bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin Resistance Is the Main Characteristic of Metabolically Unhealthy Obesity (MUO) Associated with NASH in Patients Undergoing Bariatric Surgery
Authors: Schmitz Sophia M. , Storms Sebastian , Koch Alexander , Stier Christine , Kroh Andreas , Rheinwalt Karl P. , Schipper Sandra , Hamesch Karim , Ulmer Tom F. , Neumann Ulf P. , Alizai Patrick H.
Published: May 2023

(1) Background: Metabolically healthy obesity (MHO) is a concept that applies to obese patients without any elements of metabolic syndrome (metS). In turn, metabolically unhealthy obesity (MUO) defines the presence of elements of metS in obese patients. The components of MUO can be divided into subgroups regarding the elements of inflammation, lipid and glucose metabolism and cardiovascular disease. MUO patients appear to be at greater risk of developing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) compared to MHO patients. The aim of this study was to evaluate the influence of different MUO components on NAFLD and NASH in patients with morbid obesity undergoing bariatric surgery. (2) Methods: 141 patients undergoing bariatric surgery from September 2015 and October 2021 at RWTH Aachen university hospital (Germany) were included. Patients were evaluated pre-operatively for characteristics of metS and MUO (HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension). Intraoperatively, a liver biopsy was taken from the left liver lobe and evaluated for the presence of NAFLD or NASH. In ordinal regression analyses, different factors were evaluated for their influence on NAFLD and NASH. (3) Results: Mean BMI of the patients was 52.3 kg/m2 (36–74.8, SD 8.4). Together, the parameters HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension accounted for a significant amount of variance in the outcome, with a likelihood ratio of χ2 (9) = 41.547, p < 0.001, for predicting the presence of NASH. Only HOMA was an independent predictor of NASH (B = 0.102, SE = 0.0373, p = 0.007). Evaluation of steatosis showed a similar trend (likelihood ratio χ2 (9) = 40.272, p < 0.001). Independent predictors of steatosis were HbA1c (B = 0.833, SE = 0.343, p = 0.015) and HOMA (B = 0.136, SE = 0.039, p < 0.001). (4) Conclusions: The above-mentioned model, including components of MUO, was significant for diagnosing NASH in patients with morbid obesity undergoing bariatric surgery. Out of the different subitems, HOMA independently predicted the presence of NASH and steatosis, while HbA1c independently predicted steatosis and fibrosis. Taken together, the parameter of glucose metabolism appears to be more accurate for the prediction of NASH than the parameters of lipid metabolism, inflammation or the presence of cardiovascular disease.
The Concentration of Pro- and Antiangiogenic Factors in Saliva and Gingival Crevicular Fluid Compared to Plasma in Patients with Peripheral Artery Disease and Type 2 Diabetes
Authors: Gregorczyk-Maga Iwona , Szustkiewicz-Karoń Aleksandra , Gajda Mateusz , Kapusta Maria , Maga Wojciech , Schönborn Martyna
Published: May 2023

Several studies have investigated various biomarkers in relation to peripheral artery disease (PAD) for disease stratification and early-onset detection. In PAD, angiogenesis is required for tissue restoration and tissue perfusion. Considering changes in angiogenesis in patients with PAD, angiogenic factors could be explored as one of the new prognostic molecules. In recent studies, saliva and gingival crevicular fluid (GCF) have gained recognition as new, easily obtained diagnostic materials. This study aimed to compare the levels of selected circulating angiogenic factors (VEGF-A, PDGF-BB, and ANG-1) in unstimulated whole saliva (WS) and GCF versus plasma at three points in time to find possible correlations between their concentrations among patients with PAD and diabetes type 2 in 32 patients with Rutherford stages 5 and 6. A significant positive correlation has been demonstrated between circulating PDGF-BB levels in GCF and plasma. In most cases, comorbidities do not have an impact on the change in general correlation for the whole group. Our results clearly showed that GCF could be a good source for PDGF assessment. However, future studies with a larger number of subjects are warranted to confirm this finding and identify the most accurate angiogenic biomarkers in saliva or GCF that could be applied in clinical practice.
Insight into the Inter-Organ Crosstalk and Prognostic Role of Liver-Derived MicroRNAs in Metabolic Disease Progression
Authors: Goncalves Bruno de Souza , Meadows Avery , Pereira Duane G. , Puri Raghav , Pillai Sneha S.
Published: May 2023

Dysfunctional hepatic metabolism has been linked to numerous diseases, including non-alcoholic fatty liver disease, the most common chronic liver disorder worldwide, which can progress to hepatic fibrosis, and is closely associated with insulin resistance and cardiovascular diseases. In addition, the liver secretes a wide array of metabolites, biomolecules, and microRNAs (miRNAs) and many of these secreted factors exert significant effects on metabolic processes both in the liver and in peripheral tissues. In this review, we summarize the involvement of liver-derived miRNAs in biological processes with an emphasis on delineating the communication between the liver and other tissues associated with metabolic disease progression. Furthermore, the review identifies the primary molecular targets by which miRNAs act. These consolidated findings from numerous studies provide insight into the underlying mechanism of various metabolic disease progression and suggest the possibility of using circulatory miRNAs as prognostic predictors and therapeutic targets for improving clinical intervention strategies.
Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder
Authors: De Marchi Fabiola , Franjkic Toni , Schito Paride , Russo Tommaso , Nimac Jerneja , Chami Anna A. , Mele Angelica , Vidatic Lea , Kriz Jasna , Julien Jean-Pierre , Apic Gordana , Russell Robert B. , Rogelj Boris , Cannon Jason R. , Baralle Marco , Agosta Federica , Hecimovic Silva , Mazzini Letizia , Buratti Emanuele , Munitic Ivana
Published: May 2023

Proteinopathy and neuroinflammation are two main hallmarks of neurodegenerative diseases. They also represent rare common events in an exceptionally broad landscape of genetic, environmental, neuropathologic, and clinical heterogeneity present in patients. Here, we aim to recount the emerging trends in amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) spectrum disorder. Our review will predominantly focus on neuroinflammation and systemic immune imbalance in ALS and FTD, which have recently been highlighted as novel therapeutic targets. A common mechanism of most ALS and ~50% of FTD patients is dysregulation of TAR DNA-binding protein 43 (TDP-43), an RNA/DNA-binding protein, which becomes depleted from the nucleus and forms cytoplasmic aggregates in neurons and glia. This, in turn, via both gain and loss of function events, alters a variety of TDP-43-mediated cellular events. Experimental attempts to target TDP-43 aggregates or manipulate crosstalk in the context of inflammation will be discussed. Targeting inflammation, and the immune system in general, is of particular interest because of the high plasticity of immune cells compared to neurons.
Simple, Fast and Convenient Magnetic Bead-Based Sample Preparation for Detecting Viruses via Raman-Spectroscopy
Authors: Pahlow Susanne , Richard-Lacroix Marie , Hornung Franziska , Köse-Vogel Nilay , Mayerhöfer Thomas G. , Hniopek Julian , Ryabchykov Oleg , Bocklitz Thomas , Weber Karina , Ehricht Ralf , Löffler Bettina , Deinhardt-Emmer Stefanie , Popp Jürgen
Published: May 2023

We introduce a magnetic bead-based sample preparation scheme for enabling the Raman spectroscopic differentiation of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-positive and -negative samples. The beads were functionalized with the angiotensin-converting enzyme 2 (ACE2) receptor protein, which is used as a recognition element to selectively enrich SARS-CoV-2 on the surface of the magnetic beads. The subsequent Raman measurements directly enable discriminating SARS-CoV-2-positive and -negative samples. The proposed approach is also applicable for other virus species when the specific recognition element is exchanged. A series of Raman spectra were measured on three types of samples, namely SARS-CoV-2, Influenza A H1N1 virus and a negative control. For each sample type, eight independent replicates were considered. All of the spectra are dominated by the magnetic bead substrate and no obvious differences between the sample types are apparent. In order to address the subtle differences in the spectra, we calculated different correlation coefficients, namely the Pearson coefficient and the Normalized cross correlation coefficient. By comparing the correlation with the negative control, differentiating between SARS-CoV-2 and Influenza A virus is possible. This study provides a first step towards the detection and potential classification of different viruses with the use of conventional Raman spectroscopy.
Irritability Moderates the Association between Cognitive Flexibility Task Performance and Related Prefrontal Cortex Activation in Young Children
Authors: Li Yanwei , Grabell Adam S. , Perlman Susan B.
Published: May 2023

The association between cognitive flexibility and related neural functioning has been inconsistent. This is particularly true in young children, where previous studies have found heterogenous results linking behavior and neural function, raising the possibility of unexplored moderators. The current study explored the moderating role of dimensional irritability in the association between cognitive flexibility task performance and prefrontal activation in young children. A total of 106 3- to 7-year-old children were recruited to complete a custom-designed, child-adapted, cognitive flexibility task, and 98 of them were included in the data analysis. The children’s dorsolateral prefrontal cortex activation was monitored using functional near-infrared spectroscopy, and their levels of irritability were reported by parents using the MAP-DB Temper Loss subscale. Results indicated that the mean reaction time of the cognitive flexibility task was negatively correlated with concurrent prefrontal activation. No evidence was found for the association between task accuracy and prefrontal activation. Moreover, irritability moderated the association between the mean reaction time and prefrontal activation. Children high in irritability exhibited a stronger negative association between the mean reaction time and related prefrontal activation than children low in irritability. The moderating model suggested a novel affective–cognitive interaction to investigate the associations between cognitive task performance and their neural underpinnings.
A Machine Learning Approach to the Diagnosis of Autism Spectrum Disorder and Multi-Systemic Developmental Disorder Based on Retrospective Data and ADOS-2 Score
Authors: Briguglio Marilena , Turriziani Laura , Currò Arianna , Gagliano Antonella , Di Rosa Gabriella , Caccamo Daniela , Tonacci Alessandro , Gangemi Sebastiano
Published: May 2023

Early and accurate diagnosis of autism spectrum disorders (ASD) and tailored therapeutic interventions can improve prognosis. ADOS-2 is a standardized test for ASD diagnosis. However, owing to ASD heterogeneity, the presence of false positives remains a challenge for clinicians. In this study, retrospective data from patients with ASD and multi-systemic developmental disorder (MSDD), a term used to describe children under the age of 3 with impaired communication but with strong emotional attachments, were tested by machine learning (ML) models to assess the best predictors of disease development as well as the items that best describe these two autism spectrum disorder presentations. Maternal and infant data as well as ADOS-2 score were included in different ML testing models. Depending on the outcome to be estimated, a best-performing model was selected. RIDGE regression model showed that the best predictors for ADOS social affect score were gut disturbances, EEG retrievals, and sleep problems. Linear Regression Model showed that term pregnancy, psychomotor development status, and gut disturbances were predicting at best for the ADOS Repetitive and Restricted Behavior score. The LASSO regression model showed that EEG retrievals, sleep disturbances, age at diagnosis, term pregnancy, weight at birth, gut disturbances, and neurological findings were the best predictors for the overall ADOS score. The CART classification and regression model showed that age at diagnosis and weight at birth best discriminate between ASD and MSDD.
A Cross-Sectional Study Using STROBE Platform to Examine Sleep Characteristics, Mental Health and Academic Performance of Female Applied Medical Sciences Students in the Southwest of Saudi Arabia
Authors: Esht Vandana , Alshehri Mohammed M. , Bautista Marissa J. , Sharma Abhishek , Alshamrani Meshal , Alenazi Aqeel M. , Alqahtani Bader A. , Alhowimel Ahmed S. , Hakamy Ali , Abdelwahab Siddig Ibrahim
Published: May 2023

Background: Medical students are expected to excel in their academics. Hence exposing them to a certain amount of strain may sometimes cause sleep disruptions. The purpose of this study was to determine the sleep quality among Saudi Applied Medical Sciences students and its potential connections with their academic performance and mental health. Methods: This online cross-sectional questionnaire-based study was conducted at Jazan University’s College of Applied Medical Sciences in Saudi Arabia. The Pittsburgh Sleep Quality Index (PSQI), a known indicator of sleep quality, a validated mental health measure; Depression Anxiety Stress Scales-21 (DASS-21), and Academic Performance Scale (APS) with 89 internal consistencies were included in the questionnaire. The cumulative grade point average (GPA) was also used as a covariate to evaluate students’ academic success. Results: 112 people responded (response rate = 93%), and 105 of them presented comprehensive information about their backgrounds, way of life, academic standing, sleep patterns, and mental health. Participants’ average GPA and APS scores were 4.23 ± 0.52 and 33.16 ± 5.63, respectively. The mean global PSQI score was 6.47 with 2.34 of standard deviation (SD). The majority of individuals (60%) had poor sleep quality particularly due to abnormal sleep latency and lesser sleep duration, as determined by their PSQI score. The prevalence rates for depression, anxiety, and stress were higher; 53%, 54% and 40%, respectively. Both depression and anxiety were substantially correlated with poor sleep quality (p-value = 0.008, p-value = 0.01, respectively). Sleep quality had no significant effect on GPA while global PSQI and depression were significantly negatively correlated with an APS score of participants (p-value = 0.007 and 0.015, respectively). Conclusions: Higher rates of poor sleep quality and psychologically negative emotions were prevalent. Unhealthy sleep patterns were linked to increased levels of anxiety and depression. Self-perceived academic performance was negatively impacted by inadequate sleep and negative emotions, despite the fact that the GPA results were unaffected.
Experimental Study of the Concrete Cracking Behavior of an Immersed Tunnel under Fire
Authors: Duan Jintao , Qiu Peiyun , Liu Jianyong , Wu Xin
Published: May 2023

This study investigates the impact of fire on the cracking behavior of immersed tunnels. A reduced-scale (1:5) model of an immersed tunnel was constructed to conduct fire tests in both traffic tubes using the HCinc curve as the applied fire. Temperature field changes were carefully monitored during the test by thermocouples and infrared thermography on the outer surface of the tunnel’s ceiling. The continuous temperature field and temperature changes in the concrete cracks were recorded by infrared thermography. By integrating the temperature field distribution in concrete and the behavior of concrete cracking, an analysis of the depth of concrete cracking in the immersed tunnel under fire was conducted. The concrete cracks exceeded 150 mm at 95 min of the fire test. The results indicate that the inner concrete exposed to fire undergoes thermal expansion, leading to tensile cracking of the outer concrete. Additionally, the fire-exposed surface of the tunnel is vulnerable to cracking due to a temperature decrease. Thus, the design of fire resistance of immersed tunnels should take into consideration the potential for concrete cracking caused by thermal strain.
Working Stress Measurement of Prestressed Rebars Using the Magnetic Resonance Method
Authors: Xia Junfeng , Zhang Senhua , Liao Leng , Liu Huiling , Sun Yisheng
Published: May 2023

Prestressed rebars are usually used to apply vertical prestress to concrete to prevent web cracking. The reduction of working stress will affect the durability of the structure. However, the existing working stress detection methods for prestressed rebars still need to be improved. To monitor the working stress of rebars, a magnetic resonance sensor was introduced to carry out experimental research. The correlation between rebar stress and the sensor’s induced voltage was theoretically analyzed using the magnetoelastic effect and magnetic resonance theory. A working stress monitoring method for prestressed rebars based on magnetic resonance was proposed. Working stress monitoring experiments were carried out for 16 mm, 18 mm, and 20 mm diameter rebars. The results showed that the induced voltage peak-to-peak value and the rebar prestress were nonlinearly correlated under different working conditions. Correlations between the characteristic indicators and the rebar working stress were obtained using nonlinear and linear fit. The cubic polynomial segmented fit outperformed the gradient overall linear fit, with the goodness of fit R2 greater than 0.96. The average relative error values of working stress monitoring were less than 5% under different working conditions. This provides a new method for working stress measurement of vertical prestressed rebars.
Damage Identification of Concrete Arch Dams Based on Wavelet Packets and Neural Networks
Authors: Si Zhihao , Pan Jianwu , Yang Xi
Published: May 2023

A dam may be damaged by occasional extreme loads such as major earthquakes or terrorist attacks during its service. According to the needs of emergency assessment, this paper studies a rapid damage identification method for damage location and damage degree in concrete arch dams which is based on the dynamic characteristics of concrete arch dam data, using wavelet transform, wavelet packet decomposition, a BP neural network and D-S evidence theory for damage identification and related experimental verification. The results show that the relative difference of the curvature mode (δφk), the wavelet coefficient (Wfk) and the relative difference of the wavelet packet energy (δKk) can effectively identify the damage position of the arch dam, and δφk in the first four modalities has the best overall recognition effect; Wfk requires a high number of measurement points, which should be at least 64 or as close as possible; δKk has a better damage recognition effect than the first two at the same number of measurement points. D-S evidence theory significantly improves the damage identification effect and reduces the misjudgment of the single-damage method. The trained neural network can effectively identify the damage degree based on the data of one measuring point when there is a single damage instance, and the number of measuring points should be no fewer than two when there is double damage. The test results verify the feasibility of the method in this paper, which can provide a theoretical basis for a post-disaster emergency assessment information system of concrete arch dams.
Effect of Elevated Temperatures on Mechanical Properties of Spliced and Non-Spliced Steel Reinforcements: Experimental Study
Authors: Thongchom Chanachai , Kongwat Suphanut , Jaitrong Jongchai , Keawsawasvong Suraparb , Bui Linh Van Hong , Stitmannaithum Boonchai , Mousa Saeed
Published: May 2023

Steel reinforcement is an essential part of reinforced concrete, providing structural strength. In case of fire, the steel reinforcement severely loses its mechanical properties, leading to structural collapse in some elevated temperatures. Thus, this work mainly investigates the mechanical properties of spliced and non-spliced steel reinforcements after being exposed to 500 °C, 700 °C, and 900 °C. The results show that the mechanical properties of steel reinforcements significantly change after exposure to temperatures exceeding 500 °C, and the diameter of steel reinforcements does not considerably affect post-fire properties. The proposed equations from previous work were also compared to the testing results in terms of post-fire stress–strain curves and mechanical properties, resulting in overestimation at temperatures of 700 °C and 900 °C. The study finds that using a mechanical coupler has the potential to increase the residual yield strength at a temperature of 500 °C, but it lacks post-fire elongation at a temperature of 700 °C due to observed failure behavior after testing. Furthermore, the failure occurred at the mechanical couplers when the exposure temperature reached 700 °C. The modulus of elasticity of non-splices was the most critical parameter, which was maximally different by 23.9% compared to non-spliced steel reinforcements.
Optimizing Interfaces of Construction Processes by Digitalization Using the Example of Hospital Construction in Germany
Authors: Hartmann Sabine , Gossmann Dirk , Kalmuk Suzan , Klemt-Albert Katharina
Published: May 2023

In hospital construction, additional challenges must be considered, such as an increased number of stakeholders and building trades, such as medical and laboratory technology. Due to the increasing requirements and challenges, associated construction processes are becoming more intricate. Especially for complex building types, the effects of this development are clearly noticeable and cause considerable disruptions to the construction process. A main difficulty constitutes the missing definition of the interfaces of building trades and participants. In the present study, interfaces in hospital construction were identified and analyzed by guided interviews with experts from the health sector. The qualitative content analysis, according to Mayring, was used for the evaluation to derive appropriate solution approaches. This paper presents the interfaces using the example of hospital construction in Germany and general approaches of optimization. Hereby, the digital method Building Information Modeling (BIM) plays a decisive role in the optimization of interfaces, especially in complex buildings. Furthermore, a task and building trade control matrix is required to better coordinate the interfaces. The identified approach intends to alleviate potential disputes and misunderstandings among stakeholders, as well as to improve time and financial predictability, which are particularly valuable during inflationary periods.
Improved Data-Driven Building Daily Energy Consumption Prediction Models Based on Balance Point Temperature
Authors: Yang Hao , Ran Maoyu , Feng Haibo
Published: May 2023

The data-driven models have been widely used in building energy analysis due to their outstanding performance. The input variables of the data-driven models are crucial for their predictive performance. Therefore, it is meaningful to explore the input variables that can improve the predictive performance, especially in the context of the global energy crisis. In this study, an algorithm for calculating the balance point temperature was proposed for an apartment community in Xiamen, China. It was found that the balance point temperature label (BPT label) can significantly improve the daily energy consumption prediction accuracy of five data-driven models (BPNN, SVR, RF, LASSO, and KNN). Feature importance analysis showed that the importance of the BPT label accounts for 25%. Among all input variables, the daily minimum temperature is the decisive factor that affects energy consumption, while the daily maximum temperature has little impact. In addition, this study also provides recommendations for selecting these model tools under different data conditions: when the input variable data is insufficient, KNN has the best predictive performance, while BPNN is the best model when the input data is sufficient.
Drug Repurposing in Oncology: A Systematic Review of Randomized Controlled Clinical Trials
Authors: Ioakeim-Skoufa Ignatios , Tobajas-Ramos Natalia , Menditto Enrica , Aza-Pascual-Salcedo Mercedes , Gimeno-Miguel Antonio , Orlando Valentina , González-Rubio Francisca , Fanlo-Villacampa Ana , Lasala-Aza Carmen , Ostasz Ewelina , Vicente-Romero Jorge
Published: May 2023

Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development procedures, reducing time and risk. This systematic review identified the most recent randomized controlled clinical trials that focus on drug repurposing in oncology. We found that only a few clinical trials were placebo-controlled or standard-of-care-alone-controlled. Metformin has been studied for potential use in various types of cancer, including prostate, lung, and pancreatic cancer. Other studies assessed the possible use of the antiparasitic agent mebendazole in colorectal cancer and of propranolol in multiple myeloma or, when combined with etodolac, in breast cancer. We were able to identify trials that study the potential use of known antineoplastics in other non-oncological conditions, such as imatinib for severe coronavirus disease in 2019 or a study protocol aiming to assess the possible repurposing of leuprolide for Alzheimer’s disease. Major limitations of these clinical trials were the small sample size, the high clinical heterogeneity of the participants regarding the stage of the neoplastic disease, and the lack of accounting for multimorbidity and other baseline clinical characteristics. Drug repurposing possibilities in oncology must be carefully examined with well-designed trials, considering factors that could influence prognosis.
Calprotectin in Patients with Rheumatic Immunomediated Adverse Effects Induced by Checkpoints Inhibitors
Authors: Frade-Sosa Beatriz , Chacur Chafik Alejandro , Augé Josep M. , Ponce Andrés , Sarmiento-Monroy Juan C. , Azuaga Ana Belén , Sapena Nuria , Ramírez Julio , Ruiz-Esquide Virginia , Morlà Rosa , Farietta Sandra , Corzo Patricia , Cañete Juan D. , Sanmartí Raimon , Gómez-Puerta José A.
Published: May 2023

Background: this is an exploratory study to evaluate calprotectin serum levels in patients with rheumatic immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) treatment. Methods: this is a retrospective observational study including patients with irAEs rheumatic syndromes. We compared the calprotectin levels to those in a control group of patients with RA and with a control group of healthy individuals. Additionally, we included a control group of patients treated with ICI but without irAEs to check calprotectin levels. We also analysed the performance of calprotectin for the identification of active rheumatic disease using receiver operating characteristic curves (ROC). Results: 18 patients with rheumatic irAEs were compared to a control group of 128 RA patients and another group of 29 healthy donors. The mean calprotectin level in the irAE group was 5.15 μg/mL, which was higher than the levels in both the RA group (3.19 μg/mL) and the healthy group (3.81 μg/mL) (cut-off 2 μg/mL). Additionally, 8 oncology patients without irAEs were included. In this group, calprotectin levels were similar to those of the healthy controls. In patients with active inflammation, the calprotectin levels in the irAE group were significantly higher (8.43 μg/mL) compared to the RA group (3.94 μg/mL). ROC curve analysis showed that calprotectin had a very good discriminatory capacity to identify inflammatory activity in patients with rheumatic irAEs (AUC of 0.864). Conclusions: the results suggest that calprotectin may serve as a marker of inflammatory activity in patients with rheumatic irAEs induced by treatment with ICIs.
Deciphering the Role of the Anaphylatoxin C3a: A Key Function in Modulating the Tumor Microenvironment
Authors: Hanna Jolimar , Ah-Pine Franck , Boina Chailas , Bedoui Yosra , Gasque Philippe , Septembre-Malaterre Axelle
Published: May 2023

The complement system plays a crucial role in cancer development. Our study investigated the role of C3a anaphylatoxin on the tumor microenvironment. Our models consisted of mesenchymal stem cells (MSC-like, 3T3-L1), macrophages (Raw 264.7 Blue, (RB)) and tumor cells (melanoma B16/F0). Recombinant mouse (Mo) C3a (rC3a) was produced in CHO cells transfected with a Mo-IL10-signal peptide-Mo C3a plasmid construct. The effects of rC3a, IFN-γ, TGF-β1, and LPS were tested on the expression of C3, C3aR, PI3K, cytokines, chemokines, transcription factors, antioxidant defense mechanisms, angiogenesis and macrophage polarization (M1/M2). 3T3-L1 expressed the highest levels of C3, while C3aR was expressed more by RB. Interestingly, expression of C3/3T3-L1 and C3aR/RB was markedly upregulated by IFN-γ. rC3a was found to upregulate the expression of anti-inflammatory cytokines (IL-10) on 3T3-L1 and TGF-β1 on RB. rC3a also upregulated the expression of pro-inflammatory cytokines in RB. The expression of CCL-5 increased in 3T3-L1 in response to rC3a. On RB, rC3a did not alter M1/M2 polarization but upregulated the expression of antioxidant defense genes, HO-1, and VEGF. C3/C3a produced mainly by MSC may play a critical role in TME remodeling by stimulating both anti-inflammatory and proangiogenic activities of tumor stromal cells.
Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice
Authors: Chen Anna , Neuwirth Ines , Herndler-Brandstetter Dietmar
Published: May 2023

Cancer immunotherapy has brought significant clinical benefits to numerous patients with malignant disease. However, only a fraction of patients experiences complete and durable responses to currently available immunotherapies. This highlights the need for more effective immunotherapies, combination treatments and predictive biomarkers. The molecular properties of a tumor, intratumor heterogeneity and the tumor immune microenvironment decisively shape tumor evolution, metastasis and therapy resistance and are therefore key targets for precision cancer medicine. Humanized mice that support the engraftment of patient-derived tumors and recapitulate the human tumor immune microenvironment of patients represent a promising preclinical model to address fundamental questions in precision immuno-oncology and cancer immunotherapy. In this review, we provide an overview of next-generation humanized mouse models suitable for the establishment and study of patient-derived tumors. Furthermore, we discuss the opportunities and challenges of modeling the tumor immune microenvironment and testing a variety of immunotherapeutic approaches using human immune system mouse models.
Antibody Response to the SARS-CoV-2 Vaccine and COVID-19 Vulnerability during the Omicron Pandemic in Patients with CLL: Two-Year Follow-Up of a Multicenter Study
Authors: Mauro Francesca R. , Giannarelli Diana , Galluzzo Clementina M. , Visentin Andrea , Frustaci Anna M. , Sportoletti Paolo , Vitale Candida , Reda Gianluigi , Gentile Massimo , Levato Luciano , Murru Roberta , Armiento Daniele , Molinari Maria C. , Proietti Giulia , Pepe Sara , De Falco Filomena , Mattiello Veronica , Barabino Luca , Amici Roberta , Coscia Marta , Tedeschi Alessandra , Girmenia Corrado , Trentin Livio , Baroncelli Silvia
Published: May 2023

High morbidity and mortality due to COVID-19 were described in the pre-vaccination era in patients with chronic lymphocytic leukemia (CLL). To evaluate COVID-19 morbidity after the SARS-CoV-2 vaccine, we carried out a prospective study in 200 CLL patients. The median age of patients was 70 years; 35% showed IgG levels ≤ 550 mg/dL, 61% unmutated IGHV, and 34% showed TP53 disruption. Most patients, 83.5%, were previously treated, including 36% with ibrutinib and 37.5% with venetoclax. The serologic response rates to the second and third dose of the vaccine were 39% and 53%, respectively. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19, 36.5% during the Omicron pandemic, and 10% had subsequent COVID-19 events. Severe COVID-19 requiring hospitalization was recorded in 26% of patients, and 4% died. Significant and independent factors associated with the response to the vaccine and vulnerability to COVID-19 were age (OR: 0.93; HR: 0.97) and less than 18 months between the start of targeted agents and vaccine (OR: 0.17; HR: 0.31). TP53 mutation and ≥two prior treatments also emerged as significant and independent factors associated with an increased risk of developing COVID-19 (HR: 1.85; HR: 2.08). No statistical difference in COVID-19 morbidity was found in patients with or without antibody response to the vaccine (47.5% vs. 52.5%; p = 0.21). Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in CLL patients.
Radiation-Induced Brain Injury: Age Dependency of Neurocognitive Dysfunction Following Radiotherapy
Authors: Rübe Claudia , Raid Silvia , Palm Jan , Rübe Christian
Published: May 2023

Cranial radiotherapy is a known risk factor for neurocognitive impairment in cancer survivors. Although radiation-induced cognitive dysfunction is observed in patients of all ages, children seem to be more vulnerable than adults to suffering age-related deficits in neurocognitive skills. So far, the underlying mechanisms by which IR negatively influences brain functions as well as the reasons for the profound age dependency are still insufficiently known. We performed a comprehensive Pubmed-based literature search to identify original research articles that reported on age dependency of neurocognitive dysfunction following cranial IR exposure. Numerous clinical trials in childhood cancer survivors indicate that the severity of radiation-induced cognitive dysfunction is clearly dependent on age at IR exposure. These clinical findings were related to the current state of experimental research providing important insights into the age dependency of radiation-induced brain injury and the development of neurocognitive impairment. Research in pre-clinical rodent models demonstrates age-dependent effects of IR exposure on hippocampal neurogenesis, radiation-induced neurovascular damage and neuroinflammation.
Predicting Lymph Node Metastasis Status from Primary Muscle-Invasive Bladder Cancer Histology Slides Using Deep Learning: A Retrospective Multicenter Study
Authors: Zheng Qingyuan , Jian Jun , Wang Jingsong , Wang Kai , Fan Junjie , Xu Huazhen , Ni Xinmiao , Yang Song , Yuan Jingping , Wu Jiejun , Jiao Panpan , Yang Rui , Chen Zhiyuan , Liu Xiuheng , Wang Lei
Published: May 2023

Background: Accurate prediction of lymph node metastasis (LNM) status in patients with muscle-invasive bladder cancer (MIBC) before radical cystectomy can guide the use of neoadjuvant chemotherapy and the extent of pelvic lymph node dissection. We aimed to develop and validate a weakly-supervised deep learning model to predict LNM status from digitized histopathological slides in MIBC. Methods: We trained a multiple instance learning model with an attention mechanism (namely SBLNP) from a cohort of 323 patients in the TCGA cohort. In parallel, we collected corresponding clinical information to construct a logistic regression model. Subsequently, the score predicted by the SBLNP was incorporated into the logistic regression model. In total, 417 WSIs from 139 patients in the RHWU cohort and 230 WSIs from 78 patients in the PHHC cohort were used as independent external validation sets. Results: In the TCGA cohort, the SBLNP achieved an AUROC of 0.811 (95% confidence interval [CI], 0.771–0.855), the clinical classifier achieved an AUROC of 0.697 (95% CI, 0.661–0.728) and the combined classifier yielded an improvement to 0.864 (95% CI, 0.827–0.906). Encouragingly, the SBLNP still maintained high performance in the RHWU cohort and PHHC cohort, with an AUROC of 0.762 (95% CI, 0.725–0.801) and 0.746 (95% CI, 0.687–0.799), respectively. Moreover, the interpretability of SBLNP identified stroma with lymphocytic inflammation as a key feature of predicting LNM presence. Conclusions: Our proposed weakly-supervised deep learning model can predict the LNM status of MIBC patients from routine WSIs, demonstrating decent generalization performance and holding promise for clinical implementation.
Improving the Stability of Ru-Doped Ni-Based Catalysts for Steam Methane Reforming during Daily Startup and Shutdown Operation
Authors: Kim Tae-Young , Lee Jong-Heon , Jo Seongbin , Kim Jueon , Woo Jin-Hyeok , Dhanusuraman Ragupathy , Kim Jae-Chang , Lee Soo-Chool
Published: May 2023

In this study, a Ru-doped Ni pellet-type catalyst was prepared to produce hydrogen via steam methane reforming (SMR). A small amount of Ru addition on the Ni catalyst improved Ni dispersion, thus affording a higher catalytic activity than that of the Ni catalyst. During the daily startup and shutdown (DSS) operations, the CH4 conversion of Ni catalysts significantly decreased because of Ni metal oxidation to NiAl2O4, which is not reduced completely at 700 °C. Conversely, the oxidized Ni species in the Ru–Ni catalyst can be reduced under SMR conditions because of H2 spillover from the surface of Ru onto the surface of Ni. Consequently, the addition of a small quantity of Ru to the Ni catalyst can improve the catalytic activity and stability during the DSS operation.
Fuel Consumption and Emission Reduction for Non-Road Diesel Engines with Electrically Heated Catalysts
Authors: Lee Kyoungbok , Lee Jongin , Lee Sangho , Oh Kwangchul , Jang Sungwook
Published: May 2023

In this study, an exhaust system compliant with future regulations was developed for a non-road 110PS engine with a Tier-4f aftertreatment system, and the emission characteristics of the engine were investigated in the non-road transient mode (NRTC). For the system to comply with future exhaust regulations, a DPF was installed, and an electrical heated catalyst (EHC) device was installed to manage exhaust gas temperature. The emission characteristics of exhaust gas were examined according to the power and applied duration of EHC, and the effects of catalyst coating and the urea water solution (UWS) injection map on NOx reduction, NH3 slip, and N2O emissions in NRTC mode were investigated. The application of a 4 kW class EHC system enables the lowering of the injection starting temperature of the UWS, as reliable gas heating (heating duration control) is guaranteed. When the injection starting temperature (based on the SCR inlet temperature) was set to 150 °C, NSR map, (III) in conjunction with the operation of the EHC, effectively achieved significant NOx reduction in NRTC mode without deposit and wetting occurring in the mixer and exhaust pipe. Regarding changes in EHC power from 3 kW to 4 kW, it was observed that a NOx reduction of 0.05 g/kWh occurs in the cold NRTC mode, but in the hot NRTC mode, it was found that the relative decrease in the UWS is due to the increased NO2 conversion efficiency as a result of the oxidation catalyst, making 3 kW more advantageous. Furthermore, due to the increase in NO2 concentration caused by the oxidation catalyst and the increase in the low-temperature injected UWS, NH4NO3 was formed, which resulted in an increase in PM emissions and a significant increase in N2O emissions around an exhaust temperature of 250 °C. When the EHC power was set to 3 kW and the volume of oxidation catalyst and the amount of UWS injection were adjusted, applying EHC in the NRTC mode resulted in an additional NOx reduction of 58.6% and 88.4% in cold and hot modes, respectively, compared with not using EHC, with a fuel penalty of approximately 1.67%, while limiting the peak concentrations of N2O and NH3.
Modification of Copper-Ceria Catalyst via Reverse Microemulsion Method and Study of the Effects of Surfactant on WGS Catalyst Activity
Authors: Oo Wathone , Park Ji Hye , Sonia Zakia Akter , Win May Zaw , Cho Dooyong , Yi Kwang Bok
Published: May 2023

Some major drawbacks encountered in the synthesis of copper-ceria (Cu-CeO2)-based Water Gas Shift (WGS) catalyst via the conventional Impregnation (IMP) method are aggregate formation and nanoparticles’ instability. These lead to the poor interaction between Copper and Ceria, thereby impeding the catalytic activity with the inefficient utilization of active sites. To overcome these drawbacks, in this study, we described the synthesis of the Cu-CeO2 catalyst via the Reverse Microemulsion (RME) method with the help of the organic surfactant. This development of insights and strategies resulted in the preparation of porous particles with uniform size distribution and improved interaction within the composites, which were evident through XRD, XPS, BET Surface area, TPR, TEM and SEM analysis results. Remarkably, the optimum 20% Cu-CeO2 catalyst prepared by RME method was found to have superior Water Gas Shift (WGS) catalytic activity than the conventionally Impregnated catalyst when their CO conversion efficiencies were tested in WGS reaction at different feed gas compositions with and without CO2. Moreover, the 20% Cu-CeO2 sample prepared by RME method exhibited sustained catalytic activity throughout the entire 48 h period without any signs of deactivation. This observation highlights RME method as the potential pathway for developing more effective nanoparticle catalysts for hydrogen production, contributing to the growing demand for clean and sustainable energy sources.
Waste-to-Resources: Leaching of Cobalt from Spent Cobalt Oxide Catalyst
Authors: Małolepsza Dominika , Rzelewska-Piekut Martyna , Emmons-Burzyńska Magdalena , Regel-Rosocka Magdalena
Published: May 2023

This article presents studies on the recovery of cobalt from a spent cobalt oxide catalyst, left after the preparation of industrial catalysts. Apart from cobalt, the tested material contained iron, copper, zinc, and nickel. Leaching was proposed as a simple and feasible operation to treat the spent cobalt oxide. The 0.1–8.0 M H2SO4 solutions were applied as leaching agents at an ambient temperature and at 70 °C. An 8.0 M H2SO4 solution at 70 °C leached two-fold more Co(II) than a 0.1 M H2SO4 solution at the same temperature. Similar to Co(II), regardless of the leaching temperature, the Fe ion was leached more efficiently with 4.0 or 8.0 M H2SO4 than with a 0.1 M acid. It should be emphasized that the Co(II) content in the solution after leaching was predominant at >90% (~4800 mg/dm3), compared to other metal ions. The ANOVA analysis indicated that both the sulfuric(VI) acid concentration and temperature had a significant effect on the leaching efficiency. An increase in acid concentration from 0.1 to 8 M and the temperature of leaching (from ambient to 70 °C) had a positive effect on the Co leaching efficiency (an increase from ~20 to almost 50%). The proposed hydrometallurgical treatment of the spent cobalt oxide catalyst is a response to the waste-to-resource (WTR) approach.
β-Catenin Elicits Drp1-Mediated Mitochondrial Fission Activating the Pro-Apoptotic Caspase-1/IL-1β Signalosome in Aeromonas hydrophila-Infected Zebrafish Macrophages
Authors: Sharma Shagun , Kumar Manmohan , Kumar Jai , Mazumder Shibnath
Published: May 2023

Canonical Wnt signaling plays a major role in regulating microbial pathogenesis. However, to date, its involvement in A. hydrophila infection is not well known. Using zebrafish (Danio rerio) kidney macrophages (ZKM), we report that A. hydrophila infection upregulates wnt2, wnt3a, fzd5, lrp6, and β-catenin (ctnnb1) expression, coinciding with the decreased expression of gsk3b and axin. Additionally, increased nuclear β-catenin protein accumulation was observed in infected ZKM, thereby suggesting the activation of canonical Wnt signaling in A. hydrophila infection. Our studies with the β-catenin specific inhibitor JW67 demonstrated β-catenin to be pro-apoptotic, which initiates the apoptosis of A. hydrophila-infected ZKM. β-catenin induces NADPH oxidase (NOX)-mediated ROS production, which orchestrates sustained mitochondrial ROS (mtROS) generation in the infected ZKM. Elevated mtROS favors the dissipation of the mitochondrial membrane potential (ΔΨm) and downstream Drp1-mediated mitochondrial fission, leading to cytochrome c release. We also report that β-catenin-induced mitochondrial fission is an upstream regulator of the caspase-1/IL-1β signalosome, which triggers the caspase-3 mediated apoptosis of the ZKM as well as A. hydrophila clearance. This is the first study suggesting a host-centric role of canonical Wnt signaling pathway in A. hydrophila pathogenesis wherein β-catenin plays a primal role in activating the mitochondrial fission machinery, which actively promotes ZKM apoptosis and helps in containing the bacteria.
Neuropathic-like Nociception and Spinal Cord Neuroinflammation Are Dependent on the TRPA1 Channel in Multiple Sclerosis Models in Mice
Authors: Dalenogare Diéssica Padilha , Souza Monteiro de Araújo Daniel , Landini Lorenzo , Titiz Mustafa , De Siena Gaetano , De Logu Francesco , Geppetti Pierangelo , Nassini Romina , Trevisan Gabriela
Published: May 2023

Background: Transient receptor potential ankyrin 1 (TRPA1) activation is implicated in neuropathic pain-like symptoms. However, whether TRPA1 is solely implicated in pain-signaling or contributes to neuroinflammation in multiple sclerosis (MS) is unknown. Here, we evaluated the TRPA1 role in neuroinflammation underlying pain-like symptoms using two different models of MS. Methods: Using a myelin antigen, Trpa1+/+ or Trpa1−/− female mice developed relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) (Quil A as adjuvant) or progressive experimental autoimmune encephalomyelitis (PMS)-EAE (complete Freund’s adjuvant). The locomotor performance, clinical scores, mechanical/cold allodynia, and neuroinflammatory MS markers were evaluated. Results: Mechanical and cold allodynia detected in RR-EAE, or PMS-EAE Trpa1+/+ mice, were not observed in Trpa1−/− mice. The increased number of cells labeled for ionized calcium-binding adapter molecule 1 (Iba1) or glial fibrillary acidic protein (GFAP), two neuroinflammatory markers in the spinal cord observed in both RR-EAE or PMS-EAE Trpa1+/+ mice, was reduced in Trpa1−/− mice. By Olig2 marker and luxol fast blue staining, prevention of the demyelinating process in Trpa1−/− induced mice was also detected. Conclusions: Present results indicate that the proalgesic role of TRPA1 in EAE mouse models is primarily mediated by its ability to promote spinal neuroinflammation and further strengthen the channel inhibition to treat neuropathic pain in MS.