bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of toll-like receptors as prognostic biomarkers in gastric cancer: high tissue TLR5 predicts a better outcome
Authors: Kasurinen Aaro , Hagström Jaana , Laitinen Alli , Kokkola Arto , Böckelman Camilla , Haglund Caj 
Published: August 2019

AbstractToll-like receptors (TLRs), key proteins in innate immunity, appear to contribute to the inflammatory environment in carcinogenesis. Thus, we aimed to evaluate the tissue expressions of TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 as potential prognostic biomarkers in gastric cancer. We applied immunohistochemistry to study tissue samples from 313 patients operated on for gastric adenocarcinoma between 2000 and 2009 at the Department of Surgery, Helsinki University Hospital, Finland. A high expression of each TLR studied associated with the high expression of each other and with the intestinal-type histology (p < 0.001 for all). Five-year disease-specific survival among patients with a high TLR5 was 53.4% (95% confidence interval [CI] 43.4–63.4), whereas among patients with a low TLR5 it was 37.6% (95% CI 30.0–45.2; p = 0.014). A high TLR5 expression functioned as a marker of a better prognosis, particularly among those with a stage II disease (hazard ratio [HR] 0.33; 0.13–0.83; p = 0.019) or an intestinal-type cancer (HR 0.58; 95% CI 0.34–0.98; p = 0.043). In this study we show, for the first time, that a high TLR5 tissue expression may identify gastric cancer patients with a better prognosis, particularly among those with a stage II disease or an intestinal-type cancer.
Fundamental differences in patterns of retinal ageing between primates and mice
Authors: Kam Jaimie Hoh , Weinrich Tobias W. , Shinhmar Harpreet , Powner Michael B. , Roberts Nicholas W. , Aboelnour Asmaa , Jeffery Glen 
Published: August 2019

AbstractPhotoreceptors have high metabolic demands and age rapidly, undermining visual function. We base our understanding mainly on ageing mice where elevated inflammation, extracellular deposition, including that of amyloid beta, and rod and cone photoreceptor loss occur, but cones are not lost in ageing primate although their function declines, revealing that primate and mouse age differently. We examine ageing primate retinae and show elevated stress but low inflammation. However, aged primates have a >70% reduction in adenosine triphosphate (ATP) and a decrease in cytochrome c oxidase. There is a shift in cone mitochondrial positioning and glycolytic activity increases. Bruch’s membrane thickens but unlike in mice, amyloid beta is absent. Hence, reduced ATP may explain cone functional decline in ageing but their retained presence offers the possibility of functional restoration if they can be fuelled appropriately to restore cellular function. This is important because as humans we largely depend on cone function to see and are rarely fully dark adapted. Presence of limited aged inflammation and amyloid beta deposition question some of the therapeutic approaches taken to resolve problems of retinal ageing in humans and the possible lack of success in clinical trials in macular degeneration that have targeted inflammatory agents.
Preclinical studies on metal based anticancer drugs as enabled by integrated metallomics and metabolomics
Authors: Galvez Luis , Rusz Mate , Schwaiger-Haber Michaela , El Abiead Yasin , Hermann Gerrit , Jungwirth Ute , Berger Walter , Keppler Bernhard K , Jakupec Michael A , Koellensperger Gunda 
Published: August 2019

Abstract
Resistance development is a major obstacle for platinum-based chemotherapy, with the anticancer drug oxaliplatin being no exception. Acquired resistance is often associated with altered drug accumulation. In this work we introduce a novel -omics workflow enabling the parallel study of platinum drug uptake and its distribution between nucleus/protein and small molecule fraction along with metabolic changes after different treatment time points. This integrated metallomics/metabolomics approach is facilitated by a tailored sample preparation workflow suitable for preclinical studies on adherent cancer cell models. Inductively coupled plasma mass spectrometry monitors the platinum drug, while the metabolomics tool-set is provided by hydrophilic interaction liquid chromatography combined with high-resolution Orbitrap mass spectrometry. The implemented method covers biochemical key pathways of cancer cell metabolism as shown by a panel of &gt;130 metabolite standards. Furthermore, the addition of yeast-based 13C-enriched internal standards upon extraction enabled a novel targeted/untargeted analysis strategy. In this study we used our method to compare an oxaliplatin sensitive human colon cancer cell line (HCT116) and its corresponding resistant model. In the acquired oxaliplatin resistant cells distinct differences in oxaliplatin accumulation correlated with differences in metabolomic rearrangements. Using this multi-omics approach for platinum-treated samples facilitates the generation of novel hypotheses regarding the susceptibility and resistance towards oxaliplatin.
MiR-34b inhibits the proliferation and promotes apoptosis in colon cancer cells by targeting Wnt/β-catenin signaling pathway
Authors: Ye Kailun , Xu Chunhua , Hui Tongguan 
Published: August 2019

Abstract
Colon cancer is one of the leading cause of cancer deaths that is severely threatening human health. Several microRNAs (miRNAs) have been found to be associated with the tumor genesis of colon cancer. The present study determined the expression of miR-34b in patients with colon cancer and studied the molecular mechanism of miR-34b in the proliferation and apoptosis of human colon cancer Caco-2 cells in vitro. In colon cancer patients, the expression of miR-34b was decreased in tumor tissues when compared with the adjacent non-tumor tissues. Furthermore, overexpression of miR-34b inhibited proliferation, migration and invasion, while promoted apoptosis in colon cancer cells. The online bioinformatics sites predicted possible regulatory genes of miR-34b and luciferase reporter assay verify that β-catenin was a direct target of miR-34b. Furthermore, miR-34b overexpression significantly decreased the expression of genes associated with Wnt/β-catenin signaling pathway. In conclusion, our results suggest that miR-34b may inhibit migration and invasion of human colon cancer cells by regulating Wnt/β-catenin signaling and miR-34b may be a key target for the treatment and diagnosis of colon cancer.
Neuroanatomical Correlates of Childhood Stuttering: MRI Indices of White and Gray Matter Development That Differentiate Persistence Versus Recovery
Authors: Garnett Emily O. , Chow Ho Ming , Chang Soo-Eun 
Published: August 2019

PurposeWe review two recent neuroanatomical studies of children who stutter (CWS), one that examines white matter integrity and the other that focuses on cortical gray matter morphology. In both studies, we sought to examine differences between children whose stuttering persists (“persistent”), children who recovered from stuttering (“recovered”), and their nonstuttering peers (“controls”).MethodBoth of the reviewed studies use data from a large pediatric sample spanning preschool- to school-age children (3–10 years old at initial testing). Study 1 focused on surface-based measures of cortical size (thickness) and shape (gyrification) using structural magnetic resonance imaging, whereas Study 2 utilized diffusion tensor imaging to examine white matter integrity.ResultsIn both studies, the main difference that emerged between CWS and fluent peers encompassed left hemisphere speech motor areas that are interconnected via the arcuate fasciculus. In the case of white matter integrity, the temporoparietal junction and posterior superior temporal gyrus, both connected via the left arcuate fasciculus, and regions along the corpus callosum that contain fibers connecting bilateral motor regions were significantly decreased in white matter integrity in CWS compared to controls. In the morphometric study, children who would go on to have persistent stuttering specifically had lower cortical thickness in ventral motor and premotor areas of the left hemisphere.ConclusionThese results point to aberrant development of cortical areas involved in integrating sensory feedback with speech movements in CWS and differences in interhemispheric connectivity between the two motor cortices. Furthermore, developmental trajectories in these areas seem to diverge between persistent and recovered cases.
Limited Pre-Speech Auditory Modulation in Individuals Who Stutter: Data and Hypotheses
Authors: Max Ludo , Daliri Ayoub 
Published: August 2019

PurposeWe review and interpret our recent series of studies investigating motor-to-auditory influences during speech movement planning in fluent speakers and speakers who stutter. In those studies, we recorded auditory evoked potentials in response to probe tones presented immediately prior to speaking or at the equivalent time in no-speaking control conditions. As a measure of pre-speech auditory modulation (PSAM), we calculated changes in auditory evoked potential amplitude in the speaking conditions relative to the no-speaking conditions. Whereas adults who do not stutter consistently showed PSAM, this phenomenon was greatly reduced or absent in adults who stutter. The same between-group difference was observed in conditions where participants expected to hear their prerecorded speech played back without actively producing it, suggesting that the speakers who stutter use inefficient forward modeling processes rather than inefficient motor command generation processes. Compared with fluent participants, adults who stutter showed both less PSAM and less auditory–motor adaptation when producing speech while exposed to formant-shifted auditory feedback. Across individual participants, however, PSAM and auditory–motor adaptation did not correlate in the typically fluent group, and they were negatively correlated in the stuttering group. Interestingly, speaking with a consistent 100-ms delay added to the auditory feedback signal–normalized PSAM in speakers who stutter, and there no longer was a between-group difference in this condition.ConclusionsCombining our own data with human and animal neurophysiological evidence from other laboratories, we interpret the overall findings as suggesting that (a) speech movement planning modulates auditory processing in a manner that may optimize its tuning characteristics for monitoring feedback during speech production and, (b) in conditions with typical auditory feedback, adults who stutter do not appropriately modulate the auditory system prior to speech onset. Lack of modulation of speakers who stutter may lead to maladaptive feedback-driven movement corrections that manifest themselves as repetitive movements or postural fixations.
Functional Parcellation of the Speech Production Cortex
Authors: Tourville Jason A. , Nieto-Castañón Alfonso , Heyne Matthias , Guenther Frank H. 
Published: August 2019

Neuroimaging has revealed a core network of cortical regions that contribute to speech production, but the functional organization of this network remains poorly understood.

Purpose
We describe efforts to identify reliable boundaries around functionally homogenous regions within the cortical speech motor control network in order to improve the sensitivity of functional magnetic resonance imaging (fMRI) analyses of speech production and thus improve our understanding of the functional organization of speech production in the brain.

Method
We used a bottom-up, data-driven approach by pooling data from 12 previously conducted fMRI studies of speech production involving the production of monosyllabic and bisyllabic words and pseudowords that ranged from single vowels and consonant–vowel pairs to short sentences (163 scanning sessions, 136 unique participants, 39 different speech conditions). After preprocessing all data through the same pipeline and registering individual contrast maps to a common surface space, hierarchical clustering was applied to contrast maps randomly sampled from the pooled data set in order to identify consistent functional boundaries across subjects and tasks. Boundary completion was achieved by applying adaptive smoothing and watershed segmentation to the thresholded population-level boundary map. Hierarchical clustering was applied to the mean within–functional region of interest (fROI) response to identify networks of fROIs that respond similarly during speech.

Results
We identified highly reliable functional boundaries across the cortical areas involved in speech production. Boundary completion resulted in 117 fROIs in the left hemisphere and 109 in the right hemisphere. Clustering of the mean within-fROI response revealed a core sensorimotor network flanked by a speech motor planning network. The majority of the left inferior frontal gyrus clustered with the visual word form area and brain regions (e.g., anterior insula, dorsal anterior cingulate) associated with detecting salient sensory inputs and choosing the appropriate action.

Conclusion
The fROIs provide insight into the organization of the speech production network and a valuable tool for studying speech production in the brain by improving within-group and between-groups comparisons of speech-related brain activity.

Supplemental Material

https://doi.org/10.23641/asha.9402674
Analysis and design of the DCM operation boost PFC converter with magnetic control
Authors: Wei Yuqi , Luo Quanming , Wang Jie , Pengju Sun 
Published: August 2019

In this study, a novel control scheme for the discontinuous conduction mode (DCM) operation boost power factor correction (PFC) converter is proposed. Instead of adopting constant duty cycle (CDC) control, variable duty cycle control or frequency control, the magnetic control or variable inductor control is adopted to regulate the output voltage, so CDC and switching frequency can be implemented for the switch. The operation principles of the proposed control scheme are discussed in details, and the analysis of the input current, power factor, boundary condition and design considerations are presented. In addition, the modelling of the variable inductor and the DCM operation boost PFC converter with variable inductor are derived in detail, by linearising the non‐linear components, the model of the DCM operation boost PFC converter with the proposed control scheme can be obtained, and the design procedures of the PI controller are presented. Finally, a 70 W experimental prototype is built to verify the theoretical analysis and the effectiveness of the proposed control scheme.
Deflection characterisation of rotary systems using ground‐based radar
Authors: Ochieng Francis X. , Jiang Haoyang , Hancock Craig M. , Roberts Gethin W. , Le Kernec Julien , Tang Xu , de Ligt Huib 
Published: August 2019

In the last two decades, an increase in large rotary machines/systems has been witnessed. To ensure safe operation of these systems especially due to extreme stress caused by centrifugal forces as well as the wind or water loadings, regular structural health monitoring (SHM) of the unbalanced parameters, particularly at the blade tips is necessary. For this, the use of non‐contact sensors provides the most appropriate approach; however, millimetric out‐of‐plane deflection monitoring using non‐contact sensors at distances >1 m has not been comprehensively addressed for rotary systems, like wind turbines. This study presents a modelling environment to simulate radar returns to analyse rotary systems. Employing Sammon mapping as a dimensionality reduction procedure in conjunction with 2D visualisation, the study demonstrates the characterisation of dynamic deflection parameters using a fast, portable ground‐based interferometric radar (GBR). Comparisons between the GBR results with those of a Leica AR20 GPS indicate a divergence ±12.79 mm. The study utilises SHM framework to acquire, normalise, extract, and validate GBR signals within an SHM framework for structures under test or for deflection validation of the new system. Further, it contributes to the non‐contact structural fatigue damage detection during design, testing, and operating stages of rotary structures blade tips.
Snare combined with endoscopic clips in endoscopic resection of gastric submucosal tumor: a method of tumor traction
Authors: Zhang Qiang , Cai Jian-qun , Wang Zhen , Xiao Bing , Bai Yang 
Published: August 2019

Abstract
Background and study aims Mucosal traction as a supportive technique is very useful for endoscopists during endoscopy. For gastric submucosal tumor (SMT), our team explored a method of pulling the SMT with a snare combined with endoclips (PSMT-SE). This study preliminarily explored its feasibility to assist resection of gastric SMT.
Patients and methods Operation-related data from patients who underwent gastric SMT removal assisted by PSMT-SE at the Gastrointestinal Endoscopy Center of Guangzhou Nanfang Hospital, China between January 2017 and October 2018 were retrospectively collected: tumor size and location, origin of tumor, total operation time, en bloc resection rate, intraoperative and postoperative complications.
Results Forty-two gastric SMTs in 41 patients were included in this study. Fifteen tumors were located in the gastric fundus, 11 in the gastric body, two in the gastric angle, 10 in the gastric antrum, and four in the greater curvature of the gastric fundus and the body junction. Further, 11 tumors originated from the submucosa and 31 originated from the muscularis propria. Endoscopic submucosal dissection and endoscopic full-thickness resection assisted by PSMT-SE were performed to resect 30 and 12 tumors, respectively. PSMT-SE could effectively expose the surgical field. Median diameter of resected tumors was 2.0 (0.7) cm, the total operation time was 45.5 (27.0) min, and the en bloc resection rate was 100 %. No intraoperative or postoperative complications were observed.
Conclusion PSMT-SE is a potentially useful method for assisting resection of gastric SMT with tumor traction. Further prospective studies with large sample sizes are warranted.
Two-step ESD: an option for en-bloc resection of extensive colorectal laterally spreading tumors
Authors: Kawaguti Fabio S. , Okazaki Ossamu , Miyajima Nelson T. , Segateli Vanderlei , Marques Carlos F.S. , Nahas Caio S.R. , Martins Bruno C. , Nahas Sergio C. , Junior Ulysses R. , Filho Fauze M. 
Published: August 2019

Abstract
Background and study aims Endoscopic submucosal dissection (ESD) is considered feasible and safe for treatment of colorectal laterally spreading tumors (LST), However it remains a challenge in case of extensive lesions even for experts. This study aimed to describe a new method to facilitate ESD of extensive colorectal LSTs. Between July 2010 and January 2018, 140 patients underwent ESD for colorectal LSTs. Four of them were submitted to two-step ESD and were included in this retrospective study. The submucosal dissection of lesions larger than 12 cm started and continued until the medical team decided to pause the procedure and continue it in a second step. The second procedure was performed 2 days after to finish the en-bloc resection.Three patients were male, with mean age of 67.2y (± 2.2). All lesions were located in the rectum, with a mean size of 153.7 mm (± 33.8). En-bloc and curative resection were successfully achieved in all cases. Mean duration of the first step of the procedure was 255 minutes (± 61.8), and mean duration of the second step was 205 minutes (± 205). Overall mean duration of both steps was 460 minutes (± 168). Mean dissected area in the first step of the procedure was approximately 55 % of the lesion. No adverse events were observed. In conclusion, our results suggest that performing ESD in two steps could be a feasible and safe option for exceptional cases in which is not possible to finish the procedure in one step, avoiding the morbidity of surgical treatment.
Vom Neurastheniker zum Bipolaren: Kaiser Wilhelm II. im Spiegel psychiatrischer Diagnosen des 19. und 20. Jahrhunderts
Authors: Bruns Florian , Karenberg Axel 
Published: August 2019

ZusammenfassungBereits kurz nach der Thronbesteigung Wilhelms II. im Jahr 1888 wurden Stimmen laut, die den Geisteszustand des deutschen Kaisers infrage stellten. Der von ihm entlassene Reichskanzler Bismarck gehörte zu den ersten, die Zweifel an der Zurechnungsfähigkeit des Monarchen in Umlauf brachten. Das exzentrische Auftreten Wilhelms II. lud zu manchen Spekulationen ein und schnell wurden Vergleiche mit dem bayerischen König Ludwig II. hergestellt, der 1886 für geisteskrank und amtsunfähig erklärt worden war. Der Historiker Ludwig Quidde verfasste 1894 eine Abhandlung über römischen Cäsarenwahnsinn, die auf Wilhelm II. gemünzt war und große Bekanntheit erlangte. Andere Zeitgenossen beschrieben den Kaiser als Neurastheniker, während einige Psychiater ihm nach seiner Abdankung eine manisch-depressive Erkrankung zuschrieben. In welchem Maße die Spekulationen über eine psychische Erkrankung Wilhelms II. zutrafen, lässt sich nicht mehr ermitteln. Die ad personam gerichteten Angriffe dienten seinen Gegnern als Mittel der politischen Auseinandersetzung und erreichten 1918/19 einen Höhepunkt, als über die Verantwortung für den verlorenen Ersten Weltkrieg gestritten wurde. Das Beispiel Wilhelms II. zeigt, dass sich Expertise und Deutungsmacht der Psychiatrie Anfang des 20. Jahrhunderts bis in die Politik ausdehnten. Der Fall verweist überdies auf die Problematik psychiatrischer Ferndiagnosen und erinnert an die notwendige Trennung von psychiatrischem und politischem Urteil.
Practice patterns and predictors of prophylactic endoscopic clip usage during polypectomy
Authors: Forbes Nauzer , Hilsden Robert J. , Kaplan Gilaad G. , James Matthew T. , Lethebe Cord , Maxwell Courtney , Heitman Steven J. 
Published: August 2019

Abstract
Background and study aims Prophylactic endoscopic clips are commonly placed during polypectomy to reduce risk of delayed bleeding, although evidence to support this practice is unclear. Our study aimed to: (1) identify variables associated with prophylactic clip use; (2) explore variability between endoscopists’ clipping practices and (3) study temporal trends in prophylactic clip use.
Patients and methods This was a retrospective cohort study in a high-volume unit dedicated to screening-related colonoscopies. Colonoscopies involving polypectomy from 2008 to 2014 were reviewed. The primary outcome was prophylactic clipping status, both at the patient level and per polyp. Hierarchical regression models yielded adjusted odds ratios (AORs) to determine predictors of prophylactic clipping.
Results A total of 8,366 colonoscopies involving 19,129 polypectomies were included. Polyp size ≥ 20 mm was associated with higher clip usage (AOR 2.94; 95 % CI: 2.43, 3.54) compared to polyps < 10 mm. Right-sided polyps were more likely to be clipped (AOR 2.78; 95 % CI: 2.34, 3.30) relative to the rectum. Surgeons clipped less than gastroenterologists (OR 0.52; 95 % CI: 0.44, 0.63). From 2008 to 2014, the crude proportion of prophylactically clipped cases increased by 7.4 % (95 % CI: 7.1, 7.6) from 1.9 % to 9.3 %. Significant inter-endoscopist variability in clipping practices was observed, notably, for polyps < 10 mm.
Conclusions Prophylactic clip usage was correlated with established risk factors for delayed bleeding. Significantly increased clip usage over time was shown. Given that evidence does not clearly support prophylactic clipping, there is a need to educate practitioners and limit healthcare resource utilization.