bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wavelet pressure reactivity index: a validation study
Authors: Liu Xiuyun , Czosnyka Marek , Donnelly Joseph , Cardim Danilo , Cabeleira Manuel , Hutchinson Peter J. , Hu Xiao , Smielewski Peter , Brady Ken 
Published: April 2018

Key points
The brain is vulnerable to damage from too little or too much blood flow. A physiological mechanism termed cerebral autoregulation (CA) exists to maintain stable blood flow even if cerebral perfusion pressure (CPP) is changing.
A robust method for assessing CA is not yet available. There are still some problems with the traditional measure, the pressure reactivity index (PRx).
We introduce a new method, the wavelet transform method (wPRx), to assess CA using data from two sets of controlled hypotension experiments in piglets: one set had artificially manipulated arterial blood pressure (ABP) oscillations; the other group were spontaneous ABP waves.
A significant linear relationship was found between wPRx and PRx in both groups, with wPRx providing a more stable result for the spontaneous waves.
Although both methods showed similar accuracy in distinguishing intact and impaired CA, it seems that wPRx tends to perform better than PRx, although not significantly so.
AbstractWe present a novel method to monitor cerebral autoregulation (CA) using the wavelet transform (WT). The new method is validated against the pressure reactivity index (PRx) in two piglet experiments with controlled hypotension. The first experiment (n = 12) had controlled haemorrhage with artificial stationary arterial blood pressure (ABP) and intracranial pressure (ICP) oscillations induced by sinusoidal slow changes in positive end‐expiratory pressure (‘PEEP group’). The second experiment (n = 17) had venous balloon inflation during spontaneous, non‐stationary ABP and ICP oscillations (‘non‐PEEP group’). The wavelet transform phase shift (WTP) between ABP and ICP was calculated in the frequency range 0.0067–0.05 Hz. Wavelet semblance, the cosine of WTP, was used to make the values comparable to PRx, and the new index was termed wavelet pressure reactivity index (wPRx). The traditional PRx, the running correlation coefficient between ABP and ICP, was calculated. The result showed a significant linear relationship between wPRx and PRx in the PEEP group (R = 0.88) and non‐PEEP group (R = 0.56). In the non‐PEEP group, wPRx showed better performance than PRx in distinguishing cerebral perfusion pressure (CPP) above and below the lower limit of autoregulation (LLA). When CPP was decreased below LLA, wPRx increased from 0.43 ± 0.28 to 0.69 ± 0.12 (P = 0.003) while PRx increased from 0.07 ± 0.21 to 0.27 ± 0.37 (P = 0.04). Moreover, wPRx provided a more stable result than PRx (SD of PRx was 0.40 ± 0.07, and SD of wPRx was 0.28 ± 0.11, P = 0.001). Assessment of CA using wavelet‐derived phase shift between ABP and ICP is feasible.
Unexpected Replication Boost by Simeprevir for Simeprevir-Resistant Variants in Genotype 1a Hepatitis C Virus
Authors: Murai Kazuhisa , Shimakami Tetsuro , Welsch Christoph , Shirasaki Takayoshi , Liu Fanwei , Kitabayashi Juria , Tanaka Shiho , Funaki Masaya , Omura Hitoshi , Nishikawa Tomoki , Sumiyadorj Ariunaa , Honda Masao , Kaneko Shuichi 
Published: April 2018

ABSTRACT
Simeprevir is a novel NS3/4A protease inhibitor (PI) of hepatitis C virus (HCV). The baseline polymorphism NS3-Q80K is frequently observed in genotype (GT) 1a HCV and often associated with treatment failure in simeprevir-containing regimens. We aimed to elucidate mechanisms of treatment failure due to NS3-Q80K. We included a Q80R mutation in our study and generated a series of Huh-7.5 cell lines, each of which harbored either wild-type GT 1a strain H77S.3 or the Q80K or Q80R variant. The cells were cultured with increasing concentrations of simeprevir, and NS3 domain sequences were determined. The mutations identified by sequence analyses were subsequently introduced into H77S.3. The sensitivity of each mutant to the NS3/4A PIs simeprevir, asunaprevir, grazoprevir, and paritaprevir was analyzed. We introduced the mutations into GT 1b strain N.2 and compared the sensitivity to simeprevir with that of GT 1a strain H77S.3. While simeprevir treatment selected mutations at residue D168, such as D168A/V in the wild-type virus, an additional mutation at residue R155, R155K, was selected in Q80K/R variants at simeprevir concentrations of <2.5 μM. Sensitivity analyses showed that simeprevir concentrations of <1 μM significantly boosted the replication of Q80K/R R155K variants. Interestingly, this boost was not observed with the other NS3/4A PIs or in Q80R R155Q/G/T/W variants or GT 1b isolates. The boosted replication of the Q80K+R155K variant by simeprevir could be related to treatment failure in simeprevir-containing antiviral treatments in GT 1a HCV-infected patients with the NS3-Q80K polymorphism. This result provides new insight into how resistance-associated variants can cause treatment failure.
Vibrio Ecology in the Neuse River Estuary, North Carolina, Characterized by Next-Generation Amplicon Sequencing of the Gene Encoding Heat Shock Protein 60 (
hsp60
)
Authors: Jesser Kelsey J. , Noble Rachel T. 
Published: April 2018

ABSTRACT

Of marine eubacteria, the genus
Vibrio
is intriguing because member species are relevant to both marine ecology and human health. Many studies have touted the relationships of
Vibrio
to environmental factors, especially temperature and salinity, to predict total
Vibrio
abundance but lacked the taxonomic resolution to identify the relationships among species and the key drivers of
Vibrio
dynamics. To improve next-generation sequencing (NGS) surveys of
Vibrio
, we have conducted both 16S small subunit rRNA and heat shock protein 60 (
hsp60
) amplicon sequencing of water samples collected at two well-studied locations in the Neuse River Estuary, NC. Samples were collected between May and December 2016 with enhanced sampling efforts in response to two named storms. Using
hsp60
sequences, 21
Vibrio
species were identified, including the potential human pathogens
V. cholerae
,
V. parahaemolyticus
, and
V. vulnificus
. Changes in the
Vibrio
community mirrored seasonal and storm-related changes in the water column, especially in response to an influx of nutrient-rich freshwater to the estuary after Hurricane Matthew, which initiated dramatic changes in the overall
Vibrio
community. Individual species dynamics were wide ranging, indicating that individual
Vibrio
taxa have unique ecologies and that total
Vibrio
abundance predictors are insufficient for risk assessments of potentially pathogenic species. Positive relationships between
Vibrio
, dinoflagellates, and
Cyanobacteria
were identified, as were intraspecies associations, which further illuminated the interactions of cooccurring
Vibrio
taxa along environmental gradients.

IMPORTANCE
The objectives of this research were to utilize a novel approach to improve sequence-based surveys of
Vibrio
communities and to demonstrate the usefulness of this approach by presenting an analysis of
Vibrio
dynamics in the context of environmental conditions, with a particular focus on species that cause disease in humans and on storm effects. The methods presented here enabled the analysis of
Vibrio
dynamics with excellent taxonomic resolution and could be incorporated into future ecological studies and risk prediction strategies for potentially pathogenic species. Next-generation sequencing of
hsp60
and other innovative sequence-based approaches are valuable tools and show great promise for studying
Vibrio
ecology and associated public health risks.
Interleukin-22 Immunotherapy during Severe Influenza Enhances Lung Tissue Integrity and Reduces Secondary Bacterial Systemic Invasion
Authors: Barthelemy Adeline , Sencio Valentin , Soulard Daphnée , Deruyter Lucie , Faveeuw Christelle , Le Goffic Ronan , Trottein François 
Published: April 2018

ABSTRACT
Severe bacterial (pneumococcal) infections are commonly associated with influenza and are significant contributors to the excess morbidity and mortality of influenza. Disruption of lung tissue integrity during influenza participates in bacterial pulmonary colonization and dissemination out of the lungs. Interleukin-22 (IL-22) has gained considerable interest in anti-inflammatory and anti-infection immunotherapy over the last decade. In the current study, we investigated the effect of exogenous IL-22 delivery on the outcome of pneumococcal superinfection postinfluenza. Our data show that exogenous treatment of influenza virus-infected mice with recombinant IL-22 reduces bacterial dissemination out of the lungs but is without effect on pulmonary bacterial burden. Reduced systemic bacterial dissemination was linked to reinforced pulmonary barrier functions, as revealed by total protein measurement in the bronchoalveolar fluids, intratracheal fluorescein isothiocyanate-dextran tracking, and histological approaches. We describe an IL-22-specific gene signature in the lung tissue of influenza A virus (IAV)-infected (and naive) mice that might explain the observed effects. Indeed, exogenous IL-22 modulates the gene expression profile in a way that suggests reinforcement of tissue integrity. Our results open the way to alternative approaches for limiting postinfluenza bacterial superinfection, particularly, systemic bacterial invasion.
Depot-specific characteristics of adipose tissue-derived stromal cells in thyroid-associated orbitopathy
Authors: Wong Janice Siu Chong , Chu Wai Kit , Li Benjamin Fuk-Loi , Pang Chi-Pui , Chong Kelvin Kam-lung 
Published: April 2018

BackgroundThyroid-associated orbitopathy (TAO) causes inflammatory fibroproliferation of periocular connective tissues. We compared adipose tissue-derived stem/stromal cells (ADSCs) from three adipose depots of each patient with TAO on mesenchymal, myofibrogenic, adipogenic properties and associated hyaluronan (HA) synthesis.MethodsADSCs were generated from periocular (eyelid, orbital) and subcutaneous (abdominal) adipose tissues of three patients with TAO. Mesenchymal markers were characterised by reverse transcription-PCR and immunofluorescent staining. A 3-week adipogenic induction was evaluated by Nile red staining and quantitative PCR (qPCR) of peroxisome proliferator-activated receptor (PPARγ), adiponectin and hyaluronan synthase (HAS)-2. A 7-day myofibrogenic induction was assayed by immunofluorescent staining and qPCR of α-smooth muscle actin (α-SMA).ResultsADSCs from all depots expressed similar levels of mesenchymal markers CD44, CD90 and CD105 (p=0.288, p=0.43 and p=0.837, respectively). After adipogenic induction, intracellular lipid increased for more than 32% and PPARγ mRNA showed more than twofold increase from all three depots. However, adiponectin and HAS-2 mRNA levels were significantly higher in the eyelid and orbital ADSCs than those from the subcutaneous ADSCs after induction (2.4×107, 3.9×106 folds vs below detection limit; 63.3-fold, 26.1-fold, vs 33% reduction, respectively; all p=0.002). Significantly more myofibroblasts and higher mRNA level of α-SMA were obtained from the orbital and eyelid compared with the subcutaneous ADSCs during myofibrogenic induction (80.2%, 70.6% vs 29.3%; 30.2-fold, 24.2-fold vs 1.7-fold, respectively; all p=0.002).ConclusionADSCs from different adipose depots of the same donors exhibited similar mesenchymal phenotypes but differed significantly in adipogenic, myofibrogenic potentials and associated HA synthesis. These depot-specific characteristics of ADSCs may contribute to site-specific adipose tissue involvement in TAO.
Domains of health-related quality of life in age-related macular degeneration: a qualitative study in the Chinese cultural context
Authors: Bian Wei , Wan Junli , Smith Graeme , Li Shiying , Tan Mingqiong , Zhou Fengjiao 
Published: April 2018

ObjectiveTo explore which areas of health-related quality of life were affected in Chinese patients, and to identify whether the areas are well covered by validated questionnaires.DesignA qualitative study based on semistructured interviews was conducted. A qualitative thematic analysis following the approach of Colaizzi was used to analyse the interview data for significant statements and phrases. The themes and subthemes organised from the analysis were then compared by using the following current instruments: National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), Macular Disease Quality of life Questionnaire (MacDQoL) and Low-Luminance Questionnaire (LLD).Participants and settingTwenty-one patients with age-related macular degeneration were recruited from the eye clinic of Southwest Eye Hospital in Chongqing, mainland China.ResultsThe mean age of the participants was 69.8 years (range 57–82 years) and the duration of the disease ranged from 3 months to 6 years. The qualitative analysis revealed nine important domains including symptoms, difficulties with daily activities, depending on others, depression and uncertainty, optimism and hope, social isolation, role change, family support and financial burden. However, all the three questionnaires were insufficient to capture the full extent of quality of life issues of Chinese patients with AMD, and MacDQoL covered more domains when compared with NEI-VFQ-25 and LLD.ConclusionThe domains of concepts important to people with AMD in the Chinese culture are not fully represented in the three widely used questionnaires. Nine important domains were identified for the assessment of quality of life and should be considered when assessing the impact of AMD on Chinese individuals. Further studies are needed to develop an AMD quality of life questionnaire, better tailored to the needs and culture of Chinese patients.
Adoption of a novel surgical innovation into clinical practice: protocol for a qualitative systematic review examining surgeon views
Authors: Lewis Thomas L , Furness Hugh N , Miller George W , Parsons Nicholas , Seers Kate , Underwood Martin , Metcalfe Andrew J 
Published: April 2018

IntroductionEfficient adoption of clinically effective novel surgical innovations has great potential benefits for patients. Factors affecting the adoption of surgical innovation are not well understood and proposed models of adoption do not accurately correlate with historical evidence. This protocol is for a systematic review that aims to identify the qualitative evidence relating to surgeon views regarding the adoption of novel surgical innovation into clinical practice.Methods and analysisA systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance will be performed. Two independent reviewers will search the following databases: MEDLINE, Embase, Science Direct, Scopus, Web of Science and the Cochrane Library of Systematic Reviews. Inclusion criteria are studies which report on the views of surgeons who adopt a novel surgical innovation into clinical practice. Each article will be screened for inclusion and assessed according to a Critical Appraisal Skills Programme tool. Data will be synthesised and analysed according to thematic analysis. Given the anticipated yield of a small heterogeneous body of evidence meeting the eligibility criteria for the review, a narrative-based summary is planned.Ethics and disseminationThis review does not require formal ethical approval as it does not involve direct patient contact or patient-identifiable data. The results of this review will be published in a peer-reviewed journal and presented at relevant conferences. The results will also inform an empirical qualitative study exploring surgeon and other stakeholder views regarding the introduction of novel surgical technology and procedures into clinical practice.PROSPERO registration numberCRD42017076715.
Hospital admissions associated with medication non-adherence: a systematic review of prospective observational studies
Authors: Mongkhon Pajaree , Ashcroft Darren M , Scholfield C Norman , Kongkaew Chuenjid 
Published: April 2018

BackgroundMedication non-adherence in ambulatory care has received substantial attention in the literature, but less so as it affects acute care. Accordingly, we aimed to estimate the frequency with which non-adherence to medication contributes to hospital admissions.MethodsWe searched the Cochrane Library, EMBASE, Cumulative Index to Nursing and Allied Health Literature, International Pharmaceutical Abstracts and PubMed (until December 2017) to identify prospective observational studies that examined prevalence rates of hospital admissions associated with medication non-adherence. A quality assessment was performed using an expanded Crombie checklist. Data extraction covered patterns, circumstances, and patient and other key characteristics of non-adherence. Pooled estimates were obtained using a random-effect model.ResultsOf 24 included studies, 8 were undertaken in North America, 7 from Europe, 6 from Asia and 3 from Australia. Most studies (79%) were rated as low risk of bias. All but three studies used combination measures to detect non-adherence, but approaches to assess preventability varied considerably. Across the studies, there was high heterogeneity among prevalence estimates (χ2=548, df 23, p<0.001, I2=95.8%). The median prevalence rate of hospital admissions associated with non-adherence was 4.29% (IQR 3.22%–7.49%), with prevalence rates ranging from 0.72% to 10.79%. By definition, almost all of these admissions were considered preventable. The underlying causes contributing to these admissions included medication cost and side effects, and non-adherence most often involved cardiovascular medicines.ConclusionsHospital admissions associated with non-adherence to medication are a common problem. This systematic review highlights important targets for intervention. Greater attention could be focused on adherence to medication during the hospital stay as part of an enhanced medication reconciliation process. Standardisation in study methods and definitions is needed to allow future comparisons among settings; future studies should also encompass emerging economies.
Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis
Authors: Lannagan Tamsin R M , Lee Young K , Wang Tongtong , Roper Jatin , Bettington Mark L , Fennell Lochlan , Vrbanac Laura , Jonavicius Lisa , Somashekar Roshini , Gieniec Krystyna , Yang Miao , Ng Jia Q , Suzuki Nobumi , Ichinose Mari , Wright Josephine A , Kobayashi Hiroki , Putoczki Tracey L , Hayakawa Yoku , Leedham Simon J , Abud Helen E , Yilmaz Ömer H , Marker Julie , Klebe Sonja , Wirapati Pratyaksha , Mukherjee Siddhartha , Tejpar Sabine , Leggett Barbara A , Whitehall Vicki L J , Worthley Daniel L , Woods Susan L 
Published: April 2018

ObjectiveSerrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF, and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein.DesignWe use organoid culture combined with CRISPR/Cas9 genome engineering to sequentially introduce genetic alterations associated with serrated CRC and which regulate the stem cell niche, senescence and DNA mismatch repair.ResultsTargeted biallelic gene alterations were verified by DNA sequencing. Organoid growth in the absence of niche factors was assessed, as well as analysis of downstream molecular pathway activity. Orthotopic engraftment of complex organoid lines, but not BrafV600E alone, quickly generated adenocarcinoma in vivo with serrated features consistent with human disease. Loss of the essential DNA mismatch repair enzyme, Mlh1, led to microsatellite instability. Sphingolipid metabolism genes are differentially regulated in both our mouse models of serrated CRC and human CRC, with key members of this pathway having prognostic significance in the human setting.ConclusionWe generate rapid, complex models of serrated CRC to determine the contribution of specific genetic alterations to carcinogenesis. Analysis of our models alongside patient data has led to the identification of a potential susceptibility for this tumour type.
Mapping the contribution and strategic distribution patterns of neuroimaging features of small vessel disease in poststroke cognitive impairment
Authors: Shi Lin , Zhao Lei , Yeung Fu Ki , Wong Shun Yiu , Chan Ronald K T , Tse Ming Fai , Chan Sze Chun , Kwong Yee Ching , Li Ka Chun , Liu Kai , Abrigo Jill M , Lau Alexander Y L , Wong Adrian , Lam Bonnie Y K , Leung Thomas W H , Fu Jianhui , Chu Winnie C W , Mok Vincent C T 
Published: April 2018

ObjectivesIndividual neuroimaging features of small vessel disease (SVD) have been reported to influence poststroke cognition. This study aimed to investigate the joint contribution and strategic distribution patterns of multiple types of SVD imaging features in poststroke cognitive impairment.MethodsWe studied 145 first-ever ischaemic stroke patients with MRI and Montreal Cognitive Assessment (MoCA) examined at baseline. The local burdens of acute ischaemic lesion (AIL), white matter hyperintensity, lacune, enlarged perivascular space and cross-sectional atrophy were quantified and entered into support vector regression (SVR) models to associate with the global and domain scores of MoCA. The SVR models were optimised with feature selection through 10-fold cross-validations. The contribution of SVD features to MoCA scores was measured by the prediction accuracy in the corresponding SVR model after optimisation.ResultsThe combination of the neuroimaging features of SVD contributed much more to the MoCA deficits on top of AILs compared with individual SVD features, and the cognitive impact of different individual SVD features was generally similar. As identified by the optimal SVR models, the important SVD-affected regions were mainly located in the basal ganglia and white matter around it, although the specific regions varied for MoCA and its domains.ConclusionsMultiple types of SVD neuroimaging features jointly had a significant impact on global and domain cognitive functionings after stroke on top of AILs. The map of strategic cognitive-relevant regions of SVD features may help clinicians to understand their complementary impact on poststroke cognition.