bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution in clinical presentation of inflammatory bowel disease over time at diagnosis: a multicenter cohort study
Authors: Nahon Stéphane , Ramtohul Toulsie , Paupard Thierry , Belhassan Mehdi , Clair Emeline , Abitbol Vered 
Published: July 2018

Introduction
Delayed diagnosis of inflammatory bowel disease (IBD) has become a major issue, particularly in terms of the presence of nonspecific and heterogeneous clinical signs. This study aimed to identify changes over time in the epidemiological characteristics and clinical presentation of IBD in a French cohort.

Patients and methods
Sociodemographic data from patients at three French hospitals (age, sex, country of origin, smoking habits) and characteristics of IBD [diagnostic delay, phenotype, location, first symptoms, first test suggesting diagnosis (endoscopy, imaging examination)] were collected in a computerized database (Focus_MICI). Four diagnostic time periods were assessed: <2000, 2000–2004, 2005–2009, and >2009.

Results
Among the 926 patients analyzed, 638 (<2000, n=181; 2000–2004, n=104; 2005–2009, n=147; >2009, n=206) had Crohn’s disease (CD) and 288 (<2000, n=54; 2000–2004, n=39; 2005–2009, n=80; >2009, n=115) had ulcerative colitis (UC). For CD, statistically significant differences over time were observed for (a) the first revealing disease symptom [more frequent abdominal pain vs. chronic diarrhea (P<0.001)], (b) first investigation suggestive of diagnosis [more frequent computed tomography vs. colonoscopy (P<0.001)], and (c) CD behavior [more frequent inflammatory vs. stricturing/penetrating forms (P<0.001)]. No significant differences over time were observed for UC variables.

Conclusion
In this large multicenter cohort study clinical diagnostic presentation of CD has changed over time. By contrast, there were no changes in the UC clinical presentation.
Description and Factors Associated With Missed Nursing Care in an Acute Care Community Hospital
Authors: Duffy Joanne R. , Culp Stacey , Padrutt Tom 
Published: July 2018

OBJECTIVE
The aims of this study are to describe and evaluate the factors associated with missed nursing care in an acute care community hospital.

BACKGROUND
Despite RNs’ accountability for high-quality patient care in hospitals, missed nursing care is widespread, jeopardizing patient safety and health system costs. Better understanding of the factors associated with missed nursing care may provide nurse leaders with opportunities for improvement.

METHODS
Using a cross-sectional correlational study design, 138 RNs were randomly sampled during May-June 2017.

RESULTS
The extent of missed nursing care is consistent with other studies, was greater on medical-surgical and telemetry units compared with specialty units, and was negatively associated with staffing/resources, satisfaction with current position, and collegial nurse-physician relationships.

CONCLUSION
Findings suggest urgent nurse leader action and future research.
Patient Trust of the Muslim Nurse
Authors: Hansbrough Wendy B. , Kray Gina , Katib Faten 
Published: July 2018

OBJECTIVEThis quantitative study examined patients’ trust of a nurse who represents the Muslim faith by wearing the hijab.BACKGROUNDPresumptions about nurse trustworthiness based on religious affiliation may impede the effectiveness of the nurse-patient relationship and diminish the ability of nursing care to promote patient’s feelings of well-being.METHODSHospitalized participants were randomly given a picture of a nurse either wearing the hijab or not. They completed a survey to measure their level of trust considering the nurse in the picture.RESULTSNo difference was found in trust of the nurse between groups or in trust analyzed for between-group characteristics. In the hijab picture group, the older the patient, the lower the trust of the nurse.CONCLUSIONSThe results may reflect the general trust of nurses as an ethical and honest professional group. A high level of general trust may transcend stereotypes toward a Muslim nurse.
Reversible solidification of fission yeast cytoplasm after prolonged nutrient starvation
Authors: Heimlicher Maria B. , Bächler Mirjam , Ibeneche-Nnewihe Chieze , Florin Ernst-Ludwig , Hoenger Andreas , Brunner Damian 
Published: July 2018

AbstractCells depend on a highly ordered organization of their content and they must develop strategies to maintain the anisotropic distribution of organelles during periods of nutrient shortage. One of these strategies, observed in bacteria and in yeast cells with acutely interrupted energy production, is to solidify the cytoplasm. Here, we describe a different type of cytoplasm solidification that occurs in fission yeast cells having slowly run out of nutrients after multiple days of culturing. It provides the most profound reversible cytoplasmic solidification of yeast cells described to date. Our data suggest the involvement of a matrix with a certain mesh size that immobilizes cellular components in a size-dependent manner. We provide experimental evidence that cells need time, intrinsic nutrients and intrinsic energy sources to enter this state in the absence of external sources. Such cytoplasmic solidification may provide a robust means to protect cellular architecture in dormant cells.
SOD1 activity thresholds and TOR signalling modulate VAP(P58S) aggregation via ROS-induced proteasomal degradation in a Drosophila model of Amyotrophic Lateral Sclerosis
Authors: Chaplot Kriti , Pimpale Lokesh , Ramalingam Balaji , Deivasigamani Senthilkumar , Kamat Siddhesh S. , Ratnaparkhi Girish S. 
Published: July 2018

AbstractFamilial Amyotrophic Lateral Sclerosis (F-ALS) is an incurable, late onset motor neuron disease, linked strongly to various causative genetic loci. ALS8 codes for a missense mutation, P56S, in VAMP-associated Protein B (VAPB) that causes the protein to misfold and form cellular aggregates. Uncovering genes and mechanisms that affect aggregation dynamics would greatly help increase our understanding of the disease and lead to potential therapeutics.Here, we develop a quantitative high-throughput, Drosophila S2R+ cell-based kinetic assay coupled with fluorescent microscopy to score for genes involved in the modulation of aggregates of fly ortholog, VAP(P58S), tagged with GFP. As proof of principle, we conducted a targeted RNAi screen against 900 genes, consisting of VAP genetic interactors, other ALS loci, as also genes involved in proteostasis. The screen identified 150 hits that modify aggregation, including the ALS loci SOD1, TDP43 and also genes belonging to the TOR pathway.To validate these modifiers, we developed a system to measure the extent of VAP(P58S) aggregation in the Drosophila third instar larval brain using the UAS-GAL4 system, followed by quantitative imaging of cellular inclusions. We find that reduction of SOD1 activity or decreased TOR signalling reduces aggregation. Interestingly, we find that increase in cellular reactive oxygen species (ROS) levels, assessed by measuring oxidation of cellular lipids and proteins, in response to SOD1 knockdown or by inhibition of TOR signalling appears to be the trigger for clearing of aggregates. The mechanism of aggregate clearance is, primarily, the proteasomal machinery, and not autophagy. Increase in VAP, but not VAP(P58S) levels, appears to elevate ROS, which may in turn regulate VAP transcription in a feedback loop.We have thus uncovered an interesting interplay between SOD1, ROS and TOR signalling that regulates the dynamics of VAP aggregation. Mechanistic processes underlying such cellular regulatory networks will lead us to a better understanding of initiation and progression of ALS.
Golden Orbweavers Ignore Biological Rules: Phylogenomic and Comparative Analyses Unravel a Complex Evolution of Sexual Size Dimorphism
Authors: Kuntner Matjaž , Hamilton Chris A. , Ren-Chung Cheng , Gregorič Matjaž , Lupše Nik , Lokovšek Tjaša , Lemmon Emily Moriarty , Lemmon Alan R. , Agnarsson Ingi , Coddington Jonathan A. , Bond Jason E. 
Published: July 2018

AbstractInstances of sexual size dimorphism (SSD) provide the context for rigorous tests of biological rules of size evolution, such as Cope’s Rule (phyletic size increase), Rensch’s Rule (allometric patterns of male and female size), as well as male and female body size optima. In certain spider groups, such as the golden orbweavers (Nephilidae), extreme female-biased SSD (eSSD, female:male body length ≥ 2) is the norm. Nephilid genera construct webs of exaggerated proportions which can be aerial, arboricolous, or intermediate (hybrid). First, we established the backbone phylogeny of Nephilidae using 367 Anchored Hybrid Enrichment (AHE) markers, then combined these data with classical markers for a reference species-level phylogeny. Second, we used the phylogeny to test Cope and Rensch’s Rules, sex specific size optima, and the coevolution of web size, type, and features with female and male body size and their ratio, SSD. Male, but not female, size increases significantly over time, and refutes Cope’s Rule. Allometric analyses reject the converse, Rensch’s Rule. Male and female body sizes are uncorrelated. Female size evolution is random, but males evolve towards an optimum size (3.2–4.9 mm). Overall, female body size correlates positively with absolute web size. However, intermediate sized females build the largest webs (of the hybrid type), giant female Nephila and Trichonephila build smaller webs (of the aerial type), and the smallest females build the smallest webs (of the arboricolous type). We propose taxonomic changes based on the criteria of clade age, monophyly and exclusivity, classification information content, diagnosability, and arachnological community practice. We resurrect the family Nephilidae Simon 1894 that contains Clitaetra Simon 1889, the Cretaceous Geratonephila Poinar & Buckley 2012, Herennia Thorell 1877, Indoetra Kuntner 2006, new rank, Nephila Leach 1815, Nephilengys L. Koch 1872, Nephilingis Kuntner 2013, and Trichonephila Dahl 1911, new rank. We propose the new clade Orbipurae to contain Araneidae Clerck 1757, Phonognathidae Simon 1894, new rank, and Nephilidae. Nephilid female gigantism is a phylogenetically-ancient phenotype (over 100 ma), as is eSSD, though their magnitudes vary by lineage and, to some extent, biogeographically.
CorShrink: Empirical Bayes shrinkage estimation of correlations, with applications
Authors: Dey Kushal K. , Stephens Matthew 
Published: July 2018

AbstractEstimation of correlation matrices and correlations among variables is a ubiquitous problem in statistics. In many cases – especially when the number of observations is small relative to the number of variables – some kind of shrinkage or regularization is necessary to improve estimation accuracy. Here, we propose an Empirical Bayes shrinkage approach, CorShrink, which adaptively learns how much to shrink correlations by combining information across all pairs of variables. One key feature of CorShrink, which distinguishes it from most existing methods, is its flexibility in dealing with missing data. Indeed, CorShrink explicitly accounts for varying amounts of missingness among pairs of variables. Numerical studies suggest CorShrink is competitive with other popular correlation shrinkage methods, even when there is no missing data. We illustrate CorShrink on gene expression data from GTEx project, which suffers from extensive missing observations, and where existing methods struggle. We also illustrate its flexibility by applying it to estimate cosine similarities between word vectors from word2vec models, thereby generating more accurate word similarity rankings.
Varicose veins of lower extremities: insights from the first large-scale genetic study
Authors: Shadrina Alexandra S. , Sharapov Sodbo Z. , Shashkova Tatiana I. , Tsepilov Yakov A. 
Published: July 2018

AbstractVaricose veins of lower extremities (VVs) are a common multifactorial vascular disease. Genetic factors underlying VVs development remain largely unknown. Here we report the first large-scale study of VVs performed on a freely available genetic data of 408,455 European-ancestry individuals. We identified 7 reliably associated loci that explain 10% of the SNP-based heritability, and prioritized the most likely causal genesCASZ1, PPP3R1, EBF1, STIM2, andHFE. Genetic correlation analysis confirmed known epidemiological associations and found genetic overlap with various traits including fluid intelligence score, educational attainment, smoking, and pain. Finally, we observed causal effects of height, weight, both fat and fat-free mass, and plasma levels of MICB and CD209 proteins.
Covalent Modification and Regulation of the Nuclear Receptor Nurr1 by a Dopamine Metabolite
Authors: Bruning John M. , Wang Yan , Oltrabella Francesca , Tian Boxue , Kholodar Svetlana A. , Liu Harrison , Bhattacharya Paulomi , Guo Su , Holton James M. , Fletterick Robert J. , Jacobson Matthew P. , England Pamela M. 
Published: July 2018

SUMMARYNurr1, a nuclear receptor essential for the development, maintenance, and survival of midbrain dopaminergic neurons, is a potential therapeutic target for Parkinson’s disease, a neurological disorder characterized by the degeneration of these same neurons. Efforts to identify Nurr1 agonists have been hampered by the recognition that it lacks several classic regulatory elements of nuclear receptor function, including the canonical ligand-binding pocket. Here we report that the dopamine metabolite 5,6-dihydroxyindole (DHI) binds directly to and modulates the activity of Nurr1. Using biophysical assays and x-ray crystallography we show that DHI binds to the ligand binding domain within a non-canonical pocket, forming a covalent adduct with Cys566. In cultured cells and zebrafish, DHI stimulates Nurr1 activity, including the transcription of target genes underlying dopamine homeostasis. These findings suggest avenues for developing synthetic Nurr1 ligands to ameliorate the symptoms and progression of Parkinson’s disease.
Epi-fluorescence Microscopy of Single Molecule DNA Denaturation in situ
Authors: Sharma Pulkit 
Published: July 2018

AbstractDNA can be denatured by two main methods which are: a) denaturation in solution (invitro) and b) denaturation on a slide surface (in-situ). Additionally, DNA can also be denatured in gels with urea. The method to be used depends on various factors such as the application, the source of the DNA, the length, and the techniques available to confirm the extent of denaturation. Verification of the extent of denaturation is important because of the following factors: 1) increases the chances of hybridization (especially for short probes), 2) prevents the loss of expensive probes (if the target site is not denatured then, the probes will not hybridize and will only cause a high a background), 3) a higher degree of denaturation allows for more probes to be used and therefore, more information can be derived after hybridization, and 4) essential to maximize due to extremely short probe length. It is important to ensure that DNA morphology is preserved after denaturation in order for the probes to hybridise and also for ensuring proper statistical analysis for high throughput applications. In this work, various experimental conditions for in situ denaturation of single molecule DNA is presented.Significance StatementThe significance of this work is that it emphasizes on the importance of denaturation of target genomic DNA in DNA fibre FISH (fluorescence in situ hybridisation) experiments. If the quality of the target DNA is poor after denaturation or the target DNA is not properly denatured, then it will be very difficult or impossible to hybridize the probe DNA during FISH experiments. This will affect the final results for DNA FISH. Additionally, it is the first time that single DNA combed molecules have been shown to be denatured in situ. Most of the past work has been on gels only. Thus the work is both unique and significant.
Inducing controlled cell cycle arrest and re-entry during asexual proliferation ofPlasmodium falciparummalaria parasites
Authors: van Biljon Riëtte , Niemand Jandeli , Wyk Roelof van , Clark Katherine , Verlinden Bianca , Abrie Clarissa , Grüning Hilde von , Smidt Werner , Smit Annél , Reader Janette , Painter Heather , Llinás Manuel , Doerig Christian , Birkholtz Lyn-Marié 
Published: July 2018

ABSTRACTThe life cycle of the malaria parasitePlasmodium falciparumis tightly regulated, oscillating between stages of intense proliferation and quiescence. Cyclic 48-hour asexual replication ofPlasmodiumis markedly different from cell division in higher eukaryotes, and mechanistically poorly understood. Here, we report tight synchronisation of malaria parasites during the early phases of the cell cycle by exposure to DL-α-difluoromethylornithine (DFMO), which results in the depletion of polyamines. This induces an inescapable cell cycle arrest in G1(~15 hours post-invasion) by blocking G1/S transition. Cell cycle-arrested parasites enter a quiescent G0-like state but, upon addition of exogenous polyamines, re-initiate their cell cycle in a coordinated fashion. This ability to halt malaria parasites at a specific point in their cell cycle, and to subsequently trigger re-entry into the cell cycle, provides a valuable framework to investigate cell cycle regulation in these parasites. We therefore used gene expression analyses to show that re-entry into the cell cycle involves expression of Ca2+-sensitive (cdpk4andpk2)and mitotic kinases (nimaandark2),with deregulation of the pre-replicative complex associated with expression ofpk2. Changes in gene expression could be driven through transcription factors MYB1 and two ApiAP2 family members. This new approach to parasite synchronisation therefore expands our currently limited toolkit to investigate cell cycle regulation in malaria parasites.
Comprehensive analysis of immune evasion in breast cancer by single-cell RNA-seq
Authors: Yin Jianhua , Li Zhisheng , Yan Chen , Fang Enhao , Wang Ting , Zhou Hanlin , Luo Weiwei , Zhou Qing , Zhang Jingyu , Hu Jintao , Jin Haoxuan , Wang Lei , Zhao Xing , Li Jiguang , Qi Xiaojuan , Zhou Wenbin , Huang Chen , He Chenyang , Yang Huanming , Kristiansen Karsten , Hou Yong , Zhu Shida , Zhou Dongxian , Wang Ling , Dean Michael , Wu Kui , Hu Hong , Li Guibo 
Published: July 2018

AbstractThe tumor microenvironment is composed of numerous cell types, including tumor, immune and stromal cells. Cancer cells interact with the tumor microenvironment to suppress anticancer immunity. In this study, we molecularly dissected the tumor microenvironment of breast cancer by single-cell RNA-seq. We profiled the breast cancer tumor microenvironment by analyzing the single-cell transcriptomes of 52,163 cells from the tumor tissues of 15 breast cancer patients. The tumor cells and immune cells from individual patients were analyzed simultaneously at the single-cell level. This study explores the diversity of the cell types in the tumor microenvironment and provides information on the mechanisms of escape from clearance by immune cells in breast cancer.One Sentence SummaryLandscape of tumor cells and immune cells in breast cancer by single cell RNA-seq
Asymmetric perirenal brown adipose dormancy in adult humans is defined by local sympathetic activity
Authors: Jespersen Naja Z. , Feizi Amir , Andersen Eline S. , Heywood Sarah , Hattel Helle B. , Daugaard Søren , Bagi Per , Feldt-Rasmussen Bo , Schultz Heidi S. , Hansen Ninna S. , Krogh-Madsen Rikke , Pedersen Bente K. , Petrovic Natasa , Nielsen Søren , Scheele Camilla 
Published: July 2018

AbstractWe here detect dormant brown adipose tissue (BAT) in adult humans, occurring in most of the perirenal fat depot and characterized by a unilocular morphology. This phenotype was contrasted by multilocular BAT accumulating near the adrenal gland. Transcriptomic analysis revealed a gene expression profile of unilocular BAT that was approaching, yet was still distinct from, the expression profile of subcutaneous white adipose tissue (WAT). Candidate gene signatures were recapitulated in a murine model of unilocular brown fat induced by thermoneutrality and high fat diet. We identified SPARC as a candidate adipokine representing a dormant BAT state in the absence of sympathetic activation and CLSTN3 as a novel marker for multilocular BAT. Brown fat precursor cells were present in the entire perirenal fat depot, regardless of state. When differentiated in vitro, these cells responded to acute norepinephrine stimulation by increasing UCP1 gene expression and uncoupled respiration, confirming a BAT phenotype. We thus propose a mechanism for the reduction of functionally competent BAT in adult humans and we provide a solid data set for future research on factors that can reactivate dormant BAT as a potential strategy for combatting obesity and metabolic disease.
Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window
Authors: Lucas Emma S , Vrljicak Pavle , Muter Joanne , Diniz-da-Costa Maria M , Brighton Paul J , Kong Chow-Seng , Lipecki Julia , Fishwick Katherine , Odendaal Joshua , Ewington Lauren J. , Quenby Siobhan , Ott Sascha , Brosens Jan J 
Published: July 2018

AbstractBreakdown of the feto-maternal interface in early pregnancy causes miscarriage. The cycling endometrium becomes poised to transition to a pregnant state during the midluteal implantation window, coinciding with differentiation of stromal cells into decidual cells (DC) and emergence of senescent decidual cells (snDC). Emerging evidence suggests that DC engage uterine natural killer cells to eliminate their senescent counterparts, thus enabling formation of a robust decidual matrix in pregnancy. To examine if failure to constrain snDC during the peri-implantation window increases the risk of miscarriage, we reconstructed the decidual pathway at single-cell levelin vitroand demonstrated that, without immune surveillance, secondary senescence rapidly transforms DC into progesterone-resistant cells that abundantly express extracellular matrix remodelling factors. Additional single-cell analysis of midluteal endometrium identifiedDIO2andSCARA5as marker genes of a diverging decidual responsein vivo. Finally, we report a conspicuous link between a pro-senescent decidual response in luteal phase endometrium and recurrent pregnancy loss, suggesting that pre-pregnancy screening and intervention may reduce the burden of miscarriage.
Complement C3-targeted gene therapy restricts onset and progression of neurodegeneration in chronic mouse glaucoma
Authors: Bosco Alejandra , Anderson Sarah R , Breen Kevin T , Romero Cesar O , Steele Michael R , Chiodo Vince A , Boye Sanford L , Hauswirth William W , Tomlinson Stephen , Vetter Monica L 
Published: July 2018

ABSTRACTDysregulation of the complement system is implicated in neurodegeneration, including human and animal glaucoma. Optic nerve and retinal damage in glaucoma is preceded by local complement upregulation and activation, but whether targeting this early innate immune response could have therapeutic benefit remains undefined. Because complement signals through three pathways that intersect at complement C3 activation, here we targeted this step to restore complement balance in the glaucomatous retina, and to determine its contribution to degeneration onset and/or progression. To achieve this, we combined adeno-associated viral retinal gene therapy with the targeted C3 inhibitor CR2-Crry. We show that intravitreal injection of AAV2.CR2-Crry produced sustained Crry overexpression in the retina, and reduced deposition of the activation product complement C3d on retinal ganglion cells and the inner retina of DBA/2J mice. This resulted in neuroprotection of retinal ganglion cell axons and somata despite continued intraocular pressure elevation, suggesting a direct restriction of neurodegeneration onset and progression, and significant delay to terminal disease stages. Our study uncovers a damaging effect of complement C3 or downstream complement activation in glaucoma and establishes AAV2.CR2-Crry as a viable therapeutic strategy to target pathogenic C3-mediated complement activation in the glaucomatous retina.