bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of Endothelial α1AMPK Reverses the Vascular Protective Effects of Exercise by Causing eNOS Uncoupling
Authors: Jansen Thomas , Kvandová Miroslava , Schmal Isabella , Kalinovic Sanela , Stamm Paul , Kuntic Marin , Foretz Marc , Viollet Benoit , Daiber Andreas , Oelze Matthias , Keaney John F. , Münzel Thomas , Schulz Eberhard , Kröller-Schön Swenja
Published: December 2021

Voluntary exercise training is an effective way to prevent cardiovascular disease, since it results in increased NO bioavailability and decreased reactive oxygen species (ROS) production. AMP-activated protein kinase (AMPK), especially its α1AMPK subunit, modulates ROS-dependent vascular homeostasis. Since endothelial cells play an important role in exercise-induced changes of vascular signaling, we examined the consequences of endothelial-specific α1AMPK deletion during voluntary exercise training. We generated a mouse strain with specific deletion of α1AMPK in endothelial cells (α1AMPKflox/flox x TekCre+). While voluntary exercise training improved endothelial function in wild-type mice, it had deleterious effects in mice lacking endothelial α1AMPK indicated by elevated reactive oxygen species production (measured by dihydroethidum fluorescence and 3-nitrotyrosine staining), eNOS uncoupling and endothelial dysfunction. Importantly, the expression of the phagocytic NADPH oxidase isoform (NOX-2) was down-regulated by exercise in control mice, whereas it was up-regulated in exercising α1AMPKflox/flox x TekCre+ animals. In addition, nitric oxide bioavailability was decreased and the antioxidant/protective nuclear factor erythroid 2-related factor 2 (Nrf-2) response via heme oxygenase 1 and uncoupling protein-2 (UCP-2) was impaired in exercising α1AMPKflox/flox x TekCre+ mice. Our results demonstrate that endothelial α1AMPK is a critical component of the signaling events that enable vascular protection in response to exercise. Moreover, they identify endothelial α1AMPK as a master switch that determines whether the effects of exercise on the vasculature are protective or detrimental.
Parenteral Antioxidant Supplementation at Birth Improves the Response to Intranasal Vaccination in Newborn Dairy Calves
Authors: Nayak Arpita , Abuelo Angel
Published: December 2021

Newborn calves experience oxidative stress throughout the first month of their life, which is known to decrease lymphocyte functions relevant to vaccine responsiveness. Thus, this study aimed to determine the extent to which parenteral antioxidant supplementation given at birth improves the response to an intranasal viral vaccine in the first month of life of newborn dairy calves. For this, 21 calves were randomly assigned at birth to one of two commercially available antioxidant micronutrient supplements or a placebo group receiving 0.9% sterile saline (n = 7/group). Serum and nasal secretion samples were collected before administration of treatments and an intranasal vaccine against respiratory viruses (bovine herpesvirus type 1, bovine syncytial respiratory virus, and parainfluenza 3), and once weekly for the first four weeks of age. Systemic redox balance was determined in serum. Immunoglobulin A specific for bovine herpesvirus 1 and bovine syncytial respiratory virus was quantified in nasal secretions as a proxy to intranasal vaccine responsiveness. Our results showed that parenteral administration of antioxidants at birth improved calves’ redox balance. Additionally, calves receiving antioxidant supplementation had higher concentrations of immunoglobulin A in their nasal secretions than calves in the control group. Thus, we conclude that supplementation of calves with antioxidants at birth could be a practical strategy to improve intranasal vaccine response. Future larger studies should evaluate the extent to which this increased mucosal response to intranasal vaccination could result in decreased calf morbidity and mortality.
The Role of Buoyancy Induced Instability in Transpirational Cooling Applications
Authors: Wanstall C. Taber , Johnson Phillip R.
Published: December 2021

Transpirational cooling is an effective thermal protection method in hypersonic vehicles. In order to properly manage the high heat load, an understanding of the convective flow regimes as well as the thermophysical properties of the working fluid are required. Often, the vehicle’s fuel is re-purposed as the coolant or working fluid that is passed through the porous media. If the geometry is such that the coolant is heated from below, buoyancy-induced instability can ensue resulting in a mixed convection phenomena. Transpirational cooling applications require a unique analysis which combines a Darcy–Forchheimer relationship for the momentum relation, a flowing base state which introduces non-negligible convective terms for the energy equation, and a novel consideration of a cubic density dependence on temperature. This latter feature is justified by fitting thermodynamic data for typical transpirational cooling conditions. A base state solution is provided and the onset of instability is investigated using linear stability analysis. The governing equations are solved utilizing multiple methods, comparing results from a combination of analytical solutions, finite difference, power series, and Chebyshev methods. Results demonstrate excellent consistency in predictions across these methods and indicate that including non-linear density effects promote a stabilizing effect. Finally, the effect of varying the net through-flow in the porous media is investigated.
The 12th International Conference on Instrumental Analysis—Modern Trends and Applications (20–23 September 2021, Virtual Event)
Authors: Mitrakas Manassis , Ochsenkühn-Petropoulou Maria
Published: December 2021

The 12th International Conference on “Instrumental Methods of Analysis” www [...]
The Strong Precipitation of the Dry Warm Front Cyclone in Syria and Its Prediction by Data Mining Modeling
Authors: Wang Jianhong , Alakol Nour , Wang Xing , He Dongpo , Kumar Kanike Raghavendra , Miao Chunsheng
Published: December 2021

The Eastern inland of Syria has a Mediterranean climate in the north and a tropical desert climate in the south, which results in a dry south and wet north climate feature, especially in winter. The circulation dynamics analysis of 16 winter strong precipitation events shows that the key system is the dry and warm front cyclone. In most cases (81–100% of the 16 cases), the moisture content in the northern part of the cyclone is higher than that in the southern part (influenced by the Mediterranean climate zone). The humidity in the middle layer is higher than that near the surface (uplifting of the dry warm front), and the thickness of the wet layer and the vertical ascending layer obviously expands upward (as shown by the satellite cloud top reflection). These characteristics lead to the moisture thermodynamic instability in the eastern part of the cyclone (dry and warm air at low level and wet and cold air at upper level). The cyclone flow transports momentum to the local humid layer of the Mediterranean climate belt and then causes unstable conditions and strong rainfall. Considering the limitations of the Syrian ground station network, the NCEP/CFSR global reanalysis data and MODIS aqua-3 cloud parameter data are used to build a multi-source factor index of winter precipitation from 2002 to 2016. A decision tree prediction model is then established and the factors index is constructed into tree shapes by the nodes and branches through calculating rules of information entropy. The suitable tree shape models are adjusted and selected by an automated training and testing process. The forecast model can classify rainfall with a forecast accuracy of more than 90% for strong rainfall over 30 mm.
Risk Management Assessment Improves the Cost-Effectiveness of Invasive Species Prioritisation
Authors: Robertson Peter A. , Mill Aileen C. , Adriaens Tim , Moore Niall , Vanderhoeven Sonia , Essl Franz , Booy Olaf
Published: December 2021

International agreements commit nations to control or eradicate invasive alien species. The scale of this challenge exceeds available resources and so it is essential to prioritise the management of invasive alien species. Species prioritisation for management typically involves a hierarchy of processes that consider the likelihood and scale of impact (risk assessment) and the feasibility, costs and effectiveness of management (risk management). Risk assessment processes are widely used, risk management less so, but are a crucial component of resource decision making. To assess the cost-effectiveness of prioritisation, we considered 26 high-risk species considered for eradication from Great Britain (GB) with pre-existing risk assessment and risk management outputs. We extracted scores to reflect the overall risk to GB posed by the species, together with the estimated cost and the overall feasibility of eradication. We used these to consider the relative reduction in risk per unit cost when managing prioritised species based on different criteria. We showed that the cost-effectiveness of prioritisation within our sample using risk assessment scores alone, performed no better than a random ranking of the species. In contrast, prioritisation including management feasibility produced nearly two orders of magnitude improvement compared to random. We conclude that basing management actions on priorities based solely on risk assessment without considering management feasibility risks the inefficient use of limited resources. In this study, the cost-effectiveness of species prioritisation for action was greatly increased by the inclusion of risk management assessment.
A Review on Microbial Products and Their Perspective Application as Antimicrobial Agents
Authors: Rani Alka , Saini Khem Chand , Bast Felix , Varjani Sunita , Mehariya Sanjeet , Bhatia Shashi Kant , Sharma Neeta , Funk Christiane
Published: December 2021

Microorganisms including actinomycetes, archaea, bacteria, fungi, yeast, and microalgae are an auspicious source of vital bioactive compounds. In this review, the existing research regarding antimicrobial molecules from microorganisms is summarized. The potential antimicrobial compounds from actinomycetes, particularly Streptomyces spp.; archaea; fungi including endophytic, filamentous, and marine-derived fungi, mushroom; and microalgae are briefly described. Furthermore, this review briefly summarizes bacteriocins, halocins, sulfolobicin, etc., that target multiple-drug resistant pathogens and considers next-generation antibiotics. This review highlights the possibility of using microorganisms as an antimicrobial resource for biotechnological, nutraceutical, and pharmaceutical applications. However, more investigations are required to isolate, separate, purify, and characterize these bioactive compounds and transfer these primary drugs into clinically approved antibiotics.
Erectile Function and Sexual Behavior: A Review of the Role of Nitric Oxide in the Central Nervous System
Authors: Melis Maria Rosaria , Argiolas Antonio
Published: December 2021

Nitric oxide (NO), the neuromodulator/neurotransmitter formed from l-arginine by neuronal, endothelial and inducible NO synthases, is involved in numerous functions across the body, from the control of arterial blood pressure to penile erection, and at central level from energy homeostasis regulation to memory, learning and sexual behavior. The aim of this work is to review earlier studies showing that NO plays a role in erectile function and sexual behavior in the hypothalamus and its paraventricular nucleus and the medial preoptic area, and integrate these findings with those of recent studies on this matter. This revisitation shows that NO influences erectile function and sexual behavior in males and females by acting not only in the paraventricular nucleus and medial preoptic area but also in extrahypothalamic brain areas, often with different mechanisms. Most importantly, since these areas are strictly interconnected with the paraventricular nucleus and medial preoptic area, send to and receive neural projections from the spinal cord, in which sexual communication between brain and genital apparatus takes place, this review reveals that central NO participates in concert with neurotransmitters/neuropeptides to a neural circuit controlling both the consummatory (penile erection, copulation, lordosis) and appetitive components (sexual motivation, arousal, reward) of sexual behavior.
Evaluation of ATOX1 as a Potential Predictive Biomarker for Tetrathiomolybdate Treatment of Breast Cancer Patients with High Risk of Recurrence
Authors: Blockhuys Stéphanie , Hildesjö Camilla , Olsson Hans , Vahdat Linda , Wittung-Stafshede Pernilla
Published: December 2021

Copper plays a key role in cancer metastasis, which is the most common cause of cancer death. Copper depletion treatment with tetrathiomolybdate (TM) improved disease-free survival in breast cancer patients with high risk of recurrence in a phase II clinical trial. Because the copper metallochaperone ATOX1 was recently reported to drive breast cancer cell migration and breast cancer migration is a critical factor in metastasis, we tested if ATOX1 expression levels in primary tumor tissue could predict the TM treatment outcome of breast cancer patients at high risk of recurrence. We performed ATOX1 immunohistochemical staining of breast tumor material (before TM treatment) of 47 patients enrolled in the phase II TM clinical trial and evaluated ATOX1 expression levels in relation with patient outcome after TM treatment. Our results show that higher ATOX1 levels in the tumor cell cytoplasm correlate with a trend towards better event-free survival after TM treatment for triple-negative breast cancer patients and patients at stage III of disease. In conclusion, ATOX1 may be a potential predictive biomarker for TM treatment of breast cancer patients at high risk of recurrence and should be tested in a larger cohort of patients.
Neutrophil Extracellular Traps in Skin Diseases
Authors: Ogawa Youichi , Muto Yoshinori , Kinoshita Manao , Shimada Shinji , Kawamura Tatsuyoshi
Published: December 2021

Neutrophils are the primary innate immune cells, and serve as sentinels for invading pathogens. To this end, neutrophils exert their effector functions via phagocytosis, degranulation, reactive oxygen species generation, and neutrophil extracellular trap (NET) release. Pathogens and pathogen-derived components trigger NET formation, leading to the clearance of pathogens. However, NET formation is also induced by non-related pathogen proteins, such as cytokines and immune complexes. In this regard, NET formation can be induced under both non-sterile and sterile conditions. NETs are enriched by components with potent cytotoxic and inflammatory properties, thereby occasionally damaging tissues and cells and dysregulating immune homeostasis. Research has uncovered the involvement of NETs in the pathogenesis of several connective tissue diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and ANCA-associated vasculitis. In dermatology, several skin diseases clinically develop local or systemic sterile pustules and abscesses. The involvement of neutrophils and subsequent NET formation has recently been elucidated in these skin diseases. Therefore, this review highlights the NETs in these neutrophil-associated diseases.
SIRT1 Contributes as an Invasiveness Marker in Pituitary Adenoma
Authors: Vaiciulis Domantas , Vilkeviciute Alvita , Gedvilaite Greta , Glebauskiene Brigita , Kriauciuniene Loresa , Liutkeviciene Rasa
Published: December 2021

The aim of the study was to find the association between SIRT1 concentration, SIRT1 rs3758391, rs3818292, rs7895833 polymorphisms and clinical manifestations of pituitary adenoma (PA). The study included 108 patients with PA and 216 healthy individuals. Using commercial kits, DNA was extracted from peripheral blood leukocytes. To determine the PA and control group subjects genotypes was used real-time PCR method, for SIRT concentration measurement we used ELISA method. The statistical data analysis was completed using the “BM SPSS Statistics 20.0” software. Results: We performed statistical analysis of SNPs in the patient and healthy controls and patients’ subgroups and found statistically significant differences in rs7895833 genotype (A/A, A/G, G/G) distributions between the active PA and control groups (67.9%, 24.6%, 5.7% vs. 72.2%, 27.3%, 0.5%; p = 0.02) Also, the results showed that the rs7895833 G/G genotype is associated with about 13-fold increased odds of active PA development compared to the A/A (OR = 13.95% CI: 1.314–128.632; p = 0.028) and both A/A and A/G genotypes (OR = 12.9; 95% CI: 1.314–126.624; p = 0.028). There is ample evidence that SIRT1 in the pituitary and other target organs modifies the synthesis, secretion, and activity of hormones to trigger adaptive responses, thus we decided to include this in our study. When determining the serum concentration of SIRT1, we did not find a statistically significant difference between the PA group and the control group. SIRT1 serum level was statistically significantly higher in women with PA than in healthy control women (1.115 (3.748) vs. 136 (0.211); p = 0.008). To conclude—SIRT1 rs7895833 G/G genotype is associated with about 13-fold increased odds of active PA development compared to the A/A and both A/A and A/G genotypes. SIRT1 serum levels are higher in women with PA than in healthy women.
Epithelial-to-Mesenchymal Transition Mediates Resistance to Maintenance Therapy with Vinflunine in Advanced Urothelial Cell Carcinoma
Authors: Font Albert , Ruiz de Porras Vicenç , Valderrama Begoña P. , Ramirez Jose Luis , Nonell Lara , Virizuela José Antonio , Anido Urbano , González-del-Alba Aránzazu , Lainez Nuria , Llorente Maria del Mar , Jiménez Natalia , Mellado Begoña , García-Donas Jesus , Bellmunt Joaquim
Published: December 2021

In the phase II MAJA trial, maintenance therapy with vinflunine resulted in longer progression-free survival compared to best supportive care in advanced urothelial cell carcinoma (aUCC) patients who did not progress after first-line platinum-based chemotherapy. However, despite an initial benefit observed in some patients, unequivocal resistance appears which underlying mechanisms are presently unknown. We have performed gene expression and functional enrichment analyses to shed light on the discovery of these underlying resistance mechanisms. Differential gene expression profile of eight patients with poor outcome and nine with good outcome to vinflunine administered in the MAJA trial were analyzed. RNA was isolated from tumor tissue and gene expression was assessed by microarray. Differential expression was determined with linear models for microarray data. Gene Set Enrichment Analysis (GSEA) was used for the functional classification of the genes. In vitro functional studies were performed using UCC cell lines. Hierarchical clustering showed a differential gene expression pattern between patients with good and poor outcome to vinflunine treatment. GSEA identified epithelial-to-mesenchymal transition (EMT) as the top negatively enriched hallmark in patients with good outcome. In vitro analyses showed that the polyphenol curcumin downregulated EMT markers and sensitized UCC cells to vinflunine. We conclude that EMT mediates resistance to vinflunine and suggest that the reversion of this process could enhance the effect of vinflunine in aUCC patients.
The Complex Network between Inflammation and Colorectal Cancer: A Systematic Review of the Literature
Authors: Percario Rossana , Panaccio Paolo , di Mola Fabio Francesco , Grottola Tommaso , Di Sebastiano Pierluigi
Published: December 2021

Background: colorectal cancer (CRC) has a multifactorial etiology which comprises microbiota, genetic predisposition, diet, environmental factors, and last but not least, a substantial contribution by inflammation. The aim of this study is to conduct a systematic review of the literature regarding the strong link between inflammation and colorectal cancer. Methods: A systematic review of the literature on PubMed (Medline), Scopus, Cochrane and EMBase databases was performed, following the PRISMA 2020 guidelines. Each paper was reviewed by two groups of researchers in a single-blind format by using a pre-planned Microsoft© Excel® grid. Results: Using automated research filters, 14,566 studies were included, but 1% was found significant by the reviewers. Seventy pathways of inflammation were described in the sequence of inflammation-carcinogenesis, and anti-tumorigenic molecules were also found. Conclusion: several studies suggest a strong role of inflammation in the tumorigenesis of colorectal cancer through different pathways: this may have a diagnostic and clinical role and also therapeutic purpose in preventing carcinogenesis by treating inflammation. In vitro tests support this theory, even if many other clinical trials are necessary. The present paper was registered in the OpenScience Framework registry (Identifier: DOI 10.17605/OSF.IO/2KG7T).
Timing of the Pubertal Growth Spurt and Prostate Cancer
Authors: Célind Jimmy , Bygdell Maria , Martikainen Jari , Styrke Johan , Damber Jan-Erik , Kindblom Jenny M. , Ohlsson Claes
Published: December 2021

Previous studies of pubertal timing and the risk of prostate cancer have used self-reported markers of pubertal development, recalled in mid-life, and the results have been inconclusive. Our aim was to evaluate the age at the pubertal growth spurt, an objective marker of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. This population-based cohort study included 31,971 men with sufficient height measurements to calculate age at peak height velocity (PHV). Outcomes were accessed through national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions with follow up starting at 20 years of age. In total, 1759 cases of prostate cancer including 449 high-risk were diagnosed during follow up. Mean follow up was 42 years (standard deviation 10.0). Compared to quintiles 2–4 (Q2–4), men in the highest age at PHV quintile (Q5) had lower risk of prostate cancer (HR 0.83, 95% CI 0.73–0.94), and of high-risk prostate cancer (0.73; 0.56–0.94). In an exploratory analysis with follow up starting at age at PHV, late pubertal timing was no longer associated with reduced risk of prostate cancer. Later pubertal timing was associated with reduced risk of prostate cancer and especially high-risk prostate cancer. We propose that the risk of prostate cancer might be influenced by the number of years with exposure to adult levels of sex steroids.
Sensor-Embedded Face Masks for Detection of Volatiles in Breath: A Proof of Concept Study
Authors: Di Zazzo Lorena , Magna Gabriele , Lucentini Martina , Stefanelli Manuela , Paolesse Roberto , Di Natale Corrado
Published: December 2021

The correlation between breath volatilome and health is prompting a growing interest in the development of sensors optimized for breath analysis. On the other hand, the outbreak of COVID-19 evidenced that breath is a vehicle of infection; thus, the introduction of low-cost and disposable devices is becoming urgent for a clinical implementation of breath analysis. In this paper, a proof of concept about the functionalization of face masks is provided. Porphyrin-based sensors are among the most performant devices for breath analysis, but since porphyrins are scarcely conductive, they make use of costly and bulky mass or optical transducers. To overcome this drawback, we introduce here a hybrid material made of conducting polymer and porphyrins. The resulting material can be easily deposited on the internal surface of standard FFP face masks producing resistive sensors that retain the chemical sensitivity of porphyrins implementing their combinatorial selectivity for the identification of volatile compounds and the classification of complex samples. The sensitivity of sensors has been tested with respect to a set of seven volatile compounds representative of diverse chemical families. Sensors react to all compounds but with a different sensitivity pattern. Functionalized face masks have been tested in a proof-of-concept test aimed at identifying changes of breath due to the ingestion of beverages (coffee and wine) and solid food (banana- and mint-flavored candies). Results indicate that sensors can detect volatile compounds against the background of normal breath VOCs, suggesting the possibility to embed sensors in face masks for extensive breath analysis
Effect of Regorafenib on P2X7 Receptor Expression and Different Oncogenic Signaling Pathways in a Human Breast Cancer Cell Line: A Potential of New Insight of the Antitumor Effects of Regorafenib
Authors: Salahuddin Muhammed M. , Omran Gamal A. , Helmy Maged W. , Houssen Maha E.
Published: December 2021

Background: Breast cancer is the most common malignancy in women worldwide. P2X7 is a transmembrane receptor expressed in breast cancer and activated by the ATP tumor microenvironment, driving cell proliferation, angiogenesis, and metastasis via different signaling pathways. The role of the P2X7 receptor, hypoxia, and autophagy in regulating tumor progression is controversial. The multikinase inhibitor regorafenib prevents the activation of numerous kinases involved in angiogenesis, proliferation, and metastasis. The present study aimed to evaluate the modulatory effect of regorafenib on the hypoxia/angiogenesis/P2X7R/autophagy axis on the MCF7 breast cancer cell line and its impact on different signaling pathways involved in breast cancer pathogenesis. Methods: The levels of VEGF, VEGFR, PI3K, NF-κB, HIF-1α, and LC3-II were analyzed using ELISA, and caspase-3 activity was also assessed colorimetrically. Phosphorylated (p)-p38 MAPK and purinergic ligand-gated ion channel 7 (P2X7) receptor protein expression levels were analyzed via Western blotting. Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of Beclin 1 (BECN1), LC3-II, and sequestosome 1 (p62). Results: Regorafenib reduced MCF7 cell viability in a dose-dependent manner. Furthermore, regorafenib significantly reduced levels of PI3K, NF-κB, VEGF, VEGFR, P2X7 receptor, and p-p38 MAPK protein expression, and markedly reduced p62 mRNA expression levels. However, regorafenib significantly increased caspase-3 activity, as well as BECN1 and LC3-II mRNA expression levels. Conclusions: Regorafenib was demonstrated to possibly exhibit antitumor activity on the breast cancer cell line via modulation of the P2X7/HIF-1α/VEGF, P2X7/P38, P2X7/ERK/NF-κB, and P2X7/beclin 1 pathways.
A Retrospective Comparative Analysis of Outcomes and Prognostic Factors in Adult and Pediatric Patients with Osteosarcoma
Authors: Testa Stefano , Hu Benjamin D. , Saadeh Natalie L. , Pribnow Allison , Spunt Sheri L. , Charville Gregory W. , Bui Nam Q. , Ganjoo Kristen N.
Published: December 2021

Osteosarcoma is the most common primary bone malignancy in both children and adults. Despite introduction of intensive multimodal treatment with chemotherapy and surgery, outcomes are still poor, especially for patients with metastatic disease and adults. Hence, there is an ongoing need for better prognostic markers and outcome data to inform management decisions in both the adult and pediatric setting. Here, we retrospectively analyzed 112 patients with bone osteosarcoma treated at two large adult and pediatric tertiary academic centers between 1989 and 2019. Patients were divided into an adult (≥18 years) and pediatric (<18 years) cohort for comparison. Our aim was to evaluate predictors of outcomes in pediatric and adult patients, with a specific focus on the role of methotrexate when added to a combination of doxorubicin-cisplatin; the prognostic value of tumor necrosis after neoadjuvant chemotherapy; and outlining any differences in outcomes between adults and pediatric patients that could inform clinical management. Adult patients treated with methotrexate-doxorubicin-cisplatin and those treated with doxorubicin-cisplatin had similar 5-year PFS (26%, 95%CI: 45.5%–10% vs. 50%, 95%CI: 69.6%–26.2%, p = 0.1) and 5-year OS (63%, 95%CI: 82%–34%, vs. 78%, 95%CI: 90.6%–52.6%, p = 0.5). In the adult cohort, there was no difference between patients with ≥90% necrosis and <90% necrosis in either 5-year PFS (42%, 95%CI: 71.1%–11.3% vs. 38%, 95%CI: 57.7%–18.2%, p = 0.4) or 5-year OS (85%, 95%CI: 97.8%–33.4% vs. 56%, 95%CI: 76.8%–27.6%, p = 0.4). In the pediatric cohort, compared to patients with <90% necrosis, those with ≥90% necrosis had significantly better 5-year PFS (30%, 95%CI: 49.3%–14.1% vs. 55%, 95%CI: 73.9%–38.5%, p = 0.003) and 5-year OS (64%, 95%CI: 80.8%–41.1% vs. 78%, 95%CI: 92%–60.9%, p = 0.04). Adult and pediatric patients had similar 5-year OS (69%, 95%CI: 83.2%–49.8% vs. 73%, 95%CI: 83.2%–59.3%, p = 0.8) and 5-year PFS (37%, 95%CI: 52.4%–22.9% vs. 43%, 95%CI: 56.2%–30.4% p = 0.3) even though the proportion of patients with ≥90% necrosis after neoadjuvant chemotherapy was higher for children compared to adults (60.3% vs. 30%, OR: 3.54, 95%CI: 1.38–8.46, p = 0.006). In conclusion, in adult patients, the addition of methotrexate to doxorubicin and cisplatin did not correlate with a significant survival benefit, questioning the therapeutic value of methotrexate overall. Our study confirms the prognostic utility of percent tumor necrosis after neoadjuvant chemotherapy in pediatric patients but not in adult patients. Lastly, this is one of the few reported studies where patients with osteosarcoma younger and older than 18 years had similar PFS and OS.
Reference Values of Native T1 at 3T Cardiac Magnetic Resonance—Standardization Considerations between Different Vendors
Authors: Tribuna Liliana , Oliveira Pedro Belo , Iruela Alba , Marques João , Santos Paulo , Teixeira Tiago
Published: December 2021

This study aimed at establishing native T1 reference values for a Canon Vantage Galan 3T system and comparing them with previously published values from different vendors. A total of 20 healthy volunteers (55% Women; 33.9 ± 11.1 years) underwent left ventricular T1 mapping at 3T MR. A MOLLI 5(3)3 sequence was used, acquiring three short-axis slices. Native T1 values are shown as means (±standard deviation) and Student’s independent samples t-test was used to test gender differences in T1 values. Pearson’s correlation coefficient analysis was used to compare two processes of T1 analysis. The results show a global native T1 mean value of 1124.9 ± 55.2 ms (exponential analysis), that of women being statistically higher than men (1163 ± 30.5 vs. 1077.9 ± 39.5 ms, respectively; p < 0.001). There were no specific tendencies for T1 times in different ventricular slices. We found a strong correlation (0.977, p < 0.001) with T1 times derived from parametric maps (1136.4 ± 60.2 ms). Native T1 reference values for a Canon 3T scanner were provided, and they are on par with those already reported from other vendors for a similar sequence. We also found a correlation between native T1 and gender, with higher values for women.
Preoperative Evaluation and Surgical Simulation for Osteochondritis Dissecans of the Elbow Using Three-Dimensional MRI-CT Image Fusion Images
Authors: Kohyama Sho , Nishiura Yasumasa , Hara Yuki , Ogawa Takeshi , Ikumi Akira , Okano Eriko , Totoki Yasukazu , Yoshii Yuichi , Yamazaki Masashi
Published: December 2021

We used our novel three-dimensional magnetic resonance imaging-computed tomography fusion images (3D MRI-CT fusion images; MCFIs) for detailed preoperative lesion evaluation and surgical simulation in osteochondritis dissecans (OCD) of the elbow. Herein, we introduce our procedure and report the findings of the assessment of its utility. We enrolled 16 men (mean age: 14.0 years) and performed preoperative MRI using 7 kg axial traction with a 3-Tesla imager and CT. Three-dimensional-MRI models of the humerus and articular cartilage and a 3D-CT model of the humerus were constructed. We created MCFIs using both models. We validated the findings obtained from the MCFIs and intraoperative findings using the following items: articular cartilage fissures and defects, articular surface deformities, vertical and horizontal lesion diameters, the International Cartilage Repair Society (ICRS) classification, and surgical procedures. The MCFIs accurately reproduced the lesions and correctly matched the ICRS classification in 93.5% of cases. Surgery was performed as simulated in all cases. Preoperatively measured lesion diameters exhibited no significant differences compared to the intraoperative measurements. MCFIs were useful in the evaluation of OCD lesions and detailed preoperative surgical simulation through accurate reproduction of 3D structural details of the lesions.
Using IVIM Parameters to Differentiate Prostate Cancer and Contralateral Normal Tissue through Fusion of MRI Images with Whole-Mount Pathology Specimen Images by Control Point Registration Method
Authors: Lee Cheng-Chun , Chang Kuang-Hsi , Chiu Feng-Mao , Ou Yen-Chuan , Hwang Jen-I. , Hsueh Kuan-Chun , Fan Hueng-Chuen
Published: December 2021

The intravoxel incoherent motion (IVIM) model may enhance the clinical value of multiparametric magnetic resonance imaging (mpMRI) in the detection of prostate cancer (PCa). However, while past IVIM modeling studies have shown promise, they have also reported inconsistent results and limitations, underscoring the need to further enhance the accuracy of IVIM modeling for PCa detection. Therefore, this study utilized the control point registration toolbox function in MATLAB to fuse T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) MRI images with whole-mount pathology specimen images in order to eliminate potential bias in IVIM calculations. Sixteen PCa patients underwent prostate MRI scans before undergoing radical prostatectomies. The image fusion method was then applied in calculating the patients’ IVIM parameters. Furthermore, MRI scans were also performed on 22 healthy young volunteers in order to evaluate the changes in IVIM parameters with aging. Among the full study cohort, the f parameter was significantly increased with age, while the D* parameter was significantly decreased. Among the PCa patients, the D and ADC parameters could differentiate PCa tissue from contralateral normal tissue, while the f and D* parameters could not. The presented image fusion method also provided improved precision when comparing regions of interest side by side. However, further studies with more standardized methods are needed to further clarify the benefits of the presented approach and the different IVIM parameters in PCa characterization.
Similarity Changes Analysis for Heart Rate Fluctuation Regularity as a New Screening Method for Congestive Heart Failure
Authors: Liu Zeming , Chen Tian , Wei Keming , Liu Guanzheng , Liu Bin
Published: December 2021

Congestive heart failure (CHF) is a chronic cardiovascular condition associated with dysfunction of the autonomic nervous system (ANS). Heart rate variability (HRV) has been widely used to assess ANS. This paper proposes a new HRV analysis method, which uses information-based similarity (IBS) transformation and fuzzy approximate entropy (fApEn) algorithm to obtain the fApEn_IBS index, which is used to observe the complexity of autonomic fluctuations in CHF within 24 h. We used 98 ECG records (54 health records and 44 CHF records) from the PhysioNet database. The fApEn_IBS index was statistically significant between the control and CHF groups (p < 0.001). Compared with the classical indices low-to-high frequency power ratio (LF/HF) and IBS, the fApEn_IBS index further utilizes the changes in the rhythm of heart rate (HR) fluctuations between RR intervals to fully extract relevant information between adjacent time intervals and significantly improves the performance of CHF screening. The CHF classification accuracy of fApEn_IBS was 84.69%, higher than LF/HF (77.55%) and IBS (83.67%). Moreover, the combination of IBS, fApEn_IBS, and LF/HF reached the highest CHF screening accuracy (98.98%) with the random forest (RF) classifier, indicating that the IBS and LF/HF had good complementarity. Therefore, fApEn_IBS effusively reflects the complexity of autonomic nerves in CHF and is a valuable CHF assessment tool.
Modified Horizontal Well Productivity Model for a Tight Gas Reservoir Subjected to Non-Uniform Damage and Turbulence
Authors: Osisanya Samuel O. , Ayokunle Ajayi Temitope , Ghosh Bisweswar , Suboyin Abhijith
Published: December 2021

Tight gas reservoirs are finding greater interest with the advancement of technology and realistic prediction of flow rate and pressure from such wells are critical in project economics. This paper presents a modified productivity equation for tight gas horizontal wells by modifying the mechanical skin factor to account for non-uniform formation damage along with the incorporation of turbulence effect in the near-wellbore region. Hawkin’s formula for calculating skin factor considers the radius of damage as a constant value, which is less accurate in low-permeability tight gas reservoirs. This paper uses a multi-segment horizontal well approach to develop the local skin factors and the equivalent skin factor by equating the total production from the entire horizontal well to the sum of the flow from individual segmented damaged zones along the well length. Conical and horn-shaped damaged profiles are used to develop the equivalent skin used in the horizontal well productivity equation. The productivity model is applied to a case study involving the development of a tight gas field with horizontal wells. The influence of the horizontal well length, damaged zone permeability, drainage area, reservoir thickness, and wellbore diameter on the calculated equivalent skin (of a non-uniform skin distribution) and the flow rate (with turbulence and no turbulence) are investigated. The results obtained from this investigation show significant potential to assist in making practical decisions on the favorable parameters for the success of the field development in terms of equivalent skin factor, flow rate, and inflow performance relationships (IPR).
Flow Stability in a Miniature Centrifugal Pump under the Periodic Pulse Flow
Authors: Li Kunhang , Xu Wenqian , Dou Hua-Shu
Published: December 2021

The flow behavior inside a miniature centrifugal pump, under a periodic pulse flow rate, was studied by means of numerical simulation. For a given incoming periodic pulse flow with a sine wave, the performance of the centrifugal pump was investigated in the section with increasing flow and the section with decreasing flow, and the special points of the flow rate and the periodic flow were identified. Further, the energy gradient method and the Q-criterion were adopted to analyze the internal vertical structure and flow stability. It was found that the regions with large variations in velocity and total pressure were mainly located at the leading edge of the suction surface and the middle area of the pressure surface of the blades. Irregular pressure fluctuation frequency under the periodic pulse flow was shown; this was mainly concentrated in the low-frequency zones close to the impeller’s rotational frequency. In addition, for the same flow rate in the periodic pulse flow, the pressure frequency fluctuation for the increasing flow rate section was higher than that observed for the decreasing flow rate section. It was found that the most unstable sections appeared in the first half-period of the flow rate variation (large flow rate), according to the distributions of the Q criteria of the vortex and the energy gradient function K. In this section, motions of strong vortices led to large gradients of the mechanical energy.
Assessment of Fuel Cells’ State of Health by Low-Frequency Noise Measurements
Authors: Szewczyk Arkadiusz , Gaweł Łukasz , Darowicki Kazimierz , Smulko Janusz
Published: December 2021

We proposed applying low-frequency (flicker) noise in proton-exchange membrane fuel cells under selected loads to assess their state of health. The measurement set-up comprised a precise data acquisition board and was able to record the DC voltage and its random component at the output. The set-up estimated the voltage noise power spectral density at frequencies up to a few hundred mHz. We observed the evolution of the electrical parameters of selected cells of different qualities. We confirmed that flicker noise intensity varied the most (more than 10 times) and preceded changes in the impedance or a drop in the output DC voltage (less than 2 times). The data were observed for current loads (from 0.5 to 32 A) far from the permissible load. We deduce that the method can be utilised in industrial conditions to monitor the state of health of the selected cells by noise analysis. The method can be used in real-time when the flicker noise is measured within the range of a few Hz and requires a reasonable amount of averaging time to estimate its power spectral density. The presented method of flicker noise measurement has considerable potential for use in innovative ways of fuel cell quality monitoring.
Design of Clean Steel Production with Hydrogen: Impact of Electricity System Composition
Authors: Toktarova Alla , Göransson Lisa , Johnsson Filip
Published: December 2021

In Europe, electrification is considered a key option to obtain a cleaner production of steel at the same time as the electricity system production portfolio is expected to consist of an increasing share of varying renewable electricity (VRE) generation, mainly in the form of solar PV and wind power. We investigate cost-efficient designs of hydrogen-based steelmaking in electricity systems dominated by VRE. We develop and apply a linear cost-minimization model with an hourly time resolution, which determines cost-optimal operation and sizing of the units in hydrogen-based steelmaking including an electrolyser, direct reduction shaft, electric arc furnace, as well as storage for hydrogen and hot-briquetted iron pellets. We show that the electricity price following steelmaking leads to savings in running costs but to increased capital cost due to investments in the overcapacity of steel production units and storage units for hydrogen and hot-briquetted iron pellets. For two VRE-dominated regions, we show that the electricity price following steel production reduces the total steel production cost by 23% and 17%, respectively, as compared to continuous steel production at a constant level. We also show that the cost-optimal design of the steelmaking process is dependent upon the electricity system mix.
Forecast of the Impact of Electric Car Battery Performance and Infrastructural and Demographic Changes on Cumulative Accessibility for the Five Most Populous Cities in Poland
Authors: Rosik Piotr , Goliszek Sławomir , Komornicki Tomasz , Duma Patryk
Published: December 2021

The purpose of this study is to compare (1) technological factors (the ranges offered by the batteries of three popular electric vehicles in Poland); (2) infrastructure improvements; and (3) demographic changes and their impact on accessibility in the context of the ranges of labor markets within the 30, 60, and 90 min isochrones in moderate driving mode for the five largest cities in Poland using cumulative accessibility. We conclude that technological developments result in a much greater improvement in accessibility than demographic and infrastructural change. This is already visible with the 30 to 60 min isochrones, in particular when using the BMW in Cracow (with a more than 36% improvement in accessibility). Even greater changes, reaching as much as over 90%, are observed for the 60–90 min isochrones. The analysis shows that the shift in electromobility may be constrained by parallel demographic processes, dispersion of population in suburban areas, and the development of road infrastructure. The novelty of the approach stems from the fact that it is based on three above mentioned key factors that influence the accessibility of labor markets for EV users in the largest cities up to 2030.
Effect of Climate Change and Occupant Behaviour on the Environmental Impact of the Heating and Cooling Systems of a Real Apartment. A Parametric Study through Life Cycle Assessment
Authors: Fajilla Gianmarco , Borri Emiliano , De Simone Marilena , Cabeza Luisa F. , Bragança Luís
Published: December 2021

Climate change has a strong influence on the energy consumption of buildings, affecting both the heating and cooling demand in the actual and future scenario. In this paper, a life cycle assessment (LCA) was performed to evaluate the influence of both the occupant behaviour and the climate change on the environmental impact of the heating and cooling systems of an apartment located in southern Italy. The analysis was conducted using IPCC GWP and ReCiPe indicators as well as the Ecoinvent database. The influence of occupant behaviour was included in the analysis considering different usage profiles during the operational phase, while the effect of climate change was considered by varying the weather file every thirty years. The adoption of the real usage profiles showed that the impact of the systems was highly influenced by the occupant behaviour. In particular, the environmental impact of the heating system appeared more influenced by the operation hours, while that of the cooling system was more affected by the natural ventilation schedules. Furthermore, the influence of climate change demonstrated that more attention has to be dedicated to the cooling demand that in the future years will play an ever-greater role in the energy consumption of buildings.
Co-Optimizing Battery Storage for Energy Arbitrage and Frequency Regulation in Real-Time Markets Using Deep Reinforcement Learning
Authors: Miao Yushen , Chen Tianyi , Bu Shengrong , Liang Hao , Han Zhu
Published: December 2021

Battery energy storage systems (BESSs) play a critical role in eliminating uncertainties associated with renewable energy generation, to maintain stability and improve flexibility of power networks. In this paper, a BESS is used to provide energy arbitrage (EA) and frequency regulation (FR) services simultaneously to maximize its total revenue within the physical constraints. The EA and FR actions are taken at different timescales. The multitimescale problem is formulated as two nested Markov decision process (MDP) submodels. The problem is a complex decision-making problem with enormous high-dimensional data and uncertainty (e.g., the price of the electricity). Therefore, a novel co-optimization scheme is proposed to handle the multitimescale problem, and also coordinate EA and FR services. A triplet deep deterministic policy gradient with exploration noise decay (TDD–ND) approach is used to obtain the optimal policy at each timescale. Simulations are conducted with real-time electricity prices and regulation signals data from the American PJM regulation market. The simulation results show that the proposed approach performs better than other studied policies in literature.