bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE INFLAMMATORY MICROENVIRONMENT IN SCREEN-DETECTED PREMALIGANT ADENOMATOUS POLYPS: EARLY RESULTS FROM THE INTEGRATED TECHNOLOGIES FOR IMPROVED POLYP SURVEILLANCE (INCISE) PROJECT
Authors: Mansouri David , McSorley Stephen T , Park James H , Orange Clare , Horgan Paul G , McMillan Donald C , Edwards Joanne 
Published: August 2020

AbstractIntroductionAround 40% of patients who attend for colonoscopy following a positive stool screening test have adenomatous polyps. Identifying which patients have a higher propensity for malignant transformation is currently poorly understood. The aim of the present study was to assess whether the type and intensity of inflammatory infiltrate differs between high-grade (HGD) and low-grade dysplastic (LGD) screen detected adenomas.MethodsA representative sample of 207 polyps from 134 individuals were included from a database of all patients with adenomas detected through the first round of the Scottish Bowel Screening Programme (SBoSP) in NHS GG&C (April 2009 to April 2011).Inflammatory cell phenotype infiltrate was assessed by immunohistochemistry for CD3+, CD8+, CD45+ and CD68+ in a semi-quantitative manner at 20x resolution. Immune-cell infiltrate was graded as absent, weak, moderate or strong.Patient and polyp characteristics and inflammatory infiltrate were then compared between HGD and LGD polyps.ResultsCD3+ infiltrate was significantly higher in HGD polyps compared to LGD polyps (74% vs 69%, p<0.05). CD8+ infiltrate was significantly higher in HGD polyps compared to LGD polyps (36% vs 13%, p<0.001) where as CD45+ infiltrate was not significantly different(69% vs 64%, p=0.401). There was no significant difference in CD68+ infiltrate (p=0.540) or total inflammatory cell infiltrate (calculated from CD3+ and CD68+) (p=0.226).ConclusionsThis study reports an increase in CD3+ and CD8+ infiltrate with progression from LGD to HGD in colonic adenomas. It may therefore have a use in the prognostic stratification and treatment of dysplastic polyps.
Pathway for Enhanced Recovery after Spinal Surgery-A Systematic Review of Evidence for use of Individual Components
Authors: Licina Ana , Silvers Andrew , Laughlin Harry , Russell Jeremy , Wan Crispin 
Published: August 2020

AbstractBackgroundEnhanced recovery in spinal surgery (ERSS) has shown promising improvements in clinical and economical outcomes. We have proposed an ERSS pathway based on societal recommendations and qualitative reviews. We aimed to delineate the clinical efficacy of individual pathway components in ERSS through a systematic narrative review.MethodsWe included systematic reviews and meta-analysis, randomized controlled trials, non-randomized controlled studies, and observational studies in adults and pediatric patients evaluating any one of the 22 pre-defined care components. Our primary outcomes included all-cause mortality, morbidity outcomes (e.g., pulmonary, cardiac, renal, surgical complications), patient-reported outcomes and experiences (e.g., pain, quality of care experience), and health services outcomes (e.g., length of stay and costs). We searched the following databases (1990 onwards)MEDLINE, EMBASE, and Cochrane Library (Cochrane Database of Systematic Reviews and CENTRAL). Two reviewers independently screened all citations, full-text articles, and abstracted data. A narrative synthesis was provided. Where applicable, we constructed Evidence Profile (EP) tables for each individual element. Due to clinical and methodological heterogeneity, we did not conduct a meta-analyses. Confidence in cumulative evidence for each component of the pathway was classified according to the GRADE system.ResultsWe identified 5423 relevant studies excluding duplicates as relating to the 22 pre-defined components of enhanced recovery in spinal surgery. We included 664 studies in the systematic review. We found specific evidence within the context of spinal surgery for 14/22 proposed components. Evidence was summarized in EP tables for 12/22 components. We performed thematic synthesis without EP for 6/22 elements. We identified appropriate societal guidelines for the remainder of the components.DiscussionWe identified the following components with high quality of evidence as per GRADE system: pre-emptive analgesia, peri-operative blood conservation (antifibrinolytic use), surgical site preparation and antibiotic prophylaxis. There was moderate level of evidence for implementation of prehabilitation, minimally invasive surgery, multimodal perioperative analgesia, intravenous lignocaine and ketamine use as well as early mobilization. This review allows for the first formalized evidence-based unified protocol in the field of ERSS.Further studies validating the multimodal ERSS framework are essential to guide the future evolution of care in patients undergoing spinal surgery.
Caloric Restriction Remodels Energy Metabolic Pathways of Gut Microbiota and Promotes Host Autophagy
Authors: Yang Yuping , Chen Shaoqiu , Liu Yumin , Hou Yuanlong , Xie Xie , Zhang Xia , Zhao Aihua , Zheng Xiaojiao , Liu Jiajian , Chen Tianlu , Yuan Tianma , Yu Hongjing , Wang Chongchong , Sun Yifan , Wang Jingcheng , Wang Xiaoyan , Jia Wei 
Published: August 2020

AbstractCalorie restriction (CR) can improve the metabolic balance of adults and elevate the relative abundance of probiotic bacteria in the gut while promoting longevity. However, the interaction between remodeled intestinal flora and metabolic improvement, as well as the mechanism for probiotic bacterial increase, are still unclear. In this study, using a metabolomics platform, we demonstrate for the first time, that CR leads to increased levels of malate and its related metabolites in biological samples. Next, we investigated the effects of CR on the gut microbial genome and the expression of mRNA related to energy metabolism which revealed a partially elevated TCA cycle and a subsequently promoted glyoxylate cycle, from which large amounts of malate can be produced to further impact malate related pathways in the host liver. Through the identification of key “hungry” metabolites produced by the gut microbiota that function in the promotion of autophagy in the host, further insight has been gained about a functional metabolic network important for both host-microbial symbiosis and maintenance of host health.
Pancreatic α and β cells are globally phase-locked
Authors: Ren Huixia , Li Yanjun , Han Chengsheng , Yu Yi , Shi Bowen , Peng Xiaohong , Wu Shufang , Yang Xiaojing , Kim Sneppen , Chen Liangyi , Tang Chao 
Published: August 2020

SUMMARYThe Ca2+modulated pulsatile secretion of glucagon and insulin by pancreatic α and β cells plays a key role in glucose homeostasis. However, how α and β cells coordinate via paracrine interaction to produce various Ca2+oscillation patterns is still elusive. Using a microfluidic device and transgenic mice in which α and β cells were labeled with different colors, we were able to record islet Ca2+signals at single cell level for long times. Upon glucose stimulation, we observed heterogeneous Ca2+oscillation patterns intrinsic to each islet. After a transient period, the oscillations of α and β cells were globally phase-locked, i.e., the two types of cells in an islet each oscillate synchronously but with a phase shift between the two. While the activation of α cells displayed a fixed time delay of ~20 s to that of β cells, β cells activated with a tunable delay after the α cells. As a result, the tunable phase shift between α and β cells set the islet oscillation period and pattern. Furthermore, we demonstrated that the phase shift can be modulated by glucagon. A mathematical model of islet Ca2+oscillation taking into consideration of the paracrine interaction was constructed, which quantitatively agreed with the experimental data. Our study highlights the importance of cell-cell interaction to generate stable but tunable islet oscillation patterns.
Differential GLP-1R binding and activation by peptide and non-peptide agonists
Authors: Zhang Xin , Belousoff Matthew J. , Zhao Peishen , Kooistra Albert J. , Truong Tin T. , Ang Sheng Yu , Underwood Christina Rye , Egebjerg Thomas , Šenel Petr , Stewart Gregory D. , Liang Yi-Lynn , Glukhova Alisa , Venugopal Hari , Christopoulos Arthur , Furness Sebastian G. B. , Miller Laurence J. , Reedtz-Runge Steffen , Langmead Christopher J. , Gloriam David E. , Danev Radostin , Sexton Patrick M. , Wootten Denise 
Published: August 2020

SUMMARYPeptide drugs targeting class B1 GPCRs can treat multiple diseases, however there remains substantial interest in the development of orally delivered non-peptide drugs. Here we reveal unexpected overlap between signalling and regulation of the glucagon-like peptide-1 (GLP-1) receptor by the non-peptide agonist, PF 06882961, and GLP-1 that was not observed for another compound, OWL-833. Both compounds are currently in clinical trials for treatment of type 2 diabetes. High resolution cryo-EM structures reveal the binding sites for PF-06882961 and GLP-1 substantially overlap, whereas OWL-833 adopts a unique binding mode with a more open receptor conformation at the extracellular face. Structural differences involving extensive water-mediated hydrogen bond networks could be correlated to functional data to understand how PF 06882961, but not OWL-833, can closely mimic the pharmacological properties of GLP-1. These findings will facilitate rational structure-based discovery of non-peptide agonists targeting class B GPCRs.
EPOC outside the shield: comparing the performance of a consumer-grade EEG device in shielded and unshielded environments
Authors: Wehrman Jordan , Sörensen Sidsel , de Lissa Peter , Badcock Nicholas A. 
Published: August 2020

AbstractLow-cost, portable electroencephalographic (EEG) headsets have become commercially available in the last 10 years. One such system, Emotiv’s EPOC, has been modified to allow event-related potential (ERP) research. Because of these innovations, EEG research may become more widely available in non-traditional settings. Although the EPOC has previously been shown to provide data comparable to research-grade equipment and has been used in real-world settings, how EPOC performs without the electrical shielding used in research-grade laboratories is yet to be systematically tested. In the current article we address this gap in the literature by asking participants to perform a simple EEG experiment in shielded and unshielded contexts. The experiment was the observation of human versus wristwatch faces which were either inverted or noninverted. This method elicited the face-sensitive N170 ERP.In both shielded and unshielded contexts, the N170 amplitude was larger when participants viewed human faces and peaked later when a human face was inverted. More importantly, Bayesian analysis showed no difference in the N170 measured in the shielded and unshielded contexts. Further, the signal recorded in both contexts was highly correlated. The EPOC appears to reliably record EEG signals without a purpose-built electrically-shielded room or laboratory-grade preamplifier.
Improved online event detection and differentiation by a simple gradient-based nonlinear transformation: Implications for the biomedical signal and image analysis
Authors: Sokolova Anastasia , Uljanitski Yuri , Kayumov Airat R. , Bogachev Mikhail I 
Published: August 2020

ABSTRACTDespite recent success in advanced signal analysis technologies, simple and universal methods are still of interest in a variety of applications. Wearable devices including biomedical monitoring and diagnostic systems suitable for long-term operation are prominent examples, where simple online signal analysis and early event detection algorithms are required. Here we suggest a simple and universal approach to the online detection of events represented by abrupt bursts in long-term observational data series. We show that simple gradient-based transformations obtained as a product of the signal and its derivative lead to the improved accuracy of the online detection of any significant bursts in the observational data series irrespective of their particular shapes. We provide explicit analytical expressions characterizing the performance of the suggested approach in comparison with the conventional solutions optimized for particular theoretical scenarios and widely utilized in various signal analysis applications. Moreover, we estimate the accuracy of the gradient-based approach in the exact positioning of single ECG cycles, where it outperforms the conventional Pan-Tompkins algorithm in its original formulation, while exhibiting comparable detection effectiveness. Finally, we show that our approach is also applicable to the comparative analysis of lanes in electrophoretic gel images widely used in life sciences and molecular diagnostics like restriction fragment length polymorphism (RFLP) and variable number tandem repeats (VNTR) methods. A simple software tool for the semi-automated electrophoretic gel image analysis based on the proposed gradient based methodology is freely available online athttps://bitbucket.org/rogex/sds-page-image-analyzer/downloads/.
Placental and fetal characteristics of the Ohia mouse line recapitulate outcomes in human hypoplastic left heart syndrome
Authors: Wilson Rebecca L , Troja Weston , Courtney Jennifer , Williams Alyssa , Jones Helen N 
Published: August 2020

AbstractCongenital heart defects (CHDs) are the most common birth defect worldwide. The morbidity and mortality associated with these defects is compounded by increased frequency of fetal growth abnormalities. In the Ohia mouse model of hypoplastic left heart syndrome (HLHS), the double homozygous genotype is embryonically lethal at mid-pregnancy; a time in which optimal establishment of the placenta is crucial to fetal survival. We aimed to characterize placental and fetal growth and development in the double heterozygous genotype (Sap130m/+Pcdha9m/+)to determine whether the genetic mutations associated with HLHS in the Ohia mouse also affect the placenta. The frequency of fetuses with reduced weight near term was shifted in theSap130m/+Pcdha9m/+fetuses compared to wildtype. This shift in fetal weight distribution in theSap130m/+Pcdha9m/+fetuses was associated with reduced labyrinth region area (P<0.001) and reduced fetal capillary density (P<0.001) in the placentas. Positive correlations were observed between fetal weight and placenta mRNA expression of several nutrient transporters in theSap130m/+Pcdha9m/+fetuses but not observed in the wildtype. Increased protein expression of Slc7a5 (P<0.05) and Slc7a8 (P<0.05) was also found in the placenta ofSap130m/+Pcdha9m/+fetuses. This data shows, despite a potential compensatory mechanism to increase nutrient transport, abhorrent placental vascularization leads to inadequate fetal growth in the Ohia mouse model. Such differences are similar to findings in studies of human placentas and highlights the importance of this mouse model in continuing to understand the developmental links and disruptions to the heart-placenta axis.
Characteristics of fMRI responses to visual stimulation in anesthetized vs. awake mice
Authors: Dinh Thi Ngoc Anh , Jung Won Beom , Shim Hyun-Ji , Kim Seong-Gi 
Published: August 2020

AbstractThe functional characteristics of the mouse visual system have not previously been well explored using fMRI. In this research, we examined 9.4 T BOLD fMRI responses to visual stimuli of varying pulse durations (1 – 50 ms) and temporal frequencies (1 – 10 Hz) under ketamine and xylazine anesthesia, and compared fMRI responses of anesthetized and awake mice. Under anesthesia, significant positive BOLD responses were detected bilaterally in the major structures of the visual pathways, including the dorsal lateral geniculate nuclei, superior colliculus, lateral posterior nucleus of thalamus, primary visual area, and higher-order visual area. BOLD responses increased slightly with pulse duration, were maximal at 3 – 5 Hz stimulation, and significantly decreased at 10 Hz, which were all consistent with previous neurophysiological findings. When the mice were awake, the BOLD fMRI response was faster in all active regions and stronger in the subcortical areas compared with the anesthesia condition. In the V1, the BOLD response was biphasic for 5 Hz stimulation and negative for 10 Hz stimulation under wakefulness, whereas prolonged positive BOLD responses were observed at both frequencies under anesthesia. Unexpected activation was detected in the extrastriate postrhinal area and non-visual subiculum complex under anesthesia, but not under wakefulness. Widespread positive BOLD activity under anesthesia likely results from the disinhibition and sensitization of excitatory neurons induced by ketamine. Overall, fMRI can be a viable tool for mapping brain-wide functional networks.
Mitochondrial determinants of response and resistance to venetoclaxpluscytarabine duplet therapy in acute myeloid leukemia
Authors: Bosc Claudie , Gadaud Noémie , Bousard Aurélie , Sabatier Marie , Cognet Guillaume , Saland Estelle , Farge Thomas , Boet Emeline , Gotanègre Mathilde , Aroua Nesrine , Mouchel Pierre-Luc , Larrue Clément , Jarrou Latifa , Rambow Florian , Cabon Florence , Nicot Nathalie , Vergez François , Tamburini Jérôme , Fournié Jean-Jacques , Kaoma Tony , Marine Jean-Christophe , Récher Christian , Stuani Lucille , Joffre Carine , Sarry Jean-Emmanuel 
Published: August 2020

AbstractThe development of resistance to conventional and targeted therapy represents a major clinical barrier in treatment of acute myeloid leukemia (AML). We show that the resistance to cytarabine (AraC) and its associated mitochondrial phenotype were reversed by genetic silencing or pharmacological inhibition of BCL2 in a caspase-dependent manner. BCL2-inhibitor venetoclax (VEN) enhancement of AraC efficacy was independent of differentiation phenotype, a characteristic of response to another combination of VEN with hypomethylating agents (HMA). Furthermore, transcriptional profiles of patients with low response to VEN+AraC mirrored those of low responders to VEN+HMA in clinical trials. OxPHOS was found to be a patient stratification marker predictive of effective response to VEN+AraC but not to VEN+AZA. Importantly, whereas three cell subpopulations specifically emerged in VEN+AraC residual disease and were characterized by distinct developmental and transcriptional programs largely driven by MITF, E2F4 and p53 regulons, they each encoded proteins involved in assembly of NADH dehydrogenase complex. Notably, treatment of VEN+AraC-persisting AML cells with an ETCI inhibitor significantly increased the time-to-relapsein vivo. These findings provide the scientific rationale for new clinical trials of VEN+AraC combinations, especially in patients relapsing or non-responsive to chemotherapy, or after failure of frontline VEN+HMA regimen.
Deuterated rhodamines for protein labelling in nanoscopy
Authors: Roßmann Kilian , Akkaya Kerem C. , Charbonnier Corentin , Eichhorst Jenny , Jones Ben , Lehmann Martin , Broichhagen Johannes 
Published: August 2020

ABSTRACTRhodamine molecules are setting benchmarks in fluorescence microscopy. Herein, we report the deuterium (d12) congeners of tetramethyl(silicon)rhodamine, obtained by isotopic labelling of the four methyl groups, which improves photophysical (i.e.brightness, lifetimes) and chemical (i.e.bleaching) properties. We explore this finding for SNAP- and Halo-tag labelling, and highlight enhanced properties in several applications, such as Förster resonance energy transfer, fluorescence activated cell sorting, fluorescence lifetime microscopy and stimulated emission depletion nanoscopy. We envision deuteration as a generalizable concept to improve existing and develop new Chemical Biology Probes.
High accuracy determination of photoelectric cross sections, X-ray absorption fine structure and nanostructure analysis of zinc selenide using the X-ray extended range technique
Authors: Sier Daniel , Cousland Geoffrey P. , Trevorah Ryan M. , Ekanayake Ruwini S. K. , Tran Chanh Q. , Hester James R. , Chantler Christopher T. 
Published: August 2020

Measurements of mass attenuation coefficients and X-ray absorption fine structure (XAFS) of zinc selenide (ZnSe) are reported to accuracies typically better than 0.13%. The high accuracy of the results presented here is due to our successful implementation of the X-ray extended range technique, a relatively new methodology, which can be set up on most synchrotron X-ray beamlines. 561 attenuation coefficients were recorded in the energy range 6.8–15 keV with measurements concentrated at the zinc and selenium pre-edge, near-edge and fine-structure absorption edge regions. This accuracy yielded detailed nanostructural analysis of room-temperature ZnSe with full uncertainty propagation. Bond lengths, accurate to 0.003 Å to 0.009 Å, or 0.1% to 0.3%, are plausible and physical. Small variation from a crystalline structure suggests local dynamic motion beyond that of a standard crystal lattice, noting that XAFS is sensitive to dynamic correlated motion. The results obtained in this work are the most accurate to date with comparisons with theoretically determined values of the attenuation showing discrepancies from literature theory of up to 4%, motivating further investigation into the origin of such discrepancies.
Preliminary data of a preschool teacher-screening checklist for autism spectrum disorder in Singapore
Authors: Nah Yong-Hwee 
Published: August 2020

Purpose
There are limited tools developed for preschool teachers to aid them in identifying these children with possible autism spectrum disorder (ASD). This study aims to describe the development and present preliminary data of a checklist for ASD screening for preschool teachers (CAPT-S) in Singapore that is easy for preschool teachers to use to identify ASD in mainstream preschoolers from 3 to 6 years old.

Design/methodology/approach
This study adopted a cross-sectional questionnaire design. The CAPT-S is a 12-item checklist based on the current Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition criteria and derived from a survey in a previous study that examined preschool teachers’ perceptions of challenging behaviors in preschoolers with ASD in Singapore. Participants consisted of 63 preschool teachers (mean age = 29.4 years; SD = 9.8) teaching in mainstream preschool centers located in Singapore, and they were asked to use the CAPT-S to rate their students on a four-point Likert scale on frequency of observed behavior.

Findings
Preliminary results indicated construct validity was demonstrated and high reliability in terms of internal consistency and moderate test–retest reliability of the CAPT-S. Diagnostic validity of the CAPT-S was also established, even after controlling for variables such as working experience and time spent working with that student. The optimal cutoff score of 24 produced high sensitivity and specificity.

Originality/value
The present study adds an important contribution to the literature on using preschool teachers as an additional informant in the screening process of ASD. The CAPT-S may be suitable for preschool teachers to use to identify children with possible ASD, although future studies would need to be conducted to examine its effectiveness.