bluuebunny/crossref_metadata_2025_split huggingface dataset:
The crosstalk between the Notch, Wnt, and SHH signaling pathways in regulating the proliferation and regeneration of sensory progenitor cells in the mouse cochlea
Authors: Wu Jingfang , Li Wen , Guo Luo , Zhao Liping , Sun Shan , Li Huawei 
Published: July 2021

AbstractSensory hair cells (HCs) are highly susceptible to damage by noise, ototoxic drugs, and aging. Although HCs cannot be spontaneously regenerated in adult mammals, previous studies have shown that signaling pathways are involved in HC regeneration in the damaged mouse cochlea. Here, we used a Notch antagonist (DAPT), a Wnt agonist (QS11), and recombinant Sonic hedgehog (SHH) protein to investigate their concerted actions underlying HC regeneration in the mouse cochlea after neomycin-induced damage both in vivo and in vitro. With DAPT, the numbers of HCs increased, and supporting cell (SC) proliferation was seen in both the intact and damaged cochlear sensory epithelia, while these numbers were unchanged in the presence of QS11. When simultaneously treated with DAPT and QS11, the number of HCs increased dramatically, and much greater SC proliferation was seen in the cochlear epithelium. In transgenic mice with both Notch1 conditional knockout and β-catenin over-expression, cochlear SC proliferation and HC regeneration were more obvious than in either Notch1 knockout or β-catenin over-expressing mice separately. When cochleae were treated with DAPT, QS11, and SHH together, SC proliferation was even greater, and this proliferation was seen in both the HC region and the greater epithelial ridge. High-throughput RNA sequencing was used to identify the differentially expressed genes between all groups, and the results showed that the SHH and Wnt signaling pathways are involved in SC proliferation. Our study suggests that co-regulation of the Notch, Wnt, and SHH signaling pathways promotes extensive cell proliferation and regeneration in the mouse cochlea.
Development of an integrated model of care for allogeneic stem cell transplantation facilitated by eHealth—the SMILe study
Authors: Leppla Lynn , Schmid Anja , Valenta Sabine , Mielke Juliane , Beckmann Sonja , Ribaut Janette , Teynor Alexandra , Dobbels Fabienne , Duerinckx Nathalie , Zeiser Robert , Engelhardt Monika , Gerull Sabine , De Geest Sabina ,   the SMILe study team, Bolliger Dora , Chalandon Yves , De DGeest Sabina , Degen Sabine , Dobbels Fabienne , Duerinckx Nathalie , Engelhardt Monika , Fürmann Margerita , Gerull Sabine , Grossmann Florian , Hasemann Monika , Heidegger Philipp , Hermann Anja , Hobelsberger Sandra , Husel Mylen , Koehly Katharina , Lemcke Marina , Leppla Lynn , Maier Birgit , Mamez Anne-Claire , Masouridi Stavoula , Mielke Juliane , Nair Gyathri , Neupert Daniela , Passweg Jakob , Pschenitza Stefan , Reitwiessner Sigrun , Ribaut Jannette , Rockstein Dennis , Schanz Urs , Schmid Anja , Schoemans Helen , Schulz Tobias , Schumacher Vanessa , Senft Yulia , Teynor Alexandra , Valenta Sabine , Werlitz Viktor , Witzig-Brändli Verena , Zeiser Robert 
Published: July 2021

Abstract
Purpose
Allogeneic stem cell transplantation would benefit from re-engineering care towards an integrated eHealth-facilitated care model. With this paper we aim to: (1) describe the development of an integrated care model (ICM) in allogeneic SteM-cell-transplantatIon faciLitated by eHealth (SMILe) by combining implementation, behavioral, and computer science methods (e.g., contextual analysis, Behavior Change Wheel, and user-centered design combined with agile software development); and (2) describe that model’s characteristics and its application in clinical practice.

Methods
The SMILe intervention’s development consisted of four steps, with implementation science methods informing each: (1) planning its set-up within a theoretical foundation; (2) using behavioral science methods to develop the content; (3) choosing and developing its delivery method (human/technology) using behavioral and computer science methods; and (4) describing its characteristics and application in clinical practice.

Results
The SMILe intervention is embedded within the eHealth enhanced Chronic Care Model, entailing four self-management intervention modules, targeting monitoring and follow-up of important medical and symptom-related parameters, infection prevention, medication adherence, and physical activity. Interventions are delivered partly face-to-face by a care coordinator embedded within the transplant team, and partly via the SMILeApp that connects patients to the transplant team, who can monitor and rapidly respond to any relevant changes within 1 year post-transplant.

Conclusion
This paper provides stepwise guidance on how implementation, behavioral, and computer science methods can be used to develop interventions aiming to improve care for stem cell transplant patients in real-world clinical settings. This new care model is currently being tested in a hybrid I effectiveness-implementation trial.
Alteration of protein expression and spliceosome pathway activity during Barrett’s carcinogenesis
Authors: Stingl Christoph , Bureo Gonzalez Angela , Güzel Coşkun , Phoa Kai Yi Nadine , Doukas Michail , Breimer Gerben Eise , Meijer Sybren Lodewijk , Bergman Jacques Johannes , Luider Theo Marten 
Published: July 2021

Abstract
Background
Barrett’s esophagus (BE) is a known precursor lesion and the strongest risk factor for esophageal adenocarcinoma (EAC), a common and lethal type of cancer. Prediction of risk, the basis for efficient intervention, is commonly solely based on histologic examination. This approach is challenged by problems such as inter-observer variability in the face of the high heterogeneity of dysplastic tissue. Molecular markers might offer an additional way to understand the carcinogenesis and improve the diagnosis—and eventually treatment. In this study, we probed significant proteomic changes during dysplastic progression from BE into EAC.

Methods
During endoscopic mucosa resection, epithelial and stromal tissue samples were collected by laser capture microdissection from 10 patients with normal BE and 13 patients with high-grade dysplastic/EAC. Samples were analyzed by mass spectrometry-based proteomic analysis. Expressed proteins were determined by label-free quantitation, and gene set enrichment was used to find differentially expressed pathways. The results were validated by immunohistochemistry for two selected key proteins (MSH6 and XPO5).

Results
Comparing dysplastic/EAC to non-dysplastic BE, we found in equal volumes of epithelial tissue an overall up-regulation in terms of protein abundance and diversity, and determined a set of 226 differentially expressed proteins. Significantly higher expressions of MSH6 and XPO5 were validated orthogonally and confirmed by immunohistochemistry.

Conclusions
Our results demonstrate that disease-related proteomic alterations can be determined by analyzing minute amounts of cell-type-specific collected tissue. Further analysis indicated that alterations of certain pathways associated with carcinogenesis, such as micro-RNA trafficking, DNA damage repair, and spliceosome activity, exist in dysplastic/EAC.
Medication use and risk of proximal colon cancer: a systematic review of prospective studies with narrative synthesis and meta-analysis
Authors: Harewood Rhea , Disney Ruth , Kinross James , von Wagner Christian , Cross Amanda J. 
Published: July 2021

Abstract
Purpose
Evidence of differences in the etiology of, and poorer survival from, proximal colon compared to the distal colorectum, necessitates research into its risk factors. This systematic review summarizes the evidence on medication use and proximal colon cancer risk.

Methods
MEDLINE and EMBASE were searched for prospective studies investigating nine medication groups, namely non-steroidal anti-inflammatory drugs (NSAIDs), exogenous hormones, i.e., hormone replacement therapy (HRT) or oral contraceptives (OCs), statins, proton pump inhibitors, anti-hypertensives, metformin (an antidiabetic), antidiarrheals or laxatives, and the risk of proximal colon cancer. Narrative synthesis and meta-analyses, using random effects models to estimate risk ratios (RRs) and 95% confidence intervals (CIs), were conducted.

Results
Twenty nine publications investigating NSAIDs (n = 13), exogenous hormones [HRT (n = 9) or OCs (n = 4)] statins (n = 5), anti-hypertensives (n = 1), and metformin (n = 1) were included. Summary RRs reported a protective effect of aspirin use (RR 0.80, 95% CI 0.73–0.89) but no associations between HRT (RR 0.92, 95% CI 0.83–1.02), OC (RR 1.06, 95% CI 0.98–1.14) or statin use (RR 0.94, 95% CI 0.67–1.31), and proximal colon cancer incidence compared to never/non-use. One study on metformin and one on anti-hypertensives reported no association. Sources of between-study heterogeneity included study design, period of exposure ascertainment, exposure source, and exposure comparison, but this exploration was hindered by the small numbers of studies.

Conclusion
Despite some studies on NSAID or HRT use, evidence on the impact of a range of medications on proximal colon cancer risk is limited. This highlights the need for more research to inform chemoprevention strategies.
Revisiting a Three-Player Pursuit-Evasion Game
Authors: Szőts János , Savkin Andrey V. , Harmati István 
Published: July 2021

AbstractWe consider the game of a holonomic evader passing between two holonomic pursuers. The optimal trajectories of this game are known. We give a detailed explanation of the game of kind’s solution and present a computationally efficient way to obtain trajectories numerically by integrating the retrograde path equations. Additionally, we propose a method for calculating the partial derivatives of the Value function in the game of degree. This latter result applies to differential games with homogeneous Value.
Arch bridges subject to pier settlements: continuous vs. piecewise rigid displacement methods
Authors: Malena Marialaura , Angelillo Maurizio , Fortunato Antonio , de Felice Gianmarco , Mascolo Ida 
Published: July 2021

AbstractSettlements severely affect historic masonry arch bridges worldwide. There are countless examples of structural dislocations and ruins in recent years due to severe settlements at the base of pier foundations, often caused by shipworm infestation of wooden foundations or scouring and riverbed erosion phenomena. The present paper proposes an original way to approach the failure analysis of settled masonry arch bridges. The proposed method combines two different 2D numerical models for the prediction of masonry arch bridge capacity against settlements and for safety assessment. The first one is the Piecewise Rigid Displacement method, i.e. a block-based limit analysis approach using the well known Heyman's hypotheses; the second one is a continuous Finite Element approach. The case study of the four-span Deba Bridge (Spain, 2018) failure is presented with the aim to illustrate how the methods work. The failure analysis produced satisfactory results by applying both methods separately, in confirmation of their reliability. Their combination also allowed to obtain a significantly reduction in computational cost and an improvement of prediction accuracy. A sensitivity and a path-following analysis were also performed with the aim to demonstrate the robustness of the presented method. The obtained simulations highlighted that the results do not depend on the friction angle and that a proper prediction of the evolution of the structural behavior can be obtained only taking into account geometric nonlinearities. Such results demonstrate once again that in settled masonry arches geometry prevails over the mechanical parameters. The current study paves the way for the fruitful use of the proposed approaches for a wider range of applications, as, for example, the mechanism identification or the displacement capacity assessment of masonry structures under overloading as seismic loads.
Hard versus soft impact modeling of vibro-impact systems with a moving base
Authors: Okolewski Andrzej , Blazejczyk-Okolewska Barbara 
Published: July 2021

AbstractSoft and hard impact models applied to modeling of vibro-impact systems with a moving base are discussed. The conditions under which two collision models are equivalent in terms of equal energy dissipation are derived. These conditions differ from those presented in the literature. It is shown that in the case of a stiff, harmonically moving base with a low rate of energy dissipation, both methods yield the same results, but an application of the soft impact model to either the base with low stiffness or even the stiff base with a high rate of energy dissipation leads to different results from the ones for the hard impact model.
Finding the Gap: Immigrant Integration Outcomes and Settlement Service Provision in the Republic of Ireland
Authors: Gilmartin Mary , Dagg Jennifer 
Published: July 2021

AbstractImmigrant integration is increasingly assessed through integration outcomes, which assess the degree of convergence of the experiences of immigrants and non-immigrants within a country. Integration processes – for example, settlement services in key areas such as employment, education and social inclusion – help to enhance integration outcomes. In this paper, we use the example of the Republic of Ireland to show that the relationship between desired integration outcomes and the provision of settlement services needs considerably more attention. We present immigrant integration outcomes for specific regions and groups of immigrants derived from existing large-scale data sets. We then use publicly available data on existing settlement services to assess the extent to which settlement services address key areas of immigrant integration outcomes. We demonstrate that there are considerable gaps in the provision of appropriate settlement services that could support the enhancement of key integration outcomes, such as the quality of work, language proficiency and housing. If immigrant integration outcomes are to be improved, the relationship between outcomes and settlement service provision has to be better coordinated and targeted to address the structural barriers faced by particular groups of immigrants and by immigrants living in particular regions.
Ruelle Zeta Functions of Hyperbolic Manifolds and Reidemeister Torsion
Authors: Müller Werner 
Published: July 2021

AbstractThis paper is concerned with the behavior of twisted Ruelle zeta functions of compact hyperbolic manifolds at the origin. Fried proved that for an orthogonal acyclic representation of the fundamental group of a compact hyperbolic manifold, the twisted Ruelle zeta function is holomorphic at $$s=0$$

s
=
0

and its value at $$s=0$$

s
=
0

equals the Reidemeister torsion. He also established a more general result for orthogonal representations, which are not acyclic. The purpose of the present paper is to extend Fried’s result to arbitrary finite dimensional representations of the fundamental group. The Reidemeister torsion is replaced by the complex-valued combinatorial torsion introduced by Cappell and Miller.
Developments in Biological Mechanisms and Treatments for Negative Symptoms and Cognitive Dysfunction of Schizophrenia
Authors: Wu Qiongqiong , Wang Xiaoyi , Wang Ying , Long Yu-Jun , Zhao Jing-Ping , Wu Ren-Rong 
Published: July 2021

AbstractThe causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade. The first part of this review summarizes the pathogenesis of schizophrenia, especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics. The second part describes the novel medications and several advanced physical therapies (e.g., transcranial magnetic stimulation and transcranial direct current stimulation) for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.
Predicting the substituent effects in the optical and electrochemical properties of N,N′-substituted isoindigos
Authors: Kiss Ferdinand L. , Corbet Brian P. , Simeth Nadja A. , Feringa Ben L. , Crespi Stefano 
Published: July 2021

AbstractIsoindigo, the structural isomer of the well-known dye indigo, has seen a major revival recently because of the increasing interest of its use as a potential drug core structure and for the development of organic photovoltaic materials. Highly beneficial for diverse applications are its facile synthesis, straightforward functionalisation and the broad absorption band in the visible range. Moreover, its intrinsic electron deficiency renders isoindigo a promising acceptor structure in bulk heterojunction architectures. Here we present new insights into the substituent effects of N-functionalised isoindigos, developing a reliable and fast in silico screening approach of a library of compounds. Using experimental UV–Vis and electrochemical data increased the accuracy of the TD-DFT method employed. This procedure allowed us to accurately predict the optical and electrochemical properties of N-functionalised isoindigos and the elucidation of the relationship between substituent effects and electronic properties.
Graphic abstract
OnabotulinumtoxinA Improves Quality of Life in Chronic Migraine: The PREDICT Study
Authors: Boudreau Guy , Finkelstein Ian , Graboski Corrie , Ong May , Christie Suzanne , Sommer Katherine , Bhogal Meetu , Davidovic Goran , Becker Werner J. 
Published: July 2021

ABSTRACTBackground:The PREDICT study assessed real-world, long-term health-related quality of life in adults with chronic migraine (CM) receiving onabotulinumtoxinA.Methods:Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA for CM. OnabotulinumtoxinA (155–195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Primary endpoint: mean change in Migraine-Specific Quality of Life Questionnaire (MSQ) at treatment 4 (Tx4) versus baseline. Secondary endpoints: mean change in MSQ at final visit versus baseline, and headache days.Results:184 participants (average age 45 years; 84.8% female; 94.6% Caucasian) received ≥1 onabotulinumtoxinA treatment; 150 participants completed 4 treatments (1 year) and 123 completed all 7 treatment cycles (2 years). Mean (SD) onabotulinumtoxinA dose per treatment cycle was 171 (18) U and treatment interval was 13.2 (1.8) weeks. Baseline mean (SD) 20.9 (6.7) headache days/month decreased (Tx1: −3.5 [6.3]; Tx4: −6.5 [6.6]; p < 0.0001 versus baseline). Mean (SD) increased from baseline in MSQ at Tx4 (restrictive: 21.5 [24.3], preventive: 19.5 [24.7], emotional: 22.9 [32.9]) and the final visit (restrictive: 21.3 [23.0], preventive: 19.2 [23.7], emotional: 27.4 [30.7]), exceeding minimal important differences (all p < 0.0001). Seventy-seven (41.8%) participants reported 168 treatment-emergent adverse events (TEAEs); 38 TEAEs (12.0%) were considered treatment-related. Four (2.2%) participants reported six serious TEAEs; none were considered treatment-related. No new safety signals were identified.Conclusions:Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA for CM in Canada improved MSQ scores and reduced headache frequency and severity, adding to the body of evidence on the long-term safety and effectiveness of onabotulinumtoxinA for CM.
Assessing the effects of Bt maize on the non-target pest Rhopalosiphum maidis by demographic and life-history measurement endpoints
Authors: Lanzoni Alberto , Bosi Sara , Bregola Valeria , Camastra Francesco , Ciaramella Angelo , Staiano Antonino , Dinelli Giovanni , Burgio Giovanni 
Published: July 2021

AbstractThe most commercialized Bt maize plants in Europe were transformed with genes which express a truncated form of the insecticidal delta-endotoxin (Cry1Ab) from the soil bacterium Bacillus thuringiensis (Bt) specifically against Lepidoptera. Studies on the effect of transgenic maize on non-target arthropods have mainly converged on beneficial insects. However, considering the worldwide extensive cultivation of Bt maize, an increased availability of information on their possible impact on non-target pests is also required. In this study, the impact of Bt-maize on the non-target corn leaf aphid, Rhopalosiphum maidis, was examined by comparing biological traits and demographic parameters of two generations of aphids reared on transgenic maize with those on untransformed near-isogenic plants. Furthermore, free and bound phenolics content on transgenic and near-isogenic plants were measured. Here we show an increased performance of the second generation of R. maidis on Bt-maize that could be attributable to indirect effects, such as the reduction of defense against pests due to unintended changes in plant characteristics caused by the insertion of the transgene. Indeed, the comparison of Bt-maize with its corresponding near-isogenic line strongly suggests that the transformation could have induced adverse effects on the biosynthesis and accumulation of free phenolic compounds. In conclusion, even though there is adequate evidence that aphids performed better on Bt-maize than on non-Bt plants, aphid economic damage has not been reported in commercial Bt corn fields in comparison to non-Bt corn fields. Nevertheless, Bt-maize plants can be more easily exploited by R. maidis, possibly due to a lower level of secondary metabolites present in their leaves. The recognition of this mechanism increases our knowledge concerning how insect-resistant genetically modified plants impact on non-target arthropods communities, including tritrophic web interactions, and can help support a sustainable use of genetically modified crops.
Analysis of malaria clinical−epidemiological predictors in individuals from Brazilian Amazon
Authors: Lisbôa Paulo Guilherme Souza , Medeiros Janaina Maria Rodrigues , de Souza Arthur Vinícius , dos Santos Bruno Fernando Barros , Sanches Henrique Otávio Coutinho , da Rocha Juliane Lúcia Gomes , Correa Junior Wender de Jesus Pena , Costa Gabriela Góes , Chaves Tania do Socorro Souza , da Silva Ventura Ana Maria Revoredo , Libonati Rosana Maria Feio 
Published: July 2021

AbstractThis research aims to determine whether the combination of epidemiological and clinical features can predict malaria. Diagnostic investigation detected 22.3% of individuals with Plasmodium vivax (P. vivax) malaria, with significant predominance of the male gender. The malaria triad (fever, chills and headache) had a more expressive frequency (81.1%) in individuals with positive thick blood than those with negative thick blood smear (65.1%), although there was no statistical significance. Among the variables analysed as predictive for positive thick blood smear, it was observed that personal history of travel to an endemic malaria area and past malaria infection (PMI) were significantly associated with malaria, even in multiple logistic regression. Fever had the higher sensitivity (94.6%) and past malaria history had the greater specificity (68.2%), with accuracy of 23.5% and 67.5%, respectively. In combined analysis, fever with chills had the highest sensitivity (91.9%), but low accuracy (38.5%). High specificity (91.5%) was found in the association of malaria triad, PMI and history of travel to endemic malaria area (which along with anorexia, was higher 94.6%), with good accuracy (80.7%), suggesting that the screening of patients for performing thick blood smear can be based on these data. The epidemiological features and the malaria triad (fever, chills and headache) can be predictors for identification of malaria patients, concurring to precocious diagnosis and immediate treatment of individuals with malaria.