bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal Long-Chain Fatty Acids Act as a Direct Signal To Modulate Expression of the
Salmonella
Pathogenicity Island 1 Type III Secretion System
Authors: Golubeva Yekaterina A. , Ellermeier Jeremy R. , Cott Chubiz Jessica E. , Slauch James M. 
Published: February 2016

ABSTRACT

Salmonella enterica
serovar Typhimurium uses the
Salmonella
pathogenicity island 1 (SPI1) type III secretion system (T3SS) to induce inflammatory diarrhea and bacterial uptake into intestinal epithelial cells. The expression of
hilA
, encoding the transcriptional activator of the T3SS structural genes, is directly controlled by three AraC-like regulators, HilD, HilC, and RtsA, each of which can activate
hilD
,
hilC
,
rtsA
, and
hilA
genes, forming a complex feed-forward regulatory loop. Expression of the SPI1 genes is tightly controlled by numerous regulatory inputs to ensure proper timing in production of the T3SS apparatus. Loss of FadD, an acyl coenzyme A (acyl-CoA) synthetase required for degradation of long-chain fatty acids (LCFAs), was known to decrease
hilA
expression. We show that free external LCFAs repress expression of
hilA
independently of FadD and the LCFA degradation pathway. Genetic and biochemical evidence suggests that LCFAs act directly to block primarily HilD activity. Further analyses show that in the absence of FadD,
hilA
expression is downregulated due to endogenous production of free LCFAs, which are excreted into the culture medium via TolC and then transported back into the bacterial cell via FadL. A
fadL
mutant is more virulent than the wild-type strain in mouse oral competition assays independently of LCFA degradation, showing that, in the host, dietary LCFAs serve as a signal for proper regulation of SPI1 expression, rather than an energy source.

IMPORTANCE
To cause disease,
Salmonella
must respond to diverse environmental cues to express its invasion machinery at the appropriate location in the host intestine. We show that host intestinal free long-chain fatty acids (LCFAs) affect
Salmonella
invasion by reducing expression of the SPI1 type III secretion system, acting primarily via the AraC-like activator HilD. Degradation of LCFAs is not required for this regulation, showing that free LCFAs serve as a cue to proper intestinal localization to invade host epithelial cells and not as a nutrient source.
Surgical complications and their impact on patients’ psychosocial well-being: a systematic review and meta-analysis
Authors: Pinto Anna , Faiz Omar , Davis Rachel , Almoudaris Alex , Vincent Charles 
Published: February 2016

ObjectiveSurgical complications may affect patients psychologically due to challenges such as prolonged recovery or long-lasting disability. Psychological distress could further delay patients’ recovery as stress delays wound healing and compromises immunity. This review investigates whether surgical complications adversely affect patients’ postoperative well-being and the duration of this impact.MethodsThe primary data sources were ‘PsychINFO’, ‘EMBASE’ and ‘MEDLINE’ through OvidSP (year 2000 to May 2012). The reference lists of eligible articles were also reviewed. Studies were eligible if they measured the association of complications after major surgery from 4 surgical specialties (ie, cardiac, thoracic, gastrointestinal and vascular) with adult patients’ postoperative psychosocial outcomes using validated tools or psychological assessment. 13 605 articles were identified. 2 researchers independently extracted information from the included articles on study aims, participants’ characteristics, study design, surgical procedures, surgical complications, psychosocial outcomes and findings. The studies were synthesised narratively (ie, using text). Supplementary meta-analyses of the impact of surgical complications on psychosocial outcomes were also conducted.Results50 studies were included in the narrative synthesis. Two-thirds of the studies found that patients who suffered surgical complications had significantly worse postoperative psychosocial outcomes even after controlling for preoperative psychosocial outcomes, clinical and demographic factors. Half of the studies with significant findings reported significant adverse effects of complications on patient psychosocial outcomes at 12 months (or more) postsurgery. 3 supplementary meta-analyses were completed, 1 on anxiety (including 2 studies) and 2 on physical and mental quality of life (including 3 studies). The latter indicated statistically significantly lower physical and mental quality of life (p<0.001) for patients who suffered surgical complications.ConclusionsSurgical complications appear to be a significant and often long-term predictor of patient postoperative psychosocial outcomes. The results highlight the importance of attending to patients’ psychological needs in the aftermath of surgical complications.
Impact of visual acuity on developing literacy at age 4–5 years: a cohort-nested cross-sectional study
Authors: Bruce Alison , Fairley Lesley , Chambers Bette , Wright John , Sheldon Trevor A 
Published: February 2016

ObjectivesTo estimate the prevalence of poor vision in children aged 4–5 years and determine the impact of visual acuity on literacy.DesignCross-sectional study linking clinical, epidemiological and education data.SettingSchools located in the city of Bradford, UK.ParticipantsPrevalence was determined for 11 186 children participating in the Bradford school vision screening programme. Data linkage was undertaken for 5836 Born in Bradford (BiB) birth cohort study children participating both in the Bradford vision screening programme and the BiB Starting Schools Programme. 2025 children had complete data and were included in the multivariable analyses.Main outcome measuresVisual acuity was measured using a logMAR Crowded Test (higher scores=poorer visual acuity). Literacy measured by Woodcock Reading Mastery Tests-Revised (WRMT-R) subtest: letter identification (standardised).ResultsThe mean (SD) presenting visual acuity was 0.14 (0.09) logMAR (range 0.0–1.0). 9% of children had a presenting visual acuity worse than 0.2logMAR (failed vision screening), 4% worse than 0.3logMAR (poor visual acuity) and 2% worse than 0.4logMAR (visually impaired). Unadjusted analysis showed that the literacy score was associated with presenting visual acuity, reducing by 2.4 points for every 1 line (0.10logMAR) reduction in vision (95% CI −3.0 to −1.9). The association of presenting visual acuity with the literacy score remained significant after adjustment for demographic and socioeconomic factors reducing by 1.7 points (95% CI −2.2 to −1.1) for every 1 line reduction in vision.ConclusionsPrevalence of decreased visual acuity was high compared with other population-based studies. Decreased visual acuity at school entry is associated with reduced literacy. This may have important implications for the children's future educational, health and social outcomes.
ABCG2 and ABCB1 Limit the Efficacy of Dasatinib in a PDGF-B–Driven Brainstem Glioma Model
Authors: Mittapalli Rajendar K. , Chung Alexander H. , Parrish Karen E. , Crabtree Donna , Halvorson Kyle G. , Hu Guo , Elmquist William F. , Becher Oren J. 
Published: February 2016

Abstract
Dasatinib is a multikinase inhibitor in clinical trials for glioma, and thus far has failed to demonstrate significant efficacy. We investigated whether the ABC efflux transporters ABCG2 and ABCB1 expressed in the blood–brain barrier (BBB), are limiting the efficacy of dasatinib in the treatment of glioma using genetic and pharmacologic approaches. We utilized a genetic brainstem glioma mouse model driven by platelet-derived growth factor-B and p53 loss using abcg2/abcb1 wild-type (ABC WT) or abcg2/abcb1 knockout mice (ABC KO). First, we observed that brainstem glioma tumor latency is significantly prolonged in ABC KO versus ABC WT mice (median survival of 47 vs. 34 days). Dasatinib treatment nearly doubles the survival of brainstem glioma-bearing ABC KO mice (44 vs. 80 days). Elacridar, an ABCG2 and ABCB1 inhibitor, significantly increases the efficacy of dasatinib in brainstem glioma-bearing ABC WT mice (42 vs. 59 days). Pharmacokinetic analysis demonstrates that dasatinib delivery into the normal brain, but not into the tumor core, is significantly increased in ABC KO mice compared with ABC WT mice. Surprisingly, elacridar did not significantly increase dasatinib delivery into the normal brain or the tumor core of ABC WT mice. Next, we demonstrate that the tight junctions of the BBB of this model are compromised as assessed by tissue permeability to Texas Red dextran. Finally, elacridar increases the cytotoxicity of dasatinib independent of ABCG2 and ABCB1 expression in vitro. In conclusion, elacridar improves the efficacy of dasatinib in a brainstem glioma model without significantly increasing its delivery to the tumor core. Mol Cancer Ther; 15(5); 819–29. ©2016 AACR.
Identification of a Small Molecule That Overcomes HdmX-Mediated Suppression of p53
Authors: Karan Goutam , Wang Huaiyu , Chakrabarti Amit , Karan Sukanya , Liu Zhigang , Xia Zhiqiang , Gundluru Mahesh , Moreton Stephen , Saunthararajah Yogen , Jackson Mark W. , Agarwal Mukesh K. , Wald David N. 
Published: February 2016

Abstract
Inactivation of the p53 tumor suppressor by mutation or overexpression of negative regulators occurs frequently in cancer. As p53 plays a key role in regulating proliferation or apoptosis in response to DNA-damaging chemotherapies, strategies aimed at reactivating p53 are increasingly being sought. Strategies to reactivate wild-type p53 include the use of small molecules capable of releasing wild-type p53 from key, cellular negative regulators, such as Hdm2 and HdmX. Derivatives of the Hdm2 antagonist Nutlin-3 are in clinical trials. However, Nutlin-3 specifically disrupts Hdm2-p53, leaving tumors harboring high levels of HdmX resistant to Nutlin-3 treatment. Here, we identify CTX1, a novel small molecule that overcomes HdmX-mediated p53 repression. CTX1 binds directly to HdmX to prevent p53–HdmX complex formation, resulting in the rapid induction of p53 in a DNA damage–independent manner. Treatment of a panel of cancer cells with CTX1 induced apoptosis or suppressed proliferation and, importantly, CTX1 demonstrates promising activity as a single agent in a mouse model of circulating primary human leukemia. CTX1 is a small molecule HdmX inhibitor that demonstrates promise as a cancer therapeutic candidate. Mol Cancer Ther; 15(4); 574–82. ©2016 AACR.
STAT1 and NF-κB Inhibitors Diminish Basal Interferon-Stimulated Gene Expression and Improve the Productive Infection of Oncolytic HSV in MPNST Cells
Authors: Jackson Joshua D. , Markert James M. , Li Li , Carroll Steven L. , Cassady Kevin A. 
Published: February 2016

Abstract
Interferon-stimulated genes (ISG) encode diverse proteins that mediate intrinsic antiviral resistance in infected cells. Here it was hypothesized that malignant peripheral nerve sheath tumor (MPNST) cells resist the productive infection of oncolytic herpes simplex virus (oHSV) through activation of the JAK/STAT1 pathway and resultant upregulation of ISGs. Multiple human and mouse MPNST cells were used to explore the relationship between STAT1 activation and the productive infection of Δγ134.5 oHSVs. STAT1 activation in response to oHSV infection was found to associate with diminished Δγ134.5 oHSVs replication and spread. Multiday pretreatment, but not cotreatment, with a JAK inhibitor significantly improved viral titer and spread. ISG expression was found to be elevated prior to infection and downregulated when treated with the inhibitor, suggesting that the JAK/STAT1 pathway is active prior to infection. Conversely, upregulation of ISG expression in normally permissive cells significantly decreased oHSV productivity. Finally, a possible link between NF-κB pathway activation and ISG expression was established through the expression of inhibitor of kB (IκB) which decreased basal STAT1 transcription and ISG expression. These results demonstrate that basal ISG expression prior to infection contributes to the resistance of Δγ134.5 oHSVs in MPNST cells.
Implications: Although cancer-associated ISG expression has been previously reported to impart resistance to chemotherapy and radiotherapy, these data show that basal ISG expression also contributes to oncolytic HSV resistance. Mol Cancer Res; 14(5); 482–92. ©2016 AACR.
Observed Tropical Cyclone Size Revisited
Authors: Chavas Daniel R. , Lin Ning , Dong Wenhao , Lin Yanluan 
Published: February 2016

Abstract
This work revisits the statistics of observed tropical cyclone outer size in the context of recent advances in our theoretical understanding of the storm wind field. The authors create a new dataset of the radius of 12 m s−1 winds based on a recently updated version of the QuikSCAT ocean wind vector database and apply an improved analytical outer wind model to estimate the outer radius of vanishing wind. The dataset is then applied to analyze the statistical distributions of the two size metrics as well as their dependence on environmental parameters, with a specific focus on testing recently identified parameters possessing credible theoretical relationships with tropical cyclone size. The ratio of the potential intensity to the Coriolis parameter is found to perform poorly in explaining variation of size, with the possible exception of its upper bound, the latter of which is in line with existing theory. The rotating radiative–convective equilibrium scaling of Khairoutdinov and Emanuel is also found to perform poorly. Meanwhile, mean storm size is found to increase systematically with the relative sea surface temperature, in quantitative agreement with the results of a recent study of storm size based on precipitation area. Implications of these results are discussed in the context of existing tropical climate theory. Finally, an empirical dependence of the central pressure deficit on outer size is found in line with past work.
Surface-based brain morphometry and diffusion tensor imaging in schizoaffective disorder
Authors: Landin-Romero Ramón , Canales-Rodríguez Erick J , Kumfor Fiona , Moreno-Alcázar Ana , Madre Mercè , Maristany Teresa , Pomarol-Clotet Edith , Amann Benedikt L 
Published: February 2016

Background: The profile of grey matter abnormalities and related white-matter pathology in schizoaffective disorder has only been studied to a limited extent. The aim of this study was to identify grey- and white-matter abnormalities in patients with schizoaffective disorder using complementary structural imaging techniques. Methods: Forty-five patients meeting Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition criteria and Research Diagnostic Criteria for schizoaffective disorder and 45 matched healthy controls underwent structural-T1 and diffusion magnetic resonance imaging to enable surface-based brain morphometry and diffusion tensor imaging analyses. Analyses were conducted to determine group differences in cortical volume, cortical thickness and surface area, as well as in fractional anisotropy and mean diffusivity. Results: At a threshold of p = 0.05 corrected, all measures revealed significant differences between patients and controls at the group level. Spatial overlap of abnormalities was observed across the various structural neuroimaging measures. In grey matter, patients with schizoaffective disorder showed abnormalities in the frontal and temporal lobes, striatum, fusiform, cuneus, precuneus, lingual and limbic regions. White-matter abnormalities were identified in tracts connecting these areas, including the corpus callosum, superior and inferior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus and cingulum bundle. Conclusion: The spatial overlap of abnormalities across the different imaging techniques suggests widespread and consistent brain pathology in schizoaffective disorder. The abnormalities were mainly detected in areas that have commonly been reported to be abnormal in schizophrenia, and to some extent in bipolar disorder, which may explain the clinical and aetiological overlap in these disorders.
Implementation of a Pediatric Posttonsillectomy Pain Protocol in a Large Group Practice
Authors: Luk Lauren J. , Mosen David , MacArthur Carol J. , Grosz Anna H. 
Published: February 2016

ObjectiveIn response to the increased risk of respiratory failure and death after tonsillectomy related to codeine use, Kaiser Permanente Northwest restricted use of opioids in patients <7 years old via electronic health record (EHR). However, opioids could be prescribed at physician discretion by overriding the EHR. This study aims to examine protocol compliance in a large group practice using EHR order sets and complication rates as compared with historical data.Study DesignCase series with chart review.SettingAmbulatory care within a health maintenance organization.Subjects and MethodsProcedural codes were used to identify children <7 years old who underwent tonsillectomy or adenotonsillectomy approximately 1.5 years before and after implementation of EHR protocol (n = 437). Primary outcome was opioid pain prescriptions received by patients. Secondary outcomes were emergency or urgent care utilization, postoperative bleeding, nausea, vomiting, dehydration, death, and reasons for prescribing opioid pain medication after EHR protocol implementation. Chi‐square analysis and Fischer’s exact testing were used to compare differences in event rates.ResultsImplementation of an age‐based narcotic protocol significantly decreased physician narcotic prescribing from 82.2% to 15.4% (P <. 0001). The most common reason for narcotic prescription after the intervention was the report of inadequate pain control by phone call (35%). There was no significant difference in rate of emergency or urgent care utilization between pre‐ and postimplementation groups (4% vs 6%, P =. 29).ConclusionsImplementation of an age‐based narcotic restriction for posttonsillectomy patients using an EHR order set is an effective and safe way to influence physician prescription practices.
Radiologic Evidence of Cochlear Implant Bone Bed Formation Following the Subperiosteal Temporal Pocket Technique
Authors: Turanoglu Artunc Kaan , Yigit Ozgur , Acioglu Engin , Okbay Ahmet Mufit 
Published: February 2016

ObjectiveTo compare the thicknesses of bone beneath the internal receiver stimulator (IRS) with the symmetric contralateral unimplanted side in postoperative temporal high‐resolution computed tomography (CT) and/or cranial CT of the patients for whom cochlear implants were secured by the subperiosteal temporal pocket technique.Study DesignCase series with chart review.SettingTertiary care hospital, cochlear implant referral center.SubjectsCochlear‐implanted pediatric patients with postoperative temporal high‐resolution CT and/or cranial CT were reviewed. The study group included 10 patients with Clarion devices (Advanced Bionics, Valencia, California).MethodsThicknesses of bone were recorded independently by 2 radiologists in the standardized coordinates of proximal, middle, and distal segments of both the IRS bed and the contralateral unimplanted side in each patient. Bone thickness differences in the proximal, middle, and distal segments of IRS were investigated. Any correlation between bone thickness differences and patient age at implantation or duration of implantation was also investigated.ResultsMean values of bone thicknesses obtained from the IRS side and contralateral unimplanted side were, respectively, as follows: 2.40 ± 0.80 mm and 4.17 ± 1.10 mm in the proximal segment (P =. 0001); 1.48 ± 0.33 mm and 3.02 ± 0.85 mm in the middle segment (P =. 0001); and 2.13 ± 0.41 mm and 3.40 ± 0.61 mm in the distal segment (P =. 006). Significant positive correlation was found between patient age at implantation and decrement values in the distal segments (r = 0.681, P =. 03).ConclusionThe subperiosteally secured IRS eventually creates its own well on the skull vault. This new radiologic evidence shows that device migration risk decreases over time, and it supports the findings of other clinical series showing device stability using the subperiosteal pocket technique.
Occupational therapy and emergency departments: A critical review of the literature
Authors: James Kirstin , Jones Derek , Kempenaar Larissa , Preston Jenny , Kerr Susan 
Published: February 2016

Introduction Occupational therapy is emerging as a profession within the context of emergency care, specifically within emergency departments. Emerging professional practice should be underpinned by an evidence base supported by research. As such, this critical review examines, analyses and summarises published and unpublished research concerning occupational therapy in Emergency Departments in order to support emerging practice. Method Research evidence was sought from database platforms, the Internet and grey sources by searching using key words and search terms. Critical analysis of each piece of evidence was undertaken and the analyses were synthesised into a critical review of the literature. Results Twenty-three potentially relevant papers were found, 16 met the criteria for further inclusion and seven were critically analysed. The quality of the papers varied and often lacked sufficient methodological detail for robust review. Although not all study sample sizes were small, variable methodological quality means findings can only be taken into professional practice with caution. Conclusion Based on current evidence, there can only be a limited understanding of occupational therapy, including practice models and efficacy, within emergency departments at this time. There is a need for large-scale, well-designed research studies of occupational therapy within emergency departments.
Minimizing Matrix Effects for the Accurate Quantification of 25-Hydroxyvitamin D Metabolites in Dried Blood Spots by LC-MS/MS
Authors: Kvaskoff David , Heath Alicia K , Simila Henry A , Ko Pauline , English Dallas R , Eyles Darryl W 
Published: February 2016

Abstract

BACKGROUND
The noncalcemic actions of vitamin D in multiple organs are now widely recognized. Vitamin D status has been linked with a wide variety of conditions, which has led to an increasing demand for vitamin D screening. In particular, there is intense interest in the impact of vitamin D on a variety of developmental conditions. The most readily accessible pediatric samples are dried blood spots, and health organizations are increasingly archiving such samples for later assessment of the antecedents of disease.

METHODS
In 2009, we developed a method to quantify the major circulatory form of vitamin D, 25-hydroxyvitamin D, in archived dried blood spots. Over the last 6 years, we have made substantial alterations to the published method to enhance throughput, sensitivity, and assay robustness.

RESULTS
With the alterations, the assay was 3 times faster than the previously published assay and had a &gt;10-fold increase in signal strength. Intraassay imprecision decreased from 13.4% to 6.9%, and there was a 5-fold reduction in interfering phospholipids. In actual use over 2 years, the assay showed an interassay imprecision of 11.6%.

CONCLUSIONS
This assay has performed reliably over the past 6 years. The practical changes we have made should allow clinical chemists to successfully adapt this method.