bluuebunny/crossref_metadata_2025 huggingface dataset:
Formulation of a Simulated Wastewater Influent Composition for Use in the Research of Technologies for Managing Wastewaters Generated during Manned Long-Term Space Exploration and Other Similar Situations—Literature-Based Composition Development
Authors: Shrestha Bimi , Hernandez Rafael , Fortela Dhan Lord B. , Sharp Wayne , Chistoserdov Andrei , Gang Daniel , Revellame Emmanuel , Holmes William E. , Zappi Mark E.
Published: January 2023

The prospect of humans inhabiting planetary bodies is gaining interest among research and development communities, with the moon being considered as a transitory base camp and Mars the next planet humans will inhabit. NASA’s Mission to Mars program is set to have humans inhabiting Mars within on-planet space camps by the Year 2030, which has tremendously increased research and development for space exploration—including research oriented toward human life support in long-term planetary lodging camps. The sustenance of human life on Mars will not be trivial due to the unavailability of an appropriate atmosphere and usable water. This situation requires a self-sustaining human life support system that can provide the basic needs such are breathable air, potable water, food, and energy. The feasibility of sending a payload with resources adequate to support long-term human inhabitation is not reasonable, which means every resource within a Mars space camp is valuable, including human-produced wastes. A biorefinery system that treats wastewater and can also produce valuable products such as oxygen, food, and energy offers a form of circular utilization of valuable resources. To conduct research for such systems requires a wastewater influent that is representative of the wastewater to be generated by the space crew within this isolated, confined environment, which is different from what is generated on Earth due to limited variability in diet, human activity, and lifestyle in this confined area. Collection of actual wastewater influent from an isolated environment supporting humans is challenging. Additionally, to ensure a safe working environment in the laboratory and avoid the imposed threat of handling actual human feces, the proposed synthetic, non-human feces containing wastewater influent formulation offers an easy-to-produce and safer-to-handle option. This paper reviews several synthetic wastewater compositions that have been formulated for space exploration purposes. None of the formulations were found to be realistic nor adequate for a space-camp-type scenario. Thus, the formulation of a synthetic wastewater for simulating a wastewater influent from a human space-based camp is proposed in this paper. In addition, the physical, chemical, and biodegradation characteristics of the final formulation designed are presented to illustrate the value of the proposed influent formulation.
High-Level Production of Soluble Cross-Reacting Material 197 in Escherichia coli Cytoplasm Due to Fine Tuning of the Target Gene’s mRNA Structure
Authors: Khodak Yulia Alexandrovna , Ryazanova Alexandra Yurievna , Vorobiev Ivan Ivanovich , Kovalchuk Alexander Leonidovich , Ovechko Nikolay Nikolaevich , Aparin Petr Gennadievich
Published: January 2023

Cross-reacting material 197 (CRM197) is a non-toxic mutant of the diphtheria toxin and is widely used as a carrier protein in conjugate vaccines. This protein was first obtained from the supernatant of the mutant Corynebacterium diphtheriae strain. This pathogenic bacteria strain is characterized by a slow growth rate and a relatively low target protein yield, resulting in high production costs for CRM197. Many attempts have been made to establish high-yield protocols for the heterologous expression of recombinant CRM197 in different host organisms. In the present work, a novel CRM197-producing Escherichia coli strain was constructed. The target protein was expressed in the cytoplasm of SHuffle T7 E. coli cells without any additional tags and with a single potential mutation—an additional Met [−1]. The fine tuning of the mRNA structure (the disruption of the single hairpin in the start codon area) was sufficient to increase the CRM197 expression level several times, resulting in 150–270 mg/L (1.1–2.0 mg/g wet biomass) yields of pure CRM197 protein. Besides the high yield, the advantages of the obtained expression system include the absence of the necessity of CRM197 refolding or tag removal. Thus, an extensive analysis of the mRNA structure and the removal of the unwanted hairpins in the 5′ area may significantly improve the target protein expression rate.
Arcuate Fasciculus Microstructure Predicts Alcohol Dependence Risk through Higher IQ
Authors: Ikuta Toshikazu , Kessler Paige B. , Swoboda Alexandria M. , Fisher Amy K.
Published: January 2023

IQ has been found to correlate with alcohol consumption, with a higher IQ being a risk for alcohol misuse. Furthermore, recent research has shown that the microstructure of the arcuate fasciculus is associated with IQ. This study therefore aimed to examine the association between the arcuate fasciculus microstructure, IQ, and alcohol dependence risk. In this study, we performed probabilistic tractography between Wernicke’s and Broca’s areas in the left and right hemispheres to examine the association of the arcuate fasciculus’s integrity with IQ and alcohol dependence risk, using DTI data from 344 individuals. Data regarding IQ were obtained from the Wechsler Abbreviated Scale of Intelligence (WASI-II). Alcohol substance involvement (SI) score was derived using the National Institute on Drug Abuse (NIDA) Quick Screen and was used as an index for alcohol dependence risk. Both the left arcuate fasciculus and IQ were found to have a significant association with alcohol dependence risk. A mediation analysis revealed that this association between the left arcuate fasciculus microstructure and an alcohol dependence risk was mediated by IQ. It is suggested that the left arcuate fasciculus microstructure is associated with IQ which is associated with alcohol dependence risk. While alcohol consumption is known to be robustly toxic to the brain, the left arcuate fasciculus shows exceptional characteristics in which its microstructure integrity is positively associated with an alcohol dependence risk through higher IQ. Clinical implications are discussed.
Neo-Piagetian Predictors of Students’ Performance in Science Learning: Evidence from Primary Education
Authors: Vaiopoulou Julie , Tsikalas Themistocles , Stamovlasis Dimitrios , Papageorgiou George
Published: January 2023

This study explores primary school pupils’ knowledge recall and interpretation skills regarding chemical and physical phenomena, in relation to three psychometric variables: logical thinking, field dependence/field independence, and divergent thinking. The participants (N = 375) were in the fifth and sixth grades (aged 11–12) taking an introductory course in science, and they were involved in three tasks related to combustion, dissolution, and mixture separation. The pupils had to complete an instrument, in which they were asked to describe and interpret the phenomena involved in the tasks. Two achievement variables were recorded separately, one relating to knowledge recall and the other to the interpretation of the phenomena. In addition, the participants completed the corresponding psychometric tests. Correlational and multiple linear regression analysis showed that the dependent measures were associated with the cognitive variables, while path and mediation analysis showed the direct and indirect effects of the neo-Piagetian constructs on the dimensions of knowledge and interpretations. The main implications of the findings are theoretical and concern the role of the operationalized mental resources in learning the specific subject matter. Moreover, the results inform teaching practices and curricula designs, and they point out the learning difficulties ascending from the individual differences under study. Further discussion on conceptual change is provided.
A TRIZ-Supported Concept and Protocol Development for Roof Tile Transportation and Inspection Systems
Authors: Phuah Zhi Yuan , Ng Poh Kiat , Prasetio Murman Dwi , Liew Kia Wai , Lim Boon Kian , Oktafiani Ayudita , Salma Sheila Amalia , Safrudin Yunita Nugrahaini
Published: January 2023

Currently, the use of manual labour in the transportation and inspection systems of leading roof tile manufacturing companies in Indonesia is still prevalent. Manual labour is usually labour-intensive, has higher risks of musculoskeletal disorders, and produces frequent occurrences of errors and losses. Furthermore, the current studies of suitable concepts and test protocols for roof tile transportation at the manufacturing stage as well as their inspection systems are not practicable in Indonesia. There is also no study that has used the theory of inventive problem-solving (TRIZ) in the development of concepts and protocols for roof tile transportation and inspection systems. Using TRIZ as a supporting tool, this study investigated the development of a transportation system to be employed during the manufacturing of the roof tile and a test protocol for their usability in Indonesian companies to overcome this concern. The study included screening and scoring concepts and usability test protocols identified from the existing literature, with the support of TRIZ tools such as the engineering contradiction, contradiction matrix, and inventive principles. Thus, the finalised concept comprised a belt conveyor system (Inventive Principle 20: Continuity of Useful Action) with a flipping mechanism for transportation and a vision-based camera for inspection. Results of the study showed that the concept excelled in cost, durability, reliability, versatility, low risk to the product, efficiency, and safety. The t-test protocol (Inventive Principle 23: Feedback) was selected based on the results due to its versatility in testing efficiency, reliability, and productivity. It was concluded that this concept has the potential to alleviate roof tile workers of physical work and reduce the prevalence of musculoskeletal disorders.
Weathering Mechanisms of Porous Marl Stones in Coastal Environments and Evaluation of Conservation Treatments as Potential Adaptation Action for Facing Climate Change Impact
Authors: Michalopoulou Anastasia , Markantonis Iason , Vlachogiannis Diamando , Sfetsos Athanasios , Kilikoglou Vassilis , Karatasios Ioannis
Published: January 2023

This work presents the methodological approach followed for the study of the interaction of natural stone monuments with the local microclimate (exposure to RH, temperature alterations, wind, marine aerosol). This was implemented with the documentation of the associated weathering phenomena and the study of historic climate data of the area. The paper is focused on the main weathering mechanisms of the marly limestone at the Hellenistic theater of Zea in Piraeus, Greece. Based on the weathering phenomena identified, the development of the appropriate mitigation strategy was based on the physical, chemical and mechanical characterization of the natural stones, along with the evaluation of different conservation treatments, considering the characteristics of the coastal environment. Considering the mineralogy of marly limestones, silane-based materials were selected for providing both consolidation and water repellency effects. The evaluation of the conservation treatments was based on the modification of microstructural and water-related properties of natural stone samples, along with their consequent effect on their durability against accelerated aging tests. The results indicated that the design of migration actions proved to be multivariable parameter, depending on the intrinsic stone properties, the environmental parameters and the conservation efficacy of the treatments.
Effect of Precompression and Material Uncertainty on the In-Plane Behavior of URM Pier–Spandrel Systems
Authors: Pulatsu Bora , Gonen Semih , Parisi Fulvio
Published: January 2023

Theoretical and experimental studies on loadbearing masonry walls have shown the significant influence of the axial load level (i.e., precompression) and wall aspect ratio on in-plane lateral resistance. Nonetheless, the impact of the precompression and spatial variability of the material properties needs to be further investigated at the scale of walls with openings. This study presents a stochastic analysis of unreinforced (URM) pier–spandrel systems subjected to both axial loads on piers and lateral loads, considering the spatial variation in material properties. A discontinuum-based computational model was utilized to assess the force–displacement behavior of a benchmark pier–spandrel structure under different vertical precompression levels on piers. A total of 750 simulations were carried out to propagate material uncertainties in lateral load analysis. The proposed modeling strategy, based on the discrete element method, explicitly represents joint openings, sliding, and crushing phenomena at the contact points defined between the adjacent discrete rigid blocks. According to the validated computational modeling strategy, meaningful inferences were made regarding the effect of the precompression level on the maximum displacement and ultimate lateral load-carrying capacity of the benchmark URM pier–spandrel system. The results showed that vertical pressure on piers had considerable influence on the displacement ductility of the system while yielding less variation in the displacement capacity. Furthermore, the appealing feature of the spatial probabilistic analysis is noted in the variation in the lateral load-carrying capacity of the structural system.
PVRIG Expression Is an Independent Prognostic Factor and a New Potential Target for Immunotherapy in Hepatocellular Carcinoma
Authors: Birnbaum David Jeremie , Picard Maelle , Da Costa Quentin , Delayre Thomas , Finetti Pascal , Cabaud Olivier , Agavnian Emilie , De Rauglaudre Bernadette , Denicolaï Emilie , Bertucci François , Mamessier Emilie
Published: January 2023

Hepatocellular carcinoma (HCC) is a frequent and deadly cancer in need of new treatments. Immunotherapy has shown promising results in several solid tumors. The TIGIT/DNAM-1 axis gathers targets for new immune checkpoint inhibitors (ICIs). Here, we aimed at highlighting the potential of this axis as a new therapeutic option for HCC. For this, we built a large transcriptomic database of 683 HCC samples, clinically annotated, and 319 normal liver tissues. We interrogated this database for the transcriptomic expression of each member of the TIGIT/DNAM-1 axis and tested their prognostic value for survival. We then focused on the most discriminant one for these criteria, i.e., PVRIG, and analyzed the clinical characteristics, the disease-free and overall survivals, and biological pathways associated with PVRIG High tumors. Among all members of the TIGIT/DNAM-1 axis, PVRIG expression was higher in tumors than in normal liver, was heterogeneous across tumors, and was the only member with independent prognostic value for better survival. PVRIG High tumors were characterized by a higher lymphocytic infiltrate and enriched for signatures associated with tertiary lymphoid structures and better anti-tumor immune response. These results suggest that patients with PVRIG High tumors might be good candidates for immune therapy involving ICIs, notably ICIs targeting the TIGIT/DNAM-1 axis. Further functional and clinical validation is urgently required.
Developments in the Surgical Approach to Staging and Resection of Rhabdomyosarcoma
Authors: Terwisscha van Scheltinga Sheila , Rogers Timothy , Smeulders Naima , deCorti Federica , Guerin Florent , Craigie Ross , Burrieza Gabriela Guillén , Smeele Ludi , Hol Marinka , van Rijn Rick , Fuchs Joerg , Seitz Guido , Schmidt Andreas , Timmermann Beate , Tunn Per-Ulf , Chargari Cyrus , Dávila Fajardo Raquel , Slater Olga , Gains Jenny , Merks Hans
Published: January 2023

Although survival after rhabdosarcoma treatment has improved over the years, one third of patients still develop locoregional relapse. This review aims to highlight developments pertaining to staging and local treatment of specific RMS tumor sites, including head and neck, chest/trunk, bladder-prostate, female genito-urinary, perianal, and extremity sites.
Thrombospondin-2 as a Predictive Biomarker for Hepatocellular Carcinoma after Hepatitis C Virus Elimination by Direct-Acting Antiviral
Authors: Matsumae Takayuki , Kodama Takahiro , Tahata Yuki , Myojin Yuta , Doi Akira , Nishio Akira , Yamada Ryoko , Nozaki Yasutoshi , Oshita Masahide , Hiramatsu Naoki , Morishita Naoki , Ohkawa Kazuyoshi , Hijioka Taizo , Sakakibara Mitsuru , Doi Yoshinori , Kakita Naruyasu , Yakushijin Takayuki , Sakamori Ryotaro , Hikita Hayato , Tatsumi Tomohide , Takehara Tetsuo
Published: January 2023

We evaluated the value of secreted glycoprotein thrombospondin-2 (TSP-2) to predict hepatocellular carcinoma (HCC) occurrence in chronic hepatitis C (CHC) patients after Hepatitis C virus (HCV) elimination by direct-acting antiviral agents (DAAs). A total of 786 CHC patients without an HCC history who achieved a sustained virological response (SVR) with DAAs were randomly assigned 2:1, with 524 patients as the derivation cohort and 262 patients as the validation cohort. Serum TSP-2 levels at the end of treatment were measured by enzyme-linked immunosorbent assay (ELISA). In the derivation cohort, the cumulative HCC rate was significantly higher in the high TSP-2 group than in the low TSP-2 group. Multivariate Cox proportional hazards analysis revealed that TSP-2, α-fetoprotein (AFP), and the fibrosis-4 (FIB-4) index were independent HCC risk factors. The area under the receiver operating characteristic curve (AUROC) of the score calculated from these three factors (AFT score) for predicting HCC was 0.83, which was significantly higher than that of each factor alone (TSP-2: 0.70, AFP: 0.72, FIB-4: 0.69). The AFT score was used to stratify patients according to the risk of HCC occurrence in the validation cohort. Lastly, in patients with a FIB-4 index < 3.25, the serum TSP-2 levels could be used to identify those patients with a high risk of HCC occurrence. Serum TSP-2 levels are a predictive biomarker of HCC occurrence in CHC patients after HCV elimination by DAA treatment. The AFT score using TSP-2, AFP, and the FIB-4 index may identify those who require HCC surveillance.
Highly Metastatic Subpopulation of TNBC Cells Has Limited Iron Metabolism and Is a Target of Iron Chelators
Authors: Wang Yuze , Ohara Toshiaki , Chen Yuehua , Hamada Yusuke , Li Chunning , Fujisawa Masayoshi , Yoshimura Teizo , Matsukawa Akihiro
Published: January 2023

Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate a possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo. Lung metastasis was further significantly reduced, leading to the hypothesis that iron metabolism between metastatic and non-metastatic cells may be different. An analysis of existing database demonstrated that the expression of iron-uptake genes was significantly suppressed in TNBC cells that metastasized to lymph nodes or lungs compared to those in primary tumors. A highly metastatic clone of the murine 4T1 TNBC cells (4T1-HM) did not proliferate well under iron-rich or iron-depleted conditions by iron chelators compared to a low-metastatic clone (4T1-LM). Bulk RNA-seq analysis of RNA from 4T1-HM and 4T1-LM cells suggested that the PI3K-AKT pathway might be responsible for this difference. Indeed, DFX suppressed the proliferation via the AKT-mTOR pathway in 4T1-HM and the human MDA-MB-231 cells, a human mesenchymal-like TNBC cell line. DFX also suppressed the growth of 4T1-HM tumors in comparison to 4T1-LM tumors, and reduced lung metastases after surgical resection of primary 4T1 tumors. These results indicated, for the first time, that highly metastatic TNBC cells have limited iron metabolism, and they can be more effectively targeted by iron chelators.
The Use of Artificial Intelligence (AI) in the Radiology Field: What Is the State of Doctor–Patient Communication in Cancer Diagnosis?
Authors: Derevianko Alexandra , Pizzoli Silvia Francesca Maria , Pesapane Filippo , Rotili Anna , Monzani Dario , Grasso Roberto , Cassano Enrico , Pravettoni Gabriella
Published: January 2023

Background: In the past decade, interest in applying Artificial Intelligence (AI) in radiology to improve diagnostic procedures increased. AI has potential benefits spanning all steps of the imaging chain, from the prescription of diagnostic tests to the communication of test reports. The use of AI in the field of radiology also poses challenges in doctor–patient communication at the time of the diagnosis. This systematic review focuses on the patient role and the interpersonal skills between patients and physicians when AI is implemented in cancer diagnosis communication. Methods: A systematic search was conducted on PubMed, Embase, Medline, Scopus, and PsycNet from 1990 to 2021. The search terms were: (“artificial intelligence” or “intelligence machine”) and “communication” “radiology” and “oncology diagnosis”. The PRISMA guidelines were followed. Results: 517 records were identified, and 5 papers met the inclusion criteria and were analyzed. Most of the articles emphasized the success of the technological support of AI in radiology at the expense of patient trust in AI and patient-centered communication in cancer disease. Practical implications and future guidelines were discussed according to the results. Conclusions: AI has proven to be beneficial in helping clinicians with diagnosis. Future research may improve patients’ trust through adequate information about the advantageous use of AI and an increase in medical compliance with adequate training on doctor–patient diagnosis communication.
Baseline [68Ga]Ga-PSMA-11 PET/CT before [177Lu]Lu-PSMA-617 Radioligand Therapy: Value of PSMA-Uptake Thresholds in Predicting Targetable Lesions
Authors: Groener Daniel , Schneider Sina , Baumgarten Justus , Happel Christian , Klimek Konrad , Mader Nicolai , Nguyen Ngoc Christina , Wichert Jennifer , Mandel Philipp , Tselis Nikolaos , Grünwald Frank , Sabet Amir
Published: January 2023

Baseline uptake on prostate-specific membrane antigen (PSMA)-targeted imaging is a prerequisite for radioligand therapy (RLT) with [177Lu]Lu-PSMA-617. This study aims to quantify lesion-based response to RLT in relation to pretreatment standard molecular imaging metrics derived from [68Ga]Ga-PSMA-11 PET/CT. Sixty-one patients with mCRPC underwent [68Ga]Ga-PSMA-11 PET/CT imaging before and after a median of 4 (IQR 2–6) RLT cycles. Maximum and mean standardized uptake values (SUVmax, SUVmean), as well as tumor-to-liver ratio (TLR), were assessed. A median of 12 (IQR 7–17) lesions was analyzed per patient, resulting in a total of 718 lesions. Lesions with ≥30% SUVmax decline or falling below the blood pool uptake were considered responsive; ≥30% SUVmax increase marked lesion progression. Additionally, 4-point visual scoring was performed according to E-PSMA consensus. In total, 550/718 (76.6%) lesions responded to RLT, including 389/507 (76.7%) bone metastases and 143/181 (79.0%) lymph node metastases. Baseline SUVmax, SUVmean, and TLR values were associated with lesion response by a moderate but significant correlation (rs = 0.33, p < 0.001, rs = 0.32, p < 0.001, and rs = 0.31, p < 0.001, respectively). For the classification of lesion progression based on baseline PSMA uptake, receiver operating characteristics (ROC) found SUVmax, SUVmean, and TLR to have comparable discriminatory value (AUC 0.85, 0.87, and 0.83). Of 42 tumor sites with baseline uptake below the liver (V-score < 2), 19/42 (45.2%) were responsive, 9/42 (21.4%) were stable, and 14/42 (33.3%) showed progression, leaving liver uptake a threshold with low prognostic value for the identification of RLT-refractory lesions (PPV 33%). This was observed accordingly for various liver uptake-based thresholds, including TLR < 1.5, <2.0 with a PPV at 24%, 20%, respectively. Standard uptake parameters quantified by routine baseline [68Ga]Ga-PSMA-11 PET/CT are moderately associated with post-treatment lesion response to [177Lu]Lu-PSMA-617. Commonly applied liver-based uptake thresholds have limited value in predicting refractory lesions at individual tumor sites.
Ex Vivo Functional Assay for Evaluating Treatment Response in Tumor Tissue of Head and Neck Squamous Cell Carcinoma
Authors: Capala Marta E. , Pachler Katrin S. , Lauwers Iris , de Korte Maarten A. , Verkaik Nicole S. , Mast Hetty , Jonker Brend P. , Sewnaik Aniel , Hardillo Jose A. , Keereweer Stijn , Monserez Dominiek , Koljenovic Senada , Mostert Bianca , Verduijn Gerda M. , Petit Steven , van Gent Dik C.
Published: January 2023

Background: Head and neck squamous cell carcinoma (HNSCC) displays a large heterogeneity in treatment response, and consequently in patient prognosis. Despite extensive efforts, no clinically validated model is available to predict tumor response. Here we describe a functional test for predicting tumor response to radiation and chemotherapy on the level of the individual patient. Methods: Resection material of 17 primary HNSCC patients was cultured ex vivo, irradiated or cisplatin-treated, after which the effect on tumor cell vitality was analyzed several days after treatment. Results: Ionizing radiation (IR) affected tumor cell growth and viability with a clear dose-response relationship, and marked heterogeneity between tumors was observed. After a single dose of 5Gy, proliferation in IR-sensitive tumors dropped below 30% of the untreated level, while IR-resistant tumors maintained at least 60% of proliferation. IR-sensitive tumors showed on average a twofold increase in apoptosis, as well as an increased number and size of DNA damage foci after treatment. No differences in the homologous recombination (HR) proficiency between IR-sensitive and –resistant tumors were detected. Cisplatin caused a decrease in proliferation, as well as induction of apoptosis, again with marked variation between the samples. Conclusions: Our functional ex vivo assay discriminated between IR-sensitive and IR-resistant HNSCC tumors, and may also be suitable for predicting response to cisplatin. Its predictive value is currently under investigation in a prospective clinical study.
Sphingosine-1-Phosphate Recruits Macrophages and Microglia and Induces a Pro-Tumorigenic Phenotype That Favors Glioma Progression
Authors: Arseni Lavinia , Sharma Rakesh , Mack Norman , Nagalla Deepthi , Ohl Sibylle , Hielscher Thomas , Singhal Mahak , Pilz Robert , Augustin Hellmut , Sandhoff Roger , Herold-Mende Christel , Tews Björn , Lichter Peter , Seiffert Martina
Published: January 2023

Glioblastoma is the most aggressive brain tumor in adults. Treatment failure is predominantly caused by its high invasiveness and its ability to induce a supportive microenvironment. As part of this, a major role for tumor-associated macrophages/microglia (TAMs) in glioblastoma development was recognized. Phospholipids are important players in various fundamental biological processes, including tumor–stroma crosstalk, and the bioactive lipid sphingosine-1-phosphate (S1P) has been linked to glioblastoma cell proliferation, invasion, and survival. Despite the urgent need for better therapeutic approaches, novel strategies targeting sphingolipids in glioblastoma are still poorly explored. Here, we showed that higher amounts of S1P secreted by glioma cells are responsible for an active recruitment of TAMs, mediated by S1P receptor (S1PR) signaling through the modulation of Rac1/RhoA. This resulted in increased infiltration of TAMs in the tumor, which, in turn, triggered their pro-tumorigenic phenotype through the inhibition of NFkB-mediated inflammation. Gene set enrichment analyses showed that such an anti-inflammatory microenvironment correlated with shorter survival of glioblastoma patients. Inhibition of S1P restored a pro-inflammatory phenotype in TAMs and resulted in increased survival of tumor-bearing mice. Taken together, our results establish a crucial role for S1P in fine-tuning the crosstalk between glioma and infiltrating TAMs, thus pointing to the S1P–S1PR axis as an attractive target for glioma treatment.
Combining Multi-Shell Diffusion with Conventional MRI Improves Molecular Diagnosis of Diffuse Gliomas with Deep Learning
Authors: Karami Golestan , Pascuzzo Riccardo , Figini Matteo , Del Gratta Cosimo , Zhang Hui , Bizzi Alberto
Published: January 2023

The WHO classification since 2016 confirms the importance of integrating molecular diagnosis for prognosis and treatment decisions of adult-type diffuse gliomas. This motivates the development of non-invasive diagnostic methods, in particular MRI, to predict molecular subtypes of gliomas before surgery. At present, this development has been focused on deep-learning (DL)-based predictive models, mainly with conventional MRI (cMRI), despite recent studies suggesting multi-shell diffusion MRI (dMRI) offers complementary information to cMRI for molecular subtyping. The aim of this work is to evaluate the potential benefit of combining cMRI and multi-shell dMRI in DL-based models. A model implemented with deep residual neural networks was chosen as an illustrative example. Using a dataset of 146 patients with gliomas (from grade 2 to 4), the model was trained and evaluated, with nested cross-validation, on pre-operative cMRI, multi-shell dMRI, and a combination of the two for the following classification tasks: (i) IDH-mutation; (ii) 1p/19q-codeletion; and (iii) three molecular subtypes according to WHO 2021. The results from a subset of 100 patients with lower grades gliomas (2 and 3 according to WHO 2016) demonstrated that combining cMRI and multi-shell dMRI enabled the best performance in predicting IDH mutation and 1p/19q codeletion, achieving an accuracy of 75 ± 9% in predicting the IDH-mutation status, higher than using cMRI and multi-shell dMRI separately (both 70 ± 7%). Similar findings were observed for predicting the 1p/19q-codeletion status, with the accuracy from combining cMRI and multi-shell dMRI (72 ± 4%) higher than from each modality used alone (cMRI: 65 ± 6%; multi-shell dMRI: 66 ± 9%). These findings remain when we considered all 146 patients for predicting the IDH status (combined: 81 ± 5% accuracy; cMRI: 74 ± 5%; multi-shell dMRI: 73 ± 6%) and for the diagnosis of the three molecular subtypes according to WHO 2021 (combined: 60 ± 5%; cMRI: 57 ± 8%; multi-shell dMRI: 56 ± 7%). Together, these findings suggest that combining cMRI and multi-shell dMRI can offer higher accuracy than using each modality alone for predicting the IDH and 1p/19q status and in diagnosing the three molecular subtypes with DL-based models.
The Role of Pharmacotherapy in Treatment of Meningioma: A Systematic Review
Authors: Shahbandi Ataollah , Shah Darsh S. , Hadley Caroline C. , Patel Akash J.
Published: January 2023

The safety and efficacy of various pharmacotherapeutic regimens on refractory meningiomas have been the focus of investigations. We present a comprehensive review of the previous efforts and the current state of ongoing clinical trials. A PRISMA-compliant review of the MEDLINE and ClinicalTrial.gov databases of the National Library of Medicine were performed. The primary outcomes of interest for included articles were radiographic response, overall survival, progression-free survival, six-month progression-free survival, and adverse events. Overall, 34 completed trials and 27 ongoing clinical trials were eligible. Six-month progression-free survival was reported in 6–100% of patients in the completed studies. Hematological disorders were the most common adverse events. Of the ongoing clinical trials identified, nine studies are phase I clinical trials, eleven are phase II trials, two are phase I and II trials, one is phase II and III, and two trials do not have a designated phase. Currently, there is no effective chemotherapy for refractory or recurrent meningiomas. Several promising targeted agents have been developed and are currently being investigated in the hope of identifying novel therapeutic strategies for the treatment of this pathology.
New In Situ Catalysts Based on Nitro Functional Pyrazole Derivatives and Copper (II) Salts for Promoting Oxidation of Catechol to o-Quinone
Authors: Titi Abderrahim , Zaidi Kaoutar , Alzahrani Abdullah Y. A. , El Kodadi Mohamed , Yousfi El Bekkaye , Moliterni Anna , Hammouti Belkheir , Touzani Rachid , Abboud Mohamed
Published: January 2023

Herein, new substituted ligands based on pyrazole (L1–L4) were synthesized via a one-step by condensing (1H-pyrazole-1-yl) methanol with different primary amine compounds. The present work utilized the catalytic properties of the in situ complexes formed by these ligands with various copper (II) salts viz. Cu(CH3COO)2, CuSO4, CuCl2, and Cu(NO3)2 for the oxidation of catechol to o-quinone. The studies showed that the catalytic activities depend on the nature and concentration of the ligand, the nature of the counterion, and the solvent. It was observed that the complex formed by L2 and Cu(CH3COO)2 exhibited good catalytic activity in methanol with Vmax of 41.67 µmol L−1 min−1 and Km of 0.02 mol L−1.
Template-Assisted SnO2: Synthesis, Composition, and Photoelectrocatalytical Properties
Authors: Gribov Evgenii , Koshevoy Evgeny , Chikunova Iuliia , Parmon Valentin
Published: January 2023

A series of tin oxides were synthesized with polystyrene microspheres (250 nm) as the template. It was shown that an increase in the template content led to increasing specific pore volume and to the formation of bimodal pore structure with pores of 9 and 70 nm in diameter. Addition of cetyltrimethylammonium bromide (CTAB) during synthesis led to the formation of friable structures (SEM data), to an increase in the average pore diameter from 19 to 111 nm, and to the formation of macropores of 80–400 nm in size. All materials had similar surface properties and cassiterite structure with 5.9–10.8 nm coherent scattering region (XRD data). Flat-band potentials of the samples were determined and their photoelectrocatalytic properties to oxidation of water and methanol were studied in the potential range of 0.4–1.6 V RHE. It was shown that the sample obtained using CTAB was characterized by lower flat-band potential value, but appeared significantly higher photocurrent in methanol oxidation, which resulted from enhanced macro-meso-porous structure to facilitate methanol pore diffusion.
Catalytic Activity of Ni Based Materials Prepared by Different Methods for Hydrogen Production via the Water Gas Shift Reaction
Authors: Tojira Opas , Tepamatr Pannipa
Published: January 2023

Water gas shift reactions (WGS) were evaluated over Ni/CeO2 and Ni/CeSmO catalysts for hydrogen production. The effects of catalyst preparation method and Sm loading were investigated. The Ni/ceria and Ni/CeSmO catalysts were synthesized by combustion, sol gel and sol gel-combustion method. After WGS tests, the catalysts were determined the carbon deposition by thermogravimetric analysis. The thermogravimetric analysis and temperature programmed NH3 desorption showed that addition of Sm promoter made higher the weak acid sites and lower the amount of carbon deposition than the unpromoted catalyst due to it being easily removed. CO chemisorption result indicated that Ni/Ce5%SmO catalyst prepared by combustion method has the highest Ni metal dispersion and metallic surface area compared to the other catalysts. The enhancement of WGS activity of this catalyst is due to more surface active sites being exposed to reactants. Furthermore, H2-temperature programmed reduction analysis confirmed an easiest reduction of this catalyst. This behavior accelerates the redox process at the ceria surface and enhances the oxygen vacancy concentration. The catalytic activity measurements exhibited that the optimum Sm loading was 5% wt. and the best catalyst preparation was the combustion method. The high surface area and small crystallite size of the 5%Ni/Ce5%SmO (combustion) catalyst resulted in sufficient dispersion, which closely related to the WGS activity of the catalyst.
The Distinct Assignments for Hsp90α and Hsp90β: More Than Skin Deep
Authors: Chang Cheng , Tang Xin , Woodley David T. , Chen Mei , Li Wei
Published: January 2023

For decades, the undisputable definition of the cytosolic Hsp90α and hsp90β proteins being evolutionarily conserved, ATP-driven chaperones has ruled basic research and clinical trials. The results of recent studies, however, have fundamentally challenged this paradigm, not to mention the spectacular failures of the paradigm-based clinical trials in cancer and beyond. We now know that Hsp90α and Hsp90β are both ubiquitously expressed in all cell types but assigned for distinct and irreplaceable functions. Hsp90β is essential during mouse development and Hsp90α only maintains male reproductivity in adult mice. Neither Hsp90β nor Hsp90α could substitute each other under these biological processes. Hsp90β alone maintains cell survival in culture and Hsp90α cannot substitute it. Hsp90α also has extracellular functions under stress and Hsp90β does not. The dramatic difference in the steady-state expression of Hsp90 in different mouse organs is due to the variable expressions of Hsp90α. The lowest expression of Hsp90 is less than 2% and the highest expression of Hsp90 is 9% among non-transformed cell lines. The two linker regions only take up less than 5% of the Hsp90 proteins, but harbor 21% of the total amino acid substitutions, i.e., 40% in comparison to the 86% overall amino acid homology. A full understanding of the distinctions between Hsp90α and Hsp90β could lead to new, safe and effective therapeutics targeting Hsp90 in human disorders such as cancer. This is the first comprehensive review of a comparison between the two cytosolic Hsp90 isoforms.
The Nuclear Transporter Importin 13 Can Regulate Stress-Induced Cell Death through the Clusterin/KU70 Axis
Authors: Gajewska Katarzyna A. , Jans David A. , Wagstaff Kylie M.
Published: January 2023

The cellular response to environmental stresses, such as heat and oxidative stress, is dependent on extensive trafficking of stress-signalling molecules between the cytoplasm and nucleus, which potentiates stress-activated signalling pathways, eventually resulting in cell repair or death. Although Ran-dependent nucleocytoplasmic transport mediated by members of the importin (IPO) super family of nuclear transporters is believed to be responsible for nearly all macromolecular transit between nucleus and cytoplasm, it is paradoxically known to be significantly impaired under conditions of stress. Importin 13 (IPO13) is a unique bidirectional transporter that binds to and releases cargo in a Ran-dependent manner, but in some cases, cargo release from IPO13 is affected by loading of another cargo. To investigate IPO13′s role in stress-activated pathways, we performed cell-based screens to identify a multitude of binding partners of IPO13 from human brain, lung, and testes. Analysis of the IPO13 interactome intriguingly indicated more than half of the candidate binding partners to be annotated for roles in stress responses; these included the pro-apoptotic protein nuclear clusterin (nCLU), as well as the nCLU-interacting DNA repair protein KU70. Here, we show, for the first time, that unlike other IPOs which are mislocalised and non-functional, IPO13 continues to translocate between the nucleus and cytoplasm under stress, retaining the capacity to import certain cargoes, such as nCLU, but not export others, such as KU70, as shown by analysis using fluorescence recovery after photobleaching. Importantly, depletion of IPO13 reduces stress-induced import of nCLU and protects against stress-induced cell death, with concomitant protection from DNA damage during stress. Overexpression/FACS experiments demonstrate that nCLU is dependent on IPO13 to trigger stress-induced cell death via apoptosis. Taken together, these results implicate IPO13 as a novel functional nuclear transporter in cellular stress, with a key role thereby in cell fate decision.
Antibody Properties Associate with Clinical Phenotype in LGI1 Encephalitis
Authors: Ludewig Susann , Salzburger Leonie , Goihl Alexander , Rohne Jana , Leypoldt Frank , Bittner Daniel , Düzel Emrah , Schraven Burkhart , Reinhold Dirk , Korte Martin , Körtvélyessy Péter
Published: January 2023

Autoimmune encephalitis (AE) associated with autoantibodies against leucine-rich glioma-inactivated protein-1 (LGI1) can present with faciobrachial dystonic seizures (FBDS) and/or limbic encephalitis (LE). The reasons for this heterogeneity in phenotypes are unclear. We performed autoantibody (abs) characterization per patient, two patients suffering from LE and two from FBDS, using isolated antibodies specified with single amino acid epitope mapping. Electrophysiological slice recordings were conducted alongside spine density measurements, postsynaptic Alpha-amino-3-hydoxy-5-methyl-4-isoaxole-proprionate-receptors (AMPA-R) and N-methyl-D-aspartate-receptors receptor (NMDA-R) cluster counting. These results were correlated with the symptoms of each patient. While LGI1 abs from LE patients mainly interacted with the Leucine-rich repeat section of LGI1, abs from both FBDS patients also recognized the Epitempin section as well. Six-hour incubation of mouse hippocampal slices with LE patients autoantibodies but not from the FBDS patients resulted in a significant decline in long-term potentiation (p = 0.0015) or short-term plasticity at CA3-CA1 neurons and in decreased hippocampal synaptic density. Cluster differentiation showed no decrease in postsynaptic AMPA-R and NMDA-R. LGI1 autoantibodies selected by phenotype show an almost distinct epitope pattern, elicit disparate functional effects on hippocampal neurons, and cause divergent effects on spine density. This data illuminates potential pathomechanisms for disease heterogeneity in LGI1 AE.
Activation of β2-Adrenergic Receptors in Microglia Alleviates Neuropathic Hypersensitivity in Mice
Authors: Damo Elisa , Agarwal Amit , Simonetti Manuela
Published: January 2023

Drugs enhancing the availability of noradrenaline are gaining prominence in the therapy of chronic neuropathic pain. However, underlying mechanisms are not well understood, and research has thus far focused on α2-adrenergic receptors and neuronal excitability. Adrenergic receptors are also expressed on glial cells, but their roles toward antinociception are not well deciphered. This study addresses the contribution of β2-adrenergic receptors (β2-ARs) to the therapeutic modulation of neuropathic pain in mice. We report that selective activation of β2-ARs with Formoterol inhibits pro-inflammatory signaling in microglia ex vivo and nerve injury-induced structural remodeling and functional activation of microglia in vivo. Systemic delivery of Formoterol inhibits behaviors related to neuropathic pain, such as mechanical hypersensitivity, cold allodynia as well as the aversive component of pain, and reverses chronically established neuropathic pain. Using conditional gene targeting for microglia-specific deletion of β2-ARs, we demonstrate that the anti-allodynic effects of Formoterol are primarily mediated by microglia. Although Formoterol also reduces astrogliosis at late stages of neuropathic pain, these functions are unrelated to β2-AR signaling in microglia. Our results underline the value of developing microglial β2-AR agonists for relief from neuropathic pain and clarify mechanistic underpinnings.
Influence of the Feedstock Preparation on the Properties of Highly Filled Alumina Green-Body and Sintered Parts Produced by Fused Deposition of Ceramic
Authors: Heim Thomas , Kern Frank
Published: January 2023

This paper investigates new approaches for the blending and plastification of ceramic powder with a binder to form fused deposition of ceramic (FDC) feedstock. The fabrication of highly filled ceramic filaments was accomplished using the granulation by agitation technique, followed by twin-screw extruder homogenization and single-screw extruder filament extrusion. The feedstocks are based on alumina (Al2O3) powders, which were prepared with an industrial binder through three different routes: wet granulation, melt granulation and melt granulation with a suspension. After printing cubic samples and tensile test specimens on a commercial fused deposition modelling (FDM) printer, the properties of the resulting green-body and sintered parts were investigated. The green-body mechanical values are compared with results from commercially available filaments. Mixing the binder with the alumina powder and surfactant in a suspension produces the lowest viscosity and the best elongation at break.
Special Issue: Advanced Multielement Coatings, Deposition, Materials, Applications
Authors: El Garah Mohamed , Sanchette Frederic
Published: January 2023

Improving the properties of materials used in engineering and in industry is the main axe of materials science [...]
Co40Fe40Y20 Nanofilms’ Structural, Magnetic, Electrical, and Nanomechanical Characteristics as a Function of Annealing Temperature and Thickness
Authors: Liu Wen-Jen , Chang Yung-Huang , Chiang Chia-Chin , Chen Yuan-Tsung , Liu Yu-Chi , Ou Sin-Liang , Li Sin-Yan , Chi Po-Wei
Published: January 2023

To investigate the correlations between different thicknesses and heat treatments, this study used a sputtering method to create CoFeY films. The results of X-ray diffraction (XRD) revealed the appearance of oxide peaks at 2θ = 47.7°, 54.5°, and 56.3° in agreement with YFeO3 (212), Co2O3 (422), and Co2O3 (511), respectively. The findings also demonstrated a relationship between the low-frequency alternative-current magnetic susceptibility (χac) values and the thickness of the CoFeY thin films. At a thickness of 50 nm and an annealing temperature of 300 °C, the ideal value of ac was 0.159. The presence of Y and the thickness impact were both evident in the χac value, which improved spin-exchange coupling as well as grain refining. With increasing thickness, the resistance decreased. At 300 °C and 40 nm in thickness, this film has a maximum surface energy of 31.2 mJ/mm2. The hardness of the 50-nm films reached a maximum of 16.67 GPa when annealed at 100 °C. Due to the high χac, strong adhesion, good nanomechanical properties, and low resistivity, the optimal conditions were determined to be 50 nm with annealing at 300 °C.
Functionally Gradient Material Fabrication Based on Cr, Ti, Fe, Ni, Co, Cu Metal Layers via Spark Plasma Sintering
Authors: Shichalin Oleg O. , Papynov Evgeniy K. , Buravlev Igor Yu. , Buravleva Anastasiya A. , Chuklinov Sergey V. , Gridasova Ekaterina A. , Pogodaev Anton V. , Nepomnyushchaya Valreiia A. , Kornakova Zlata E. , Lembikov Alexey O. , Gritsuk Danila V. , Kapustina Olesya V. , Gribanova Sofia S. , Shi Yun
Published: January 2023

The paper presents a method of obtaining functionally graded material (FGM) of heterogeneous (layered) type based on joined metals Cr-Ti-Fe-Co-Ni-Cu using spark plasma sintering (SPS) technology. The structure, elemental and phase composition of FGM obtained on the basis of joined metals with different values of the temperature coefficient of linear expansion (CTLE) were studied by SEM, EDS and XRD methods with regard to the phase states of the alloy system. Based on the Vickers microhardness data, the evaluation of the mechanical characteristics of FGM in the whole sample body and locally at the contact boundaries of the joined metals was carried out. The results of the study are new and represent a potential for FGM, as well as functionally graded coatings (FGC), which have special physical, chemical and mechanical properties and are highly demanded for the manufacture of structures and products for industrial applications.