bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Multiple-Axis Contour Error Suppression Method Based on Composite Layered Control
Authors: Chen Ke , Xiao Bo , Liu Xuelian , Wang Chunyang , Liang Shuning , Xia Chaoxiang
Published: November 2023

With the widespread application of multi-axis machining in the industrial manufacturing, aerospace, and military equipment sectors, the demand for machining ultra-precision components has been steadily increasing. Contour errors directly impact the quality of machined parts. In conventional multi-axis motion control systems based on cross-coupling, it is conventionally assumed that all individual axes are of equal significance during machine processing. However, in practical machining scenarios, diverse machining trajectories and accuracy requirements give rise to distinct control necessities for each axis. This complication leads to challenges in ensuring a consistent single-plane contour, thereby constraining the elevation of the overall contour accuracy. To address this issue, this study proposes a multi-axis contour error suppression method based on composite hierarchical control. The approach advocated in this paper initially ensures the precision of single-axis position control through the development of an advanced S-shaped function-based sliding-mode disturbance observer. Building on this foundation, the three-dimensional spatial contour is segregated into upper and lower layers. Subsequently, dedicated fuzzy PID cross-coupling controllers are devised for each layer. The experimental outcomes substantiate that in comparison to conventional cross-coupling control methods, the method introduced in this study, rooted in composite hierarchical control, not only guarantees the accuracy of single-plane contours but also further enhances the overall contour precision.
The Effect of Meteorological Features on Pollution Characteristics of PM2.5 in the South Area of Beijing, China
Authors: Yang Zhichen , Yang Xuejun , Xu Chaofan , Wang Qinghai
Published: November 2023

Based on the air quality monitoring data and meteorological data, the pollution characteristics of PM2.5 in southern Beijing and relationships between PM2.5 levels and meteorological features were analyzed. The results showed that during the investigation period, daily air quality was characterized as “excellent” and “favorable” (<75 µg m−3) on 77% of days in southern Beijing, and there were only two days with serious air pollution (>250 µg m−3). The PM2.5 concentration displayed obvious monthly variations with the highest concentration in November and the lowest concentration in August. When PM2.5 pollution episodes occurred (>75 µg m−3) in this area, the wind direction was often south and southeast with low wind speed (<3 m∙s−1), followed by southwest wind; in addition, the air temperature was low (<10 °C) and the relative humidity was high (>75%). The air quality of the study area was affected by the pollution transmission form the surrounding areas, especially the southeastern and the southern transmission paths. The PM2.5 concentration was positively correlated with SO2, NO2 and CO, and negatively correlated with O3. Therefore, to further improve the air quality in the study area, it is necessary to coordinate the control of PM2.5 and O3.
A Refined Atmospheric Weighted Average Temperature Model Considering Multiple Factors in the Qinghai–Tibet Plateau Region
Authors: Tian Kunjun , Xiong Si , Wang Zhengtao , Zhang Bingbing , Han Baomin , Guo Bing
Published: November 2023

The Qinghai–Tibet Plateau region has significant altitude fluctuations and complex climate changes. However, the current global weighted average temperature (Tm) model does not fully consider the impact of meteorological and elevation factors on it, resulting in existing models being unable to accurately predict the Tm in the region. Therefore, this study constructed a weighted average temperature refinement model (XTm) related to surface temperature, water vapor pressure, geopotential height, annual variation, and semi-annual variation based on measured data from 13 radiosonde stations in the Qinghai–Tibet Plateau region from 2008 to 2017. Using the Tm calculated via the numerical integration method of radiosonde observations in the Qinghai–Tibet Plateau region from 2018 to 2019 as a reference value, the quality of the XTm model was tested and compared with the Bevis model and GPT2w (global pressure and temperature 2 wet) model. The results show that for 13 modeling stations, the bias and root-mean-square (RMS) values of the XTm model were −0.02 K and 2.83 K, respectively; compared with the Bevis, GPT2-1, and GPT2w-5 models, the quality of XTm was increased by 47%, 38%, and 47%, respectively. For the four non-modeling stations, the average bias and RMS values of the XTm model were 0.58 K and 2.78 K, respectively; compared with the other three Tm models, the RMS values and the mean bias were both minimal. In addition, the XTm model was also used to calculate the global navigation satellite system (GNSS) precipitable water vapor (PWV), and its average values for the theoretical RMSPWV and RMSPWV/PWV generated by water vapor calculation were 0.11 mm and 1.03%, respectively. Therefore, in the Qinghai–Tibet Plateau region, the XTm model could predict more accurate Tm values, which, in turn, is important for water vapor monitoring.
Variation of Electron Density in the D-Region Using Kunming MF Radar under Low Solar Activity
Authors: Tang Zhimei , Li Na , Wang Jianyuan , Ding Zonghua , Dai Liandong , Zhao Lei , Chen Jinsong
Published: November 2023

So far, the least is known about the D-region ionosphere out of the entire ionosphere due to the lack of a conventional detecting method and continuous data accumulation. Medium frequency (MF) radar is an important conventional tool for understanding the D-region ionosphere by measuring the electron density (Ne) within the height range of 60–90 km. To investigate the statistical variation of the D-region, especially at the mid-low latitude area, this study presents the statistical variations in the D-region Ne with the solar zenith angle (SZA), season, and altitude observed by Kunming MF radar (25.6° N, 103.8° E) under low solar activity (2008–2009). The diurnal variation of Ne behaves like typical diurnal changes, which are closely consistent with the SZA. The outstanding feature, the diurnal asymmetry phenomenon, significantly appears in different seasons and at different altitudes. The Ne has obvious semi-annual characteristics, and is larger in summer and fall and the smallest in winter. Compared to other seasons, the variation in the Ne with altitude is the most stable in summer. Due to the impacts of the highest SZA, the value of Ne in winter is the smallest, with a maximum value of less than 300 electrons/cm3, and the largest in summer and fall, with a maximum of 472 electrons/cm3. Particularly, the peaks of Ne above 76 km do not always appear at the time when the SZA is the smallest (at noon). Both the simulations by the International Reference Ionosphere (IRI2016) and observations using MF radar present a strong positive correlation with solar radiation. Meanwhile, it cannot be ignored that there were still large differences between the simulations and observations. To quantitatively analyze the differences between the observations and simulations, the observed value was subtracted from the simulated value. The results show that the maximum value between them was up to 350 electrons/cm3, and the minimum difference appeared at around 72 km, with a value less than 100 electrons/cm3. However, below 66 km, the observations were larger than the simulations, which were, on the contrary, above 76 km.
Biological Prosthesis (Hollow 3D-Printed Titanium Custom-Made Prosthesis and Bone Graft) for Humeral Reconstruction in Pediatric Oncologic Patients: Surgical Indications and Results
Authors: Beltrami Giovanni , Rajan Sreeraj , Nucci Anna Maria , Galeotti Alberto , Guido Davide , Campanacci Domenico , Innocenti Marco
Published: November 2023

This study presents the mid-term outcomes of a novel “biological prosthesis” for pediatric humerus reconstruction after major bone tumor removal. This approach involves a hollow 3D-printed titanium custom-made prosthesis combined with bone grafting. The primary aim was to preserve and revitalize the unaffected autologous proximal or distal humeral stump. Between 2017 and 2021, we treated five pediatric patients (mean age 11.2 years; range 7–17) with humeral bone sarcomas. A one-stage surgical procedure involved tumor resection and implanting a hollow 3D-printed custom-made prosthesis. In two cases, we preserved the proximal humerus; in two, the distal part; and in one, both. Graft materials included homologous bone chips in three cases and free vascularized fibular grafts in two cases. All patients were clinically and radiographically assessed after a mean follow-up of 32.2 months (range of 14–68). No significant complications were observed, and no implant revisions were needed. Osseointegration was evident in all cases within eight months post-surgery; vascular support for the remaining autologous stump was demonstrated in all cases. Our hollow 3D-printed custom-made prosthesis and bone grafting offer the potential for partial or complete articular surface preservation. This approach encourages revascularization of the epiphysis, leading to satisfactory outcomes in humerus reconstruction within the pediatric population.
Effects of rTMS Intervention on Functional Neuroimaging Activities in Adolescents with Major Depressive Disorder Measured Using Resting-State fMRI
Authors: Lu Fengmei , Cui Qian , Zou Yang , Guo Yuanhong , Luo Wei , Yu Yue , Gao Jingjing , Cai Xiao , Fu Linna , Yuan Shuai , Huang Juan , Zhang Yajun , Xie Jing , Sheng Wei , Tang Qin , Gao Qing , He Zongling , Chen Huafu
Published: November 2023

Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) is commonly used for the clinical treatment of major depressive disorder (MDD). The neuroimaging biomarkers and mechanisms of rTMS are still not completely understood. This study aimed to explore the functional neuroimaging changes induced by rTMS in adolescents with MDD. A total of ten sessions of rTMS were administrated to the L-DLPFC in thirteen adolescents with MDD once a day for two weeks. All of them were scanned using resting-state functional magnetic resonance imaging at baseline and after rTMS treatment. The regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and the subgenual anterior cingulate cortex (sgACC)-based functional connectivity (FC) were computed as neuroimaging indicators. The correlation between changes in the sgACC-based FC and the improvement in depressive symptoms was also analyzed. After rTMS treatment, ReHo and ALFF were significantly increased in the L-DLPFC, the left medial prefrontal cortex, bilateral medial orbital frontal cortex, and the left ACC. ReHo and ALFF decreased mainly in the left middle occipital gyrus, the right middle cingulate cortex (MCC), bilateral calcarine, the left cuneus, and the left superior occipital gyrus. Furthermore, the FCs between the left sgACC and the L-DLPFC, the right IFGoper, the left MCC, the left precuneus, bilateral post-central gyrus, the left supplementary motor area, and the left superior marginal gyrus were enhanced after rTMS treatment. Moreover, the changes in the left sgACC-left MCC FC were associated with an improvement in depressive symptoms in early improvers. This study showed that rTMS treatment in adolescents with MDD causes changes in brain activities and sgACC-based FC, which may provide basic neural biomarkers for rTMS clinical trials.
Cardioprotective Effect against Ischemia–Reperfusion Injury of PAK-200, a Dihydropyridine Analog with an Inhibitory Effect on Cl− but Not Ca2+ Current
Authors: Namekata Iyuki , Tamura Miku , Kase Jyunya , Hamaguchi Shogo , Tanaka Hikaru
Published: November 2023

We examined the effects of a dihydropyridine analog, PAK-200, on guinea pig myocardium during experimental ischemia and reperfusion. In isolated ventricular cardiomyocytes, PAK-200 (1 μM) had no effect on the basal peak inward and steady-state currents but inhibited the isoprenaline-induced time-independent Cl− current. In the right atria, PAK-200 had no effect on the beating rate and the chronotropic response to isoprenaline. In an ischemia–reperfusion model with coronary-perfused right ventricular tissue, a decrease in contractile force and a rise in tension were observed during a period of 30-min no-flow ischemia. Upon reperfusion, contractile force returned to less than 50% of preischemic values. PAK-200 had no effect on the decline in contractile force during the no-flow ischemia but reduced the rise in resting tension. PAK-200 significantly improved the recovery of contractile force after reperfusion to about 70% of the preischemic value. PAK-200 was also shown to attenuate the decrease in tissue ATP during ischemia. Treatment of ventricular myocytes with an ischemia-mimetic solution resulted in depolarization of the mitochondrial membrane potential and an increase in cytoplasmic and mitochondrial Ca2+ concentrations. PAK-200 significantly delayed these changes. Thus, PAK-200 inhibits the cAMP-activated chloride current in cardiac muscle and may have protective effects against ischemia–reperfusion injury through novel mechanisms.
The Characterization of R2R3-MYB Genes in Ammopiptanthus nanus Uncovers That the miR858-AnaMYB87 Module Mediates the Accumulation of Anthocyanin under Osmotic Stress
Authors: Sumbur Batu , Gao Fei , Liu Qi , Feng Dandan , Bing Jie , Dorjee Tashi , Li Xuting , Sun Huigai , Zhou Yijun
Published: November 2023

R2R3-MYB transcription factors (TFs) participate in the modulation of plant development, secondary metabolism, and responses to environmental stresses. Ammopiptanthus nanus, a leguminous dryland shrub, tolerates a high degree of environmental stress, including drought and low-temperature stress. The systematic identification, structural analysis, evolutionary analysis, and gene profiling of R2R3-MYB TFs under cold and osmotic stress in A. nanus were performed. Up to 137 R2R3-MYB TFs were identified and clustered into nine clades, with most A. nanus R2R3-MYB members belonging to clade VIII. Tandem and segmental duplication events drove the expansion of the A. nanus R2R3-MYB family. Expression profiling revealed that multiple R2R3-MYB genes significantly changed under osmotic and cold stress conditions. MiR858 and miR159 targeted 88 R2R3-MYB genes. AnaMYB87, an miR858-targeted clade VIII R2R3-MYB TF, was up-regulated under both osmotic and cold stress. A transient expression assay in apples showed that the overexpression of AnaMYB87 promoted anthocyanin accumulation. A luciferase reporter assay in tobacco demonstrated that AnaMYB87 positively affected the transactivation of the dihydroflavonol reductase gene, indicating that the miR858-MYB87 module mediates anthocyanin accumulation under osmotic stress by regulating the dihydroflavonol reductase gene in A. nanus. This study provides new data to understand the roles of R2R3-MYB in plant stress responses.
Aerobic Exercise and Neuropathic Pain: Insights from Animal Models and Implications for Human Therapy
Authors: Ruimonte-Crespo Jorge , Plaza-Manzano Gustavo , Díaz-Arribas María José , Navarro-Santana Marcos José , López-Marcos José Javier , Fabero-Garrido Raúl , Seijas-Fernández Tamara , Valera-Calero Juan Antonio
Published: November 2023

This narrative review explores the complex relationship between aerobic exercise (AE) and neuropathic pain (NP), particularly focusing on peripheral neuropathies of mechanical origin. Pain, a multifaceted phenomenon, significantly impacts functionality and distress. The International Association for the Study of Pain’s definition highlights pain’s biopsychosocial nature, emphasizing the importance of patient articulation. Neuropathic pain, arising from various underlying processes, presents unique challenges in diagnosis and treatment. Our methodology involved a comprehensive literature search in the PubMed and SCOPUS databases, focusing on studies relating AE to NP, specifically in peripheral neuropathies caused by mechanical forces. The search yielded 28 articles and 1 book, primarily animal model studies, providing insights into the efficacy of AE in NP management. Results from animal models demonstrate that AE, particularly in forms like no-incline treadmill and swimming, effectively reduces mechanical allodynia and thermal hypersensitivity associated with NP. AE influences neurophysiological mechanisms underlying NP, modulating neurotrophins, cytokines, and glial cell activity. These findings suggest AE’s potential in attenuating neurophysiological alterations in NP. However, human model studies are scarce, limiting the direct extrapolation of these findings to human neuropathic conditions. The few available studies indicate AE’s potential benefits in peripheral NP, but a lack of specificity in these studies necessitates further research. In conclusion, while animal models show promising results regarding AE’s role in mitigating NP symptoms and influencing underlying neurophysiological mechanisms, more human-centric research is required. This review underscores the need for targeted clinical trials to fully understand and harness AE’s therapeutic potential in human neuropathic pain, especially of mechanical origin.
Anti-Osteoarthritis Mechanism of the Nrf2 Signaling Pathway
Authors: Saha Sarmistha , Rebouh Nazih Y.
Published: November 2023

Osteoarthritis (OA) is a chronic degenerative disease and the primary pathogenic consequence of OA is inflammation, which can affect a variety of tissues including the synovial membrane, articular cartilage, and subchondral bone. The development of the intra-articular microenvironment can be significantly influenced by the shift of synovial macrophages between pro-inflammatory and anti-inflammatory phenotypes. By regulating macrophage inflammatory responses, the NF-κB signaling route is essential in the therapy of OA; whereas, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway appears to manage the relationship between oxidative stress and inflammation. Additionally, it has been demonstrated that under oxidative stress and inflammation, there is a significant interaction between transcriptional pathways involving Nrf2 and NF-κB. Studying how Nrf2 signaling affects inflammation and cellular metabolism may help us understand how to treat OA by reprogramming macrophage behavior because Nrf2 signaling is thought to affect cellular metabolism. The candidates for treating OA by promoting an anti-inflammatory mechanism by activating Nrf2 are also reviewed in this paper.
Iodixanol as a New Contrast Agent for Cyanoacrylate Embolization: A Preliminary In Vivo Swine Study
Authors: Guillen Kévin , Comby Pierre-Olivier , Oudot Alexandra , Salsac Anne-Virginie , Falvo Nicolas , Virely Thierry , Poupardin Olivia , Guillemin Mélanie , Chevallier Olivier , Loffroy Romaric
Published: November 2023

N-butyl cyanoacrylate (NBCA) is a lipophilic, permanent embolic glue that must be opacified for fluoroscopic guidance. Empirically, lipophilic Lipiodol Ultra Fluid® (LUF) has been added to produce a single-phase physically stable mixture. Varying the dilution ratio allows control of glue polymerization kinetics. LUF is far more costly than water-soluble iodinated contrast agents (ICAs). Our purpose was to evaluate whether a water-soluble nonionic iso-osmolar ICA could be used instead. We embolized both renal arteries of six swine using 1:3 NBCA–LUF or NBCA–iodixanol in 1:1, 1:3, and 1:7 ratios. We used both micro-computed tomography to assess the distality of glue penetration and indexed cast ratio and histology to assess distality, arterial obliteration, vessel-wall damage, and renal-parenchyma necrosis. Glue–LUF produced significantly greater indexed cast ratio and renal-artery ROI values and a significantly shorter cast-to-capsule distance. The injected volume was significantly greater with 1:7 iodixanol than with the other mixtures. No significant differences were found for histological evidence of artery obliteration, vessel-wall damage, or renal-parenchyma necrosis. This is the first study dealing with ICA alone as a contrast agent for cyanoacrylate embolization, compared to LUF. More research is needed to determine whether water-soluble nonionic iodinated agents can be used for human NBCA embolization given the good safety profile, availability, and low cost of ICA.
In Vitro Chondrogenesis Induction by Short Peptides of the Carboxy-Terminal Domain of Transforming Growth Factor β1
Authors: Pitou Maria , Papachristou Eleni , Bratsios Dimitrios , Kefala Georgia-Maria , Tsagkarakou Anastasia S. , Leonidas Demetrios D. , Aggeli Amalia , Papadopoulos Georgios E. , Papi Rigini M. , Choli-Papadopoulou Theodora
Published: November 2023

Τransforming growth factor β1 (TGF-β1) comprises a key regulator protein in many cellular processes, including in vivo chondrogenesis. The treatment of human dental pulp stem cells, separately, with Leu83-Ser112 (C-terminal domain of TGF-β1), as well as two very short peptides, namely, 90-YYVGRKPK-97 (peptide 8) and 91-YVGRKP-96 (peptide 6) remarkably enhanced the chondrogenic differentiation capacity in comparison to their full-length mature TGF-β1 counterpart either in monolayer cultures or 3D scaffolds. In 3D scaffolds, the reduction of the elastic modulus and viscous modulus verified the production of different amounts and types of ECM components. Molecular dynamics simulations suggested a mode of the peptides’ binding to the receptor complex TβRII-ALK5 and provided a possible structural explanation for their role in inducing chondrogenesis, along with endogenous TGF-β1. Further experiments clearly verified the aforementioned hypothesis, indicating the signal transduction pathway and the involvement of TβRII-ALK5 receptor complex. Real-time PCR experiments and Western blot analysis showed that peptides favor the ERK1/2 and Smad2 pathways, leading to an articular, extracellular matrix formation, while TGF-β1 also favors the Smad1/5/8 pathway which leads to the expression of the metalloproteinases ADAMTS-5 and MMP13 and, therefore, to a hypertrophic chondrocyte phenotype. Taken together, the two short peptides, and, mainly, peptide 8, could be delivered with a scaffold to induce in vivo chondrogenesis in damaged articular cartilage, constituting, thus, an alternative therapeutic approach for osteoarthritis.
The Possible Role of Prescribing Medications, Including Central Nervous System Drugs, in Contributing to Male-Factor Infertility (MFI): Assessment of the Food and Drug Administration (FDA) Pharmacovigilance Database
Authors: Baldini Sara , Khattak Ahmed , Capogrosso Paolo , Antonini Gabriele , Dehò Federico , Schifano Fabrizio , Schifano Nicolò
Published: November 2023

Background: A wide range of medications may have a possible role in the development of male-factor infertility (MFI), including various antineoplastic agents, testosterone/anabolic steroids, immunosuppressive drugs/immunomodulators, glucocorticosteroids, non-steroidal anti-inflammatory drugs, opiates, antiandrogenic drugs/5-alpha-reductase inhibitors, various antibiotics, antidepressants, antipsychotics, antiepileptic agents and others. We aimed at investigating this issue from a pharmacovigilance-based perspective. Methods: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the drugs associated the most with MFI individual reports. Only those drugs being associated with more than 10 MFI reports were considered for the disproportionality analysis. Proportional Reporting Ratios (PRRs) and their confidence intervals were computed for all the drugs identified in this way in January 2023. Secondary, ‘unmasking’, dataset analyses were carried out as well. Results: Out of the whole database, 955 MFI reports were identified, 408 (42.7%) of which were associated with 20 medications, which had more than 10 reports each. Within this group, finasteride, testosterone, valproate, diethylstilbestrol, mechloretamine, verapamil, lovastatin and nifedipine showed significant levels of actual disproportionate reporting. Out of these, and before unmasking, the highest PRR values were identified for finasteride, diethylstilbestrol and mechloretamine, respectively, with values of 16.0 (12.7–20.3), 14.3 (9.1–22.4) and 58.7 (36.3–95.9). Conclusions: A variety of several medications, a number of which were already supposed to be potentially linked with MFI based on the existing evidence, were associated with significant PRR levels for MFI in this analysis. A number of agents which were previously hypothesized to be associated with MFI were not represented in this analysis, suggesting that drug-induced MFI is likely under-reported to regulatory agencies. Reproductive medicine specialists should put more effort into the detection and reporting of these adverse drug reactions.
Animacy Processing in Autism: Event-Related Potentials Reflect Social Functioning Skills
Authors: Peristeri Eleni , Andreou Maria , Ketseridou Smaranda-Nafsika , Machairas Ilias , Papadopoulou Valentina , Stravoravdi Aikaterini S. , Bamidis Panagiotis D. , Frantzidis Christos A.
Published: November 2023

Though previous studies with autistic individuals have provided behavioral evidence of animacy perception difficulties, the spatio-temporal dynamics of animacy processing in autism remain underexplored. This study investigated how animacy is neurally encoded in autistic adults, and whether potential deficits in animacy processing have cascading deleterious effects on their social functioning skills. We employed a picture naming paradigm that recorded accuracy and response latencies to animate and inanimate pictures in young autistic adults and age- and IQ-matched healthy individuals, while also employing high-density EEG analysis to map the spatio-temporal dynamics of animacy processing. Participants’ social skills were also assessed through a social comprehension task. The autistic adults exhibited lower accuracy than controls on the animate pictures of the task and also exhibited altered brain responses, including larger and smaller N100 amplitudes than controls on inanimate and animate stimuli, respectively. At late stages of processing, there were shorter slow negative wave latencies for the autistic group as compared to controls for the animate trials only. The autistic individuals’ altered brain responses negatively correlated with their social difficulties. The results suggest deficits in brain responses to animacy in the autistic group, which were related to the individuals’ social functioning skills.
Targeting Microglia/Macrophages Notch1 Protects Neurons from Pyroptosis in Ischemic Stroke
Authors: Chen Ran , Zhu Hua , Wang Zhihui , Zhang Yonggang , Wang Jin , Huang Yingao , Gu Lijuan , Li Changyong , Xiong Xiaoxing , Jian Zhihong
Published: November 2023

Background and Aims: The immune-inflammatory cascade and pyroptosis play an important role in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). The maintenance of immune homeostasis is inextricably linked to the Notch signaling pathway, but whether myeloid Notch1 affects microglia polarization as well as neuronal pyroptosis in CIRI is not fully understood. This study was designed to clarify the role of myeloid Notch1 in CIRI, providing new therapeutic strategies for ischemic stroke. Methods and Results: Myeloid-specific Notch1 knockout (Notch1M-KO) mice and the floxed Notch1 (Notch1FL/FL) mice were subjected to middle cerebral artery occlusion (MCAO). After 3 days of CIRI, we evaluated the neurological deficit score and cerebral infarction volume. Immunofluorescence staining was used to detect the expression of Notch1 and microglial subtype markers. Cerebral infiltrating macrophages were detected by flow cytometry. RT-qPCR was used to detect pro-inflammatory cytokines. Western blot was used to detect the expression of pyroptosis related proteins. The Notch1-siRNA transfected BV2 cells were co-cultured with HT22 cells to investigate the potential mechanisms by which microglial Notch1 affects neuronal pyroptosis induced by anoxia/reoxygenation in vitro. We found that Notch1 was activated in cerebral microglia/macrophages after CIRI. Myeloid Notch1 deficiency decreased the cerebral infarct volume (24.17 ± 3.29 vs. 36.17 ± 2.27, p < 0.001), neurological function scores (2.33 ± 0.47 vs. 3.17 ± 0.37, p < 0.001) and the infiltration of peripheral monocytes/macrophages (3.26 ± 0.53 vs. 5.67 ± 0.57, p < 0.01). Strikingly, myeloid-specific Notch1 knockout alleviated pyroptosis. Compared with microglia M1, increased microglia M2 were detected in the ischemic penumbra. In parallel in vitro co-culture experiments, we found that Notch1 knockdown in microglial BV2 cells inhibited anoxia/reoxygenation-induced JAK2/STAT3 activation and pyroptosis in hippocampal neuron HT22 cells. Conclusions: Our findings elucidate the underlying mechanism of the myeloid Notch1 signaling pathway in regulating neuronal pyroptosis in CIRI, suggesting that targeting myeloid-specific Notch1 is an effective strategy for the treatment of ischemic stroke.
Integrating Aerial and 3D Data into a Data-Driven Decision-Making Workflow for Nature-Based Stormwater Solutions
Authors: Edelman Harry , Rosén Lasse , Nyman Emil , Leskinen Piia
Published: November 2023

Urbanization and climate change have increased the need for stormwater management and nature-based solutions. Decisions made at the project level impact the emergence of the systemic traits of the stormwater network and the functionality of the catchment areas in urban planning. To that end, it is vital to introduce the decision-making tools for analysing both the utilities and amenities of nature-based solutions (NBS) to increase their adoption to reduce the peak loads in the stormwater system and, to that end, mitigate the impacts of climate change. There is a deficiency in employing a software-based approach to analyse the qualitative and quantitative aspects of NBSs to back up design decisions. This paper demonstrates a workflow using drone-based photogrammetry, 3D modelling, and simulation software to generate visual and functional models assisting in informed decision-making in the design of stormwater systems as functional landscape architecture. Using aerial data from drones and modelled design solutions, the proposed workflow simulates rain events, infiltration, evaporation, water flow, and the accumulation of stormwater in a way that allows the visual and quantified analysis of detailed landscape architecture designs. The paper provides an example of a rooftop site simulation demonstrating the infiltration and flow of water to the drainage. The visual decision-making method provided can aid in investment decisions for functional landscape design in support of stormwater management.
Experimental and Numerical Investigation of Hygrothermal Transfer through Bio-Based Materials: An Application to Wood–Cement Walls
Authors: Bakkour Amer , Ouldboukhitine Salah-Eddine , Biwole Pascal , Godi Gael , Amziane Sofiane
Published: November 2023

In the context of the energy transition, new construction materials are emerging, notably bio-based materials such as wood concrete. This paper investigates the hygrothermal performance of walls constructed with wood–cement concrete. First, the thermal properties of wooden concrete, namely thermal conductivity, effusivity, and diffusivity, are experimentally characterized in both dry and wet conditions. Second, in situ measurements are carried out on a house in Lyon, a city in France, constructed with mono-layered wood–cement walls. This involves monitoring the temperature and relative humidity levels both inside and outside the building, as well as at three distinct positions within the wood walls over a 6-month period (from 20 April 2023 to 20 October 2023). The hygrothermal analysis at the center of the wall reveals that the wood wall effectively moderates fluctuations in the external temperature and relative humidity. Following this, a numerical study is performed to check the reliability of the adopted Reduced Heat, Air, and Mass (HAM) model to reproduce the hygrothermal performance of the wood–cement wall. The results show a strong agreement between the simulated and measured data, confirming the applicability of the ‘Reduced HAM’ model for the prediction of the hygrothermal behavior of wood–cement walls.
Review and Updates on Systemic Mastocytosis and Related Entities
Authors: Li Julie Y. , Ryder Christopher B. , Zhang Hailing , Cockey Samuel G. , Hyjek Elizabeth , Moscinski Lynn C. , Sagatys Elizabeth , Song Jinming
Published: November 2023

Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. The new ICC classifies SM slightly differently. The diagnosis of SM requires the integration of bone marrow morphologic, immunophenotypic, and molecular findings, as well as clinical signs and symptoms. Moreover, understanding the wide range of clinical presentations for patients with mast cell disorders is necessary for accurate and timely diagnosis. This review provides an updated overview of mast cell disorders, with a special emphasis on SM, including the latest approaches to diagnosis, prognostic stratification, and management of this rare disease.
Plasma Immune Proteins and Circulating Tumor DNA Predict the Clinical Outcome for Non-Small-Cell Lung Cancer Treated with an Immune Checkpoint Inhibitor
Authors: Stensgaard Simone , Thomsen Astrid , Helstrup Sofie , Meldgaard Peter , Sorensen Boe S.
Published: November 2023

Immunotherapy has altered the therapeutic landscape for patients with non-small-cell lung cancer (NSCLC). The immune checkpoint inhibitor pembrolizumab targets the PD-1/PD-L1 signaling axis and produces durable clinical responses, but reliable biomarkers are lacking. Using 115 plasma samples from 42 pembrolizumab-treated patients with NSCLC, we were able to identify predictive biomarkers. In the plasma samples, we quantified the level of 92 proteins using the Olink proximity extension assay and circulating tumor DNA (ctDNA) using targeted next-generation sequencing. Patients with an above-median progression-free survival (PFS) had significantly higher expressions of Fas ligand (FASLG) and inducible T-cell co-stimulator ligand (ICOSLG) at baseline than patients with a PFS below the median. A Kaplan–Meier analysis demonstrated that high levels of FASLG and ICOSLG were predictive of longer PFS and overall survival (OS) (PFS: 10.83 vs. 4.49 months, OS: 27.13 vs. 18.0 months). Furthermore, we identified a subgroup with high expressions of FASLG and ICOSLG who also had no detectable ctDNA mutations after treatment initiation. This subgroup had significantly longer PFS and OS rates compared to the rest of the patients (PFS: 25.71 vs. 4.52 months, OS: 34.62 vs. 18.0 months). These findings suggest that the expressions of FASLG and ICOSLG at baseline and the absence of ctDNA mutations after the start of treatment have the potential to predict clinical outcomes.
Adaptation Time as a Determinant of the Dosimetric Effectiveness of Online Adaptive Radiotherapy for Bladder Cancer
Authors: Khouya Aymane , Pöttgen Christoph , Hoffmann Christian , Ringbaek Toke Printz , Lübcke Wolfgang , Indenkämpen Frank , Guberina Maja , Guberina Nika , Gauler Thomas , Stuschke Martin , Santiago Garcia Alina
Published: November 2023

Interfraction anatomic deformations decrease the precision of radiotherapy, which can be improved by online adaptive radiation therapy (oART). However, oART takes time, allowing intrafractional deformations. In this study on focal radiotherapy for bladder cancer, we analyzed the time effect of oART on the equivalent uniform dose in the CTV (EUDCTV) per fraction and for the accumulated dose distribution over a treatment series as measure of effectiveness. A time-dependent digital CTV model was built from deformable image registration (DIR) between pre- and post-adaptation imaging. The model was highly dose fraction-specific. Planning target volume (PTV) margins were varied by shrinking the clinical PTV to obtain the margin-specific CTV. The EUDCTV per fraction decreased by—4.4 ± 0.9% of prescribed dose per min in treatment series with a steeper than average time dependency of EUDCTV. The EUDCTV for DIR-based accumulated dose distributions over a treatment series was significantly dependent on adaptation time and PTV margin (p < 0.0001, Chi2 test for each variable). Increasing adaptation times larger than 10 min by five minutes requires a 1.9 ± 0.24 mm additional margin to maintain EUDCTV for a treatment series. Adaptation time is an important determinant of the precision of oART for one half of the bladder cancer patients, and it should be aimed at to be minimized.
Inflammation and Immunity Gene Expression Patterns and Machine Learning Approaches in Association with Response to Immune-Checkpoint Inhibitors-Based Treatments in Clear-Cell Renal Carcinoma
Authors: Dovrolis Nikolas , Katifelis Hector , Grammatikaki Stamatiki , Zakopoulou Roubini , Bamias Aristotelis , Karamouzis Michalis V. , Souliotis Kyriakos , Gazouli Maria
Published: November 2023

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Despite the rapid evolution of targeted therapies, immunotherapy with checkpoint inhibition (ICI) as well as combination therapies, the cure of metastatic ccRCC (mccRCC) is infrequent, while the optimal use of the various novel agents has not been fully clarified. With the different treatment options, there is an essential need to identify biomarkers to predict therapeutic efficacy and thus optimize therapeutic approaches. This study seeks to explore the diversity in mRNA expression profiles of inflammation and immunity-related circulating genes for the development of biomarkers that could predict the effectiveness of immunotherapy-based treatments using ICIs for individuals with mccRCC. Gene mRNA expression was tested by the RT2 profiler PCR Array on a human cancer inflammation and immunity crosstalk kit and analyzed for differential gene expression along with a machine learning approach for sample classification. A number of mRNAs were found to be differentially expressed in mccRCC with a clinical benefit from treatment compared to those who progressed. Our results indicate that gene expression can classify these samples with high accuracy and specificity.
Small Antibodies with Big Applications: Nanobody-Based Cancer Diagnostics and Therapeutics
Authors: Zhang Qian , Zhang Nan , Xiao Han , Wang Chen , He Lian
Published: November 2023

Monoclonal antibodies (mAbs) have exhibited substantial potential as targeted therapeutics in cancer treatment due to their precise antigen-binding specificity. Despite their success in tumor-targeted therapies, their effectiveness is hindered by their large size and limited tissue permeability. Camelid-derived single-domain antibodies, also known as nanobodies, represent the smallest naturally occurring antibody fragments. Nanobodies offer distinct advantages over traditional mAbs, including their smaller size, high stability, lower manufacturing costs, and deeper tissue penetration capabilities. They have demonstrated significant roles as both diagnostic and therapeutic tools in cancer research and are also considered as the next generation of antibody drugs. In this review, our objective is to provide readers with insights into the development and various applications of nanobodies in the field of cancer treatment, along with an exploration of the challenges and strategies for their prospective clinical trials.
Research Progress on the Mechanism of Anti-Tumor Immune Response Induced by TTFields
Authors: Lan Yue , Zhang Shaomin , Pan Yun , Wang Minmin , Chen Guangdi
Published: November 2023

Tumor treating fields (TTFields), a biophysical therapy technology that uses alternating electric fields to inhibit tumor proliferation, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of newly diagnosed or recurrent glioblastomas (GBM) and malignant pleural mesotheliomas (MPM). Clinical trials have confirmed that TTFields are effective in slowing the tumor growth and prolonging patient survival. In recent years, many researchers have found that TTFields can induce anti-tumor immune responses, and their main mechanisms include upregulating the infiltration ratio and function of immune cells, inducing the immunogenic cell death of tumor cells, modulating immune-related signaling pathways, and upregulating the expression of immune checkpoints. Treatment regimens combining TTFields with tumor immunotherapy are emerging as a promising therapeutic approach in clinical practice. Given the increasing number of recently published studies on this topic, we provide an updated review of the mechanisms and clinical implications of TTFields in inducing anti-tumor immune responses. This review not only has important reference value for an in-depth study of the anticancer mechanism of TTFields but also provides insights into the future clinical application of TTFields.
Towards Cancer Nanoradiopharmaceuticals—Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels
Authors: Rurarz Beata Paulina , Urbanek Kinga Anna , Karczmarczyk Urszula , Raczkowska Joanna , Habrowska-Górczyńska Dominika Ewa , Kozieł Marta Justyna , Kowalska Karolina , Kadłubowski Sławomir , Sawicka Agnieszka , Maurin Michał , Piastowska-Ciesielska Agnieszka Wanda , Ulański Piotr
Published: November 2023

Despite the tremendous development of oncology, prostate cancer remains a debilitating malignancy. One of the most promising approaches to addressing this issue is to exploit the advancements of nanomedicine in combination with well-established nuclear medicine and radiotherapy. Following this idea, we have developed a radioisotope nanocarrier platform of electron-beam-synthesized nanogels based on poly(acrylic acid). We have developed a functionalization protocol, showing the very high (>97%) efficiency of the conjugation in targeting a ligand–bombesin derivative. This engineered peptide can bind gastrin-releasing peptide receptors overexpressed in prostate cancer cells; moreover, it bears a radioisotope-chelating moiety. Our nanoplatform exhibits very promising performance in vitro; the radiolabeled nanocarriers maintained high radiochemical purity of >90% in both the labeling buffer and human serum for up to 14 days. The application of the targeted nanocarrier allowed also effective and specific uptake in PC-3 prostate cancer cells, up to almost 30% after 4 h, which is a statistically significant improvement in comparison to carrier-free radiolabeled peptides. Although our system requires further studies for more promising results in vivo, our study represents a vital advancement in radionanomedicine—one of many steps that will lead to effective therapy for castration-resistant prostate cancer.
Identifying Genetic Mutation Status in Patients with Colorectal Cancer Liver Metastases Using Radiomics-Based Machine-Learning Models
Authors: Wesdorp Nina , Zeeuw Michiel , van der Meulen Delanie , van ‘t Erve Iris , Bodalal Zuhir , Roor Joran , van Waesberghe Jan Hein , Moos Shira , van den Bergh Janneke , Nota Irene , van Dieren Susan , Stoker Jaap , Meijer Gerrit , Swijnenburg Rutger-Jan , Punt Cornelis , Huiskens Joost , Beets-Tan Regina , Fijneman Remond , Marquering Henk , Kazemier Geert ,   on behalf of the Dutch Colorectal Cancer Group Liver Expert Panel
Published: November 2023

For patients with colorectal cancer liver metastases (CRLM), the genetic mutation status is important in treatment selection and prognostication for survival outcomes. This study aims to investigate the relationship between radiomics imaging features and the genetic mutation status (KRAS mutation versus no mutation) in a large multicenter dataset of patients with CRLM and validate these findings in an external dataset. Patients with initially unresectable CRLM treated with systemic therapy of the randomized controlled CAIRO5 trial (NCT02162563) were included. All CRLM were semi-automatically segmented in pre-treatment CT scans and radiomics features were calculated from these segmentations. Additionally, data from the Netherlands Cancer Institute (NKI) were used for external validation. A total of 255 patients from the CAIRO5 trial were included. Random Forest, Gradient Boosting, Gradient Boosting + LightGBM, and Ensemble machine-learning classifiers showed AUC scores of 0.77 (95%CI 0.62–0.92), 0.77 (95%CI 0.64–0.90), 0.72 (95%CI 0.57–0.87), and 0.86 (95%CI 0.76–0.95) in the internal test set. Validation of the models on the external dataset with 129 patients resulted in AUC scores of 0.47–0.56. Machine-learning models incorporating CT imaging features could identify the genetic mutation status in patients with CRLM with a good accuracy in the internal test set. However, in the external validation set, the models performed poorly. External validation of machine-learning models is crucial for the assessment of clinical applicability and should be mandatory in all future studies in the field of radiomics.
A Review on the Use of Catalysis for Biogas Steam Reforming
Authors: Nogales-Delgado Sergio , Álvez-Medina Carmen María , Montes Vicente , González Juan Félix
Published: November 2023

Hydrogen production from natural gas or biogas, at different purity levels, has emerged as an important technology with continuous development and improvement in order to stand for sustainable and clean energy. Regarding biogas, which can be obtained from multiple sources, hydrogen production through the steam reforming of methane is one of the most important methods for its energy use. In that sense, the role of catalysts to make the process more efficient is crucial, normally contributing to a higher hydrogen yield under milder reaction conditions in the final product. The aim of this review is to cover the main points related to these catalysts, as every aspect counts and has an influence on the use of these catalysts during this specific process (from the feedstocks used for biogas production or the biodigestion process to the purification of the hydrogen produced). Thus, a thorough review of hydrogen production through biogas steam reforming was carried out, with a special emphasis on the influence of different variables on its catalytic performance. Also, the most common catalysts used in this process, as well as the main deactivation mechanisms and their possible solutions are included, supported by the most recent studies about these subjects.
Bile Acids in Autoimmune Liver Disease: Unveiling the Nexus of Inflammation, Inflammatory Cells, and Treatment Strategies
Authors: Zhou Tianhao , Ismail AbdiGhani , Francis Heather
Published: November 2023

As bile acids not solely play an essential role in nutrition absorption, but also in regulating metabolic functions as well as immune response, bile acids and their signaling pathways are increasingly acknowledged as potential therapeutic targets in the context of chronic liver diseases. Bile acid receptors such as G protein bile acid-activated receptor 1 and farnesoid X receptor are expressed in different immune cells engaged in innate immunity. Recently, a series of studies have revealed distinct functions of bile acids and bile acid receptors within the adaptive immune system. In addition, a variety of molecules targeting bile acid receptors and transporters are currently in advanced stages of clinical development. Autoimmune liver diseases including conditions like primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis can lead to chronic inflammation, fibrosis, and even cirrhosis and liver failure. In this review, we focus on the role of bile acids in the inflammatory aspects of autoimmune liver diseases.