bluuebunny/crossref_metadata_2025_split huggingface dataset:
TANGO1 and SEC12 are co-packaged with procollagen I to facilitate the generation of large COPII carriers
Authors: Yuan Lin , Kenny Samuel J , Hemmati Juliet , Xu Ke , Schekman Randy 
Published: September 2018

AbstractLarge COPII-coated vesicles serve to convey the large cargo procollagen I (PC1) from the endoplasmic reticulum (ER). The link between large cargo in the lumen of the ER and modulation of the COPII machinery remains unresolved. TANGO1 is required for procollagen (PC) secretion and interacts with PC and COPII on opposite sides of the ER membrane, but evidence suggests that TANGO1 is retained in the ER, and not included in normal size (<100nm) COPII vesicles. Here we show that TANGO1 is exported out of the ER in large COPII-coated PC1 carriers, and retrieved back to the ER by the retrograde coat, COPI, mediated by the C-terminal RDEL retrieval sequence of HSP47. TANGO1 is known to target the COPII initiation factor SEC12 to ER exit sites through an interacting protein, cTAGE5. SEC12 is important for the growth of COPII vesicles, but it is not sorted into small budded vesicles. We found both cTAGE5 and SEC12 were exported with TANGO1 in large COPII carriers. In contrast to its exclusion from small transport vesicles, SEC12 was particularly enriched around ER membranes and large COPII carriers that contained PC1. We constructed a split GFP system to recapitulate the targeting of SEC12 to PC1 via the luminal domain of TANGO1. The minimal targeting system enriched SEC12 around PC1 and generated large PC1 carriers. We conclude that TANGO1, cTAGE5, and SEC12 are co-packed with PC1 into COPII carriers to increase the size of COPII thus ensuring the capture of large cargo.
Population genomic structure and genome-wide linkage disequilibrium in farmed Atlantic salmon (Salmo salarL.) using dense SNP genotypes
Authors: Barria Agustin , López Maria E. , Yoshida Grazyella , Carvalheiro Roberto , Yáñez José M. 
Published: September 2018

AbstractChilean Farmed Atlantic salmon (Salmo salar) populations were established with individuals of both European and North American origins. These populations are expected to be highly genetically differentiated due to evolutionary history and poor gene flow between ancestral populations from different continents. The extent and decay of linkage disequilibrium (LD) among single nucleotide polymorphism (SNP) impacts the implementation of genome-wide association studies and genomic selection and provides relevant information about demographic processes of fish populations. We assessed the population structure and characterized the extent and decay of LD in three Chilean commercial populations of Atlantic salmon with North American (NAM), Scottish (SCO) and Norwegian (NOR) origin. A total of 151 animals were genotyped using a 159K SNP Axiom® myDesign™ Genotyping Array. A total of 40K, 113K and 136 K SNP markers were used for NAM, SCO and NOR populations, respectively. The principal component analysis explained 86.7% of the genetic diversity between populations, clearly discriminating between populations of North American and European origin, and also between European populations. Admixture analysis showed that the Scottish and North American populations likely come from one ancestral population, while the Norwegian population probably originated from more than one. NAM had the lowest effective size, followed by SCO and NOR. Large differences in the LD decay were observed between populations of North American and European origin. A r2threshold of 0.2 was estimated for marker pairs separated by 8,000 Kb, 42 and 64 Kb in the NAM, NOR and SCO populations, respectively. In this study we show that this SNP panel can be used to detect association between markers and traits of interests and also to capture high-resolution information for genome-enabled predictions. Also, we suggest the feasibility to achieve higher prediction accuracies by using a small SNP data set as was used with the NAM population.
CYP3A4‐mediated effects of rifampicin on the pharmacokinetics of vilaprisan and its UGT1A1‐mediated effects on bilirubin glucuronidation in humans
Authors: Chattopadhyay Niladri , Kanacher Tobias , Casjens Manuela , Frechen Sebastian , Ligges Sandra , Zimmermann Torsten , Rottmann Antje , Ploeger Bart , Höchel Joachim , Schultze‐Mosgau Marcus‐Hillert 
Published: September 2018

AimsThe primary aim of the present study was to quantify the effects of rifampicin, a strong cytochrome P450 (CYP) 3A4 inducer, on the pharmacokinetics of the new selective progesterone receptor modulator, vilaprisan. In addition, the effects of rifampicin on the glucuronidation of bilirubin, an endogenous UDP‐glucuronosyltransferase family 1 member A1 (UGT1A1) substrate, were explored.MethodsThis was an open‐label, two‐period study in 12 healthy postmenopausal women. Subjects received a single oral dose of vilaprisan 4 mg in each period. In period 2, administration of vilaprisan was preceded and followed by rifampicin 600 mg day–1. A subtherapeutic dose of midazolam (1 mg) was coadministered with vilaprisan to monitor CYP3A4 induction. Details of the administration and sampling schedule were optimized by means of a physiologically based pharmacokinetic model. Plasma concentrations of vilaprisan, midazolam, and 1′‐ hydroxy‐midazolam were measured and rifampicin‐associated changes in the glucuronidation of bilirubin were determined.ResultsAs predicted by our model, the coadministration of rifampicin was associated with a substantial decrease in exposure to vilaprisan and midazolam – indicated by the following point estimates (90% confidence intervals) for the area under the plasma concentration–time curve from zero to the time of the last quantifiable concentration ratio with or without rifampicin: 0.040 (0.0325, 0.0505) for vilaprisan and 0.144 (0.117, 0.178) for midazolam. Further, it was associated with an increase in bilirubin glucuronidation, indicating that UGT1A1 was induced.ConclusionsThe exposure to vilaprisan was reduced by 96%. Such a reduction is likely to render the drug therapeutically ineffective. Therefore, it is recommended that the use of strong CYP3A4 inducers is avoided when taking vilaprisan.
Effect of multiple‐dose osimertinib on the pharmacokinetics of simvastatin and rosuvastatin
Authors: Harvey R. Donald , Aransay Noemi Reguart , Isambert Nicolas , Lee Jong‐Seok , Arkenau Tobias , Vansteenkiste Johan , Dickinson Paul A. , Bui Khanh , Weilert Doris , So Karen , Thomas Karen , Vishwanathan Karthick 
Published: September 2018

AimWe report on two Phase 1, open‐label, single‐arm studies assessing the effect of osimertinib on simvastatin (CYP3A substrate) and rosuvastatin (breast cancer resistance protein substrate [BCRP] substrate) exposure in patients with advanced epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer who have progressed after treatment with an EGFR tyrosine kinase inhibitor, to determine, upon coadministration, whether osimertinib could affect the exposure of these agents.MethodsFifty‐two patients in the CYP3A study (pharmacokinetic [PK] analysis, n = 49), and 44 patients in the BCRP study were dosed (PK analysis, n = 44). In the CYP3A study, patients received single doses of simvastatin 40 mg on Days 1 and 31, and osimertinib 80 mg once daily on Days 3–32. In the BCRP study, single doses of rosuvastatin 20 mg were given on Days 1 and 32, and osimertinib 80 mg once daily on Days 4–34.ResultsGeometric least squares mean (GLSM) ratios (90% confidence intervals) of simvastatin plus osimertinib for area under the plasma concentration–time curves from zero to infinity (AUC) were 91% (77–108): entirely contained within the predefined no relevant effect limits, and Cmax of 77% (63, 94) which was not contained within the limits. GLSM ratios of rosuvastatin plus osimertinib for AUC were 135% (115–157) and Cmax were 172 (146, 203): outside the no relevant effect limits.ConclusionsOsimertinib is unlikely to have any clinically relevant interaction with CYP3A substrates and has a weak inhibitory effect on BCRP. No new safety concerns were identified in either study.
Porcine cytochrome 2A19 and 2E1
Authors: Burkina Viktoriia , Rasmussen Martin Krøyer , Oliinychenko Yelyzaveta , Zamaratskaia Galia 
Published: September 2018

AbstractCytochrome P450 (CYP) is a major group of enzymes, which conduct Phase I metabolism. Among commonly used animal models, the pig has been suggested as the most suitable model for investigating drug metabolism in human beings. Moreover, porcine CYP2A19 and CYP2E1 are responsible for the biotransformation of both endogenous and exogenous compounds such as 3‐methylindole (skatole), sex hormones and food compounds. However, little is known about the regulation of porcine CYP2A19 and CYP2E1. In this MiniReview, we summarise the current knowledge about the regulation of porcine CYP2A19 and CYP2E1 by environmental, biological and dietary factors. Finally, we reflect on the need for further research, to clarify the interaction between active feed components and the porcine CYP system.
A Survey on Data‐Driven 3D Shape Descriptors
Authors: Rostami R. , Bashiri F. S. , Rostami B. , Yu Z. 
Published: September 2018

AbstractRecent advances in scanning device technologies and improvements in techniques that generate and synthesize 3D shapes have made 3D models widespread in various fields including medical research, biology, engineering, etc. 3D shape descriptors play a fundamental role in many 3D shape analysis tasks such as point matching, establishing point‐to‐point correspondence, shape segmentation and labelling, and shape retrieval to name a few. Various methods have been proposed to calculate succinct and informative descriptors for 3D models. Emerging data‐driven techniques use machine learning algorithms to construct accurate and reliable shape descriptors. This survey provides a thorough review of the data‐driven 3D shape descriptors from the machine learning point of view and compares them in different criteria. Also, a comprehensive taxonomy of the existing descriptors is proposed based on the exploited machine learning algorithms. Advantages and disadvantages of each category have been discussed in detail. Besides, two alternative categorizations from the data type and the application perspectives are presented. Finally, some directions for possible future research are also suggested.
Psychometric properties of a questionnaire (HEMO‐FISS‐QoL) to evaluate the burden associated with haemorrhoidal disease and anal fissures
Authors: Abramowitz L. , Bouchard D. , Siproudhis L. , Trompette M. , Pillant H. , Bord C. , Senejoux C. A. , Favreau‐Weltzer C. , Berdeaux G. , Zkik A. 
Published: September 2018

AbstractAimCurrent questionnaires designed to evaluate the burden of haemorrhoidal disease ignore symptoms such as bleeding, pain and itching. A specific questionnaire is needed to evaluate the global impact of anal disorders on patients’ daily lives.MethodWe developed a questionnaire (HEMO‐FISS‐QoL) to assess the symptom burden of anal disorders and administered it to 256 patients (mean age 46.2 years; men 60.4%) with haemorrhoidal disease (67.2%), anal fissure (29.3%) or both (3.5%). Psychometric properties were evaluated by testing the acceptability, construct validity and reliability of the questionnaire. Principal components and multi‐trait analyses were used to identify dimensions and to assess construct validity. Backward Cronbach alpha curves and a graded response model were used to reduce the number of items and modalities. External validity was evaluated against SF‐12 and the Psychological Global Well‐Being Index (PGWBI) using Spearman's correlation coefficient.ResultsPrincipal component analysis defined four dimensions: physical disorders, psychology, defaecation and sexuality. The number of questions was reduced from 38 to 23. The HEMO‐FISS‐QoL scores correlated well with those of the SF‐12 and PGWBI (P < 0.001). Cronbach's coefficients (all > 0.7) reflected good internal reliability of the different dimensions. The total score increased with the severity of the anal disorders and with their consequences (days off work and personal spending related to the disease).ConclusionThe HEMO‐FISS‐QoL questionnaire reliably evaluates the global impact of haemorrhoids and anal fissures on patients’ daily lives. This simple tool may prove useful for treatment evaluation in clinical trials and daily practice.
Impact of endoscopic ultrasound‐guided fine‐needle biopsy on the diagnosis of subepithelial tumors: A propensity score‐matching analysis
Authors: Inoue Tadahisa , Okumura Fumihiro , Sano Hitoshi , Mizushima Takashi , Tsukamoto Hironobu , Fujita Yasuaki , Ibusuki Mayu , Kitano Rena , Kobayashi Yuji , Ishii Norimitsu , Ito Kiyoaki , Yoneda Masashi 
Published: September 2018

Background and AimImmunohistological evaluations are essential for diagnosing subepithelial tumors (SET). However, endoscopic ultrasound‐guided sampling using fine‐needle aspiration (FNA) needles is limited in its ability to procure core tissue for immunostaining. Fine‐needle biopsy (FNB) needles may mitigate this limitation. The present study aimed to examine the efficacy of FNB needles for procuring samples that enable the diagnosis of SET.MethodsOne hundred sixty patients were included in the study and separated into those whose samples were obtained using FNB needles (FNB group) and those whose samples were procured using FNA needles (FNA group). Groups were compared regarding the conclusive diagnosis rate and unwarranted resection rate. Propensity score matching was introduced to reduce selection bias.ResultsRates at which conclusive diagnoses were reached through adequate immunohistological evaluations were 82% and 60% in the FNB and FNA groups, respectively; this difference was significant (P = 0.013). Unwarranted resection rate was significantly lower in the FNB group (2%) than in the FNA group (14%; P = 0.032). Multivariate analyses showed that lesions ≤20 mm were a significant risk factor for lower conclusive diagnosis rates following the use of FNB needles (P = 0.017).ConclusionsFine‐needle biopsy needles can be useful for obtaining samples that facilitate the diagnosis of SET and for avoiding unwarranted resections. However, FNB needles may be less advantageous for small SET.
Real‐world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group
Authors: Akahane Takehiro , Kurosaki Masayuki , Itakura Jun , Tsuji Keiji , Joko Kouji , Kimura Hiroyuki , Nasu Akihiro , Ogawa Chikara , Kojima Yuji , Hasebe Chitomi , Wada Shuichi , Uchida Yasushi , Sohda Tetsuro , Suzuki Hideyuki , Yoshida Hideo , Kusakabe Atsunori , Tamada Takashi , Kobashi Haruhiko , Mitsuda Akeri , Kondo Masahiko , Shigeno Masaya , Ide Yasushi , Morita Atsuhiro , Kitamura Tadashi , Abe Takehiko , Izumi Namiki 
Published: September 2018

AimThis study aimed to describe the real‐world efficacy and safety of sofosbuvir (SOF) + ribavirin (RBV) for chronic hepatitis C, genotype 2.MethodsThis was a retrospective analysis of a nationwide, multicenter registry including 914 hepatitis C genotype 2 Japanese patients treated with SOF + RBV for 12 weeks. The rate of sustained virologic response at 12 weeks after treatment (SVR12), incidence of adverse events, and changes in serological parameters were analyzed.ResultsTreatment was completed in 98.9% of patients. Ribavirin dose reduction was required in 29.7% of patients. The SVR12 rate was 96.8% in the intention‐to‐treat population and 97.6% in the per‐protocol population. Factors associated with SVR12 were absence of advanced fibrosis (odds ratio, 5.76, P = 0.003) and interferon‐treatment‐naïve status (odds ratio, 4.79, P = 0.017). Dose reduction or total adherence of RBV was not associated with SVR. The resistance‐associated substitution S282 T in NS5B was not detected in any patient at virologic failure. Serum albumin levels significantly increased, and the degree of increase was greater in patients with advanced fibrosis than in those without (0.21 ± 0.32 vs. 0.05 ± 0.29, P < 0.0001). Alpha‐fetoprotein decreased significantly at end of treatment (P < 0.0001), and the degree of decrease was greater in patients with advanced fibrosis than in those without (21.7 ± 60.8 vs. 2.5 ± 15.5, P < 0.001). The most commonly reported adverse event was anemia (13.7%).ConclusionsTreatment with SOF + RBV was highly effective and safe in Japanese patients with HCV genotype 2 infection.
Evaluation of postoperative pain intensity following occlusal reduction in teeth associated with symptomatic irreversible pulpitis and symptomatic apical periodontitis: a randomized clinical study
Authors: Emara R. S. , Abou El Nasr H. M. , El Boghdadi R. M. 
Published: September 2018

AbstractAimTo assess the effect of occlusal reduction on postoperative pain following two visits root canal treatment in posterior mandibular teeth with symptomatic irreversible pulpitis and symptomatic apical periodontitis in a randomized clinical trial.MethodologyThis trial was conducted in the outpatient clinic of the Endodontic Department of the Faculty of Oral and Dental Medicine, Cairo University in Egypt. Forty‐four‐patients diagnosed with symptomatic irreversible pulpitis and symptomatic apical periodontitis were randomly assigned into two equal groups. The occlusal surfaces of teeth in the intervention group were reduced; whilst those assigned to the control group were left intact. Canal instrumentation was completed in the first visit using Revo‐S rotary nickel–titanium files, and pain intensity was assessed using a visual analogue scale (VAS) at 6, 12, 24 and 48 h. Canal filling was completed 7 days later, and pain intensity was assessed at 6 and 12 h. A placebo was given and analgesics were prescribed to be administered in case of severe postoperative pain. Data were analysed using Independent t‐test, chi‐square and Fisher Exact tests.ResultsThe mean pain scores within the two groups were associated with a significant continuous decrease over time. Following both instrumentation and canal filling, the mean pain scores in the intervention group were lower than those in the control group at all follow‐up periods and this difference was only significant at 12 h (P = 0.021 and P = 0.015, respectively).ConclusionsOcclusal reduction reduced levels of postoperative pain in posterior mandibular teeth with symptomatic pulpitis and apical periodontitis only 12 h following both canal preparation and root filling.
Palpebral cutaneous melanomas: a review of 17 cases from a tertiary center
Authors: Tas Faruk , Erturk Kayhan 
Published: September 2018

AbstractBackgroundMelanomas arising from eyelid skin are exceptionally rare, accounting for <1% of eyelid malignancies and all cutaneous melanomas. The aim of this study was to identify the histopathological features and clinical behaviors of the palpebral skin melanoma patients from a single tertiary institution.Patients and methodsSeventeen Caucasian patients diagnosed with eyelid cutaneous melanoma were analyzed retrospectively.ResultsThe median age of patients was 59 years, and females were predominant (n = 11). The most frequent localization of the lesions was the lower eyelid (n = 8). Nodular (n = 4), lentigo maligna (n = 3), and the superficial spreading melanoma (n = 3) were the most common histopathological subtypes. Only three patients had in situ melanomas. Tumor infiltrating lymphocytes were present in most of the patients; however, only a few cases had lymphovascular invasion. Regional lymph node involvement was present in two patients, and distant metastasis was found in only one patient. Four patients (24%) had disease relapses during follow‐up, all of which were locoregional. The median relapse‐free survival (RFS) time and 5‐year RFS rate were 26.3 months and 60.4%, respectively. Two patients (12%) died. Median OS time was 32.1 months, and 5‐year OS rate was 84%. Being elderly (older than 60 years of age) (P = 0.05), lesion originating from canthus compared to eyelid (P = 0.03) and presence of recurrence in follow‐up (P = 0.04) have been found as poor prognostic indicators for OS.ConclusionPalpebral skin melanoma is associated with favorable clinical features, and it is correlated with better survival rates.
Nuclear simple sequence repeat markers are superior to DNA barcodes for identification of closely related Rhododendron species on the same mountain
Authors: Wang Ji , Luo Jian , Ma Ya‐Zhen , Mao Xing‐Xing , Liu Jian‐Quan 
Published: September 2018

AbstractAccurate species delimitation of sampled biological material is critical for a range of studies. Although the DNA barcodes developed in recent years are useful for identifying numerous well differentiated species that have not experienced frequent gene flow, they fail to delimit recently diverged species, especially those with extensive introgressions. Here we use five Rhododendron species growing together on the same mountain as a model system to compare the species delimitation effectiveness of the DNA barcodes (internal transcribed spacer, matK, psbA‐trnH, and rbcL) previously proposed versus 15 pairs of microsatellite markers. Using these markers, we genotyped 129 individuals, which were members of five species according to morphological identification. We identified five simple sequence repeat genetic clusters (independently evolving lineages) corresponding to the morphological identification. However, we found that numerous individuals contained cryptic hybrid introgressions from the other species. The four DNA barcodes could not delimit three out of four closely related species that showed clear morphological differentiation and cryptic introgressions. Even after excluding all cryptic hybrids, two closely related species could not be successfully identified. The low discrimination ability of the DNA barcodes for closely related Rhododendron species could result from two, not mutually exclusive factors: introgressive hybridization and incomplete lineage sorting. Our results highlight the importance of simple sequence repeat markers in delimiting closely related species and identifying cryptic introgressions in the absence of morphological changes.