bluuebunny/crossref_metadata_2025 huggingface dataset:
An Empirical Investigation on Growth and Institutional Structure Relations in Central Asian and Caucasian Countries
Authors: ÇUHADAR Pınar , (KIRAN) BULĞURCU Berna
Published: September 2023

Whether economic and political institutions have an impact on countries' economic growth performances is one of the important research topics discussed in the literature. Former socialist Central Asian and Caucasian countries trying to adapt into market economy have not yet completed their transition processes, but they have managed to grow their economies in comparison to previous periods. The aim of this study is to analyse the relationship between the growth performances and institutional structures of the Central Asian and Caucasian countries of Azerbaijan, Armenia, Georgia, Kazakhstan, Kyrgyzstan and Tajikistan between the years 2000-2018 by using the decision variables of civil rights, economic freedom, political stability, rule of law and GDP per capita. According to the analysis results obtained via Grey Relational Analysis method by assigning equal importance to all variables, Kazakhstan is found to be the highest-ranking country among all examined countries for all periods. The authoritarian tendencies that these countries have shown during their market economy transitions with regards to matters related to institutional structure have been found to be the reason why countries’ economic efforts have failed to yield results
Quality of life and needs in caregivers: results from the prospective multicentric open-label randomized study of Informal Caregivers of Elderly patients (ICE study).
Authors: Pozet Astrid , Darnis Sophie , Bonnet Magalie , Meurisse Aurélia , Dabakuyo-Yonli Tienhan Sandrine , Lejeune Catherine , Fagnoni Philippe , Gaimard Maryse , Manckoundia Patrick , Quibel Clémence , Marchand Mélanie , Anota Amélie , Nerich Virginie
Published: September 2023

Objectives. To assess health-related quality of life (QoL) in caregivers of elderly patients with chronic disabilities receiving, or not receiving, social worker support.
Methods. This multicenter open-label randomized study assigned caregivers to receive an information booklet, exclusively, or with social worker support. Caregivers completed Short Form-36 (SF-36) and Hospital Anxiety Depression Scale quarterly, and Zarit Burden Interview each semester, for 24 months. We reported caregiver QoL mean changes at 12 and 24 months (M12, M24). Longitudinal QoL analysis up to M24 used mixed models for repeated measures (MMRM).
Results. Among the 179 caregivers randomized from 2015 to 2019, the SF-36 physical and mental component summary showed no significant changes at M12 and M24, in terms of neither anxiety nor burden. However, depression significantly increased (M12: 1.4±4.0; M24:1.7±4.1) with significant adjusted mean increase using MMRM at M24: 3.4 [0.6-2.5] in the control group, exclusively.
Conclusion. These findings call for better recognition of the social support to prevent caregiver QoL deterioration and alleviate their depression early in the course of the disease.
Trial registration number: This study was registered retrospectively with ClinicalTrials.gov NCT02626377 on 9th December 2015.
Augmented Ant Colony Algorithm for Virtual Drug Discovery
Authors: Donati Luca , Fackeldey Konstantin , Weber Marcus
Published: September 2023

Docking is a fundamental problem in computational biology and drug discovery that seeks to predict a ligand’s binding mode and affinity to a target protein. However, the large search space size and the complex-ity of the underlying physical interactions make docking a challenging task. Here, we review a docking method, based on the ant colony opti-mization algorithm, that ranks a set of candidate ligands by solving a minimization problem for each ligand individually. In addition, we pro-pose an augmented version that takes into account all energy functions collectively, allowing only one minimization problem to be solved. The results show that our modification outperforms in accuracy and efficiency.
Seawater composition variation in the eastern Sichuan evaporite formation basin
Authors: Zhao Haitong , Tian Heming
Published: September 2023

The Hechuan Depression is a secondary depression in central eastern Sichuan and belongs to the Nanchong salt area (central Sichuan salt-forming zone). Palaeotethys seawater entered the secondary depression, and the subbasin gradually became shallower with tectonic changes. In this paper, the content of Sr ranges from 130 to 1316 ppm, which indicates that the water‒rock interaction time was long. The Br content of Jianglingjiang halite ranges from 108 to 191 ppm, and the Br content of the salt rock is mainly controlled by the Br concentration in concentrated seawater. The 1000Br/Cl ratio ranges from 0.18 to 0.51, which has reached the potassium mineral precipitation stage. The global environmental conditions of the Early Triassic were inherited from the late Permian with high temperature, anoxia, water stagnation and other environmental factors. The Sr isotopes of halite samples show that the ratios range from 0.708147 to 0.708256. By comparing the early Triassic SIS curve, which is consistent with the trend between the Smithian and Spathian, it can be basically determined that the evaporites were deposited in the Olenekian.
SEATANI: hazards from seamounts in SouthEast Asia, Taiwan, and Andaman and Nicobar Islands (eastern India)
Authors: Verolino Andrea , Wee Su Fen , Jenkins Susanna , Costa Fidel , Switzer Adam
Published: September 2023

Submarine volcanism makes up approximately 85% of volcanism taking place on Earth, and its eruptions can be particularly hazardous, with the potential to cause large-scale sector collapse of the volcanic edifice, tsunamis, and ash dispersal. Recent examples include the eruptions in Japan and in the Kingdom of Tonga in 2021 and 2022 respectively, but there has been little to no study of submarine volcanoes in Southeast Asia and its surroundings. Here we provide a compilation of 466 seamounts from the region, from different published sources, through the SEATANI dataset (Southeast Asia + Taiwan + Andaman & Nicobar Islands). We use this newly compiled dataset to assess on a regional basis the seamount hazard potential and exposure potential as a springboard for future more quantitative hazard studies for the region. The hazard potential was assessed through seamount morphological/structural analyses, to determine the seamount evolution stage and, grade of maturity. The exposure potential was evaluated through two different approaches: An areal analysis of the number of assets within a 100 km radius of each seamount; and the development of a hazard-weighted seamount density map to highlight potential areas of interest for future more-in-depth studies. Our results show that there are several potentially hazardous seamounts in this region, and Taiwan had the highest hazard and exposure potential, for all assets considered, while Philippines, Indonesia and Vietnam have relatively high exposure potential for submarine communication cables and ship traffic density. The results from this work serve as a first step for southeast Asian and neighbouring countries to become more resilient against and prepared for submarine volcanic eruptions in the region.
Phase Transfer Catalysts Shift the Pathway to Transmetalation in Biphasic Suzuki-Miyaura Cross-Couplings
Authors: Hein Jason , Shi Yao , Derasp Joshua , Maschmeyer Tristan
Published: September 2023

The Suzuki-Miyaura coupling (SMC) is arguably the most widely used C-C bond forming reaction. Numerous mechanistic studies of the SMC have enabled the use of exceptionally low catalyst loadings while significantly expanding its functional group tolerance. However, the dominant mode of transmetalation operative in SMCs remains controversial and likely depends on the particular conditions employed. Herein we report a detailed mechanistic study of a palladium catalyzed SMC under biphasic reaction conditions. The use of phase transfer catalysts (PTC) resulted in a remarkable 12-fold rate enhancement in the targeted system. Studying the speciation of the arylboron nucleophile and the palladium catalyst revealed that a shift from an oxo-palladium based transmetalation to a boronate based pathway lies at the root of this activity. Furthermore, the robustness of our monitoring platform enabled us to study the impact of different water loadings in biphasic settings. We found that increasing the proportion of the aqueous phase results in significant rate enhancements, contrary to the reaction conditions typically employed in the literature. This rate acceleration matched or surpassed those achieved by manipulating the nature of the organoboron nucleophile. The importance of these findings was highlighted by achieving an exceptionally broad substrate scope with benzylic electrophiles using a 10-fold reduction in catalyst loading relative to literature precedent.
Biocatalytic stereocontrolled head-to-tail cyclizations as a tool for streamlined hybrid synthesis of terpenes
Authors: Hauer Bernhard , Schneider Andreas , Lystbæk Thomas , Markthaler Daniel , Hansen Niels
Published: September 2023

The stereocontrolled cationic cyclization cascade is a vital step in the modular biogenesis of terpenes, as it defines the carbon skeleton's three-dimensional structure in one atom-economical step. While nature has adopted this strategy for eons, state-of-the-art synthetic routes to asymmetrically access cyclic terpenes still rely predominantly on sequential multi-step scaffold remodelling of a few abundant precursors. Herein, we bridge this long-standing methodological gap and demonstrate the target-oriented synthesis ability of the squalene-hopene cyclase. Our mechanistic insights show that the biocatalytic head-to-tail cyclization is highly customizable by mechanism-guided enzyme engineering and substrate-focused setup engineering. As a result, we demonstrate two- or three-step hybrid synthetic routes of pheromones, fragrances, and drug candidates by merging a stereocontrolled cyclization with interdisciplinary synthetic and catalytic methods. This biomimetic strategy significantly reduces the synthesis effort to terpenes and provides rapid access to thousands of head-to-tail-fused scaffolds.
Intrinsic dichroism in amorphous and crystalline solids with helical light
Authors: Jain Ashish , Bégin Jean-Luc , Corkum Paul , Karimi Ebrahim , Brabec Thomas , Bhardwaj Ravi
Published: September 2023

Amorphous solids do not exhibit long-range order due to the disordered arrangement of atoms. As a result, they lack translational and rotational symmetry on a macroscopic scale and are isotropic, meaning their physical properties remain the same in all directions. Because of their lack of symmetry, differential absorption of polarized light, called dichroism, is not known to exist in amorphous solids. However, they possess short- to medium-range order that can cause them to exhibit some features similar to crystalline solids. Using helical light beams that carry orbital angular momentum as a probe, we demonstrate that dichroism is intrinsic to both amorphous and crystalline solids. We show that in the nonlinear regime, angle-dependent absorption of helical light can map the crystal symmetry - a macroscopic feature, whereas helical dichroism is responsive to the short- to medium- range order whose existence is explained in terms of interband multiphoton-assisted tunneling. We also demonstrate that the helical dichroism signal is sensitive to chirality and its strength can be controlled and tuned using a superposition of OAM and Gaussian beams. Our research challenges the conventional knowledge that dichroism does not exist in amorphous solids and enables to manipulate the optical properties of solids, opening new opportunities for development of chiroptical spectroscopy.
Steel Slag as a Construction Material for Sustainable Deveploment: A State of Art
Authors: Kalane Saurabh Pramod , Shekokar Shubhangi R
Published: September 2023

In India large amount of iron & steel slags are generated from steel industry and disposed in the yards of production units. Due to limited use, these slag materials occupy largest areas and also causing environmental pollution. These slag materials can be possible to use in construction industry effectively. In this paper, a thorough review has been carried out on the work done by various researchers on the use of steel slag as a construction material. Steel slag has good properties such as high bearing strength, excellent soundness & abrasion resistance. Steel slag aggregate material can hold heat for a longer period than natural aggregate due to their high heat capacity. In this review, it was revealed that the compressive strength of concrete increases when slag is substituted with natural aggregate, reaching its maximum strength at 40% slag. It is recommended that steel slag can be used as an alternate material to replace a portion of the aggregate in concrete. This will help to reduce construction expenses and ensure the safe disposal of steel slag so as to achieve sustainability.
Antibody and antibody fragments Site Specific Conjugation using New Q-tag Substrate of Bacterial Transglutaminase.
Authors: Alaoui Said El , Sivado Eva , Alaoui Meddy El , Jallas Anne-Catherine , Mebarki Lamia , Dyson Michael R. , Perez Franck , Valsesia-Wittmann Sandrine
Published: September 2023

During the last few years Antibody Drug Conjugates (ADCs) have become one of the most active and very promising therapeutic weapons. Lessons learned from the traditional chemical conjugations (via lysine or cysteine residues of the antibodies) and the clinical studies of the developed ADCs have recently paved the way to the improvement of the conjugation technologies. Use of site-specific conjugation is considered as the promising path for improving the design and development of homogeneous ADCs with controlled Drug-Antibody ratio (DAR). Moreover, some of these conjugations can be applied to antibody fragments such as Fab, scfv and VHH for which random and chemical conjugation showed significant limitations. In this study, we identified a novel small peptide substrate (Q-tag) with high affinity and specificity of bacterial transglutaminase which can be genetically fused to different formats of antibodies of interest for the development of enzymatic site-specific conjugation we named “CovIsolink” platform. We describe the synthesis of chemically defined drugs conjugation in which the site and stoichiometry of conjugation are controlled using a genetically encoded Q-tag peptide with specific amino acids which serves as a substrate of bacterial transglutaminase. This approach has enabled the generation of homogeneous conjugates with DAR 1,7 for full IgG and 0,8 drug ratio for Fab, scfv and VHH antibody fragments without the presence of significant amounts of unconjugated antibody and fragments. As a proof of concept, Q-tagged anti Her-2 (human IgG1 (Trastuzumab) and the corresponding fragments (Fab, scfv and VHH) were engineered and conjugated with different aminated-payloads. The corresponding Cov-ADCs were evaluated in series of in vitro and in vivo assays, demonstrating similar tumor cell killing potency as Trastuzumab emtansine (Kadcyla®) even with lower drug-to-antibody ratio (DAR).
The decreasing transport of the Deep Western Boundary Current in the subpolar Atlantic
Authors: Koman Gregory , Bower Amy , Holliday N. Penny , Furey Heather , Fu Yao , Biló Tiago
Published: September 2023

The Deep Western Boundary Current (DWBC) – the primary component of the lower limb of the Atlantic Meridional Overturning Circulation – flows along the eastern flank of Greenland from a combination of Denmark Strait Overflow Water and Iceland Scotland Overflow Water. The Overturning in the Subpolar North Atlantic Program (OSNAP) has continuously measured the DWBC since 2014 using current meters, temperature/salinity sensors, and acoustic doppler current profilers. This mooring array located near Cape Farewell also incorporates data from the Ocean Observatories Initiative’s Global Irminger Sea Array to create the longest continuous observations of the DWBC closest to where Iceland Scotland Overflow Water and Denmark Strait Overflow water first merge. This study reveals that the DWBC has decreased by 26% over the first six years of OSNAP observations primarily due to a thinning of the traditionally defined DWBC layer (σθ > 27.8 kg m-3) due to a known freshening signal moving through the subpolar region. Despite this decrease, the Atlantic Meridional Overturning Circulation as calculated by OSNAP has remained relatively steady over the same period. Ultimately, the reason for this difference is due to the methods used to define these two circulations. Finding such notably different trends for two seemingly dependent circulations raises the question of how to best define these transports.
Skin-inspired all-natural ionic biogel
Authors: Ying Yibin , Lan Lingyi , Ping Jianfeng , Li Huiyan , Wang Chengjun , Li Guang , Song Jizhou
Published: September 2023

Natural material-based hydrogels are considered ideal candidates for building robust bio-interfaces due to their environmentally sustainable nature and biocompatibility. However, these hydrogels often suffer from limitations such as weak mechanical strength, low water resistance, and poor ionic conductivity. Here, inspired by the role of natural moisturizing factor (NMF) in skin, we propose a simple yet versatile strategy to fabricate all-natural ionic biogel that is highly resilient, ionically conductive, anti-dehydrated, and fully degradable, without requiring any chemical modification. A well-balanced combination of gelatin and NMF gives rise to a significant enhancement in the mechanical strength, ionic conductivity, and water retention capacity of the biogel than pure gelatin hydrogel. The biogel manifests temperature-controlled reversible fluid-gel transition properties due to the triple-helix junctions of gelatin, which enables in situ gelation on various substrates, resulting in conformal contact and dynamic compliance with curved surfaces. Due to its salutary properties, the biogel can serve as an effective and biocompatible interface for high-quality and long-term electrophysiological signal recording. These findings provide a general and scalable strategy for the design of natural material-based hydrogels with tailored functionalities to meet diverse application needs.
An 11-GRG Predicting Model for UCEC Prognosis
Authors: Su Hailan , Qiao Zhenguo
Published: September 2023

Background Endometrial cancer (EC) is indeed one of the most prevalent gynecological malignancies. Further research is required to gain insights into the molecular pathways involved in EC tumorigenesis and to develop more accurate prognostic prediction methods.Method Data from the Cancer Genome Atlas( TCGA) database was used and validated using two GEO datasets, specifically GSE6008 and GSE17025. Various bioinformatics analyses were performed, including the Least Absolute Shrinkage and Selection Operator regression (lasso) regression, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis Gene Set Variation Analysis (GSVA), gene set enrichment analysis (GSEA), protein-protein interaction (PPI) network analysis, COX regression, calibration curves, and decision curve analysis (DCA). These analyses aimed to explore the associations and functions of GRGs in EC development, as well as develop a predictive model for prognosis assessment.Results There were 11 GRGs identified as significantly associated with EC by the Lasso regression, GSEA, and PPI. The further analysis identifies 61 miRNA molecules, 24 RBPs, 139 TFs, and 21 potential drugs or molecular compounds that might have links to these 11 key genes. These 11 GRGs were made into a Cox regression prediction model, among which the PGK2 shows significantly higher utility than other variables. Calibration analysis and DCA indicate that the clinical predictive performance of this 11-GRGs multivariate Cox regression model is highest at 5 years, followed by 3 years and 1 year. There were 6 genes (GPI, HK1, NUP188, PDHA1, PDHA2, PGK2) that exhibited higher predictive accuracy in time-dependent ROC curves.Conclusion The highly enriched GRGs that have been identified might provide a new understanding of the development of EC and its treatment. Moreover, the 11-GRGs model that has been constructed holds significant clinical implications for evaluating prognosis and providing specific therapy guidance to individuals with EC. Among the variables in the 11-GRG model, PGK2 demonstrates notably higher usefulness, highlighting its potential clinical value in EC.
Fabricating a hepatocyte-targeted fullerene derivative as a new lipid droplet regulator
Authors: Li Hongliang , Zou Toujun , Wan Juan , Liao Rufang , Qu Weiyi , Yang Jinjie , Zhang Xiang , Bai Lan , Zhou Junjie , Tian Tian , Tang Qinchao , Zhang Yufeng , Zhao Chong , Yao Xinxin , Cai Zhiwei , Tian Song , Jiang Jingwei , Cheng Xu , Hu Yufeng , Yang Hailong , Zhang Ejuan , Zhang Xiao-Jing , Xu Haibo , She Zhi-Gang
Published: September 2023

Lipid droplets (LDs) are crucial organelles in organisms and hold a critical function in modulating intracellular lipid metabolism and bioenergetic regulation. The homeostasis of LDs directly participates in the onset and progression of non-alcoholic steatohepatitis (NASH) and other metabolic disorders. However, no pharmacological approaches have been developed to target LDs-related dysfunction for metabolic diseases. Here, we systemically screened biocompatible nanoparticles for anti-LDs formation capacities, and identified a carboxyl fullerene derivative, named four malonate groups-substituted C70 fullerene (QF70), as the most potent lead. Notably, QF70 could be directly internalized into hepatocytes and facilitate lysosomal degradation of perilipin-2 (PLIN2), the key molecule in LDs formation and stability. More importantly, oral administration of QF70 robustly blocked both diet- and Leptin deficiency-induced NASH development with significant improvement in obesity and insulin resistance. We further validated the clinical application potential of QF70 in NASH related metabolic disorders in a non-primate model. To our knowledge, this is the first-in-class demonstration for a nanoparticle based agent as a LDs homeostasis-targeted therapeutic to treat metabolic diseases.
May brood desertion be ruled by partner parenting capability in a polygamous songbird? An experimental study
Authors: Zheng Jia , Wang Hui , Jiang Jiayao , Versteegh Maaike A. , Zhou Zhuoya , Zhang Zhengwang , Chen De , Komdeur Jan
Published: September 2023

Parents confront multiple aspects of offspring demands and need to coordinate different parental care tasks. Biparental care is considered to evolve under circumstances where one parent is not competent for all tasks and cannot efficiently raise offspring. However, this hypothesis is difficult to test, as uniparental and biparental care rarely coexist. Chinese penduline tits (Remiz consobrinus) provide such a system where both parental care types occur. Here, we experimentally investigated whether parents in biparental nests is less capable of caring than parents in uniparental nests. We monitored parenting efforts at (1) naturally uniparental and biparental nests and (2) biparental nests before and during the temporary removal of a parent. We found that total feeding frequency and brooding duration were similar for natural uniparental and biparental nests. Feeding frequency, but not brooding duration, contributed significantly to nestling mass. In line with this, parental removal revealed that the remaining parents at biparental nests fully compensated for the partner’s feeding absence but not for brooding duration. This reflects that the manipulated parents are confronted with a trade-off between feeding and brooding and were selected to invest in the more influential one. However, such a trade-off was not observed in parents of natural uniparental care nests. The different capabilities of a parent independently coordinating feeding and brooding tasks indicated that parents from biparental and uniparental nests experienced different environmental conditions.
Responses of Marine Trophic Levels to the Combined Effects of Ocean Acidification and Warming
Authors: Hollander Johan , Hu Nan , Bourdeau Paul
Published: September 2023

Marine organisms are simultaneously exposed to anthropogenic stressors associated with ocean acidification and warming with likely interactive effects. Although new research has started to uncover how marine primary producers, herbivores, and predators are responding to climate change, we still do not have a comprehensive understanding of general patterns across trophic levels in response to multiple stressors. Yet, marine species from different trophic levels with dissimilar characteristics and evolutionary history are likely to respond differently to climatic stressors.Our study represents the first meta-analysis of multiple stressor studies to target comparisons of mean effects and identification of interaction types among marine trophic levels. The meta-analysis revealed a number of key results: (1) Predators are the most tolerant level in response to individual and combined effects of ocean acidification and warming; (2) synergistic interactions (16%) are less common than additive (40%) and antagonistic (44%) interactions; (3) interaction types vary among trophic levels, with the proportion of synergistic interactions decreasing with increasing trophic level; (4) for interactive effects, calcifying and non-calcifying species show similar patterns across trophic levels; and (5) trophic levels respond to stressors differently along a latitudinal gradient. This study emphasizes the importance of considering stressor interactions and trophic levels in conservation actions. Contrary to many predictions, which has suggested synergistic effects predominate multiple stressors, this research demonstrates that the interaction effect between ocean acidification (OA) and ocean warming (OW) can sometimes mitigate or even reduce negative effects, with additive and antagonistic interactions dominating. Our study provides new knowledge for understanding how multiple stressors may interactively affect marine trophic levels and highlighting the need for further research and a deeper understanding of multiple stressors in conservation efforts.
Effects of yoga on impulsivity in patients with and without mental disorders: a systematic review and meta-analysis of randomized clinical trials
Authors: Machado Yuri de Castro , Oliveira Mariana , Lima Jogiely Larissa Ferreira , Barghav Hermant , Varambally Shivarama , de Miranda Débora Marques , Romano-Silva Marco Aurélio
Published: September 2023

Background
Yoga can be used as a complementary intervention to conventional treatments, whether pharmacological or non-pharmacological. Sustained practice of yoga can generate a series of benefits for individuals' quality of life and improve their physical fitness.
Objective
To investigate the potential effects of yoga as an adjunct intervention in conditions involving impulse control issues, such as attention deficit hyperactivity disorder (ADHD), borderline personality disorder, bipolar affective disorder, and substance use disorders.
Methods
We performed a systematic review and meta-analysis of placebo-controlled, randomized trials of yoga in patients with impulsivity. PubMed, Web of Science, and Science Direct databases were searched for trials published up to January, 2023. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. The effect size was determined using unbiased Hedges' g with 95% confidence intervals (CIs) to assess different measurements of impulsivity.
Results
Out of 277 database results, 6 RCT were included in systematic review and 4, in meta-analysis. To assess the level of attention and impulsiveness, the following scales were analyzed: Barratt Impulsiveness, UPPS-P Impulsive Behavior scale, Conners’ Continuous Performance Test IIª and Conners’ Parent Rating Scale–Revised: Long. There was no significant effect in effect sizes from four studies on the effects of yoga on impulsivity didn’t show a significant effect (g = -0.06; 95% CI, -0.37–0.24; p = 0.69).
Conclusions
Yoga didn’t have a significant improvement in impulsivity when compared to placebo. There are many tools to assess impulsivity, but they mean different concepts and domains consisting in a weakness on comparison of yoga effects.
PROSPERO registration: CRD42023389088
Metabolic remodeling by the PD-L1 inhibitor BMS-202 significantly inhibits cell malignancy in human glioblastoma
Authors: Ji Tianhai , Yang Xueou , Wang Wenjun
Published: September 2023

Recent crystallographic studies have shown that BMS-202, a small molecule compound with a methoxy-1-pyridine chemical structure, interacts well with PD-L1 dimerization. However, its roles and mechanisms of BMS-202 in glioma have not yet been reported. The aims of this work were to study BMS-202 antitumor activity and its underlying mechanisms in glioma. In the study, the multi-omics and bioinformatics tools, a series of experiments, including CCK-8, flow cytometry, co-immunoprecipitation, siRNA transfection, PCR, western blot, and cell migration and invasion, were performed to investigate the underlying mechanisms of BMS-202 in glioma. BMS-202 was shown to inhibit glioma cell proliferation and invasion. Mechanistically, BMS-202 downregulated PD-L1 expression on the GBM cell surface and regulated PD-L1/AKT/BCAT1 signaling pathways in an mTOR-independent manner. BMS-202 is expected to delay metabolism and extend life span. Thus, our data identify that BMS-202 potentially acts as an effective candidate for patients diagnosed with GBM.
Effect of Cu and Fe PM components on mitochondrial dynamics in human colon CaCo-2 cells
Authors: Cervellati Franco , Benedusi Mascia , Casoni Alice , Trinchera Giulia , Vallese Andrea , Ferrara Francesca , Pietrogrande Maria Chiara , Valacchi Giuseppe
Published: September 2023

Atmospheric particulate matter (PM) is one of the most dangerous air pollutants of anthropogenic origin; it consists of a heterogeneous mixture of inorganic and organic components, including transition metals and polycyclic aromatic hydrocarbons. Although previous studies have been focused on effect of exposure to highly concentrated PM on respiratory and cardiovascular systems, emerging evidence supports a significant impact of air pollution on gastrointestinal (GI) tract connecting the exposure to outdoor stressors with conditions such as appendicitis, colorectal cancer, and inflammatory bowel disease. In general, it has been postulated that the main mechanism involved in PM toxicity consists in an OxInflammatory response and this has been also suggested for the GI tract. In the present study we want to analyze the effect of specific redox-active PM components, such as copper (Cu) and iron (Fe), in human intestinal cells by focusing on ultrastructural integrity, redox homeostasis and modulation of some markers related to mitochondria dynamics. According to our study in CaCo2 cells, the exposure to the Cu- and Fe-PM components and their combination induced ultrastructural alterations in the endoplasmic reticulum with an additive effect when the cells were exposed to both PM (Cu and Fe). In addition, the expression and the protein levels of genes involved in mitochondria dynamic were clearly affected by the exposure. In particular, Mitofusin 1 and OPA1 increased after the single exposure and the combination of both particles showed an additive effect. Opposite trend was noticed for PINK and PARKIN. In general, our data suggest that acute exposure to specific Cu and Fe metals, can induce morphological and molecular damage in CaCo-2 cells confirming the correlation noticed between living in polluted area and incidence of gastrointestinal tract conditions.
Dynamic Partial Order Reduction Based on Interference Solution
Authors: Yang Xu , Ye Chen
Published: September 2023

In verifying the process of concurrent programs, dynamic partial order reduction (DPOR) exhaustively explores all the interactions of the equivalent execution traces in the concurrent system through dynamic judgment. Existing DPOR algorithms strive for optimal exploration (i.e., exploring only one interleaving per equivalence class), leading to exponential redundancy in the interleaving, state-space explosion, and memory overflow. In this study, the Interference Solution (IntSo) algorithm is proposed to achieve linear memory consumption by exploring only one interleaving per equivalence class through the exchange of causally-happened-before (CHB) conflicting relationships. In the sequential consistency memory model, the IntSo algorithm realizes parallelism while curtailing time and memory consumption in data-independent scenarios, as well as maximum path lengths. Empirical validation using GenMC demonstrates that the IntSo algorithm compares favorably with state-of-the-art techniques in terms of time and memory, fulfills linear time complexity, and reduces memory consumption by more than 30%.
Association of Social Vulnerability Index and Masking Adherence Among Children Enrolled in COVID-19 Community Research Partnership Study
Authors: Dantuluri Keerti L. , Buahin Asare , Uschner Diane , DeWitt Michael , Rossman Whitney , Dunn Connell O. , Hetherington Timothy C. , Priem Jennifer , Castri Paola , Lagarde William H. , Gibbs Michael , Ahmed Amina
Published: September 2023

Background: Individuals with high social vulnerability index (SVI) have poorer outcomes with COVID-19. Masking reduces transmission of COVID-19 among children, but how SVI plays a role in masking behavior is unknown. We aimed to measure the association of SVI with masking adherence among children during the COVID-19 pandemic.
Methods: We conducted a multi-site, prospective syndromic surveillance study among children aged 2 – 17 years in the Southeastern United States by daily electronic surveys which solicited symptoms of COVID-19-like illness, infection with or exposure to SARS-CoV-2, masking habits, and any receipt of COVID-19 vaccines. Parents/guardians submitted surveys for their children; adolescents 13 years and older could opt to submit their own surveys. Multivariable and univariate linear models were used to measure the associations of different predictors such as SVI with masking adherence.
Results: 1,461 children from 6 states and 55 counties predominately from North and South Carolina were included in the analysis. Most children in the cohort were 5 – 11years old, non-Hispanic White, from urban counties, and with low-moderate SVI. Overall masking adherence decreased over time, and older children had higher masking adherence throughout the study period compared with younger children. Children who resided in urban counties had greater masking adherence throughout the study period than those who resided in suburban or rural counties. Masking adherence was higher among children with both low and medium SVI than those with high SVI.
Conclusions: Despite being at risk for more severe outcomes with COVID-19, children with high SVI had lower levels of masking adherence compared to those with low SVI. Our findings highlight opportunities for improved and targeted messaging in these vulnerable communities.
Endoscopic spinal cord untethering using a 1 cm skin incision technique in pediatrics: A technical case report
Authors: Ishisaka Eitaro , Tahara Shigeyuki , Tsukiyama Atsushi , Nozaki Toshiki , Hattori Yujiro , Morita Akio , Murai Yasuo
Published: September 2023

Background
Spinal cord untethering by sectioning the filum terminale is commonly performed in tethered cord syndrome patients with minor abnormalities such as filar lipoma, thickened filum terminale, and low conus medullaris.
Our endoscopic surgical technique, using the interlaminar approach, allows for sectioning the filum terminale through a very small skin incision. To our knowledge, this procedure has not been previously reported. This is the first case report involving a 1 cm skin incision.
Case presentation
A 9-month-old male patient was referred to our neurosurgical department due to a coccygeal dimple. MRI revealed a thickened fatty filum. After considering the treatment options for this patient, the parents agreed to spinal cord untethering. A midline 1 cm skin incision was made at the L4/5 vertebral level. Untethering by sectioning the filum terminale was performed by full endoscopic surgery using the interlaminar approach. The procedure was uneventful and there were no postoperative complications.
Conclusions
In terms of visibility and minimizing invasiveness, our surgical technique of using the interlaminar approach with endoscopy allows for untethering by sectioning the filum terminale through a very small skin incision.
Cell type-specific DNA replication initiation and termination in human primary cancer whole genomes
Authors: Peifer Martin , Yang Tsun-Po , Etich Julia , Acht Torsten , Cartolano Maria , George Julie , Thomas Roman , Fischer Matthias
Published: September 2023

The understanding of where exactly, and how differently, DNA replication starts and ends in the cancer genomes remain limited. Although DNA sequences that underwent somatic alterations across human primary cancers have been comprehensively studied, the entire accurately replicated sequences of the same primary cancer genomes have not been widely explored. Here, we present a novel in silico framework to assess the tumour replication timing (RT) programme directly using 256 primary cancer whole genomes across three tumour types. We introduce a novel bootstrap-based replication fork directionality (RFD) method to model the bi-directional replication, and simultaneously map the replication origin and terminus domains at 1 kb resolution. ﻿Unexpectedly, our high-resolution results suggest that the genome-wide distribution of termination zones (TZs) is tightly coordinated with the initiation zones (IZs) in both normal and cancer genomes, which has not been previously reported using in vitro directional sequencing of Okazaki fragments (OK-seq) method. Overall, our data demonstrate that the cell type specificity of the tumour replication timing domains is preserved in closely related normal tissues and in lineage-specific cancer cell lines. Finally, comparing altered replication initiations between normal and cancer genomes, our data identifies delocalisation of replication initiations near highly expressed proliferation-associated PIF1 gene in small cell lung cancer (SCLC) genome, suggesting a potential cancer-specific target.
Repurposing dimethyl fumarate as an antiepileptogenic and disease-modifying treatment for drug-resistant epilepsy
Authors: Sandouka Sereen , Singh Prince Kumar , Saadi Aseel , Taiwo Rhoda Olowe , Sheeni Yara , Zhang Taige , Deeb Larin , Guignet Michelle , White Steve H. , Shekh-Ahmad Tawfeeq
Published: September 2023

Background
Epilepsy affects over 65 million people worldwide and significantly burdens patients, caregivers, and society. Drug-resistant epilepsy occurs in approximately 30% of patients and growing evidence indicates that oxidative stress contributes to the development of such epilepsies. Activation of the Nrf2 pathway, which is involved in cellular defense, offers a potential strategy for reducing oxidative stress and epilepsy treatment. Dimethyl fumarate (DMF), an Nrf2 activator, exhibits antioxidant and anti-inflammatory effects and is used to treat multiple sclerosis.
Methods
The expression of Nrf2 and its related genes in vehicle or DMF treated rats were determined via RT-PCR and Western blot analysis. Neuronal cell death was evaluated by immunohistochemical staining. The effects of DMF in preventing the onset of epilepsy and modifying the disease were investigated in the kainic acid-induced status epilepticus model of temporal lobe epilepsy in rats.
The open field, elevated plus maze and T-Maze spontaneous alterations tests were used for behavioral assessments.
Results
We demonstrate that administration of DMF following status epilepticus increased Nrf2 activity, attenuated status epilepticus-induced neuronal cell death, and decreased seizure frequency and the total number of seizures compared to vehicle-treated animals. Moreover, DMF treatment reversed epilepsy-induced behavioral deficits in the treated rats.
Moreover, DMF treatment even when initiated well after the diagnosis of epilepsy, reduced symptomatic seizures long after the drug was eliminated from the body.
Conclusions
Taken together, these findings suggest that DMF, through the activation of Nrf2, has the potential to serve as a therapeutic target for preventing epileptogenesis and modifying epilepsy.
Evaluation of large language models for discovery of gene set function
Authors: Pratt Dexter , Hu Mengzhou , Alkhairy Sahar , Lee Ingoo , Pillich Rudolf , Bachelder Robin , Ideker Trey
Published: September 2023

Gene set analysis is a mainstay of functional genomics, but it relies on manually curated databases of gene functions that are incomplete and unaware of biological context. Here we evaluate the ability of OpenAI’s GPT-4, a Large Language Model (LLM), to develop hypotheses about common gene functions from its embedded biomedical knowledge. We created a GPT-4 pipeline to label gene sets with names that summarize their consensus functions, substantiated by analysis text and citations. Benchmarking against named gene sets in the Gene Ontology, GPT-4 generated very similar names in 50% of cases, while in most remaining cases it recovered the name of a more general concept. In gene sets discovered in ‘omics data, GPT-4 names were more informative than gene set enrichment, with supporting statements and citations that largely verified in human review. The ability to rapidly synthesize common gene functions positions LLMs as valuable functional genomics assistants.
Unexpected long-term variations of Saturn’s ring current revealed by energetic neutral atom imaging
Authors: Yue C.
Published: September 2023

In a magnetosphere, the inhomogeneity of the magnetic field leads to gradient and curvature drifts of charged particles. Ions and electrons drift in opposite directions, leading to a transverse current known as the “ring current”, whose radial profile, intensity and thickness depend on the properties of the plasma ions and electrons. Ring current is an essential part of Saturn’s magnetospheric current system. Previous studies have used in-situ magnetic field or charged particle measurements to analyze its characteristics, and constructed corresponding distribution models. However, those models can only present a long-term average of the ring current distribution due to the limited spatial coverage from individual spacecraft orbits. In contrast, energetic neutral atom (ENA) imaging provides us with a complementary and effective method to observe the global distribution of energetic particles, which enables statistics over a shorter interval. In this study, we make use of ENA imaging observations from Cassini to statistically analyze the ring current, which reveals previously unexpected long-term variations. We suggest these variations are driven by both solar cycle and seasonal variations, which may influence the energetic particle acceleration process, primarily magnetic reconnection.
Statin Improves Early-Phase Obesity-Induced Renal Injury via Restoring Autophagy Failure Through Rho/Rho Kinase/mTOR Pathway Inhibition
Authors: Yasuda Marie , Tokuyama Hirobumi , Kanda Takeshi , Hasegawa Kazuhiro , Wakino Shu , Itoh Hiroshi , Hayashi Kaori , Adachi Keika , Yasuda Itaru
Published: September 2023

Obesity-induced renal injury serves as a preceding phase to the majority of diabetic nephropathy. We investigated the cascading pathophysiology of renal dysfunction induced by obesity and, as a result, identified the significant role of disrupted autophagy within the proximal tubular cells. In mice subjected to obesity induction through a high-fat diet, we observed weight gain, increased adipose tissue mass, decreased glucose tolerance, and insulin resistance, accompanied by the expression of albuminuria. This was further associated with glomerular hypertrophy and tubular epithelial cell enlargement. Among the histological changes, the most prominent was the enlargement of tubular epithelial cells, within which we witnessed substantial lipid accumulation in lysosomes. This observation indicated signs of autophagy dysfunction, raising the possibility that mTOR-mediated autophagy impairment in obesity could be a significant factor in renal function deterioration. Therapeutic intervention with statins, inhibiting the Rho/Rho kinase, simultaneously suppressed the Rho and mTOR cascades, ameliorating autophagy dysfunction. This intervention led to histological improvements and a reduction in albuminuria. The potential of statins to ameliorate changes in tubular and glomerular structures induced by obesity became evident, suggesting their viability as an effective therapeutic strategy for obesity- induced renal injury.
Systemic inflammation plays a central role in sarcopenia and prognosis of patients with metastatic colorectal cancer: A retrospective study
Authors: Yang Ran , Tang Hui-juan , Qiu Wen-li , Ma Yu-yang , Shu Peng
Published: September 2023

Background
Systemic inflammatory response (SIR) affects the prognosis of metastatic colorectal cancer (mCRC) and is reportedly a crucial triggering factor for sarcopenia. Furthermore, sarcopenia has recently been reported to be associated with shorter overall survival in patients with mCRC; however, the existing evidence is insufficient and inconsistent. Therefore, we aimed to investigate the impact of the body composition of patients on the prognosis of mCRC in relation to the SIR.
Methods
This retrospective study collected data from 317 patients with mCRC in China between January 2015 and 2020. The data of patients at baseline and after three cycles of first-line treatment were evaluated, primarily including modified Glasgow Prognostic Score (mGPS) [inflammation level calculated using C-reactive protein (CRP) and albumin], body composition parameters [total adipose tissue index, total adipose tissue density, skeletal muscle index (SMI), and skeletal muscle density (SMD)], and overall survival. The Kaplan–Meier survival curve was drawn to verify the predictive effect of mGPS on overall survival. Furthermore, non-parametric tests and the empirical cumulative distribution function were used to evaluate the relationship between mGPS and body composition and univariate and multivariate Cox regression analysis was used to determine the factors related to the prognosis of mCRC.
Results
In our cohort, the survival curve showed that the baseline mGPS had a strong predictive effect on overall survival. The empirical cumulative distribution function showed that a high mGPS level was associated with a low baseline SMD and SMI and a low SMI after treatment, indicating a significant correlation between sarcopenia and mGPS. Univariate analysis showed that factors affecting prognosis included CRP, albumin, mGPS, and specific body compositions. In multivariate analysis, only mGPS retained independent prognostic value, and a high baseline mGPS level indicated poor prognosis.
Conclusions
Regarding SIR, we found that body composition and overall survival were affected in patients with mCRC, and sarcopenia and poor prognosis had no direct causal relationship. Furthermore, mGPS was found to be a simple and effective prognostic factor; therefore, it should be monitored during treatment. These findings could help clinicians formulate effective individualised anti-inflammatory strategies and improve the prognosis of mCRC.