bluuebunny/crossref_metadata_2025 huggingface dataset:
Geological structure of karst stratigraphical windows at Škocjan Caves, Slovenia
Authors: Šebela Stanka , Novak Uroš
Published: March 2023

Within the UNESCO Škocjan Caves, detailed geological structural mapping of the cave passages and of the surface above the cave revealed interesting structural-lithological characteristics of two major collapse dolines, Velika Dolina and Mala Dolina. As a result of the karst processes effects and the formation of collapse dolines, older—stratigraphically lower—carbonates of the Sežana Formation (K22−4) crop out at the surface, underlying rocks of the younger Lipica Formation (K24−5). Here we do not recognize karst windows only in a geomorphological sense but, acknowledging the characteristic lithostratigraphical relationships involved, we suggest use of the new expression “karst stratigraphical window”. Recognizing that karstic areas contain numerous collapse dolines and other doline types, we presume that many more examples of karst stratigraphical windows exist, and that these are distinct from tectonic windows. Our study showed the importance that during the making of detailed geological surface maps of karst areas, it is essential to examine features such as collapse dolines, which may be identified as karst stratigraphical windows. Therefore, providing additional geological data, information about the stratigraphic boundaries and geological structure, in areas without abundance of outcropping rocks is resulting in a more inclusive and comprehensive geological maps.
From total quality management to Quality 4.0: A systematic literature review and future research agenda
Authors: Liu Hu-Chen , Liu Ran , Gu Xiuzhu , Yang Miying
Published: March 2023

Quality 4.0 is an emerging concept that has been increasingly appreciated because of the intensification of competition, continually changing customer requirements and technological evolution. It deals with aligning quality management practices with the emergent capabilities of Industry 4.0 to improve cost, time, and efficiency and increase product quality. This article aims to comprehensively review extant studies related to Quality 4.0 to uncover current research trends, distil key research topics, and identify areas for future research. Thus, 46 journal articles extracted from the Scopus database from 2017 to 2022 were collected and reviewed. A descriptive analysis was first performed according to the year-wise publication, sources of publication, and research methods. Then, the selected articles were analyzed and classified according to four research themes: Quality 4.0 concept, Quality 4.0 implementation, quality management in Quality 4.0, and Quality 4.0 model and application. By extracting the literature review findings, we identify the Quality 4.0 definitions and features, develop the quality curve theory, and highlight future research opportunities. This study supports practitioners, managers, and academicians in effectively recognizing and applying Quality 4.0 to enhance customer satisfaction, achieve innovation enterprise efficiency, and increase organizational competitiveness in the era of Industry 4.0.
Regulated adsorption sites using atomically single cluster over biochar for efficient elemental mercury uptake
Authors: Li Jiaxing , Li Hongli , Xu Haomiao , Hong Qinyuan , Ji Leipeng , Liu Zhisong , Qiu Yixiang , Huang Wenjun , Yan Naiqiang , Qu Zan
Published: March 2023

Carbon-based materials have been widely used in gaseous pollutant removal because of their sufficient surface functional groups; however, its removal efficiency for elemental mercury (Hg0) is low. In this study, we fabricated biomass using a chelated coupled pyrolysis strategy and further constructed the regulated adsorption sites for gaseous Hg0 uptake. A series of Mnδ-N2O2/BC with different manganese cluster sizes demonstrated that manganese clusters anchored on biochar acted as highly active and durable adsorbents for Hg0 immobilization, which increased the adsorption efficiency of Hg0 by up to 50%. Shrimp- and crab-based biochar adsorbents exhibited excellent Hg0 removal because of their chitosan-like structure. In particular, small Mn clusters and oxygen species around the defect led to a boost in the Hg0 adsorption by carbon. The results of density functional theory calculation revealed that the presence of oxygen in the carbon skeleton can tune the electrons of small-sized Mn clusters, thereby promoting the affinity of mercury atoms. The newly developed Mnδ-N2O2/BCshrimp had an adsorption capacity of 7.98–11.52 mg g−1 over a broad temperature range (50–200 °C) and showed a high tolerance to different industrial flue gases (H2O, NO, HCl, and SO2). These results provide novel green and low-carbon disposal methods for biomass resource utilization and industrial Hg0 emission control.

Graphical Abstract
Multifaceted applications of biochar in environmental management: a bibliometric profile
Authors: Kumar Abhishek , Bhattacharya Tanushree , Shaikh Wasim Akram , Roy Arpita , Chakraborty Sukalyan , Vithanage Meththika , Biswas Jayanta Kumar
Published: March 2023

Biochar is a carbon-containing material prepared through thermal treatment of biomass in limited supply of oxygen, and used for an array of applications including waste management, climate change mitigation, soil fertility improvement, bio-energy production, and contaminant remediation. The data related to biochar, its production, and the wide applicability were collected using Web of Science Core Collection Database (on 25/10/2022), while bibliometric network analysis was performed using VOSviewer software to analyse year-wise, author-wise, country-wise, and journal-wise publication trends, construct keyword co-occurrence maps, and identify research areas receiving greater focus. Further, the applications of biochar were reviewed and mechanistic insights were provided. Some of the findings include: > 50% of documents (> 13,000) getting published in the past 3 years, > 90% of documents (> 21,000) being research articles, ~ 50% of publications (> 10,000) being related to environmental sciences, pyrolysis being the most widely used (~ 40% articles) production technique (followed by carbonization, gasification, combustion, and torrefaction), China being the most active country in terms of publications (> 11,000), and biochar being mostly used for removing contaminants (followed by soil improvement, waste management, energy production, and climate change mitigation). Various strengths, weaknesses, opportunities, and threats (SWOT analysis) of biochar production and wide-ranging applicability were identified. Lastly, gaps were identified including the need for performing elaborate life cycle assessments, exploring machine learning and artificial intelligence for upgrading conversion technology and producing application-specific biochar, and investigating mechanistic aspects of soil-biochar interactions and nano-scale transformation of biochar. The study covers a broad spectrum of biochar applicability to identify areas receiving lesser attention, which could guide the future researchers for augmenting biochar research.

Graphical Abstract
Machine learning-based seismic response and performance assessment of reinforced concrete buildings
Authors: Kazemi F. , Asgarkhani N. , Jankowski R.
Published: March 2023

Complexity and unpredictability nature of earthquakes makes them unique external loads that there is no unique formula used for the prediction of seismic responses. Hence, this research aims to implement the most well-known Machine Learning (ML) methods in Python software to propose a prediction model for seismic response and performance assessment of Reinforced Concrete Moment-Resisting Frames (RC MRFs). To prepare 92,400 data points of training dataset for developing data-driven techniques, Incremental Dynamic Analyses (IDAs) were performed considering 165 RC MRFs with two-, to twelve-Story elevations having the bay lengths of 5.0 m, 6.1 m, and 7.6 m assuming near-fault seismic excitations. Then, important structural features were considered in datasets to train and test the ML-based prediction models, which were improved with innovative techniques. The results show that improved algorithms have higher R
2 values for estimating the Maximum Interstory Drift Ratio (IDRmax), and two improved algorithms of artificial neural networks and extreme gradient boosting can estimate the Median of IDA curves (M-IDAs) of RC MRFs, which can be used to estimate the seismic limit-state capacity and performance assessment of existing or newly constructed RC buildings. To validate the generality and accuracy of the proposed ML-based prediction model, a five-Story RC building with different input features was used, and the results are promising. Therefore, graphical user interface is introduced as user-friendly tool to help researchers in estimating the seismic limit-state capacity of RC buildings, while reducing the computational cost and analytical efforts.
Effect of integrated sustainable land management technologies on households’ food security in the North Gojjam sub-basin, Blue Nile River
Authors: Ewunetu Alelgn , Simane Belay , Abebe Gebeyehu
Published: March 2023

Integrated Sustainable Land Management (ISLM) is progressively viewed as a key strategy to boost food security in Ethiopia and feed its growing population. By understanding this logical ground, this paper examines the effect of ISLM technologies adoption on household food security. The study relies on cross-sectional household-level data collected from 414 randomly selected household heads across three districts to analyze this issue. An Endogenous Switching Regression (ESR) model coupled with the Full Information Maximum Likelihood (FIML) technique was applied to analyze the required data. The finding shows that the adoption of ISLM technologies has significantly increased food security. It specifically increases food consumption expenditure in households by ETB (national currency in Ethiopia; as of August 2021, 1 ETB is equal to approximately USD $0.02) 38.3 (27%) when compared to households that do not adopt groups. Similarly, it increases the adopter households’ dietary diversity by 14.5%. Furthermore, it plays a significant role in reducing the food gap period by one and a half months per year and the food insecurity access scale by 46% points in the north Gojjam sub-basin for those who adopted versus those who did not adopt. The policy implication is that the adoption of ISLM technologies can improve rural household food security and may be used as a means of reducing rural poverty. As a result, the adoption of ISLM technologies should have been promoted in the study area and elsewhere by inspiring land users by accessing external agricultural inputs at the right time and place to increase small-scale land productivity.
Kramer-type sampling theorems associated with higher-order differential equations
Authors: Markett Clemens
Published: March 2023

For many decades, Kramer’s sampling theorem has been attracting enormous interest in view of its important applications in various branches. In this paper we present a new approach to a Kramer-type theory based on spectral differential equations of higher order on an interval of the real line. Its novelty relies partly on the fact that the corresponding eigenfunctions are orthogonal with respect to a scalar product involving a classical measure together with a point mass at a finite endpoint of the domain. In particular, a new sampling theorem is established, which is associated with a self-adjoint Bessel-type boundary value problem of fourth-order on the interval [0, 1]. Moreover, we consider the Laguerre and Jacobi differential equations and their higher-order generalizations and establish the Green-type formulas of the differential operators as an essential key towards a corresponding sampling theory.
Carbon dioxide capture from the Kraft mill limekiln: process and techno-economic analysis
Authors: Parkhi Amod , Young David , Cremaschi Selen , Jiang Zhihua
Published: March 2023

In this work, a techno-economic assessment of carbon dioxide capture from limekiln flue gas of a pulp and paper mill (Mill A) and a linerboard mill (Mill B) using a Monoethanolamine (MEA) absorption desorption process was carried out. We coupled the ASPEN Plus simulator with a derivative-free optimization (DFO) tool to identify the optimal configuration for minimizing the total capture cost. The capture costs were calculated using CAPCOST, a modular program for equipment cost estimation, and appropriate coefficients. Eight degrees of freedom, the direct contact cooler stages, the absorber stages, the stripper stages, the solvent lean loading, the solvent weight concentration, the stripper inlet temperature, the flue gas inlet temperature, and the amount of CO2 captured, were selected for process and flowsheet optimization. Additionally, we evaluated the effect of steam integration and Sect. 45Q of the existing federal tax credit for carbon capture and sequestration on CO2 capture costs. The total capture costs per tonne of CO2 were $64.9 for Mill A and $69.7 for Mill B. When steam integration and Sect. 45Q are considered, the costs dropped to − $2.5 and $2.6 for Mill A and Mill B, respectively. The sensitivity of CO2 capture cost to changes in the inlet flue gas flowrate, flue gas CO2 mol%, and the electricity and MEA prices were investigated. The sensitivity analysis results revealed that the capture costs vary from − $5.9 to $5.9 per tonne of CO2 captured.
Design methodology of standing-wave thermoacoustic refrigerator: theoretical analysis
Authors: Kamil Mohanad Q. , Yahya Samir Gh. , Azzawi Itimad D. J.
Published: March 2023

Thermoacoustic refrigeration systems are one of the best alternative solutions for conventional refrigeration systems that are harmful to the environment and humans due to global warming and ozone layer depletion issues. Thermoacoustic technology can be considered a renewable and clean technology with a promising future for its many advantages. A thermoacoustic refrigerator converts acoustic energy to thermal energy (creating a cooling effect). In the present research, the focus is on the design of a standing-wave thermoacoustic refrigerator driven by an ordinary loudspeaker using the numerical simulation program DELTAEC with the concern of building the apparatus at a low cost. In addition, investigating the influence of some crucial parameters on cooling power and thermal/overall performance. Hence, the designed thermoacoustic refrigerator performed well in respect of cooling power and coefficient of performance. It has achieved a cooling power of 134.34 W with a temperature difference between the ambient and cold heat exchangers of 25 K at a COP of 1.956 and the overall efficiency (electrical power converted into cooling power) amounted to 113.43%. The achieved cooling power and COP could be significant when compared to others’ results.
Unsupervised Ensemble Learning Improves Discriminability of Stochastic Neighbor Embedding
Authors: Wang Jian , Zhao Hui , Zhang Yinghui , Wang Hongjun , Guo Jin
Published: March 2023

The purpose of feature learning is to obtain effective representation of the raw data and then improve the performance of machine learning algorithms such as clustering or classification. Some of the existing feature learning algorithms use discriminant information in the data to improve the representation of data features, but the discrimination of the data feature representation is not enough. In order to further enhance the discrimination, discriminant feature learning based on t-distribution stochastic neighbor embedding guided by pairwise constraints (pcDTSNE) is proposed in this paper. pcDTSNE introduces pairwise constraints by clustering ensemble and uses these pairwise constraints to impose penalties on the objective function, which makes sample points in the mapping space present stronger discrimination. In order to verify the feature learning performance of pcDTSNE, extensive experiments are carried out on several public data sets. The experimental results show that the expression ability of data representation generated by pcDTSNE is further improved.
Effect of Non-pharmaceutical Interventions on COVID-19 in Rwanda: An Observational Study
Authors: Rwagasore Edson , Nsekuye Olivier , Rutagengwa Alfred , El-Khatib Ziad
Published: March 2023

Background

On 11 March 2020, COVID-19 was declared as a pandemic by the World Health Organization (WHO). The first case was identified in Rwanda on 24 March 2020. Three waves of COVID-19 outbreak have been observed since the identification of the first case in Rwanda. During the COVID-19 epidemic, the country of Rwanda has implemented many Non-Pharmaceutical Interventions (NPIs) that appear to be effective. However, a study was needed to investigate the effect of non-pharmaceutical interventions applied in Rwanda to guide ongoing and future responses to epidemics of this emerging disease across the World.

Methods

A quantitative observational study was conducted by conducting analysis of COVID-19 cases reported daily in Rwanda from 24 March 2020 to 21 November 2021. Data used were obtained from the official Twitter account of Ministry Health and the website of Rwanda Biomedical Center. Frequencies of COVID-19 cases and incidence rates were calculated, and to determine the effect of non-pharmaceutical interventions on changes in COVID-19 cases an interrupted time series analysis was used.

Results

Rwanda has experienced three waves of COVID-19 outbreak from March 2020 to November 2021. The major NPIs applied in Rwanda included lockdowns, movement restriction among districts and Kigali City, and curfews. Of 100,217 COVID-19 confirmed cases as of 21 November 2021, the majority were female 51,671 (52%) and 25,713 (26%) were in the age group of 30–39, and 1866 (1%) were imported cases. The case fatality rate was high among men (n = 724/48,546; 1.5%), age > 80 (n = 309/1866; 17%) and local cases (n = 1340/98,846; 1.4%). The interrupted time series analysis revealed that during the first wave NPIs decreased the number of COVID-19 cases by 64 cases per week. NPIs applied in the second wave decreased COVID-19 cases by 103 per week after implementation, while in the third wave after NPIs implementation, a significant decrease of 459 cases per week was observed.

Conclusion

The early implementation of lockdown, restriction of movements and putting in place curfews may reduce the transmission of COVID-19 across the country. The NPIs implemented in Rwanda appear to be effectively containing the COVID-19 outbreak. Additionally, setting up the NPIs early is important to prevent further spread of the virus.
Trustworthy artificial intelligence
Authors: Simion Mona , Kelp Christoph
Published: March 2023

This paper develops an account of trustworthy AI. Its central idea is that whether AIs are trustworthy is a matter of whether they live up to their function-based obligations. We argue that this account serves to advance the literature in a couple of important ways. First, it serves to provide a rationale for why a range of properties that are widely assumed in the scientific literature, as well as in policy, to be required of trustworthy AI, such as safety, justice, and explainability, are properties (often) instantiated by trustworthy AI. Second, we connect the discussion on trustworthy AI in policy, industry, and the sciences with the philosophical discussion of trustworthiness. We argue that extant accounts of trustworthiness in the philosophy literature cannot make proper sense of trustworthy AI and that our account compares favourably with its competitors on this front.
Preparation of reed straw hydrochar adsorbent and its environmental impact assessment
Authors: Wang Jing , Zang Yufei , Zhang Jiawen , Chen Feiyong , Liu Guanhong , Liu Bing , Matsumoto Toru
Published: March 2023

Hydrothermal carbonization technology has attracted increasingly the amount of attention due to its efficient conversion of biomass resources. Such technology benefits both the economy and the environment. In this study, hydrothermal carbonization of reed was conducted in a hydrothermal reactor under laboratory conditions. The factors that control the hydrochar yield and the efficiency of methylene blue adsorption, such as temperature, residence time, and solid-liquid ratio were investigated. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the structure of the reed hydrochar. The experimental results indicated that the order of the factors affecting hydrochar yield was as follows: residence time > maximum temperature > solid-liquid ratio. The order of factors that determine the extent of methylene blue adsorption was: solid-liquid ratio > maximum temperature > residence time. The optimum condition for hydrochar production was with a reaction temperature at 260 °C, a residence time of 2 h, and a solid-liquid ratio of 1:10. The optimum condition for the highest amount of methylene blue adsorption was with a reaction temperature at 260 °C, a residence time of 1 h, and a solid-liquid ratio of 1:10. The SEM imaging revealed a pore structure at the surface of the hydrochar comprising carbon microspheres and multilayer structure. Whereas the FTIR analysis indicated that the hydrochar had a high number of oxygen-containing surface functional groups. The environmental impact of the reed hydrochar preparation process was evaluated using the life cycle assessment approach by the SimaPro 9.2.0.2 software. The results revealed that the hydrothermal carbonization process majorly impacted the toxicity to the environment, the land use and the global warming. Future optimization of the hydrothermal carbonization process should focus on: (1) reducing the energy consumption during this process; (2) evaluating the environmental impact of the hydrochar-producing system, including the resource recycling of the by-products during this process.
Outcome of Stem Cell Transplantation in HTLV-1-Associated North American Adult T-Cell Leukemia/Lymphoma
Authors: Bazarbachi Abdul-Hamid , Reef Daniel , Narvel Hiba , Patel Riya , Al Hamed Rama , Vikash Sindhu , Neupane Karun , Atalla Eleftheria , Thakkar Astha , Rahman Shafia , Shah Urvi , Adrianzen-Herrera Diego , Quinn Ryann , Zareef Sumaira , Rabinovich Emma , De Castro Alyssa , Joseph Felisha , Gillick Kailyn , Mustafa Jennat , Khatun Fariha , Lombardo Amanda , Townsend-Nugent Latoya , Abreu Michelly , Chambers Nicole , Elkind Richard , Shi Yang , Wang Yanhua , Derman Olga , Gritsman Kira , Steidl Ulrich , Goldfinger Mendel , Kornblum Noah , Shastri Aditi , Mantzaris Ioannis , Bachier-Rodriguez Liza , Shah Nishi , Cooper Dennis , Verma Amit , Ye Bihui Hilda , Janakiram Murali , Sica Roberto Alejandro
Published: March 2023

Adult T-cell leukemia/lymphoma (ATLL) remains challenging to treat and has dismal outcome. Allogeneic stem-cell transplantation (allo-SCT) has promising results, but data remain scarce. In this single-center retrospective analysis of 100 patients with ATLL from north America (67 acute, 22 lymphomatous), 17 underwent allo-SCT and 5 autologous SCT (ASCT), with a median follow-up of 65 months. Post-transplant 3-years relapse incidence (RI) and non-relapse mortality (NRM) were 51% and 37%, respectively, and 3-year progression-free survival (PFS) and overall survival (OS) were 31% and 35%, respectively. ASCT 1-year RI was 80% compared to 30% in allo-SCT (p = 0.03). After adjusting for immortal-time bias, allo-SCT had significantly improved OS (HR = 0.4, p = 0.01). In exploratory multivariate analysis, patients achieving first complete response and Karnofsky score ≥ 90 had significantly better outcomes, as did Black patients, compared to Hispanics, who had worse outcome. In transplanted patients, 14 died within 2 years, 4 of which ASCT recipients. Our data are the largest ATLL transplant cohort presented to date outside of Japan and Europe. We show that allo-SCT, but not ASCT, is a valid option in select ATLL patients, and can induce long term survival, with 40% of patients alive after more than 5 years.
Formation of Electron Zebra Stripes Observed on 8 September 2017
Authors: Pandya Megha , Ebihara Yusuke , Tanaka Takashi , Manweiler Jerry W.
Published: March 2023

Zebra stripes are the characteristic structures having repeated hills and valleys in the electron flux intensities observed below L = 3. We delineate the fundamental properties and evolution of electron zebra stripes by modeling advection using time‐dependent electric fields provided by a global magnetohydrodynamics simulation. At the beginning of the simulation, the electrons were uniformly distributed in longitude. Some electrons moved inward due to enhanced westward electric field transients in the premidnight‐postdawn region. The inwardly displaced electrons were confined in a narrow longitudinal range and underwent grad‐B and curvature drifts. For any specific fixed position, the electrons periodically passed through the point with an energy dependent period, giving rise to the hills and valleys in the electron differential flux also known as zebra stripes. The valleys of the zebra stripes are composed of the electrons that underwent outward displacement, or no significant radial displacement. On the nightside, the duskside convection cell is skewed toward dawn in the equatorward of the auroral oval, and the westward electric field becomes dominant in the postdawn region, which results in the inward motion of the electrons. The spatial distribution of the westward electric field is consistent with observation. Zebra stripes are a mixture of the electrons that have and have not experienced inward transport due to solar wind‐inner magnetosphere coupling by way of the ionosphere.
Reducing the Ionospheric Contamination Effects on the Column O/N2 Ratio and Its Application to the Identification of Non‐Migrating Tides
Authors: Krier Christopher S. , England Scott L. , Meier R. R. , Frey Harald U.
Published: March 2023

Prior investigations have attempted to characterize the longitudinal variability of the column number density ratio of atomic oxygen to molecular nitrogen (O/N2) in the context of non‐migrating tides. The retrieval of thermospheric O/N2 from far ultra‐violet (FUV) emissions assumes production is due to photoelectron impact excitation on O and N2. Consequently, efforts to characterize the tidal variability in O/N2 have been limited by ionospheric contamination from O+ + e radiative recombination at afternoon local times (LT) around the equatorial ionization anomaly. The retrieval of O/N2 from FUV observations by the Ionospheric Connection Explorer (ICON) provides an opportunity to address this limitation. In this work, we derive modified O/N2 datasets to delineate the response of thermospheric composition to non‐migrating tides as a function of LT in the absence of ionospheric contamination. We assess estimates of the ionospheric contribution to 135.6 nm emission intensities based on either Global Ionospheric Specification (GIS) electron density, International Reference Ionosphere (IRI) model output, or observations from the Extreme Ultra‐Violet imager (EUV) onboard ICON during March and September equinox conditions in 2020. Our approach accounts for any biases between the ionospheric and airglow datasets. We found that the ICON‐FUV data set, corrected for ionospheric contamination based on GIS, uncovered a previously obscured diurnal eastward wavenumber 2 tide in a longitudinal wavenumber 3 pattern at March equinox in 2020. This finding demonstrates not only the necessity of correcting for ionospheric contamination of the FUV signals but also the utility of using GIS for the correction.
Height Determination of a Blue Discharge Observed by ASIM/MMIA on the International Space Station
Authors: Bai Xue , Füllekrug Martin , Chanrion Olivier , Soula Serge , Peverell Adam , Mashao Dakalo , Kosch Michael , Husbjerg Lasse , Østgaard Nikolai , Neubert Torsten , Reglero Victor
Published: March 2023

We analyze simultaneous photometric observations of thundercloud discharges from the Modular Multispectral Imaging Array of the Atmosphere‐Space Interactions Monitor (ASIM) on board the International Space Station with ground‐based vertical electric field measurements in South Africa on 3 February 2019 at 23:00–23:05 UTC. During this time, ASIM flew over an extended thunderstorm front of several hundreds of kilometers and recorded a blue discharge with the photometer at 337 nm which emitted strong electric fields. It is found that the rising edge of the blue photomultiplier tube light pulse allows the estimation of the blue discharge height: ∼10.9–16.5 km which is constrained by cloud top height in a range of ∼13.3–16.7 km deduced from infrared radiometry on board the geostationary Meteosat satellite. The electric field measurements are used to infer the height of the blue discharge to be ∼16.0–18.8 km by use of skywave arrival times. It is shown that the height determinations are consistent with each other within the measurement uncertainties and the possible presence of an overshooting cloud top is discussed. The height of blue discharges is important to better understand how they can affect the chemistry in the upper troposphere.
CAR links hypoxia signaling to improved survival after myocardial infarction
Authors: Freiberg Fabian , Thakkar Meghna , Hamann Wiebke , Lopez Carballo Jacobo , Jüttner Rene , Voss Felizia K. , Becher Peter M. , Westermann Dirk , Tschöpe Carsten , Heuser Arnd , Rocks Oliver , Fischer Robert , Gotthardt Michael
Published: March 2023

The coxsackievirus and adenovirus receptor (CAR) mediates homo- and heterotopic interactions between neighboring cardiomyocytes at the intercalated disc. CAR is upregulated in the hypoxic areas surrounding myocardial infarction (MI). To elucidate whether CAR contributes to hypoxia signaling and MI pathology, we used a gain- and loss-of-function approach in transfected HEK293 cells, H9c2 cardiomyocytes and CAR knockout mice. CAR overexpression increased RhoA activity, HIF-1α expression and cell death in response to chemical and physical hypoxia. In vivo, we subjected cardiomyocyte-specific CAR knockout (KO) and wild-type mice (WT) to coronary artery ligation. Survival was drastically improved in KO mice with largely preserved cardiac function as determined by echocardiography. Histological analysis revealed a less fibrotic, more compact lesion. Thirty days after MI, there was no compensatory hypertrophy or reduced cardiac output in hearts from CAR KO mice, in contrast to control mice with increased heart weight and reduced ejection fraction as signs of the underlying pathology. Based on these findings, we suggest CAR as a therapeutic target for the improved future treatment or prevention of myocardial infarction.
Social disadvantage during pregnancy: effects on gestational age and birthweight
Authors: Luby Joan L. , England Sarah K. , Barch Deanna M. , Warner Barbara B. , Rogers Cynthia , Smyser Christopher D. , Triplett Regina , Arora Jyoti , Smyser Tara A. , Slavich George M. , Zhao Peinan , Stout Molly , Herzog Erik , Miller J. Philip
Published: March 2023

Objective

Whether psychosocial adversity during pregnancy impacts fetal health outcomes at birth remains underexplored. This is a critical issue given significant social disadvantage and psychosocial stress faced by pregnant women worldwide.

Study design

Measures of social disadvantage and psychological factors, and medical/reproductive and nutritional health status in pregnant women were obtained at each trimester. Using Structural Equation Modeling (SEM), we investigated the relationship of forms of adversity to each other and to infant gestational age, and birthweight.

Results

Among 399 singletons, Social Disadvantage significantly predicted gestational age (p = 0.003), and residual birthweight (p = 0.006). There was a 0.4 week decrease in gestational age and a 3% decrease in birthweight for each standard deviation increase in Social Disadvantage.

Conclusion

Significant negative effects of social adversity on the developing fetus were found. Notably, these effects emerged despite good prenatal care and after accounting for maternal age and medical reproductive risk factors.
Viral inactivation by irradiation rays
Authors: Liu Kai-Kai , Shan Chong-Xin
Published: March 2023

Viral infection can lead to serious illness and death around the world, as exemplified by the spread of COVID-19. Using irradiation rays can inactive virions through ionizing and non-ionizing effect. The application of light in viral inactivation and the underlying mechanisms are reviewed by the research group of Dayong Jin from University of Technology Sydney.
Family-based analysis of the contribution of rare and common genetic variants to school performance in schizophrenia
Authors: Rammos Alexandros , Kirov George , Hubbard Leon , Walters James T. R. , Holmans Peter , Owen Michael J. , O’Donovan Michael C. , Rees Elliott
Published: March 2023

Impaired cognition in schizophrenia is associated with worse functional outcomes. While genetic factors are known to contribute to variation in cognition in schizophrenia, few rare coding variants with strong effects have been identified, and the relative effects from de novo, inherited and non-transmitted alleles are unknown. We used array and exome sequencing data from 656 proband-parent trios to examine the contribution of common and rare variants to school performance, and by implication cognitive function, in schizophrenia. Parental transmission of common alleles contributing to higher educational attainment (p value = 0.00015; OR = 2.63) and intelligence (p value = 0.00009; OR = 2.80), but not to schizophrenia, were associated with higher proband school performance. No significant effects were seen for non-transmitted parental common alleles. Probands with lower school performance were enriched for damaging de novo coding variants in genes associated with developmental disorders (DD) (p value = 0.00026; OR = 11.6). Damaging, ultra-rare coding variants in DD genes that were transmitted or non-transmitted from parents, had no effects on school performance. Among probands with lower school performance, those with damaging de novo coding variants in DD genes had a higher rate of comorbid mild intellectual disability (p value = 0.0002; OR = 15.6). Overall, we provide evidence for rare and common genetic contributions to school performance in schizophrenia. The strong effects for damaging de novo coding variants in DD genes provide further evidence that cognitive impairment in schizophrenia has a shared aetiology with developmental disorders. Furthermore, we report no evidence in this sample that non-transmitted parental common alleles for cognitive traits contributed to school performance in schizophrenia via indirect effects on the environment.
The gut microbiome modulates the transformation of microglial subtypes
Authors: Huang Yu , Wu Jing , Zhang Hanping , Li Yifan , Wen Lu , Tan Xunmin , Cheng Ke , Liu Yiyun , Pu Juncai , Liu Lanxiang , Wang Haiyang , Li Wenxia , Perry Seth W. , Wong Ma-Li , Licinio Julio , Zheng Peng , Xie Peng
Published: March 2023

Clinical and animal studies have shown that gut microbiome disturbances can affect neural function and behaviors via the microbiota–gut–brain axis, and may be implicated in the pathogenesis of several brain diseases. However, exactly how the gut microbiome modulates nervous system activity remains obscure. Here, using a single-cell nucleus sequencing approach, we sought to characterize the cell type–specific transcriptomic changes in the prefrontal cortex and hippocampus derived from germ-free (GF), specific pathogen free, and colonized-GF mice. We found that the absence of gut microbiota resulted in cell-specific transcriptomic changes. Furthermore, microglia transcriptomes were preferentially influenced, which could be effectively reversed by microbial colonization. Significantly, the gut microbiome modulated the mutual transformation of microglial subpopulations in the two regions. Cross-species analysis showed that the transcriptome changes of these microglial subpopulations were mainly associated with Alzheimer’s disease (AD) and major depressive disorder (MDD), which were further supported by animal behavioral tests. Our findings demonstrate that gut microbiota mainly modulate the mutual transformation of microglial subtypes, which may lead to new insights into the pathogenesis of AD and MDD.
Oxytocin effects on amygdala reactivity to angry faces in males and females with antisocial personality disorder
Authors: Jeung-Maarse Haang , Schmitgen Mike M. , Schmitt Ruth , Bertsch Katja , Herpertz Sabine C.
Published: March 2023

The amygdala is a key region in current neurocircuitry models of reactive aggression as it is crucially involved in detecting social threat and provocation. An increased amygdala reactivity to angry faces has been reported in aggression-prone individuals and the neuropeptide oxytocin (OT) could dampen anger-related amygdala reactivity in a number of mental disorders. One example is the antisocial personality disorder (ASPD) which has so far only been studied in limited numbers. To address the question whether OT can normalize amygdala hyperreactivity to emotional faces, we conducted a functional magnetic resonance imaging experiment with 20 men and 18 women with ASPD and 20 male and 20 female healthy control (HC) participants in a double-blind, randomized, placebo (PLC)-controlled within-subject design. Participants were exposed to an emotion classification task (fearful, angry, and happy faces) after receiving an intranasal dose (24 IU) of synthetic OT or PLC. We found OT to attenuate right amygdala hyperactivity to angry faces in participants with ASPD to such an extent that the intensity of amygdala activity in the ASPD group in the OT condition decreased to the level of amygdala activity in the PLC condition in the HC group. There was also a trend that OT effects were generally larger in women than in men. These findings suggest that OT differentially modulates the amygdala following social threatening or provoking cues in dependence of psychopathology (ASPD vs. HC) and sex (male vs. female). Particularly female ASPD patients could benefit from OT in the treatment of reactive aggression.
The D-amino acid oxidase inhibitor luvadaxistat improves mismatch negativity in patients with schizophrenia in a randomized trial
Authors: O’Donnell Patricio , Dong Cheng , Murthy Venkatesha , Asgharnejad Mahnaz , Du Xiaoming , Summerfelt Ann , Lu Hong , Xu Lin , Wendland Jens R. , Dunayevich Eduardo , Buhl Derek L. , Litman Robert , Hetrick William P. , Hong L. Elliot , Rosen Laura B.
Published: March 2023

Several attempts have been made to enhance N-methyl-D-aspartate (NMDA) receptor function in schizophrenia, but they have yielded mixed results. Luvadaxistat, a D-amino acid oxidase (DAAO) inhibitor that increases the glutamate co-agonist D-serine levels, is being developed for the treatment of cognitive impairment associated with schizophrenia. We conducted a biomarker study in patients, assessing several endpoints related to physiological outcomes of NMDA receptor modulation to determine whether luvadaxistat affects neural circuitry biomarkers relevant to NMDA receptor function and schizophrenia. This was a randomized, placebo-controlled, double-blind, two-period crossover phase 2a study assessing luvadaxistat 50 mg and 500 mg for 8 days in 31 patients with schizophrenia. There were no treatment effects of luvadaxistat at either dose in eyeblink conditioning, a cerebellar-dependent learning measure, compared with placebo. We observed a nominally significant improvement in mismatch negativity (MMN) and a statistical trend to improvement for auditory steady-state response at 40 Hz, in both cases with 50 mg, but not with 500 mg, compared with placebo. Although the data should be interpreted cautiously owing to the small sample size, they suggest that luvadaxistat can improve an illness-related circuitry biomarker at doses associated with partial DAAO inhibition. These results are consistent with 50 mg, but not higher doses, showing a signal of efficacy in cognitive endpoints in a larger phase 2, 12-week study conducted in parallel. Thus, MMN responses after a short treatment period may predict cognitive function improvement. MMN and ASSR should be considered as biomarkers in early trials addressing NMDA receptor hypofunction.
Serine/threonine kinase TBK1 promotes cholangiocarcinoma progression via direct regulation of β-catenin
Authors: Gao Chong-Qing , Chu Zhen-Zhen , Zhang Di , Xiao Yang , Zhou Xing-Yan , Wu Jun-Ru , Yuan Hui , Jiang Yu-Chuan , Chen Dong , Zhang Ji-Chun , Yao Nan , Chen Kai-Yun , Hong Jian
Published: March 2023

Cholangiocarcinoma (CCA) is a highly heterogeneous and metastatic malignancy with a poor prognosis even after curative hepatectomy. Studies exploring its pathogenesis and identifying effective therapeutic targets are urgently needed. In this study, we found that TANK-binding kinase 1 (TBK1), a serine/threonine-protein kinase, showed a dynamic increase during the different stages of murine spontaneous CCA carcinogenesis (hyperplasia, dysplasia, and CCA). TBK1 was upregulated in human tissues, including intrahepatic (n = 182) and extrahepatic (n = 40) CCA tissues, compared with nontumor tissues, and the elevated expression of TBK1 was positively correlated with larger tumour diameter, lymph node metastasis, and advanced TNM stage. Functional studies indicated that TBK1 promoted CCA growth and metastasis both in vitro and in vivo. TBK1 directly interacts with β-catenin, promoting its phosphorylation at the S552 site and its nuclear translocation, which further activates EMT-related transcriptional reprogramming. GSK-8612, a TBK1 inhibitor or a kinase-inactivating mutation, effectively suppresses the above processes. In addition, we found that low-density lipoprotein receptor (LDLR), which mediates the endocytosis of cholesterol, was upregulated in CCA. Therefore, we designed a cholesterol-conjugated DNA/RNA heteroduplex oligonucleotide targeting TBK1 (Cho-TBK1-HDO), which could accumulate in CCA cells via LDLR, reduce the TBK1 mRNA level and inhibit intrahepatic metastasis of CCA. Besides, in the experimental group of 182 ICC patients, high TBK1 expression combined with high nuclear β-catenin expression predicted a worse prognosis. In summary, TBK1 might serve as a potential prognostic biomarker and therapeutic target for patients with CCA.
Epigenomic mapping identifies an enhancer repertoire that regulates cell identity in bladder cancer through distinct transcription factor networks
Authors: Neyret-Kahn Hélène , Fontugne Jacqueline , Meng Xiang Yu , Groeneveld Clarice S. , Cabel Luc , Ye Tao , Guyon Elodie , Krucker Clémentine , Dufour Florent , Chapeaublanc Elodie , Rapinat Audrey , Jeffery Daniel , Tanguy Laura , Dixon Victoria , Neuzillet Yann , Lebret Thierry , Gentien David , Davidson Irwin , Allory Yves , Bernard-Pierrot Isabelle , Radvanyi François
Published: March 2023

Muscle-invasive bladder cancer (BLCA) is an aggressive disease. Consensus BLCA transcriptomic subtypes have been proposed, with two major Luminal and Basal subgroups, presenting distinct molecular and clinical characteristics. However, how these distinct subtypes are regulated remains unclear. We hypothesized that epigenetic activation of distinct super-enhancers could drive the transcriptional programs of BLCA subtypes. Through integrated RNA-sequencing and epigenomic profiling of histone marks in primary tumours, cancer cell lines, and normal human urothelia, we established the first integrated epigenetic map of BLCA and demonstrated the link between subtype and epigenetic control. We identified the repertoire of activated super-enhancers and highlighted Basal, Luminal and Normal-associated SEs. We revealed super-enhancer-regulated networks of candidate master transcription factors for Luminal and Basal subgroups including FOXA1 and ZBED2, respectively. FOXA1 CRISPR-Cas9 mutation triggered a shift from Luminal to Basal phenotype, confirming its role in Luminal identity regulation and induced ZBED2 overexpression. In parallel, we showed that both FOXA1 and ZBED2 play concordant roles in preventing inflammatory response in cancer cells through STAT2 inhibition. Our study furthers the understanding of epigenetic regulation of muscle-invasive BLCA and identifies a co-regulated network of super-enhancers and associated transcription factors providing potential targets for the treatment of this aggressive disease.
Overexpression of tripartite motif-containing 47 (TRIM47) confers sensitivity to PARP inhibition via ubiquitylation of BRCA1 in triple negative breast cancer cells
Authors: Liu Fengen , Xie Binhui , Ye Rong , Xie Yuankang , Zhong Baiyin , Zhu Jinrong , Tang Yao , Lin Zelong , Tang Huiru , Wu Ziqing , Li Heping
Published: March 2023

Triple-negative breast cancers (TNBC) frequently harbor defects in DNA double-strand break repair through homologous recombination (HR), such as BRCA1 dysfunction. However, less than 15% of TNBC patients were found to carry BRCA1 mutation, indicating that there are other mechanisms regulating BRCA1-deficient in TNBC. In the current study, we shown that overexpression of TRIM47 correlates with progression and poor prognosis in triple-negative breast cancer. Moreover, we demonstrated that TRIM47 directly interacts with BRCA1 and induces ubiquitin-ligase-mediated proteasome turnover of BRCA1, subsequently leads to a decrease of BRCA1 protein levels in TNBC. Moreover, the downstream gene expression of BRCA1, such as p53, p27, p21 was significantly reduced in the overexpression of TRIM47 cell lines but increased in TRIM47-deleted cells. Functionally, we found that overexpression of TRIM47 in TNBC cells confers an exquisite sensitivity to olaparib, an inhibitor of poly-(ADP-ribose)-polymerase (PARP), but TRIM47 inhibition significantly confers TNBC cells resistance to olaparib both in vitro and in vivo. Furthermore, we showed that overexpression of BRCA1 significant increase the olaparib resistance in TRIM47-overexpression-induced PARP inhibitions sensitivity. Taken together, our results uncover a novel mechanism for BRCA1-deficient in TNBC and targeting TRIM47/BRCA1 axis may be a promising prognostic factor and a valuable therapeutic target for TNBC.
Involvement of the pro-oncogenic enzyme fatty acid synthase in the hallmarks of cancer: a promising target in anti-cancer therapies
Authors: Vanauberg Dimitri , Schulz Céline , Lefebvre Tony
Published: March 2023

An accelerated de novo lipogenesis (DNL) flux is a common characteristic of cancer cells required to sustain a high proliferation rate. The DNL enzyme fatty acid synthase (FASN) is overexpressed in many cancers and is pivotal for the increased production of fatty acids. There is increasing evidences of the involvement of FASN in several hallmarks of cancer linked to its ability to promote cell proliferation via membranes biosynthesis. In this review we discuss about the implication of FASN in the resistance to cell death and in the deregulation of cellular energetics by increasing nucleic acids, protein and lipid synthesis. FASN also promotes cell proliferation, cell invasion, metastasis and angiogenesis by enabling the building of lipid rafts and consequently to the localization of oncogenic receptors such as HER2 and c-Met in membrane microdomains. Finally, FASN is involved in immune escape by repressing the activation of pro-inflammatory cells and promoting the recruitment of M2 macrophages and T regulatory cells in the tumor microenvironment. Here, we provide an overview of the involvement of the pro-oncogenic enzyme in the hallmarks of cancer making FASN a promising target in anti-cancer therapy to circumvent resistance to chemotherapies.