bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning Domain Ethical Principles from Interactions with Users
Authors: Dyoub Abeer , Costantini Stefania , Lisi Francesca Alessandra 
Published: November 2022

AbstractDrawing 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

AbstractThe 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

AbstractThe 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

AbstractBackgroundAccess 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.MethodsIn 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.ResultsA 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.ConclusionsThis 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

AbstractWhy 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

Abstract

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

AbstractThe 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

AbstractTransient 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

AbstractThe 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

AbstractBreast 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

AbstractBasal-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

AbstractTechnologies 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

AbstractInflammation 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.
Antifouling graphene oxide membranes for oil-water separation via hydrophobic chain engineering
Authors: Yang Chao , Long Mengying , Ding Cuiting , Zhang Runnan , Zhang Shiyu , Yuan Jinqiu , Zhi Keda , Yin Zhuoyu , Zheng Yu , Liu Yawei , Wu Hong , Jiang Zhongyi 
Published: November 2022

AbstractEngineering surface chemistry to precisely control interfacial interactions is crucial for fabricating superior antifouling coatings and separation membranes. Here, we present a hydrophobic chain engineering strategy to regulate membrane surface at a molecular scale. Hydrophilic phytic acid and hydrophobic perfluorocarboxylic acids are sequentially assembled on a graphene oxide membrane to form an amphiphilic surface. The surface energy is reduced by the introduction of the perfluoroalkyl chains while the surface hydration can be tuned by changing the hydrophobic chain length, thus synergistically optimizing both fouling-resistance and fouling-release properties. It is found that the surface hydration capacity changes nonlinearly as the perfluoroalkyl chain length increases from C4 to C10, reaching the highest at C6 as a result of the more uniform water orientation as demonstrated by molecular dynamics simulations. The as-prepared membrane exhibits superior antifouling efficacy (flux decline ratio <10%, flux recovery ratio ~100%) even at high permeance (~620 L m−2 h−1 bar−1) for oil-water separation.
CSF tau microtubule-binding region identifies pathological changes in primary tauopathies
Authors: Horie Kanta , Barthélemy Nicolas R. , Spina Salvatore , VandeVrede Lawren , He Yingxin , Paterson Ross W. , Wright Brenton A. , Day Gregory S. , Davis Albert A. , Karch Celeste M. , Seeley William W. , Perrin Richard J. , Koppisetti Rama K. , Shaikh Faris , Lago Argentina Lario , Heuer Hilary W. , Ghoshal Nupur , Gabelle Audrey , Miller Bruce L. , Boxer Adam L. , Bateman Randall J. , Sato Chihiro 
Published: November 2022

AbstractDespite recent advances in fluid biomarker research in Alzheimer’s disease (AD), there are no fluid biomarkers or imaging tracers with utility for diagnosis and/or theragnosis available for other tauopathies. Using immunoprecipitation and mass spectrometry, we show that 4 repeat (4R) isoform-specific tau species from microtubule-binding region (MTBR-tau275and MTBR-tau282) increase in the brains of corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal lobar degeneration (FTLD)-MAPTand AD but decrease inversely in the cerebrospinal fluid (CSF) of CBD, FTLD-MAPTand AD compared to control and other FTLD-tau (for example, Pick’s disease). CSF MTBR-tau measures are reproducible in repeated lumbar punctures and can be used to distinguish CBD from control (receiver operating characteristic area under the curve (AUC) = 0.889) and other FTLD-tau, such as PSP (AUC = 0.886). CSF MTBR-tau275and MTBR-tau282may represent the first affirmative biomarkers to aid in the diagnosis of primary tauopathies and facilitate clinical trial designs.