bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simple clinical model predicts incident hepatic steatosis in a community‐based cohort: The Framingham Heart Study
Authors: Long Michelle T. , Pedley Alison , Massaro Joseph M. , Hoffmann Udo , Ma Jiantao , Loomba Rohit , Chung Raymond T. , Benjamin Emelia J. 
Published: January 2018

AbstractBackground and AimsThe factors associated with incident hepatic steatosis are not definitively known. We sought to determine factors associated with incident hepatic steatosis, as measured on computed tomography, in the community.MethodsWe studied Framingham Heart Study participants without heavy alcohol use or baseline hepatic steatosis who underwent computed tomography scans between 2002‐2005 (baseline) and 2008‐2011 (follow‐up). We performed a stepwise logistic regression procedure to determine the predictors associated with incident hepatic steatosis.ResultsWe included 685 participants (mean age: 45.0 ± 6.2 years, 46.8% women). The incidence of hepatic steatosis in our sample was 17.1% over a mean 6.3 years of follow‐up. Participants who developed hepatic steatosis had more adverse cardiometabolic profiles at baseline compared to those free of hepatic steatosis at follow‐up. Multivariable stepwise regression analysis showed that a simple clinical model including age, sex, body mass index, alcohol consumption and triglycerides was predictive of incident hepatic steatosis (C statistic = 0.791, 95% CI: 0.748‐0.834). A complex clinical model, which included visceral adipose tissue volume and liver phantom ratio added to the simple clinical model, and had improved discrimination for predicting incident hepatic steatosis (C statistic = 0.826, 95% CI: 0.786‐0.866, P < .0001).ConclusionsThe combination of demographic, clinical and imaging characteristics at baseline was predictive of incident hepatic steatosis. The use of our predictive model may help identify those at increased risk for developing hepatic steatosis who may benefit from risk factor modification although further investigation is warranted.
Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes
Authors: Arunagiri Anoop , Haataja Leena , Cunningham Corey N. , Shrestha Neha , Tsai Billy , Qi Ling , Liu Ming , Arvan Peter 
Published: January 2018

AbstractThe endoplasmic reticulum (ER) is broadly distributed throughout the cytoplasm of pancreatic beta cells, and this is where all proinsulin is initially made. Healthy beta cells can synthesize 6000 proinsulin molecules per second. Ordinarily, nascent proinsulin entering the ER rapidly folds via the formation of three evolutionarily conserved disulfide bonds (B7–A7, B19–A20, and A6–A11). A modest amount of proinsulin misfolding, including both intramolecular disulfide mispairing and intermolecular disulfide‐linked protein complexes, is a natural by‐product of proinsulin biosynthesis, as is the case for many proteins. The steady‐state level of misfolded proinsulin—a potential ER stressor—is linked to (1) production rate, (2) ER environment, (3) presence or absence of naturally occurring (mutational) defects in proinsulin, and (4) clearance of misfolded proinsulin molecules. Accumulation of misfolded proinsulin beyond a certain threshold begins to interfere with the normal intracellular transport of bystander proinsulin, leading to diminished insulin production and hyperglycemia, as well as exacerbating ER stress. This is most obvious in mutant INS gene–induced Diabetes of Youth (MIDY; an autosomal dominant disease) but also likely to occur in type 2 diabetes owing to dysregulation in proinsulin synthesis, ER folding environment, or clearance.
Framework for laboratory harmonization of folate measurements in low‐ and middle‐income countries and regions
Authors: Pfeiffer Christine M. , Zhang Mindy , Jabbar Shameem 
Published: January 2018

AbstractThe measurement of serum and red blood cell folate, two commonly used biomarkers of folate status in populations, is complicated by analytical and data interpretation challenges. Folate results show poor comparability across laboratories, even using the same analytical technique. The folate microbiologic assay produces accurate results and requires simple instrumentation. Thus, it could be set up and maintained in low‐ and middle‐income country laboratories. However, the assay has to be harmonized through the use of common critical reagents (e.g., microorganism and folate calibrator) in order to produce comparable results across laboratories and over time, so that the same cutoff values can be applied across surveys. There is a limited need for blood folate measurements in a country owing to the periodic nature of surveys. Having a network of regional resource laboratories proficient in conducting the folate microbiologic assay and willing and able to perform service work for other countries will be the most efficient way to create an infrastructure wherein qualified laboratories produce reliable blood folate data. Continuous participation of these laboratories in a certification program can verify and document their proficiency. If the resource laboratories conduct the work on a fee‐for‐service basis, they could become self‐sustaining in the long run.
Agrin and LRP4 antibodies as new biomarkers of myasthenia gravis
Authors: Yan Min , Xing Guang‐Lin , Xiong Wen‐Cheng , Mei Lin 
Published: January 2018

AbstractMyasthenia gravis (MG) is a common disorder that affects the neuromuscular junction. It is caused by antibodies against acetylcholine receptor and muscle‐specific tyrosine kinase; however, some MG patients do not have antibodies against either of the proteins. Recent studies have revealed antibodies against agrin and its receptor LRP4—both critical for neuromuscular junction formation and maintenance—in MG patients from various populations. Results from experimental autoimmune MG animal models indicate that anti‐LRP4 antibodies are causal to MG. Clinical studies have begun to reveal the significance of the new biomarkers. With their identification, MG appears to be a complex disease entity that can be classified into different subtypes with different etiology, each with unique symptoms. Future systematic studies of large cohorts of well‐diagnosed MG patients are needed to determine whether each subtype of patients would respond to different therapeutic strategies. Results should contribute to the goal of precision medicine for MG patients. Anti‐agrin and anti‐LRP4 antibodies are also detectable in some patients with amyotrophic lateral sclerosis or Lou Gehrig's disease; however, whether they are a cause or response to the disorder remains unclear.
Comparative effectiveness clinical trials to advance treatment of myasthenia gravis
Authors: Guptill Jeffrey T. , Raja Shruti , Sanders Donald B. , Narayanaswami Pushpa 
Published: January 2018

AbstractMyasthenia gravis (MG) presents many challenges for establishing treatment efficacy through clinical trials. Among these are the rarity and heterogeneity of the disease, spontaneous fluctuations, prolonged latency to effect for many immunosuppressive drugs, and the uncertain generalizability of results from randomized controlled trials (RCTs). Prospective observational study designs may overcome some of these limitations, but attention is required to ensure that internal validity is not compromised. Observational comparative effectiveness research (CER) utilizes data obtained during routine clinical care to evaluate the effectiveness of interventions in real‐life practice conditions, thereby improving generalizability to the clinic. Compared with RCTs, observational CER studies may be less resource intensive and costly. Recent advances that have improved the feasibility of CER studies for MG are (1) the development of MG common data elements, (2) the publication of international consensus guidance for MG treatment, and (3) the development of a web‐based REDCap database that can be shared and adapted to standardize data collection. This infrastructure could be used for multisite comparisons of commonly used therapies and provides longitudinal information on patient‐ and clinician‐centered MG outcome measures. A challenge is to design studies that address the potential limitations of observational trials, such as confounding and selection and information bias.
Western lifestyle and immunopathology of multiple sclerosis
Authors: Matveeva Olga , Bogie Jeroen F.J. , Hendriks Jerome J.A. , Linker Ralf A. , Haghikia Aiden , Kleinewietfeld Markus 
Published: January 2018

AbstractThere is increasing evidence for a sudden and unprecedented rise in the incidence of multiple sclerosis (MS) in Westernized countries over the past decades, emphasizing the role of environmental factors. Among many candidates, rapid changes in dietary habits seem to play a role in the pathogenesis of MS. Here, we summarize and discuss the available evidence for the role of dietary nutrients, such as table salt, fatty acids, and flavonoids, in the development and pathogenesis of MS. We also discuss new and emerging risk factors accompanying Western lifestyle, such as shift work, sleep, and circadian disruption.
Serological and experimental studies in different forms of myasthenia gravis
Authors: Vincent Angela , Huda Saif , Cao Michelangelo , Cetin Hakan , Koneczny Inga , Rodriguez‐Cruz Pedro , Jacobson Leslie , Viegas Stuart , Jacob Saiju , Woodhall Mark , Nagaishi Akiko , Maniaol Angelina , Damato Valentina , Leite M. Isabel , Cossins Judith , Webster Richard , Palace Jacqueline , Beeson David 
Published: January 2018

AbstractAntibodies to the acetylcholine receptor (AChR) have been recognized for over 40 years and have been important in the diagnosis of myasthenia gravis (MG), and its recognition in patients of different ages and thymic pathologies. The 10–20% of patients who do not have AChR antibodies are now known to comprise different subgroups, the most commonly reported of which is patients with antibodies to muscle‐specific kinase (MuSK). The use of cell‐based assays has extended the repertoire of antibody tests to clustered AChRs, low‐density lipoprotein receptor–related protein 4, and agrin. Autoantibodies against intracellular targets, namely cortactin, titin, and ryanodine receptor (the latter two being associated with the presence of thymoma), may also be helpful as biomarkers in some patients. IgG4 MuSK antibodies are clearly pathogenic, but the coexisting IgG1, IgG2, and IgG3 antibodies, collectively, have effects that question the dominance of IgG4 as the sole pathologic factor in MuSK MG. After a brief historical review, we define the different subgroups and summarize the antibody characteristics. Experiments to demonstrate the in vitro and in vivo pathogenic roles of MuSK antibodies are discussed.
Sedation for magnetic resonance imaging using propofol with or without ketamine at induction in pediatrics—A prospective randomized double‐blinded study
Authors: Schmitz Achim , Weiss Markus , Kellenberger Christian , O`Gorman Tuura Ruth , Klaghofer Richard , Scheer Ianina , Makki Malek , Sabandal Carola , Buehler Philipp Karl 
Published: January 2018

SummaryIntroductionDeep sedation using propofol has become a standard technique in children. This double‐blinded randomized clinical trial aims to compare the clinical effects of propofol‐mono‐sedation vs a combination of propofol and ketamine at induction and a reduced propofol infusion rate for maintenance in children undergoing diagnostic magnetic resonance imaging.MethodsChildren aged from 3 months to 10 years scheduled as outpatients for elective magnetic resonance imaging with deep sedation were included. They were randomized into 2 groups, receiving either 1 mg/kg ketamine at induction, then a propofol infusion rate of 5 mg/kg/h or a propofol infusion rate of 10 mg/kg/h without prior ketamine. Time to full recovery (modified Aldrete score = 10) was the primary outcome. Further outcomes were quality of induction, immobilization during image acquisition, recovery, postoperative nausea and vomiting, emergence delirium using the Pediatric Anesthesia Emergence Delirium scale, vital signs and adverse cardiorespiratory events. All patients and parents as well as anesthetists, imaging technicians, and postsedation personnel were blinded. Data are given as median (range).ResultsIn total, 347 children aged 4.0 (0.25‐10.9) years, weighing 15.6 (5.3‐54) kg, ASA classification I, II, or III (141/188/18) were included. The ketamine‐propofol group showed significantly shorter recovery times (38 (22‐65) vs 54 (37‐77) minutes; median difference 14 (95% CI: 8, 20) minutes; P < .001), better quality of induction, and higher blood pressure, but higher incidence of movement requiring additional sedative drugs. There were no significant differences in respiratory side effects, cardiovascular compromise, emergence delirium, or postoperative nausea and vomiting.ConclusionBoth sedation concepts proved to be reliable with a low incidence of side effects. Ketamine at induction with a reduced propofol infusion rate leads to faster postanesthetic recovery.
WRKY1 acts as a key component improving resistance against Alternaria solani in wild tomato, Solanum arcanum Peralta
Authors: Shinde Balkrishna A. , Dholakia Bhushan B. , Hussain Khalid , Aharoni Asaph , Giri Ashok P. , Kamble Avinash C. 
Published: January 2018

SummaryEarly blight (EB), caused by Alternaria solani, is a major threat to global tomato production. In comparison with cultivated tomato (Solanum lycopersicum), a wild relative, S. arcanum exhibits strong resistance against EB. However, molecular cascades operating during EB resistance in wild or cultivated tomato plants are largely obscure. Here, we provide novel insight into spatio‐temporal molecular events in S. arcanum against A. solani. Transcriptome and co‐expression analysis presented 33‐WRKYs as promising candidates of which 12 SaWRKYs displayed differential expression patterns in resistant and susceptible accessions during EB disease progression. Among these, SaWRKY1 exhibited induced expression with significant modulation in xyloglucan endotrans hydrolase 5 (XTH5) and MYB2 expressions that correlated with the disease phenotypes. Electro‐mobility shift assay confirmed physical interaction of recombinant SaWRKY1 to SaXTH5 and SaMYB2 promoters. Comparative WRKY1 promoter analysis between resistant and susceptible plants revealed the presence of crucial motifs for defence mechanism exclusively in resistant accession. Additionally, many defence‐related genes displayed significant expression variations in both the accessions. Further, WRKY1 overexpressing transgenic plants exhibited higher levels of EB resistance while RNAi silencing lines had increased susceptibility to A. solani with altered expression of XTH5 and MYB2. Overall, these findings demonstrate the positive influence of WRKY1 in improving EB resistance in wild tomato and this could be further utilized as a potential target through genetic engineering to augment protection against A. solani in crop plants.
Injuries in Dutch elite field hockey players: A prospective cohort study
Authors: Delfino Barboza S. , Nauta J. , van der Pols M. J. , van Mechelen W. , Verhagen E. A. L. M. 
Published: January 2018

This study describes the prevalence, incidence density, severity, and nature of injuries in elite field hockey players over the Dutch 2015–2016 season. Eighty players answered a baseline questionnaire and were subsequently followed up every 2 weeks to report the hours spent on training/competition and experienced injuries, which were registered using the Oslo Sports Trauma Research Centre Questionnaire on Health Problems. Of the 74 players included in the analysis, 52 (70%) reported 112 injuries. Eighty‐seven injuries (78%) received medical attention, and 56 (50%) led to training/competition time‐loss. Thirty‐four injuries (30%) hampered players’ availability to train and compete. Most of the injuries (74%) were not caused by any contact. The mean prevalence of injury was 29% (95% confidence interval [CI] 3–55) for all, 9% (95% CI 0–20) for acute, and 14% (95% CI 0–36) for overuse injuries. Players sustained 3.5 (95% CI 2.5–4.5) new acute injuries per 1000 hours of training and 12.3 (95% CI 7.6–17.0) per 1000 hours of competition. The median of the severity score was 28 from 100 (25%–75% interquartile range [IQR] 16–42) for all, 35 (IQR 23–53) for acute, and 21 (IQR 16–31) for overuse injuries. On average, 1 in 4 elite field hockey players experiences an injury within a 2‐week period during the season. Although acute injuries are common, overuse injuries pose a comparable problem in elite field hockey. As injuries are a burden on players’ health and may hamper performance and availability to train and compete, prevention is of great importance.
3D imaging of cleared human skin biopsies using light‐sheet microscopy: A new way to visualize in‐depth skin structure
Authors: Abadie S. , Jardet C. , Colombelli J. , Chaput B. , David A. , Grolleau J.‐L. , Bedos P. , Lobjois V. , Descargues P. , Rouquette J. 
Published: January 2018

AbstractBackgroundHuman skin is composed of the superimposition of tissue layers of various thicknesses and components. Histological staining of skin sections is the benchmark approach to analyse the organization and integrity of human skin biopsies; however, this approach does not allow 3D tissue visualization. Alternatively, confocal or two‐photon microscopy is an effective approach to perform fluorescent‐based 3D imaging. However, owing to light scattering, these methods display limited light penetration in depth. The objectives of this study were therefore to combine optical clearing and light‐sheet fluorescence microscopy (LSFM) to perform in‐depth optical sectioning of 5 mm‐thick human skin biopsies and generate 3D images of entire human skin biopsies.Materials and MethodsA benzyl alcohol and benzyl benzoate solution was used to successfully optically clear entire formalin fixed human skin biopsies, making them transparent. In‐depth optical sectioning was performed with LSFM on the basis of tissue‐autofluorescence observations. 3D image analysis of optical sections generated with LSFM was performed by using the Amira® software.ResultsThis new approach allowed us to observe in situ the different layers and compartments of human skin, such as the stratum corneum, the dermis and epidermal appendages. With this approach, we easily performed 3D reconstruction to visualise an entire human skin biopsy. Finally, we demonstrated that this method is useful to visualise and quantify histological anomalies, such as epidermal hyperplasia.ConclusionThe combination of optical clearing and LSFM has new applications in dermatology and dermatological research by allowing 3D visualization and analysis of whole human skin biopsies.
Optical clearing agent reduces scattering of light by the stratum corneum and modulates the physical properties of coenocytes via hydration
Authors: Lee S.‐H. , Jun S.‐H. , Yeom J. , Park S.‐G. , Lee C.‐K. , Kang N.‐G. 
Published: January 2018

AbstractBackgroundThe interaction between light and the skin determine how the skin looks to the human eye. Light can be absorbed, scattered, and reflected by different components of the skin in a variety of different ways. Here, we focus on the scattering properties of the outmost layer, the stratum corneum (SC). However, we currently have limited methods with which to distinguish the scattering of light by SC from the changes due to other components of the skin.Materials and methodsDark‐field images of tape‐striped corneocytes were used in vitro to study the differences in light scattered by the SC and other skin components. Several optical clearing agents (OCAs) were tested for their ability to reduce light scattering. Physical properties of the SC (water content, keratin configuration, and volume) after OCA treatment were investigated using FT‐IR, confocal Raman microscopy, and 3D laser microscopy.ResultsUrea derivatives, several reducing sugars, and sugar alcohols, which were used as OCA in optics and also used as humectants in cosmetic area, could reduce scattering. However, unlike dehydration in optics, penetration of water into the keratin was increased at low OCA concentrations. In such conditions, the volume of corneocytes was increased but their stiffness was reduced.ConclusionBy analyzing the tape‐striped SC, we were able to measure the changes in the optical and physical properties of corneocytes in response to OCAs. Hydration of the SC layer by OCAs reduces light scattering from the corneocytes and would be helpful in moisturizing the skin and helping the skin look healthy.
Combination of FEM simulations and shearography for defect detection on artwork
Authors: Buchta D. , Heinemann C. , Pedrini G. , Krekel C. , Osten W. 
Published: January 2018

AbstractDigital shearography is an interferometric technique, which is often used for defect detection on composite structures. The measurement is fast and non‐destructive and thus suitable for the application to cultural heritage. However, a major drawback of the technique is the indirect measurement, because surface strain is used to detect subsurface defects. So the determination of depth, size, and type of the defects is rather difficult. To overcome this issue, we use a combination of finite element method simulation and shearographic measurement. Due to the comparison of both data sets, the inverse problem can be solved in a more reliable way. In this paper, we investigate the application of finite element method simulation for an improved defect detection on anisotropic material. We validate the technique on a wooden sample with notches on the backside.
Combined morphological and thermal analysis of lava flows: A way to boost understanding of emplacement dynamics
Authors: Tarquini Simone , Coppola Diego 
Published: January 2018

AbstractDuring emplacement, lavas modify the pre‐existing topography and release a large amount of heat. In spite of the relevance of both heat and mass release, combined morphological and thermal analyses have been seldom carried out at a flow‐field scale. Here, we consider a channelised lava flow unit formed at Mt Etna during the 2001 flank eruption, and we show that, by combining a morphological analysis of the pre‐ and post‐emplacement topography with the analysis of the syn‐eruptive thermal signature, critical insights about the processes driving mass and heat dissipation can be derived. Our results suggest that, in the considered lava flow, the pre‐emplacement slope controls heat dissipation and can influence the thickness of the final lava deposit, with possible implications for hazard assessment. The width of the lava channel, instead, appears less sensitive to the pre‐emplacement slope, and tends to regularly increase with increasing distance from the vent.
An efficient analytical method for computing the Boltzmann entropy of a landscape gradient
Authors: Gao Peichao , Zhang Hong , Li Zhilin 
Published: January 2018

AbstractEntropy is a central concept in thermodynamics and plays a fundamental role in understanding nature. It is commonly computed using Shannon's equation, and has been widely used to characterize disorder and to bridge the gap between disorder and thermodynamic interpretations. However, the thermodynamic basis of Shannon entropy is questioned by researchers, and it is suggested to use Boltzmann entropy as an alternative. Very recently, the first and only computation method has been proposed for the Boltzmann entropy of a landscape gradient, but the method is not efficient as it involves a series of numerical processes, which are computation‐intensive and time‐consuming. To improve it, a novel method is proposed in this study by developing an analytical solution to the key mathematical problem of the original method and incorporating a parallelization strategy. Experimental results demonstrate that the proposed method is both effective and efficient. Developed based on the proposed method, a software tool (as well as its source code) is released for free use. The proposed method and the developed tool shall contribute to an easy computation of the Boltzmann entropies of not only landscape gradients, but also remote sensing images and other quantitative raster data.