bluuebunny/crossref_metadata_2025_split huggingface dataset:
Public perceptions on carbon removal from focus groups in 22 countries
Authors: Low Sean , Fritz Livia , Baum Chad M. , Sovacool Benjamin K. 
Published: April 2024

AbstractCarbon removal is emerging as a pillar of governmental and industry commitments toward achieving Net Zero targets. Drawing from 44 focus groups in 22 countries, we map technical and societal issues that a representative sample of publics raise on five major types of carbon removal (forests, soils, direct air capture, enhanced weathering, and bioenergy with carbon capture and storage), and how these translate to preferences for governance actors, mechanisms, and rationales. We assess gaps and overlaps between a global range of public perceptions and how carbon removal is currently emerging in assessment, innovation, and decision-making. In conclusion, we outline key societal expectations for informing assessment and policy: prioritize public engagement as more than acceptance research; scrutiny and regulation of industry beyond incentivizing innovation; systemic coordination across sectors, levels, and borders; and prioritize underlying causes of climate change and interrelated governance issues.
Kataegis in clinical and molecular subgroups of primary breast cancer
Authors: Veerla Srinivas , Staaf Johan 
Published: April 2024

AbstractKataegis is a hypermutation phenomenon characterized by localized clusters of single base pair substitution (SBS) reported in multiple cancer types. Despite a high frequency in breast cancer, large-scale analyses of kataegis patterns and associations with clinicopathological and molecular variables in established breast cancer subgroups are lacking. Therefore, WGS profiled primary breast cancers (n = 791) with associated clinical and molecular data layers, like RNA-sequencing data, were analyzed for kataegis frequency, recurrence, and associations with genomic contexts and functional elements, transcriptional patterns, driver alterations, homologous recombination deficiency (HRD), and prognosis in tumor subgroups defined by ER, PR, and HER2/ERBB2 status. Kataegis frequency was highest in the HER2-positive(p) subgroups, including both ER-negative(n)/positive(p) tumors (ERnHER2p/ERpHER2p). In TNBC, kataegis was neither associated with PAM50 nor TNBC mRNA subtypes nor with distant relapse in chemotherapy-treated patients. In ERpHER2n tumors, kataegis was associated with aggressive characteristics, including PR-negativity, molecular Luminal B subtype, higher mutational burden, higher grade, and expression of proliferation-associated genes. Recurrent kataegis loci frequently targeted regions commonly amplified in ER-positive tumors, while few recurrent loci were observed in TNBC. SBSs in kataegis loci appeared enriched in regions of open chromatin. Kataegis status was not associated with HRD in any subgroup or with distinct transcriptional patterns in unsupervised or supervised analysis. In summary, kataegis is a common hypermutation phenomenon in established breast cancer subgroups, particularly in HER2p subgroups, coinciding with an aggressive tumor phenotype in ERpHER2n disease. In TNBC, the molecular implications and associations of kataegis are less clear, including its prognostic value.
Multi-project wafers for flexible thin-film electronics by independent foundries
Authors: Çeliker Hikmet , Dehaene Wim , Myny Kris 
Published: April 2024

AbstractFlexible and large-area electronics rely on thin-film transistors (TFTs) to make displays1–3, large-area image sensors4–6, microprocessors7–11, wearable healthcare patches12–15, digital microfluidics16,17and more. Although silicon-based complementary metal–oxide–semiconductor (CMOS) chips are manufactured using several dies on a single wafer and the multi-project wafer concept enables the aggregation of various CMOS chip designs within the same die, TFT fabrication is currently lacking a fully verified, universal design approach. This increases the cost and complexity of manufacturing TFT-based flexible electronics, slowing down their integration into more mature applications and limiting the design complexity achievable by foundries. Here we show a stable and high-yield TFT platform for the fabless manufacturing of two mainstream TFT technologies, wafer-based amorphous indium–gallium–zinc oxide and panel-based low-temperature polycrystalline silicon, two key TFT technologies applicable to flexible substrates. We have designed the iconic 6502 microprocessor in both technologies as a use case to demonstrate and expand the multi-project wafer approach. Enabling the foundry model for TFTs, as an analogy of silicon CMOS technologies, can accelerate the growth and development of applications and technologies based on these devices.
Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers
Authors: Ferretti Stephane , Hamon Jacques , de Kanter Ruben , Scheufler Clemens , Andraos-Rey Rita , Barbe Stephanie , Bechter Elisabeth , Blank Jutta , Bordas Vincent , Dammassa Ernesta , Decker Andrea , Di Nanni Noemi , Dourdoigne Marion , Gavioli Elena , Hattenberger Marc , Heuser Alisa , Hemmerlin Christelle , Hinrichs Jürgen , Kerr Grainne , Laborde Laurent , Jaco Isabel , Núñez Eloísa Jiménez , Martus Hans-Joerg , Quadt Cornelia , Reschke Markus , Romanet Vincent , Schaeffer Fanny , Schoepfer Joseph , Schrapp Maxime , Strang Ross , Voshol Hans , Wartmann Markus , Welly Sarah , Zécri Frédéric , Hofmann Francesco , Möbitz Henrik , Cortés-Cros Marta 
Published: April 2024

AbstractThe Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens1–6. Despite advances in treatment with immune checkpoint inhibitors7–10, there is an unmet need in the treatment of MSI cancers11–14. Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative hit-finding and lead-optimization strategy. HRO761 is a potent, selective, allosteric WRN inhibitor that binds at the interface of the D1 and D2 helicase domains, locking WRN in an inactive conformation. Pharmacological inhibition by HRO761 recapitulated the phenotype observed by WRN genetic suppression, leading to DNA damage and inhibition of tumour cell growth selectively in MSI cells in a p53-independent manner. Moreover, HRO761 led to WRN degradation in MSI cells but not in microsatellite-stable cells. Oral treatment with HRO761 resulted in dose-dependent in vivo DNA damage induction and tumour growth inhibition in MSI cell- and patient-derived xenograft models. These findings represent preclinical pharmacological validation of WRN as a therapeutic target in MSI cancers. A clinical trial with HRO761 (NCT05838768) is ongoing to assess the safety, tolerability and preliminary anti-tumour activity in patients with MSI colorectal cancer and other MSI solid tumours.
PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function
Authors: Morotti Matteo , Grimm Alizee J. , Hope Helen Carrasco , Arnaud Marion , Desbuisson Mathieu , Rayroux Nicolas , Barras David , Masid Maria , Murgues Baptiste , Chap Bovannak S. , Ongaro Marco , Rota Ioanna A. , Ronet Catherine , Minasyan Aspram , Chiffelle Johanna , Lacher Sebastian B. , Bobisse Sara , Murgues Clément , Ghisoni Eleonora , Ouchen Khaoula , Bou Mjahed Ribal , Benedetti Fabrizio , Abdellaoui Naoill , Turrini Riccardo , Gannon Philippe O. , Zaman Khalil , Mathevet Patrice , Lelievre Loic , Crespo Isaac , Conrad Marcus , Verdeil Gregory , Kandalaft Lana E. , Dagher Julien , Corria-Osorio Jesus , Doucey Marie-Agnes , Ho Ping-Chih , Harari Alexandre , Vannini Nicola , Böttcher Jan P. , Dangaj Laniti Denarda , Coukos George 
Published: April 2024

AbstractExpansion of antigen-experienced CD8+ T cells is critical for the success of tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer1. Interleukin-2 (IL-2) acts as a key regulator of CD8+ cytotoxic T lymphocyte functions by promoting expansion and cytotoxic capability2,3. Therefore, it is essential to comprehend mechanistic barriers to IL-2 sensing in the tumour microenvironment to implement strategies to reinvigorate IL-2 responsiveness and T cell antitumour responses. Here we report that prostaglandin E2 (PGE2), a known negative regulator of immune response in the tumour microenvironment4,5, is present at high concentrations in tumour tissue from patients and leads to impaired IL-2 sensing in human CD8+ TILs via the PGE2 receptors EP2 and EP4. Mechanistically, PGE2 inhibits IL-2 sensing in TILs by downregulating the IL-2Rγc chain, resulting in defective assembly of IL-2Rβ–IL2Rγc membrane dimers. This results in impaired IL-2–mTOR adaptation and PGC1α transcriptional repression, causing oxidative stress and ferroptotic cell death in tumour-reactive TILs. Inhibition of PGE2 signalling to EP2 and EP4 during TIL expansion for ACT resulted in increased IL-2 sensing, leading to enhanced proliferation of tumour-reactive TILs and enhanced tumour control once the cells were transferred in vivo. Our study reveals fundamental features that underlie impairment of human TILs mediated by PGE2 in the tumour microenvironment. These findings have therapeutic implications for cancer immunotherapy and cell therapy, and enable the development of targeted strategies to enhance IL-2 sensing and amplify the IL-2 response in TILs, thereby promoting the expansion of effector T cells with enhanced therapeutic potential.
Alternative splicing of CARM1 regulated by LincGET-guided paraspeckles biases the first cell fate in mammalian early embryos
Authors: Wang Jiaqiang , Zhang Yiwei , Gao Jiaze , Feng Guihai , Liu Chao , Li Xueke , Li Pengcheng , Liu Zhonghua , Lu Falong , Wang Leyun , Li Wei , Zhou Qi , Liu Yusheng 
Published: April 2024

AbstractThe heterogeneity of CARM1 controls first cell fate bias during early mouse development. However, how this heterogeneity is established is unknown. Here, we show that Carm1 mRNA is of a variety of specific exon-skipping splicing (ESS) isoforms in mouse two-cell to four-cell embryos that contribute to CARM1 heterogeneity. Disruption of paraspeckles promotes the ESS of Carm1 precursor mRNAs (pre-mRNAs). LincGET, but not Neat1, is required for paraspeckle assembly and inhibits the ESS of Carm1 pre-mRNAs in mouse two-cell to four-cell embryos. We further find that LincGET recruits paraspeckles to the Carm1 gene locus through HNRNPU. Interestingly, PCBP1 binds the Carm1 pre-mRNAs and promotes its ESS in the absence of LincGET. Finally, we find that the ESS seen in mouse two-cell to four-cell embryos decreases CARM1 protein levels and leads to trophectoderm fate bias. Our findings demonstrate that alternative splicing of CARM1 has an important role in first cell fate determination.
Chromosome-level genome assembly of the yellow-cheek carp Elopichthys bambusa
Authors: Li Shunyao , Xiong Xuemei , Qiu Siyu , Shen Zhigang , He Yan , Gao Zexia , Wan Shiming 
Published: April 2024

AbstractYellow-cheek carp (Elopichthys bambusa) is a typical large and ferocious carnivorous fish endemic to East Asia, with high growth rate, nutritional value and economic value. In this study, a chromosome-level genome of yellow-cheek carp was generated by combining PacBio reads, Illumina reads and Hi-C data. The genome size is 827.63 Mb with a scaffold N50 size of 33.65 Mb, and 99.51% (823.61 Mb) of the assembled sequences were anchored to 24 pseudo-chromosomes. The genome is predicted to contain 24,153 protein-coding genes, with 95.54% having functional annotations. Repeat elements account for approximately 55.17% of the genomic landscape. The completeness of yellow-cheek carp genome assembly is highlighted by a BUSCO score of 98.4%. This genome will help us understand the genetic diversity of yellow-cheek carp and facilitate its conservation planning.
A new commercial boundary dataset for metropolitan areas in the USA and Canada, built from open data
Authors: Jeong Byeonghwa , Allen Jeff , Chapple Karen 
Published: April 2024

AbstractThe purpose of this study is to define the geographic boundaries of commercial areas by creating a consistent definition, combining various commercial area types, including downtowns, retail centres, financial districts, and other employment subcentres. Our research involved the collection of office, retail and job density data from 69 metropolitan regions across USA and Canada. Using this data, we conducted an unsupervised image segmentation model and clustering methods to identify distinctive commercial geographic boundaries. As a result, we identified 23,751 commercial areas, providing a detailed perspective on the commercial landscape of metropolitan areas in the USA and Canada. In addition, the generated boundaries were successfully validated through comparison with previously established commerce-related boundaries. The output of this study has implications for urban and regional planning and economic development, delivering valuable insights into the overall commercial geography in the region. The commercial boundary and used codes are freely available on the School of Cities Github, and users can reuse, reproduce and modify the boundaries.
Optimization and modelling of magnesium oxide (MgO) photocatalytic degradation of binary dyes using response surface methodology
Authors: Kwang Benno Park Hyeong , Kumar Pushpendra , Kebaili Imen , Boukhris Imed , Hwan Joo Yun , Hyun Sung Tae , Kumar Anuruddh 
Published: April 2024

AbstractTextile industry dye effluent contains a mixture of different kinds of dyes. Many times, photocatalysis is targeted as a solution for the treatment of dye effluent from the textile industry. Many researches have been published related to the photocatalysis of single textile dyes but in the real-world scenario, effluent is a mixture of dyes. Magnesium oxide (MgO) is used as a photocatalyst to treat a mixture (binary solution) of Methylene blue (MB) and Methylene violet (MV) along with individual MB and MV dyes in this article. MgO shows remarkable photocatalytic activity at about 93 and 88% for MB and MV dye in binary solution within 135 min. Furthermore, to study the influence of process parameters, experiments are designed with the help of the central composite design (CCD), and Response surface methodology (RSM) is used to study the interactions between parameters. For this study, five parameters are selected i.e., Photocatalyst dosage, initial concentration of both dyes, time of exposure to the light source, and pH of the binary solution. The photocatalytic process is also optimized and finally optimization of process parameters is validated with an experiment. The result of the validation experiment is very close to the predicted photocatalytic activity.
Long extrachromosomal circular DNA identification by fusing sequence-derived features of physicochemical properties and nucleotide distribution patterns
Authors: Abbasi Ahtisham Fazeel , Asim Muhammad Nabeel , Ahmed Sheraz , Dengel Andreas 
Published: April 2024

AbstractLong extrachromosomal circular DNA (leccDNA) regulates several biological processes such as genomic instability, gene amplification, and oncogenesis. The identification of leccDNA holds significant importance to investigate its potential associations with cancer, autoimmune, cardiovascular, and neurological diseases. In addition, understanding these associations can provide valuable insights about disease mechanisms and potential therapeutic approaches. Conventionally, wet lab-based methods are utilized to identify leccDNA, which are hindered by the need for prior knowledge, and resource-intensive processes, potentially limiting their broader applicability. To empower the process of leccDNA identification across multiple species, the paper in hand presents the very first computational predictor. The proposed iLEC-DNA predictor makes use of SVM classifier along with sequence-derived nucleotide distribution patterns and physicochemical properties-based features. In addition, the study introduces a set of 12 benchmark leccDNA datasets related to three species, namely Homo sapiens (HM), Arabidopsis Thaliana (AT), and Saccharomyces cerevisiae (SC/YS). It performs large-scale experimentation across 12 benchmark datasets under different experimental settings using the proposed predictor, more than 140 baseline predictors, and 858 encoder ensembles. The proposed predictor outperforms baseline predictors and encoder ensembles across diverse leccDNA datasets by producing average performance values of 81.09%, 62.2% and 81.08% in terms of ACC, MCC and AUC-ROC across all the datasets. The source code of the proposed and baseline predictors is available at https://github.com/FAhtisham/Extrachrosmosomal-DNA-Prediction. To facilitate the scientific community, a web application for leccDNA identification is available at https://sds_genetic_analysis.opendfki.de/iLEC_DNA/.
Failure probability analysis of high fill levee considering multiple uncertainties and correlated failure modes
Authors: Sun Ruirui , Reheman Yimingjiang , Wang Xiaoling , Fei Kaixuan , Zhou Jinjun , Jiao Ding 
Published: April 2024

AbstractSuch complex causative factors in current failure probability models are represented by simply random uncertainty and completely independent or correlation of failure modes, which can often limit the model utility. In this study, we developed a methodology to construct failure probability models for high fill levees, incorporating the identification of uncertainties and an analysis of failure modes. Based on quantification of stochastic-grey-fuzzy uncertainties, probability analysis involved with overtopping, instability and seepage failure modes was implemented combined with probability and non-probability methods. Given that the interaction among failure modes typically exhibits nonlinear behavior, rather than linear correlation or complete independence, a simple methodology for the binary Copula function was established and implemented in MATLAB. This methodology was applied to the high fill segments of a long-distance water transfer project characterized by high population density. It shows that the failure probability of a single failure mode is overestimated when uncertainties are not considered, because of the randomness and fuzziness of some parameters and the greyness of information. Meanwhile, it is found that the magnitude of failure probability related to levee breach is overestimated without respect to failure modes correlation, especially when the probabilities of seepage and instability are both significant and closely aligned.
Mobile monitoring system detects the disease activity pattern and shows the association with clinical outcomes in patients with newly diagnosed Crohn’s disease
Authors: Lee Yoo Jin , Kwak Sang Gyu , Kim Eun Soo , Kim Sung Kook , Lee Hyun Seok , Chung Yun Jin , Jang Byung Ik , Kim Kyeong Ok , Kim Jeongseok , Jo Hyeong Ho , Kim Eun Young 
Published: April 2024

AbstractWe aimed to determine whether Crohn’s disease (CD) activity patterns assessed via a web-based symptom diary can help predict clinical outcomes in patients with newly diagnosed CD. Patients diagnosed with CD within the preceding 3 months were prospectively enrolled at four tertiary centers. All patients recorded their symptoms on a website using a smartphone at least once a week. The index outcomes were disease-related admission and surgery during follow-up. The disease activity from enrollment to outcome or last follow-up was reviewed for pattern analysis. Cox regression analysis was used to identify the predictors of disease outcomes. A total of 102 patients were enrolled. During a median follow-up period of 42 months, 25 (24.5%) and 6 (5.9%) patients required admission and surgery, respectively. Poor activity pattern was an independent predictor of disease-related hospitalization (adjusted hazard ratio [aHR], 3.96; 95% confidence interval [CI] 1.5–10.45; p = 0.005). A poor activity pattern (aHR, 19.48; 95% CI 1.86–203.95; p = 0.013) and female sex (aHR, 11.28; 95% CI 1.49–85.01; p = 0.018) were found to be independent predictors of bowel resection. CD disease activity patterns monitored through the mobile monitoring system may help predict clinical outcomes, such as disease-related hospitalization and surgery, in patients with newly diagnosed CD.
Biological toxicity of sulfamethoxazole in aquatic ecosystem on adult zebrafish (Danio rerio)
Authors: Zhou Jie , Yun Xiao , Wang Jiting , Li Qi , Wang Yanli , Zhang Wenjing , Fan Zhicheng 
Published: April 2024

AbstractThis study evaluated the impacts of sulfamethoxazole (SMX) on antioxidant, immune, histopathological dynamic changes, and gut microbiota of zebrafish. SMX was carried out five groups: 0 (C), 3 mg/L (T3), 6 mg/L (T6), 12 mg/L (T12), and 24 mg/L (T24), with 5 replicates per group for an 8-weeks chronic toxicity test. It was found that SMX is considered to have low toxicity to adult zebrafish. SMX with the concentration not higher than 24 mg/L has no obvious inhibitory effect on the growth of fish. Under different concentrations of SMX stress, oxidative damage and immune system disorder were caused to the liver and gill, with the 12 and 24 mg/L concentration being the most significant. At the same time, it also causes varying degrees of pathological changes in both intestinal and liver tissues. As the concentration of SMX increases, the composition and abundance of the gut microbiota in zebrafish significantly decrease.
Tackling new psychoactive substances through metabolomics: UHPLC-HRMS study on natural and synthetic opioids in male and female murine models
Authors: Di Francesco Gaia , Montesano Camilla , Vincenti Flaminia , Bilel Sabrine , Corli Giorgia , Petrella Greta , Cicero Daniel Oscar , Gregori Adolfo , Marti Matteo , Sergi Manuel 
Published: April 2024

AbstractNovel psychoactive substances (NPS) represent a broad class of drugs new to the illicit market that often allow passing drug-screening tests. They are characterized by a variety of structures, rapid transience on the drug scene and mostly unknown metabolic profiles, thus creating an ever-changing scenario with evolving analytical targets. The present study aims at developing an indirect screening strategy for NPS monitoring, and specifically for new synthetic opioids (NSOs), based on assessing changes in endogenous urinary metabolite levels as a consequence of the systemic response following their intake. The experimental design involved in-vivo mice models: 16 animals of both sex received a single administration of morphine or fentanyl. Urine was collected before and after administration at different time points; the samples were then analysed with an untargeted metabolomics LC-HRMS workflow. According to our results, the intake of opioids resulted in an elevated energy demand, that was more pronounced on male animals, as evidenced by the increase in medium and long chain acylcarnitines levels. It was also shown that opioid administration disrupted the pathways related to catecholamines biosynthesis. The observed alterations were common to both morphine and fentanyl: this evidence indicate that they are not related to the chemical structure of the drug, but rather on the drug class. The proposed strategy may reinforce existing NPS screening approaches, by identifying indirect markers of drug assumption.