bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Oxygenation on Ex Vivo Kidneys Undergoing Hypothermic Machine Perfusion
Authors: Patel Kamlesh , Smith Thomas B. , Neil Desley A.H. , Thakker Alpesh , Tsuchiya Yugo , Higgs Ellen B. , Hodges Nikolas J. , Ready Andrew R. , Nath Jay , Ludwig Christian 
Published: November 2018

Background
Supplemental oxygenation of the standard hypothermic machine perfusion (HMP) circuit has the potential to invoke favorable changes in metabolism, optimizing cadaveric organs before transplantation.

Methods
Eight pairs of porcine kidneys underwent 18 hours of either oxygenated (HMP/O2) or aerated (HMP/Air) HMP in a paired donation after circulatory death model of transplantation. Circulating perfusion fluid was supplemented with the metabolic tracer universally labeled glucose.
Perfusate, end-point renal cortex, and medulla samples underwent metabolomic analysis using 1-dimension and 2-dimension nuclear magnetic resonance experiments in addition to gas chromatography-mass spectrometry. Analysis of 13C-labeled metabolic products was combined with adenosine nucleotide levels and differences in tissue architecture.

Results
Metabolomic analysis revealed significantly higher concentrations of universally labeled lactate in the cortex of HMP/Air versus HMP/O2 kidneys (0.056 mM vs 0.026 mM, P < 0.05). Conversely, newly synthesized [4,5-13C] glutamate concentrations were higher in the cortex of HMP/O2 kidneys inferring relative increases in tricarboxylic acid cycle activity versus HMP/Air kidneys (0.013 mmol/L vs 0.003 mmol/L, P < 0.05). This was associated with greater amounts of adenoside triphosphate in the cortex HMP/O2 versus HMP/Air kidneys (19.8 mmol/mg protein vs 2.8 mmol/mg protein, P < 0.05). Improved flow dynamics and favorable ultrastructural features were also observed in HMP/O2 kidneys. There were no differences in thiobarbituric acid reactive substances and reduced glutathione levels, tissue markers of oxidative stress, between groups.

Conclusions
The supplementation of perfusion fluid with high-concentration oxygen (95%) results in a greater degree of aerobic metabolism versus aeration (21%) in the nonphysiological environment of HMP, with reciprocal changes in adenoside triphosphate levels.
Racial Disparities in the Administration of ECT in Texas, 1998–2013
Authors: Dennis Paul A. , Thomas Shaun N. , Husain Mustafa M. , Dennis Nora M. 
Published: November 2018

Objective
Electroconvulsive therapy (ECT) is a treatment of choice for severe depression but has been underutilized among black patients. This study investigates racial disparities in the administration of ECT in the state of Texas between 1998 and 2013 using population data.

Design
Data from the Texas Department of State Health Services were obtained corresponding to the use for all ECT conducted in nonfederal settings during the period from January 2, 1998, to August 30, 2013. The data set comprised quarterly reports generated for each patient, totaling 27,931 patient quarters. Using year-by-year intercensal population estimates for the state of Texas, ECT treatments per capita were compared among black, white, Latina/Latino, and other individuals during this time period.

Results
Significantly more white patients were treated each quarter than minority patients (P < 0.001), with Latina/Latino patients recording fewer treatment quarters than any other racial group (P < 0.005). Large discrepancies in diagnosis by race were observed. Black patients were less likely than white and Latina/Latino patients to be diagnosed with depression and 4 times as likely as white patients to carry a diagnosis of schizophrenia.

Conclusions
Concordant with previous data, large racial disparities in the administration of ECT were found in this Texas data set. Despite the limited nature of this data set, these results suggest that continued investigation is required to determine factors responsible for these disparities.
Transnasal Humidified Rapid-Insufflation Ventilatory Exchange During Electroconvulsive Therapy
Authors: Jonker Yori , Rutten Dennis J. , van Exel Eric R. , Stek Max L. , de Bruin Paul E. , Huitink Johannes M. 
Published: November 2018

Background
In electroconvulsive therapy (ECT), a generalized seizure is provoked under general anesthesia. Standard airway management is done by face mask ventilation, but this is difficult during generalized seizure. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) is a method to increase apnea tolerance and permit apnea oxygenation. We hypothesize that THRIVE can oxygenate the patient during ECT and that it is comfortable for patients.

Methods
In this single-center feasibility study, 13 patients with a pharmacotherapy-resistant depressive disorder underwent 20 ECT sessions with the use of THRIVE. They received general anesthesia under standard monitoring and transcutaneous carbon dioxide monitoring. Afterward, they completed a survey comparing their prior experience with face mask oxygenation.

Results
There were no desaturations during the procedure, and patient comfort showed no difference in comparison to face mask. Compared with data from earlier ECT with face mask ventilation in the same patient, THRIVE did not seem to shorten seizure duration.

Conclusions
THRIVE is a novel, safe oxygenation method during ECT.
Synthesis, SAR and Docking Studies of Substituted Aryl phenylthiazolyl phenylcarboxamide as PTP-1B Inhibitors
Authors: Varshney Kanika , Gupta Amit K. , Rawat Arun , Srivastava Rohit , Mishra Akansha , Saxena Mridula , Srivastava Arvind K. , Jain Sudha , Saxena Anil K. 
Published: November 2018

AbstractInspired by the potent PTP1B inhibitory activity reported in a novel series of substituted aryl thiazolyl phenylsulphonamides(I), sulfonyl moiety in the most active compound (I, R= OCH3, R1= CF3, 73.6% PTP1B inhibition) was replaced by benzoyl group (region B) to afford compoundIIwhich showed lesser activity (50.5% PTP1B inhibition). To optimize the activity, further structural modifications were done on compoundIIat region A, B and C to design and synthesize a series of 24 aryl phenylthiazolyl phenylcarboxamides for evaluation against PTP1B enzyme. Among these compounds six compounds showed good PTP1B inhibitory activity in the order of compound38 > 30 > 29 > 37 > 22 > 19. The lowest energy conformer of compound38at PTP1B active site shows favorable binding similar to known PTP1B binders and explains its selectivity towards PTP1B. Compound38also showed promising antihyperglycemic, antidyslipidemic and insulin resistant reversal activitiesin vivoin STZ model and db/db mice model. Altogether, the compound38present an excellent candidate for future PTP1B targeted drug discovery.
Modeling Attention Control Using A Convolutional Neural Network Designed After The Ventral Visual Pathway
Authors: Yu Chen-Ping , Liu Huidong , Samaras Dimitris , Zelinsky Gregory 
Published: November 2018

AbstractRecently we proposed that people represent object categories using category-consistent features (CCFs), those features that occur both frequently and consistently across a categorys exemplars [70]. Here we designed a Convolutional Neural Network (CNN) after the primate ventral stream (VsNet) and used it to extract CCFs from 68 categories of objects spanning a three-level category hierarchy. We evaluated VsNet against people searching for the same targets from the same 68 categories. Not only did VsNet replicate our previous report of stronger attention guidance to subordinate-level targets, with its more powerful CNN-CCFs it was able to predict attention control to individual target categories–the more CNN-CCFs extracted for a category, the faster gaze was directed to the target. We also probed VsNet to determine where in its network of layers these attention control signals originate. We found that CCFs extracted from VsNet’s V1 layer contributed most to guiding attention to targets cued at the subordinate (e.g., police car) and basic (e.g., car) levels, but that guidance to superordinate-cued (e.g., vehicle) targets was strongest using CCFs from the CIT+AIT layer. We also identified the image patches eliciting the strongest filter responses from areas V4 and higher and found that they depicted representative parts of an object category (e.g., advertisements appearing on top of taxi cabs). Finally, we found that VsNet better predicted attention control than comparable CNN models, despite having fewer convolutional filters. This work shows that a brain-inspired CNN can predict goal-directed attention control by extracting and using category-consistent features.
PEDIA: Prioritization of Exome Data by Image Analysis
Authors: Hsieh Tzung-Chien , Mensah Martin Atta , Pantel Jean Tori , Peter Krawitz ,   the PEDIA consortium, Aguilar Dione , Bar Omri , Bayat Allan , Becerra-Solano Luis , Bentzen Heidi Beate , Biskup Saskia , Borisov Oleg , Braaten Oivind , Ciaccio Claudia , Coutelier Marie , Cremer Kirsten , Danyel Magdalena , Daschkey Svenja , David-Eden Hilda , Devriendt Koenraad , Dölken Sandra , Douzgou Sofia , Đukić Dejan , Ehmke Nadja , Fauth Christine , Fischer-Zirnsak Björn , Fleischer Nicole , Gabriel Heinz , Graul-Neumann Luitgard , Gripp Karen W. , Gurovich Yaron , Gusina Asya , Haddad Nechama , Hajjir Nurulhuda , Hanani Yair , Hertzberg Jakob , Konstanze Hoertnagel , Howell Janelle , Ivanovski Ivan , Kaindl Angela , Kamphans Tom , Kamphausen Susanne , Karimov Catherine , Kathom Hadil , Keryan Anna , Khalil Salma-Gamal , Knaus Alexej , Köhler Sebastian , Kornak Uwe , Lavrov Alexander , Leitheiser Maximilian , Lyon J. Gholson , Mangold Elisabeth , Marín Reina Purificación , Martinez Carrascal Antonio , Mitter Diana , Morlan Herrador Laura , Nadav Guy , Nöthen Markus , Orrico Alfredo , Ott Claus-Eric , Park Kristen , Peterlin Borut , Pölsler Laura , Raas-Rothschild Annick , Revencu Nicole , Ringmann Fagerberg Christina , Robinson Peter Nick , Rosnev Stanislav , Rudnik Sabine , Rudolf Gorazd , Schatz Ulrich , Schossig Anna , Schubach Max , Shanoon Or , Sheridan Eamonn , Smirin-Yosef Pola , Spielmann Malte , Suk Eun-Kyung , Sznajer Yves , Thiel Christian Thomas , Thiel Gundula , Verloes Alain , Vrecar Irena , Wahl Dagmar , Weber Ingrid , Winter Korina , Wiśniewska Marzena , Wollnik Bernd , Yeung Ming Wai , Zhao Max , Zhu Na , Zschocke Johannes , Mundlos Stefan , Horn Denise 
Published: November 2018

AbstractPhenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. Here, we introduce an approach, driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features and the disease-causing mutations and simulated multiple exomes of different ethnic backgrounds. With the additional use of similarity scores from computer-assisted analysis of frontal photos, we were able to achieve a top-10-accuracy rate for the disease-causing gene of 99 %. As this performance is significantly higher than without the information from facial pattern recognition, we make gestalt scores available for prioritization via an API.
Hayai-Annotation Plants: an ultra-fast and comprehensive gene annotation system in plants
Authors: Ghelfi Andrea , Shirasawa Kenta , Hirakawa Hideki , Isobe Sachiko 
Published: November 2018

SummaryHayai-Annotation Plants is a browser-based interface for an ultra-fast and accurate gene annotation system for plant species using R. The pipeline combines the sequence-similarity searches, using USEARCH against UniProtKB (taxonomy Embryophyta), with a functional annotation step. Hayai-Annotation Plants provides five layers of annotation: 1) gene name; 2) gene ontology terms consisting of its three main domains (Biological Process, Molecular Function, and Cellular Component); 3) enzyme commission number; 4) protein existence level; 5) and evidence type. In regard to speed and accuracy, Hayai-Annotation Plants annotated Arabidopsis thaliana (Araport11, representative peptide sequences) within five minutes with an accuracy of 96.4 %.Availability and ImplementationThe software is implemented in R and runs on Macintosh and Linux systems. It is freely available at https://github.com/kdri-genomics/Hayai-Annotation-Plants under the GPLv3 license.
Fetal and trophoblast PI3Kp110α have distinct roles in regulating resource supply to the growing fetus
Authors: Lopez-Tello Jorge , Perez-Garcia Vicente , Khaira Jaspreet , Kusinski Laura C. , Cooper Wendy N. , Andreani Adam , Grant Imogen , de Liger Edurne Fernandez , Hemberger Myriam , Sandovici Ionel , Constancia Miguel , Sferruzzi-Perri Amanda N. 
Published: November 2018

AbstractPrevious studies suggest that the placental supply of nutrients to the fetus adapts according to fetal demand. However, the signaling events underlying placental adaptations remain largely unknown. Earlier work in mice has revealed that loss of the phosphoinositide 3-kinase p110α impairs feto-placental growth but placental nutrient supply is adaptively increased. Here we explore the role of p110α in the epiblast-derived (fetal) and trophoblast lineages of the conceptus in relation to feto-placental growth and placental development and transfer function. Using conditional gene manipulations to knock-down p110α either by ∼50% or ∼100% in the fetal lineages and/or trophoblast, this study shows that p110α in the fetus is essential for prenatal development and a major regulator of placental phenotype in mice. Complete loss of fetal p110α caused embryonic death, whilst heterozygous loss resulted in fetal growth restriction and impaired placental formation and nutrient transport. Loss of trophoblast p110α also resulted in abnormal placental development, although fetuses were viable. However, in response to complete loss of trophoblast p110α, the placenta failed to transport sufficient amino acid to match fetal demands for growth. Using RNA-seq, we identified several genes downstream of p110α in the trophoblast that are important in adapting placental phenotype to support fetal growth. Further work using CRISPR/Cas9 genome targeting showed that loss of p110α differentially affects the expression of genes in trophoblast and embryonic stem cells. Our findings thus reveal important, but distinct roles for p110α signaling in the different compartments of the conceptus, which control fetal resource acquisition and ultimately affect healthy growth.One Sentence SummaryFetal and trophoblast p110α modify resource allocation
A Novel Class of Inferior Colliculus Principal Neurons Labeled in Vasoactive Intestinal Peptide-Cre Mice
Authors: Goyer David , Silveira Marina A. , George Alexander P. , Beebe Nichole L. , Edelbrock Ryan M. , Malinski Peter T. , Schofield Brett R. , Roberts Michael T. 
Published: November 2018

AbstractLocated in the midbrain, the inferior colliculus (IC) is the hub of the central auditory system. Although the IC plays important roles in speech processing, sound localization, and other auditory computations, the organization of the IC microcircuitry remains largely unknown. Using a multifaceted approach in mice, we have identified vasoactive intestinal peptide (VIP) neurons as a novel class of IC principal neurons. VIP neurons are glutamatergic stellate cells with sustained firing patterns. Their extensive axons project to long-range targets including the auditory thalamus, auditory brainstem, superior colliculus, and periaqueductal gray. Using optogenetic circuit mapping, we found that VIP neurons integrate input from the contralateral IC and the dorsal cochlear nucleus. The dorsal cochlear nucleus also drove feedforward inhibition to VIP neurons, indicating that inhibitory circuits within the IC shape the temporal integration of ascending inputs. Thus, VIP neurons are well-positioned to influence auditory computations in a number of brain regions.
Cholesterol-dependent enrichment of understudied erythrocytic stages of humanPlasmodiumparasites
Authors: Brown Audrey C. , Moore Christopher C. , Guler Jennifer L. 
Published: November 2018

AbstractPlasmodiumprotozoan parasites undergo rounds of asexual replication inside human erythrocytes, progressing from ring stage, to trophozoites and schizonts, before egress and reinvasion. Given the discovery of ring-specific artemisinin tolerance and quiescence inPlasmodium falciparum, there is great urgency to better understand ring stage biology. However, the lack of an effective enrichment method has left rings and related parasite stages understudied compared to their late stage counterparts, which can be easily isolated due to their paramagnetic properties. Here, a method for separatingall Plasmodiuminfected erythrocytes from uninfected erythrocytes is presented. This approach takes advantage of streptolysin-O (SLO) to preferentially lyse uninfected erythrocytes as previously shown by Jackson,et al.Following lytic treatment, Percoll gradient centrifugation removes lysed cells, leaving an intact cell population enriched in infected erythrocytes. ThisSLO-Percoll (SLOPE) method is effective on stages from the entire erythrocytic cycle, including previously inaccessible forms such as circulating rings from malaria-infected patients and artemisinin-induced quiescent parasites. Furthermore, the utility of SLOPE is extended to multiple media formulations used for the propagation of two humanPlasmodiumspecies. The alteration of external cholesterol levels modulates SLOPE effectiveness, demonstrating the role of erythrocyte membrane cholesterol in lytic discrimination. Importantly, enrichment does not impact parasite viability, which establishes the non-toxic nature of SLOPE. Targeted metabolomics of SLOPE-enriched ring stage samples confirms the impact on treated samples; parasite-derived metabolites are increased and contaminating host material is reduced compared to non-enriched samples.ImportanceMalaria is caused by infection with protozoanPlasmodiumparasites and is responsible for over 400,000 deaths annually. The availability of effective antimalarial drugs is critical to the reduction of malaria-related mortality, yet widespread resistance highlights the need for the continued study ofPlasmodiumbiology. The SLOPE method is an accessible, scalable, rapid (30-40min), and non-toxic enrichment method that is broadly effective on many erythrocytic stages. This method is ideal for use upstream of a variety of sensitive analyses, which will increase experimental quality in virtually all areas of asexualPlasmodiumparasite research. Further, because the consumption of cholesterol is a common characteristic of other intracellular parasites (both bacteria and other protozoa), SLOPE holds potential for extension to other relevant pathogens.
TSD: A computational tool to study the complex structural variants using PacBio targeted sequencing data
Authors: Meng Guofeng , Tan Ying , Fan Yue , Wang Yan , Yang Guang , Fanning Gregory , Qiu Yang 
Published: November 2018

ABSTRACTThe PacBio sequencing is a powerful approach to study the DNA or RNA sequences in a longer scope. It is especially useful in exploring the complex structural variants generated by random integration or multiple rearrangement of internal or external sequences. However, there is still no tool designed to uncover their structural organization in the host genome. Here, we present a tool, TSD, for complex structural variant discovery using PacBio targeted sequencing data. It allows researchers to identify and visualize the genomic structures of targeted sequences by unlimited splitting, alignment and assembly of long PacBio reads. Application to the sequencing data derived from an HBV integrated human cell line(PLC/PRF/5) indicated that TSD could recover the full profile of HBV integration events, especially for the regions with the complex human-HBV genome integrations and multiple HBV rearrangements. Compared to other long read analysis tools, TSD showed a better performance for detecting complex genomic structural variants. TSD is publicly available at: https://github.com/menggf/tsd
Pan-Cancer Repository of Validated Natural and Cryptic mRNA Splicing Mutations
Authors: Shirley Ben C. , Mucaki Eliseos J. , Rogan Peter K. 
Published: November 2018

AbstractWe present a major public resource of mRNA splicing mutations validated according to multiple lines of evidence of abnormal gene expression. Likely mutations present in all tumor types reported in the Cancer Genome Atlas (TCGA) were identified based on the comparative strengths of splice sites in tumor versus normal genomes and then validated by respectively comparing counts of splice junction spanning and abundance of transcript reads in RNA-Seq data from matched tissues and tumors lacking these mutations. The comprehensive resource features 351,423 of these validated mutations, the majority of which (69.1%) are not featured in the Single Nucleotide Polymorphism Database (dbSNP 150). There are 117,951 unique mutations which weaken or abolish natural splice sites, and 244,415 mutations which strengthen cryptic splice sites (10,943 affect both simultaneously). 27,803 novel or rare flagged variants (with <1% population frequency in dbSNP) were observed in multiple tumor tissue types. Single variants or chromosome ranges can be queried using a Global Alliance for Genomics and Health (GA4GH)-compliant web Beacon, Validated Splicing Mutations, either separately or in aggregate alongside other beacons through the public Beacon Network (http://www.beacon-network.org/#/search?beacon=cytognomix), as well as through our website (https://validsplicemut.cytognomix.com/).
Osteocyte death and bone overgrowth in mice lacking Fibroblast Growth Factor Receptors 1 and 2 in mature osteoblasts and osteocytes
Authors: McKenzie Jennifer , Smith Craig , Karuppaiah Kannan , Langberg Joshua , Silva Matthew J. , Ornitz David M. 
Published: November 2018

AbstractFibroblast Growth Factor (FGF) signaling pathways have well established roles in skeletal development, with essential functions in both chondrogenesis and osteogenesis. In mice, previous conditional knockout studies suggested distinct roles for FGF receptor 1 (FGFR1) signaling at different stages of osteogenesis and a role for FGFR2 in osteoblast maturation. However, the potential for redundancy among FGFRs and the mechanisms and consequences of stage-specific osteoblast lineage regulation were not addressed. Here, we conditionally inactivateFgfr1andFgfr2in mature osteoblasts with an Osteocalcin-Cre or Dentin matrix protein 1-CreER driver. We find that young mice lacking both receptors or only FGFR1 are phenotypically normal. However, after 6 weeks of age theseFgfr1/Fgfr2double- andFgfr1single-conditional knockout mice develop a high bone mass phenotype with increased periosteal apposition, increased endocortical woven bone with increased porosity, and biomechanical properties that reflect increased bone mass but impaired material properties. Histopathological and gene expression analyses show that this phenotype is preceded by a striking loss of osteocytes, and gradual activation of the Wnt/βCatenin signaling pathway. These data identify a role for FGFR1 signaling in mature osteoblasts/osteocytes that is required for osteocyte survival during postnatal bone growth.