bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model‐based‐systems‐engineering for conceptual design: An integrative approach
Authors: Shoshany‐Tavory Sharon , Peleg Eran , Zonnenshain Avigdor , Yudilevitch Gil 
Published: April 2023

AbstractConceptual‐Design is an early development phase, where innovation and creativeness shape the future system/product. Model‐Based‐Conceptual‐Design (MBCD) attempts to use best‐practices of Model‐Based‐Systems‐Engineering (MBSE) to gain the envisioned benefits of model connectivity. Using MBSE supporting tools can transform Conceptual‐Design into a digital‐engineered process but may impede creativity and innovation. Concurrently, the design domain offers specific methods and tools for innovative Conceptual‐Design. In the current study, we explore an existing Conceptual‐Design framework and offer MBSE interpretation and tools extensions needed for its digital implementation. Through such exploration we highlight MBCD specific insights and discuss modeling‐innovation interrelations. The implementation was accomplished using a domain‐specific enabling software package on top of a market‐accepted UML/SysML platform, extending the language definitions, where appropriate. The framework guided extensions allow generation of innovative bottom‐up alternatives, solution integration, and solutions’ comparison. The use of modeling is shown to offer clearer process definition, specific methods assistance, and alternative ranking—both manually and automatically. Consequently, MBCD is accomplished, which supports innovation, while being digitally connected to full‐scale‐development models and the organizational assets at large. Through integration into the orderly Systems‐Engineering process, traceability is maintained, and repeated iterations are supported, where conceptual decisions may be revisited. Additionally, through the introduction of an assets’ catalog, cross‐organizational knowledge sharing is accomplished. The paper presents samples of the extensions, using a simplified example of technology design for Future Firefighting. The value of incorporating Conceptual‐Design specific methodology and tools is evaluated through feedback from multiple domain experts. Discussion and future research directions are offered.
Madecassoside ameliorates cisplatin‐induced nephrotoxicity by inhibiting activation of the mitogen activated protein kinase pathway
Authors: Yuan Hui , Zhao Yingying , Li Shumin , Qin Jun , Yu Xiaowen 
Published: April 2023

AbstractNephrotoxicity is a major side effect of cisplatin. Apoptosis, oxidative stress, inflammation, and the MAPK signaling pathway activation are concerned with the pathophysiology of cisplatin‐induced acute kidney injury (AKI). Madecassoside (MA), an active constituent of Centella asiatica, has anti‐oxidative and anti‐inflammatory effects. The present research aim to investigate the underlying protective mechanisms of MA on cisplatin nephrotoxicity. Pretreatment of mice with MA markedly ameliorated cisplatin‐induced renal tubular cell injury evidenced by the improvement of kidney function and kidney morphology and blocked upregulation of kidney injury biomarkers (kidney injury molecule 1 (KIM‐1) and neutrophil gelatinase‐associated lipocalin (NGAL)). Cisplatin‐induced renal cell apoptosis, inflammation, and oxidative stress were also prevented by MA treatment. Consistent with the in vivo results, MA pretreatment attenuated cisplatin‐induced renal cell apoptosis, oxidative stress, and inflammation. Transcriptome analysis using RNA‐sequencing suggested that the MAPK signaling pathway was the most affected, and MA could inhibit cisplatin‐induced MAPK signaling pathway activation in vivo and in vitro. In summary, MA treatment ameliorated cisplatin‐induced renal tubular damage possibly by decreasing activation of the MAPK signaling pathway, suggesting its potential for the treatment of AKI.
NEDD4L inhibits migration, invasion, cisplatin resistance and promotes apoptosis of bladder cancer cells by inactivating the p62/Keap1/Nrf2 pathway
Authors: Wu Qi , Zhang Huijiang , You Shengjie , Xu Zhaoyu , Liu Xiang , Chen Xuedong , Zhang Weili , Ye Junjie , Li Peng , Zhou Xiaoqing 
Published: April 2023

AbstractPurposeThis study identified the function of neural precursor cell expressed developmentally down‐regulated 4‐like (NEDD4L) on bladder cancer (BLCA).MethodsNEDD4L expression in BLCA patients was scrutinized. The function of NEDD4L on the viability, apoptosis, migration and invasion of BLCA cells was evaluated by cell counting kit‐8, flow cytometry and Transwell assays. The effect of NEDD4L on the cisplatin (DDP) resistance of the DDP‐resistant BLCA cells was explored. The influence of NEDD4L on the p62/Keap1/Nrf2 pathway activity in BLCA cells was tested by Western blot. Rescue experiments were implemented to verify whether NEDD4L regulated BLCA cell malignant behavior by mediating the Keap1/Nrf2 pathway activity via p62. The effect of NEDD4L on the growth and the p62/Keap1/Nrf2 pathway activity in vivo was researched in xenograft tumor nude mice models.ResultsThe down‐regulated NEDD4L in BLCA patients was associated with unfavorable survival. NEDD4L suppressed the viability (inhibition rate 57.1%/49.0%), migration (inhibition rate 49.7%/77.1%), invasion (inhibition rate 50.6%/75.7%), promoted the apoptosis of T24/5637 cells (promotion rate 243.8%/201.9%), reduced IC 50 of DDP‐resistant T24/5637 cells from 132.2/101.8 to 57.81/59.71 μM, respectively, and inactivated the p62/Keap1/Nrf2 pathway in T24/5637 cells. p62 up‐regulation partially abrogated the inhibition of NEDD4L on the Keap1/Nrf2 pathway activity, the malignant behavior of BLCA cells, and the DDP resistance of DDP‐resistant BLCA cells. NEDD4L overexpression inhibited the tumor growth and the p62/Keap1/Nrf2 pathway activity in vivo in BLCA.ConclusionNEDD4L inhibits the progression of BLCA by inactivating the p62/Keap1/Nrf2 pathway. It may be an effective target for BLCA treatment.
Integrated metabolomics and transcriptomics reveal glyphosate based‐herbicide induced reproductive toxicity through disturbing energy and nucleotide metabolism in mice testes
Authors: Qi Lei , Li Yupeng , Dong Yanmei , Ma Shuli , Li Gang 
Published: April 2023

AbstractGlyphosate is a widely used herbicide that has deleterious effects on animal reproduction. However, details regarding the systematic mechanisms of glyphosate‐induced reproductive toxicity are limited. This study aimed to investigate the toxic effects of glyphosate‐based herbicide (GBH) on reproduction in mice exposed to 0 (control group), 50 (low‐dose group), 250 (middle‐dose group), and 500 (high‐dose group) mg/kg/day GBH for 30 days. Toxicological parameters, metabolomics, and transcriptomics were performed to reveal GBH‐induced reproductive toxicity. Our findings demonstrated that GBH exposure damaged mitochondrial pyknosis and the nuclear membrane of spermatogonia. GBH triggered a significant increase in sperm malformations in the high‐dose group. Omics data showed that GBH impaired the Krebs cycle and respiratory chain, blocked pyruvate metabolism and glycolysis/gluconeogenesis, and influenced the pentose phosphate pathway and nucleotide synthesis and metabolism. Overall, the multi‐omics results revealed systematic and comprehensive evidence of the adverse effects of GBH exposure, providing new insights into the reproductive toxicity of organophosphorus pesticides.
Organoids technology for advancing the clinical translation of cancer nanomedicine
Authors: Zhao Dong‐Kun , Liang Jie , Huang Xiao‐Yi , Shen Song , Wang Jun 
Published: April 2023

AbstractThe past decades have witnessed the rapid development and widespread application of nanomedicines in cancer treatment; however, the clinical translation of experimental findings has been low, as evidenced by the low percentage of commercialized nanomedicines. Incomplete understanding of nanomedicine‐tumor interactions and inappropriate evaluation models are two important challenges limiting the clinical translation of cancer nanomedicines. Currently, nanomedicine‐tumor interaction and therapeutic effects are mainly investigated using cell lines or mouse models, which do not recapitulate the complex tumor microenvironment in human patients. Thus, information obtained from cell lines and mouse models cannot provide adequate guidance for the rational redesign of nanomedicine. Compared with other preclinical models, tumor organoids constructed from patient‐derived tumor tissues are superior in retaining the key histopathological, genetic, and phenotypic features of the parent tumor. We speculate that organoid technology would help elucidate nanomedicine‐tumor interaction in the tumor microenvironment and guide the design of nanomedicine, making it a reliable tool to accurately predict drug responses in patients with cancer. This review highlighted the advantages of drug delivery systems in cancer treatment, challenges limiting the clinical translation of antitumor nanomedicines, and potential application of patient‐derived organoids (PDO) in nanomedicine. We propose that combining organoids and nanotechnology would facilitate the development of safe and effective cancer nanomedicines and accelerate their clinical application. This review discussed the potential translational value of integrative research using organoids and cancer nanomedicine.This article is categorized under:
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Preparation of Experiments: Addition and In Situ Production of Trace Gases and Oxidants in the Gas Phase
Authors: Bell David M. , Cirtog Manuela , Doussin Jean-François , Fuchs Hendrik , Illmann Jan , Muñoz Amalia , Patroescu-Klotz Iulia , Picquet-Varrault Bénédicte , Ródenas Mila , Saathoff Harald 
Published: April 2023

AbstractPreparation of the air mixture used in chamber experiments requires typically the injection of trace gases into a bath gas. In this chapter, recommendations and standard protocols are given to achieve quantitative injections of gaseous, liquid or solid species. Various methods to produce ozone, nitrate radicals and hydroxyl radicals are discussed. Short-lived oxidants need to be produced during the experiment inside the chamber from pre-cursor species. Because highly reactive oxidants like hydroxyl radicals are challenging to detect an alternative method for the quantification of radical concentrations using trace molecules is described.
Analysis of Chamber Data
Authors: Seakins Paul , Allanic Arnaud , Jammoul Adla , Mellouki Albelwahid , Muñoz Amalia , Rickard Andrew R. , Doussin Jean-François , Kleffmann Jorg , Kangasluoma Juha , Lehtipalo Katrianne , Cain Kerrigan , Dada Lubna , Kulmala Markku , Cazaunau Mathieu , Newland Mike J. , Ródenas Mila , Wiesen Peter , Jorga Spiro , Pandis Spyros , Petäjä Tuukka 
Published: April 2023

AbstractIn this chapter, we focus on aspects of analysis of typical simulation chamber experiments and recommend best practices in term of data analysis of simulation chamber results relevant for both gas phase and particulate phase atmospheric chemistry. The first two sections look at common gas-phase measurements of relative rates and product yields. The simple yield expressions are extended to account for product removal. In the next two sections, we examine aspects of particulate phase chemistry looking firstly at secondary organic aerosol (SOA) yields including correction for wall losses, and secondly at new particle formation using a variety of methods. Simulations of VOC oxidation processes are important components of chamber work and one wants to present methods that lead to fundamental chemistry and not to specific aspects of the chamber that the experiment was carried out in. We investigate how one can analyse the results of a simulation experiment on a well-characterized chemical system (ethene oxidation) to determine the chamber-specific corrections. Finally, we look at methods of analysing photocatalysis experiments, some with a particular focus on NOx reduction by TiO2-doped surfaces. In such systems, overall reactivity is controlled by both chemical processes and transport. Chambers can provide useful practical information, but care needs to be taken in extrapolating results to other conditions. The wider impact of surfaces on photosmog formation is also considered.
Conclusions
Authors: Doussin Jean-François 
Published: April 2023

AbstractIn this conclusion, we present the long journey of the scientific community toward a precise understanding of the chemistry at work in atmospheric simulation chamber starting from the early definition and objections about the use of these complex installations to the progress made recently through the EUROCHAMP projects. It summarizes how the need for a careful characterization that was identified as early as 30 to 40 years ago are now on a good way to be fullfilled. it also briefly reviews the major progress made in our understanding of atmospheric chemistry thanks to chamber activities. It finally concludes with the recent advances shaping the way the future use of atmospheric simulation chambers extending their application to emerging scientific issues as well as better simulating the complexity of the real atmosphere including interfaces and considering longer timescales. .
Performing Weedist
Authors: Li Kwan Queenie , Cunningham Joel Austin 
Published: April 2023

AbstractThe world is currently facing a wave of data centre construction. Fuelled by an explosion of data production and the emergence of edge computing, our cities are witnessing the materialisation of new architectural typologies that increasingly convolute notions of digital and bodily distinction. Whilst the last 2 decades have seen the proliferation of separate human and post-human urban environments, here we consider the agency and performativity of human communities within increasingly tangled contexts. As edge computing continues to bring the material reality of data processing closer to our physical bodies, perhaps its time to reassess who, or what, our cities now serve. In an age of unprecedented digital transformation, when our identities seem to be ever more intangible, how we might perform within environments that are increasingly catering to our digital rather than bodily needs? Today, the Anthropocene expels nature to the periphery. Tomorrow, humans become marginalised—“weeds”, thriving in an epoch of data.
Prognostic value of the liver fibrosis marker fibrosis-5 index in patients with severe isolated tricuspid regurgitation: comparison with fibrosis-4 index
Authors: Nakashima Mitsutaka , Miyoshi Toru , Tanakaya Machiko , Saito Takaaki , Katayama Yusuke , Sakuragi Satoru , Takaya Yoichi , Ito Hiroshi 
Published: April 2023

AbstractThe fibrosis-4 index (FIB4), a liver fibrosis maker, has been shown to be associated with the prognosis in patients with severe isolated tricuspid regurgitation (TR). Recent study showed that the fibrosis-5 index (FIB5), which was calculated by albumin, alkaline phosphatase, aspartate transaminase, alanine aminotransferase and platelet count, had better prognostic value than FIB4 in patients with heart failure. The aim of this study was to evaluate the usefulness of FIB5 index for predicting prognosis in patients with severe isolated TR and compare the prognostic value between the FIB4 and the FIB5 in those patients. This was a dual-center, retrospective study. 113 consecutive outpatients with severe isolated TR (mean age, 65.8 years; 47.8% male) were analyzed. Major adverse cardiovascular events (MACEs) were defined as the composite of cardiovascular death, hospitalization for heart failure, myocardial infarction, and stroke. During a median follow-up of 3.0 years, 41 MACEs occurred. Patients with MACEs had a lower the FIB5 than patients without MACEs. The multivariate Cox analysis revealed that the FIB5 < -4.30 was significantly associated with higher incidence of MACEs after adjusted by confounding factors. Receiver-operating characteristic curve analyses showed that prognostic values did not differ between the FIB5 and the FIB4 in whole patients and in patients aged ≥ 70 years; while, in patients aged < 70 years, the FIB5 had better prognostic value than the FIB4. The FIB5 may be a useful predictor of MACEs in patients with severe isolated TR.
Research highlight: surgical outcomes of gluteal VY plasty after extensive abdominoperineal resection or total pelvic exenteration
Authors: Gielen Anke H. C. , Colier Evie , Qiu Shan S. , Keymeulen Kristien B. M. I. , Stassen Laurents P. S. , Melenhorst Jarno 
Published: April 2023

Abstract
Objective
To describe a suitable alternative technique for reconstruction of the pelvic floor after extensive resection. To review our outcomes of gluteal VY plasty in the reconstruction of the pelvic floor after extensive abdominoperineal resection (conventional or extralevator abdominoperineal resection, total pelvic exenteration, or salvage surgery).

Design
Retrospective cohort study.

Setting
An academic hospital and tertiary referral centre for the treatment of locally advanced or locally recurrent rectal cancer, and salvage surgery in The Netherlands.

Patients
Forty-one consecutive patients who underwent a pelvic floor reconstruction with gluteal VY plasty at Maastricht University Medical Centre between January 2017 and February 2021 were included. The minimum duration of follow-up was 2 years.

Main outcome measures
Perineal herniation is the primary outcome measure. Furthermore, the occurrence of minor and major postoperative complications and long-term outcomes were retrospectively assessed.

Results
Thirty-five patients (85.4%) developed one or more complications of whom twenty-one patients experienced minor complications and fourteen patients developed major complications. Fifty-seven percent of complications was not related to the VY reconstruction. Six patients (14.6%) recovered without any postoperative complications during follow-up. Three patients developed a perineal hernia.

Conclusions
A gluteal VY plasty is a suitable technique for reconstruction of the pelvic floor after extensive perineal resections resulting in a low perineal hernia rate, albeit the complication rate remains high in this challenging group of patients.
Tumor suppressor miR-218 directly targets epidermal growth factor receptor (EGFR) expression in triple-negative breast cancer, sensitizing cells to irradiation
Authors: Wischmann Franz-Josef , Troschel Fabian M. , Frankenberg Maj , Kemper Björn , Vijaya Kumar Archana , Sicking Mark , Ibrahim Sherif Abdelaziz , Kiesel Ludwig , Götte Martin , Eich Hans Theodor , Greve Burkhard 
Published: April 2023

Abstract
Purpose
MicroRNA-218 (miR-218) is a key regulator of numerous processes relevant to tumor progression. In the present study, we aimed to characterize the relationship between miR-218 and the Epidermal Growth Factor Receptor (EGFR) as well as to understand downstream effects in triple-negative breast cancer (TNBC).

Methods
We assessed miR-218 and EGFR expression in cell lines and publicly available primary breast cancer gene expression data. We then overexpressed miR-218 in two TNBC cell lines and investigated effects on EGFR and downstream mitogen-activated protein (MAP) kinase signaling. Luciferase reporter assay was used to characterize a direct binding interaction between miR-218 and EGFR mRNA. Digital holographic microscopy helped investigate cell migration and dry mass after miR-218 overexpression. Cell division and invasion were assessed microscopically, while radiation response after miR-218 overexpression alone or combined with additional EGFR knockdown was investigated via clonogenic assays.

Results
We found an inverse correlation between EGFR expression and miR-218 levels in cell lines and primary breast cancer tissues. MiR-218 overexpression resulted in a downregulation of EGFR via direct binding of the mRNA. Activation of EGFR and downstream p44/42 MAPK signaling were reduced after pre-miR-218 transfection. Cell proliferation, motility and invasiveness were inhibited whereas cell death and mitotic catastrophe were upregulated in miR-218 overexpressing cells compared to controls. MiR-218 overexpressing and EGFR siRNA-treated cells were sensitized to irradiation, more than miR-218 overexpressing cells alone.

Conclusion
This study characterizes the antagonistic relationship between miR-218 and EGFR. It also demonstrates downstream functional effects of miR-218 overexpression, leading to anti-tumorigenic cellular changes.
Joint-product representation learning for domain generalization in classification and regression
Authors: Chen Sentao , Chen Liang 
Published: April 2023

AbstractIn this work, we study the problem of generalizing a prediction (classification or regression) model trained on a set of source domains to an unseen target domain, where the source and target domains are different but related,i.e, the domain generalization problem. The challenge in this problem lies in the domain difference, which could degrade the generalization ability of the prediction model. To tackle this challenge, we propose to learn a neural network representation function to align a joint distribution and a product distribution in the representation space, and show that such joint-product distribution alignment conveniently leads to the alignment of multiple domains. In particular, we align the joint distribution and the product distribution under the$$L^{2}$$L2-distance, and show that this distance can be analytically estimated by exploiting its variational characterization and a linear variational function. This allows us to comfortably align the two distributions by minimizing the estimated distance with respect to the network representation function. Our experiments on synthetic and real-world datasets for classification and regression demonstrate the effectiveness of the proposed solution. For example, it achieves the best average classification accuracy of 82.26% on the text dataset Amazon Reviews, and the best average regression error of 0.114 on the WiFi dataset UJIIndoorLoc.
Varying stages of ecological succession in lakes subdivided by volcanic eruptions at Akan Caldera, Japan
Authors: Wakana Isamu , Kadono Yasuro , Urabe Jotaro , Tamura Yuki , Suzuki Yoshifusa , Yamada Hiroyuki , Oyama Yoichi , Wada Keiji , Hasegawa Takeshi , Ohara Masashi 
Published: April 2023

AbstractEcological succession within lakes generally proceeds as eutrophication and shallowing occur and the aquatic biota of the lakes is altered. The eutrophication rate depends on the lake size and the area and fertility of the watershed. If the watershed fertility of several different lakes is equivalent and the lakes’ formation time and initial environment are similar, the trophic status of each lake is expected to increase over time depending on the ratio of the watershed area to lake size. To test this supposition, we surveyed the topography and water quality of 10 lakes of varying sizes in Akan Caldera, Japan, which were formed thousands of years ago by fragmentation due to volcanic eruptions within the caldera. The ratio of the accumulated watershed area to lake size was positively correlated with total phosphorus concentration, an indicator of trophic status, and lake types were classified as oligotrophic, mesotrophic, eutrophic, and dystrophic. In addition, 21 species of macrophytes were found in the lakes, and the species composition of each lake was divided into five types corresponding to combinations of the lake types. The discovery of such diversity in a group of lakes with a similar origin paves the way for new comparative studies.