bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of EGFR-reprogrammable temozolomide-resistant cells in a model of glioblastoma
Authors: Gong Lingli , Yin Ying , Chen Cheng , Wan Quan , Xia Die , Wang Mei , Pu Zhening , Zhang Bo , Zou Jian 
Published: October 2022

AbstractTemozolomide (TMZ) resistance is a major clinical challenge for glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) mediated DNA damage repair is a key mechanism for TMZ resistance. However, MGMT-null GBM patients remain resistant to TMZ, and the process for resistance evolution is largely unknown. Here, we developed an acquired TMZ resistant xenograft model using serial implantation of MGMT-hypermethylated U87 cells, allowing the extraction of stable, TMZ resistant (TMZ-R) tumors and primary cells. The derived tumors and cells exhibited stable multidrug resistance both in vitro and in vivo. Functional experiments, as well as single-cell RNA sequencing (scRNA-seq), indicated that TMZ treatment induced cellular heterogeneity including quiescent cancer stem cells (CSCs) in TMZ-R tumors. A subset of these were labeled by NES+/SOX2+/CADM1+ and demonstrated significant advantages for drug resistance. Further study revealed that Epidermal Growth Factor Receptor (EGFR) deficiency and diminished downstream signaling may confer this triple positive CSCs subgroup’s quiescent phenotypes and chemoresistance. Continuous EGF treatment improved the chemosensitivity of TMZ-R cells both in vitro and in vivo, mechanically reversing cell cycle arrest and reduced drug uptake. Further, EGF treatment of TMZ-R tumors favorably normalized the response to TMZ in combination therapy. Here, we characterize a unique subgroup of CSCs in MGMT-null experimental glioblastoma, identifying EGF + TMZ therapy as a potential strategy to overcome cellular quiescence and TMZ resistance, likely endowed by deficient EGFR signaling.
Translation and natural selection of micropeptides from long non-canonical RNAs
Authors: Patraquim Pedro , Magny Emile G. , Pueyo José I. , Platero Ana Isabel , Couso Juan Pablo 
Published: October 2022

AbstractLong noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but lacking canonical coding sequences. Apparently unable to produce peptides, lncRNA function seems to rely only on RNA expression, sequence and structure. Here, we exhaustively detect in-vivo translation of small open reading frames (small ORFs) within lncRNAs using Ribosomal profiling during Drosophila melanogaster embryogenesis. We show that around 30% of lncRNAs contain small ORFs engaged by ribosomes, leading to regulated translation of 100 to 300 micropeptides. We identify lncRNA features that favour translation, such as cistronicity, Kozak sequences, and conservation. For the latter, we develop a bioinformatics pipeline to detect small ORF homologues, and reveal evidence of natural selection favouring the conservation of micropeptide sequence and function across evolution. Our results expand the repertoire of lncRNA biochemical functions, and suggest that lncRNAs give rise to novel coding genes throughout evolution. Since most lncRNAs contain small ORFs with as yet unknown translation potential, we propose to rename them “long non-canonical RNAs”.
Exploring species-level infant gut bacterial biodiversity by meta-analysis and formulation of an optimized cultivation medium
Authors: Alessandri Giulia , Fontana Federico , Mancabelli Leonardo , Lugli Gabriele Andrea , Tarracchini Chiara , Argentini Chiara , Longhi Giulia , Viappiani Alice , Milani Christian , Turroni Francesca , van Sinderen Douwe , Ventura Marco 
Published: October 2022

AbstractIn vitro gut cultivation models provide host-uncoupled, fast, and cost-efficient solutions to investigate the effects of intrinsic and extrinsic factors impacting on both composition and functionality of the intestinal microbial ecosystem. However, to ensure the maintenance and survival of gut microbial players and preserve their functions, these systems require close monitoring of several variables, including oxygen concentration, pH, and temperature, as well as the use of a culture medium satisfying the microbial nutritional requirements. In this context, in order to identify the macro- and micro-nutrients necessary for in vitro cultivation of the infant gut microbiota, a meta-analysis based on 1669 publicly available shotgun metagenomic samples corresponding to fecal samples of healthy, full-term infants aged from a few days to three years was performed to define the predominant species characterizing the “infant-like” gut microbial ecosystem. A subsequent comparison of growth performances was made using infant fecal samples that contained the most abundant bacterial taxa of the infant gut microbiota, when cultivated on 18 different culture media. This growth analysis was performed by means of flow cytometry-based bacterial cell enumeration and shallow shotgun sequencing, which allowed the formulation of an optimized growth medium, i.e., Infant Gut Super Medium (IGSM), which maintains and sustains the infant gut microbial biodiversity under in vitro growth conditions. Furthermore, this formulation was used to evaluate the in vitro effect of two drugs commonly used in pediatrics, i.e., acetaminophen and simethicone, on the taxonomic composition of the infant gut microbiota.
Regulation of viable/inactivated/lysed probiotic Lactobacillus plantarum H6 on intestinal microbiota and metabolites in hypercholesterolemic mice
Authors: Li Yue , Chen Mengling , Ma Yuxuan , Yang Yue , Cheng Ying , Ma Huijing , Ren Dayong , Chen Ping 
Published: October 2022

AbstractEvidence suggests that probiotic interventions reduce non-communicable diseases (NCDs) risk. However, its therapeutic effect and mechanism are still unclear. To evaluate the hypocholesterolemic effect of Lactobacillus plantarum H6 (L.p H6), a new commercial patent strain capable of preventing hypercholesterolemia, and its mechanism in depth, three states of the strain were prepared, namely, viable (vH6), heat-inactivated (iH6), and ultrasonically-lysed (uH6) bacteria cells. The results showed that v/i/uH6 cells could lower serum and liver blood lipid levels, alleviate liver damage and improve glucose tolerance test (GTT) and insulin tolerance test (ITT) indexes. v/i/uH6 cells improved the gut microbial composition and significantly reduced the Firmicutes to Bacteroidetes ratio (F/B ratio) in feces. In particular, Muribaculaceae may be a potential biomarker for effective cholesterol reduction. Also, the recovery of these biochemical indices and gut microbiome was found following fecal microbiota transplantation (FMT) using stool from vH6 treated mice. The v/i/uH6 cells increased the intestinal flora metabolism of vitamins-cofactors, as well as amino acids, while decreasing the relative content of primary bile acids. The Pearson correlation analysis showed that norank_f__Muribaculaceae and Lactobacillus had a negative correlation with blood lipid levels. Overall, v/i/uH6 cells were effective in improving hypercholesterolemia in mice, and this effect was attributed partly to the regulation of intestinal microbiota and metabolites related to lipid metabolism. Our findings provided a theoretical basis for the industrial development of probiotics and postbiotics and the treatment of cholesterol diseases.
Admixture has obscured signals of historical hard sweeps in humans
Authors: Souilmi Yassine , Tobler Raymond , Johar Angad , Williams Matthew , Grey Shane T. , Schmidt Joshua , Teixeira João C. , Rohrlach Adam , Tuke Jonathan , Johnson Olivia , Gower Graham , Turney Chris , Cox Murray , Cooper Alan , Huber Christian D. 
Published: October 2022

AbstractThe role of natural selection in shaping biological diversity is an area of intense interest in modern biology. To date, studies of positive selection have primarily relied on genomic datasets from contemporary populations, which are susceptible to confounding factors associated with complex and often unknown aspects of population history. In particular, admixture between diverged populations can distort or hide prior selection events in modern genomes, though this process is not explicitly accounted for in most selection studies despite its apparent ubiquity in humans and other species. Through analyses of ancient and modern human genomes, we show that previously reported Holocene-era admixture has masked more than 50 historic hard sweeps in modern European genomes. Our results imply that this canonical mode of selection has probably been underappreciated in the evolutionary history of humans and suggest that our current understanding of the tempo and mode of selection in natural populations may be inaccurate.
Millennial-scale climate variability over land overprinted by ocean temperature fluctuations
Authors: Hébert R. , Herzschuh U. , Laepple T. 
Published: October 2022

AbstractVariations in regional temperature have widespread implications for society, but our understanding of the amplitude and origin of long-term natural variability is insufficient for accurate regional projections. This is especially the case for terrestrial temperature variability, which is currently thought to be weak over long timescales. By performing spectral analysis on climate reconstructions, produced using sedimentary pollen records from the Northern Hemisphere over the last 8,000 years, coupled with instrumental data, we provide a comprehensive estimate of regional temperature variability from annual to millennial timescales. We show that short-term random variations are overprinted by strong ocean-driven climate variability on multi-decadal and longer timescales. This may cause substantial and potentially unpredictable regional climatic shifts in the coming century, in contrast to the relatively muted and homogeneous warming projected by climate models. Due to the marine influence, regions characterized by stable oceanic climate at sub-decadal timescales experience stronger long-term variability, and continental regions with higher sub-decadal variability show weaker long-term variability. This fundamental relationship between the timescales provides a unique insight into the emergence of a marine-driven low-frequency regime governing terrestrial climate variability and sets the basis to project the amplitude of temperature fluctuations on multi-decadal timescales and longer.
Observation of vortices and vortex stripes in a dipolar condensate
Authors: Klaus Lauritz , Bland Thomas , Poli Elena , Politi Claudia , Lamporesi Giacomo , Casotti Eva , Bisset Russell N. , Mark Manfred J. , Ferlaino Francesca 
Published: October 2022

AbstractQuantized vortices are a prototypical feature of superfluidity that have been observed in multiple quantum gas experiments. But the occurrence of vortices in dipolar quantum gases—a class of ultracold gases characterized by long-range anisotropic interactions—has not been reported yet. Here we exploit the anisotropic nature of the dipole–dipole interaction of a dysprosium Bose–Einstein condensate to induce angular symmetry breaking in an otherwise cylindrically symmetric pancake-shaped trap. Tilting the magnetic field towards the radial plane deforms the cloud into an ellipsoid, which is then set into rotation. At stirring frequencies approaching the radial trap frequency, we observe the generation of dynamically unstable surface excitations, which cause angular momentum to be pumped into the system through vortices. Under continuous rotation, the vortices arrange into a stripe configuration along the field, in close agreement with numerical simulations.
An all-Africa dataset of energy model “supply regions” for solar photovoltaic and wind power
Authors: Sterl Sebastian , Hussain Bilal , Miketa Asami , Li Yunshu , Merven Bruno , Ben Ticha Mohammed Bassam , Elabbas Mohamed A. Eltahir , Thiery Wim , Russo Daniel 
Published: October 2022

AbstractWith solar and wind power generation reaching unprecedented growth rates globally, much research effort has recently gone into a comprehensive mapping of the worldwide potential of these variable renewable electricity (VRE) sources. From a perspective of energy systems analysis, the locations with the strongest resources may not necessarily be the best candidates for investment in new power plants, since the distance from existing grid and road infrastructures and the temporal variability of power generation also matter. To inform energy planning and policymaking, cost-optimisation models for energy systems must be fed with adequate data on potential sites for VRE plants, including costs reflective of resource strength, grid expansion needs and full hourly generation profiles. Such data, tailored to energy system models, has been lacking up to now. In this study, we present a new open-source and open-access all-Africa dataset of “supply regions” for solar photovoltaic and onshore wind power to feed energy models and inform capacity expansion planning.
Exploration of various roles of hypoxia genes in osteosarcoma
Authors: Ma Jimin , Guo Ziming , Yang Xuefei , Zhu Yakun 
Published: October 2022

AbstractOsteosarcoma is a primary malignant tumor that often metastasizes in orthopedic diseases. Although multi-drug chemotherapy and surgical treatment have significantly improved the survival and prognosis of patients with osteosarcoma, the survival rate is still very low due to frequent metastases in patients with osteosarcoma. In-depth exploration of the relationship between various influencing factors of osteosarcoma is very important for screening promising therapeutic targets. This study used multivariate COX regression analysis to select the hypoxia genes SLC2A1 and FBP1 in patients with osteosarcoma, and used the expression of these two genes to divide the patients with osteosarcoma into high-risk and low-risk groups. Then, we first constructed a prognostic model based on the patient's risk value and compared the survival difference between the high expression group and the low expression group. Second, in the high expression group and the low expression group, compare the differences in tumor invasion and inflammatory gene expression between the two groups of immune cells. Finally, the ferroptosis-related genes with differences between the high expression group and the low expression group were screened, and the correlation between these genes was analyzed. In the high-risk group, immune cells with higher tumor invasiveness, macrophages M0 and immune cells with lower invasiveness included: mast cell resting, regulatory T cells (Tregs) and monocytes. Finally, among genes related to ferroptosis, we found AKR1C2, AKR1C1 and ALOX15 that may be related to hypoxia. These ferroptosis-related genes were discovered for the first time in osteosarcoma. Among them, the hypoxia gene FBP1 is positively correlated with the ferroptosis genes AKR1C1 and ALOX15, and the hypoxia gene SLC2A1 is negatively correlated with the ferroptosis genes AKR1C2, AKR1C1 and ALOX15. This study constructed a prognostic model based on hypoxia-related genes SLC2A1 and FBP1 in patients with osteosarcoma, and explored their correlation with immune cells, inflammatory markers and ferroptosis-related genes. This indicates that SLC2A1 and FBP1 are promising targets for osteosarcoma research.
Efficacy and safety of apatinib in patients with recurrent or metastatic head and neck squamous cell carcinoma: a retrospective multi-center study
Authors: Liu Zijing , Zheng Zhuangzhuang , Dong Lihua , Guo Xiao , Jia Xiaojing , Wang Jianfeng , Meng Lingbin , Cui Xiangyan , Jiang Xin 
Published: October 2022

AbstractApatinib is a novel antiangiogenic agent that targets vascular endothelial growth factor 2. The aim of our study was to explore the efficacy and safety of apatinib in the treatment of patients with recurrence or metastasis (R/M) inoperable head and neck squamous cell carcinoma (HNSCC). This multi-center retrospective study analyzed 53 cases of recurrent or metastatic inoperable HNSCC who had progressed or recurred after undergoing standard radiotherapy, chemotherapy, and immunotherapy treated with apatinib from March 2017 to August 2021. Patients continued apatinib until the time of disease progression or onset of intolerable adverse events. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR) and incidence of adverse events. Univariable and multivariable analyses were performed to determine prognostic factors. The main adverse events were counted, and the severity of the adverse reactions was evaluated. Fifty-three patients with recurrent or metastatic inoperable R/M HNSCC who had progressed or recurred after standard radiotherapy, chemotherapy, and immunotherapy were included. The ORR was 15.1%, and the DCR was 86.8%. The median PFS was 4.4 months (95% confidence interval [CI] 3.7–5.0 months) and the median OS was 6.6 months (95% CI 5.3–7.9 months). The number of apatinib lines was an influencing factor for both PFS and OS, and the Eastern Cooperative Oncology Group (ECOG) score, tumor differentiation, and apatinib duration were only the influencing factors for OS. Of these, only the ECOG score was an independent predictor of OS. The most common adverse reactions were hypertension (39.6%), hand-foot syndrome (32.1%), fatigue (32.1%), oral ulcers (28.3%), and nausea and vomiting (20.8%). Most adverse reactions were grade 1 or 2. Apatinib mesylate has good efficacy for recurrent/metastatic inoperable HNSCC as second-line and above-line treatment. ECOG score was an independent prognostic factors of OS in patients who were treated with apatinib. In addition, the adverse effects of apatinib mesylate were relatively mild.
Drug transporters OAT1 and OAT3 have specific effects on multiple organs and gut microbiome as revealed by contextualized metabolic network reconstructions
Authors: Jamshidi Neema , Nigam Sanjay K. 
Published: October 2022

AbstractIn vitro and in vivo studies have established the organic anion transporters OAT1 (SLC22A6, NKT) and OAT3 (SLC22A8) among the main multi-specific “drug” transporters. They also transport numerous endogenous metabolites, raising the possibility of drug-metabolite interactions (DMI). To help understand the role of these drug transporters on metabolism across scales ranging from organ systems to organelles, a formal multi-scale analysis was performed. Metabolic network reconstructions of the omics-alterations resulting from Oat1 and Oat3 gene knockouts revealed links between the microbiome and human metabolism including reactions involving small organic molecules such as dihydroxyacetone, alanine, xanthine, and p-cresol—key metabolites in independent pathways. Interestingly, pairwise organ-organ interactions were also disrupted in the two Oat knockouts, with altered liver, intestine, microbiome, and skin-related metabolism. Compared to older models focused on the “one transporter-one organ” concept, these more sophisticated reconstructions, combined with integration of a multi-microbial model and more comprehensive metabolomics data for the two transporters, provide a considerably more complex picture of how renal “drug” transporters regulate metabolism across the organelle (e.g. endoplasmic reticulum, Golgi, peroxisome), cellular, organ, inter-organ, and inter-organismal scales. The results suggest that drugs interacting with OAT1 and OAT3 can have far reaching consequences on metabolism in organs (e.g. skin) beyond the kidney. Consistent with the Remote Sensing and Signaling Theory (RSST), the analysis demonstrates how transporter-dependent metabolic signals mediate organ crosstalk (e.g., gut-liver-kidney) and inter-organismal communication (e.g., gut microbiome-host).
New insight into the swimming kinematics of wild Green sea turtles (Chelonia mydas)
Authors: van der Geest Nick , Garcia Lorenzo , Nates Roy , Godoy Daniel A. 
Published: October 2022

AbstractBiomechanically, sea turtles could be perceived as birds of the ocean as they glide and flap their forelimbs to produce the necessary forces required for locomotion, making sea turtles an interesting animal to study. However, being an endangered species makes studying the sea turtle's biomechanics a complex problem to solve, both technically and ethically, without causing disturbance. This work develops a novel, non-invasive procedure to develop full three-dimensional kinematics for wild sea turtles by filming the animals in Australia's Great Barrier Reef using underwater drones without disturbing them. We found that the wild animals had very different swimming patterns than previous studies on juveniles in captivity. Our findings show that the flipper goes through a closed-loop trajectory with extended sweeping of the flipper tip towards the centre of the carapace to create a clapping motion. We have named this the “sweep stroke” and in contrast to previously described four-stage models, it creates a five-stage cycle swimming locomotion model. The model presented here could lead to a better comprehension of the sea turtle propulsion methods and their fluid–structure interaction.
SILA: a system for scientific image analysis
Authors: Moreira Daniel , Cardenuto João Phillipe , Shao Ruiting , Baireddy Sriram , Cozzolino Davide , Gragnaniello Diego , Abd-Almageed Wael , Bestagini Paolo , Tubaro Stefano , Rocha Anderson , Scheirer Walter , Verdoliva Luisa , Delp Edward 
Published: October 2022

AbstractA great deal of the images found in scientific publications are retouched, reused, or composed to enhance the quality of the presentation. In most instances, these edits are benign and help the reader better understand the material in a paper. However, some edits are instances of scientific misconduct and undermine the integrity of the presented research. Determining the legitimacy of edits made to scientific images is an open problem that no current technology can perform satisfactorily in a fully automated fashion. It thus remains up to human experts to inspect images as part of the peer-review process. Nonetheless, image analysis technologies promise to become helpful to experts to perform such an essential yet arduous task. Therefore, we introduce SILA, a system that makes image analysis tools available to reviewers and editors in a principled way. Further, SILA is the first human-in-the-loop end-to-end system that starts by processing article PDF files, performs image manipulation detection on the automatically extracted figures, and ends with image provenance graphs expressing the relationships between the images in question, to explain potential problems. To assess its efficacy, we introduce a dataset of scientific papers from around the globe containing annotated image manipulations and inadvertent reuse, which can serve as a benchmark for the problem at hand. Qualitative and quantitative results of the system are described using this dataset.