bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mendelian randomization with fine‐mapped genetic data: Choosing from large numbers of correlated instrumental variables
Authors: Burgess Stephen , Zuber Verena , Valdes‐Marquez Elsa , Sun Benjamin B , Hopewell Jemma C 
Published: September 2017

ABSTRACTMendelian randomization uses genetic variants to make causal inferences about the effect of a risk factor on an outcome. With fine‐mapped genetic data, there may be hundreds of genetic variants in a single gene region any of which could be used to assess this causal relationship. However, using too many genetic variants in the analysis can lead to spurious estimates and inflated Type 1 error rates. But if only a few genetic variants are used, then the majority of the data is ignored and estimates are highly sensitive to the particular choice of variants. We propose an approach based on summarized data only (genetic association and correlation estimates) that uses principal components analysis to form instruments. This approach has desirable theoretical properties: it takes the totality of data into account and does not suffer from numerical instabilities. It also has good properties in simulation studies: it is not particularly sensitive to varying the genetic variants included in the analysis or the genetic correlation matrix, and it does not have greatly inflated Type 1 error rates. Overall, the method gives estimates that are less precise than those from variable selection approaches (such as using a conditional analysis or pruning approach to select variants), but are more robust to seemingly arbitrary choices in the variable selection step. Methods are illustrated by an example using genetic associations with testosterone for 320 genetic variants to assess the effect of sex hormone related pathways on coronary artery disease risk, in which variable selection approaches give inconsistent inferences.
Evolutionarily derived networks to inform disease pathways
Authors: Graham Britney E. , Darabos Christian , Huang Minjun , Muglia Louis J. , Moore Jason H. , Williams Scott M. 
Published: September 2017

ABSTRACTMethods to identify genes or pathways associated with complex diseases are often inadequate to elucidate most risk because they make implicit and oversimplified assumptions about underlying models of disease etiology. These can lead to incomplete or inadequate conclusions. To address this, we previously developed human phenotype networks (HPN), linking phenotypes based on shared biology. However, such visualization alone is often uninterpretable, and requires additional filtering. Here, we expand the HPN to include another method, evolutionary triangulation (ET). ET utilizes the hypothesis that alleles affecting disease risk in multiple populations are distributed consistently with differences in disease prevalence and compares allele frequencies among populations and their relationship to phenotype prevalence. We hypothesized that combining these methods will increase our ability to detect genetic patterns of association in complex diseases. We combined HPN and ET to identify network patterns associated with type 2 diabetes mellitus (T2DM), a leading cause of death worldwide. Fasting glucose, a continuous trait, was used as a proxy for T2DM and differs significantly among continental populations. The combined method identified several diabetes‐related traits and several phenotypes related to cardiovascular diseases, for which diabetes is a major risk factor. ET‐HPN found more phenotypes related to our target and related phenotypes than the application of either method alone. Not only could we detect phenotype connections related to T2DM, but we also identified phenotypes that are distributed in parallel to it, e.g., amyotrophic lateral sclerosis. Our analyses showed that ET‐filtered HPN provides information that neither technique can individually.
Brain structural correlates of irritability: Findings in a large healthy cohort
Authors: Besteher Bianca , Squarcina Letizia , Spalthoff Robert , Bellani Marcella , Gaser Christian , Brambilla Paolo , Nenadić Igor 
Published: September 2017

AbstractIrritability and nonviolent aggression are common behavioral features across the population, yet there is limited neurobiological research into subclinical phenotypes representing the lower edge of a symptom continuum ranging from slight irritability to criminal violence. We studied brain structural correlates of irritability in a large healthy cohort to test the hypothesis of associations with fronto‐limbic brain structures implicated in mood regulation. In a large multicenter effort, we recruited 409 mentally healthy adults from the community, who received T1‐weighted high‐resolution 3 T MRI scans. These structural scans were automatically preprocessed for voxel‐ and surface‐based morphometry measurements with the CAT 12 toolbox implemented in SPM 12. Subclinical aggressive symptoms were assessed using the SCL‐90‐R aggression/hostility subscale and then correlated with cortical volume (VBM), and cortical thickness and gyrification. VBM analysis showed significant (P < 0.05, FDR‐corrected at peak‐level) positive correlations of cortical volume with SCL‐90‐R aggression subscale values in large clusters spanning bilateral anterior cingulate and orbitofrontal cortices and left lingual and postcentral gyri. Surface‐based morphometry yielded mostly uncorrected positive correlations with cortical thickness in bilateral precentral gyri and with gyrification in left insula and superior temporal gyrus. Our findings imply an association of subclinical aggressive symptoms with cortical volume in areas important for emotion awareness and regulation, which might also be related to cortical adaptation to mental stress. These results overlap with several findings on impulsive aggression in patients suffering from affective and disruptive behavior disorders. They also suggest a biological symptom continuum manifesting in these brain areas. Hum Brain Mapp 38:6230–6238, 2017. © 2017 Wiley Periodicals, Inc.
Correlation among ocular surface disease, xerostomia, and nasal symptoms in patients with differentiated thyroid carcinoma subjected to radioiodine therapy: A prospective comparative study
Authors: da Fonseca Fabricio Lopes , Yamanaka Patricia Kazue , Mazoti Luciana , Arakawa‐Sugueno Lica , Kato Juliana Mika , Matayoshi Suzana 
Published: September 2017

AbstractBackgroundSome complications of radioiodine therapy have been reported, but the involvement of the eyes and adnexa is rarely discussed. The purpose of this study was to determine the correlation among ocular surface changes, xerostomia, and changes in the nasal mucosa associated with radioiodine therapy.MethodsPatients subjected to radioiodine therapy (group 1) or not subjected (group 2) were prospectively evaluated by examinations of the ocular surface and tear film, saliva production, and nasal endoscopy. Ocular and nasal symptoms and xerostomia were evaluated using questionnaires.ResultsEvaluation of the ocular surface did not indicate significant differences between the groups. Nasal endoscopy revealed higher mucosal pallor in group 1 and worsening of the endoscopic appearance. Worsening of ocular symptoms and nasal symptoms, xerostomia, and a significant decrease in salivary production was also observed in group 1.ConclusionSubjective worsening of xerostomia, xerophthalmia, nasal symptoms, and changes in the nasal mucosa in group 1 was observed.
Prognostic nomogram for disease‐specific survival of carcinoma ex pleomorphic adenoma of the salivary gland
Authors: Hu Yu‐Hua , Li Wei , Zhang Chun‐Ye , Xia Rong‐Hui , Tian Zhen , Wang Li‐Zhen , Xie Lu , Li Jiang 
Published: September 2017

AbstractBackgroundThe purpose of this study was to establish an effective prognostic nomogram for carcinoma ex pleomorphic adenoma (Ca‐ex‐PA) of the salivary gland.MethodsThe nomogram was based on a retrospective study on 223 patients who underwent surgical operation for Ca‐ex‐PA from 2001 to 2010. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C‐index) and calibration curve. The results were validated using bootstrap resampling and a prospective study on 111 patients operated on from 2011 to 2012.ResultsOn multivariate analysis of the primary cohort, independent factors for disease‐specific survival (DSS) were age, tumor diameter, degree of capsule invasion, lymph node metastasis, and the interaction between tumor site and histological subtype, which were all selected into the nomogram. The C‐index of the nomogram for predicting DSS was 0.90 and 0.86 in the primary cohort and validation cohort, respectively.ConclusionThe proposed nomogram resulted in more accurate prognostic predictions for patients with Ca‐ex‐PA.
Cysteine‐rich buccal gland protein suppressed the proliferation, migration and invasion of hela cells through akt pathway
Authors: Han Jianmei , Liu Yu , Jiang Qi , Xiao Rong 
Published: September 2017

AbstractCysteine‐rich buccal gland protein (CRBGP) as a member of cysteine‐rich secretory proteins (CRISPs) superfamily was isolated from the buccal glands of Lampetra japonica, the blood suckers in the marine. Previous studies showed CRBGP could suppress angiogenesis probably due to its ion channel blocking activity. Whether CRBGP could also affect the activity of tumor cells has not been reported yet. In this study, CRBGP suppressed the proliferation of Hela cells with an IC50 of 6.7 μM by inducing apoptosis. Both microscopic observation and Western blot indicated that CRBGP was able to induce the nuclei shrinking, downregulate the protein level of BCL2 and caspase 3 as well as upregulate the level of BAX in Hela cells, suggested that CRBGP might induce apoptosis of Hela cells in a mitochondrial‐dependent pathway. Furthermore, CRBGP could disturb F‐actin organization, which would finally cause the Hela cells to lose their shape and to lessen their abilities on adhesion, migration and invasion. Finally, CRBGP was shown to reduce the phosphorylation level of Akt, which indicated that CRBGP might inhibit the proliferation and metastasis of Hela cells through Akt pathway. CRBGP, as a voltage‐gated sodium channel blocker, also possesses the anti‐tumor abilities which provided information on the effects and action manner of the other CRISPs. © 2017 IUBMB Life, 69(11):856–866, 2017
Nanofibrous scaffolds with biomimetic structure
Authors: Khalili Shahla , Nouri Khorasani Saied , Razavi Mohammad , Hashemi Beni Batol , Heydari Fariba , Tamayol Ali 
Published: September 2017

AbstractThis research studies the effect of using a grid‐like pattern as a collector on increasing the pore size of the electrospun gelatin/cellulose acetate/elastin scaffolds. The morphological study showed an enlargement in pore size and a decline in fiber diameter in comparison with the scaffold fabricated using conventional flat sheet collectors. The use of the pattern increased the swelling ratio and degradation rate of the scaffold. Investigating the tensile properties of scaffolds revealed that the patterned collector increased the elongation at break up to 145%. In vitro experiments revealed the patterned scaffold as a good substrate for attachment and proliferation of fibroblast cells. Overall, our results indicated that the patterned scaffold of gelatin/cellulose acetate/elastin could provide a better microenvironment for fibroblast cells compared to the conventional scaffolds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 370–376, 2018.
Multiple senses of community and acculturation strategies among migrants
Authors: Mannarini Terri , Talò Cosimo , Mezzi Monica , Procentese Fortuna 
Published: September 2017

AbstractBased on the theoretical framework of multiple psychological sense of community (MPSOC) and acculturation models, the study explored the relationships between territorial (TPSOC) and ethnic PSOC (EPSOC) and the acculturation behaviors of 2 groups of immigrants who settled in Italy, namely, Albanians (N = 230) and Sri Lankans (N = 131). Based on survey data and quantitative analyses (general linear models), TPSOC and EPSOC were considered first separately and then combined, according to a bidimensional model of MPSOC that resulted in four combinations (dual membership, receiving society membership, ethnic membership, and no membership). The findings highlighted significant variations across groups. Among Albanian participants, both TPSOC and EPSOC were positively associated with integration and negatively with marginalization. Dual membership was positively associated with integration, prevailing ethnic membership with separation, and no membership with marginalization. Among Sri Lankan participants, EPSOC showed a positive association with separation. Dual membership was associated with marginalization, prevailing receiving society membership with assimilation, prevailing ethnic membership with separation, and no membership with integration.
Paroxetine‐induced QTc prolongation
Authors: Otsuka Yuji 
Published: September 2017

AbstractThere have been only two previous reports of paroxetine‐induced corrected QT (QTc) prolongation on electrocardiogram (ECG). Here, we report a 43‐year‐old woman with QTc prolongation (476 ms). She had taken 50 mg of paroxetine for 17 days. Three days after discontinuation of paroxetine, QTc returned to within the normal limits (396 ms). Paroxetine blocks the human ether‐a‐go‐go‐related gene (HERG) channels. Genetic polymorphisms of channels related to cardiac function are involved in drug‐induced QTc prolongation. Moreover, autonomic nervous system instability due to unstable psychotic symptoms may also affect QTc. These factors are related to this rare event induced by paroxetine.
Standardized ileal digestibility and digestible indispensable amino acid score of porcine and bovine hydrolyzates in pigs
Authors: Bindari Yugal Raj , Lærke Helle Nygaard , Nørgaard Jan Værum 
Published: September 2017

AbstractBACKGROUNDThe use of protein hydrolyzates in food and feed ingredients is a growing area of interest. The present study was conducted aiming to determine the standardized ileal digestibility (SID) and to evaluate protein quality of porcine and bovine hydrolyzates. The SID values were determined in pigs and these values were used to calculate digestible indispensable amino acid score (DIAAS) values.RESULTSThe SID of crude protein of hydrolyzates of porcine plasma, bovine muscle, bovine collagen, porcine heart and porcine muscle was 0.81, 0.84, 0.79, 0.79 and 0.91, respectively. Based on the DIAAS, hydrolyzates of porcine plasma and porcine heart (DIAAS = 87 and 76) are considered as good quality protein sources for younger children. For older children, adolescents and adults, the hydrolyzates of bovine muscle and porcine heart (DIAAS = 81 and 87) are considered as good quality protein sources and the hydrolyzate of porcine plasma (DIAAS = 102) is considered as a high quality protein source.CONCLUSIONDIAAS values indicate that the porcine and bovine hydrolyzates tested in the present study have low and medium to high protein values and also that the protein products can be included in human nutrition. © 2017 Society of Chemical Industry
Incidental Findings on Routine Targeted Neonatal Echocardiography Performed in Preterm Neonates Younger Than 29 Weeks’ Gestation
Authors: Smith Aisling , Breatnach Colm R. , James Adam T. , Franklin Orla , El‐Khuffash Afif 
Published: September 2017

ObjectivesThe aim of this study was to quantify the rate of incidental findings identified on elective research echocardiography performed on neonates younger than 29 weeks’ gestation.MethodsWe conducted a retrospective study of echocardiographic examinations performed within the first 24 hours of age on neonates younger than 29 weeks’ gestation over a 3‐year period for research purposes. Incidental echocardiographic findings and pertinent clinical data were recorded.ResultsEchocardiographic examinations performed on 145 neonates were retrospectively reviewed. Forty‐three neonates (30%) had a total of 54 unexpected findings (37%). Most comprised malpositioned umbilical venous catheters, where the tip was located in the left atrium. The remainder of the conditions identified included unsuspected congenital heart disease, liver hematomas, and unexpected pulmonary hypertension.ConclusionsThere is a high rate of incidental findings identified on screening echocardiograms. Routine targeted neonatal echocardiographic screening of preterm neonates may be warranted to identify the considerable likelihood of asymptomatic findings.
Temporal bone histopathology of furosemide ototoxicity
Authors: Santos Felipe , Nadol Joseph B. 
Published: September 2017

ObjectivesTo describe the human temporal bone pathology in two patients who incurred furosemide induced ototoxicity.Patients1) A 46‐year‐old woman in acute liver and renal failure treated with high doses of furosemide for anasarca who developed a rapidly progressive severe‐to‐profound asymmetric sensorineural hearing loss. 2) A 65‐year‐old woman with undifferentiated small cell carcinoma of the lung who received intravenous furosemide 1 day prior to death for pulmonary edema.InterventionsRemoval of temporal bones, histologic processing, and light microscopy of temporal bones.Main Outcome MeasuresTemporal bone histopathology and correlation with clinical and audiometric data.ResultsAll three temporal bones demonstrated edema and cystic changes in the stria vascularis. In the first case the furosemide exposure was associated with hearing loss and the pathological changes were more extensive including cystic changes in the Hensen's cells, collapse of Reissner's membrane and the tectorial membrane and diffuse loss of inner and outer hair cells with only modest reduction in the spiral ganglion cell population. In the second case, without attributable hearing loss, there was only modest reduction in hair cell and spiral ganglion cell counts. Pathological changes were not observed in the ampullae of the semicircular canals or epithelium of the saccular or utricular maculae in either case.ConclusionsThe temporal bone pathologic correlate for furosemide‐induced ototoxicity is edema and cystic degeneration of the stria vascularis. The degree of degenerative change appears dose‐dependent. We infer that pathological changes may occur in the absence of a measurable immediate clinical effect.Level of EvidenceNA.
Wnt/β‐catenin and ERK pathway activation: A possible mechanism of photobiomodulation therapy with light‐emitting diodes that regulate the proliferation of human outer root sheath cells
Authors: Kim Jung E. , Woo Young J. , Sohn Ki M. , Jeong Kwan H. , Kang Hoon 
Published: September 2017

BackgroundOuter root sheath cells (ORSCs) play important roles in maintaining hair follicle structure and provide support for the bulge area. The hair growth promoting effects of photobiomodulation therapy (PBMT) have been reported, but the mechanisms for this in human ORCs (hORSCs) have rarely been studied.ObjectiveThe aim of this study was to investigate the effect of various wavelengths of light‐emitting diode (LED) irradiation on human ORSCs (hORSCs).MethodsLED irradiation effects on hORSC proliferation and migration were examined with MTT assay, BrdU incorporation assay and migration assays. hORSCs were irradiated using four LED wavelengths (415, 525, 660, and 830 nm) with different low energy levels. LED irradiation effects on the expression of molecules associated with the Wnt/β‐catenin signaling and ERK pathway, hair stem cell markers, and various growth factors and cytokines in hORSCs were examined with real‐time PCR and Western blot assay. The effect of the LED‐irradiated hORSCs on cell proliferation of human dermal papilla cells (hDPCs) was examined with co‐culture and MTT assay.ResultsPBMT with LED light variably promoted hORSC proliferation and suppressed cell apoptosis depending on energy level. LED irradiation induced Wnt5a, Axin2, and Lef1 mRNA expression and β‐catenin protein expression in hORSCs. Phosphorylation of ERK, c‐Jun, and p38 in hORSCs was observed after LED light irradiation, and ERK inhibitor treatment before irradiation reduced ERK and c‐Jun phosphorylation. Red light‐treated hORSCs showed substantial increase in IL‐6, IL‐8, TNF‐a, IGF‐1, TGF‐β1, and VEGF mRNA. Light irradiation at 660 and 830 nm projected onto hORSCs accelerated in vitro migration. LED‐irradiated hORSCs increased hDPCs proliferation when they were co‐cultured. The conditioned medium from LED‐irradiated hORSCs was sufficient to stimulate hDPCs proliferation.ConclusionThese results demonstrate that LED light irradiation induced hORSC proliferation and migration and inhibited apoptosis in vitro. The growth‐promoting effects of LEDs on hORSCs appear to be associated with direct stimulation of the Wnt5a/β‐catenin and ERK signaling pathway. Lasers Surg. Med. 49:940–947, 2017. © 2017 Wiley Periodicals, Inc.
Electronic Interactions of n‐Doped Perylene Diimide Groups Appended to Polynorbornene Chains: Implications for Electron Transport in Organic Electronics
Authors: Nguyen Minh T. , Biberdorf Joshua D. , Holliday Bradley J. , Jones Richard A. 
Published: September 2017

AbstractA polymer consisting of a polynorbornene backbone with perylene diimide (PDI) pendant groups on each monomeric unit is synthesized via ring opening metathesis polymerization. The PDI pendant groups along the polymer backbone, studied by UV–vis absorption, fluorescence emission, and electron paramagnetic resonance spectroscopy in addition to electrochemical methods, show evidence of molecular aggregation and corresponding electronic coupling with neighboring groups, which forms pathways for efficient electron transport from one group to another in a specific reduced form. When n‐doped, the title polymer shows redox conductivity of 5.4 × 10−3 S cm−1, comparable with crystalline PDI materials, and is therefore a promising material for use in organic electronics.
In vivo MRS for the assessment of mouse colon using a dedicated endorectal coil: initial findings
Authors: Dorez Hugo , Ratiney Hélène , Canaple Laurence , Saint‐Jalmes Hervé , Gaillard Sophie , Moussata Driffa , Sablong Raphaël , Beuf Olivier 
Published: September 2017

Inflammatory bowel disease is a common group of inflammation conditions that can affect the colon and the rectum. These pathologies require a careful follow‐up of patients to prevent the development of colorectal cancer. Currently, conventional endoscopy is used to depict alterations of the intestinal walls, and biopsies are performed on suspicious lesions for further analysis (histology). MRS enables the in vivo analysis of biochemical content of tissues (i.e. without removing any samples). Combined with dedicated endorectal coils (ERCs), MRS provides new ways of characterizing alterations of tissues.An MRS in vivo protocol was specifically set up on healthy mice and on mice chemically treated to induce colitis. Acquisitions were performed on a 4.7 T system using a linear volume birdcage coil for the transmission of the B1 magnetic field, and a dedicated ERC was used for signal reception. Colon‐wall complex, lumen and visceral fat were assessed on healthy and treated mice with voxel sizes ranging from 0.125 μL to 2 μL while keeping acquisition times below 3 min.The acquired spectra show various biochemical contents such as α‐ and β‐methylene but also glycerol backbone and diacyl. Choline was detected in tumoral regions. Visceral fat regions display a high lipid content with no water, whereas colon‐wall complex exhibits both high lipid and high water contents.To the best of our knowledge, this is the first time that in vivo MRS using an ERC has been performed in the assessment of colon walls and surrounding structures. It provides keys for the in vivo characterization of small local suspicious lesions and offers complementary solutions to biopsies.