bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Cholesterol Synthesis in HepG2 Cells by GINST—Decreasing HMG‐CoA Reductase Expression Via AMP‐Activated Protein Kinase
Authors: Han Joon‐Seung , Sung Jong Hwan , Lee Seung Kwon 
Published: October 2017

AbstractGINST, a hydrolyzed ginseng extract, has been reported to have antidiabetic effects and to reduce hyperglycemia and hyperlipidemia. Hypercholesterolemia is caused by diet or genetic factors and can lead to atherosclerosis and coronary heart disease. Thus, the purpose of this study is to determine whether GINST and the ginsenoside metabolite, IH‐901 (compound K), reduce cholesterol synthesis in HepG2 cells and the signal transduction pathways involved. Concentrations of cholesterol were measured by using an enzymatic method. Expression levels of sterol regulatory element‐binding protein 2 (SREBP2), HMG‐CoA reductase (HMGCR), peroxisome proliferators‐activated receptor γ (PPARγ), CCAAT/enhancer‐binding proteins α (C/EBPα), GAPDH, and phosphorylation of AMP‐activated protein kinase α (AMPKα), protein kinase B (PKB, also known as Akt), and mechanistic target of rapamycin complex 1 (mTORC1) were measured using western blot. Total cholesterol concentration decreased after GINST treatment for 24 and 48 h. Expression of HMGCR decreased more with GINST than with the inhibitors, U18666A and atorvastatin, after 48 h in a dose‐dependent manner. Phosphorylation of AMPKα increased 2.5x by GINST after 360 min of treatment, and phosphorylation of Akt decreased after 120 and 360 min. We separated compound K from GINST extracts flash chromatography. Compound K decreased cholesterol synthesis in HepG2 cells at 24 and 48 h. Therefore, we conclude that GINST inhibits cholesterol synthesis in HepG2 cells by decreasing HMGCR expression via AMPKα activation.Practical ApplicationGINST, a hydrolyzed ginseng extract, can inhibit cholesterol synthesis in liver cells via activation of AMPKα. IH‐901 (compound K), which is the main component with bioactivity in GINST, also has anticholesterol effects. Thus, we suggest that GINST can be used to reduce hypercholesterolemia.
Estimation of the Potential Effectiveness of Lowering the Blood Alcohol Concentration (BAC) Limit for Driving from 0.08 to 0.05 Grams per Deciliter in the United States
Authors: Fell James C. , Scherer Michael 
Published: October 2017

BackgroundIn 2013, the National Transportation Safety Board (NTSB) issued a report recommending that states lower the illegal blood alcohol concentration (BAC) limit for driving from 0.08 to 0.05 g/dl. The NTSB concluded that there is a strong evidence‐based foundation for a BAC limit of 0.05 or lower. Most industrialized nations have already enacted a 0.05 illegal BAC limit. This study was undertaken to contribute to the scientific evidence as to whether lowering the BAC limit to 0.05 will be an effective alcohol policy in the United States.MethodsWe accomplished our objective by: (i) conducting a meta‐analysis of qualifying international studies to estimate the range and distribution of the most likely effect size from a reduction to 0.05 BAC or lower; (ii) translating this synthesis toward estimating the effects of reducing the current 0.08 BAC limit to 0.05 in the United States; and (iii) estimating the life‐saving benefits of the proposed 0.03 reduction in the driving limit from 0.08 to 0.05 BAC.ResultsIn our meta‐analysis of studies on lowering the BAC limit in general, we found a 5.0% decline in nonfatal alcohol‐related crashes, a 9.2% decline in fatal alcohol‐related crashes from lowering the BAC to 0.08, and an 11.1% decline in fatal alcohol‐related crashes from lowering the BAC to 0.05 or lower. We estimate that 1,790 lives would be saved each year if all states adopted a 0.05 BAC limit.ConclusionsThis study provides strong evidence of the relationship between lowering the BAC limit for driving and the general deterrent effect on alcohol‐related crashes.
Impulsive Personality Traits Mediate the Relationship Between Adult Attention‐Deficit/Hyperactivity Symptoms and Alcohol Dependence Severity
Authors: Daurio Allison M. , Aston Sean A. , Schwandt Melanie L. , Bukhari Mohammad O. , Bouhlal Sofia , Farokhnia Mehdi , Lee Mary R. , Leggio Lorenzo 
Published: October 2017

BackgroundWhile the role of attention‐deficit/hyperactivity disorder (ADHD) as a risk factor for developing alcohol use disorder (AUD) has been established, the underlying pathways connecting the two are still not fully understood. Overlapping constructs such as impulsivity may explain the increased risk for developing AUD in individuals with ADHD.MethodsIn this study, we assessed whether adult ADHD symptoms increase the odds of having a diagnosis of AUD. Furthermore, we tested whether facets of impulsivity explained the relationship between ADHD symptoms and alcohol dependence (AD) severity.ResultsIn a logistic regression of 749 participants (464 = AD, 285 = controls), overall adult ADHD symptoms, and more specifically, symptoms of hyperactivity/restlessness and problems with self‐concept, increased the odds of having a diagnosis of AD. Within the AD sample, we found that impulsivity mediated the relationship between adult ADHD symptoms and AD severity. In particular, negative and positive urgency meditated the relationship of overall adult ADHD symptoms, and symptoms of hyperactivity/restlessness and problems with self‐concept with AD severity.ConclusionsThese results highlight the importance of looking at cohorts of ADHD symptoms and facets of impulsivity to assess the risk of developing AUD. They also suggest potential avenues for intervention strategies in individuals with preexisting adult ADHD symptoms who are seeking treatment for AUD.
Posterior corneal surface differences between non‐laser in situ keratomileusis (LASIK) and 10‐year post‐LASIK myopic eyes
Authors: Dai Ma‐Li , Wang Qin‐mei , Lin Zu‐Shun , Yu Ye , Huang Jin‐hai , Savini Giacomo , Zhang Jia , Wang Ling , Xu Chen‐chen 
Published: October 2017

AbstractPurposeTo evaluate the posterior corneal surface differences between non‐laser in situ keratomileusis (LASIK) and 10‐year post‐LASIK myopic eyes.MethodsThe study included 130 eyes from 65 patients, who were treated with myopic LASIK 10 years ago. In addition, 130 eyes from 65 unoperated myopic patients of matching present age and preoperative refraction were divided into control group. Data on the posterior corneal surface and anterior chamber were obtained from Pentacam software and compared between the groups. Postoperative visual acuity (VA) and refractive error were also analysed.ResultsThe mean preoperative spherical equivalent (SE) was −6.99 ± 1.78 dioptre (D) in the LASIK group. Ten years after surgery, the mean SE was −0.45 ± 1.22 D, the efficacy index was 0.98, and the safety index was 1.01. The posterior corneal elevations of the LASIK group at 2 mm corneal diameter were significantly lower than those of the control group. However, posterior corneal elevations at 6 mm corneal diameter were higher in the LASIK group than the controls (p < 0.01 for all). The mean Q‐values of posterior corneal surface demonstrated significant positive direction compared to that of control eyes at 6 and 7 mm corneal diameters (p < 0.05 for both). At the thinnest point of the cornea, the anterior chamber depths were shallower in the LASIK group than in controls. Meanwhile, the anterior chamber volumes (ACV) were smaller in the LASIK group than in the control group.ConclusionOur results demonstrated that the posterior corneal surface tends to show signs of central flattening and peripheral steepening 10 years after myopic LASIK surgery compared to that of non‐operated myopic eyes.
Colectomy prior to diagnosis of primary sclerosing cholangitis is associated with improved prognosis in a nationwide cohort study of 2594 PSC‐IBD patients
Authors: Nordenvall C. , Olén O. , Nilsson P. J. , von Seth E. , Ekbom A. , Bottai M. , Myrelid P. , Bergquist A. 
Published: October 2017

SummaryBackgroundDespite the close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), the association between colectomy and the prognosis of PSC remains controversial.AimTo explore whether colectomy prior to PSC‐diagnosis is associated with transplant‐free survival.MethodsA nationwide cohort study in Sweden including all patients aged 18 to 69 years in whom both PSC and IBD was diagnosed between 1987 and 2014 was undertaken. Each patient was followed from date of both PSC and IBD diagnoses until liver transplantation or death, or 31 December 2014. Patients with colon in situ, and colectomy prior to PSC‐diagnosis were compared. Survival analyses were performed using the Kaplan‐Meier method and multivariable Cox regression models.ResultsOf the 2594 PSC‐IBD patients, 205 patients were treated with colectomy before PSC‐diagnosis. During follow‐up, liver transplantations were performed in 327 patients and 509 died. The risk of liver transplantation or death was lower in patients treated with colectomy prior to PSC‐diagnosis (HR 0.71, 95% CI 0.53‐0.95) than in patients with colon in situ. Male gender, longer time between IBD and PSC‐diagnosis and older age were all associated with an increased risk of liver transplantation or death. Colectomy after PSC‐diagnosis was however not associated with an increased risk of liver transplantation or death during long‐term follow‐up.ConclusionsIn PSC‐IBD patients, colectomy prior to PSC‐diagnosis is associated with a decreased risk of liver transplantation or death.
Parental Autonomy Support in Two Cultures: The Moderating Effects of Adolescents’ Self‐Construals
Authors: Marbell‐Pierre Kristine N. , Grolnick Wendy S. , Stewart Andrew L. , Raftery‐Helmer Jacquelyn N. 
Published: October 2017

Parental autonomy support has been related to positive adolescent outcomes, however, its relation to outcomes in collectivist cultural groups is unclear. This study examined relations of specific autonomy supportive behaviors and outcomes among 401 adolescents (Mage = 12.87) from the United States (N = 245) and collectivist‐oriented Ghana (N = 156). It also examined whether adolescents’ self‐construals moderated the relations of specific types of autonomy support with outcomes. Factor analyses indicated two types of autonomy support: perspective taking/open exchange and allowance of decision making/choice. In both countries, perspective taking/open exchange predicted positive outcomes, but decision making/choice only did so in the United States. With regard to moderation, the more independent adolescents’ self‐construals, the stronger the relations of decision making/choice to parental controllingness and school engagement.
Haematological indices and haematinic levels after mini gastric bypass: a matched comparison with Roux‐en‐Y gastric bypass
Authors: Madhok B. M. , Mahawar K. K. , Hadfield J. N. , Courtney M. , Stubbing‐Moore A. , Koshy S. , Small P. K. 
Published: October 2017

SummaryMany surgeons believe mini gastric bypass (MGB) is more likely to cause micronutrient malabsorption compared to Roux‐en‐Y gastric bypass (RYGB). Till date, there is no published study evaluating haematological indices and haematinic levels in patients undergoing MGB and comparing these with a matched cohort of RYGB. Two hundred patients who underwent MGB between October 2012 and October 2015 were matched to 200 patients who underwent RYGB for age, sex, body mass index and time of surgery. We then compared haemoglobin, mean corpuscular volume, iron, ferritin, vitamin B12 and folic acid levels preoperatively and at 6 monthly intervals after surgery until 2 years. The percentage total weight loss was significantly higher in the MGB group compared to the RYGB group at all time points. At 2 years, MGB and RYGB both led to an increase in anaemia rates but the difference was only significant for MGB group. Compared to RYGB, MGB patients were more likely to be anaemic at 2 years, although the difference was not significant statistically (16.6% vs. 12.7%; P value = 0.55). There was a trend for lower iron and folate levels in MGB group compared to RYGB group but the difference was statistically significant at some of the time periods only (significantly lower folate at 6 and 12 months and lower iron at 6 months in the MGB group). MGB leads to a significant increase in anaemia rates in a supplemented cohort. There is a trend towards lower iron and folate levels and higher anaemia rates in MGB group in comparison with RYGB. Larger studies with longer follow‐up should evaluate results of MGB with a shorter biliopancreatic limb.
Marine Noise Budgets in Practice
Authors: Merchant Nathan D. , Faulkner Rebecca C. , Martinez Roi 
Published: October 2017

AbstractMany countries have made statutory commitments to ensure that underwater noise pollution is at levels which do not harm marine ecosystems. Nevertheless, coordinated action to manage cumulative noise levels is lacking, despite broad recognition of the risks to ecosystem health. We attribute this impasse to a lack of quantitative management targets—or “noise budgets”—which regulatory decision‐makers can work toward, and propose a framework of risk‐based noise exposure indicators which make such targets possible. These indicators employ novel noise exposure curves to quantify the proportion of a population or habitat exposed, and the associated exposure duration. This methodology facilitates both place‐based and ecosystem‐based approaches, enabling the integration of noise management into marine spatial planning, risk assessment of population‐level consequences, and cumulative effects assessment. Using data from the first international assessment of impulsive noise activity, we apply this approach to herring spawning and harbor porpoise in the North Sea.
‘It is an entrustment’: Broad consent for genomic research and biobanks in sub‐Saharan Africa
Authors: Tindana Paulina , Molyneux Sassy , Bull Susan , Parker Michael 
Published: October 2017

AbstractIn recent years, there has been an increase in the establishment of biobanks for genetic and genomic studies around the globe. One example of this is the Human Heredity and Health in Africa Initiative (H3Africa), which has established biobanks in the sub‐region to facilitate future indigenous genomic studies. The concept of ‘broad consent’ has been proposed as a mechanism to enable potential research participants in biobanks to give permission for their samples to be used in future research studies. However, questions remain about the acceptability of this model of consent. Drawing on findings from empirical research about the role of trust in decision‐making, we argue that an account of entrustment may be an appropriate way of addressing current challenges of seeking consent for biobank research in Africa. We propose a set of key points to consider that can support the proposed entrustment framework.
Combination therapy incorporating Bcl‐2 inhibition with Venetoclax for the treatment of refractory primary plasma cell leukemia with t (11;14)
Authors: Gonsalves Wilson I. , Buadi Francis K. , Kumar Shaji K. 
Published: October 2017

AbstractPrimary plasma cell leukemia (pPCL) is the most aggressive form of the plasma cell (PC) malignancy, multiple myeloma (MM). It has been commonly associated with the presence of a chromosome translocation involving the immunoglobulin heavy chain (IgH) locus on 14q32, that is t (11;14). Results from early phase clinical trials utilizing the selective Bcl‐2 inhibitor, venetoclax, as a single agent in patients with relapsed MM have had remarkable efficacy among patients with t (11;14) abnormality. The present case demonstrates the ability of a combination regimen incorporating Bcl‐2 inhibition with daratumumab, bortezomib, venetoclax, and dexamethasone to induce a rapid and very deep hematologic response in a pPCL patient with t (11;14), even in a setting of very refractory disease. This case highlights the need to further study Bcl‐2 inhibition‐based therapy as an option for therapy in patients with pPCL with t (11;14).
An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome
Authors: Hollander Peter , Rostgaard Klaus , Smedby Karin E. , Molin Daniel , Loskog Angelica , de Nully Brown Peter , Enblad Gunilla , Amini Rose‐Marie , Hjalgrim Henrik , Glimelius Ingrid 
Published: October 2017

AbstractObjectiveThe classical Hodgkin lymphoma (cHL) tumor microenvironment shows an ongoing inflammatory response consisting of varying degrees of infiltrating eosinophils, mast cells, macrophages, regulatory T lymphocytes (Tregs), and activated lymphocytes surrounding the malignant cells. Herein, different immune signatures are characterized and correlated with treatment outcome.MethodsTumor‐infiltrating leukocytes were phenotyped in biopsies from 459 patients with cHL. Time to progression (TTP) (primary progression, relapse, or death from cHL) and overall survival were analyzed using Cox proportional hazards regression.ResultsThe leukocyte infiltration in the microenvironment was highly diverse between patients and was categorized in 4 immune signatures (active, anergic, innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter TTP (median 12.9‐year follow‐up) in age‐adjusted analyses (hazard ratio = 1.82; 95% confidence interval 1.05‐3‐15). Epstein‐Barr virus (EBV)‐positive cases had higher proportions of macrophages and activated lymphocytes than EBV negative, but neither of those leukocytes predicted prognosis.ConclusionsAbundant Tregs (anergic signature) indicate a shorter TTP, particularly in younger patients. This is probably due to a reduced ability of the immune system to attack the tumor cells. Our data warrant further investigation if these suggested immune signatures could predict outcome of immunotherapy such as immune checkpoint inhibitors.
Structural brain abnormalities in genetic generalized epilepsies: A systematic review and meta‐analysis
Authors: Nuyts Shauni , D'Souza Wendyl , Bowden Stephen C. , Vogrin Simon J. 
Published: October 2017

SummaryAccording to the International League Against Epilepsy (ILAE) definition, no structural abnormalities are present on a standard brain magnetic resonance image in genetic generalized epilepsy (GGE) patients. However, recent studies raise contradictory evidence with increasing use of quantitative magnetic resonance imaging techniques. Following PRISMA guidelines, a systematic, quantitative review was conducted using 28 peer‐reviewed, case–control studies published after 1989. Furthermore, a meta‐analysis with a random‐effect model revealed differences in structural brain abnormalities between GGE patients and controls. Significant structural differences between GGE and healthy controls were observed with volume reductions in whole brain, thalamus, putamen, caudate, pallidum, and supplementary motor area. Furthermore, gray matter volume reduction in the right and left hemispheres, thalamus, and insula, and surface area reduction in the caudal anterior cingulate cortex were revealed, along with gray matter increase in the medial frontal gyrus. Due to methodological differences, findings should be interpreted with caution. Nevertheless, contrary to the ILAE definition, it would appear that structural brain abnormalities may be present in GGE patients. Findings are consistent with a hypothesis regarding the underlying involvement of the thalamocortical networks in the generation of generalized spike‐wave discharges, but structural abnormalities appear to extend outside these regions to potentially involve attention and other cognitive domains.
Refinement of the subunit interaction network within the nucleosome remodelling and deacetylase (NuRD) complex
Authors: Torrado Mario , Low Jason K. K. , Silva Ana P. G. , Schmidberger Jason W. , Sana Maryam , Sharifi Tabar Mehdi , Isilak Musa E. , Winning Courtney S. , Kwong Cherry , Bedward Max J. , Sperlazza Mary J. , Williams David C. , Shepherd Nicholas E. , Mackay Joel P. 
Published: October 2017

The nucleosome remodelling and deacetylase (NuRD) complex is essential for the development of complex animals. NuRD has roles in regulating gene expression and repairing damaged DNA. The complex comprises at least six proteins with two or more paralogues of each protein routinely identified when the complex is purified from cell extracts. To understand the structure and function of NuRD, a map of direct subunit interactions is needed. Dozens of published studies have attempted to define direct inter‐subunit connectivities. We propose that conclusions reported in many such studies are in fact ambiguous for one of several reasons. First, the expression of many NuRD subunits in bacteria is unlikely to lead to folded, active protein. Second, interaction studies carried out in cells that contain endogenous NuRD complex can lead to false positives through bridging of target proteins by endogenous components. Combining existing information on NuRD structure with a protocol designed to minimize false positives, we report a conservative and robust interaction map for the NuRD complex. We also suggest a 3D model of the complex that brings together the existing data on the complex. The issues and strategies discussed herein are also applicable to the analysis of a wide range of multi‐subunit complexes.EnzymesMicrococcal nuclease (MNase), EC 3.1.31.1; histone deacetylase (HDAC), EC 3.5.1.98.
Curriculum content in geriatric dentistry in USA dental schools
Authors: Ettinger Ronald L. , Goettsche Zachary S. , Qian Fang 
Published: October 2017

ObjectivesThe aim of this study was to re‐examine the teaching of geriatric dentistry in the USA dental schools, to identify curriculum content and compare the findings to previous reports.MethodsAll dental schools in the United States were contacted via email with a questionnaire to assess the teaching of geriatric dentistry. Non‐responding schools were sent a minimum of three reminder emails to complete the survey. A statistical analysis was performed. Descriptive statistics were conducted to profile the variables of interest. Bivariate analysis was performed to explore if any of the variables were related using Fisher's exact test, non‐parametric Wilcoxon rank‐sum test and the Kruskal‐Wallis test.ResultsFifty‐six of the 67 dental schools completed the questionnaire. Geriatric dentistry was taught in all dental schools; for 92.8%, the course was compulsory. We found that 62.5% were teaching it as an independent course, 25% as an organised series of lectures and 8.9% as occasional lectures in parts of other courses. Clinically, 84.2% have some form of compulsory education in geriatric dentistry. Public schools were marginally associated with an increased interest in expanding the geriatric dentistry curriculum (P = .078). No differences were found between these variables and school location.ConclusionsGeriatric dentistry is now required in 92.8% of dental schools. The teaching of traditional topics has not changed much; however, the number of gerontological topics has increased. Clinical teaching needs to be expanded, as in only 57.1% of schools was it a requirement. The ageing imperative will require research to determine the impact of teaching on services to the geriatric community.