bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular and behavioral responses to novelty stress after single or dual orexin receptor blockade in the rat
Authors: Carrive Pascal , Bieg Irfan 
Published: June 2021

Orexins play a critical role in the regulation of arousal by acting on two receptors, OX1 and OX2. We have previously reported that blockade of OX1 and OX2 with the dual receptor antagonist Almorexant reduces the cardiovascular and behavioral responses to novelty stress. The aim of the study was to compare Almorexant to two new selective OX1 and OX2 antagonists. Rats implanted with telemetric probes were given i.p. injections of either Almorexant, ACT‐335827 (OX1 antagonist, Actelion Pharmaceuticals), or EMPA (OX2 antagonist, Roche) and after 2.5 hours were subjected to novelty stress for 30 min. In vehicle‐injected rats, Novelty increased locomotor activity, blood pressure and heart rate. At 30 mg/kg, Almorexant (n=12) significantly reduced the locomotor and cardiac responses, but neither ACT‐335827 (n=12) nor EMPA (n=8) nor a cocktail of ACT‐335827 and EMPA (n=8) had any significant effect. At 100 mg/kg, Almorexant (n=10) significantly reduced all three responses, ACT‐335827 (n=9), the pressor and cardiac but not locomotor response, EMPA (n=10) the cardiac response only and the cocktail of ACT‐335827 and EMPA (n=11) all three responses at the same magnitude as Almorexant. Thus, systemic blockade of one orexin receptor alone is not sufficient to produce the same effect as blockade of both receptors, at least for novelty stress. The two receptors may act synergistically.Supported by NHMRC‐Australia
The Efficacy of the Mediterranean Diet on Obesity Outcomes: A Meta‐Analysis
Authors: Garcia Marissa , Shook Julia , Kerstetter Jane , Kenny Anne , Bihuniak Jessica , Huedo‐Medina Tania 
Published: June 2021

ObjectiveThe impact of a Mediterranean Diet (MD) on obesity is inconclusive. Therefore, the current study was designed to assess the efficacy of this intervention in reducing obesity outcomes and identify moderators of intervention efficacy.MethodsWe reviewed 16 out of 83 articles published between 1994 and 2014 that met the inclusion criteria, including pre‐ and post‐measurements of weight, waist circumference (WC), or Body Mass Index (BMI), use of the Mediterranean Diet as a dietary intervention and sufficient statistical information to calculate effect sizes. Effect size (d+) was calculated as the standardized mean difference of pre‐ and post‐dietary intervention adjusting for small sample size. All data were analyzed using random‐effects assumptions.ResultsAnalysis of 16 reports shows that out of the 2,852 participants, 67.6% were female with an average mean age of 44.5 years (SD=9.8). A majority (75%) of the studies analyzed were conducted in Europe. There were significant decreases in weight, BMI, and WC from baseline to follow‐up with the use of the Mediterranean Diet as the intervention (d+= ‐0.53, 95% CI from ‐0.79 to ‐0.25; d+= ‐0.49, 95% CI from ‐0.75 to ‐0.24; d+= ‐0.43, 95% CI from ‐0.75 to ‐0.09, respectively). Length of the intervention explained more than 50% of the variability of the effect sizes; the longer the intervention, the greater the reduction in obesity outcomes by 0.01 standard deviation of the effect per week.ConclusionsIn addition to the well‐known antiatherogenic effects of the MD, this diet appears to be effective in reducing obesity outcomes with increased effects when followed for longer periods of time.
Maternal Multiple Micronutrient Supplementation and Children's Cognition at Age 9‐12 Years in Indonesia
Authors: Prado E , Sebayang S , Apriatni M , Hidayati N , Adawiyah S , Islamiyah A , Siddiq S , Harefa B , Alcock K , Ullman M , Muadz H , Shankar A 
Published: June 2021

Many micronutrients, including zinc, iodine, and B‐vitamins, are needed for the rapid brain development that occurs during gestation and infancy, laying a foundation for lifelong brain function. Few studies have examined the long‐term cognitive effects of maternal multiple micronutrient (MMN) supplements, compared to the current practice in many countries of iron and folic acid (IFA) supplementation. In 2001‐2004, in the SUMMIT trial, midwives in Indonesia were randomly assigned to distribute daily IFA or MMN from pregnancy through three months postpartum. We tested 3687 children of SUMMIT participants at 9‐12 years of age. Adjusting for midwife cluster, data collector, child age and gender, and home environment, children of mothers given MMN scored higher in visual attention (B=0.11, p < .01) and arithmetic (B=0.10, p=.05) compared to IFA. We observed positive effects on verbal ability (B=0.17, p=.02) in children of mothers who were undernourished at enrollment and on sustained attention (B=0.10, p=.04) and letter/word recognition (B=0.23, p=.04) in children of mothers who were anemic, consistent with previously observed effects on pre‐school cognition in these groups. We found positive effects on speed of sentence reading in children of well‐nourished mothers (B=0.11, p = .04), consistent with effects on birth weight in this group. No effects were found on fine motor ability, socio‐emotional scores, or several measures of executive function.Funded by Grand Challenges Canada
Suppressive Effects of Novel Oridonin Derivative CYD0625 on Activated Hepatic Stellate Cells
Authors: Wang Xiaofu , Bohanon Fredrick , Kandathiparampil Arlene , Rastellini Cristiana , Ding Chunyong , Ding Ye , Zhou Jia , Radhakrishnan Ravi 
Published: June 2021

The natural compound oridonin has been proven to possess anti‐neoplastic and anti‐inflammatory properties. Previously, we described that oridonin caused apoptosis, inhibition of cell proliferation and down‐regulation of extracellular matrix proteins (ECM) in activated hepatic stellate cells (HSC). In this study, we investigated the potentially more potent derivative CYD0625 in vitro.MethodsCell proliferation was measured by Alamar Blue assay. Cell apoptosis was detected by staining with Yo‐Pro‐1 and propidium iodide. Immunoblot and immunofluorescence staining were performed for cellular protein expression.ResultsTreatment of CYD0625 significantly inhibited LX‐2 cells proliferation in a dose‐ and time‐dependent manner with ~20–fold greater potency than oridonin. Similar results were observed in HSC‐T6 cells, whereas 1 μM of CYD0625 treatment had no effect on the human hepatocyte cell line C3A. CYD0625 induced LX‐2 cells apoptosis and S‐phase cell cycle arrest, and it was associated with activation of cell cycle inhibitory proteins p21, p16. The myofibroblast marker protein α‐smooth muscle actin and major ECM proteins collagen type I and fibronectin were markedly down‐regulated by CYD0625. Interestingly, treatment of HSC with CYD0625 at a low dosage (0.1 μM), significantly suppressed collagen type I expression in LX‐2 cells. Furthermore, pre‐treatment with CYD0625 blocked PDGF‐BB‐induced collagen type I and fibronectin expression in LX‐2 cells.
imageConclusionIn comparison with oridonin, its novel derivative CYD0625 could be a more potent and safer hepatic anti‐fibrosis agent.
Impacts of Granulocyte‐Colony Stimulating Factor combined with Erythropoietin on neural regeneration after traumatic brain injury in rats
Authors: Duan Hubin , Hao Chunyan , Lu Gui , Li Shuzhen , Wang Suping , Liu Yueting 
Published: June 2021

ObjectiveTo investigate the effect of G‐CSF and EPO combination therapy on functional recovery and nerve cell regeneration after traumatic brain injury in ratsMethods100 male rats were divided into Sham group, TBI group, EPO treatment group(E group ), G‐CSF treatment group(G group), and EPO combined G‐CSF group(E+G group), Neurological function was assessed using a modified neurological severity score(mNSS) before rats were sacrificed. Immunofluorescence measurement was used to detect newly proliferation cells number and its direction of differentiation by BrdU single positive cells and BrdU/NeuN or BrdU/GFAP double positive cells.ResultsThe mNSS scores of each treatment group was lower than TBI group.The BrdU positive cells in E+G group was significantly higher than other groups. Compared the groups of brain tissue BrdU/NeuN and BrdU/GFAP double positive cells number, E+G group were higher than other groups , E group and G group were higher than Sham group and TBI group.ConclusionCombined use of EPO and G‐CSF can obviously improve functional recovery and promote the brain nerve cell regeneration differentiating to neurons and astrocytes in the injury boundary zone.
Fast Food, Fat and Sugar Sweetened Beverage Items are Related to Children's Dietary Energy Density
Authors: Shilts Mical , Styne Dennis , Drake Christiana , Aden Christopher , Townsend Marilyn 
Published: June 2021

To reduce risk of pediatric obesity, valid assessment tools are needed. This study tested the validity of a brief fast food, fat and sugar sweetened beverage screening tool for use by low‐income parents of preschool age children. Parents (n=144) from Head Start and WIC participated in the study. Cross‐sectional data collection included the parent self‐administered 12‐item Healthy Kids (HK) Fast Food and Fat tool and three 24‐hour recalls used to calculate dietary energy density. The tool, with a Cronbach alpha of 0.81, included assessment of eating fast food, sugar sweetened beverage consumption, and snacking on cookies, chips and candy. Linear regression analysis revealed a significant relationship (R2 = 0.29, p<0.003) between the HK tool and child dietary energy density. In this sample, the Healthy Kids Fast Food and Fat tool was an adequate measure of the child's dietary energy density which is ultimately related to obesity. The tool could be used for program evaluation in Federal Food Assistance and Education programs and as a screener for risky behaviors to target in counseling appointments.This project was supported by Agriculture and Food Research Initiative Grant no. 2010‐85215‐20658 from the USDA National Institute of Food and Agriculture, obesity – 93330.
Does Pollution Exacerbate Obesity Risks? A Systematic Review and Meta‐analysis
Authors: Smith Kelsey , Qu Weidong , Ren Xuefeng , Wang Youfa 
Published: June 2021

Objectives:Environmental pollutants may have contributed to the global obesity epidemic. We examined associations between chemical pollutants and obesity in human subjects and related mechanisms, and provided recommendations for future research and interventions.Methods:Systematic review of relevant human subject studies published since 1995 by searching PubMed and MEDLINE®.Results:We identified 24 articles (including cross‐sectional, case‐control,cohort studies) and reported on associations between pollutants and obesity: 20 studies found positive associations between obesity and chemicals, such as polychlorinated biphenyl (PCBs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), polychlorinated dibenzodioxins (PCDDs), hexachlorobenzene, dieldrin, chlordane, bisphenol A (BPA), arsenic, and hexachlorocyclohexane. The rest found inverse or null association between obesity and the chemicals. Some studies reported positive associations with odds ratios (ORs) ranging from 1‐3, while some reported reverse associations of OR=0.38 (0.16,0.91). Certain chemicals, such as BPA, were more likely to have high ORs; where as highly chlorinated PCBs were more likely to have negative ORs. Effects of chemicals on the endocrine system and obesity varied by substance, exposure level, measure of adiposity, and subject characteristics (eg, sex, age).ConclusionsAccumulated evidences show positive associations between pollutants and obesity. Additional, large, long‐term, follow‐up cohort studies are needed to assess impacts of chemical pollutants on obesity risk and the mechanisms.
Extraction of Anti‐cancer Water Soluble Compounds from Rumex Crispus
Authors: Bhandari Mukund , Clack Beatrice 
Published: June 2021

Colorectal cancer is the third leading cause of cancer death in the United States in both men and women. In 2014,the estimated number of new cases is 96,830 and estimated death is 50,310 (American Cancer Society, 2014) which indicates a dire need of anticancer compounds with less side effects. Previous studies shows Rumex crispus as a promising source of anticancer compounds (Duke, J. 2003). In this study, water soluble compounds from Rumex crispus roots were extracted using Accelerated Solvent Extraction (ASE) and cell viability assay was performed for preliminary screening on human colorectal adenocarcinoma (DLD‐1 ATCC® CCL‐221TM) cell line which showed positive killing effect after treatment with extract. Extracts obtained from ASE were further purified and separated using reverse phase High Performance Liquid Chromatography (HPLC). Cell viability assays were performed on all the HPLC collected fractions and the fractions with positive killing activity were further screened for caspase‐3/7 assay to show that cell death was through apoptosis. Two HPLC fractions were found to be positive with more than four fold increase in caspase‐3/7 activity. Further analysis by Mass Spectrometry (MS) shows number and masses of compounds for future purification and identification.Funding Source: Office of Research and Sponsored Projects, SFASU and Ed and Gwen Cole, Nacogdoches, TX.
Association Between Omega‐3 Index and Type 2 Diabetes in Older Overweight/Obese People is Sex Dependent
Authors: Garg Manohar , Abbott Kylie , Veysey Martin , Lucock Mark , Niblett Suzanne , King Katrina , Burrows Tracy 
Published: June 2021

The association between dietary omega‐3 polyunsaturated fatty acid (n‐3PUFA) deficiency and insulin resistance, and type 2 diabetes (T2D) is unclear. The aim of this study was to determine whether there is an association between erythrocyte n‐3PUFA levels (Omega‐3 Index) and T2D in older adults.A cross‐sectional sample of older adults aged 65‐95 years (n=548) was analysed. Outcome measures included: Omega‐3 index (O3I; %EPA + %DHA); fasting blood glucose; plasma insulin; and HbA1c. HOMA‐IR was calculated to determine insulin sensitivity. Odds ratio (OR) for T2D was calculated for each quartile of O3I using the lowest quartile as a reference.There was a significant inverse association between O3I and T2D in overweight and obese females, with an OR for T2D for the first to fourth quartiles respectively: 1.0 (reference), 0.82 (95% CI, 0.31‐2.18), 0.56 (95% CI, 0.21‐1.52), 0.22 (95% CI, 0.06‐0.82) (P‐trend=0.015). Similar trends were seen in overweight males however the relationship did not reach significance. After adjusting for BMI, no associations were found between O3I and fasting blood glucose, insulin, HbA1c or HOMA‐IR.Higher erythrocyte n‐3PUFA status may be protective against obesity‐related insulin resistance and T2D in females. Further research is warranted to further elucidate sex differences and determine whether dietary interventions to improve the O3I may delay or prevent the development of T2D.
Effects of Epigallocatechin Gallate Nanocarriers on Liver Cholesterol Content in LDL Receptor Null Mice
Authors: Cao Jun , Zhang Jia , Li Chuan , Wang Shu 
Published: June 2021

ObjectivesOur macrophage‐targeting epigallocatechin gallate (EGCG) nanocarriers (E‐nano) have anti‐atherogenic bioactivities. But their effects on liver cholesterol content are unknown. This study aims to investigate the impact of non‐targeting and targeting E‐nano at low or high doses on liver cholesterol content in LDL receptor null (LDLr‐/‐) mice.MethodsLDLr‐/‐ mice received weekly intravenous injection of the following 10 treatments for 20 weeks: saline, high dose (25 mg/kg body weight) of EGCG (EGCG‐H), E‐nano (E‐nano‐H), void‐nano (V‐nano‐H), macrophage‐targeting E‐nano (TE‐nano‐H), macrophage targeting V‐nano (TV‐nano‐H), and low dose (10 mg/kg body weight) of E‐nano (E‐nano‐L), V‐nano (V‐nano‐L), macrophage‐targeting E‐nano (TE‐nano‐L), macrophage‐targeting V‐nano (TV‐nano‐L). Liver lipids were extracted by a chloroform/methanol mixture. Half of lipids were used to measure total cholesterol (TC), and the other half of lipids were used to measure free cholesterol (FC) using a HPLC system. Cholesteryl ester (CE) was calculated as TC minus FC.ResultsCompared to saline, E‐nano‐H significantly decreased liver TC content. All macrophage targeting V‐nano and E‐nano did not change liver cholesterol content.imageConclusionsE‐nano‐H, but not EGCG‐H and TE‐nano‐H, significantly decreased liver TC content in LDLr‐/‐ mice.
The Effect of Different Round Window Sealants on Cochlear Mechanics Over Time
Authors: Mclean Timothy , Clamp Philip , Campbell Luke , Hampson Amy , Chambers Scott , Collins Aaron , Bester Christofer , O’Leary Stephen 
Published: June 2021

Background:
This project investigated the effects of round window membrane (RWM) sealants after surgical incision, with a focus on audiological thresholds, ossicular mechanics, and the impact upon cochlear function and pathology.

Methods:
Twenty-eight guinea pigs were randomly allocated to one of three sealant groups (muscle, n = 7; fascia, n = 7, Tisseel, n = 8) or an unsealed control group (n = 6). Preoperative hearing was measured using auditory brainstem responses (ABRs). The ossicular chain and RWM were exposed surgically, and Laser Doppler Vibrometry (LDV) measurements were obtained from the long process of the incus. The RWM was incised then sealed (or left unsealed) according to group. ABR testing and LDV measurements were repeated 4 and 12 weeks after surgery. At 12 weeks all cochleae were harvested.

Results:
ABR thresholds deteriorated over time in all groups. Overall, group was not statistically significant (p = 0.064). There was no significant effect by group on LDV measurements (p = 0.798). Histopathological analyses of the RWM showed that the fascia group had more extensive fibrosis than other groups (Independent-Samples Median Test, p = 0.001). However, there were minimal differences in the outer hair cell counts between the different intervention groups.

Conclusions:
All the interventions appeared to be safe while none affected the cochlear mechanics or hearing thresholds in a statistically significant manner.
Fatigue in Children With Unilateral and Bilateral Hearing Loss
Authors: Sindhar Sampat , Friesen Tzyynong L. , Carpenter Delaney , Kesser Bradley , Lieu Judith E. C. 
Published: June 2021

Objective:
To determine whether children with unilateral hearing loss (UHL) experience similar levels fatigue as children with bilateral hearing loss (BHL) or normal-hearing (NH).

Design:
Cross-sectional study.

Setting:
Two tertiary care otolaryngology practices.

Participants:
Children, 5 to 18 years old, with UHL or BHL and their parents.

Main Outcome Measures:
PedsQL Multidimensional Fatigue Scale (MFS) survey.

Results:
Overall response rate was 90/384 (23%). Mean age of child participants was 10.7 years old (standard deviations [SD] 3.1); 38 (42%) were men and 52 (58%) were women. Sixty-nine (77%) children had UHL, 21 (23%) had BHL. Children with BHL (mean 65, SD 21) and UHL (mean 75, SD 17) reported greater levels of fatigue than children with NH (BHL difference –15, 95% confidence interval [CI] –25 to –5; UHL difference –6, 95% CI –13–1.2). Parent-proxy reports for children with BHL (mean 67, SD 20) and UHL (mean 76, SD 20) reported more fatigue than NH (BHL difference –22, 95% CI –33 to –12; UHL difference –14; 95% CI –20 to –8). Sub-section scores for general, sleep, and cognitive fatigue were higher for children with BHL and UHL than NH.

Conclusion and Relevance:
Children with UHL and BHL reported significantly more fatigue than children with NH, and children with BHL reported more fatigue than UHL. These findings underscore the need to increase auditory rehabilitation and educational resources for children with UHL and support the use of the PedsQL MFS questionnaire as a measure to follow disability experienced by children with HL as they undergo hearing rehabilitation.
Validation of a Simulation Model for Robotic Sacrocolpopexy
Authors: Tarr Megan E. , Anderson-Montoya Brittany L. , Vilasagar Smitha , Myers Erinn M. 
Published: June 2021

Objective
We sought to validate a simulation model for robotic sacrocolpopexy (RSCP) that includes multiple steps: presacral dissection/mesh attachment, vaginal mesh attachment, and peritoneal closure.

Methods
An RSCP training model was developed. Female pelvic medicine and reconstructive surgery (FPMRS) experts and current FPMRS fellows were videotaped using the model; sessions were timed and scored using the Global Evaluative Assessment of Robotic Skills (GEARS) by 3 surgeon reviewers masked to participants’ identities. Construct validity was measured by comparing performance on the model between experts and trainees. Interrater reliability was determined by calculating intraclass correlation coefficients for total GEARS scores. Face validity was assessed by a postprocedure questionnaire.

Results
Experts included 9 board-certified FPMRS physicians experienced in RSCP; trainees were 17 fellows. Experts practiced at 7 different institutions in the United States, and the majority (5/7) taught fellows. Trainees were from 7 institutions and in various years of training: postgraduate year (PGY) 5 (n = 6), PGY 6 (n = 5), and PGY 7 (n = 6). Experts’ performances were rated significantly higher for total GEARS scores and for relevant domains of the GEARS scale. Intraclass correlation coefficient for the 3 reviewer pairs (0.96–0.99) indicated high interrater reliability. All participants “agreed/strongly agreed” that the model closely approximated live RSCP surgery and was useful for teaching and learning the procedure, indicating high face validity.

Conclusions
This novel, multistep simulation model demonstrated construct validity and high interrater reliability. Face validity was also established. Consequently, this RSCP model could be used for surgical training and assessment of these discrete surgical skill steps.
An assessment of phase field fracture: crack initiation and growth
Authors: Kristensen Philip K. , Niordson Christian F. , Martínez-Pañeda Emilio 
Published: June 2021

The phase field paradigm, in combination with a suitable variational structure, has opened a path for using Griffith’s energy balance to predict the fracture of solids. These so-called phase field fracture methods have gained significant popularity over the past decade, and are now part of commercial finite element packages and engineering fitness- for-service assessments. Crack paths can be predicted, in arbitrary geometries and dimensions, based on a global energy minimization—without the need for ad hoc criteria. In this work, we review the fundamentals of phase field fracture methods and examine their capabilities in delivering predictions in agreement with the classical fracture mechanics theory pioneered by Griffith. The two most widely used phase field fracture models are implemented in the context of the finite element method, and several paradigmatic boundary value problems are addressed to gain insight into their predictive abilities across all cracking stages; both the initiation of growth and stable crack propagation are investigated. In addition, we examine the effectiveness of phase field models with an internal material length scale in capturing size effects and the transition flaw size concept. Our results show that phase field fracture methods satisfactorily approximate classical fracture mechanics predictions and can also reconcile stress and toughness criteria for fracture. The accuracy of the approximation is however dependent on modelling and constitutive choices; we provide a rationale for these differences and identify suitable approaches for delivering phase field fracture predictions that are in good agreement with well-established fracture mechanics paradigms.
This article is part of a discussion meeting issue ‘A cracking approach to inventing new tough materials: fracture stranger than friction’.