bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social Housing Fraud in England
Authors: Pass Mark 
Published: March 2020

Abstract
Social tenancy fraud is believed to cost UK taxpayers an estimated £1.8 billion annually, based upon estimates of prevalence and cost from over 5 years ago. Despite this, there is currently no centrally collected or published data on social tenancy fraud. The aim of this research was to investigate the amount of social tenancy frauds investigated, detected and prosecuted by local authorities in England. This was undertaken by means of documentary analysis, following Freedom of Information requests to the 198 local authorities who hold social housing stock. The research confirmed the findings of previous studies, that social tenancy fraud is a particular problem within London, as well as being increasingly detected in other urban areas. It was found that the amount of social tenancy fraud detected nationally has increased significantly in recent years, doubling since 2009. It is unclear, however, whether this indicates that social tenancy fraud is a growing problem or if the response has improved. This research has also identified a myriad of avenues in which further research would be of value, especially with respect to local government transparency which this research has found, despite recent initiatives, to be lacking.
Lymphopenia in primary Sjögren’s syndrome is associated with premature aging of naïve CD4+ T cells
Authors: Fessler Johannes , Fasching Patrizia , Raicht Andrea , Hammerl Sabrina , Weber Jennifer , Lackner Angelika , Hermann Josef , Dejaco Christian , Graninger Winfried B , Schwinger Wolfgang , Stradner Martin H 
Published: March 2020

Abstract

Objective
To investigate peripheral lymphopenia, a frequent finding in primary Sjögren’s syndrome (pSS) associated with higher disease activity and increased mortality.

Methods
Prospective, cross-sectional study of consecutive patients with pSS (n = 66) and healthy controls (n = 181). Lymphocyte subsets were analysed by flow cytometry, naïve (CD45RA+) and memory (CD45RO+) CD4+ T cells were purified by MACS technology. In vitro proliferation and senescence-associated β-galactosidase (SABG) were assessed by flow cytometry. Telomere length and TCR excision circles (TREC) were measured by real-time PCR. Telomerase activity was analysed according to the telomeric repeat amplification protocols (TRAP).

Results
In pSS, lymphopenia mainly affected naïve CD4+ T cells. We noted a lower frequency of proliferating naïve CD4+ T cells ex vivo and decreased homeostatic proliferation in response to IL-7 stimulation in vitro. Furthermore, naïve CD4+ T cells exhibited signs of immune cell aging including shortened telomeres, a reduction in IL-7R expression and accumulation of SABG. The senescent phenotype could be explained by telomerase insufficiency and drastically reduced levels of T-cell receptor excision circles (TRECs), indicating a history of extensive post-thymic cell division. TRECs correlated with the number of naïve CD4+ T cells linking the extend of earlier proliferation to the inability to sustain normal cell numbers.

Conclusion
In pSS, evidence for increased proliferation of naïve CD4+ T cells earlier in life is associated with a senescent phenotype unable to sustain homeostasis. The lack of naïve CD4+ T cells forms the basis of lymphopenia frequently observed in pSS.
Validity and reliability of a sensor-based electronic spinal mobility index for axial spondyloarthritis
Authors: Gardiner Philip V , Small Dawn , Muñoz-Esquivel Karla , Condell Joan , Cuesta-Vargas Antonio , Williams Jonathan , Machado Pedro M , Garrido-Castro Juan L 
Published: March 2020

Abstract

Objective
To evaluate the validity and reliability of inertial measurement unit (IMU) sensors in the assessment of spinal mobility in axial spondyloarthritis (axSpA).

Methods
A repeated measures study design involving 40 participants with axSpA was used. Pairs of IMU sensors were used to measure the maximum range of movement at the cervical (Cx) and lumbar (Lu) spine. A composite IMU score was defined by combining the IMU measures. Conventional metrology and physical function assessment were performed. Validation was assessed considering the agreement of IMU measures with conventional metrology and correlation with physical function. Reliability was assessed using intra-class correlation coefficients (ICCs).

Results
The composite IMU score correlated closely (r = 0.88) with the BASMI. Conventional Cx rotation and lateral flexion tests correlated closely with IMU equivalents (r = 0.85, 0.84). All IMU movement tests correlated strongly with BASFI, while this was true for only some of the BASMI tests. The reliability of both conventional and IMU tests (except for chest expansion) ranged from good to excellent. Test–retest ICCs for individual conventional tests varied between 0.57 and 0.91, in comparison to a range from 0.74 to 0.98 for each of the IMU tests. Each of the composite regional IMU scores had excellent test–retest reliability (ICCs=0.94–0.97), comparable to the reliability of the BASMI (ICC=0.96).

Conclusion
Cx and Lu spinal mobility measured using wearable IMU sensors is a valid and reliable assessment in multiple planes (including rotation), in patients with a wide range of axSpA severity.
Forecasting the Equity Premium: Mind the News!*
Authors: Adämmer Philipp , Schüssler Rainer A 
Published: March 2020

AbstractWe introduce a novel strategy to predict monthly equity premia that is based on extracted news from more than 700,000 newspaper articles, which were published in The New York Times and Washington Post between 1980 and 2018. We propose a flexible data-adaptive switching approach to map a large set of different news-topics into forecasts of aggregate stock returns. The information that is embedded in our extracted news is not captured by established economic predictors. Compared with the prevailing historical mean between 1999 and 2018, we find large out-of-sample (OOS) gains with an ROOS2 of 6.52% and sizeable utility gains for a mean–variance investor. The empirical results indicate that geopolitical news are at times more valuable than economic news to predict the equity premium and we also find that forecasting gains arise in down markets.
Estimate the incubation period of coronavirus 2019 (COVID-19)
Authors: Men Ke , Wang Xia , Yihao Li , Zhang Guangwei , Hu Jingjing , Gao Yanyan , Han Henry 
Published: March 2020

AbstractMotivationWuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus (COVID-19). It is being treated as a Class A infectious disease though it was classified as Class B according to the Infectious Disease Prevention Act of China. Accurate estimation of the incubation period of the coronavirus is essential to the prevention and control. However, it remains unclear about its exact incubation period though it is believed that symptoms of COVID-19 can appear in as few as 2 days or as long as 14 or even more after exposure. The accurate incubation period calculation requires original chain-of-infection data that may not be fully available in the Wuhan regions. In this study, we aim to accurately calculate the incubation period of COVID-19 by taking advantage of the chain-of-infection data, which is well-documented and epidemiologically informative, outside the Wuhan regions.MethodsWe acquired and collected officially reported COVID-19 data from 10 regions in China except for Hubei province. To achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. We excluded those without relevant epidemiological descriptions, working or living in Wuhan for a long time, or hard to determine the possible exposure time. We proposed a Monte Caro simulation approach to estimate the incubation of COVID-19 as well as employed nonparametric ways. We also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups.ResultThe incubation period of COVID-19 did not follow general incubation distributions such as lognormal, Weibull, and Gamma distributions. We estimated that the mean and median of its incubation were 5.84 and 5.0 days via bootstrap and proposed Monte Carlo simulations. We found that the incubation periods of the groups with age>=40 years and age<40 years demonstrated a statistically significant difference. The former group had a longer incubation period and a larger variance than the latter. It further suggested that different quarantine time should be applied to the groups for their different incubation periods. Our machine learning analysis also showed that the two groups were linearly separable. incubation of COVID-19 along with previous statistical analysis. Our results further indicated that the incubation difference between males and females did not demonstrate a statistical significance.
Subtype-specific epigenomic landscape and 3D genome structure in bladder cancer
Authors: Iyyanki Tejaswi , Zhang Baozhen , Jin Qiushi , Yang Hongbo , Liu Tingting , Wang Xiaotao , Xu Jie , Song Fan , Luan Yu , Yamashita Hironobu , Wang Lu , Warrick Joshua , Raman Jay , Meeks Joshua J. , Degraff David , Yue Feng 
Published: March 2020

AbstractMuscle-invasive bladder cancers have recently been characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. For example, FOXA1, GATA3, and PPARG have been shown to be essential for luminal subtype-specific regulation and subtype switching, while TP63 and STAT3 are critical for basal subtype bladder cancer. Despite these advances, the underlying epigenetic mechanism and 3D chromatin architecture for subtype-specific regulation in bladder cancers remains largely unknown. Here, we determined the genome-wide transcriptome, enhancer landscape, TF binding profiles (FOXA1 and GATA3) in luminal and basal subtypes of bladder cancers. Furthermore, we mapped genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors, for the first time in bladder cancer. We showed that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct TF binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identified a novel clinically relevant transcriptional factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other luminal-specific genes (such as FOXA1, GATA3, and PPARG) and affects cancer cell proliferation and migration. In summary, our work shows a subtype-specific epigenomic and 3D genome structure in urinary bladder cancers and suggested a novel link between the circadian TF NPAS2 and a clinical bladder cancer subtype.
Non-Langmuir kinetics of DNA surface hybridization
Authors: Vanjur L. , Carzaniga T. , Casiraghi L. , Chiari M. , Zanchetta G. , Buscaglia M. 
Published: March 2020

AbstractHybridization of complementary single strands of DNA represents a very effective natural molecular recognition process widely exploited for diagnostic, biotechnology and nanotechnology applications. A common approach relies on the immobilization on a surface of single stranded DNA probes that bind complementary targets in solution. However, despite the deep knowledge on DNA interactions in bulk solution, the modelling of the same interactions on a surface are still challenging and perceived as strongly system-dependent. Here we show that a two dimensional analysis of the kinetics of hybridization, performed at different target concentration and probe surface density by a label-free optical biosensor, reveals peculiar features inconsistent with an ideal Langmuir-like behaviour. We propose a simple non-Langmuir kinetic model accounting for an enhanced electrostatic repulsion originating from the surface immobilization of nucleic acids and for steric hindrance close to full hybridization of the surface probes. The analysis of the kinetic data by the model enables to quantify the repulsive potential at the surface, as well as to retrieve the kinetic parameters of isolated probes. We show that the strength and the kinetics of hybridization at large probe density can be improved by a 3D immobilization strategy of probe strands with a double stranded linker.Statement of SignificanceHybridization of nucleic acids strands with complementary sequences is a fundamental biological process and is also widely exploited for diagnostic purposes. Despite the availability of effective models for the equilibrium strength of freely diffusing strands, a general predictive model for surface hybridization is still missing. Moreover, the kinetics of hybridization is not fully understood neither in solution nor on a surface. In this work we show that the analysis of the kinetics of hybridization on a surface reveals and enables to quantify two main additional contributions: electrostatic repulsion and steric hindrance. These are general effects expected to occur not only on a surface but in any condition with large density of nucleic acids, comparable to that of the cellular nucleus.
Yolk sac erythromyeloid progenitors sustain erythropoiesis throughout embryonic life
Authors: Soares-da-Silva Francisca , Burlen-Defranoux Odile , Elsaid Ramy , Iturri Lorea , Freyer Laina , Sismeiro Odile , Pinto-do-Ó Perpétua , Gomez-Perdiguero Elisa , Cumano Ana 
Published: March 2020

AbstractThe first hematopoietic cells are produced in the yolk sac and are thought to be rapidly replaced by the progeny of hematopoietic stem cells. Here we document that hematopoietic stem cells do not contribute significantly to erythrocyte production up until birth. Lineage tracing of yolk sac-derived erythromyeloid progenitors, that also contribute to tissue resident macrophages, shows a progeny of highly proliferative erythroblasts, that after intra embryonic injection, rapidly differentiate. These progenitors, similar to hematopoietic stem cells, arec-Mybdependent and are developmentally restricted as they are not found in the bone marrow. We show that erythrocyte progenitors of yolk sac origin require lower concentrations of erythropoietin than their hematopoietic stem cell-derived counterparts for efficient erythrocyte production. Consequently, fetal liver hematopoietic stem cells fail to generate megakaryocyte and erythrocyte progenitors. We propose that large numbers of yolk sac-derived erythrocyte progenitors have a selective advantage and efficiently outcompete hematopoietic stem cell progeny in an environment with limited availability of erythropoietin.
Manganese complex [Mn(CO)3(tpa-κ3N)]Br increases antibiotic sensitivity in multidrug resistantStreptococcus pneumoniae
Authors: Liakopoulos Apostolos , La Ragione Roberto M. , Nagel Christoph , Schatzschneider Ulrich , Rozen Daniel E. , Betts Jonathan W. 
Published: March 2020

AbstractThe emergence of multidrug-resistance (MDR) inStreptococcus pneumoniaeclones and non-vaccine serotypes is of increasing concern, necessitating the development of novel treatment strategies. Here, we determined the efficacy of the Mn complex [Mn(CO)3(tpa-κ3N)]Br against MDRS. pneumoniaestrains. Our data showed that [Mn(CO)3(tpa-κ3N)]Br hasin vitroandin vivoantibacterial activity and has the potential to be used in combination with currently available antibiotics to increase their effectiveness against MDRS. pneumoniae.
Spatially-Resolved Live Cell Tagging and Isolation Using Protected Photoactivatable Cell Dyes
Authors: Genshaft Alex S , Ziegler Carly G. K. , Tzouanas Constantine N. , Mead Benjamin E. , Jaeger Alex M. , Navia Andrew W. , King Ryan P. , Jacks Tyler , Van Humbeck Jeffrey F. , Shalek Alex K. 
Published: March 2020

ABSTRACTWhether culturedin vitroor part of a complex tissuein vivo, a cell’s phenotype and function are significantly influenced by dynamic interactions with its microenvironment. To explicitly examine how a cell’s spatiotemporal activity impacts its behavior, we developed and validated a strategy termed SPACECAT—Spatially PhotoActivatable Color Encoded Cell Address Tags—to annotate, track, and isolate specific cells in a non-destructive, viability-preserving manner. In SPACECAT, a biological sample is immersed in a photocaged fluorescent molecule, and cells within a location of interest are labeled for further study by uncaging that molecule with user-patterned near-UV light. SPACECAT offers high spatial precision and temporal stability across diverse cell and tissue types, and is compatible with common downstream assays, including flow cytometry and single-cell RNA-Seq. Illustratively, we leveraged this approach in patient-derived intestinal organoids, a spatially complex system less amenable to genetic manipulations, to select for crypt-like regions enriched in stem-like and actively mitotic cells. Moreover, we demonstrate its applicability and utility onex vivotissue sections from four healthy organs and an autochthonous lung tumor model, uncovering spatially-biased gene expression patterns among immune cell subsets and identifying rare myeloid phenotypes enriched around tumor/healthy border regions. In sum, our method provides a minimally invasive and broadly applicable approach to link cellular spatiotemporal features and/or behavioral phenotypes with diverse downstream assays, enabling fundamental insights into the connections between tissue microenvironments and biological (dys)function.
Population Specific Adaptations in Venom Production to Abiotic Stressors in a Widely Distributed Cnidarian
Authors: Sachkova Maria Y. , Macrander Jason , Surm Joachim M. , Aharoni Reuven , Menard-Harvey Shelcie S. , Klock Amy , Leach Whitney B. , Reitzel Adam M. , Moran Yehu 
Published: March 2020

AbstractNematostella vectensisis a sea anemone (Actiniaria, Cnidaria) inhabiting estuaries over a broad geographic range where environmental conditions such as temperatures and salinity vary widely. In cnidarians, antagonistic interactions with predators and prey are mediated by their venom, which may be metabolically expensive. In this study, we challengedNematostellapolyps with heat, salinity, UV light stressors and a combination of all three to determine how abiotic stressors impact toxin expression for individuals collected across this species’ range. Transcriptomics and proteomics revealed that the highly abundant toxin Nv1 was the most downregulated gene under heat stress conditions in multiple populations. Physiological measurements demonstrated that venom is metabolically costly to produce suggesting that downregulating venom expression under stressful conditions may be advantageous. Strikingly, under a range of abiotic stressors, individuals from different geographic locations along this latitudinal cline modulate venom production levels differently in a pattern reflecting local adaptation.
Thecis-regulatory codes of response to combined heat and drought stress inArabidopsis thaliana
Authors: Azodi Christina B. , Lloyd John P. , Shiu Shin-Han 
Published: March 2020

ABSTRACTPlants respond to their environment by dynamically modulating gene expression. A powerful approach for understanding how these responses are regulated is to integrate information aboutcis-regulatory elements (CREs) into models calledcis-regulatory codes. Transcriptional response to combined stress is typically not the sum of the responses to the individual stresses. However,cis-regulatory codes underlying combined stress response have not been established. Here we modeled transcriptional response to single and combined heat and drought stress inArabidopsis thaliana. We grouped genes by their pattern of response (independent, antagonistic, synergistic) and trained machine learning models to predict their response using putative CREs (pCREs) as features (median F-measure = 0.64). We then developed a deep learning approach to integrate additional omics information (sequence conservation, chromatin accessibility, histone modification) into our models, improving performance by 6.2%. While pCREs important for predicting independent and antagonistic responses tended to resemble binding motifs of transcription factors associated with heat and/or drought stress, important synergistic pCREs resembled binding motifs of transcription factors not known to be associated with stress. These findings demonstrate howin silicoapproaches can improve our understanding of the complex codes regulating response to combined stress and help us identify prime targets for future characterization.
Models for Eco-evolutionary Extinction Vortices and their Detection
Authors: Nabutanyi Peter , Wittmann Meike J. 
Published: March 2020

AbstractThe smaller a population is, the faster it looses genetic variation due to genetic drift. Loss of genetic variation can reduce population growth rate, making populations even smaller and more vulnerable to loss of genetic variation, and so on. Ultimately, the population can be driven to extinction by this “eco-evolutionary extinction vortex”. So far, extinction vortices due to loss of genetic variation have been mainly described verbally. However, quantitative models are needed to better understand when such vortices arise and to develop methods for detecting them. Here we propose quantitative eco-evolutionary models, both individual-based simulations and analytic approximations, that link loss of genetic variation and population decline. Our models assume stochastic population dynamics and multi-locus genetics with different forms of balancing selection. Using mathematical analysis and simulations, we identify parameter combinations that exhibit strong interactions between population size and genetic variation as populations decline to extinction and match our definition of an eco-evolutionary vortex, i.e. the per-capita population decline rates and per-locus fixation rates increase with decreasing population size and number of polymorphic loci. We further highlight cues and early warning signals that may be useful in identifying populations undergoing an eco-evolutionary extinction vortex.
The pd-l1/pd-1 axis blocks neutrophil cytotoxicity in cancer
Authors: Gershkovitz Maya , Yajuk Olga , Fainsod-Levi Tanya , Granot Zvi 
Published: March 2020

ABSTRACTThe PD-L1/PD-1 axis was shown to promote tumor growth and progression via the inhibition of anti-tumor immunity. Blocking this axis was shown to be beneficial in maintaining the anti-tumor functions of the adaptive immune system. Still, the consequences of blocking the PD-L1/PD-1 axis on innate immune responses remain largely unexplored. In this context, neutrophils were shown to consist of different subpopulations, which possess either pro- and anti-tumor properties. PD-L1-expressing neutrophils are considered pro-tumor as they can suppress cytotoxic T-cells. That said, we found that PD-L1 expression is not limited to tumor promoting neutrophils but is also evident in anti-tumor neutrophils. We show that neutrophil cytotoxicity is effectively and efficiently blocked by tumor cell expressed PD-1. Furthermore blocking of either neutrophil PD-L1 or tumor cell PD-1 maintains neutrophil cytotoxicity resulting in enhanced tumor cell apoptosis. Importantly, we show that tumor cell PD-1 blocks neutrophil cytotoxicity and promotes tumor growth via a mechanism independent of adaptive immunity. Taken together, these findings highlight the therapeutic potential of enhancing anti-tumor innate immune responses via blocking of the PD-L1/PD-1 axis.