bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exsanguination From an Ulcerated, Atypical, Superficial Venous Malformation
Authors: Ma Li , Milne Nathan , Strutton Geoffrey , Ong Beng Beng 
Published: October 2018

Abstract
Venous malformations (VMs) are the most common vascular malformations, and their diagnosis can be challenging. They may develop in any region of the body, with highly variable clinical presentations. Although they typically present early in life, many case reports have documented the sudden appearance of a previously unrecognized venous malformation in adulthood. Pain is the major complaint in most of the cases, and other complications include phlebolith formation and bleeding. To our knowledge, fatal hemorrhage from a VM has not previously been reported in the medical literature. We present a case of exsanguination from a previously undiagnosed lower limb superficial VM. This case stresses the importance of proper diagnosis and management of VM.
Diagnostic Rate of Autoinflammatory Diseases Evaluated by Fever Patterns in Pediatric- and Adult-Onset Patients
Authors: Miyamae Takako , Hanaya Aki , Kawamoto Manabu , Tani Yumi , Kawaguchi Yasushi , Yamanaka Hisashi 
Published: October 2018

Objectives
This is a noncomparative study performed to determine if fever pattern is related to a diagnosis of autoinflammatory disease (AID) in pediatric- and adult-onset patients.

Methods
The final diagnosis of patients suspected to have AID was evaluated against gene polymorphisms known to be responsible for AID, clinical manifestations, and fever pattern, in our institute from 2005 to 2016. Genomic DNA was isolated from patients' peripheral blood, and polymerase chain reaction was used to amplify the indicated exons of 12 genes: MEFV, TNFRSF1A, MVK, NLRP3, NOD2, LI1RN, IL36RN, PSMB8, NALP12, PSTPIP1, TNFAIP3, and NLRC4. Genetic polymorphisms of the above genes were examined.

Results
All 210 individuals (135 pediatric onset and 75 adult onset) were classified into the following 3 subgroups: (1) periodic fever (n = 74 and 25 for pediatric and adult onset, respectively), (2) recurrent fever lacking a regular period (n = 47 and 41), and (3) persistent fever (n = 14 and 9). Diagnosis of AID was highest in subgroup 1 (70.2% and 36.0% for pediatric and adult onset, respectively), followed by subgroup 2(29.8% and 17.1%), including PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) (n = 34 and 1), familial Mediterranean fever (n = 22 and 13), cryopyrin-associated periodic syndrome (n = 6 and 1), and tumor necrosis factor receptor–associated periodic syndrome (n = 3 and 1 for pediatric and adult onset, respectively). None were diagnosed with AID in subgroup 3.

Conclusions
Autoinflammatory disease was more likely to be diagnosed in pediatric-onset patients compared with adult-onset patients. In both age-onset groups, AID was primarily identified in patients with periodic fever and never diagnosed in patients with persistent fever. Our findings indicate that fever pattern is a useful factor to estimate the probability of AID.
Prostate-Specific Membrane Antigen–Positive Manifestations of Chronic Beryllium Lung Disease
Authors: Huang Kai , Baur Alexander DJ , Furth Christian 
Published: October 2018

Abstract
Three years after prostatectomy, a 78-year-old man with initial high-risk prostate cancer and new increasing prostate-specific antigen levels underwent 68Ga-prostate-specific membrane antigen (PSMA) PET/CT. Imaging revealed PSMA-positive pelvic, ascending retroperitoneal and left supraclavicular lymph nodes consistent with metastases. Additionally, there was PSMA-positive lymphadenopathy (hilar and mediastinal) and pulmonary changes (fibrotic and nodular) in which histopathology excluded metastases. A lymphocyte proliferation test was indicative of beryllium sensitization. Chronic beryllium lung disease—a multisystem granulomatous inflammatory disease mainly affecting the lungs—could be established in this patient with occupational exposure to beryllium. This case shows that manifestations of berylliosis can also be PSMA positive.
Is the Neutrophil-to-Lymphocyte Ratio Associated With Increased Morbidity After Colorectal Surgery?
Authors: Benlice Cigdem , Onder Akin , Babazade Rovnat , Hrabe Jennifer , Stocchi Luca , Steele Scott , Gorgun Emre 
Published: October 2018

Purpose:
We aimed to evaluate the association between preoperative and postoperative neutrophil-to-lymphocyte ratio (NLR) and 30-day postoperative complications after colorectal surgery.

Methods:
Patients undergoing elective colorectal surgery between January, 2010 and December, 2014 were identified. Patients who had preoperative and postoperative days 1 and 2 (Postoperative day [POD]-1, POD-2) NLR were included in the study. Primary study outcomes were optimal NLR cutoff values at preop, POD-1, and POD-2.

Results:
A total of 1328 patients met the inclusion criteria. Of those, 518 (39%) patients experienced at least one postoperative complication. Sex (P<0.001), diabetes mellitus (DM) (P<0.001), diagnosis (P=0.001), operation type (P=0.03), and open surgery (P<0.001) were statistically associated with higher NLR (POD-1, P=0.02; POD2, P=0.01). DM (OR, 1.97; 95%CI, 1.27-3.08; P=0.003] and NLR on POD-2≥9.2 (OR, 1.43; 95%CI, 1.03-1.98; P=0.02) were significantly related to postoperative complications.

Conclusions:
NLR may provide clinicians with an additional tool for identifying patients at high risk for postoperative complications after elective colorectal surgery. Routine use of NLR may lead to early intervention and potentially improve the management of complications after colorectal surgery.
Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter
Authors: Sato-Hashimoto Miho , Nozu Tomomi , Toriba Riho , Horikoshi Ayano , Akaike Miho , Kawamoto Kyoko , Hirose Ayaka , Hayashi Yuriko , Nagai Hiromi , Shimizu Wakana , Saiki Ayaka , Ishikawa Tatsuya , Elhanbaly Ruwaida , Kotani Takenori , Murata Yoji , Saito Yasuyuki , Naruse Masae , Shibasaki Koji , Oldenborg Pre-Arne , Jung Steffen , Matozaki Takashi , Fukazawa Yugo , Ohnishi Hiroshi 
Published: October 2018

AbstractA characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα knockout mice exhibited the same phenotype, suggesting the interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage in the white matter, but resulted in the increased expression of genes characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.
Variation in tolerance to parasites in natural Asian tiger mosquito populations and its effect on vectorial capacity
Authors: Dharmarajan Guha , Walker Kathryne D. , Lehmann Tovi 
Published: October 2018

AbstractThe vectorial capacity of mosquitoes depends upon the magnitude of reduction of parasite load upon infection through resistance mechanisms (e.g., immune-mediated killing) and the ability of mosquitoes to offset infection-mediated costs through tolerance mechanisms (e.g., tissue repair). Here we use a common-garden experimental framework to measure variation in resistance and tolerance to dog heartworm (Dirofilaria immitis) between natural Aedes albopictus mosquito populations representing areas of low and high transmission intensity. Our data revealed that survival to the extrinsic incubation period, the earliest time point at which infective L3 larvae develop, significantly differed between populations (ranging from 10-60%) when mosquitoes infected with D. immitis at both the low (15 microfilaria/μl blood) and high (30 microfilaria/μl blood) infection dose (Dose: χ2 = 191.473; P < 0.001; Population: χ2 = 24.485; P = 0.001; Dose × Population: χ2 = 35.566; P = 0.001). Contrary to expectations, we found that mosquito populations with highest resistance (i.e., greatest reduction in parasite load) also exhibited highest mortality upon infection (F1,12 = 6.781, P = 0.023; Dose: F1,12 = 6.747; P = 0.023; Mortality × Dose: F1,12 = 0.111, P = 0.744). Expressing the effect of the number of killed (NKILLED) and live (NLIVE) parasite on survival of mosquitoes from the different population, we document a significant inter-population variation in the survival cost of additional parasite (i.e., tolerance to infection (NLIVE × Population: χ2 = 22.845; P = 0.002; NKILLED × Population: χ2 = 31.959; P = < 0.001; NLIVE × NKILLED × Population: χ2 = 22.266; P = 0.002), in conjunction with negative relationship between tolerance and resistance (Resistance: F1,12 = 11.870, P = 0.005; Dose: F1,12 = 16.0170, P = 0.002; Resistance × Dose: F1,12 = 9.699, P =0.009). Importantly, populations from areas with high transmission intensity (as measured by parasite prevalence in dogs) showed elevated tolerance (Prevalence: F1,12 = 9.5, P = 0.012; Prevalence2: F1,12 = 4.353, P = 0.064; Dose: F1,12 = 38.855, P = <0.001), and these populations were also associated with increased vectorial capacity (Tolerance: F1,12 = 8.175, P = 0.014; Dose: F1,12 = 0.005, P = 0.946; Tolerance × Dose: F1,12 = 0.920, P = 0.356). Consequently, our data indicate that spatial variation in disease transmission intensity is linked to the evolution of tolerance in natural mosquito populations, which in turn can feedback to impact disease risk.
Immigration from the metacommunity affects bdelloid rotifer community dynamics most
Authors: Debortoli Nicolas , De Laender Frederik , Van Doninck Karine 
Published: October 2018

AbstractDispersal is an important driver of local community dynamics. It has been proposed that, for communities composed of microscopic organisms, dispersal could well be the dominant process, outpacing local processes driven by environmental conditions and species interactions. This is because microscopic organisms often reproduce asexually, fostering rapid colonization, and are easily dispersed by water or air current. We studied the case of bdelloid rotifers belonging to the genus Adineta, microscopic asexual animals with dried stages that are easily dispersed by wind to investigate the relative effects of dispersal and local processes on their community dynamics. To this end, we constructed a classic competition model to theoretically examine how spatial and local biodiversity dynamics varied with fitness and dispersal characteristics of bdelloid Adineta species. Next, we compared our predictions with an experimental dataset containing spatio-temporal Adineta community dynamics from the wild. This comparison suggested that immigration from the local meta-community was the most critical parameter under the conditions tested. One Adineta vaga species, abundant in the surrounding area, rapidly colonized our experimental habitats and dominated most of the communities. We also ran the model under different levels of environmental conditions (permissive, intermediate and harsh) to simulate seasonal community variability and found that communities experience important bottlenecks yearly in winter but that the same community re-established. The dissimilarities observed between roof communities suggest differences in adaptation or immigration capacities. Besides their asexual reproduction and extreme desiccation tolerance, a key characteristic of bdelloid ecology identified here, is the spatio-temporal dynamic of abundant bdelloid clones present in the meta-community that rapidly colonize empty patches to establish new populations.
A physiology-based model of bile acid metabolism shows altered tissue concentrations after drug administration and in specific genotype subgroups
Authors: Baier V. , Cordes H. , Thiel C. , Neumann U. , Blank L.M. , Kuepfer L. 
Published: October 2018

AbstractDrug-induced liver injuries (DILI) are an important issue in drug development and patient safety and often lead to termination of drug-development programs or late withdrawals of drugs. Since DILI events are hard to diagnose in preclinical settings, a need for alternative prediction methods such as computational modeling emerges. Impairment of bile acid (BA) metabolism, known as cholestasis, is a frequent form of DILI. Being rather a systemic then a single organ related disease, whole-body physiology-based modeling is a predestined approach for cholestasis modeling. The objectives of the presented study were 1) the development of a physiology-based model for human bile acid metabolism, 2) model validation and characterization for a virtual population, and 3) prediction and quantification of the effects of genetic predispositions and drug interaction on bile acid metabolism. The developed physiology-based bile acid (PBBA) model is based on the standard PBPK model of PKSim® and describes the bile acid circulation in a healthy reference individual. Active processes such as the hepatic synthesis, gallbladder emptying upon meal intake, transition through the gastrointestinal tract, reabsorption into the liver, distribution within the body, and excretion are included. The kinetics of active processes for the surrogate BA glycochenodeoxycholic acid were fitted to time-concentration profiles of blood BA levels reported in literature. The robustness of our PBBA model is underlined by the comparison of simulated plasma BA concentrations in a virtual population of 1,000 healthy individuals with reported data. In addition to plasma concentrations, the PBBA model allows simulations of BA exposure in relevant tissues like the liver and can therefore enhance the mechanistic understanding of cholestasis. This feature was used to analyse the reported increased risk of cholestatic DILI in Benign Recurrent Intrahepatic Cholestasis type 2 (BRIC2) patients. Simulations of the PBBA model suggest a higher susceptibility of BRIC2 patients towards cholestatic DILI due to BA accumulation in hepatocytes. Apart from these intrinsic effects, drug-interactions and their effect on the systemic bile acid metabolism were simulated by combining the PBBA model with a drug PBPK model of cyclosporine A (CsA). The results of which confirmed the reported higher risk of developing DILI as a consequence of CsA intake. Altogether, the presented model enhances our mechanistic understanding of cholestasis, allows the identification of drug-interactions leading to altered BA levels in blood and organs, and could be used to prevent clinical cases of cholestasis and enhance patient safety.
MeShClust2: Application of alignment-free identity scores in clustering long DNA sequences
Authors: James Benjamin T. , Girgis Hani Z. 
Published: October 2018

ABSTRACTGrouping sequences into similar clusters is an important part of sequence analysis. Widely used clustering tools sacrifice quality for speed. Previously, we developed MeShClust, which utilizes k-mer counts in an alignment-assisted classifier and the mean-shift algorithm for clustering DNA sequences. Although MeShClust outperformed related tools in terms of cluster quality, the alignment algorithm used for generating training data for the classifier was not scalable to longer sequences. In contrast, MeShClust2 generates semi-synthetic sequence pairs with known mutation rates, avoiding alignment algorithms. MeShClust2clustered 3600 bacterial genomes, providing a utility for clustering long sequences using identity scores for the first time.
Crossover recombination and synapsis are linked by adjacent regions within the N terminus of the Zip1 synaptonemal complex protein
Authors: Voelkel-Meiman Karen , Cheng Shun-Yun , Parziale Melanie , Morehouse Savannah J. , Feil Arden , Davies Owen R. , Muyt Arnaud de , Borde Valérie , MacQueen Amy J. 
Published: October 2018

AbstractAccurate chromosome segregation during meiosis relies on the prior establishment of at least one crossover recombination event between homologous chromosomes, which is often associated with the meiosis-specific MutSγ complex. The recombination intermediates that give rise to MutSγ interhomolog crossovers are embedded within a hallmark meiotic prophase structure called the synaptonemal complex (SC), but the mechanisms that coordinate the processes of SC assembly (synapsis) and crossover recombination remain poorly understood. Among known central region building blocks of the budding yeast SC, the Zip1 protein is unique for its SC-independent role in promoting MutSγ crossovers. Here we report that adjacent regions within Zip1’s unstructured N terminus encompass its crossover and SC assembly functions. We previously showed that deletion of Zip1 residues 21-163 abolishes tripartite SC assembly and prevents the robust SUMOylation of the SC central element component, Ecm11, but allows excess MutSγ crossover recombination. We find the reciprocal phenotype when Zip1 residues 2-9 or 10-14 are deleted; in these mutants SC assembles and Ecm11 is hyperSUMOylated, but MutSγ crossovers are strongly diminished. Interestingly, Zip1 residues 2-9 or 2-14 are required for the normal localization of Zip3, a putative E3 SUMO ligase and pro-MutSγ crossover factor, to Zip1 polycomplex structures and to recombination initiation sites. By contrast, deletion of Zip1 residues 15-20 does not detectably prevent Zip3’s localization at Zip1 polycomplex and supports some MutSγ crossing over but prevents normal SC assembly and robust Ecm11 SUMOylation. These results highlight distinct N terminal regions that are differentially critical for Zip1’s roles in crossover recombination and SC assembly; we speculate that the adjacency of these regions enables Zip1 to serve as a liaison, facilitating crosstalk between the two processes by bringing crossover recombination and synapsis factors in close proximity to one another.
Arginine methylation of DDX5 RGG/RG motif by PRMT5 regulates RNA:DNA resolution
Authors: Mersaoui Sofiane Y. , Yu Zhenbao , Coulombe Yan , Karam Martin , Busatto Franciele F. , Masson Jean-Yves , Richard Stéphane 
Published: October 2018

AbstractAberrant transcription-associated RNA:DNA hybrid (R-loop) formation often lead to catastrophic conflicts during replication resulting in DNA double strand breaks and genome instability. To prevent such conflicts, these hybrids require dissolution by helicases and/or RNaseH. Little information is known about how these helicases are regulated. Herein, we identify DDX5, an RGG/RG motif containing DEAD-box family of RNA helicase, as a crucial player in R-loop resolution. We define at the mechanistic level the function of DDX5 in R-loop resolution. In vitro, recombinant DDX5 resolves R-loops in an ATP-dependent manner leading to R-loop degradation by the XRN2 exoribonuclease. DDX5 deficient cells accumulated R-loops at loci known to form R-loops using RNA:DNA immunoprecipitation (DRIP)-qPCR and increased RNaseH sensitive RAD51 foci. PRMT5, an arginine methyltransferase, associated with DDX5 and methylated its RGG/RG motif. This motif was required to associate with XRN2 and resolve cellular R-loops. Furthermore, PRMT5 deficient cells accumulated R-loops, as detected by DRIP-qPCR resulting in increased gH2AX foci. Our findings define a new mechanism by which an RNA helicase, DDX5, is modulated by arginine methylation to resolve R-loops.
Staphylococcus aureus PSMα3 Cross-α Fibril Polymorphism and Determinants of Cytotoxicity
Authors: Tayeb-Fligelman Einav , Salinas Nir , Tabachnikov Orly , Landau Meytal 
Published: October 2018

SummaryThe phenol-soluble modulin (PSM) peptide family, secreted by Staphylococcus aureus, performs various virulence activities, some mediated by the formation of amyloid fibrils of diverse architectures. Specifically, PSMα1 and PSMα4 structure the S. aureus biofilm by assembling into robust cross-β amyloid fibrils. PSMα3, the most cytotoxic member of the family, assembles into cross-α fibrils in which α-helices stack into tightly mated sheets, mimicking the cross-β architecture. Here we demonstrated that massive T-cell deformation and death is linked with PSMα3 aggregation and co-localization with cell membranes. Our extensive mutagenesis analyses supported the role of positive charges, and especially Lys17, in interactions with the membrane, and suggested their regulation by inter- and intra-helical electrostatic interactions within the cross-α fibril. We hypothesize that PSMα3 cytotoxicity is governed by the ability to form cross-α fibrils and involves a dynamic process of co-aggregation with cell membrane, rupturing it.HighlightsThe cytotoxic S. aureus PSMα3 assembles into cross-α fibrilsCross-α fibril polymorphism and mutations-induced secondary structure switchingRegulation by cross-α fibril inter- and intra-helical electrostatic interactionsToxicity as a putative dynamic process of PSMα3 co-aggregation with membranes
KCF-Convoy: efficient Python package to convert KEGG Chemical Function and Substructure fingerprints
Authors: Sato Masayuki , Suetake Hirotaka , Kotera Masaaki 
Published: October 2018

AbstractMotivationIn silico methodologies to assess pharmaceutical activity and toxicity are increasingly important in QSAR, and many chemical fingerprints have been developed to tackle this problem. Among them, KEGG Chemical Function and Substructure (KCF-S) has been shown to perform well in some pharmaceutical and metabolic studies. However, the software that generates KCF-S fingerprints has limited usability: the input file must be Molfile or SDF format, and the output is only a text file.ResultsWe established a new Python package, KCF-Convoy, to generate KCF format and KCF-S fingerprints from Molfile, SDF, SMILES, and InChI seamlessly. The obtained KCF-S was used in a number of supervised machine-learning methods to distinguish herbicides from other pesticides, and to find characteristic substructures in taxonomy groups.AvailabilityKCF-Convoy is implemented as a Python package freely available at https://github.com/KCF-Convoy and the user can use the package management system “pip” and also the Docker environment.Contactmaskot@chemsys.t.u-tokyo.ac.jp