bluuebunny/crossref_metadata_2025 huggingface dataset:
N2O Temporal Variability from the Middle Troposphere to the Middle Stratosphere Based on Airborne and Balloon-Borne Observations during the Period 1987–2018
Authors: Krysztofiak Gisèle , Catoire Valéry , Dudok de Wit Thierry , Kinnison Douglas E. , Ravishankara A. R. , Brocchi Vanessa , Atlas Elliot , Bozem Heiko , Commane Róisín , D’Amato Francesco , Daube Bruce , Diskin Glenn S. , Engel Andreas , Friedl-Vallon Felix , Hintsa Eric , Hurst Dale F. , Hoor Peter , Jegou Fabrice , Jucks Kenneth W. , Kleinböhl Armin , Küllmann Harry , Kort Eric A. , McKain Kathryn , Moore Fred L. , Obersteiner Florian , Ramos Yenny Gonzalez , Schuck Tanja , Toon Geoffrey C. , Viciani Silvia , Wetzel Gerald , Williams Jonathan , Wofsy Steven C.
Published: March 2023

Nitrous oxide (N2O) is the fourth most important greenhouse gas in the atmosphere and is considered the most important current source gas emission for global stratospheric ozone depletion (O3). It has natural and anthropogenic sources, mainly as an unintended by-product of food production activities. This work examines the identification and quantification of trends in the N2O concentration from the middle troposphere to the middle stratosphere (MTMS) by in situ and remote sensing observations. The temporal variability of N2O is addressed using a comprehensive dataset of in situ and remote sensing N2O concentrations based on aircraft and balloon measurements in the MTMS from 1987 to 2018. We determine N2O trends in the MTMS, based on observations. This consistent dataset was also used to study the N2O seasonal cycle to investigate the relationship between abundances and its emission sources through zonal means. The results show a long-term increase in global N2O concentration in the MTMS with an average of 0.89 ± 0.07 ppb/yr in the troposphere and 0.96 ± 0.15 ppb/yr in the stratosphere, consistent with 0.80 ppb/yr derived from ground-based measurements and 0.799 ± 0.024 ppb/yr ACE-FTS (Atmospheric Chemistry Experiment Fourier Transform Spectrometer) satellite measurements.
A Multipurpose Simulation Approach for Hybrid Electric Vehicles to Support the European CO2 Emissions Framework
Authors: Tansini Alessandro , Fontaras Georgios , Millo Federico
Published: March 2023

Hybrid Electric Vehicles (HEVs) are a prominent solution for reducing CO2 emissions from transport in Europe. They are equipped with at least two propulsion energy converters, an Internal Combustion Engine (ICE) and one or more Electric Machines (EMs), operated in a way to exploit synergies and achieve fuel efficiency. Because of the variety in configurations and strategies, the use of simulation is essential for vehicle development and characterisation of energy consumption. This paper introduces a novel simulation approach to estimate the CO2 emissions from different hybrid architectures (series, parallel, power-split) and electrification degrees (mild, full, plug-in and range extender) that is relatively simple, flexible and accurate. The approach identifies the optimal power split between the energy converters for any given time in a driving cycle according to three evaluation levels: supervisor, ICE manager and optimiser. The latter relies on the Equivalent Consumption Minimisation Strategy (ECMS) and the limitations imposed by the other two layers. Six light-duty HEVs with different hybrid architectures were tested to support the development of the approach. The results show an indicative accuracy of ±5%, enabling to run assessments of hybrid powertrain solutions and supporting regulatory and consumer information initiatives.
Bioaerosols: Composition, Meteorological Impact, and Transport
Authors: Romano Salvatore
Published: March 2023

The characterization and the main properties of biogenic airborne particles (or bioaerosols) comprising both living and dead microorganisms (such as bacteria, fungi, viruses, pollen, and microbial fragments) are currently of increasing interest in the scientific community [...]
The Source Apportionment of Heavy Metals in Surface Dust in the Main District Bus Stops of Tianshui City Based on the Positive Matrix Factorization Model and Geo-Statistics
Authors: Li Chunyan , Wang Xinmin , Xiao Shun , Wang Hai
Published: March 2023

For the pollution assessment and quantitative source apportionment of heavy metals in surface dust, a total of 52 surface dust samples were collected from bus stops in Tianshui City. The geoaccumulation index (Igeo) and potential ecological risk index (RI) were used to analyze the pollution levels caused by heavy metals. The Positive Matrix Factorization (PMF) of the receptor modeling and geo-statistics were employed to analyze the source of the heavy metals. The results were as follows. ① Except for Mn, Co and V, the mean concentrations of other heavy metals have exceeded the local background value of Gansu. The percentage of excessive concentrations of Cu, Zn, Sr, Ba and Pb in the samples was 100%, and that of Cr, Ni and As were 96.15%, 94.23%, and 96.15%, respectively. ② Semivariogram model fitting showed that the block-based coefficients of Cu, Zn, Sr, Ba, Pb, Cr, Ni, and As were between 0.25 and 0.75, indicating that they were mainly affected by human factors. The high values of Pb, Zn, Ni and As were mainly distributed in the eastern part of the study area, and the high values of Cu, Sr, Ba and Cr were distributed in a spot-like pattern in the study area. ③ The Igeo results showed that As, Cu, Zn, and Pb were the main contamination factors, and the optimized RI showed that the heavy metals were the overall ecological risk of intensity, among which Pb, As and Cu were the main ecological factors and should be taken as the priority control objects. ④ Based on the PMF, there are four main sources of eleven heavy metals. V, Mn, and Co were attributed to natural sources, accounting for 18.33%; Cu, Sr, and Ba were from mixed sources of pollution from transportation and industrial alloy manufacturing, accounting for 26.99%; Cr and Ni were from sources of construction waste pollution, accounting for 17.17%, As, Zn and Pb were mainly produced by coal-traffic mixed pollution emissions, accounting for 37.52%. Overall, the study area was dominated by coal-traffic emissions.
Developmental Pharmacokinetics of Antibiotics Used in Neonatal ICU: Focus on Preterm Infants
Authors: Butranova Olga I. , Ushkalova Elena A. , Zyryanov Sergey K. , Chenkurov Mikhail S.
Published: March 2023

Neonatal Infections are among the most common reasons for admission to the intensive care unit. Neonatal sepsis (NS) significantly contributes to mortality rates. Empiric antibiotic therapy of NS recommended by current international guidelines includes benzylpenicillin, ampicillin/amoxicillin, and aminoglycosides (gentamicin). The rise of antibacterial resistance precipitates the growth of the use of antibiotics of the Watch (second, third, and fourth generations of cephalosporines, carbapenems, macrolides, glycopeptides, rifamycins, fluoroquinolones) and Reserve groups (fifth generation of cephalosporines, oxazolidinones, lipoglycopeptides, fosfomycin), which are associated with a less clinical experience and higher risks of toxic reactions. A proper dosing regimen is essential for effective and safe antibiotic therapy, but its choice in neonates is complicated with high variability in the maturation of organ systems affecting drug absorption, distribution, metabolism, and excretion. Changes in antibiotic pharmacokinetic parameters result in altered efficacy and safety. Population pharmacokinetics can help to prognosis outcomes of antibiotic therapy, but it should be considered that the neonatal population is heterogeneous, and this heterogeneity is mainly determined by gestational and postnatal age. Preterm neonates are common in clinical practice, and due to the different physiology compared to the full terms, constitute a specific neonatal subpopulation. The objective of this review is to summarize the evidence about the developmental changes (specific for preterm and full-term infants, separately) of pharmacokinetic parameters of antibiotics used in neonatal intensive care units.
The McGurk Illusion: A Default Mechanism of the Auditory System
Authors: Iqbal Zunaira J. , Shahin Antoine J. , Bortfeld Heather , Backer Kristina C.
Published: March 2023

Recent studies have questioned past conclusions regarding the mechanisms of the McGurk illusion, especially how McGurk susceptibility might inform our understanding of audiovisual (AV) integration. We previously proposed that the McGurk illusion is likely attributable to a default mechanism, whereby either the visual system, auditory system, or both default to specific phonemes—those implicated in the McGurk illusion. We hypothesized that the default mechanism occurs because visual stimuli with an indiscernible place of articulation (like those traditionally used in the McGurk illusion) lead to an ambiguous perceptual environment and thus a failure in AV integration. In the current study, we tested the default hypothesis as it pertains to the auditory system. Participants performed two tasks. One task was a typical McGurk illusion task, in which individuals listened to auditory-/ba/ paired with visual-/ga/ and judged what they heard. The second task was an auditory-only task, in which individuals transcribed trisyllabic words with a phoneme replaced by silence. We found that individuals’ transcription of missing phonemes often defaulted to ‘/d/t/th/’, the same phonemes often experienced during the McGurk illusion. Importantly, individuals’ default rate was positively correlated with their McGurk rate. We conclude that the McGurk illusion arises when people fail to integrate visual percepts with auditory percepts, due to visual ambiguity, thus leading the auditory system to default to phonemes often implicated in the McGurk illusion.
Extracellular Vesicles as Biomarkers in Head and Neck Squamous Cell Carcinoma: From Diagnosis to Disease-Free Survival
Authors: Chen Bojie , Leung Leanne Lee , Qu Xinyu , Chan Jason Ying-Kuen
Published: March 2023

Head and neck squamous cell carcinomas (HNSCCs) arising from different anatomical sites present with different incidences and characteristics, which requires a personalized treatment strategy. Despite the extensive research that has conducted on this malignancy, HNSCC still has a poor overall survival rate. Many attempts have been made to improve the outcomes, but one of the bottlenecks is thought to be the lack of an effective biomarker with high sensitivity and specificity. Extracellular vesicles (EVs) are secreted by various cells and participate in a great number of intercellular communications. Based on liquid biopsy, EV detection in several biofluids, such as blood, saliva, and urine, has been applied to identify the existence and progression of a variety of cancers. In HNSCC, tumor-derived EVs exhibit many functionalities by transporting diverse cargoes, which highlights their importance in tumor screening, the determination of multidisciplinary therapy, prediction of prognosis, and evaluation of therapeutic effects. This review illustrates the classification and formation of EV subtypes, the cargoes conveyed by these vesicles, and their respective functions in HNSCC cancer biology, and discloses their potential as biomarkers during the whole process of tumor diagnosis, treatment, and follow-up.
Impact of Microscopically Positive (≤1 mm) Distal Margins on Disease Recurrence in Rectal Cancer Treated by Neoadjuvant Chemoradiotherapy
Authors: Sorrentino Luca , Sileo Annaclara , Daveri Elena , Battaglia Luigi , Guaglio Marcello , Centonze Giovanni , Sabella Giovanna , Patti Filippo , Villa Sergio , Milione Massimo , Belli Filiberto , Cosimelli Maurizio
Published: March 2023

Background: The adequate distal resection margin is still controversial in rectal cancer treated by neoadjuvant chemoradiotherapy (nCRT). The aim of this study was to assess the impact of a distal margin of ≤1 mm on locoregional recurrence-free survival (LRRFS). Methods: Among 255 patients treated with nCRT and surgery at the National Cancer Institute of Milan, 83 (32.5%) had a distal margin of ≤1 mm and 172 (67.5%) had a distal margin of >1 mm. Survival analyses were performed to assess the impact of distal margin on 5-year LRRFS, as well as Cox survival analysis. The role of distal margin on survival was analyzed according to different tumor regression grades (TRGs). Results: The overall 5-year LRRFS rate was 77.6% with a distal margin of ≤1 mm vs. 88.3% with a distal margin of >1 mm (Log-rank p = 0.09). Only stage ypT4 was an independent predictor of worse LRRFS (HR 15.14, p = 0.026). The 5-year LRRFS was significantly lower in TRG3–5 patients with a distal margin of ≤1 mm compared to those with a distal margin of >1 mm (68.5% vs. 84.2%, p = 0.027), while no difference was observed in case of TRG1–2 (p = 0.77). Conclusions: Low-responder rectal cancers after nCRT still require a distal margin of >1 mm to reduce the high likelihood of local relapse.
Application of Machine Learning for Differentiating Bone Malignancy on Imaging: A Systematic Review
Authors: Ong Wilson , Zhu Lei , Tan Yi Liang , Teo Ee Chin , Tan Jiong Hao , Kumar Naresh , Vellayappan Balamurugan A. , Ooi Beng Chin , Quek Swee Tian , Makmur Andrew , Hallinan James Thomas Patrick Decourcy
Published: March 2023

An accurate diagnosis of bone tumours on imaging is crucial for appropriate and successful treatment. The advent of Artificial intelligence (AI) and machine learning methods to characterize and assess bone tumours on various imaging modalities may assist in the diagnostic workflow. The purpose of this review article is to summarise the most recent evidence for AI techniques using imaging for differentiating benign from malignant lesions, the characterization of various malignant bone lesions, and their potential clinical application. A systematic search through electronic databases (PubMed, MEDLINE, Web of Science, and clinicaltrials.gov) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 34 articles were retrieved from the databases and the key findings were compiled and summarised. A total of 34 articles reported the use of AI techniques to distinguish between benign vs. malignant bone lesions, of which 12 (35.3%) focused on radiographs, 12 (35.3%) on MRI, 5 (14.7%) on CT and 5 (14.7%) on PET/CT. The overall reported accuracy, sensitivity, and specificity of AI in distinguishing between benign vs. malignant bone lesions ranges from 0.44–0.99, 0.63–1.00, and 0.73–0.96, respectively, with AUCs of 0.73–0.96. In conclusion, the use of AI to discriminate bone lesions on imaging has achieved a relatively good performance in various imaging modalities, with high sensitivity, specificity, and accuracy for distinguishing between benign vs. malignant lesions in several cohort studies. However, further research is necessary to test the clinical performance of these algorithms before they can be facilitated and integrated into routine clinical practice.
Cellular Therapies in Chronic Lymphocytic Leukemia and Richter’s Transformation: Recent Developments in Chimeric Antigen Receptor T-Cells, Natural Killer Cells, and Allogeneic Stem Cell Transplant
Authors: Coombs Catherine C. , Easaw Saumya , Grover Natalie S. , O’Brien Susan M.
Published: March 2023

Cellular therapies can be viewed as both the newest and oldest techniques for treating chronic lymphocytic leukemia (CLL) and Richter’s transformation (RT). On one hand, allogeneic hematopoietic stem cell transplantation (alloHSCT) has been available for decades, though its use is diminishing with the increasing availability of effective novel targeted agents, especially in CLL. Among newer techniques, chimeric antigen receptor T-cells (CAR-T) have demonstrated astounding efficacy in several hematologic malignancies, leading to FDA approval and use in clinical practice. However, though CLL is the earliest disease type for which CAR-T were studied, development has been slower and has yet to lead to regulatory approval. Owing partially to its rarity but also due to the aggressive behavior of RT, CAR-T in RT have only been minimally explored. Here, we will focus on the applications of cellular therapies in CLL and RT, specifically reviewing more recent data related to alloHSCT in the novel-agent era and CAR-T cell development in CLL/RT, focusing on safety and efficacy successes and limitations. We will review strategies to improve upon CAR-T efficacy and discuss ongoing trials utilizing CAR-T in CLL/RT, as well as emerging technologies, such as allogeneic CAR-T and natural killer CAR (CAR NK) cells.
Subgroup Analysis of Overall Survival among Smoking and Non-Smoking Elderly Patients with HNSCC
Authors: Graessle Raphaela , Stromberger Carmen , Beck Marcus , Heiland Max , Hofmann Veit M. , Olze Heidi , Dommerich Steffen , Gauger Ulrich , Piwonski Iris , Coordes Annekatrin
Published: March 2023

Smoking is a leading cause of head and neck squamous cell carcinoma (HNSCC). However, non-smokers are also affected by HNSCC, and the prognostic factors applicable to older non-smokers with HNSCC are largely unknown. The aim of this study was to determine predictors of overall survival (OS) in patients both with and without a smoking history aged 70 and over at initial diagnosis. Retrospective data of patients aged ≥70 (initial diagnoses 2004–2018) were examined. Evaluated predictors included tumour stage, biological age, health and therapy. A total of 688 patients (520 smokers, 168 non-smokers) were included with a median age of 74. The 5-year OS was 39.6%. Non-smokers had significantly improved OS compared to smokers (52.0% versus 36.0%, p < 0.001). Disease-free survival (DFS) differed significantly between both groups (hazard ratio = 1.3; 95%CI 1.04–1.626). TNM stage and the recommended therapies (curative versus palliative) were comparable. The proportion of p16-positive oropharyngeal carcinomas was significantly higher in non-smokers (76.7% versus 43.8%, p < 0.001). Smokers were significantly more likely to be men (p < 0.001), drinkers (p < 0.001), and have poorer health status (Karnofsky performance status, KPS, p = 0.023). They were also more likely to have additional tumours (p = 0.012) and lower treatment adherence (p = 0.038). Important predictors of OS identified in both groups, were, among others, alcohol abuse, KPS, Charlson comorbidity index, site of primary tumour, UICC stage and treatment received. Elderly non-smokers are also affected by HNSCC, however, both OS and DFS are increased compared to smokers.
Drugs That Mimic Hypoxia Selectively Target EBV-Positive Gastric Cancer Cells
Authors: Cordes Blue-leaf A. , Bilger Andrea , Kraus Richard J. , Ward-Shaw Ella T. , Labott Madeline R. , Lee Shinhyo , Lambert Paul F. , Mertz Janet E.
Published: March 2023

Latent infection of Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cell cancers, including 10% of gastric carcinomas. We previously reported that hypoxia inducible factor-1α (HIF-1α) induces EBV’s latent-to-lytic switch and identified several HIF-1α-stabilizing drugs that induce this viral reactivation. Here, we tested three classes of these drugs for preferential killing of the EBV-positive gastric cancer AGS-Akata cell line compared to its matched EBV-negative AGS control. We observed preferential killing with iron chelators [Deferoxamine (DFO); Deferasirox (DFX)] and a prolyl hydroxylase inhibitor (BAY 85-3934 (Molidustat)), but not with a neddylation inhibitor [MLN4924 (Pevonedistat)]. DFO and DFX also induced preferential killing of the EBV-positive gastric cancer AGS-BDneo and SNU-719 cell lines. Preferential killing was enhanced when low-dose DFX (10 μM) was combined with the antiviral prodrug ganciclovir. DFO and DFX induced lytic EBV reactivation in approximately 10% of SNU-719 and 20-30% of AGS-Akata and AGS-BDneo cells. However, neither DFO nor DFX significantly induced synthesis of lytic EBV proteins in xenografts grown in NSG mice from AGS-Akata cells above the level observed in control-treated mice. Therefore, these FDA-approved iron chelators are less effective than gemcitabine at promoting EBV reactivation in vivo despite their high specificity and efficiency in vitro.
Overexpression of YEATS2 Remodels the Extracellular Matrix to Promote Hepatocellular Carcinoma Progression via the PI3K/AKT Pathway
Authors: Liu Xin , Hu Yi , Li Cairong , Chen Jiayu , Liu Xiaohong , Shen Yang , Xu Yangtao , Chen Wenliang , Xu Ximing
Published: March 2023

Hepatocellular carcinoma (HCC) is one of the most common cancers and the fourth leading cause of death in men. YEATS domain containing 2 (YEATS2) gene encodes a scaffolding subunit of the ATAC complex. We found that YEATS2 was upregulated in HCC tissues and was associated with a poor prognosis. However, the role of YEATS2 in HCC remains unclear. The purpose of this study was to investigate the effect of YEATS2 on the progression of HCC and to elucidate its related mechanisms. We found that overexpression of YEATS2 promoted tumor cell proliferation, migration, and invasion through the PI3K/AKT signaling pathway and regulation of extracellular matrix. These findings help to understand the role of YEATS2 in HCC, and YEATS2 may become a new target for HCC therapy.
Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System
Authors: Barbieri Maria Antonietta , Sorbara Emanuela Elisa , Russo Giulia , Cicala Giuseppe , Franchina Tindara , Santarpia Mariacarmela , Silvestris Nicola , Spina Edoardo
Published: March 2023

Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of neuropsychiatric adverse drug reactions (ADRs) for TKIs through the analysis of European individual case safety reports (ICSRs). All ICSRs collected in EudraVigilance up to 31 December 2021 with one TKI having GISTs as an indication (imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP)) were included. A disproportionality analysis was performed to assess the frequency of reporting for each TKI compared to all other TKIs. The number of analyzed ICSRs was 8512, of which 57.9% were related to IM. Neuropsychiatric ADRs were reported at least once in 1511 ICSRs (17.8%). A higher reporting probability of neuropsychiatric ADRs was shown for AVA. Most neuropsychiatric ADRs were known, except for a higher frequency of lumbar spinal cord and nerve root disorders (reporting odds ratio, ROR 4.46; confidence interval, CI 95% 1.58–12.54), olfactory nerve disorders (8.02; 2.44–26.33), and hallucinations (22.96; 8.45–62.36) for AVA. The analyses of European ICSRs largely confirmed the safety profiles of TKIs in GISTs, but some ADRs are worthy of discussion. Further studies are needed to increase the knowledge of the neuropsychiatric disorders of newly approved TKIs.
Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients with Pancreatic Cancer or Suspected Related Hereditary Syndromes: Historical Prospective Analysis
Authors: Dal Buono Arianna , Poliani Laura , Greco Luana , Bianchi Paolo , Barile Monica , Giatti Valentina , Bonifacio Cristiana , Carrara Silvia , Malesci Alberto , Laghi Luigi
Published: March 2023

We investigate the prevalence of germline mutations in cancer predisposition genes in patients with pancreatic ductal adenocarcinoma (PDAC) or suspected related hereditary syndromes. Methods: we enrolled for NGS with an Illumina TrueSight Cancer panel comprising 19 CPGs and 113 consecutive subjects referred to cancer genetic clinics for metastatic PDAC, early onset PDAC, suspected hereditary syndrome, or positive family history. Results: Overall, 23 (20.1%) subjects were carriers of 24 pathogenetic variants (PVs). We found 9 variants in BRCA2 (37.5%), 6 in CDKN2A (25%), 3 in ATM (12.5%), 2 in BRCA1 (8.3%), 1 in CHEK2 (4.1%), 1 in PALB2 (4.1%), 1 in MITF (4.1%), and 1 in FANCM (4.1%). A double PV (BRCA1 plus BRCA2) was found in 1 subject. We observed a nearly 30% (16/55) mutational rate in the subgroup of subjects tested for the suspected syndromes (PDAC and other synchronous or metachronous tumors or an indicative family history), and the frequency was significantly higher than that in patients with only metastatic PDAC (p = 0.05). In our cohort, 39 variants of unknown significance (VUS) were identified, most of which (16/39, 41%) in genes belonging to the Lynch syndrome spectrum. Conclusion: A clinically relevant proportion of pancreatic cancer is associated with mutations in known predisposition genes. Guidelines instructing on an adequate selection for accessing genetic testing are eagerly needed. The heterogeneity of mutations identified in this study reinforces the value of using a multiple-gene panel in pancreatic cancer.
Replication of Real-World Evidence in Oncology Using Electronic Health Record Data Extracted by Machine Learning
Authors: Benedum Corey M. , Sondhi Arjun , Fidyk Erin , Cohen Aaron B. , Nemeth Sheila , Adamson Blythe , Estévez Melissa , Bozkurt Selen
Published: March 2023

Meaningful real-world evidence (RWE) generation requires unstructured data found in electronic health records (EHRs) which are often missing from administrative claims; however, obtaining relevant data from unstructured EHR sources is resource-intensive. In response, researchers are using natural language processing (NLP) with machine learning (ML) techniques (i.e., ML extraction) to extract real-world data (RWD) at scale. This study assessed the quality and fitness-for-use of EHR-derived oncology data curated using NLP with ML as compared to the reference standard of expert abstraction. Using a sample of 186,313 patients with lung cancer from a nationwide EHR-derived de-identified database, we performed a series of replication analyses demonstrating some common analyses conducted in retrospective observational research with complex EHR-derived data to generate evidence. Eligible patients were selected into biomarker- and treatment-defined cohorts, first with expert-abstracted then with ML-extracted data. We utilized the biomarker- and treatment-defined cohorts to perform analyses related to biomarker-associated survival and treatment comparative effectiveness, respectively. Across all analyses, the results differed by less than 8% between the data curation methods, and similar conclusions were reached. These results highlight that high-performance ML-extracted variables trained on expert-abstracted data can achieve similar results as when using abstracted data, unlocking the ability to perform oncology research at scale.
Clinical Determinants of Extraurinary Tract Recurrence and Survival after Radical Surgery for pT2 Upper Tract Urothelial Carcinoma
Authors: Huang Yun-Ching , Liu Jui-Ming , Liu Hui-Ying , Chang Yin-Lun , Chen Chih-Shou , Ho Dong-Ru , Wu Chun-Te , Chen Miao-Fen , Wang Hung-Jen , Luo Hao-Lun
Published: March 2023

Background: Oncologic outcomes for pT2N0M0 upper tract urothelial carcinoma (UTUC) after nephroureterectomy are not well defined, with most previous studies focused on a heterogeneous population. Therefore, we aimed to investigate the clinical determinants of extraurinary tract recurrence and survival after radical surgery in patients with localized UTUC. Methods: We retrospectively identified 476 patients with pT2N0M0 UTUC who underwent radical nephroureterectomy or ureterectomy between October 2002 and March 2022. To evaluate the prognostic impact, patients were divided into renal pelvic, ureteral, and both-region (renal pelvis plus synchronous ureter) groups based on tumor location. The outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Associations were evaluated using multivariable Cox regression analyses for prognostic factors and Kaplan–Meier analyses for survival curves. Results: The renal pelvic, ureteral, and both-region groups consisted of 151 (31.7%), 314 (66.0%), and 11 (2.3%) patients, respectively. Kaplan–Meier analyses comparing the three tumor types showed significant differences in 5-year RFS (83.6% vs. 73.6% vs. 52.5%, p = 0.013), CSS (88.6% vs. 80.7% vs. 51.0%, p = 0.011), and OS (83.4% vs. 70.1% vs. 45.6%, p = 0.002). Multivariable analyses showed that age >60 years, previous bladder cancer history, ureteral involvement (ureteral and both-regional groups), and positive surgical margins were significant negative prognostic factors for the studied outcomes. Conclusions: Patients with pT2 UTUC and presence of ureteral involvement had more frequent disease relapse. Subsequent adjuvant therapy regimens and close follow-up in patients with negative prognostic factors are warranted despite complete pathological removal of the tumor.
Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms
Authors: Reccia Isabella , Pai Madhava , Kumar Jayant , Spalding Duncan , Frilling Andrea
Published: March 2023

Tumour heterogeneity is a common phenomenon in neuroendocrine neoplasms (NENs) and a significant cause of treatment failure and disease progression. Genetic and epigenetic instability, along with proliferation of cancer stem cells and alterations in the tumour microenvironment, manifest as intra-tumoural variability in tumour biology in primary tumours and metastases. This may change over time, especially under selective pressure during treatment. The gastroenteropancreatic (GEP) tract is the most common site for NENs, and their diagnosis and treatment depends on the specific characteristics of the disease, in particular proliferation activity, expression of somatostatin receptors and grading. Somatostatin receptor expression has a major role in the diagnosis and treatment of GEP-NENs, while Ki-67 is also a valuable prognostic marker. Intra- and inter-tumour heterogeneity in GEP-NENS, however, may lead to inaccurate assessment of the disease and affect the reliability of the available diagnostic, prognostic and predictive tests. In this review, we summarise the current available evidence of the impact of tumour heterogeneity on tumour diagnosis and treatment of GEP-NENs. Understanding and accurately measuring tumour heterogeneity could better inform clinical decision making in NENs.
Sex Differences in Survival from Neuroendocrine Neoplasia in England 2012–2018: A Retrospective, Population-Based Study
Authors: White Benjamin E. , Russell Beth , Remmers Sebastiaan , Rous Brian , Chandrakumaran Kandiah , Wong Kwok F. , Van Hemelrijck Mieke , Srirajaskanthan Rajaventhan , Ramage John K.
Published: March 2023

Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England’s National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73–5.90) to 10.26 (6.6–14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor.
Caudal Regression Syndrome—A Narrative Review: An Orthopedic Point of View
Authors: Jasiewicz Barbara , Kacki Wojciech
Published: March 2023

Abnormalities in cellular differentiation during embryo-fetal period may lead to various malformations of the spine. Caudal regression syndrome (CRS) is a group of defects with premature growth/development termination of the vertebral column. CRS can be divided into three types: sirenomelia, complete absence of the sacrum and partial absence of the sacrum. Genitourinary and gastrointestinal anomalies are common, with neurogenic bladder and bowel incontinence. Treatment of patients with CRS is complex and multidisciplinary and should be comprehensive. The most common orthopedic problems are: spinal deformity (kyphosis and scoliosis), spinopelvic instability and lower limbs deformities.
We Know How to Do Conservation—We Just Need to Do More of It!
Authors: Rodríguez Jon Paul , Sucre Bibiana , Mileham Kira , Sánchez-Mercado Ada , De Andrade Nahomy , Jabado Rima W.
Published: March 2023

For decades, even centuries, people have taken deliberate, targeted actions for the conservation and management of species and ecosystems [...]
Entrapped in Olive-Harvesting Nets: A Case of a Grass Snake Natrix natrix from an Olive-Growing Greek Aegean Island
Authors: Zevgolis Yiannis G. , Christopoulos Apostolos
Published: March 2023

Despite a recent shift towards sustainable practices to support the conservation of traditional olive groves, little is known about their potential threats to herpetofauna species. On the island of Lesvos, one of the main olive-growing islands in the Mediterranean, olive cultivation often prioritizes the expeditious harvesting of olives with minimal or no supplementary intervention, resulting in their generally suboptimal management, a component of which also pertains to the olive nets that, in many cases, remain dispersed and unfurled throughout the groves. This particular practice affects the species living in the olive groves, making them more prone to risks related to their accidental trapping. In this study, we report the first case of a Grass snake being inadvertently trapped in an olive net laid out on an olive grove. The position of the snake under the net, within a folded tipping, made it difficult for it to escape, and it became increasingly entangled. Based on this incident, it is plausible to assume that similar cases may occur in areas where nets are used in olive groves, both in Greece and other olive-growing countries. Further systematic research is necessary to determine the extent of this issue.
Density and Bleaching of Corals and Their Relationship to the Coral Symbiotic Community
Authors: Britayev Temir A. , Petrochenko Roman A. , Burmistrova Yulia A. , Nguyen Thanh Hai , Lishchenko Fedor V.
Published: March 2023

Corals provide an important habitat for diverse fauna. The habitat is especially rich in branching species. Each colony harbors several species and dozens of individuals, forming an integrated symbiotic community. Factors affecting the diversity and abundance of coral symbionts are poorly understood. The present study tested experimentally the relationship between the population density of coral Pocillopora verrucosa and the diversity and abundance of symbionts in planted coral fragments exposed for three months. Colony size and bleaching were also considered as two additional factors. We demonstrated that, even at the early stage of colony formation, the diversity of obligate symbionts on planted corals in Nha Trang Bay was higher than the diversity of any other studied local faunas of the world’s ocean. Species richness and the abundance of symbionts were positively related to colony size and density, while no impact of bleaching was found. Species richness and the abundance of obligate symbionts increased with host population density, while in facultative symbionts, these indices decreased. We hypothesized that the negative effect of host population density on species richness and the abundance of facultative symbionts is caused by the competitive pressure of obligates, which increases with their abundance. The reasons for the different responses of obligate and facultative symbionts to host density were considered.
Quantile-Adaptive Sufficient Variable Screening by Controlling False Discovery
Authors: Yuan Zihao , Chen Jiaqing , Qiu Han , Huang Yangxin
Published: March 2023

Sufficient variable screening rapidly reduces dimensionality with high probability in ultra-high dimensional modeling. To rapidly screen out the null predictors, a quantile-adaptive sufficient variable screening framework is developed by controlling the false discovery. Without any specification of an actual model, we first introduce a compound testing procedure based on the conditionally imputing marginal rank correlation at different quantile levels of response to select active predictors in high dimensionality. The testing statistic can capture sufficient dependence through two paths: one is to control false discovery adaptively and the other is to control the false discovery rate by giving a prespecified threshold. It is computationally efficient and easy to implement. We establish the theoretical properties under mild conditions. Numerical studies including simulation studies and real data analysis contain supporting evidence that the proposal performs reasonably well in practical settings.
Toward the Smart City Ecosystem Model
Authors: Kociuba Dagmara , Sagan Mariusz , Kociuba Waldemar
Published: March 2023

This study aims to present the processes and mechanisms of creating smart city ecosystems by examining the complex strategic choices and interactions among stakeholders operating at different levels of governance and engagement. Based on the literature review and in-depth analyses of a case study (Lublin, Eastern Poland), we demonstrate that the implementation of tailored strategic thinking using adaptation to global trends, exploitation of development potentials and niches, and stakeholders’ involvement allows for coordination and mobilization of development processes leading to the creation of effective smart city ecosystems. In line with the defined smart city challenges, with the application of a three-stage research program, we create an implementable Smart City Ecosystem Model (SCEM). The contributions of the study are as follows: (1) it provides new insights into smart governance, leadership in creating a sustainable and human smart city; (2) it analyzes strategic choices in the creation of a stakeholder ecosystem and competitive business ecosystems based on smart specializations, providing new opportunities for the design and implementation of smart city strategies. Therefore, this study provides a new multidimensional policy framework for smart cities at both strategic and operational levels that can improve the holistic management of smart and sustainable cities and communities.
Validation of the Quasi-Two-Level Operation for a Flying Capacitor Converter in Medium-Voltage Applications
Authors: Mersche Stefan Christoph , Schwendemann Rüdiger , Hiller Marc
Published: March 2023

Standard medium-voltage converters are operated at low switching frequencies using bulky passive components. One concept to change this involves the quasi-two-level operation (Q2O) of multilevel converters that use fast-switching semiconductors to minimize the need for passive components. The flying capacitor converter (FCC) uses SiC semiconductors and operates with Q2O to minimize passive components. In this paper, two different quasi-two-level algorithms are analyzed. A medium-voltage prototype was built and low-voltage and medium-voltage measurements were used to validate the concept. A particular focus is on the overvoltage, the dv/dt behavior of the converter, as well as the dynamic behavior.
A Misalignment Tolerate Integrated S-S-S-Compensated WPT System with Constant Current Output
Authors: Yuan Zhaoyang , Yang Qingxin , Zhang Xian , Ma Xianjie , Wang Ran , Xue Ming , Zhang Pengcheng
Published: March 2023

This paper proposes a cooperative (Cx) coil design for the series-series-series (S-S-S)-compensated wireless power transfer (WPT) system to improve the horizontal misalignment tolerance and the system efficiency. The Cx coil is formed by four series-connected rectangular coils and integrated into the transmitter (Tx) coil to provide a coupling variation opposite to that of the Tx coil, obtaining the constant equivalent mutual inductance (MI). The design overcomes the problem that the decoupling-designed intermediate coil does not participate in system energy delivery under the well-aligned condition. A misalignment tolerant design with the zero-phase-angle (ZPA) input and load-independent constant current (CC) output conditions is presented based on the Delta-Wye network transform and linear regression. A comparison between the proposed design and a two-coil system using a similar amount of copper, i.e., the Tx coil plus the Cx coil, is made. Finally, a 218.08 W/85.85 kHz scaled-down prototype with the proposed Cx coil is demonstrated to validate the performance and effectiveness of the design. The proposed design can maintain at over 82% efficiency, and offer the ZPA input and load-independent CC output within a misalignment tolerant range of 50% of the length of the receiver coil, as the load varies from 10 Ω to 25 Ω.
Bayesian Regularization Neural Network-Based Machine Learning Approach on Optimization of CRDI-Split Injection with Waste Cooking Oil Biodiesel to Improve Diesel Engine Performance
Authors: Dharmalingam Babu , Annamalai Santhoshkumar , Areeya Sukunya , Rattanaporn Kittipong , Katam Keerthi , Show Pau-Loke , Sriariyanun Malinee
Published: March 2023

The present study utilized response surface methodology (RSM) and Bayesian neural network (BNN) to predict the characteristics of a diesel engine powered by a blend of biodiesel and diesel fuel. The biodiesel was produced from waste cooking oil using a biocatalyst synthesized from vegetable waste through the wet impregnation technique. A multilevel central composite design was utilized to predict engine characteristics, including brake thermal efficiency (BTE), nitric oxide (NO), unburned hydrocarbons (UBHC), smoke emissions, heat release rate (HRR), and cylinder peak pressure (CGPP). BNN and the logistic–sigmoid activation function were used to train the experimental data in the artificial neural network (ANN) model, and the errors and correlations of the predicted models were calculated. The study revealed that the biocatalyst was capable of producing a maximum yield of 93% at 55 °C under specific reaction conditions, namely a reaction time of 120 min, a stirrer speed of 900 rpm, a catalyst loading of 7 wt.%, and a molar ratio of 1:9. Further, the ANN model was found to exhibit comparably lower prediction errors (0.001–0.0024), lower MAPE errors (3.14–4.6%), and a strong correlation (0.984–0.998) compared to the RSM model. B100-80%-20% was discovered to be the best formulation for emission property, while B100-90%-10% was the best mix for engine performance and combustion at 100% load. In conclusion, this study found that utilizing the synthesized biocatalyst led to attaining a maximum biodiesel yield. Furthermore, the study recommends using ANN and RSM techniques for accurately predicting the characteristics of a diesel engine.
A Two-Layer Optimization Strategy for Battery Energy Storage Systems to Achieve Primary Frequency Regulation of Power Grid
Authors: Chen Wei , Sun Na , Ma Zhicheng , Liu Wenfei , Dong Haiying
Published: March 2023

A two-layer optimization strategy for the battery energy storage system is proposed to realize primary frequency regulation of the grid in order to address the frequency fluctuation problem caused by the power dynamic imbalance between the power system and load when a large number of new energy sources are connected to the grid. An integrated control mode combining virtual sag control and virtual inertia control is proposed in the adaptive regulation layer to provide fast frequency support for the grid while effectively reducing steady-state frequency difference fluctuation. The equal consumption micro-increment criterion is used in the equalization control layer to distribute the energy output of each group while maintaining a good battery charge level. The results of the final simulation in Matlab/Simulink show that the proposed control strategy can effectively improve the system’s primary frequency regulation performance.
Enhancing the Energy Efficiency of Wastewater Treatment Plants through the Optimization of the Aeration Systems
Authors: Campo Giuseppe , Miggiano Antonella , Panepinto Deborah , Zanetti Mariachiara
Published: March 2023

The current geopolitical landscape of the European Union has made it clear that the energy sector must be a top priority in EU policy, especially in light of the sudden escalation of Russian–Ukrainian conflicts. Energy efficiency has been used as the first tool of EU policy to tackle energy and climate crises, given the issues surrounding energy vulnerability and the need to limit gas emissions that contribute to climate change. The white certificate mechanism in Italy has played a pivotal role in encouraging measures to achieve the country’s energy-saving goals. Given the high energy requirements of Wastewater Treatment Plants (WWTPs), especially for aeration in the biological section, this paper examines the replacement of the air distribution system for a large WWTP as a viable intervention. In order to provide economic perspective for the plant, both the discounted Payback Period (dPBP) and the Net Present Value (NPV) were calculated for the investment. When viewed through an economic lens, the dPBP metric exhibits values that span from less than 1 year to nearly 4.5 years. Additionally, the investment’s cost-effectiveness was emphasized by the NPV, which, depending on the factors considered, can exceed 17.5 million euros. Finally, given the centrality of the theme of climate change, the avoided greenhouse gas emissions generated by the efficiency intervention were calculated, according to the GHG Protocol, resulting in a quantity of avoided emissions equivalent to over 57,770 tonnes of CO2e. These results highlight important achievements in terms of both the cost-effectiveness of the plant and the reduction of greenhouse gas emissions.
Practical Approximation of Sheet Losses Taking into Account the Guillotine and Laser Cutting Effect
Authors: Dems Maria , Komeza Krzysztof , Szulakowski Jacek
Published: March 2023

Reducing losses in electrical devices is essential for reducing global energy consumption. Losses in the core of electrical machines constitute a significant part of the overall losses—their share increases with the number of machines powered by PWM converters, especially for high-speed machines. Limiting core losses requires precise determination at the design stage of the device. Achieving this goal is possible thanks to numerical or analytical simulation. A necessary input for this process is the correct determination of the properties of the core material. The sheet loss, however, changes due to the machining process, primarily punching. The subject of the work is to develop a sufficiently accurate approximation of electrical steel sheet-specific loss, taking into account the effects of cutting and the width of a given machine element for a wide range of induction and frequency. The method also enables the extrapolation of losses for higher frequencies relevant from the point of view of generating losses in the machine. The developed loss approximation can be used in the finite element simulation and in applying analytical methods. The technique can be successfully used for many grades of non-oriented sheet metal, provided that the requirements specified in the work are met. The proposed approximation allows us to determine the loss of a sample of a certain width in a wide range of magnetic induction magnitude and frequency with an accuracy not worse than 4%.