bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Patient Safety Culture Scale for Chinese Primary Health Care Institutions: Development, Validity and Reliability
Authors: Cheng Siyu , Hu Yinhuan , Pfaff Holger , Lu Chuntao , Fu Qiang , Wang Liuming , Li Dehe , Xia Shixiao 
Published: May 2020

Background
Existing patient safety culture assessment tools are mostly developed in western countries and may not be suitable for Chinese primary health care institutions. Primary care plays an important role in China’s medical system, and a targeted tool for its patient safety culture is urgently needed.

Objective
The aim of the study was to develop a dependable instrument to assess the patient safety culture in Chinese primary health care institutions.

Methods
Three phases were undertaken to develop the scale. The first phase developed a pilot scale by literature review, focus groups, and 2-round Delphi expert consultation. The second phase conducted a pilot survey. The third phase carried out a formal survey to test reliability and validity, involving 369 participants from 9 primary health care institutions.

Results
The final scale included 32 items under 7 dimensions. For reliability, the Cronbach α coefficients among dimensions varied from 0.754 to 0.926, and the Cronbach α for the scale was 0.940. For content validity, the corrected item-level content validity varied between 0.64 and 1, the scale-level content validity index/universal agreement was 0.625, and the scale-level content validity index/average was 0.93. For construct validity, the Spearman correlations of dimension-total score varied between 0.129 and 0.851, all Spearman correlations of the dimension-total score were greater than that of interdimensions and the Spearman correlations of item-total score ranged from 0.042 to 0.775. The results of the confirmatory factor analysis indicated that the model fitted well.

Conclusions
The Patient Safety Culture Scale for Chinese primary health care institutions demonstrated good reliability and acceptable validity; thus, it can be used as an assessment instrument for patient safety culture in Chinese primary health care institutions.
FDG PET/CT in Anaplastic Lymphoma Kinase–Positive Anaplastic Large Cell Lymphoma
Authors: Angamuthu Meivel , Kaur Kanwaljeet , Tripathi Madhavi , Meena Jagdish Prasad , Seth Rachna , Kumar Rakesh 
Published: May 2020

Abstract
Anaplastic large cell lymphoma (ALCL) is a rare non-Hodgkin’s lymphoma, with rearrangements of the anaplastic lymphoma kinase gene in 60%–85% of systemic cases. We report an 11-year-old boy with ALCL in whom serial FDG PET/CT revealed partial response and complete metabolic response at interim and end of treatment, respectively. However, the patient relapsed within 2 weeks, confirmed by cytology. Because of the inherent aggressive nature of ALCL, possibility of an early relapse should always be kept in mind.
Emerging Attack and Management Strategies for Nuclear Medicine in Responding to COVID-19—ACNM Member Experience and Advice
Authors: Lu Yang , Zhu Xiaohua , Yan Sean Xuexian , Lan Xiaoli 
Published: May 2020

Abstract
As the World Health Organization declared COVID-19 as “global pandemic,” it is important for everyone, including nuclear medicine personnel, to know how to stop transmission, contain, and prevent the spread of COVID-19. We reach out to our ACNM (American College of Nuclear Medicine) international members from Wuhan, China and Singapore, who have participated in dealing with COVID-19 for the last 2 months, to learn from their lessons and experiences, so to provide advice to all ACNM members for their clinical practice and management strategies in responding to COVID-19.
Focal 18F-NaF PET Prostate Activity in the Setting of Prostate Adenocarcinoma
Authors: Chiang Jason , Gershenson Jonathan P. , Lewis Michael S. , Vahidi Kiarash , Berenji Gholam R. 
Published: May 2020

Abstract
A 72-year-old man with a family history of prostate cancer and initial diagnosis of favorable intermediate risk prostate cancer via biopsy in 2017 elected for active surveillance. Two years later, he underwent prostate biopsy showing intermediate-risk cT1c Nx Mx lesion with Gleason score 3 + 4 = 7 (5 core positive). Transrectal ultrasound showed a prostate volume 28 mL, and the prostate-specific antigen was 8.1. Patient elected to proceed with combination radiation therapy and androgen deprivation therapy.
Using the Preparedness Assessment for the Transition Home After Stroke Instrument to Identify Stroke Caregiver Concerns Predischarge: Uncertainty, Anticipation, and Cues to Action
Authors: Camicia Michelle , Lutz Barbara J. , Harvath Theresa A. , Joseph Jill G. 
Published: May 2020

Abstract

Purpose
The aim of the study was to better understand caregivers’ concerns about long-term implications of stroke and the caregiving role after completing the Preparedness Assessment for the Transition Home After Stroke (PATH-s).

Design/Methods
In this qualitative study, cognitive interviews were conducted with 20 stroke caregivers who completed the PATH-s tool as part of an instrument validation study. Data were analyzed for salient themes related to their perceptions about stroke and the caregiving role.

Findings
Interviews yielded robust narrative data describing how the PATH-s items aided caregivers in recognizing potential issues and concerns about stroke and the caregiving role. Caregivers experienced uncertainty about the long-term stroke prognosis, which provoked anticipation and cues to action to begin addressing their concerns.

Conclusions/Clinical Relevance
Completing the PATH-s helped caregivers identify concerns regarding the long-term implications of stroke and their caregiving role. It may serve as an important assessment tool to assist rehabilitation nurses to better understand and address caregiver needs predischarge.
Clinical Value of Serum LHPP-associated miR-765 in the Prognosis of Laparoscopic or Open Hepatectomy for Hepatocellular Carcinoma
Authors: Yan Jingting , He Liyan , Li Guang , Peng Xiuda , Li Wei , Liu Xianrong , Yang Dunxue , Liu Jin , Zhang Peng , Lu Xianzhou 
Published: May 2020

Purpose:
The current study aims to investigate the effect of tumor suppressor LHPP-associated microRNA (miR)-765 on the prognosis of laparoscopic hepatectomy (LH) or open hepatectomy (OH) for hepatocellular carcinoma (HCC).

Materials and Methods:
A total of 160 patients with HCC were enrolled and randomly divided into the LH or OH group. According to the operation time, these patients were followed up for 12 months, and the number of deaths and the corresponding death time during the follow-up period were counted.

Results:
The authors found that the LHPP gene levels in HCC tissues were lower than that in adjacent normal tissues, whereas miR-765 was overexpressed in HCC tissue. Overexpression of miR-765 promoted the epithelial-mesenchymal transition and proliferation and inhibited apoptosis of HCC through directly downregulating LHPP expression. Serum miR-765 expression level was significantly associated with lymph node metastasis and histologic grading. Survival analysis showed that the overall survival rate in 12 months after the operation was significantly lower in the OH-high miR-765 group (P<0.05).

Conclusion:
For patients with a low miR-765 level, both LH and OH are available, otherwise, LH is more recommended.
FLEXIQuant-LF: Robust Regression to Quantify Protein Modification Extent in Label-Free Proteomics Data
Authors: Kahnert Konstantin , Schlaffner Christoph N. , Muntel Jan , Chauhan Ruchi , Renard Bernhard Y. , Steen Judith A. , Steen Hanno 
Published: May 2020

AbstractImprovements in LC-MS/MS methods and technology have enabled the identification of thousands of modified peptides in a single experiment. However, protein regulation by post-translational modifications (PTMs) is not binary, making methods to quantify the modification extent crucial to understanding the role of PTMs. Here, we introduce FLEXIQuant-LF, a software tool for large-scale identification of differentially modified peptides and quantification of their modification extent without prior knowledge of the type of modification. We developed FLEXIQuant-LF using label-free quantification of unmodified peptides and robust linear regression to quantify the modification extent of peptides. As proof of concept, we applied FLEXIQuant-LF to data-independent-acquisition (DIA) data of the anaphase promoting complex/cyclosome (APC/C) during mitosis. The unbiased FLEXIQuant-LF approach to assess the modification extent in quantitative proteomics data provides a better understanding of the function and regulation of PTMs. The software is available at https://github.com/SteenOmicsLab/FLEXIQuantLF.
Multi-scale modeling shows that dielectric differences make NaV channels faster than KV channels
Authors: Catacuzzeno Luigi , Sforna Luigi , Franciolini Fabio , Eisenberg Robert S. 
Published: May 2020

AbstractThe generation of action potentials in excitable cells requires different activation kinetics of voltage gated Na (NaV) and K (KV) channels. NaV channels activate much faster and allow the initial Na+ influx that generates the depolarizing phase and propagates the signal. Recent experimental results suggest that the molecular basis for this kinetic difference is an amino acid side chain located in the gating pore of the voltage sensor domain, which is a highly conserved isoleucine in KV channels, but an equally highly conserved threonine in NaV channels. Mutagenesis suggests that the hydrophobicity of this side chain in Shaker KV channels regulates the energetic barrier that gating charges need to overcome to move through the gating pore, and ultimately the rate of channel opening. We use a multi-scale modeling approach to test this hypothesis. We use high resolution molecular dynamics to study the effect of the mutation on polarization charge within the gating pore. We then incorporate these results in a lower resolution model of voltage gating to predict the effect of the mutation on the movement of gating charges. The predictions of our hierarchical model are fully consistent with the tested hypothesis, thus suggesting that the faster activation kinetics of NaV channels comes from a stronger dielectric polarization by threonine (NaV channel) produced as the first gating charge enters the gating pore, compared to isoleucine (KV channel).eTOC SummaryVoltage-gated Na+ channels activate faster than K+ channels in excitable cells. Catacuzzeno et al. develop a model that shows how the dielectric properties of a divergent side-chain produce this difference in speed.
Genome-scale phylogeny and contrasting modes of genome evolution in the fungal phylum Ascomycota
Authors: Shen Xing-Xing , Steenwyk Jacob L. , LaBella Abigail L. , Opulente Dana A. , Zhou Xiaofan , Kominek Jacek , Li Yuanning , Groenewald Marizeth , Hittinger Chris Todd , Rokas Antonis 
Published: May 2020

AbstractAscomycota, the largest and best-studied phylum of fungi, contains three subphyla: Saccharomycotina (budding yeasts), Pezizomycotina (filamentous fungi), and Taphrinomycotina (fission yeasts); organisms from all three subphyla have been invaluable as models in diverse fields (e.g., biotechnology, cell biology, genetics, and medicine). Despite its importance, we still lack a comprehensive genome-scale phylogeny or understanding of the similarities and differences in the mode of genome evolution within this phylum. To address these gaps, we examined 1,107 genomes from Saccharomycotina (332), Pezizomycotina (761), and Taphrinomycotina (14) species to infer the Ascomycota phylogeny, estimate its timetree, and examine the evolution of key genomic properties. We inferred a robust genome-wide phylogeny that resolves several contentious relationships and estimated that the Ascomycota last common ancestor likely originated in the Ediacaran (~563 ± 68 million years ago). Comparisons of genomic properties revealed that Saccharomycotina and Pezizomycotina, the two taxon-rich subphyla, differed greatly in their genome properties. Saccharomycotina typically have smaller genomes, lower GC contents, lower numbers of genes, and higher rates of molecular sequence evolution compared to Pezizomycotina. Ancestral state reconstruction showed that the genome properties of the Saccharomycotina and Pezizomycotina last common ancestors were very similar, enabling inference of the direction of evolutionary change. For example, we found that a lineage-specific acceleration led to a 1.6-fold higher evolutionary rate in Saccharomycotina, whereas the 10% difference in GC content between Saccharomycotina and Pezizomycotina genomes stems from a trend toward AT bases within budding yeasts and toward GC bases within filamentous fungi. These results provide a robust evolutionary framework for understanding the diversification of the largest fungal phylum.
Effects of the GluN2B antagonist, Ro 25-6981, on extinction consolidation following adolescent- or adult-onset methamphetamine self-administration in male and female rats
Authors: Westbrook Sara R. , Gulley Joshua M. 
Published: May 2020

AbstractPrevious work suggests adolescent rats have deficient extinction consolidation relative to adults. Although the mechanisms underlying this age difference are currently unknown, studies in adult rats have implicated GluN2B-containing NMDA receptor function in extinction consolidation of drug-associated memory. Importantly, GluN2B neurotransmission emerges during adolescent development, and drugs of abuse during adolescence may delay the development of extinction consolidation by disrupting the ontogeny of GluN2B function. Here, we trained Sprague-Dawley rats of both sexes to self-administer methamphetamine (METH, 0.1 mg/kg/infusion i.v.) beginning during adolescence [postnatal (P) day 41] or adulthood (P91). Rats were given short access (2 h) to self-administer METH in seven daily sessions followed by fourteen sessions with long access (6 h). Subsequently, rats underwent four daily 30-min extinction sessions with immediate post-session injections of either a GluN2B antagonist (Ro25-6981; 6 mg/kg, i.p.) or a vehicle solution. After four daily 2-h extinction sessions, a priming injection (1 mg/kg METH, i.p.) was given prior to a final 2-h reinstatement session. During LgA, adolescent-onset rats earn more METH than adult-onset rats and display greater drug-loading behavior. Rats reduced their drug-seeking behavior across extinction sessions, with no significant group differences. Rats reinstated drug-seeking following the METH priming injection, with females displaying greater reinstatement than males. These results do not support oura priorihypothesis that adolescent-onset METH use disrupts the ontogeny of GluN2B transmission and contributes to age-of-onset differences in extinction of METH-seeking. However, our findings suggest that age-of-onset contributes to excessive METH-taking, while sex confers vulnerability to relapse to METH-seeking.
A growth-based, high-throughput selection platform enables remodeling of 4-hydroxybenzoate hydroxylase active site
Authors: Maxel Sarah , Aspacio Derek , King Edward , Zhang Linyue , Acosta Ana Paula , Li Han 
Published: May 2020

ABSTRACTWe report an aerobic, growth-based selection platform founded on NADP(H) redox balance restoration inEscherichia coli, and demonstrate its application in high-throughput evolution of oxygenase. A single round of selection enabledPseudomonas aeruginoasa4-hydroxybenzoate hydroxylase (PobA) to accept 3,4-dihydroxybenzoic acid efficiently, an essential step toward gallic acid biosynthesis. The best variant DA015 exhibited more than 5-fold higher catalytic efficiency compared to previously engineered enzymes. Structural modeling suggests precise re-organization of active site hydrogen bond network, which is difficult to obtain without deep navigation of combinatorial sequence space. We envision universal application of this selection platform in engineering NADPH-dependent oxidoreductases.
Listeria monocytogenespersonalized cancer vaccines drive therapeutic immune responses to cancer derived neoantigens
Authors: Coder Brandon , Pryshchep Olga , Kelkar Dipti , Filippova Elena , Ju Xiaoming , Balli David , Mottershead Cristina , Ramos Kim , Thambi Nithya , Cheng Zhiyong , Lugt Bryan Vander , Lesch Justin , Liu Xian , DeVoss Jason , Cooke Keegan , Liu Siyuan , Zhan Jinghui , Mitchell Petia , Villarreal Daniel O , Hayes Sandra M. , Johnston James A , Petit Robert , Phee Hyewon , Princiotta Michael F. 
Published: May 2020

AbstractBackgroundRecent advances in the field of cancer immunotherapy have identified CD8+T cell responses against tumor-specific mutations as a key driver of tumor regression and overall survival. ADXS-NEO is a personalizedListeria monocytogenes(Lm)-based immunotherapy designed to target a patient’s mutation-derived tumor-specific neoantigens. The objective of this study is to demonstrate the feasibility of using the ADXS-NEO platform to target tumor-specific point mutations and control tumor growth by generating neoantigen-specific T cell responses using a pre-clinical mouse tumor model.MethodsWhole-exome sequencing of the MC38 mouse tumor cell line identified 2870 unique non-synonymous mutations. The netMHCcons algorithm was used to predict 137 potential neoantigens. We validated 20 immunogenic neoantigens either by peptide immunization followed by ELISPOT or by the presence of CD8+T cells recognizing the neoantigen peptide following checkpoint inhibitor treatment. Two ADXS-NEO vectors were constructed; Lm20, targeting 20 validated immunogenic neoantigens, and Lm19, targeting most of the non-validated NSMs.ResultsBoth Lm19 & Lm20 significantly slowed tumor growth in C57BL/6 mice compared to control. An accumulation of ADXS-NEO-specific TILs was observed in tumor bearing mice treated with either Lm19 or Lm20. Examination of the tumor microenvironment in Lm19 or Lm20 treated mice revealed a decrease in the frequency and absolute number of Tregs, TAMs, MDSCs, and PD1highexhausted CD8+T cells as well as an increase in the frequency and absolute number of effector CD8+T cells, relative to control.ConclusionADXS-NEO is a potent immunotherapy capable of driving immune responses against tumor-specific mutations and leading to tumor control in mice.
Leukemia cell of origin influences apoptotic priming and sensitivity to LSD1 inhibition
Authors: Cai Sheng F. , Chu S. Haihua , Goldberg Aaron D. , Parvin Salma , Koche Richard P. , Glass Jacob L. , Stein Eytan M. , Tallman Martin S. , Sen Filiz , Famulare Christopher , Cusan Monica , Huang Chun-Hao , Chen Chun-Wei , Zou Lihua , Cordner Keith B. , DelGaudio Nicole L. , Durani Vidushi , Kini Mitali , Rex Madison , Tian Helen S. , Zuber Johannes , Baslan Timour , Lowe Scott W. , Rienhoff Hugh Y. , Letai Anthony , Levine Ross L. , Armstrong Scott A. 
Published: May 2020

SummaryPrevious studies have established that the cell of origin of oncogenic transformation is a determinant of therapeutic sensitivity. However, the mechanisms governing cell-of-origin-driven differences in therapeutic response have not been delineated. Leukemias initiating in hematopoietic stem cells (HSC) are less sensitive to cytotoxic chemotherapy and express high levels of the transcription factorEvi1compared to leukemias derived from myeloid progenitors. Here, we compared drug sensitivity and expression profiles of murine and human leukemias initiated in either HSCs or myeloid progenitors to reveal a novel function forEvi1in modulating p53 protein stability and activity. HSC-derived leukemias exhibit decreased apoptotic priming, attenuated p53 transcriptional output, and resistance to lysine-specific demethylase 1 inhibitors in addition to classical genotoxic stresses. p53 loss-of-function inEvi1lowprogenitor-derived leukemias induces resistance to LSD1 inhibition. By contrast,Evi1highleukemias are sensitized to LSD1 inhibition by the BH3 mimetic venetoclax, resulting in enhanced apoptosis and greater reductions in disease burden. Our findings demonstrate a cell-of-origin determined novel role forEVI1in p53 wild-type cancers in reducing p53 function and provide a strategy to circumvent drug resistance in high-risk, chemoresistantEVI1highAML.
Neural encoding of task-dependent errors during adaptive learning
Authors: Kao Chang-Hao , Lee Sangil , Gold Joshua I. , Kable Joseph W. 
Published: May 2020

AbstractEffective learning requires using errors in a task-dependent manner, for example adjusting to errors that result from unpredicted environmental changes but ignoring errors that result from environmental stochasticity. Where and how the brain represents errors in a task-dependent manner and uses them to guide behavior are not well understood. We imaged the brains of human participants performing a predictive-inference task with two conditions that had different sources of errors. Their performance was sensitive to this difference, including more choice switches after fundamental changes versus stochastic fluctuations in reward contingencies. Using multi-voxel pattern classification, we identified task-dependent representations of error magnitude and past errors in posterior parietal cortex. These representations were distinct from representations of the resulting behavioral adjustments in dorsomedial frontal, anterior cingulate, and orbitofrontal cortex. The results provide new insights into how the human brain represents errors in a task-dependent manner and guides subsequent adaptive behavior.
Molecular Basis for N-terminal Alpha-Synuclein Acetylation by Human NatB
Authors: Deng Sunbin , Pan Buyan , Gottlieb Leah , Petersson E. James , Marmorstein Ronen 
Published: May 2020

AbstractNatB is one of three major N-terminal acetyltransferase (NAT) complexes (NatA-NatC), which co-translationally acetylate the N-termini of eukaryotic proteins. Its substrates account for about 21% of the human proteome, including well known proteins such as actin, tropomyosin, CDK2, and α-synuclein (αSyn). Human NatB (hNatB) mediated N-terminal acetylation of αSyn has been demonstrated to play key roles in Parkinson’s disease pathogenesis and as a potential therapeutic target for hepatocellular carcinoma. Here we report the cryo-EM structure of hNatB bound to a CoA-αSyn conjugate, together with structure-guided analysis of mutational effects on catalysis. This analysis reveals functionally important differences with human NatA andCandida albicansNatB, resolves key hNatB protein determinants for αSyn N-terminal acetylation, and identifies important residues for substrate-specific recognition and acetylation by NatB enzymes. These studies have implications for developing small molecule NatB probes and for understanding the mode of substrate selection by NAT enzymes.