bluuebunny/crossref_metadata_2025_split huggingface dataset:
VON HIPPEL–LINDAU DISEASE
Authors: Aronow Mary E. , Wiley Henry E. , Gaudric Alain , Krivosic Valerie , Gorin Michael B. , Shields Carol L. , Shields Jerry A. , Jonasch Eric W. , Singh Arun D. , Chew Emily Y. 
Published: May 2019

Purpose:
To provide an update summarizing the biologic pathways governing von Hippel–Lindau (VHL) disease pathogenesis and to provide an overview of systemic manifestations as well as screening recommendations.

Methods:
A PubMed search of the English language literature was reviewed using the following search terms: von Hippel–Lindau, von Hippel–Lindau disease, and VHL. Of 6,696 publications, the most current and pertinent information related to the pathogenesis and systemic aspects of VHL disease were included in this review.

Results:
von Hippel–Lindau disease is one of the most frequently occurring multisystem familial cancer syndromes. The disease results from germline mutation in the VHL tumor suppressor gene on the short arm of chromosome 3. Mutation in the VHL gene affects multiple cellular processes including transcriptional regulation, extracellular matrix formation, apoptosis, and, in particular, the cellular adaptive response to hypoxia. As a result, there is widespread development of vascular tumors affecting the retina, brain, and spine, as well as a spectrum of benign and malignant tumors and/or cysts in visceral organs.

Conclusion:
The ophthalmologist plays a key role in VHL disease diagnosis, as retinal hemangioblastoma is frequently the first disease manifestation. Screening guidelines for individuals with known VHL disease, and those at risk of VHL disease, help to ensure early detection of potentially vision-threatening and life-threatening disease.
Stability and Sterility of Extemporaneously Prepared Nonpreserved Cefazolin, Ceftazidime, Vancomycin, Amphotericin B, and Methylprednisolone Eye Drops
Authors: Ratprasatporn Nitee , Wittayalertpanya Supeecha , Khemsri Wondee , Chatsuwan Tanittha , Chongpison Yuda , Chamsai Tasanee , Wattanakijkarn Mayura , Chansangpetch Sunee 
Published: May 2019

Purpose:
To determine in-use stability and sterility of fortified cefazolin, ceftazidime, vancomycin, amphotericin B, and methylprednisolone eye drops in a simulated inpatient setting with and without a mobile refrigerated container (MR).

Methods:
Each drug was prepared and divided into 4 groups: 1) simulated patient use with the MR group: stored at 4°C and kept in the MR during drug administration, 2) simulated patient use without the MR (NoMR) group: stored at 4°C and no MR, 3) refrigerated control group: stored at 4°C, and 4) room temperature control group: stored at room temperature. Stability and sterility data were evaluated at days 0, 4, 7, 14, 21, and 28. Linear mixed-effects model and survival analysis were performed.

Results:
Median time to 10% loss of concentration for in-use medications (MR/NoMR groups) was >28/27.9, 22.2/22.2, 19.4/19.4, 10.18/<4, and >28/>28 days for cefazolin, ceftazidime, vancomycin, amphotericin B, and methylprednisolone, respectively. There was no significant difference in the predicted concentration loss per day among all groups for vancomycin and methylprednisolone (all P > 0.05). For the other study medications, all room temperature control groups, the cefazolin NoMR group, and the ceftazidime NoMR group had significantly greater predicted concentration loss per day compared with the refrigerated control groups (all P ≤ 0.02). Culture results were negative for all drugs throughout the study.

Conclusions:
The NoMR group showed that the drug significantly degraded rapidly for cefazolin, ceftazidime, and amphotericin B. Implementation of MR could decrease the predicted loss of concentration per day for cefazolin and ceftazidime. In vitro antimicrobial activity and sterility were retained for 28 days.
The Challenge of Autoimmune Pancreatitis
Authors: Pagliari Danilo , Cianci Rossella , Rigante Donato 
Published: May 2019

Abstract
Autoimmune pancreatitis (AIP) is a rare disorder characterized by prompt clinical response to corticosteroids. Lost tolerance to a variety of pancreatic antigens and subsequent development of autoantibodies are presumably involved in the initiation of AIP. Even pediatric patients have been reported with features of AIP, and awareness of this disorder is increasing among different clinicians. The terms lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis refer to the different histologic patterns of AIP, named type 1 and type 2, respectively. A combination of serologic, radiologic, and histologic investigations is needed to assess diagnosis of AIP and rule out neoplastic disorders. In addition, type 1 AIP can be distinguished by raised levels of serum immunoglobulin G4 and should be considered as part of systemic immunoglobulin G4–related disease. Conversely, type 2 AIP is frequently reported in younger patients and has less clear immune-mediated pathogenetic mechanisms. The natural history of pediatric AIP is obscure, and the diagnostic usefulness of different autoimmune abnormalities found in adults with AIP is limited for children. Tips to manage pediatric patients with AIP have been recently drafted through a set of recommendation statements. This review describes the current data about AIP and the pathogenic contribution of specific autoantibodies expressly in the pediatric population.
An Integrative Literature Review of Psychiatric Rapid Response Teams and Their Implementation for De-escalating Behavioral Crises in Nonpsychiatric Hospital Settings
Authors: Choi Kristen R. , Omery Anna K. , Watkins Anne Marie 
Published: May 2019

OBJECTIVE
To synthesize articles exploring the implementation of psychiatric rapid response teams (RRTs) for behavioral crises in hospital settings.

BACKGROUND
Psychiatric/behavioral crises in nonpsychiatric hospital settings can lead to restraint use, staff injuries, and poor patient outcomes. Psychiatric RRTs may provide a solution, but they are a new, understudied intervention, and their implementation varies across institutions.

METHODS
A systematic, integrative literature review of nursing and biomedical literature yielded 7 articles about psychiatric RRTs. Data were extracted on RRT structure, processes, outcomes, and implementation.

RESULTS
Psychiatric RRTs were structured as a nurse-led, interdisciplinary intervention. When implemented using evidence-based models, they reduced security calls, restraint use, and staff injuries while moderately improving staff knowledge and self-efficacy. RRTs that included education, debriefing, and role modeling appeared to increase staff behavioral management skills and eventually reduced the need for RRTs.

CONCLUSIONS
Psychiatric RRTs have demonstrated promise in quality improvement projects for reducing adverse outcomes related to behavioral health in hospitals.
Nurse Manager Succession Planning
Authors: LaCross Erin , Hall Norma , Boerger Judith A. 
Published: May 2019

OBJECTIVE
Perceived readiness to transition to nurse manager roles and demonstrated leadership behaviors were evaluated among participants in a nurse manager succession planning pilot cohort.

BACKGROUND
Equipping nurses within an organization with the leadership competencies to transition to the next role is essential as we face an impending nurse and nurse leader shortage.

METHODS
Quasi-experimental and correlational design methods were used to measure changes in readiness of nurses to enter nurse manager roles over a 90-day pilot.

RESULTS
Participants' perceived readiness to transition to nurse manager roles and demonstrated leadership behaviors increased between days 1 and 90 of the program. Statistically significant increases were attributed to their participation in the nurse manager succession planning pilot cohort.

CONCLUSIONS
This study contributes to the literature regarding nurse manager succession planning. Further research should be conducted so that succession planning for nurse managers becomes not only achievable but also expected.
Severe Trauma and Hemorrhage Leads to Platelet Dysfunction and Changes in Cyclic Nucleotides in The Rat
Authors: Darlington Daniel N. , Wu Xiaowu , Keesee Jeffrey D. , Cap Andrew P. 
Published: May 2019

ABSTRACT

Introduction:
Rats subjected to polytrauma and hemorrhage develop a coagulopathy that is similar to acute coagulopathy of trauma in humans, and is associated with a rise in prothrombin time and a fall in clot strength. Because platelet aggregation accounts for a major proportion of clot strength, we set out to characterize the effects of polytrauma on platelet function.

Methods:
Sprague-Dawley rats were anesthetized with isoflurane. Polytrauma included laparotomy and damage to 10 cm of the small intestines, right and medial liver lobes, right leg skeletal muscle, femur fracture, and hemorrhage (40% of blood volume). No resuscitation was given. Blood samples were taken before and after trauma for the measurement of impedance electrode aggregometry, and intracellular levels of cyclic adenosine and guanosine monophosphate (cAMP, cGMP), inositol trisphosphate (IP3), and adenosine and guanosine triphosphates (ATP, GTP).

Results:
Polytrauma significantly increased the response of collagen (24%) and thrombin (12%) to stimulate platelet aggregation. However, aggregation to adenosine diphosphate (ADP) or arachidonic acid (AA) was significantly decreased at 2 (52% and 46%, respectively) and 4 h (45% and 39%). Polytrauma and hemorrhage also led to a significant early rise in cAMP (101 ± 11 to 202 ± 29 pg/mL per 1,000 platelets), mirrored by a decrease in cGMP (7.8 ± 0.9 to 0.6 ± 0.5). In addition, there was a late fall in ATP (8.1 ± 0.7 to 2.2 ± 0.6 ng/mL per 1,000 platelets) and GTP (1.5 ± 0.2 to 0.3 ± 0.1). IP3 rose initially, and then fell back to baseline.

Conclusions:
Polytrauma and hemorrhage led to a deficit in the platelet aggregation response to ADP and AA after trauma, likely due to the early rise in cAMP, and a later fall in energy substrates, and may explain the decrease in clot strength and impaired hemostasis observed after severe trauma.
Content tuning in the medial temporal lobe cortex: Voxels that perceive, retrieve
Authors: Schultz Heidrun , Tibon Roni , LaRocque Karen F. , Gagnon Stephanie A. , Wagner Anthony D. , Staresina Bernhard P. 
Published: May 2019

AbstractHow do we recall vivid details from our past based only on sparse cues? Research suggests that the phenomenological reinstatement of past experiences is accompanied by neural reinstatement of the original percept. This process critically depends on the medial temporal lobe (MTL). Within the MTL, perirhinal cortex (PRC) and parahippocampal cortex (PHC) are thought to support encoding and recall of objects and scenes, respectively, with the hippocampus (HC) serving as a content-independent hub. If the fidelity of recall indeed arises from neural reinstatement of perceptual activity, then successful recall should preferentially draw upon those neural populations within content-sensitive MTL cortex that are tuned to the same content during perception. We tested this hypothesis by having eighteen human participants undergo functional magnetic resonance imaging (fMRI) while they encoded and recalled objects and scenes paired with words. Critically, recall was cued with the words only. While HC distinguished successful from unsuccessful recall of both objects and scenes, PRC and PHC were preferentially engaged during successful vs. unsuccessful object and scene recall, respectively. Importantly, within PRC and PHC, this content-sensitive recall was predicted by content tuning during perception: Across PRC voxels, we observed a positive linear relationship between object tuning during perception and successful object recall, while across PHC voxels, we observed a positive linear relationship between scene tuning during perception and successful scene recall. Our results thus highlight content-based roles of MTL cortical regions for episodic memory and reveal a direct mapping between content-specific tuning during perception and successful recall.
Integrated Metabolomic and Transcriptomic Profiling Reveals Novel Activation-Induced Metabolic Networks in Human T cells
Authors: Hiemer S. , Jatav S. , Jussif J. , Alley J. , Lathwal S. , Piotrowski M. , Janiszewski J. , Kibbey R. , Alves T. , Dumlao D. , Jha A. , Bandukwala H. 
Published: May 2019

AbstractThe targeting of metabolic pathways is emerging as an exciting new approach for modulating immune cell function and polarization states. In this study, carbon tracing and systems biology approaches integrating metabolomic and transcriptomic profiling data were used to identify adaptations in human T cell metabolism important for fueling pro-inflammatory T cell function. Results of this study demonstrate that T cell receptor (TCR) stimulation leads to a significant increase in glucose and amino acid metabolism that trigger downstream biosynthetic processes. Specifically, increased expression of several enzymes such as CTPS1, IL4I1, and ASL results in the reprogramming of amino acid metabolism. Additionally, the strength of TCR signaling resulted in different metabolic enzymes utilized by T cells to facilitate similar biochemical endpoints. Furthermore, this study shows that cyclosporine represses the pathways involved in amino acid and glucose metabolism, providing novel insights on the immunosuppressive mechanisms of this drug. To explore the implications of the findings of this study in clinical settings, conventional immunosuppressants were tested in combination with drugs that target metabolic pathways. Results showed that such combinations increased efficacy of conventional immunosuppressants. Overall, the results of this study provide a comprehensive resource for identifying metabolic targets for novel combinatorial regimens in the treatment of intractable immune diseases.
Structural basis for ligand-induced inactivation of protein tyrosine receptor type Z (PTPRZ): Physiological relevance of head-to-toe RPTP dimerization
Authors: Fujikawa Akihiro , Sugawara Hajime , Tanga Naomi , Ishii Kentaro , Kuboyama Kazuya , Uchiyama Susumu , Suzuki Ryoko , Noda Masaharu 
Published: May 2019

ABSTRACTProtein tyrosine phosphatase receptor type Z (PTPRZ) has two receptor isoforms (PTPRZ-A and -B) containing tandem PTP-D1 and -D2 domains intracellularly, with only D1 being active. Pleiotrophin (PTN) binding to the extracellular region of PTPRZ leads to the inactivation of PTPase, thereby inducing oligodendrocyte precursor cell (OPC) differentiation and myelination in the CNS. However, the mechanisms responsible for the ligand-induced inactivation of PTPRZ remain unclear. We herein revealed that the crystal structure of the intracellular region of PTPRZ (PTPRZ-ICR) showed the “head-to-toe”-type dimer conformation, with D2 masking the catalytic site of D1. Mass spectrometry (MS) revealed that PTPRZ-ICR proteins remained in monomer-dimer equilibrium in aqueous solution, and a substrate-derived inhibitory peptide or competitive inhibitor (SCB4380) specifically bound to the monomer form in a 1:1 stoichiometric ratio, supporting the “head-to-toe dimerization” model for inactivation. A D2 deletion (ΔD2) or dimer interface mutation (DDKK) disrupted dimer formation, while the binding of SCB4380 was maintained. Similar to wild-type PTPRZ-B, monomer-biased PTPRZ-B-ΔD2 and PTPRZ-B-DDKK mutants efficiently dephosphorylated p190RhoGAP at Tyr-1105 when co-expressed in BHK-21 cells. The catalytic activities of these mutants were not suppressed by a treatment with PTN, but were inhibited by the cell-permeable PTPase inhibitor NAZ2329. The PTN treatment did not enhance OPC differentiation in primary cultured glial cells prepared from ΔD2 or catalytically-inactive CS mutant knock-in mice. Our results indicate that PTN-induced PTPRZ inactivation is attained by dimer formation of the intracellular tandem PTP domains in the head-to-toe configuration, which is physiologically relevant to the control of OPC differentiation in vivo.
Prefrontal attentional saccades explore space rhythmically
Authors: Gaillard Corentin , Ben Hadj Hassen Sameh , Di Bello Fabio , Bihan-Poudec Yann , VanRullen Rufin , Ben Hamed Suliann 
Published: May 2019

SummaryRecent studies suggest that attention samples space rhythmically through oscillatory interactions in the frontoparietal network. However, the precise mechanism through which the prefrontal cortex, at the source of attention control signals, organizes this rhythmic exploration of space remains unknown. We show that, when decoded at a high spatial (0.1°) and temporal resolution (50ms), the prefrontal covert attentional spotlight, aka the mind’s eye, continuously explores space at an alpha 7-12 Hz rhythm. When sensory events are presented at a specific optimal phase (resp. anti-phase) with respect to this rhythm, sensory encoding and behavioral report are accurate (resp. poor). We propose that this rhythmic prefrontal attentional spotlight dynamics corresponds to a continuous overt exploration of space via alpha-clocked attentional saccades. These attentional saccades are highly flexible, their pattern of space exploration depending both on within-trial and across-task contingencies. These results are discussed in the context of exploration and exploitation strategies and prefrontal top-down attentional control.HighlightsThe decoded prefrontal attentional spotlight samples visual space in rhythmic cyclesThis rhythmic attentional exploration predicts neuronal sensory processing accuracyThis rhythmic attentional exploration predicts overt behavioral accuracyThese rhythmic cycles define alpha-clocked attentional saccadesSpace exploration by attentional saccades is highly flexible and under top-down control
Characterization of a regulatory T cells molecular meta-signature identifies the pro-enkephalin gene as a novel marker in mice
Authors: Aubert Nicolas , Salomon Benoit L. , Marodon Gilles 
Published: May 2019

AbstractRegulatory T cells (Treg) are crucial in the proper balance of the immune system. A better characterization of Treg-specific genes should extend our knowledge on their complex biology. However, to date there is no consensual Treg signature in the literature. Here, we extracted a molecular Treg meta-signature relative to CD4+ conventional T cell from 8 different but comparable publicly available microarray datasets. We confirmed the validity of our result using the much larger but less stringent Immuno-Navigator database. However, many genes of the Treg meta-signature were also expressed at the protein level by other immune cell subsets, as assessed by mass cytometry, with the noticeable exceptions of Il2ra, Ctla4, and Tnfrsf9. Surprisingly, the proenkephalin (Penk) gene was a prominent member of this restricted Treg meta-signature. Further analysis of public datasets and of our own RNA sequencing experiments confirms that Penk was over expressed by Treg in various murine tissues, including thymic Treg. Interestingly, Penk expression was increased in intra tumoral Treg whereas it was down modulated in the central nervous system of mice suffering from EAE. Finally, we propose a mechanistic model linking TNFR signaling and the transcription factor Batf in the regulation of Penk expression in Treg. Altogether, our results provide the first Treg meta-signature in mice and identifies Penk as a novel and unexpected Treg marker.
BaRTv1.0: an improved barley reference transcript dataset to determine accurate changes in the barley transcriptome using RNA-seq
Authors: Rapazote-Flores Paulo , Bayer Micha , Milne Linda , Mayer Claus-Dieter , Fuller John , Guo Wenbin , Hedley Pete E , Morris Jenny , Halpin Claire , Kam Jason , McKim Sarah M. , Zwirek Monika , Casao M. Cristina , Barakate Abdellah , Schreiber Miriam , Stephen Gordon , Zhang Runxuan , Brown John WS , Waugh Robbie , Simpson Craig G 
Published: May 2019

AbstractBackgroundTime consuming computational assembly and quantification of gene expression and splicing analysis from RNA-seq data vary considerably. Recent fast non-alignment tools such as Kallisto and Salmon overcome these problems, but these tools require a high quality, comprehensive reference transcripts dataset (RTD), which are rarely available in plants.ResultsA high-quality, non-redundant barley gene RTD and database (Barley Reference Transcripts – BaRTv1.0) has been generated. BaRTv1.0, was constructed from a range of tissues, cultivars and abiotic treatments and transcripts assembled and aligned to the barley cv. Morex reference genome (Mascher et al., 2017). Full-length cDNAs from the barley variety Haruna nijo (Matsumoto et al., 2011) determined transcript coverage, and high-resolution RT-PCR validated alternatively spliced (AS) transcripts of 86 genes in five different organs and tissue. These methods were used as benchmarks to select an optimal barley RTD. BaRTv1.0-Quantification of Alternatively Spliced Isoforms (QUASI) was also made to overcome inaccurate quantification due to variation in 5’ and 3’ UTR ends of transcripts. BaRTv1.0-QUASI was used for accurate transcript quantification of RNA-seq data of five barley organs/tissues. This analysis identified 20,972 significant differentially expressed genes, 2,791 differentially alternatively spliced genes and 2,768 transcripts with differential transcript usage.ConclusionA high confidence barley reference transcript dataset consisting of 60,444 genes with 177,240 transcripts has been generated. Compared to current barley transcripts, BaRTv1.0 transcripts are generally longer, have less fragmentation and improved gene models that are well supported by splice junction reads. Precise transcript quantification using BaRTv1.0 allows routine analysis of gene expression and AS.