bluuebunny/crossref_metadata_2025 huggingface dataset:
Come back to stay: landscape connectivity analysis for the Eurasian otter (Lutra lutra) in the western Alps
Authors: Leoncini Fabio , Semenzato Paola , Di Febbraro Mirko , Loy Anna , Ferrari Caterina
Published: November 2022

Assessing landscape connectivity allows defining the degree to which the landscape facilitates or impedes the movement of a species between resource patches. In this phase of climate change and biodiversity crisis, maintaining landscape connectivity by restoring and protecting connecting areas and corridors is a key strategy to ensure the survival of many species. The Eurasian otter (Lutra lutra) is a freshwater top predator that is slowly recovering after a dramatic decline occurred in central and southern Europe in the last century. To assess the chances of otter recolonization of the western Alps, we analyzed environmental connectivity by applying electrical circuit theory to an expert-based resistance surface using the Circuitscape software. The study area included southeastern France, northwestern Italy, and Switzerland. We produced a cumulative current flow map and a gap analysis was also conducted to highlight the “conservation gaps” for optimal corridors. The results revealed that the orography of the landscape was the main factor influencing the quantity and quality of the pathways in the western Alpine landscapes. As main corridors were concentrated on valley bottoms, human pressure could severely diminish animal movement. Despite this, some heavily populated areas showed high connectivity values. Some important pathways did not fall within protected areas, potentially hindering otter dispersal and highlighting the need to expand the system of protected areas in the Alpine arc. Recolonization of Alpine territories by otters can therefore only occur if connectivity and environmental suitability combine to ensure the animals' survival over time.
The Invisible Patient: Concerns about Donor Exploitation in Stem Cell Research
Authors: Segerdahl Pär
Published: November 2022

As embryonic stem cell research is commercialized, the stem cell debate may shift focus from concerns about embryo destruction to concerns about exploitation of the women who donate eggs and embryos for research. Uncomfortable with the polarization of the embryo debate, this paper proposes a more “contemplative” approach than intellectual debate to concerns about exploitation. After examining pitfalls of rigid intellectual positions on exploitation, the paper investigates the possibility of a broader understanding of donation for research where patients are seen as the intended beneficiaries of the donation. Together with other actors, research is perceived as mediating altruistic gift relationships that extend from donors to patients. The paper explores how this broader perspective on “donation for research” can open up new possibilities of understanding donation and addressing risks of exploitation.
“Neural Noise” in Auditory Responses in Young Autistic and Neurotypical Children
Authors: Dwyer Patrick , Vukusic Svjetlana , Williams Zachary J. , Saron Clifford D. , Rivera Susan M.
Published: November 2022

Elevated “neural noise” has been advanced as an explanation of autism and autistic sensory experiences. However, functional neuroimaging measures of neural noise may be vulnerable to contamination by recording noise. This study explored variability of electrophysiological responses to tones of different intensities in 127 autistic and 79 typically-developing children aged 2–5 years old. A rigorous data processing pipeline, including advanced visualizations of different signal sources that were maximally independent across different time lags, was used to identify and eliminate putative recording noise. Inter-trial variability was measured using median absolute deviations (MADs) of EEG amplitudes across trials and inter-trial phase coherence (ITPC). ITPC was elevated in autism in the 50 and 60 dB intensity conditions, suggesting diminished (rather than elevated) neural noise in autism, although reduced ITPC to soft 50 dB sounds was associated with increased loudness discomfort. Autistic and non-autistic participants did not differ in MADs, and indeed, the vast majority of the statistical tests examined in this study yielded no significant effects. These results appear inconsistent with the neural noise account.
Lipschitz Carnot-Carathéodory Structures and their Limits
Authors: Antonelli Gioacchino , Le Donne Enrico , Nicolussi Golo Sebastiano
Published: November 2022

In this paper we discuss the convergence of distances associated to converging structures of Lipschitz vector fields and continuously varying norms on a smooth manifold. We prove that, under a mild controllability assumption on the limit vector-fields structure, the distances associated to equi-Lipschitz vector-fields structures that converge uniformly on compact subsets, and to norms that converge uniformly on compact subsets, converge locally uniformly to the limit Carnot-Carathéodory distance. In the case in which the limit distance is boundedly compact, we show that the convergence of the distances is uniform on compact sets. We show an example in which the limit distance is not boundedly compact and the convergence is not uniform on compact sets. We discuss several examples in which our convergence result can be applied. Among them, we prove a subFinsler Mitchell’s Theorem with continuously varying norms, and a general convergence result for Carnot-Carathéodory distances associated to subspaces and norms on the Lie algebra of a connected Lie group.
Radiometal-theranostics: the first 20 years*
Authors: Roesch Frank , Martin Marcel
Published: November 2022

This review describes the basic principles of radiometal-theranostics and its dawn based on the development of the positron-emitting 86Y and 86Y-labeled radiopharmaceuticals to quantify biodistribution and dosimetry of 90Y-labeled analogue therapeutics. The nuclear and inorganic development of 86Y (including nuclear and cross section data, irradiation, radiochemical separation and recovery) led to preclinical and clinical evaluation of 86Y-labeled citrate and EDTMP complexes and yielded organ radiation doses in terms of mGy/MBq 90Y. The approach was extended to [86/90Y]Y-DOTA-TOC, yielding again yielded organ radiation doses in terms of mGy/MBq 90Y. The review further discusses the consequences of this early development in terms of further radiometals that were used (68Ga, 177Lu etc.), more chelators that were developed, new biological targets that were addressed (SSTR, PSMA, FAP, etc.) and subsequent generations of radiometal-theranostics that resulted out of that.
Variance reduction for Metropolis–Hastings samplers
Authors: Alexopoulos Angelos , Dellaportas Petros , Titsias Michalis K.
Published: November 2022

We introduce a general framework that constructs estimators with reduced variance for random walk Metropolis and Metropolis-adjusted Langevin algorithms. The resulting estimators require negligible computational cost and are derived in a post-process manner utilising all proposal values of the Metropolis algorithms. Variance reduction is achieved by producing control variates through the approximate solution of the Poisson equation associated with the target density of the Markov chain. The proposed method is based on approximating the target density with a Gaussian and then utilising accurate solutions of the Poisson equation for the Gaussian case. This leads to an estimator that uses two key elements: (1) a control variate from the Poisson equation that contains an intractable expectation under the proposal distribution, (2) a second control variate to reduce the variance of a Monte Carlo estimate of this latter intractable expectation. Simulated data examples are used to illustrate the impressive variance reduction achieved in the Gaussian target case and the corresponding effect when target Gaussianity assumption is violated. Real data examples on Bayesian logistic regression and stochastic volatility models verify that considerable variance reduction is achieved with negligible extra computational cost.
Kapsner Complementation: An Algebraic Take on Kapsner Strong Logics
Authors: Tedder Andrew
Published: November 2022

Kapsner strong logics, originally studied in the context of connexive logics, are those in which all formulas of the form$$A\rightarrow \lnot A$$A→¬Aor$$\lnot A\rightarrow A$$¬A→Aare unsatisfiable, and in any model at most one of$$A\rightarrow B, A\rightarrow \lnot B$$A→B,A→¬Bis satisfied. In this paper, such logics are studied algebraically by means of algebraic structures in which negation is modeled by an operator$$\lnot $$¬s.t. any elementais incomparable with$$\lnot a$$¬a. A range of properties which are (in)compatible with such operators are studied, and examples are given; finally, the question of which further operators can be added to such structures is broached.
Welche Rahmenbedingungen braucht die Förderung von Kindern mit Lernschwierigkeiten?
Authors: Schmidt Laura Maria
Published: November 2022

Dieser Artikel der Zeitschrift Gruppe. Interaktion. Organisation. beschreibt einen organisationssoziologisch fundierten Analyserahmen für die Untersuchung und den Vergleich von Fördersystemen für Lernende mit einer Lese-Rechtschreib-Störung/Lese-Rechtschreib-Schwäche (LRS). Es wird ein Vorgehen beschrieben, mit dem eine wissenschaftlich, bildungspolitisch und schulpraktisch relevante Fragestellung an den Schnittstellen von Organisation, Team und Individuum bearbeitet werden kann. Betroffene benötigen beim Schriftspracherwerb zusätzliche über den Regelunterricht hinausgehende Förderung. Aufgrund der benötigten Individualisierung außerhalb eines sonderpädagogischen Förderbedarfs stellt diese einen Sonderfall inklusiver Praxis dar. Die Unterstützung wird in verschiedenen Ländern sowohl innerhalb als auch alternativ außerhalb der Schule organisiert. Dabei entstehen länderübergreifende Unterschiede in der Trias aus Organisation, professionellen Normen und staatlicher Regulation.
(Wie) Können Weiterbildungsorganisationen die Professionalität ihrer Lehrenden durch professionelle Lerngemeinschaften unterstützen?
Authors: Hahnrath Eva , Herbrechter Dörthe
Published: November 2022

Dieser Beitrag der Zeitschrift Gruppe. Interaktion. Organisation. (GIO) rückt das arbeitsplatznahe, auf kollegial-kooperativem Lernen basierende Personalentwicklungskonzept der professionellen Lerngemeinschaften (PLGen) in den Mittelpunkt, das bislang vor allem für die Professionalitätsentwicklung von Lehrkräften in Schulen erprobt und in seiner Wirksamkeit erforscht worden ist. Auch wenn sich die Weiterbildung in Deutschland z. B. gemessen an der Zahl ihrer Organisationen und Beschäftigten inzwischen zum größten Bildungsbereich entwickelt hat, finden solche berufsbegleitenden Personalentwicklungsmaßnahmen „near the job“ bislang noch kaum Anwendung. Dies ist insofern bemerkenswert, als die Lehrenden in der Weiterbildung keine standardisierten Qualifizierungsprogramme durchlaufen und überwiegend frei-/nebenberuflich agieren, so dass Weiterbildungsorganisationen auf ‚ihre‘ Lehrenden formal kaum Einfluss nehmen können, obgleich sie einen erheblichen Beitrag zur Erreichung des Organisationsziels („gute Bildung für Erwachsene“) leisten. Vor diesem Hintergrund exploriert der Beitrag die PLG-Implementierbarkeit aus der Perspektive von Führungskräften und Lehrenden der Weiterbildung, um zum einen das grundsätzliche Implementationsinteresse relevanter Akteure zu explorieren und zum anderen auch feldspezifisches Wissen für die Entwicklung eines PLG-Implementationskonzepts zu generieren. Unsere Analyse basiert auf strukturierten Leitfadeninterviews (N = 23), die wir inhaltsanalytisch deduktiv-induktiv ausgewertet haben. Die Ergebnisse zeigen überwiegend positive Einschätzungen der PLG-Implementierbarkeit in das Feld der Weiterbildung. Zudem weisen sie u. a. auf eine hohe Relevanz kooperationsbezogener Überzeugungen für die grundsätzliche PLG-Beteiligungsmotivation der Lehrenden und auf eine zentrale Schlüsselfunktion der Führungskräfte für die Anregung der PLG-Implementation hin, die abschließend insbesondere mit Blick auf Folgen für die organisationalen Rahmenbedingungen der Zusammenarbeit diskutiert werden.
Mobility Intersections: Gender, Family, Culture and Location in the Gauteng City-Region
Authors: Parker Alexandra , Rubin Margot
Published: November 2022

The morphology of many South African cities has changed little over the last 25 years: with some of the poorest communities still living on the peripheries in informal settlements and old townships. The resulting spatial mismatch, with difficulties of access and mobility, has been recorded and engaged with elsewhere; the day-to-day implications for households and families have been less well-considered. In work that was undertaken between March 2019 and February 2020 using a mixed-method approach that included focus groups, a smartphone mobility app, mapping and qualitative interviews, as well as, the use of other on-line communication platforms such as WhatsApp to gather data, the team looked at the intersection between mobility, access and household dynamics. Results surface and highlight how old spatial planning logics have direct impact on contemporary spatial footprints, mobility patterns and transit choices. Former ‘White’ neighbourhoods, designed to be relatively self-contained and meet the needs of the suburban population, still ensure relatively small spatial footprints that are car-reliant. While those living in older informal settlements and townships still have the burden of long distances to access economic and often educational advancement. Similarly, the historical layout of transport modes continues to affect the day-to-day decisions of modal choice. However, these spatial patterns and historical transit planning are overlaid with gender expectations and gendered divisions of labour—as women continue to carry most of the childcare and domestic responsibilities and men continue to feel the necessity for household income provision. Thus, historical and continued segregation in the city-region intersects with diverse dimensions of race, class and culture to perpetuate widespread gendered mobility patterns in the Gauteng City-Region.
The efficacy and safety of caplacizumab in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura: an open-label phase 2/3 study
Authors: Miyakawa Yoshitaka , Imada Kazunori , Ichikawa Satoshi , Uchiyama Hitoji , Ueda Yasunori , Yonezawa Akihito , Fujitani Shigeki , Ogawa Yoshiyuki , Matsushita Tadashi , Asakura Hidesaku , Nishio Kenji , Suzuki Kodai , Hashimoto Yasuhiro , Murakami Hidenori , Tahara Sayaka , Tanaka Tomoyuki , Matsumoto Masanori
Published: November 2022

Caplacizumab is an anti-von Willebrand factor humanized single-variable-domain immunoglobulin fragment whose efficacy and safety in immune-mediated thrombotic thrombocytopenia purpura (iTTP) have been demonstrated in international studies. This prospective, open-label phase 2/3 study evaluated caplacizumab 10 mg administered daily during plasma exchange and for 30 days afterward, in combination with immunosuppressive treatment, in Japanese adults with a clinical diagnosis of iTTP (new or recurrent). The primary endpoint was prevention of iTTP recurrence; key secondary endpoints included time to platelet count response, time to organ damage normalization, and safety. Among 21 treated patients, 1 of 15 (6.7%) evaluable patients developed iTTP recurrence. Median time to normalization was 2.79 days for platelet count and 2.65 days for organ damage markers (n = 15). Treatment-emergent adverse events (TEAEs) were mostly mild to moderate in severity; the most frequently reported caplacizumab-related TEAEs were increased alanine aminotransferase, epistaxis, and gastrointestinal hemorrhage (all in 9.5% of patients). At least one bleeding event was reported in 7 of 21 patients (33%). Caplacizumab was effective in Japanese patients with iTTP, with a low rate of iTTP recurrence, rapid normalization of platelet counts and organ damage markers, and no unexpected TEAEs. Trial registration: ClinicalTrials.gov identifier, NCT04074187.
Cricetodontinae (Rodentia, Mammalia) of the Miocene Tagay fauna (Olkhon Island, Lake Baikal, Eastern Siberia)
Authors: Daxner-Höck Gudrun , Mörs Thomas , López-Guerrero Paloma , Erbajeva Margarita A.
Published: November 2022

The collection of fossil Rodentia from the Miocene Tagay fauna comprises Aplodontidae, Mylagaulidae, Sciuridae, Gliridae, Castoridae, Eomyidae and Cricetodontinae. Represented by three taxa the Cricetodontinae dominate the rodent assemblage of the Tagay fauna. The fossils were collected by wet-screening of test samples along the section Tagay-1 at Tagay Bay of Olkhon Island. Here, we report on the medium-sized Democricetodon cf. lindsayi, the very small Democricetodon sp. and the large Gobicricetodon filippovi. The primitive dental pattern of D. cf. lindsayi and G. filippovi suggest archaic members of the genera, and an age around the Early/Middle Miocene transition.
Economic Ripple Effects of Individual Disasters and Disaster Clusters
Authors: Zhang Zhengtao , Li Ning , Wang Ming , Liu Kai , Huang Chengfang , Zhuang Linmei , Liu Fenggui
Published: November 2022

Disaster clusters refer to major disasters that cluster in space and time without any linkage, resulting in large direct damage and economic ripple effects (EREs). However, the cumulative EREs caused by a disaster cluster may not be equal to the summation EREs of the individual disasters within a cluster. We constructed a global economic ripple input-output model suitable for the analysis of disaster clusters and demonstrated the extent of this difference with the example of two typical catastrophes that occurred in 2011 (the Great East Japan Earthquake and the Great Thailand Flood), within an interval of only 136 days. The results indicate that: (1) The EREs suffered by 11 of the 35 countries affected (30%) are “1 + 1 > 2”, and “1 + 1 < 2” for 24 of the 35 countries affected (70%). This indicates that there is a significant difference between the cumulative and the summation losses. The difference is related to factors such as trade distance, economic influence of disaster-affected sectors, and trade ties; (2) The EREs are more than two times the direct loss and have an industrial dependence, mostly aggregated in key sectors with strong industrial influence and fast trade times in the industrial chain; and (3) Additional EREs due to the extension of the recovery period will be aggregated in countries with close trade ties to the disaster-affected country, further magnifying the difference.
Associations Between Cohabitation, Marriage, and Suspected Crime: a Longitudinal Within-Individual Study
Authors: Airaksinen Jaakko , Aaltonen Mikko , Tarkiainen Lasse , Martikainen Pekka , Latvala Antti
Published: November 2022

The effects of marriage on criminal behavior have been studied extensively. As marriages today are typically preceded by cohabiting relationships, there is a growing need to clarify how different relationship types are associated with criminality, and how these effects may be modified by relationship duration, partner’s criminality, and crime type. We used Finnish longitudinal register data and between- and within-individual analyses to examine how cohabitation and marriage were associated with suspected crime. The data included 638,118 residents of Finland aged 0–14 in 2000 and followed for 17 years for a suspected crime: having been suspected of violent, drug, or any crime. Between-individual analyses suggested that those who were cohabiting or married had a 40–65% lower risk of being suspected of a crime compared to those who were single, depending on the type of crime. The within-individual analysis showed a 25–50% lower risk for suspected crime when people were cohabiting or married compared to time periods when they were single. Those in a relationship with a criminal partner had 11 times higher risk for suspected crime than those in a relationship with a non-criminal partner. Forming a cohabiting relationship with a non-criminal partner was associated with reduced criminality. The risk reduction was not fully explained by selection effects due to between-individual differences. Marriage did not introduce further reduction to criminality. Our findings demonstrate that selection effects partly explain the association between relationship status and criminality but are also compatible with a causal effect of cohabitation on reduced risk of being suspected of a crime.
Hydraulic stimulation strategies in enhanced geothermal systems (EGS): a review
Authors: Jia Yunzhong , Tsang Chin-Fu , Hammar Axel , Niemi Auli
Published: November 2022

In enhanced geothermal systems (EGS), the natural permeability of deep rocks is normally not high enough and needs to be increased. Permeability increase can be achieved through various stimulation methods, such as hydraulic, chemical, and thermal stimulation. Among these, hydraulic stimulation is the most commonly used technique to increase both reservoir permeability and the specific area for heat exchange. A comprehensive understanding of the underlying processes towards an optimization of hydraulic stimulation performance while minimizing the potential of unwanted induced seismicity is a critical prerequisite for a successful development of any EGS site. In this paper, we review the hydraulic stimulation strategies that have been developed and implemented for EGS. We begin with a description of the underlying mechanisms through which the permeability and heat exchange area increases are achieved. We then discuss the mechanisms of fluid injection-induced seismicity during and after a hydraulic stimulation operation. After that, alternative hydraulic stimulation strategies, namely conventional hydraulic stimulation, multi-stage fracturing, and cyclic soft stimulation, are reviewed based on current research in theoretical studies as well as, laboratory, and in-situ field experiments. Finally, some representative EGS projects are reviewed, focusing on fluid injection strategies, seismic responses, and reservoir permeability enhancement performance. The review shows the importance and need of (a) a comprehensive geological characterization of the natural fracture system including the nearby fault zones as well as the in-situ stress conditions, prior to the development of the site, (b) a proper design of the well arrangement, such as the positioning of the injection and production wells, and (c) the selection of an appropriate fluid injection strategy for the system at hand.
How the Design of an Organizational Context Helps to Attain Contextual Ambidexterity
Authors: Möller Klaus , Schmid Flavia , Seehofer Theresa Maria , Wenig Philipp
Published: November 2022

This study empirically investigates the relationships of control levers (belief and boundary systems, Simons 1995) and control context (social and performance management context, Gibson and Birkinshaw 2004) with contextual ambidexterity and firm performance. Based on cross-sectional survey data from 198 listed companies in Austria, Germany, and Switzerland, a structural equation model is used to test the hypothesized relationships. We find that the emphasis on formal boundary systems and an informal social context are positively related to contextual ambidexterity, which positively affects firm performance. In contrast, belief systems and performance management context do not influence contextual ambidexterity. Further, we find no support for dynamic tensions, neither between the two control levers nor in the control context.
Genesis of Smectites associated with a Coal Seams Succession in the Neogene Orhaneli and Keles Coal Deposits (Bursa), NW Turkey
Authors: Erkoyun Hülya , Kadir Selahattin , Külah Tacit
Published: November 2022

The Bursa-Orhaneli and Keles-Harmanalan coal deposits were developed in swampy and fluvial-lacustrine environments in western Anatolia under the E–W-trending graben zone during the Neogene. The present study aimed to determine the mineralogical and geochemical properties of clays interlayering the coal seams to define the origin of clay minerals, in particular, smectite. These deposits, comprising argillaceous sediment, marl, coal seam, mudstone, organic-rich shale, and sandstone, were deposited in a lacustrine environment accompanied by volcanogenic materials. The characteristics of sediments and their parent rocks were examined using X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy, palynology, and chemical analyses. The association of abundant smectite with quartz, amphibole, accessory chlorite, and a decrease in feldspar in fluvial-lacustrine sediments compared to those in the smectite accompanied by feldspar and volcanic glass and the absence of quartz and amphibole in the pyroclastic units suggest that smectite had detrital and authigenic origins. Flaky smectite shows either detrital, irregularly outlined coating and filling pores of terrigenous sediments or in situ precipitation edging resorbed feldspar and devitrified volcanic glass. Chemical analyses of the smectite-rich fraction show montmorillonite compositions with an average structural formula of: (Ca0.42Na0.25K0.08)(Al2.76Fe0.47Mg0.59Ti0.07Mn0.002)(Si7.65Al0.35)O20(OH)4.

The positive correlation of Al2O3 vs. TiO2 and K2O vs. Rb may be related to the abundant detrital input. Feldspar and biotite were replaced by illite during diagenesis.

An increase in the Ni/Co and V/(V + Ni) ratios in the altered units also suggest oxic, suboxic to anoxic conditions, under the control of a dry, warm to subtropical climate in fresh water and lakes during the Late Eocene to Middle Miocene. The slight enrichment of light rare earth elements (LREE) compared to heavy rare earth elements (HREE) with positive Eu and positive/negative Ce anomalies reflect fractional crystallization of feldspar. The δ18O and δD values of smectite and illite fractions and the wide range of δ34S isotope values (–1.5 to 15‰) for pyrite and chalcopyrite associated with coal indicate a signature of both diagenetic and partial hydrothermal origin.
Mentoring for INnovative Design Solutions (MINDS): Key Design Considerations and Collaborative Teamwork across Universities for Clinical Translation
Authors: Fernandez-Fernandez Alicia , Murfee Walter Lee , LaMack Jeffrey A. , Murray Teresa A.
Published: November 2022

The main purpose of this paper is to share the Mentoring for INnovative Design Solutions (MINDS) Scholars Program developed by Alpha Eta Mu Beta, the International Biomedical Engineering Honor Society. The program’s goals are to (1) introduce biomedical engineering students to an open-ended design experience as part of interuniversity teams with industry and faculty mentors, and (2) develop the ability to create designs considering clinical translatability on teams with different backgrounds and areas of expertise. MINDS uses an experiential learning approach to (1) enrich student curricular experiences through inter-institutional collaboration, (2) build engineering design skills, including three key design considerations for clinical/commercial success: intellectual property protection, regulatory strategy, and market identification; and (3) emphasize the importance of end-user considerations. From 2015 to 2022, MINDS has involved 131 students from 50 universities and 22 faculty and industry mentors. Pre- and post-program surveys show statistically significant improvements in understanding of the design process, regulatory strategy, intellectual property protection, market definition, and key product requirements and features. Students also improved communication and teamwork skills. Many students indicated that MINDS participation made them more likely to choose careers that involve product development and/or entrepreneurship. Students attained a working ability to integrate market needs, regulatory strategy, and intellectual property considerations into the design process. They also further developed soft skills, such as conflict resolution, time management, and effective communication through the challenges of inter-institutional collaboration. Additionally, the program heightened their awareness of how biomedical devices and technologies can benefit society.
Learning Domain Ethical Principles from Interactions with Users
Authors: Dyoub Abeer , Costantini Stefania , Lisi Francesca Alessandra
Published: November 2022

Drawing from practical philosophy, we argue that AI-based systems could develop ethical decision-making and judgment capabilities by learning from experience. This has inspired our work which combines answer set programming and inductive logic programming to learn domain ethical principles from the interactions with users in the context of a dialogue system.
The algebraic dynamics of the pentagram map
Authors: WEINREICH MAX H.
Published: November 2022

The pentagram map, introduced by Schwartz [The pentagram map. Exp. Math.1(1) (1992), 71–81], is a dynamical system on the moduli space of polygons in the projective plane. Its real and complex dynamics have been explored in detail. We study the pentagram map over an arbitrary algebraically closed field of characteristic not equal to 2. We prove that the pentagram map on twisted polygons is a discrete integrable system, in the sense of algebraic complete integrability: the pentagram map is birational to a self-map of a family of abelian varieties. This generalizes Soloviev’s proof of complex integrability [F. Soloviev. Integrability of the pentagram map. Duke Math. J.162(15) (2013), 2815–2853]. In the course of the proof, we construct the moduli space of twisted n-gons, derive formulas for the pentagram map, and calculate the Lax representation by characteristic-independent methods.
Updated estimates of biotic diversity and endemism for Madagascar—revisited after 20 years
Authors: Goodman Steven M.
Published: November 2022

The terrestrial and marine biotypes of Madagascar are critical priorities for conservation, with almost unparalleled levels of endemism, species diversity and human threat for a land area of its size. Field inventories and molecular-based research conducted from the mid 1980s to present have greatly expanded knowledge of the country's biota, for some groups with nearly exponential growth in measures of species diversity. I provide updated measures of estimated species diversity between a book with 289 contributors, published in 2003 (The Natural History of Madagascar), and a full-scale update with 539 contributors, published in 2022 (The New Natural History of Madagascar). I compare biodiversity information presented in the new book with data from the earlier book, providing insight into scientific advancements, and revised estimates of species richness and endemism of a range of taxonomic groups.
Automated mobile virtual reality cognitive behavior therapy for aviophobia in a natural setting: a randomized controlled trial
Authors: Donker T. , Fehribach J.R. , van Klaveren C. , Cornelisz I. , Toffolo M. B. J. , van Straten A. , van Gelder J.-L.
Published: November 2022

Background

Access to evidence-based psychological treatment is a challenge worldwide. We assessed the effectiveness of a fully automated aviophobia smartphone app treatment delivered in combination with a $5 virtual reality (VR) viewer.

Methods

In total, 153 participants from the Dutch general population with aviophobia symptoms and smartphone access were randomized in a single-blind randomized controlled trial to either an automated VR cognitive behavior therapy (VR-CBT) app treatment condition (n = 77) or a wait-list control condition (n = 76). The VR-CBT app was delivered over a 6-week period in the participants' natural environment. Online self-report assessments were completed at baseline, post-treatment, at 3-month and at 12-month follow-up. The primary outcome measure was the Flight Anxiety Situations Questionnaire (FAS). Analyses were based on intent-to-treat.

Results

A significant reduction of aviophobia symptoms at post-test for the VR-CBT app compared with the control condition [p < 0.001; d = 0. 98 (95% CI 0.65–1.32)] was demonstrated. The dropout rate was 21%. Results were maintained at 3-month follow-up [within-group d = 1.14 (95% CI 0.46–1.81)] and at 12-month follow-up [within-group d = 1.12 (95% CI 0.46–1.79)]. Six participants reported adverse effects of cyber sickness symptoms.

Conclusions

This study is the first to show that fully automated mobile VR-CBT therapy delivered in a natural setting can maintain long-term effectiveness in reducing aviophobia symptoms. In doing so, it offers an accessible and scalable evidence-based treatment solution that can be applied globally at a fraction of the cost of current treatment alternatives.
Making the rich pay? Social democracy and wealth taxation in Europe in the aftermath of the great financial crisis
Authors: Elsässer Lea , Fastenrath Florian , Rehm Miriam
Published: November 2022

Why is taxing the rich so difficult despite rising inequality and public support for progressive taxation? Recent research has mostly focused on the ‘demand side’ of electoral tax politics, showing that economic crises can increase public demands for progressive taxation in contemporary societies. Complementing this research, we focus on the political ‘supply side’, investigating the conditions under which social democratic parties take up these calls and translate them into policy. Studying wealth taxation in the course of the global financial crisis, we argue that whether parties pushed for taxing wealth crucially depended on intra-party struggles between the (office-seeking) leadership and the (policy-seeking) left wing. Only if the leadership became convinced that redistributive tax policy was electorally promising, did the social democratic parties fight for implementing wealth taxes. We evaluate this theoretical proposition in a comparative analysis of wealth tax policies in Austria, Germany and Spain in 2008–2015.
Clozapine haematological monitoring for neutropenia: a global perspective
Authors: Oloyede Ebenezer , Blackman Graham , Whiskey Eromona , Bachmann Christian , Dzahini Olubanke , Shergill Sukhi , Taylor David , McGuire Philip , MacCabe James
Published: November 2022

Aims

Clozapine is licensed for treatment-resistant psychosis and remains underutilised. This may berelated to the stringent haematological monitoring requirements that are mandatory in most countries. We aimed to compare guidelines internationally and develop a novel Stringency Index. We hypothesised that the most stringent countries would have increased healthcare costs and reduced prescription rates.

Method

We conducted a literature review and survey of guidelines internationally. Guideline identification involved a literature review and consultation with clinical academics. We focused on the haematological monitoring parameters, frequency and thresholds for discontinuation and rechallenge after suspected clozapine-induced neutropenia. In addition, indicators reflecting monitoring guideline stringency were scored and visualised using a choropleth map. We developed a Stringency Index with an international panel of clozapine experts, through a modified-Delphi-survey. The Stringency Index was compared to health expenditure per-capita and clozapine prescription per 100 000 persons.

Results

One hundred twocountries were included, from Europe (n = 35), Asia (n = 24), Africa (n = 20), South America (n = 11), North America (n = 7) and Oceania and Australia (n = 5). Guidelines differed in frequency of haematological monitoring and discontinuation thresholds. Overall, 5% of included countries had explicit guidelines for clozapine-rechallenge and 40% explicitly prohibited clozapine-rechallenge. Furthermore, 7% of included countries had modified discontinuation thresholds for benign ethnic neutropenia. None of the guidelines specified how long haematological monitoring should continue. The most stringent guidelines were in Europe, and the least stringent were in Africa and South America. There was a positive association (r = 0.43, p < 0.001) between a country's Stringency Index and healthcare expenditure per capita.

Conclusions

Recommendations on how haematological function should be monitored in patients treated with clozapine vary considerably between countries. It would be useful to standardise guidelines on haematological monitoring worldwide.
Barts and The London School of Medicine and Dentistry
Authors: Coulthard Paul
Published: November 2022

The Institute of Dentistry at Barts and The School of Medicine and Dentistry, Queen Mary University of London, has seen much change since 1857 when surgeon dentist, H. J. Barrett, was appointed to The London to oversee the extraction of teeth. However, the mission remains the same: provision of excellent patient care through our education and research to improve the oral health and general health of our local population, but also with global impact.

The Institute of Dentistry is embedded in a fundamentally multidisciplinary environment of the wider university and this is reflected in our research activity. The available complementary skills in cell and molecular biology, microbiology, materials science, chemistry, biophysics, clinical science and population health allows us to undertake basic science research, patient- and population-based research and clinical biometric research.

Our Centre for Teaching and Innovation is a catalyst for educational research, including that related to new technologies and the expansion of e-learning, to ultimately inform local practice and the experience of our students.
Lysosomal damage drives mitochondrial proteome remodelling and reprograms macrophage immunometabolism
Authors: Bussi Claudio , Heunis Tiaan , Pellegrino Enrica , Bernard Elliott M. , Bah Nourdine , Dos Santos Mariana Silva , Santucci Pierre , Aylan Beren , Rodgers Angela , Fearns Antony , Mitschke Julia , Moore Christopher , MacRae James I. , Greco Maria , Reinheckel Thomas , Trost Matthias , Gutierrez Maximiliano G.
Published: November 2022

Transient lysosomal damage after infection with cytosolic pathogens or silica crystals uptake results in protease leakage. Whether limited leakage of lysosomal contents into the cytosol affects the function of cytoplasmic organelles is unknown. Here, we show that sterile and non-sterile lysosomal damage triggers a cell death independent proteolytic remodelling of the mitochondrial proteome in macrophages. Mitochondrial metabolic reprogramming required leakage of lysosomal cathepsins and was independent of mitophagy, mitoproteases and proteasome degradation. In an in vivo mouse model of endomembrane damage, live lung macrophages that internalised crystals displayed impaired mitochondrial function. Single-cell RNA-sequencing revealed that lysosomal damage skewed metabolic and immune responses in alveolar macrophages subsets with increased lysosomal content. Functionally, drug modulation of macrophage metabolism impacted host responses to Mycobacterium tuberculosis infection in an endomembrane damage dependent way. This work uncovers an inter-organelle communication pathway, providing a general mechanism by which macrophages undergo mitochondrial metabolic reprograming after endomembrane damage.
DNA methylation-based classification of sinonasal tumors
Authors: Jurmeister Philipp , Glöß Stefanie , Roller Renée , Leitheiser Maximilian , Schmid Simone , Mochmann Liliana H. , Payá Capilla Emma , Fritz Rebecca , Dittmayer Carsten , Friedrich Corinna , Thieme Anne , Keyl Philipp , Jarosch Armin , Schallenberg Simon , Bläker Hendrik , Hoffmann Inga , Vollbrecht Claudia , Lehmann Annika , Hummel Michael , Heim Daniel , Haji Mohamed , Harter Patrick , Englert Benjamin , Frank Stephan , Hench Jürgen , Paulus Werner , Hasselblatt Martin , Hartmann Wolfgang , Dohmen Hildegard , Keber Ursula , Jank Paul , Denkert Carsten , Stadelmann Christine , Bremmer Felix , Richter Annika , Wefers Annika , Ribbat-Idel Julika , Perner Sven , Idel Christian , Chiariotti Lorenzo , Della Monica Rosa , Marinelli Alfredo , Schüller Ulrich , Bockmayr Michael , Liu Jacklyn , Lund Valerie J. , Forster Martin , Lechner Matt , Lorenzo-Guerra Sara L. , Hermsen Mario , Johann Pascal D. , Agaimy Abbas , Seegerer Philipp , Koch Arend , Heppner Frank , Pfister Stefan M. , Jones David T. W. , Sill Martin , von Deimling Andreas , Snuderl Matija , Müller Klaus-Robert , Forgó Erna , Howitt Brooke E. , Mertins Philipp , Klauschen Frederick , Capper David
Published: November 2022

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs.
Breast cancer plasticity is restricted by a LATS1-NCOR1 repressive axis
Authors: Aylon Yael , Furth Noa , Mallel Giuseppe , Friedlander Gilgi , Nataraj Nishanth Belugali , Dong Meng , Hassin Ori , Zoabi Rawan , Cohen Benjamin , Drendel Vanessa , Salame Tomer Meir , Mukherjee Saptaparna , Harpaz Nofar , Johnson Randy , Aulitzky Walter E. , Yarden Yosef , Shema Efrat , Oren Moshe
Published: November 2022

Breast cancer, the most frequent cancer in women, is generally classified into several distinct histological and molecular subtypes. However, single-cell technologies have revealed remarkable cellular and functional heterogeneity across subtypes and even within individual breast tumors. Much of this heterogeneity is attributable to dynamic alterations in the epigenetic landscape of the cancer cells, which promote phenotypic plasticity. Such plasticity, including transition from luminal to basal-like cell identity, can promote disease aggressiveness. We now report that the tumor suppressor LATS1, whose expression is often downregulated in human breast cancer, helps maintain luminal breast cancer cell identity by reducing the chromatin accessibility of genes that are characteristic of a “basal-like” state, preventing their spurious activation. This is achieved via interaction of LATS1 with the NCOR1 nuclear corepressor and recruitment of HDAC1, driving histone H3K27 deacetylation near NCOR1-repressed “basal-like” genes. Consequently, decreased expression of LATS1 elevates the expression of such genes and facilitates slippage towards a more basal-like phenotypic identity. We propose that by enforcing rigorous silencing of repressed genes, the LATS1-NCOR1 axis maintains luminal cell identity and restricts breast cancer progression.
Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas
Authors: Kern Joseph G. , Tilston-Lunel Andrew M. , Federico Anthony , Ning Boting , Mueller Amy , Peppler Grace B. , Stampouloglou Eleni , Cheng Nan , Johnson Randy L. , Lenburg Marc E. , Beane Jennifer E. , Monti Stefano , Varelas Xaralabos
Published: November 2022

Basal-like breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells that undergo basal plasticity through poorly understood mechanisms. Using genetic mouse models and ex vivo primary organoid cultures, we show that conditional co-deletion of the LATS1 and LATS2 kinases, key effectors of Hippo pathway signaling, in mature mammary luminal epithelial cells promotes the development of Krt14 and Sox9-expressing basal-like carcinomas that metastasize over time. Genetic co-deletion experiments revealed that phenotypes resulting from the loss of LATS1/2 activity are dependent on the transcriptional regulators YAP/TAZ. Gene expression analyses of LATS1/2-deleted mammary epithelial cells notably revealed a transcriptional program that associates with human basal-like breast cancers. Our study demonstrates in vivo roles for the LATS1/2 kinases in mammary epithelial homeostasis and luminal-basal fate control and implicates signaling networks induced upon the loss of LATS1/2 activity in the development of basal-like breast cancer.
Gene activation guided by nascent RNA-bound transcription factors
Authors: Liang Ying , Xu Haiyue , Cheng Tao , Fu Yujuan , Huang Hanwei , Qian Wenchang , Wang Junyan , Zhou Yuenan , Qian Pengxu , Yin Yafei , Xu Pengfei , Zou Wei , Chen Baohui
Published: November 2022

Technologies for gene activation are valuable tools for the study of gene functions and have a wide range of potential applications in bioengineering and medicine. In contrast to existing methods based on recruiting transcriptional modulators via DNA-binding proteins, we developed a strategy termed Narta (nascent RNA-guided transcriptional activation) to achieve gene activation by recruiting artificial transcription factors (aTFs) to transcription sites through nascent RNAs of the target gene. Using Narta, we demonstrate robust activation of a broad range of exogenous and endogenous genes in various cell types, including zebrafish embryos, mouse and human cells. Importantly, the activation is reversible, tunable and specific. Moreover, Narta provides better activation potency of some expressed genes than CRISPRa and, when used in combination with CRISPRa, has an enhancing effect on gene activation. Quantitative imaging illustrated that nascent RNA-directed aTFs could induce the high-density assembly of coactivators at transcription sites, which may explain the larger transcriptional burst size induced by Narta. Overall, our work expands the gene activation toolbox for biomedical research.
Inflammation promotes resistance to immune checkpoint inhibitors in high microsatellite instability colorectal cancer
Authors: Sui Qiaoqi , Zhang Xi , Chen Chao , Tang Jinghua , Yu Jiehai , Li Weihao , Han Kai , Jiang Wu , Liao Leen , Kong Lingheng , Li Yuan , Hou Zhenlin , Zhou Chi , Zhang Chenzhi , Zhang Linjie , Xiao Binyi , Mei Weijian , Xu Yanbo , Qin Jiayi , Zheng Jian , Pan Zhizhong , Ding Pei-Rong
Published: November 2022

Inflammation is a common medical complication in colorectal cancer (CRC) patients, which plays significant roles in tumor progression and immunosuppression. However, the influence of inflammatory conditions on the tumor response to immune checkpoint inhibitors (ICI) is incompletely understood. Here we show that in a patient with high microsatellite instability (MSI-H) CRC and a local inflammatory condition, the primary tumor progresses but its liver metastasis regresses upon Pembrolizumab treatment. In silico investigation prompted by this observation confirms correlation between inflammatory conditions and poor tumor response to PD-1 blockade in MSI-H CRCs, which is further validated in a cohort of 62 patients retrospectively enrolled to our study. Inhibition of local but not systemic immune response is verified in cultures of paired T cells and organoid cells from patients. Single-cell RNA sequencing suggests involvement of neutrophil leukocytes via CD80/CD86-CTLA4 signaling in the suppressive immune microenvironment. In concordance with this finding, elevated neutrophil-to-lymphocyte ratio indicates inhibited immune status and poor tumor response to ICIs. Receiver operating characteristic curve further demonstrates that both inflammatory conditions and a high NLR could predict a poor response to ICIs in MSI- CRCs, and the predictive value could be further increased when these two predictors are combined. Our study thus suggests that inflammatory conditions in MSI-H CRCs correlate with resistance to ICIs through neutrophil leukocyte associated immunosuppression and proposes both inflammatory conditions and high neutrophil-to-lymphocyte ratio as clinical features for poor ICI response.