bluuebunny/crossref_metadata_2025 huggingface dataset:
Cervical cancer screening improvements with self-sampling during the COVID-19 pandemic
Authors: Elfström Miriam , Gray Penelope Grace , Dillner Joakim
Published: December 2023

Background:

At the onset of the COVID-19 pandemic cervical screening in the capital region of Sweden was canceled for several months. A series of measures to preserve and improve the cervical screening under the circumstances were instituted, including a switch to screening with HPV self-sampling to enable screening in compliance with social distancing recommendations.

Methods:

We describe the major changes implemented, which were (1) nationwide implementation of HPV screening, (2) switch to primary self-sampling instead of clinician sampling, (3) implementation of HPV screening in all screening ages, and (4) combined HPV vaccination and HPV screening in the cervical screening program.

Results:

A temporary government regulation allowed primary self-sampling with HPV screening in all ages. In the Stockholm region, 330,000 self-sampling kits were sent to the home address of screening-eligible women, instead of an invitation to clinician sampling. An increase in organized population test coverage was seen (from 54% to 60% in just 1 year). In addition, a national campaign for faster elimination of cervical cancer with concomitant screening and vaccination for women in ages 23–28 was launched.

Conclusions:

The COVID-19 pandemic necessitated major changes in the cervical cancer preventive strategies, where it can already be concluded that the strategy with organized primary self-sampling for HPV has resulted in a major improvement of population test coverage.

Funding:

Funded by the Swedish Association of Local Authorities and Regions, the Swedish Cancer Society, the European Union’s Horizon 2020 Research and Innovation Program, the Swedish government, and the Stockholm county.
A reservoir of timescales emerges in recurrent circuits with heterogeneous neural assemblies
Authors: Stern Merav , Istrate Nicolae , Mazzucato Luca
Published: December 2023

The temporal activity of many physical and biological systems, from complex networks to neural circuits, exhibits fluctuations simultaneously varying over a large range of timescales. Long-tailed distributions of intrinsic timescales have been observed across neurons simultaneously recorded within the same cortical circuit. The mechanisms leading to this striking temporal heterogeneity are yet unknown. Here, we show that neural circuits, endowed with heterogeneous neural assemblies of different sizes, naturally generate multiple timescales of activity spanning several orders of magnitude. We develop an analytical theory using rate networks, supported by simulations of spiking networks with cell-type specific connectivity, to explain how neural timescales depend on assembly size and show that our model can naturally explain the long-tailed timescale distribution observed in the awake primate cortex. When driving recurrent networks of heterogeneous neural assemblies by a time-dependent broadband input, we found that large and small assemblies preferentially entrain slow and fast spectral components of the input, respectively. Our results suggest that heterogeneous assemblies can provide a biologically plausible mechanism for neural circuits to demix complex temporal input signals by transforming temporal into spatial neural codes via frequency-selective neural assemblies.
N-WASP-dependent branched actin polymerization attenuates B-cell receptor signaling by increasing the molecular density of receptor clusters
Authors: Bhanja Anshuman , Seeley-Fallen Margaret K , Lazzaro Michelle , Upadhyaya Arpita , Song Wenxia
Published: December 2023

Antigen-induced B-cell receptor (BCR) signaling is critical for initiating and regulating B-cell activation. The actin cytoskeleton plays essential roles in BCR signaling. Upon encountering cell-surface antigens, actin-driven B-cell spreading amplifies signaling, while B-cell contraction following spreading leads to signal attenuation. However, the mechanism by which actin dynamics switch BCR signaling from amplification to attenuation is unknown. Here, we show that Arp2/3-mediated branched actin polymerization is required for mouse splenic B-cell contraction. Contracting B-cells generate centripetally moving actin foci from lamellipodial F-actin networks in the plasma membrane region contacting antigen-presenting surfaces. Actin polymerization driven by N-WASP, but not WASP, initiates these actin foci and facilitates non-muscle myosin II recruitment to the contact zone, creating actomyosin ring-like structures. B-cell contraction increases BCR molecular density in individual clusters, leading to decreased BCR phosphorylation. Increased BCR molecular density reduced levels of the stimulatory kinase Syk, the inhibitory phosphatase SHIP-1, and their phosphorylated forms in individual BCR clusters. These results suggest that N-WASP-activated Arp2/3, coordinating with myosin, generates centripetally moving foci and contractile actomyosin ring-like structures from lamellipodial networks, enabling contraction. B-cell contraction attenuates BCR signaling by pushing out both stimulatory kinases and inhibitory phosphatases from BCR clusters, providing novel insights into actin-facilitated signal attenuation.
Machine learning of dissection photographs and surface scanning for quantitative 3D neuropathology
Authors: Gazula Harshvardhan , Tregidgo Henry FJ , Billot Benjamin , Balbastre Yael , Williams-Ramirez Jonathan , Herisse Rogeny , Deden-Binder Lucas J , Casamitjana Adria , Melief Erica J , Latimer Caitlin S , Kilgore Mitchell D , Montine Mark , Robinson Eleanor , Blackburn Emily , Marshall Michael S , Connors Theresa R , Oakley Derek H , Frosch Matthew P , Young Sean I , Van Leemput Koen , Dalca Adrian V , Fischl Bruce , MacDonald Christine L , Keene C Dirk , Hyman Bradley T , Iglesias Juan E
Published: December 2023

We present open-source tools for three-dimensional (3D) analysis of photographs of dissected slices of human brains, which are routinely acquired in brain banks but seldom used for quantitative analysis. Our tools can: (1) 3D reconstruct a volume from the photographs and, optionally, a surface scan; and (2) produce a high-resolution 3D segmentation into 11 brain regions per hemisphere (22 in total), independently of the slice thickness. Our tools can be used as a substitute for ex vivo magnetic resonance imaging (MRI), which requires access to an MRI scanner, ex vivo scanning expertise, and considerable ﬁnancial resources. We tested our tools on synthetic and real data from two NIH Alzheimer’s Disease Research Centers. The results show that our methodology yields accurate 3D reconstructions, segmentations, and volumetric measurements that are highly correlated to those from MRI. Our method also detects expected diﬀerences between post mortem conﬁrmed Alzheimer’s disease cases and controls. The tools are available in our widespread neuroimaging suite ‘FreeSurfer’ (https://surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools).
Sensorimotor mechanisms selective to numerosity derived from individual differences
Authors: Anobile Giovanni , Petrizzo Irene , Paiardini Daisy , Burr David , Cicchini Guido Marco
Published: December 2023

We have previously shown that after few seconds of adaptation by finger-tapping, the perceived numerosity of spatial arrays and temporal sequences of visual objects displayed near the tapping region is increased or decreased, implying the existence of a sensorimotor numerosity system (Anobile et al., 2016). To date, this mechanism has been evidenced only by adaptation. Here, we extend our finding by leveraging on a well-established covariance technique, used to unveil and characterize ‘channels’ for basic visual features such as colour, motion, contrast, and spatial frequency. Participants were required to press rapidly a key a specific number of times, without counting. We then correlated the precision of reproduction for various target number presses between participants. The results showed high positive correlations for nearby target numbers, scaling down with numerical distance, implying tuning selectivity. Factor analysis identified two factors, one for low and the other for higher numbers. Principal component analysis revealed two bell-shaped covariance channels, peaking at different numerical values. Two control experiments ruled out the role of non-numerical strategies based on tapping frequency and response duration. These results reinforce our previous reports based on adaptation, and further suggest the existence of at least two sensorimotor number channels responsible for translating symbolic numbers into action sequences.
Protein language model-embedded geometric graphs power inter-protein contact prediction
Authors: Si Yunda , Yan Chengfei
Published: December 2023

Accurate prediction of contacting residue pairs between interacting proteins is very useful for structural characterization of protein–protein interactions. Although significant improvement has been made in inter-protein contact prediction recently, there is still a large room for improving the prediction accuracy. Here we present a new deep learning method referred to as PLMGraph-Inter for inter-protein contact prediction. Specifically, we employ rotationally and translationally invariant geometric graphs obtained from structures of interacting proteins to integrate multiple protein language models, which are successively transformed by graph encoders formed by geometric vector perceptrons and residual networks formed by dimensional hybrid residual blocks to predict inter-protein contacts. Extensive evaluation on multiple test sets illustrates that PLMGraph-Inter outperforms five top inter-protein contact prediction methods, including DeepHomo, GLINTER, CDPred, DeepHomo2, and DRN-1D2D_Inter, by large margins. In addition, we also show that the prediction of PLMGraph-Inter can complement the result of AlphaFold-Multimer. Finally, we show leveraging the contacts predicted by PLMGraph-Inter as constraints for protein–protein docking can dramatically improve its performance for protein complex structure prediction.
Multi-day neuron tracking in high-density electrophysiology recordings using earth mover’s distance
Authors: Yuan Augustine Xiaoran , Colonell Jennifer , Lebedeva Anna , Okun Michael , Charles Adam S , Harris Timothy D
Published: December 2023

Accurate tracking of the same neurons across multiple days is crucial for studying changes in neuronal activity during learning and adaptation. Advances in high-density extracellular electrophysiology recording probes, such as Neuropixels, provide a promising avenue to accomplish this goal. Identifying the same neurons in multiple recordings is, however, complicated by non-rigid movement of the tissue relative to the recording sites (drift) and loss of signal from some neurons. Here, we propose a neuron tracking method that can identify the same cells independent of firing statistics, that are used by most existing methods. Our method is based on between-day non-rigid alignment of spike-sorted clusters. We verified the same cell identity in mice using measured visual receptive fields. This method succeeds on datasets separated from 1 to 47 days, with an 84% average recovery rate.
Sex differences in discrimination behavior and orbitofrontal engagement during context-gated reward prediction
Authors: Peterson Sophie , Maheras Amanda , Wu Brenda , Chavira Jose , Keiflin Ronald
Published: December 2023

Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, post-traumatic stress disorder, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here, we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two auditory reward-predictive cues was informed by the presence, or absence, of a visual contextual feature (LIGHT: X+/DARK: X−/LIGHT: Y−/DARK: Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex (OFC) compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between the speed of acquisition and the robustness of performance in the contextual modulation of cued reward seeking. The different distribution of sexes along the fast learning ↔ steady performance continuum might reflect different levels of engagement of the OFC, and might have implications for our understanding of sex differences in psychiatric disorders.
Guidelines for a participatory Smart City model to address Amazon’s urban environmental problems
Authors: da Silva Jonas Gomes
Published: December 2023

Climate change is a global challenge, and the Brazilian Amazon Forest is a particular concern due to the possibility of reaching a tipping point that could amplify environmental crises. Despite many studies on the Amazon Forest, this research was conducted in Manaus, the capital of Amazonas state, to address five gaps, including the lack of local citizen consultation on urban environmental issues, Smart Cities, decarbonization, and disruptive technologies. This study holds significance for the academy community, government bodies, policymakers, and investors, as it offers novel insights into the Amazon region and proposes a model to engage citizens in Smart Cities. This model could also guide other municipalities aspiring for participatory sustainable development with a decarbonization focus, mitigating future risks, and protecting future generations. Basically, it is an explanatory and applied study that employs mixed methods, including literature, bibliometric and documentary reviews, two questionnaires, and descriptive statistical approaches, organized in four phases to reach the following goals: (a) provide information on the main challenges facing humanity, the Brazilian Amazon state, and the city of Manaus; (b) identify the best Smart City approaches for engaging citizens in solving urban problems; (c) contextualize and consult Manaus City Hall about the effectiveness of the Smart City project; (d) investigate the perceptions of citizens living in Manaus on the main city’s environmental problems, as well as their level of knowledge and interest on issues related to Smart Cities, decarbonization, and disruptive technologies; (e) propose a participatory Smart City model with recommendations. Among the result, the study found that the term “Smart City” dominates scholarly publications among nineteen urban-related terms, and the five main environmental problems in Manaus are an increase in stream pollution, garbage accumulation, insufficient urban afforestation, air pollution, and traffic congestion. Although citizens are willing to help, the majority lack knowledge on Smart City and Decarbonized City issues, but there is a considerable interest in training related to these issues, as well as disruptive technologies. It was found that Amsterdam, Melbourne, Montreal, San Francisco, Seoul, and Taipei all have a formal model to engage citizens in solving their urban problems. The main conclusion is that, after 6 years, the Smart City Project in Manaus is a political fallacy, as no model, especially with a citizen participatory approach, has been effectively adopted. In addition, after conducting a literature and documentary review and analyzing 25 benchmark Smart Cities, the P5 model and the Citizen Engagement Kit model are proposed with 120 approaches and guidelines for addressing the main environmental problems by including Manaus’ citizens in the Smart City and/or decarbonization journey.
Transcriptomic and metabolomic differences between banana varieties which are resistant or susceptible to Fusarium wilt
Authors: Tian Dandan , Qin Liuyan , Verma Krishan K. , Wei Liping , Li Jialin , Li Baoshen , Zhou Wei , He Zhangfei , Wei Di , Huang Sumei , Long Shengfeng , Huang Quyan , Li Chaosheng , Wei Shaolong
Published: December 2023

Background

Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense race 4 (Foc4), is the most lethal disease of bananas in Asia.

Methods

To better understand the defense response of banana to Fusarium wilt, the transcriptome and metabolome profiles of the roots from resistant and susceptible bananas inoculated with Foc4 were compared.

Results

After Foc4 inoculation, there were 172 and 1,856 differentially expressed genes (DEGs) in the Foc4-susceptible variety (G1) and Foc4-resistant variety (G9), respectively. In addition, a total of 800 DEGs were identified between G1 and G9, which were mainly involved in the oxidation-reduction process, cell wall organization, phenylpropanoid biosynthesis, and lipid and nitrogen metabolism, especially the DEGs of Macma4_08_g22610, Macma4_11_g19760, and Macma4_03_g06480, encoding non-classical arabinogalactan protein; GDSL-like lipase; and peroxidase. In our study, G9 showed a stronger and earlier response to Foc4 than G1. As the results of metabolomics, lipids, phenylpropanoids and polyketides, organic acids, and derivatives played an important function in response to Fusarium wilt. More importantly, Macma4_11_g19760 might be one of the key genes that gave G9 more resistance to Foc4 by a lowered expression and negative regulation of lipid metabolism. This study illustrated the difference between the transcriptomic and metabolomic profiles of resistant and susceptible bananas. These results improved the current understanding of host-pathogen interactions and will contribute to the breeding of resistant banana plants.
Mass mortality event of the giant barrel sponge Xestospongia sp.: population dynamics and size distribution in Koh Phangan, Gulf of Thailand
Authors: Mueller Jasmin S. , Grammel Paul-Jannis , Bill Nicolas , Rohde Sven , Schupp Peter J.
Published: December 2023

Marine sponges are prominent organisms of the benthic coral reef fauna, providing important ecosystem services. While there have been increasing reports that sponges are becoming one of the dominant benthic organisms in some locations and ecoregions (e.g. Caribbean), they can be impacted by changing environmental conditions. This study presents the first documentation of a mass mortality event of the barrel sponge Xestospongia sp. in the lower Gulf of Thailand and its consequences on population dynamics and size distribution. Two anthropogenic impacted reefs (Haad Khom and Mae Haad) of the island Koh Phangan and two anthropogenic non-impacted reefs of the islands Koh Yippon and Hin Yippon within the Mu Ko Ang Thong Marine National Park were surveyed in the years 2015 and 2016. The results showed a strong shift in population densities at Koh Phangan. Fatal “bleaching” ending up in mass mortality was observed for these reefs in 2015. Xestospongia sp. abundance decreased from 2015 to 2016 by 80.6% at Haad Khom and by 98.4% at Mae Haad. Sponges of all sizes were affected, and mortality occurred regardless of the survey depth (4 and 6 m). However, Xestospongia population densities in the Marine Park were at a constant level during the surveys. The abundances in 2015 were 65% higher at the Marine Park than at Koh Phangan and 92% higher in 2016. The most likely causes of the mass mortality event was a local harmful algal bloom event, pathogens, undetected local higher water temperatures, or a combination of these factors, whereas sea surface temperature analyses showed no marine heatwave during the observed mass mortality event in 2015. Considering the ecological importance of sponges such as Xestospongia sp., long-term monitoring of reefs and their environmental parameters should be implemented to prevent such mass die-offs.
New insights into the role of GSK-3β in the brain: from neurodegenerative disease to tumorigenesis
Authors: Lai Shenjin , Wang Peng , Gong Jingru , Zhang Shuaishuai
Published: December 2023

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase widely expressed in various tissues and organs. Unlike other kinases, GSK-3 is active under resting conditions and is inactivated upon stimulation. In mammals, GSK-3 includes GSK-3 α and GSK-3β isoforms encoded by two homologous genes, namely, GSK3A and GSK3B. GSK-3β is essential for the control of glucose metabolism, signal transduction, and tissue homeostasis. As more than 100 known proteins have been identified as GSK-3β substrates, it is sometimes referred to as a moonlighting kinase. Previous studies have elucidated the regulation modes of GSK-3β. GSK-3β is involved in almost all aspects of brain functions, such as neuronal morphology, synapse formation, neuroinflammation, and neurological disorders. Recently, several comparatively specific small molecules have facilitated the chemical manipulation of this enzyme within cellular systems, leading to the discovery of novel inhibitors for GSK-3β. Despite these advancements, the therapeutic significance of GSK-3β as a drug target is still complicated by uncertainties surrounding the potential of inhibitors to stimulate tumorigenesis. This review provides a comprehensive overview of the intricate mechanisms of this enzyme and evaluates the existing evidence regarding the therapeutic potential of GSK-3β in brain diseases, including Alzheimer’s disease, Parkinson’s disease, mood disorders, and glioblastoma.
Optimal Progressivity of Public Pension Benefit and Labor Income Tax
Authors:   Bay Area International Business School, Beijing Normal University, Lee Insook
Published: December 2023

This paper characterizes optimal progressivity of public pension benefit and labor income tax, which leads to intra- and inter-generational redistributions. The optimal progressivity of public pension benefit and that of labor income tax mutually depend on each other. The optimal ratio of public pension benefit progressivity to labor income tax progressivity is not constant rate of time discounting. Optimal public pension benefit is more progressive than optimal labor income tax. Whereas effects of pre-government inequality on the optimal progressivity of public pension benefit and that of labor income tax are positive, effect of population aging on them is theoretically ambiguous.
Social-Cultural Capital and Domain Satisfaction
Authors:   Universidad de Granada, Navarro María
Published: December 2023

We analyze the relevance of social resources in different domain satisfactions (finances, job, health, housing, and leisure) as well as the possible sources of endogeneity in the relationship between the two concepts, the differential effect of factors across domains, and the correlation between the domains. The findings could be important to improve citizens’ quality of life. First, we find that social contacts are less relevant in domain satisfactions after controlling for endogeneity problems, while trust and worries remain relevant. Thus, it is convenient to control for endogeneity problems when analyzing satisfaction. Secondly, there are small differences across the effects of most factors on the different domain satisfactions, which are correlated.
Modelización de los factores que afectan al fraude fiscal con técnicas de minería de datos: aplicación al Impuesto de la Renta en España
Authors:   Instituto de Estudios Fiscales-Universidad Rey Juan Carlos, Pérez César , Delgado María Jesús ,   Universidad Rey Juan Carlos, Lucas Sonia de ,   Universidad Autónoma de Madrid
Published: December 2023

This paper presents a proposal to model and predict the behavior of Personal Income Tax (IRPF) tax-payers with data mining techniques. Decision trees and discriminant analysis are combined to quantify each taxpayer's propensity to fraud using the tax components with the highest incidence of fraud. The model achieves an average efficiency in predictions of more than 89%, allowing respondents to be segmented by level of propensity to fraud. The proposal can be used in the audit and control process carried out by the Tax Agency.
Clinician Adherence to Hypertension Screening and Care Guidelines
Authors: Sudharsanan Nikkil , Pillai Vasanthi Subramonia , Favaretti Caterina , Jose Jithin , Jose Sandra , McConnell Margaret , Ali Mohammed K.
Published: December 2023

This quality improvement study assesses opportunistic blood pressure measurement, communication of blood pressure reading to adult patients, and recommendation for a follow-up visit at health care facilities in 2 major cities in India.
Comparative Analysis of Various Spider Silks in Regard to Nerve Regeneration: Material Properties and Schwann Cell Response
Authors: Stadlmayr Sarah , Peter Karolina , Millesi Flavia , Rad Anda , Wolf Sonja , Mero Sascha , Zehl Martin , Mentler Axel , Gusenbauer Claudia , Konnerth Johannes , Schniepp Hannes C. , Lichtenegger Helga , Naghilou Aida , Radtke Christine
Published: December 2023

Peripheral nerve reconstruction through the employment of nerve guidance conduits with Trichonephila dragline silk as a luminal filling has emerged as an outstanding preclinical alternative to avoid nerve autografts. Yet, it remains unknown whether the outcome is similar for silk fibers harvested from other spider species. This study compares the regenerative potential of dragline silk from two orb‐weaving spiders, Trichonephila inaurata and Nuctenea umbratica, as well as the silk of the jumping spider Phidippus regius. Proliferation, migration, and transcriptomic state of Schwann cells seeded on these silks are investigated. In addition, fiber morphology, primary protein structure, and mechanical properties are studied. The results demonstrate that the increased velocity of Schwann cells on Phidippus regius fibers can be primarily attributed to the interplay between the silk's primary protein structure and its mechanical properties. Furthermore, the capacity of silk fibers to trigger cells toward a gene expression profile of a myelinating Schwann cell phenotype is shown. The findings for the first time allow an in‐depth comparison of the specific cellular response to various native spider silks and a correlation with the fibers’ material properties. This knowledge is essential to open up possibilities for targeted manufacturing of synthetic nervous tissue replacement.
Design Criteria for Architected Materials with Programmable Mechanical Properties Within Theoretical Limit Ranges
Authors: Yin Peng , Li Baotong , Hong Jun , Jing Hui , Li Bang , Liu Honglei , Chen Xiaoming , Lu Yang , Shao Jinyou
Published: December 2023

Architected materials comprising periodic arrangements of cells have attracted considerable interest in various fields because of their unconventional properties and versatile functionality. Although some better properties may be exhibited when this homogeneous layout is broken, most such studies rely on a fixed material geometry, which limits the design space for material properties. Here, combining heterogeneous and homogeneous assembly of cells to generate tunable geometries, a hierarchically architected material (HAM) capable of significantly enhancing mechanical properties is proposed. Guided by the theoretical model and 745 752 simulation cases, generic design criteria are introduced, including dual screening for unique mechanical properties and careful assembly of specific spatial layouts, to identify the geometry of materials with extreme properties. Such criteria facilitate the potential for unprecedented properties such as Young's modulus at the theoretical limit and tunable positive and negative Poisson's ratios in an ultra‐large range. Therefore, this study opens a new paradigm for materials with extreme mechanical properties.
Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate, Pancreatic, and Lung Cancers
Authors: Bi Jianling , Witt Emily , McGovern Megan K. , Cafi Arielle B. , Rosenstock Lauren L. , Pearson Anna B. , Brown Timothy J. , Karasic Thomas B. , Absler Lucas C. , Machkanti Srija , Boyce Hannah , Gallo David , Becker Sarah L. , Ishida Keiko , Jenkins Joshua , Hayward Alison , Scheiflinger Alexandra , Bodeker Kellie L. , Kumar Ritesh , Shaw Scott K. , Jabbour Salma K. , Lira Vitor A. , Henry Michael D. , Tift Michael S. , Otterbein Leo E. , Traverso Giovanni , Byrne James D.
Published: December 2023

Modulation of autophagy, specifically its inhibition, stands to transform the capacity to effectively treat a broad range of cancers. However, the clinical efficacy of autophagy inhibitors has been inconsistent. To delineate clinical and epidemiological features associated with autophagy inhibition and a positive oncological clinical response, a retrospective analysis of patients is conducted treated with hydroxychloroquine, a known autophagy inhibitor. A direct correlation between smoking status and inhibition of autophagy with hydroxychloroquine is identified. Recognizing that smoking is associated with elevated circulating levels of carbon monoxide (CO), it is hypothesized that supplemental CO can amplify autophagy inhibition. A novel, gas‐entrapping material containing CO in a pre‐clinical model is applied and demonstrated that CO can dramatically increase the cytotoxicity of autophagy inhibitors and significantly inhibit the growth of tumors when used in combination. These data support the notion that safe, therapeutic levels of CO can markedly enhance the efficacy of autophagy inhibitors, opening a promising new frontier in the quest to improve cancer therapies.
Mechanically and Thermally Stable Cathode Electrolyte Interphase Enables High‐temperature, High‐voltage Li||LiCoO2 Batteries
Authors: Wu Daxiong , Zhu Chunlei , Wang Huaping , Huang Junda , Jiang Gaoxue , Yang Yulu , Yang Gaojing , Tang Dongliang , Ma Jianmin
Published: December 2023

The development of high‐energy‐density Li||LiCoO2 batteries is severely limited by the instability of cathode electrolyte interphase (CEI) at high voltage and high temperature. Here we propose a mechanically and thermally stable CEI by electrolyte designing for achieving the exceptional performance of Li||LiCoO2 batteries at 4.6 V and 70 °C. 2,4,6‐tris(3,4,5‐trifluorophenyl)boroxin (TTFPB) as the additive could preferentially enter into the first shell structure of PF6− solvation and be decomposed on LiCoO2 surface at low oxidation potential to generate a LiBxOy‐rich/LiF‐rich CEI. The LiBxOy surface layer effectively maintained the integrity of CEI and provided excellent mechanical and thermal stability while abundant LiF in CEI further improved the thermal stability and homogeneity of CEI. Such CEI drastically alleviated the crack and regeneration of CEI and irreversible phase transformation of the cathode. As expected, the Li||LiCoO2 batteries with the tailored CEI achieved 91.9 % and 74.0 % capacity retention after 200 and 150 cycles at 4.6 and 4.7 V, respectively. Moreover, such batteries also delivered an unprecedented high‐temperature performance with 73.6 % capacity retention after 100 cycles at 70 °C and 4.6 V.
Selective and Efficient CO2 Electroreduction to Formate on Copper Electrodes Modified by Cationic Gemini Surfactants
Authors: Zhang Xiudong , Yan Xupeng , Chen Peng , Zhang Pei , Kang Xinchen , Ma Jun , Chen Chunjun , Han Buxing
Published: December 2023

Electroreduction of CO2 into valuable chemicals and fuels is a promising strategy to mitigate energy and environmental problems. However, it usually suffers from unsatisfactory selectivity for a single product and inadequate electrochemical stability. Herein, we report the first work to use cationic Gemini surfactants as modifiers to boost CO2 electroreduction to formate. The selectivity, activity and stability of the catalysts can be all significantly enhanced by Gemini surfactant modification. The Faradaic efficiency (FE) of formate could reach up to 96 %, and the energy efficiency (EE) could achieve 71 % over the Gemini surfactants modified Cu electrode. In addition, the Gemini surfactants modified commercial Bi2O3 nanosheets also showed an excellent catalytic performance, and the FE of formate reached 91 % with a current density of 510 mA cm−2 using the flow cell. Detailed studies demonstrated that the double quaternary ammonium cations and alkyl chains of the Gemini surfactants played a crucial role in boosting electroreduction CO2, which can not only stabilize the key intermediate HCOO* but also provide an easy access for CO2. These observations could shine light on the rational design of organic modifiers for promoted CO2 electroreduction.
Study on quantitative structure–activity relationship of amine surfactants in coal reverse flotation
Authors: Shen Liang , Li Zihan , Gong Jiabao , Liu Lingyun , Qiao Erle , Liu Yifang , Min Fanfei
Published: December 2023

With the deterioration of underground coal quality, hundreds of millions of tons of coal slime in China need to be treated using flotation methods every year. However, the design and selection of coal slurry flotation collectors lack theoretical guidance. In this paper, the quantitative structure–activity relationship (QSAR) model between the molecular structure descriptors of collectors and the flotation recovery and selectivity index is established by using pure kaolinite/clean coal flotation experiments and molecular simulation techniques. Flotation results showed that the flotation recovery rate of kaolinite by collectors with larger head group size, such as DDMAC, DDP, and DTAC, is higher than that of the other collectors with smaller head group size. DDA, DDP, and DD have similar flotation capabilities for clean coal, and their selectivity was slightly better than others. The QSAR model between the molecular structure descriptor and the selectivity index was successfully constructed by combining flotation experiments and molecular simulation results. The reliability of this model has been proven through theoretical analysis and flotation experiments. The molecular simulation results indicate that all eight collectors can advertise on 001 (−) surface of kaolinite, but the final advertisement configuration is different. DDA has less coverage on the surface of kaolinite. When the collector is DDA, the concentration of water molecules near the 001 (−) surface of kaolinite is the highest, indicating that the collector DDA has the weakest effect on improving the hydrophobicity of the 001 (−) surface of kaolinite. DDMAC and DDBAC have the best facilitation to the surface hydrophobicity of kaolinite 001 (−). The research results have theoretical guidance significance for the selection and design of mineral flotation collectors.
Resveratrol‐loaded decellularized ovine pericardium: ECM introduced for tissue engineering
Authors: Khazaei Mozafar , Alizadeh Morteza , Rezakhani Leila
Published: December 2023

An ideal scaffold for skin tissue engineering should have a suitable potential for antibacterial activity, no hemolysis, sufficient porosity for air exchange, water retention capacity, and a suitable swelling rate to maintain tissue moisture. Considering this issue, our study used decellularized ovine pericardial tissue's extracellular matrix (ECM). These scaffolds were decellularized with sodium dodecyl sulfate (SDS) and sodium deoxycholate (SD) detergents along with vacuum methods. Following imaging with scanning electron microscopy (SEM), analysis of the mechanical properties, and the measurement of the amount of DNA, collagen, and glycosaminoglycan (GAG), our study observed that the three‐dimensional (3D) structure of ECM was largely preserved. Resveratrol (RES) 400 µg/µL was loaded into the above scaffold, and analysis revealed that scaffolds containing RES and with vacuum reported higher antibacterial properties, a higher swelling rate, and increased water retention capacity. The biocompatibility and hemocompatibility properties of the above scaffolds also reported a significant difference between methods of decellularization.
Verfügbarkeitsmodell A10/A24: modellbasierte Projektabwicklung über den Lebenszyklus
Authors: Tschickardt Thomas
Published: December 2023

Die BIM‐basierte Projektabwicklung im Infrastrukturbau, besonders in Ausführungs‐ und Erhaltungsphasen, befindet sich in der Erprobungsphase. Das Projekt Verfügbarkeitsmodell A10/A24 ist ein nationales Pilotprojekt der DEGES im Auftrag der Autobahn GmbH im Auftrag der Bundesrepublik Deutschland, um Leistungsniveau 1 des Stufenplans Digitales Planen und Bauen umzusetzen. Es ist das erste Projekt, das Planung, Ausführung und Erhaltung nahtlos mit BIM durchführt und somit über bisherige Pilotprojekte hinausgeht. Die Verkehrsfreigabe des Projekts erfolgte am 11. November 2022 zwischen Neuruppin und Pankow. Die Planungs‐ und Ausführungsphase wurde an einem Bauabschnitt kontinuierlich mit BIM umgesetzt. In den nächsten 25 Jahren wird das Erhaltungsmanagement auf Basis des Übergabemodells durchgeführt, inkl. Zustandsdaten, Schäden und Erhaltungsmaßnahmen. Im Folgenden werden Erkenntnisse aus der Implementierung und Umsetzung des BIM‐Projekts vorgestellt.
Validated spectrofluorimetric method for the determination of netilmicin based on its interaction with o‐phthalaldehyde/mercaptoethanol: Evaluation of the method's greenness
Authors: Salem AlSalem Huda , Saad Binkadem Mona , Talal Al‐Goul Soha , Obaydo Reem H. , El Hamd Mohamed A. , Katamesh Noha S. , Abdel‐Lateef Mohamed A.
Published: December 2023

In this study, netilmicin (NTM) was selectively assessed in its dosage forms after a facile derivatization reaction. The proposed approach was based on the interaction between NTM and o‐phthalaldehyde/2‐mercaptoethanol (Roth's reagent). The reaction product was fluorometrically measured at λemission of 434 nm after λexcitation of 338 nm. All reaction conditions for achieving the optimum fluorescence switch‐on activity were visualized and monitored. Moreover, the method was validated under ICH guidelines, and was linear over the range 30–210 ng/ml after plotting netilmicin concentrations against the corresponding fluorescence intensity values. In addition, the selectivity of the developed method was investigated against either the co‐formulated drug (dexamethasone) or a common ophthalmic drop excipient (benzalkonium chloride) without interference from either of them. Furthermore, the developed method was applied to assay netilmicin in various samples of pharmaceutical eye drops with good recovery. Finally, multicriteria greenness and whiteness metrics were used to evaluate the sustainability, greenness, and whiteness of the approach. The applied tools were the AGREE algorithm, the RGB 12 algorithm, and HEXAGON.
Stability indicating reversed‐phase‐high‐performance liquid chromatography method development and validation for pyridostigmine bromide and sodium benzoate in oral solution
Authors: Chintala Vaishnavi
Published: December 2023

The present study focuses on the development of a simple, rapid, specific, and stability‐indicating HPLC method for the simultaneous analysis of pyridostigmine bromide (PGB) and sodium benzoate (SBN) in oral liquid dosage forms. Analytical techniques should enhance sensitivity and specificity for the estimation of pharmaceutical drug products. Stress studies were conducted under various International Conference on Harmonization (ICH) conditions for evaluation. The further optimized HPLC method was validated in accordance with the current ICH guidelines. Chromatographic separation was accomplished using a mobile phase consisting of a 950:50 v/v ratio of perchloric acid buffer and acetonitrile as mobile phase‐A, and 100% acetonitrile as mobile phase‐B. The flow rate is 1.0 mL/min, and the injection volume is 20 μL. Detection of components was carried out at 220 nm for PGB and 228 nm for SBN. The validated HPLC method demonstrated high specificity, with linearity ranging between 24 and 72 μg/mL for PGB and 5.2–15.6 μg/mL for SBN. The correlation coefficient for both drugs exceeded 0.999. The method demonstrated high accuracy, exceeding 97%. In stress studies, PGB was found to be sensitive to alkaline stress conditions. The results reveal the successful applicability of the current method for the estimation of PGB and SBN in its marketed formulation, which can be reasonably inferred to assess other formulation systems.
The role of thrombomodulin in modulating ITGB3 expression and its implications for triple‐negative breast cancer progression
Authors: Chang Yu‐Jia , Prince G. M. Shazzad Hossain , Wei Po‐Li , Batzorig Uyanga , Huang Chien‐Yu , Hung Chin‐Sheng , Chang Tung‐Cheng
Published: December 2023

Triple‐negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC) compared to other BC subtypes in clinical settings. Currently, there are no effective therapeutic strategies for TNBC treatment. Therefore, there is an urgent need to identify suitable biomarkers or therapeutic targets for TNBC patients. Thrombomodulin (TM) plays a role in cancer progression and metastasis in many different cancers. However, the role of TM in TNBC is not yet fully understood. First, silenced‐TM in MDA‐MB‐231 cells caused an increase in proliferative and metastatic activity. In contrast, overexpression of TM in Hs578T cells caused a reduction in proliferation, invasion, and migration rate. Using RNA‐seq analysis, we found that Integrin beta 3 (ITGB3) expression may be a downstream target of TM. Furthermore, we found an increase in ITGB3 levels in TM‐KD cells by QPCR and western blot analysis but a decrease in ITGB3 levels in TM‐overexpressing cells. We found phospho‐smad2/3 levels were increased in TM‐KD cells but decreased in TM‐overexpressing cells. This implies that TM negatively regulates ITGB3 levels through the activation of the smad2/3 pathway. Silencing ITGB3 in TM‐KD cells caused a decrease in proliferation and migration. Finally, we found that higher ITGB3 levels were correlated with poor overall survival and relapse‐free survival in patients with TNBC. Our results indicated a novel regulatory relationship between TM and ITGB3 in TNBC.
S‐induced Phase Change Forming In2O3/In2S3 Heterostructure for Photoelectrochemical Glucose Sensor
Authors: Wang Bingrong , Zhang Nan , Wang Yifeng , Chen Delun , Qi Junlei , Tu Jinchun
Published: December 2023

In the past several decades, Photoelectrochemical (PEC) sensing still remains a great challenge to design highly‐efficient semiconductor photocatalysts via a facile method. It is of much importance to design and synthesize various novel nanostructured sensing materials for further improving the response performance. Herein, we present an In2O3/In2S3 heterostructure obtained by combining microwave assisted hydrothermal method with S‐induced phase change, whose energy band and electronic structure could be adjusted by changing the S content. Combining theoretical calculation and spectroscopic techniques, the introduction of sulfur was proved to produce multifunctional interfaces, inducing the change of phase, oxygen vacancies and band gap, which accelerates the separation of photoexcited carriers and reduces their recombination, improving the electronic injection efficiency around the interface of In2O3/In2S3. As anticipated, an enhanced glucose response performance with a photocurrent of 0.6 mA cm−2, a linear range of 0.1–1 mM and a detection limit as low as 14.5 μM has been achieved based on the In2O3/In2S3 heterostructure, which is significant superior over its pure In2O3 and S‐doped In2O3 counterparts. This efficient interfacial strategy may open a new route to manipulate the electrical structure, and energy band structure regulation of sensing material to improve the performance of photoelectrodes for PEC.
Type‐I protein arginine methyltransferase inhibition primes anti‐programmed cell death protein 1 immunotherapy in triple‐negative breast cancer
Authors: Zhang Sheyu , Guo Lu , Zhang Ziwen , Liu Xueying , Chen Wenjun , Wei Yong , Wang Xiaojia , Wu Qin
Published: December 2023

Background

Immune‐checkpoint blockade (ICB) therapy shows promise for treating aggressive triple‐negative breast cancer (TNBC). However, only some patients benefit from ICB, revealing an urgent need for identifying novel strategies for sensitizing patients to ICB. Previously, the authors demonstrated that type‐I protein arginine methyltransferases (PRMTs) regulated antiviral innate‐immune responses in TNBC by altering RNA splicing. This study aimed to explore the effects of targeting type‐I PRMTs on the tumor microenvironment (TME) and the efficacy of ICB therapy against TNBC.

Methods

Single‐cell transcriptomic analysis was performed to investigate the effects of type‐I PRMT inhibition on the TME, especially T‐cell subsets. Single‐cell T‐cell receptor sequencing was performed to analyze the diversity and dynamics of the T‐cell repertoire. A syngeneic murine model of TNBC was used to evaluate the therapeutic efficacy and immune memory effect of combining a type‐I PRMT inhibitor (MS023) with an anti‐programmed cell death protein 1 (PD‐1) antibody.

Results

Type‐I PRMT inhibition combined with anti–PD‐1 therapy reduced tumor growth. Mechanistically, type‐I PRMT inhibition reshaped the TME. Increased CD8 T‐cell infiltration was verified using flow cytometry. Increased clonotypes and clonal diversity were also observed after MS023 treatment, which contributed to immune memory following combination treatment.

Conclusions

Targeting type‐I PRMT can potentially improve immunotherapeutic efficacies in patients with TNBC. By enhancing the tumor immunogenicity and promoting a more favorable immune microenvironment, this combined approach may enable more patients with TNBC to benefit from immunotherapies.
Enzyme‐Assisted Supercritical Fluid Extraction of Flavonoids from Apple Pomace (Malus×domestica)
Authors: Mikšovsky Philipp , Kornpointner Christoph , Parandeh Zahra , Goessinger Manfred , Bica‐Schröder Katharina , Halbwirth Heidi
Published: December 2023

Herein an enzyme‐assisted supercritical fluid extraction (EA‐SFE) was developed using the enzyme mix snailase to obtain flavonols and dihydrochalcones, subgroups of flavonoids, from globally abundant waste product apple pomace. Snailase, a commercially available mix of 20–30 enzymes, was successfully used to remove the sugar moieties from quercetin glycosides, kaempferol glycosides, phloridzin and 3‐hydroxyphloridzin. The resulting flavonoid aglycones quercetin, kaempferol, phloretin and 3‐hydroxyphloretin were extracted using supercritical carbon dioxide (scCO2) and minimum amounts of polar cosolvents. A sequential process of enzymatic hydrolysis and supercritical fluid extraction was developed, and the influence of the amount of snailase, pre‐treatment of apple pomace, the time for enzymatic hydrolysis, the amount and type of cosolvent and the time for extraction, was studied. This revealed that even small amounts of snailase (0.25 %) provide a successful cleavage of sugar moieties up to 96 % after 2 h of enzymatic hydrolysis followed by supercritical fluid extraction with small amounts of methanol as cosolvent, leading up to 90 % of the total extraction yields after 1 h extraction time. Ultimately, a simultaneous process of EA‐SFE successfully demonstrates the potential of snailase in scalable scCO2 extraction processes for dry and wet apple pomace with satisfactory enzyme activity, even under pressurized conditions.