bluuebunny/crossref_metadata_2025_split huggingface dataset:
Will the Real Coeliac Disease Please Stand Up? Coeliac Disease Prevalence in the German LIFE Child Study
Authors: Händel Norman , Mothes Thomas , Petroff David , Baber Ronny , Jurkutat Anne , Flemming Gunter , Kiess Wieland , Hiemisch Andreas , Körner Antje , Schlumberger Wolfgang , Thiery Joachim , Wolf Johannes 
Published: June 2018

ABSTRACTObjectives:Assessing the seroprevalence and the prevalence of definite coeliac disease (CD) in the German LIFE Child Health study cohort including immunoglobulin A (IgA) antibodies against tissue transglutaminase (IgA‐TTG) in addition to IgG antibodies against deamidated gliadin peptides (IgG‐DGP) and human leukocyte antigen (HLA)‐DQ2/8 genotyping.Methods:Samples from children and adolescents were first screened for IgA‐TTG and IgG‐DGP. If IgA‐TTG was above 0.5 times the upper limit of normal and/or IgG‐DGP was positive, IgA antibodies against endomysium (IgA‐EmA) were measured, and HLA was genotyped. In patients with only IgG‐DGP positivity, total IgA was assayed. Subjects with suspicious results were followed up serologically and, in case of repeatedly positive antibody results, invited for a personal interview. Further diagnostic data were obtained independent from our study.Results:We screened 2363 children's blood samples collected from 2011 to 2015. The seroprevalence, that is, IgA‐TTG and/or IgA‐EmA positivity or IgG‐DGP positivity with IgA <0.05 g/L, was 1.57% (95% confidence interval [CI95%] 1.14–2.15). The prevalence of suspected CD, that is, seroprevalence and compatible HLA genotype with hitherto unknown mucosal damage, was 1.35% (CI95% 0.96–1.91). Definite CD, that is, seropositivity accompanied by positive intestinal biopsy or IgA‐TTG ≥ 10 × upper limit of normal, was found in 0.42% (CI95% 0.22–0.80). Seven children claimed to have CD. The HLA haplotype, however, matched in only 4 of them resulting in an overall CD prevalence of at least 0.59% (CI95% 0.34–1.02). Thirteen unclear cases remained; therefore, the prevalence may even be higher.Conclusions:The prevalence of definite CD in a population‐representative German cohort is higher than previously described. HLA‐DQ typing is helpful to identify false‐positive IgA‐TTG patients negative for IgA‐EmA and/or IgG‐DGP under screening conditions and unmasks possible misdiagnoses of CD.
Low Insulin‐like Growth Factor‐1 Influences Fatigue and Quality of Life in Children With Inflammatory Bowel Disease
Authors: Lucia Casadonte Chantal J. , Brown Jeffrey , Strople Jennifer , Neighbors Katie , Fei Lin , Alonso Estella M. 
Published: June 2018

ABSTRACTObjective:Fatigue is common among patients with inflammatory bowel disease (IBD). Proinflammatory cytokines are elevated in chronic inflammation and can induce “sickness behaviors,” such as fatigue. Chronic inflammatory states also lead to growth hormone resistance, demonstrated by low levels of insulin‐like growth factor (IGF‐1) and elevated growth hormone. This study evaluated the relationship between IGF‐1, proinflammatory cytokine levels, and fatigue in patients with IBD.Methods:In this prospective study children with IBD, ages 10 to 16 years, were recruited from a subspecialty ambulatory clinic. Participants and their parents completed age‐appropriate generic and disease‐specific health‐related quality of life (HRQOL) instruments. Serum samples obtained at the same encounter were analyzed for Th17 cytokine and IGF‐1 levels. HRQOL scores were compared to a healthy sample and HRQOL scores and cytokine levels were compared by IGF‐1 z score quartiles.Results:A total of 67 patients with IBD were recruited, median age of 13.7 years (interquartile range, 11.7–15.3). Forty‐eight (72%) had inactive disease based on Physician Global Assessment. Patients with IBD reported lower generic HRQOL (P = 0.0006) and more fatigue (P = 0.0004) than a healthy sample. Patients with IGF‐1 z scores in the lowest quartile had significantly lower disease‐specific HRQOL (P = 0.01) and more fatigue (P = 0.02) than the remainder of the cohort. Serum interleukin (IL)‐10, IL‐17A, IL‐6, and interferon‐γ were significantly higher in patients with IBD with IGF‐1 z scores in the lowest quartile (P < 0.05).Conclusions:Children with subclinical IBD experience more fatigue and lower generic HRQOL than healthy children. Lower IGF‐1 z scores are associated with more fatigue, and this relationship may be mediated through proinflammatory cytokines.
Diffuse 18F-FDG Avidity in Liver Associated With X-Linked Protoporphyria on PET/CT
Authors: Fu Zhanli , Liu Meng , Chen Xueqi , Yang Xing , Li Qian 
Published: June 2018

Abstract
An 18F-FDG PET/CT was performed on a 43-year-old woman with photosensitive skin rash, abnormal liver function, and pancytopenia, which demonstrated prominent hepatomegaly, splenomegaly, and diffuse liver 18F-FDG avidity. The liver biopsy revealed intrahepatic cholestasis with biliary fibrosis resulting from the deposition of protoporphyrin. X-linked erythroid-specific 5-aminolevulinate synthase gene analysis proved the diagnosis of X-linked protoporphyria.
Evidence of Prostate-Specific Membrane Antigen Expression in Metastatic Differentiated Thyroid Cancer Using 68Ga-PSMA-HBED-CC PET/CT
Authors: Verma Priyanka , Malhotra Gaurav , Agrawal Ritesh , Sonavane Sunita , Meshram Vilas , Asopa Ramesh V. 
Published: June 2018

Purpose of the Report
Prostate-specific membrane antigen (PSMA) overexpression is not restricted to prostate cancer, but it has also been demonstrated in gliomas, lung cancer, and in tumor neovasculature. Systematic studies exploring PSMA uptake in thyroid tumors are lacking. The aim of this pilot study was to assess PSMA expression in patients with metastatic differentiated thyroid cancer (mDTC).

Materials and Methods
Ten patients of mDTC harboring 32 lesions (5 men; age range, 38–65 years; mean age, 50 years) underwent prospective evaluation with radioiodine (131I), 18F-FDG PET, and 68Ga-PSMA-HBED-CC PET scans as per the institution protocol. PSMA expression (SUVmax) was compared with 18F-FDG and 131I scan findings in all patients.

Results
Lesions were radioiodine avid in 8 patients, whereas 2 were classified as thyroglobulin elevation with negative iodide scintigraphy (TENIS) patients. All patients with iodine-avid metastatic disease showed substantial PSMA uptake. PSMA PET detected 30/32 total lesions (93.75%; SUVmax ranging from 4.86 to 101.81 with median SUVmax of 31.35), whereas FDG PET/CT was positive in 23/32 lesions (81.85%). Twenty-one (70%) of 30 lesions that showed PSMA expression were localized to the bones. PSMA localized a lesion in each of the 2 TENIS patients similar to FDG PET scan.

Conclusions

68Ga-PSMA-HBED-CC PET/CT is a potentially useful imaging modality in patients of mDTC with most (70%) of PSMA expressing metastasis being localized to the bones. PSMA PET/CT could be useful for identifying patients with limited therapeutic options (eg, TENIS) who might benefit from PSMA-targeted radionuclide therapy.
Persistent Vaginal Leakage in the Setting of an Apical Vaginal Sinus Tract: A Case Report
Authors: Bastawros Dina , Beano Hamza , Kennelly Michael J. , Stepp Kevin J.E. 
Published: June 2018

Abstract
Fistulas are defined as abnormal connections between 2 organ, vessels, or structures. They can often present in the genitourinary tract as a result of iatrogenic injury during pelvic surgery. A 46-year-old female presents many years after a hysterectomy for persistent vaginal leakage with concern for a vesicovaginal fistula. Computed tomography urogram, intravenous retrograde pyelogram, and cystoscopy were negative for vesicovaginal fistula; however, a vaginal sinus tract was noted and further explored. This case report will describe the use of both laparoscopy and concomitant vaginoscopy to diagnose and, ultimately, surgically excise a salpingovaginal fistula.
Deep clustering of protein folding simulations
Authors: Bhowmik Debsindhu , Gao Shang , Young Michael T , Ramanathan Arvind 
Published: June 2018

AbstractWe examine the problem of clustering biomolecular simulations using deep learning techniques. Since biomolecular simulation datasets are inherently high dimensional, it is often necessary to build low dimensional representations that can be used to extract quantitative insights into the atomistic mechanisms that underlie complex biological processes. In this paper, we use a convolutional variational autoencoder (CVAE) to learn low dimensional, biophysically relevant latent features from long time-scale protein folding simulations in an unsupervised manner. We demonstrate our approach on three model protein folding systems, namely the Fs-peptide (14μs aggregate sampling), villin head piece (single trajectory of 125μs) and the mixedβ-β-α(BBA) protein (223 + 102μs sampling across two independent trajectories). In these systems, we show that the CVAE latent features learned correspond to distinct conformational substates along the protein folding pathways. The CVAE model predicts nearly 89% of all contacts within the folding trajectories correctly, while being able to extract folded, unfolded and potentially misfolded states in an unsupervised manner. Further, the CVAE model can be used to learn latent features of protein folding that can be applied to other independent trajectories, making it particularly attractive for identifying intrinsic features that correspond to conformational substates that share similar structural features. Together, we show that the CVAE model can quantitatively describe complex biophysical processes such as protein folding.
Quantifying Platelet Margination in Diabetic Blood Flow
Authors: Chang H.-Y. , Yazdani A. , Li X.J. , Douglas K. A. A. , Mantzoros C. S. , Karniadakis G. E. 
Published: June 2018

ABSTRACTPatients with type 2 diabetes mellitus (T2DM) develop thrombotic abnormalities strongly associated with cardiovascular diseases. In addition to the changes of numerous coagulation factors such as elevated levels of thrombin and fibrinogen, the abnormal rheological effects of red blood cells (RBCs) and platelets flowing in blood are crucial in platelet adhesion and thrombus formation in T2DM. An important process contributing to the latter is the platelet margination. We employ the dissipative particle dynamics method to seamlessly model cells, plasma, and vessel walls. We perform a systematic study on the RBC and platelet transport in cylindrical vessels by considering different cell shapes, sizes and RBC deformabilities in healthy and T2DM blood, as well as variable flowrates and hematocrit. In particular, we use cellular-level RBC and platelet models with parameters derived from patient-specific data and present a sensitivity study. We find T2DM RBCs, which are less deformable compared to normal RBCs, lower the transport of platelets toward the vessel walls whereas platelets with higher mean volume (often observed in T2DM) lead to enhanced margination. Furthermore, increasing the flowrate or hematocrit enhances platelet margination. We also investigated the effect of platelet shape and observed a non-monotonic variation with the highest near-wall concentration corresponding to platelets with moderate aspect ratio of 0.38. We examine the role of white blood cells (WBCs), whose count is increased notably in T2DM patients. We find that WBC rolling or WBC adhesion tend to decrease platelet margination due to hydrodynamic effects. To the best of our knowledge, such simulations of blood including all blood cells have not been performed before, and our quantitative findings can help separate the effects of hydrodynamic interactions from adhesive interactions, and potentially shed light on the associated pathological processes in T2DM such as increased inflammatory response, platelet activation and adhesion, and ultimately thrombus formation.
Engineered resistance to Zika virus in transgenicAe. aegyptiexpressing a polycistronic cluster of synthetic miRNAs
Authors: Buchman Anna , Gamez Stephanie , Li Ming , Antoshechkin Igor , Lee Shin-Hang , Wang Shin-Wei , Chen Chun-Hong , Klein Melissa J. , Duchemin Jean-Bernard , Paradkar Prasad N. , Akbari Omar S. 
Published: June 2018

AbstractRecent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection withWolbachiato reduce population size and/or vectoring competency, and gene drive based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered microRNAs (miRNAs) targeting ZIKV is expressed and fully processed following a blood meal inAe. aegypti, ensuring the formation of mature synthetic miRNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineeredAe. aegyptimosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.One Sentence SummaryHere we describe the generation ofAe. aegyptimosquitoes that are engineered to confer reduced vector competence to Zika virus (ZIKV) and we discuss how such engineering approach can be used to combat the major health burden of ZIKV and potentially other arboviruses in the future.
Tissue-specific cis-regulatory divergence implicates a fatty acid elongase necessary for inhibiting interspecies mating inDrosophila
Authors: Combs Peter A. , Krupp Joshua J. , Khosla Neil M. , Bua Dennis , Petrov Dmitri A. , Levine Joel D. , Fraser Hunter B. 
Published: June 2018

AbstractPheromones known as cuticular hydrocarbons are a major component of reproductive isolation inDrosophila. Individuals from morphologically similar sister species produce different sets of hydrocarbons that allow potential mates to identify them as a suitable partner. In order to explore the molecular mechanisms underlying speciation, we performed RNA-seq in F1 hybrids to measure tissue-specific cis-regulatory divergence between the sister speciesD. simulansandD. sechellia. By focusing on cis-regulatory changes specific to female oenocytes, we rapidly identified a small number of candidate genes. We found that one of these, the fatty acid elongaseeloF, broadly affects both the complement of hydrocarbons present onD. sechelliafemales and the propensity ofD. simulansmales to mate with those females. In addition, knockdown ofeloFin the more distantly relatedD. melanogasterled to a similar shift in hydrocarbons as well as lower interspecific mate discrimination byD. simulansmales. Thus, cis-regulatory changes ineloFappear to be a major driver in the sexual isolation ofD. simulansfrom multiple other species. More generally, our RNA-seq approach proved to be far more efficient than QTL mapping in identifying candidate genes; the same framework can be used to pinpoint cis-regulatory drivers of divergence in a wide range of traits differing between any interfertile species.
Developing a modern data workflow for evolving data
Authors: Yenni Glenda M. , Christensen Erica M. , Bledsoe Ellen K. , Supp Sarah R. , Diaz Renata M. , White Ethan P. , Ernest S.K. Morgan 
Published: June 2018

AbstractData management and publication are core components of the research process. An emerging challenge that has received limited attention in biology is managing, working with, and providing access to data under continual active collection. “Evolving data” present unique challenges in quality assurance and control, data publication, archiving, and reproducibility. We developed a evolving data workflow for a long-term ecological study that addresses many of the challenges associated with managing this type of data. We do this by leveraging existing tools to: 1) perform quality assurance and control; 2) import, restructure, version, and archive data; 3) rapidly publish new data in ways that ensure appropriate credit to all contributors; and 4) automate most steps in the data pipeline to reduce the time and effort required by researchers. The workflow uses two tools from software development, version control and continuous integration, to create a modern data management system that automates the pipeline.
Synergistic Recruitment of UbcH7~Ub and Phosphorylated Ubl Domain Triggers Parkin Activation
Authors: Condos Tara E.C. , Dunkerley Karen M. , Aisha Freeman E. , Barber Kathryn R. , Aguirre Jacob D. , Chaugule Viduth K. , Xiao Yiming , Konermann Lars , Walden Helen , Shaw Gary S. 
Published: June 2018

ABSTRACTThe mechanism of activation and ubiquitin conjugation by the E3 ligase parkin is pivotal to understand the molecular pathology of early-onset Parkinson’s disease. Parkin is normally autoinhibited but is activated by the kinase PINK1 that phosphorylates parkin’s N-terminal ubiquitin-like (pUbl) domain and ubiquitin. How these alter the structure of parkin to allow recruitment of an E2~Ub conjugate to enhance ubiquitination is an unresolved question. We present the structure of an incoming E2~Ub conjugate with the phospho-ubiquitin bound C-terminus of parkin (R0RBR). We show the UbcH7~Ub conjugate is recruited by R0RBR parkin in the open state whereby conjugated ubiquitin binds to the RING1/IBR interface. Further, NMR experiments indicate there is re-modelling near the RING0/RING2 interface remote from the E2-binding site. This, and parkin phosphorylation lead to rapid reactivity of the RING2(Rcat) catalytic cysteine in parkin, needed for ubiquitin transfer. Parkin phosphorylation also leads to relocation and weak interaction of the pUbl domain with the RING0 domain that is enhanced upon E2~Ub recruitment indicating these events act synergistically to drive parkin activity.
An introduced crop plant is driving diversification of the virulent bacterial pathogenErwinia tracheiphila
Authors: Shapiro Lori R. , Paulson Joseph N. , Arnold Brian J. , Scully Erin D. , Zhaxybayeva Olga , Pierce Naomi , Rocha J. , Klepac-Ceraj Vanja , Holton Kristina , Kolter Roberto 
Published: June 2018

AbstractErwinia tracheiphilais the causal agent of bacterial wilt of cucurbits, an economically important phytopathogen affecting few cultivated Cucurbitaceae host plant species in temperate Eastern North America. However, essentially nothing is known aboutE. tracheiphilapopulation structure or genetic diversity. To address this shortcoming, a representative collection of 88E. tracheiphilaisolates was gathered from throughout its geographic range, and their genomes were sequenced. Phylogenomic analysis revealed three genetic clusters with distincthrpT3SS virulence gene repertoires, host plant association patterns, and geographic distributions. The low genetic variation within each cluster suggests a recent population bottleneck followed by population expansion. We showed that in the field and greenhouse, cucumber (Cucumis sativus), which was introduced to North America by early Spanish conquistadors, is the most susceptible host plant species, and the only species susceptible to isolates from all three lineages. The establishment of large agricultural populations of highly susceptibleC. sativusin temperate Eastern North America may have facilitated the original emergence ofE. tracheiphilainto cucurbit agro-ecosystems, and this introduced plant species may now be acting as a highly susceptible reservoir host. Our findings have broad implications for agricultural sustainability by drawing attention to how worldwide crop plant movement, agricultural intensification and locally unique environments may affect the emergence, evolution, and epidemic persistence of virulent microbial pathogens.ImportanceErwinia tracheiphilais a virulent phytopathogen that infects two genera of cucurbit crop plants,Cucurbitaspp. (pumpkin and squash) andCucumisspp. (muskmelon and cucumber). One of the unusual ecological traits of this pathogen is that it is limited to temperate Eastern North America. Here, we complete the first large-scale sequencing of anE. tracheiphilaisolate collection. From phylogenomic, comparative genomic, and empirical analyses, we find that introducedCucumisspp. crop plants are driving the diversification ofE. tracheiphilainto multiple, closely related lineages. Together, the results from this study show that locally unique biotic (plant population) and abiotic (climate) conditions can drive the evolutionary trajectories of locally endemic pathogens in unexpected ways.
Long-read viral metagenomics enables capture of abundant and microdiverse viral populations and their niche-defining genomic islands
Authors: Warwick-Dugdale Joanna , Solonenko Natalie , Moore Karen , Chittick Lauren , Gregory Ann C. , Allen Michael J. , Sullivan Matthew B. , Temperton Ben 
Published: June 2018

AbstractMarine viruses impact global biogeochemical cycles via their influence on host community structure and function, yet our understanding of viral ecology is constrained by limitations in culturing of important hosts and the lack of a ‘universal’ gene to facilitate community surveys. Short-read viral metagenomic studies have provided clues to viral function and first estimates of global viral gene abundance and distribution. However, short-read assemblies are confounded by populations with high levels of strain evenness and nucleotide diversity (microdiversity), limiting assembly of some of the most abundant viruses on Earth. Assembly across genomic islands which likely contain niche-defining genes that drive ecological speciation is also challenging. While such populations and features are successfully captured by single-virus genomics and fosmid-based approaches, both techniques require considerable cost and technical expertise. Here we established a low-cost, low-input, high throughput alternative method for improving assembly of viral metagenomics using long read technology. Named ‘VirION’ (Viral, long-read metagenomics via MinION sequencing), our sequencing approach and complementary bioinformatics pipeline (i) increased number and completeness of assembled viral genomes compared to short-read sequencing methods; (ii) captured populations of abundant viruses with high microdiversity missed by short-read methods and (iii) captured more and longer genomic islands than short-read methods. Thus, VirION provides a high throughput and cost-effective alternative to fosmid and single-virus genomic approaches to more comprehensively explore viral communities in nature.
Linkage disequilibrium connects genetic records of relatives typed with disjoint genomic marker sets
Authors: Kim Jaehee , Edge Michael D. , Algee-Hewitt Bridget F. B. , Li Jun Z. , Rosenberg Noah A. 
Published: June 2018

AbstractIn familial searching in forensic genetics, a query DNA profile is tested against a database to determine whether it represents a relative of a database entrant. We examine the potential for using linkage disequilibrium to identify pairs of profiles as belonging to relatives when the query and database rely on nonoverlapping genetic markers. Considering data on individuals genotyped with both microsatellites used in forensic applications and genome-wide SNPs, we find that ~30-32% of parent–offspring pairs and ~35-36% of sib pairs can be identified from the SNPs of one member of the pair and the microsatellites of the other. The method suggests the possibility of performing familial searches of microsatellite databases using query SNP profiles, or vice versa. It also reveals that privacy concerns arising from computations across multiple databases that share no genetic markers in common entail risks not only for database entrants, but for their close relatives as well.