bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Metabolites and Faecal Microbial Communities in Nonpregnant and Early Gestation Ewes in Highly Cold Areas
Authors: Wu Zhiwu , Yang Yanyan , Wang Biao , Gebeyew Kefyalew , Tang Shaoxun , Han Xuefeng , He Zhixiong , Tan Zhiliang
Published: November 2023

Ewes undergo complex metabolic changes during pregnancy. Understanding the specific process of these changes is a necessary prerequisite in ewes for regulating and intervening in order to maintain pregnancies. However, there have been relatively few studies on the specific changes that occur in nutritional metabolism in pregnant ewes during early gestation, especially for some landrace ewes in highly cold areas. Therefore, this study aimed to (1) elucidate the changes in metabolites and microbial communities in pregnant ewes during early gestation using metabolomics and 16S ribosomal RNA gene (rDNA) amplicon sequencing approaches, and to (2) discover novel early pregnancy-induced biomarkers in the blood and faeces. Rams were placed together with ewes on D0 and removed on D45. During early gestation, blood and faecal samples were collected from ewes in a highly cold area for analysing the metabolites and microbial communities; these were retrospectively classified as the early gestation pregnant (EP) ewe group or the nonpregnant (NP) ewe group based on the lambing status recorded during the expected delivery period. The differences in the plasma biochemical parameters, plasma metabolites, and faecal microbial communities of pregnant and nonpregnant ewes were characterised. The GC, IL-6, O-acetyl-l-serine, L-glutamine, and 6-acetamido-2-oxohexanoic acid were screened out as potential biomarkers for evaluating the occurrence of early pregnancy. These novel early pregnancy-induced metabolites discovered in ewes might allow for the development of technologies to detect early pregnancies in sheep in highly cold areas.
CardioRVAR: A New R Package and Shiny Application for the Evaluation of Closed-Loop Cardiovascular Interactions
Authors: Chao-Écija Alvaro , López-González Manuel Víctor , Dawid-Milner Marc Stefan
Published: November 2023

CardioRVAR is a new R package designed for the complete evaluation of closed-loop cardiovascular interactions and baroreflex sensitivity estimated from continuous non-invasive heart rate and blood pressure recordings. In this work, we highlight the importance of this software tool in the context of human cardiovascular and autonomic neurophysiology. A summary of the main algorithms that CardioRVAR uses are reviewed, and the workflow of this package is also discussed. We present the results obtained from this tool after its application in three clinical settings. These results support the potential clinical and scientific applications of this tool. The open-source tool can be downloaded from a public GitHub repository, as well as its specific Shiny application, CardioRVARapp. The open-source nature of the tool may benefit the future continuation of this work.
From Animal Models to Clinical Trials: The Potential of Antimicrobials in Multiple Sclerosis Treatment
Authors: Raghib Muhammad Faraz , Bernitsas Evanthia
Published: November 2023

Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS). Microbes, including bacteria and certain viruses, particularly Epstein–Barr virus (EBV), have been linked to the pathogenesis of MS. While there is currently no cure for MS, antibiotics and antivirals have been studied as potential treatment options due to their immunomodulatory ability that results in the regulation of the immune process. The current issue addressed in this systematic review is the effect of antimicrobials, including antibiotics, antivirals, and antiparasitic agents in animals and humans. We performed a comprehensive search of PubMed, Google Scholar, and Scopus for articles on antimicrobials in experimental autoimmune encephalomyelitis animal models of MS, as well as in people with MS (pwMS). In animal models, antibiotics tested included beta-lactams, minocycline, rapamycin, macrolides, and doxycycline. Antivirals included acyclovir, valacyclovir, and ganciclovir. Hydroxychloroquine was the only antiparasitic that was tested. In pwMS, we identified a total of 24 studies, 17 of them relevant to antibiotics, 6 to antivirals, and 1 relevant to antiparasitic hydroxychloroquine. While the effect of antimicrobials in animal models was promising, only minocycline and hydroxychloroquine improved outcome measures in pwMS. No favorable effect of the antivirals in humans has been observed yet. The number and size of clinical trials testing antimicrobials have been limited. Large, multicenter, well-designed studies are needed to further evaluate the effect of antimicrobials in MS.
A Radiotherapy Dose Map-Guided Deep Learning Method for Predicting Pathological Complete Response in Esophageal Cancer Patients after Neoadjuvant Chemoradiotherapy Followed by Surgery
Authors: Yap Wing-Keen , Hsiao Ing-Tsung , Yap Wing-Lake , Tsai Tsung-You , Lu Yi-An , Yang Chan-Keng , Peng Meng-Ting , Su En-Lin , Cheng Shih-Chun
Published: November 2023

Esophageal cancer is a deadly disease, and neoadjuvant chemoradiotherapy can improve patient survival, particularly for patients achieving a pathological complete response (ypCR). However, existing imaging methods struggle to accurately predict ypCR. This study explores computer-aided detection methods, considering both imaging data and radiotherapy dose variations to enhance prediction accuracy. It involved patients with node-positive esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy and surgery, with data collected from 2014 to 2017, randomly split into five subsets for 5-fold cross-validation. The algorithm DCRNet, an advanced version of OCRNet, integrates RT dose distribution into dose contextual representations (DCR), combining dose and pixel representation with ten soft regions. Among the 80 enrolled patients (mean age 55.68 years, primarily male, with stage III disease and middle-part lesions), the ypCR rate was 28.75%, showing no significant demographic or disease differences between the ypCR and non-ypCR groups. Among the three summarization methods, the maximum value across the CTV method produced the best results with an AUC of 0.928. The HRNetV2p model with DCR performed the best among the four backbone models tested, with an AUC of 0.928 (95% CI, 0.884–0.972) based on 5-fold cross-validation, showing significant improvement compared to other models. This underscores DCR-equipped models’ superior AUC outcomes. The study highlights the potential of dose-guided deep learning in ypCR prediction, necessitating larger, multicenter studies to validate the results.
Allopurinol versus Febuxostat: A New Approach for the Management of Hepatic Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease
Authors: Al-Shargi Amani , El Kholy Amal A. , Adel Abdulmoneim , Hassany Mohamed , Shaheen Sara M.
Published: November 2023

Metabolic dysfunction-associated steatotic liver disease (MASLD) includes patients with hepatic steatosis and at least one of five cardiometabolic risk factors. Xanthine oxidase (XO) represents a treatment target for MASLD. We aimed to evaluate the effect of two xanthine oxidase inhibitors, allopurinol and febuxostat, plus lifestyle modifications compared to lifestyle modifications alone on improving steatosis. Ninety MASLD patients were assigned to one of three groups for three months. Patients with hyperuricemia were given either allopurinol 100 mg or febuxostat 40 mg daily, along with lifestyle modifications. The third control group was only given lifestyle modifications, excluding all patients with hyperuricemia due to ethical concerns. The primary outcome was to measure the change in the controlled attenuation parameter (CAP) score as an indicator of steatosis from baseline after three months. The secondary outcome was to measure the change in serum uric acid (SUA) three months from baseline. The study found that the CAP score decreased significantly in the allopurinol group (p = 0.009), but the decline in the febuxostat or lifestyle groups was non-significant (p = 0.189 and 0.054, respectively). The SUA levels were significantly reduced in both the allopurinol and febuxostat groups (p < 0.001), with no statistical difference between the two groups (p = 0.496).
Maximizers’ Reactance to Algorithm-Recommended Options: The Moderating Role of Autotelic vs. Instrumental Choices
Authors: Kim Kaeun
Published: November 2023

The previous literature has provided mixed findings regarding whether consumers appreciate or are opposed to algorithms. The primary goal of this paper is to address these inconsistencies by identifying the maximizing tendency as a critical moderating variable. In Study 1, it was found that maximizers, individuals who strive for the best possible outcomes, exhibit greater reactance toward algorithm-recommended choices than satisficers, those who are satisfied with a good-enough option. This increased reactance also resulted in decreased algorithm adoption intention. Study 2 replicated and extended the findings from Study 1 by identifying the moderating role of choice goals. Maximizers are more likely to experience reactance to algorithm-recommended options when the act of choosing itself is intrinsically motivating and meaningful (i.e., autotelic choices) compared to when the decision is merely a means to an end (i.e., instrumental choices). The results of this research contribute to a nuanced understanding of how consumers with different decision-making styles navigate the landscape of choice in the digital age. Furthermore, it offers practical insights for firms that utilize algorithmic recommendations in their businesses.
Pathways by Which Self-Compassion Improves Positive Body Image: A Qualitative Analysis
Authors: Raque Trisha L. , Lamphere Brooke , Motzny Christine , Kauffmann Julia , Ziemer Kathryn , Haywood Shaakira
Published: November 2023

The current study applied consensual qualitative research–modified to essays written by 51 college women completing an expressive writing intervention over three time points for a total of 153 essays to identify how increases in self-compassion improve body image. A qualitative coding team tracked changes in affect and cognition over three time points. The results demonstrated that college women consistently expressed body acceptance and psychological flexibility. Additionally, the participants expressed important increases in mindfulness as well as decreases in social influences, feelings of separation, negative health behaviors, and attention to media messages. Decreases were found in their expressions of body functionality, love and kindness toward their body, and internal locus of control. These findings suggest pathways through which self-compassion may improve women’s body image by increasing mindfulness and decreasing the negative ways of relating to one’s body, specifically in the areas of media, clothing, make-up, and negative social interactions.
Nanomechanical Behavior of Pentagraphyne-Based Single-Layer and Nanotubes through Reactive Classical Molecular Dynamics
Authors: de Sousa José Moreira , Brandão Wjefferson Henrique da Silva , Silva Weverson Lucas Aguiar Paula , Ribeiro Júnior Luiz Antônio , Galvão Douglas Soares , Pereira Júnior Marcelo Lopes
Published: November 2023

A novel 2D carbon allotrope, pentagraphyne (PG-yne), was introduced in a recent theoretical study. This unique structure is derived from pentagraphene by incorporating acetylenic linkages between sp3 and sp2 hybridized carbon atoms. Given its intriguing electronic and structural properties, it is imperative to investigate the mechanical characteristics and thermal responses of PG-yne in both monolayer and nanotube configurations, which encompass different chiralities and diameters. We conducted fully atomistic reactive molecular dynamics (MD) simulations employing the ReaxFF potential to address these aspects. Our findings reveal that Young’s modulus of PG-yne monolayers stands at approximately 51 GPa at room temperature. In contrast, for the studied nanotubes, regardless of their chirality, it hovers around 45 GPa. Furthermore, our observations indicate that PG-yne-based systems feature an extensive and relatively flat plastic region before reaching the point of total fracture, irrespective of their topology. Regarding their thermal properties, we identified a melting point at approximately 3600 K, accompanied by a phase transition around 1100 K.
Advances in Early Breast Cancer Risk Profiling: From Histopathology to Molecular Technologies
Authors: Pescia Carlo , Guerini-Rocco Elena , Viale Giuseppe , Fusco Nicola
Published: November 2023

Early breast cancer (BC) is the definition applied to breast-confined tumors with or without limited involvement of locoregional lymph nodes. While risk stratification is essential for guiding clinical decisions, it can be a complex endeavor in these patients due to the absence of comprehensive guidelines. Histopathological analysis and biomarker assessment play a pivotal role in defining patient outcomes. Traditional histological criteria such as tumor size, lymph node involvement, histological type and grade, lymphovascular invasion, and immune cell infiltration are significant prognostic indicators. In addition to the hormone receptor, HER2, and—in specific scenarios—BRCA1/2 testing, molecular subtyping through gene expression profiling provides valuable insights to tailor clinical decision-making. The emergence of “omics” technologies, applicable to both tissue and liquid biopsy samples, has broadened our arsenal for evaluating the risk of early BC. However, a pressing need remains for standardized methodologies and integrated pathological models that encompass multiple analytical dimensions. In this study, we provide a detailed examination of the existing strategies for early BC risk stratification, intending to serve as a practical guide for histopathologists and molecular pathologists.
The Evolution of Affordable Technologies in Liquid Biopsy Diagnostics: The Key to Clinical Implementation
Authors: Alexandrou George , Mantikas Katerina-Theresa , Allsopp Rebecca , Yapeter Calista Adele , Jahin Myesha , Melnick Taryn , Ali Simak , Coombes R. Charles , Toumazou Christofer , Shaw Jacqueline A. , Kalofonou Melpomeni
Published: November 2023

Cancer remains a leading cause of death worldwide, despite many advances in diagnosis and treatment. Precision medicine has been a key area of focus, with research providing insights and progress in helping to lower cancer mortality through better patient stratification for therapies and more precise diagnostic techniques. However, unequal access to cancer care is still a global concern, with many patients having limited access to diagnostic tests and treatment regimens. Noninvasive liquid biopsy (LB) technology can determine tumour-specific molecular alterations in peripheral samples. This allows clinicians to infer knowledge at a DNA or cellular level, which can be used to screen individuals with high cancer risk, personalize treatments, monitor treatment response, and detect metastasis early. As scientific understanding of cancer pathology increases, LB technologies that utilize circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) have evolved over the course of research. These technologies incorporate tumour-specific markers into molecular testing platforms. For clinical translation and maximum patient benefit at a wider scale, the accuracy, accessibility, and affordability of LB tests need to be prioritized and compared with gold standard methodologies in current use. In this review, we highlight the range of technologies in LB diagnostics and discuss the future prospects of LB through the anticipated evolution of current technologies and the integration of emerging and novel ones. This could potentially allow a more cost-effective model of cancer care to be widely adopted.
Robotic Stereotactic Radiotherapy for Intracranial Meningiomas—An Opportunity for Radiation Dose De-Escalation
Authors: Grzbiela Hanna , Nowicka Elzbieta , Gawkowska Marzena , Tarnawska Dorota , Tarnawski Rafal
Published: November 2023

Objective: To evaluate the possibility of dose de-escalation, with consideration of the efficacy and safety of robotic stereotactic CyberKnife radiotherapy in patients diagnosed with intracranial meningiomas. Methods: The study group consisted of 172 patients (42 men and 130 women) treated in III Radiotherapy and Chemotherapy Clinic of Maria Sklodowska-Curie National Research Institute of Oncology in Gliwice between January 2011 and July 2018. The qualification for dose de-escalation was based on MRI (magnetic resonance imaging) features: largest tumor diameter less than 5 cm, well-defined tumor margins, no edema, and no brain infiltration. The age of patients was 21–79 years (median 59 years) at diagnosis and 24–80 years (median 62 years) at radiotherapy. Sixty-seven patients (Group A) were irradiated after initial surgery. Histopathological findings were meningioma grade WHO 1 in 51 and WHO 2 in 16 cases. Group B (105 patients) had no prior surgery and the diagnosis was based on the typical features of meningioma on MRI. All patients qualified for the robotic stereotactic CyberKnife radiotherapy, and the total dose received was 18 Gy in three fractions to reference isodose 78–92%. Results: Follow-up period was 18 to 124 months (median 67.5 months). Five- and eight-year progression free survival was 90.3% and 89.4%, respectively. Two patients died during the follow-up period. Progression of tumor after radiotherapy was registered in 16 cases. Four patients required surgery due to progressive disease, and three of them were progression free during further follow-up. Twelve patients received a second course of robotic radiotherapy, 11 of them had stable disease, and one patient showed further tumor growth but died of heart failure. Crude progression free survival after both primary and secondary treatment was 98.8%. Radiotherapy was well-tolerated: acute toxicity grade 1/2 (EORTC-RTOG scale) was seen in 10.5% of patients. We did not observe any late effects of radiotherapy. Conclusion: Stereotactic CyberKnife radiotherapy with total dose of 18 Gy delivered in three fractions showed comparable efficacy to treatment schedules with higher doses. This could support the idea of dose de-escalation in the treatment of intracranial meningiomas.
Robot-Assisted Radical Prostatectomy by Lateral Approach: Technique, Reproducibility and Outcomes
Authors: Rodríguez Socarrás Moisés , Gómez Rivas Juan , Reinoso Elbers Javier , Espósito Fabio , Llanes Gonzalez Luis , Monsalve Diego M. Carrion , Fernandez Del Alamo Julio , Ruiz Graña Sonia , Juarez Varela Jorge , Coria Daniel , Cuadros Rivera Vanesa , Gastón Richard , Gómez Sancha Fernando
Published: November 2023

Background: Radical prostatectomy by lateral approach allows performing a prostatectomy through a buttonhole, with direct access to the seminal vesicle and fully sparing the anterior pubovesical complex. Our aim is to show the results of reproducing the technique of robotic radical prostatectomy by lateral approach, in terms of intraoperative, postoperative, oncological and functional parameters. Methods: We analyzed 513 patients submitted to robotic radical prostatectomy by lateral approach from January 2015 to March 2021, operated on by two surgeons in our institution. The oncological and functional results of both surgeons were compared. Results: When comparing both surgeons, the rate of positive surgical margins (PSM) was 32.87% and 37.9% and significant surgical margins (PSM > 2 mm) were 5.88% and 7.58% (p = 0.672) for surgeon 1 and surgeon 2, respectively. Immediate continence was 86% and 85% and sexual potency at one year 73% and 72%, with a similar rate of complications for surgeon 1 and 2. Conclusions: Radical prostatectomy by the lateral approach technique with preservation of the anterior pubovesical complex is reproducible and offers good oncological and functional results.
Expression of Soluble Form of Aurora A as a Predictive Factor for Neoadjuvant Therapy in Breast Cancer Patients: A Single-Center Pilot Study
Authors: Winter Pawel , Fuksiewicz Malgorzata , Jagiello-Gruszfeld Agnieszka , Nowecki Zbigniew , Kotowicz Beata
Published: November 2023

Purpose: To search for new predictive breast cancer biomarkers. We analyzed the serum concentrations of biomarkers involved in carcinogenesis, which can also be targeted by therapy. Methods: In a single-center prospective study, the serum levels of Aurora A, thymidine kinase 1, and human epidermal growth factor receptor type 3 (HER3) were determined in 119 women with BC before neoadjuvant treatment using ELISA kits. Results: The following clinical data were analyzed: age; TNM; the expression of ER, PGR, HER2, and Ki67; histological grade (G); and the response to neoadjuvant treatment (NAT) in the residual tumor burden classification (RCB). A complete pathological response (pCR) was achieved after NAT in 41 patients (34%). The highest proportion of the patients with a confirmed pCR was found for triple negative breast cancer (TNBC) (62.5%); non-luminal HER2-positive (52.6%) cancer subtypes (p = 0.0003); and in the G3 group (50%; p = 0.0078). The patients with higher levels of Aurora A were more likely to achieve pCR (p = 0.039). In the multivariate analysis, the serum Aurora A levels ≥ 4.75 ng/mL correlated with a higher rate of pCR (OR: 3.5; 95% CI: 1.2–10.1; p = 0.023). Conclusions: We showed that in a biologically heterogeneous group of BC patients, the pretreatment serum Aurora A levels were of significant value in predicting the response to NAT.
Review on Recent Advances in the Removal of Organic Drugs by Advanced Oxidation Processes
Authors: Umair Muhammad , Kanwal Tayyaba , Loddo Vittorio , Palmisano Leonardo , Bellardita Marianna
Published: November 2023

In recent years, due to the high consumption of drugs both for human needs and for their growing use, especially as regards antibiotics, in the diet of livestock, water pollution has reached very high levels and attracted widespread attention. Drugs have a stable chemical structure and are recalcitrant to many treatments, especially biological ones. Among the methods that have shown high efficiency are advanced oxidation processes (AOPs) which are, among other things, inexpensive and eco-friendly. AOPs are based on the production of reactive oxygen species (ROS) able to degrade organic pollutants in wastewater. The main problem related to the degradation of drugs is their partial oxidation to compounds that are often more harmful than their precursors. In this review, which is not intended to be exhaustive, we provide an overview of recent advances in the removal of organic drugs via advanced oxidation processes (AOPs). The salient points of each process, highlighting advantages and disadvantages, have been summarized. In particular, the use of AOPs such as UV, ozone, Fenton-based AOPs and heterogeneous photocatalysis in the removal of some of the most common drugs (tetracycline, ibuprofen, oxytetracycline, lincomycin) has been reported.
SIRT1 Prevents R-Loops during Chronological Aging by Modulating DNA Replication at rDNA Loci
Authors: Thakur Bhushan L. , Kusi Nana A. , Mosavarpour Sara , Zhu Roger , Redon Christophe E. , Fu Haiqing , Dhall Anjali , Pongor Lorinc S. , Sebastian Robin , Indig Fred E. , Aladjem Mirit I.
Published: November 2023

In metazoans, the largest sirtuin, SIRT1, is a nuclear protein implicated in epigenetic modifications, circadian signaling, DNA recombination, replication, and repair. Our previous studies have demonstrated that SIRT1 binds replication origins and inhibits replication initiation from a group of potential initiation sites (dormant origins). We studied the effects of aging and SIRT1 activity on replication origin usage and the incidence of transcription–replication collisions (creating R-loop structures) in adult human cells obtained at different time points during chronological aging and in cancer cells. In primary, untransformed cells, SIRT1 activity declined and the prevalence of R-loops rose with chronological aging. Both the reduction in SIRT1 activity and the increased abundance of R-loops were also observed during the passage of primary cells in culture. All cells, regardless of donor age or transformation status, reacted to the short-term, acute chemical inhibition of SIRT1 with the activation of excessive replication initiation events coincident with an increased prevalence of R-loops. However, cancer cells activated dormant replication origins, genome-wide, during long-term proliferation with mutated or depleted SIRT1, whereas, in primary cells, the aging-associated SIRT1-mediated activation of dormant origins was restricted to rDNA loci. These observations suggest that chronological aging and the associated decline in SIRT1 activity relax the regulatory networks that protect cells against excess replication and that the mechanisms protecting from replication–transcription collisions at the rDNA loci manifest as differentially enhanced sensitivities to SIRT1 decline and chronological aging.
Potential Crosstalk between the PACAP/VIP Neuropeptide System and Endoplasmic Reticulum Stress—Relevance to Multiple Sclerosis Pathophysiology
Authors: Withana Minduli , Castorina Alessandro
Published: November 2023

Multiple sclerosis (MS) is an immune-mediated disorder characterized by focal demyelination and chronic inflammation of the central nervous system (CNS). Although the exact etiology is unclear, mounting evidence indicates that endoplasmic reticulum (ER) stress represents a key event in disease pathogenesis. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally related neuropeptides that are abundant in the CNS and are known to exert neuroprotective and immune modulatory roles. Activation of this endogenous neuropeptide system may interfere with ER stress processes to promote glial cell survival and myelin self-repair. However, the potential crosstalk between the PACAP/VIP system and ER stress remains elusive. In this review, we aim to discuss how these peptides ameliorate ER stress in the CNS, with a focus on MS pathology. Our goal is to emphasize the importance of this potential interaction to aid in the identification of novel therapeutic targets for the treatment of MS and other demyelinating disorders.
Chronological Changes in Gonadotropin-Releasing Hormone 1, Gonadotropins, and Sex Steroid Hormones along the Brain–Pituitary–Gonadal Axis during Gonadal Sex Differentiation and Development in the Longtooth Grouper, Epinephelus bruneus
Authors: Xu Wengang , Chuda Hisashi , Soyano Kiyoshi , Zeng Jun , Mei Weiping , Zou Huafeng
Published: November 2023

(1) Fshβ and Lhβ showed stronger signals and higher transcript levels from 590 to 1050 dph than at earlier stages, implying their active involvement during primary oocyte development. (2) Fshβ and Lhβ at lower levels were detected during the phases of ovarian differentiation and oogonial proliferation. (3) E2 concentrations increased significantly at 174, 333, and 1435 dph, while T concentrations exhibited significant increases at 174 and 333 dph. These findings suggest potential correlations between serum E2 concentrations and the phases of oogonial proliferation and pre-vitellogenesis.
High-Level Production of scFv-Fc Antibody Using an Artificial Promoter System with Transcriptional Positive Feedback Loop of Transactivator in CHO Cells
Authors: Ying Binbin , Kawabe Yoshinori , Zheng Feiyang , Amamoto Yuki , Kamihira Masamichi
Published: November 2023

With the increasing demand for therapeutic antibodies, CHO cells have become the de facto standard as producer host cells for biopharmaceutical production. High production yields are required for antibody production, and developing a high-titer production system is increasingly crucial. This study was established to develop a high-production system using a synthetic biology approach by designing a gene expression system based on an artificial transcription factor that can strongly induce the high expression of target genes in CHO cells. To demonstrate the functionality of this artificial gene expression system and its ability to induce the high expression of target genes in CHO cells, a model antibody (scFv-Fc) was produced using this system. Excellent results were obtained with the plate scale, and when attempting continuous production in semi-continuous cultures using bioreactor tubes with high-cell-density suspension culture using a serum-free medium, high-titer antibody production at the gram-per-liter level was achieved. Shifting the culture temperature to a low temperature of 33 °C achieved scFv-Fc concentrations of up to 5.5 g/L with a specific production rate of 262 pg/(cell∙day). This artificial gene expression system should be a powerful tool for CHO cell engineering aimed at constructing high-yield production systems.
A High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening
Authors: Fisher Christine R. , Mba Medie Felix , Luu Rebeccah J. , Gaibler Robert B. , Mulhern Thomas J. , Miller Caitlin R. , Zhang Chelsea J. , Rubio Logan D. , Marr Elizabeth E. , Vijayakumar Vidhya , Gabriel Elizabeth P. , Lopez Quezada Landys , Zhang Chun-Hui , Anderson Karen S. , Jorgensen William L. , Alladina Jehan W. , Medoff Benjamin D. , Borenstein Jeffrey T. , Gard Ashley L.
Published: November 2023

COVID-19 emerged as a worldwide pandemic in early 2020, and while the rapid development of safe and efficacious vaccines stands as an extraordinary achievement, the identification of effective therapeutics has been less successful. This process has been limited in part by a lack of human-relevant preclinical models compatible with therapeutic screening on the native virus, which requires a high-containment environment. Here, we report SARS-CoV-2 infection and robust viral replication in PREDICT96-ALI, a high-throughput, human primary cell-based organ-on-chip platform. We evaluate unique infection kinetic profiles across lung tissue from three human donors by immunofluorescence, RT-qPCR, and plaque assays over a 6-day infection period. Enabled by the 96 devices/plate throughput of PREDICT96-ALI, we also investigate the efficacy of Remdesivir and MPro61 in a proof-of-concept antiviral study. Both compounds exhibit an antiviral effect against SARS-CoV-2 in the platform. This demonstration of SARS-CoV-2 infection and antiviral dosing in a high-throughput organ-on-chip platform presents a critical capability for disease modeling and therapeutic screening applications in a human physiology-relevant in vitro system.
Effect of Bias Voltage on Structure, Mechanical Properties, and High-Temperature Water Vapor Corrosion of AlCrNbSiTi High Entropy Alloy Coatings
Authors: Wang Xuanzheng , Zeng Zhong , Wang Haobin , Bai Haiping , Li Wentao , Li Yonghao , Wang Ziwei , Chen Yanming , Yang Bing
Published: November 2023

Fuel cladding tubes are devices used in reactors to encapsulate fuel clots and transmit heat to coolants. However, zirconium alloy materials which are widely used in the fuel cladding pipe of pressurized water reactors have noticeable safety risks in resisting design basis accidents. Therefore, it is very important to improve the corrosion resistance of fuel envelope tubes to high-temperature water vapor oxidation. High-entropy alloys are considered to be a potential protective coating material for cladding tubes. In this study, AlCrNbSiTi high-entropy alloy (HEA) coatings were prepared by magnetron sputtering at different bias voltages. The effect of bias on coating morphologies, structure, mechanical properties, and resistance to high-temperature water vapor corrosion were studied. Experimental results showed that the bias significantly affects the coating surface roughness. In terms of mechanical properties, the sample at 50 V bias exhibited maximum hardness and elastic modulus of 18.2 GPa and 232.4 GPa, respectively. The highest adhesive force of the coating to the substrate of 36 N was obtained at 100 V bias. The optimum water vapor corrosion resistance of the AlCrNbSiTi HEA coating was achieved at 50 V bias, in which sample-point corrosion was the main corrosion failure mechanism.
Microstructure and Tribological Performance of HVAF-Sprayed Ti-6Al-4V Coatings
Authors: Owoseni Tunji A. , Ciudad de Lara Irene , Mathiyalagan Sribalaji , Björklund Stefan , Joshi Shrikant
Published: November 2023

Ti-6Al-4V is a widely used titanium alloy in aviation and bio/chemical applications for its attractive mechanical and corrosion resistance properties. The use of Ti-6Al-4V as a coating for repair purposes through thermal spray techniques provides a unique productivity opportunity. A repair coating must be dense to provide the required in-service functionalities, such as resistance to wear. The High Velocity Air Fuel (HVAF) thermal spray technique deposits dense coatings with reduced concern for oxide inclusions. This work presents an investigation of the microstructure, dry sliding, and solid particle erosive wear performance of four different coatings engineered through the configuration of the nozzle of an HVAF spray gun, based on the length of the nozzle and the size of the nozzle exit. A long nozzle length and wide nozzle exit mean increased inflight dwell time and reduced average inflight temperature for the sprayed particles, respectively—a reversed configuration means the opposite. The tested coatings showed a porosity of less than 2%. The sliding and erosion wear performance of the densest of the coatings compares to that of the bulk material tested under the same conditions. Electron microscopy was used to investigate the driving mechanisms for the performance of the respective coatings. The implications of the results are discussed for the potential adoption of HVAF-sprayed coatings in metal component repair.
Cold Spray Process for Co-Deposition of Copper and Aluminum Particles
Authors: Hu Shijie , Li Hongjun , Zhang Liying , Xu Yuzhen
Published: November 2023

Mixed-particle spraying has been applied to various aspects of industrial cold spraying for a long time. Due to the complexity of mixed-particle simulations, most studies only consider dozens of particles when considering particle collisions. This paper combines computational fluid dynamics and a discrete element method to analyze the entire trajectories of mixed particles. With simulations involving over one hundred thousand particles, we accurately tracked the three-dimensional positions and velocities of each particle, effectively visualizing their journey from feeder to substrate. By comparing the particles’ velocities to their critical velocities, we could directly assess the deposition efficiency, achieving a comprehensive and accurate simulation of the complete cold spray process. The numerical model was validated using a multi-experimental analysis. The particle distribution and deposition area from the numerical model matched well with the experimental data. It was found that the mutual collision of copper and aluminum particles increased the number of copper particles, surpassing the critical velocity in the mixed powder by 24.2%. When copper particles and aluminum particles collided, the displacement of aluminum particles was more than three times that of copper particles in the direction perpendicular to the jet. This collision caused the aluminum particles to be more dispersed.
Study of Decay Mechanisms and Rules of Recycled Asphalt Pavement via a Full-Scale Experiment
Authors: Xia Quanping , Gao Jiangping , Zhang Qigong , Xu Bin , Sun Qiang , Sun Ke , Yuan Zhaodi
Published: November 2023

Under the influence of long-term vehicle loads and large attenuation degrees, asphalt pavement performance gradually decreases, which leads to failure in fulfilling the appropriate requirements and, in turn, may affect driving safety. The purpose of this paper was to study the attenuation mechanism and rule of styrene–butadiene–styrene (SBS)-modified recycled asphalt pavement, so as to determine the applicable position and rational utilization of recycled asphalt mixture. To achieve this goal, two structures were designed, and full-scale experiments were carried out. The performance of the field test road based on accelerated loading testing (ALT) was analyzed through field monitoring data. The fatigue characteristics of stone matrix asphalt-13 (SMA-13) and asphalt concrete-20 (AC-20) mixtures before and after accelerated loading were studied via the trabecular bending fatigue test and dynamic modulus test. The microscopic components in the asphalt mixtures were determined via thin-layer chromatography on chromarods with flame ionization detection (TLC-FID). The results showed that the fatigue properties of recycled asphalt mixture can meet the requirements of ordinary asphalt mixtures and meet the technical standards of asphalt pavement design. With the increase in loading times, the British pendulum number (BPN) value of the two structures tended to be stable, and the BPN of Plan 2 was six less than that of Plan 1. Under the same test conditions, the fatigue life sequence of the recycled asphalt mixture under different loading frequencies was 20 Hz > 10 Hz > 5 Hz. The contents of four components in the reclaimed asphalt mixture were similar to those in the ordinary asphalt mixture. The light component of the reclaimed asphalt mixture of SMA-13 was reduced by 11.69%, and the light component of the ordinary asphalt mixture of SMA-13 was reduced by 15.29% through the full-scale test. In summary, recycled asphalt mixture should not be applied to the upper layer of pavement but can be rationalized in the middle layer and the bottom layer of pavement.
Research Progress on the Application of Graphene Quantum Dots
Authors: Tan Xiangyu , Zhou Fangrong , Li Wenyun , Ao Gang , Xu Xiaowei , Yang Le
Published: November 2023

Graphene quantum dots (GQDs) are sets of carbon quantum dots derived from graphene or graphene oxide, and they have obvious graphene lattice properties. The number of layers in GQDs is generally no more than five layers, and the diameter size of GQDs is generally less than 10 nm. GQDs have stable photoluminescence characteristics, high specific surface areas, high conductivity levels and adjustable band gaps, and they can be used in sensing systems such as ion detection sensing, optical biosensing, electrochemical biosensing and electronic sensing. Based on the research status of GQDs in recent years and the application background of sensing systems, this review paper focuses on the synthesis strategies, sizes, chemical compositions, crystal structures, optical properties and sensor applications of GQDs.
Characterization and Efficacy of Essential Oil-Based Cosmetic Formulations for Acne-Prone Skin
Authors: Infante Victor Hugo Pacagnelli , Darvin Maxim E. , Maia Campos Patrícia M. B. G.
Published: November 2023

This randomized, placebo-controlled, double-blind clinical in vivo study aimed to evaluate the clinical efficacy of a cosmetic formulation for non-inflammatory acne using essential oils. Fifty-three male participants were divided into four groups: a formulation containing a mixture of four essential oils (4EO), Melaleuca alternifolia (M.a.), nanoemulsion of M. alternifolia (Nanoem.), and a placebo group. The participants applied the formulation daily for 90 days and non-invasive skin imaging techniques were employed to assess the outcomes. Skin microrelief images and reflectance confocal microscopy images were captured in the malar region, and Raman spectroscopy was used to analyze the terpene composition of the essential oils, oil mixture, and nanoemulsion. The results indicated that the nanoemulsion, M.a. essential oil, and 4EO formulation effectively reduced the overall number of comedone and improved follicular hyperkeratinization. The nanoemulsion of M.a. demonstrated the most promising outcomes in reducing comedone areas, especially in the infundibular region. This effect could be attributed to the presence of terpinene-4-ol in the essential oil and the enhanced penetration provided by the nanoemulsion formulation. These findings suggest that cosmetic formulations containing essential oils, particularly in nanoemulsion form, have potential against mild acne. This study contributes to our understanding of the relationship between terpene composition and clinical activity, highlighting the importance of innovative delivery systems.
Secure Instruction and Data-Level Information Flow Tracking Model for RISC-V
Authors: Nicholas Geraldine Shirley , Aklekar Dhruvakumar Vikas , Thakar Bhavin , Saqib Fareena
Published: November 2023

With the proliferation of electronic devices, third-party intellectual property (3PIP) integration in the supply chain of the semiconductor industry and untrusted actors/fields have raised hardware security concerns that enable potential attacks, such as unauthorized access to data, fault injection and privacy invasion. Different security techniques have been proposed to provide resilience to secure devices from potential vulnerabilities; however, no one technique can be applied as an overarching solution. We propose an integrated Information Flow Tracking (IFT) technique to enable runtime security to protect system integrity by tracking the flow of data from untrusted communication channels. Existing hardware-based IFT schemes are either fine-, which are resource-intensive, or coarse-grained models, which have minimal precision logic, providing either control-flow or data-flow integrity. No current security model provides multi-granularity due to the difficulty in balancing both the flexibility and hardware overheads at the same time. This study proposes a multi-level granularity IFT model that integrates a hardware-based IFT technique with a gate-level-based IFT (GLIFT) technique, along with flexibility, for better precision and assessments. Translation from the instruction level to the data level is based on module instantiation with security-critical data for accurate information flow behaviors without any false conservative flows. A simulation-based IFT model is demonstrated, which translates the architecture-specific extensions into a compiler-specific simulation model with toolchain extensions for Reduced Instruction Set Architecture (RISC-V) to verify the security extensions. This approach provides better precision logic by enhancing the tagged mechanism with 1-bit tags and implementing an optimized shadow logic that eliminates the area overhead by tracking the data for only security-critical modules.
Gamete Recognition Gene Divergence Yields a Robust Eutherian Phylogeny across Taxonomic Levels
Authors: Roberts Emma K. , Wright Emily A. , Worsham Asha E. , Hardy Daniel M. , Bradley Robert D.
Published: November 2023

The extraordinary morphological diversity among extant mammals poses a challenge for studies of speciation, adaptation, molecular evolution, and reproductive isolation. Despite the recent wealth of molecular studies on mammalian phylogenetics, uncertainties remain surrounding both ancestral and more recent divergence events that have proven difficult to resolve. Multi-gene datasets, especially including genes that are highly divergent, often provide increased support for higher-level affinities within Mammalia; however, such analyses require vast amounts of genomic sequence data and at times, intensive, high-performance computational effort. Furthermore, despite the large-scale efforts dedicated to comprehensive, multi-gene phylogenetic analyses using a combination of mitochondrial, nuclear, and other sequences (e.g., tRNA, ultra-conserved elements, and transposable elements), many relationships across Mammalia remain highly controversial. To offer another approach and provide a phylogenetic solution to this longstanding issue, here we present a phylogenetic tool based on a single reproductive molecular marker, zonadhesin (gene: Zan), one of two known mammalian speciation genes, which encodes the rapidly evolving sperm protein zonadhesin that mediates species-specific adhesion to the egg and thereby promotes reproductive isolation among placental mammals (Eutheria). Topological comparison of Zan Maximum Likelihood phylogenies to a nearly complete mammalian supertree confirmed Zan’s striking phylogenetic utility and resolution at both deeper and more terminal nodes in the placental mammalian phylogeny. This single gene marker yielded an equivalent and/or superiorly supported topology in comparison to a supertree generated using DNA sequences from a supermatrix of 31 genes from 5911 species (extinct and extant). Resolution achieved with this new phylogenetic approach provides unique insights into the divergence of both early and recent mammalian radiations. Finally, and perhaps most importantly, the utility of zonadhesin as a singular molecular marker was especially useful in clades where sufficient taxon sampling is impossible to achieve, and where only a subset of members of the mammalian species tree is available. The eutherian relationships presented here provide a foundation for future studies in the reconstruction of mammalian classifications, including reproductive isolation, hybridization, and biodiversification of species.
The Usefulness of the Eosinophilic Esophagitis Histology Scoring System in Predicting Response to Proton Pump Inhibitor Monotherapy in Children with Eosinophilic Esophagitis
Authors: Jevtić Jovan , Ristić Nina , Pavlović Vedrana , Svorcan Jovana , Milovanovich Ivan , Radusinović Milica , Popovac Nevena , Simić Ljubica , Ćirović Aleksandar , Đuknić Miloš , Životić Maja , Poljašević Nevena , Obradović Danilo , Filipović Jelena , Janković Radmila
Published: November 2023

Background: Eosinophilic esophagitis (EoE) is an immune-mediated esophageal disease with rising incidence. While proton pump inhibitors (PPIs) are the first-line treatment, a significant proportion of patients do not respond. This study aimed to determine if the EoE Histology Scoring System (EoEHSS) can predict PPI responsiveness. Methods: A cross-sectional study was conducted on 89 pediatric patients diagnosed with EoE between 2016 and 2022. Patients were categorized into PPI responders (PPIREoE) and non-responders (PPINREoE) based on post-treatment biopsies. EoEHSS values from biopsies of the esophagus (distal, middle, and proximal segments) were compared between the two groups. Results: No significant differences in EoEHSS scores were observed for the distal and proximal esophagus between the groups. However, the middle esophagus showed a significantly higher EoEHSS grade score in the PPINREoE group, indicating a more pronounced disease severity. Specific histological features, particularly eosinophilic abscesses and surface layering of the middle segment of the esophagus, were significantly different between the groups. Conclusions: Performing a biopsy of each esophageal segment, particularly the middle, is crucial for diagnostic precision and predicting PPI responsiveness. The EoEHSS can serve as a valuable tool in predicting therapy response, emphasizing the need for personalized therapeutic approaches in EoE management.