bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining procalcitonin with the qSOFA and sepsis mortality prediction
Authors: Yu Hua , Nie Lu , Liu Aibo , Wu Kuihai , Hsein Yenh-Chen , Yen Debra W. , Lee Meng-tse G. , Lee Chien-Chang 
Published: June 2019

Abstract
To investigate whether procalcitonin (PCT) can improve the performance of quick sequential organ failure assessment (SOFA) score in predicting sepsis mortality, we conducted a retrospective multicenter cohort study with independent validation in a prospectively collected cohort in 3 tertiary medical centers. Patients with presumed sepsis were included. Serum PCT levels were measured at admission. Quick SOFA score and systemic inflammatory response syndrome (SIRS) criteria were calculated for each patient. PCT levels were assigned into 0, 1, and 2 points for a serum level of <0.25, 0.25 to 2, and >2 ng/mL, and added to the quick sepsis-related organ failure assessment (qSOFA) score. The incremental value of PCT to qSOFA was then evaluated by logistic regression, receiver-operating characteristic (ROC) curve, and reclassification analysis.
In all, 1318 patients with presumed severe infection were enrolled with a 30-day mortality of 13.5%. Serum level of PCT showed a high correlation with qSOFA score and 30-day inhospital mortality. The area under the ROC curve was 0.56 for SIRS criteria, 0.67 for qSOFA score, and 0.73 for qSOFA_PCT in predicting 30-day mortality. The risk prediction improvement was reflected by a net reclassification improvement of 35% (17%–52%). Incorporation of PCT into the qSOFA model could raise the sensitivity to 86.5% (95% confidence interval 80.6%–91.2%). In the validation cohort, qSOFA_PCT greatly improved the sensitivity to 90.9%.
A simple modification of qSOFA score by adding the ordinal scale of PCT value to qSOFA could greatly improve the suboptimal sensitivity problem of qSOFA and may serve as a quick screening tool for early identification of sepsis.
Diagnosis and management of linear scleroderma in children
Authors: Peña-Romero Adriana G. , García-Romero Maria T. 
Published: June 2019

Purpose of review
Linear scleroderma is the most common subtype of localized scleroderma (LoS) in children. It can be associated with extracutaneous manifestations and long-term sequelae. Thus, appropriate diagnosis and management are key to improve the prognosis. In this review, we summarize the most relevant recent publications for the diagnosis, evaluation of disease activity and adequate management of patients with linear scleroderma.

Recent findings
There are specific clinical features that indicate activity in LoS; dermoscopy and Wood's lamp may be useful. Summarizing, scoring methods seem to provide the most adequate assessment of LoS; but several biomarkers that correlate with activity have been studied: E-selectin and IL-2 receptor, CD34+ dermal dendritic cells and Th/Th1 immunophenotype with decreased T helper (Th2), T regulatory (Tregs), B and natural killer (NK) cells. Recent studies propose hydroxychloroquine monotherapy and tocilizumab as potential therapeutic options.

Summary
Clinical evaluation, both physical exam and history, is the most important aspect in diagnosing and assessing activity of linear scleroderma. Clinical scoring methods may be most useful for evaluation of activity; eventually, other biomarkers could be relevant in clinical practice. For most patients with linear scleroderma, the first choice of treatment is methotrexate, but physical therapy, plastic surgery and/or orthopedic management are key to improve residual limitations and quality of life.

Video abstract

http://links.lww.com/MOP/A35.
The past, present, and future of costimulation blockade in organ transplantation
Authors: Schroder Paul M. , Fitch Zachary W. , Schmitz Robin , Choi Ashley Y. , Kwun Jean , Knechtle Stuart J. 
Published: June 2019

Purpose of review
Manipulating costimulatory signals has been shown to alter T cell responses and prolong graft survival in solid organ transplantation. Our understanding of and ability to target various costimulation pathways continues to evolve.

Recent findings
Since the approval of belatacept in kidney transplantation, many additional biologics have been developed targeting clinically relevant costimulation signaling axes including CD40-CD40L, inducible costimulator-inducible costimulator ligand (ICOS-ICOSL), and OX40-OX40L. Currently, the effects of costimulation blockade on posttransplant humoral responses, tolerance induction, and xenotransplantation are under active investigation. Here, we will discuss these pathways as well as preclinical and clinical outcomes of biologics targeting these pathways in organ transplantation.

Summary
Targeting costimultion is a promising approach for not only controlling T cell but also B cell responses. Consequently, costimulation blockade shows considerable potential for improving outcomes in antibody-mediated rejection and xenotransplantation.
Outcomes of Children With Chronic Intestinal Failure
Authors: Jo Sz‐Ying C. , McCallum Zoe , Shalley Helen , Peterkin Megan , Rogers Elizabeth , Paxton Georgia , Wong Theodoric , Bines Julie E. 
Published: June 2019

ABSTRACTBackground and Aims:The aim of the study was to aid decisions on prognosis and transplantation; this study describes the outcome of children with intestinal failure managed by the multidisciplinary intestinal rehabilitation program at the Royal Children's Hospital, Melbourne.Methods:Retrospective review of children requiring parenteral nutrition (PN) for >3 months who were assessed for home PN between 1991 and 2011.Results:A total of 51 children were included. Forty‐two (82%) had short bowel syndrome (SBS), 5 (10%) had chronic intestinal pseudo‐obstruction syndrome, and 4 (8%) had congenital enteropathies. Median small bowel length for patients with SBS was 45 cm (interquartile range 30–80) or 23.9% of the expected length for age (interquartile range 17.0%–40.6%). Overall survival rate was 84% (43/51). Mortality in children (n = 7) occurred after a median of 13.2 months (range 6.2–29.2) with intestinal failure–associated liver disease (IFALD) being the only predictor (P = 0.001). Out of 50 children 21 (42%) had IFALD. Children who were premature (P = 0.013), had SBS (P = 0.038), and/or frequent sepsis (P = 0.014) were more likely to develop IFALD. PN weaning occurred in 27 of 35 (77%) SBS survivors, after a median of 10.8 months (up to 8.2 years), with longer residual small bowel (P = 0.025), preservation of the ileocecal valve (P = 0.013) and colon (P = 0.011) being predictors. None of 5 (0%) patients with chronic intestinal pseudo‐obstruction syndrome and 2 of 4 (50%) patients with congenital enteropathies weaned off PN. Overall sepsis rate was 7.3 episodes/1000 line days. Frequency of sepsis and longevity of central lines improved with time as patients grew older (both P < 0.001).Conclusions:Long‐term PN with intestinal rehabilitation was effective in treating most children with intestinal failure. Children with severe refractory IFALD may have benefited from intestinal transplantation.
The Use of Tranexamic Acid (TXA) for the Management of Hemorrhage in Trauma Patients in the Prehospital Environment: Literature Review and Descriptive Analysis of Principal Themes
Authors: Stansfield Rachel , Morris Danielle , Jesulola Emmanuel 
Published: June 2019

ABSTRACT
Tranexamic acid (TXA) is an antifibrinolytic agent used to prevent traumatic exsanguination. It was first introduced to clinical practice for the management of patients with bleeding disorders, especially adapted to reduce bleeding in hemophiliacs undergoing oral surgical interventions. TXA exerts its action on the coagulation process by competitively inhibiting plasminogen activation, thereby reducing conversion of plasminogen into plasmin. This ultimately prevents fibrinolysis and reduces hemorrhage. Thus, TXA may be well suited for the management of traumatic hemorrhage in the prehospital setting.
Despite multiplicity of studies on the use of TXA in clinical practice, there is no consensus regarding the use of TXA for the management of hemorrhage in trauma patients in the prehospital environment. Thus, a review on this topic was warranted. An extensive literature search yielded 14 full journal articles which met the inclusion criteria. These articles were thoroughly analyzed and the following themes were identified: “dose of TXA administration,” “route of TXA administration,” “optimal window of TXA administration,” “safety of TXA use,” “clinical effectiveness of TXA application,” and the “feasibility of TXA use in the prehospital setting.”
Overall, to achieve the best possible outcomes, the literature supports the use of a loading dose of 1 g of TXA, followed by 1 g infusion over 8 h, given by intravenous administration within a 3-h window period of traumatic injury. TXA is very effective and safe to use in the prehospital setting, and its use is clinically and economically feasible.
Temporal Trends and Clinical Outcomes Associated with Vasopressor and Inotrope Use in The Cardiac Intensive Care Unit
Authors: Jentzer Jacob C. , Wiley Brandon , Bennett Courtney , Murphree Dennis H. , Keegan Mark T. , Kashani Kianoush B. , Bell Malcolm R. , Barsness Gregory W. 
Published: June 2019

ABSTRACTBackground:The use of norepinephrine may be associated with better outcomes in some patients with shock. We sought to determine whether norepinephrine was associated with lower mortality in unselected cardiac intensive care unit (CICU) patients compared with other vasopressors, and whether patterns of vasopressor and inotrope usage in the CICU have changed over time.Methods:We retrospectively evaluated consecutive adult patients admitted to a tertiary care hospital CICU from January 1, 2007 to December 31, 2015. Vasoactive drug doses were quantified using the peak Vasoactive-Inotropic Score (VIS). Temporal trends were assessed using the Cochran–Armitage trends test and multivariable logistic regression was used to determine predictors of hospital mortality.Results:We included 10,004 patients with a mean age of 67 ± 15 years; vasoactive drugs were used in 2,468 (24.7%) patients. Use of norepinephrine increased over time, whereas dopamine utilization decreased (P < 0.001 for trends). After adjustment for illness severity and other variables, the peak VIS was a predictor of hospital mortality across the entire population (unit odds ratio [OR] 1.013, 95% confidence interval [CI], 1.009–1.017,P < 0.001) and among patients receiving vasoactive drugs (OR 1.018, 95% CI, 1.013–1.022,P < 0.001). Among patients receiving vasoactive drugs, norepinephrine was associated with a lower risk of hospital mortality (OR 0.66, 95% CI, 0.49–0.90,P = 0.008) after adjustment for illness severity and peak VIS.Conclusions:Vasoactive drug use in CICU patients has a dose-dependent association with short-term mortality. Use of norepinephrine in CICU patients is associated with decreased odds of death when compared with other vasoactive drugs.
Learner Satisfaction and Experience With a High-definition Telescopic Camera During Vaginal Procedures: A Randomized Controlled Trial
Authors: Hobson Deslyn T. G. , Meriwether Kate V. , Gaskins Jeremy T. , Uddin M. Nazir , Stewart J. Ryan , Gupta Ankita S. , Francis Sean L. 
Published: June 2019

Objective
The aim of this study was to compare learner satisfaction and experience with a table-mounted, projecting, high-definition telescopic camera system (VITOM) versus traditional learner observation during vaginal surgery.

Methods
Medical student and resident learners were randomized to vaginal surgery observation with or without the use of VITOM. We collected data on learner characteristics and their experience with vaginal surgery. After the surgery, learners completed the faculty/preceptor and working environment domains of the Veterans Affairs Learner’s Perceptions Survey (VA LPS). The primary outcome was learners who were “very satisfied” on the VA LPS faculty/preceptor domain. We queried their ability to observe the surgery and satisfaction with learning in the operating room using a 100-mm visual analog scale.

Results
Ninety-two learners completed the study (n = 44 VITOM, n = 48 no VITOM). There was no significant difference between groups in the proportion of learners “very satisfied” on the VA LPS faculty/preceptor domain (93.2% VITOM vs 91.5% no VITOM; odds ratio, 1.27; 95% confidence interval, 0.20–9.19; P = 0.99). Learners in the VITOM group were more likely to report ability to see what the main surgeon was doing (93.2% VITOM vs 62.5% no VITOM; odds ratio, 8.02; 95% confidence interval, 2.07–46.32; P < 0.01). Using the visual analog scale, learners in the VITOM group reported higher satisfaction with learning in the operating room (median, 96 [interquartile range, 89–100] VITOM vs median, 80 [interquartile range, 57–98] no VITOM; P < 0.01).

Conclusion
The use of a table-mounted, projecting, telescopic camera system during vaginal surgery showed no difference in learner satisfaction on validated questionnaires but resulted in improved experience and visualization.
tRNAnalysis: A flexible pre-processing and next-generation sequencing data analysis pipeline for transfer RNA
Authors: James-Bott Anna , Cribbs Adam P. 
Published: June 2019

AbstractMany tools have been developed to analyse small RNA sequencing data, however it remains a challenging task to accurately process reads aligning to small RNA due to their short-read length. Most pipelines have been developed with miRNA analysis in mind and there are currently very few workflows focused on the analysis of transfer RNAs. Moreover, these workflows suffer from being low throughput, difficult to install and lack sufficient visualisation to make the output interpretable. To address these issues, we have built a comprehensive and customisable small RNA-seq data analysis pipeline, with emphasis on the analysis of tRNAs. The pipeline takes as an input a fastq file of small RNA sequencing reads and performs successive steps of mapping and alignment to transposable elements, gene transcripts, miRNAs, snRNAs, rRNA and tRNAs. Subsequent steps are then performed to generate summary statistics on reads of tRNA origin, which are then visualised in a html report. Unlike other low-throughput analysis tools currently available, our high-throughput method allows for the simultaneous analysis of multiple samples and scales with the number of input files. tRNAnalysis is command line runnable and is implemented predominantly using Python and R. The source code is available at https://github.com/Acribbs/tRNAnalysis.
Essential gene networks in acute myeloid leukemia identified using a microRNA-knockout CRISPR library screen
Authors: Gabra Martino , Pastrello Chiara , Machado Nicole , Chow Jonathan Tak-Sum , Kotlyar Max , Tokar Tomas , Jurisica Igor , Salmena Leonardo 
Published: June 2019

AbstractMicroRNAs (miRNA) are small RNAs that function as key modulators of gene expression. Due to their promiscuity of binding, a single miRNA may regulate several genes and hence, multiple pathways simultaneously. In addition, the 3’-UTR of mRNA can be recognized by several miRNA for suppression or degradation. We built a microRNA-only Knock-out (miRKo) CRISPR/Cas-9 library to identify essential miRNA in Acute Myeloid Leukemia (AML) using OCI-AML2, OCI-AML3 and U937 cell lines as in vitro models. 10 miRNA were identified to be essential in our screen among all three cell lines: miR-19b-1, -19b-2, 29b-2, -302a, -3678, -3713, -3910-1, -4447, -4718 and -6795. By using weighted degrees of association, we identified pathway hubs that uniquely affect all 3 cell lines by integrating miRNA:mRNA networks using mirDIP and pathway analysis using pathDIP. Through the miRKo screen, network membership analyses and biological anticorrelation scoring through patient data analysis, we identified RRP2CA, RPS6KB-1, CREB1, RPM1A, MAPK10, MAP3K2, ITCH, FBX-W7, NR3C1 and XIAP as likely targets of the essential miRNA in AML; and signal transduction, apoptosis, TGF-beta signalling and MAPK signalling as candidate essential pathways in AML.
Mesenchymal stem cells suppress leukemia via macrophage-mediated functional restoration of bone marrow microenvironment
Authors: Xia Chengxiang , Wang Tongjie , Cheng Hui , Dong Yong , Weng Qitong , Sun Guohuan , Zhou Peiqing , Wang Kaitao , Liu Xiaofei , Geng Yang , Ma Shihui , Hao Sha , Xu Ling , Guan Yuxian , Du Juan , Du Xin , Li Yangqiu , Zhu Xiaofan , Shi Yufang , Xu Sheng , Wang Demin , Cheng Tao , Wang Jinyong 
Published: June 2019

AbstractBone marrow (BM) mesenchymal stem cells (MSCs) are critical components of the BM microenvironment and play an essential role in supporting hematopoiesis. Dysfunction of MSCs is associated with the impaired BM microenvironment that promotes leukemia development. However, whether and how restoration of the impaired BM microenvironment can inhibit leukemia development remain unknown. Using an established leukemia model and the RNA-seq analysis, we discovered functional degeneration of MSCs during leukemia progression. Importantly, intra-BM instead of systemic transfusion of donor healthy MSCs restored the BM microenvironment, thus systemically altering cytokine expression patterns, improving normal hematopoiesis, reducing tumor burden, and ultimately prolonging survival of the leukemia-bearing mice. Donor MSC treatment restored the function of host MSCs and reprogrammed host macrophages to fulfill tissue-repair function. Transfusion of MSC-reprogrammed macrophages largely recapitulated the therapeutic effects of MSCs. Further, we found that donor MSCs reprogrammed macrophages to reduce leukemia burden through autocrine of IL-6. Taken together, our study reveals that donor MSCs reprogram host macrophages to restore the BM microenvironment and inhibit leukemia development, thus offering rationales for local MSC administration as a potentially effective therapy for leukemia.Key PointsKey Point 1: Intra-BM transfusion of MSCs restores the BM microenvironment, improves thrombopoiesis, and suppresses MDS/MPN initiated by Nras mutation.Key Point 2: Donor MSCs reprogram macrophages to restore the BM microenvironment, improve thrombopoiesis, and suppress leukemia.
Auditory attention alterations in migraine: a behavioral and MEG/EEG study
Authors: Masson Rémy , Lévêque Yohana , Demarquay Geneviève , ElShafei Hesham , Fornoni Lesly , Lecaignard Françoise , Morlet Dominique , Bidet-Caulet Aurélie , Caclin Anne 
Published: June 2019

AbstractObjectivesTo evaluate alterations of top-down and/or bottom-up attention in migraine and their cortical underpinnings.Methods19 migraineurs between attacks and 19 matched control participants performed a task evaluating jointly top-down and bottom-up attention, using visually-cued target sounds and unexpected task-irrelevant distracting sounds. Behavioral responses and MEG/EEG were recorded. Event-related potentials and fields (ERPs/ERFs) were processed and source reconstruction was applied to ERFs.ResultsAt the behavioral level, neither top-down nor bottom-up attentional processes appeared to be altered in migraine. However, migraineurs presented heightened evoked responses following distracting sounds (orienting component of the N1 and Re-Orienting Negativity, RON) and following target sounds (orienting component of the N1), concomitant to an increased recruitment of the right temporo-parietal junction. They also displayed an increased effect of the cue informational value on target processing resulting in the elicitation of a negative difference (Nd).ConclusionsMigraineurs appear to display increased bottom-up orienting response to all incoming sounds, and an enhanced recruitment of top-down attention.SignificanceThe interictal state in migraine is characterized by an exacerbation of the orienting response to attended and unattended sounds. These attentional alterations might participate to the peculiar vulnerability of the migraine brain to all incoming stimuli.HighlightsMigraineurs performed as well as healthy participants in an attention task.However, EEG markers of both bottom-up and top-down attention are increased.Migraine is also associated with a facilitated recruitment of the right temporo-parietal junction.
Integration of a FT expression cassette into CRISPR/Cas9 construct enables fast generation and easy identification of transgene-free mutants in Arabidopsis
Authors: Cheng Yuxin , Zhang Na , Hussain Saddam , Ahmed Sajjad , Yang Wenting , Wang Shucai 
Published: June 2019

AbstractThe CRISPR/Cas9 genome editing technique has been widely used to generate transgene-free mutants in different plant species. Several different methods including fluorescence marker-assisted visual screen of transgene-free mutants and programmed self-elimination of CRISPR/Cas9 construct have been use to increase the efficiency of genome edited transgene-free mutants isolation, but the overall time length required to obtain transgene-free mutants has remained unchanged in these methods. We report here a method for fast generation and easy identification of transgene-free mutants in Arabidopsis. By generating and using a single FT expression cassette-containing CRISPR/Cas9 construct, we targeted two sites of the AITR1 gene. We obtained many early bolting plants in T1 generation, and found that about two thirds of these plants have detectable mutations. We then analyzed T2 generations of two representative lines of genome edited early bolting T1 plants, and identified plants without early bolting phenotype, i.e., transgene-free plants, for both lines. Further more, homologues aitr1 mutants were successful obtained for both lines from these transgene-free plants. Taken together, these results suggest that the method described here enables fast generation, and at the mean time, easy identification of transgene-free mutants in plants.