bluuebunny/crossref_metadata_2025 huggingface dataset:
VMAT-Based Planning Allows Sparing of a Spatial Dose Pattern Associated with Radiation Pneumonitis in Patients Treated with Radiotherapy for a Locally Advanced Lung Cancer
Authors: Bourbonne Vincent , Lucia Francois , Jaouen Vincent , Bert Julien , Pradier Olivier , Visvikis Dimitris , Schick Ulrike
Published: August 2022

Introduction: In patients treated with radiotherapy for locally advanced lung cancer, respect for dose constraints to organs at risk (OAR) insufficiently protects patients from acute pulmonary toxicity (APT), such toxicities being associated with a potential impact on the treatment’s completion and the patient’s quality of life. Dosimetric planning does not take into account regional lung functionality. An APT prediction model combining usual dosimetry features with the mean dose (DMeanPmap) received by a voxel-based volume (Pmap) localized in the posterior right lung has been previously developed. A DMeanPmap of ≥30.3 Gy or a predicted APT probability (ProbAPT) of ≥8% were associated with a higher risk of APT. In the present study, the authors aim to demonstrate the possibility of decreasing the DMeanPmap via a volumetric arctherapy (VMAT)-based adapted planning and evaluate the impact on the risk of APT. Methods: Among the 207 patients included in the initial study, only patients who presented with APT of ≥grade 2 and with a probability of APT ≥ 8% based on the prediction model were included. Dosimetry planning was optimized with a new constraint (DMeanPmap < 30.3 Gy) added to the usual constraints. The initial and optimized treatment plans were compared using the t-test for the independent variables and the non-parametric Mann–Whitney U test otherwise, regarding both doses to the OARs and PTV (Planning Target Volume) coverage. Conformity and heterogeneity indexes were also compared. The risk of APT was recalculated using the new dosimetric features and the APT prediction model. Results: Dosimetric optimization was considered successful for 27 out of the 44 included patients (61.4%), meaning the dosimetric constraint on the Pmap region was achieved without compromising the PTV coverage (p = 0.61). The optimization significantly decreased the median DMeanPmap from 28.8 Gy (CI95% 24.2–33.4) to 22.1 Gy (CI95% 18.3–26.0). When recomputing the risk of APT using the new dosimetric features, the optimization significantly reduced the risk of APT (p < 0.0001) by reclassifying 43.2% (19/44) of the patients. Conclusion: Our approach appears to be both easily implementable on a daily basis and efficient at reducing the risk of APT. Regional radiosensitivity should be considered in usual lung dose constraints, opening the possibility of new treatment strategies, such as dose escalation or innovative treatment associations.
Efficacy of Transarterial Chemoembolization Combined with Molecular Targeted Agents for Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis
Authors: Zhang Zhenzhen , Wu Yanfang , Zheng Tanghui , Chen Xiaochun , Chen Guobin , Chen Hong , Guo Xinkun , Zheng Susu , Xie Xiaoying , Zhang Boheng
Published: August 2022

Transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) is the mainstay treatment for unresectable hepatocellular carcinoma (uHCC). However, studies investigating different combinations of agents have shown inconsistent results. Here, we used network meta-analysis (NMA) to compare different agents across 41 studies (36 cohort studies and five RCTs) in 11,540 patients. Multiple RCTs and cohort studies were searched to evaluate TACE combined with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and tumor response. NMA used a random-effects consistency model to pool evidence from direct and indirect comparisons. Hazard ratio (HR) and relative risks (RR) with 95% confidence intervals (CI) were analyzed. Further, heterogeneity and publication bias analyses were performed and agents were ranked. TACE plus lenvatinib provided the maximal OS (Rank probability: 0.7559), PFS (Rank probability: 0.8595), CR (Rank probability: 0.4179), and DCR (Rank probability: 0.3857). TACE plus anlotinib demonstrated the highest PR (p = 0.62649) and ORR (p = 0.51158). SD was more often associated with TACE plus sorafenib (Rank probability: 0.601685). TACE plus lenvatinib provides optimal treatment for uHCC based on the highest ranking of OS, PFS, and DCR rates. However, given the lack of statistically significant OS benefit, shared decision making should include other TKIs as acceptable alternatives.
COVID-19 and Adult Acute Leukemia: Our Knowledge in Progress
Authors: Modemann Franziska , Ghandili Susanne , Schmiedel Stefan , Weisel Katja , Bokemeyer Carsten , Fiedler Walter
Published: August 2022

The majority of publications regarding SARS-CoV-2 infections in adult patients with acute leukemia (AL) refer to hematological patients in general and are not focused on acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). We herein report a review of the current literature on adult AL patients infected with SARS-CoV-2. Overall, SARS-CoV-2-associated mortality ranges from 20–52% in patients with adult AL. AML patients have a particularly high COVID-19-related mortality. Of note, most of the available data relate to the pre-vaccination era and to variants before Omicron. The impact of COVID-19 infections on AL treatment is rarely reported. Based on the few studies available, treatment delay does not appear to be associated with an increased risk of relapse, whereas therapy discontinuation was associated with worse outcomes in AML patients. Therefore, the current recommendations suggest delaying systemic AL treatment in SARS-CoV-2-positive patients until SARS-CoV-2 negativity, if immediate AL treatment is not required. It is recommended to offer vaccination to all AL patients; the reported antibody responses are around 80–96%. Seronegative patients should additionally receive prophylactic administration of anti-SARS-CoV-2 monoclonal antibodies. Patients with AL infected with SARS-CoV-2 should be treated early with antiviral therapy to prevent disease progression and enable the rapid elimination of the virus.
Reprogrammed Lipid Metabolism and the Lipid-Associated Hallmarks of Colorectal Cancer
Authors: Salita Timothy , Rustam Yepy H. , Mouradov Dmitri , Sieber Oliver M. , Reid Gavin E.
Published: August 2022

Lipids have diverse structures, with multifarious regulatory functions in membrane homeostasis and bioenergetic metabolism, in mediating functional protein–lipid and protein–protein interactions, as in cell signalling and proliferation. An increasing body of evidence supports the notion that aberrant lipid metabolism involving remodelling of cellular membrane structure and changes in energy homeostasis and signalling within cancer-associated pathways play a pivotal role in the onset, progression, and maintenance of colorectal cancer (CRC) and their tumorigenic properties. Recent advances in analytical lipidome analysis technologies have enabled the comprehensive identification and structural characterization of lipids and, consequently, our understanding of the role they play in tumour progression. However, despite progress in our understanding of cancer cell metabolism and lipidomics, the key lipid-associated changes in CRC have yet not been explicitly associated with the well-established ‘hallmarks of cancer’ defined by Hanahan and Weinberg. In this review, we summarize recent findings that highlight the role of reprogrammed lipid metabolism in CRC and use this growing body of evidence to propose eight lipid metabolism-associated hallmarks of colorectal cancer, and to emphasize their importance and linkages to the established cancer hallmarks.
Precision Medicine in Metastatic Colorectal Cancer: Targeting ERBB2 (HER-2) Oncogene
Authors: Torres-Jiménez Javier , Esteban-Villarrubia Jorge , Ferreiro-Monteagudo Reyes
Published: August 2022

Colorectal cancer (CRC) is the third most common cancer in terms of incidence rate in adults and the second most common cause of cancer-related death in Europe. The treatment of metastatic CRC (mCRC) is based on the use of chemotherapy, anti-vascular endothelial growth factor (VEGF), and anti-epidermal growth factor receptor (EGFR) for RAS wild-type tumors. Precision medicine tries to identify molecular alterations that could be treated with targeted therapies. ERBB2 amplification (also known as HER-2) has been identified in 2–3% of patients with mCRC, but there are currently no approved ERBB2-targeted therapies for mCRC. The purpose of this review is to describe the molecular structure of ERBB2, clinical features of these patients, diagnosis of ERBB2 alterations, and the most relevant clinical trials with ERBB2-targeted therapies in mCRC.
Advances in Management and Therapeutics of Cutaneous Basal Cell Carcinoma
Authors: Chen Olivia M. , Kim Keemberly , Steele Chelsea , Wilmas Kelly M. , Aboul-Fettouh Nader , Burns Carrick , Doan Hung Quoc , Silapunt Sirunya , Migden Michael R.
Published: August 2022

Basal cell carcinoma (BCC), the most common cancer in humans, is a malignant neoplasm of cells derived from the basal layer of the epidermis. Tumor characteristics such as histologic subtype, primary versus recurrent tumor, anatomic location, size, and patient attributes determine the risk level and acceptable treatment options. Surgical options offer histologic confirmation of tumor clearance. Standard excision provides post-treatment histologic assessment, while Mohs micrographic surgery (MMS) provides complete margin assessment intraoperatively. Additional treatment options may be employed in the correct clinical context. Small and low-risk BCCs, broad field cancerization, locally-advanced disease, metastatic disease, cosmetic concerns, or morbidity with surgical approaches raise consideration of other treatment modalities. We review herein a range of treatment approaches and advances in treatments for BCC, including standard excision, MMS, electrodesiccation and curettage, ablative laser treatment, radiation therapy, targeted molecular therapies, topical therapies, field therapies, immunotherapy, and experimental therapies.
Emerging Roles of the Nervous System in Gastrointestinal Cancer Development
Authors: Wan Chunhua , Yan Xiaoqin , Hu Baoying , Zhang Xinhua
Published: August 2022

Our understanding of the fascinating connection between nervous system and gastrointestinal (GI) tumorigenesis has expanded greatly in recent years. Recent studies revealed that neurogenesis plays an active part in GI tumor initiation and progression. Tumor-driven neurogenesis, as well as neurite outgrowth of the pre-existing peripheral nervous system (PNS), may fuel GI tumor progression via facilitating cancer cell proliferation, chemoresistance, invasion and immune escape. Neurotransmitters and neuropeptides drive the activation of various oncogenic pathways downstream of neural receptors within cancer cells, underscoring the importance of neural signaling pathways in GI tumor malignancy. In addition, neural infiltration also plays an integral role in tumor microenvironments, and contributes to an environment in favor of tumor angiogenesis, immune evasion and invasion. Blockade of tumor innervation via denervation or pharmacological agents may serve as a promising therapeutic strategy against GI tumors. In this review, we summarize recent findings linking the nervous system to GI tumor progression, set the spotlight on the molecular mechanisms by which neural signaling fuels cancer aggressiveness, and highlight the importance of targeting neural mechanisms in GI tumor therapy.
The Construction and Validation of Nomogram to Predict the Prognosis with Small-Cell Lung Cancer Followed Surgery
Authors: Wu Lei-Lei , Chen Wu-Tao , Li Chong-Wu , Song Si-Hui , Xu Shu-Quan , Wan Sheng-Peng , Liu Zhi-Yuan , Lin Wei-Kang , Li Kun , Li Zhi-Xin , Xie Dong
Published: August 2022

This study constructed and validated a prognostic model to evaluate the survival of small-cell lung cancer (SCLC) patients following surgery, and shed light on the strategy of postoperative radiotherapy. A total of 882 patients from Shanghai Pulmonary Hospital and the Surveillance, Epidemiology and End Results database after lung resection were selected. Multivariable Cox analysis was used to identify the indicators affecting long-term survival in patients. A nomogram was constructed to predict the prognosis of eligible patients. Indices of concordance (C-index) was used to access the predictive ability of cancer-specific survival (CSS) for the prognostic model. CSS discrimination in the prognostic model was comparable in the training and validation cohorts (C-index = 0.637[NORAD-T], 0.660[NORAD-V], 0.656[RAD] and 0.627[our hospital], respectively. Stratification based on the cutoff value of the nomogram yielded low- and high-risk subgroups in four cohorts. For patients in the high-risk group, postoperative radiotherapy was considered a survival-promoting strategy (unadjusted HR 0.641, 95% CI 0.469–0.876, p = 0.0046). In the low-risk group, however, the implementation of radiotherapy barely had an influence on CSS. In conclusion, the nomogram we constructed and validated could predict the prognosis of SCLC patients followed surgery and identify high-risk patients who were likely to benefit from postoperative radiotherapy.
Identification of Src as a Therapeutic Target in Oesophageal Adenocarcinoma through Functional Genomic and High-Throughput Drug Screening Approaches
Authors: McCabe Niamh H. , Stevenson Leanne , Scanlon Enya , Douglas Rosalie , Kennedy Susanna , Keminer Oliver , Windshügel Björn , Zisterer Daniela , Kennedy Richard D. , Blayney Jaine K. , Turkington Richard C.
Published: August 2022

Drug resistance limits the effectiveness of oesophageal adenocarcinoma (OAC) chemotherapies, leading to a poor prognosis for this disease. Elucidation of the underlying resistance mechanisms is key to enabling the identification of more effective treatments. This study, therefore, aims to identify novel therapeutic and/or chemotherapy sensitising drug targets in OAC. Transcriptional data from a cohort of 273 pre-treatment OAC biopsies, from patients who received neoadjuvant chemotherapy followed by surgical resection, were analysed using gene set enrichment analysis (GSEA) to determine differential gene expression between responding and non-responding OAC tumours. From this, 80 genes were selected for high-throughput siRNA screening in OAC cell lines with or without standard chemotherapy treatment. In parallel, cell viability assays were performed using a panel of FDA-approved drugs and combination index (CI) values were calculated to evaluate drug synergy with standard chemotherapy. Mechanisms of synergy were investigated using western blot, propidium iodide flow cytometry, and proliferation assays. Taken together, the screens identified that targeting Src, using either siRNA or the small molecule inhibitor dasatinib, enhanced the efficacy of chemotherapy in OAC cells. Further in vitro functional analysis confirmed Src inhibition to be synergistic with standard OAC chemotherapies, 5-fluorouracil (5-FU), and cisplatin (CDDP). In conclusion, a compound screen together with a functional genomic approach identified Src as a potential chemosensitising target in OAC, which could be assessed in a clinical study for poor prognosis OAC patients.
A Novel Risk Score Model of Lactate Metabolism for Predicting over Survival and Immune Signature in Lung Adenocarcinoma
Authors: Jiang Zhou , Luo Yongzhong , Zhang Lemeng , Li Haitao , Pan Changqie , Yang Hua , Cheng Tianli , Chen Jianhua
Published: August 2022

Background: The role of lactate acid in tumor progression was well proved. Recently, it was found that lactate acid accumulation induced an immunosuppressive microenvironment. However, these results were based on a single gene and it was unclear that lactate acid genes were associated with immunotherapy and able to predict overall survival. Methods: Genes and survival data were acquired from TCGA, GEO and GENECARDS. PCA and TSNE were used to distinguish sample types according to lactate metabolism-associated gene expression. A Wilcox-test examined the expression differences between normal and tumor samples. The distribution in chromatin and mutant levels were displayed by Circo and MAfTools. The lactate metabolism-associated gene were divided into categories by consistent clustering and visualized by Cytoscape. Immune cell infiltration was evaluated by CIBERSORT and LM22 matrix. Enrichment analysis was performed by GSVA. We used the ConsensusClusterPlus package for consistent cluster analysis. A prognostic model was constructed by Univariate Cox regression and Lasso regression analysis. Clinical specimens were detected their expression of genes in model by IHC. Results: Most lactate metabolism-associated gene were significantly differently expressed between normal and tumor samples. There was a strong correlation between the expression of lactate metabolism-associated gene and the abundance of immune cells. We divided them into two clusters (lactate.cluster A,B) with significantly different survival. The two clusters showed a difference in signal, immune cells, immune signatures, chemokines, and clinical features. We identified 162 differential genes from the two clusters, by which the samples were divided into three categories (gene.cluster A,B,C). They also showed a difference in OS and immune infiltration. Finally, a risk score model that was composed of six genes was constructed. There was significant difference in the survival between the high and low risk groups. ROC curves of 1, 3, 5, and 10 years verified the model had good predictive efficiency. Gene expression were correlated with ORR and PFS in patients who received anti-PD-1/L1. Conclusion: The lactate metabolism-associated genes in LUAD were significantly associated with OS and immune signatures. The risk scoring model that was constructed by us was able to well identify and predict OS and were related with anti-PD-1/L1 therapy outcome.
CDC20-Mediated hnRNPU Ubiquitination Regulates Chromatin Condensation and Anti-Cancer Drug Response
Authors: Wavelet-Vermuse Cindy , Odnokoz Olena , Xue Yifan , Lu Xinghua , Cristofanilli Massimo , Wan Yong
Published: August 2022

Cell division cycle 20 (CDC20) functions as a critical cell cycle regulator. It plays an important role in cancer development and drug resistance. However, the molecular mechanisms by which CDC20 regulates cellular drug response remain poorly understood. Chromatin-associated CDC20 interactome in breast cancer cells was analyzed by using affinity purification coupled with mass spectrometry. hnRNPU as a CDC20 binding partner was validated by co-immunoprecipitation and immunostaining. The molecular domain, comprising amino acid residues 461–653, on hnRNPU required for its interaction with CDC20 was identified by mapping of interactions. Co-immunoprecipitation showed that CDC20-mediated hnRNPU ubiquitination promotes its interaction with the CTCF and cohesin complex. The effects of CDC20–hnRNPU on nuclear size and chromatin condensation were investigated by analyzing DAPI and H2B-mCherry staining, respectively. The role of CDC20–hnRNPU in tumor progression and drug resistance was examined by CCK-8 cell survival and clonogenic assays. Our study indicates that CDC20-mediated ubiquitination of hnRNPU modulates chromatin condensation by regulating the interaction between hnRNPU and the CTCF–cohesin complex. Dysregulation of the CDC20–hnRNPU axis contributes to tumor progression and drug resistance.
Evaluation of a Program of Aquatic Motor Games in the Improvement of Motor Competence in Children from 4 to 5 Years Old
Authors: Simón-Piqueras Juan Ángel , Prieto-Ayuso Alejandro , Gómez-Moreno Elena , Martínez-López María , Gil-Madrona Pedro
Published: August 2022

The present study aimed to verify whether a program of initiation to the aquatic environment composed of motor games (motor stories, learning environments and motor circuits) is more effective in the acquisition of aquatic skills in early childhood education than a traditional program. For this purpose, the Escala de Competencia Motriz Acuática for 4–5 year-old children was used before and after both programs. This scale has two factors, one named Familiarization, linked to more elementary aquatic abilities, and the Immersion factor, which integrates more advanced aquatic abilities. The two programs were used as independent variables, and there was a sample of 17 children over six weeks. The results show that both programs improved the acquisition of aquatic skills. The program that integrated motor games impacted the improvement of skills related to the Immersion factor significantly more.
Hungarian Linguistic, Cross-Cultural, and Age Adaptation of the Patient Satisfaction with Health Care in Inflammatory Bowel Disease Questionnaire (CACHE) and the Medication Adherence Report Scale (MARS)
Authors: Dohos Dóra , Váradi Alex , Farkas Nelli , Erős Adrienn , Párniczky Andrea , Schäfer Eszter , Kosaras Éva , Czelecz Judit , Hegyi Péter , Sarlós Patrícia
Published: August 2022

Background: The TRANS-IBD study examines the superiority of joint transition visits, with drug adherence and patient satisfaction among the outcome measures. Our aim was a cross-cultural, age- and disease-specific adaptation of the ‘Medication Adherence Rating Scale’ (MARS) and ‘Patient satisfaction with health care in inflammatory bowel disease questionnaire’ (CACHE) questionnaires in patients with inflammatory bowel disease (IBD). Methods: Linguistic and cultural adaptation using test and re-test procedures were performed. Internal consistency with Cronbach’s α coefficients, confirmatory factor analyses with root Mean Square Error of Approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI) were determined. Results: A total of 122 adolescents and 164 adults completed the questionnaires (47.5% male, mean age 17 ± 1; and 29.3% male, mean age 38 ± 11, respectively). In the MARS questionnaire, Cronbach’s α scores were found good in adolescents (0.864) and acceptable in adults (0.790), while in the CACHE questionnaire, scores were rated as excellent in both populations (0.906 and 0.945, respectively). The test-retest reliabilities were satisfactory in both groups (MARS questionnaire: r = 0.814 and r = 0.780, CACHE questionnaire: r = 0.892 and r = 0.898, respectively). RMSEA showed poor fit values in the MARS questionnaire and reasonable fit values in the CAHCE questionnaire, CFI and TLI had statistically acceptable results. Conclusion: Age-and disease-specific Hungarian versions of the questionnaires were developed, which are appropriate tools for TRANS-IBD RCT and daily IBD care.
Neonatal Abstinence Syndrome: Prevention, Management and Outcomes: From Birth to Adulthood
Authors: Allegaert Karel , Oei Ju-Lee
Published: August 2022

Neonatal abstinence syndrome (NAS), or—when specifically focused on opioids—neonatal opioid withdrawal syndrome (NOWS) is a withdrawal syndrome in neonates after birth causally related to the in utero exposure to drugs of dependence, and the subsequent acute interruption at delivery [...]
Efficacy of a Robot-Assisted Intervention in Improving Learning Performance of Elementary School Children with Specific Learning Disorders
Authors: Papadopoulou Maria T. , Karageorgiou Elpida , Kechayas Petros , Geronikola Nikoleta , Lytridis Chris , Bazinas Christos , Kourampa Efi , Avramidou Eleftheria , Kaburlasos Vassilis G. , Evangeliou Athanasios E.
Published: August 2022

(1) Background: There has been significant recent interest in the potential role of social robots (SRs) in special education. Specific Learning Disorders (SpLDs) have a high prevalence in the student population, and early intervention with personalized special educational programs is crucial for optimal academic achievement. (2) Methods: We designed an intense special education intervention for children in the third and fourth years of elementary school with a diagnosis of a SpLD. Following confirmation of eligibility and informed consent, the participants were prospectively and randomly allocated to two groups: (a) the SR group, for which the intervention was delivered by the humanoid robot NAO with the assistance of a special education teacher and (b) the control group, for which the intervention was delivered by the special educator. All participants underwent pre- and post-intervention evaluation for outcome measures. (3) Results: 40 children (NAO = 19, control = 21, similar baseline characteristics) were included. Pre- and post-intervention evaluation showed comparable improvements in both groups in cognition skills (decoding, phonological awareness and reading comprehension), while between-group changes favored the NAO group only for some phonological awareness exercises. In total, no significant changes were found in any of the groups regarding the emotional/behavioral secondary outcomes. (4) Conclusion: NAO was efficient as a tutor for a human-supported intervention when compared to the gold-standard intervention for elementary school students with SpLDs.
Integrative Multi-Omics Analysis for the Determination of Non-Muscle Invasive vs. Muscle Invasive Bladder Cancer: A Pilot Study
Authors: Yu Evan Yi-Wen , Zhang Hao , Fu Yuanqing , Chen Ya-Ting , Tang Qiu-Yi , Liu Yu-Xiang , Zhang Yan-Xi , Wang Shi-Zhi , Wesselius Anke , Li Wen-Chao , Zeegers Maurice P. , Xu Bin
Published: August 2022

Objectives: The molecular landscape of non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer based on molecular characteristics is essential but poorly understood. In this pilot study we aimed to identify a multi-omics signature that can distinguish MIBC from NMIBC. Such a signature can assist in finding potential mechanistic biomarkers and druggable targets. Methods: Patients diagnosed with NMIBC (n = 15) and MIBC (n = 11) were recruited at a tertiary-care hospital in Nanjing from 1 April 2021, and 31 July 2021. Blood, urine and stool samples per participant were collected, in which the serum metabolome, urine metabolome, gut microbiome, and serum extracellular vesicles (EV) proteome were quantified. The differences of the global profiles and individual omics measure between NMIBC vs. MIBC were assessed by permutational multivariate analysis and the Mann–Whitney test, respectively. Logistic regression analysis was used to assess the association of each identified analyte with NMIBC vs. MIBC, and the Spearman correlation was used to investigate the correlations between identified analytes, where both were adjusted for age, sex and smoking status. Results: Among 3168 multi-omics measures that passed the quality control, 159 were identified to be differentiated in NMIBC vs. MIBC. Of these, 46 analytes were associated with bladder cancer progression. In addition, the global profiles showed significantly different urine metabolome (p = 0.029), gut microbiome (p = 0.036), and serum EV (extracellular vesicles) proteome (p = 0.039) but not serum metabolome (p = 0.059). We also observed 17 (35%) analytes that had been developed as drug targets. Multiple interactions were obtained between the identified analytes, whereas for the majority (61%), the number of interactions was at 11–20. Moreover, unconjugated bilirubin (p = 0.009) and white blood cell count (p = 0.006) were also shown to be different in NMIBC and MIBC, and associated with 11 identified omics analytes. Conclusions: The pilot study has shown promising to monitor the progression of bladder cancer by integrating multi-omics data and deserves further investigations.
Liver Cancer-Specific Isoform of Serine Protease Inhibitor Kazal for the Detection of Hepatocellular Carcinoma: Results from a Pilot Study in Patients with Dysmetabolic Liver Disease
Authors: Caviglia Gian Paolo , Nicolosi Aurora , Abate Maria Lorena , Carucci Patrizia , Rosso Chiara , Rolle Emanuela , Armandi Angelo , Aneli Serena , Olivero Antonella , Risso Alessandra , Ribaldone Davide Giuseppe , Fermer Christian , Saracco Giorgio Maria , Gaia Silvia , Bugianesi Elisabetta
Published: August 2022

Reliable non-invasive biomarkers for the surveillance of patients at risk of hepatocellular carcinoma (HCC) development represent an unmet medical need. Recently, the liver-cancer-specific isoform of serine protease inhibitor Kazal (LC-SPIK) has been proposed as a valuable biomarker for the detection of HCC in patients with chronic liver disease of viral etiology. In the present study, we assessed the diagnostic accuracy of LC-SPIK, alone or in combination with standard serologic biomarkers (i.e., alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II, PIVKA-II), for the detection of HCC among patients with dysmetabolic liver disease. A total of 120 patients with non-alcoholic fatty liver disease (NAFLD), including 62 patients with a diagnosis of HCC and 58 with cirrhosis but without tumor, were retrospectively analyzed. The serum levels of LC-SPIK were measured by enzyme-linked immunosorbent assay (ImCare Biotech, Doylestown, PA). The serum LC-SPIK values were significantly different between patients with HCC (24.3, 17.6–39.8 ng/mL) and those with cirrhosis but without tumor (11.7, 8.7–18.2 ng/mL) (p < 0.001). By receiver operating characteristic curve analysis, we observed an area under the curve (AUC) of 0.841 for the detection of HCC; the combination with PIVKA-II further increased the accuracy to AUC = 0.926 (cross-validation). The promising results observed in the present pilot study foster additional research to investigate the usefulness of LC-SPIK for the stratification of the risk of HCC development in patients with NAFLD and advanced liver disease.
T-Cell Assay after COVID-19 Vaccination Could Be a Useful Tool? A Pilot Study on Interferon-Gamma Release Assay in Healthcare Workers
Authors: Seraceni Silva , Zocca Elena , Cervone Tamara Emanuela , Tomassetti Flaminia , Polidori Isabella , Valisi Massimiliano , Broccolo Francesco , Calugi Graziella , Bernardini Sergio , Pieri Massimo
Published: August 2022

Background: SARS-CoV-2 T-cells are crucial for long-term protection against reinfection. The aim was to demonstrate the Interferon-gamma Release Assay (IGRA) test could be useful for vaccination monitoring. Methods: In a prospective cohort of 98 vaccinated healthcare workers for SARS-CoV-2, we selected 23 people in low-antibodies (Group 1, N = 8), high-antibodies (Group 2, N = 9), and negative control groups (Group 3, N = 6). SARS-CoV-2-specific humoral and cellular responses were analyzed at 8 months after two doses of Pfizer BioNTech, evaluating anti-RBD (Receptor Binding Domain) and RBD-ACE2 (Angiotensin Converting Enzyme-2) blocking antibodies in sera through a Chemiluminescence Immunoassay (CLIA) and T-cells through the IGRA test in heparinized plasma. Moreover, lymphocyte subtyping was executed by a flow cytometer. Statistical analysis was performed. Results: The data confirmed that RBD and RBD-ACE2 blocking ACE2 antibody levels of Group 1 were significantly lower than Group 2; p < 0.001. However, T-cells showed no significant difference between Group 1 and Group 2. Conclusions: This work suggests the need for new strategies for booster doses administration.
Influence of Transfer Entropy in the Short-Term Prediction of Financial Time Series Using an ∊-Machine
Authors: Zavala-Díaz José Crispín , Pérez-Ortega Joaquín , Almanza-Ortega Nelva Nely , Pazos-Rangel Rodolfo , Rodríguez-Lelís José María
Published: August 2022

Predicting the values of a financial time series is mainly a function of its price history, which depends on several factors, internal and external. With this history, it is possible to build an ∊-machine for predicting the financial time series. This work proposes considering the influence of a financial series through the transfer of entropy when the values of the other financial series are known. A method is proposed that considers the transfer of entropy for breaking the ties that occur when calculating the prediction with the ∊-machine. This analysis is carried out using data from six financial series: two American, the S&P 500 and the Nasdaq; two Asian, the Hang Seng and the Nikkei 225; and two European, the CAC 40 and the DAX. This work shows that it is possible to influence the prediction of the closing value of a series if the value of the influencing series is known. This work showed that the series that transfer the most information through entropy transfer are the American S&P 500 and Nasdaq, followed by the European DAX and CAC 40, and finally the Asian Nikkei 225 and Hang Seng.
Information Processing Using Networks of Chemical Oscillators
Authors: Gorecki Jerzy
Published: August 2022

I believe the computing potential of systems with chemical reactions has not yet been fully explored. The most common approach to chemical computing is based on implementation of logic gates. However, it does not seem practical because the lifetime of such gates is short, and communication between gates requires precise adjustment. The maximum computational efficiency of a chemical medium is achieved if the information is processed in parallel by different parts of it. In this paper, I review the idea of computing with coupled chemical oscillators and give arguments for the efficiency of such an approach. I discuss how to input information and how to read out the result of network computation. I describe the idea of top-down optimization of computing networks. As an example, I consider a small network of three coupled chemical oscillators designed to differentiate the white from the red points of the Japanese flag. My results are based on computer simulations with the standard two-variable Oregonator model of the oscillatory Belousov–Zhabotinsky reaction. An optimized network of three interacting oscillators can recognize the color of a randomly selected point with >98% accuracy. The presented ideas can be helpful for the experimental realization of fully functional chemical computing networks.
Bearing Fault Diagnosis Based on an Enhanced Image Representation Method of Vibration Signal and Conditional Super Token Transformer
Authors: Li Jiaying , Liu Han , Liang Jiaxun , Dong Jiahao , Pang Bin , Hao Ziyang , Zhao Xin
Published: August 2022

Multipoint Optimal Minimum Entropy Deconvolution Adjusted (MOMEDA) is an advanced deconvolution method, which can effectively inhibit the interference of background noise and distinguish the fault period by calculating the multipoint kurtosis values. However, multipoint kurtosis (MKurt) could lead to misjudgment since it is sensitive to spurious noise spikes. Considering that L-kurtosis has good robustness with noise, this paper proposes a multipoint envelope L-kurtosis (MELkurt) method for establishing the temporal features. Then, an enhanced image representation method of vibration signals is proposed by employing the Gramian Angular Difference Field (GADF) method to convert the MELkurt series into images. Furthermore, to effectively learn and extract the features of GADF images, this paper develops a deep learning method named Conditional Super Token Transformer (CSTT) by incorporating the Super Token Transformer block, Super Token Mixer module, and Conditional Positional Encoding mechanism into Vision Transformer appropriately. Transfer learning is introduced to enhance the diagnostic accuracy and generalization capability of the designed CSTT. Consequently, a novel bearing fault diagnosis framework is established based on the presented enhanced image representation and CSTT. The proposed method is compared with Vision Transformer and some CNN-based models to verify the recognition effect by two experimental datasets. The results show that MELkurt significantly improves the fault feature enhancement ability with superior noise robustness to kurtosis, and the proposed CSTT achieves the highest diagnostic accuracy and stability.
Transfering Targeted Maximum Likelihood Estimation for Causal Inference into Sports Science
Authors: Dijkhuis Talko B. , Blaauw Frank J.
Published: August 2022

Although causal inference has shown great value in estimating effect sizes in, for instance, physics, medical studies, and economics, it is rarely used in sports science. Targeted Maximum Likelihood Estimation (TMLE) is a modern method for performing causal inference. TMLE is forgiving in the misspecification of the causal model and improves the estimation of effect sizes using machine-learning methods. We demonstrate the advantage of TMLE in sports science by comparing the calculated effect size with a Generalized Linear Model (GLM). In this study, we introduce TMLE and provide a roadmap for making causal inference and apply the roadmap along with the methods mentioned above in a simulation study and case study investigating the influence of substitutions on the physical performance of the entire soccer team (i.e., the effect size of substitutions on the total physical performance). We construct a causal model, a misspecified causal model, a simulation dataset, and an observed tracking dataset of individual players from 302 elite soccer matches. The simulation dataset results show that TMLE outperforms GLM in estimating the effect size of the substitutions on the total physical performance. Furthermore, TMLE is most robust against model misspecification in both the simulation and the tracking dataset. However, independent of the method used in the tracking dataset, it was found that substitutes increase the physical performance of the entire soccer team.
Optimization of Cockpit Ventilation for Polar Cruise Ships in Combination with Windscreen Defogging and Cabin Comfort Considerations
Authors: Shi Hong , Zhang Qianwei , Xu Wenbing , Liu Meinan , Pan Jiashuang , Yuan Jie , Yang Kaijie
Published: August 2022

Polar cruise ships are exposed to extreme external conditions during voyages, resulting in cockpit windscreens that are prone to fogging and frosting, seriously affecting the driver’s vision and even threatening navigation safety. However, the current research mainly focuses on cabin comfort, ignoring the coupling of defogging and comfort. Accordingly, this paper combines cockpit-windshield-defogging design and cockpit comfort considerations, and proposes 108 orthogonal-ventilation design parameters based on the four basic ventilation methods. The effects of different air supply parameters on comfort and anti-fog characteristics are investigated by using fluid dynamics simulation methods. The entropy weight–TOPSIS algorithm is employed to find the optimal ventilation parameters. The results show that the “Down-supply up-return type vertical jet” air supply method corresponding to an air supply velocity of 1 m/s, an air supply temperature of 297 K, and an air supply relative humidity of 30% has the smallest Euclidean distance di+ from the positive ideal solution, and the largest Euclidean distance di− from the negative ideal solution; thus, it obtains a higher ci and the highest priority. This air supply method provides the best thermal comfort for the drivers, as well as the best anti-fogging and defogging effect. The results can be useful to provide suggestions for the future design of the air-conditioning systems in polar cruise ships.
Hydrothermal Carbonization
Authors: Reza M. Toufiq
Published: August 2022

Over the past decade, hydrothermal carbonization (HTC) has emerged as a promising thermochemical pathway for treating and converting wet wastes into fuel, materials, and chemicals [...]
Kinematic and Dynamic Simulation Analysis of Modified Conventional Beam Pumping Unit
Authors: Xu Jinchao , Li Wei , Meng Siyuan
Published: August 2022

The large net torque fluctuations in the reducer output shafts of conventional beam pumping units and the existence of negative torque are the decisive factors that lead to their low efficiency and high energy consumption. This study developed a positive torque modulation scheme for conventional beam pumping units, which was based on the principle of the follow-up secondary balance of the connecting rod. The CYJ10-4.2-53HF conventional beam pumping unit was selected as the research object. The kinematic and dynamic simulation analysis of the modified pumping unit was carried out using ADAMS software. The results showed that secondary balance torque curves could realize the function of “peak cutting and valley filling” for the curves after the primary balance and that the modified pumping unit could achieve a full-cycle positive value for the reducer output shaft and verify the feasibility of our modulation scheme. A secondary balance offset angle of 315° was the best choice as the amplitude of the torque curve clearly increased and the phase remained basically the same when the radius of the mass center of the secondary balance increased. Therefore, when the offset angle value of the secondary balance weight was determined, the radius of the mass center could be changed by adjusting the position of the secondary balance weight to achieve the balance adjustment.
Accurate Circuit Parameter Determination of a Resonant Power Frequency Converter for High-Voltage and Partial Discharge Tests
Authors: Leelachariyakul Banyat , Yutthagowith Peerawut
Published: August 2022

For high-voltage (HV) and partial discharge (PD) tests on high-voltage equipment, a resonant power frequency converter has recently been developed. A single-phase power frequency converter with a resonant tuning and filter circuit and an HV testing transformer comprise the developed system. A difficulty in the tuning and filter circuit design is the unknown testing system circuit parameters, including unknown parasitic inductance, capacitance, and internal resistance. In this paper, a system with a voltage rating of 75 kVrms, apparent power of 40 kVA, and an operating frequency from 50 Hz to 200 Hz is considered for determination of the equivalent circuit parameters. From the determined circuit parameters, the appropriate resonant tuning and filter circuit was designed effectively. The transfer functions of the input and output testing voltages, along with the transfer impedance of the input voltage and signal voltage of the PD measuring port, were analyzed. The system design was verified by experiments with a voltage transformer. The gain of the transfer impedance was about 15 and 4 at the testing frequencies of 50 Hz and 200 Hz, respectively. With the proper design, it is possible to generate an output voltage waveform that is almost entirely sinusoidal and has a background noise level of under 1 pC. According to the experimental results, the system design of the resonant converter and the method for determining the equivalent circuit are very helpful for the HV and PD tests of voltage transformers in actual practice.
Evaluation of the Energy Consumption and Fractal Characteristics of Different Length-Diameter Ratios of Coal under Dynamic Impact
Authors: Yuan Qiupeng , Wang Lei , Xie Guangxiang , Gu Shuhao , Khan Naseer Muhammad , Jiao Zhenhua , Liu Huaiqian
Published: August 2022

Coal samples having the same diameter (50 mm) and different length-diameter ratios (l/d), i.e., 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1.0 were tested under dynamic uniaxial impact compression using the Split Hopkinson Pressure Bar (SHPB) experimental system. This study evaluates: (a) The effects of l/d on the energy consumption law and fractal characteristics of coal crushing; (b) The effects of l/d and stress balance on energy dissipation; (c) The effects of l/d and energy consumption density on the fractal characteristics of coal crushing. The findings under different l/d are as follows: (1) The coal samples show similar stress–strain curve shapes in stages including elastic, plastic, and failure stage, which is an “open” shape, the proportion of plastic stage increases, and strain-softening occurs; (2) The dynamic compression dissipation energy and energy consumption ratio of coal shows the same trend, showing two stages with the increase of length-diameter ratio, which increases linearly in the first stage and overall decreases step-by-step; (3) The average particle size increases while fractal dimension of fragmentation decreases linearly, which endorses the decreasing trend of fragmentation degree; (4) It is determined that there is a power relationship between fractal dimension and energy dissipation density; (5) A new index Crushing Density Energy Efficiency (CDEE) is proposed, which can be used to characterize the rock-breaking efficiency of crushing energy consumption under different conditions. This index is inversely proportional to l/d. The research results can provide a basis for the design of top coal caving mining, and the determination of blasting parameters.
Good Practices to Counteract Epidemic Emergency in Mining Companies in Poland
Authors: Bąk Patrycja
Published: August 2022

The date assumed as the beginning of the pandemic in Poland is 4 March 2020, the date of the first confirmed case of the virus. This article presents the actions undertaken by the management of underground hard coal mining plants concerning the risk of epidemic related to SARS-CoV-2. This work shows a set of implemented recommendations, guidelines and decisions, which were established after the appearance of the first wave of cases in Poland. What is more, it discusses measures aiming at reducing the risk of spreading the coronavirus among the mineworkers. The suggestions for different variants of the decision-making process concerning the pandemic and which have an enormous impact on the operating expenses of the company are also made. The paper presents the results of the study on actions taken in individual mining companies and good work practices recommended to be applied.
Effects of Cap-and-Trade Mechanism and Financial Gray Rhino Threats on Insurer Performance
Authors: Chen Shi , Huang Fu-Wei , Lin Jyh-Horng
Published: August 2022

This paper develops a capped barrier option model to examine how a cap-and-trade mechanism affects an insurer’s guaranteed rate-setting behavior and policyholder protection in a financial gray rhino environment. Toward sustainability, the insurer explicitly captures the credit risk from the borrowing firms, participating in the cap-and-trade scheme to reduce carbon emissions, an essential issue of carbon emission and environmental protection when facing gray rhino threats. In addition, the energy economics and policy analysis are from the fund-providing insurer’s perspective. Green lending policies and life insurance policy loans (i.e., disintermediation related to insurance stability) are crucial to managers and regulators, particularly bridging the borrowing-firm carbon transactions for carbon emission reductions toward sustainability. We show that the shrinking regulatory cap of the cap-and-trade scheme harms policyholder protection, adversely affecting insurance stability. The harm becomes more serious when the gray rhino threat on borrowing firms becomes significant. An increase in policy loans decreases the insurer’s interest margin and policyholder protection. However, increasing the gray rhino threat decreases life insurance policies at a reduced guaranteed rate but increases policyholder protection, contributing to insurance stability. Therefore, the government can use the cap-and-trade scheme to control carbon emissions and improve the environment, but it harms policyholder protection. We suggest that, for example, the government should subsidize the insurer for green lending, affecting insurance stability.