Search Results (20)

Background: Colorectal cancer is among the most prevalent causes of tumor-related deaths worldwide. Antiangiogenic therapy represents a cornerstone of metastatic CRC treatment, and biomarkers are advocated for the optimization of this therapeutic strategy. Methods: In this observational prospective study, we employed an optimized flow cytometry protocol to investigate the prognostic and predictive potential of blood circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs), and related subsets in a cohort of patients with metastatic colorectal cancer (n = 40). Results: Computational FC analysis revealed a differential enrichment of blood cell clusters with a CD34+/CD45dim/CD117(c-kit)+ phenotype between responders and non-responders both to antiangiogenic and non-antiangiogenic treatments. Intriguingly, our results show that a high percentage of annexin V-negative cells in a putative circulating progenitor population with a CD34+/CD45dim/CD117+ phenotype was correlated with a reduced response to systemic anticancer treatments (p = 0.015) and worse overall survival (log-rank p = 0.03). In addition, we observed increased blood concentrations of CD34+/CD45dim/CD117+/annexin V- cells in patients with a higher number of metastatic sites (p = 0.03). Conclusions: Overall, these findings hold promise for the identification of novel circulating biomarkers to develop more personalized treatment approaches in patients with metastatic colorectal cancer. Full article

The general-purpose Compact Muon Solenoid (CMS) detector at the Large Hadron Collider (LHC) at CERN is used to study the production of new particles in proton–proton collisions at an LHC center of mass energy of 13.6 TeV. The detector includes a magnet based on a 6 m diameter superconducting solenoid coil operating at a current of 18.164 kA. This current creates a central magnetic flux density of 3.8 T that allows for the high-precision measurement of the momenta of the produced charged particles using tracking and muon subdetectors. The CMS magnet contains a 10,000 ton flux-return yoke of dodecagonal shape made from the assembly of construction steel blocks distributed in several layers. These steel blocks are magnetized with the solenoid returned magnetic flux and wrap the muons escaping the hadronic calorimeters of total absorption. To reconstruct the muon trajectories, and thus to measure the muon momenta, the drift tube and cathode strip chambers are located between the layers of the steel blocks. To describe the distribution of the magnetic flux in the magnet yoke layers, a three-dimensional computer model of the CMS magnet is used. To validate the calculations, special measurements are performed, with the flux loops wound in 22 cross-sections of the flux-return yoke blocks. The measured voltages induced in the flux loops during the CMS magnet ramp-ups and -downs, as well as during the superconducting coil fast discharges, are integrated over time to obtain the initial magnetic flux densities in the flux loop cross-sections. The measurements obtained during the seven standard ramp-downs of the magnet were analyzed in 2018. From that time, three fast discharges occurred during the standard ramp-downs of the magnet. This allows us to single out the contributions of the eddy currents, induced in steel, to the flux loop voltages registered during the fast discharges of the coil. Accounting for these contributions to the flux loop measurements during intentionally triggered fast discharges in 2006 allows us to perform the validation of the CMS magnet computer model with better precision. The technique for the flux loop measurements and the obtained results are presented and discussed. The method for measuring magnetic flux density in steel blocks described in this study is innovative. The experience of 3D modeling and measuring the magnetic field in steel blocks of the magnet yoke, as part of a muon detector system, has good prospects for use in the construction and operation of particle detectors for the Future Circular Electron–Positron Collider and the Circular Electron–Positron Collider. Full article

Introduction: The vertebral cartilage endplate (CEP), crucial for intervertebral disc health, is prone to degeneration linked to chronic low back pain, disc degeneration, and Modic changes (MC). While it is known that disc cells express toll-like receptors (TLRs) that recognize pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), it is unclear if CEP cells (CEPCs) share this trait. The CEP has a higher cell density than the disc, making CEPCs an important contributor. This study aimed to identify TLRs on CEPCs and their role in pro-inflammatory and catabolic gene expression. Methods: Gene expression of TLR1–10 was measured in human CEPs and expanded CEPCs using quantitative polymerase chain reaction. Additionally, surface TLR expression was measured in CEPs grouped into non-MC and MC. CEPCs were stimulated with tumor necrosis factor alpha, interleukin 1 beta, small-molecule TLR agonists, or the 30 kDa N-terminal fibronectin fragment. TLR2 signaling was inhibited with TL2-C29, and TLR2 protein expression was measured with flow cytometry. Results: Ex vivo analysis found all 10 TLRs expressed, while cultured CEPCs lost TLR8 and TLR9 expression. TLR2 expression was significantly increased in MC1 CEPCs, and its expression increased significantly after pro-inflammatory stimulation. Stimulation of the TLR2/6 heterodimer upregulated TLR2 protein expression. The TLR2/1 and TLR2/6 ligands upregulated pro-inflammatory genes and matrix metalloproteases (MMP1, MMP3, and MMP13), and TLR2 inhibition inhibited their upregulation. Endplate resorptive capacity of TLR2 activation was confirmed in a CEP explant model. Conclusions: The expression of TLR1–10 in CEPCs suggests that the CEP is susceptible to PAMP and DAMP stimulation. Enhanced TLR2 expression in MC1, and generally in CEPCs under inflammatory conditions, has pro-inflammatory and pro-catabolic effects, suggesting a potential role in disc degeneration and MC. Full article

Ovarian cancer (OC) remains the most fatal disease of gynaecologic malignant tumours. The neovasculature in the tumour microenvironment principally comprises endothelial cells. Haematogenous cancer metastases are significantly impacted by tumour neovascularisation, which predominantly depends on the tumour-derived endothelial vasculogenesis. There is an urgent need for biomarkers for the diagnosis, prognosis and prediction of drug response. Endothelial cells play a key role in angiogenesis and other forms of tumour vascularisation. Subtypes of circulating endothelial cells may provide interesting non-invasive biomarkers of advanced OC that might have the potential to be included in clinical analysis for patients’ stratification and therapeutic management. In this review, we summarise the reported studies on circulating endothelial subtypes in OC, detailing their isolation methods as well as their potential diagnostic, prognostic, predictive and therapeutic utility for clinical application. We highlight key biomarkers for the identification of circulating endothelial cell subtypes and their targets for therapies and critically point out future challenges. Full article

Interest in searches for Charged Lepton Flavor Violation (CLFV) has continued in the past few decades since the observation of CLFV would indicate a new physics Beyond the Standard Model (BSM). As several future lepton colliders with high luminosity have been proposed, the search for CLFV will reach an unprecedented level of precision. Many BSM models allow CLFV processes at the tree level, such as the R-parity-violating (RPV) Minimal Supersymmetric Standard Model (MSSM), which is a good choice for benchmarking. In this paper, we perform a detailed fast Monte Carlo simulation study on RPV-induced CLFV processes at future lepton colliders, including a 240 $\mathrm{GeV}$ circular electron positron collider (CEPC) and a 6 or 14 $\mathrm{TeV}$ Muon Collider. As a result, we found that the upper limits on the $\tau$-related RPV couplings will be significantly improved, while several new limits on RPV couplings can be set, which are inaccessible by low-energy experiments. Full article

Endothelial progenitor cells (EPCs) are circulating cells of various origins that possess the capacity for renewing and regenerating the endothelial lining of blood vessels. During physical activity, in response to factors such as hypoxia, changes in osmotic pressure, and mechanical forces, endothelial cells undergo intense physiological stress that results in endothelial damage. Circulating EPCs participate in blood vessel repair and vascular healing mainly through paracrine signalling. Furthermore, physical activity may play an important role in mobilising this important cell population. In this narrative review, we summarise the current knowledge on the biology of EPCs, including their characteristics, assessment, and mobilisation in response to both chronic and acute physical activity in healthy individuals. Full article

Low back pain (LBP) is associated with the degeneration of human intervertebral discs (IVDs). Despite progress in the treatment of LBP through spinal fusion, some cases still end in non-fusion after the removal of the affected IVD tissue. In this study, we investigated the hypothesis that the remaining IVD cells secrete BMP inhibitors that are sufficient to inhibit osteogenesis in autologous osteoblasts (OBs) and bone marrow mesenchymal stem cells (MSCs). A conditioned medium (CM) from primary human IVD cells in 3D alginate culture was co-cultured with seven donor-matched OB and MSCs. After ten days, osteogenesis was quantified at the transcript level using qPCR to measure the expression of bone-related genes and BMP antagonists, and at the protein level by alkaline phosphatase (ALP) activity. Additionally, cells were evaluated histologically using alizarin red (ALZR) staining on Day 21. For judging ALP activity and osteogenesis, the Noggin expression in samples was investigated to uncover the potential causes. The results after culture with the CM showed significantly decreased ALP activity and the inhibition of the calcium deposit formation in alizarin red staining. Interestingly, no significant changes were found among most bone-related genes and BMP antagonists in OBs and MSCs. Noteworthy, Noggin was relatively expressed higher in human IVD cells than in autologous OBs or MSCs (relative to autologous OB, the average fold change was in 6.9, 10.0, and 6.3 in AFC, CEPC, and NPC, respectively; and relative to autologous MSC, the average fold change was 2.3, 3.4, and 3.2, in AFC, CEPC, and NPC, respectively). The upregulation of Noggin in residual human IVDs could potentially inhibit the osteogenesis of autologous OB and MSC, thus inhibiting the postoperative spinal fusion after discectomy surgery. Full article

Social media has been widely used to design and publish pro-environment campaigns; the goal is to spread awareness about environmental issues and explain how customers can change their consumption behavior to protect the environment. Customers’ engagement with pro-environmental campaigns (CEPC) on social media is crucial to achieving these objectives. Limited studies have examined the factors that could increase CEPC, and its effects, on pro-environmental consumption behavior. The available literature suggests the antecedents of social media engagement, but is restricted to brands/products. Based on these findings, this study explores the effects of advertising attractiveness, advertising-based skepticism, online interaction propensity, and privacy concerns on CEPC. This study also suggests that customers’ engagement with pro-environmental consumption-related content can be defined as a pro-environmental experience that could lead to pro-environmental consumption. The study was based on a sample of 262 responses from online users; the results indicated that CEPC is largely affected by advertising attractiveness, advertising skepticism, and online interaction propensity. The study further established that pro-environment consumption is a potential outcome of CPEC. This study contributes to the existing literature by providing insight into ways in which activist groups can inspire consumers to engage with pro-environment content and exploring whether that engagement translates into a pro-environment intention. Full article

Moyamoya arteriopathy (MMA) is a rare cerebrovascular disorder that causes recurrent ischemic and hemorrhagic strokes, leading young patients to severe neurological deficits. The pathogenesis of MMA is still unknown. The disease onset in a wide number of pediatric cases raises the question of the role of genetic factors in the disease’s pathogenesis. In these patients, MMA’s clinical course, or progression, is largely unclear. By performing a comprehensive molecular and cellular profile in the plasma and CSF, respectively, of MMA pediatric patients, our study is aimed at assessing the levels of circulating endothelial progenitor cells (cEPC) and the release of selected proteins at an early disease stage to clarify MMA pathogenesis and progression. We employed cytofluorimetric methods and immunoassays in pediatric MMA patients and matched control subjects by age and sex. We detected increased levels of cEPC in peripheral blood and an upregulation of angiogenic markers in CSF (i.e., angiopoietin-2 and VEGF-A). This finding is probably associated with deregulated angiogenesis, as stated by the moderate severity of collateral vessel network development (Suzuki III-IV). The absence of significant modulation of neurofilament light in CSF led us to rule out the presence of substantial neuronal injury in MMA children. Despite the limited cohort of pediatric patients, we found some peculiar cellular and molecular characteristics in their blood and CSF samples. Our findings may be confirmed by wider and perspective studies to identify predictive or prognostic circulating biomarkers and potential therapeutic targets for personalized care of MMA pediatric patients. Full article

Based on the particle-flow paradigm, a new hadronic calorimeter (HCAL) with scintillating glass tiles is proposed to address major challenges from precision measurements of jets at the future lepton colliders, such as the Circular Electron Positron Collider (CEPC). Tiles of high-density scintillating glass, with a high-energy sampling fraction, can significantly improve the hadronic energy resolution in the low-energy region (typically below 10 GeV for major jet components at Higgs factories). The hadronic energy resolution of single hadrons and the effects of key parameters of scintillating glass have been evaluated in the Geant4 full simulation, followed by the physics benchmark studies on the Higgs boson with jets in the final state. R&D efforts of scintillating glass materials are ongoing within a dedicated collaboration since 2021 with the aim to achieve a high light yield, a high density, and a low cost. Measurements have been performed for the first batches of scintillating glass samples including the light yield, emission and scintillation spectra, scintillation decay times, and cosmic responses. An optical simulation model of a single scintillating glass tile has been established to provide guidance in the development of scintillating glass. Highlights of the expected detector performance and the latest scintillating glass developments are presented in this contribution. Full article

In this manuscript, I give a short summary on scenarios with new physics scalars that could be investigated at future $e^{+}{e}^{-}$ colliders. I concentrate on cases where at least one of the additional scalars has a mass below 125 GeV, and discuss both models where this could be realized, as well as studies which focus on such scenarios. This work is based on several overview talks I recently gave at the CEPC workshop, FCC week and ECFA future collider workshop, as well as a Snowmass White Paper. Full article

Medium-temperature (mid-T) furnace baking was conducted at 650 MHz superconducting radio-frequency (SRF) cavity for circular electron positron collider (CEPC), which enhanced the cavity unloaded quality factor (Q₀) significantly. In the vertical test (2.0 K), Q₀ of 650 MHz cavity reached 6.4 × 10¹⁰ at 30 MV/m, which is remarkably high at this unexplored frequency. Additionally, the cavity quenched at 31.2 MV/m finally. There was no anti-Q-slope behavior after mid-T furnace baking, which is characteristic of 1.3 GHz cavities. The microwave surface resistance (R_S) was also studied, which indicated both very low Bardeen–Cooper–Schrieffer (BCS) and residual resistance. The recipe of cavity process in this paper is simplified and easy to duplicate, which may benefit the SRF community. Full article

A circular electron positron collider (CEPC) will adopt hundreds of 650-MHz superconducting cavities with high quality factor (Q) and accelerating gradient (E_acc). Two 650-MHz single-cell cavities made of fine-grain niobium were first treated via buffered chemical polishing (BCP), which was easy and convenient. However, the vertical test results could not meet the specification of the CEPC (4 × 10¹⁰ at 22 MV/m). Therefore, electro-polishing (EP) of 650-MHz single-cell cavities was conducted, which was complicated but remarkably effective. Both 650-MHz single-cell cavities achieved state-of-the-art gradients of 35 MV/m after the EP process, which is extremely high for large elliptical cavities (frequency < 1 GHz). One cavity achieved an intrinsic quality factor (Q₀) of 4.5 × 10¹⁰ at 22.0 MV/m, which was higher than the CEPC spec. The other cavity obtained a lower Q₀ of 3.4 × 10¹⁰ at 22.0 MV/m, which may have resulted from the cancellation of high-temperature annealing. Full article

In this paper, a comprehensive life-cycle assessment (LCA) is carried out in order to evaluate the multiple environmental-health impacts of the biological wastewater treatment of the fish-processing industry throughout its life cycle. To this aim, the life-cycle impact assessment method based on endpoint modeling (LIME) was considered as the main LCA model. The proposed methodology is based on an endpoint modeling framework that uses the conjoint analysis to calculate damage factors for human health, social assets, biodiversity, and primary production, based on Indonesia’s local data inventory. A quantitative microbial risk assessment (QMRA) is integrated with the LIME modeling framework to evaluate the damage on human health caused by five major biological treatment technologies, including chemical-enhanced primary clarification (CEPC), aerobic-activated sludge (AS), up-flow anaerobic sludge blanket (UASB), ultrafiltration (UF) and reverse osmosis (RO) in this industry. Finally, a life-cycle costing (LCC) is carried out, considering all the costs incurred during the lifetime. The LCA results revealed that air pollution and gaseous emissions from electricity consumption have the most significant environmental impacts in all scenarios and all categories. The combined utilization of the UF and RO technologies in the secondary and tertiary treatment processes reduces the health damage caused by microbial diseases, which contributes significantly to reducing overall environmental damage. Full article

Cardiovascular disease (CVD) correlates with inflammation and a reduction in circulating endothelial progenitor cells (cEPCs). Recently, CVD was shown to be the main cause of mortality in individuals with type 1 diabetes (T1DM). In animals, miR-342 was shown to exert an anti-inflammatory effect in CVD. Hypothesis: miR-342-3p/-5p are downregulated in subclinical CVD (T1DM), whereas inflammatory cytokines are upregulated. We studied miR -342 -3p/5p in plasma/peripheral blood mononuclear cells (PBMCs) in 29 T1DM and 20 controls (HC). Vascular health was measured by fibronectin adhesion assay (FAA), cEPCs (CD45^dimCD34⁺133⁺ cells) and by assessing inflammation and tissue inhibition of metalloproteases (TIMP-1). In T1DM IL-7, IL-8, TNFα and VEGF-C were increased in plasma. MiR-342-3p/-5p were downregulated in PBMCs in T1DM, but not in plasma. PANX2, chemokine receptors CXCR1/2 mRNAs, were increased in PBMCs in T1DM. MiR-342-3p was negatively correlated with TIMP-1, IL-6, IL-8, TNF-α, HbA_1c and CXCR2, whilst miR-342-5p was negatively correlated with TIMP-1, IL-6, IL-8 and HbA_1c. There was a positive correlation among miR-342-3p, FAA and cEPCs, and between miR-342-5p and cEPCs. ROC curve analyses showed significant downregulation of miR-342-3p/-5p at HbA_1c > 46.45 mmol/mol, indicating their potential as biomarkers for subclinical CVD. Our findings validated animal studies and confirmed the proangiogenic properties of miR-342-3p/-5p. MiR-342-3p/-5p-based intervention or monitoring may prove to be beneficial in managing CVD. Full article