bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogenotrophic methanogenesis is the key process in the obligately syntrophic consortium of the anaerobic ameba Pelomyxa schiedti
Authors: Treitli Sebastian C , Hanousková Pavla , Beneš Vladimír , Brune Andreas , Čepička Ivan , Hampl Vladimír
Published: August 2023

Pelomyxa is a genus of anaerobic amoebae that live in consortia with multiple prokaryotic endosymbionts. Although the symbionts represent a large fraction of the cellular biomass, their metabolic roles have not been investigated. Using single-cell genomics and transcriptomics, we have characterized the prokaryotic community associated with P. schiedti, which is composed of two bacteria, Candidatus Syntrophus pelomyxae (class Deltaproteobacteria) and Candidatus Vesiculincola pelomyxae (class Clostridia), and a methanogen, Candidatus Methanoregula pelomyxae. Fluorescence in situ hybridization and electron microscopy showed that Ca. Vesiculincola pelomyxae is localized inside vesicles, whereas the other endosymbionts occur freely in the cytosol, with Ca. Methanoregula pelomyxae enriched around the nucleus. Genome and transcriptome-based reconstructions of the metabolism suggests that the cellulolytic activity of P. schiedti produces simple sugars that fuel its own metabolism and the metabolism of a Ca. Vesiculincola pelomyxae, while Ca. Syntrophus pelomyxae energy metabolism relies on degradation of butyrate and isovalerate from the environment. Both species of bacteria and the ameba use hydrogenases to transfer the electrons from reduced equivalents to hydrogen, a process that requires a low hydrogen partial pressure. This is achieved by the third endosymbiont, Ca. Methanoregula pelomyxae, which consumes H2 and formate for methanogenesis. While the bacterial symbionts can be successfully eliminated by vancomycin treatment without affecting the viability of the amoebae, treatment with 2-bromoethanesulfonate, a specific inhibitor of methanogenesis, killed the amoebae, indicating the essentiality of the methanogenesis for this consortium.
Targeted inhibition of protein synthesis renders cancer cells vulnerable to apoptosis by unfolded protein response
Authors: Gsottberger Franziska , Meier Christina , Ammon Anna , Parker Scott , Wendland Kerstin , George Rebekka , Petkovic Srdjan , Mellenthin Lisa , Emmerich Charlotte , Lutzny-Geier Gloria , Metzler Markus , Mackensen Andreas , Chandramohan Vidyalakshmi , Müller Fabian
Published: August 2023

Cellular stress responses including the unfolded protein response (UPR) decide over the fate of an individual cell to ensure survival of the entire organism. During physiologic UPR counter-regulation, protective proteins are upregulated to prevent cell death. A similar strategy induces resistance to UPR in cancer. Therefore, we hypothesized that blocking protein synthesis following induction of UPR substantially enhances drug-induced apoptosis of malignant cells. In line, upregulation of the chaperone BiP was prevented by simultaneous arrest of protein synthesis in B cell malignancies. Cytotoxicity by immunotoxins—approved inhibitors of protein synthesis—was synergistically enhanced in combination with UPR-inducers in seven distinct hematologic and three solid tumor entities in vitro. Synergistic cell death depended on mitochondrial outer membrane permeabilization via BAK/BAX, which correlated with synergistic, IRE1α-dependent reduction of BID, accompanied by an additive fall of MCL-1. The strong synergy was reproduced in vivo against xenograft mouse models of mantle cell lymphoma, Burkitt’s lymphoma, and patient-derived acute lymphoblastic leukemia. In contrast, synergy was absent in blood cells of healthy donors suggesting a tumor-specific vulnerability. Together, these data support clinical evaluation of blocking stress response counter-regulation using inhibitors of protein synthesis as a novel therapeutic strategy.
The DDUP protein encoded by the DNA damage-induced CTBP1-DT lncRNA confers cisplatin resistance in ovarian cancer
Authors: Ren Liangliang , Qing Xingrong , Wei Jihong , Mo Haixin , Liu Yuanji , Zhi Yaofeng , Lu Wenjie , Zheng Mingzhu , Zhang Weijian , Chen Yuan , Zhang Yuejiao , Pan Taijin , Zhong Qian , Li Ronggang , Zhang Xin , Ruan Xiaohong , Yu Ruyuan , Li Jun
Published: August 2023

Sustained activation of DNA damage response (DDR) signaling has been demonstrated to play vital role in chemotherapy failure in cancer. However, the mechanism underlying DDR sustaining in cancer cells remains unclear. In the current study, we found that the expression of the DDUP microprotein, encoded by the CTBP1-DT lncRNA, drastically increased in cisplatin-resistant ovarian cancer cells and was inversely correlated to cisplatin-based therapy response. Using a patient-derived human cancer cell model, we observed that DNA damage-induced DDUP foci sustained the RAD18/RAD51C and RAD18/PCNA complexes at the sites of DNA damage, consequently resulting in cisplatin resistance through dual RAD51C-mediated homologous recombination (HR) and proliferating cell nuclear antigen (PCNA)-mediated post-replication repair (PRR) mechanisms. Notably, treatment with an ATR inhibitor disrupted the DDUP/RAD18 interaction and abolished the effect of DDUP on prolonged DNA damage signaling, which resulted in the hypersensitivity of ovarian cancer cells to cisplatin-based therapy in vivo. Altogether, our study provides insights into DDUP-mediated aberrant DDR signaling in cisplatin resistance and describes a potential novel therapeutic approach for the management of platinum-resistant ovarian cancer.
USP14 governs CYP2E1 to promote nonalcoholic fatty liver disease through deubiquitination and stabilization of HSP90AA1
Authors: Wei Dongqin , Tian Xin , Zhu Longbo , Wang Han , Sun Chao
Published: August 2023

Nonalcoholic fatty liver disease (NAFLD) begins with excessive triglyceride accumulation in the liver, and overly severe hepatic steatosis progresses to nonalcoholic steatohepatitis (NASH), which is characterized by lipid peroxidation, inflammation, and fibrosis. Ubiquitin-specific proteinase 14 (USP14) regulates inflammation, hepatocellular carcinoma and viral infection, but the effect of USP14 on NAFLD is unknown. The aim of this study was to reveal the role of USP14 in the progression of NAFLD and its underlying mechanism. We demonstrated that hepatic USP14 expression was significantly increased in NAFLD in both humans and mice. Hepatic USP14 overexpression exacerbated diet-induced hepatic steatosis, inflammation and fibrosis in mice, in contrast to the results of hepatic USP14 knockdown. Furthermore, palmitic/oleic acid-induced lipid peroxidation and inflammation in hepatocytes were markedly increased by USP14 overexpression but decreased by USP14 knockdown. Notably, in vivo or in vitro data show that USP14 promotes NAFLD progression in a cytochrome p4502E1 (CYP2E1)-dependent manner, which exacerbates hepatocyte oxidative stress, impairs the mitochondrial respiratory chain and inflammation by promoting CYP2E1 protein levels. Mechanistically, we demonstrated by immunoprecipitation and ubiquitination analysis that USP14 inhibits the degradation of heat shock protein 90 alpha family class A member 1 (HSP90AA1) by decreasing its lysine 48-linkage ubiquitination. Meanwhile, upregulation of HAP90AA1 protein promotes CYP2E1 protein accumulation. Collectively, our data indicate that an unknown USP14-HSP90AA1-CYP2E1 axis contributes to NAFLD progression, and we propose that inhibition of USP14 may be an effective strategy for NASH treatment.
Assembly landscape for the bacterial large ribosomal subunit
Authors: Sheng Kai , Li Ning , Rabuck-Gibbons Jessica N. , Dong Xiyu , Lyumkis Dmitry , Williamson James R.
Published: August 2023

Assembly of ribosomes in bacteria is highly efficient, taking ~2-3 min, but this makes the abundance of assembly intermediates very low, which is a challenge for mechanistic understanding. Genetic perturbations of the assembly process create bottlenecks where intermediates accumulate, facilitating structural characterization. We use cryo-electron microscopy, with iterative subclassification to identify intermediates in the assembly of the 50S ribosomal subunit from E. coli. The analysis of the ensemble of intermediates that spans the entire biogenesis pathway for the 50 S subunit was facilitated by a dimensionality reduction and cluster picking approach using PCA-UMAP-HDBSCAN. The identity of the cooperative folding units in the RNA with associated proteins is revealed, and the hierarchy of these units reveals a complete assembly map for all RNA and protein components. The assembly generally proceeds co-transcriptionally, with some flexibility in the landscape to ensure efficiency for this central cellular process under a variety of growth conditions.
Universal patterns in egocentric communication networks
Authors: Iñiguez Gerardo , Heydari Sara , Kertész János , Saramäki Jari
Published: August 2023

Tie strengths in social networks are heterogeneous, with strong and weak ties playing different roles at the network and individual levels. Egocentric networks, networks of relationships around an individual, exhibit few strong ties and more weaker ties, as evidenced by electronic communication records. Mobile phone data has also revealed persistent individual differences within this pattern. However, the generality and driving mechanisms of social tie strength heterogeneity remain unclear. Here, we study tie strengths in egocentric networks across multiple datasets of interactions between millions of people during months to years. We find universality in tie strength distributions and their individual-level variation across communication modes, even in channels not reflecting offline social relationships. Via a simple model of egocentric network evolution, we show that the observed universality arises from the competition between cumulative advantage and random choice, two tie reinforcement mechanisms whose balance determines the diversity of tie strengths. Our results provide insight into the driving mechanisms of tie strength heterogeneity in social networks and have implications for the understanding of social network structure and individual behavior.
Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype
Authors: Oh Ki , Yoo Yun Jae , Torre-Healy Luke A. , Rao Manisha , Fassler Danielle , Wang Pei , Caponegro Michael , Gao Mei , Kim Joseph , Sasson Aaron , Georgakis Georgios , Powers Scott , Moffitt Richard A.
Published: August 2023

Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, understanding of underlying signals driving distinct immune and stromal landscapes is still incomplete. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence. Patients with activated stroma are synonymous with higher myofibroblastic and immunogenic fibroblasts, and furthermore show increased M2-like macrophages and regulatory T-cells. Contrastingly, patients with ‘normal’ stroma show M1-like recruitment, elevated effector and exhausted T-cells. To aid interoperability of future studies, we provide a pretrained cell type classifier and an atlas of subtype-based signaling factors that we also validate in mouse data. Ultimately, this work leverages the heterogeneity among single-cell studies to create a comprehensive view of the orchestra of signaling interactions governing PDAC.
The challenge of population aging for mitigating deaths from PM2.5 air pollution in China
Authors: Xu Fangjin , Huang Qingxu , Yue Huanbi , Feng Xingyun , Xu Haoran , He Chunyang , Yin Peng , Bryan Brett A.
Published: August 2023

Estimating the health burden of air pollution against the background of population aging is of great significance for achieving the Sustainable Development Goal 3.9 which aims to substantially reduce the deaths and illnesses from air pollution. Here, we estimated spatiotemporal changes in deaths attributable to PM2.5 air pollution in China from 2000 to 2035 and examined the drivers. The results show that from 2019 to 2035, deaths were projected to decease 15.4% (6.6%–20.7%, 95% CI) and 8.4% (0.6%–13.5%) under the SSP1-2.6 and SSP5-8.5 scenario, respectively, but increase 10.4% (5.1%–20.5%) and 18.1% (13.0%–28.3%) under SSP2-4.5 and SSP3-7.0 scenarios. Population aging will be the leading contributor to increased deaths attributable to PM2.5 air pollution, which will counter the positive gains achieved by improvements in air pollution and healthcare. Region-specific measures are required to mitigate the health burden of air pollution and this requires long-term efforts and mutual cooperation among regions in China.
Nanocompartment-confined polymerization in living systems
Authors: Chen Yun , Zuo Mengxuan , Chen Yu , Yu Peiyuan , Chen Xiaokai , Zhang Xiaodong , Yuan Wei , Wu Yinglong , Zhu Wei , Zhao Yanli
Published: August 2023

Polymerization in living systems has become an effective strategy to regulate cell functions and behavior. However, the requirement of high concentrations of monomers, the existence of complicated intracorporal interferences, and the demand for extra external stimulations hinder their further biological applications. Herein, a nanocompartment-confined strategy that provides a confined and secluded environment for monomer enrichment and isolation is developed to achieve high polymerization efficiency, reduce the interference from external environment, and realize broad-spectrum polymerizations in living systems. For exogenous photopolymerization, the light-mediated free-radical polymerization of sodium 4-styrenesulfonate induces a 2.7-fold increase in the reaction rate with the protection of a confined environment. For endogenous hydrogen peroxide-responsive polymerization,p‑aminodiphenylamine hydrochloride embedded in a nanocompartment not only performs a 6.4-fold higher reaction rate than that of free monomers, but also activates an effective second near-infrared photoacoustic imaging-guided photothermal immunotherapy at tumor sites. This nanocompartment-confined strategy breaks the shackles of conventional polymerization, providing a universal platform for in vivo synthesis of polymers with diverse structures and functions.
Design of stretchable and self-powered sensing device for portable and remote trace biomarkers detection
Authors: Huang Wenxi , Ding Qiongling , Wang Hao , Wu Zixuan , Luo Yibing , Shi Wenxiong , Yang Le , Liang Yujie , Liu Chuan , Wu Jin
Published: August 2023

Timely and remote biomarker detection is highly desired in personalized medicine and health protection but presents great challenges in the devices reported so far. Here, we present a cost-effective, flexible and self-powered sensing device for H2S biomarker analysis in various application scenarios based on the structure of galvanic cells. The sensing mechanism is attributed to the change in electrode potential resulting from the chemical adsorption of gas molecules on the electrode surfaces. Intrinsically stretchable organohydrogels are used as solid-state electrolytes to enable stable and long-term operation of devices under stretching deformation or in various environments. The resulting open-circuit sensing device exhibits high sensitivity, low detection limit, and excellent selectivity for H2S. Its application in the non-invasive halitosis diagnosis and identification of meat spoilage is demonstrated, emerging great commercial value in portable medical electronics and food security. A wireless sensory system has also been developed for remote H2S monitoring with the participation of Bluetooth and cloud technologies. This work breaks through the shortcomings in the traditional chemiresistive sensors, offering a direction and theoretical foundation for designing wearable sensors catering to other stimulus detection requirements.
Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography
Authors: Rössler Annika , Netzl Antonia , Knabl Ludwig , Bante David , Wilks Samuel H. , Borena Wegene , von Laer Dorothee , Smith Derek J. , Kimpel Janine
Published: August 2023

Since emergence of the initial SARS-CoV-2 BA.1, BA.2 and BA.5 variants, Omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged Omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent Omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants.
Hydrodynamic finite-size scaling of the thermal conductivity in glasses
Authors: Fiorentino Alfredo , Pegolo Paolo , Baroni Stefano
Published: August 2023

In the past few years, the theory of thermal transport in amorphous solids has been substantially extended beyond the Allen-Feldman model. The resulting formulation, based on the Green-Kubo linear response or the Wigner-transport equation, bridges this model for glasses with the traditional Boltzmann kinetic approach for crystals. The computational effort required by these methods usually scales as the cube of the number of atoms, thus severely limiting the size range of computationally affordable glass models. Leveraging hydrodynamic arguments, we show how this issue can be overcome through a simple formula to extrapolate a reliable estimate of the bulk thermal conductivity of glasses from finite models of moderate size. We showcase our findings for realistic models of paradigmatic glassy materials.
A decade of urban fires: Portuguese events between 2013 and 2022
Authors: Bispo Regina , Marques Filipe J. , Penha Alexandre , Espadinha-Cruz Pedro , Grilo António
Published: August 2023

This study describes a dataset containing urban fire events that took place in mainland Portugal between 2013 and 2022. The Regulation n.º3317-A/2018, established by the Portuguese National Emergency and Civil Protection Authority (Autoridade Nacional de Emergência e Proteção Civil, ANEPC), defines the Operations Management System (Sistema de Gestão de Operações, SGO). Among other attributions, this system allows to manage the lyfe-cycle of the urban fire events, from ignition to extinction, through the Operations Decision Support System (Sistema de Apoio Ã Decisão Operacional, SADO). This system supports the systematic collection of a minimum set of data on each event. All instances included in the dataset were retrieved from SADO. To make the data suitable for analytic purposes, several pre-processing actions were taken, including the steps of data transformation and cleaning. The dataset was further validated by a set of technical procedures aiming to verify both data correctness and utility. The final dataset provides the most recent multi-year record of Portuguese urban fires including 27 variables on 72641 events.
A randomized trial that compared brain activity, efficacy and plausibility of open-label placebo treatment and cognitive reappraisal for reducing emotional distress
Authors: Schienle Anne , Kogler Wolfgang , Wabnegger Albert
Published: August 2023

Placebo pills can reduce emotional distress even when recipients have been informed about the inert nature of the treatment. However, before such open-label placebos (OLPs) can be recommended for general clinical use, their efficacy and acceptability need to be further investigated and compared with established methods for emotion regulation, such as cognitive reappraisal (CR). The current study with functional magnetic resonance imaging compared the effects of an OLP pill with CR for reducing a specific form of emotional distress: disgust. Participants (150 healthy females) were randomly allocated to one of three groups, all of which were exposed to disgusting and neutral images (OLP, CR, PV: passive viewing). It was tested whether the three groups would differ in brain activity and reported disgust. Ratings for the perceived efficacy and plausibility of treatment were also compared between OLP and CR. Both OLP and CR increased the activity in a cognitive control region, the ventrolateral prefrontal cortex. Relative to PV and OLP, CR reduced activity in the putamen and pallidum. These regions play an important role in decoding disgust signals from different modalities. Self-reports indicated that CR was perceived as a more effective and plausible intervention strategy than OLP. In conclusion, CR was a superior method for disgust regulation compared to OLP, both on the subjective as well as the neurobiological level. Future OLP studies are needed to test whether the observed effects generalize to other forms of emotional distress.
Methyl carbamates of phosphatidylethanolamines and phosphatidylserines reveal bacterial contamination in mitochondrial lipid extracts of mouse embryonic fibroblasts
Authors: Castellaneta Andrea , Porcelli Vito , Losito Ilario , Barile Serena , Maresca Alessandra , Del Dotto Valentina , Guadalupi Ludovica Sofia , Calvano Cosima Damiana , Carelli Valerio , Palmieri Luigi , Cataldi Tommaso R. I.
Published: August 2023

The occurrence of methyl carbamates of phosphatidylethanolamines and phosphatidylserines in the lipid extract of mitochondria obtained from mouse embryonic fibroblasts was ascertained by hydrophilic interaction liquid chromatography with electrospray ionization single and multi-stage mass spectrometry, performed using sinergically a high resolution (quadrupole-Orbitrap) and a low resolution (linear ion trap) spectrometer. Two possible routes to the synthesis of methyl carbamates of phospholipids were postulated and evaluated: (i) a chemical transformation involving phosgene, occurring as a photooxidation by-product in the chloroform used for lipid extraction, and methanol, also used for the latter; (ii) an enzymatic methoxycarbonylation reaction due to an accidental bacterial contamination, that was unveiled subsequently on the murine mitochondrial sample. A specific lipid extraction performed on a couple of standard phosphatidyl-ethanolamines/-serines, based on purposely photo-oxidized chloroform and deuterated methanol, indicated route (i) as negligible in the specific case, thus highlighting the enzymatic route related to bacterial contamination as the most likely source of methyl carbamates. The unambiguous recognition of the latter might represent the starting point toward a better understanding of their generation in biological systems and a minimization of their occurrence when an artefactual formation is ascertained.
Dynamical system analysis of interacting dark energy in LRS Bianchi type I cosmology
Authors: Rathore Shivangi , Singh S. Surendra
Published: August 2023

This paper deals with an interacting dark energy (DE) model in Locally rotationally symmetric (LRS) Bianchi type I cosmological model with scalar field in the form of an exponential potential. We reduce the transformation equations to an independent system of ordinary differential equations by appropriate alteration of the variables to setup the complementary dynamical system and after that we also calculate the critical points of the system. We get six critical points when our coupling parameter is positive. And we get two critical points when our coupling parameter is negative. And dark energy behaves like a perfect fluid for all the critical points. And after that we analyzed all the critical points by calculating the eigenvalues of the Jacobian matrix and we find out that out of these eight critical points, six critical points are stable, which shows that our Universe is accelerating. And two (2) critical points are unstable. We also present the phase plot analysis.
Neuronal diversity can improve machine learning for physics and beyond
Authors: Choudhary Anshul , Radhakrishnan Anil , Lindner John F. , Sinha Sudeshna , Ditto William L.
Published: August 2023

Diversity conveys advantages in nature, yet homogeneous neurons typically comprise the layers of artificial neural networks. Here we construct neural networks from neurons that learn their own activation functions, quickly diversify, and subsequently outperform their homogeneous counterparts on image classification and nonlinear regression tasks. Sub-networks instantiate the neurons, which meta-learn especially efficient sets of nonlinear responses. Examples include conventional neural networks classifying digits and forecasting a van der Pol oscillator and physics-informed Hamiltonian neural networks learning Hénon–Heiles stellar orbits and the swing of a video recorded pendulum clock. Such learned diversity provides examples of dynamical systems selecting diversity over uniformity and elucidates the role of diversity in natural and artificial systems.
Metagenomic profiling pipelines improve taxonomic classification for 16S amplicon sequencing data
Authors: Odom Aubrey R. , Faits Tyler , Castro-Nallar Eduardo , Crandall Keith A. , Johnson W. Evan
Published: August 2023

Most experiments studying bacterial microbiomes rely on the PCR amplification of all or part of the gene for the 16S rRNA subunit, which serves as a biomarker for identifying and quantifying the various taxa present in a microbiome sample. Several computational methods exist for analyzing 16S amplicon sequencing. However, the most-used bioinformatics tools cannot produce high quality genus-level or species-level taxonomic calls and may underestimate the potential accuracy of these calls. We used 16S sequencing data from mock bacterial communities to evaluate the sensitivity and specificity of several bioinformatics pipelines and genomic reference libraries used for microbiome analyses, concentrating on measuring the accuracy of species-level taxonomic assignments of 16S amplicon reads. We evaluated the tools DADA2, QIIME 2, Mothur, PathoScope 2, and Kraken 2 in conjunction with reference libraries from Greengenes, SILVA, Kraken 2, and RefSeq. Profiling tools were compared using publicly available mock community data from several sources, comprising 136 samples with varied species richness and evenness, several different amplified regions within the 16S rRNA gene, and both DNA spike-ins and cDNA from collections of plated cells. PathoScope 2 and Kraken 2, both tools designed for whole-genome metagenomics, outperformed DADA2, QIIME 2 using the DADA2 plugin, and Mothur, which are theoretically specialized for 16S analyses. Evaluations of reference libraries identified the SILVA and RefSeq/Kraken 2 Standard libraries as superior in accuracy compared to Greengenes. These findings support PathoScope and Kraken 2 as fully capable, competitive options for genus- and species-level 16S amplicon sequencing data analysis, whole genome sequencing, and metagenomics data tools.
Reproducibility of continuous glucose monitoring results under real-life conditions in an adult population: a functional data analysis
Authors: Matabuena Marcos , Pazos-Couselo Marcos , Alonso-Sampedro Manuela , Fernández-Merino Carmen , González-Quintela Arturo , Gude Francisco
Published: August 2023

Continuous glucose monitoring systems (CGM) are a very useful tool to understand the behaviour of glucose in different situations and populations. Despite the widespread use of CGM systems in both clinical practice and research, our understanding of the reproducibility of CGM data remains limited. The present work examines the reproducibility of the results provided by a CGM system in a random sample of a free-living adult population, from a functional data analysis approach. Functional intraclass correlation coefficients (ICCs) and their 95% confidence intervals (CI) were calculated to assess the reproducibility of CGM results in 581 individuals. 62% were females 581 participants (62% women) mean age 48 years (range 18–87) were included, 12% had previously been diagnosed with diabetes. The inter-day reproducibility of the CGM results was greater for subjects with diabetes (ICC 0.46 [CI 0.39–0.55]) than for normoglycaemic subjects (ICC 0.30 [CI 0.27–0.33]); the value for prediabetic subjects was intermediate (ICC 0.37 [CI 0.31–0.42]). For normoglycaemic subjects, inter-day reproducibility was poorer among the younger (ICC 0.26 [CI 0.21–0.30]) than the older subjects (ICC 0.39 [CI 0.32–0.45]). Inter-day reproducibility was poorest among normoglycaemic subjects, especially younger normoglycaemic subjects, suggesting the need to monitor some patient groups more often than others.
Targeted gene expression profiling for accurate endometrial receptivity testing
Authors: Meltsov Alvin , Saare Merli , Teder Hindrek , Paluoja Priit , Arffman Riikka K. , Piltonen Terhi , Laudanski Piotr , Wielgoś Mirosław , Gianaroli Luca , Koel Mariann , Peters Maire , Salumets Andres , Krjutškov Kaarel , Palta Priit
Published: August 2023

Expressional profiling of the endometrium enables the personalised timing of the window of implantation (WOI). This study presents and evaluates a novel analytical pipeline based on a TAC-seq (Targeted Allele Counting by sequencing) method for endometrial dating. The expressional profiles were clustered, and differential expression analysis was performed on the model development group, using 63 endometrial biopsies spanning over proliferative (PE, n = 18), early-secretory (ESE, n = 18), mid-secretory (MSE, n = 17) and late-secretory (LSE, n = 10) endometrial phases of the natural cycle. A quantitative predictor model was trained on the development group and validated on sequenced samples from healthy women, consisting of 52 paired samples taken from ESE and MSE phases and five LSE phase samples from 31 individuals. Finally, the developed test was applied to 44 MSE phase samples from a study group of patients diagnosed with recurrent implantation failure (RIF). In validation samples (n = 57), we detected displaced WOI in 1.8% of the samples from fertile women. In the RIF study group, we detected a significantly higher proportion of the samples with shifted WOI than in the validation set of samples from fertile women, 15.9% and 1.8% (p = 0.012), respectively. The developed model was evaluated with an average cross-validation accuracy of 98.8% and an accuracy of 98.2% in the validation group. The developed beREADY screening model enables sensitive and dynamic detection of selected transcriptome biomarkers, providing a quantitative and accurate prediction of endometrial receptivity status.
Experimental study on anisotropic unloading mechanical behavior of bedded sandstone
Authors: Fang Jingcheng , Deng Huafeng , Wang Wei , Li Jianlin , Assefa Eleyas
Published: August 2023

Sandstone is a kind of bedded rock mass commonly used in engineering. The deformation and strength of bedded sandstone impose some problems during excavation. In this study, triaxial unloading tests were conducted on rock specimens (considering seven different bedding angles (β)). The results revealed the following key points: (1) At a constant confining pressure, the elastic modulus was gradually increasing when the bedding angle increased. Furthermore, after initial decreasing, the deformation modulus was increased and had a U-shaped distribution. (2) During the unloading of the axial compression, the rate of axial strain variations was initially increased and then decreased while the bedding angle increased (it has exhibited an inverted U-shaped distribution). However, the peak strength, cohesion, and angle of internal friction of rock specimens showed an initial decreasing and then increasing trend. (3) During the loading and unloading stages, the confining pressure reduces the anisotropy of bedded rock masses. (4) In the triaxial unloading test, the failure of rock specimens can be classified into four modes. When there was a large intersection angle between the bedding plane and the unloading direction, failure developed at the bedding planes.
A novel binding site between the voltage-dependent calcium channel CaV1.2 subunit and CaVβ2 subunit discovered using a new analysis method for protein–protein interactions
Authors: Murakami Agnieszka M. , Nagatomo Katsuhiro , Miyoshi Ichro , Itagaki Shirou , Niwa Yasutaka , Murakami Manabu
Published: August 2023

We developed a new method to analyze protein–protein interactions using a dual-inducible prokaryotic expression system. To evaluate protein–protein binding, a chimeric fusion toxin gene was constructed using a DNase-treated short DNA fragment (epitope library) and CcdB, which encodes a DNA topoisomerase II toxin. Protein–protein interactions would affect toxin activity, resulting in colony formation. Using this novel system, we found a new binding site in the voltage-dependent calcium channel α1 subunit (CaV1.2) for the voltage-dependent calcium channel β2 subunit. Prokaryotic expression screening of the β2 subunit using an epitope library of CaV1.2 resulted in two overlapping clones of the C-terminal sequence of CaV1.2. In vitro overlay and immunoprecipitation analyses revealed preferential binding of the C-terminal sequences of CaV1.2 and β2.
Change of temperature field around different drainage structures in cold region tunnel based on model testing
Authors: Zhu Jinhuan , Zhang Xuelan , Liu Lanjun , Tan Lizhen , Liu Lulu
Published: August 2023

Improper layout of drainage structures and inadequate insulation measures in cold tunnels can result in varying degrees of frost formation during operation. This study focuses on the Hongtoushan highway tunnel as an example, where the distribution characteristics of the temperature field around the lower drainage structure under different arrangements are investigated through indoor model testing. The results indicate that there is a significant hysteresis phenomenon in temperature changes across the cross-section as the burial depth increases. With an increase in the burial depth of the surrounding rock, the hysteresis time of temperature changes gradually elongates. The temperature variation pattern can be approximated by a cubic polynomial. In the vertical section, as the tunnel depth increases, the temperature of the surrounding rock in the lower part of the tunnel gradually rises while the amplitude of temperature change diminishes. The temperature near the centerline is relatively lower compared to the sides, where the temperature gradually increases moving away from the centerline.
Self-serving reward and punishment: evidence from the laboratory
Authors: Chen Jianing , Lian Zeng , Zheng Jie
Published: August 2023

Reward for altruism and punishment for selfishness are crucial components for the maintenance of society. Past studies have provided strong evidence that people are willing to incur costs to punish selfish behaviors and to reward altruistic behaviors, but how their willingness to do so depends on their relationship with the individuals conducting the anti-social or pro-social behaviors is much less explored. To probe into this question, we devised a three-stage experiment that combined a revised dictator game and third-party reward or punishment. We employed two payoff frameworks, alignment and conflict, and analyzed how third-party’s willingness to reward and punish differed when their interests were either aligned or in conflict with the first-party under observation. We found that due to considerations for personal interests, third-party’s reward and punishment levels deviated from what was deemed “legitimate” by society, that is, the level of reward and punishment that enhances society’s intrinsic motivations to comply with social norms and act pro-socially. When an anti-social behavior was observed, third-party punished less severely under the alignment framework than under the conflict framework; when a pro-social behavior was observed, third-party demonstrated self-serving reward under the alignment framework, but they rewarded altruistically under the conflict framework. These findings provided evidence for third-party’s self-serving reward and punishment.
ABCD2 score has equivalent stroke risk prediction for anterior circulation TIA and posterior circulation TIA
Authors: Cao Shuang , Zhao Lu , Pei Lulu , Gao Yuan , Fang Hui , Liu Kai , Liu Hao , Yang Shuxiang , Sun Shilei , Wu Jun , Song Bo , Xu Yuming
Published: August 2023

Transient ischemic attack (TIA) was clinically divided into anterior circulation (AC) or posterior circulation (PC). Previous study reported that ABCD2 score could predict the stroke risk after AC-TIA but might have limitation for PC-TIA. We aimed to classify TIA depending on neuroimaging and assess the value of ABCD2 score for predicting stroke risk in different territories. Research data was from TIA database of the First Affiliated Hospital of Zhengzhou University. TIA patients with acute infarction on diffuse weighted imaging [that is, transient symptoms with infarction (TSI)] were divided into anterior and posterior circulation groups according to the location of infarction. The outcome was recurrent stroke within 7 and 90 days. The predictive power of ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses. Overall, 382 AC-TSI and 112 PC-TSI patients were included. There were 38 (9.9%) AC-TSI patients and 11(9.8%) PC-TSI patients who had recurrent stroke at 7 days, and 66 (17.3%) AC-TSI patients and 19 (17.0%) PC-TSI patients who had recurrent stroke within 90 days. At 7 days, the AUC for ABCD2 score was 0.637 (95% confidence interval CI 0.554–0.720) in anterior circulation and 0.683 (95% CI 0.522–0.845) in posterior circulation. The C statistics for ABCD2 score in the two groups were not statistically significant (Z =  − 0.499; P = 0.62). Similar result was found when the outcome time-point was set at 90 days. ABCD2 score could predict the short-term risk of recurrent stroke after AC-TSI and PC-TSI, and had similar predictive abilities for AC-TSI and PC-TSI.
Integrated geotechnical and mineralogical evaluation of the subgrade of some failed pavements along Enugu-Onitsha expressway Southeastern Nigeria
Authors: Ukor Kelechi Paulinus , Igwe Ogbonnaya , Onwuka Obialo Solomon , Nzereogu Stella Kosi , Eze Kelechi Nnaji , Echezona Pearl Elochukwu
Published: August 2023

This research is focused on the constant pavement failure in parts of the Enugu-Onitsha expressway. The failed portions are constructed on the natural subgrade known to be the Shale of Enugu and Mamu formations southeastern Nigeria. Five samples each were obtained from the formations and were subjected to geotechnical test, mineralogical analysis, scanning electron microscopy (SEM) and, statistical analysis. The outcome of the geotechnical test revealed that the liquid limits (LL) are of high plasticity with values ranging from 57.69 to 62.61% and 53.57 to 56.24%, plasticity index (PI) values ranging from 20.32 to 24.37% and 13.37 to 15.32%, Slake durability index (SDI) values ranging from 0.55 to 31.8% and 63.4 to 71.6%, for Enugu and Mamu Shales respectively. From the Unconfined compressive strength (UCS) test, the cohesion (C) values ranged from 37.36 to 43.89 kPa and 24.22 to 27.07 kPa, soaked California bearing ratio (CBR) values ranged from 1.03 to 1.22% and 0.90 to 1.60% for Enugu and Mamu Shales, respectively. The test results are not in the range of specification of the Nigerian Federal Ministry of Works and Housing (FMWH) Nigeria standard for pavement construction. X-ray diffraction (XRD) analysis revealed major minerals to be quartz and kaolinite. Moreover, kaolinite disperses and migrates when moist hence geotechnical failure. Images from Scanning electron microscopy revealed the presence of micropores and fractures which can be used as an inference to the geotechnical test results. Statistical analysis of key geotechnical parameters such as SDI, PI, C, and CBR revealed a strong correlation either positively or negatively with each other. The evaluated results pointed out that the underlined natural subgrade is poor for pavement construction, and thus requires improvement.
Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma
Authors: Zhao Ruiying , Xu Yunhua , Chen Yedan , Zhang Jiajun , Teng Fei , Liao Sha , Chen Shengnan , Wu Qian , Xiang Chan , Pang Jiaohui , Shang Zhanxian , Zhao Jikai , Bao Hairong , Bao Hua , Shao Yang , Lu Shun , Han Yuchen
Published: August 2023

The genomic origin and development of the biphasic lung adenosquamous carcinoma (ASC) remain inconclusive. Here, we derived potential evolutionary trajectory of ASC through whole-exome sequencing, Stereo-seq, and patient-derived xenografts. We showed that EGFR and MET activating mutations were the main drivers in ASCs. Phylogenetically, these drivers and passenger mutations found in both components were trunk clonal events, confirming monoclonal origination. Comparison of multiple lesions also revealed closer genomic distance between lymph node metastases and the ASC component with the same phenotype. However, as mutational signatures of EGFR-positive lung squamous carcinomas (LUSCs) were more comparable to EGFR-positive ASCs than to wild-type LUSCs, we postulated different origination of these LUSCs, with ASC being the potential intermediate state of driver-positive LUSCs. Spatial transcriptomic profiling inferred transformation from adenocarcinoma to squamous cell carcinoma, which was then histologically captured in vivo. Together, our results explained the development of ASC and provided insights into future clinical decisions.
Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells
Authors: Sarma Sudeep , Catella Carly M. , San Pedro Ellyce T. , Xiao Xingqing , Durmusoglu Deniz , Menegatti Stefano , Crook Nathan , Magness Scott T. , Hall Carol K.
Published: August 2023

Infections by Clostridioides difficile, a bacterium that targets the large intestine (colon), impact a large number of people worldwide. Bacterial colonization is mediated by two exotoxins: toxins A and B. Short peptides that can be delivered to the gut and inhibit the biocatalytic activity of these toxins represent a promising therapeutic strategy to prevent and treat C. diff. infection. We describe an approach that combines a Peptide Binding Design (PepBD) algorithm, molecular-level simulations, a rapid screening assay to evaluate peptide:toxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block Toxin A in colon epithelial cells. One peptide, SA1, is found to block TcdA toxicity in primary-derived human colon (large intestinal) epithelial cells. SA1 binds TcdA with a KD of 56.1 ± 29.8 nM as measured by surface plasmon resonance (SPR).
Quantum reference frames for an indefinite metric
Authors: de la Hamette Anne-Catherine , Kabel Viktoria , Castro-Ruiz Esteban , Brukner Časlav
Published: August 2023

The current theories of quantum physics and general relativity on their own do not allow us to study situations in which the gravitational source is quantum. Here, we propose a strategy to determine the dynamics of objects in the presence of mass configurations in superposition, and hence an indefinite spacetime metric, using quantum reference frame (QRF) transformations. Specifically, we show that, as long as the mass configurations in the different branches are related via relative-distance-preserving transformations, one can use an extension of the current framework of QRFs to change to a frame in which the mass configuration becomes definite. Assuming covariance of dynamical laws under quantum coordinate transformations, this allows to use known physics to determine the dynamics. We apply this procedure to find the motion of a probe particle and the behavior of clocks near the mass configuration, and thus find the time dilation caused by a gravitating object in superposition. Comparison with other models shows that semi-classical gravity and gravitational collapse models do not obey the covariance of dynamical laws under quantum coordinate transformations.
Grain-boundary topological superconductor
Authors: Amundsen Morten , Juričić Vladimir
Published: August 2023

Majorana zero modes (MZMs) are of central importance for modern condensed matter physics and quantum information due to their non-Abelian nature, which thereby offers the possibility of realizing topological quantum bits. We here show that a grain boundary (GB) defect can host a topological superconductor (SC), with a pair of cohabitating MZMs at its end when immersed in a parent two-dimensional gapped topological SC with the Fermi surface enclosing a nonzero momentum. The essence of our proposal lies in the magnetic-field driven hybridization of the localized MZMs at the elementary blocks of the GB defect, the single lattice dislocations, due to the MZM spin being locked to the Burgers vector. Indeed, as we show through numerical and analytical calculations, the GB topological SC with two localized MZMs emerges in a finite range of both the angle and magnitude of the external magnetic field. Our work demonstrates the possibility of defect-based platforms for quantum information technology and opens up a route for their systematic search in future.
Reconfigurable reservoir computing in a magnetic metamaterial
Authors: Vidamour I. T. , Swindells C. , Venkat G. , Manneschi L. , Fry P. W. , Welbourne A. , Rowan-Robinson R. M. , Backes D. , Maccherozzi F. , Dhesi S. S. , Vasilaki E. , Allwood D. A. , Hayward T. J.
Published: August 2023

In-materia reservoir computing (RC) leverages the intrinsic physical responses of functional materials to perform complex computational tasks. Magnetic metamaterials are exciting candidates for RC due to their huge state space, nonlinear emergent dynamics, and non-volatile memory. However, to be suitable for a broad range of tasks, the material system is required to exhibit a broad range of properties, and isolating these behaviours experimentally can often prove difficult. By using an electrically accessible device consisting of an array of interconnected magnetic nanorings- a system shown to exhibit complex emergent dynamics- here we show how reconfiguring the reservoir architecture allows exploitation of different aspects the system’s dynamical behaviours. This is evidenced through state-of-the-art performance in diverse benchmark tasks with very different computational requirements, highlighting the additional computational configurability that can be obtained by altering the input/output architecture around the material system.
Focusing ion funnel-assisted ambient electrospray enables high-density and uniform deposition of non-spherical gold nanoparticles for highly sensitive surface-enhanced Raman scattering
Authors: Akbali Baris , Boisdon Cedric , Smith Barry L. , Chaisrikhwun Boonphop , Wongravee Kanet , Vilaivan Tirayut , Lima Cassio , Huang Chen-Han , Chen Tsan-Yao , Goodacre Royston , Maher Simon
Published: August 2023

Ambient ion funnel combined with electrospray enables direct, intact, large-area, high-density and uniform deposition of nanoparticles, offering a general approach to fabricate high-performance substrates for surface-enhanced Raman scattering (SERS).
Fast and reversible solvent-vapor-induced 1D to 2D transformation in emissive Ag(i)-organic networks
Authors: Rogovoy Maxim I. , Rakhmanova Mariana I. , Sadykov Evgeniy H. , Carignan Gia M. , Bagryanskaya Irina Yu. , Li Jing , Artem’ev Alexander V.
Published: August 2023

Unprecedently fast and reversible solvent-vapour-induced 1D to 2D transformation of Ag(i)-organic frameworks is reported. The interconvertible frameworks exhibit an outstandingly bright cyan and blue room temperature phosphorescence.