bluuebunny/crossref_metadata_2025_split huggingface dataset:
Animal model and bioinformatics analyses suggest the TIMP1/MMP9 axis as a potential biomarker in oral squamous cell carcinoma
Authors: Xu Guoqiang , Wei Jianing , Huangfu Bing , Gao Jiping , Wang Xiaotang , Xiao Lanfei , Xuan Ruijing , Chen Zhaoyang , Song Guohua 
Published: October 2020

AbstractOral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck. However, the molecular mechanism underlying its development and progression is yet unclear. Genes that are differentially expressed, that is, differentially expressed genes (DEGs), between normal and diseased tissues are believed to be involved in disease development and progression. To identify the DEGs in OSCC and explore their role in occurrence and progression, we established a Chinese hamster OSCC model, determined the DEG, screened the identified DEGs, and performed Gene Ontology (GO) and KEGG enrichment analyses. A protein–protein interaction (PPI) network was generated to screen potential candidate genes. We then analyzed the expression, tumor stage and prognosis of candidate genes using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, we verified the candidate DEGs by quantitative real‐time PCR and Gene Expression Omnibus analysis. The results showed 194 significantly DEGs, 140 enriched GO terms, and 8 KEGG pathways, which suggested that OSCC was closely related to the immune system, cell migration, and extracellular matrix. GEPIA and PPI network analysis revealed that SPP1, TNC, and ACTA1 were significantly related to tumor staging; SPP1, tissue inhibitors of matrix metallopeptidases (MMPs) 1 (TIMP1), and ACTA1 were closely related to prognosis. The scores for the top five highest degree genes were close, and the TIMP1/MMP9 axis appeared to be at the center of the PPI network, indicating that expression changes in the TIMP1/MMP9 axis and related genes may be involved in tumor invasion and metastasis. These findings provide novel insights into the mechanism of oral cancer.
Cerebrospinal Fluid Levels of Prodynorphin‐Derived Peptides are Decreased in Huntington's Disease
Authors: Al Shweiki MHD Rami , Oeckl Patrick , Pachollek Adrian , Steinacker Petra , Barschke Peggy , Halbgebauer Steffen , Anderl‐Straub Sarah , Lewerenz Jan , Ludolph Albert C. , Bernhard Landwehrmeyer Georg , Otto Markus 
Published: October 2020

ABSTRACTRESULTSHuntingtonʼs disease (HD) is a devastating neurodegenerative disorder characterized by a selective loss of striatal medium spiny projection neurons (MSNs). Prodynorphin (PDYN) is enriched in a subpopulation of striatal MSNs. Postmortem brains of HD patients and rodent models have been demonstrated to have reduced levels of PDYN transcripts and the neuropeptide dynorphin.RESULTSGiven the unmet need for novel pharmacodynamic HD biomarkers in the context of experimental huntingtin (htt)‐lowering therapies, we investigated the levels of PDYN‐derived peptides and neurofilament light (NfL) chain in the cerebrospinal fluid (CSF) from HD patients (n = 16), matched controls (n = 55), and patients with other neurodegenerative disorders (n = 70).ResultsPDYN‐derived peptide levels were found to be substantially decreased in HD patients (P < 0.0001 in comparison to controls), whereas the NfL levels were elevated in all neurodegenerative disorders.ConclusionsOur study suggests decreased PDYN‐derived peptide levels in the CSF as a more specific biomarker for HD in comparison to NfL. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Spatializing immigrant integration outcomes
Authors: Gilmartin Mary , Dagg Jennifer 
Published: October 2020

AbstractMeasurements of immigrant integration outcomes generally occur at the national scale and, to a lesser extent, at the urban scale. This paper argues that immigrant integration outcomes should be measured at other scales in order to better understand how the process of integration is affected by where people live. It uses existing large‐scale data sets for the Republic of Ireland to show differences in integration outcomes, measured using the Zaragoza indicators, for three of the country's eight NUTS 3 regions. The analysis shows that there are marked differences in immigrant integration outcomes across regions and highlights the different regional barriers to and enablers of integration. The paper concludes that geographers should advocate for a more nuanced understanding of immigrant integration as a spatialized process and should insist on the importance of making relevant data available at a range of spatial scales.
POMzites: A roadmap for inverse design in metal oxide chemistry
Authors: Vilà‐Nadal Laia 
Published: October 2020

AbstractComputationally exploring the space generated by the self‐assembly of known molecular metal oxides and the ability to predict new architectures is a challenging task. As a proof of concept, here, we propose narrowing it down to a new family of all‐inorganic porous materials named POMzites. Structures with new topologies, but aiming for pure inorganic systems, will be targeted initially. POMzites are composed of ring‐shaped tungsten oxide building blocks connected with transition metal linkers forming zero to three dimensional frameworks. Despite POMzites and zeolites having similar structures, the library of POMzites is an order of magnitude smaller than that of zeolites (14 POMzites vs 213 zeolites). The idea proposed in this perspective article is to accelerate the discovery of new POMzite porous frameworks materials using inverse design approaches.
Looking Ahead: China Becoming a High-Income Economy
Authors: Zhou Shaojie , Hu Angang 
Published: October 2020

AbstractNearly four decades of reform and opening-up shows that China is one of the few successful cases of development. First, sustained high growth became a reality in China. China’s GNP grew by 32.19 times from 1978 to 2016 at constant prices, that is, an annual increase of 9.6%, of which the annual GDP growth hit 9.9% and 7.8% from 1978 to 2010 (high-speed growth) and from 2011 to 2016 (moderately high-speed growth) respectively on average.
Dynamic scale anomalous transport in QCD with electromagnetic background
Authors: Kawaguchi Mamiya , Matsuzaki Shinya , Huang Xu-Guang 
Published: October 2020

Abstract
We discuss phenomenological implications of the anomalous transport induced by the scale anomaly in QCD coupled to an electromagnetic (EM) field, based on a dilaton effective theory. The scale anomalous current emerges in a way perfectly analogous to the conformal transport current induced in a curved spacetime background, or the Nernst current in Dirac and Weyl semimetals — both current forms are equivalent by a “Weyl transformation”. We focus on a spatially homogeneous system of QCD hadron phase, which is expected to be created after the QCD phase transition and thermalization. We find that the EM field can induce a dynamic oscillatory dilaton field which in turn induces the scale anomalous current. As the phenomenological applications, we evaluate the dilepton and diphoton productions induced from the dynamic scale anomalous current, and find that those productions include a characteristic peak structure related to the dynamic oscillatory dilaton, which could be tested in heavy ion collisions. We also briefly discuss the out-of-equilibrium particle production created by a nonadiabatic dilaton oscillation, which happens in a way of the so-called tachyonic preheating mechanism.
A long neck principle for Riemannian spin manifolds with positive scalar curvature
Authors: Cecchini Simone 
Published: October 2020

AbstractWe develop index theory on compact Riemannian spin manifolds with boundary in the case when the topological information is encoded by bundles which are supported away from the boundary. As a first application, we establish a “long neck principle” for a compact Riemannian spin n-manifold with boundary X, stating that if $${{\,\mathrm{scal}\,}}(X)\ge n(n-1)$$

scal

(
X
)
≥
n
(
n
-
1
)

and there is a nonzero degree map into the sphere $$f:X\rightarrow S^n$$

f
:
X
→

S
n

which is strictly area decreasing, then the distance between the support of $$\text {d}f$$

d
f

and the boundary of X is at most $$\pi /n$$

π
/
n

. This answers, in the spin setting and for strictly area decreasing maps, a question recently asked by Gromov. As a second application, we consider a Riemannian manifold X obtained by removing k pairwise disjoint embedded n-balls from a closed spin n-manifold Y. We show that if $${{\,\mathrm{scal}\,}}(X)>\sigma >0$$

scal

(
X
)
>
σ
>
0

and Y satisfies a certain condition expressed in terms of higher index theory, then the radius of a geodesic collar neighborhood of $$\partial X$$

∂
X

is at most $$\pi \sqrt{(n-1)/(n\sigma )}$$

π

(
n
-
1
)
/
(
n
σ
)

. Finally, we consider the case of a Riemannian n-manifold V diffeomorphic to $$N\times [-1,1]$$

N
×
[
-
1
,
1
]

, with N a closed spin manifold with nonvanishing Rosenebrg index. In this case, we show that if $${{\,\mathrm{scal}\,}}(V)\ge \sigma >0$$

scal

(
V
)
≥
σ
>
0

, then the distance between the boundary components of V is at most $$2\pi \sqrt{(n-1)/(n\sigma )}$$

2
π

(
n
-
1
)
/
(
n
σ
)

. This last constant is sharp by an argument due to Gromov.
A novel fungal gene regulation system based on inducible VPR-dCas9 and nucleosome map-guided sgRNA positioning
Authors: Schüller Andreas , Wolansky Lisa , Berger Harald , Studt Lena , Gacek-Matthews Agnieszka , Sulyok Michael , Strauss Joseph 
Published: October 2020

Abstract
Programmable transcriptional regulation is a powerful tool to study gene functions. Current methods to selectively regulate target genes are mainly based on promoter exchange or on overexpressing transcriptional activators. To expand the discovery toolbox, we designed a dCas9-based RNA-guided synthetic transcription activation system for Aspergillus nidulans that uses enzymatically disabled “dead” Cas9 fused to three consecutive activation domains (VPR-dCas9). The dCas9-encoding gene is under the control of an estrogen-responsive promoter to allow induction timing and to avoid possible negative effects by strong constitutive expression of the highly active VPR domains. Especially in silent genomic regions, facultative heterochromatin and strictly positioned nucleosomes can constitute a relevant obstacle to the transcriptional machinery. To avoid this negative impact and to facilitate optimal positioning of RNA-guided VPR-dCas9 to targeted promoters, we have created a genome-wide nucleosome map from actively growing cells and stationary cultures to identify the cognate nucleosome-free regions (NFRs). Based on these maps, different single-guide RNAs (sgRNAs) were designed and tested for their targeting and activation potential. Our results demonstrate that the system can be used to regulate several genes in parallel and, depending on the VPR-dCas9 positioning, expression can be pushed to very high levels. We have used the system to turn on individual genes within two different biosynthetic gene clusters (BGCs) which are silent under normal growth conditions. This method also opens opportunities to stepwise activate individual genes in a cluster to decipher the correlated biosynthetic pathway.

Keypoints
• An inducible RNA-guided transcriptional regulator based on VPR-dCas9 was established in Aspergillus nidulans.
• Genome-wide nucleosome positioning maps were created that facilitate sgRNA positioning.
• The system was successfully applied to activate genes within two silent biosynthetic gene clusters.
Intersecting Lorenz curves and aversion to inverse downside inequality
Authors: Chiu W. Henry 
Published: October 2020

AbstractThis paper defines and characterizes the concept of an increase in inverse downside inequality and show that, when the Lorenz curves of two income distributions intersect, how the change from one distribution to the other is judged by an inequality index exhibiting inverse downside inequality aversion often depends on the relative strengths of its aversion to inverse downside inequality and inequality aversion. For the class of linear inequality indices, of which the Gini coefficient is a member, a measure characterizing the strength of an index’s aversion to inverse downside inequality against its own inequality aversion is shown to determine the ranking by the index of two distributions whose Lorenz curves cross once. The precise condition under which the same result generalizes to the case of multiple-crossing Lorenz curves is also identified.
Effects and moderators of the Olweus bullying prevention program (OBPP) in Germany
Authors: Ossa Fanny Carina , Jantzer Vanessa , Eppelmann Lena , Parzer Peter , Resch Franz , Kaess Michael 
Published: October 2020

AbstractBullying is a common and significant risk factor for mental and physical health problems. The aim of the outlined study was to evaluate the German version of the Olweus Bullying Prevention Program (OBPP) and to investigate potential moderators of its effectiveness. 23 schools started with the implementation and all students were invited to complete the Olweus Bullying Questionnaire annually. For our analyses, the data from grades 5 to 9 were used (t0: n = 5759; t1: n = 5416; t2: n = 4894). 16 out of the 23 schools completed the 18-months implementation period. The effectiveness of the program statistically depended on its complete implementation (χ2(2) = 7.62, p = 0.022). In the group of non-completers, the prevalence of victimization did not change during the observation period of 2 years (χ2(2) = 4.64, p = 0.099). In the group of the completer schools, a significant decrease in bullying between t0 and t1 was found for victims (t0: 9.14%; t1: 6.87%; OR = 0.74; 95% CI 0.62–0.88; p = 0.001) and perpetrators (t0: 6.16%; t1: 4.42%; OR = 0.70; 95% CI 0.55–0.89; p = 0.004). After 24 months (t2), this decrease could be retained (victims: t2: 6.83%; OR = 0.73; 95%CI = 0.61–0.88; p = 0.001; perpetrators: t2: 4.63%; OR = 0.72; 95% CI 0.57–0.92; p = 0.009). Furthermore, we found the following moderators of program effectiveness in the completer schools: (1) gender (with a stronger decrease among victimized girls; p = 0.004) and (2) school grade (with a stronger decrease of victimization among grades 5–7; p = 0.028). The German version of the OBPP significantly reduced the bullying prevalence in the completer schools. Effective prevention needs time and resources: fulfilling the 18-months implementation period was the basis for positive results.
Insight into the influence of local streambed heterogeneity on hyporheic-zone flow characteristics
Authors: Earon Robert , Riml Joakim , Wu Liwen , Olofsson Bo 
Published: October 2020

AbstractInteraction between surface water and groundwater plays a fundamental role in influencing aquatic chemistry, where hyporheic exchange processes, distribution of flow paths and residence times within the hyporheic zone will influence the transport of mass and energy in the surface-water/groundwater system. Geomorphological conditions greatly influence hyporheic exchange, and heterogeneities such as rocks and clay lenses will be a key factor for delineating the hyporheic zone. Electrical resistivity tomography (ERT) and ground-penetrating radar (GPR) were used to investigate the streambed along a 6.3-m-long reach in order to characterise geological layering and distinct features which may influence parameters such as hydraulic conductivity. Time-lapse ERT measurements taken during a tracer injection demonstrated that geological features at the meter-scale played a determining role for the hyporheic flow field. The penetration depth of the tracer into the streambed sediment displayed a variable spatial pattern in areas where the presence of highly resistive anomalies was detected. In areas with more homogeneous sediments, the penetration depth was much more uniformly distributed than observed in more heterogeneous sections, demonstrating that ERT can play a vital role in identifying critical hydraulic features that may influence hyporheic exchange processes. Reciprocal ERT measurements linked variability and thus uncertainty in the modelled resistivity to the spatial locations, which also demonstrated larger variability in the tracer penetration depth, likely due to local heterogeneity in the hydraulic conductivity field.
Evolution as a Solution: Franco Andrea Bonelli, Lamarck, and the Origin of Man in Early-Nineteenth-Century Italy
Authors: Forgione Fabio 
Published: October 2020

AbstractFranco Andrea Bonelli, a disciple of Lamarck, was one of the few naturalists who taught and disseminated transformism in Italy in the early nineteenth century. The explanation of the history of life on Earth offered by Lamarck’s theory was at odds with the Genesis narrative, while the issue of man’s place in nature raised heated debates. Bonelli sought to reconcile science and religion through his original interpretation of the variability of species, but he also focused on anthropological subjects. Following Blumenbach’s studies, he investigated the differences within the human species and explored the topic of humans’ alleged superiority over animals. The origin of human beings, their history, and their relationship with the rest of life were thus read in light of transformism. According to Bonelli, such questions would not do irreparable damage to the new theory. On the contrary, he considered evolution not only acceptable but even necessary to protect the Holy Texts from certain dangerous trends in anthropological and zoological research.
BRD4 modulates vulnerability of triple-negative breast cancer to targeting of integrin-dependent signaling pathways
Authors: Zhang Yang , Xu Bingwei , Shi Junfeng , Li Jieming , Lu Xinlan , Xu Li , Yang Helen , Hamad Nevean , Wang Chi , Napier Dana , He Shuixiang , Liu Chunming , Liu Zeyi , Qian Hai , Chen Li , Wei Xiaowei , Zheng Xucai , Huang Jian-An , Thibault Olivier , Craven Rolf , Wei Dongping , Pan Yueyin , Zhou Binhua P. , Wu Yadi , Yang Xiuwei H. 
Published: October 2020

Abstract
Purpose
Stemming from a myriad of genetic and epigenetic alterations, triple-negative breast cancer (TNBC) is tied to poor clinical outcomes and aspires for individualized therapies. Here we investigated the therapeutic potential of co-inhibiting integrin-dependent signaling pathway and BRD4, a transcriptional and epigenetic mediator, for TNBC.

Methods
Two independent patient cohorts were subjected to bioinformatic and IHC examination for clinical association of candidate cancer drivers. The efficacy and biological bases for co-targeting these drivers were interrogated using cancer cell lines, a protein kinase array, chemical inhibitors, RNAi/CRISPR/Cas9 approaches, and a 4 T1-Balb/c xenograft model.

Results
We found that amplification of the chromosome 8q24 region occurred in nearly 20% of TNBC tumors, and that it coincided with co-upregulation or amplification of c-Myc and FAK, a key effector of integrin-dependent signaling. This co-upregulation at the mRNA or protein level correlated with a poor patient survival (p < 0.0109 or p < 0.0402, respectively). Furthermore, we found that 14 TNBC cell lines exhibited high vulnerabilities to the combination of JQ1 and VS-6063, potent pharmacological antagonists of the BRD4/c-Myc and integrin/FAK-dependent pathways, respectively. We also observed a cooperative inhibitory effect of JQ1 and VS-6063 on tumor growth and infiltration of Ly6G+ myeloid-derived suppressor cells in vivo. Finally, we found that JQ1 and VS-6063 cooperatively induced apoptotic cell death by altering XIAP, Bcl2/Bcl-xl and Bim levels, impairing c-Src/p130Cas-, PI3K/Akt- and RelA-associated signaling, and were linked to EMT-inducing transcription factor Snail- and Slug-dependent regulation.

Conclusion
Based on our results, we conclude that the BRD4/c-Myc- and integrin/FAK-dependent pathways act in concert to promote breast cancer cell survival and poor clinical outcomes. As such, they represent promising targets for a synthetic lethal-type of therapy against TNBC.
Einflussgrößen auf die Bestimmung des Angiotensin-Converting Enzyme (ACE) bei pulmonalen und extrapulmonalen Erkrankungen
Authors: Oremek G. M. , Passek K. , Bendels M. H. , Ohlendorf D. 
Published: October 2020

ZusammenfassungIm Rahmen der Serie „Biomarker“, die im Zentralblatt für Arbeitsmedizin und Ergonomie publiziert wird, ist das Angiotensin-Converting Enzyme (ACE) zugehörig als häufiger Marker in der Diagnostik von pulmonalen und extrapulmonalen Erkrankungen. Die Bestimmung von ACE stellt einen wesentlichen Bestandteil der Diagnostik von pulmonalen und extrapulmonalen Erkrankungen dar. Der Einfluss von Tabakkonsum, Medikamenten, Zink-Chelatoren auf die ACE-Konzentration wird eruiert. ACE erwies sich als Marker mit einer hohen Sensitivität und Spezifität bei Lungenerkrankungen.
Radical Flexibility and Relationality as Responses to Education in Times of Crisis
Authors: Veletsianos George , Houlden Shandell 
Published: October 2020

AbstractAs educational institutions negotiate numerous challenges resulting from the current pandemic, many are beginning to wonder what the future of education may look like. We contribute to this conversation by arguing for flexible education and considering how it can support better—more equitable, just, accessible, empowering, imaginative—educational futures. At a time of historical disorder and uncertainty, we argue that what we need is a sort of radical flexibility as a way to create life-sustaining education, not just for some, but for all, and not just for now, but far into the future. We argue that such an approach is relational, and centers justice and trust. Furthermore, we note that radical flexibility is systemic and hopeful, and requires wide-ranging changes in practices in addition to the application of new technologies.
Physician–patient shared decision making, patient satisfaction, and adoption of new health technology in China
Authors: Wei Yan , Ming Jian , Shi Lizheng , Ke Xiong , Sun Hui , Chen Yingyao 
Published: October 2020

ObjectiveTo examine the association between physician–patient treatments shared decision making (SDM), patient satisfaction, and adoption of a new health technology.MethodsA cross-sectional study was conducted from July 2016 to October 2016 in Fujian Province and Shanghai, in Eastern China. A total of 542 physicians and 619 patients in eleven hospitals were surveyed. Patients and their treating physicians completed self-reported questionnaires on patient–physician SDM, satisfaction with treatment decision making and adoption of a new health technology. Correlation analysis, multivariate logistic regression and multivariate linear regression were performed.ResultsThe majority (68.20 percent) of patients preferred SDM. Involvement of patients in SDM was positively associated with their satisfaction with treatment decision making (p < .001) and adoption of a new health technology (p < .05). Better concordance between their preference and actual SDM was positively associated with patients' adoption behavior (p < .05), but no statistically significant association was found between concordance and satisfaction.ConclusionSDM was the most important predictor of patients' satisfaction with decision making and adoption of a new health technology. Therefore, better communication between physicians and patients is recommended to improve their SDM, increase patient satisfaction and to assist with the adoption of new technologies. Training healthcare provider and teaching communication skills in working with patients in the initial stage of technology diffusion is required.