bluuebunny/crossref_metadata_2025 huggingface dataset:
DBCC2: an improved difficulty-based cooperative co-evolution for many-modal optimization
Authors: Qiao Yingying , Luo Wenjian , Lin Xin , Xu Peilan , Preuss Mike
Published: January 2023

Evolutionary multimodal optimization algorithms aim to provide multiple solutions simultaneously. Many studies have been conducted to design effective evolutionary algorithms for solving multimodal optimization problems. However, optimization problems with many global and acceptable local optima have not received much attention. This type of problem is undoubtedly challenging. In this study, we focus on problems with many optima, the so-called many-modal optimization problems, and this study is an extension of our previous conference work. First, a test suite including additively nonseparable many-modal optimization problems and partially additively separable many-modal optimization problems is designed. Second, an improved difficulty-based cooperative co-evolution algorithm (DBCC2) is proposed, which dynamically estimates the difficulties of subproblems and allocates the computational resources during the search. Experimental results show that DBCC2 has competitive performance.
The Imagery and Politics of Sexual Violence in Early Renaissance Italy
Authors: Bokody Péter
Published: January 2023

This book is the first comprehensive study of images of rape in Italian painting at the dawn of the Renaissance. Drawing on a wide range of primary sources, Péter Bokody examines depictions of sexual violence in religion, law, medicine, literature, politics, and history writing produced in kingdoms (Sicily and Naples) and city-republics (Florence, Siena, Lucca, Bologna and Padua). Whilst misogynistic endorsement characterized many of these visual discourses, some urban communities condemned rape in their propaganda against tyranny. Such representations of rape often link gender and aggression to war, abduction, sodomy, prostitution, pregnancy, and suicide. Bokody also traces how the new naturalism in painting, introduced by Giotto, increased verisimilitude, but also fostered imagery that coupled eroticism and violation. Exploring images and texts that have long been overlooked, Bokody's study provides new insights at the intersection of gender, policy, and visual culture, with evident relevance to our contemporary condition.
Politics, Murder and Love in an Italian Family
Authors: Bosworth R.J.B.
Published: January 2023

What did it mean to live with fascism, communism, and totalitarianism in modern Italy? And what should we learn from the experiences of a martyred liberal democrat father and his communist son? Through the prism of a single, exceptional family, the Amendolas, R.J.B. Bosworth reveals the heart of twentieth-century Italian politics. Giovanni and Giorgio Amendola, father and son, were both highly capable and dedicated Anti-Fascists. Each failed to make it to the top of the Italian political pyramid but nevertheless played a major part in Italy's history. Both also had rich but contrasting private lives. Each married a foreign and accomplished woman: Giovanni, a woman from a distinguished German-Russian intellectual family; Giorgio, a Parisian working class girl, who, to him, embodied Revolution. This vivid and engaging biographical study explores the highs and lows of a family that was at the centre of Italian politics over several generations. Tracing the complex relationship between Anti-Fascist politics and the private lives of individuals and of the family, Politics, Murder and Love in an Italian Family offers a profound portrait of a century of Italian life.
Costs of two vancomycin-resistant enterococci outbreaks in an academic hospital
Authors: van der Pol Simon , Lokate Mariëtte , Postma Maarten J. , Friedrich Alex W.
Published: January 2023

Objective:

In early 2017, the University Medical Center Groningen, the Netherlands, had an outbreak of 2 strains of vancomycin-resistant enterococci (VRE) that spread to various wards. In the summer of 2018, the hospital was again hit by a VRE outbreak, which was detected and controlled early. However, during both outbreaks, fewer patients were admitted to the hospital and various costs were incurred. We quantified the costs of the 2017 and 2018 VRE outbreaks.

Design:

Using data from various sources in the hospital and interviews, we identified and quantified the costs of the 2 outbreaks, resulting from tests, closed beds (opportunity costs), cleaning, additional personnel, and patient isolation.

Setting:

The University Medical Center Groningen, an academic hospital in the Netherlands.

Results:

The total costs associated with the 2017 outbreak were estimated to be €335,278 (US $356,826); the total costs associated with the 2018 outbreak were estimated at €149,025 (US $158,602).

Conclusions:

The main drivers of the costs were the opportunity costs due to the reduction in admitted patients, testing costs, and cleaning costs. Although the second outbreak was considerably shorter, the costs per day were similar to those of the first outbreak. Major investments are associated with the VRE control measures, and an outbreak of VRE can lead to considerable costs for a hospital. Aggressively screening and isolating patients who may be involved in an outbreak of VRE may reduce the overall costs and improve the continuity of care within the hospital.
A 100-PW compressor based on single-pass single-grating pair
Authors: Du Shuman , Shen Xiong , Liang Wenhai , Wang Peng , Liu Jun , Li Ruxin
Published: January 2023

A multistep pulse compressor (MPC) based on a single-pass single-grating pair (SSGP) is proposed to simplify the entire multi-petawatt (PW) compressor. Only one grating pair with relatively long perpendicular distance is used to generate the same amount of spectral chirp compared with a four-grating main compressor. As SSGP compressor induces the largest spatial chirp, it can introduce the best beam-smoothing effect to the laser beam on the last grating. When considering the diffraction loss of only two gratings, the total compression efficiency of the SSGP compressor is even larger than that of a four-grating main compressor. Furthermore, the wavefront aberration induced by the SSGP compressor can be better compensated by using deformable mirrors; however, it is difficult or complicated to be well compensated in a four-grating compressor. Approximately 50–100 PW laser pulses can be obtained using this SSGP-based multistage-smoothing MPC with a single laser beam.
Checklist of parasites associated with ʻreptiles’ in Northeast Brazil
Authors: Lacerda G. M. C. , Santana J. de A. , de Araujo Filho J. A. , Ribeiro S. C
Published: January 2023

Reptiles, as well as other vertebrate groups, harbour a significant diversity of parasitic organisms, from nematodes and other helminths to viruses and bacteria. The Northeast is one of the richest regions in Brazil in terms of the reptile diversity, number of species and endemism. Parasites are diverse organisms and knowledge about the parasitic fauna of vertebrates is an important factor in understanding the ecological relationships between hosts and the environment. Studies on the parasitic fauna of reptiles in South America have increased in the past few years. The present review is a compilation of 122 studies published from 1924 to 2021. We present information on 101 species of reptiles from five groups (amphisbaenians, crocodile, testudines, snakes and lizards) and 183 parasitic taxa belonging to four phyla: Nematoda; Arthropoda; Platyhelminthes; and Acanthocephala. Nematodes were the most frequently recorded species. Lizards and snakes had more records of parasitism and higher levels of parasite richness and diversity. Ceará was the state with most studies and recorded cases of parasite–host association. The Caatinga and Atlantic Forest were the most investigated environments. The objective of this review was to contribute knowledge on the parasitic biodiversity in reptiles from Northeast Brazil, which may help identify gaps in our knowledge and guide future studies.
Deserving more? A vignette study on the role of self-interest and deservingness opinions for popular support for wealth taxation in Germany
Authors: Sachweh Patrick , Eicher Debora
Published: January 2023

This paper investigates which factors shape popular support for the taxation of wealth in Germany, a country with one of the highest levels of wealth inequality in Western Europe. Although public support for progressive taxation in general is strong, no tax on personal net wealth is currently levied. Against this backdrop, we ask how objective and subjective self-interest, information about wealth inequality and deservingness valuations regarding the wealthy affect popular support for a personal wealth tax. Particular attention is paid to the interaction between self-interest and deservingness. Using original survey data and a vignette design, we find that subjective self-interest is more important than objective self-interest, and that providing information on aggregate wealth inequality can shift the attitudes of those who are otherwise indifferent in favour of wealth taxation. Furthermore, deservingness valuations impact support for taxation in important ways. Factors indicating meritocratic wealth accumulation reduce support, and this is especially pronounced among low-status respondents. By contrast, while non-meritocratic factors increase support for taxation, these effects are largely off-set in privileged groups. Altogether, these findings suggest that self-interest and deservingness valuations impact attitudes towards wealth taxation in opposing directions, and that providing information to those otherwise indifferent might increase redistributive preferences.
Charities’ income during the COVID-19 pandemic: administrative evidence for England and Wales
Authors: Clifford David , McDonnell Diarmuid , Mohan John
Published: January 2023

This paper provides a detailed overview of how the COVID-19 pandemic has affected the income of charitable organisations – an under-researched theme within social policy, which thus far has largely focused on the impact of the pandemic on individuals’ and households’ wellbeing. It analyses a unique longitudinal dataset that follows through time c.90,000 charities in England and Wales. The results, for the first time, illustrate the scale of the pandemic’s financial impact on the charitable sector: the median charity experienced a 13% real decline in annual income, while a charity at the 25th percentile of the annual relative growth distribution experienced an income decline of 43%. Importantly these annual declines are much more sizeable than those associated with the Great Recession and subsequent period of public spending austerity. Smaller charities, particularly those with an income under £100k, have been most significantly affected. The declines have been pervasive, extending across most fields of charitable activity, though certain charitable fields have seen particularly acute declines. While there has rightly been considerable emphasis on the important role of voluntary action in responding to the pandemic, this new empirical evidence helps to communicate the extent of the recent challenges faced by the charitable sector.
Institutional earmarks: the earmark moratorium and federal highway spending
Authors: McLaughlin Peter T.
Published: January 2023

In 2010, the United States Congress placed a moratorium on earmarks – congressionally mandated spending projects. But did the earmark moratorium actually rid public policy of earmarks? I use earmark data and 2010–2020 state-level highway funding metrics to examine the relationship between previously expired transportation earmarks and federal highway funding during the earmark moratorium. Earmarks in the 2005 surface transportation law (SAFETEA-LU) continued to benefit certain states in 2020, even though the projects technically expired in 2009. This is because the funding “formulas” established by all post-2009 surface transportation laws were fully determined by the highway allocation percentage each state received in the preceding year, inclusive of earmarks. Further, I find the relationship between SAFETEA-LU earmarks and state funding disparities strengthened from 2010 to 2020, meaning the expired earmarks increased in policy significance during the moratorium. Highly earmarked states became even more advantaged after the earmarks were institutionalised into the highway funding formula.
Multidisciplinary concurrent optimization framework for multi-phase building design process
Authors: Muthumanickam Naveen Kumar , Duarte Jose Pinto , Simpson Timothy W.
Published: January 2023

Modern day building design projects require multidisciplinary expertise from architects and engineers across various phases of the design (conceptual, preliminary, and detailed) and construction processes. The Architecture Engineering and Construction (AEC) community has recently shifted gears toward leveraging design optimization techniques to make well-informed decisions in the design of buildings. However, most of the building design optimization efforts are either multidisciplinary optimization confined to just a specific design phase (conceptual/preliminary/detailed) or single disciplinary optimization (structural/thermal/daylighting/energy) spanning across multiple phases. Complexity in changing the optimization setup as the design progresses through subsequent phases, interoperability issues between modeling and physics-based analysis tools used at later stages, and the lack of an appropriate level of design detail to get meaningful results from these sophisticated analysis tools are few challenges that limit multi-phase multidisciplinary design optimization (MDO) in the AEC field. This paper proposes a computational building design platform leveraging concurrent engineering techniques such as interactive problem structuring, simulation-based optimization using meta models for energy and daylighting (machine learning based) and tradespace visualization. The proposed multi-phase concurrent MDO framework is demonstrated by using it to design and optimize a sample office building for energy and daylighting objectives across multiple phases. Furthermore, limitations of the proposed framework and future avenues of research are listed.
Monthly credit from and deposits in Swedish commercial banks, 1875-2020
Authors: Ahnland Lars
Published: January 2023

Since the global financial crisis in 2008, there has been an elevated interest in private debt and as a macroeconomic variable. In light of the lack of high-frequency data, this study presents a unique monthly time series dataset on credit from and deposits in Swedish commercial banks from 1875 to 2020, covering 1,752 monthly observations and most of Swedish commercial banking history. In a first application, the study examines to what extent money in Sweden has been exogenous, created independently of demand by the central bank, or endogenous, created in response to demand by commercial banks, during different institutional settings. The results, derived via cointegration and impulse-response functions, show that though the relationship between deposits and credit has changed over time, both theories often hold validity simultaneously. While changes in deposits often have had significant impact on credit, the opposite has also been true. There are, however, differences between different regulatory regimes, as well as for different groups of banks.
How social infrastructure saves lives: a quantitative analysis of Japan's 3/11 disasters
Authors: Aldrich Daniel P.
Published: January 2023

Observers have long debated how societies should invest resources to safeguard citizens and property, especially in the face of increasing shocks and crises. This article explores how social infrastructure – the spaces and places that help build and maintain social ties and trust, allowing societies to coordinate behavior – plays an important role in our communities, especially in mitigating and recovering from shocks. An analysis of quantitative data on more than 550 neighborhoods across the three Japanese prefectures most affected by the tsunami of 11 March 2011 shows that, controlling for relevant factors, community centers, libraries, parks, and other social infrastructure measurably and cheaply reduced mortality rates among the most vulnerable population. Investing in social infrastructure projects would, based on this data, save more lives during a natural hazard than putting the same money into standard, gray infrastructure such as seawalls. Decision makers at national, regional, and local levels should expand spending on facilities such as libraries, community centers, social businesses, and public parks to increase resilience to multiple types of shocks and to further enhance the quality of life for residents.
Paleoclimate Changes in the Pacific Northwest Over the Past 36,000 Years From Clumped Isotope Measurements and Model Analysis
Authors: Lopez‐Maldonado Ricardo , Bateman Jesse Bloom , Ellis Andre , Bader Nicholas E. , Ramirez Pedro , Arnold Alexandrea , Ajoku Osinachi , Lee Hung‐I , Jesmok Gregory , Upadhyay Deepshikha , Mitsunaga Bryce , Elliott Ben , Tabor Clay , Tripati Aradhna
Published: January 2023

Since the last glacial period, North America has experienced dramatic changes in regional climate, including the collapse of ice sheets and changes in precipitation. We use clumped isotope (∆47) thermometry and carbonate δ18O measurements of glacial and deglacial pedogenic carbonates from the Palouse Loess to provide constraints on hydroclimate changes in the Pacific Northwest. We also employ analysis of climate model simulations to help us further provide constraints on the hydroclimate changes in the Pacific Northwest. The coldest clumped isotope soil temperatures T(47) (13.5 ± 1.9°C to 17.1 ± 1.7°C) occurred ∼34,000–23,000 years ago. Using a soil‐to‐air temperature transfer function, we estimate Last Glacial Maximum (LGM) mean annual air temperatures of ∼−5.5°C and warmest average monthly temperatures (i.e., mean summer air temperatures) of ∼4.4°C. These data indicate a regional warming of 16.4 ± 2.6°C from the LGM to the modern temperatures of 10.9°C, which was about 2.5–3 times the global average. Proxy data provide locality constraints on the boundary of the cooler anticyclone induced by LGM ice sheets, and the warmer cyclone in the Eastern Pacific Ocean. Climate model analysis suggests regional amplification of temperature anomalies is due to the proximal location of the study area to the Laurentide Ice Sheet margin and the impact of the glacial anticyclone on the region, as well as local albedo. Isotope‐enabled model experiments indicate variations in water δ18O largely reflect atmospheric circulation changes and enhanced rainout upstream that brings more depleted vapor to the region during the LGM.
Aurora Detection From Nighttime Lights for Earth and Space Science Applications
Authors: Kalb Virginia , Kosar Burcu , Collado‐Vega Yaireska , Davidson Carol
Published: January 2023

This research leverages data from the Day/Night Band (DNB) of the Visible Infrared Imaging Radiometer (VIIRS) instrument onboard the Suomi National Polar‐orbiting Partnership (S‐NPP) satellite. We demonstrate the value of mining the VIIRS DNB for aurora and describe our use of unsupervised machine learning to create a binary mask for aurora occurrence. This mask can be used to flag aurora‐contaminated observations for NASA's nighttime lights products for Earth science applications. The identification of auroral regions can also be used for Space Weather applications, for example, for comparison with aurora forecast model and with other satellite‐ or ground‐based aurora observations. The DNB is a broadband channel that is sensitive to wavelengths from 500 to 900 nm, which covers most of the visible light spectrum, and as the name implies, captures light even at night with a sensitivity at the nanowatt level. This band is suitable for aurora observations since the light emitted by the aurora tends to be dominated by emissions from atomic oxygen, resulting in a greenish glow at a wavelength of 557.7 nm, especially at an altitude of 110 km. This study compares the global nighttime derived aurora regions for 17 and 18 March with the NOAA Space Weather Prediction Center's (SWPC) probability product for the St. Patrick's Day geomagnetic storm in 2015. VIIRS sensors are slated to be added to the next generation of polar‐orbiting operational satellites. Our novel automated approach to aurora identification opens up an efficient way to leverage this unique data source.
SIGMA: Spectral Interpretation Using Gaussian Mixtures and Autoencoder
Authors: Tung Po‐Yen , Sheikh Hassan A. , Ball Matthew , Nabiei Farhang , Harrison Richard J.
Published: January 2023

Identification of unknown micro‐ and nano‐sized mineral phases is commonly achieved by analyzing chemical maps generated from hyperspectral imaging data sets, particularly scanning electron microscope—energy dispersive X‐ray spectroscopy (SEM‐EDS). However, the accuracy and reliability of mineral identification are often limited by subjective human interpretation, non‐ideal sample preparation, and the presence of mixed chemical signals generated within the electron‐beam interaction volume. Machine learning has emerged as a powerful tool to overcome these problems. Here, we propose a machine‐learning approach to identify unknown phases and unmix their overlapped chemical signals. This approach leverages the guidance of Gaussian mixture modeling clustering fitted on an informative latent space of pixel‐wise elemental data points modeled using a neural network autoencoder, and unmixes the overlapped chemical signals of phases using non‐negative matrix factorization. We evaluate the reliability and the accuracy of the new approach using two SEM‐EDS data sets: a synthetic mixture sample and a real‐world particulate matter sample. In the former, the proposed approach successfully identifies all major phases and extracts background‐subtracted single‐phase chemical signals. The unmixed chemical spectra show an average similarity of 83.0% with the ground truth spectra. In the second case, the approach demonstrates the ability to identify potentially magnetic Fe‐bearing particles and their background‐subtracted chemical signals. We demonstrate a flexible and adaptable approach that brings a significant improvement to mineralogical and chemical analysis in a fully automated manner. The proposed analysis process has been built into a user‐friendly Python code with a graphical user interface for ease of use by general users.
Toward Better Understanding of the Ferrofluid Impregnation Process and Potential Artefacts—A Prerequisite for Reliable Interpretation of Magnetic Pore Fabrics
Authors: Pugnetti M. , Prieto M. , Mäder U. , Biedermann A. R.
Published: January 2023

Magnetic pore fabrics (MPFs) serve as efficient proxy for pore alignment and preferential flow directions. Anisotropy of magnetic susceptibility of impregnated samples reflects the shape and arrangement of ferrofluid‐filled pores. Reliable interpretation requires that the entire connected pore space is reached by ferrofluid. This study investigates impregnation efficiencies of various methods (standard vacuum, pressure injection, magnetic flowthrough, and resin impregnation) and ferrofluids (water‐based versus oil‐based) on sandstone and calcarenite with different wettabilities. Mass‐based and susceptibility‐based impregnation efficiencies further evaluate the influence of impregnation time and flow rate. Because directional impregnation may introduce artificial fabrics, mutually perpendicular cores were measured, and subsamples served to capture spatial variability. Impregnation efficiencies vary between <1% and >100%, with resin impregnation and pressure injection using oil‐based ferrofluids being least efficient. Oil‐based ferrofluid generally leads to lower susceptibility‐based compared to mass‐based impregnation efficiencies, suggesting particle filtering. Water‐based ferrofluids show larger ranges of susceptibility‐based compared to mass‐based impregnation efficiencies. In particular, impregnation efficiencies >100% exclusively occur for susceptibility‐based impregnation efficiencies of water‐based ferrofluid, using either standard vacuum or pressure injection methods. MPFs after magnetic flowthrough impregnation reflect the impregnation direction rather than pore fabric. A major challenge is to apply enough force to reach sufficiently high impregnation efficiencies without creating MPFs that do not represent pore fabrics. While we cannot define a best practice for ferrofluid impregnation yet, this study improves our understanding of the impregnation process, and provides experimental procedures to identify artifacts.
Formation of a biofilm matrix network shapes polymicrobial interactions
Authors: Wang Lijun , Wang Hongxia , Zhang Hua , Wu Hui
Published: January 2023

Staphylococcus aureus colonizes the same ecological niche as many commensals. However, little is known about how such commensals modulate staphylococcal fitness and persistence. Here we report a new mechanism that mediates dynamic interactions between a commensal streptococcus and S. aureus. Commensal Streptococcus parasanguinis significantly increased the staphylococcal biofilm formation in vitro and enhanced its colonization in vivo. A streptococcal biofilm-associated protein BapA1, not fimbriae-associated protein Fap1, is essential for dual-species biofilm formation. On the other side, three staphylococcal virulence determinants responsible for the BapA1-dependent dual-species biofilm formation were identified by screening a staphylococcal transposon mutant library. The corresponding staphylococcal mutants lacked binding to recombinant BapA1 (rBapA1) due to lower amounts of eDNA in their culture supernatants and were defective in biofilm formation with streptococcus. The rBapA1 selectively colocalized with eDNA within the dual-species biofilm and bound to eDNA in vitro, highlighting the contributions of the biofilm matrix formed between streptococcal BapA1 and staphylococcal eDNA to dual-species biofilm formation. These findings have revealed an additional new mechanism through which an interspecies biofilm matrix network mediates polymicrobial interactions.
Risk of second primary malignancies in patients with chronic lymphocytic leukemia: a population-based study in the Netherlands, 1989-2019
Authors: van der Straten Lina , Levin Mark-David , Dinnessen Manette A. W. , Visser Otto , Posthuma Eduardus F. M. , Doorduijn Jeanette K. , Langerak Anton W. , Kater Arnon P. , Dinmohamed Avinash G.
Published: January 2023

The longevity of patients with chronic lymphocytic leukemia (CLL) has improved progressively over the past decades, making it essential to understand long-term health outcomes, such as second primary malignancies (SPMs). Therefore, this nationwide, population-based study assessed the risk of SPM development in CLL patients diagnosed during 1989-2019 in the Netherlands compared to the expected number of malignancies in an age-, sex-, and period-matched group from the general Dutch population. In 24,815 CLL patients followed for 162,698.49 person-years, 4369 SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.63 (95% confidence interval [CI] 1.59–1.68). This elevated risk was observed for solid (SIR, 1.67; 95% CI, 1.65–1.75) and hematological SPMs (SIR 1.42; 95% CI, 1.24–1.62). The highest risk for SPMs was noted beyond five years post-diagnosis (SIR, 1.70; 95% CI, 1.62–1.77), for male individuals (SIR, 1.70; 95% CI, 1.64–1.77), and patients aged 18–69 years (SIR, 1.92; 95% CI, 1.79–2.05). The risk of SPMs was higher in CLL patients who received anti-neoplastic therapy (SIR, 2.12; 95% CI, 1.96–2.28), as compared with those who did not (SIR, 1.58; 95% CI, 1.53–1.63). Routine surveillance activities and tailored interventions to counteract the increased morbidity and excess mortality associated with SPMs are essential for improving long-term outcomes in CLL patients.
CircIFNGR2 enhances proliferation and migration of CRC and induces cetuximab resistance by indirectly targeting KRAS via sponging to MiR-30b
Authors: Zhang Qi , Zheng Yifeng , Liu Jiajia , Tang Xiaoxiao , Wang Yuan , Li Xianzheng , Li Huibin , Zhou Xiaoying , Tang Shiru , Tang Yitao , Wang Xiaoyan , He Han , Li Tingting
Published: January 2023

Currently the clinical efficacy of colorectal cancer (CRC) which is the most common malignant tumors over the world has not reached an ideal level. Cetuximab, the monoclonal antibody targeting the extracellular domain of EGFR, has shown its great efficacy in the promotion of apoptosis and the inhibition of tumor cells-like characteristics in numerous cancers. However certain KRAS wild-type CRC patients unexpectedly show cetuximab resistance and the specific mechanism remains unclear. Circular RNAs (circRNAs) as the promising novel type of biomarkers in the cancer diagnosis and therapy, have been reported to be related with the drug resistance. In this study, with wondering the mechanism of cetuximab resistance in KRAS wild-type CRC patients, we evaluate the impact of circIFNGR2 on CRC and detect the association among circIFNGR2, miR-30b and KRAS via various experiments such as RT-qPCR, immunohistochemistry, luciferase assays, cell functional experiments and xenograft model. We conclude that circIFNGR2 induces cetuximab resistance in colorectal cancer cells by indirectly regulating target gene KRAS by sponging miR-30b at the post-transcriptional level. It is thus suggested that inhibition of circIFNGR2 can be a promising therapeutic strategy for malignant CRC patients with cetuximab resistance.
Structural basis of transcription recognition of a hydrophobic unnatural base pair by T7 RNA polymerase
Authors: Oh Juntaek , Kimoto Michiko , Xu Haoqing , Chong Jenny , Hirao Ichiro , Wang Dong
Published: January 2023

Bacteriophage T7 RNA polymerase (T7 RNAP) is widely used for synthesizing RNA molecules with synthetic modifications and unnatural base pairs (UBPs) for a variety of biotechnical and therapeutic applications. However, the molecular basis of transcription recognition of UBPs by T7 RNAP remains poorly understood. Here we focused on a representative UBP, 7-(2-thienyl)-imidazo[4,5-b]pyridine (Ds) and pyrrole 2-carbaldehyde (Pa), and investigated how the hydrophobic Ds–Pa pair is recognized by T7 RNAP. Our kinetic assays revealed that T7 RNAP selectively recognizes the Ds or Pa base in the templates and preferentially incorporates their cognate unnatural base nucleotide substrate (PaTP or DsTP) over natural NTPs. Our structural studies reveal that T7 RNAP recognizes the unnatural substrates at the pre-insertion state in a distinct manner compared to natural substrates. These results provide mechanistic insights into transcription recognition of UBP by T7 RNAP and provide valuable information for designing the next generation of UBPs.
The interferon stimulated gene-encoded protein HELZ2 inhibits human LINE-1 retrotransposition and LINE-1 RNA-mediated type I interferon induction
Authors: Luqman-Fatah Ahmad , Watanabe Yuzo , Uno Kazuko , Ishikawa Fuyuki , Moran John V. , Miyoshi Tomoichiro
Published: January 2023

Some interferon stimulated genes (ISGs) encode proteins that inhibit LINE-1 (L1) retrotransposition. Here, we use immunoprecipitation followed by liquid chromatography-tandem mass spectrometry to identify proteins that associate with the L1 ORF1-encoded protein (ORF1p) in ribonucleoprotein particles. Three ISG proteins that interact with ORF1p inhibit retrotransposition: HECT and RLD domain containing E3 ubiquitin-protein ligase 5 (HERC5); 2′−5′-oligoadenylate synthetase-like (OASL); and helicase with zinc finger 2 (HELZ2). HERC5 destabilizes ORF1p, but does not affect its cellular localization. OASL impairs ORF1p cytoplasmic foci formation. HELZ2 recognizes sequences and/or structures within the L1 5′UTR to reduce L1 RNA, ORF1p, and ORF1p cytoplasmic foci levels. Overexpression of WT or reverse transcriptase-deficient L1s lead to a modest induction of IFN-α expression, which is abrogated upon HELZ2 overexpression. Notably, IFN-α expression is enhanced upon overexpression of an ORF1p RNA binding mutant, suggesting ORF1p binding might protect L1 RNA from “triggering” IFN-α induction. Thus, ISG proteins can inhibit retrotransposition by different mechanisms.
Preclinical development of kinetin as a safe error-prone SARS-CoV-2 antiviral able to attenuate virus-induced inflammation
Authors: Souza Thiago Moreno L. , Pinho Vagner D. , Setim Cristina F. , Sacramento Carolina Q. , Marcon Rodrigo , Fintelman-Rodrigues Natalia , Chaves Otavio A. , Heller Melina , Temerozo Jairo R. , Ferreira André C. , Mattos Mayara , Momo Patrícia B. , Dias Suelen S. G. , Gesto João S. M. , Pereira-Dutra Filipe , Viola João P. B. , Queiroz-Junior Celso Martins , Guimarães Lays Cordeiro , Chaves Ian Meira , Guimarães Pedro Pires Goulart , Costa Vivian Vasconcelos , Teixeira Mauro Martins , Bou-Habib Dumith Chequer , Bozza Patrícia T. , Aguillón Anderson R. , Siqueira-Junior Jarbas , Macedo-Junior Sergio , Andrade Edineia L. , Fadanni Guilherme P. , Tolouei Sara E. L. , Potrich Francine B. , Santos Adara A. , Marques Naiani F. , Calixto João B. , Rabi Jaime A.
Published: January 2023

Orally available antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary because of the continuous circulation of new variants that challenge immunized individuals. Because severe COVID-19 is a virus-triggered immune and inflammatory dysfunction, molecules endowed with both antiviral and anti-inflammatory activity are highly desirable. We identified here that kinetin (MB-905) inhibits the in vitro replication of SARS-CoV-2 in human hepatic and pulmonary cell lines. On infected monocytes, MB-905 reduced virus replication, IL-6 and TNFα levels. MB-905 is converted into its triphosphate nucleotide to inhibit viral RNA synthesis and induce error-prone virus replication. Coinhibition of SARS-CoV-2 exonuclease, a proofreading enzyme that corrects erroneously incorporated nucleotides during viral RNA replication, potentiated the inhibitory effect of MB-905. MB-905 shows good oral absorption, its metabolites are stable, achieving long-lasting plasma and lung concentrations, and this drug is not mutagenic nor cardiotoxic in acute and chronic treatments. SARS-CoV-2-infected hACE-mice and hamsters treated with MB-905 show decreased viral replication, lung necrosis, hemorrhage and inflammation. Because kinetin is clinically investigated for a rare genetic disease at regimens beyond the predicted concentrations of antiviral/anti-inflammatory inhibition, our investigation suggests the opportunity for the rapid clinical development of a new antiviral substance for the treatment of COVID-19.
Efficient quantum information probes of nonequilibrium quantum criticality
Authors: M. Oliveira Miguel , Ribeiro Pedro , Kirchner Stefan
Published: January 2023

Quantum information-based approaches, in particular the fidelity, have been flexible probes for phase boundaries of quantum matter. A major hurdle to a more widespread application of fidelity and other quantum information measures to strongly correlated quantum materials is the inaccessibility of the fidelity susceptibility to most state-of-the-art numerical methods. This is particularly apparent away from equilibrium where, at present, no general critical theory is available and many standard techniques fail. Motivated by the usefulness of quantum information-based measures we show that a widely accessible quantity, the single-particle affinity, is able to serve as a versatile instrument to identify phase transitions beyond Landau’s paradigm. We demonstrate that it not only is able to signal previously identified nonequilibrium phase transitions but also has the potential to detect hitherto unknown phases in models of quantum matter far from equilibrium.
Embankment deformation characteristics analysis of an expressway widening project near a pond
Authors: Wu Chunwei , Zhang Dufeng , Xia Han , Luo Junhui , Huang Haifeng , Qin Da
Published: January 2023

New and old subgrade stability is a crucial problem for widening projects in soft soil foundations because uncoordinated deformations can cause serious engineering accidents, even disasters. In order to ensure the stability of a widening expressway project near a pond in the Qinbei section, a series of on-site investigations, lab tests, and numerical analyses was performed. The settlement and displacement of on-site monitoring were carried out during the construction period to verify the analyzed results. It was found that the uneven settlement caused heavy settlement and displacement of the embankment; thus, net cracks and longitudinal cracks occurred in the expressway. The new embankment was also affected by the weak foundation; therefore, the foundation should be reinforced before the construction of the widening part. Considering the economy and effectiveness of the widening project, the replacement method was recommended for the weak foundation reinforcement based on the numerical analysis and on-site motoring results. Water pumping had a significant effect on the settlement of the embankment. Water pumping caused seepage in the foundation and increased the effective stress of the soil, making the foundation more consolidated. The pond slope should be reinforced before the construction of the embankment because it was not confined by the surrounding soil. Therefore, the slope soil could not provide sufficient passive soil pressure and easily slide.
Reinfection rate in a cohort of healthcare workers over 2 years of the COVID-19 pandemic
Authors: Guedes Ana Rubia , Oliveira Maura S. , Tavares Bruno M. , Luna-Muschi Alessandra , Lazari Carolina dos Santos , Montal Amanda C. , de Faria Elizabeth , Maia Fernando Liebhart , Barboza Antonio dos Santos , Leme Mariana Deckers , Tomazini Francis M. , Costa Silvia Figueiredo , Levin Anna S.
Published: January 2023

In this large cohort of healthcare workers, we aimed to estimate the rate of reinfections by SARS-CoV-2 over 2 years of the COVID-19 pandemic. We investigated the proportion of reinfections among all the cases of SARS-CoV-2 infection from March 10, 2020 until March 10, 2022. Reinfection was defined as the appearance of new symptoms that on medical evaluation were suggestive of COVID-19 and confirmed by a positive RT-PCR. Symptoms had to occur more than 90 days after the previous infection. These 2 years were divided into time periods based on the different variants of concern (VOC) in the city of São Paulo. There were 37,729 medical consultations due to COVID-19 at the hospital’s Health Workers Services; and 25,750 RT-PCR assays were performed, of which 23% (n = 5865) were positive. Reinfection by SARS-CoV-2 was identified in 5% (n = 284) of symptomatic cases. Most cases of reinfection occurred during the Omicron period (n = 251; 88%), representing a significant increase on the SARS-CoV-2 reinfection rate before and during the Omicron variant period (0.8% vs. 4.3%; p < 0.001). The mean interval between SARS-CoV-2 infections was 429 days (ranged from 122 to 674). The Omicron variant spread faster than Gamma and Delta variant. All SARS-CoV-2 reinfections were mild cases.
Genomic analysis as a tool to infer disparate phylogenetic origins of dysembryoplastic neuroepithelial tumors and their satellite lesions
Authors: Lee Yeajina , Yang Jeyul , Choi Seung Ah , Kim Seung‐Ki , Park Sung-Hye , Park Hyun Joo , Kim Jong-Il , Phi Ji Hoon
Published: January 2023

Dysembryoplastic neuroepithelial tumor (DNET) is a low-grade brain tumor commonly associated with drug-resistant epilepsy. About half of DNETs are accompanied by tiny nodular lesions separated from the main mass. The existence of these satellite lesions (SLs) has shown a strong association with tumor recurrence, suggesting that they are true tumors. However, it is not known whether SLs represent multiple foci of progenitor tumor cell extension and migration or a multifocal development of the main DNET. This study was designed to elucidate the histopathology and pathogenesis of SLs in DNETs. Separate biopsies from the main masses and SLs with DNET were analyzed. We performed comparative lesion sequencing and phylogenetic analysis. FGFR1 K656E and K655I mutations or duplication of the tyrosine kinase domain was found in all 3 DNET patients and the main masses and their SLs shared the same FGFR1 alterations. The phylogenic analysis revealed that the SLs developed independently from their main masses. It is possible that the main mass and its SLs were separated at an early stage in oncogenesis with shared FGFR1 alterations, and then they further expanded in different places. SLs of DNET are true tumors sharing pathogenic mutations with the main masses. It is plausible that multifocal tumor development takes place in the dysplastic cortex containing cells with a pathogenic genetic alteration.
Automatic segmentation and measurement of pressure injuries using deep learning models and a LiDAR camera
Authors: Liu Tom J. , Wang Hanwei , Christian Mesakh , Chang Che-Wei , Lai Feipei , Tai Hao-Chih
Published: January 2023

Pressure injuries are a common problem resulting in poor prognosis, long-term hospitalization, and increased medical costs in an aging society. This study developed a method to do automatic segmentation and area measurement of pressure injuries using deep learning models and a light detection and ranging (LiDAR) camera. We selected the finest photos of patients with pressure injuries, 528 in total, at National Taiwan University Hospital from 2016 to 2020. The margins of the pressure injuries were labeled by three board-certified plastic surgeons. The labeled photos were trained by Mask R-CNN and U-Net for segmentation. After the segmentation model was constructed, we made an automatic wound area measurement via a LiDAR camera. We conducted a prospective clinical study to test the accuracy of this system. For automatic wound segmentation, the performance of the U-Net (Dice coefficient (DC): 0.8448) was better than Mask R-CNN (DC: 0.5006) in the external validation. In the prospective clinical study, we incorporated the U-Net in our automatic wound area measurement system and got 26.2% mean relative error compared with the traditional manual method. Our segmentation model, U-Net, and area measurement system achieved acceptable accuracy, making them applicable in clinical circumstances.
Examination of human osteoarchaeological remains as a feasible source of polar and apolar metabolites to study past conditions
Authors: Badillo-Sanchez Diego , Ruber Maria Serrano , Davies-Barrett Anna M. , Sandhu Jatinderpal K. , Jones Donald J. L. , Hansen Martin , Inskip Sarah A.
Published: January 2023

Metabolomics is a modern tool that aids in our understanding of the molecular changes in organisms. Archaeological science is a branch of archaeology that explores different archaeological materials using modern analytical tools. Human osteoarchaeological material are a frequent finding in archaeological contexts and have the potential to offer information about previous human populations, which can be illuminating about our current condition. Using a set of samples comprising different skeletal elements and bone structures, here we explore for the first time the possibility of extracting metabolites from osteoarchaeological material. Here, a protocol for extraction and measurement of extracted polar and less-polar/apolar metabolites by ultra-high performance liquid chromatography hyphenated to high resolution mass spectrometry is presented to measure the molecules separated after a reversed phase and hydrophilic interaction liquid chromatography column. Molecular information was obtained, showing that osteoarchaeological material is a viable source of molecular information for metabolomic studies.
Predictive impact of different acute cannabis intoxication effects with regard to abstinence motivation and cessation of use
Authors: Schnell Thomas , Grömm Christina-Marie , Klöckner Nils
Published: January 2023

Cannabis use is a common risk factor for psychoses. But although prevalence of consumption as well as potency of cannabis increased, the incidence of schizophrenia remained stable. The discontinuation hypothesis suggests that a potential increase of psychoses incidence may be relativized by more frequent cessation of consumption due to higher rates of adverse psychosis-like intoxication effects (PLE), caused by stronger cannabis. A mixed methods online survey was administered to 441 current and past users to analyze the predictive impact of different acute intoxication effects regarding abstinence motivation/cessation of use. Our hypothesis was that PLE would be experienced as the most aversive intoxication effect and therefore have the highest predictive significance. Possible confounds were included (craving, patterns of consumption and sociodemographics). Further analyzes compared past versus current users regarding the quality of intoxication effects, suggesting that past users retrospectively experienced more unpleasant experiences than current users. Free-text data explored subjective reasons for abstinence. We found that paranoid/dysphoric intoxication effects were most predictive for abstinence motivation. Less predictive were psychosis-like intoxication effects such as hallucinations. Group comparisons revealed significant more unpleasurable and less positive intoxication effects in past users compared with current users. Current users with the intention to stop consumption showed significantly more paranoia/dysphoria intoxication compared to users with no intention to stop use. As a conclusion, different intoxication experiences have different effects on abstinence motivation and substance use behavior. They therefore provide a focus that should be increasingly integrated into treatment concepts.
Partial COVID-19 closure of a national park reveals negative influence of low-impact recreation on wildlife spatiotemporal ecology
Authors: Anderson Alissa K. , Waller John S. , Thornton Daniel H.
Published: January 2023

Human presence exerts complex effects on the ecology of species, which has implications for biodiversity persistence in protected areas experiencing increasing human recreation levels. However, the difficulty of separating the effect on species of human presence from other environmental or disturbance gradients remains a challenge. The cessation of human activity that occurred with COVID-19 restrictions provides a ‘natural experiment’ to better understand the influence of human presence on wildlife. Here, we use a COVID-19 closure within a heavily visited and highly protected national park (Glacier National Park, MT, USA) to examine how ‘low-impact’ recreational hiking affects the spatiotemporal ecology of a diverse mammal community. Based on data collected from camera traps when the park was closed and then subsequently open to recreation, we found consistent negative responses to human recreation across most of our assemblage of 24 species, with fewer detections, reduced site use, and decreased daytime activity. Our results suggest that the dual mandates of national parks and protected areas to conserve biodiversity and promote recreation have potential to be in conflict, even for presumably innocuous recreational activities. There is an urgent need to understand the fitness consequences of these spatiotemporal changes to inform management decisions in protected areas.