bluuebunny/crossref_metadata_2025 huggingface dataset:
Hamiltonian formulation of relativistic magnetohydrodynamic accretion on a general spherically symmetric and static black hole: quantum effects on shock states
Authors: Azreg-Aïnou Mustapha , Jamil Mubasher , Noda Sousuke
Published: November 2024

In this paper, our aim is to extend our earlier work [Ahmed et al. in Eur. Phys. J. C 76:280, 2016], investigating an axisymmetric plasma flow with angular momentum onto a spherical black hole. To accomplish that goal, we focus on the case in which the ideal magnetohydrodynamic approximation is valid, utilizing certain conservation laws which arise from particular symmetries of the system. After formulating a Hamiltonian of the physical system, we solve the Hamilton equations and look for critical solutions of (both in and out) flows. Reflecting the difference from the Schwarzschild spacetime, the positions of sonic points (fast magnetosonic point, slow magnetosonic point, Alfvén point) are altered. We explore several kinds of flows including critical, non-critical, global, magnetically arrested and shock induced. Lastly, we analyze the shock states near a specific quantum corrected Schwarzschild black hole and determine that quantum effects do not favor shock states by pushing the shock location outward.
Demonstration of magnetically silent optically pumped magnetometers for the TUCAN electric dipole moment experiment
Authors: Klassen Wolfgang , Ahmed Shomi , Grehan Kiera Pond , Hovde Chris , Madison Kirk W. , Mammei Russell R. , Martin Jeffery W. , McCrea Mark , Mohammadi Tahereh , Momose Takamasa , Opsahl Patrick , Ostapchuk David C. M.
Published: November 2024

We report the performance of a magnetically silent optically pumped cesium magnetometer with a statistical sensitivity of 3.5 pT/$$\sqrt{\textrm{Hz}}$$

Hz

at 1 Hz and a stability of 90 fT over 150 s of measurement. Optical pumping with coherent, linearly-polarized, resonant light leads to a relatively long-lived polarized ground state of the cesium vapour contained in a measurement cell. The state precesses at its Larmor frequency in the magnetic field to be measured. Nonlinear magneto-optical rotation then leads to the rotation of the plane of polarization of a linearly polarized probe laser beam. The rotation angle is modulated at twice the Larmor frequency. A measurement of this frequency constitutes an absolute measurement of the magnetic field magnitude. Featuring purely optical operation, non-magnetic construction, low noise floor, and high stability, this sensor will be used for the upcoming TUCAN electric dipole moment experiment and other highly sensitive magnetic applications. Novel aspects of the system include commercial construction and the ability to operate up to 24 sensors on a single probe laser diode.
Anisotropic charge transport in strongly magnetized relativistic matter
Authors: Ghosh Ritesh , Shovkovy Igor A.
Published: November 2024

We investigate electrical charge transport in hot magnetized plasma using first-principles quantum field theoretical methods. By employing Kubo’s linear response theory, we express the electrical conductivity tensor in terms of the fermion damping rate in the Landau-level representation. Utilizing leading-order results for the damping rates from a recent study within a gauge theory, we derive the transverse and longitudinal conductivities for a strongly magnetized plasma. The analytical expressions reveal drastically different mechanisms that explain the high anisotropy of charge transport in a magnetized plasma. Specifically, the transverse conductivity is suppressed, while the longitudinal conductivity is enhanced by a strong magnetic field. As in the case of zero magnetic field, longitudinal conduction is determined by the probability of charge carriers to remain in their quantum states without damping. In contrast, transverse conduction critically relies on quantum transitions between Landau levels, effectively lifting charge trapping in localized Landau orbits. We examine the temperature and magnetic field dependence of the transverse and longitudinal electrical conductivities over a wide range of parameters and investigate the effects of a nonzero chemical potential. Additionally, we extend our analysis to strongly coupled quark-gluon plasma and study the impact of the coupling constant on the anisotropy of electrical charge transport.
Detecting the late Frasnian
semichatovae
Event on the deep shelf of north Gondwana
Authors: Girard Catherine , Antonio Paul , Camps Pierre , Cornée Jean-Jacques , Feist Raimund , Leredde Christine
Published: November 2024

The
semichatovae
Event is a mid–late Frasnian (Late Devonian) episode of a major marine transgression that coincides with the spread of the conodont
Palmatolepis semichatovae
. The occurrence of this species and the associated event were therefore proposed to define the Middle–Late Frasnian boundary. As this species is not found on the north Gondwana platforms, this event is documented only on the Laurussia marine outer shelves. As such, it is not known in the Frasnian reference section within the Upper Quarry Coumiac, located in the Montagne Noire (southern France). In this contribution, we have used a multidisciplinary approach that combines sedimentology, conodont assemblages, magnetic susceptibility and concentrations of certain elements that are indicative of detrital components to precisely date this event in the absence of
Palmatolepis semichatovae
by means of global-scale correlations. We found that a significant part of the environmental signal has been preserved in the strata, and we could locate the
semichatovae
transgressive event in the cross-section in the lower part of Zone FZ 11. During this period of recurrent environmental perturbations, conodonts responded to sea-level changes only above a certain depth threshold, which is reached only with the
semichatovae
event.
Neural Kernel Regression for Consistent Monte Carlo Denoising
Authors: Wang Qi , Qiao Pengju , Huo Yuchi , Zhai Shiji , Xie Zixuan , Hua Wei , Bao Hujun , Liu Tao
Published: November 2024

Unbiased Monte Carlo path tracing that is extensively used in realistic rendering produces undesirable noise, especially with low samples per pixel (spp). Recently, several methods have coped with this problem by importing unbiased noisy images and auxiliary features to neural networks to either predict a fixed-sized kernel for convolution or directly predict the denoised result. Since it is impossible to produce arbitrarily high spp images as the training dataset, the network-based denoising fails to produce high-quality images under high spp. More specifically, network-based denoising is inconsistent and does not converge to the ground truth as the sampling rate increases. On the other hand, the post-correction estimators yield a blending coefficient for a pair of biased and unbiased images influenced by image errors or variances to ensure the consistency of the denoised image. As the sampling rate increases, the blending coefficient of the unbiased image converges to 1, that is, using the unbiased image as the denoised results. However, these estimators usually produce artifacts due to the difficulty of accurately predicting image errors or variances with low spp. To address the above problems, we take advantage of both kernel-predicting methods and post-correction denoisers. A novel kernel-based denoiser is proposed based on distribution-free kernel regression consistency theory, which does not explicitly combine the biased and unbiased results but constrain the kernel bandwidth to produce consistent results under high spp. Meanwhile, our kernel regression method explores bandwidth optimization in the robust auxiliary feature space instead of the noisy image space. This leads to consistent high-quality denoising at both low and high spp. Experiment results demonstrate that our method outperforms existing denoisers in accuracy and consistency.
A Systematic Literature Review on Blockchain-based Smart Contracts: Platforms, Applications, and Challenges
Authors: Singh Renu , Gupta Ashlesha , Mittal Poonam
Published: November 2024

Blockchain technology has rapidly emerged with a multitude of applications, among which smart contracts have garnered considerable attention. Smart contracts represent a promising solution for streamlining trade and business transactions between untrusted parties without intermediaries. These self-executing pieces of code automatically execute predefined actions when specific conditions are met. Despite the growing enthusiasm for blockchain and smart contracts, researchers believe this powerful combination has not yet reached its full potential. Hence, a systematic study is conducted to explore the various facets of blockchain-based smart contracts comprehensively. The research follows the PRISMA framework and employs two primary approaches: bibliometric analysis and systematic literature review. The process was initiated by formulating targeted search queries within the Scopus database, identifying a total of 1,949 publications spanning from January 2019 to August 2023. Subsequently, a bibliometric analysis was conducted on these publications using VOSViewer and Biblioshiny. Further, the full text of these publications was meticulously screened to isolate those with a significant focus on smart contracts. This led to the identification of 48 publications, each offering unique insights into various smart contract applications. Upon further examination, it was observed that the majority of these publications held rankings within the China Computer Federation, which refers to the qualitative research work in this domain. The study concludes with the current state of blockchain-based smart contracts, their platforms, applications, and challenges and reveals the substantial potential in handling tasks with predefined conditions and security requirements.
Deep Learning Algorithms for Breast Cancer Detection in a UK Screening Cohort: As Stand-alone Readers and Combined with Human Readers
Authors: Hickman Sarah E. , Payne Nicholas R. , Black Richard T. , Huang Yuan , Priest Andrew N. , Hudson Sue , Kasmai Bahman , Juette Arne , Nanaa Muzna , Gilbert Fiona J.
Published: November 2024

Stand-alone deep learning algorithms achieved noninferior performance as individual readers and, when combined with human readers, matched double-reading accuracy in mammographic screening.
Analysis of On-Resistance in 650-V Enhancement-Mode Active-Passivation p-GaN Gate HEMT
Authors: Wu Yanlin , Yang Junjie , Yu Jingjing , Chang Hao , Yang Xuelin , Wang Jinyan , Hao Yilong , Shen Bo , Zhou David , Wang Maojun , Wei Jin
Published: November 2024

This work investigates the resistance distribution of the E-mode GaN-on-Si active-passivation (AP) p-GaN gate high-electron-mobility transistor (HEMT) using the transfer length method (TLM). The AP-HEMT has a unique active-passivation layer that is electrically connected to the p-GaN gate and covers most area of the device. The active-passivation layer changes the way the 2DEG is generated in the device, so the constitution of the device R
ON is expected to differ from the conventional p-GaN gate HEMT (Conv-HEMT). According to our study, the sheet resistance of the 2DEG under the active-passivation layer is lower than that of the access region, leading to the reduced R
ON in AP-HEMT compared to Conv-HEMT. The temperature dependence of the resistance is also investigated. Additionally, AP-HEMT exhibits an improved reverse conduction performance across the temperature range of 25 °C to 150 °C, due to the reduced gate-to-drain resistance in the device.
Impaired endothelial function contributes to cardiac dysfunction: role of mitochondrial dynamics
Authors: Gutierrez-Huerta Cristhian A. , Quiroz-Delfi Giovanni , Faleel Fathima Dhilhani Mohammed , Beyer Andreas M.
Published: November 2024

The endothelial microvasculature is essential for the regulation of vasodilation and vasoconstriction, and improved functioning of the endothelium is linked to improved outcomes for individuals with coronary artery disease (CAD). People with endothelial dysfunction exhibit a loss of nitric oxide (NO)-mediated vasodilation, achieving vasodilation instead through mitochondria-derived H2O2. Mitochondrial dynamics is an important autoregulatory mechanism that contributes to mitochondrial and endothelial homeostasis and plays a role in the formation of reactive oxygen species (ROS), including H2O2. Dysregulation of mitochondrial dynamics leads to increased ROS production, decreased ATP production, impaired metabolism, activation of pathological signal transduction, impaired calcium sensing, and inflammation. We hypothesize that dysregulation of endothelial mitochondrial dynamics plays a crucial role in the endothelial microvascular dysfunction seen in individuals with CAD. Therefore, proper regulation of endothelial mitochondrial dynamics may be a suitable treatment for individuals with endothelial microvascular dysfunction, and we furthermore postulate that improving this microvascular dysfunction will directly improve outcomes for those with CAD.
Impaired antiviral immunity in frequent exacerbators of chronic obstructive pulmonary disease
Authors: Finney Lydia J. , Fenwick Peter , Kemp Samuel V. , Singanayagam Aran , Edwards Michael R. , Belchamber Kylie B. R. , Kebadze Tatiana , Regis Eteri , Donaldson Gavin D. , Mallia Patrick , Donnelly Louise E. , Johnston Sebastian L. , Wedzicha Jadwiga A.
Published: November 2024

COPD exacerbations are commonly triggered by viral infections. Some patients with COPD have frequent exacerbations leading to rapid lung function decline and increased mortality. In this study, antiviral responses (interferons) from bronchial epithelial cells and alveolar macrophages were reduced in patients with COPD compared with healthy participants and further reduced in patients with COPD with frequent exacerbations. Impaired antiviral immunity may lead to frequent COPD exacerbations. Targeted vaccinations and antiviral therapy may reduce exacerbations in COPD.
Citrullinated and malondialdehyde-acetaldehyde-modified fibrinogen activates macrophages and promotes profibrotic responses in human lung fibroblasts
Authors: Aripova Nozima , Duryee Michael J. , Zhou Wenxian , England Bryant R. , Hunter Carlos D. , Klingemann Lauren E. , Aripova Nigina , Nelson Amy J. , Katafiasz Dawn , Bailey Kristina L. , Poole Jill A. , Thiele Geoffrey M. , Mikuls Ted R.
Published: November 2024

This report demonstrates that fibrinogen simultaneously harboring two common posttranslational modifications activates macrophages to secrete platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β. Resulting cross talk between activated macrophages and human lung fibroblasts leads to marked increases in extracellular matrix deposition. These protein modifications are abundant and colocalize in lung tissues from patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD), and the results suggest that agents targeting citrullination and/or malondialdehyde-acetaldehyde (MAA) adduct formation could represent novel therapeutic strategies.
Quantifying the time course of changes in maximal skin wettedness with 7 days of heat acclimation
Authors: Lynch Grant P. , Mavros Yorgi , Jay Ollie
Published: November 2024

Significant increases in ωmax were observed as early as 3 days into a 7-day heat acclimation protocol. These data are the first to report dynamic changes in ωmax with progressive heat acclimation and provide new information about ωmax levels between the standard “unacclimated” and “acclimated” states in existing heat stress models.
Investigation of Thermal Degradation Properties and Chemical Kinetic Characteristics of Biomass Pyrolysis via TG/DTG and FTIR Techniques: Sesame Stalks as Potential Source of Bioenergy in Ethiopia
Authors: Gesese Tesfa Nega , Getahun Eshetu , Getahun Alelign Anmaw
Published: November 2024

The dependence on fossil fuels and the overexploitation of it is a bottlenecked problem of the globe leading to finding alternative renewable resources that may be used as an energy source in place of fossil fuels. Thermogravimetric analysis (TGA) is a technique used to identify potential renewable energy sources. This study investigated the kinetic, thermodynamic parameters, and pyrolysis characteristics of sesame stalk (SS) biomass pyrolysis using thermogravimetric (%) (TG)‐derivative thermogravimetry (DTG) techniques. The pyrolysis was carried out at different heating rates (15, 20, and 25°C/min). The chemical kinetics parameters were determined using isoconversional model‐free methods, including Kissinger–Akahira–Sunose (KAS), the Ozawa–Flynn–Wall (OFW), and model fitting techniques like the Coats–Redfern (CR) model. The thermodynamic parameters (∆H, ∆G, and ∆S) were calculated using kinetic data. The average activation energy for SS biomass was found to be 77.96 and 84.15 kJ/mole for the KAS and OFW methods, respectively. The activation energy (E) for SS biomass from the integral method varied between 29.61–142.58 kJ/mole for reaction order models and 4.90–122.33 kJ/mole for diffusion models. The distributions of pre‐exponential factor (A) for the reaction order models are virtually normal in the range of 0.2–0.7, upon the Eα values obtained using the OFW and KAS approach. The average value of enthalpy, Gibbs free energy, and entropy of SS were also reported. The study suggests that SSs are a potential biomass for sustainable bioenergy production, and kinetic and thermodynamic data are crucial for reactor design for the pyrolysis of SSs.
Correcting Class III Malocclusion Using Multiloop Edgewise Archwire (MEAW) Combines Temporary Anchorage Devices (TADs) With Modified Class III Elastics for Camouflage Treatment of in Adolescent: A Case Report
Authors: Le Lam Nguyen , Do Thao Thi , Le Khanh Phuong Vu
Published: November 2024

Introduction: One of the most difficult types of malocclusion to cure is Class III malocclusion. Maxillary protraction is a common component of orthodontic/surgical treatments for Class III individuals since maxillary retrognathia is the primary factor contributing to their condition.

Objective: A Vietnamese girl of 16 years old presented with severe symptoms of anterior crossbite and Class III malocclusion of the skeletal and dental structures. Among the dental characteristics were a prognathic mandible, retrognathic maxilla, and proclined lower incisors. The medical history revealed no abnormalities.

Methods: Since the patient refused to undergo orthognathic surgery, we suggested using multiloop edgewise archwire (MEAW), which combines temporary anchorage devices (TADs) with modified Class III elastics for camouflage treatment of Class III malocclusion.

Results: This case illustrated the use of TADs. MEAW combines TADs with modified Class III elastics for camouflage therapy. It is a potentially effective treatment option for adolescents diagnosed with Class III skeletal malocclusion.
Unusual Metastasis of Pancreatic Adenocarcinoma Into the Bladder: Two Case Reports and Literature Review
Authors: Zarli Mohamadhusni , Porto Joao G. , Blachman-Braun Ruben , Kryvenko Oleksandr N. , Shah Hemendra N.
Published: November 2024

We described two patients diagnosed with rare bladder metastasis (BM) from pancreatic adenocarcinoma, a prevalent neoplastic disease primarily associated with ductal adenocarcinoma. The overall prognosis for those patients with metastasis is very poor, with a 5‐year survival rate of < 3%. The scarcity of cases in the literature makes this series a significant contribution as it presents the first documented instance of BM originating from pancreatobiliary ampullary cancer and a rare case associated with the Krukenberg tumor. Additionally, we extensively reviewed the literature on the infrequent metastasis of pancreatic cancer to the bladder and provided details of those nine previously reported cases. Given its unusual nature, this report highlights the importance of considering BM in patients with a history of pancreatic carcinoma who present with new‐onset hematuria or upper tract obstruction, stressing the need for comprehensive evaluation and timely management.
Phenolic Profiling and Inhibitory Activities of Cholinesterase and β‐Amyloid Aggregation in Ziziphus Species Fruit Fractions
Authors: El Maaiden Ezzouhra
Published: November 2024

In recent years, there has been growing interest in the potential of medicinal plants for preventing and treating neurodegenerative diseases. This study investigated the neuroprotective properties of aqueous extracts derived from the pulp, seed, and almonds of Ziziphus spina-christi (L.) Desf. and Ziziphus lotus (L.) Lam. These extracts were assessed in vitro for their impact on acetylcholinesterase, butyrylcholinesterase, and β‐amyloid aggregation, all key factors associated with neurodegenerative disorders (NDs). Given the strong connection between NDs and oxidative damage, as well as the role of metal accumulation in exacerbating oxidative stress and amyloid plaque formation, the antioxidant abilities of the extracts were also evaluated using various methods including ferric‐reducing antioxidant power, cupric‐reducing antioxidant capacity, and metal chelating assays. Furthermore, the study analyzed the total phenolic and flavonoid contents using standard spectrophotometric techniques, and the secondary metabolite composition was examined through UHPLC‐DAD analysis. To better understand the relationship between different plant species and their organ types with specific phenolic compounds and biological activities, principal component analysis (PCA) was employed for data analysis. Results revealed the presence of 25 secondary metabolites categorized into phenolic and flavonoid compounds. Interestingly, the seed extracts exhibited the highest bioactivity, significantly inhibiting antioxidant and cholinergic enzymes. In addition, almond extracts displayed promising antiamyloidogenic properties, effectively suppressing oligomers, fibrillation of Aβ42, and the amyloid cascade. In conclusion, this study highlights the potential of seed and almond extracts from Z. spina-christi (L.) Desf. and Z. lotus (L.) Lam. as valuable sources of natural compounds with neuroprotective properties against neurodegenerative diseases.
Specific Detection of RHDV GI.1 and GI.2 by RT‐LAMP‐CRISPR/Cas12a Platform
Authors: Wu Mengting , Chen Mengmeng , Qiu Rulong , Ge Lei , Fan Zhiyu , Hu Bo , Wei Houjun , Li Yiming , Wang Fang , Song Yanhua
Published: November 2024

Rabbit hemorrhagic disease is a highly contagious and acute fatal disease caused by rabbit hemorrhagic disease virus (RHDV). The first outbreak of RHDV2 in 2020 has posed a serious threat to the rabbit breeding industry in China. An effective and specific detection strategy for RHDV GI.1 (RHDV1) and GI.2 (RHDV2) is urgently needed. In this study, we established a reverse transcription loop‐mediated isothermal amplification (RT‐LAMP)‐CRISPR/Cas12a‐based dual readout portable detection platform. The platform showed excellent specificity to identify RHDV1 and RHDV2 strains and no cross‐reaction with other prevalent pathogens of rabbit. The detection limit for RHDV1 and RHDV2 by RT‐LAMP‐CRISPR/Cas12a could reach 10 copies/μl of the VP60 gene per reaction. Furthermore, 74 clinical samples were detected for both RHDV1 and RHDV2. RT‐LAMP‐CRISPR/Cas12a‐based dual readout portable detection platform showed 25.68% (19/74) RHDV1‐positive samples, 43.24% (32/74) RHDV2‐positive samples, and 8.11% (6/74) RHDV1/RHDV2 double positive samples, respectively. The coincidence rates of detection RHDV1 and RHDV2 between RT‐LAMP‐CRISPR/Cas12a and quantitative real‐time‐polymerase chain reaction (qPCR) were both 97.30%. RT‐LAMP‐CRISPR/Cas12a showed higher sensitivity and detection rate compared with qPCR. Moreover, the results were visible to the naked eye within 1.5 h combined with lateral flow strips (LFSs) and visual fluorescence. The RT‐LAMP‐CRISPR/Cas12a portable platform has the advantages of high sensitivity, specificity, fast, low equipment requirements, which can be used in clinical practice in rural areas and resource‐limited settings.
Characterization of Coping with Primary Dysmenorrhea in Women according to Their Level of Physical Activity: A Cross-Sectional Observational Study
Authors: Ibáñez-Vera Alfonso Javier , Cobertera-Pintor María , Tejero-Olalla Lorena del Carmen , Díaz-Mohedo Esther
Published: November 2024

Introduction: Primary dysmenorrhea (PD) is one of the most common gynecological pathologies in women. The aim was to determine the differences in coping with PD in women who practice high-intensity sport, compared to women who are less physically active. Methods: This was a cross-sectional observational study. A total of 476 women were recruited and administered a Google Form multiple-choice questionnaire divided into six sections. The following scales were used: Numerical Pain Rating Scale (NPRS), Pain Catastrophizing Scale (PCS), Menstruation-related Quality of Life Questionnaire (MQOL-22), Tampa Scale for Kinesiophobia (TSK), and Borg scale. Results: The 389 participants meeting the inclusion criteria were divided into three groups according to their score in Borg test: high-intensity physical activity group (n = 178), moderate-intensity physical activity group (n = 101), and low-intensity physical activity group (n = 110) for those scoring under 4. ANOVA analysis showed statistical significance only for PCS (p = 0.024). Tukey group per group comparison determined differences between high-intensity physical activity group and low-intensity physical activity group regarding PCS (p = 0.018). Spearman correlation analysis showed a high relation between PCS and NPRS (r = 0.664) and between MQOL-22 and NPRS (r = −0.562). Conclusion: The intensity of the exercise training does not influence PD-related pain perception nor kinesiophobia. High-intensity exercise reduces catastrophizing when compared with sedentary or low-intensity exercise. Level of catastrophizing is highly related with perceived pain and quality of life in menstruation in these PD patients.
Combination Therapy with Secretome of Reovirus-Infected Mesenchymal Stem Cells and Metformin Improves Anticancer Effects of Irinotecan on Colorectal Cancer Cells in vitro
Authors: Elhamipour Maliheh , Soleimanjahi Hoorieh , Abdoli Asghar , Sharifi Negar , Karimi Hesam , Soleyman Jahi Saeed , Kvistad Ruth
Published: November 2024

Introduction: Irinotecan, a topoismorase 1 inhibitor, has been used for the treatment of colorectal cancer. It was shown that monotherapy alone is largely ineffective. The combination therapy was used for antitumor activity. The synergistic anticancer effects of oncolytic reovirus-infected secretome in combination with irinotecan and metformin are evaluated in vitro. The aim of research was to assess anticancer impacts of ReoT3D, irinotecan, metformin in combination, against murine colorectal cancer cells (CT26). Methods: The L929 and the CT26 colorectal cancerous cell lines were treated in vitro with irinotecan, metformin, the Dearing strain of reovirus serotype 3 (ReoT3D) (V), and the secretome of intact (S) or reovirus-infected murine adipose-derived mesenchymal stem cells (SV). The cell viability was measured by MTT, and the apoptosis rate was analyzed by annexin V-FITC staining and flow cytometry 48 and 72 h after treatment. Results: We found that cells exposed to a combination of SV+Met+I had significantly lower cell viability and higher apoptosis rates as compared to cells exposed to Met+I, 48 and 72 h. These results suggest that metformin in combination with irinotecan and reovirus produces a synergistic effect on cell death, and adding reovirus-infected secretome (SV) to a Met+I regimen induces a higher apoptosis rate compared to Met+I alone. Based on the results, the combination of SV+Met+I has induced more apoptosis than S, SV, SV+I, and SV+Met. Also, all of the combined treatments induced apoptosis significantly versus secretome alone. Discussion: In this in vitro study, we found that the combination of T3D reovirus (oncolytic virus) and metformin with the anticancer drug irinotecan resulted in higher rates of growth inhibition and apoptosis induction in the colorectal cancer cell line. This synergistic effect was even more pronounced when using the combination of secretome derived from reovirus-infected AD-MSCs, metformin, and irinotecan. Conclusion: We highlight that the combination of ReoT3D-derived secretome with irinotecan and metformin showed a synergistic anticancer effect on the CT26 cell line, and this strategy may be considered as a new approach against colorectal cancer in the in vitro and in vivo in future studies.
Development and Validation of a Coagulation Risk Prediction Model for Anticoagulant-Free Hemodialysis: Enhancing Hemodialysis Safety for Patients
Authors: Chen Shufan , Chen Yun , Zhang Wei , Li Haihan , Guo Zining , Ling Keyu , Yu Xiaoli , Liu Fei , Zhu Xiaoping
Published: November 2024

Introduction: This study aimed to develop and validate a risk prediction model for predicting the likelihood of coagulation in patients undergoing anticoagulant-free hemodialysis (HD). Anticoagulant-free HD technique is necessary in patients with contraindications to systemic therapy. Coagulation is a complication of this technique. Unfortunately, no predictive model is currently available to assess the risk of coagulation in anticoagulant-free HD. Methods: We retrospectively analyzed the clinical data from 299 HD sessions involving 164 patients who underwent anticoagulant-free HD between January 2022 and June 2023. To identify the risk factors for coagulation in anticoagulant-free HD, a univariate analysis was performed on 18 independent variables. Logistic regression was used to establish predictive models by identifying factors contributing to coagulation in anticoagulant-free HD. A calibration curve was drawn using regression coefficients and 1,000 bootstrap repetitions to validate our model internally. The performance of the prediction model was evaluated using receiver operating characteristic, area under the curve (AUC), and decision curve analysis (DCA). Results: The incidence of coagulation in patients on anticoagulant-free HD was 35.1%. Logistic regression analysis showed that platelet (PLT), hematocrit (HCT) levels, dialysate type, and age were risk factors for coagulation in anticoagulant-free HD patients (p < 0.05). The Hosmer-Lemeshow test showed p = 0.29, and the AUC is 0.76 (95% CI 0.70–0.80). The optimal critical value was 0.40, yielding a sensitivity of 61.0%, a specificity of 80.4%, and a Youden index of 0.41. Conclusion: In anticoagulant-free HD, there were numerous risk factors and a 35.1% occurrence of coagulation. The constructed coagulation risk prediction model exhibited good predictive and clinical utility and could serve as a reference for the initial assessment and screening of coagulation risk in anticoagulant-free HD.
A Case of Aqueductal Stenosis with Bilateral Papilledema and Abducens Nerve Palsies without Headache
Authors: Nakata Daisuke , Okada Hiroshi , Doi Takayuki , Shimada Yoshiaki , Tanikawa Atsuhiro , Horiguchi Masayuki , Ito Yasuki
Published: November 2024

Introduction: We report a case of aqueductal stenosis presenting with bilateral papilledema and diplopia, notably without headache. Case Presentation: A 16-year-old girl with no relevant medical history presented with a 1-week history of binocular diplopia without any loss of visual acuity in either eye. At the time of her visit, she had no symptoms of headache or vomiting. Examination of eye movements revealed bilateral abduction deficits and fundoscopic examination showed bilateral optic disc swelling. Non-contrast computed tomography of the head indicated hydrocephalus. Contrast-enhanced magnetic resonance imaging of the head revealed significant dilatation of the lateral and third ventricles but not in the fourth ventricle. Sagittal T2-weighted imaging with constructive interference in the steady state showed membranous occlusion of the cerebral aqueduct. The patient underwent an endoscopic third ventriculostomy. Binocular diplopia improved during the early postoperative period. Conclusion: Aqueductal stenosis should be considered in the differential diagnosis for patients presenting with bilateral papilledema and abducens nerve palsies, even in the absence of headache or other neurological findings.
Hypoxia-Treated Adipose Mesenchymal Stem Cells Derived Exosomes Enhance the Therapeutic Effects on Unilateral Ureteral Obstruction Mice
Authors: Zhang Chi , Cai Longjun , Ma Meimei , Xie Xiaohui , Wang Junsheng , Zhang Yuanyuan
Published: November 2024

Introduction: The exosomes from adipose-derived mesenchymal stem cells (AMSCs) had therapeutic effects. However, whether the exosomes derived from hypoxia-treated AMSCs could improve renal functions in unilateral ureteral obstruction (UUO) mice remains unclear. Methods: The exosomes were characterized using a transmission electron microscope and Western blot. Its size distribution was determined using the Zetasizer Nano ZS analysis system. The differentiation ability was assessed by alkaline phosphatase and oil red staining. Consequently, the function of exosomes in inhibiting inflammatory factors was evaluated using an enzyme-linked immunosorbent assay, and apoptosis inhibition was evaluated by Western blot. Finally, the function of exosomes to ameliorate kidney fibrosis was evaluated using quantitative reverse transcription polymerase chain reaction, Western blot, hematoxylin-eosin staining, and Masson staining. Results: The cultured AMSCs could differentiate into osteoblast and adipocyte. Meanwhile, the cultured AMSCs could effectively secrete the exosomes, which were characterized by around 110 nm diameter and surface marker expression. Exosomes derived from hypoxia-treated AMSCs improved renal functions in UUO mice. The mechanism exploration revealed that exosomes could decrease the TNF-α and IL-6 and inhibit cell apoptosis. Finally, the fibrosis-associated protein was reversed, and the renal dysfunctions were ameliorated in UUO mice. Conclusion: The exosomes derived from the hypoxia-treated AMSCs have a better effect than those from normal AMSCs in ameliorating renal dysfunctions in UUO mice.
Association between Monocyte-to-Lymphocyte Ratio and Inflammation in Chronic Kidney Disease: A Cross-Sectional Study
Authors: Zhou Qin , Shao Xiaofei , Xu Li , Zou Hequn , Chen Wenli
Published: November 2024

Introduction: Inflammation plays a key role in chronic kidney disease (CKD). Monocyte-to-lymphocyte ratio (MLR) is a novel inflammatory marker. The purpose of this study was to evaluate the relationship between MLR and inflammation in CKD patients. Methods: In total, 1,809 subjects were recruited from Wanzhai Town, Zhuhai City, between December 2017 and March 2018 for a cross-sectional survey. Patients were categorized based on the absence (hypersensitive C-reactive protein [hsCRP] level ≦3 mg/L) or presence (hsCRP level >3 mg/L) of inflammation. Logistic regression models and MLR quartiles were used to explore the relationship between MLR and inflammation in CKD patients. Results: Among 1,809 subjects, 403 (22.2%) had CKD. Significant differences in systolic blood pressure, estimated glomerular filtration rate, white blood cell (WBC), neutrophil, monocyte, MLR, and interleukin-6 (IL-6) levels were observed between noninflammatory group and inflammatory group. The highest MLR quartile had higher Scr, WBC, neutrophil, monocyte, IL-6, and hsCRP values and lower eGFR and lymphocyte values. Comparing the lowest quartile of MLR, the OR (95% CI) of inflammation risk in the highest quartile was 2.30 (1.24–4.27) after adjustment for confounding factors. The area under the curve of MLR for predicting inflammation was 0.631. The cutoff point for the MLR was 0.153. Conclusion: A high MLR was significantly and independently associated with inflammation in patients with CKD, making MLR a potential marker for inflammation in this demographic. MLR may also predict the severity of CKD.
Survivorship in Chimeric Antigen Receptor T-Cell Therapy Recipients: Infections, Secondary Malignancies, and Non-Relapse Mortality
Authors: Tix Tobias , Subklewe Marion , von Bergwelt-Baildon Michael , Rejeski Kai
Published: November 2024

Background: Chimeric antigen receptor (CAR) T-cell therapy has significantly advanced the treatment of hematologic malignancies, offering curative potential for patients with relapsed or refractory disease. However, the long-term survivorship of these patients is marked by unique challenges, particularly immune deficits and infectious complications, second primary malignancies (SPMs), and non-relapse mortality (NRM). Understanding and addressing these risks is paramount to improving patient outcomes and quality of life. Summary: This review explores the incidence and risk factors for NRM and long-term complications following CAR T-cell therapy. Infections are the leading cause of NRM, accounting for over 50% of cases, driven by neutropenia, hypogammaglobulinemia, and impaired cellular immunity. SPMs, including secondary myeloid and T-cell malignancies, are increasingly recognized, prompting the FDA to issue a black box warning, although their direct link to CAR T cells remains disputed. While CAR T-cell-specific toxicities like cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome contribute to morbidity, they represent only a minority of NRM cases. The management of these complications is critical as CAR T-cell therapy is being evaluated for broader use, including in earlier treatment lines and for non-malignant conditions like autoimmune diseases. Key Messages: CAR T-cell therapy has revolutionized cancer treatment, but survivorship is complicated by infections, SPMs, and ultimately endangered by NRM. Prophylactic strategies, close monitoring, and toxicity management strategies are key to improving long-term outcomes.
Safety and Efficacy of Thrombectomy in Vietnamese Stroke Patients Selected through Perfusion Imaging with an Onset Time between 6 and 24 Hours
Authors: Pham Binh Nguyen , Tran Hang T. Minh , Nguyen An Thai Thanh , Pham Huan Nguyen , Truong Anh Tuan Le , Nguyen Trung Quoc , Nguyen Huong Bich Thi , Nguyen Tri Quang , Do Huy Quoc , Le Tra Vu Son , Tran Vu Thanh , Nguyen Ryan Anh-Quang , Nguyen Huy , Nguyen Thang Ba , Nguyen Thang Huy
Published: November 2024

Introduction: Recent trials have demonstrated the remarkable benefit of endovascular treatment (EVT) up to 24 h in patients with large vessel occlusion (LVO) and target mismatch profiles; however, benefits of late-window EVT in Vietnamese population remain poorly understood. This study aims to evaluate the real-world outcomes of EVT in acute ischemic stroke (AIS) patients selected using perfusion imaging within the 6–24-h window. Methods: This is a prospective study of consecutive patients with anterior circulation LVO stroke who underwent EVT within 6–24 h after last known well between August 2022 and March 2024. Patients were selected based on the DAWN/DEFUSE-3 criteria (Perfusion-RAPID, iSchemaView). The primary outcome was the proportion of patients with functional independence at 90 days (modified Rankin Scale score of 0–2). The secondary outcomes were successful reperfusion defined by thrombolysis in cerebral infarction (TICI) ≥2b on the final procedure and subgroup analysis between good (hypoperfusion intensity ratio [HIR] <0.4) and poor collaterals (HIR ≥0.4) groups. Safety outcomes were mortality rate and symptomatic intracranial hemorrhage (sICH). Results: Of 122 enrolled patients, 68% met inclusion criteria of DEFUSE-3 trial, 61% met DAWN trial criteria. Mean age was 66 years, median baseline NIHSS was 13, median time from stroke onset to hospital arrival was 12.55 h (9.50–16.48), and median infarct volume was 11.5 mL. The rate of functional independence at 90 days was 45.9%. Successful reperfusion (TICI score of ≥2b) was achieved by 83.6% of cases. The 90-day mortality rate was 10.7%; sICH was reported in 8 patients (6.6%). Patients with good collaterals had better functional outcome. Conclusions: This real-world observational study suggests that late-window EVT may be safe and effective in eligible Vietnamese patients selected based on perfusion imaging, thus supporting its practical use in this patient population. HIR is a robust indicator of collateral status and could made it a valuable addition to stroke imaging workup in clinical setting.
Perfusion Staining Methods for Visualization of Intact Microvascular Networks in Whole Mount Skeletal Muscle Preparations
Authors: Hyde-Lay Barbara M. , Charter Mackenzie E. , Murrant Coral L.
Published: November 2024

Introduction: Visualization of the intact microvascular network in skeletal muscle requires labeling the entire network in whole mount preparations where muscle fibre length can be set to near optimal but the tools to do this are not clear. Methods: We intravascularly injected CD-1 mice with different fluorescently labelled lectins (fluorescent isolectin GS-IB4 [ISO], wheat germ agglutinin [WGA], lycopersicon esculentum [LYCO]) or FITC-labelled gel. Soleus, extensor digitorum longus, diaphragm, gluteus maximus and cremaster muscles were excised, pinned at optimal sarcomere length and viewed using fluorescence microscopy. Results: WGA and LYCO were effective at labeling the entire vascular network with WGA labeling capillaries more brightly. ISO labelled the arteriolar vasculature and early segments of the capillaries but not the full length of the capillaries or the venular network. FITC-labelled gel was effective at labelling the microvascular network but not all small vessels were consistently labelled. The pattern of staining for each labelling method was similar across all muscle fibre-types tested. Conclusions: WGA was optimal for perfusion labeling and visualization of the intact microvascular network in whole mount skeletal muscle preparations and can be used in combination with ISO to distinguish the arteriolar and venous sides of the network.
Surface Rendering of Cross-Sectional Imaging and Medical Illustration for Perinatal Planning in Conjoined Twins
Authors: Luks Francois I. , Monteagudo Julie , Collins Scott , Eyerly-Webb Stephanie A. , Howley Lisa W. , Lillegard Joseph B. , Lobeck Inna N. , Beninati Michael J.
Published: November 2024

Introduction: Surface rendering of diagnostic imaging data can reveal hidden conditions with an almost life-like realism. However, early gestation images alone are often insufficient to accurately predict postnatal anatomy. Yet, time-sensitive decisions may have to be made before detailed imaging becomes possible. In this case series, we evaluate how combining medical illustration with cross-sectional diagnostic imaging can enhance the accuracy and clinical value of early visualization of conjoined twins. Methods: Early gestation magnetic resonance imaging scans underwent semiautomated computerized post hoc manipulation to allow the medical illustrator to create the most effective images of the twins. Results: Four sets of conjoined twins were diagnosed before 17 weeks. Surface modeling allowed spatial manipulation of the twins to highlight their anatomic connections. Further volumetric enhancement and critical interpretation of the models assisted the illustrator in creating life-like, accurate images of the twins. These illustrations allowed parents to visualize the likely presentation at birth and helped the multidisciplinary team to plan postnatal management. Conclusion: Surface rendering and surface modeling can be combined with medical illustration to create realistic, informative images of developing fetuses, using a level of detail that is tailored to the intended audience. This may be particularly useful in visualizing complex anomalies like conjoined twins.
Emerging Role of SH3BP2 as Regulator of Immune and Nonimmune Cells in Nephrotic Syndrome
Authors: Srivastava Tarak , Sharma Mukut
Published: November 2024

Background: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are major forms of nephrotic syndrome that remain difficult to treat. MCD and FSGS have distinct but also overlapping clinical, histological, metabolic, and molecular features. Effective use of immunosuppressive drugs, activated immune cells, altered cytokine profiles, and upregulated signaling pathways suggest a link between immune dysfunction and nephrotic syndrome, but the exact mechanism of immunopathogenesis is unclear. Immune dysfunction is an area of ongoing research for identifying novel molecular targets for treating nephrotic syndrome. However, the available animal models do not directly address the role of immune dysfunction in nephrotic syndrome. Summary: Genetic analysis indicates that heterogeneous genes related to the podocyte-specific proteins may indirectly cause damage to filtration barrier and influence the onset and progression of nephrotic syndrome. SH3BP2 protein regulates several pathways through its role as a scaffold for many signaling mediators and enzymes. SH3BP2 is expressed in immune as well as in nonimmune cells including podocytes. The role of SH3BP2 is discussed in the context of cells and molecules of adaptive and innate immune systems. Available information on the importance of SH3BP2 in diseases other than nephrotic syndrome and its role in the immunopathogenesis of human nephrotic syndrome are summarized. We outline the key features of a transgenic mouse strain with a gain-in-function mutation (Sh3bp2KI/KI) as a potential model to study immunopathogenesis of nephrotic syndrome. Key Messages: Non-receptor, non-catalytic proteins such as SH3BP2 are a novel group of proteins that regulate the innate and adaptive immune responses in nephrotic syndrome. New evidence suggests a critical role of SH3BP2 in immunopathogenesis of nephrotic syndrome. Our recent results demonstrate that transgenic mice (Sh3bp2KI/KI) with a gain-in-function mutation will likely be a unique model to study immunopathogenesis of nephrotic syndrome.
Functional Role of the Incisive Duct in Neonatal Dogs
Authors: Sanmartín-Vázquez Eva , Ortiz-Leal Irene , Torres Mateo V. , Kalak Patrycja , Kubiak-Nowak Dominika , Dzięcioł Michał , Sanchez-Quinteiro Pablo
Published: November 2024

Introduction: The detection of chemical signals by the vomeronasal organ (VNO) is critical for mammals from an early age, influencing behaviors such as suckling and recognition of the mother. Located at the base of the nasal cavity, the VNO features a duct covered with a sensory epithelium. A critical aspect of VNO functionality is the efficient access of stimuli from the nasal and oral cavities to the receptors. In adult dogs, it has been demonstrated how the vomeronasal duct (VD) communicates to the environment through the incisive duct (ID). In newborn puppies, the existence of functional communication between the ID and the VD has not been confirmed to date, raising doubts about the potential physiological obliteration of the ID. Determining this aspect is necessary to evaluate the role played by chemocommunication in the survival and socialization of puppies. Methods: This study employs serial histological staining to examine the presence and functionality of the ID in neonatal dogs. Additionally, a histochemical study was conducted using periodic acid-Schiff and Alcian Blue staining, along with labeling with six lectins to characterize the expression of glycoconjugates in the incisive papilla and in the area between the ID and the VD. Results: The histological study has confirmed both the existence of functional communication between both ducts in perinatal puppies and the dual functional communication of the ID with the oral and nasal cavities. Lectin labeling has allowed for the characterization of the glycoconjugate expression profile in the papilla and ID, showing significant differences between lectins. Conclusion: The ID is associated with a sophisticated cartilaginous complex that prevents its collapse, as well as erectile tissue that acts as a cushion, facilitating its action under pressure induced by sampling behaviors such as tonguing. This investigation demonstrates the communicative capabilities of the VNO during the perinatal stage in dogs.