bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesonephric-Like Adenocarcinoma of the Endometrium: Diagnostic Advances to Spot This Wolf in Sheep’s Clothing. A Review of the Literature
Authors: Deolet Ellen , Van Dorpe Jo , Van de Vijver Koen
Published: February 2021

Mesonephric-like adenocarcinoma is a recently described rare neoplasm occurring in the uterine corpus and ovary. This under-recognized subtype of carcinoma can be very challenging to diagnose. In mesonephric adenocarcinoma a variety of growth patterns can be present within the same tumor, as a result of which they can be misinterpreted and diagnosed as low-grade endometrioid adenocarcinoma, clear cell carcinoma, or even serous carcinoma and carcinosarcoma. We report a case of mesonephric-like adenocarcinoma misdiagnosed as a low-grade endometrioid endometrial adenocarcinoma that had an early local recurrence and metastasized to the liver and the lungs. Histopathological, immunohistochemical and molecular analysis were performed and compared to published literature, providing a comprehensive overview of the current knowledge. Databases (Pubmed, Web of Science, Google Scholar) were searched with a combination of the following search terms: mesonephric-like, mesonephric, adenocarcinoma, carcinoma, uterine body, uterine corpus, endometrium. Mesonephric-like adenocarcinoma is a difficult-to-diagnose entity. Advanced diagnostics, including improved morphologic, immunohistochemical and molecular knowledge can help develop new therapeutic strategies against this specific subtype of endometrial cancer with an aggressive clinical behavior.
Accuracy of Dynamic Computer-Assisted Implant Placement: A Systematic Review and Meta-Analysis of Clinical and In Vitro Studies
Authors: Schnutenhaus Sigmar , Edelmann Cornelia , Knipper Anne , Luthardt Ralph G.
Published: February 2021

The aim of this systematic review and meta-analysis is to analyze the accuracy of implant placement using computer-assisted dynamic navigation procedures. An electronic literature search was carried out, supplemented by a manual search. The literature search was completed in June 2020. The results of in vitro and clinical studies were recorded separately from each other. For inclusion in the review, the studies had to examine at least the prosthetically relevant parameters for angle deviation, as well as global deviation or lateral deviation at the platform of the implant. Sixteen of 320 articles were included in the investigation: nine in vitro and seven clinical studies. The meta-analysis showed values of 4.1° for the clinical studies (95% CI, 3.12–5.10) and 3.7° for the in vitro studies (95% CI, 2.31–5.10) in terms of the angle deviation. The global deviation at the implant apex of the implant was 1.00 mm for the clinical studies (95% CI, 0.83–1.16) and 0.91 mm for the in vitro studies (95% CI, 0.60–1.12). These values indicate no significant difference between the clinical and in vitro studies. The results of this systematic review show a clinical accuracy of dynamic computer-assisted navigation that is comparable to that of static navigation. However, the dynamic navigation systems show a great heterogeneity that must be taken into account. Moreover, currently there are few clinical data available. Therefore, further investigations into the practicability of dynamic navigation seem necessary.
The Safety of Pharmacological and Surgical Treatment of Diabetes in Patients with Diabetic Retinopathy—A Review
Authors: Matuszewski Wojciech , Baranowska-Jurkun Angelika , Stefanowicz-Rutkowska Magdalena Maria , Gontarz-Nowak Katarzyna , Gątarska Ewa , Bandurska-Stankiewicz Elżbieta
Published: February 2021

Background. Diabetes mellitus (DM) is a non-infectious pandemic of the modern world; it is estimated that in 2045 it will affect 10% of the world’s population. As the prevalence of diabetes increases, the problem of its complications, including diabetic retinopathy (DR), grows. DR is a highly specific neurovascular complication of diabetes that occurs in more than one third of DM patients and accounts for 80% of complete vision loss cases in the diabetic population. We are currently witnessing many groundbreaking studies on new pharmacological and surgical methods of treating diabetes. Aim. The aim of the study is to assess the safety of pharmacological and surgical treatment of DM in patients with DR. Material and methods. An analysis of the data on diabetes treatment methods currently available in the world literature and their impact on the occurrence and progression of DR. Results. A rapid decrease in glycaemia leads to an increased occurrence and progression of DR. Its greatest risk accompanies insulin therapy and sulfonylurea therapy. The lowest risk of DR occurs with the use of SGLT2 inhibitors; the use of DPP-4 inhibitors and GLP-1 analogues is also safe. Patients undergoing pancreatic islet transplants or bariatric surgeries require intensive monitoring of the state of the eye, both in the perioperative and postoperative period. Conclusions. It is of utmost importance to individualize therapy in diabetic patients, in order to gradually achieve treatment goals with the use of safe methods and minimize the risk of development and progression of DR.
Steroid-Resistant Graves’ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience
Authors: Pérez-Moreiras José V. , Varela-Agra María , Prada-Sánchez M. Consuelo , Prada-Ramallal Guillermo
Published: February 2021

This study aimed to assess the effectiveness and safety of tocilizumab use for the treatment of active steroid-resistant Graves’ orbitopathy (GO). A retrospective longitudinal study was conducted by reviewing the medical records at a single center between November 2009 and December 2018. A total of 114 patients with steroid-resistant Graves’ orbitopathy were examined and treated with tocilizumab, of which 54 adults met the inclusion criteria. No concomitant medication for the treatment of orbitopathy was used. The main primary outcomes included changes from baseline in the Clinical Activity Score (CAS) and thyrotropin receptor antibody (TRAb) levels throughout therapy with tocilizumab. The absolute responses to treatment were defined as the achievement of CAS ≤ 1 and TRAb ≤ 10 U/L. A composite ophthalmic score including CAS, proptosis, eyelid retraction, and diplopia was used to evaluate individual improvement in GO. Adverse drug reactions were also assessed. Analysis of the patient’s CAS and TRAb levels showed meaningful reductions during tocilizumab treatment. Differences between values at baseline and subsequent time points were statistically significant (p < 0.001 for all comparisons). The absolute CAS response (CAS = 0 or 1) was achieved in 74% (37/50) of patients after the fourth dose of tocilizumab (at week 16), with a TRAb response being achieved in 55% (23/42) of patients. The relative CAS response (reduction ≥ 2 points) was achieved in 90.9% of patients (40/44) after the first dose of tocilizumab (at week 4). Measurements of proptosis (reduction ≥ 2 mm in 78% of patients, 42/54) and eyelid retraction (reduction ≥ 2 mm in 75%, 33/44), and the prevalence of diplopia (improvement in 68%, 19/28) were significantly reduced after the last dose of tocilizumab (p < 0.001 for all comparisons). GO improved in 98% (53/54) of patients when at least two criteria of the composite evaluation were required. Four patients exhibited disease recurrence, defined as an increase in CAS of ≥2 points in the six months following the date of inactivation. Most adverse drug reactions were mild or moderate in severity. In conclusion, our data suggest that a course of at least 4 months (one monthly dose) of tocilizumab therapy provides a significant benefit to patients with active moderate-to-severe steroid-resistant GO.
Medication-Related Problems in Older People with Multimorbidity in Catalonia: A Real-World Data Study with 5 Years’ Follow-Up
Authors: Troncoso-Mariño Amelia , Roso-Llorach Albert , López-Jiménez Tomás , Villen Noemí , Amado-Guirado Ester , Fernández-Bertolin Sergio , Carrasco-Ribelles Lucía A. , Borras Josep Ma , Violán Concepción
Published: February 2021

Aging, multimorbidity, and polypharmacy are associated with medication-related problems (MRPs). This study aimed to assess the association that multimorbidity and mortality have with MRPs in older people over time. We followed multimorbid, older (65–99 years) people in Catalonia from 2012 to 2016, using longitudinal data and Cox models to estimate adjusted hazard ratios (HR). We reviewed electronic health records to collect explanatory variables and MRPs (duplicate therapy, drug–drug interactions, potentially inappropriate medications (PIM), and contraindicated drugs in chronic kidney disease (CKD) or liver disease). There were 723,016 people (median age: 74 years; 58.9% women) who completed follow-up. We observed a significant (p < 0.001) increase in the proportion with at least one MRP (2012: 66.9% to 2016: 75.5%); contraindicated drugs in CKD (11.1 to 18.5%) and liver disease (3.9 to 5.3%); and PIMs (62.5 to 71.1%), especially drugs increasing fall risk (67.5%). People with ≥10 diseases had more MRPs (in 2016: PIMs, 89.6%; contraindicated drugs in CKD, 34.4%; and in liver disease, 9.3%). All MRPs were independently associated with mortality, from duplicate therapy (HR 1.06; 95% confidence interval (CI) 1.04–1.08) to interactions (HR 1.60; 95% CI 1.54–1.66). Ensuring safe pharmacological treatment in elderly, multimorbid patient remains a challenge for healthcare systems.
Exploring the Relationship between Biologics and Postoperative Surgical Morbidity in Ulcerative Colitis: A Review
Authors: Quaresma Abel Botelho , Baraúna Fernanda da Silva Barbosa , Teixeira Fábio Vieira , Saad-Hossne Rogério , Kotze Paulo Gustavo
Published: February 2021

Background: With the paradigm shift related to the overspread use of biological agents in the treatment of inflammatory bowel diseases (IBD), several questions emerged from the surgical perspective. Whether the use of biologicals would be associated with higher rates of postoperative complications in ulcerative colitis (UC) patients still remains controversial. Aims: We aimed to analyze the literature, searching for studies that correlated postoperative complications and preoperative exposure to biologics in UC patients, and synthesize these data qualitatively in order to check the possible impact of biologics on postoperative surgical morbidity in this population. Methods: Included studies were identified by electronic search in the PUBMED database according to the PRISMA (Preferred Items of Reports for Systematic Reviews and Meta-Analysis) guidelines. The quality and bias assessments were performed by MINORS (methodological index for non-randomized studies) criteria for non-randomized studies. Results: 608 studies were initially identified, 22 of which were selected for qualitative evaluation. From those, 19 studies (17 retrospective and two prospective) included preoperative anti-TNF. Seven described an increased risk of postoperative complications, and 12 showed no significant increase postoperative morbidity. Only three studies included surgical UC patients with previous use of vedolizumab, two retrospective and one prospective, all with no significant correlation between the drug and an increase in postoperative complication rates. Conclusions: Despite conflicting results, most studies have not shown increased complication rates after abdominal surgical procedures in patients with UC with preoperative exposure to biologics. Further prospective studies are needed to better establish the impact of preoperative biologics and surgical complications in UC.
Recent Advances and Clinical Application of Color Scanning Laser Ophthalmoscope
Authors: Terasaki Hiroto , Sonoda Shozo , Tomita Masatoshi , Sakamoto Taiji
Published: February 2021

Scanning laser ophthalmoscopes (SLOs) have been available since the early 1990s, but they were not commonly used because their advantages were not enough to replace conventional color fundus photography. In recent years, color SLOs have improved significantly, and the colored SLO images are obtained by combining multiple SLO images taken by lasers of different wavelengths. A combination of these images of different lasers can create an image that is close to that of the real ocular fundus. One advantage of the advanced SLOs is that they can obtain images with a wider view of the ocular fundus while maintaining a high resolution even through non-dilated eyes. The current SLOs are superior to the conventional fundus photography in their ability to image abnormal alterations of the retina and choroid. Thus, the purpose of this review was to present the characteristics of the current color SLOs and to show how that can help in the diagnosis and the following of changes after treatments. To accomplish these goals, we will present our findings in patients with different types of retinochoroidal disorders.
Local Anesthetics and Recurrence after Cancer Surgery-What’s New? A Narrative Review
Authors: Müller Sarah D. , Ziegler Jonathan S. H. , Piegeler Tobias
Published: February 2021

The perioperative use of regional anesthesia and local anesthetics is part of almost every anesthesiologist’s daily clinical practice. Retrospective analyses and results from experimental studies pointed towards a potential beneficial effect of the local anesthetics regarding outcome—i.e., overall and/or recurrence-free survival—in patients undergoing cancer surgery. The perioperative period, where the anesthesiologist is responsible for the patients, might be crucial for the further course of the disease, as circulating tumor cells (shed from the primary tumor into the patient’s bloodstream) might form new micro-metastases independent of complete tumor removal. Due to their strong anti-inflammatory properties, local anesthetics might have a certain impact on these circulating tumor cells, either via direct or indirect measures, for example via blunting the inflammatory stress response as induced by the surgical stimulus. This narrative review highlights the foundation of these principles, features recent experimental and clinical data and provides an outlook regarding current and potential future research activities.
Impact of Desert Dust Events on the Cardiovascular Disease: A Systematic Review and Meta-Analysis
Authors: Domínguez-Rodríguez Alberto , Báez-Ferrer Néstor , Abreu-González Pedro , Rodríguez Sergio , Díaz Rocío , Avanzas Pablo , Hernández-Vaquero Daniel
Published: February 2021

Background: Whether or not inhalation of airborne desert dust has adverse health effects is unknown. The present study, based on a systematic review and meta-analysis, was carried out to assess the influence desert dust on cardiovascular mortality, acute coronary syndrome, and heart failure. Methods: A systematic search was made in PubMed and Embase databases for studies published before March 2020. Studies based on daily measurements of desert dust were identified. The meta-analysis evaluated the impact of desert dust on cardiovascular events the same day (lag 0) of the exposure and during several days after the exposure (lags 1 to 5). The combined impact of several days of exposure was also evaluated. The incidence rate ratio (IRR) with 95% confidence intervals (CI) was calculated using the inverse variance random effects method. Results: Of the 589 identified titles, a total of 15 studies were selected. The impact of desert dust on the incidence of cardiovascular mortality was statistically significant (IRR = 1.018 (95%CI 1.008–1.027); p < 0.001) in lag 0 of the dust episode, in the following day (lag 1) (IRR = 1.005 (95%CI 1.001–1.009); p = 0.022), and during both days combined (lag 0–1) (IRR = 1.015 (95%CI 1.003–1.028); p = 0.014). Conclusions: The inhalation to desert dust results in a 2% increase (for every 10 µg/m3) in cardiovascular mortality risk.
The Clinical and Histopathological Features of Cutaneous Immune-Related Adverse Events and Their Outcomes
Authors: Hashimoto Hiroki , Ito Takamichi , Ichiki Toshio , Yamada Yuichi , Oda Yoshinao , Furue Masutaka
Published: February 2021

Immune checkpoint inhibitors (ICIs) cause a variety of inflammatory eruptions. The understanding of ICI-induced inflammatory eruptions with detailed histopathological findings is not adequate, particularly in Asian populations. In this study, we retrospectively reviewed 51 patients who were histopathologically diagnosed with cutaneous immune-related adverse events (irAEs) following ICI therapy between 2014 and 2020 at the Department of Dermatology of Kyushu University Hospital. Of the 51 patients (30 men, 21 women), maculopapular rash (38/51, 74.5%), erythema multiforme (2/51, 3.9%), lichenoid reaction (3/51, 5.9%), psoriasiform reaction (3/51, 5.9%), bullous pemphigoid (3/51, 5.9%), scleroderma-like reaction (1/51, 2.0%), and Stevens–Johnson syndrome (1/51, 2.0%) were observed. The clinical and histopathological findings of these eruptions were equivalent to typical cases of common drug eruptions. The onset of maculopapular rash was relatively early (more than half of events occurred within 1 month), whereas lichenoid reactions and autoimmune diseases occurred relatively late (4–8 months). With appropriate treatment and/or interruption of ICIs, most rashes improved (50/51, 98.0%). The ICI-induced inflammatory eruptions shared similar clinical and histopathological features with classical inflammatory eruptions, but a variety of inflammatory eruptions may occur with different degrees of severity. Dermatologists play an important role in providing specialized care for cutaneous irAEs.
Clinical Factors Associated with Atrial Fibrillation Detection on Single-Time Point Screening Using a Hand-Held Single-Lead ECG Device
Authors: Boriani Giuseppe , Palmisano Pietro , Malavasi Vincenzo Livio , Fantecchi Elisa , Vitolo Marco , Bonini Niccolo’ , Imberti Jacopo F. , Valenti Anna Chiara , Schnabel Renate B. , Freedman Ben
Published: February 2021

Our aim was to assess the prevalence of unknown atrial fibrillation (AF) among adults during single-time point rhythm screening performed during meetings or social recreational activities organized by patient groups or volunteers. A total of 2814 subjects (median age 68 years) underwent AF screening by a handheld single-lead ECG device (MyDiagnostick). Overall, 56 subjects (2.0%) were diagnosed with AF, as a result of 12-lead ECG following a positive/suspected recording. Screening identified AF in 2.9% of the subjects ≥ 65 years. None of the 265 subjects aged below 50 years was found positive at AF screening. Risk stratification for unknown AF based on a CHA2DS2VASc > 0 in males and >1 in females (or CHA2DS2VA > 0) had a high sensitivity (98.2%) and a high negative predictive value (99.8%) for AF detection. A slightly lower sensitivity (96.4%) was achieved by using age ≥ 65 years as a risk stratifier. Conversely, raising the threshold at ≥75 years showed a low sensitivity. Within the subset of subjects aged ≥ 65 a CHA2DS2VASc > 1 in males and >2 in females, or a CHA2DS2VA > 1 had a high sensitivity (94.4%) and negative predictive value (99.3%), while age ≥ 75 was associated with a marked drop in sensitivity for AF detection.
Bayesian Meta-Analysis of Myopia Control with Multifocal Lenses
Authors: Varnas Saulius , Gu Xiaomeng , Metcalfe Andrew
Published: February 2021

The aim of this study is to provide reliable guidelines for the mean percentage efficacy together with the 95% credibility interval in slowing down progression of myopia by a specific intervention over defined time periods, derived from a substantial number of randomised controlled clinical trials (RCTs) with consistent outcomes. Multifocal spectacles and contact lenses represent interventions with the largest number of RCTs carried out. Our meta-analyses considered 10 RCTs involving 1662 children which have tested the efficacy of progressive addition spectacle lenses (PALs). In a separate model for comparison purposes nine RCTs with 982 children trialling soft multifocal contact lenses (MFCLs) were analysed. Bayesian random-effects hierarchical models were fitted. The highest efficacy in retarding progression of the scaled sphere equivalent refraction was achieved after 12 M follow-up with the mean 28% reduction in progression and the 95% credibility interval between 21% and 35%. For comparison, the 95% credibility interval for the mean efficacy of soft MFCLs at 12 M follow up is 21% to 37%. We conclude that both multifocal spectacle and contact lenses moderately slow down progression of myopia, relative to single-vision spectacle lenses (SVLs) in the first 12 months after intervention. The relative efficacy of PALs tends to weaken after the first 12 months.
Early Ileocecal Resection Is an Effective Therapy in Isolated Crohn’s Disease
Authors: Kelm Matthias , Anger Friedrich , Eichlinger Robin , Brand Markus , Kim Mia , Reibetanz Joachim , Krajinovic Katica , Germer Christoph-Thomas , Schlegel Nicolas , Flemming Sven
Published: February 2021

Despite the increasing incidence and prevalence of Crohn’s Disease (CD), no curative options exist and treatment remains complex. While therapy has mainly focused on medical approaches in the past, growing evidence reveals that in cases of limited inflammation, surgery can suffice as an alternative primary treatment. We retrospectively assessed the disease course and outcomes of 103 patients with terminal Ileitis who underwent primary surgery (n = 29) or received primary medical treatment followed by surgery (n = 74). Primary endpoint was the need for immunosuppressive medication after surgical treatment (ileocecal resection, ICR) during a two-years follow-up. Rates for laparoscopic ICR were enhanced in case of early surgery, but no differences were seen for postoperative complications. In case of immunosuppressive medication, patients with ICR at an early state of disease needed significantly less anti-inflammatory medication during the two-year postoperative follow-up compared to patients who were primarily treated medically. Furthermore, in a subgroup analysis for patients with localized ileocecal disease manifestation, early surgery consistently resulted in a decreased amount of medical therapy postoperatively. In conclusion primary ICR is safe and effective in patients with limited CD, and the need for immunosuppressive medication during the postoperative follow-up is low compared to patients receiving surgery at a later stage of disease.
Subcutaneous, Paracardiac, and Epicardial Fat CT Density Before/After Contrast Injection: Any Correlation with CAD?
Authors: Monti Caterina Beatrice , Capra Davide , Malavazos Alexis , Florini Giorgia , Parietti Carlo , Schiaffino Simone , Sardanelli Francesco , Secchi Francesco
Published: February 2021

Adipose tissue, in particular epicardial adipose tissue, has been identified as a potential biomarker of cardiovascular pathologies such as coronary artery disease (CAD) in the light of its metabolic activity and close anatomic and pathophysiologic relationship to the heart. Our purpose was to evaluate epicardial adipose tissue density at both unenhanced and contrast-enhanced computed tomography (CT), along with CT densities of paracardiac and subcutaneous adipose tissue, as well as the relations of such densities with CAD. We retrospectively reviewed patients who underwent cardiac CT at our institution for CAD assessment. We segmented regions of interest on epicardial, paracardiac, and subcutaneous adipose tissue on unenhanced and contrast-enhanced scans. A total of 480 patients were included, 164 of them presenting with CAD. Median epicardial adipose tissue density measured on contrast-enhanced scans (−81.5 HU; interquartile range −84.9 to −78.0) was higher than that measured on unenhanced scans (−73.4 HU; −76.9 to −69.4) (p < 0.001), whereas paracardiac and subcutaneous adipose tissue densities were not (p ≥ 0.055). Patients with or without CAD, did not show significant differences in density of epicardial, paracardiac, and subcutaneous adipose tissue either on unenhanced or contrast-enhanced scans (p ≥ 0.092). CAD patients may experience different phenomena (inflammation, fibrosis, increase in adipose depots) leading to rises or drops in epicardial adipose tissue density, resulting in variations that are difficult to detect.
Fatigue Life Prediction for Carbon-SMC and Carbon-FRP by Considering Elastic Modulus Degradation
Authors: Im Yeong Cheol , Kim Dong Yeop , Lim Sang Won , Yoon Sang Jae , Choi Chi Hoon , Kim Myung Hyun
Published: February 2021

In the automotive industry, being lightweight has become an important design factor with the enhancement of environmental regulations. As a result, many studies on the application of composite materials are in progress. Among them, interest in carbon materials, such as carbon sheet molding compound (C-SMC) and carbon-fiber-reinforced plastic (CFRP), which have excellent strength and stiffness, is increasing. However, CFRP is a material that makes it difficult to secure economic feasibility due to its relatively high manufacturing costs and limited mass production, despite its excellent mechanical strength and durability. As a result, many studies have been conducted on C-SMC as an alternative carbon composite material that can be easily mass-produced. In this regard, this study intended to conduct a study on evaluating the fatigue strength of C-SMC and CFRP among mechanical properties due to the lack of clear failure criteria for fatigue design. We investigated the tensile and fatigue strengths of C-SMC and CFRP, respectively. In the case of C-SMC, the mechanical strength tests were conducted for two different width conditions to evaluate the cutting effect and the machining methods to assess the effects of the edge conditions. To evaluate the fatigue failure assessment criteria, the stiffness drop and elastic modulus degradation criteria were applied for each fatigue test result from the C-SMC and CFRP. The results confirmed that the rationality of the failure criteria in terms of the stiffness drop and the application of the fatigue life prediction of C-SMC based on elastic modulus degradation demonstrated promising results.
Preliminary Studies on Graphene-Reinforced 3D Products Obtained by the One-Stage Sacrificial Template Method for Bone Reconstruction Applications
Authors: Mocanu Aura-Cătălina , Miculescu Florin , Stan George E. , Ciocoiu Robert-Cătălin , Corobea Mihai Cosmin , Miculescu Marian , Ciocan Lucian Toma
Published: February 2021

The bone remodeling field has shifted focus towards the delineation of products with two main critical attributes: internal architectures capable to promote fast cell colonization and good mechanical performance. In this paper, Luffa-fibers and graphene nanoplatelets were proposed as porogen template and mechanical reinforcing agent, respectively, in view of framing 3D products by a one-stage polymer-free process. The ceramic matrix was prepared through a reproducible technology, developed for the conversion of marble resources into calcium phosphates (CaP) powders. After the graphene incorporation (by mechanical and ultrasonication mixing) into the CaP matrix, and Luffa-fibers addition, the samples were evaluated in both as-admixed and thermally-treated form (compact/porous products) by complementary structural, morphological, and compositional techniques. The results confirmed the benefits of the two agents’ addition upon the compact products’ micro-porosity and the global mechanical features, inferred by compressive strength and elastic modulus determinations. For the porous products, overall optimal results were obtained at a graphene amount of <1 wt.%. Further, no influence of graphene on fibers’ ability to generate at high temperatures internal interconnected-channels-arrays was depicted. Moreover, its incorporation led to a general preservation of structural composition and stability for both the as-admixed and thermally-treated products. The developed CaP-reinforced structures sustain the premises for prospective non- and load-bearing biomedical applications.
Radiomics and Prostate MRI: Current Role and Future Applications
Authors: Cutaia Giuseppe , La Tona Giuseppe , Comelli Albert , Vernuccio Federica , Agnello Francesco , Gagliardo Cesare , Salvaggio Leonardo , Quartuccio Natale , Sturiale Letterio , Stefano Alessandro , Calamia Mauro , Arnone Gaspare , Midiri Massimo , Salvaggio Giuseppe
Published: February 2021

Multiparametric prostate magnetic resonance imaging (mpMRI) is widely used as a triage test for men at a risk of prostate cancer. However, the traditional role of mpMRI was confined to prostate cancer staging. Radiomics is the quantitative extraction and analysis of minable data from medical images; it is emerging as a promising tool to detect and categorize prostate lesions. In this paper we review the role of radiomics applied to prostate mpMRI in detection and localization of prostate cancer, prediction of Gleason score and PI-RADS classification, prediction of extracapsular extension and of biochemical recurrence. We also provide a future perspective of artificial intelligence (machine learning and deep learning) applied to the field of prostate cancer.
Hull Shape Design Optimization with Parameter Space and Model Reductions, and Self-Learning Mesh Morphing
Authors: Demo Nicola , Tezzele Marco , Mola Andrea , Rozza Gianluigi
Published: February 2021

In the field of parametric partial differential equations, shape optimization represents a challenging problem due to the required computational resources. In this contribution, a data-driven framework involving multiple reduction techniques is proposed to reduce such computational burden. Proper orthogonal decomposition (POD) and active subspace genetic algorithm (ASGA) are applied for a dimensional reduction of the original (high fidelity) model and for an efficient genetic optimization based on active subspace property. The parameterization of the shape is applied directly to the computational mesh, propagating the generic deformation map applied to the surface (of the object to optimize) to the mesh nodes using a radial basis function (RBF) interpolation. Thus, topology and quality of the original mesh are preserved, enabling application of POD-based reduced order modeling techniques, and avoiding the necessity of additional meshing steps. Model order reduction is performed coupling POD and Gaussian process regression (GPR) in a data-driven fashion. The framework is validated on a benchmark ship.
Land Cover Effects on Selected Nutrient Compounds in Small Lowland Agricultural Catchments
Authors: Łaszewski Maksym , Fedorczyk Michał , Gołaszewska Sylwia , Kieliszek Zuzanna , Maciejewska Paulina , Miksa Jakub , Zacharkiewicz Wiktoria
Published: February 2021

The influence of landscape on nutrient dynamics in rivers constitutes an important research issue because of its significance with regard to water and land management. In the current study spatial and temporal variability of N-NO3 and P-PO4 concentrations and their landscape dependence was documented in the Świder River catchment in central Poland. From April 2019 to March 2020, water samples were collected from fourteen streams in the monthly timescale and the concentrations of N-NO3 and P-PO4 were correlated with land cover metrics based on the Corine Land Cover 2018 and Sentinel 2 Global Land Cover datasets. It was documented that agricultural lands and forests have a clear seasonal impact on N-NO3 concentrations, whereas the effect of meadows was weak and its direction was dependent on the dataset. The application of buffer zones metrics increased the correlation performance, whereas Euclidean distance scaling improved correlation mainly for forest datasets. The concentration of P-PO4 was not significantly related with land cover metrics, as their dynamics were driven mainly by hydrological conditions. The obtained results provided a new insight into landscape–water quality relationships in lowland agricultural landscape, with a special focus on evaluating the predictive performance of different land cover metrics and datasets.
Forest and Arborescent Scrub Habitats of Special Interest for SCIs in Central Spain
Authors: Cano-Ortiz Ana , Musarella Carmelo M. , Piñar Fuentes Jose C. , Quinto Canas Ricardo , Pinto Gomes Carlos J. , Spampinato Giovanni , Ighbareyeh Jehad Mahmoud Hussein , del Río Sara , Cano Eusebio
Published: February 2021

The habitat of the several territories in Ciudad Real (Castilla-La Mancha, Spain) are studued through the and mapping (scale 1:10.000) and vegetation analysis. The distribution and surface of the habitat presents in the Sites of Community Interest (SCIs), as well as pressures, threats, trends, and state of conservation are described. These site contributes significantly to the maintenance or restoration at a favourable conservation status of a natural habitat type or of a species of community intesess.These specially protected areas are part of the Natura 2000 network. We discuss the diversity of forest habitats characterized by species of the genus Quercus L., focusing only on the plant communities in the Habitats Directive 92/43/EEC of 1992, regarding the conservation of fauna and flora and habitats of interest owing to their endemic or rare character. Habitats and species must be studied in combination to ensure the maximum reliability of the results. We concentrate on habitats with low representation in the territory as a consequence of their rarity or endemicity. We study the following habitats of special interest: 9230—Mediterranean-Ibero-Atlantic and Galaico-Portuguese oak woods of Quercus robur and Quercus pyrenaica; 9240—Iberian oaks of Quercus faginea and Quercus canariensis; 9320—Thermomediterranean forests of Olea and Ceratonia (Iberian Peninsula, Balearic and Canary Islands); 9540—Mediterranean pine forests of endemic Pinus pinaster (Pinus pinaster subsp. acutisquama); 9560—Endemic forests with Juniperus spp.; 5210. Arborescent scrub with Juniperus spp.
Mapping Impacts of Human Activities from Nighttime Light on Vegetation Cover Changes in Southeast Asia
Authors: Xia Nan , Li Manchun , Cheng Liang
Published: February 2021

It is commonly believed that the impacts of human activities have decreased the natural vegetation cover, while some promotion of the vegetation growth has also been found. In this study, negative or positive correlations between human impacts and vegetation cover were tested in the Southeast Asia (SEA) region during 2012–2018. The Visible Infrared Imaging Radiometer Suite—Day/Night Band (VIIRS/DNB) nocturnal data were used as a measure of human activities and the moderate resolution imaging spectroradiometer (MODIS)/normalized difference vegetation index (NDVI) diurnal data were used as a measure of vegetation cover. The temporal segmentation method was introduced to calculate features of two sets of time series with spatial resolution of about 500 m, including the overall trend, maximum trend, start date, and change duration. The regions with large variation in human activities (V-change region) were first extracted by the Gaussian fitted method, and 8.64% of the entire SEA (VIIRS overall trend <−0.2 or >0.4) was set as the target analysis area. According to statistics, the average overall VIIRS trend for the V-change region in SEA was about 2.12, with a slight NDVI increment. The time lag effect was also found between vegetation cover and human impacts change, with an average of 10.26 months. Our results indicated a slight green overall trend in the SEA region over the most recent 7 years. The spatial pattern of our trend analysis results can be useful for vegetation management and regional planning.
Where Did Life Begin? Testing Ideas in Prebiotic Analogue Conditions
Authors: Deamer David
Published: February 2021

Publications related to the origin of life are mostly products of laboratory research and have the tacit assumption that the same reactions would have been possible on the early Earth some 4 billion years ago. Can this assumption be tested? We cannot go back in time, but we are able to venture out of the laboratory and perform experiments in natural conditions that are presumably analogous to the prebiotic environment. This brief review describes initial attempts to undertake such studies and some of the lessons we have learned.
Blood Biomarkers to Predict Long-Term Mortality after Ischemic Stroke
Authors: Ramiro Laura , Abraira Laura , Quintana Manuel , García-Rodríguez Paula , Santamarina Estevo , Álvarez-Sabín Jose , Zaragoza Josep , Hernández-Pérez María , Ustrell Xavier , Lara Blanca , Terceño Mikel , Bustamante Alejandro , Montaner Joan
Published: February 2021

Stroke is a major cause of disability and death globally, and prediction of mortality represents a crucial challenge. We aimed to identify blood biomarkers measured during acute ischemic stroke that could predict long-term mortality. Nine hundred and forty-one ischemic stroke patients were prospectively recruited in the Stroke-Chip study. Post-stroke mortality was evaluated during a median 4.8-year follow-up. A 14-biomarker panel was analyzed by immunoassays in blood samples obtained at hospital admission. Biomarkers were normalized and standardized using Z-scores. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with long-term mortality and mortality due to stroke. In the multivariate analysis, the independent predictors of long-term mortality were age, female sex, hypertension, glycemia, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Independent blood biomarkers predictive of long-term mortality were endostatin > quartile 2, tumor necrosis factor receptor-1 (TNF-R1) > quartile 2, and interleukin (IL)-6 > quartile 2. The risk of mortality when these three biomarkers were combined increased up to 69%. The addition of the biomarkers to clinical predictors improved the discrimination (integrative discriminative improvement (IDI) 0.022 (0.007–0.048), p < 0.001). Moreover, endostatin > quartile 3 was an independent predictor of mortality due to stroke. Altogether, endostatin, TNF-R1, and IL-6 circulating levels may aid in long-term mortality prediction after stroke.
New Species Can Broaden Myelin Research: Suitability of Little Skate, Leucoraja erinacea
Authors: Möbius Wiebke , Hümmert Sophie , Ruhwedel Torben , Kuzirian Alan , Gould Robert
Published: February 2021

Although myelinated nervous systems are shared among 60,000 jawed vertebrates, studies aimed at understanding myelination have focused more and more on mice and zebrafish. To obtain a broader understanding of the myelination process, we examined the little skate, Leucoraja erinacea. The reasons behind initiating studies at this time include: the desire to study a species belonging to an out group of other jawed vertebrates; using a species with embryos accessible throughout development; the availability of genome sequences; and the likelihood that mammalian antibodies recognize homologs in the chosen species. We report that the morphological features of myelination in a skate hatchling, a stage that supports complex behavioral repertoires needed for survival, are highly similar in terms of: appearances of myelinating oligodendrocytes (CNS) and Schwann cells (PNS); the way their levels of myelination conform to axon caliber; and their identity in terms of nodal and paranodal specializations. These features provide a core for further studies to determine: axon–myelinating cell communication; the structures of the proteins and lipids upon which myelinated fibers are formed; the pathways used to transport these molecules to sites of myelin assembly and maintenance; and the gene regulatory networks that control their expressions.
De Novo Transcriptome Profiling of Brain Tissue from the Annual Killifish Nothobranchius guentheri
Authors: Guvatova Zulfiia G. , Fedorova Maria S. , Vershinina Yulia S. , Pudova Elena A. , Lipatova Anastasiya V. , Volodin Vsevolod V. , Gladysh Natalya S. , Tokarev Artemiy T. , Kornev Alexey B. , Pavlov Vladislav S. , Bakhtogarimov Ildar R. , Krysanov Evgeny Y. , Moskalev Alexey A. , Krasnov George S. , Kudryavtseva Anna V.
Published: February 2021

Nothobranchius is a genus of small annual killifish found in Africa. Due to the relatively short lifespan, as well as easy breeding and care, Nothobranchius fish are becoming widely used as a vertebrate model system. Studying the genome and transcriptome of these fish is essential for advancing the field. In this study, we performed de novo transcriptome assembly of brain tissues from Nothobranchius guentheri using Trinity. Annotation of 104,271 potential genes (with transcripts longer than 500 bp) was carried out; for 24,967 genes (53,654 transcripts), in which at least one GO annotation was derived. We also analyzed the effect of a long-term food supplement with Torin 2, second-generation ATP-competitive inhibitor of mTOR, on the gene expression changes in brain tissue of adult N. guentheri. Overall, 1491 genes in females and 249 genes in males were differently expressed under Torin 2-supplemented diet. According to the Gene Set Enrichment Analysis (GSEA), the majority of identified genes were predominantly involved in the regulation of metabolic process, dendritic spine maintenance, circadian rhythms, retrotransposition, and immune response. Thus, we have provided the first transcriptome assembly and assessed the differential gene expression in response to exposure to Torin 2, which allow a better understanding of molecular changes in the brain tissues of adult fish in the mTOR pathway inhibition.
Geometrically Constrained Skyrmions
Authors: Pathak Swapneel Amit , Hertel Riccardo
Published: February 2021

Skyrmions are chiral swirling magnetization structures with nanoscale size. These structures have attracted considerable attention due to their topological stability and promising applicability in nanodevices, since they can be displaced with spin-polarized currents. However, for the comprehensive implementation of skyrmions in devices, it is imperative to also attain control over their geometrical position. Here we show that, through thickness modulations introduced in the host material, it is possible to constrain three-dimensional skyrmions to desired regions. We investigate skyrmion structures in rectangular FeGe platelets with micromagnetic finite element simulations. First, we establish a phase diagram of the minimum-energy magnetic state as a function of the external magnetic field strength and the film thickness. Using this understanding, we generate preferential sites for skyrmions in the material by introducing dot-like “pockets” of reduced film thickness. We show that these pockets can serve as pinning centers for the skyrmions, thus making it possible to obtain a geometric control of the skyrmion position. This control allows for stabilization of skyrmions at positions and in configurations that they would otherwise not attain. Our findings may have implications for technological applications in which skyrmions are used as units of information that are displaced along racetrack-type shift register devices.
Property Checking with Interpretable Error Characterization for Recurrent Neural Networks
Authors: Mayr Franz , Yovine Sergio , Visca Ramiro
Published: February 2021

This paper presents a novel on-the-fly, black-box, property-checking through learning approach as a means for verifying requirements of recurrent neural networks (RNN) in the context of sequence classification. Our technique steps on a tool for learning probably approximately correct (PAC) deterministic finite automata (DFA). The sequence classifier inside the black-box consists of a Boolean combination of several components, including the RNN under analysis together with requirements to be checked, possibly modeled as RNN themselves. On one hand, if the output of the algorithm is an empty DFA, there is a proven upper bound (as a function of the algorithm parameters) on the probability of the language of the black-box to be nonempty. This implies the property probably holds on the RNN with probabilistic guarantees. On the other, if the DFA is nonempty, it is certain that the language of the black-box is nonempty. This entails the RNN does not satisfy the requirement for sure. In this case, the output automaton serves as an explicit and interpretable characterization of the error. Our approach does not rely on a specific property specification formalism and is capable of handling nonregular languages as well. Besides, it neither explicitly builds individual representations of any of the components of the black-box nor resorts to any external decision procedure for verification. This paper also improves previous theoretical results regarding the probabilistic guarantees of the underlying learning algorithm.
Nonlocal Reaction–Diffusion Models of Heterogeneous Wealth Distribution
Authors: Banerjee Malay , Petrovskii Sergei V. , Volpert Vitaly
Published: February 2021

Dynamics of human populations can be affected by various socio-economic factors through their influence on the natality and mortality rates, and on the migration intensity and directions. In this work we study an economic–demographic model which takes into account the dependence of the wealth production rate on the available resources. In the case of nonlocal consumption of resources, the homogeneous-in-space wealth–population distribution is replaced by a periodic-in-space distribution for which the total wealth increases. For the global consumption of resources, if the wealth redistribution is small enough, then the homogeneous distribution is replaced by a heterogeneous one with a single wealth accumulation center. Thus, economic and demographic characteristics of nonlocal and global economies can be quite different in comparison with the local economy.
Zero-Hopf Bifurcation in a Generalized Genesio Differential Equation
Authors: Diab Zouhair , Guirao Juan L. G. , Vera Juan A.
Published: February 2021

The purpose of the present paper is to study the presence of bifurcations of zero-Hopf type at a generalized Genesio differential equation. More precisely, by transforming such differential equation in a first-order differential system in the three-dimensional space R3, we are able to prove the existence of a zero-Hopf bifurcation from which periodic trajectories appear close to the equilibrium point located at the origin when the parameters a and c are zero and b is positive.
Life Insurance and Subsistence Consumption with an Exponential Utility
Authors: Lee Ho-Seok
Published: February 2021

In this paper, we derive an explicit solution to the utility maximization problem of an individual with mortality risk and subsistence consumption constraint. We adopt an exponential utility for the individual’s consumption and the martingale and duality method is employed. From the explicit solution, we exhibit how the mortality intensity and subsistence consumption constraint affect, separately and together, portfolio, consumption and life insurance purchase.
A Longitudinal Study of the Bladder Cancer Applying a State-Space Model with Non-Exponential Staying Time in States
Authors: Montoro-Cazorla Delia , Pérez-Ocón Rafael , Pereira das Neves-Yedig Alicia
Published: February 2021

A longitudinal study for 847 bladder cancer patients for a period of fifteen years is presented. After the first surgery, the patients undergo successive ones (recurrences). A state-model is selected for analyzing the evolution of the cancer, based on the distribution of the times between recurrences. These times do not follow exponential distributions, and are approximated by phase-type distributions. Under these conditions, a multidimensional Markov process governs the evolution of the disease. The survival probability and mean times in the different states (levels) of the disease are calculated empirically and also by applying the Markov model, the comparison of the results indicate that the model is well-fitted to the data to an acceptable significance level of 0.05. Two sub-cohorts are well-differenced: those reaching progression (the bladder is removed) and those that do not. These two cases are separately studied and performance measures calculated, and the comparison reveals details about the characteristics of the patients in these groups.