 55% (95% CI [35%, 73%]) and 80% (95% CI [55%, 93%]) for 0, 1, 2 and 3 parameters, respectively (AUC = 0.79 [0.69–0.89], P < 0.0001). These results were confirmed by analyzing the 139 later sessions included in the study.

Conclusions

The SOCRATE score based on 3 easy-to-use bedside parameters correlates with the risk of IHI. By improving risk stratification of IHI, this score could help clinicians to manage intermittent hemodialysis initiation in critically ill AKI patients.
Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study
Authors: Grensemann Jörn , Busse David , König Christina , Roedl Kevin , Jäger Walter , Jarczak Dominik , Iwersen-Bergmann Stefanie , Manthey Carolin , Kluge Stefan , Kloft Charlotte , Fuhrmann Valentin
Published: April 2020

Background

Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Adequate dosing of antimicrobial therapy is of central importance to improve outcome. Liver failure may alter antibiotic drug concentrations via changes of drug distribution and elimination. We studied the pharmacokinetics of meropenem in critically ill patients with ACLF during continuous veno-venous hemodialysis (CVVHD) and compared it to critically ill patients without concomitant liver failure (NLF).

Methods

In this prospective cohort study, patients received meropenem 1 g tid short-term infusion (SI). Meropenem serum samples were analyzed by high-performance liquid chromatography. A population pharmacokinetic analysis was performed followed by Monte Carlo simulations of (A) meropenem 1 g tid SI, (B) 2 g loading plus 1 g prolonged infusion tid (C) 2 g tid SI, and (D) 2 g loading and continuous infusion of 3 g/day on days 1 and 7. Probability of target attainment (PTA) was assessed for 4× the epidemiological cut-off values for Enterobacterales (4 × 0.25 mg/L) and Pseudomonas spp. (4 × 2 mg/L).

Results

Nineteen patients were included in this study. Of these, 8 patients suffered from ACLF. A two-compartment model with linear clearance from the central compartment described meropenem pharmacokinetics. The peripheral volume of distribution (V2) was significantly higher in ACLF compared to NLF (38.6L versus 19.7L, p = .05). PTA for Enterobacterales was achieved in 100% for all dosing regimens. PTA for Pseudomonas spp. in ACLF on day 1/7 was: A: 18%/80%, B: 94%/88%, C: 85%/98% D: 100%/100% and NLF: A: 48%/65%, B: 91%/83%, C: 91%/93%, D: 100%/100%.

Conclusion

ALCF patients receiving CVVHD had a higher V2 and may require a higher loading dose of meropenem. For Pseudomonas, high doses or continuous infusion are required to reach PTA in ACLF patients.
Conditions for prosperity and depression of a stochastic R&D model under regime switching
Authors: Zhang Mengqing , Zhang Qimin
Published: April 2020

The stochastic research and development (R&D) model plays an important role in economic growth theories. To explain the growth performance of the economy under regime switching, we first establish sufficient criteria that ensure economic prosperity, nonprosperity and depression in the R&D model disturbed by white and color noise. Then, we determine the threshold between prosperity and depression. Furthermore, we estimate an upper bound of the growth rates of technological progress and capital accumulation in the prosperity case. The results indicate that color noise sensitively impacts the growth performance of the economy in the R&D model. Finally, numerical simulations are conducted to verify our theoretical work.
Orthorexic tendencies are linked with difficulties with emotion identification and regulation
Authors: Vuillier L. , Robertson S. , Greville-Harris M.
Published: April 2020

Background

Orthorexia nervosa (ON) is characterised by an unhealthy obsession with healthy eating and while it is not recognised as an eating disorder (or any disorder), current research is exploring similarities and differences with such disorders. The literature has shown that individuals with eating disorders have difficulties identifying and describing emotions (known as alexithymia) as well as regulating them. However no research to date has looked at whether people with orthorexic tendencies also suffer from difficulties with emotions. In this paper, we refer to people with orthorexic tendencies but do not assume that their healthy eating is at a pathological level needing clinical attention.

Methods

The current study examined this by asking 196 healthy adults with an interest in healthy eating to complete four questionnaires to measure ON (ORTO-15 – reduced to ORTO-7CS), eating psychopathology (EAT-26), alexithymia (TAS-20) and emotion dysregulation (DERS-16).

Results

We found that difficulties identifying and regulating emotions was associated with symptoms of ON, similar to what is found in other eating disorders. We suggest that ON behaviours may be used as a coping strategy in order to feel in control in these participants who have poor emotion regulation abilities.

Conclusions

Our results show that individuals with ON tendencies may share similar difficulties with emotions compared to other eating disorders. While important, our results are limited by the way we measured ON behaviours and we recommend that further research replicate our findings once a better and more specific tool is developed and validated to screen for ON characteristics more accurately.
Prevalence and heritability of handedness in a Hong Kong Chinese twin and singleton sample
Authors: Zheng Mo , McBride Catherine , Ho Connie Suk-Han , Chan Jonathan Ka-Chun , Choy Kwong Wai , Paracchini Silvia
Published: April 2020

Background

Left-handedness prevalence has been consistently reported at around 10% with heritability estimates at around 25%. Higher left-handedness prevalence has been reported in males and in twins. Lower prevalence has been reported in Asia, but it remains unclear whether this is due to biological or cultural factors. Most studies are based on samples with European ethnicities and using the preferred hand for writing as key assessment. Here, we investigated handedness in a sample of Chinese school children in Hong Kong, including 426 singletons and 205 pairs of twins, using both the Edinburgh Handedness Inventory and Pegboard Task.

Results

Based on a binary definition of writing hand, we found a higher prevalence of left-handedness (8%) than what was previously reported in Asian datasets. We found no evidence of increased left-handedness in twins, but our results were in line with previous findings showing that males have a higher tendency to be left-handed than females. Heritability was similar for both hand preference (21%) and laterality indexes (22%). However, these two handedness measures present only a moderate correlation (.42) and appear to be underpinned by different genetic factors.

Conclusion

In summary, we report new reference data for an ethnic group usually underrepresented in the literature. Our heritability analysis supports the idea that different measures will capture different components of handedness and, as a consequence, datasets assessed with heterogeneous criteria are not easily combined or compared.
Unilateral intranigral administration of β-sitosterol β-D-glucoside triggers pathological α-synuclein spreading and bilateral nigrostriatal dopaminergic neurodegeneration in the rat
Authors: Soto-Rojas Luis O. , Martínez-Dávila Irma A. , Luna-Herrera Claudia , Gutierrez-Castillo María E. , Lopez-Salas Francisco E. , Gatica-Garcia Bismark , Soto-Rodriguez Guadalupe , Bringas Tobon María Elena , Flores Gonzalo , Padilla-Viveros America , Bañuelos Cecilia , Blanco-Alvarez Víctor Manuel , Dávila-Ayala José , Reyes-Corona David , Garcés-Ramírez Linda , Hidalgo-Alegria Oriana , De La Cruz-lópez Fidel , Martinez-Fong Daniel
Published: April 2020

The spreading and accumulation of α-synuclein and dopaminergic neurodegeneration, two hallmarks of Parkinson’s disease (PD), have been faithfully reproduced in rodent brains by chronic, oral administration of β-sitosterol β-D-glucoside (BSSG). We investigated whether a single injection of BSSG (6 μg BSSG/μL DMSO) in the left substantia nigra of Wistar rats causes the same effects. Mock DMSO injections and untreated rats formed control groups. We performed immunostainings against the pathological α-synuclein, the dopaminergic marker tyrosine hydroxylase (TH), the neuroskeleton marker β-III tubulin, the neurotensin receptor type 1 (NTSR1) as non-dopaminergic phenotype marker and Fluro-Jade C (F-J C) label for neurodegeneration. Using β-galactosidase (β-Gal) assay and active caspase-3 immunostaining, we assessed cell death mechanisms. Golgi-Cox staining was used to measure the density and types of dendritic spines of striatal medium spiny neurons. Motor and non-motor alterations were also evaluated. The study period comprised 15 to 120 days after the lesion. In the injured substantia nigra, BSSG caused a progressive α-synuclein aggregation and dopaminergic neurodegeneration caused by senescence and apoptosis. The α-synuclein immunoreactivity was also present within microglia cells. Decreased density of dopaminergic fibers and dendritic spines also occurred in the striatum. Remarkably, all the histopathological changes also appeared on the contralateral nigrostriatal system, and α-synuclein aggregates were present in other brain regions. Motor and non-motor behavioral alterations were progressive. Our data show that the stereotaxic BSSG administration reproduces PD α-synucleinopathy phenotype in the rat. This approach will aid in identifying the spread mechanism of α-synuclein pathology and validate anti-synucleinopathy therapies.
Adoption of pro-environmental behaviors among farmers: application of Value–Belief–Norm theory
Authors: Rezaei-Moghaddam Kurosh , Vatankhah Nasim , Ajili Abdolazim
Published: April 2020

Background

The clean and pro-environmental technologies are one of the crucial instruments to produce healthy food without any chemicals. Recycling the agricultural residues by composting them is a clean and pro-environmental technology. Local rich compost as a clean and pro-environmental technology is the factor which strengthens agricultural soils in terms of organic materials and healthier crops production. The current study aims to analyze farmers’ pro-environmental behaviors concerning the adoption of clean technology of local rich compost in Fars province, the south of Iran, in order to protect soil and produce healthy crops.

Methodology

The statistical society of the study includes the farmers who produce and adopt the technology of local rich compost in this province. The sample included 130 framers from 30 villages of Fars counties. The study was conducted by multi-stage random sampling and the data were gathered through a survey using questionnaires.

Results

Given the results, the most pro-environmental behaviors among the farmers are the environmental activism behavior. Therefore, among the pro-environmental behaviors, they intend to attend extension classes and join the farmers’ groups more. The average of chemical fertilizers consumption decreased significantly after adoption of the local rich compost.

Conclusion

Based on the study model, “perceived behavioral control”, “social and moral norms”, as well as “extension education” had a significant effect on the farmers’ intent to continue to produce the clean and pro-environmental technologies. The current study presents some recommendations for adoption of the clean and pro-environmental technologies.
Antimicrobials administration time in patients with suspected sepsis: is faster better? An analysis by propensity score
Authors: Ascuntar Johana , Mendoza Deibie , Jaimes Fabián
Published: April 2020

Background

Early use of antimicrobials is a critical intervention in the treatment of patients with sepsis. The exact time of initiation is controversial and its early administration may be a difficult task in crowded emergency departments (ED). The aim of this study was to estimate, using a matched propensity score, the effect on hospital mortality of administration of antimicrobials within 1 or 3 hours, in patients admitted to the ED with sepsis.

Methods

This was a secondary analysis of a multicenter prospective cohort. Patients included in the study were older than 18 years, hospitalized between 2014 and 2016 with suspected sepsis, and admitted to ED of three tertiary care university hospitals in Medellín, Colombia. A propensity score analysis for administration of antimicrobials, both within 1 and 3 h of admission by the ED, was fitted with 28 variables related with clinical attention and physiological changes. As a sensitivity analysis, a logistic regression model was fitted for antimicrobial use adjusted both by propensity score and confounding variables.

Results

The study cohort was composed of 2454 patients with a median age of 62 years (IQR = 46–74). Among them, 32% (n = 781) received antibiotics within 3 h and 14% (n = 340) within the first hour. The main diagnoses were urinary tract infection (28%, n = 682) and pneumonia (27%, n = 671). Blood cultures were obtained in 87% (n = 2140) and yielded positive in 29% (n = 629), mainly with Escherichia coli (37%, n = 230), Staphylococcus aureus (21%, n = 132), and Klebsiella pneumoniae (10.2%, n = 64). The hospital mortality rate was 11.5% (n = 283). There were no significant differences in mortality, after adjustment, using antimicrobials either in the first hour (OR 1.03; 95% CI = 0.63; 1.70) or 3 h (OR 0.85; 95% CI = 0.61; 1.20). There were no changes with different models for sensitivity analysis.

Conclusions

Despite the obvious constraints given for sample size and residual confounding, our results suggest that we need a more comprehensive approach to sepsis and its treatment, considering early detection, multiple interventions, and goals beyond the simple time-to-antimicrobials.
Tree diversity effects on forest productivity increase through time because of spatial partitioning
Authors: Tatsumi Shinichi
Published: April 2020

Background

Experimental manipulations of tree diversity have often found overyielding in mixed-species plantations. While most experiments are still in the early stages of stand development, the impacts of tree diversity are expected to accumulate over time. Here, I present findings from a 31-year-old tree diversity experiment (as of 2018) in Japan.

Results

I find that the net diversity effect on stand biomass increased linearly through time. The species mixture achieved 64% greater biomass than the average monoculture biomass 31 years after planting. The complementarity effect was positive and increased exponentially with time. The selection effect was negative and decreased exponentially with time. In the early stages (≤ 3 years), the positive complementarity effect was explained by enhanced growths of early- and mid-successional species in the mixture. Later on (≥ 15 years), it was explained by their increased survival rates owing to vertical spatial partitioning — i.e. alleviation of self-thinning via canopy stratification. The negative selection effect resulted from suppressed growths of late-successional species in the bottom layer.

Conclusions

The experiment provides pioneering evidence that the positive impacts of diversity-driven spatial partitioning on forest biomass can accumulate over multiple decades. The results indicate that forest biomass production and carbon sequestration can be enhanced by multispecies afforestation strategies.
Chitosan hydrogel encapsulated with LL-37 peptide promotes deep tissue injury healing in a mouse model
Authors: Yang Xu , Guo Jing-Lin , Han Jing , Si Rui-Juan , Liu Pan-Pan , Zhang Zi-Rui , Wang Ai-Min , Zhang Ju
Published: April 2020

Background

LL-37 peptide is a member of the human cathelicidin family, and has been shown to promote the healing of pressure ulcers. However, the low stability of this peptide within the wound environment limits its clinical use. Chitosan (CS) hydrogel is commonly used as a base material for wound dressing material.

Methods

CS hydrogel (2.5% w/v) was encapsulated with LL-37. Cytotoxicity of the product was examined in cultured NIH3T3 fibroblasts. Effects on immune response was examined by measuring tumor necrosis factor-α (TNF-α) release from RAW 264.7 macrophages upon exposure to lipopolysaccharides. Antibacterial activity was assessed using Staphylococcus aureus. Potential effect on pressure ulcers was examined using a mouse model. Briefly, adult male C57BL/6 mice were subjected to skin pressure using magnets under a 12/12 h schedule for 21 days. Mice were randomized to receive naked LL-37 (20 μg), chitosan gel containing 20-μg LL-37 (LL-37/CS hydrogel) or hydrogel alone under the ulcer bed (n = 6). A group of mice receiving no intervention was also included as a control.

Results

LL-37/CS hydrogel did not affect NIH3T3 cell viability. At a concentration of 1–5 μg/ml, LL-37/CS inhibited TNF-α release from macrophage. At 5 μg/ml, LL-37/CS inhibited the growth of Staphylococcus aureus. The area of the pressure ulcers was significantly lower in mice receiving LL-37/CS hydrogel in comparison to all other 3 groups on days 11 (84.24% ± 0.25%), 13 (56.22% ± 3.91%) and 15 (48.12% ± 0.28%). Histological examination on days 15 and 21 showed increased epithelial thickness and density of newly-formed capillary with naked LL-37 and more so with LL-37/CS. The expression of key macromolecules in the process of angiogenesis (i.e., hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A)) in wound tissue was increased at both the mRNA and protein levels.

Conclusion

Chitosan hydrogel encapsulated with LL-37 is biocompatible and could promote the healing of pressure ulcers.
Cross cultural adaptation and validation of burn specific health scale- brief in Nepali (BSHS-B-Np)
Authors: Shakya Regan , Manandhar Misu , Dangol Roshan , Shrestha Archana
Published: April 2020

Background

Burns are a global health problem affecting the survivors and disrupting many aspects of their lives. It is the second most common injury in rural Nepal accounting 5% of disabilities. Burn Specific Health Scale (BSHS) is a valid and most commonly used tool to measure Health Related Quality of Life (HRQoL) of the patient with Burns. BSHS- B (Brief) has been translated, culturally adapted and validated in multiple languages but not in Nepali. Therefore we aim to translate, culturally adapt and validate the BSHS-B in Nepali language (BSHS-B-Np).

Methods

Standard guideline was followed to translate the scale into Nepali language. One hundred eleven participants were evaluated to establish the psychometric properties of BSHS-B-Np. Internal consistency, test retest, content validity, discriminant validity and construct validity were assessed using Cronbach’s alpha, Interclass correlation coefficient, Factor analysis, Spearman rank test, and Mann- Whitney U test respectively.

Results

The Cronbach’s alpha for BSHS-B-Np was 0.93. Test retest inter-class correlation coefficient was between 0.92 and 0.98. The principal component factor analysis with varimax rotation resulted in separation of nine factors explaining 75.19% of total variance. BSHS-B-Np showed good discriminant validity in 35 out of 36 domain correlations confirming the construct of the scale. Furthermore, the scale was able to discriminate between face, upper limb and lower limb injury (p < 0.05).

Conclusions

BSHS-B-Np is a reliable and valid scale for Nepali burns survivors to assess their health related quality of life.
Pan bread quality as affected by some nano and fermented-nano food industries by-products
Authors: Yousif El-Sayed I. , Yaseen Attia A. , Abdel-Fatah Abdel-Fatah A. , Shouk Abdel-Hafeez A. , Gadlla Mohamed G. , Mohammad Ayman A.
Published: April 2020

Background

Rapid development of nanotechnology is expected to transform many areas of food technology with increasing investment and market share. Also, phytochemical-rich foods have attracted consumer’s attention due to their ability to promote benefits for human health. So, in this study, the suitability of some food industry by-products [nano-wheat bran (NWB), nano-wheat germ (NWG), fermented nano-rice bran (FNRB), fermented nano-carrot pomace (FNCP), and fermented nano-pomegranate peel (FNPP)] as supplements for pan bread was investigated.

Results

Loaf volume significantly (p≤ 0.05) decreased, while loaf weight increased by increasing the level of all tested materials as compared to control bread. Hardness and chewiness of bread samples increased, while springiness and cohesiveness decreased by increasing the level of replacement of all nano-materials. The control bread had the lowest value of alkaline water retention capacity (AWRC) being 326, 292, 265, and 237%, respectively for 3, 24, 48, and 72 h of storage time at room temperature. At all levels of replacing, noticeable increase of AWRC was detected as well as retarding staling rate of bread during storage.

Conclusion

The sensory evaluation results of bread indicated that functional pan bread with acceptable quality could be prepared from NWB, NWG, and FNRB up to 15% and FNCB and FNPP up to 5% replacement level.
Methane potential and degradation kinetics of fresh and excavated municipal solid waste from a tropical landfill in Colombia
Authors: Sandoval-Cobo John J. , Casallas-Ojeda Miguel R. , Carabalí-Orejuela Lina , Muñoz-Chávez Anyi , Caicedo-Concha Diana M. , Marmolejo-Rebellón Luis F. , Torres-Lozada Patricia
Published: April 2020

The optimization of degradation processes and the management of leachate and biogas produced in landfills are key aspects for the establishment of more sustainable municipal solid waste (MSW) disposal in developing countries. In this study, biochemical methane potential (BMP) tests were used to evaluate CH4 production potential and degradation kinetics of fresh waste (FW) and five-year aged excavated waste (EW) samples from a tropical controlled landfill with compositional characteristics of developing countries. BMP tests with reconstituted samples of the biodegradable fraction of both MSW types were performed at three substrate/inoculum (S/I) ratios (0.3, 0.5 and 1.0 g VS substrate g− 1 VS inoculum), and CH4 generation parameters were determined using the first-order and modified Gompertz kinetic models. After 30-d, the best BMP results were reached at S/I ratios of 0.5 and 1.0, with cumulative CH4 productions of 528 and 433 mL CH4 g− 1 VS for FW, respectively; and 151 and 135 mL CH4 g− 1 VS for EW, respectively. The first-order kinetic model provided a good fit to BMP results for FW, whereas the modified Gompertz model showed a better adjustment to the BMP data for EW. Calculated first-order CH4 generation rates for FW and EW were in the range 0.19–0.36 and 0.23–0.25 d− 1, respectively. These results evidence the high biodegradability and CH4 potential of FW disposed of in a tropical landfill in Colombia and the reduced BMP of EW despite a relatively short period after disposal under conventional landfill operation conditions.
Reliability of MRI in detection and differentiation of acute neonatal/pediatric encephalopathy causes among neonatal/pediatric intensive care unit patients
Authors: Hassan Tamir A. , Mohey Nesreen
Published: April 2020

Background

Causes of encephalopathy in neonates/pediatrics include hypoxic-ischemic injury (which is the most frequent cause and is defined as any impairment to the brain caused by insufficient blood flow and oxygenation), trauma, metabolic disorders, and congenital and infectious diseases. The aim of this study is to evaluate the value of MRI in detection and possible differentiation of different non-traumatic, non-infectious causes of acute neonatal/pediatric encephalopathy among NICU/PICU patients.

Results

This retrospective study included 60 selected patients according to the study inclusion and exclusion criteria; all presented with positive MRI findings for non-traumatic, non-infectious acute brain injury. Females (32, 53.3%) were affected more than males (28, 46.7%) with a mean age of 1.1 ± 1.02 years; all presented with variable neurological symptoms and signs that necessitate neonatal intensive care unit/pediatric intensive care unit (NICU/PICU) admission. The final diagnosis of the study group patients were hypoxic ischemia injury (HII) in 39 patients (65%), metachromatic leukodystrophy in 6 patients (10%), biotin-thiamine-responsive basal ganglia disease (BTBGD) and Leigh disease each in 4 patients (6.7%), periventricular leukomalacia (PVL) in 3 patients (5%), and mitochondrial encephalopathy with lactic acidosis and stroke-like episodes syndrome (MELAS) and non-ketotic hyperglycinemia (NKH) each in 2 patients (3.3%).

Conclusion

Much attention should be paid to pediatric non-traumatic brain injuries. MRI is a safe modality and should be the first radiological investigation if neurological causes are suggested but should be aided by meticulous clinical evaluation and dedicated laboratory investigations for better characterization and differentiation of various causes of non-traumatic, non-infective brain encephalopathy among NICU/PICU patients. When interpreting MRI, it is essential to have thorough relevant clinical data, gestational age at birth which is prognostic of the pattern of hypoxic-ischemic injury, and the time lag between the onset of HII and the time of performing the MR study.
Audit expectation gap: an empirical analysis
Authors: Olojede Paul , Erin Olayinka , Asiriuwa Osariemen , Usman Momoh
Published: April 2020

The financial debacles that occurred in the companies like Enron, WorldCom, and Xerox in the USA, Lehman Brothers, Polly Peck in the UK and African Petroleum Plc., Cadbury Plc., in Nigeria had created public distrust with the auditors. The era when the auditor will say ‘trust me’ and that being accepted is over. Now, they must earn the public trust. This study provides an empirical analysis of the scope and nature of audit expectation gap in Nigeria. We used a descriptive and survey research design to achieve the objective of the study. We also collected data through primary source, using structured questionnaire. The study used Mann–Whitney U test and Kolmogorov–Smirnov Z test for the analysis of data and test of normality of distribution, respectively. The results confirmed that audit expectation gap exists in Nigeria, and the new auditor’s report did not have any serious impact in reducing the gap. From the outcome of this study, the audit expectation gap primarily arose from the unreasonable expectation of the users due to their lack of understanding of the roles of auditors. We recommend the launching of a new business-reporting model geared towards releasing more non-financial information to the public and with clear description of the role of independent audit.
Cutting to the Front of the Line: Immunotherapy for Childhood Acute Lymphoblastic Leukemia
Authors: McNeer Jennifer L. , Rau Rachel E. , Gupta Sumit , Maude Shannon L. , O’Brien Maureen M.
Published: April 2020

Although many children and young adults with B-cell acute lymphoblastic leukemia (B-ALL) are cured with modern, risk-adapted chemotherapy regimens, 10% to 15% of patients will experience relapse or have refractory disease. Recent efforts to further intensify cytotoxic chemotherapy regimens in the frontline setting have failed as a result of excessive toxicity or lack of improvement in efficacy. As a result, novel approaches will be required to achieve cures in more newly diagnosed patients. Multiple immune-based therapies have demonstrated considerable efficacy in the setting of relapsed or refractory (R/R) disease, including CD19 targeting with blinatumomab and tisagenlecleucel and CD22 targeting with inotuzumab ozogamicin. These agents are now under investigation by the Children’s Oncology Group (COG) in clinical trials for newly diagnosed B-ALL, with integration into standard chemotherapy regimens based on clinically and biology-based risk stratification as well as disease response.
Case Report: High-concentration Insulin Glargine Overdose Complicated by Hepatic Steatosis
Authors: Endall Ryan , McCallum Roland , Burgess John
Published: April 2020

The use of high-concentration formulations of insulin is becoming more prevalent in the management of patients with diabetes mellitus. Situations of intentional overdose utilizing these agents pose particular challenges because of the altered pharmacology at large doses and the potential complications arising thereof.

A patient with type 1 diabetes mellitus self-administered 4050 units of high-concentration (300 units/mL) insulin glargine, in addition to coingestants. The patient subsequently required 7 days of high-dose dextrose infusion in order to avoid hypoglycemia, with no further insulin needed during this period. The patient also developed reversible hepatic steatosis secondary to the prolonged use of high-dose dextrose.

Owing to the altered pharmacology of high-concentration insulin glargine when administered at large doses in cases of intentional overdose, patients are likely to require a much longer period of supplemental dextrose support than may otherwise be expected when these agents are used at therapeutic doses. The complication of hepatic injury in the form of steatosis also needs to be considered in these patients, and should prompt the use of adaptive prescriptions of intravenous dextrose where possible.
Romantic Wales and the Imperial Picturesque
Authors: Heimlich Timothy
Published: April 2020

This essay argues that the aesthetic category named the picturesque was first systematized in a Welsh colonial context and that picturesque looking always reflects, to some degree, its initially imperialist function. While the picturesque rapidly acceded to a preeminent place in British travel and landscape writing, its rise was contested by Welsh and working-class writers like the antiquarian poet Richard Llwyd (1752–1835). By conspicuously failing to impose picturesque features on a carefully historicized landscape, Llwyd’s poem Beaumaris Bay (1800) lays bare the picturesque’s antihistorical drive to eradicate local difference. Renewed critical attention to early attempts to establish an antipicturesque aesthetic may uncover important precursors to present-day postcolonial and transnational theory, precursors that can enrich the ongoing global turn in literary history.