bluuebunny/crossref_metadata_2025 huggingface dataset:
Ergebnisse einer Pilotstudie zur Rolle der Therapieerwartung bei der interdisziplinären multimodalen Schmerztherapie bei chronischem Rückenschmerz
Authors: Maser Dustin , Müller Daniel , Bingel Ulrike , Müßgens Diana
Published: October 2021

Hintergrund

Chronische Rückenschmerzen sind eine schwerwiegende und global sehr häufig auftretende Erkrankung mit enormen persönlichen sowie sozioökonomischen Auswirkungen. Die interdisziplinäre multimodale Schmerztherapie (IMST) ist eines der wenigen evidenzbasierten Behandlungsverfahren für chronische Schmerzen. Obwohl bekannt ist, dass Schmerzen sowie deren Chronifizierung und Behandlung von den persönlichen Erwartungen der Patienten beeinflusst werden, gibt es wenige etablierte Interventionen oder Richtlinien für eine aktive Modulation dieses Effekts.

Ziel der Arbeit

Wir möchten mit dieser Arbeit die Rolle der Erwartung als Prädiktor für Schmerzen sowie schmerzbezogene Beeinträchtigung in der klinischen Praxis verdeutlichen und präsentieren hierzu beispielhaft explorative Pilotdaten einer Beobachtungskohorte unserer Klinik.

Material und Methoden

Die Untersuchung zeigt erste Daten einer prospektiven longitudinalen Beobachtungsstudie bestehend aus bis zu 41 Patienten mit chronischen Rückenschmerzen, die im Setting einer IMST am Essener Rückenschmerz-Zentrum behandelt wurden. Es wurden Daten zum Zeitpunkt der Aufnahme (T0) und der Entlassung (T1) sowie drei Monate nach Therapieende (T2) erhoben. Primäre Endpunkte waren die Schmerzintensität und die Schmerzbeeinträchtigung. Zusätzlich erfassten wir die Therapieerwartung zum Zeitpunkt der Aufnahme als möglichen Prädiktor. Die Bedeutung der vor der Therapie erhobenen Therapieerwartung wurde mittels linearer Regression erfasst.

Ergebnisse

Die IMST führte zu einer signifikanten Besserung in Bezug auf die Schmerzintensität und -beeinträchtigung. Der Effekt auf die Schmerzintensität war über den Zeitraum von drei Monaten nach Therapieende anhaltend und die Beeinträchtigung sank in diesem Zeitraum weiter signifikant.

Diskussion

Erwartung war ein signifikanter Prädiktor für die Abnahme der Schmerzintensität und erklärte ca. 15 % der Varianz. In der klinischen Praxis sollten daher valide Methoden etabliert werden, negative Erwartungen zu reduzieren und positive Erwartungen zu fördern.
Diffusive gradients in thin films predicts crop response better than calcium-acetate-lactate extraction
Authors: Hill Benjamin , Santner Jakob , Spiegel Heide , Puschenreiter Markus , Wenzel Walter W.
Published: October 2021

Soil P testing has been widely used to predict crop yields, P uptake, and fertilizer demands in agriculture. Diffusive gradients in thin films (DGT) provides a zero-sink soil P test which mimics diffusion-controlled plant uptake and has previously been found to predict P availability to crops better than conventional quantity-based P tests in highly weathered Australian, though not in European soils. Here we tested the performance of DGT and the Austrian and German standard P quantity test calcium acetate lactate (CAL) to explain the variation of crop yield and P uptake response of winter wheat (Triticum aestivum L.) and spring barley (Hordeum vulgare L.) in long-term P fertilization experiments at four different sites in eastern Austria. Phosphorus extracted with DGT (P-DGT) and CAL (P-CAL) correlated well in similar soils but not across sites with large variation in soil and site properties such as carbonate equivalent and water availability. The predictive power of DGT for barley (R2 = 0.42) and wheat grain yield (R2 = 0.32), and P uptake in wheat grains (R2 = 0.36) was clearly superior to that of the CAL, and less dependent on soil properties. The better performance of DGT compared to the quantity test is consistent with diffusion-limited P uptake in the water-limited cultivated soils of eastern Austria. The critical values of P deficiency derived from the Mitscherlich-type fits for barley and wheat at 80% relative yield are 64.9 and 26.2 µg L−1, respectively, consistent with differential P demands of the crops.
Officiality and strategic ambiguity in language policy: exploring migrant experiences in Andorra and Luxembourg
Authors: Hawkey James , Horner Kristine
Published: October 2021

This article examines de jure language officialization policies in Andorra and Luxembourg, and addresses how these are discursively reproduced, sustained or challenged by members of resident migrant communities in the two countries. Although the two countries bear similarities in their small size, extensive multilingualism and the pride of place accorded to the ‘small’ languages of Catalan and Luxembourgish respectively, they have adopted different strategies as regards according official status to the languages spoken there. We start by undertaking a close reading of language policy documents and highlight the ways that they are informed by ‘strategic ambiguity’, wherein certain key elements are deliberately left open to interpretation via a range of textual strategies. We then conduct a thematic analysis of individual speaker testimonies to understand how this strategic ambiguity impacts on the ways that speakers negotiate fluid multilingual practices while also having to navigate rigid monolingual regimes. In given contexts, these hierarchies privilege Catalan in Andorra and Luxembourgish in Luxembourg, particularly in relation to the regimentation of migrants' linguistic behaviour. In this way, the paper provides insights into the complex ideological fields in which small languages are situated and demonstrates the ways in which language policy is intertwined with issues of power and dominance.
Case report on postmortem fentanyl measurement after overdose with more than 67 fentanyl patches
Authors: Peeters L. E. J. , Vleut I. T. , Tan G. E. , Croes E. A. , Bethlehem C.
Published: October 2021

Purpose

Fentanyl is an analgesic that is frequently prescribed, which resulted in non-intentional as well as intentional misuse and deaths. Here, we present a postmortem case of a patient who clearly died of a fentanyl overdose due to an extensive number of fentanyl patches combined with oral intake of fentanyl and cocaine. We aimed to show how postmortem analysis can be used to interpret postmortem fentanyl concentrations in unique cases like the one we present.

Case description

A 23-year-old male was found dead in his bedroom with 67 non-prescribed patches of fentanyl on his body. In the room, there also were fentanyl tablets of 100 µg and cocaine powder, which had possibly also been taken by the deceased. To confirm the cause of death, urine and subclavian blood were retrieved to perform a standard postmortem toxicology screening. The toxicological screening revealed the presence of several drugs, including cocaine, fentanyl, lidocaine and paracetamol. Further analysis of the quantitative postmortem values of fentanyl with ultra-performance liquid chromatography-tandem mass spectrometry revealed a fentanyl concentration of 57.9 µg/L. Considering several issues around postmortem drug analyses, this value seemed to be in line with concentrations found in previously reported postmortem cases.

Conclusion

We were able to confirm the expected cause of death with an extensive toxicological screening in combination with the circumstantial evidence. We identified fentanyl as most important cause for the fatal outcome in this specific case and simultaneously contributed to the limited availability of knowledge on postmortem fentanyl concentrations.
SUBiNN: a stacked uni- and bivariate kNN sparse ensemble
Authors: Elsten Tiffany , de Rooij Mark
Published: October 2021

Nearest Neighbor classification is an intuitive distance-based classification method. It has, however, two drawbacks: (1) it is sensitive to the number of features, and (2) it does not give information about the importance of single features or pairs of features. In stacking, a set of base-learners is combined in one overall ensemble classifier by means of a meta-learner. In this manuscript we combine univariate and bivariate nearest neighbor classifiers that are by itself easily interpretable. Furthermore, we combine these classifiers by a Lasso method that results in a sparse ensemble of nonlinear main and pairwise interaction effects. We christened the new method SUBiNN: Stacked Uni- and Bivariate Nearest Neighbors. SUBiNN overcomes the two drawbacks of simple nearest neighbor methods. In extensive simulations and using benchmark data sets, we evaluate the predictive performance of SUBiNN and compare it to other nearest neighbor ensemble methods as well as Random Forests and Support Vector Machines. Results indicate that SUBiNN often outperforms other nearest neighbor methods, that SUBiNN is well capable of identifying noise features, but that Random Forests is often, but not always, the best classifier.
Experiences of LGBTQ+ individuals in sports in Germany
Authors: Hartmann-Tews Ilse , Menzel Tobias , Braumüller Birgit
Published: October 2021

There is growing international evidence that lesbian, gay, bisexual, transgender, queer, and sexually/gender diverse (LGBTQ+) people regularly experience discrimination in sports. However, there is a lack of empirical research with regard to the sports situation in Germany. Based on a quantitative survey of 858 self-identifying LGBTQ+ individuals, the present research is the first to provide a comprehensive picture of the experiences of LGBTQ+ people in sports in Germany. To add distinctive knowledge to the international research, this analysis considers differences within the group of LGBTQ+ people and between various sports settings (i.e., organizational framework, team vs individual sports, and performance level. Two research questions are addressed: (1) What micro- and meso-level factors affect the witnessing of homo-/transnegative language and the prevalence of homo-/transnegative incidents in respondents’ sports activities? (2) What micro- and meso-level factors affect respondents’ feelings of being offended by homo-/transnegative language and what behavioral consequences (i.e., refraining from specific sports and reactions to homo-/transnegative episodes) can be observed among different LGBTQ+ subgroups? The data reveal the impact of the sports context on the perception of homo-/transnegative language but not on negative experiences. Moreover, there is a higher prevalence of gay compared to lesbian athletes with regard to the perception of homo-/transnegative language in their sports and a higher prevalence of gay athletes and non-cisgender (transgender) athletes with regard to homo-/transnegative experiences in sport compared to lesbian and cisgender athletes. The empirical evidence confirms and deepens international findings. Moreover, the data assist the Sport Ministers Conference’s goal of increasing initiatives to tackle the exclusion and discrimination faced by LGBTQ+ people in sports.
Comprehensive analysis of the MIR4435-2HG/miR-1-3p/MMP9/miR-29-3p/DUXAP8 ceRNA network axis in hepatocellular carcinoma
Authors: Zhang Li , Hu Shangshang , Chen Jiasheng , Ma Shasha , Liu Fanghong , Liu Chuanmiao , Gao Yu
Published: October 2021

A growing number of studies have shown that competitive endogenous RNA (ceRNA) regulatory networks might play important roles during the process of hepatocellular carcinoma (HCC). This study assessed the role of the ceRNA network in immune cell infiltration in HCC. Immune-related gene sets were downloaded from Molecular Signatures Database, and differentially expressed genes were screened based on TCGA HCC transcriptome data. The corresponding miRNAs with low expression and good prognostic implications, and the corresponding lncRNAs with high expression and poor prognostic were identified to construct ceRNA networks. The networks were utilized for clinical correlation analysis and risk model construction, and the CIBERSORT algorithm was applied to assess immune cell infiltration. In this study, the mRNA-miRNA-lncRNA model was used to construct a ceRNA network in HCC using immune-related differentially expressed mRNAs. Assessment of the MIR4435-2HG/hsa-miR-1-3p/MMP9/hsa-miR-29-3p/DUXAP8 ceRNA network axis in HCC showed that a high risk/poor prognosis was significantly correlated with tumor stage and invasion depth. MMP9 was positively correlated with resting M0 macrophages and NK cells and negatively correlated with activated mast cells, resting mast cells, monocytes and activated NK cells. DUXAP8 was positively correlated with M2 macrophages and negatively correlated with MIR4435-2HG, which was positively correlated with M2 macrophages and negatively correlated with activated mast cells, CD8 T cells and follicular helper T cells. The correlation of the MIR4435-2HG/hsa-miR-1-3p/MMP9/hsa-miR-29-3p/DUXAP8 ceRNA network axis with immune cell infiltration provides further information on the mechanism of HCC development. The result might improve our understanding the interactions between immune related genes and non-coding RNAs in the occurrence and development of HCC, and the relevant RNAs might be used as diagnostic and prognostic biomarkers and molecular targets in HCC patients.
Sand Casting Implementation of Two-Dimensional Digital Code Direct-Part-Marking Using Additively Manufactured Tags
Authors: Uyan Tekin , Jalava Kalle , Orkas Juhani , Otto Kevin
Published: October 2021

Statistical quality control is used in foundries to identify special cause defects and root causes by correlating process input variations with casting defects. A difficulty exists in associating process data collected with individual cast parts as the parts are processed through the foundry and then out into the supply chain. Typically, alphanumeric labels for marking castings and manual identification of the castings with route-paper based tracing approaches have been used. Such manual-based systems make root cause analysis of quality defect issues tedious. This study presents the development of a semi-automated approach using 3D printed sand mold inserts shaped as 2D matrix codes which thereby permit directly cast identification code into the parts. This enables automated part tracking at the very beginning of the casting process including mold making. Automated scan based tracking of parts through a foundry and subsequent supply chain allows for statistical process data collected to also be associated with each part processed with unique identification, building upon the part history and pedigree.
Sampling strategy for fuzzy numbers in the context of surrogate models
Authors: Oberleiter Thomas , Willner Kai
Published: October 2021

The paper presents an investigation of the accuracy of surrogate models for systems with uncertainties, where the uncertain parameters are represented by fuzzy numbers. Since the underlying fuzzy arithmetic using $$\alpha$$
α
-level optimisation requires a large number of system evaluations, the use of numerically expensive systems becomes prohibitive with a higher number of fuzzy parameters. However, this problem can be overcome by employing less expensive surrogate models, where the accuracy of the surrogate depends strongly on the choice of the sampling points. In order to find a sufficiently accurate surrogate model with as few as possible sampling points, the influence of various sampling strategies on the accuracy of the fuzzy evaluation is investigated. As well suited for fuzzy systems, the newly developed Fuzzy Oriented Sampling Shift method is presented and compared with established sampling strategies. For the surrogate models radial basis functions and a Kriging model are employed. As test cases, the Branin and the Camelback function with fuzzy parameters are used, which demonstrate the varying accuracy for different sampling strategies. A more application oriented example of a finite element simulation of a deep drawing process is given in the end.
Relationships between neighborhood collective efficacy and adolescent suicidal ideation
Authors: Lee Ji Hyeon
Published: October 2021

Introduction

Until now, South Korean adolescent suicidal ideation literature has focused mainly on individual‐level characteristics. Little is known about the contextual effects of social integration and social regulation on an individual's suicide behavior in South Korea as identified through the use of Durkheim's sociological insights. This study drew on Durkheim's suicide and collective efficacy theories and analyzed the effects of the structural characteristics and collective efficacy of neighborhoods on adolescents’ suicidal ideation.

Methods

The data analyzed was from three sources: the 2013 Korean National Survey of the Present Status of Children (n = 1,915; 50.41% girls; mean age = 13.04 years), government census data from the Korea Statistical Information System, and administrative data from the Korea Ministry of Health and Welfare. The Hierarchical Generalized Linear Model was used to investigate the effects of neighborhood structural characteristics and collective efficacy on adolescent suicidal ideation.

Results

There were no significant associations between neighborhood characteristics such as concentrated poverty, divorce rate, and residential instability; however, adoles cents' perceptions of collective efficacy in neighborhoods was associated with lower suicidal ideation after accounting for individual adolescent differences.

Conclusion

The findings provide significant implications for the prevention of suicide in adolescents and suggest that enhancing the collective efficacy of neighborhoods through community‐based intervention may be an important target of future suicide prevention strategies in South Korea.
Common Postzygotic Mutational Signatures in Healthy Adult Tissues Related to Embryonic Hypoxia
Authors: Hong Yaqiang , Zhang Dake , Zhou Xiangtian , Chen Aili , Abliz Amir , Bai Jian , Wang Liang , Hu Qingtao , Gong Kenan , Guan Xiaonan , Liu Mengfei , Zheng Xinchang , Lai Shujuan , Qu Hongzhu , Zhao Fuxin , Hao Shuang , Wu Zhen , Cai Hong , Hu Shaoyan , Ma Yue , Zhang Junting , Ke Yang , Wang Qian-Fei , Chen Wei , Zeng Changqing
Published: October 2021

Postzygotic mutations are acquired in normal tissues throughout an individual’s lifetime and hold clues for identifying mutagenic factors. Here, we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals. In blood, sperm, and muscle cells, we resolved three common types of mutational signatures. Signatures A and B represent clock-like mutational processes, and the polymorphisms of epigenetic regulation genes influence the proportion of signature B in mutation profiles. Notably, signature C, characterized by C>T transitions at GpCpN sites, tends to be a feature of diverse normal tissues. Mutations of this type are likely to occur early during embryonic development, supported by their relatively high allelic frequencies, presence in multiple tissues, and decrease in occurrence with age. Almost none of the public datasets for tumors feature this signature, except for 19.6% of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Moreover, the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α. Thus, embryonic hypoxia may explain this novel signature across multiple normal tissues. Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites; and individuals’ genetic background may also influence their postzygotic mutation profiles.
In the shadow of the base:Teaching war to the children of soldiers
Authors: Gibbs Brian , Hilburn Jeremy
Published: October 2021

The primary objective of this article is to detail how two teachers in the same school site, in the American Southeast, taught war to the children of soldiers. Taken from an extensive qualitative case study involving eight teachers, this article examines the pedagogies engaged in by two teachers who expressed a desire to teach war more critically to their students. Critically here means but is not exclusive to raising student consciousness to issues of war not typically taught including investigating how power, race, gender, and sex operate in war, more closely examining decisions evaluating them for their justness or unjustness. In short a more authentic exploration of war. One teacher engaged a pedagogy of tension the other a pedagogy of facts. Both resulted in a less than critical examination of war. A pedagogy of tension reflected this teacher's reaction to pressure from the community and fear of surfacing or inflicting trauma upon students. A pedagogy of facts reflected the second teachers’ beliefs that focusing teaching on facts will allow her to teach a more critical rendition of war. A qualitative empirical study, data was collected through interview and classroom observation.
Training infectious diseases fellows for a new era of hospital epidemiology
Authors: Martin Elise M. , Snyder Graham M.
Published: October 2021

Training programs for infectious diseases fellows pursuing a career in infection prevention and control and hospital epidemiology are grounded in mentorship and organizational experience. In this commentary, we propose a competency-based framework for creating structured learning for infectious diseases fellows pursuing hospital epidemiology and related fields.
Varieties of Constitutionalism in Asia
Authors: Li-ann Thio
Published: October 2021

Western liberal constitutionalism, the dominant vision of which is rights-oriented and court centric is hegemonic to the discourse. While important, this is a particular rather than total expression of constitutionalism which conflates constitutionalism with liberalism and treat this as paradigmatic. This may obscure all other non-liberal models or fuel their dismissal as sham constitutions. A third space must be found, without collapsing anti-constitutionalist, illiberal despotism with no objective limits on power into the sphere of constitutionalism, and without equating judicial review with constitutionalism. To that end, this article seeks to advance the project of pluralising understandings of constitutionalism, drawing from the rich variety of constitutional experiments in Asia, with its multiplicity of religions, political ideologies government systems, cultures, and levels of economic development. Against an idealised model of liberal constitutionalism deployed as an organisational tool to highlight features of non-liberal constitutionalism in their full variety, the article examines three typologies of constitutionalism: religious, socialist and communitarian. In so doing, the idea of normatively desirable and defensible constitutionalist models is investigated, through an inquiry that goes beyond text and courts to other sites of constitutional practice and governance.
Lutter autrement contre la corruption transnationale: potentiel et défis du système de sanctions de la Banque mondiale
Authors: GRIGORYAN LOUISA , MANIRABONA AMISSI M.
Published: October 2021

Depuis le milieu des années 1990, les principales Banques multilatérales de développement (BMD) jouent un rôle actif dans la lutte contre la corruption transnationale. La Banque mondiale (BM), suivie par les autres grandes banques régionales de développement, ont mis au point un système de sanctions appliqué aux entreprises et individus qui se livrent à des pratiques de corruption dans le cadre des projets d’investissements qu’elles financent. Les cinq grandes BMD ont récemment harmonisé leurs stratégies de lutte contre la corruption dans leurs opérations, en adoptant des définitions harmonisées des pratiques répréhensibles et des principes et directives communs pour les enquêtes. En 2010, ces dernières ont établi un système d’application mutuelle des décisions d’exclusion. Il s’agit clairement de mesures considérables prises au niveau multilatéral qui contribuent à lutter contre le problème de la corruption. Il est donc pertinent d’évaluer leur efficacité. Après avoir procédé à un examen approfondi et à une analyse critique du système de sanctions de la BM, le présent article conclut que malgré son importance, il n’est pas encore à la hauteur de ses ambitions de sanctionner et dissuader les acteurs internationaux corrompus. Par conséquent, l’article propose des solutions visant à améliorer ce système dont la nécessité n’est plus à démontrer.
Melting temperature changes during slip across subglacial cavities drive basal mass exchange
Authors: Rempel Alan W. , Meyer Colin R. , Riverman Kiya L.
Published: October 2021

The importance of glacier sliding has motivated a rich literature describing the thermomechanical interactions between ice, liquid water and bed materials. Early recognition of the gradient in melting temperature across small bed obstacles led to focused studies of regelation. An appreciation for the limits on ice deformation rates downstream of larger obstacles highlighted a role for cavitation, which has subsequently gained prominence in descriptions of subglacial drainage. Here, we show that the changes in melting temperature that accompany changes in normal stress along a sliding ice interface near cavities and other macroscopic drainage elements cause appreciable supercooling and basal mass exchange. This provides the basis of a novel formation mechanism for widely observed laminated debris-rich basal ice layers.
Native Bondage, Narrative Mobility: African American Accounts of Indian Captivity
Authors: HAAS ASTRID
Published: October 2021

The article studies African American narratives of indigenous captivity from its emergence in the mid-eighteenth century to the mid-nineteenth. Taking accounts by Briton Hammon, John Marrant, Henry Bibb, and James Beckwourth as examples, the essay charts the development of this body of writings, its distinction from white-authored narratives, and its contribution to North American autobiography. In so doing, the article argues that the black-authored texts strategically employed only certain elements of the Indian captivity narrative and that they blended these with aspects of other types of Western autobiography to claim black people's agency and discursive authority in white-dominated print culture.
Bottlenose dolphins in the Netherlands come from two sides: across the North Sea and through the English Channel
Authors: Hoekendijk Jeroen P. A. , Leopold Mardik F. , Cheney Barbara J.
Published: October 2021

On 19 July 2019 an estimated 20 bottlenose dolphins (Tursiops truncatus) were observed in the Marsdiep, a tidal inlet connecting the North Sea and the Dutch Wadden Sea, between Den Helder and the island of Texel. Photographs and video recordings were made and nine individuals were matched with known dolphins from the Moray Firth, NE Scotland. These are the first matches of this east coast of Scotland population outside the UK and Ireland. Subsequent observations of individuals from this group show that at least some of the animals have returned to Scottish waters, while others were photographed in Danish waters. Furthermore, we report on a photo identification match of a solitary bottlenose dolphin between France and the Netherlands. These matches suggest that bottlenose dolphins, in the Netherlands, originate from two different genetically distinct populations: ‘Coastal South’ and ‘Coastal North’. This evidence of previously unknown long-range movements may have important implications for the conservation and management of this species in European waters.
New dualities from old: generating geometric, Petrie, and Wilson dualities and trialities of ribbon graphs
Authors: Abrams Lowell , Ellis-Monaghan Joanna A.
Published: October 2021

We define a new ribbon group action on ribbon graphs that uses a semidirect product of a permutation group and the original ribbon group of Ellis-Monaghan and Moffatt to take (partial) twists and duals, or twuals, of ribbon graphs. A ribbon graph is a fixed point of this new ribbon group action if and only if it is isomorphic to one of its (partial) twuals. This extends the original ribbon group action, which only used the canonical identification of edges, to the more natural setting of self-twuality up to isomorphism. We then show that every ribbon graph has in its orbit an orientable embedded bouquet and prove that the (partial) twuality properties of these bouquets propagate through their orbits. Thus, we can determine (partial) twualities via these one vertex graphs, for which checking isomorphism reduces simply to checking dihedral group symmetries. Finally, we apply the new ribbon group action to generateallself-trial ribbon graphs on up to seven edges, in contrast with the few, large, very high-genus, self-trial regular maps found by Wilson, and by Jones and Poultin. We also show how the automorphism group of a ribbon graph yields self-dual, -petrial or –trial graphs in its orbit, and produce an infinite family of self-trial graphs that do not arise as covers or parallel connections of regular maps, thus answering a question of Jones and Poulton.
ON SIMON NELSON PATTEN’S PROGRESSIVISM: A NOTE
Authors: Fiorito Luca , Vatiero Massimiliano
Published: October 2021

This article is an attempt to offer an assessment of the main coordinates of Simon Nelson Patten’s views on democracy and biological determinism. This will allow us to better delineate the differences—as well as the affinities—between Patten and the core of progressives discussed by Thomas C. Leonard in a series of path-breaking contributions, culminating in his Illiberal Reformers: Race, Eugenics, and American Economics in the Progressive Era. It is our contention that even within the persisting intricacies, ambiguities, and contradictions of Patten’s expository style, it is possible to trace a shift in some aspects of his ideas—a gradual evolution that makes his peculiar brand of progressivism different from that of his most “illiberal” counterparts.
A Replication Study on Coral δ11B and B/Ca and Their Variation in Modern and Fossil Porites: Implications for Coral Calcifying Fluid Chemistry and Seawater pH Changes Over the Last Millennium
Authors: Chen Xuefei , Deng Wenfeng , Kang Huiling , Zeng Ti , Zhang Le , Zhao Jian‐xin , Wei Gangjian
Published: October 2021

Boron systematics offer a unique opportunity to reveal coral calcifying fluid (CF) chemistry and seawater pH (pHsw). Here, we assess the intercolony differences of skeletal δ11B and B/Ca, and examine their variation in modern and fossil Porites spp. collected from the east Hainan Island in the northern South China Sea (SCS), to explore changes in coral CF chemistry and pHsw over the last millennium. This enables us to assess whether ocean acidification (OA) has disturbed the ability of corals to control their CF chemistry, and whether splicing coral δ11B‐pH records can trace long‐term pHsw variability. We demonstrate that coral boron systematics bear remarkable intercolony differences, with mean offset as high as 1.05‰ for δ11B and 183.1 μmol/mol for B/Ca. With this in mind, we show that fossil corals exhibit no significant difference in their CF carbonate chemistry, but all have systematically higher CF pH (pHcf, by an average of 0.12 units) and almost equivalent CF dissolved inorganic carbon (DICcf) concentration, compared to modern corals. This suggests greater OA impacts on coral pHcf but less noticeable effects on DICcf. In addition, the ∼0.12 decline in pHcf translates to about 0.24 reduction in pHsw, similar to another coral‐based estimate (∼0.24) from south Hainan Island, corroborating significant OA in the northern SCS since the industrial era. Nevertheless, we find that pHsw in the east Hainan Island has staged a recovery from 1980 to 2010, slowing down the OA pace, highlighting important roles of other local forcing on pHsw regulation.
Multi-omics driven predictions of response to acute phase combination antidepressant therapy: a machine learning approach with cross-trial replication
Authors: Joyce Jeremiah B. , Grant Caroline W. , Liu Duan , MahmoudianDehkordi Siamak , Kaddurah-Daouk Rima , Skime Michelle , Biernacka Joanna , Frye Mark A. , Mayes Taryn , Carmody Thomas , Croarkin Paul E. , Wang Liewei , Weinshilboum Richard , Bobo William V. , Trivedi Madhukar H. , Athreya Arjun P.
Published: October 2021

Combination antidepressant pharmacotherapies are frequently used to treat major depressive disorder (MDD). However, there is no evidence that machine learning approaches combining multi-omics measures (e.g., genomics and plasma metabolomics) can achieve clinically meaningful predictions of outcomes to combination pharmacotherapy. This study examined data from 264 MDD outpatients treated with citalopram or escitalopram in the Mayo Clinic Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) and 111 MDD outpatients treated with combination pharmacotherapies in the Combined Medications to Enhance Outcomes of Antidepressant Therapy (CO-MED) study to predict response to combination antidepressant therapies. To assess whether metabolomics with functionally validated single-nucleotide polymorphisms (SNPs) improves predictability over metabolomics alone, models were trained/tested with and without SNPs. Models trained with PGRN-AMPS’ and CO-MED’s escitalopram/citalopram patients predicted response in CO-MED’s combination pharmacotherapy patients with accuracies of 76.6% (p < 0.01; AUC: 0.85) without and 77.5% (p < 0.01; AUC: 0.86) with SNPs. Then, models trained solely with PGRN-AMPS’ escitalopram/citalopram patients predicted response in CO-MED’s combination pharmacotherapy patients with accuracies of 75.3% (p < 0.05; AUC: 0.84) without and 77.5% (p < 0.01; AUC: 0.86) with SNPs, demonstrating cross-trial replication of predictions. Plasma hydroxylated sphingomyelins were prominent predictors of treatment outcomes. To explore the relationship between SNPs and hydroxylated sphingomyelins, we conducted multi-omics integration network analysis. Sphingomyelins clustered with SNPs and metabolites related to monoamine neurotransmission, suggesting a potential functional relationship. These results suggest that integrating specific metabolites and SNPs achieves accurate predictions of treatment response across classes of antidepressants. Finally, these results motivate functional investigation into how sphingomyelins might influence MDD pathophysiology, antidepressant response, or both.
ATP-citrate lyase promotes axonal transport across species
Authors: Even Aviel , Morelli Giovanni , Turchetto Silvia , Shilian Michal , Bail Romain Le , Laguesse Sophie , Krusy Nathalie , Brisker Ariel , Brandis Alexander , Inbar Shani , Chariot Alain , Saudou Frédéric , Dietrich Paula , Dragatsis Ioannis , Brone Bert , Broix Loïc , Rigo Jean-Michel , Weil Miguel , Nguyen Laurent
Published: October 2021

Microtubule (MT)-based transport is an evolutionary conserved process finely tuned by posttranslational modifications. Among them, α-tubulin acetylation, primarily catalyzed by a vesicular pool of α-tubulin N-acetyltransferase 1 (Atat1), promotes the recruitment and processivity of molecular motors along MT tracks. However, the mechanism that controls Atat1 activity remains poorly understood. Here, we show that ATP-citrate lyase (Acly) is enriched in vesicles and provide Acetyl-Coenzyme-A (Acetyl-CoA) to Atat1. In addition, we showed that Acly expression is reduced upon loss of Elongator activity, further connecting Elongator to Atat1 in a pathway regulating α-tubulin acetylation and MT-dependent transport in projection neurons, across species. Remarkably, comparable defects occur in fibroblasts from Familial Dysautonomia (FD) patients bearing an autosomal recessive mutation in the gene coding for the Elongator subunit ELP1. Our data may thus shine light on the pathophysiological mechanisms underlying FD.
Epigenetic modifications affect the rate of spontaneous mutations in a pathogenic fungus
Authors: Habig Michael , Lorrain Cecile , Feurtey Alice , Komluski Jovan , Stukenbrock Eva H.
Published: October 2021

Mutations are the source of genetic variation and the substrate for evolution. Genome-wide mutation rates appear to be affected by selection and are probably adaptive. Mutation rates are also known to vary along genomes, possibly in response to epigenetic modifications, but causality is only assumed. In this study we determine the direct impact of epigenetic modifications and temperature stress on mitotic mutation rates in a fungal pathogen using a mutation accumulation approach. Deletion mutants lacking epigenetic modifications confirm that histone mark H3K27me3 increases whereas H3K9me3 decreases the mutation rate. Furthermore, cytosine methylation in transposable elements (TE) increases the mutation rate 15-fold resulting in significantly less TE mobilization. Also accessory chromosomes have significantly higher mutation rates. Finally, we find that temperature stress substantially elevates the mutation rate. Taken together, we find that epigenetic modifications and environmental conditions modify the rate and the location of spontaneous mutations in the genome and alter its evolutionary trajectory.
Next generation of tumor-activating type I IFN enhances anti-tumor immune responses to overcome therapy resistance
Authors: Cao Xuezhi , Liang Yong , Hu Zhenxiang , Li Huiyu , Yang Jiaming , Hsu Eric J. , Zhu Jiankun , Zhou Jin , Fu Yang-Xin
Published: October 2021

Type I interferon is promising in treating different kinds of tumors, but has been limited by its toxicity, lack of tumor targeting, and very short half-life. To target tumors, reduce systemic toxicity, and increase half-life, here we engineer a masked type I IFN-Fc (ProIFN) with its natural receptor connected by a cleavable linker that can be targeted by tumor-associated proteases. ProIFN has a prolonged serum half-life and shows an improved tumor-targeting effect. Interestingly, ProIFN-treated mice show enhanced DC cross-priming and significant increased CD8+ infiltration and effector function in the tumor microenvironment. ProIFN is able to improve checkpoint blockade efficacy in established tumors, as well as radiation efficacy for both primary and metastatic tumors. ProIFN exhibits superior long-term pharmacokinetics with minimal toxicity in monkeys. Therefore, this study demonstrates an effective tumor-activating IFN that can increase targeted immunity against primary tumor or metastasis and reduce periphery toxicity to the host.
Structure-controllable growth of nitrogenated graphene quantum dots via solvent catalysis for selective C-N bond activation
Authors: Moon Byung Joon , Kim Sang Jin , Lee Aram , Oh Yelin , Lee Seoung-Ki , Lee Sang Hyun , Kim Tae-Wook , Hong Byung Hee , Bae Sukang
Published: October 2021

Photophysical and photochemical properties of graphene quantum dots (GQDs) strongly depend on their morphological and chemical features. However, systematic and uniform manipulation of the chemical structures of GQDs remains challenging due to the difficulty in simultaneous control of competitive reactions, i.e., growth and doping, and the complicated post-purification processes. Here, we report an efficient and scalable production of chemically tailored N-doped GQDs (NGs) with high uniformity and crystallinity via a simple one-step solvent catalytic reaction for the thermolytic self-assembly of molecular precursors. We find that the graphitization of N-containing precursors during the formation of NGs can be modulated by intermolecular interaction with solvent molecules, the mechanism of wh ich is evidenced by theoretical calculations and various spectroscopic analyses. Given with the excellent visible-light photoresponse and photocatalytic activity of NGs, it is expected that the proposed approach will promote the practical utilization of GQDs for various applications in the near future.
Method for assessing atomic sources of flicker noise in superconducting qubits
Authors: Reshef Almog , Caspary Toroker Maytal
Published: October 2021

Flicker noise causes decoherence in Josephson junction-based superconducting qubits, thus limiting their practical potential as building blocks for quantum computers. This is due to limited length and complexity of executable algorithms, and increased dependency on error-correcting measures. Therefore, identifying and subsiding the atomic sources of flicker noise are of great importance to the development of this technology. We developed a method that combines ab initio DFT calculations and quantum dynamics to model charge transport across a Josephson junction, by which it is possible to more accurately assess different defects as sources of flicker noise. We demonstrate the use of our method in an investigation of various atomic defects, including vacancies, trapping, and substitutions, in an Al|Al2O3|Al Josephson junction. This demonstration both reveals weaknesses in previous attempts to pinpoint the atomic sources of flicker noise and highlights new candidates.
Effect of an anti-adhesion agent on vision-based assessment of cervical adhesions after thyroid surgery: randomized, placebo-controlled trial
Authors: Yu Hyeong Won , Lee Dongheon , Lee Keunchul , Kim Su-jin , Chai Young Jun , Kim Hee Chan , Choi June Young , Lee Kyu Eun
Published: October 2021

Many patients experience cervical adhesions after thyroid surgery. To date, however, no studies have objectively measured the effects of anti-adhesion agents on cervical adhesion symptoms. This study evaluated the effects of an anti-adhesion agent on cervical adhesions after thyroid surgery, as determined using a system that measures the extent of marker movement objectively. One hundred patients were randomized in a 1:1 ratio to undergo thyroid surgery with or without the anti-adhesion agent Collabarrier. Using specially manufactured recording equipment, the position of the marker on neck skin was measured before surgery, and 2 weeks, 3 months, and 9 months after surgery. Relative change in marker distance, calculated by subtracting the marker position before surgery from the marker positions 2 weeks, 3 months, and 9 months after surgery, differed significantly in the groups of patients who underwent thyroid surgery with and without the anti-adhesion agent (P < 0.05). A novel measuring system can objectively evaluate the effectiveness of a thyroid anti-adhesion agent. The anti-adhesion agent used significantly reduced adhesions compared with the control group. The trial is registered at www.cris.nih.go.kr (KCT0005745; date of registration, 08/01/2021).
The effect of age on the association between daily gait speed and abdominal obesity in Japanese adults
Authors: Kinoshita Keita , Ozato Naoki , Yamaguchi Tohru , Sudo Motoki , Yamashiro Yukari , Mori Kenta , Kumagai Mika , Sawada Kaori , Katsuragi Yoshihisa , Imoto Seiya , Ihara Kazushige , Nakaji Shigeyuki
Published: October 2021

The aim of this work was to investigate the effect of age on the association between daily gait speed (DGS) and abdominal obesity defined by visceral fat area (VFA). A cross-sectional study was performed using data from an annual community-based health check-up. A total of 699 participants aged 20–88 years were enrolled in this analysis. DGS was assessed using tri-axial accelerometers worn for ≥ 7 days with at least 10 measuring hours each day. VFA was measured using a visceral fat meter. Since DGS differed significantly with age, the participants were divided into two groups: younger adults (YA), aged 20–49 years, and older adults (OA), aged 50–88 years. The association between DGS and VFA differed significantly with age (r = 0.099 for YA and r =  − 0.080 for OA; test for difference between correlation coefficients, P = 0.023). In OA, the adjusted odds ratio of abdominal obesity (VFA ≥ 100 cm2) was 0.40 (95% confidence interval 0.18, 0.88, P = 0.022) for the highest DGS quartile (DGS ≥ 1.37 m/s) compared to that for the lowest quartile (DGS < 1.11 m/s), whereas no significant association was found in YA. These data could aid in raising awareness of the self-management of obesity via DGS monitoring, especially in OA.
Cardiovascular risk moderates the effect of aerobic exercise on executive functions in older adults with subcortical ischemic vascular cognitive impairment
Authors: Barha Cindy K. , Dao Elizabeth , Marcotte Lauren , Hsiung Ging-Yuek Robin , Tam Roger , Liu-Ambrose Teresa
Published: October 2021

Aerobic training (AT) can promote cognitive function in adults with Subcortical Ischemic Vascular Cognitive Impairment (SIVCI) by modifying cardiovascular risk factors. However, pre-existing cardiovascular health may attenuate the benefits of AT on cognitive outcomes in SIVCI. We examined whether baseline cardiovascular risk moderates the effect of a 6-month progressive AT program on executive functions with a secondary analysis of a randomized controlled trial in 71 adults, who were randomized to either: (1) 3×/week progressive AT; or (2) education program (CON). Three executive processes were measured: (1) response inhibition by Stroop Test; (2) working memory by digits backward test; and (3) set shifting by the Trail Making Test. Baseline cardiovascular risk was calculated using the Framingham cardiovascular disease (CVD) Risk Score (FCRS), and participants were classified as either low risk (< 20% FCRS score; LCVR) or high risk (≥ 20% FCRS score; HCVR). A complete case analysis (n = 58) was conducted using an analysis of covariance (ANCOVA) to evaluate between-group differences in the three executive processes. A significant interaction was found between cardiovascular risk group and intervention group (AT or CON) for the digit span backward and the Trail Making Test. AT improved performance compared with CON in those with LCVR, while in those with HCVR, AT did not improve performance compared with CON. Baseline cardiovascular risk significantly moderates the efficacy of AT on cognition. Our findings highlight the importance of intervening early in the disease course of SIVCI, when cardiovascular risk may be lower, to reap maximum benefits of aerobic exercise.
Oxytocinergic cells of the posterior hypothalamic paraventricular nucleus participate in the food entrained clock
Authors: Caba Mario , Meza Enrique , Escobar Carolina , Jiménez Angeles , Caba-Flores Mario Daniel , Moreno-Cortés María Luisa , Melo Angel I.
Published: October 2021

The mechanisms underlying food anticipatory activity are still poorly understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON), medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; in contrast, OT cells in the PVNp showed c-Fos activationin anticipation tofood access, which persisted in RF-F subjects. We conclude that OT and non-OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.