bluuebunny/crossref_metadata_2025 huggingface dataset:
Exemplifying Stratified Deforestation in Four Protected Areas in Madagascar
Authors: Rafanoharana Serge C. , Andrianambinina Fatany Ollier D. , Rasamuel Henintsoa Andry , Rakotoarijaona Mamy A. , Ganzhorn Jörg U. , Waeber Patrick O. , Wilmé Lucienne
Published: August 2021

Protected areas (PAs) are a cornerstone for conservation biodiversity. Madagascar, as a hotspot for biodiversity, has a network of 114 terrestrial protected areas covering the main forest types occurring on the island. Deforestation continues unabated despite the network covering 11% of the island. Here we present a case study approach reporting on four PAs from the humid forests, dry western forests, and southwestern dry and spiny forests and thickets. To describe deforestation in and around the case sites, we have considered a time window of 30 years for analysis, focusing on six years with reliable data: 1990, 2000, 2010, 2015 (the year of latest PA network update), and 2017. We have considered forest versus other land covers within the PAs in “buffers” at a distance of 500 m, 2.5 km, 5 km, and 10 km from the border of the PA. These buffers were set from the border towards the center of the PA (inside the PAs) and from the border outside the PAs. The smallest PAs, Kasijy (IUCN IV), and Behara Tranomaro (no IUCN category), showed the least forest loss. Tsaratanana (IUCN I) had the highest deforestation rates within the last two years of analysis, with deforestation concentrated in the core area. Ranobe PK-32 (no IUCN category), originally with the largest forest extent, has lost most of its forest cover and showed the highest annual deforestation rate (3.5%) between 2015 and 2017. All four cases prove to be very challenging to manage. Future conservation activities require tailored interventions to account for site-specific current and potential future threats, as detailed in this contribution.
Pathogenic DNM1L Variant (1085G>A) Linked to Infantile Progressive Neurological Disorder: Evidence of Maternal Transmission by Germline Mosaicism and Influence of a Contemporary in cis Variant (1535T>C)
Authors: Piccoli Claudia , Scrima Rosella , D’Aprile Annamaria , Chetta Massimiliano , Cela Olga , Pacelli Consiglia , Ripoli Maria , D’Andrea Giovanna , Margaglione Maurizio , Bukvic Nenad , Capitanio Nazzareno
Published: August 2021

Mitochondria are dynamic organelles undergoing continuous fusion and fission with Drp1, encoded by the DNM1L gene, required for mitochondrial fragmentation. DNM1L dominant pathogenic variants lead to progressive neurological disorders with early exitus. Herein we report on the case of a boy affected by epileptic encephalopathy carrying two heterozygous variants (in cis) of the DNM1L gene: a pathogenic variant (PV) c.1085G>A (p.Gly362Asp) accompanied with a variant of unknown significance (VUS) c.1535T>C (p.Ile512Thr). Amplicon sequencing of the mother’s DNA revealed the presence of the PV and VUS in 5% of cells, with the remaining cells presenting only VUS. Functional investigations performed on the patient and his mother’s cells unveiled altered mitochondrial respiratory chain activities, network architecture and Ca2+ homeostasis as compared with healthy unrelated subjects’ samples. Modelling Drp1 harbouring the two variants, separately or in combination, resulted in structural changes as compared with Wt protein. Considering the clinical history of the mother, PV transmission by a maternal germline mosaicism mechanism is proposed. Altered Drp1 function leads to changes in the mitochondrial structure and bioenergetics as well as in Ca2+ homeostasis. The novel VUS might be a modifier that synergistically worsens the phenotype when associated with the PV.
Glutamine Metabolism Regulators Associated with Cancer Development and the Tumor Microenvironment: A Pan-Cancer Multi-Omics Analysis
Authors: Zou Jingwen , Du Kunpeng , Li Shaohua , Lu Lianghe , Mei Jie , Lin Wenping , Deng Min , Wei Wei , Guo Rongping
Published: August 2021

Background: In recent years, metabolic reprogramming has been identified as a hallmark of cancer. Accumulating evidence suggests that glutamine metabolism plays a crucial role in oncogenesis and the tumor microenvironment. In this study, we aimed to perform a systematic and comprehensive analysis of six key metabolic node genes involved in the dynamic regulation of glutamine metabolism (referred to as GLNM regulators) across 33 types of cancer. Methods: We analyzed the gene expression, epigenetic regulation, and genomic alterations of six key GLNM regulators, including SLC1A5, SLC7A5, SLC3A2, SLC7A11, GLS, and GLS2, in pan-cancer using several open-source platforms and databases. Additionally, we investigated the impacts of these gene expression changes on clinical outcomes, drug sensitivity, and the tumor microenvironment. We also attempted to investigate the upstream microRNA–mRNA molecular networks and the downstream signaling pathways involved in order to uncover the potential molecular mechanisms behind metabolic reprogramming. Results: We found that the expression levels of GLNM regulators varied across cancer types and were related to several genomic and immunological characteristics. While the immune scores were generally lower in the tumors with higher gene expression, the types of immune cell infiltration showed significantly different correlations among cancer types, dividing them into two clusters. Furthermore, we showed that elevated GLNM regulators expression was associated with poor overall survival in the majority of cancer types. Lastly, the expression of GLNM regulators was significantly associated with PD-L1 expression and drug sensitivity. Conclusions: The elevated expression of GLNM regulators was associated with poorer cancer prognoses and a cold tumor microenvironment, providing novel insights into cancer treatment and possibly offering alternative options for the treatment of clinically refractory cancers.
Glacial Erosion Rates Determined at Vorab Glacier: Implications for the Evolution of Limestone Plateaus
Authors: Steinemann Olivia , Martinez Alicia , Picotti Vincenzo , Vockenhuber Christof , Ivy-Ochs Susan
Published: August 2021

Understanding how fast glaciers erode their bedrock substrate is one of the key elements in reconstructing how the action of glaciers gives mountain ranges their shape. By combining cosmogenic nuclide concentrations determined in glacially abraded bedrock with a numerical model, we quantify glacial erosion rates over the last 15 ka. We measured cosmogenic 36Cl in fourteen samples from the limestone forefield of the Vorab glacier (Eastern Alps, Switzerland). Determined glacial erosion rates range from 0.01 mm a−1 to 0.16 mm a−1. These glacial abrasion rates differ quite markedly from rates measured on crystalline bedrock (>1 mm a−1), but are similarly low to the rates determined on the only examined limestone plateau so far, the Tsanfleuron glacier forefield. Our data, congruent with field observations, suggest that the Vorab glacier planed off crystalline rock (Permian Verrucano) overlying the Glarus thrust. Upon reaching the underlying strongly karstified limestone the glacier virtually stopped eroding its bed. We attribute this to immediate drainage of meltwater into the karst passages below the glacier, which inhibits sliding. The determined glacial erosion rates underscore the relationship between geology and the resulting landscape that evolves, whether high elevation plateaus in limestone terrains or steep-walled valleys in granitic/gneissic areas.
The History and Challenges of SCP-ECG: The Standard Communication Protocol for Computer-Assisted Electrocardiography
Authors: Rubel Paul , Fayn Jocelyne , Macfarlane Peter W. , Pani Danilo , Schlögl Alois , Värri Alpo
Published: August 2021

Ever since the first publication of the standard communication protocol for computer-assisted electrocardiography (SCP-ECG), prENV 1064, in 1993, by the European Committee for Standardization (CEN), SCP-ECG has become a leading example in health informatics, enabling open, secure, and well-documented digital data exchange at a low cost, for quick and efficient cardiovascular disease detection and management. Based on the experiences gained, since the 1970s, in computerized electrocardiology, and on the results achieved by the pioneering, international cooperative research on common standards for quantitative electrocardiography (CSE), SCP-ECG was designed, from the beginning, to empower personalized medicine, thanks to serial ECG analysis. The fundamental concept behind SCP-ECG is to convey the necessary information for ECG re-analysis, serial comparison, and interpretation, and to structure the ECG data and metadata in sections that are mostly optional in order to fit all use cases. SCP-ECG is open to the storage of the ECG signal and ECG measurement data, whatever the ECG recording modality or computation method, and can store the over-reading trails and ECG annotations, as well as any computerized or medical interpretation reports. Only the encoding syntax and the semantics of the ECG descriptors and of the diagnosis codes are standardized. We present all of the landmarks in the development and publication of SCP-ECG, from the early 1990s to the 2009 International Organization for Standardization (ISO) SCP-ECG standards, including the latest version published by CEN in 2020, which now encompasses rest and stress ECGs, Holter recordings, and protocol-based trials.
Allogeneic Stem Cell Transplantation for MDS
Authors: Villar Sara , Robin Marie
Published: August 2021

Myelodysplastic syndromes are clonal disorders with morphological dysplasia, a variable degree of cytopenia and a risk of transformation to acute myeloid leukemia. Prognosis is very variable and is defined by blast count, cytopenia, cytogenetics and more recently by somatic mutations, with IPSS or revised IPSS score being the most widely used to assess disease risk. HSCT remains the only curative treatment to date, with high-risk patients obtaining the biggest benefit. However, NRM should be carefully assessed before indicating the transplant in this usually old population, where organ toxicity and comorbid conditions are to be considered. Multi-domain assessment tools, such as CGA (comprehensive geriatric assessment) and EBMT score, are useful in this context and might guide physician decisions regarding the transplant. Indeed, with the development of reduced intensity conditioning regimens, the number of patient candidates for an HSCT has increased. Regarding pre-transplant treatment, patients with a blast excess > 10% might be treated with HMAs or chemotherapy, although there are no randomized trials confirming the benefit of this approach, even when achieving a complete response. Concerning donor choice, matched sibling donors continue to be the first option, although matched unrelated donors, and more recently haploidentical donors, have proven to be valid options and should be offered in the absence of a related donor. Relapse remains the main cause of transplantation failure. MRD assessment and pre-emptive or prophylactic use of HMA or other targeted inhibitors with or without DLI are accepted strategies to reduce relapse risk, but the prognosis in this context remains dismal, and is the subject for several ongoing clinical protocols.
The Impact of Self-Efficacy, Optimism, Resilience and Perceived Stress on Academic Performance and Its Subjective Evaluation: A Cross-Sectional Study
Authors: Popa-Velea Ovidiu , Pîrvan Irina , Diaconescu Liliana Veronica
Published: August 2021

This study aimed to highlight the contribution of self-efficacy, optimism, resilience and perceived stress on academic performance (GPA) at medical undergraduate students. Additionally, we investigated the relationship established between abovementioned variables, gender and position in the academic cycle and the factors associated with satisfaction regarding own academic results. 118 students (25 men, 93 women, mean age 22.863, SD = 1.763) participated in the study. They were administered the General Self-Efficacy Scale (G-SES), the Revised Life Orientation test (LOT-R), the Brief Resilience Scale (BRS) and the Perceived Stress Scale (PSS). t, Wilcoxon-Mann-Whitney, chi-square tests, and linear regressions were performed, in order to test the strength of the hypothesized associations. Data analysis demonstrates a significant association between low optimism, low resilience, high perceived stress and poor academic performance. Even though preclinical students displayed greater perceived stress, it negatively correlated to GPA only in clinical students, this indicating a possible accumulation of stress-related effects. No gender differences were met for the studied variables. Students in clinical cycle were significantly less satisfied about their own performance. These results indicate solid associations between psychosocial variables and academic performance, and differences in the subjective evaluation of own performance, suggesting key points to address, when designing interventions against academic stress.
Gaussian Process Regression-Based Structural Response Model and Its Application to Regional Damage Assessment
Authors: Park Sangki , Jung Kichul
Published: August 2021

Seismic activities are serious disasters that induce natural hazards resulting in an incalculable amount of damage to properties and millions of deaths. Typically, seismic risk assessment can be performed by means of structural damage information computed based on the maximum displacement of the structure. In this study, machine learning models based on GPR are developed in order to estimate the maximum displacement of the structures from seismic activities and then used to construct fragility curves as an application. During construction of the models, 13 features of seismic waves are considered, and six wave features are selected to establish the seismic models with the correlation analysis normalizing the variables with the peak ground acceleration. Two models for six-floor and 13-floor buildings are developed, and a sensitivity analysis is performed to identify the relationship between prediction accuracy and sampling size. A 10-fold cross-validation method is used to evaluate the model performance, using the R-squared, root mean squared error, Nash criterion, and mean bias. Results of the six-parameter-based model apparently indicate a similar performance to that of the 13-parameter-based model for the two types of buildings. The model for the six-floor building affords a steadily enhanced performance by increasing the sampling size, while the model for the 13-floor building shows a significantly improved performance with a sampling size of over 200. The results indicate that the heighted structure requires a larger sampling size because it has more degrees of freedom that can influence the model performance. Finally, the proposed models are successfully constructed to estimate the maximum displacement, and applied to obtain fragility curves with various performance levels. Then, the regional seismic damage is assessed in Gyeonjgu city of South Korea as an application of the developed models. The damage assessment with the fragility curve provides the structural response from the seismic activities, which can assist in minimizing damage.
Integration and Analysis of Multi-Modal Geospatial Secondary Data to Inform Management of at-Risk Archaeological Sites
Authors: Guiney Rebecca , Santucci Elettra , Valman Samuel , Booth Adam , Birley Andrew , Haynes Ian , Marsh Stuart , Mills Jon
Published: August 2021

Climate change poses an imminent physical risk to cultural heritage sites and their surrounding landscape through intensifying environmental processes such as damaging wetting and drying cycles that disrupt archaeological preservation conditions, and soil erosion which threatens to expose deposits and alter the archaeological context of sites. In the face of such threats, geospatial techniques such as GIS, remote sensing, and spatial modelling have proved invaluable tools for archaeological research and cultural heritage monitoring. This paper presents the application of secondary multi-source and multi-temporal geospatial data within a processing framework to provide a comprehensive assessment of geophysical risk to the Roman fort of Magna, Carvoran, UK. An investigation into the ancient hydraulic system at Magna was carried out with analysis of vegetation change over time, and spatio-temporal analysis of soil erosion risk at the site. Due to COVID-19 restrictions in place at the time of this study, these analyses were conducted using only secondary data with the aim to guide further archaeological research, and management and monitoring strategies for the stakeholders involved. Results guided inferences about the ancient hydraulic system, providing insights regarding how to better manage the site at Magna in the future. Analysis of soil erosion allowed the identification of hot spot areas, indicating a future increase in rates of erosion at Magna and suggesting a seasonal period of higher risk of degradation to the site. Results have proven that freely available multi-purpose national-scale datasets are sufficient to create meaningful insights into archaeological sites where physical access to the site is inhibited. This infers the potential to carry out preliminary risk assessment to inform future site management practices.
Correlated Dynamics in Ionic Liquids by Means of NMR Relaxometry: Butyltriethylammonium bis(Trifluoromethanesulfonyl)imide as an Example
Authors: Kruk Danuta , Masiewicz Elzbieta , Lotarska Sylwia , Markiewicz Roksana , Jurga Stefan
Published: August 2021

1H and 19F spin-lattice relaxation experiments have been performed for butyltriethylammonium bis(trifluoromethanesulfonyl)imide in the temperature range from 258 to 298 K and the frequency range from 10 kHz to 10 MHz. The results have thoroughly been analysed in terms of a relaxation model taking into account relaxation pathways associated with 1H–1H, 19F–19F and 1H–19F dipole–dipole interactions, rendering relative translational diffusion coefficients for the pairs of ions: cation–cation, anion–anion and cation–anion, as well as the rotational correlation time of the cation. The relevance of the 1H–19F relaxation contribution to the 1H and 19F relaxation has been demonstrated. A comparison of the diffusion coefficients has revealed correlation effects in the relative cation–anion translational movement. It has also turned out that the translational movement of the anions is faster than of cations, especially at high temperatures. Moreover, the relative cation–cation diffusion coefficients have been compared with self-diffusion coefficients obtained by means of NMR (Nuclear Magnetic Resonance) gradient diffusometry. The comparison indicates correlation effects in the relative cation–cation translational dynamics—the effects become more pronounced with decreasing temperature.
Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy
Authors: Xia Wentao , Tao Zixuan , Zhu Bin , Zhang Wenxiang , Liu Chang , Chen Siyu , Song Mingming
Published: August 2021

Cancer is one of the primary causes of worldwide human deaths. Most cancer patients receive chemotherapy and radiotherapy, but these treatments are usually only partially efficacious and lead to a variety of serious side effects. Therefore, it is necessary to develop new therapeutic strategies. The emergence of nanotechnology has had a profound impact on general clinical treatment. The application of nanotechnology has facilitated the development of nano-drug delivery systems (NDDSs) that are highly tumor selective and allow for the slow release of active anticancer drugs. In recent years, vehicles such as liposomes, dendrimers and polymer nanomaterials have been considered promising carriers for tumor-specific drug delivery, reducing toxicity and improving biocompatibility. Among them, polymer nanoparticles (NPs) are one of the most innovative methods of non-invasive drug delivery. Here, we review the application of polymer NPs in drug delivery, gene therapy, and early diagnostics for cancer therapy.
The Role of Histone Deacetylase 3 Complex in Nuclear Hormone Receptor Action
Authors: Ishii Sumiyasu
Published: August 2021

Nuclear hormone receptors (NRs) regulate transcription of the target genes in a ligand-dependent manner in either a positive or negative direction, depending on the case. Deacetylation of histone tails is associated with transcriptional repression. A nuclear receptor corepressor (N-CoR) and a silencing mediator for retinoid and thyroid hormone receptors (SMRT) are the main corepressors responsible for gene suppression mediated by NRs. Among numerous histone deacetylases (HDACs), HDAC3 is the core component of the N-CoR/SMRT complex, and plays a central role in NR-dependent repression. Here, the roles of HDAC3 in ligand-independent repression, gene repression by orphan NRs, NRs antagonist action, ligand-induced repression, and the activation of a transcriptional coactivator are reviewed. In addition, some perspectives regarding the non-canonical mechanisms of HDAC3 action are discussed.
Lignin/Carbohydrate Complex Isolated from Posidonia oceanica Sea Balls (Egagropili): Characterization and Antioxidant Reinforcement of Protein-Based Films
Authors: Mirpoor Seyedeh Fatemeh , Restaino Odile Francesca , Schiraldi Chiara , Giosafatto Concetta Valeria L. , Ruffo Francesco , Porta Raffaele
Published: August 2021

A lignin fraction (LF) was extracted from the sea balls of Posidonia oceanica (egagropili) and extensively dialyzed and characterized by FT-IR and NMR analyses. LF resulted water soluble and exhibited a brownish-to-black color with the highest absorbance in the range of 250–400 nm, attributed to the chromophore functional groups present in the phenylpropane-based polymer. LF high-performance size exclusion chromatography analysis showed a highly represented (98.77%) species of 34.75 kDa molecular weight with a polydispersity index of 1.10 and an intrinsic viscosity of 0.15. Quantitative analysis of carbohydrates indicated that they represented 28.3% of the dry weight of the untreated egagropili fibers and 72.5% of that of LF. In particular, eight different monosaccharides were detected (fucose, arabinose, rhamnose, galactose, glucose, xylose, glucosamine and glucuronic acid), glucuronic acid (46.6%) and rhamnose (29.6%) being the most present monosaccharides in the LF. Almost all the phenol content of LF (113.85 ± 5.87 mg gallic acid eq/g of extract) was water soluble, whereas around 22% of it consisted of flavonoids and only 10% of the flavonoids consisted of anthocyanins. Therefore, LF isolated from egagropili lignocellulosic material could be defined as a water-soluble lignin/carbohydrate complex (LCC) formed by a phenol polymeric chain covalently bound to hemicellulose fragments. LCC exhibited a remarkable antioxidant activity that remained quite stable during 6 months and could be easily incorporated into a protein-based film and released from the latter overtime. These findings suggest egagropili LCC as a suitable candidate as an antioxidant additive for the reinforcement of packaging of foods with high susceptibility to be deteriorated in aerobic conditions.
Correction: Izquierdo et al. Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over Generations. Int. J. Mol. Sci. 2021, 22, 1453
Authors: Izquierdo Vanesa , Palomera-Ávalos Verónica , Pallàs Mercè , Griñán-Ferré Christian
Published: August 2021

The author wishes to make the following correction to this paper [...]
Physical Activity Behaviour in 50- to 74-Year-Olds: Differences between Employed and Retired Individuals
Authors: Spiteri Karl , Xerri de Caro John , England Kathleen , Calleja Neville , Smith Lee , Grafton Kate , Broom David R.
Published: August 2021

(1) Objectives: The study aimed to examine data from Malta’s Health Interview Survey (HIS) to assess differences between persons in employment and those retired, across different time periods. (2) Methods: A repeat cross-sectional design was adopted. Data that were collected over a period of 12 years included three cross-sectional HIS waves (2002, 2008 and 2014). Data were analysed cross-sectionally and longitudinally using multilevel analysis. (3) Results: In total, 4690 participants between the ages of 50 and 74 years provided data on physical activity (PA). A statistical difference was found between those employed and retired, with the latter undertaking less PA MET min per week in 2002 and 2008. There was no difference in 2014. When adjusting for covariates, people in employment carried out less PA MET min per week (OR-0.16–−0.02) compared to retired individuals. Using multilevel modelling, this study shows that individual factors such BMI and long-standing illness are predictors of PA behaviour as opposed to time trends. (4) Conclusion: Retirement can increase PA measured in MET minutes per week. Individual factors such as BMI, long-standing health problems and self-rated health could be causing the higher levels seen in the employed population during the studied period.
Controversy and Consideration of Refractive Surgery in Patients with Heritable Disorders of Connective Tissue
Authors: Moshirfar Majid , Barke Matthew R. , Huynh Rachel , Waite Austin J. , Ply Briana , Ronquillo Yasmyne C. , Hoopes Phillip C.
Published: August 2021

Heritable Disorders of Connective Tissue (HDCTs) are syndromes that disrupt connective tissue integrity. They include Osteogenesis Imperfecta (OI), Ehlers Danlos Syndrome (EDS), Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS), Epidermolysis Bullosa (EB), Stickler Syndrome (STL), Wagner Syndrome, and Pseudoxanthoma Elasticum (PXE). Because many patients with HDCTs have ocular symptoms, commonly myopia, they will often present to the clinic seeking refractive surgery. Currently, corrective measures are limited, as the FDA contraindicates laser-assisted in-situ keratomileusis (LASIK) in EDS and discourages the procedure in OI and MFS due to a theoretically increased risk of post-LASIK ectasia, poor wound healing, poor refractive predictability, underlying keratoconus, and globe rupture. While these disorders present with a wide range of ocular manifestations that are associated with an increased risk of post-LASIK complications (e.g., thinned corneas, ocular fragility, keratoconus, glaucoma, ectopia lentis, retinal detachment, angioid streaks, and ocular surface disease), their occurrence and severity are highly variable among patients. Therefore, an HDCT diagnosis should not warrant an immediate disqualification for refractive surgery. Patients with minimal ocular manifestations can consider LASIK. In contrast, those with preoperative signs of corneal thinning and ocular fragility may find the combination of collagen cross-linking (CXL) with either photorefractive keratotomy (PRK), small incision lenticule extraction (SMILE) or a phakic intraocular lens (pIOL) implant to be more suitable options. However, evidence of refractive surgery performed on patients with HDCTs is limited, and surgeons must fully inform patients of the unknown risks and complications before proceeding. This paper serves as a guideline for future studies to evaluate refractive surgery outcomes in patients with HDCTs.
Rituximab Induction and Maintenance in ANCA-Associated Vasculitis: State of the Art and Future Perspectives
Authors: Treppo Elena , Binutti Marco , Agarinis Roberto , De Vita Salvatore , Quartuccio Luca
Published: August 2021

Antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases characterized by inflammation of the vascular wall. The pathogenesis of AAV is strongly associated with B cell-derived ANCAs; thus, Rituximab (RTX) has become a promising drug in the induction and maintenance treatment of AAV. The purpose of this review is to describe the efficacy and safety of RTX in the induction of remission and maintenance therapy of AAV. Herein, we summarize the randomized controlled trials that have contributed to the refinement of the use of RTX in AAV in the past decades. RTX has been proven to be effective both in new-onset disease and in relapsing disease. Although the optimal duration of AAV maintenance therapy remains unknown, the ANCAs and the B-cell repopulation may offer support for the administration of further RTX cycles (or not). The safety of RTX is comparable with cyclophosphamide, with the advantage of a low risk of malignancy and no concern for fertility. In conclusion, RTX now plays an important role in the induction and maintenance therapy of AAV. Optimizing RTX-based treatment strategies in AAV is one of the main goals of the current research in AAV.
Evaluation of Biomarkers of Severity in Patients with COVID-19 Infection
Authors: Yamamoto Akitaka , Wada Hideo , Ichikawa Yuhuko , Mizuno Hikaru , Tomida Masaki , Masuda Jun , Makino Katsutoshi , Kodama Shuji , Yoshida Masamichi , Fukui Shunsuke , Moritani Isao , Inoue Hidekazu , Shiraki Katsuya , Shimpo Hideto
Published: August 2021

Object: Although many Japanese patients infected with coronavirus disease 2019 (COVID-19) only experience mild symptoms, in some cases a patient’s condition deteriorates, resulting in a poor outcome. This study examines the behavior of biomarkers in patients with mild to severe COVID-19. Methods: The disease severity of 152 COVID-19 patients was classified into mild, moderate I, moderate II, and severe, and the behavior of laboratory biomarkers was examined across these four disease stages. Results: The median age and male/female ratio increased with severity. The mortality rate was 12.5% in both moderate II and severe stages. Underlying diseases, which were not observed in 45% of mild stage patients, increased with severity. An ROC analysis showed that C-reactive protein (CRP), ferritin, procalcitonin (PCT), hemoglobin (Hb) A1c, albumin, and lactate dehydrogenase (LDH) levels were significantly useful for the differential diagnosis of mild/moderate I stage and moderate II/severe stage. In the severe stage, Hb levels, coagulation time, total protein, and albumin were significantly different on the day of worsening from those observed on the day of admission. The frequency of hemostatic biomarker abnormalities was high in the severe disease stage. Conclusion: The evaluation of severity is valuable, as the mortality rate was high in the moderate II and severe stages. The levels of CRP, ferritin, PCT, albumin, and LDH were useful markers of severity, and hemostatic abnormalities were frequently observed in patients in the severe disease stage.
Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes
Authors: Kaczmarek-Ryś Marta , Hryhorowicz Szymon Tytus , Lis Emilia , Banasiewicz Tomasz , Paszkowski Jacek , Borejsza-Wysocki Maciej , Walkowiak Jarosław , Cichy Wojciech , Krokowicz Piotr , Czkwianianc Elżbieta , Hnatyszyn Andrzej , Krela-Kaźmierczak Iwona , Dobrowolska Agnieszka , Słomski Ryszard , Pławski Andrzej
Published: August 2021

The genetic background and the determinants influencing the disease form, course, and onset of inflammatory bowel disease (IBD) remain unresolved. We aimed to determine the NOD2 gene haplotypes and their relationship with IBD occurrence, clinical presentation, and onset, analyzing a cohort of 578 patients with IBD, including children, and 888 controls. Imaging or endoscopy with a histopathological confirmation was used to diagnose IBD. Genotyping was performed to assess the differences in genotypic and allelic frequencies. Linkage disequilibrium was analyzed, and associations between haplotypes and clinical data were evaluated. We emphasized the prevalence of risk alleles in all analyzed loci in patients with Crohn disease (CD). Interestingly, c.2722G>C and c.3019_3020insC alleles were also overrepresented in ulcerative colitis (UC). T-C-G-C-insC, T-C-G-T-insC, and T-T-G-T-wt haplotypes were correlated with the late-onset form of CD (OR = 23.01, 5.09, and 17.71, respectively), while T-T-G-T-wt and C-C-G-T-wt were prevalent only in CD children (OR = 29.36, and 12.93, respectively; p-value = 0.001). In conclusion, the presence of c.3019_3020insC along with c.802C>T occurred as the most fundamental contributing diplotype in late-onset CD form, while in CD children, the mutual allele in all predisposing haplotypes was the c.2798 + 158T. Identifying the unique, high-impact haplotypes supports further studies of the NOD2 gene, including haplotypic backgrounds.
BK Virus and Cytomegalovirus Coinfections in Kidney Transplantation and Their Impact on Allograft Loss
Authors: Herrera Sabina , Bernal-Maurandi Javier , Cofan Frederic , Ventura Pedro , Marcos Maria Angeles , Linares Laura , Cuesta Genoveva , Diekmann Fritz , Moreno Asunción , Bodro Marta
Published: August 2021

We aimed to ascertain the interaction and effects of combined reactivations of BK virus and cytomegalovirus on kidney graft function. All consecutive kidney transplant recipients (KTR) between 2003 and 2016 were included. Of 1976 patients who received a kidney transplant, 23 (1.2%) presented BKV-associated nephropathy (BKVAN). Factors independently associated with BKVAN were diabetes mellitus (odds ratios (OR) 3.895%, confidence intervals (CI) (1.4–10.5)), acute allograft rejection (OR 2.8 95%, CI (1.1–7.6)) and nephrostomy requirement (OR 4.195%, CI (1.3–13)). Cytomegalovirus infection was diagnosed in 19% of KTR patients. Recipients with BKVAN presented more frequently with cytomegalovirus (CMV) infection compared to patients without BKVAN (39% vs. 19%, p = 0.02). Acute allograft rejection (OR 2.95%, CI (1.4–2.4)) and nephrostomy requirement (OR 2.95%, CI (1.2–3)) were independently associated with CMV infection. Sixteen patients (69%) with BKVAN had graft dysfunction at one-year post-transplant and eight of them (35%) lost their graft. Patients presenting with BKVAN and graft loss presented more frequently a cytomegalovirus infection (OR 2.295%, CI (1.3–4.3)). In conclusion, we found a relation between CMV infection and graft loss in patients presenting BKVAN, suggesting that patients with CMV reactivation should be actively screened for BKV.
Morbidity and Mortality in Patients over 90 Years of Age Following Posterior Stabilization for Acute Traumatic Odontoid Type II Fractures: A Retrospective Study with a Mean Follow-Up of Three Years
Authors: Issa Mohammed , Kiening Karl L. , Unterberg Andreas W. , Scherer Moritz , Younsi Alexander , Fedorko Stepan , Oskouian Rod J. , Chapman Jens R. , Ishak Basem
Published: August 2021

Odontoid type II fractures represent the most common cervical spine injuries in the elderly. The decision for surgical treatment in very elderly patients is still controversial. The aim of this study was to assess morbidity and mortality in patients over 90 years of age undergoing CT-guided posterior stabilization for unstable odontoid type II fractures. A total of 15 patients with an acute traumatic odontoid type II fracture who received surgical treatment for unstable odontoid type II fractures were retrospectively analyzed. Complications, morbidity, and mortality as well as length of ICU and hospital stay were determined. Clinical follow-up evaluation was based on outpatient presentation and information from family members and general practitioners. Finally, we conducted a comparison of complications rates between patients over 90 years of age and patients between 65 and 89 years old with a type II odontoid fracture after CT-guided posterior stabilization in our institution. The mean age was 91.4 years. Patients were predominately female (87%). In-hospital deaths did not occur. The average length of the hospital stay was 13.4 days and 1.9 days for the ICU. Blood transfusion was necessary in two patients (13%). Two patients (13%) developed urinary tract infection, one patient (7%) a delirium, and another epistaxis (7%). One patient (7%) developed pneumonic sepsis and fully recovered within several weeks. The mean follow-up was 36 months (range 9–72 months). Implant-related complications developed in one patient (7%). Five patients died during the follow-up period, with an average time to death of 26.6 months. Postoperative bracing was not needed in any of the patients. Posterior stabilization of unstable odontoid fractures type II using CT-guided navigation in patients over 90 years of age is a safe and effective procedure with low complications and mortality rates.
Efficacy of Remdesivir-Containing Therapy in Hospitalized COVID-19 Patients: A Prospective Clinical Experience
Authors: Russo Alessandro , Binetti Erica , Borrazzo Cristian , Cacciola Elio Gentilini , Battistini Luigi , Ceccarelli Giancarlo , Mastroianni Claudio Maria , d’Ettorre Gabriella
Published: August 2021

Objectives: Remdesivir is currently approved for the treatment of COVID-19. The recommendation for using remdesivir in patients with COVID-19 was based on the in vitro and in vivo activity of this drug against SARS-CoV-2. Methods: This was a prospective observational study conducted on a population of patients hospitalized for COVID-19. The primary endpoint of this study was the impact of remdesivir-containing therapy on 30-day mortality; the secondary endpoint was the impact of remdesivir-containing therapy on the need for high-flow oxygen therapy (HFNC), non-invasive ventilation (NIV), or mechanical ventilation. The data were analyzed after propensity score matching. Results: A total of 407 patients with SARS-CoV-2 pneumonia were consecutively enrolled. Out of these, 294 (72.2%) were treated with remdesivir and 113 (27.8%) were not. Overall, 61 patients (14.9%) were treated during hospitalization with HFNC, NIV, or mechanical ventilation, while 30-day mortality was observed in 21 patients (5.2%). Univariate analysis of patients treated with remdesivir or not showed no differences in 30-day mortality (4% vs. 6%, p = 0.411) in the two study groups. Cox regression analysis, after propensity score matching, showed that therapies, including remdesivir-containing therapy, were not statistically associated with 30-day survival or mortality. The Kaplan–Meier curves of 30-day survival in patients treated with remdesivir or not before (p = 0.24) and after (p = 0.88) propensity score matching showed no differences between the two study groups. Finally, patients treated with remdesivir or not showed the same need for HFNC/NIV or mechanical ventilation. Conclusions: This real-life experience of remdesivir use in hospitalized patients with COVID-19 was not associated with significant increases in rates of survival or reduced use of HFNC/NIV or mechanical ventilation compared with patients treated with other therapies not including remdesivir.
The Role of the Functional Head Impulse Test with and without Optokinetic Stimuli in Vestibular Migraine and Acute Unilateral Vestibulopathy: Discovering a Dynamic Visual Dependence
Authors: Casani Augusto Pietro , Lazzerini Francesco , Marconi Ottavia , Vernassa Nicola
Published: August 2021

(1) Background: Visually induced vertigo (i.e., vertigo provoked by moving visual scenes) can be considered a noticeable feature of vestibular migraines (VM) and can be present in patients suffering from acute unilateral vestibulopathy (AUV). Hypersensitivity to moving or conflicting visual stimulation is named visual dependence. (2) Methods: Visuo-vestibular interactions were analyzed via the functional Head Impulse Test (fHIT) with and without optokinetic stimulation (o-fHIT) in 25 patients with VM, in 20 subjects affected by AUV, and in 20 healthy subjects. We calculated the percentage of correct answers (%CA) without and with the addition of the optokinetic background (OB). (3) In VM groups, the %CA on the fHIT was 92.07% without OB and 73.66% with OB. A significant difference was found between %CA on the deficit side and that on the normal side in AUV, both without OB and with OB. (4) Conclusions: The fHIT results in terms of %CA with and without OB could be useful to identify the presence of a dynamic visual dependence, especially in patients suffering from VM. The difference in %CA with and without OB could provide instrumental support to help correctly identify subjects suffering from VM. We propose the use of the fHIT in clinical practice whenever there is a need to highlight a condition of dynamic visual dependence.
When SUV Matters: FDG PET/CT at Baseline Correlates with Survival in Soft Tissue and Ewing Sarcoma
Authors: Hack Ruben I. , Becker Anton S. , Bode-Lesniewska Beata , Exner G. Ulrich , Müller Daniel A. , Ferraro Daniela A. , Warnock Geoffrey I. , Burger Irene A. , Britschgi Christian
Published: August 2021

Introduction: The role of positron-emission tomography/computed-tomography (PET/CT) in the management of sarcomas and as a prognostic tool has been studied. However, it remains unclear which metric is the most useful. We aimed to investigate if volume-based PET metrics (Tumor volume (TV) and total lesions glycolysis (TLG)) are superior to maximal standardized uptake value (SUVmax) and other metrics in predicting survival of patients with soft tissue and bone sarcomas. Materials and Methods: In this retrospective cohort study, we screened over 52′000 PET/CT scans to identify patients diagnosed with either soft tissue, bone or Ewing sarcoma and had a staging scan at our institution before initial therapy. We used a Wilcoxon signed-rank to assess which PET/CT metric was associated with survival in different patient subgroups. Receiver-Operating-Characteristic curve analysis was used to calculate cutoff values. Results: We identified a total of 88 patients with soft tissue (51), bone (26) or Ewing (11) sarcoma. Median age at presentation was 40 years (Range: 9–86 years). High SUVmax was most significantly associated with short survival (defined as <24 months) in soft tissue sarcoma (with a median and range of SUVmax 12.5 (8.8–16.0) in short (n = 18) and 5.5 (3.3–7.2) in long survival (≥24 months) (n = 31), with (p = 0.001). Similar results were seen in Ewing sarcoma (with a median and range of SUVmax 12.1 (7.6–14.7) in short (n = 6) and 3.7 (3.5–5.5) in long survival (n = 5), with (p = 0.017). However, no PET-specific metric but tumor-volume was significantly associated (p = 0.035) with survival in primary bone sarcomas (with a median and range of 217 cm3 (186–349) in short survival (n = 4) and 60 cm3 (22–104) in long survival (n = 19), with (p = 0.035). TLG was significantly inversely associated with long survival only in Ewing sarcoma (p = 0.03). Discussion: Our analysis shows that the outcome of soft tissue, bone and Ewing sarcomas is associated with different PET/CT metrics. We could not confirm the previously suggested superiority of volume-based metrics in soft tissue sarcomas, for which we found SUVmax to remain the best prognostic factor. However, bone sarcomas should probably be evaluated with tumor volume rather than FDG PET activity.
An Intelligent Web Service Composition and Resource-Optimization Method Using K-Means Clustering and Knapsack Algorithms
Authors: Alhadid Issam , Khwaldeh Sufian , Al Rawajbeh Mohammad , Abu-Taieh Evon , Masa’deh Ra’ed , Aljarah Ibrahim
Published: August 2021

Service-oriented architecture (SOA) has emerged as a flexible software design style. SOA focuses on the development, use, and reuse of small, self-contained, independent blocks of code called web services that communicate over the network to perform a certain set of simple tasks. Web services are integrated as composite services to offer complex tasks and to provide the expected services and behavior in addition to fulfilling the clients’ requests according to the service-level agreement (SLA). Web service selection and composition problems have been a significant area of research to provide the expected quality of service (QoS) and to meet the clients’ expectations. This research paper presents a hybrid web service composition model to solve web service selection and composition problems and to optimize web services’ resource utilization using k-means clustering and knapsack algorithms. The proposed model aims to maximize the service compositions’ QoS and minimize the number of web services integrated within the service composition using the knapsack algorithm. Additionally, this paper aims to track the service compositions’ QoS attributes by evaluating and tracking the web services’ QoS using the reward function and, accordingly, use the k-means algorithm to decide to which cluster the web service belongs. The experimental results on a real dataset show the superiority and effectiveness of the proposed algorithm in comparison with the results of the state–action–reward–state–action (SARSA) and multistage forward search (MFS) algorithms. The experimental results show that the proposed model reduces the average time of the web service selection and composition processes to 37.02 s in comparison to 47.03 s for the SARSA algorithm and 42.72 s for the MFS algorithm. Furthermore, the average of web services’ resource utilization results increased by 4.68% using the proposed model in comparison to the resource utilization by the SARSA and MFS algorithms. In addition, the experimental results showed that the average number of service compositions using the proposed model improved by 26.04% compared with the SARSA and MFS algorithms.
On the Amplitude Amplification of Quantum States Corresponding to the Solutions of the Partition Problem
Authors: Mezzini Mauro , Paulet Jose J. , Cuartero Fernando , Cruz Hernan I. , Pelayo Fernando L.
Published: August 2021

In this paper we investigate the effects of a quantum algorithm which increases the amplitude of the states corresponding to the solutions of the partition problem by a factor of almost two. The study is limited to one iteration.
The Reducibility Concept in General Hyperrings
Authors: Cristea Irina , Kankaraš Milica
Published: August 2021

By using three equivalence relations, we characterize the behaviour of the elements in a hypercompositional structure. With respect to a hyperoperation, some elements play specific roles: their hypercomposition with all the elements of the carrier set gives the same result; they belong to the same hypercomposition of elements; or they have both properties, being essentially indistinguishable. These equivalences were first defined for hypergroups, and here we extend and study them for general hyperrings—that is, structures endowed with two hyperoperations. We first present their general properties, we define the concept of reducibility, and then we focus on particular classes of hyperrings: the hyperrings of formal series, the hyperrings with P-hyperoperations, complete hyperrings, and (H,R)-hyperrings. Our main aim is to find conditions under which these hyperrings are reduced or not.