bluuebunny/crossref_metadata_2025 huggingface dataset:
MoS2-Carbon Nanodots as a New Electrochemiluminescence Platform for Breast Cancer Biomarker Detection
Authors: Gutiérrez-Gálvez Laura , Sulleiro Manuel Vázquez , Gutiérrez-Sánchez Cristina , García-Nieto Daniel , Luna Mónica , Pérez Emilio M. , García-Mendiola Tania , Lorenzo Encarnación
Published: March 2023

In this work, we present the combination of two different types of nanomaterials, 2D molybdenum disulfide nanosheets (MoS2-NS) and zero-dimensional carbon nanodots (CDs), for the development of a new electrochemiluminescence (ECL) platform for the early detection and quantification of the biomarker human epidermal growth factor receptor 2 (HER2), whose overexpression is associated with breast cancer. MoS2-NS are used as an immobilization platform for the thiolated aptamer, which can recognize the HER2 epitope peptide with high affinity, and CDs act as coreactants of the anodic oxidation of the luminophore [Ru(bpy)3]2+. The HER2 biomarker is detected by changes in the ECL signal of the [Ru(bpy)3]2+/CD system, with a low detection limit of 1.84 fg/mL and a wide linear range. The proposed method has been successfully applied to detect the HER2 biomarker in human serum samples.
The Inhibition Effects of Sodium Nitroprusside on the Survival of Differentiated Neural Stem Cells through the p38 Pathway
Authors: Jiao Lingling , Xu Tongying , Du Xixun , Chen Xi , Jiao Qian , Jiang Hong
Published: March 2023

Nitric oxide (NO) is a crucial factor in regulating neuronal development. However, certain effects of NO are complex under different physiological conditions. In this study, we used differentiated neural stem cells (NSCs), which contained neural progenitor cells, neurons, astrocytes, and oligodendrocytes, to observe the physiological effects of sodium nitroprusside (SNP) on the early developmental stage of the nervous system. After SNP treatment for 24 h, the results showed that SNP at 100 μM, 200 μM, 300 μM, and 400 μM concentrations resulted in reduced cell viability and increased cleaved caspase 3 levels, while no significant changes were found at 50 μM. There were no effects on neuronal differentiation in the SNP-treated groups. The phosphorylation of p38 was also significantly upregulated with SNP concentrations of 100 μM, 200 μM, 300 μM, and 400 μM, with no changes for 50 μM concentration in comparison with the control. We also observed that the levels of phosphorylation increased with the increasing concentration of SNP. To further explore the possible role of p38 in SNP-regulated survival of differentiated NSCs, SB202190, the antagonist of p38 mitogen-activated protein kinase, at a concentration of 10 mM, was pretreated for 30 min, and the ratio of phosphorylated p38 was found to be decreased after treatment with SNP. Survival and cell viability increased in the SB202190 and SNP co-treated group. Taken together, our results suggested that p38 is involved in the cell survival of NSCs, regulated by NO.
Sex Differences in Cognitive-Motor Dual-Task Training Effects and in Brain Processing of Semi-Elite Basketball Players
Authors: Lucia Stefania , Aydin Merve , Di Russo Francesco
Published: March 2023

In the current study, we aimed at evaluating the possible sex differences in cognitive-motor dual-task training (CMDT) effects on the sport and cognitive performance of semi-elite basketball athletes. Moreover, we investigated the CMDT effects on proactive brain processing using event-related potential (ERP) analysis. Fifty-two young basketball athletes (age 16.3 years) were randomly assigned into an experimental (Exp) group performing the CMDT, and a control (Con) group executing standard motor training. Before and after a 5-week training intervention, participants’ motor performance was evaluated using dribbling tests. Cognitive performance was assessed by measuring response time and accuracy in a discrimination response task (DRT). Brain activity related to motor and cognitive preparation was measured through the Bereitschaftspotential (BP) and the prefrontal negativity (pN) ERP components. The CMDT involved the simultaneous execution of dribbling exercises and cognitive tasks which were realized using interactive technologies on the court. Results showed that both groups had some enhancements from pre- to post-tests, but only the Exp group enhanced in the dribbling exercise. In the DRT after the CMDT, females performed faster than males in the Exp group. All groups, except for the Con group of males, performed the DRT more accurately after the training. According to the ERP results, in the Exp group of males and in Exp and Con group of females, we found an increase in pN amplitude (associated with better accuracy); in the Exp group of females and in Exp and Con group of males, we found an increase in BP (associated with better response time). In conclusion, the present study endorsed the efficacy of the proposed CMDT protocol on both the sport and cognitive performance of semi-elite basketball players and showed that the neural basis of these benefits may be interpreted as sex-related compensatory effects.
Lurasidone Augmentation of Clozapine in Schizophrenia—Retrospective Chart Review
Authors: Siwek Marcin , Chrobak Adrian Andrzej , Gorostowicz Aleksandra , Król Patrycja , Dudek Dominika
Published: March 2023

The aim of our study was to evaluate the effectiveness of lurasidone augmentation of clozapine in treatment-resistant schizophrenia (SZ) in a retrospective chart review. From the medical records of 916 SZ patients, we identified 16 individuals treated with a combination of clozapine and lurasidone. The detailed clinical data are described separately for each patient. We compared the Clinical Global Impression—Severity (CGI-S) scores between three points of observation: before the treatment and one month and two months after its initiation. CGI Improvement (CGI-I) scores were used to evaluate the treatment response between the first and last points of observation. The vast majority of patients (14/16, 87.5%) responded to lurasidone augmentation of clozapine (CGI-I scores 1 or 2). Therapeutic effects were observable after 3–12 weeks of treatment (median 6 (4–6)). A reduction in CGI-S scores was observed after the first month of observation. There was an observable reduction in positive, depressive and anxiety symptoms, as well as an improvement in psychosocial functioning. Two patients discontinued treatment due to side effects. Our study suggests that lurasidone augmentation of clozapine may lead to improvements in a broad range of SZ symptom dimensions.
Epithelial–Mesenchymal Transition Expression Profile Stratifies Human Glioma into Two Distinct Tumor-Immune Subtypes
Authors: Ren Changyuan , Chang Xin , Li Shouwei , Yan Changxiang , Fu Xiaojun
Published: March 2023

Glioma is the primary tumor with the highest incidence and the worst prognosis in the human central nervous system. Epithelial–mesenchymal transition (EMT) and immune responses are two crucial processes that contribute to it having the worst prognosis. However, a comprehensive correlation between these two processes remains elusive. The mRNA expression profiles and corresponding clinical data of patients with glioma were downloaded from public databases. EMT-related genes were collected and provided in the dbEMT database. Risk scores, Lasso regression, and enrichment analysis were conducted for functional validation. In our study, we used unsupervised clustering of EMT gene expression profiles to classify gliomas into two subtypes. We assessed the reliability of this classification system by testing it in three independent cohorts. Each subtype had different clinical and immune system characteristics. The study suggests a possible link between EMT and immune responses in gliomas.
tDCS Anodal Stimulation of the Right Dorsolateral Prefrontal Cortex Improves Creative Performance in Real-World Problem Solving
Authors: Guo Jiayue , Luo Jiani , An Yi , Xia Tiansheng
Published: March 2023

Brain regions associated with creativity is a focal point in research related to the field of cognitive neuroscience. Previous studies have paid more attention to the role of activation of the left dorsolateral prefrontal cortex in creativity tasks, which are mostly abstract conceptual tasks, and less attention to real-world creativity tasks. The right dorsolateral prefrontal cortex is involved in functions such as visuospatial processing, which may have a positive impact on innovative solutions to real-world problems. In this study, tDCS technology was used to explore the effect of anodal stimulation of the right dorsolateral prefrontal cortex on design creativity performance in a real-word problem-solving task related to product design. The experimental task comprised three stages, of which the first two were idea generation stages based on divergent thinking using text and graphics, respectively, whereas the third was the creative evaluation stage based on convergent thinking. Thirty-six design students were recruited to partake in the experiment. They were randomly assigned into anodal stimulation and sham stimulation groups. The results showed that anodal stimulation of the right dorsolateral prefrontal cortex produced a significant positive effect during the creative evaluation stage, promoting the usefulness of ideas (p = 0.009); thus, improving product creativity scores. However, there was no significant impact on the idea generation stage (p > 0.05), which is dominated by divergent thinking. The results suggest that activating the right dorsolateral prefrontal cortex with tDCS can improve people’s performance in creative activities by promoting convergent thinking rather than divergent thinking. It also provides further evidence that the right hemisphere of the brain has an advantage in solving complex problems that require the participation of visuospatial information.
From Academic Resilience to Academic Burnout among International University Students during the Post-COVID-19 New Normal: An Empirical Study in Taiwan
Authors: Tran Thanh Xuan , Vo Thi Thuy Tien , Ho Chen
Published: March 2023

(1) Background: In the context of the COVID-19 pandemic, it is imperative for higher education institutions to understand the socio-psychological issues of international students, a potentially vulnerable population on campuses, to assist them in pursuing their academic path while maintaining their psychological well-being. The objectives of this study were to determine the prevalence of academic burnout among international university students in Taiwan during the new normal and to explore the protective role of academic resilience. (2) Methods: Three hundred and eighty-three international university students in Taiwan were recruited and surveyed via the online self-administered questionnaire during the Fall semester of the 2022–2023 academic year. The data of sociodemographic characteristics, academic burnout, and academic resilience were collected and analyzed. (3) Results: The overall prevalence of high academic burnout was 12.01%. The majority of participants perceived significant depression and anxiety (detrimental factors) but moderate to high perception of academics and relationships (protective factors). There were significant relationships between resilience components and burnout symptoms. (4) Conclusions: Resilience may help to reduce burnout among international university students during the post-COVID-19 new normal, thereby protecting their mental health.
My Exposed Body: Psychometric Properties of the Italian Version of the Social Physique Anxiety Scale-7 among Women
Authors: Policardo Giulia Rosa , Matera Camilla , Di Gesto Cristian , Nerini Amanda
Published: March 2023

Background: Social Physique Anxiety (SPA) is the anxiety resulting from the prospect or presence of the interpersonal evaluation of one’s physique. It is a construct related to body image and body esteem. The Social Physique Anxiety Scale-7 (SPAS-7) is a self-report scale aimed at measuring the degree of anxiety that people experience when others evaluate their physique. Methods: This study aimed to investigate the factor structure (through Confirmatory Factor Analysis followed by multi-group confirmatory factorial analyses), reliability, and convergent validity of an Italian version of the SPAS-7 among a sample of women (N = 520; mean age = 33.5, SD = 10.5). Results: Confirmatory Factor Analysis attested the unidimensional factorial structure of the SPAS-7, which achieved full invariance across age groups. The strength of the inter-relationships between the SPAS-7 and measures of negative (i.e., body dissatisfaction) and positive body image (i.e., body appreciation and body compassion) provided evidence of good convergent validity. The Cronbach’s alpha was very good. Conclusion: According to our results, the Italian version of the SPAS-7 could be a valid and agile instrument for assessing self-presentational concerns associated with body image among Italian-speaking women across age.
The Effects of Mindfulness on Sensory Marketing: The Role of Mental Imagery Vividness and the Sensory Type Number
Authors: Li Bingcan , Jiang Yi , Wu Yuanzhi , Wang Lei
Published: March 2023

Mindfulness refers to paying attention to the present sensation, attention, and thoughts without judgment and is proven to enhance sensations. Although researchers began to investigate the role of mindfulness in consumer decision-making, few studies pay attention to the impact of mindfulness on the effect of sensory marketing. In the current study, we investigated whether and how mindfulness enhances the purchase intentions of sensory marketing products. We conducted three studies (n = 593) to test our hypotheses. The first study tested the correlation between trait mindfulness and the purchase intentions of sensory ads. The results showed that the level of trait mindfulness and purchase intentions were positively correlated. The second study primed the state mindfulness of participants and demonstrated that high-level state mindfulness enhanced purchase intentions, which was moderated by the number of sensory types. The third study further tested the mental imagery vividness and proved the mediating role of vividness between state mindfulness and purchase intentions. The current study shows the enhancing effect of mindfulness on purchase intentions. This effect is moderated by the number of sensory types and mediated by the vividness of mental images. Our study illustrates the critical contribution of mindfulness to promoting sensory marketing.
Experimental and Statistical Analysis of Repeated Impact Records of Hybrid Fiber-Reinforced High-Performance Concrete
Authors: Ali Sajjad H. , Abid Sallal R. , Al-Lami Karrar , Calabrese Angelo Savio , Yosri Ahmed M. , Al-Ghasham Thaar S.
Published: March 2023

The effect of fiber type and fiber hybridization on the repeated impact strength was investigated experimentally using six high-performance concrete mixtures reinforced with a 2.5% fiber volume fraction. The fiber types considered in this study included short steel fibers (SF) with 6 mm length, long SF with 15 mm length, and polypropylene (PP) fibers. The repeated impact test was conducted using a specially made automatic testing machine following the test setup recommendations of the ACI 544-2R test, where cracking (Ncr) and failure (Nf) impact numbers were recorded and the failure mode and crack pattern were observed. The results were statistically analyzed using the normality test and variations were discussed. The test results showed that specimens with pure long SF (S15) obtained the highest Ncr and Nf values, which were 20% and 327% higher than those of the mixture with pure short SF (S6) owing to the better bond between fibers and the cementitious matrix in S15. Replacing 0.5% of the mixture’s SF with PP decreased the cracking resistance by 7% to 15%, while its effect on Nf was dependent on the length of SF. In most cases, the Ncr and Nf records did not exhibit a significant departure from normal distribution, according to the Anderson-darling test.
Towards Nearly Zero-Energy Buildings in Cold Rural Mediterranean Zones: The Case of La Rioja (Spain)
Authors: López-Ochoa Luis M. , Sagredo-Blanco Enrique , Las-Heras-Casas Jesús , García-Lozano César
Published: March 2023

The European Union aims for its existing building stock to be highly energy-efficient and decarbonized by 2050 through long-term renovation strategies so that all residential buildings are nearly zero-energy buildings. The objective of this work is to determine the optimal energy renovation solution for rural residential buildings located in cold climate zones of Spain to achieve nearly zero-energy buildings. For this purpose, the energy, environmental and economic impacts of 48 energy renovation proposals in three different climate zones are assessed, taking La Rioja as a case study. Considering these impacts, the optimal solution is a solution that improves the thermal envelope, applying the life cycle cost analysis, and that uses renewable energy sources to meet thermal needs and a portion of the electrical energy needs. Under the optimal solution, overall savings of up to EUR 2.4 can be achieved for each euro invested, resulting in reductions in non-renewable primary energy consumption by up to 97%, total primary energy consumption by up to 81% and CO2 emissions by up to 97%. The methodology followed and the results obtained can serve as a guide for establishing energy renovation policies in other cold rural Mediterranean zones.
Hyperbolic Paraboloid Tensile Structure—Numerical CFD Simulation of Wind Flow in RWIND Software
Authors: Kawulok Marek , Freiherrová Nela , Horňáková Marie , Juračka David , Krejsa Martin
Published: March 2023

Tensile membrane structures combine a prestressed roofing envelope material and supporting elements. To design these structures, there is a set of recommendations in the European Design Guide for Tensile Surface Structures and some other national standards. However, currently, there is no official standard related to the design process of tensile structures in the European Union. The structure studied in this project is considered as permanent roofing of an external testing device in the shape of a simple hyperbolic paraboloid without enclosing walls. Snow and wind loads were analyzed as the most critical types of loading in the location. Determining the value of the snow load is relatively simple according to the European standard. However, in the case of the wind load, this shape is not considered in the European standard and needs to be solved experimentally or by numerical simulation in a wind tunnel. The present contribution focuses on numerical analysis of the wind flow in RFEM software and simulation of the wind tunnel in RWIND software.
Moving toward Net Zero Carbon Buildings to Face Global Warming: A Narrative Review
Authors: Tirelli Davide , Besana Daniela
Published: March 2023

The increase in global surface temperatures will surpass the 2 °C target set by the Paris Agreement unless carbon emissions are lowered to zero by 2050. To date, the building sector is responsible for 38% of all carbon emissions, thus one of the main targets is represented by the development of building strategies that can facilitate the transition toward carbon-neutral buildings. The main strategies are today represented by nearly zero energy buildings (nZEBs), zero energy buildings (ZEBs)/net zero energy buildings (NZEBs) and net zero carbon buildings (NZCBs). Particularly, NZCBs completely target zero operational and embodied carbon during their life cycles, fulfilling the leadership role in the decarbonization of the construction sector. Moreover, adopting the European Standard EN 15978:2011, carbon emissions can be precisely classified to enhance strategies aimed at reducing them. Commercial viability remains a fundamental economic driver, but the higher initial capital costs hinder the NZCBs. In addition, legislative, socio-cultural, technological, professional and geographical barriers hold back its diffusion. NZCBs can be met by a four-steps program: embodied carbon reduction, operational carbon reduction, increase in renewable energy supply and offset and carbon storage. Circular economy principles are strictly connected to design for disassembly and for adaptability to reduce embodied carbon, while passive design and solar and geothermal energy production can satisfy the renewable energy demand of the building. The aim of this narrative review is to determine and describe which is the current state of the art for NZCB definition, the drivers and barriers toward its application in a broader context and which strategies are eligible to meet the ambitious goal of zero operational and zero embodied carbon emissions.
Study on the Effect of Supplementary Cementitious Material on the Regeneration Performance of Waste Fresh Concrete
Authors: Wang Weicheng , Zhang Daoming , Liu Linqing , Zhang Xueyuan , Wang Yue
Published: March 2023

In the preparation of ready-mixed concrete, it is inevitable to produce waste fresh concrete (WFC). An efficient, low-cost and environmentally friendly recycling scheme is the key to WFC recycling. In this work, we directly added some unhardened WFC to fresh concrete to prepare recycled fresh concrete (RFC); on this basis, fly ash (FA) and nano-silica (NS) were added as supplementary cementitious material (SCM) to obtain modified recycled fresh concrete (RFC-SF). Then, the mechanical properties, slump, freeze–thaw resistance, phase structure of the hydration products and hydration process in RFC were studied. The results show that the addition of FA and NS significantly improved the comprehensive performance of RFC. Compared with RFC, the compressive strength of RFC-SF with 15% FA and 3% NS increased by 15.2% and 50.3% at 7 d and 90 d, respectively, and the splitting tensile strength increased by 20.5% and 76.4%, respectively. The slump remained above 155 mm, and the mass loss rate decreased by 42.6% after freeze–thaw cycles. XRD and FTIR analysis showed that the addition of FA and NS accelerated the hydration reaction process of RFC-SF, reduced the content of calcium hydroxide (CH) and refined the grain size of CH. RFC-SF had a denser microstructure and a lower calcium-silicon ratio in SEM and EDS tests.
Analysis of Engineering Performance and Environmental Impact of Asphalt Pavement Debonding and Ice Suppression Materials
Authors: Zhang Yemao , Zhao Xijuan , Zheng Mulian
Published: March 2023

Aiming at the maladies of high labor intensity, the low efficiency of ice and snow removal, and environmental pollution in traditional ice-deicing and snow-melting methods, we successfully developed a material that can effectively reduce the adhesive force between ice and snow with the pavement, aimed at the characteristics of the road ice de-icing and snow melting. According to the evaluation index and method of de-icing performance, we determined the ratio of the three components of the film-forming component, the adhesive component, the modified ice suppression component, and the preparation technology. It has no perfect evaluation index and method for the viscosity-reducing and ice-defending materials at present, this paper further evaluates the performance of the viscosity-reducing and ice-defending materials from the aspects of ice-deicing performance, durability, and environmental performance. The results show that the viscosity-reducing and ice-defending material has good permeability and water resistance. The material still has good ice-deicing performance after seven rounds of cycle tests at the same time, indicating that it has a good slow-release performance. It is verified that the viscosity-reducing and ice-defending materials have good durability using the low-temperature accelerated test. Finally, from the analysis and evaluation of the environmental protection performance of the viscosity-reducing and ice-defending materials, the materials have no effect on the growth of plants and their average corrosion rate is much lower than the average corrosion rate of the snow melting test piece, which means that the viscosity-reducing and ice-defending materials have good environmental performance.
Study on Horizontal Bearing Capacity of Pile Group Foundation Composed of Inclined and Straight Piles
Authors: Qiu Hongsheng , Wang Heng , Ayasrah Mo’men , Zhou Ziyu , Li Bo
Published: March 2023

In all types of new arch bridge structures, the requirements of the foundation are becoming more and more strict. Under the action of horizontal thrust, the distribution of the internal forces of the pile group in which inclined piles participate in an arch foundation is complicated. In this regard, the horizontal forces of each pile in a pile group and the horizontal bearing performance of each pile in a pile group under the action of total thrust are investigated by establishing a pile group foundation model and a p-y curve difference equation. After an in-depth analysis of the simulation results, it is found that the load distribution calculated by the finite element method is very close to that calculated by the p-y curve method, both in terms of curve shape and numerical value, indicating that the pile top load distribution is close to the actual situation. In addition, the maximum shear force of each pile body occurs at the top of the pile, and the maximum bending moment occurs at the point 1/5 away from the top of the pile. Finally, the nonlinear analysis of the p-y curve method can be well applied to the calculation of bridge pile foundations.
Technical Implications for Surgical Resection in Locally Advanced Pancreatic Cancer
Authors: de Santibañes Martín , Pekolj Juan , Sanchez Claria Rodrigo , de Santibañes Eduardo , Mazza Oscar Maria
Published: March 2023

Pancreatic ductal adenocarcinoma remains a global health challenge and is predicted to soon become the second leading cause of cancer death in developed countries. Currently, surgical resection in combination with systemic chemotherapy offers the only chance of cure or long-term survival. However, only 20% of cases are diagnosed with anatomically resectable disease. Neoadjuvant treatment followed by highly complex surgical procedures has been studied over the last decade with promising short- and long-term results in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). In recent years, a wide variety of complex surgical techniques that involve extended pancreatectomies, including portomesenteric venous resection, arterial resection, or multi-organ resection, have emerged to optimize local control of the disease and improve postoperative outcomes. Although there are multiple surgical techniques described in the literature to improve outcomes in LAPC, the comprehensive view of these strategies remains underdeveloped. We aim to describe the preoperative surgical planning as well different surgical resections strategies in LAPC after neoadjuvant treatment in an integrated way for selected patients with no other potentially curative option other than surgery.
2-Arachidonoylglycerol Modulates CXCL12-Mediated Chemotaxis in Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia
Authors: Merrien Magali , Wasik Agata M. , Melén Christopher M. , Morsy Mohammad Hamdy Abdelrazak , Sonnevi Kristina , Junlén Henna-Riikka , Christensson Birger , Wahlin Björn E. , Sander Birgitta
Published: March 2023

To survive chemotherapy, lymphoma cells can relocate to protective niches where they receive support from the non-malignant cells. The biolipid 2-arachidonoylglycerol (2-AG), an agonist for the cannabinoid receptors CB1 and CB2, is released by stromal cells in the bone marrow. To investigate the role of 2-AG in lymphoma, we analyzed the chemotactic response of primary B-cell lymphoma cells enriched from peripheral blood of twenty-two chronic lymphocytic leukemia (CLL) and five mantle cell lymphoma (MCL) patients towards 2-AG alone and/or to the chemokine CXCL12. The expression of cannabinoid receptors was quantified using qPCR and the protein levels visualized by immunofluorescence and Western blot. Surface expression of CXCR4, the main cognate receptor to CXCL12, was analyzed by flow cytometry. Phosphorylation of key downstream signaling pathways activated by 2-AG and CXCL12 were measured by Western blot in three MCL cell lines and two primary CLL samples. We report that 2-AG induces chemotaxis in 80% of the primary samples, as well as 2/3 MCL cell lines. 2-AG induced in a dose-dependent manner, the migration of JeKo-1 cell line via CB1 and CB2. 2-AG affected the CXCL12-mediated chemotaxis without impacting the expression or internalization of CXCR4. We further show that 2-AG modulated p38 and p44/42 MAPK activation. Our results suggest that 2-AG has a previously unrecognized role in the mobilization of lymphoma cells by effecting the CXCL12-induced migration and the CXCR4 signaling pathways, however, with different effects in MCL compared to CLL.
Transgenic HA-1-Specific CD8+ T-Lymphocytes Selectively Target Leukemic Cells
Authors: Pilunov Artem , Romaniuk Dmitrii S. , Shmelev Anton , Sheetikov Savely , Gabashvili Anna N. , Khmelevskaya Alexandra , Dianov Dmitry , Zornikova Ksenia , Shakirova Naina T. , Vagida Murad , Bogolyubova Apollinariya , Efimov Grigory A.
Published: March 2023

A significant share of allogeneic hematopoietic stem cell transplantations (allo-HSCT) results in the relapse of malignant disease. The T cell immune response to minor histocompatibility antigens (MiHAs) promotes a favorable graft-versus-leukemia response. The immunogenic MiHA HA-1 is a promising target for leukemia immunotherapy, as it is predominantly expressed in hematopoietic tissues and presented by the common HLA A*02:01 allele. Adoptive transfer of HA-1-specific modified CD8+ T cells could complement allo-HSCT from HA-1- donors to HA-1+ recipients. Using bioinformatic analysis and a reporter T cell line, we discovered 13 T cell receptors (TCRs) specific for HA-1. Their affinities were measured by the response of the TCR-transduced reporter cell lines to HA-1+ cells. The studied TCRs showed no cross-reactivity to the panel of donor peripheral mononuclear blood cells with 28 common HLA alleles. CD8+ T cells after endogenous TCR knock out and introduction of transgenic HA-1-specific TCR were able to lyse hematopoietic cells from HA-1+ patients with acute myeloid, T-, and B-cell lymphocytic leukemia (n = 15). No cytotoxic effect was observed on cells from HA-1- or HLA-A*02-negative donors (n = 10). The results support the use of HA-1 as a target for post-transplant T cell therapy.
Evaluation of Electrochemotherapy with Bleomycin in the Treatment of Colorectal Hepatic Metastases in a Rat Model
Authors: Spiliotis Antonios E. , Holländer Sebastian , Rudzitis-Auth Jeannette , Wagenpfeil Gudrun , Eisele Robert , Nika Spyridon , Mallis Kyriakides Orestis , Laschke Matthias W. , Menger Michael D. , Glanemann Matthias , Gäbelein Gereon
Published: March 2023

Background: The available ablative procedures for the treatment of hepatic cancer have contraindications due to the heat-sink effect and the risk of thermal injuries. Electrochemotherapy (ECT) as a nonthermal approach may be utilized for the treatment of tumors adjacent to high-risk regions. We evaluated the effectiveness of ECT in a rat model. Methods: WAG/Rij rats were randomized to four groups and underwent ECT, reversible electroporation (rEP), or intravenous injection of bleomycin (BLM) eight days after subcapsular hepatic tumor implantation. The fourth group served as Sham. Tumor volume and oxygenation were measured before and five days after the treatment using ultrasound and photoacoustic imaging; thereafter, liver and tumor tissue were additionally analysed by histology and immunohistochemistry. Results: The ECT group showed a stronger reduction in tumor oxygenation compared to the rEP and BLM groups; moreover, ECT-treated tumors exhibited the lowest levels of hemoglobin concentration compared to the other groups. Histological analyses further revealed a significantly increased tumor necrosis of >85% and a reduced tumor vascularization in the ECT group compared to the rEP, BLM, and Sham groups. Conclusion: ECT is an effective approach for the treatment of hepatic tumors with necrosis rates >85% five days following treatment.
Prognostic Value of Measurable Residual Disease in Patients with AML Undergoing HSCT: A Multicenter Study
Authors: Caballero-Velázquez Teresa , Pérez-López Olga , Yeguas Bermejo Ana , Rodríguez Arbolí Eduardo , Colado Varela Enrique , Sempere Talens Amparo , Vidriales María Belén , Solé-Rodríguez María , Quirós Caso Covadonga , Pérez López Estefanía , Reinoso Segura Marta , Prats-Martín Concepción , Montesinos Pau , Pérez-Simón Jose A.
Published: March 2023

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the best therapeutic option for many patients with acute myeloid leukemia (AML). However, relapse remains the main cause of mortality after transplantation. The detection of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) in AML, before and after HSCT, has been described as a powerful predictor of outcome. Nevertheless, multicenter and standardized studies are lacking. A retrospective analysis was performed, including 295 AML patients undergoing HSCT in 4 centers that worked according to recommendations from the Euroflow consortium. Among patients in complete remission (CR), MRD levels prior to transplantation significantly influenced outcomes, with overall (OS) and leukemia free survival (LFS) at 2 years of 76.7% and 67.6% for MRD-negative patients, 68.5% and 49.7% for MRD-low patients (MRD < 0.1), and 50.5% and 36.6% for MRD-high patients (MRD ≥ 0.1) (p < 0.001), respectively. MRD level did influence the outcome, irrespective of the conditioning regimen. In our patient cohort, positive MRD on day +100 after transplantation was associated with an extremely poor prognosis, with a cumulative incidence of relapse of 93.3%. In conclusion, our multicenter study confirms the prognostic value of MRD performed in accordance with standardized recommendations.
Systematic Review of the Short-Term versus Long-Term Duration of Antibiotic Management for Neutropenic Fever in Patients with Cancer
Authors: Ishikawa Kazuhiro , Masaki Tetsuhiro , Kawai Fujimi , Ota Erika , Mori Nobuyoshi
Published: March 2023

Early antibiotic discontinuation has been proposed in patients with hematologic malignancy with fever of unknown origin during febrile neutropenia (FN). We intended to investigate the safety of early antibiotic discontinuation in FN. Two reviewers independently searched for articles from Embase, CENTRAL, and MEDLINE on 30 September 2022. The selection criteria were randomized control trials (RCTs) comparing short- and long-term durations for FN in cancer patients, and evaluating mortality, clinical failure, and bacteremia. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. We identified eleven RCTs (comprising 1128 distinct patients with FN) from 1977 to 2022. A low certainty of evidence was observed, and no significant differences in mortality (RR 1.43, 95% CI, 0.81, 2.53, I2 = 0), clinical failure (RR 1.14, 95% CI, 0.86, 1.49, I2 = 25), or bacteremia (RR 1.32, 95% CI, 0.87, 2.01, I2 = 34) were identified, indicating that the efficacy of short-term treatment may not differ statistically from that of long-term treatment. Regarding patients with FN, our findings provide weak conclusions regarding the safety and efficacy of antimicrobial discontinuation prior to neutropenia resolution.
Molecularly Targeted Therapy in Acute Myeloid Leukemia: Current Treatment Landscape and Mechanisms of Response and Resistance
Authors: Lachowiez Curtis A. , DiNardo Courtney D. , Loghavi Sanam
Published: March 2023

Treatment for acute myeloid leukemia (AML) has evolved rapidly over the last decade as improved understanding of cytogenetic and molecular drivers of leukemogenesis refined survival prognostication and enabled development of targeted therapeutics. Molecularly targeted therapies are now approved for the treatment of FLT3 and IDH1/2-mutated AML and additional molecularly and cellularly targeted therapeutics are in development for defined patient subgroups. Alongside these welcome therapeutic advancements, increased understanding of leukemic biology and treatment resistance has resulted in clinical trials investigating combinations of cytotoxic, cellular, and molecularly targeted therapeutics resulting in improved response and survival outcomes in patients with AML. Herein, we comprehensively review the current landscape of IDH and FLT3 inhibitors in clinical practice for the treatment of AML, highlight known resistance mechanisms, and discuss new cellular or molecularly targeted therapies currently under investigation in ongoing early phase clinical trials.
Evaluating the Protective Effect of Intravesical Bacillus Calmette-Guerin against SARS-CoV-2 in Non-Muscle Invasive Bladder Cancer Patients: A Multicenter Observational Trial
Authors: Hurle Rodolfo , Soria Francesco , Contieri Roberto , Avolio Pier Paolo , Mancon Stefano , Lazzeri Massimo , Bernasconi Valentina , Mazzoli Simone , Pizzuto Giuseppe , De Bellis Matteo , Rosazza Matteo , Livoti Simone , Lupia Tommaso , Corcione Silvia , Lillaz Beatrice , De Rosa Francesco Giuseppe , Buffi Nicolò Maria , Kamat Ashish M. , Gontero Paolo , Casale Paolo
Published: March 2023

We aim to evaluate the potential protective role of intravesical Bacillus Calmette-Guerin (BCG) against SARS-CoV-2 in patients with non-muscle invasive bladder cancer (NMIBC). Patients treated with intravesical adjuvant therapy for NMIBC between January 2018 and December 2019 at two Italian referral centers were divided into two groups based on the received intravesical treatment regimen (BCG vs. chemotherapy). The study’s primary endpoint was evaluating SARS-CoV-2 disease incidence and severity among patients treated with intravesical BCG compared to the control group. The study’s secondary endpoint was the evaluation of SARS-CoV-2 infection (estimated with serology testing) in the study groups. Overall, 340 patients treated with BCG and 166 treated with intravesical chemotherapy were included in the study. Among patients treated with BCG, 165 (49%) experienced BCG-related adverse events, and serious adverse events occurred in 33 (10%) patients. Receiving BCG or experiencing systemic BCG-related adverse events were not associated with symptomatic proven SARS-CoV-2 infection (p = 0.9) nor with a positive serology test (p = 0.5). The main limitations are related to the retrospective nature of the study. In this multicenter observational trial, a protective role of intravesical BCG against SARS-CoV-2 could not be demonstrated. These results may be used for decision-making regarding ongoing and future trials.
Continuous Flow Photochemical Synthesis of 3-Methyl-4-arylmethylene Isoxazole-5(4H)-ones through Organic Photoredox Catalysis and Investigation of Their Larvicidal Activity
Authors: Sampaio Ana Beatriz S. , Mori Mônica Shigemi S. , Albernaz Lorena C. , Espindola Laila S. , Salvador Carlos Eduardo M. , Andrade Carlos Kleber Z.
Published: March 2023

Isoxazole-5(4H)-ones are heteropentacycle compounds found in several bioactive molecules with pharmaceutical and agrochemical properties. A well-known multicomponent reaction between β-ketoester, hydroxylamine, and aromatic aldehydes leads to 3-methyl-4-arylmethylene isoxazole-5(4H)-ones, in mild conditions. The initial purpose of this work was to investigate whether the reaction might be induced by light, as described in previous works. Remarkable results were obtained using a high-power lamp, reducing reaction times compared to methodologies that used heating or catalysis. Since there are many examples of successful continuous flow heterocycle synthesis, including photochemical reactions, the study evolved to run the reaction in flow conditions and scale up the synthesis of isoxazolones using a photochemical reactor set-up. Eight different compounds were obtained, and among them, three showed larvicidal activity on immature forms of Aedes aegypti in tests that investigated its growth inhibitory character. Mechanistic investigations indicate that the reactions occur through organic photoredox catalysis.
Photocatalytic CO2 Reduction to CH4 and Dye Degradation Using Bismuth Oxychloride/Bismuth Oxyiodide/Graphitic Carbon Nitride (BiOmCln/BiOpIq/g-C3N4) Nanocomposite with Enhanced Visible-Light Photocatalytic Activity
Authors: Dai Yong-Ming , Wu Wu-Tsan , Lin Yu-Yun , Wu Hsiao-Li , Chen Szu-Han , Jehng Jih-Mirn , Lin Jia-Hao , Liu Fu-Yu , Chen Chiing-Chang
Published: March 2023

The use of visible-light-driven photocatalysts in wastewater treatment, photoreduction of CO2, green solar fuels, and solar cells has elicited substantial research attention. Bismuth oxyhalide and its derivatives are a group of visible-light photocatalysts that can diminish electron–hole recombination in layered structures and boost photocatalytic activity. The energy bandgap of these photocatalysts lies in the range of visible light. A simple hydrothermal method was applied to fabricate a series of bismuth oxychloride/bismuth oxyiodide/grafted graphitic carbon nitride (BiOmCln/BiOpIq/g-C3N4) sheets with different contents of g-C3N4. The fabricated sheets were characterized through XRD, TEM, SEM-EDS, XPS, UV-vis DRS, PL, and BET. The conversion efficiency of CO2 reduction to CH4 of BiOmCln/BiOpIq of 4.09 μmol g−1 can be increased to 39.43 μmol g−1 by compositing with g-C3N4. It had an approximately 9.64 times improvement. The photodegradation rate constant for crystal violet (CV) dye of BiOmCln/BiOpIq of k = 0.0684 can be increased to 0.2456 by compositing with g-C3N4. It had an approximately 3.6 times improvement. The electron paramagnetic resonance results and the quenching effects indicated that 1O2, •OH, h+, and •O2− were active species in the aforementioned photocatalytic degradation. Because of their heterojunction, the prepared ternary nanocomposites possessed the characteristics of a heterojunction of type II band alignment.
Improving the Photocatalytic Performance of Porous Ceria under Visible Light Illumination via Mn Incorporation
Authors: Atran Amal A. , Hamdy Mohamed S.
Published: March 2023

Porous cerium oxide (ceria) nanoparticles were prepared with and without manganese (Mn) by using the flash combustion technique. Samples with different loadings (Ce/Mn ratio ranged from 100 to 10) were prepared by using a one-step process and water only as a solvent. Moreover, citric acid was utilized as a fuel in an aqueous medium, and the overall synthesis mixture was dried at 100 °C overnight and then calcinated at 550 °C for 3 h. The obtained final solid product was characterized by inductively coupled plasma (ICP), X-ray powder diffraction (XRD), diffuse reflectance ultraviolet-visible spectroscopy (DR-UV-Vis), and scanning electron microscopy (SEM), which was coupled with Energy Dispersive X-Ray Analysis (EDX), high resolution transmission electron microscopy (HR-TEM), and photoluminescence (PL) analysis. The characterization data showed that Mn ions were totally incorporated into the framework of ceria up to the applied loading. Under visible light illumination, the photocatalytic activity of the prepared samples was tested in the decolorization reaction of methyl green (MG) dye (wavelength greater than 425 nm). The results showed that increasing Mn content improved the photocatalytic activity of ceria. The sample with a Ce/Mn ratio of 10 performed 1.8 times better than bare porous ceria. Finally, the reusability of the best-performing sample was investigated in four consecutive runs without treatment, and slight deactivation was monitored after the fourth run.
From PET Bottles Waste to N-Doped Graphene as Sustainable Electrocatalyst Support for Direct Liquid Fuel Cells
Authors: Elessawy Noha A. , Backović Gordana , Hirunthanawat Janesuda , Martins Marta , Rakočević Lazar , Gouda Marwa H. , Toghan Arafat , Youssef Mohamed E. , Šljukić Biljana , Santos Diogo M. F.
Published: March 2023

Direct liquid fuel cells represent one of the most rapidly emerging energy conversion devices. The main challenge in developing fuel cell devices is finding low-cost and highly active catalysts. In this work, PET bottle waste was transformed into nitrogen-doped graphene (NG) as valuable catalyst support. NG was prepared by a one-pot thermal decomposition process of mineral water waste bottles with urea at 800 °C. Then, NG/Pt electrocatalysts with Pt loadings as low as 0.9 wt.% and 1.8 wt.% were prepared via a simple reduction method in aqueous solution at room temperature. The physical and electrochemical properties of the NG/Pt electrocatalysts are characterized and evaluated for application in direct borohydride peroxide fuel cells (DBPFCs). The results show that NG/Pt catalysts display catalytic activity for borohydride oxidation reaction, particularly the NG/Pt_1, with a number of exchanged electrons of 2.7. Using NG/Pt composite in fuel cells is anticipated to lower prices and boost the usage of electrochemical energy devices. A DBPFC fuel cell using NG/Pt_1 catalyst (1.8 wt.% Pt) in the anode achieved a power density of 75 mW cm−2 at 45 °C. The exceptional performance and economic viability become even more evident when expressed as mass-specific power density, reaching a value as high as 15.8 W mgPt−1.
Selective Catalytic Reduction of NOx by CO over Cu(Fe)/SBA-15 Catalysts: Effects of the Metal Loading on the Catalytic Activity
Authors: Souza Monique S. , Martins Antonio J. , Ribeiro Jackson Anderson S. , Campos Adriana , Oliveira Alcineia C. , Jucá Raí F. , Saraiva Gilberto D. , Torres Marco Antonio M. , Rodríguez-Castellón Enrique , Araujo Rinaldo S.
Published: March 2023

Mesoporous Cu(Fe)/SBA-15 catalysts were prepared with distinct metal loadings of ca. 2–10 wt.%. A detailed set of characterizations using X-ray diffraction (XRD), electron paramagnetic resonance (EPR), transmission electron microscopy (TEM), scanning electron microscopy coupled to energy dispersive spectroscopy (SEM-EDS), Mössbauer spectroscopy, X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy was performed to correlate the relationship among structure, electronic properties and catalytic performances. All solids were evaluated in the selective catalytic reduction of NOx in the presence of CO (CO-SCR). The influence of the metal loadings on the overall activity indicated that introducing high amounts of Fe or Cu on the catalysts was beneficial to form either CuO or α-Fe2O3 clusters. Cux/SBA-15 series exhibited more efficient activity and poison-tolerant ability during CO-SCR reaction, in contrast to Fex/SBA-15. In spite of the Fe species introduced on SBA-15 having structural features similar to those of Cu ones, low interactions among Fe nanoparticles, silica and clusters impeded the high performances of Fe10/SBA-15. XPS revealed the Fe species in a more oxidized state, indicating the stability of the solid after the catalytic tests, in agreement with EPR and Raman spectroscopy. Cu8/SBA-15 worked better, being recyclable due to the interaction of the Cu2+ ions with SBA-15, avoiding the deactivation of the catalyst.