bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Package Type on Selected Health Quality Parameters of Organic, Conventional and Wild Raspberries (Rubus idaeus L.) Frozen Stored
Authors: Kotuła Marta , Kapusta-Duch Joanna , Dziadek Michał , Nowak Ewelina , Borczak Barbara , Dziadek Kinga
Published: August 2024

Functional foods and the nutritional value of products are now very relevant for consumers. Additionally, interest in biodegradable components made from natural products has recently increased. The aim of this study was to determine the effect of different package types (with addition of films made of biopolymers enriched with natural extracts of ginger, cinnamon, and turmeric) on antioxidative properties of conventional, organic, and wild-grown raspberry fruit during frozen storage for 1-, 4-, 8-, and 12-month periods. The content of total polyphenol and anthocyanins, as well as antioxidant activity, were studied. Additionally, structural (FT-IR and UV-Vis), mechanical (tensile strength and elongation), and surface wetting angle tests of used films were studied. In all crop types, polyphenol content increased at 8 and 12 months of frozen storage in packages with an addition of biopolymer films. There was a statistically significant increase in the amount of total polyphenols in the last month of storage in the package with films with added cinnamon extract. In contrast, packages with ginger-enriched films contributed to an increase in polyphenols only in organically grown and wild raspberry fruit at the 4th, 8th, and 12th month and 8th and 12th month, respectively. The addition of films with turmeric extract increased the polyphenol content in the 8th month of frozen storage of organically grown raspberry fruit and in the 12th month of wild-grown raspberry. During frozen storage of wild raspberry fruit, an increase in anthocyanin content was observed in all cases in the 12th month. This result was almost twice as high as in the control sample. The greatest rise in the content of anthocyanins occurred when packages with films with turmeric extract were applied. Tendencies presented by this paper are not clear-cut in cases of antioxidant activity of analysed raspberries. A common feature was that, in general, after 12 months of storage, raspberries from all crops had higher and statistically significant antioxidant values compared to the first month of storage. Studies on the biocomposite films have shown that the structure of chitosan and alginate polymers was partly decomposed after 12 months, and the natural extracts and raspberry crops used had different effects on the mechanical properties of the biocomposites films. Based on the results of research that has been carried out, it can be concluded that it has not been clearly proven whether the addition of polysaccharide films to packages contributes to the increase in bioactive compounds during frozen storage.
Correction: Wang et al. Quantifying the Source Attribution of PM10 Measured Downwind of the Oceano Dunes State Vehicular Recreation Area. Atmosphere 2023, 14, 718
Authors: Wang Xiaoliang , Gillies John A. , Kohl Steven , Furtak-Cole Eden , Tupper Karl A. , Cardiel David A.
Published: August 2024

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Spatio-Temporal Variations of Indonesian Rainfall and Their Links to Indo-Pacific Modes
Authors: Ariska Melly , Suhadi  , Supari  , Irfan Muhammad , Iskandar Iskhaq
Published: August 2024

The analysis of rainfall patterns in the Indonesian region utilized the Empirical Orthogonal Function (EOF) method to identify spatial and temporal variations. The study evaluated the dynamic influence of the Tropical Indian Ocean (TIO) and the Tropical Pacific Ocean (TPO) on Indonesian rainfall using monthly data from the Southeast Asian Climate Assessment and Dataset (SACA&D) spanning from January 1981 to December 2016 and encompassing three extreme El Niño events in 1982/1983, 1997/1998 and 2015/2016. Using combined reanalysis and gridded-observation data, this study evaluates the potential impact of the two primary modes in the tropical Indo-Pacific region, namely the Indian Ocean Dipole (IOD) and the El Niño-Southern Oscillation (ENSO) on Indonesian rainfall. The analysis using the EOF method revealed two main modes with variances of 35.23% and 13.07%, respectively. Moreover, the results indicated that rainfall in Indonesia is highly sensitive to sea surface temperatures (SST) in the southeastern tropical Indian Ocean and the central Pacific Ocean (Niño3.4 and Niño3 areas), suggesting that changes in SST could significantly alter rainfall patterns in the region. This research is useful for informing government policies related to anticipating changes in rainfall variability as part of Indonesia’s preparedness for hydrometeorological disasters.
A Comprehensive Study on Winter PM2.5 Variation in the Yangtze River Delta: Unveiling Causes and Pollution Transport Pathways
Authors: Pan Yong , Zheng Jie , Fang Fangxin , Liang Fanghui , Tong Lei , Xiao Hang
Published: August 2024

To thoroughly investigate the impact of meteorological conditions and emission changes on winter PM2.5 variation in the Yangtze River Delta (YRD) from 2015 to 2019, we leveraged advanced modeling techniques, namely, the Weather Research and Forecasting (WRF) model and the Nested Air Quality Prediction Model System (NAQPMS). The results revealed that a notable trend of high-PM2.5-concentration regions shifted from coastal areas towards to the inland regions. While emission reduction can effectively reduce the concentration of PM2.5, meteorological changes exert a significant impact on PM2.5 concentration. Unfavorable meteorological changes in 2018 and 2019 emerged as crucial factors driving PM2.5 pollution in the region (up 0~50 µg·m−3). Our findings also shed light on the potential sources and transport pathways of PM2.5 pollution in key cities within the YRD, indicating that the coastal channel of Hebei–Shandong–Jiangsu and the inland channel bordering Hebei, Henan, Shandong, and Anhui serve as major contributors. Light and moderate pollution was predominantly influenced by the medium-distance coastal channel (48~70%). Remarkably, short-distance inland (19~54%) and coastal transportation (33~53%) channels emerged as the primary causes of severe PM2.5 pollution in the YRD. To effectively combat this issue, it is imperative to bolster key control and prevention measures in these regions.
Positivity-Preserving Rational Cubic Fractal Interpolation Function Together with Its Zipper Form
Authors: Sharma Shamli , Katiyar Kuldip , Sudhamsu Gadug , Wratch Manjinder Kaur , Salgotra Rohit
Published: August 2024

In this paper, a novel class of rational cubic fractal interpolation function (RCFIF) has been proposed, which is characterized by one shape parameter and a linear denominator. In interpolation for shape preservation, the proposed rational cubic fractal interpolation function provides a simple but effective approach. The nature of shape preservation of the proposed rational cubic fractal interpolation function makes them valuable in the field of data visualization, as it is crucial to maintain the original data shape in data visualization. Furthermore, we discussed the upper bound of error and explored the mathematical framework to ensure the convergence of RCFIF. Shape parameters and scaling factors are constraints to obtain the desired shape-preserving properties. We further generalized the proposed RCFIF by introducing the concept of signature, giving its construction in the form of a zipper-rational cubic fractal interpolation function (ZRCFIF). The positivity conditions for the rational cubic fractal interpolation function and zipper-rational cubic fractal interpolation function are found, which required a detailed analysis of the conditions where constraints on shape parameters and scaling factor lead to the desired shape-preserving properties. In the field of shape preservation, the proposed rational cubic fractal interpolation function and zipper fractal interpolation function both represent significant advancement by offering a strong tool for data visualization.
Thermodynamic Work of High-Grade Uterine Prolapse Patients Undergoing Transvaginal Mesh Repair with Total Hysterectomy
Authors: Lau Hui-Hsuan , Lai Cheng-Yuan , Hsieh Ming-Chun , Peng Hsien-Yu , Chou Dylan , Su Tsung-Hsien , Lee Jie-Jen , Lin Tzer-Bin
Published: August 2024

The objective benefit of transvaginal mesh with concomitant total hysterectomy (TVM-HTX) repair to high-grade uterine prolapse (UP) patients has not been fully established. This study aimed to clarify the impact of TVM-HTX on the voiding function of high-grade UP patients by comparing pre- and post-operatively measured pressure–flow and pressure–volume investigations. Urodynamic and thermodynamic studies were conducted on 15 high-grade UP patients (stage III/IV, POP-Q system) who underwent TVM-HTX (January 2019–December 2022) in a tertiary-care university hospital. The parameters analyzed included voiding resistance (Rvod), voiding pressure (Pvod), voiding flow (Fvod), voided volume (Vvod), voiding time (Tvod), and the trajectory-enclosed area of the pressure–volume loop (Apv). Post-operative results showed a significant reduction in Rvod (p < 0.001, N = 15), Pvod (p = 0.021, N = 15), and Apv (p = 0.006, N = 15), along with an increase in Fvod (p = 0.003, N = 15) and a decrease in Tvod (p < 0.001, N = 15). The operation-associated changes in Rvod (ΔRvod) correlated with alterations in Pvod and Fvod (ΔPvod and ΔFvod, r = 0.444, p = 0.004, r = 0.717, p = 0.003, respectively; both N = 15); ΔFvod correlated with the change in Tvod (ΔTvod, r = 0.629, p = 0.012, N = 15) but not with that in ΔVvod (r = 0.166, p = 0.555, N = 15). Changes in Apv (ΔApv) correlated with ΔPvod (r = 0.563, p = 0.029, N = 15) but not with ΔVvod (r = 0.353, p = 0.197, N = 15). Collectively, TVM-HTX reduced the voiding resistance, which improved the voiding efficacy and decreased the pressure gradient required for driving urine flow, thereby lessening the bladder’s workload.
Serum N-Glycan Changes in Rats Chronically Exposed to Glyphosate-Based Herbicides
Authors: Adeniyi Moyinoluwa , Gutierrez Reyes Cristian D. , Chávez-Reyes Jesús , Marichal-Cancino Bruno A. , Solomon Joy , Fowowe Mojibola , Onigbinde Sherifdeen , Flores-Rodriguez Jorge A. , Bhuiyan Md Mostofa Al Amin , Mechref Yehia
Published: August 2024

Glyphosate, the active ingredient in many herbicides, has been widely used in agriculture since the 1970s. Despite initial beliefs in its safety for humans and animals due to the absence of the shikimate pathway, recent studies have raised concerns about its potential health effects. This study aimed to identify glycomic changes indicative of glyphosate-induced toxicity. Specifically, the study focused on profiling N-glycosylation, a protein post-translational modification increasingly recognized for its involvement in various disorders, including neurological conditions. A comprehensive analysis of rat serum N-glycomics following chronic exposure to glyphosate-based herbicides (GBH) was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results revealed significant changes in the N-glycan profile, particularly in sialylated and sialofucosylated N-glycans. The analysis of N-glycans across gender subgroups provided insights into gender-specific responses to GBH exposure, with the male rats exhibiting a higher susceptibility to these N-glycan changes compared to females. The validation of significantly altered N-glycans using parallel reaction monitoring (PRM) confirmed their expression patterns. This study provides novel insights into the impact of chronic GBH exposure on serum N-glycan composition, with implications for assessing glyphosate toxicity and its potential neurological implications.
From Pathogenesis to Treatment: Targeting Type-2 Inflammation in Eosinophilic Esophagitis
Authors: Barchi Alberto , Mandarino Francesco Vito , Yacoub Mona-Rita , Albarello Luca , Massimino Luca , Savarino Edoardo Vincenzo , Ungaro Federica , Passaretti Sandro , Masclee Gwen M. C. , Danese Silvio , Bredenoord Albert J. , Vespa Edoardo
Published: August 2024

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. EoE shares a common pathogenetic mechanism with other chronic disorders pertaining to the type 2 inflammatory spectrum, such as atopic dermatitis (AD), allergic rhinitis (AR), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP). The recent advancements in EoE pathogenesis understanding have unveiled new molecular targets implied within the “atopic march” picture as well as specific to EoE. These discoveries have led to the clinical evaluation of several novel drugs (monoclonal antibodies and immune modulators), specifically aimed at the modulation of Th2 inflammation. In this comprehensive review, we have focused on the subtle mechanisms of type 2 inflammatory disorders, highlighting the similarities and differences with EoE, taking a deeper look into the evolving field of biologic therapies, already approved or under current investigation.
Beta-Blockers of Different Generations: Features of Influence on the Disturbances of Myocardial Energy Metabolism in Doxorubicin-Induced Chronic Heart Failure in Rats
Authors: Belenichev Igor , Goncharov Olexiy , Bukhtiyarova Nina , Kuchkovskyi Oleh , Ryzhenko Victor , Makyeyeva Lyudmyla , Oksenych Valentyn , Kamyshnyi Oleksandr
Published: August 2024

Beta-blockers are first-line drugs in the treatment of chronic heart failure (CHF). However, there is no consensus on the specific effects of the beta-blockers of the I-III generation on energy metabolism in CHF. The aim of this study is to conduct a study of beta-blockers of different generations on myocardial energy metabolism in experimental CHF. CHF was modeled in white outbred rats by administering doxorubicin. The study drugs were administered intragastrically—new drug Hypertril (1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide)-3.5 mg/kg, Metoprolol—15 mg/kg, Nebivolol −10 mg/kg, Carvedilol 50 mg/kg, and Bisoprolol, 10 mg/kg. In the myocardium, the main indices of energy metabolism were determined—ATP, ADP, AMP, malate, lactate, pyruvate, succinate dehydrogenase (SDH) activity, and NAD-dependent malate dehydrogenase (NAD-MDH) activity. Traditional second-generation beta-blockers (Metoprolol and Bisoprolol) did not affect the studied indices of energy metabolism, and third-generation beta-blockers with additional properties—Carvedilol and, especially, Nebivalol and Hypertril—improved myocardial energy metabolism. The obtained results will help to expand our understanding of the effect of beta-blockers of various generations used to treat cardiovascular diseases on energy metabolism, and are also an experimental justification for the practical choice of these drugs in the complex therapy of CHF.
Age-Related Differences in Prestimulus EEG Affect ERPs and Behaviour in the Equiprobable Go/NoGo Task
Authors: Barry Robert J. , De Blasio Frances M. , Clarke Adam R. , Duda Alexander T. , Munford Beckett S.
Published: August 2024

Detailed studies of the equiprobable auditory Go/NoGo task have allowed for the development of a sequential-processing model of the perceptual and cognitive processes involved. These processes are reflected in various components differentiating the Go and NoGo event-related potentials (ERPs). It has long been established that electroencephalography (EEG) changes through normal lifespan development. It is also known that ERPs and behaviour in the equiprobable auditory Go/NoGo task change from children to young adults, and again in older adults. Here, we provide a novel examination of links between in-task prestimulus EEG, poststimulus ERPs, and behaviour in three gender-matched groups: children (8–12 years), young adults (18–24 years), and older adults (59–74 years). We used a frequency Principal Component Analysis (f-PCA) to estimate prestimulus EEG components and a temporal Principal Component Analysis (t-PCA) to separately estimate poststimulus ERP Go and NoGo components in each age group to avoid misallocation of variance. The links between EEG components, ERP components, and behavioural measures differed markedly between the groups. The young adults performed best and accomplished this with the simplest EEG–ERP–behaviour brain dynamics pattern. The children performed worst, and this was reflected in the most complex brain dynamics pattern. The older adults showed some reduction in performance, reflected in an EEG–ERP–behaviour pattern with intermediate complexity between those of the children and young adults. These novel brain dynamics patterns hold promise for future developmental research.
Electroacupuncture Reduced Fibromyalgia-Pain-like Behavior through Inactivating Transient Receptor Potential V1 and Interleukin-17 in Intermittent Cold Stress Mice Model
Authors: Yeh Yu-An , Liao Hsien-Yin , Hsiao I-Han , Hsu Hsin-Cheng , Lin Yi-Wen
Published: August 2024

Fibromyalgia (FM) is a widespread musculoskeletal pain associated with psychological disturbances, the etiopathogenesis of which is still not clear. One hypothesis implicates inflammatory cytokines in increasing central and peripheral sensitization along with neuroinflammation, leading to an elevation in pro-inflammatory cytokines, e.g., interleukin-17A (IL-17A), enhanced in FM patients and animal models. The intermittent cold stress (ICS)-induced FM-like model in C57BL/6 mice has been developed since 2008 and proved to have features which mimic the clinical pattern in FM patients such as mechanical allodynia, hyperalgesia, and female predominance of pain. Electroacupuncture (EA) is an effective treatment for relieving pain in FM patients, but its mechanism is not totally clear. It was reported as attenuating pain-like behaviors in the ICS mice model through the transient receptor potential vanilloid 1 (TRPV1) pathway. Limited information indicates that TRPV1-positive neurons trigger IL-17A-mediated inflammation. Therefore, we hypothesized that the IL-17A would be inactivated by EA and TRPV1 deletion in the ICS-induced FM-like model in mice. We distributed mice into a control (CON) group, ICS-induced FM model (FM) group, FM model with EA treatment (EA) group, FM model with sham EA treatment (Sham) group, and TRPV1 gene deletion (Trpv1−/−) group. In the result, ICS-induced mechanical and thermal hyperalgesia increased pro-inflammatory cytokines including IL-6, IL-17, TNFα, and IFNγ in the plasma, as well as TRPV1, IL-17RA, pPI3K, pAkt, pERK, pp38, pJNK, and NF-κB in the somatosensory cortex (SSC) and cerebellum (CB) lobes V, VI, and VII. Moreover, EA and Trpv1−/− but not sham EA countered these effects significantly. The molecular mechanism may involve the pro-inflammatory cytokines, including IL-6, IL-17, TNFα, and IFNγ. IL-17A–IL-17RA play a crucial role in peripheral and central sensitization as well as neuroinflammation and cannot be activated without TRPV1 in the ICS mice model. EA alleviated FM-pain-like behaviors, possibly by abolishing the TRPV1- and IL-17A-related pathways. It suggests that EA is an effective and potential therapeutic strategy in FM.
Comparison of Liquefaction Damage Reduction Performance of Sheet Pile and Grouting Method Applicable to Existing Structures Using 1-G Shaking Table
Authors: Yoon Jong-Chan , Son Su-Won , Kim Jin-Man
Published: August 2024

This study conducted 1-G shaking table tests to compare methods of reducing liquefaction damage during earthquakes. The sheet pile and grouting methods were selected as applicable to existing structures. Model structures were manufactured for two-story buildings. A sine wave with an acceleration of 0.6 g and a frequency of 10 Hz was applied to the input wave. Certain experiments determined the effect of various sheet pile embedded depth ratios and grouting cement mixing ratios on reducing structural damage. The results confirmed that when the sheet pile embedded depth ratio was 0.75, the structure’s settlement decreased by approximately 79% compared to the control model. When the grouting cement mixing ratio was 0.45, the structure’s settlement decreased by approximately 85% compared to the untreated ground. In addition, the sheet pile method suppressed the increase in pore water pressure compared to the grouting method but tended to interfere with the dissipation of pore water pressure after liquefaction occurred. Additionally, comparing the effect of each method on reducing liquefaction damage revealed that the grouting method resulted in less settlement, rotation of the structure, and pore-water-pressure dissipation than the sheet pile method. Overall, the grouting method is more effective in reducing liquefaction damage than the sheet pile method. This study forms a basis for developing a liquefaction-damage reduction method applicable to existing structures in the future.
Treatments Technology and Mechanisms of East Asia Black Cotton Soil
Authors: Shang Xin , Wang Jiansheng , Chang Haolei , Zhang Weiguang
Published: August 2024

The East Asia black cotton soil (BCS) cannot be used as embankment filling directly due to its high clay content, liquid limit, plasticity index, and low CBR strength (CBR < 3%). This study evaluates the effects of treating East Asia BCS with lime, volcanic ash, or a combination of both on its engineering properties. Experiments were conducted to analyze the basic physical properties, swelling characteristics, and mechanical properties of the treated soil. Results indicate that lime addition significantly reduces the free swelling rate, improves limit moisture content, increases optimum moisture content, decreases maximum dry density, and enhances CBR value. Although volcanic ash also improves BCS performance, its effects are less pronounced than those of lime. The combined treatment with lime and volcanic ash exhibits superior performance, greatly reducing expansion potential and significantly increasing soil strength. Specifically, a mixture of 3% lime and 15% volcanic ash optimizes the liquid limit, plasticity index, and CBR value to 49.2%, 23.8, and 24.7%, respectively, meeting the JTG D30-2015 requirements and reducing construction costs. The treatment mechanisms involve hydration exothermic reactions, volcanic ash reactions, and semipermeable membrane effects, which collectively enhance the soil’s properties by producing dense, high-strength compounds.
The Impact of Visual, Thermal, and Acoustic Environments in Urban Public Spaces in Cold Regions on the Psychological Restoration of the Elderly
Authors: Bai Yang , Jin Hong
Published: August 2024

Optimizing the visual, thermal, and acoustic environments of urban public spaces in severely cold regions can significantly enhance the psychological restoration of the elderly, addressing the increasing mental health demands in an aging society. Despite its importance, the mechanisms, strategies, and seasonal effects of various environmental variables on psychological restoration remain inadequately studied. This research uses Harbin as a case study, employing field surveys and tests to systematically examine the elderly’s psychological restoration across different seasons. By integrating environmental stimulus variables with a psychological restoration evaluation model, the study investigates the impact of urban public spaces on mental health. The key findings are: (1) The spring environment of urban public spaces has the most significant positive effect on psychological restoration, with an effect size of η2 = 0.360. (2) A significant correlation exists between environmental variables and psychological restoration year-round, with the panoramic green view index in winter showing the highest positive impact (correlation coefficient = 0.301, p < 0.01). (3) The influence of environmental stimulus variables on psychological restoration varies notably across seasons; the acoustic environment in spring contributes most significantly, with an R2 = 17.03%, while visual factors dominate in winter and summer. (4) Conditional probability analysis reveals the effects of various environmental variables on psychological restoration, proposing season-specific environment optimization strategies. Based on these findings, the paper presents a model for optimizing urban public space environments in severely cold regions, aiming to maximize elderly psychological restoration by tailoring environmental stimulus variables to their mental health needs.
An Assessment of the Urban Streetscape Using Multiscale Data and Semantic Segmentation in Jinan Old City, China
Authors: Xu Yabing , Tong Hui , Liu Jianjun , Su Yangyue , Li Menglin
Published: August 2024

Urban street space is a significant component of urban public spaces and an important aspect of people’s perceptions of a city. Jinan Old City exemplifies the balance between the supply of and demand for green spaces in urban streets. The sense of comfort and the demand level of street spaces are measured via the space demand index. Open platform data, such as those from Baidu Maps and Amap, are evaluated using methods including ArcGIS network analysis and Segnet semantic segmentation. The results obtained from such evaluations indicate that, in terms of the green space supply, the overall level for Shangxin Street in Jinan is not high. Only 24% of the selected sites have an adequate green space supply. The level on Wenhua West Road is higher than that on Shangxin Street. The block on the western side of Shangxin Street has the highest green space demand, with a decreasing trend from west to east. There are several higher selection points in the middle section of Shangxin Street. The demand is lowest in the middle of Wenhua East Road. Shangxin Street’s demand is higher than that of Wenhua West Road. The supply and demand are highly matched on Wenhua West Road and poorly matched on Shangxin Street, with 44.12% of the area in the “low supply, high demand” quadrant. This study proposes targeted optimization strategies based on supply and demand, thereby providing research ideas and methods for urban renewal.
Mesoscopic Numerical Simulation of Freeze–Thaw Damage in Hydraulic Concrete
Authors: Wang Ruijun , Liu Yunhui , Liu Jun , Li Yang , Jin Ruibao , Liang Gang , Yu Ningning , Hu Jing , Zhou Hekuan , Jia Yaofei , Liu Yanxiong
Published: August 2024

To investigate the impact of freeze–thaw damage on the mechanical properties of concrete, this study utilized Python in combination with ABAQUS 2016 to generate a two-dimensional meso-scale model of concrete. Uniaxial compression tests were conducted on the concrete after freeze–thaw cycles to study the evolution of its mechanical properties. Using “relative compressive strength” as a variable, the relationships between this variable and the parameters of the freeze–thaw damage model were determined, leading to the establishment of the freeze–thaw damage model and the simulation of compressive tests on concrete after freeze–thaw cycles. This study also explored the changes in the mechanical properties of concrete with variations in ITZ parameters and coarse aggregate content. The conclusions drawn are as follows: A comparison with experimental data showed that the model ensures that the relative error of each mechanical property parameter does not exceed 7%, verifying the model’s rationality. Increasing the ratio of ITZ parameters improved the mechanical properties of the ITZ, enhancing the overall mechanical performance, but had almost no effect on the elastic modulus. Compared to ratios of 0.7 and 0.8, concrete with a ratio of 0.9 showed slower rates of decrease in compressive strength and elastic modulus and slower rates of increase in peak compressive strain after freeze–thaw cycles. The increase in coarse aggregate content had a similar effect on the strength and freeze–thaw resistance of concrete as the ratio of ITZ parameters. Concrete with a coarse aggregate content of 60% exhibited slower rates of change in mechanical properties after freeze–thaw cycles.
Significance of P53-Binding Protein 1 as a Novel Molecular Histological Marker for Hypopharyngeal Squamous Neoplasms
Authors: Kawasaki-Inomata Hiroko , Tabuchi Maiko , Norimatsu Kiyuu , Honda Tetsuro , Matsuda Katsuya , Hashiguchi Keiichi , Yamaguchi Naoyuki , Nishi Hideaki , Kumai Yoshihiko , Nakashima Masahiro , Miyaaki Hisamitsu , Nakao Kazuhiko , Akazawa Yuko
Published: August 2024

The DNA damage response protein p53-binding protein 1 (53BP1) accumulates and forms foci at double-strand DNA breaks, indicating the extent of DNA instability. However, the potential role of 53BP1 as a molecular biomarker for hypopharyngeal squamous cell carcinoma (HPSCC) diagnosis remains unknown. Here, we evaluated the potential of immunofluorescence-based analysis of 53BP1 expression to differentiate the histology of hypopharyngeal neoplasms. A total of 125 lesions from 39 surgically or endoscopically resected specimens from patients with HPSCC was histologically evaluated. 53BP1 expression in the nucleus was examined using immunofluorescence. The number of 53BP1 nuclear foci increased with the progression from non-tumorous to low-grade dysplasia, high-grade dysplasia, and squamous cell carcinoma. Unstable 53BP1 expression served as an independent factor for distinguishing lesions that required intervention. Colocalization of 53BP1 foci in proliferating cells, as assessed by Ki67, was increased in tumors ≥ 1000 µm in depth compared to those <1000 µm in depth at the tumor surface. Hence, the expression patterns of nuclear 53BP1 foci were associated with the progression of hypopharyngeal neoplasms. These findings suggest that 53BP1 could serve as an ancillary marker to support histological diagnosis and predict the factors that influence prognosis in patients with HPSCC.
Peptide Receptor Radionuclide Therapy versus Capecitabine/Temozolomide for the Treatment of Metastatic Pancreatic Neuroendocrine Tumors
Authors: Gujarathi Rushabh , Tobias Joseph , Abou Azar Sara , Keutgen Xavier M. , Liao Chih-Yi
Published: August 2024

Background: Peptide Receptor Radionuclide Therapy (PRRT), a form of Radioligand Therapy (RLT), and Capecitabine/Temozolomide (CAPTEM) are cornerstones of systemic therapy for metastatic pancreatic neuroendocrine tumors (PNETs). Data regarding comparative efficacy are lacking. Herein, we compare the efficacy of PRRT vs. CAPTEM as second-line/beyond regimens and treatment sequencing. Methods: Clinicopathologic, radiographic, and genomic data were captured for metastatic PNETs seen in our multi-disciplinary NET clinic between 2013 and 2023. The primary outcome was progression-free survival (PFS) after progression on a previous line of systemic therapy. The secondary outcomes were objective response rate (ORR), time to response (TTR), and overall survival (OS). Results: Fifty-nine cases were included. PFS was similar in the PRRT (n = 29) and CAPTEM (n = 30) groups (PRRT = 21.90 months vs. CAPTEM = 20.03 months; HR 0.99; p = 0.97). On subgroup analysis, PRRT had longer PFS in cases without extrahepatic metastases (26.47 months vs. 17.67 months; p = 0.03) and cases with a mutation in the MEN1, DAXX, and/or ATRX genes (28.43 months vs. 18.67 months; p = 0.03). PRRT had reduced PFS in patients with grade 3 disease (7.83 months vs. 16.33 months; p = 0.02). ORR did not vary significantly (34.78% vs. 40.91%; p = 0.67). CAPTEM responders showed shorter TTR (6.03 months vs. 11.15 months; p = 0.03). In patients who received both, OS did not vary based on the sequence (HR 1.20; p = 0.75). Conclusions: PFS, ORR, and OS are similar when using PRRT vs. CAPTEM as second-line-and-beyond therapy for patients with metastatic PNETs. However, patients with MEN1, DAXX, and/or ATRX mutations or without extrahepatic metastases might better benefit from PRRT and patients with grade 3 disease from CAPTEM. Candidates for surgical debulking or with tumor-induced symptoms may benefit from initial treatment with CAPTEM due to shorter TTR.
Cabozantinib Plus Nivolumab in Adult Patients with Advanced or Metastatic Renal Cell Carcinoma: A Retrospective, Non-Interventional Study in a Real-World Cohort/GUARDIANS Project
Authors: Hilser Thomas , Darr Christopher , Niegisch Günter , Schnabel Marco Julius , Foller Susan , Häuser Lorine , Zschäbitz Stefanie , Lewerich Jonas , Ivanyi Philipp , Schlack Katrin , Paffenholz Pia , Daetwyler Eveline , Niedersüß-Beke Dora , Grünwald Viktor
Published: August 2024

Introduction: Combinations of immune-checkpoint inhibitors (ICIs) are the standard of care (SOC) for treatment-naive metastatic renal cell carcinoma (mRCC) patients. In this multicenter study, we evaluated the RW safety and efficacy of cabozantinib plus nivolumab in mRCC patients. Methods: Data were retrospectively collected from twelve cancer centers in Germany, Switzerland, and Austria. Patients with advanced or mRCC were eligible. The investigator-based objective response rate (ORR) and progression free survival (PFS) were calculated from the start of the treatment to progression or death. Descriptive statistics and Kaplan–Meier (KM) plots were utilized where appropriate. Results: In total, 96 eligible patients (66.6% male) with a median age of 66.0 years were included. The most common histology was clear-cell RCC (ccRCC) in 63.4% (n = 61). A prior nephrectomy was performed in 60.4% (n = 58). ECOG 0-1 was 68.8% (n = 66). A partial response was documented in 43.8% of patients (n = 42), a stable disease in 32.3% (n = 31), and a progressive disease in 8.3% (n = 8) as the best overall response. Response data were not evaluable in 13.5% (n = 13). The median follow-up time was 12.7 months (95% CI, 10.0–15.3). The PFS rate at 6 months was 89.8% in the overall population (86.8% for ccRCC; 90.0% for non-ccRCC). Adverse events (AEs) were reported in 82.3% (n = 79) for all grades and 41.7% (n = 40) for grades 3–5. Elevated liver enzymes (34.4%), diarrhea (31.3%), and hand–foot syndrome (29.2%) were the three most frequent AEs of any grade and causality. Discussion/Conclusions: In this real-world cohort of mRCC patients, the application of cabozantinib plus nivolumab was shown to be safe and feasible. Our data support the use of cabozantinib plus nivolumab as a first-line standard therapy in mRCC patients. Major limitations were the retrospective data capture and short follow-up time of our study.
Catalytic Valorization of Organic Solid Waste: A Pilot-Scale Run of Sugarcane Bagasse
Authors: Li Zhaofei , Omidkar Ali , Song Hua
Published: August 2024

Organic solid waste treatment is crucial for enhancing environmental sustainability, promoting economic growth, and improving public health. Following our previous organic solid waste upgrading technique, a further two-step pilot-scale run, using sugarcane bagasse as the feedstock, has been successfully conducted with long-term stability. Firstly, the sugarcane bagasse was treated under mild conditions (400 °C and 1 bar of CH4), and this catalytic Methanolysis treatment resulted in a bio-oil with a yield of 60.5 wt.%. Following that, it was subjected to a catalytic Methano-Refining process (400 °C and 50 bar of CH4) to achieve high-quality renewable fuel with a liquid yield of 95.0 wt.%. Additionally, this renewable fuel can be regarded as an ideal diesel component with a high cetane number, high heating values, a low freezing point, low density and viscosity, and low oxygen, nitrogen, and sulfur contents. The successful pilot-scale catalytic upgrading of sugarcane bagasse further verified the effectiveness of this methane-assisted organic solid waste upgrading technique and confirmed the high flexibility of this innovative technology for processing a wide spectrum of agricultural and forestry residues. This study will shed light on the further valorization of organic solid waste and other carbonaceous materials.
V-ATPase Dysfunction in the Brain: Genetic Insights and Therapeutic Opportunities
Authors: Falace Antonio , Volpedo Greta , Scala Marcello , Zara Federico , Striano Pasquale , Fassio Anna
Published: August 2024

Vacuolar-type ATPase (v-ATPase) is a multimeric protein complex that regulates H+ transport across membranes and intra-cellular organelle acidification. Catabolic processes, such as endocytic degradation and autophagy, strictly rely on v-ATPase-dependent luminal acidification in lysosomes. The v-ATPase complex is expressed at high levels in the brain and its impairment triggers neuronal dysfunction and neurodegeneration. Due to their post-mitotic nature and highly specialized function and morphology, neurons display a unique vulnerability to lysosomal dyshomeostasis. Alterations in genes encoding subunits composing v-ATPase or v-ATPase-related proteins impair brain development and synaptic function in animal models and underlie genetic diseases in humans, such as encephalopathies, epilepsy, as well as neurodevelopmental, and degenerative disorders. This review presents the genetic and functional evidence linking v-ATPase subunits and accessory proteins to various brain disorders, from early-onset developmental epileptic encephalopathy to neurodegenerative diseases. We highlight the latest emerging therapeutic strategies aimed at mitigating lysosomal defects associated with v-ATPase dysfunction.
PAK4 Is Involved in the Stabilization of PD-L1 and the Resistance to Doxorubicin in Osteosarcoma and Predicts the Survival of Diagnosed Patients
Authors: Zhang Junyue , Song Yiping , Ahn Ae-Ri , Park Ho Sung , Park See-Hyoung , Moon Young Jae , Kim Kyoung Min , Jang Kyu Yun
Published: August 2024

PAK4 and PD-L1 have been suggested as novel therapeutic targets in human cancers. Moreover, PAK4 has been suggested to be a molecule closely related to the immune evasion of cancers. Therefore, this study evaluated the roles of PAK4 and PD-L1 in the progression of osteosarcomas in 32 osteosarcomas and osteosarcoma cells. In human osteosarcomas, immunohistochemical positivity for the expression of PAK4 (overall survival, p = 0.028) and PD-L1 (relapse-free survival, p = 0.002) were independent indicators for the survival of patients in a multivariate analysis. In osteosarcoma cells, the overexpression of PAK4 increased proliferation and invasiveness, while the knockdown of PAK4 suppressed proliferation and invasiveness. The expression of PAK4 was associated with the expression of the molecules related to cell cycle regulation, invasion, and apoptosis. PAK4 was involved in resistance to apoptosis under a treatment regime with doxorubicin for osteosarcoma. In U2OS cells, PAK4 was involved in the stabilization of PD-L1 from ubiquitin-mediated proteasomal degradation and the in vivo infiltration of immune cells such as regulatory T cells and PD1-, CD4-, and CD8-positive cells in mice tumors. In conclusion, this study suggests that PAK4 is involved in the progression of osteosarcoma by promoting proliferation, invasion, and resistance to doxorubicin and stabilized PD-L1 from proteasomal degradation.
NOD1 and NOD2: Essential Monitoring Partners in the Innate Immune System
Authors: Li Zhenjia , Shang Dejing
Published: August 2024

Nucleotide-binding oligomerization domain containing 1 (NOD1) and NOD2 are pivotal cytoplasmic pattern-recognition receptors (PRRs) that exhibit remarkable evolutionary conservation. They possess the ability to discern specific peptidoglycan (PGN) motifs, thereby orchestrating innate immunity and contributing significantly to immune homeostasis maintenance. The comprehensive understanding of both the structure and function of NOD1 and NOD2 has been extensively elucidated. These receptors proficiently recognize an array of damage-associated molecular patterns (DAMPs) as well as pathogen-associated molecular patterns (PAMPs), subsequently mediating inflammatory responses and autophagy. In recent years, emerging evidence has highlighted the crucial roles played by NOD1 and NOD2 in regulating infectious diseases, metabolic disorders, cancer, and autoimmune conditions, among others. Perturbation in either their loss or excessive activation can detrimentally impact immune homeostasis. This review offers a comprehensive overview of the structural characteristics, subcellular localization, activation mechanisms, and significant roles of NOD1 and NOD2 in innate immunity and related disease.
The Role of Caspases in Melanoma Pathogenesis
Authors: Szmurło Agnieszka , Dopytalska Klaudia , Szczerba Michał , Szymańska Elżbieta , Petniak Alicja , Kocki Marcin , Kocki Janusz , Walecka Irena
Published: August 2024

Melanoma (malignant melanoma, MM) is an aggressive malignant skin cancer with an increasing incidence rate. The complete pathogenesis of MM in not clear. Due to DNA damage, mutations, dysregulation of growth factors, inactivation of tumor suppressor genes, and activation of oncogenes, excessive uncontrolled growth of abnormal melanocytes occurs in melanomas. Caspases are a group of proteolytic enzymes that participate in several processes important in regulating mechanisms at the cellular level. They play a role in cell homeostasis and programmed cell death (apoptosis) and in the regulation of non-apoptotic cell death processes. Dysregulation of caspase activation plays a role in the etiology of cancers, including melanoma. Caspases can initiate and execute apoptosis and are involved in regulating cell death and controlling tumor growth. These enzymes also inhibit tumor growth by cleaving and inactivating proteins that are involved in cell proliferation and angiogenesis. Moreover, caspases are involved in the activation of immune processes through the processing and presentation of tumor antigens, which facilitates recognition of the tumor by the immune system. The role of caspases in melanoma is complex, and they may inhibit melanoma growth and progression. This work aims to review the current knowledge of the role of individual caspases in melanoma pathogenesis.
Research Status and Development Trend of Wire Arc Additive Manufacturing Technology for Aluminum Alloys
Authors: Dai Pan , Li Ao , Zhang Jianxun , Chen Runjie , Luo Xian , Wen Lei , Wang Chen , Lv Xianghong
Published: August 2024

It is difficult for traditional aluminum alloy manufacturing technology to meet the requirements of large-scale and high-precision complex shape structural parts. Wire Arc additive manufacturing technology (WAAM) is an innovative production method that presents the unique advantages of high material utilization, a large degree of design freedom, fast prototyping speed, and low cast. As a result, WAAM is suitable for near-net forming of large-scale complex industrial production and has a wide range of applications in aerospace, automobile manufacturing, and marine engineering fields. In order to serve as a reference for the further development of WAAM technology, this paper provides an overview of the current developments in WAAM both from the digital control system and processing parameters in summary of the recent research progress. This work firstly summarized the principle of simulation layering and path planning and discussed the influence of relative technological parameters, such as current, wire feeding speed, welding speed, shielding gas, and so on. It can be seen that both the welding current and wire feeding speed are directly proportional to the heat input while the travel speed is inversely proportional to the heat input. This process regulation is an important means to improve the quality of deposited parts. This paper then summarized various methods including heat input, alloy composition, and heat treatment. The results showed that in the process of WAAM, it is necessary to control the appropriate heat input to achieve minimum heat accumulation and improve the performance of the deposited parts. To obtain higher mechanical properties (tensile strength has been increased by 28%–45%), aluminum matrix composites by WAAM have proved to be an effective method. The corresponding proper heat treatment can also increase the tensile strength of WAAM Al alloy by 104.3%. In addition, mechanical properties are always assessed to evaluate the quality of deposited parts. The mechanical properties including the tensile strength, yield strength, and hardness of the deposited parts under different processing conditions have been summarized to provide a reference for the quality evaluation of the deposition. Examples of industrial products fabricated by WAAM are also introduced. Finally, the application status of WAAM aluminum alloy is summarized and the corresponding future research direction is prospected.
Bioactives in Nutricosmetics: A Focus on Caffeine from Tea to Coffee
Authors: Blanco-Llamero Cristina , Macário Hugo F. , Guedes Beatriz N. , Fathi Faezeh , Oliveira Maria Beatriz P. P. , Souto Eliana B.
Published: August 2024

Known for its stimulating effects on the nervous and cardiovascular systems, caffeine has proven remarkable versatile properties. It can be used in a wide range of different products, from anti-aging cosmetics to the pharmaceutical treatment of hair loss. Caffeine is known for its antioxidant properties and is commonly found in moisturising creams recommended as anti-aging or anti-cellulite and also for the treatment of different skin disorders, including androgenic alopecia. This bioactive is also described to be able to enhance the sunscreen scattering effect of well-known ultraviolet (UV) blockers. One of the major challenges remains its penetration capacity into deeper skin layers, which may be achieved by the use of nanosized delivery systems, yet without the risk of transdermal delivery. In this review, we discuss the nutraceutical value of caffeine in cosmetic products, so-called nutricosmetics, which grants this bioactive several advantages in several formulations, in comparison to other potential bioactives of nutricosmetic value. Furthermore, the disclosed effects of bioactives commonly found in coffee, tea, and their by-products are reviewed and discussed. The discussion concludes by highlighting the significant benefits of caffeine in the treatment of skin disorders and its potential to enhance and promote skin health.
Pathological Characteristics, Management, and Prognosis of Rectal Neuroendocrine Tumors: A Retrospective Study from a Tertiary Hospital
Authors: Cavalcoli Federica , Rausa Emanuele , Ferrari Davide , Rosa Roberto , Maccauro Marco , Pusceddu Sara , Sabella Giovanna , Cantù Paolo , Vitellaro Marco , Coppa Jorgelina , Mazzaferro Vincenzo
Published: August 2024

Background: Rectal neuroendocrine tumors (rNENs) are rare, constituting 1–2% of rectal tumors, and are often asymptomatic, leading to challenges in early diagnosis. Current management guidelines recommend endoscopic resection for small lesions and surgical intervention for larger or high-risk tumors. This study aims to retrospectively analyze the pathological characteristics, management, and prognosis of rNEN patients. Methods: Data from the Neuroendocrine Tumor Registry at a tertiary hospital in Milan, Italy from 2005 to 2023 were retrospectively analyzed. Patient demographics, disease characteristics, pathology findings, treatment details, and surveillance data were collected. Statistical analyses included descriptive statistics, multivariable binary logistic regression, and Kaplan–Meier survival analysis. Results: Forty-five patients were included, 53.3% male with a mean age of 57.5 years. Most patients were asymptomatic, with incidental diagnosis during colonoscopy. Endoscopic excision was the primary treatment modality (77.8%), with surgical resection reserved for incomplete or inappropriate endoscopic resections. Disease progression occurred in 13 patients (28.9%), with tumor-related mortality of 22.2%. Kaplan–Meier analysis showed 5- and 10-year survival rates of 68.8% and 59.1%, respectively, with corresponding progression-free survival rates of 72.8% and 54.0%. Tumor stage was significantly associated with disease progression on multivariable analysis (OR = 7.230, p = 0.039). Conclusions: This study highlights the heterogeneous presentation and prognosis of rNENs, with a substantial proportion diagnosed incidentally. Endoscopic management was predominantly utilized, aligning with current guidelines for localized tumors. Tumor stage emerged as a significant predictor of disease progression, emphasizing the importance of accurate staging for optimal management. Further research is warranted to refine management protocols and validate these findings.