bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning Prediction of Estimated Risk for Bipolar Disorders Using Hippocampal Subfield and Amygdala Nuclei Volumes
Authors: Huth Fabian , Tozzi Leonardo , Marxen Michael , Riedel Philipp , Bröckel Kyra , Martini Julia , Berndt Christina , Sauer Cathrin , Vogelbacher Christoph , Jansen Andreas , Kircher Tilo , Falkenberg Irina , Thomas-Odenthal Florian , Lambert Martin , Kraft Vivien , Leicht Gregor , Mulert Christoph , Fallgatter Andreas J. , Ethofer Thomas , Rau Anne , Leopold Karolina , Bechdolf Andreas , Reif Andreas , Matura Silke , Biere Silvia , Bermpohl Felix , Fiebig Jana , Stamm Thomas , Correll Christoph U. , Juckel Georg , Flasbeck Vera , Ritter Philipp , Bauer Michael , Pfennig Andrea , Mikolas Pavol
Published: May 2023

The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve upon the early detection of this serious disorder. Patients with manifest BD display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (n = 271, 7 sites) to compare volumes of hippocampus, amygdala and their subfields/nuclei between help-seeking subjects divided into risk groups for BD as estimated by BPSS-P, BARS and EPIbipolar. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using a linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95% CI 59.2–74.6) for 10-fold cross-validation and 61.9% (95% CI 52.0–71.9) for leave-one-site-out. Structural alterations of the hippocampus and amygdala may not be as pronounced in young people at risk; nonetheless, machine learning can predict the estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value.
Neurocognitive Suicide and Homicide Markers in Patients with Schizophrenia Spectrum Disorders: A Systematic Review
Authors: Tomé-Fernández Mario , Berbegal-Bernabeu Marina , Sánchez-Sansegundo Miriam , Zaragoza-Martí Ana , Rubio-Aparicio María , Portilla-Tamarit Irene , Rumbo-Rodríguez Lorena , Hurtado-Sánchez Jose Antonio
Published: May 2023

Suicide and homicide are considered important problems in public health. This study aims to identify the cognitive performance of suicidal and homicidal behaviors in people with schizophrenia spectrum disorders, as well as examining whether there are shared neuropsychological mechanisms. A systematic review of the recent literature was carried out from September 2012 to June 2022 using the Medline (via PubMed), Scopus, Embase, and Cochrane databases. Among the 870 studies initially identified, 23 were finally selected (15 related to suicidal behaviors and 8 to homicidal behaviors). The results evidenced a relationship between impairment of cognitive performance and homicidal behavior; meanwhile, for suicidal behaviors, no consistent results were found. High neuropsychological performance seems to act as a protective factor against violent behavior in people with schizophrenia spectrum disorders, but not against suicidal behavior; indeed, it can even act as a risk factor for suicidal behavior. To date, there is insufficient evidence that shared neurocognitive mechanisms exist. However, processing speed and visual memory seem to be affected in the presence of both behaviors.
Finite Element Analysis of Hysteretic Behavior of Superposed Shear Walls Based on OpenSEES
Authors: Yu Shaole , Zhang Yujian , Bie Junhao , Zhang Wenying , Jiang Jialei , Chen Hua , Chen Xinxi
Published: May 2023

The superimposed slab shear wall has been found to be more and more applicable in the building construction industry due to its building industrialization superiority. The hysteretic behavior of superimposed slab shear walls accounts for an important part of seismic performance analysis. This paper presents the results of a numerical study to investigate the hysteretic behavior of superimposed slab shear walls. Different calculation methods of the shear capacity of the combined interface and horizontal connection are introduced. The calculated results show that the shear capacity of the combined interface and horizontal connection is much larger than the ultimate shear capacity of a superimposed slab shear wall. Therefore, the bond slip effect of a combined interface and horizontal connection can be ignored in finite element analysis on the premise of it not affecting calculation precision. Three different theoretical analysis models, namely the vertical multi-line element model, bend–shear coupled fiber model and layered shell element model, were established in OpenSEES based on a macro-model and a micro-model. The results show that the calculated results of the vertical multi-line element model and the bend–shear coupled fiber model agree reasonably with the experiment results, whereas the calculated results of the layered shell model gave a relatively larger initial stiffness.
Development and Application of Smart Construction Objects and Management System for an Efficient and Cost-Effective Safety Management
Authors: Lee Jungwoo , Shin Dongil Peter , Park So Hyun , Byon Chan
Published: May 2023

In this study, five Smart Construction Objects (SCOs) are developed and demonstrated. The usefulness and characteristics of the developed SCOs were evaluated using a tri-axial diagram analysis method. In addition, a smart construction management system associated with the developed SCOs is proposed. The efficacy of the management system is demonstrated by applying it to various types of construction site, including tunnel construction, railway construction, and underground water tank construction. The results of the tri-axial diagram analysis showed that the developed SCOs have improved awareness and autonomy compared to previously available ones. Multiple on-site applications of the developed smart construction management system resulted in a significant reduction in the time and cost required for construction by more than 40% and 70%, respectively, compared to conventional methods. This is attributable to the simplification of construction resource management procedures, JSA (Job Security Analysis), TBM (Tool Box Meeting), PTW (Permit to Work), and nonconformity management.
Development of Hybrid Machine Learning Models for Predicting Permanent Transverse Displacement of Circular Hollow Section Steel Members under Impact Loads
Authors: Mai Sy Hung , Nguyen Duc Hanh , Tran Viet-Linh , Thai Duc-Kien
Published: May 2023

The impact effect is a crucial issue in civil engineering and has received considerable attention for decades. For the first time, this study develops hybrid machine learning models that integrate the novel Extreme Gradient Boosting (XGB) model with Particle Swam Optimization (PSO), Grey Wolf Optimizer (GWO), Moth Flame Optimizer (MFO), Jaya (JA), and Multi-Verse Optimizer (MVO) algorithms for predicting the permanent transverse displacement of circular hollow section (CHS) steel members under impact loads. The hybrid machine learning models are developed using data collected from 357 impact tests of CHS steel members. The efficacy of hybrid machine learning models is evaluated using three performance metrics. The results show that the GWO-XGB model achieves high accuracy and outperforms the other models. The values of R2, RMSE, and MAE obtained from the GWO-XGB model for the test set are 0.981, 2.835 mm, and 1.906 mm, respectively. The SHAP-based model explanation shows that the initial impact velocity of the indenter, the impact mass, and the ratio of impact position to the member length are the most sensitive parameters, followed by the yield strength of the steel member and the member length; meanwhile, member diameter and member thickness are the parameters least sensitive to the permanent transverse displacement of CHS steel members. Finally, this study develops a web application tool to help rapidly estimate the permanent transverse displacement of CHS steel members under impact loads.
Nature-Based Solutions for Carbon Neutral Climate Resilient Buildings and Communities: A Review of Technical Evidence, Design Guidelines, and Policies
Authors: Xiao Zhe , Ge Hua , Lacasse Michael , Wang Liangzhu , Zmeureanu Radu
Published: May 2023

The building sector is responsible for nearly 40% of the total global direct and indirect CO2 emissions. Urban green infrastructure, which includes features such as urban trees, vegetation, green roofs, and green facades, are examples of nature-based solutions often employed as municipal climate mitigation and adaptation strategies. This approach offers a range of cost-effective strategies for reducing municipal CO2 emissions and presents compelling public policy co-benefits such as improved urban livability and enhanced environmental conditions. For municipalities to confidently deploy these solutions at a scale necessary to achieve climate benefits, acquiring knowledge of quantifiable and demonstrated outcomes is an essential requirement. The objectives of this paper are to (1) provide a comprehensive analysis of the advantages and limitations of nature-based solutions (NBS) to address the challenge of reducing CO2 emissions; (2) evaluate existing design guidelines and policies as may be available across Canada, and that that support the of implementation of NBS in urban agglomerations; (3) identify knowledge gaps and research needs to address challenges to the implementation of NBS. In this review, suggestions and requirements as presented in these documents are examined while giving due consideration to the scientific evidence available in research papers. It was found that the adoption of NBS can contribute to carbon neutral communities through reduced building energy consumption and carbon sequestration. Supportive guidelines and policies have been developed, or are in development, to promote the implementation of NBS at the city scale, despite challenges in assessing, quantitatively, their impact due to uncertainties in data, methods, and scale. Nonetheless, existing research provides sufficient evidence to qualify the measures and suggestions outlined in the guidelines and policies described in this paper.
Performance Analysis of 3D Concrete Printing Processes through Discrete-Event Simulation
Authors: Forcael Eric , Martínez-Chabur Paula , Ramírez-Cifuentes Iván , García-Alvarado Rodrigo , Ramis Francisco , Opazo-Vega Alexander
Published: May 2023

Three-dimensional concrete printing is a technique that has been growing constantly, presenting advantages such as reduced completion times and a decreased environmental impact by eliminating the use of formworks. To carry out the process, the printing path of the extruded material and the movement of a robot must be programmed. Thus, the present research simulated these 3D concrete printing processes in a small 2-floor building of 309.06 m2 and then in a 12-floor building of 10,920 m2. To analyze the 3D printing process, discrete-event simulation was used while considering different variables such as extrusion speed and the locations of a robot mounted on tracks. The results show that when comparing the time taken for a conventional construction system to construct concrete walls and the maximum duration for 3D-printed walls, this method is 45% faster than traditional construction for a small building, but for a big building, there is a difference of 40% in favor of conventional construction; however, this was when using only 1 robot for the whole building. After running the same analyses but using 3 robots instead of 1, the total 3D concrete printing time for the big building was 80% faster in favor of the 3D concrete printing process.
ChatGPT for Fast Learning of Positive Energy District (PED): A Trial Testing and Comparison with Expert Discussion Results
Authors: Zhang Xingxing , Shah Juveria , Han Mengjie
Published: May 2023

Positive energy districts (PEDs) are urban areas which seek to take an integral approach to climate neutrality by including technological, spatial, regulatory, financial, legal, social, and economic perspectives. It is still a new concept and approach for many stakeholders. ChatGPT, a generative pre-trained transformer, is an advanced artificial intelligence (AI) chatbot based on a complex network structure and trained by the company OpenAI. It has the potential for the fast learning of PED. This paper reports a trial test in which ChatGPT is used to provide written formulations of PEDs within three frameworks: challenge, impact, and communication and dissemination. The results are compared with the formulations derived from over 80 PED experts who took part in a two-day workshop discussing many aspects of PED research and development. The proposed methodology involves querying ChatGPT with specific questions and recording its responses. Subsequently, expert opinions on the same questions are provided to ChatGPT, aiming to elicit a comparison between the two sources of information. This approach enables an evaluation of ChatGPT’s answers in relation to the insights shared by domain experts. By juxtaposing the outputs, a comprehensive assessment can be made regarding the reliability, accuracy, and alignment of ChatGPT’s responses with expert viewpoints. It is found that ChatGPT can be a useful tool for the rapid formulation of basic information about PEDs that could be used for its wider dissemination amongst the general public. The model is also noted as having a number of limitations, such as providing pre-set single answers, a sensitivity to the phrasing of questions, a tendency to repeat non-important (or general) information, and an inability to assess inputs negatively or provide diverse answers to context-based questions. Its answers were not always based on up-to-date information. Other limitations and some of the ethical–social issues related to the use of ChatGPT are also discussed. This study not only validated the possibility of using ChatGPT to rapid study PEDs but also trained ChatGPT by feeding back the experts’ discussion into the tool. It is recommended that ChatGPT can be involved in real-time PED meetings or workshops so that it can be trained both iteratively and dynamically.
IR Spectroscopy of Vacancy Clusters (Amber Centers) in CVD Diamonds Nanostructured by Fast Neutron Irradiation
Authors: Khomich Andrey A. , Khmelnitskii Roman , Kozlova Maria , Khomich Alexander V. , Ralchenko Victor
Published: May 2023

We investigated the IR absorption spectra of CVD diamond damaged by fast neutrons (>0.1 MeV) with high fluences ranging from 1 × 1018 to 2 × 1019 cm−2 and annealed at temperatures of 200 °C to 1680 °C. After annealing above 1000 °C, the formation of “amber-centers” (ACs), associated with multivacancy clusters, is detected as deduced from the appearance of a strong absorption line at 4100 cm−1. Moreover, the concentration of the ACs in the irradiated diamond can be an order of magnitude higher than that observed previously in the darkest brown natural diamonds. A number of other absorption lines, including the H1b center at 4936 cm−1 (0.612 eV) and new lines at ~5700 cm−1 (0.706 eV) and 9320 cm−1 (1.155 eV) not reported before in the literature, are observed, and their intensity evolutions at annealing temperatures are documented. At the highest fluences, all the lines show reduced intensities and broadening and spectral shifts due to a very high defect concentration and partial amorphization. The obtained experimental data can be used for the analysis of defect generation, transformations and healing in irradiated synthetic and natural diamonds.
Correction: Gubič et al. Design of New Potent and Selective Thiophene-Based KV1.3 Inhibitors and Their Potential for Anticancer Activity. Cancers 2022, 14, 2595
Authors: Gubič Špela , Hendrickx Louise Antonia , Shi Xiaoyi , Toplak Žan , Možina Štefan , Theemsche Kenny M. Van , Pinheiro-Junior Ernesto Lopes , Peigneur Steve , Labro Alain J. , Pardo Luis A. , Tytgat Jan , Tomašič Tihomir , Peterlin Mašič Lucija
Published: May 2023

In the original publication [...]
Peering through the PSMA PET Lens: The Role of the European Association of Urology Biochemical Recurrence Risk Groups after Radical Prostatectomy
Authors: Leplat Charles , Jabbour Teddy , Diamand Romain , Baudewyns Arthur , Bourgeno Henri Alexandre , Shagera Qaid Ahmed , Flamen Patrick , Roumeguere Thierry , Peltier Alexandre , Artigas Carlos
Published: May 2023

(1) Background: The European Association of Urology (EAU) biochemical recurrence (BCR) risk grouping relies on data from historical cohorts that used conventional imaging techniques. In the era of PSMA PET/CT, we compared the patterns of positivity in the two risk groups and provided insight into positivity predictive factors. (2) Methods: Data from 1185 patients who underwent 68Ga-PSMA-11PET/CT for BCR was analyzed, out of which 435 patients treated initially treated by radical prostatectomy were included in the final analysis. (3) Results: A significantly higher rate of positivity in the BCR high-risk group was observed (59% vs. 36%, p < 0.001). BCR low-risk group demonstrated more local (26% vs. 6%, p < 0.001) and oligometastatic (100% vs. 81%, p < 0.001) recurrences. The BCR risk group and PSA level at the time of PSMA PET/CT were independent predictive factors of positivity. (4) Conclusions: This study confirms that the EAU BCR risk groups have different rates of PSMA PET/CT positivity. Even with a lower rate in the BCR low-risk group, oligometastatic disease was 100% in those with distant metastases. Given the presence of discordant positivity and risk classification, integrating PSMA PET/CT positivity predictors into risk calculators for BCR might improve patient classification for subsequent treatment options. Future prospective studies are still needed to validate the above findings and assumptions.
Obesity and Fibrosis: Setting the Stage for Breast Cancer
Authors: Kuziel Genevra , Moore Brittney N. , Arendt Lisa M.
Published: May 2023

Obesity is a rising health concern and is linked to a worsened breast cancer prognosis. Tumor desmoplasia, which is characterized by elevated numbers of cancer-associated fibroblasts and the deposition of fibrillar collagens within the stroma, may contribute to the aggressive clinical behavior of breast cancer in obesity. A major component of the breast is adipose tissue, and fibrotic changes in adipose tissue due to obesity may contribute to breast cancer development and the biology of the resulting tumors. Adipose tissue fibrosis is a consequence of obesity that has multiple sources. Adipocytes and adipose-derived stromal cells secrete extracellular matrix composed of collagen family members and matricellular proteins that are altered by obesity. Adipose tissue also becomes a site of chronic, macrophage-driven inflammation. Macrophages exist as a diverse population within obese adipose tissue and mediate the development of fibrosis through the secretion of growth factors and matricellular proteins and interactions with other stromal cells. While weight loss is recommended to resolve obesity, the long-term effects of weight loss on adipose tissue fibrosis and inflammation within breast tissue are less clear. Increased fibrosis within breast tissue may increase the risk for tumor development as well as promote characteristics associated with tumor aggressiveness.
Mendelian Randomization Analyses of Chronic Immune-Mediated Diseases, Circulating Inflammatory Biomarkers, and Cytokines in Relation to Liver Cancer
Authors: Yin Qiushi , Yang Qiuxi , Shi Wenjie , Kahlert Ulf D. , Li Zhongyi , Lin Shibu , Song Qifeng , Fan Weiqiang , Wang Li , Zhu Yi , Huang Xiaolong
Published: May 2023

Liver cancer is closely linked to chronic inflammation. While observational studies have reported positive associations between extrahepatic immune-mediated diseases and systemic inflammatory biomarkers and liver cancer, the genetic association between these inflammatory traits and liver cancer remains elusive and merits further investigation. We conducted a two-sample Mendelian randomization (MR) analysis, using inflammatory traits as exposures and liver cancer as the outcome. The genetic summary data of both exposures and outcome were retrieved from previous genome-wide association studies (GWAS). Four MR methods, including inverse-variance-weighted (IVW), MR-Egger regression, weighted-median, and weighted-mode methods, were employed to examine the genetic association between inflammatory traits and liver cancer. Nine extrahepatic immune-mediated diseases, seven circulating inflammatory biomarkers, and 187 inflammatory cytokines were analyzed in this study. The IVW method suggested that none of the nine immune-mediated diseases were associated with the risk of liver cancer, with odds ratios of 1.08 (95% CI 0.87–1.35) for asthma, 0.98 (95% CI 0.91–1.06) for rheumatoid arthritis, 1.01 (95% CI 0.96–1.07) for type 1 diabetes, 1.01 (95% CI 0.98–1.03) for psoriasis, 0.98 (95% CI 0.89–1.08) for Crohn’s disease, 1.02 (95% CI 0.91–1.13) for ulcerative colitis, 0.91 (95% CI 0.74–1.11) for celiac disease, 0.93 (95% CI 0.84–1.05) for multiple sclerosis, and 1.05 (95% CI 0.97–1.13) for systemic lupus erythematosus. Similarly, no significant association was found between circulating inflammatory biomarkers and cytokines and liver cancer after correcting for multiple testing. The findings were consistent across all four MR methods used in this study. Our findings do not support a genetic association between extrahepatic inflammatory traits and liver cancer. However, larger-scale GWAS summary data and more genetic instruments are needed to confirm these findings.
Modern Surgical Techniques of Thyroidectomy and Advances in the Prevention and Treatment of Perioperative Complications
Authors: Ludwig Bartłomiej , Ludwig Maksymilian , Dziekiewicz Anna , Mikuła Agnieszka , Cisek Jakub , Biernat Szymon , Kaliszewski Krzysztof
Published: May 2023

Thyroid cancer is the most common cancer of the endocrine system, and, in recent years, there has been a phenomenon of overdiagnosis followed by subsequent overtreatment. This results in an increasing number of thyroidectomy complications being faced in clinical practice. In this paper, we present the current state of knowledge and the latest findings in the fields of modern surgical techniques, thermal ablation, the identification and assessment of parathyroid function, recurrent laryngeal nerve monitoring and treatment and perioperative bleeding. We reviewed 485 papers, from which we selected 125 papers that are the most relevant. The main merit of this article is its comprehensive view of the subject under discussion—both general, concerning the selection of the appropriate method of surgery, and particular, concerning the selection of the appropriate method of prevention or treatment of selected perioperative complications.
Overview of Molecular Detection Technologies for MET in Lung Cancer
Authors: Heydt Carina , Ihle Michaela Angelika , Merkelbach-Bruse Sabine
Published: May 2023

MET tyrosine kinase receptor pathway activation has become an important actionable target in solid tumors. Aberrations in the MET proto-oncogene, including MET overexpression, the activation of MET mutations, MET mutations that lead to MET exon 14 skipping, MET gene amplifications, and MET fusions, are known to be primary and secondary oncogenic drivers in cancer; these aberrations have evolved as predictive biomarkers in clinical diagnostics. Thus, the detection of all known MET aberrations in daily clinical care is essential. In this review, current molecular technologies for the detection of the different MET aberrations are highlighted, including the benefits and drawbacks. In the future, another focus will be on the standardization of detection technologies for the delivery of reliable, quick, and affordable tests in clinical molecular diagnostics.
Hope and Hype around Immunotherapy in Triple-Negative Breast Cancer
Authors: Jacobs Flavia , Agostinetto Elisa , Miggiano Chiara , De Sanctis Rita , Zambelli Alberto , Santoro Armando
Published: May 2023

Triple-negative breast cancer (TNBC) holds a poor prognosis compared to other breast cancer subtypes, and the development of new effective treatment strategies is an unmet medical need. TNBC has traditionally been considered not amenable to treatment with targeted agents due to a lack of actionable targets. Therefore, chemotherapy has remained the mainstay of systemic treatment for many decades. The advent of immunotherapy raised very hopeful expectations in TNBC, possibly due to higher levels of tumor-infiltrating lymphocytes, PD-L1 expression and tumor mutational burden compared to other breast cancer subtypes, that predict an effective anti-tumor immune-engagement. The results of clinical trials testing immunotherapy in TNBC led to the approval of the combination of immune checkpoint inhibitors and chemotherapy in both early and advanced settings. However, some open questions about the use of immunotherapy in TNBC still exist. These include a deeper understanding of the heterogeneity of the disease, identification of reliable predictive biomarkers of response, determination of the most appropriate chemotherapy backbone and appropriate management of potential long-term immune-related adverse events. In this review we aim to examine the available evidence on the use of immunotherapy strategies in both early and advanced TNBC, to critically discuss some of the limitations encountered in clinical research and to summarize data on novel promising immunotherapeutic strategies beyond PD-(L)1 blockade that have been investigated in the most recent trials.
A Multi-Omics Overview of Colorectal Cancer to Address Mechanisms of Disease, Metastasis, Patient Disparities and Outcomes
Authors: Yang Guang , Yu Xi (Richard) , Weisenberger Daniel J. , Lu Tao , Liang Gangning
Published: May 2023

Human colorectal cancer (CRC) is one of the most common malignancies in men and women across the globe, albeit CRC incidence and mortality shows a substantial racial and ethnic disparity, with the highest burden in African American patients. Even with effective screening tools such as colonoscopy and diagnostic detection assays, CRC remains a substantial health burden. In addition, primary tumors located in the proximal (right) or distal (left) sides of the colorectum have been shown to be unique tumor types that require unique treatment schema. Distal metastases in the liver and other organ systems are the major causes of mortality in CRC patients. Characterizing genomic, epigenomic, transcriptomic and proteomic (multi-omics) alterations has led to a better understanding of primary tumor biology, resulting in targeted therapeutic advancements. In this regard, molecular-based CRC subgroups have been developed that show correlations with patient outcomes. Molecular characterization of CRC metastases has highlighted similarities and differences between metastases and primary tumors; however, our understanding as to how to improve patient outcomes based on metastasis biology is lagging and remains a major obstacle to improving CRC patient outcomes. In this review, we will summarize the multi-omics features of primary CRC tumors and their metastases across racial and ethnic groups, the differences in proximal and distal tumor biology, molecular-based CRC subgroups, treatment strategies and challenges for improving patient outcomes.
Autotaxin Inhibition with IOA-289 Decreases Breast Tumor Growth in Mice Whereas Knockout of Autotaxin in Adipocytes Does Not
Authors: Tang Xiaoyun , Morris Andrew J. , Deken Marcel A. , Brindley David N.
Published: May 2023

Breast cancer cells produce negligible quantities of autotaxin. Instead, previous work indicated that adipocytes in the inflamed adipose tissue adjacent to breast tumors are a major source of autotaxin secretion that drives breast tumor growth, metastasis, and the loss of efficacy for chemotherapy and radiotherapy. To test this hypothesis, we used mice with an adipocyte-specific knock out of autotaxin. The lack of autotaxin secretion from adipocytes failed to decrease the growth of orthotopic E0771 breast tumors in syngeneic C57BL/6 mice and the growth and lung metastasis of spontaneous breast tumors in MMTV-PyMT mice. However, the inhibition of autotaxin with IOA-289 decreased the growth of E0771 tumors, indicating that another source of autotaxin is responsible for tumor growth. Tumor-associated fibroblasts and leukocytes produce the majority of autotoxin transcripts in the E0771 breast tumors, and we hypothesize that they are the main sources of ATX that drive breast tumor growth. Autotaxin inhibition with IOA-289 increased the numbers of CD8α+-T-cells in the tumors. This was accompanied by decreases in the concentrations of CXCL10, CCL2, and CXCL9 in the plasma and LIF, TGFβ1, TGFβ2, and prolactin in the tumors. Bioinformatics analysis of human breast tumor databases showed that autotaxin (ENPP2) is expressed mainly in endothelial cells and fibroblasts. Autotaxin expression correlated significantly with increases in IL-6 cytokine receptor ligand interactions, signaling by LIF, TGFβ, and prolactin. This confirms the relevance of results from autotaxin inhibition in the mouse model. We propose that inhibiting autotaxin activity that is derived from cells presenting breast tumors such as fibroblasts, leukocytes, or endothelial cells changes the tumor micro-environment in such a way as to inhibit tumor growth.
Mutation in the Common Docking Domain Affects MAP Kinase ERK2 Catalysis and Stability
Authors: Novak Leonore , Petrosino Maria , Pasquo Alessandra , Chaikuad Apirat , Chiaraluce Roberta , Knapp Stefan , Consalvi Valerio
Published: May 2023

The extracellular-signal-regulated kinase 2 (ERK2), a mitogen-activated protein kinase (MAPK) located downstream of the Ras-Raf-MEK-ERK signal transduction cascade, is involved in the regulation of a large variety of cellular processes. The ERK2, activated by phosphorylation, is the principal effector of a central signaling cascade that converts extracellular stimuli into cells. Deregulation of the ERK2 signaling pathway is related to many human diseases, including cancer. This study reports a comprehensive biophysical analysis of structural, function, and stability data of pure, recombinant human non-phosphorylated (NP-) and phosphorylated (P-) ERK2 wild-type and missense variants in the common docking site (CD-site) found in cancer tissues. Because the CD-site is involved in interaction with protein substrates and regulators, a biophysical characterization of missense variants adds information about the impact of point mutations on the ERK2 structure–function relationship. Most of the P-ERK2 variants in the CD-site display a reduced catalytic efficiency, and for the P-ERK2 D321E, D321N, D321V and E322K, changes in thermodynamic stability are observed. The thermal stability of NP-ERK2 and P-ERK2 D321E, D321G, and E322K is decreased with respect to the wild-type. In general, a single residue mutation in the CD-site may lead to structural local changes that reflects in alterations in the global ERK2 stability and catalysis.
Success of Checkpoint Blockade Paves the Way for Novel Immune Therapy in Malignant Pleural Mesothelioma
Authors: Rondon Lizbeth , Fu Roberto , Patel Manish R.
Published: May 2023

Malignant pleural mesothelioma (MPM) is a malignancy associated with asbestos exposure and is typically categorized as an orphan disease. Recent developments in immunotherapy with anti-PD-1 and anti-CTLA-4 antibodies, specifically with agents nivolumab and ipilimumab, have demonstrated an improvement in overall survival over the previous standard chemotherapy leading to their FDA-approval as first-line therapy for unresectable disease. For quite some time, it has been known that these proteins are not the only ones that function as immune checkpoints in human biology, and the hypothesis that MPM is an immunogenic disease has led to an expanding number of studies investigating alternative checkpoint inhibitors and novel immunotherapy for this malignancy. Early trials are also supporting the notion that therapies that target biological molecules on T cells, cancer cells, or that trigger the antitumor activity of other immune cells may represent the future of MPM treatment. Moreover, mesothelin-targeted therapies are thriving in the field, with forthcoming results from multiple trials signaling an improvement in overall survival when combined with other immunotherapy agents. The following manuscript will review the current state of immune therapy for MPM, explore the knowledge gaps in the field, and discuss ongoing novel immunotherapeutic research in early clinical trials.
Preoperative EUS vs. PET-CT Evaluation of Response to Neoadjuvant Therapy for Esophagogastric Cancer and Its Correlation with Survival
Authors: Amezcua-Hernandez Victor , Jimenez-Rosales Rita , Martinez-Cara Juan Gabriel , Garcia-Garcia Javier , Valverde Lopez Francisco , Redondo-Cerezo Eduardo
Published: May 2023

Background: The objective of our study was to investigate whether Endoscopic Ultrasonography (EUS) and Positron Emission Tomography-Computed Tomography (PET-CT) restaging can predict survival in upper gastrointestinal tract adenocarcinomas and to assess their accuracy when compared to pathology. Methods: We conducted a retrospective study on all patients who underwent EUS for staging of gastric or esophago-gastric junction adenocarcinoma between 2010 and 2021. EUS and PET-CT were performed, and preoperative TNM restaging was conducted using both procedures within 21 days prior to surgery. Disease-free survival (DFS) and overall survival (OS) were evaluated. Results: A total of 185 patients (74.7% male) were included in the study. The accuracy of EUS for distinguishing between T1-T2 and T3-T4 tumors after neoadjuvant therapy was 66.7% (95% CI: 50.3–77.8%), and for N staging, the accuracy was 70.8% (95% CI: 51.8–81.8%). Regarding PET-CT, the accuracy for N positivity was 60.4% (95% CI: 46.3–73%). Kaplan–Meier analysis revealed a significant correlation between positive lymph nodes on restaging EUS and PET-CT with DFS. Multivariate COX regression analysis identified N restaging with EUS and PET-CT, as well as the Charlson comorbidity index, as correlated factors with DFS. Positive lymph nodes on EUS and PET-CT were predictors of OS. In multivariate Cox regression analysis, the independent risk factors for OS were found to be the Charlson comorbidity index, T response by EUS, and male sex. Conclusion: Both EUS and PET-CT are valuable tools for determining the preoperative stage of esophago-gastric cancer. Both techniques can predict survival, with preoperative N staging and response to neoadjuvant therapy assessed by EUS being the main predictors.
Meningioma Grading beyond Histopathology: Relevance of Epigenetic and Genetic Features to Predict Clinical Outcome
Authors: Marastoni Elena , Barresi Valeria
Published: May 2023

Meningiomas are common tumors of the central nervous system. The grading system established by the World Health Organization (WHO) has recently included pTERT mutations and CDKN2A/B homozygous deletions as criteria for grade 3, owing to their association with increased recurrence risk. However, these alterations identify only a portion of meningiomas that are devoid of histopathological malignancy and are prone to recurrence. Over the last few years, the integration of epigenetic, genetic, transcriptomic, and proteomic profiling has led to the identification of three main groups of meningiomas with distinct clinical outcomes and peculiar genetic features. Meningiomas in the first group have the best prognosis, are distinguished by the lack of NF2 alterations and chromosomal instability, and may be responsive to cytotoxic drugs. Meningiomas in the second group have an intermediate prognosis and are characterized by NF2 alterations, mild chromosomal instability, and enrichment in immune cells. Meningiomas in the third group had the worst prognosis, displayed NF2 alterations coupled with high chromosomal instability, and were resistant to cytotoxic treatment. Classification into these three groups predicts the recurrence risk of meningiomas more accurately than WHO grading and could be applicable in routine practice, owing to the possibility of distinguishing the different groups by specific immunostaining.
Daily Aspirin Reduced the Incidence of Hepatocellular Carcinoma and Overall Mortality in Patients with Cirrhosis
Authors: Lee Chern-Horng , Hsu Chiu-Yi , Yen Tzung-Hai , Wu Tsung-Han , Yu Ming-Chin , Hsieh Sen-Yung
Published: May 2023

Background: Cirrhosis is the primary risk factor for hepatocellular carcinoma (HCC) and gastrointestinal bleeding (GI). We aimed to assess the efficacy and safety of daily aspirin on HCC occurrence, overall survival, and GI bleeding in cirrhotic patients. Methods: A total of 35,898 eligible cases were enrolled for analyses from an initial 40,603 cirrhotic patients without tumor history. Patients continuously treated with aspirin for at least 84 days were in the therapy group, whereas those without treatment were controls. A 1:2 propensity score matching by age, sex, comorbidities, drugs, and significant clinical laboratory tests with covariate assessment was used. Results: Multivariable regression analyses revealed that daily aspirin use was independently associated with a reduced risk of HCC (three-year HR 0.57; 95% CI 0.37–0.87; p = 0.0091; five-year HR 0.63, 95% CI 0.45–0.88; p = 0.0072) inversely correlated with the treatment duration [3–12 months: HR 0.88 (95% CI 0.58–1.34); 12–36 months: HR 0.56 (0.31–0.99); and ≥ 36 months: HR 0.37 (0.18–0.76)]. Overall mortality rates were significantly lower among aspirin users compared with untreated controls [three-year HR 0.43 (0.33–0.57); five-year HR 0.51 (0.42–0.63)]. Consistent results were obtained when the laboratory data were included in the propensity score for matching. Conclusions: Long-term aspirin use significantly reduced the incidence of HCC and overall mortality without increasing gastrointestinal bleeding in cirrhotic patients.
Belantamab Mafodotin: From Clinical Trials Data to Real-Life Experiences
Authors: Morè Sonia , Offidani Massimo , Corvatta Laura , Petrucci Maria Teresa , Fazio Francesca
Published: May 2023

Despite the recent approval of novel immunotherapies, such as immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable, and the acquisition of triple-refractoriness leads to really dismal outcomes in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody–drug conjugate, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial, and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials and also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real-life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations.
Neoadjuvant and Adjuvant Systemic Therapies in Loco-Regional Treatments for Hepatocellular Carcinoma: Are We at the Dawn of a New Era?
Authors: Nevola Riccardo , Delle Femine Augusto , Rosato Valerio , Kondili Loreta Anesti , Alfano Maria , Mastrocinque Davide , Imbriani Simona , Perillo Pasquale , Beccia Domenico , Villani Angela , Ruocco Rachele , Criscuolo Livio , La Montagna Marco , Russo Antonio , Marrone Aldo , Sasso Ferdinando Carlo , Marfella Raffaele , Rinaldi Luca , Esposito Nicolino , Barberis Giuseppe , Claar Ernesto
Published: May 2023

Despite maximizing techniques and patient selection, liver resection and ablation for HCC are still associated with high rates of recurrence. To date, HCC is the only cancer with no proven adjuvant or neoadjuvant therapy used in association to potentially curative treatment. Perioperative combination treatments are urgently needed to reduce recurrence rates and improve overall survival. Immunotherapy has demonstrated encouraging results in the setting of adjuvant and neoadjuvant treatments for non-hepatic malignancies. Conclusive data are not yet available in the context of liver neoplasms. However, growing evidence suggests that immunotherapy, and in particular immune checkpoint inhibitors, could represent the cornerstone of an epochal change in the treatment of HCC, improving recurrence rates and overall survival through combination treatments. Furthermore, the identification of predictive biomarkers of treatment response could drive the management of HCC into the era of a precision medicine. The purpose of this review is to analyze the state of the art in the setting of adjuvant and neoadjuvant therapies for HCC in association with loco-regional treatments in patients not eligible for liver transplantation and to hypothesize future scenarios.
Application of Biogenic TiO2 Nanoparticles as ORR Catalysts on Cathode for Enhanced Performance of Microbial Fuel Cell
Authors: Kumar Ankit , Siddiqui Tabassum , Pandit Soumya , Roy Arpita , Gacem Amel , Souwaileh Abdullah Al , Mathuriya Abhilasha Singh , Fatma Tasneem , Sharma Promila , Rustagi Sarvesh , Yadav Krishna Kumar , Jeon Byong-Hun , Park Hyun-Kyung
Published: May 2023

Microbial fuel cells (MFCs) use microorganisms to break down organic matter and generate power, which is an exciting new field of research. MFCs’ power generation relies on oxygen reduction (ORR) at the cathode. However, the slow kinetics of the ORR can severely limit the performance of MFCs. Additionally, the growth of biofilm on the cathode hampers the ORR process. In order to ensure the sustainability of MFCs over time, it is crucial to employ bifunctional catalysts that can address these issues. Biogenic titanium dioxide (TiO2) nanoparticles (NPs) were synthesized and applied to a graphite sheet cathode in this study. Cyanobacteria, Phormidium species NCCU-104, was used to bio-fabricate titanium dioxide (TiO2) nanoparticles. NPs were characterized using SEM and TEM analysis to determine their size, shape, surface morphology, and XRD. The particles had an average size of 18.11 nm, were spherical, and were well-dispersed, according to the results of the physicochemical characterization. TiO2 NPs were evaluated in MFC using different concentrations (0.5–2.5 mg/cm2) in the cathode to generate electricity and coulombic efficiency. MFC with a cathode impregnated with 2.0 mg/cm2 TiO2 NP produced maximum power density (15.2 W/m3), which was 38% more than 0.5 mg/cm2 TiO2 NP. The overall study results indicated that biogenic TiO2 nanoparticles (NPs) could be an effective and low-cost catalyst in the oxygen reduction reaction (ORR) and significantly improve biofouling. Due to its efficient and affordable contribution to the ORR, these results imply that biogenic TiO2 NPs might be a feasible alternative for improving the performance of MFCs.
Transition of the Flow Regime Inside of Monolith Microchannel Reactors Fed with Highly Turbulent Flow
Authors: Garretón Gonzalo , Maxwell Lindley , Cornejo Iván
Published: May 2023

This paper investigates the flow behaviour of monolith microchannels. Specifically, the study characterizes the flow regime within in-series monolith channels where highly turbulent flow approaches them but inside of the channels, the Reynolds number is subcritical. Results from LES and a transitional RANS model are compared to those obtained when directly assuming laminar flow inside of the channels. A space-resolved model of channels placed in series and channel Reynolds numbers ranging from 50 to 300 are considered. The results show that the flow pattern in is almost identical in the two channels and that the frequency of fluctuations tends to increase with the Reynolds number. The flow regime in both channels is unsteady laminar, containing a wide spectrum of frequencies. The tested transitional RANS model (k-kL-ω) is unable to capture the velocity fluctuations predicted by LES. Despite the differences in the velocity field prediction, the pressure drop estimation from all models is practically the same. This study provides insights into the flow behaviour of monolith reactors and is useful for reactor design and optimization.
Cyclic Carbonates through the Photo-Induced Carboxylative Cyclization of Allylic Alcohol with CO2: A Comprehensive Kinetic Study of the Reaction Mechanism by In Situ ATR-IR Spectroscopy
Authors: Grondin Joseph , Aupetit Christian , Vincent Jean-Marc , Tassaing Thierry
Published: May 2023

A one-pot multicomponent green process is investigated for the synthesis of perfluoroalkylated cyclic carbonate which merges the photo-promoted Atom Transfer Radical Addition (ATRA) of a perfluoroalkyl iodide (Rf-I) onto allyl alcohols with the Lewis-base-promoted carboxylative cyclization. The evolution of the complex mixture during the reaction was monitored by in situ ATR-IR and Raman spectroscopies that provided insights into the reaction mechanism. The effect on the kinetics and the carbonate yields of key parameters such as the stoichiometry of reagents, the nature of the Lewis base and the solvent, the temperature and the pressure were evaluated. It was found that high yields were obtained using strong Lewis bases that played both the role of activating the allyl alcohol for the generation of the allyl carbonate in the presence of CO2 and promoting the ATRA reaction through the activation of C4F9I by halogen bonding. This protocol was also extended to various unsaturated alcohols.
Non-Noble Metal and Nonmetallic Plasmonic Nanomaterials with Located Surface Plasmon Resonance Effects: Photocatalytic Performance and Applications
Authors: Li Rou , Wang Xianfeng , Chen Ming
Published: May 2023

Photocatalysts with located surface plasmon resonance effects (LSPRs) have been studied in recent years due to their superior light harvesting capacity and photocatalytic performance in solving environmental problems and energy shortages. Plasmonic-noble-based photocatalysts are limited in terms of their practical application on account of their high cost, fixed plasma frequency, and low abundance. In order to solve these shortcomings, non-noble metal and nonmetallic plasmonic photocatalysts with LSPRs and advantages such as a lower cost and wider light adsorption range from the UV to NIR region have been developed. This paper reviews the recent development of non-noble metal and nonmetallic plasmonic photocatalysts and advances the research direction of plasmonic photocatalysts to achieve high photocatalytic activity and stability, providing guidance for photocatalysis to solve environmental problems and energy shortages.