bluuebunny/crossref_metadata_2025 huggingface dataset:
Fine‐scale damage assessment of urban flooding based on the 1D/2D coupled hydrodynamic model
Authors: Dong Boliang , Xia Junqiang , Li Qijie , Wang Xiaojie
Published: December 2023

Due to the high population density and economic property in urban environments, urban flooding can result in substantial economic losses. However, accurate urban flood modeling and assessing the associated damages are challenging due to complex urban layouts and rugged topography. Furthermore, the rapid development of urban underground spaces has introduced additional complexities. To address the demanding need for accurate flood modeling and damage assessment in cities, a fine‐scale flood damage assessment method was proposed in this study, based on the 1D/2D coupled hydrodynamic model, which can not only assess the flood damage on the ground surface but also evaluate the flood loss in underground spaces. Taking the Gangxi drainage area in Wuhan City, China as a case, this study extensively discussed the flood inundation processes on the ground surface as well as in the buildings and underground spaces, under different rainfall scenarios with the return period ranging from 2 to 200 years. Based on the high spatial‐temporal hydrodynamic simulations, the flood damage degrees were evaluated for the buildings and underground spaces with different industry types. The results indicated that the inundation of buildings and underground spaces in densely built cities cannot be neglected in urban flood modeling. Buildings with public service attributes can have a higher flood damage degree, as compared with other types of buildings and underground spaces.
Celebrating 100 Years of University of Delhi (1922–2022)
Authors: Awasthi Satish K. , Biswas Parbati , Singh Brajendra K. , Deka Sasanka , Kaur‐Ghumaan Sandeep
Published: December 2023

University of Delhi (DU) has attained global recognition for its research and teaching in Chemistry. This Guest Editorial introduces the research showcased in the “Institute Feature: Celebrating 100 Years of University of Delhi (1922–2022)” ‐ a joint special collection from the European Journal of Organic Chemistry (EurJOC), European Journal of Inorganic Chemistry (EurJIC) and ChemistrySelect The collection highlights the contributions to the field of chemistry through research articles and reviews authored by faculty members from the Department of Chemistry, alumni of the department and faculty members of chemistry department of various colleges affiliated with the university, celebrating 100 years of DU.
Neutrophil‐Mimetic, ROS Responsive, and Oxygen Generating Nanovesicles for Targeted Interventions of Refractory Rheumatoid Arthritis
Authors: Tang Zhuang , Meng Shiyu , Yang Xiaoxue , Xiao Yi , Wang Wentao , Liu Yonghang , Wu Kefan , Zhang Xican , Guo Hui , Zhu Yi Zhun , Wang Xiaolin
Published: December 2023

Rheumatoid arthritis (RA) is the most prevalent inflammatory joint disease worldwide, leading to irreversible disability and even mortality. Unfortunately, current treatment regimens fail to cure RA due to low therapeutic responses and off‐target side effects. Herein, a neutrophil membrane‐cloaked, natural anti‐arthritic agent leonurine (Leo), and catalase (CAT) co‐loaded nanoliposomal system (Leo@CAT@NM‐Lipo) is constructed to remodel the hostile microenvironment for RA remission. Due to the inflammation tropism inherited from neutrophils, Leo@CAT@NM‐Lipo can target and accumulate in the inflamed joint cavity where high‐level ROS can be catalyzed into oxygen by CAT to simultaneously accelerate the drug release and alleviate hypoxia at the lesion site. Besides, the neutrophil membrane camouflaging also enhances the anti‐inflammatory potentials of Leo@CAT@NM‐Lipo by robustly absorbing pro‐arthritogenic cytokines and chemokines. Consequently, Leo@CAT@NM‐Lipo successfully alleviated paw swelling, reduced arthritis score, mitigated bone and cartilage damage, and reversed multiple organ dysfunctions in adjuvant‐induced arthritis rats (AIA) rats by synergistic effects of macrophage polarization, inflammation resolution, ROS scavenging, and hypoxia relief. Furthermore, Leo@CAT@NM‐Lipo manifested excellent biocompatibility both at the cellular and animal levels. Taken together, the study provided a neutrophil‐mimetic and ROS responsive nanoplatform for targeted RA therapy and represented a promising paradigm for the treatment of a variety of inflammation‐dominated diseases.
Sequence‐Guided Localization of DNA Hybridization Enables Highly Selective and Robust Genotyping
Authors: Wang Xuchu , Chen Tao , Ping Ying , Dai Yibei , Yu Pan , Xie Yiyi , Liu Zhenping , Sun Bohao , Duan Xiuzhi , Tao Zhihua
Published: December 2023

Genetic variations are always related to human diseases or susceptibility to therapies. Nucleic acid probes that precisely distinguish closely related sequences become an indispensable requisite both in research and clinical applications. Here, a Sequence‐guided DNA LOCalization for leaKless DNA detection (SeqLOCK) is introduced as a technique for DNA hybridization, where the intended targets carrying distinct “guiding sequences” act selectively on the probes. In silicon modeling, experimental results reveal considerable agreement (R2 = 0.9228) that SeqLOCK is capable of preserving high discrimination capacity at an extraordinarily wide range of target concentrations. Furthermore, SeqLOCK reveals high robustness to various solution conditions and can be directly adapted to nucleic acid amplification techniques (e.g., polymerase chain reaction) without the need for laborious pre‐treatments. Benefiting from the low hybridization leakage of SeqLOCK, three distinct variations with a clinically relevant mutation frequency under the background of genomic DNA can be discriminated simultaneously. This work establishes a reliable nucleic acid hybridization strategy that offers great potential for constructing robust and programmable systems for molecular sensing and computing.
Engineering Low‐Cost Organic Cathode for Aqueous Rechargeable Battery and Demonstrating the Proton Intercalation Mechanism for Pyrazine Energy Storage Unit
Authors: Niu Suyan , Wang Yao , Zhang Jianwen , Wang Yiming , Tian Yaxiong , Ju Na , Wang Haipeng , Zhao Shuya , Zhang Xinyue , Zhang Wenlong , Li Chengrui , Sun Hong‐bin
Published: December 2023

Seeking organic cathode materials with low cost and long cycle life that can be employed for large‐scale energy storage remains a significant challenge. This work has synthesized an organic compound, triphenazino[2,3‐b](1,4,5,8,9,12‐hexaazatriphenylene) (TPHATP), with as high as 87.16% yield. This compound has a highly π‐conjugated and rigid molecular structure, which is synthesized by capping hexaketocyclohexane with three molecules of 2,3‐diaminophenazine derived from low‐cost o‐phenylenediamine, and is used as a cathode material for assembling aqueous rechargeable zinc ion batteries. Both experiments and DFT calculations demonstrate that the redox mechanism of TPHATP is predominantly governed by H+ storage. The Zn‐intercalation product of nitride‐type compound, is too unstable to form in water. Moreover, the TPHATP cathode exhibits a capacity of as high as 318.3 mAh g−1 at 0.1 A g−1, and maintained a stable capacity of 111.9 mAh g−1 at a large current density of 10 A g−1 for 5000 cycles with only a decay of 0.000512% per cycle. This study provides new insights into understanding pyrazine as an active redox group and offers a potential affordable aqueous battery system for grid‐scale energy storage.
A Dual‐Responsive Morphologically‐Adaptable Nanoplatform for Targeted Delivery of Activatable Photosensitizers in Precision Photodynamic Therapy
Authors: Jiao Qishu , Zheng Yaxin , Xie Qinqing , Luo Xuan , Zhou Shuyao , Pei Shicheng , Zhang Tingting , Wu Xiaoxing , Xu Keming , Zhong Wenying
Published: December 2023

Photodynamic therapy (PDT) is an effective approach for treating melanoma. However, the photosensitizers employed in PDT can accumulate in healthy tissues, potentially causing harm to normal cells and resulting in side effects such as heightened photosensitivity. To address this, an activatable photosensitizer (PSD) by linking PpIX with a fluorescence quencher using a disulfide bond is designed. PSD responded to endogenous GSH, showing high selectivity for A375 cells. To enhance PSD's bioavailability and anticancer efficacy, an enzyme‐responsive nanoplatform based on a lonidamine‐derived self‐assembling peptide is developed. Initially, PSD and the peptide self‐assembled into nanoparticles, displaying potent tumor targeting of PSD in vivo. Upon cell uptake, these nanoparticles specifically responded to elevated cathepsin B, causing nanoparticle disintegration and releasing PSD and lonidamine prodrug (LND‐1). PSD is selectively activated by GSH for cancer‐specific fluorescence imaging and precision PDT, while LND‐1 targeted mitochondria, forming a fibrous lonidamine depot in situ and intensifying photosensitizer's cytotoxicity through ROS generation, mitochondrial dysfunction, and DNA damage. Notably, intravenous administration of LND‐1‐PEG@PSD with light irradiation significantly suppressed A375‐xenografted mouse tumor growth, with minimal systemic toxicity. Together, the synergy of activatable photosensitizer and enzyme‐responsive nanoplatform elevates PDT precision and diminishes side effects, showcasing significant potential in the realm of cancer nanomedicine.
Recent Advances on Pulsed Laser Deposition of Large‐Scale Thin Films
Authors: Yu Jing , Han Wei , Suleiman Abdulsalam Aji , Han Siyu , Miao Naihua , Ling Francis Chi‐Chung
Published: December 2023

2D thin films, possessing atomically thin thickness, are emerging as promising candidates for next‐generation electronic devices, due to their novel properties and high performance. In the early years, a wide variety of 2D materials are prepared using several methods (mechanical/liquid exfoliation, chemical vapor deposition, etc.). However, the limited size of 2D flakes hinders their fundamental research and device applications, and hence the effective large‐scale preparation of 2D films is still challenging. Recently, pulsed laser deposition (PLD) has appeared to be an impactful method for wafer‐scale growth of 2D films, owing to target‐maintained stoichiometry, high growth rate, and efficiency. In this review, the recent advances on the PLD preparation of 2D films are summarized, including the growth mechanisms, strategies, and materials classification. First, efficacious strategies of PLD growth are highlighted. Then, the growth, characterization, and device applications of various 2D films are presented, such as graphene, h‐BN, MoS2, BP, oxide, perovskite, semi‐metal, etc. Finally, the potential challenges and further research directions of PLD technique is envisioned.
Enhancing android application security: A novel approach using DroidXGB for malware detection based on permission analysis
Authors: Kumar Pawan , Singh Sukhdip
Published: December 2023

The prevalence of malicious Android applications targeting the platform has introduced significant challenges in the realm of security testing. Traditional solutions have proven insufficient in handling the growing number of malicious apps, resulting in persistent exposure of Android smartphones to evolving forms of malware. This study investigates the potential of extreme gradient boosting (XGB) in identifying complex and high‐dimensional malicious permissions. By leveraging attribute combination and selection techniques, XGBoost demonstrates promising capabilities in this area. However, enhancing the XGBoost model presents a formidable challenge. To overcome this, This research employs adaptive grey wolf optimization (AGWO) for hyper‐parameter tuning. AGWO utilizes continuous values to represent the position and movement of the grey wolf, enabling XGBoost to search for optimal hyper‐parameter values in a continuous space. The proposed approach, DroidXGB, utilizes XGBoost and AGWO to analyze permissions and identify malware Android applications. It aims to address security vulnerabilities and compares its performance with baseline algorithms and state‐of‐the‐art methods using four benchmark datasets. The results showcase DroidXGB's impressive accuracy of 98.39%, outperforming other existing methods and significantly enhancing Android malware detection and security testing capabilities.
Impact of exposure to glyphosate‐based herbicide on morphological and physiological parameters in embryonic and larval development of zebrafish
Authors: Durante Laíse da Silva , Hollmann Gabriela , Nazari Evelise Maria
Published: December 2023

Glyphosate‐based herbicides (GBH) have been commonly used in agriculture to inhibit weed growth and increase yields. However, due to the high solubility of these herbicides in water, they can reach aquatic environments, by infiltration, erosion, and/or lixiviation, affecting non target organisms. Thus, this study aimed to characterize the toxicity of GBH Roundup WG® (RWG®) during the embryonic and larval development of Danio rerio. Embryos (3 hours post fertilization, hpf–until hatching) and larvae (3 days post fertilization, dpf to 6 dpf) were exposed to concentrations of 0.065 and 6.5 mg L−1. They were evaluated for survival, hatching, spontaneous movements, heartbeat, morphology, and morphometry by in vivo photographs in microscope, cell proliferation and apoptosis by immunohistochemistry, and exploratory behavior and phototropism by video recording. Our results showed an increase in embryo and larvae mortality in those exposed to 0.065 mg L−1, as well as a reduction in spontaneous embryo movements. The larval heartbeats showed a decrease at 4 dpf in the group exposed to 0.065 mg L−1 and an increase at 5 and 6 dpf in both exposed groups. Cell proliferation was reduced in both groups exposed in embryos and only in the 0.065 mg L−1 group in larvae, while cell death increased in embryos exposed to 6.5 mg L−1. These results demonstrated the toxic effect of low concentrations of the herbicide RWG® during embryonic and larval development of non target organisms, as well as the importance of constantly reviewing acceptable limits for exposure in natural environments.
Prevalence and temporal trend of gastric preneoplastic lesions in Asia: A systematic review with meta‐analysis
Authors: Li Yunhao , Jiang Fang , Wu Chun Ying , Leung Wai K.
Published: December 2023

Background

Gastric cancer is the fifth most common cancer globally, with about 75% of cases occurring in Asia. While chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are well‐recognized preneoplastic gastric lesions, we determined the prevalence and temporal trend of CAG and IM in Asia over the past 50 years.

Methods

In this systematic review and meta‐analysis, we searched PubMed, Embase, MEDLINE, Scopus, and Web of Science for studies reporting the prevalence of CAG and IM in Asia (according to the United Nations geoscheme) published between 1970 and 2022. Heterogeneity was assessed by the I2 index and Cochran Q test. We adopted the random effects model to estimate the pooled prevalence and 95% confidence interval (CI). The slope of prevalence was estimated as a function of time in simple linear regression and weighted meta‐regression models to demonstrate the temporal trend. Studies that reported the odds ratio (OR) of Helicobacter pylori infection and CAG/IM were analyzed separately to compile a pooled OR with a 95% CI. This study was registered in INPLASY2022120028.

Results

Of the 81 studies from 19 Asian countries identified, the pooled prevalence for CAG and IM in Asia was 26.1% (95%CI: 22.7–30.0) and 22.9% (95%CI: 19.7–26.6), respectively. Over the past 5 decades, there was a significant decline in the prevalence of IM (slope in adjusted meta‐regression models: −0.79 [95%CI: −1.28 to −0.26], P = 0.003), but there was no significant change in the pooled prevalence of CAG. Within Asia, the prevalence varied significantly among different regions. Southern Asia reported the highest pooled prevalence of CAG (42.9%, 95%CI: 27.5%–67.1%), while Western Asia reported the lowest level (12.7%, 95%CI: 5.0%–32.3%). For IM, Eastern Asia reported the highest prevalence (27.1%, 95%CI: 21.1–34.9), with the lowest prevalence reported in Western Asia (3.1%; 95% CI 1.2%–8.0%). H. pylori infection was linked to CAG and IM with OR of 2.16 (95%CI: 2.09–2.22) and 1.64 (95%CI: 1.57–1.72), respectively.

Conclusion

This updated meta‐analysis showed that up to 26% of study individuals in Asia harbored preneoplastic gastric lesions. There was a declining temporal trend in the prevalence of IM, but not for CAG, in Asia.
Mechanistic Explanations in Physics: History, Scope, and Limits
Authors: Falkenburg Brigitte
Published: December 2023

Despite the scientific revolutions of the twentieth century, mechanistic explanations show a striking methodological continuity from early modern science to current scientific practice. They are rooted in the traditional method of analysis and synthesis, which was the background of Galileo’s resolutive-compositive method and Newton’s method of deduction from the phenomena. In early modern science as well as in current scientific practice, analysis aims at tracking back from the phenomena to the principles, i.e., from wholes to parts, and from effects to causes. Vice versa, synthesis aims at explaining the phenomena from the parts and their interactions. Today, mechanistic explanations are atomistic in a generalized sense. They have in common to explain higher-level phenomena in terms of lower-level components and their causal actions or activities. In quantum physics, the lower-level components are subatomic particles, and the causes are their quantum interactions. After the quantum revolution, the approach continues to work in terms of the sum rules which hold for conserved properties of the parts and the whole. My paper focuses on the successes and limitations of this approach, with a side glance at the recent generalization of mechanistic explanations in cognitive neuroscience.
The Mechanisms of Emergence
Authors: Glennan Stuart
Published: December 2023

Emergentism is often imagined to be opposed to mechanism. If some phenomenon admits of mechanistic explanation, it is thought to be ipso facto not emergent. In this paper I argue to the contrary that emergence requires mechanism. Whenever some emergent phenomenon occurs, there is a mechanism responsible for its emergence. To make this case I show how mechanisms can explain four commonly held characteristics of emergent phenomena – dependence, autonomy, novelty and holism. By looking at the various kinds of emergence-generating mechanisms, it will be possible to classify different kinds of emergent phenomena by the particular features of the mechanisms that generate them, and so to bring some order to diversity of phenomena that we call emergent.
Different Types of Mechanistic Explanation and Their Ontological Implications
Authors: Krickel Beate
Published: December 2023

One assumption of the new mechanistic approach is that there are two kinds of mechanistic explanations: etiological and constitutive ones. While the former explain phenomena in terms of their preceding causes, the latter are supposed to refer to mechanisms that constitute phenomena. Based on arguments by Kaiser and Krickel (Br J Philos Sci 68(3):745–779, 2017) and Krickel (The mechanical world, vol. 13, Springer International Publishing. https://doi.org/10.1007/978-3-030-03629-4, 2018), I will show that this view is too narrow. Indeed, three different types of explanation are usually subsumed under the label “constitutive explanation”. However, one of those types of explanation is not a version of constitutive explanation. Rather it is a variant of etiological explanation. As a result, I will show that there are four types of mechanistic explanation, two variants of etiological explanation—which I will call output mechanistic explanations and input-output mechanistic explanations—and two variants of constitutive explanation—which I will call filler mechanistic explanations and dimensioned mechanistic explanations. Keeping these apart is crucial as they come with different ontological implications. An evaluation of the mechanistic approach regarding its stance on reduction, levels, and interlevel causation crucially depends on which notion of mechanistic explanation one has in mind.
Multiplicity results for generalized quasilinear critical Schrödinger equations in $${\mathbb {R}}^N$$
Authors: Baldelli Laura , Filippucci Roberta
Published: December 2023

Multiplicity results are proved for solutions both with positive and negative energy, as well as nonexistence results, of a generalized quasilinear Schrödinger potential free equation in the entire $${\mathbb {R}}^N$$

R

N

involving a nonlinearity which combines a power-type term at a critical level with a subcritical term, both with weights. The equation has been derived from models of several physical phenomena such as superfluid film in plasma physics as well as the self-channelling of a high-power ultra-short laser in matter. Proof techniques, also in the symmetric setting, are based on variational tools, including concentration compactness principles, to overcome lack of compactness, and the use of a change of variable in order to deal with a well defined functional.
Determinanten der Inanspruchnahme der Krebsfrüherkennung von älteren Erwachsenen in Sachsen-Anhalt – Welchen Einfluss hat die Gesundheitskompetenz auf die Inanspruchnahme?
Authors: Kannengießer Lena , Ulbrich Ruben , Hasenpusch Claudia , Hrudey Ilona , Walter Svenja , Stallmann Christoph , Swart Enno , March Stefanie
Published: December 2023

Hintergrund

Um Gesundheit und damit gesellschaftliche Teilhabe zu erhalten, ist es für ältere Menschen bedeutsam, informierte gesundheitsrelevante Entscheidungen zu treffen, wie solche zur Inanspruchnahme einer Sekundärpräventionsleistung wie der Krebsfrüherkennungsuntersuchung (KFU). Nationale und internationale Studien zeigen, dass verschiedene Prädiktoren die KFU-Teilnahme bedingen. Ziel dieser Studie ist es, die KFU-Inanspruchnahme älterer Personen in einer strukturschwachen Region zu eruieren.

Methoden

2021 wurden im Rahmen einer Querschnitterhebung in je 2 städtisch und ländlich geprägten Gemeinden Sachsen-Anhalts Personen ab 55 Jahren zu Determinanten, Gründen und Barrieren der Inanspruchnahme von Präventionsleistungen befragt (n = 954). Mittels binär-logistischer Regression werden Determinanten der Inanspruchnahme von KFU analysiert.

Ergebnisse

Drei Viertel der Studienpopulation (76,6 %) nahmen nach eigenen Angaben mindestens einmal eine Leistung der Krebsfrüherkennung in Anspruch. Die multivariablen Analysen verdeutlichen maßgebliche Einflussfaktoren für eine Inanspruchnahme von KFU. Dazu gehören das Alter, partiell das Wissen über KFU, die KFU als Leistung eines Bonusprogramms der Krankenkasse, Erfahrungen mit Krebserkrankungen im engeren Umfeld, die Gedanken über die eigene Gesundheit sowie das sichere Gefühl, welches eine Teilnahme verleiht. Deskriptiv ist die ärztliche Empfehlung der stärkste Beweggrund für eine Teilnahme.

Schlussfolgerung

Die Analysen zeigen, dass die KFU im Allgemeinen von älteren Erwachsenen in Sachsen-Anhalt gut angenommen werden, die Teilnahme an diesen aber nicht mit der Gesundheitskompetenz zusammenhängt. Im Sinne des Nationalen Krebsplans sollten ältere Personen grundsätzlich bei einer informierten Entscheidung unterstützt werden, bspw. durch zielgruppengerechte ärztliche Aufklärung.
Improving hybrid rice breeding programs via stochastic simulations: number of parents, number of hybrids, tester update, and genomic prediction of hybrid performance
Authors: Fritsche-Neto Roberto , Ali Jauhar , De Asis Erik Jon , Allahgholipour Mehrzad , Labroo Marlee Rose
Published: December 2023

Key message

Schemes that use genomic prediction outperform others, updating testers increases hybrid genetic gain, and larger population sizes tend to have higher genetic gain and less depletion of genetic variance

One of the most common methods to improve hybrid performance is reciprocal recurrent selection (RRS). Genomic prediction (GP) can be used to increase genetic gain in RRS by reducing cycle length, but it is also possible to use GP to predict single-cross hybrid performance. The impact of the latter method on genetic gain has yet to be previously reported. Therefore, we compared via stochastic simulations various phenotypic and genomics-assisted RRS breeding schemes which used GP to predict hybrid performance rather than reducing cycle length, which allows minimal changes to traditional breeding schemes. We also compared three breeding sizes scenarios that varied the number of genotypes crossed within heterotic pools, the number of genotypes crossed between heterotic pools, the number of hybrids evaluated, and the number of genomic predicted hybrids. Our results demonstrated that schemes that used genomic prediction of hybrid performance outperformed the others for the average interpopulation hybrid population and the best hybrid performance. Furthermore, updating the testers increased hybrid genetic gain with phenotypic RRS. As expected, the largest breeding size tested had the highest rates of genetic improvement and the lowest decrease in additive genetic variance due to the drift. Therefore, this study demonstrates the usefulness of single-cross prediction, which may be easier to implement than rapid-cycling RRS and cyclical updating of testers. We also reiterate that larger population sizes tend to have higher genetic gain and less depletion of genetic variance.
Pesticide Mixtures in Surface Waters of Two Protected Areas in Southwestern Germany
Authors: Schemmer Anna , Wolfram Jakob , Roodt Alexis. P. , Bub Sascha , Petschick Lara L. , Herrmann Larissa Z. , Stehle Sebastian , Schulz Ralf
Published: December 2023

Pesticides enter non-target surface waters as a result of agricultural activities and may reach water bodies in protected areas. We measured in southwestern Germany pesticide concentrations after heavy rainfalls in streams of a drinking water protection area near Hausen (Freiburg) and in the catchment of the Queich (Landau), which originates from the biosphere reserve Palatinate Forest. On average, 32 (n = 21) and 21 (n = 10) pesticides were detected per sample and event in the area of Hausen (n = 56) and in the Queich catchment (n = 17), respectively. The majority of pesticides detected in > 50% of all samples were fungicides, with fluopyram being detected throughout all samples. Aquatic invertebrates exhibited highest risks with 16.1% of samples exceeding mixture toxicity thresholds, whereas risks were lower for aquatic plants (12.9%) and fish (6.5%). Mixture toxicity threshold exceedances indicate adverse ecological effects to occur at half of sites (50%). This study illustrates the presence of pesticide mixtures and highlights ecological risks for aquatic organisms in surface waters of protected areas in Germany.
Evaluating the in vitro developmental toxicity potency of a series of petroleum substance extracts using new approach methodologies (NAMs)
Authors: Fang Jing , Rietjens Ivonne M. C. M. , Carrillo Juan-Carlos , Boogaard Peter J. , Kamelia Lenny
Published: December 2023

The present study evaluates the in vitro developmental toxicity and the possible underlying mode of action of DMSO extracts of a series of highly complex petroleum substances in the mouse embryonic stem cell test (mEST), the zebrafish embryotoxicity test (ZET) and the aryl hydrocarbon receptor reporter gene assay (AhR CALUX assay). Results show that two out of sixteen samples tested, both being poorly refined products that may contain a substantial amount of 3- to 7-ring polycyclic aromatic compounds (PACs), induced sustained AhR activation in the AhR CALUX assay, and concentration-dependent developmental toxicity in both mEST and ZET. The other samples tested, representing highly refined petroleum substances and petroleum-derived waxes (containing typically a very low amount or no PACs at all), were negative in all assays applied, pointing to their inability to induce developmental toxicity in vitro. The refining processes applied during the production of highly refined petroleum products, such as solvent extraction and hydrotreatment which focus on the removal of undesired constituents, including 3- to 7-ring PACs, abolish the in vitro developmental toxicity. In conclusion, the obtained results support the hypothesis that 3- to 7-ring PACs are the primary inducers of the developmental toxicity induced by some (i.e., poorly refined) petroleum substances and that the observed effect is partially AhR-mediated.
Inevitable monokineticity of strongly singular alignment
Authors: Fabisiak Michał , Peszek Jan
Published: December 2023

We prove that certain types of measure-valued mappings are monokinetic i.e. the distribution of velocity is concentrated in a Dirac mass. These include weak measure-valued solutions to the strongly singular Cucker–Smale model with singularity of order greater or equal to the dimension of the ambient space. Consequently, we are able to answer a couple of open questions related to the singular Cucker–Smale model. First, we prove that weak measure-valued solutions to the strongly singular Cucker–Smale kinetic equation are monokinetic, under very mild assumptions that they are uniformly compactly supported and weakly continuous in time. This can be interpreted as a rigorous derivation of the macroscopic fractional Euler-alignment system from the kinetic Cucker–Smale equation without the need to perform any hydrodynamical limit. This suggests the superior suitability of the macroscopic framework to describe large-crowd limits of strongly singular Cucker–Smale dynamics. Second, we perform a direct micro- to macroscopic mean-field limit from the Cucker–Smale particle system to the fractional Euler-alignment model. This leads to the final result—the existence of weak solutions to the fractional Euler-alignment system with almost arbitrary initial data in 1D, including the possibility of a vacuum. Existence can be extended to 2D under the a priori assumption that the density of the mean-field limit has no atoms.
Derivatization procedure of estradiol with a combination of MPDNP-F and 4-dimethylaminopyridine to generate product ion containing estradiol-skeleton for reliable determination of its serum/plasma concentrations by LC/ESI-MS/MS
Authors: Kaneko Honoka , Matsuoka Hiroki , Ishige Takayuki , Kobayashi Hironori , Higashi Tatsuya
Published: December 2023

The quantification of serum/plasma estradiol (E2) is useful for the diagnosis, pathological analysis, and monitoring of the therapeutic efficacy of estrogen-dependent diseases. In this study, an improved derivatization method using 1-(2,4-dinitro-5-fluorophenyl)-4,4-dimethylpiperazinium iodide (MPDNP-F) was developed and combined with liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) for the sensitive and specific quantification of the serum/plasma E2. In the new method, the reaction time was reduced to 15 min from 90 min (two-step reaction in the previous method) by the direct reaction of MPDNP-F with E2 at 60°C in the presence of 4-dimethylaminopyridine (DMAP). DMAP served as the organic catalyst and had a less negative effect on the LC/ESI-MS/MS instrument compared to the non-volatile inorganic salt (NaHCO3), which was used in the previous method. The collision-induced dissociation of the molecular cation ([M]+) of the resulting derivative provided a product ion containing the E2-skeleton ([M–NO2–H]+), which significantly enhanced the assay sensitivity and specificity; compared to the dansyl chloride derivatization, which is the currently most-used derivatization procedure for the LC/ESI-MS/MS assays of E2, the MPDNP-F derivatization had significantly fewer interfering peaks and a clear and flat baseline in the serum sample analysis. The MPDNP-F derivatization–LC/ESI-MS/MS method enabled the precise and accurate quantification of E2 even at a 5.0 pg/mL concentration (lower limit of quantification) with a small sample volume (100 μL of serum/plasma) and had a tolerance for the matrix effect. This method was also proven to serve as a more sensitive and specific alternative to the clinically used chemiluminescence enzyme immunoassay.

Graphical Abstract
Enhancing the Conventional Culture: the Evaluation of Several Culture Media and Growth Conditions Improves the Isolation of Ruminal Bacteria
Authors: Botero Rute Lina Marcela , Caro-Quintero Alejandro , Acosta-González Alejandro
Published: December 2023

The rumen microbiota is critical in cattle digestion. Still, its low cultivability makes it difficult to study its ecological function and biotechnological potential. To improve the recovery of ruminal microorganisms, this study combined the evaluation of several cultivation parameters with metabarcoding analysis. The parameters tested comprised eight media cultures, three sample dilutions (10−2, 10−6, 10−12), and two incubation times (3 and 7 days). Bacterial populations were determined through Illumina sequencing of 16S rRNA from three biological replicates. The results indicate that none of the culture media recovered all rumen populations and that there was an altered relative abundance of the dominant phyla. In the rumen, Bacteroidetes and Firmicutes comprised 75% and 15% of the relative abundance, respectively, while in the culture media, these were 15% and 60%, respectively. Principal coordinate analysis (PCoA) of the bacterial community revealed significant shifts in population composition due to dilution, with 10−2and 10−6dilutions clustered closely while the 10−12dilution differed markedly. In contrast, incubation duration did not influence population diversity. According to the results, two media, CAN and KNT, were selected based on their ability to recover more similar populations compared to the rumen sample. The metataxonomic study showed that CAN media had consistent reproducibility over time, while KNT showed enrichment of different taxa due to the use of rumen fluid as a substrate. From these, 64 pure cultures were obtained and 54 were identified through 16S rRNA gene sequencing. BeingStreptococcusthe most frequently isolated genus, this prevalence contrasts with the liquid media composition, underscoring the importance of refining single colony isolation strategies. Although no culture medium could replicate the native rumen bacterial population perfectly, our findings highlight the potential of CAN and KNT media in recovering populations that are more closely aligned to natural rumen conditions. In conclusion, our study emphasizes the importance of integrating molecular approaches in selecting suitable cultivation media and parameters to depict rumen bacteria accurately.
Epidemiology of postoperative bleeding after endoscopic nasal and sinus surgery and factors associated with bleeding
Authors: Hemmi Tomotaka , Nomura Kazuhiro , Kobayashi Yuta , Numano Yuki , Ikeda Ryoukichi , Sugawara Mitsuru , Katori Yukio
Published: December 2023

Purpose

Endoscopic nasal and sinus surgery is a surgical procedure frequently performed by otolaryngologists. Postoperative bleeding is detrimental to both healthcare providers and patients. We investigated the epidemiology of postoperative bleeding during endoscopic nasal and sinus surgery and explored possible bleeding triggers.

Methods

We evaluated the patients who underwent endoscopic nasal and sinus surgery. Data regarding the age, sex, presence of hypertension, and abnormal coagulability, including oral anticoagulants, diagnoses, operative procedures, intraoperative use of drills and blood loss, and postoperative antimicrobial administration of eligible patients, were extracted from medical records and retrospectively reviewed.

Results

One hundred and eighty-six patients underwent endoscopic nasal or sinus surgery during the study period, and postoperative bleeding occurred in 9 patients (4.8%). Posterior nasal neurotomy (PNN) was the procedure most likely to cause postoperative bleeding (4 surgeries, 13.3%). Postoperative antimicrobial administration significantly reduced the incidence of postoperative bleeding (p = 0.04).

Conclusions

Postoperative bleeding requiring intervention occurs in 4.8% of cases, and PNN is associated with a high risk of postoperative bleeding. Wound infection is a potential cause of postoperative bleeding, and antimicrobial administration should be considered in addition to local treatment.
SMARCB1-deficient sinonasal adenocarcinoma: a rare variant of SWI/SNF-deficient malignancy often misclassified as high-grade non-intestinal-type sinonasal adenocarcinoma or myoepithelial carcinoma
Authors: Skálová Alena , Taheri Touraj , Bradová Martina , Vaněček Tomáš , Franchi Alessandro , Slouka David , Kostlivý Tomáš , de Rezende Gisele , Michálek Jaroslav , Klubíčková Natálie , Ptáková Nicola , Nemcová Antónia , Michal Michal , Agaimy Abbas , Leivo Ilmo
Published: December 2023

SMARCB1-deficient sinonasal adenocarcinoma is a rare variant of SWI/SNF-deficient malignancies with SMARCB1 loss and adenocarcinoma features. More than 200 high-grade epithelial sinonasal malignancies were retrieved. A total of 14 cases exhibited complete SMARCB1 (INI1) loss and glandular differentiation. SMARCA2 and SMARCA4 were normal, except for one case with a loss of SMARCA2. Next-generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) revealed an alteration in the SMARCB1 gene in 9/13 cases, while 2/13 were negative. Two tumors harbored SMARCB1 mutations in c.157C > T p.(Arg53Ter) and c.842G > A p.(Trp281Ter). One harbored ARID1B mutations in c.1469G > A p.(Trp490Ter) and MGA c.3724C > T p.(Arg1242Ter). Seven tumors had a SMARCB1 deletion. One carried an ESR1 mutation in c.644-2A > T, and another carried a POLE mutation in c.352_374del p.(Ser118GlyfsTer78). One case had a PAX3 mutation in c.44del p.(Gly15AlafsTer95). Histomorphology of SMARCB1-deficient adenocarcinoma was oncocytoid/rhabdoid and glandular, solid, or trabecular in 9/14 cases. Two had basaloid/blue cytoplasm and one showed focal signet ring cells. Yolk sac tumor-like differentiation with Schiller-Duval-like bodies was seen in 6/14 cases, with 2 cases showing exclusively reticular-microcystic yolk sac pattern. Follow-up of a maximum of 26 months (median 10 months) was available for 8/14 patients. Distant metastasis to the lung, liver, mediastinum, bone, and/or retroperitoneum was seen in 4/8 cases. Locoregional failure was seen in 75% of patients, with 6/8 local recurrences and 3 cervical lymph node metastases. At the last follow-up, 5 of 8 (62%) patients had died of their disease 2 to 20 months after diagnosis (median 8.2 months), and 3 were alive with the disease. The original diagnosis was usually high-grade non-intestinal-type adenocarcinoma or high-grade myoepithelial carcinoma. A correct diagnosis of these aggressive tumors could lead to improved targeted therapies with potentially better overall disease-specific survival.
One-health approach on the future application of snails: a focus on snail-transmitted parasitic diseases
Authors: Pathak Chet Raj , Luitel Himal , Utaaker Kjersti Selstad , Khanal Prabhat
Published: December 2023

Snails are fascinating molluscs with unique morphological and physiological adaptive features to cope with various environments. They have traditionally been utilized as food and feed sources in many regions of the world. The future exploitation of alternative nutrient sources, like snails, is likely to increase further. Snails, however, also serve as an intermediate host for several zoonotic parasites. A category of parasitic infections, known as snail-transmitted parasitic diseases (STPDs), is harmful to humans and animals and is mainly driven by various trematodes, cestodes, and nematodes. The environment plays a crucial role in transmitting these parasites, as suitable habitats and conditions can facilitate their growth and proliferation in snails. In light of diverse environmental settings and biologically categorized snail species, this review evaluates the dynamics of significant STPDs of zoological importance. Additionally, possible diagnostic approaches for the prevention of STPDs are highlighted. One-health measures must be considered when employing snails as an alternative food or feed source to ensure the safety of snail-based products and prevent any adverse effects on humans, animals, and the environment.
Projected costs of informal care for older people in England
Authors: Hu Bo , Cartagena-Farias Javiera , Brimblecombe Nicola , Jadoolal Shari , Wittenberg Raphael
Published: December 2023

Background

Health economics research and economic evaluation have increasingly taken a societal perspective, accounting for the economic impacts of informal care. Projected economic costs of informal care help researchers and policymakers understand better the long-term consequences of policy reforms and health interventions. This study makes projections of the economic costs of informal care for older people in England.

Methods

Data come from two national surveys: the English Longitudinal Study of Ageing (ELSA, N = 35,425) and the Health Survey for England (N = 17,292). We combine a Markov model with a macrosimulation model to make the projections. We explore a range of assumptions about future demographic and epidemiological trends to capture model uncertainty and take a Bayesian approach to capture parameter uncertainty.

Results

We estimate that the economic costs of informal care were £54.2 billion in 2019, three times larger than the expenditure on formal long-term care. Those costs are projected to rise by 87% by 2039, faster than public expenditure but slower than private expenditure on formal long-term care. These results are sensitive to assumptions about future life expectancy, fertility rates, and progression of disabilities in the population.

Conclusions

Prevention schemes aiming to promote healthy aging and independence will be important to alleviate the costs of informal care. The government should strengthen support for informal caregivers and care recipients to ensure the adequacy of care, protect the well-being of caregivers, and prevent the costs of informal care from spilling over to other sectors of the economy.
Exploiting CNN’s visual explanations to drive anomaly detection
Authors: Fraccaroli Michele , Bizzarri Alice , Casellati Paolo , Lamma Evelina
Published: December 2023

Nowadays, deep learning is a key technology for many applications in the industrial area such as anomaly detection. The role of Machine Learning (ML) in this field relies on the ability of training a network to learn to inspect images to determine the presence or not of anomalies. Frequently, in Industry 4.0 w.r.t. the anomaly detection task, the images to be analyzed are not optimal, since they contain edges or areas, that are not of interest which could lead the network astray. Thus, this study aims at identifying a systematic way to train a neural network to make it able to focus only on the area of interest. The study is based on the definition of a loss to be applied in the training phase of the network that, using masks, gives higher weight to the anomalies identified within the area of interest. The idea is to add anOverlap Coefficientto the standard cross-entropy. In this way, the more the identified anomaly is outside theArea of Interest(AOI) the greater is the loss. We call the resulting lossCross-Entropy Overlap Distance(CEOD). The advantage of adding the masks in the training phase is that the network is forced to learn and recognize defects only in the area circumscribed by the mask. The added benefit is that, during inference, these masks will no longer be needed. Therefore, there is no difference, in terms of execution times, between a standard Convolutional Neural Network (CNN) and a network trained with this loss. In some applications, the masks themselves are determined at run-time through a trained segmentation network, as we have done for instance in the "Machine learning for visual inspection and quality control" project, funded by the MISE Competence Center Bi-REX.
Embedded macrophages induce intravascular coagulation in 3D blood vessel-on-chip
Authors: Middelkamp H.H.T. , Weener H.J. , Gensheimer T. , Vermeul K. , de Heus L.E. , Albers H.J. , van den Berg A. , van der Meer A.D.
Published: December 2023

Macrophages are innate immune cells that prevent infections and help in wound healing and vascular inflammation. While these cells are natural helper cells, they also contribute to chronic diseases, e.g., by infiltrating the endothelial layer in early atherosclerosis and by promoting vascular inflammation. There is a crosstalk between inflammatory pathways and key players in thrombosis, such as platelets and endothelial cells – a phenomenon known as ‘thromboinflammation’. The role of the embedded macrophages in thromboinflammation in the context of vascular disease is incompletely understood. Blood vessels-on-chips, which are microfluidic vascular cell culture models, have been used extensively to study aspects of vascular disease, like permeability, immune cell adhesion and thrombosis. Blood perfusion assays in blood vessel-on-chip models benefit from multiple unique aspects of the models, such as control of microvessel structure and well-defined flow patterns, as well as the ability to perform live imaging. However, due to their simplified nature, blood vessels-on-chip models have not yet been used to capture the complex cellular crosstalk that is important in thromboinflammation. Using induced pluripotent stem cell-derived endothelial cells and polarized THP-1 monocytes, we have developed and systematically set up a 3D blood vessel-on-chip with embedded (lipid-laden) macrophages, which is created using sequential cell seeding in viscous finger patterned collagen hydrogels. We have set up a human whole blood perfusion assay for these 3D blood vessels-on-chip. An increased deposition of fibrin in the blood vessel-on-chip models containing lipid-laden macrophages was observed. We anticipate the future use of this advanced vascular in vitro model in drug development for early atherosclerosis or aspects of other vascular diseases.

Graphical Abstract
On the adoption and effects of source code reuse on defect proneness and maintenance effort
Authors: Giordano Giammaria , Festa Gerardo , Catolino Gemma , Palomba Fabio , Ferrucci Filomena , Gravino Carmine
Published: December 2023

Software reusability mechanisms, like inheritance and delegation in Object-Oriented programming, are widely recognized as key instruments of software design that reduce the risks of source code being affected by defects, other than to reduce the effort required to maintain and evolve source code. Previous work has traditionally employed source code reuse metrics for prediction purposes, e.g., in the context of defect prediction. However, our research identifies two noticeable limitations of the current literature. First, still little is known about the extent to which developers actually employ code reuse mechanisms over time. Second, it is still unclear how these mechanisms may contribute to explaining defect-proneness and mainten0ance effort during software evolution. We aim at bridging this gap of knowledge, as an improved understanding of these aspects might provide insights into the actual support provided by these mechanisms, e.g., by suggesting whether and how to use them for prediction purposes. We propose an exploratory study, conducted on 12Javaprojects–over 44,900 commits–of theDefects4Jdataset, aiming at (1) assessing how developers use inheritance and delegation during software evolution; and (2) statistically analyzing the impact of inheritance and delegation on fault proneness and maintenance effort. Our results let emerge various usage patterns that describe the way inheritance and delegation vary over time. In addition, we find out that inheritance and delegation are statistically significant factors that influence both source code defect-proneness and maintenance effort.