bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Lead Patterns on Mean Profiles of Wind, Temperature, and Turbulent Fluxes in the Atmospheric Boundary Layer over Sea Ice
Authors: Michaelis Janosch , Lüpkes Christof
Published: January 2022

In the polar regions, the atmospheric boundary layer (ABL) characteristics are strongly influenced by convection over leads, which are elongated channels in the sea ice covered ocean. The effects on the ABL depend on meteorological forcing and lead geometry. In non-convection-resolving models, in which several leads of potentially different characteristics might be present in a single grid cell, such surface characteristics and the corresponding ABL patterns are not resolved. Our main goal is to investigate potential implications for such models when these subgrid-scale patterns are not considered appropriately. We performed non-eddy-resolving microscale simulations over five different domains with leads of different widths separated by 100% sea ice. We also performed coarser-resolved simulations over a domain representing a few grid cells of a regional climate model, wherein leads were not resolved but accounted for via a fractional sea ice cover of 91% in each cell. Domain size and mean sea ice concentration were the same in all simulations. Differences in the domain-averaged ABL profiles and patterns of wind, temperature, and turbulent fluxes indicate a strong impact of both the leads and their geometry. Additional evaluations of different turbulence parameterizations show large effects by both gradient-independent heat transport and vertical entrainment.
Historic Storms Detected in a Changing Environment over Recent Centuries in the Belle Henriette Lagoon
Authors: Maanan Mohamed , Pouzet Pierre , Schmidt Sabine , Robin Marc
Published: January 2022

This paper explores extreme storms with marine flooding events in historical times. It focuses on the challenges associated with detecting these events with a degree of certainty in a changing environment. The paleoenvironmental changes which turned the Gulf of Pictons into the Belle Henriette lagoon have required the reconstruction of events to be based on cored sediments. This study aims to establish how sedimentological washovers can be detected in a depositional environment that has changed profoundly over recent centuries. The Belle Henriette lagoon site is unique. Despite the profound environmental changes that have taken place, the impact of storms was well preserved in the five cores extracted. Eighteen historical extreme storms with marine floods were detected in the sediment. By cross-referencing with historical archives, thirteen storms were estimated in 1990, 1940, 1896, 1876, 1859, 1838, 1820, 1811, 1751, 1711, 1645, 1469, and 1351. Five older storms dating back to 1090, 1036, 941, 809, and 581 will also be discussed. By conducting a thorough historical review, we can conclude that these extreme storms caused significant damage and had a profound impact on the socioeconomic coastal communities.
Long-Term Analysis of Tropospheric Ozone in the Urban Area of Guadalajara, Mexico: A New Insight of an Alternative Criterion
Authors: Díaz-Torres José de Jesús , Ojeda-Castillo Valeria , Hernández-Mena Leonel , Vergara-Sánchez Josefina , Saldarriaga-Noreña Hugo Albeiro , Murillo-Tovar Mario Alfonso
Published: January 2022

Tropospheric ozone is an obligatorily-regulated pollutant, to ensure health protection and better air quality. Most countries have established maximum permissible limits (MPL) equal to 0.06 or 0.070 ppmv, but these could be insufficient considering the strictest MPL of the World Health Organization (WHO) guidelines. Such concentrations may still cause health damage to some groups of the population in urban areas. Additionally, the mean value is the principal statistical parameter for monitoring air pollution. This factor may be hiding critical ozone concentrations for public health. This work examines the mean and maximum ozone based on a multi-temporal analysis, to explore the use of a maximum average value as an air quality standard. The mean ozone had a remarkably stationary contrast; while, the maximum ozone emphasized a semi-permanent state of high pollution over the year. Diurnal variation highlights the differences of frequency between the mean and maximum ozone above any MPL, which is accentuated when compared with the WHO guidelines. Under the WHO-MPL, the mean ozone underestimates the highest concentrations; while the maximum ozone represents the extremely high concentrations observed over the year. Instead, the maximum average ozone becomes moderate; this preserves the proper, but conservative high concentrations, following similar temporal patterns as the mean ozone. This parameter is proposed to be adapted as an alternative statistical criterion to prevent negative effects on public health due to high and frequent ozone concentrations in subsequent years.
Potential Anticancer Agents against Melanoma Cells Based on an As-Synthesized Thiosemicarbazide Derivative
Authors: Kozyra Paweł , Korga-Plewko Agnieszka , Karczmarzyk Zbigniew , Hawrył Anna , Wysocki Waldemar , Człapski Michał , Iwan Magdalena , Ostrowska-Leśko Marta , Fornal Emilia , Pitucha Monika
Published: January 2022

In this paper, thiosemicarbazide derivatives were synthesized as potential anticancer agents. X-ray investigations for 1-(2,4-dichlorophenoxy)acetyl-4-(2-fluorophenyl) thiosemicarbazide, 1-(2,4-dichlorophenoxy)acetyl-4-(4-metylothiophenyl)thiosemicarbazide and 1-(2,4-di chlorophenoxy)acetyl-4-(4-iodophenyl)thiosemicarbazide were carried out in order to confirm the synthesis pathways, identify their tautomeric forms, analyze the conformational preferences of molecules, and identify intra- and intermolecular interactions in the crystalline state. TLC and RP-HPLC analyses were used to determine lipophilicity. The lipophilicity analysis revealed that the 4-substituted halogen derivatives of thiosemicarbazides showed greater lipophilicity compared with 2-substituted derivatives. The optimal range of lipophilicity for biologically active compounds logkw is between 4.14 and 4.78. However, as the analysis showed, it is not a decisive parameter. The cytotoxicity of the new compounds was evaluated against both the G-361 and BJ cell lines. Cytotoxicity analyses and cell-cycle and cell apoptosis assays were performed. The MTT test demonstrated that three compounds were cytotoxic to melanoma cells and not toxic to normal fibroblasts in the concentration range used. The cell cycle analysis showed that the compounds had no significant effect on the cell cycle inhibition. An extensive gene expression analysis additionally revealed that all compounds tested downregulated the expression of dihydroorotate dehydrogenase (DHODH). DHODH is a mitochondrial enzyme involved in the de novo synthesis of pyrimidines. Due to the rapid rate of cancer cell proliferation and the increased demand for nucleotide synthesis, it has become a potential therapeutic target.
The Urokinase Plasminogen Activation System in Pancreatic Cancer: Prospective Diagnostic and Therapeutic Targets
Authors: Kumar Ashna A. , Buckley Benjamin J. , Ranson Marie
Published: January 2022

Pancreatic cancer is a highly aggressive malignancy that features high recurrence rates and the poorest prognosis of all solid cancers. The urokinase plasminogen activation system (uPAS) is strongly implicated in the pathophysiology and clinical outcomes of patients with pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic cancers. Overexpression of the urokinase-type plasminogen activator (uPA) or its cell surface receptor uPAR is a key step in the acquisition of a metastatic phenotype via multiple mechanisms, including the increased activation of cell surface localised plasminogen which generates the serine protease plasmin. This triggers multiple downstream processes that promote tumour cell migration and invasion. Increasing clinical evidence shows that the overexpression of uPA, uPAR, or of both is strongly associated with worse clinicopathological features and poor prognosis in PDAC patients. This review provides an overview of the current understanding of the uPAS in the pathogenesis and progression of pancreatic cancer, with a focus on PDAC, and summarises the substantial body of evidence that supports the role of uPAS components, including plasminogen receptors, in this disease. The review further outlines the clinical utility of uPAS components as prospective diagnostic and prognostic biomarkers for PDAC, as well as a rationale for the development of novel uPAS-targeted therapeutics.
Inhibition of Polyglutamine Misfolding with D-Enantiomeric Peptides Identified by Mirror Image Phage Display Selection
Authors: Kolkwitz Pauline Elisabeth , Mohrlüder Jeannine , Willbold Dieter
Published: January 2022

Nine heritable diseases are known that are caused by unphysiologically elongated polyglutamine tracts in human proteins leading to misfolding, aggregation and neurodegeneration. Current therapeutic strategies include efforts to inhibit the expression of the respective gene coding for the polyglutamine-containing proteins. There are, however, concerns that this may interfere with the physiological function of the respective protein. We aim to stabilize the protein’s native conformation by D-enantiomeric peptide ligands to prevent misfolding and aggregation, shift the equilibrium between aggregates and monomers towards monomers and dissolve already existing aggregates into non-toxic and functional monomers. Here, we performed a mirror image phage display selection on the polyglutamine containing a fragment of the androgen receptor. An elongated polyglutamine tract in the androgen receptor causes spinal and bulbar muscular atrophy (SBMA). The selected D-enantiomeric peptides were tested for their ability to inhibit polyglutamine-induced androgen receptor aggregation. We identified D-enantiomeric peptide QF2D-2 (sqsqwstpqGkwshwprrr) as the most promising candidate. It binds to an androgen receptor fragment with 46 consecutive glutamine residues and decelerates its aggregation, even in seeded experiments. Therefore, QF2D-2 may be a promising drug candidate for SBMA treatment or even for all nine heritable polyglutamine diseases, since its aggregation-inhibiting property was shown also for a more general polyglutamine target.
Insular Involvement in Cases of Epilepsy Surgery Failure
Authors: Li Jimmy , Reiter-Campeau Sandra , Namiranian Dina , Toffa Dènahin Hinnoutondji , Bouthillier Alain , Dubeau François , Nguyen Dang Khoa
Published: January 2022

Background: Epilepsy surgery failure is not uncommon, with several explanations having been proposed. In this series, we detail cases of epilepsy surgery failure subsequently attributed to insular involvement. Methods: We retrospectively identified patients investigated at the epilepsy monitoring units of two Canadian tertiary care centers (2004–2020). Included patients were adults who had undergone epilepsy surgeries with recurrence of seizures post-operatively and who were subsequently determined to have an insular epileptogenic focus. Clinical, electrophysiological, neuroimaging, and surgical data were synthesized. Results: We present 14 patients who demonstrated insular epileptic activity post-surgery-failure as detected by intracranial EEG, MEG, or seizure improvement after insular resection. Seven patients had manifestations evoking possible insular involvement prior to their first surgery. Most patients (8/14) had initial surgeries targeting the temporal lobe. Seizure recurrence ranged from the immediate post-operative period to one year. The main modality used to determine insular involvement was MEG (8/14). Nine patients underwent re-operations that included insular resection; seven achieved a favorable post-operative outcome (Engel I or II). Conclusions: Our series suggests that lowering the threshold for suspecting insular epilepsy may be necessary to improve epilepsy surgery outcomes. Detecting insular epilepsy post-surgery-failure may allow for re-operations which may lead to good outcomes.
Early-Age Performance of Graphene-Nanoplatelet-Modified High-Strength Concrete Cured by Electric Thermal Curing in Severe Cold Regions
Authors: Zhou Zheng , Zhang Boyi , Wang Mingzhi , Wang Wei
Published: January 2022

Concrete structure construction with a high strength grade in cold regions is a significant problem that has elicited considerable research attention. In this work, we firstly prepared steel-fiber-reinforced high-strength concrete (HSC) at −20 °C for winter concrete construction in a cold region. Specifically, the combination of graphene nanoplatelet (GNP) incorporation and electric thermal (ET) curing could effectively improve the performance when preparing high-strength concrete (GNP-HSC) at −20 °C. The optimal amount of steel fiber added in this work was determined numerically and experimentally to be 2.5 vol%. The temperature development regularity of the ET-cured sample was also recorded during the whole curing process. Mechanical property results indicated that the combination of GNP incorporation and ET curing could effectively stimulate the strength formation of HSC samples to 91.2 MPa at early age, which is remarkable for concrete construction at −20 °C. Moreover, microstructural analyses (including XRD, TG and SEM analyses) were further conducted to verify the advantages of GNP incorporation and ET curing on the hydration products, hydration degree and microstructure of HSC samples. This work provides new insights into the application of GNP as a nanoscale material to improve the performance of HSC structures at extremely low temperatures.
Acceptance Model of Artificial Intelligence (AI)-Based Technologies in Construction Firms: Applying the Technology Acceptance Model (TAM) in Combination with the Technology–Organisation–Environment (TOE) Framework
Authors: Na Seunguk , Heo Seokjae , Han Sehee , Shin Yoonsoo , Roh Youngsook
Published: January 2022

In the era of the Fourth Industrial Revolution, artificial intelligence (AI) is a core technology, and AI-based applications are expanding in various fields. This research explored the influencing factors on end-user’s intentions and acceptance of AI-based technology in construction companies using the technology acceptance model (TAM) and technology–organisation–environment (TOE) framework. The analysis of end-users’ intentions for accepting AI-based technology was verified by applying the structure equation model. According to the research results, the technological factors along with external variables and an individual’s personality had a positive influence (+) on the perceived usefulness and the perceived ease of use of end-users of AI-based technology. Conversely, environmental factors such as suggestions from others appeared to be disruptive to users’ technology acceptance. In order to effectively utilise AI-based technology, organisational factors such as the support, culture, and participation of the company as a whole were indicated as important factors for AI-based technology implementation.
Blinatumomab as a Bridge Therapy for Hematopoietic Stem Cell Transplantation in Pediatric Refractory/Relapsed Acute Lymphoblastic Leukemia
Authors: Pawinska-Wasikowska Katarzyna , Wieczorek Aleksandra , Balwierz Walentyna , Bukowska-Strakova Karolina , Surman Marta , Skoczen Szymon
Published: January 2022

Despite the progress that has been made in recent decades in the treatment of pediatric acute leukemias, e.g., converting acute lymphoblastic leukemia (ALL) from a fatal to a highly curable disease, 15–20% of children still relapse. Blinatumomab, a bispecific CD3/CD19 antibody construct, has been successfully used in relapsed/refractory r/r B-cell precursor ALL (BCP-ALL) as a bridge to hematopoietic stem cell transplantation (HSCT). We retrospectively assessed the efficacy and toxicity of blinatumomab in 13 children with r/r BCP-ALL. Between 2017 and 2021, thirteen children, aged 1–18 years, with r/r BCP-ALL were treated with blinatumomab. Two patients were administered blinatumomab for refractory relapse without complete remission (CR), one due to primary refractory disease, and ten patients were in CR with minimal residual disease (MRD) ≥ 10−3. The response rate in our cohort of patients was 85%, with subsequent feasible HSCT in 11 out of 13 children. Ten children reached MRD negativity after the first blinatumomab administration. The three-year OS for the study patients was 85% (Mantel–Cox, p < 0.001) and median follow-up was 24.5 (range: 1–47). All responders proceeded to HSCT and are alive in CR, and MRD negative. Although our study had some limitations with regard to its retrospective design and limited patient population, it clearly showed blinatumomab as not only a feasible but also an effective therapeutic option in pretreated children with r/r BCP-ALL, with a tolerable toxicity profile, paving the way for an HSCT procedure.
A Novel Urinary miRNA Biomarker for Early Detection of Colorectal Cancer
Authors: Iwasaki Hiroyasu , Shimura Takaya , Kitagawa Mika , Yamada Tamaki , Nishigaki Ruriko , Fukusada Shigeki , Okuda Yusuke , Katano Takahito , Horike Shin-ichi , Kataoka Hiromi
Published: January 2022

Since noninvasive biomarkers as an alternative to invasive colonoscopy to detect colorectal cancer (CRC) are desired, we conducted this study to determine the urinary biomarker consisting of microRNAs (miRNAs). In total, 415 age- and sex-matched participants, including 206 patients with CRC and 209 healthy controls (HCs), were randomly divided into three groups: (1) the discovery cohort (CRC, n = 3; HC, n = 6); (2) the training cohort (140 pairs); and (3) the validation cohort (63 pairs). Among 11 urinary miRNAs with aberrant expressions between the two groups, miR-129-1-3p and miR-566 were significantly independent biomarkers that detect CRC. The panel consisting of two miRNAs could distinguish patients with CRC from HC participants with an area under the curve (AUC) = 0.811 in the training cohort. This panel showed good efficacy with an AUC = 0.868 in the validation cohort. This urinary biomarker combining miR-129-1-3p and miR-566 could detect even stage 0/I CRC effectively with an AUC = 0.845. Moreover, the expression levels of both miR-129-1-3p and miR-566 were significantly higher in primary tumor tissues than in adjacent normal tissue. Our established novel biomarker consisting of urinary miR-129-1-3p and miR-566 enables noninvasive and early detection of CRC.
AXL Receptor Tyrosine Kinase as a Promising Therapeutic Target Directing Multiple Aspects of Cancer Progression and Metastasis
Authors: Goyette Marie-Anne , Côté Jean-François
Published: January 2022

The receptor tyrosine kinase AXL is emerging as a key player in tumor progression and metastasis and its expression correlates with poor survival in a plethora of cancers. While studies have shown the benefits of AXL inhibition for the treatment of metastatic cancers, additional roles for AXL in cancer progression are still being explored. This review discusses recent advances in understanding AXL’s functions in different tumor compartments including cancer, vascular, and immune cells. AXL is required at multiple steps of the metastatic cascade where its activation in cancer cells leads to EMT, invasion, survival, proliferation and therapy resistance. AXL activation in cancer cells and various stromal cells also results in tumor microenvironment deregulation, leading to modulation of angiogenesis, fibrosis, immune response and hypoxia. A better understanding of AXL’s role in these processes could lead to new therapeutic approaches that would benefit patients suffering from metastatic diseases.
Gall Bladder Disease and the Risk of Small Bowel Cancer—Results from a Nationwide Swedish Cohort Study
Authors: Emilsson Louise , Radkiewicz Cecilia , Semrad Carol E. , Joshi Amit D. , Ludvigsson Jonas F.
Published: January 2022

Background and aims: Small bowel cancer is a rare but rising malignancy. The etiology is poorly understood and there is a need for large-scale studies. Gallbladder disease (GBD), inducing localized inflammation, has been suggested to increase small bowel cancer risk. Methods: We retrieved nationwide data from Sweden’s 28 pathology departments on all adults (age 20–79) with pathology-confirmed GBD diagnosed in 1965–2017. In total 156,390 GBD patients were matched with up to 5 matched comparators from the general population and follow-up started one year after GBD diagnosis. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids. Results: During a median follow-up of 12 years, we identified 92 small bowel adenocarcinomas, 132 adenomas, and 81 carcinoid tumors in the GBD cohort. Corresponding incidence rates were 4.8, 6.9, and 4.2 per 100,000 person-years (PY), compared to 3.2, 3.2, and 1.8 in matched comparators. The adjusted HR was 1.42 (95% CI = 1.08–1.87) for small bowel adenocarcinoma, 1.79 (95% CI = 1.41–2.27) for adenoma, and 2.07 (95% CI = 1.52–2.81) for carcinoid. The excess cancer risk was most pronounced during the first year of follow-up for adenocarcinomas and during the first six years for adenomas while for carcinoids the HR peaked 10–15 years after start of follow-up. Conclusions: In this nationwide cohort study, GBD was associated with an increased risk of small bowel cancer. The excess risk of small bowel adenocarcinoma was mainly seen during the first years of follow-up while small bowel carcinoid risk peaked 11–16 years after GBD diagnosis.
Head and Neck Squamous Cell Carcinoma in Elderly Patients: Role of Radiotherapy and Chemotherapy
Authors: Fasano Morena , D’Onofrio Ida , Belfiore Maria Paola , Angrisani Antonio , Caliendo Valentina , Della Corte Carminia Maria , Pirozzi Mario , Facchini Sergio , Caterino Marianna , Guida Cesare , Nardone Valerio , Reginelli Alfonso , Cappabianca Salvatore
Published: January 2022

Head and neck squamous cell carcinomas (HNSCC) constitute the sixth most common malignancy worldwide, with approximately 25–40% of the diagnosed patients older than 70 years. HNSCC patients are often frail and frequently have multiple comorbidities due to their unhealthy lifestyle, and evidence suggests that older patients may receive less aggressive and suboptimal treatment than younger patients with the same disease status. The aim of this review is to depict and summarize the evidence regarding the different strategies that can be used in the clinical management of elderly HNSCC patients. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of clinical approaches in the context of elderly HNSCC.
Recent Advances in the Application of Enzyme Processing Assisted by Ultrasound in Agri-Foods: A Review
Authors: Córdova Andrés , Henríquez Paola , Nuñez Helena , Rico-Rodriguez Fabián , Guerrero Cecilia , Astudillo-Castro Carolina , Illanes Andrés
Published: January 2022

The intensification of processes is essential for the sustainability of the biorefinery concept. Enzyme catalysis assisted by ultrasound (US) may offer interesting opportunities in the agri-food sector because the cavitation effect provided by this technology has been shown to improve the efficiency of the biocatalysts. This review presents the recent advances in this field, focused on three main applications: ultrasound-assisted enzymatic extractions (UAEE), US hydrolysis reactions, and synthesis reactions assisted by US for the manufacturing of agri-food produce and ingredients, enabling the upgrading of agro-industrial waste. Some theoretical and experimental aspects of US that must be considered are also reviewed. Ultrasonic intensity (UI) is the main parameter affecting the catalytic activity of enzymes, but a lack of standardization for its quantification makes it unsuitable to properly compare results. Applications of enzyme catalysis assisted by US in agri-foods have been mostly concentrated in UAEE of bioactive compounds. In second place, US hydrolysis reactions have been applied for juice and beverage manufacturing, with some interesting applications for producing bioactive peptides. In last place, a few efforts have been performed regarding synthesis reactions, mainly through trans and esterification to produce structured lipids and sugar esters, while incipient applications for the synthesis of oligosaccharides show promising results. In most cases, US has improved the reaction yield, but much information is lacking on how different sonication conditions affect kinetic parameters. Future research should be performed under a multidisciplinary approach for better comprehension of a very complex phenomenon that occurs in very short time periods.
Nuclear Receptor PXR in Drug-Induced Hypercholesterolemia
Authors: Karpale Mikko , Hukkanen Janne , Hakkola Jukka
Published: January 2022

Atherosclerosis is a major global health concern. The central modifiable risk factors and causative agents of the disease are high total and low-density lipoprotein (LDL) cholesterol. To reduce morbidity and mortality, a thorough understanding of the factors that influence an individual’s cholesterol status during the decades when the arteria-narrowing arteriosclerotic plaques are forming is critical. Several drugs are known to increase cholesterol levels; however, the mechanisms are poorly understood. Activation of pregnane X receptor (PXR), the major regulator of drug metabolism and molecular mediator of clinically significant drug–drug interactions, has been shown to induce hypercholesterolemia. As a major sensor of the chemical environment, PXR may in part mediate hypercholesterolemic effects of drug treatment. This review compiles the current knowledge of PXR in cholesterol homeostasis and discusses the role of PXR in drug-induced hypercholesterolemia.
Exosome as a Delivery Vehicle for Cancer Therapy
Authors: Moon Bohyun , Chang Suhwan
Published: January 2022

Exosomes are small extracellular vesicles that are naturally produced and carry biomolecules such as proteins, microRNAs, and metabolites. Because of their small size and low level of biomolecule expression, the biological function of exosomes has only been identified recently. Despite the short history of investigation, exosomes seem to have remarkable potential as a delivery vehicle. With regards to cancer therapy, numerous antitumor agents demonstrate serious side effects (or toxicity), which has led to the unmet need for improving their selectivity and stability. Exosomes, either produced naturally or generated artificially, provide an attractive platform to load many types of molecules such as small molecules, biologics, and other therapeutic agents. Furthermore, the features of exosomes can be designed by selecting their source cells, or they can be engineered to incorporate affinity tags; thus, exosomes show promise as effective delivery vehicles for the complex tumor microenvironment. In this review, we focus on various exosomes produced from different cell types and their potential uses. Moreover, we summarize the current state of artificial exosomes as a drug carrier and provide an overview of the techniques used for their production.
New Insights from Metabolomics in Pediatric Renal Diseases
Authors: Riccio Simona , Valentino Maria Sole , Passaro Antonio Paride , Izzo Marica , Guarino Stefano , Miraglia del Giudice Emanuele , Marzuillo Pierluigi , Di Sessa Anna
Published: January 2022

Renal diseases in childhood form a spectrum of different conditions with potential long-term consequences. Given that, a great effort has been made by researchers to identify candidate biomarkers that are able to influence diagnosis and prognosis, in particular by using omics techniques (e.g., metabolomics, lipidomics, genomics, and transcriptomics). Over the past decades, metabolomics has added a promising number of ‘new’ biomarkers to the ‘old’ group through better physiopathological knowledge, paving the way for insightful perspectives on the management of different renal diseases. We aimed to summarize the most recent omics evidence in the main renal pediatric diseases (including acute renal injury, kidney transplantation, chronic kidney disease, renal dysplasia, vesicoureteral reflux, and lithiasis) in this narrative review.
Epidemiology and Surgical Management of Foreign Bodies in the Liver in the Pediatric Population: A Systematic Review of the Literature
Authors: Gigola Francesca , Grimaldi Chiara , Bici Kejd , Ghionzoli Marco , Spinelli Claudio , Muiesan Paolo , Morabito Antonino
Published: January 2022

Retention of foreign bodies (FB) in the liver parenchyma is a rare event in children but it can bring a heavy burden in terms of immediate and long-term complications. Multiple materials can migrate inside the liver. Clinical manifestations may vary, depending on the nature of the foreign body, its route of penetration and timing after the initial event. Moreover, the location of the FB inside the liver parenchyma may pose specific issues related to the possible complications of a challenging surgical extraction. Different clinical settings and the need for highly specialized surgical skills may influence the overall management of these children. Given the rarity of this event, a systematic review of the literature on this topic was conducted and confirmed the pivotal role of surgery in the pediatric population.
Nanocarriers for Sustainable Active Packaging: An Overview during and Post COVID-19
Authors: Pascuta Mihaela , Vodnar Dan
Published: January 2022

Lockdown has been installed due to the fast spread of COVID-19, and several challenges have occurred. Active packaging was considered a sustainable option for mitigating risks to food systems during COVID-19. Biopolymeric-based active packaging incorporating the release of active compounds with antimicrobial and antioxidant activity represents an innovative solution for increasing shelf life and maintaining food quality during transportation from producers to consumers. However, food packaging requires certain physical, chemical, and mechanical performances, which biopolymers such as proteins, polysaccharides, and lipids have not satisfied. In addition, active compounds have low stability and can easily burst when added directly into biopolymeric materials. Due to these drawbacks, encapsulation into lipid-based, polymeric-based, and nanoclay-based nanocarriers has currently captured increased interest. Nanocarriers can protect and control the release of active compounds and can enhance the performance of biopolymeric matrices. The aim of this manuscript is to provide an overview regarding the benefits of released active compound-loaded nanocarriers in developing sustainable biopolymeric-based active packaging with antimicrobial and antioxidant properties. Nanocarriers improve physical, chemical, and mechanical properties of the biopolymeric matrix and increase the bioactivity of released active compounds. Furthermore, challenges during the COVID-19 pandemic and a brief post-COVID-19 scenario were also mentioned.
Preparation and Characterization of Cu and Al Doped ZnO Thin Films for Solar Cell Applications
Authors: Alam Mir Waqas , Ansari Mohd Zahid , Aamir Muhammad , Waheed-Ur-Rehman Mir , Parveen Nazish , Ansari Sajid Ali
Published: January 2022

The Al- and Cu-doped ZnO nanostructured films in this study were deposited using a sputtering technique. Investigations based on X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, Hall effect measurements, and optical transmission spectroscopy was performed to analyze the structural, electrical, and optical characteristics of the prepared Al–ZnO and Cu–ZnO nanostructured films. The analyses show that doping results in enhanced conductivity as well as improved mobility in Al–ZnO and Cu–ZnO films in comparison to pure ZnO films. The Al- and Cu-doped ZnO films exhibited low resistivity (2.9 × 10−4 Ω cm for Al–ZnO and 1.7 × 10−4 Ω cm for Cu–ZnO) along with an average transmittance of around 80% in the visible spectrum. Moreover, the optical bandgaps of undoped ZnO, Al–ZnO, and Cu–ZnO nanostructures were observed as 3.3, 3.28, and 3.24 eV, respectively. Finally, solar cells were assembled by employing ZnO nanostructured thin films as photoelectrodes, resulting in efficiencies of 0.492% and 0.559% for Al–ZnO- and Cu–ZnO-based solar cells, respectively.
FDA Accelerated Approval for Malignant Hematology and Oncology Indications in the Canadian Environment
Authors: Ho Cheryl , Lim Howard J. , Regier Dean A.
Published: January 2022

Accelerated approval (AA) by the FDA enables earlier access to promising new therapies. Health Canada has a similar process. Canada implemented a national health technology assessment (HTA) for reimbursement decisions in 2011. This study evaluated regulatory and funding timelines and decisions for FDA AA cancer therapies in Canada. The FDA’s AA of malignant hematology and oncology from January 2000–December 2019 was reviewed. Dates from Health Canada, HTA decisions and provincial listings were collected. There were 94 FDA AAs, two of which were subsequently withdrawn. Of the 92 AAs, 70 received full (46)/conditional (24) Health Canada approval, and 22 were not filed. Since the introduction of HTA, 31 out of 45 of Health Canada’s approved indications underwent HTA review: 18 received a positive recommendation conditional on cost-effectiveness, 8 were not recommended and 5 were withdrawn/suspended. The median time from the AA to any Health Canada approval is 9.4 months, from any Health Canada approval to HTA decision is 5.8 months and from HTA decision to the first formulary listing is 12.0 months. The access and timeline for the first formulary listing differences were observed between the USA and Canada due to the decision of pharmaceutical companies to submit (or not) to regulatory/HTA bodies, national procedural delays with different healthcare delivery models and submission timelines. This study demonstrates that there is delayed access to promising new therapies in Canada.
Prognostic Significance of Tumor Growth Rate (TGR) in Patients with Huge Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization
Authors: Chen Guobin , Xie Xiaoying , Wang Meixia , Guo Xinkun , Zhang Zhenzhen , Zhang Lan , Zhang Boheng
Published: January 2022

The prognostic value of the tumor growth rate (TGR) in huge hepatocellular carcinoma (HHCC) patients treated with transcatheter arterial chemoembolization (TACE) as an initial treatment remains unclear. This two-center retrospective study was conducted in 97 patients suffering from HHCC. Demographic characteristics, oncology characteristics, and some serological markers were collected for analysis. The TGR was significantly linear and associated with the risk of death when applied to restricted cubic splines. The optimal cut-off value of TGR was −8.6%/month, and patients were divided into two groups according to TGR. Kaplan–Meier analysis showed that the high-TGR group had a poorer prognosis. TGR (hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.23–3.43; p = 0.006), presence of portal vein tumor thrombus (PVTT) (HR, 1.93; 95% CI, 1.13–3.27; p = 0.016), and subsequent combination therapy (HR, 0.59; 95% CI, 0.35–0.99; p = 0.047) were independent predictors of OS in the multivariate analysis. The model with TGR was superior to the model without TGR in the DCA analysis. Patients who underwent subsequent combination therapy showed a longer survival in the high-TGR group. This study demonstrated that higher TGR was associated with a worse prognosis in patients with HHCC. These findings will distinguish patients who demand more personalized combination therapy and rigorous surveillance.
Appropriateness and Economic Analysis of Conventional Circulating Biomarkers Assessment in Early Breast Cancer: A Real-World Experience from the E.Pic.A Study
Authors: Maltoni Roberta , Balzi William , Rossi Tania , Fabbri Francesco , Bravaccini Sara , Montella Maria Teresa , Massa Ilaria , Bertoni Lucia , Falcini Fabio , Altini Mattia
Published: January 2022

The risk of relapse for early breast cancer (BC) patients persists even after decades and to date, no specific and sensitive effective circulating biomarker for recurrence prediction has been identified yet. The international guidelines do not recommend the assessment of the serum tumor markers CEA and CA15-3 in the follow-up of asymptomatic early BC patients. In our institute, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, as part of the E.Pic.A study, which was designed to assess the economic appropriateness of integrated care pathways in early BC, the use of CEA and CA15-3 as circulating tumor biomarkers in early BC patients was evaluated in 1502 patients one year after surgery, from 2015 to 2018, with an overall expense of EUR 51,764. A total of EUR 47,780 (92%) was used for execution of circulating tumor markers in early BC patients with stage 0, I and II tumors, neglecting the current guidelines and considered inappropriate by our professional board. We found that no patients with stage I BC experienced relapse in the 365 days after surgery, and in any case examination of the circulating markers CEA and CA15-3 was considered crucial for diagnosis of relapse. Our findings suggest that this inadequacy is a low-value area, supporting the reallocation of economic resources for interventions of a higher value for patients.
Alien Invasive Plant Effect on Soil Fauna Is Habitat Dependent
Authors: De Almeida Tania , Forey Estelle , Chauvat Matthieu
Published: January 2022

Invasive alien plants often modify the structure of native plant communities, but their potential impact on soil communities is far less studied. In this study, we looked at the impact of invasive Asian knotweed (Reynoutria spp.) on two major soil mesofauna (Collembola) and microfauna (Nematodes) communities. We expected ingress of knotweed to differentially affect faunal groups depending on their trophic position, with the lower trophic levels being more impacted than the higher trophic groups according to the closer relationship to plants for basal trophic groups. Furthermore, we expected the knotweed impact to depend on habitat type (forest vs. meadow) with more pronounced changes in abundances of soil invertebrate in invaded meadows. Plant and soil invertebrates were sampled in six sites (three forest and three meadows) in northern France in both control and invaded plots. Our results showed that the presence of knotweed strongly reduced native plant species’ diversity and abundance. Soil fauna also responded to the invasion by Asian knotweed with different responses, as hypothesized, according to trophic position or life-forms. Furthermore, abundances of several collembolan life-forms were influenced by the interaction between the factors “Habitat” and “Knotweed”. This may explain the difficulty to easily generalize and predict the consequences of plant invasion on belowground diversity, although this is of crucial importance for alleviating negative consequences and costs of biological invasion.
Characteristics and Drivers of Soil Organic Carbon Saturation Deficit in Karst Forests of China
Authors: Zhang Limin , Wang Yang , Chen Jin , Feng Ling , Li Fangbing , Yu Lifei
Published: January 2022

Karst forests have complex and unique carbon cycle characteristics. Soil organic carbon saturation deficit (CSD) is an important indicator of soil organic carbon (SOC) sequestration potential; exploring its characteristics and driving factors is a priority theme in current research on the carbon cycles of terrestrial ecosystems. In this study, 171 topsoil samples from typical karst forests in southwest China were used as the study objects. A SOC maximum saturation capacity model was constructed using the boundary line method. The CSD is equal to the maximum saturated capacity of SOC minus the current SOC. We analyzed the CSD and its main driving factors in different regions and succession stages. The results showed that the fractions of carbon and SOC contents in the karst forests at different successional stages in descending order were as follows: climax stage > arbor stage > shrub stage > herb stage. The CSD was the highest at the herb stage in Maolan, Yuntai Mountain, and Dashahe at 83.04%, 89.99%, and 89.97%, respectively, followed by the shrub stage with 48.69%, 78.50%, and 84.95%, and the lowest at the arbor stage with 25.69%, 43.44%, and 60.49%. The main drivers of CSD in the karst forest of Maolan were litter carbon input, total nitrogen, total phosphorus, and total SOC, and were litter carbon input at Yuntai Mountain and litter carbon input and neutral phosphatase at Dashahe. The results indicate that the core driver of CSD in the karst forest is litter carbon input, and this can be adjusted in the future to regulate the carbon sequestration capacity of SOC.
Volumetric Measurements in Lung Cancer Screening Reduces Unnecessary Low-Dose Computed Tomography Scans: Results from a Single-Center Prospective Trial on 4119 Subjects
Authors: Milanese Gianluca , Sabia Federica , Ledda Roberta Eufrasia , Sestini Stefano , Marchianò Alfonso Vittorio , Sverzellati Nicola , Pastorino Ugo
Published: January 2022

This study aims to compare the low-dose computed tomography (LDCT) outcome and volume-doubling time (VDT) derived from the measured volume (MV) and estimated volume (EV) of pulmonary nodules (PNs) detected in a single-center lung cancer screening trial. MV, EV and VDT were obtained for prevalent pulmonary nodules detected at the baseline round of the bioMILD trial. The LDCT outcome (based on bioMILD thresholds) and VDT categories were simulated on PN- and screenee-based analyses. A weighted Cohen’s kappa test was used to assess the agreement between diagnostic categories as per MV and EV, and 1583 screenees displayed 2715 pulmonary nodules. In the PN-based analysis, 40.1% PNs were included in different LDCT categories when measured by MV or EV. The agreements between MV and EV were moderate (κ = 0.49) and fair (κ = 0.37) for the LDCT outcome and VDT categories, respectively. In the screenee-based analysis, 46% pulmonary nodules were included in different LDCT categories when measured by MV or EV. The agreements between MV and EV were moderate (κ = 0.52) and fair (κ = 0.34) for the LDCT outcome and VDT categories, respectively. Within a simulated lung cancer screening based on a recommendation by estimated volumetry, the number of LDCTs performed for the evaluation of pulmonary nodules was higher compared with in prospective volumetric management.
Implementing Mitigations for Improving Societal Acceptance of Urban Air Mobility
Authors: Çetin Ender , Cano Alicia , Deransy Robin , Tres Sergi , Barrado Cristina
Published: January 2022

The continuous development of technical innovations provides the opportunity to create new economic markets and a wealth of new services. However, these innovations sometimes raise concerns, notably in terms of societal, safety, and environmental impacts. This is the case for services related to the operation of unmanned aerial vehicles (UAV), which are emerging rapidly. Unmanned aerial vehicles, also called drones, date back to the first third of the twentieth century in aviation industry, when they were mostly used for military purposes. Nowadays, drones of various types and sizes are used for many purposes, such as precision agriculture, search and rescue missions, aerial photography, shipping and delivery, etc. Starting to operate in areas with low population density, drones are now looking for business in urban and suburban areas, in what is called urban air mobility (UAM). However, this rapid growth of the drone industry creates psychological fear of the unknown in some parts of society. Reducing this fear will play an important role in public acceptance of drone operations in urban areas. This paper presents the main concerns of society with regard to drone operations, as already captured in some public surveys, and proposes a list of mitigation measures to reduce these concerns. The proposed list is then analyzed, and its applicability to individual, urban, very large demonstration flights is explained, using the feedback from the CORUS-XUAM project. CORUS-XUAM will organize a set of very large drone flight demonstrations across seven European countries to investigate how to safely integrate drone operations into airspace with the support of the U-space.
A Classical Formulation of Quantum Theory?
Authors: Braasch William F. , Wootters William K.
Published: January 2022

We explore a particular way of reformulating quantum theory in classical terms, starting with phase space rather than Hilbert space, and with actual probability distributions rather than quasiprobabilities. The classical picture we start with is epistemically restricted, in the spirit of a model introduced by Spekkens. We obtain quantum theory only by combining a collection of restricted classical pictures. Our main challenge in this paper is to find a simple way of characterizing the allowed sets of classical pictures. We present one promising approach to this problem and show how it works out for the case of a single qubit.
Design and Test of an Integrated Random Number Generator with All-Digital Entropy Source
Authors: Crocetti Luca , Di Matteo Stefano , Nannipieri Pietro , Fanucci Luca , Saponara Sergio
Published: January 2022

In the cybersecurity field, the generation of random numbers is extremely important because they are employed in different applications such as the generation/derivation of cryptographic keys, nonces, and initialization vectors. The more unpredictable the random sequence, the higher its quality and the lower the probability of recovering the value of those random numbers for an adversary. Cryptographically Secure Pseudo-Random Number Generators (CSPRNGs) are random number generators (RNGs) with specific properties and whose output sequence has such a degree of randomness that it cannot be distinguished from an ideal random sequence. In this work, we designed an all-digital RNG, which includes a Deterministic Random Bit Generator (DRBG) that meets the security requirements for cryptographic applications as CSPRNG, plus an entropy source that showed high portability and a high level of entropy. The proposed design has been intensively tested against both NIST and BSI suites to assess its entropy and randomness, and it is ready to be integrated into the European Processor Initiative (EPI) chip.
Prediction of Time Series Gene Expression and Structural Analysis of Gene Regulatory Networks Using Recurrent Neural Networks
Authors: Monti Michele , Fiorentino Jonathan , Milanetti Edoardo , Gosti Giorgio , Tartaglia Gian Gaetano
Published: January 2022

Methods for time series prediction and classification of gene regulatory networks (GRNs) from gene expression data have been treated separately so far. The recent emergence of attention-based recurrent neural network (RNN) models boosted the interpretability of RNN parameters, making them appealing for the understanding of gene interactions. In this work, we generated synthetic time series gene expression data from a range of archetypal GRNs and we relied on a dual attention RNN to predict the gene temporal dynamics. We show that the prediction is extremely accurate for GRNs with different architectures. Next, we focused on the attention mechanism of the RNN and, using tools from graph theory, we found that its graph properties allow one to hierarchically distinguish different architectures of the GRN. We show that the GRN responded differently to the addition of noise in the prediction by the RNN and we related the noise response to the analysis of the attention mechanism. In conclusion, this work provides a way to understand and exploit the attention mechanism of RNNs and it paves the way to RNN-based methods for time series prediction and inference of GRNs from gene expression data.