bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversed asymmetric warming of sub-diurnal temperature over land during recent decades
Authors: Zhong Ziqian , He Bin , Chen Hans W. , Chen Deliang , Zhou Tianjun , Dong Wenjie , Xiao Cunde , Xie Shang-ping , Song Xiangzhou , Guo Lanlan , Ding Ruiqiang , Zhang Lixia , Huang Ling , Yuan Wenping , Hao Xingming , Ji Duoying , Zhao Xiang
Published: November 2023

In the latter half of the twentieth century, a significant climate phenomenon “diurnal asymmetric warming” emerged, wherein global land surface temperatures increased more rapidly during the night than during the day. However, recent episodes of global brightening and regional droughts and heatwaves have brought notable alterations to this asymmetric warming trend. Here, we re-evaluate sub-diurnal temperature patterns, revealing a substantial increase in the warming rates of daily maximum temperatures (Tmax), while daily minimum temperatures have remained relatively stable. This shift has resulted in a reversal of the diurnal warming trend, expanding the diurnal temperature range over recent decades. The intensified Tmax warming is attributed to a widespread reduction in cloud cover, which has led to increased solar irradiance at the surface. Our findings underscore the urgent need for enhanced scrutiny of recent temperature trends and their implications for the wider earth system.
Mechanism of selective recognition of Lys48-linked polyubiquitin by macrocyclic peptide inhibitors of proteasomal degradation
Authors: Lemma Betsegaw , Zhang Di , Vamisetti Ganga B. , Wentz Bryan G. , Suga Hiroaki , Brik Ashraf , Lubkowski Jacek , Fushman David
Published: November 2023

Post-translational modification of proteins with polyubiquitin chains is a critical cellular signaling mechanism in eukaryotes with implications in various cellular states and processes. Unregulated ubiquitin-mediated protein degradation can be detrimental to cellular homeostasis, causing numerous diseases including cancers. Recently, macrocyclic peptides were developed that selectively target long Lysine-48-linked polyubiquitin chains (tetra-ubiquitin) to inhibit ubiquitin-proteasome system, leading to attenuation of tumor growth in vivo. However, structural determinants of the chain length and linkage selectivity by these cyclic peptides remained unclear. Here, we uncover the mechanism underlying cyclic peptide’s affinity and binding selectivity by combining X-ray crystallography, solution NMR, and biochemical studies. We found that the peptide engages three consecutive ubiquitins that form a ring around the peptide and determined requirements for preferential selection of a specific trimer moiety in longer polyubiquitin chains. The structural insights gained from this work will guide the development of next-generation cyclic peptides with enhanced anti-cancer activity.
A single cell genomics atlas of the Drosophila larval eye reveals distinct photoreceptor developmental timelines
Authors: Bollepogu Raja Komal Kumar , Yeung Kelvin , Shim Yoon-Kyung , Li Yumei , Chen Rui , Mardon Graeme
Published: November 2023

TheDrosophilaeye is a powerful model system to study the dynamics of cell differentiation, cell state transitions, cell maturation, and pattern formation. However, a high-resolution single cell genomics resource that accurately profiles all major cell types of the larval eye disc and their spatiotemporal relationships is lacking. Here, we report transcriptomic and chromatin accessibility data for all known cell types in the developing eye. Photoreceptors appear as strands of cells that represent their dynamic developmental timelines. As photoreceptor subtypes mature, they appear to assume a common transcriptomic profile that is dominated by genes involved in axon function. We identify cell type maturation genes, enhancers, and potential regulators, as well as genes with distinct R3 or R4 photoreceptor specific expression. Finally, we observe that the chromatin accessibility between cones and photoreceptors is distinct. These single cell genomics atlases will greatly enhance the power of theDrosophilaeye as a model system.
Probabilistic computing with NbOx metal-insulator transition-based self-oscillatory pbit
Authors: Rhee Hakseung , Kim Gwangmin , Song Hanchan , Park Woojoon , Kim Do Hoon , In Jae Hyun , Lee Younghyun , Kim Kyung Min
Published: November 2023

Energy-based computing is a promising approach for addressing the rising demand for solving NP-hard problems across diverse domains, including logistics, artificial intelligence, cryptography, and optimization. Probabilistic computing utilizing pbits, which can be manufactured using the semiconductor process and seamlessly integrated with conventional processing units, stands out as an efficient candidate to meet these demands. Here, we propose a novel pbit unit using an NbOx volatile memristor-based oscillator capable of generating probabilistic bits in a self-clocking manner. The noise-induced metal-insulator transition causes the probabilistic behavior, which can be effectively modeled using a multi-noise-induced stochastic process around the metal-insulator transition temperature. We demonstrate a memristive Boltzmann machine based on our proposed pbit and validate its feasibility by solving NP-hard problems. Furthermore, we propose a streamlined operation methodology that considers the autocorrelation of individual bits, enabling energy-efficient and high-performance probabilistic computing.
The EPOS multi-disciplinary Data Portal for integrated access to solid Earth science datasets
Authors: Bailo Daniele , Paciello Rossana , Michalek Jan , Cocco Massimo , Freda Carmela , Jeffery Keith , Atakan Kuvvet
Published: November 2023

The European Plate Observing System (EPOS) is a long-term initiative aimed at integrating research infrastructures for solid Earth science in Europe. EPOS provides a sustainable, multidisciplinary user-oriented platform - the EPOS Data Portal - that facilitates data integration, access, use, and re-use, while adhering to the FAIR principles. The paper describes the key governance, community building, and technical aspects for achieving multidisciplinary data integration through the portal. It also outlines the key portal features for aggregating approximately 250 data sources from more than ten different scientific communities. The main architectural concepts underpinning the portal, namely the rich-metadata, the service-driven data provision, and the usage of semantics, are outlined. The paper discusses the challenges encountered during the creation of the portal, describes the community engagement process, and highlights the benefits to the scientific community and society. Future work includes expanding portal functionalities to include data analysis, processing, and visualization and releasing the portal as an open-source software package.
Prophylactic treatment can modify vascular risk biomarkers in high-frequency episodic and chronic migraine patients: a pilot study
Authors: González Mingot Cristina , Santos Lasaosa Sonia , Colàs Campàs Laura , Chilangua Canaval Laura , Gil Sánchez Anna , Brieva Ruiz Luis , Marzo Alonso María Cristina , Peralta Moncusi Silvia , Valls Marsal Joan , Cambray Carner Serafí , Purroy García Francisco
Published: November 2023

To evaluate whether preventive treatment can modify endothelial and oxidative biomarkers of vascular disease risk in patients with high-frequency episodic and chronic migraine. In this observational, prospective pilot study, 88 prophylactic treatment-naïve patients with episodic and chronic migraine and 56 healthy sex/age matched controls underwent ultrasonography exams and blood tests at baseline, and again in the migraine patients after 3 months’ treatment with metoprolol or topiramate. Biomarkers for endothelial function and oxidative stress were analyzed. At baseline, patients with migraine in the low-frequency episodic group had differences exclusively in nitrates 17.6 versus 27.33 µM; p = 0.046 compared to the controls. However, when comparing the group comprised of patients with high-frequency episodic migraine and chronic migraine versus controls, statistically significant differences appeared in hsCRP 2.68 versus 1.64 mg/dL; p = 0.049, vWF antigen (133% vs. 110%; p = 0.020, vWF activity (111% vs. 90%; p = 0.010) and isoprostane levels (181 vs. 238 µM; p = 0.05). Only in the chronic migraine subgroup did we found statistically significant differences in CIMT (0.60 vs. 0.54 mm; p = 0.042) which were significantly greater than in the controls. After treatment, patients who respond to preventive treatment exhibited significantly higher levels of nitrates (24.2–13.8 µM; p = 0.022) and nitrites (10.4–3.43 µM; p = 0.002) compared than non-responders. Moreover, biomarker levels improved in treatment-responsive patients with migraine; hsCRP levels decreased from 2.54 to 1.69 mg/dL (p < 0.05), vWF activity levels decreased from 124 to 103 IU/dL (p = 0.003) and prothrombin activity decreased from 1.01 to 0.93 (p = 0.01). These differences were also observed in the high-frequency and chronic migraine subgroup and reach statistical significance in the case of hsCRP, which decreased from 2.12 to 0.83 mg/dL (p = 0.048). Patients with migraines have differences in biomarker levels compared to controls, suggesting endothelial and oxidative dysfunction. The greatest differences in biomarker levels compared to controls are observed in migraine patients in the high-frequency and chronic migraine subgroups. Based on our results, preventive treatment is capable of modifying markers of endothelial dysfunction and oxidative stress in migraine patients, even in cases of chronic and high-frequency migraine.
Best practices for portfolio optimization by quantum computing, experimented on real quantum devices
Authors: Buonaiuto Giuseppe , Gargiulo Francesco , De Pietro Giuseppe , Esposito Massimo , Pota Marco
Published: November 2023

In finance, portfolio optimization aims at finding optimal investments maximizing a trade-off between return and risks, given some constraints. Classical formulations of this quadratic optimization problem have exact or heuristic solutions, but the complexity scales up as the market dimension increases. Recently, researchers are evaluating the possibility of facing the complexity scaling issue by employing quantum computing. In this paper, the problem is solved using the Variational Quantum Eigensolver (VQE), which in principle is very efficient. The main outcome of this work consists of the definition of the best hyperparameters to set, in order to perform Portfolio Optimization by VQE on real quantum computers. In particular, a quite general formulation of the constrained quadratic problem is considered, which is translated into Quadratic Unconstrained Binary Optimization by the binary encoding of variables and by including constraints in the objective function. This is converted into a set of quantum operators (Ising Hamiltonian), whose minimum eigenvalue is found by VQE and corresponds to the optimal solution. In this work, different hyperparameters of the procedure are analyzed, including different ansatzes and optimization methods by means of experiments on both simulators and real quantum computers. Experiments show that there is a strong dependence of solutions quality on the sufficiently sized quantum computer and correct hyperparameters, and with the best choices, the quantum algorithm run on real quantum devices reaches solutions very close to the exact one, with a strong convergence rate towards the classical solution, even without error-mitigation techniques. Moreover, results obtained on different real quantum devices, for a small-sized example, show the relation between the quality of the solution and the dimension of the quantum processor. Evidences allow concluding which are the best ways to solve real Portfolio Optimization problems by VQE on quantum devices, and confirm the possibility to solve them with higher efficiency, with respect to existing methods, as soon as the size of quantum hardware will be sufficiently high.
A prognostic model for ovarian neoplasms established by an integrated analysis of 1580 transcriptomic profiles
Authors: Hua Yanjiao , Cai Du , Shirley Cole Andrea , Mo Sien , Chen Ruyun , Gao Feng , Chen Fangying
Published: November 2023

Even after debulking surgery combined with chemotherapy or new adjuvant chemotherapy paired with internal surgery, the average year of disease free survival in advanced ovarian cancer was approximately 1.7 years1. The development of a molecular predictor of early recurrence would allow for the identification of ovarian cancer (OC) patients with high risk of relapse. The Ovarian Cancer Disease Free Survival Predictor (ODFSP), a predictive model constructed from a special set of 1580 OC tumors in which gene expression was assessed using both microarray and sequencing platforms, was created by our team. To construct gene expression barcodes that were resistant to biases caused by disparate profiling platforms and batch effects, we employed a meta-analysis methodology that was based on the binary gene pair technique. We demonstrate that ODFSP is a reliable single-sample predictor of early recurrence (1 year or less) using the largest pool of OC transcriptome data sets available to date. The ODFSP model showed significantly high prognostic value for binary recurrence prediction unaffected by clinicopathologic factors, with a meta-estimate of the area under the receiver operating curve of 0.64 (P  =  4.6E-05) and a D-index (robust hazard ratio) of 1.67 (P  =  9.2E-06), respectively. GO analysis of ODFSP’s 2040 gene pairs (collapsed to 886 distinct genes) revealed the involvement in small molecular catabolic process, sulfur compound metabolic process, organic acid catabolic process, sulfur compound biosynthetic process, glycosaminoglycan metabolic process and aminometabolic process. Kyoto encyclopedia of genes and genomes pathway analysis of ODFSP’s signature genes identified prominent pathways that included cAMP signaling pathway and FoxO signaling pathway. By identifying individuals who might benefit from a more aggressive treatment plan or enrolment in a clinical trial but who will not benefit from standard surgery or chemotherapy, ODFSP could help with treatment decisions.
Environmental pressures and pesticide exposure associated with an increase in the share of plant-based foods in the diet
Authors: Kesse-Guyot Emmanuelle , Allès Benjamin , Brunin Joséphine , Langevin Brigitte , Fouillet Hélène , Dussiot Alison , Berthy Florine , Reuzé Anouk , Perraud Elie , Rebouillat Pauline , Touvier Mathilde , Hercberg Serge , Mariotti François , Lairon Denis , Pointereau Philippe , Baudry Julia
Published: November 2023

Diets rich in plant-based foods are encouraged for human health and to preserve resources and the environment but the nutritional quality and safety of such diets is debated. This study aimed to model nutritionally adequate diets with increasing plant food content and to characterise the derived diets using a multicriteria approach including, nutrients intake, environmental pressures and exposure to pesticides. Using data of the NutriNet-Santé cohort (N = 29,413), we implemented stepwise optimization models to identified maximum plant-food content under nutritional constraints. Environmental indicators at the production level were derived from the DIALECTE database, and exposure to pesticide residues from plant food consumption was estimated using a contamination database. Plant-based foods contributed to 64.3% (SD = 10.6%) of energy intake in observed diets and may reach up to 95% in modelled diets without jeopardizing nutritional status. Compared to the observed situation, an increase in plant-based foods in the diets led to increases in soy-based products (+ 480%), dried fruits (+ 370%), legumes (+ 317%), whole grains (+ 251%), oils (+ 144%) and vegetables (+ 93%). Animal products decreased progressively until total eviction, except for beef (− 98%). Dietary quality (estimated using the Diet Quality Index Based on the Probability of Adequate Nutrient Intake) was improved (up to 17%) as well as GHGe (up to − 65%), energy demand (up to − 48%), and land occupation (− 56%) for production. Exposures to pesticides from plant-based foods were increased by 100% conventional production and to a much lesser extent by 100% organic production. This study shows that shifting to nutritionally-adequate plant-based diets requires an in-depth rearrangement of food groups’ consumption but allows a drastic reduction environmental impact. Increase exposure to pesticide residues and related risks can be mitigated by consuming foods produced with low pesticide input.
Dynamics, circuit design, feedback control of a new hyperchaotic system and its application in audio encryption
Authors: Fu ShiMing , Cheng XueFeng , Liu Juan
Published: November 2023

In this study, a 4D hyperchaotic system is constructed based on the foundation of a 3D Lü chaotic system. The newly devised hyperchaotic system possesses a sole equilibrium point, showcasing a simplified system structure that reduces complexity. This simplification offers a clearer opportunity for in-depth analysis of dynamic behaviors in the realm of scientific research. The proposed hyperchaotic system undergoes an in-depth examination of its dynamical characteristics, including chaotic attractors, equilibrium point stability, Lyapunov exponents’ spectrum, and bifurcation diagram. Numerical analysis results reveal that the attractor of this hyperchaotic system exhibits highly complex, non-periodic, and fractal structural dynamics. Its motion demonstrates extreme sensitivity and randomness, even within a wide range of variations in parameter d, affirming its hyperchaotic properties with two positive Lyapunov exponents. Hyperchaotic bifurcation diagrams typically exhibit highly intricate structures, such as fractals, branches, and period doubling characteristics, signifying that even minor parameter adjustments can lead to significant changes in system behavior, presenting diversity and unpredictability. Subsequently, to further investigate the practical utility of this hyperchaotic system, a linear feedback control strategy is implemented. Through linear feedback control, the hyperchaotic system is stabilized at its unique equilibrium point. Experimental validation is conducted using both computer software simulation Matlab, electronic circuit simulation Multisim, and embedded hardware STM32. The results of these experiments consistently align, providing theoretical support for the application of this hyperchaotic system in practical domains. Finally, leveraging the hyperchaotic keys generated by this hyperchaotic system, audio encryption is achieved using a cross-XOR algorithm, which is then realized on the embedded hardware platform STM32. The results show that the audio encryption scheme based on the hyperchaotic system is feasible, and the method is simple to implement, has nonlinear characteristics and certain algorithm complexity, which can be applied to audio encryption, image encryption, video encryption, and more.
Prognostic association supports indexing size measures in echocardiography by body surface area
Authors: Fung Angus S. Y. , Soundappan Dhnanjay , Loewenstein Daniel E. , Playford David , Strange Geoffrey , Kozor Rebecca , Otton James , Ugander Martin
Published: November 2023

Body surface area (BSA) is the most commonly used metric for body size indexation of echocardiographic measures, but its use in patients who are underweight or obese is questioned (body mass index (BMI) < 18.5 kg/m2 or ≥ 30 kg/m2, respectively). We aim to use survival analysis to identify an optimal body size indexation metric for echocardiographic measures that would be a better predictor of survival than BSA regardless of BMI. Adult patients with no prior valve replacement were selected from the National Echocardiography Database Australia. Survival analysis was performed for echocardiographic measures both unindexed and indexed to different body size metrics, with 5-year cardiovascular mortality as the primary endpoint. Indexation of echocardiographic measures (left ventricular end-diastolic diameter [n = 230,109] and mass [n = 224,244], left atrial volume [n = 150,540], aortic sinus diameter [n = 90,805], right atrial area [n = 59,516]) by BSA had better prognostic performance vs unindexed measures (underweight: C-statistic 0.655 vs 0.647; normal weight/overweight: average C-statistic 0.666 vs 0.625; obese: C-statistic 0.627 vs 0.613). Indexation by other body size metrics (lean body mass, height, and/or weight raised to different powers) did not improve prognostic performance versus BSA by a clinically relevant magnitude (average C-statistic increase ≤ 0.02), with smaller differences in other BMI subgroups. Indexing measures of cardiac and aortic size by BSA improves prognostic performance regardless of BMI, and no other body size metric has a clinically meaningful better performance.
Inflammatory bowel disease biomarkers revealed by the human gut microbiome network
Authors: Hu Mirko , Caldarelli Guido , Gili Tommaso
Published: November 2023

Inflammatory bowel diseases (IBDs) are complex medical conditions in which the gut microbiota is attacked by the immune system of genetically predisposed subjects when exposed to yet unclear environmental factors. The complexity of this class of diseases makes them suitable to be represented and studied with network science. In this paper, the metagenomic data of control, Crohn’s disease, and ulcerative colitis subjects’ gut microbiota were investigated by representing this data as correlation networks and co-expression networks. We obtained correlation networks by calculating Pearson’s correlation between gene expression across subjects. A percolation-based procedure was used to threshold and binarize the adjacency matrices. In contrast, co-expression networks involved the construction of the bipartite subjects-genes networks and the monopartite genes-genes projection after binarization of the biadjacency matrix. Centrality measures and community detection were used on the so-built networks to mine data complexity and highlight possible biomarkers of the diseases. The main results were about the modules ofBacteroides, which were connected in the control subjects’ correlation network,Faecalibacterium prausnitzii, where co-enzyme A became central in IBD correlation networks andEscherichia coli, whose module has different patterns of integration within the whole network in the different diagnoses.
Modelling opinion dynamics under the impact of influencer and media strategies
Authors: Helfmann Luzie , Djurdjevac Conrad Nataša , Lorenz-Spreen Philipp , Schütte Christof
Published: November 2023

Digital communication has made the public discourse considerably more complex, and new actors and strategies have emerged as a result of this seismic shift. Aside from the often-studied interactions among individuals during opinion formation, which have been facilitated on a large scale by social media platforms, the changing role of traditional media and the emerging role of “influencers” are not well understood, and the implications of their engagement strategies arising from the incentive structure of the attention economy even less so. Here we propose a novel framework for opinion dynamics that can accommodate various versions of opinion dynamics as well as account for different roles, namely that of individuals, media and influencers, who change their own opinion positions on different time scales. Numerical simulations of instances of this framework show the importance of their relative influence in creating qualitatively different opinion formation dynamics: with influencers, fragmented but short-lived clusters emerge, which are then counteracted by more stable media positions. The framework allows for mean-field approximations by partial differential equations, which reproduce those dynamics and allow for efficient large-scale simulations when the number of individuals is large. Based on the mean-field approximations, we can study how strategies of influencers to gain more followers can influence the overall opinion distribution. We show that moving towards extreme positions can be a beneficial strategy for influencers to gain followers. Finally, our framework allows us to demonstrate that optimal control strategies allow other influencers or media to counteract such attempts and prevent further fragmentation of the opinion landscape. Our modelling framework contributes to a more flexible modelling approach in opinion dynamics and a better understanding of the different roles and strategies in the increasingly complex information ecosystem.
Expression of a large coding sequence: Gene therapy vectors for Ataxia Telangiectasia
Authors: Hirch Tanja , Brander Nadine , Schenk Franziska , Pöllmann Simon J. , Reichenbach Janine , Schubert Ralf , Modlich Ute
Published: November 2023

Ataxia telangiectasia is a monogenetic disorder caused by mutations in the ATM gene. Its encoded protein kinase ATM plays a fundamental role in DNA repair of double strand breaks (DSBs). Impaired function of this kinase leads to a multisystemic disorder including immunodeficiency, progressive cerebellar degeneration, radiation sensitivity, dilated blood vessels, premature aging and a predisposition to cancer. Since allogenic hematopoietic stem cell (HSC) transplantation improved disease outcome, gene therapy based on autologous HSCs is an alternative promising concept. However, due to the large cDNA of ATM (9.2 kb), efficient packaging of retroviral particles and sufficient transduction of HSCs remains challenging.

We generated lentiviral, gammaretroviral and foamy viral vectors with a GFP.F2A.Atm fusion or a GFP transgene and systematically compared transduction efficiencies. Vector titers dropped with increasing transgene size, but despite their described limited packaging capacity, we were able to produce lentiviral and gammaretroviral particles. The reduction in titers could not be explained by impaired packaging of the viral genomes, but the main differences occurred after transduction. Finally, after transduction of Atm-deficient (ATM-KO) murine fibroblasts with the lentiviral vector expressing Atm, we could show the expression of ATM protein which phosphorylated its downstream substrates (pKap1 and p-p53).
Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors
Authors: Tajik Fatemeh , Fattahi Fahimeh , Rezagholizadeh Fereshteh , Bouzari Behnaz , Babaheidarian Pegah , Baghai Wadji Masoud , Madjd Zahra
Published: November 2023

DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. Several studies showed that the dysregulation of DDIT4 is involved in different malignancies with paradoxical expressions and roles. Therefore, this study investigated the clinical significance, prognostic, and diagnostic value of DDIT4 in different types of pancreatic tumors (PT). The expression of DDIT4 and long non-coding RNA (TPTEP1) in mRNA level was examined in 27 fresh PT samples using Real-time quantitative PCR (RT-qPCR). Moreover, 200 formalin-fixed paraffin-embedded PT tissues, as well as 27 adjacent normal tissues, were collected to evaluate the clinical significance, prognostic, and diagnosis value of DDIT4 expression by immunohistochemistry (IHC) on tissue microarrays (TMA) slides. The results of RT-qPCR showed that the expression of DDIT4 in tumor samples was higher than in normal samples which was associated with high tumor grade (P = 0.015) and lymphovascular invasion (P = 0.048). Similar to this, IHC findings for nucleus, cytoplasm, and membrane localization showed higher expression of DDIT4 protein in PT samples rather than in nearby normal tissues. A statistically significant association was detected between a high level of nuclear expression of DDIT4 protein, and lymphovascular invasion (P = 0.025), as well as advanced TNM stage (P = 0.034) pancreatic ductal adenocarcinoma (PDAC) and in pancreatic neuroendocrine tumor (PNET), respectively. In contrast, a low level of membranous expression of DDIT4 protein showed a significant association with advanced histological grade (P = 0.011), margin involvement (P = 0.007), perineural invasion (P = 0.023), as well as lymphovascular invasion (P = 0.005) in PDAC. No significant association was found between survival outcomes and expression of DDIT4 in both types. It was found that DDIT4 has rational accuracy and high sensitivity as a diagnostic marker. Our results revealed a paradoxical role of DDIT4 expression protein based on the site of nuclear and membranous expression. The findings of this research indicated that there is a correlation between elevated nuclear expression of DDIT4 and the advancement and progression of disease in patients with PT. Conversely, high membranous expression of DDIT4 was associated with less aggressive tumor behavior in patients with PDAC. However, further studies into the prognostic value and biological function of DDIT4 are needed in future studies.
Glucose restriction in Saccharomyces cerevisiae modulates the phosphorylation pattern of the 20S proteasome and increases its activity
Authors: Bicev Renata Naporano , de Souza Degenhardt Maximilia Frazão , de Oliveira Cristiano Luis Pinto , da Silva Emerson Rodrigo , Degrouard Jéril , Tresset Guillaume , Ronsein Graziella Eliza , Demasi Marilene , da Cunha Fernanda Marques
Published: November 2023

Caloric restriction is known to extend the lifespan and/or improve diverse physiological parameters in a vast array of organisms. In the yeast Saccharomyces cerevisiae, caloric restriction is performed by reducing the glucose concentration in the culture medium, a condition previously associated with increased chronological lifespan and 20S proteasome activity in cell extracts, which was not due to increased proteasome amounts in restricted cells. Herein, we sought to investigate the mechanisms through which glucose restriction improved proteasome activity and whether these activity changes were associated with modifications in the particle conformation. We show that glucose restriction increases the ability of 20S proteasomes, isolated from Saccharomyces cerevisiae cells, to degrade model substrates and whole proteins. In addition, threonine 55 and/or serine 56 of the α5-subunit, were/was consistently found to be phosphorylated in proteasomes isolated from glucose restricted cells, which may be involved in the increased proteolysis capacity of proteasomes from restricted cells. We were not able to observe changes in the gate opening nor in the spatial conformation in 20S proteasome particles isolated from glucose restricted cells, suggesting that the changes in activity were not accompanied by large conformational alterations in the 20S proteasome but involved allosteric activation of proteasome catalytic site.
Delta radiomics analysis for prediction of intermediary- and high-risk factors for patients with locally advanced cervical cancer receiving neoadjuvant therapy
Authors: Wu Rong-Rong , Zhou Yi-Min , Xie Xing-Yun , Chen Jin-Yang , Quan Ke-Run , Wei Yu-Ting , Xia Xiao-Yi , Chen Wen-Juan
Published: November 2023

This study aimed to assess the feasibility of using magnetic resonance imaging (MRI)-based Delta radiomics characteristics extrapolated from the Ax LAVA + C series to identify intermediary- and high-risk factors in patients with cervical cancer undergoing surgery following neoadjuvant chemoradiotherapy. A total of 157 patients were divided into two groups: those without any intermediary- or high-risk factors and those with one intermediary-risk factor (negative group; n = 75). Those with any high-risk factor or more than one intermediary-risk factor (positive group; n = 82). Radiomics characteristics were extracted using Ax-LAVA + C MRI sequences. The data was divided into training (n = 126) and test (n = 31) sets in an 8:2 ratio. The training set data features were selected using the Mann–Whitney U test and the Least Absolute Shrinkage and Selection Operator (LASSO) test. The best radiomics features were then analyzed to build a preoperative predictive radiomics model for predicting intermediary- and high-risk factors in cervical cancer. Three models—the clinical model, the radiomics model, and the combined clinic and radiomics model—were developed in this study utilizing the random forest Algorithm. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity were used to assess the predictive efficacy and clinical benefits of each model. Three models were developed in this study to predict intermediary- and high-risk variables associated with postoperative pathology for patients who underwent surgery after receiving neoadjuvant radiation. In the training and test sets, the AUC values assessed using the clinical model, radiomics model, and combined clinical and radiomics models were 0.76 and 0.70, 0.88 and 0.86, and 0.91 and 0.89, respectively. The use of machine learning algorithms to analyze Delta Ax LAVA + C MRI radiomics features can aid in the prediction of intermediary- and high-risk factors in patients with cervical cancer receiving neoadjuvant therapy.
Using machine learning approach for screening metastatic biomarkers in colorectal cancer and predictive modeling with experimental validation
Authors: Ahmadieh-Yazdi Amirhossein , Mahdavinezhad Ali , Tapak Leili , Nouri Fatemeh , Taherkhani Amir , Afshar Saeid
Published: November 2023

Colorectal cancer (CRC) liver metastasis accounts for the majority of fatalities associated with CRC. Early detection of metastasis is crucial for improving patient outcomes but can be delayed due to a lack of symptoms. In this research, we aimed to investigate CRC metastasis-related biomarkers by employing a machine learning (ML) approach and experimental validation. The gene expression profile of CRC patients with liver metastasis was obtained using the GSE41568 dataset, and the differentially expressed genes between primary and metastatic samples were screened. Subsequently, we carried out feature selection to identify the most relevant DEGs using LASSO and Penalized-SVM methods. DEGs commonly selected by these methods were selected for further analysis. Finally, the experimental validation was done through qRT-PCR. 11 genes were commonly selected by LASSO and P-SVM algorithms, among which seven had prognostic value in colorectal cancer. It was found that the expression of the MMP3 gene decreases in stage IV of colorectal cancer compared to other stages (P value < 0.01). Also, the expression level of the WNT11 gene was observed to increase significantly in this stage (P value < 0.001). It was also found that the expression of WNT5a, TNFSF11, and MMP3 is significantly lower, and the expression level of WNT11 is significantly higher in liver metastasis samples compared to primary tumors. In summary, this study has identified a set of potential biomarkers for CRC metastasis using ML algorithms. The findings of this research may provide new insights into identifying biomarkers for CRC metastasis and may potentially lay the groundwork for innovative therapeutic strategies for treatment of this disease.
Blink-related EEG activity measures cognitive load during proactive and reactive driving
Authors: Alyan Emad , Arnau Stefan , Reiser Julian Elias , Getzmann Stephan , Karthaus Melanie , Wascher Edmund
Published: November 2023

Assessing drivers’ cognitive load is crucial for driving safety in challenging situations. This research employed the occurrence of drivers’ natural eye blinks as cues in continuously recorded EEG data to assess the cognitive workload while reactive or proactive driving. Twenty-eight participants performed either a lane-keeping task with varying levels of crosswind (reactive) or curve road (proactive). The blink event-related potentials (bERPs) and spectral perturbations (bERSPs) were analyzed to assess cognitive load variations. The study found that task load during reactive driving did not significantly impact bERPs or bERSPs, possibly due to enduring alertness for vehicle control. The proactive driving revealed significant differences in the occipital N1 component with task load, indicating the necessity to adapt the attentional resources allocation based on road demands. Also, increased steering complexity led to decreased frontal N2, parietal P3, occipital P2 amplitudes, and alpha power, requiring more cognitive resources for processing relevant information. Interestingly, the proactive and reactive driving scenarios demonstrated a significant interaction at the parietal P2 and occipital N1 for three difficulty levels. The study reveals that EEG measures related to natural eye blink behavior provide insights into the effect of cognitive load on different driving tasks, with implications for driver safety.
Carbon-infiltrated carbon nanotubes inhibit the development of Staphylococcus aureus biofilms
Authors: Bowden Lucy C. , Evans Jocelyn G. W. , Miller Katelyn M. , Bowden Anton E. , Jensen Brian D. , Hope Sandra , Berges Bradford K.
Published: November 2023

Staphylococcus aureus forms biofilms that cause considerable morbidity and mortality in patients who receive implanted devices such as prosthetics or fixator pins. An ideal surface for such medical devices would inhibit biofilm growth. Recently, it was reported that surface modification of stainless steel materials with carbon-infiltrated carbon nanotubes (CICNT) inhibits the growth of S. aureus biofilms. The purpose of this study was to investigate this antimicrobial effect on titanium materials with CICNT coated surfaces in a variety of surface morphologies and across a broader spectrum of S. aureus isolates. Study samples of CICNT-coated titanium, and control samples of bare titanium, a common implant material, were exposed to S. aureus. Viable bacteria were removed from adhered biofilms and quantified as colony forming units. Scanning electron microscopy was used to qualitatively analyze biofilms both before and after removal of cells. The CICNT surface was found to have significantly fewer adherent bacteria than bare titanium control surfaces, both via colony forming unit and microscopic analyses. This effect was most pronounced on CICNT surfaces with an average nanotube diameter of 150 nm, showing a 2.5-fold reduction in adherent bacteria. Since S. aureus forms different biofilm structures by isolate and by growth conditions, we tested 7 total isolates and found a significant reduction in the biofilm load in six out of seven S. aureus isolates tested. To examine whether the anti-biofilm effect was due to the structure of the nanotubes, we generated an unstructured carbon surface. Significantly more bacteria adhered to a nonstructured carbon surface than to the 150 nm CICNT surface, suggesting that the topography of the nanotube structure itself has anti-biofilm properties. The CICNT surface possesses anti-biofilm properties that result in fewer adherent S. aureus bacteria. These anti-biofilm properties are consistent across multiple isolates of S. aureus and are affected by nanotube diameter. The experiments performed in this study suggest that this effect is due to the nanostructure of the CICNT surface.
Structural flexibility of apolipoprotein E-derived arginine-rich peptides improves their cell penetration capability
Authors: Takechi-Haraya Yuki , Ohgita Takashi , Usui Akiko , Nishitsuji Kazuchika , Uchimura Kenji , Abe Yasuhiro , Kawano Ryuji , Konaklieva Monika I. , Reimund Mart , Remaley Alan T. , Sato Yoji , Izutsu Ken-ichi , Saito Hiroyuki
Published: November 2023

Amphipathic arginine-rich peptide, A2-17, exhibits moderate perturbation of lipid membranes and the highest cell penetration among its structural isomers. We investigated the direct cell-membrane penetration mechanism of the A2-17 peptide while focusing on structural flexibility. We designed conformationally constrained versions of A2-17, stapled (StpA2-17) and stitched (StchA2-17), whose α-helical conformations were stabilized by chemical crosslinking. Circular dichroism confirmed that StpA2-17 and StchA2-17 had higher α-helix content than A2-17 in aqueous solution. Upon liposome binding, only A2-17 exhibited a coil-to-helix transition. Confocal microscopy revealed that A2-17 had higher cell penetration efficiency than StpA2-17, whereas StchA2-17 remained on the cell membrane without cell penetration. Although the tryptophan fluorescence analysis suggested that A2-17 and its analogs had similar membrane-insertion positions between the interface and hydrophobic core, StchA2-17 exhibited a higher membrane affinity than A2-17 or StpA2-17. Atomic force microscopy demonstrated that A2-17 reduced the mechanical rigidity of liposomes to a greater extent than StpA2-17 and StchA2-17. Finally, electrophysiological analysis showed that A2-17 induced a higher charge influx through transient pores in a planer lipid bilayer than StpA2-17 and StchA2-17. These findings indicate that structural flexibility, which enables diverse conformations of A2-17, leads to a membrane perturbation mode that contributes to cell membrane penetration.
Urinary beta 3-adrenoceptor as a diagnostic biomarker for overactive bladder in women
Authors: Liang Ching-Chung , Hsieh Wu-Chiao , Lo Tsia-Shu , Huang Ting-Xuan , Chou Yi-Chun , Huang Jing-Yi , Huang Yung-Hsin
Published: November 2023

This study was to investigate urinary beta 3-adrenoceptor concentration as a biomarker for overactive bladder (OAB) and predictor of treatment outcomes in women receiving the beta 3-adrenoceptor agonist mirabegron. The study comprised 50 women identified with OAB and 35 women considered as healthy controls. All women with OAB received daily dosage of 50 mg of mirabegron for 12 weeks. Bladder diaries, OAB-related questionnaires, and global response assessment scale (GRAS) data were collected. Urinary beta 3-adrenoceptor concentration was measured through enzyme-linked immunosorbent assay. All OAB-related questionnaires and GRAS indicated improved posttreatment urinary health. After mirabegron treatment, the frequency of micturition and urgency episodes decreased, but the urinary beta 3-adrenoceptor/creatinine (Cr) ratio increased. The urinary beta 3-adrenoceptor/creatinine ratio was identified as a sensitive biomarker for OAB with a confidence interval of 0.656 to 0.856 (p < 0.001). A negative correlation (− 0.431, p = 0.040) between this biomarker and health-related quality of life (HRQL) scores. The Beta 3-adrenoceptor/Cr levels increased significantly in the treatment-responsive group, while they remained unchanged in the unsatisfactory outcome group. This study shows that 12 weeks of mirabegron treatment improves OAB symptoms and HRQL. Furthermore, urinary beta 3-adrenoceptor concentration may be a diagnostic biomarker for OAB.
Exploring the causal relationship between inflammatory cytokines and migraine: a bidirectional, two-sample Mendelian randomization study
Authors: Fu Chong , Chen Yan , Xu Wei , Zhang Yanping
Published: November 2023

To further evaluate the causal relationships between inflammatory cytokines and migraine, we conducted a bidirectional, two-sample Mendelian randomization (MR) analysis using genetic data from publicly available genome-wide association studies (GWAS). We used several MR methods, including random-effect inverse-variance weighting (IVW), weighted median, MR-Egger, to test the causal relationships. Sensitivity analyses were also conducted to evaluate the robustness of the results. The results showed that hepatocyte growth factor (HGF) was positively associated with the risk of migraine (odds ratio [OR], 1.004; 95% confidence interval [CI], 1.001–1.008; P = 0.022). In addition, Interleukin-2 (IL-2) was considered a downstream consequence of migraine (OR, 0.012; 95% CI, 0.000–0.0929; P = 0.046). These findings suggest that HGF may be a factor associated with the etiology of migraine, while IL-2 is more likely to be involved in the downstream development of migraine.
Spatio-temporal divergence and influencing factors of agritourism integration development in Xinjiang, China
Authors: Peng Yaping , Liu Weizhong , Xiong Changjiang
Published: November 2023

Exploring the coupling and coordination relationship between agriculture and tourism industry plays an important role in formulating differentiated integration development policies and promoting regional economic development. We adopt 14 prefectures and cities in Xinjiang, China as examples, and use a coupling coordination model and generalized method of moments estimation to explore the spatial differentiation characteristics and influencing factors between agriculture and tourism industries in various prefectures and cities in Xinjiang from 2009 to 2018. The results indicate: (1) The combined development levels of agriculture and tourism in Xinjiang exhibited a similar development trend over the period, and despite fluctuations in individual years, the overall trend is still increasing. (2) The coupling degree and coordination of agriculture and tourism in various regions presented significant spatial differentiation characteristics. (3) Human capital, residents’ consumption level, and coupling coordination degree are positively correlated, while service capacity, government support, industrial foundation, and market supply and coupling coordination degree are significantly negatively correlated. Finally, based on our results, we present corresponding suggestions on how to improve the level of integrated development of agriculture and tourism in Xinjiang.
Efficacy of second-line chemotherapy after treatment with gemcitabine plus nab-paclitaxel or FOLFIRINOX in patients with metastatic pancreatic cancer
Authors: Fukahori Masaru , Okabe Yoshinobu , Shimokawa Mototsugu , Otsuka Taiga , Koga Futa , Ueda Yujiro , Nakazawa Junichi , Komori Azusa , Otsu Satoshi , Arima Shiho , Makiyama Akitaka , Taguchi Hiroki , Honda Takuya , Ushijima Tomoyuki , Miwa Keisuke , Shibuki Taro , Nio Kenta , Ide Yasushi , Ureshino Norio , Mizuta Toshihiko , Mitsugi Kenji , Shirakawa Tsuyoshi
Published: November 2023

First-line chemotherapy for patients with metastatic pancreatic cancer (MPC) includes gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX). However, the efficacy of second-line chemotherapy and the role of combination chemotherapy in clinical practice is still unknown. Data was gathered from 14 hospitals in the Kyushu area of Japan from December 2013 to March 2017. The median overall survival (mOS) from second-line treatment was contrasted between patients who received second-line chemotherapy (CT group) and those who received the best supportive care (BSC group). Furthermore, the mOS of combination chemotherapy was compared to mono chemotherapy in the CT group. To control possible bias in the selection of treatment, we performed a propensity score-adjusted analysis. A total of 255 patients received GnP or FFX as first-line chemotherapy. There were 156 in the CT group and 77 in the BSC group of these. The CT group had a significantly longer mOS than the BSC group (5.2 vs. 2.6 months; adjusted hazard ratio (HR) 0.38; 95% CI 0.27–0.54). In the CT group, 89 patients received combination chemotherapy while 67 received mono chemotherapy. The mOS did not differ significantly between the combination and mono chemotherapy groups (5.5 vs. 4.8 months; adjusted HR 0.88; 95% CI 0.58–1.33). Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination chemotherapy conferred no improvement in survival compared to mono chemotherapy.