bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol, Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents, and Carbonic Anhydrases I, II, VII, IX, and XII Inhibitors
Authors: Havránková Eva , Garaj Vladimír , Mascaretti Šárka , Angeli Andrea , Soldánová Zuzana , Kemka Miroslav , Motyčka Jozef , Brázdová Marie , Csöllei Jozef , Jampílek Josef , Supuran Claudiu T.
Published: December 2021

A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs was synthesized as potential human carbonic anhydrase (hCA) inhibitors. The compounds were evaluated on their inhibition of tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II. While the test compounds had only a negligible effect on physiologically important isoenzymes, many of the studied compounds significantly affected the hCA IX isoenzyme. Several compounds showed activity against hCA XII; (E)-4-{2-[(4-[(2,3-dihydroxypropyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (31) and (E)-4-{2-[(4-[(4-hydroxyphenyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (32) were the most effective inhibitors with KIs = 4.4 and 5.9 nM, respectively. In addition, the compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. (E)-4-[2-({4-[(4-cinnamoylphenyl)amino]-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)ethyl]benzenesulfonamide (21) (MIC = 26.33 µM) and derivative 32 (MIC range 13.80–55.20 µM) demonstrated the highest activity against all tested strains. The most active compounds were evaluated for their cytotoxicity against the Human Colorectal Tumor Cell Line (HCT116 p53 +/+). Only 4,4’-[(6-chloro-1,3,5-triazin-2,4-diyl)bis(iminomethylene)]dibenzenesulfonamide (7) and compound 32 demonstrated an IC50 of ca. 6.5 μM; otherwise, the other selected derivatives did not show toxicity at concentrations up to 50 µM. The molecular modeling and docking of active compounds into various hCA isoenzymes, including bacterial carbonic anhydrase, specifically α-CA present in VRE, was performed to try to outline a possible mechanism of selective anti-VRE activity.
Multi-Omics Approach Profiling Metabolic Remodeling in Early Systolic Dysfunction and in Overt Systolic Heart Failure
Authors: Chaanine Antoine H. , Higgins LeeAnn , Markowski Todd , Harman Jarrod , Kachman Maureen , Burant Charles , Navar L. Gabriel , Busija David , Delafontaine Patrice
Published: December 2021

Metabolic remodeling plays an important role in the pathophysiology of heart failure (HF). We sought to characterize metabolic remodeling and implicated signaling pathways in two rat models of early systolic dysfunction (MOD), and overt systolic HF (SHF). Tandem mass tag-labeled shotgun proteomics, phospho-(p)-proteomics, and non-targeted metabolomics analyses were performed in left ventricular myocardium tissue from Sham, MOD, and SHF using liquid chromatography–mass spectrometry, n = 3 biological samples per group. Mitochondrial proteins were predominantly down-regulated in MOD (125) and SHF (328) vs. Sham. Of these, 82% (103/125) and 66% (218/328) were involved in metabolism and respiration. Oxidative phosphorylation, mitochondrial fatty acid β-oxidation, Krebs cycle, branched-chain amino acids, and amino acid (glutamine and tryptophan) degradation were highly enriched metabolic pathways that decreased in SHF > MOD. Glycogen and glucose degradation increased predominantly in MOD, whereas glycolysis and pyruvate metabolism decreased predominantly in SHF. PKA signaling at the endoplasmic reticulum–mt interface was attenuated in MOD, whereas overall PKA and AMPK cellular signaling were attenuated in SHF vs. Sham. In conclusion, metabolic remodeling plays an important role in myocardial remodeling. PKA and AMPK signaling crosstalk governs metabolic remodeling in progression to SHF.
Wrapping Trust for Interoperability: A Preliminary Study of Wrapped Tokens
Authors: Caldarelli Giulio
Published: December 2021

Blockchains are traditionally blind to the real world. This implies reliance on third parties called oracles when extrinsic data are needed for smart contracts. Oracle implementation, however, is still controversial and debated due to the reintroduction of trust and a single point of failure. The blindness to the real world also makes blockchains unable to communicate with each other, preventing any form of interoperability. This limitation prevents, for example, liquidity held in Bitcoin from flowing into DeFi applications. An early approach to the interoperability issue is constituted by “wrapped tokens”, representing blockchain native tokens issued on a non-native blockchain. Similar to how oracles reintroduce trust and a single point of failure, the issuance of wrapped tokens involves third parties whose characteristics need to be considered when evaluating the advantages of “crossing-chains”. This paper provides an overview of the available wrapped tokens and the main issuing procedures. Benefits, limitations, and implications for trust are listed and discussed.
Risk-Based Criticality Assessment for Smart Critical Infrastructures
Authors: Almaleh Abdulaziz , Tipper David
Published: December 2021

Today, critical infrastructure is more interconnected, which allows more vulnerabilities in the case of disasters. In addition, the effect of one infrastructure can lead to one or more cascading failures in another infrastructure due to the dependency complexity between them. This article introduces a holistic approach using network indicators and machine learning to better understand the geographical representation of critical infrastructure. Previous work on a similar model was based on a single measure; such as in fashion, this paper introduces four measures utilized to identify the most vital geographic zone in the city. The model aims to increase resilience, focusing on the preparedness phase by assessing the essential nodes of infrastructure, which allows more space to adopt risk mitigation strategies before any disturbance event. Holding in-depth knowledge of the vital zones of small scales and accordingly ranking them will positively improve the overall system resilience.
Nanofluid Transport through a Complex Wavy Geometry with Magnetic and Permeability Effects
Authors: Iqbal Muhammad Saleem , Ghaffari Abuzar , Riaz Arshad , Mustafa Irfan , Raza Muhammad
Published: December 2021

The current article incorporates the numerical investigation of heat exchange rate and skin friction carried out through nanofluid saturated with thermally balanced porous medium over a rough horizontal surface that follows the sinusoidal waves. The effects of the external magnetic field are discussed by managing the magnetic field strength applied normally to the flow pattern. The occurring partial differential governing equations are grasped through a strong numerical scheme of the Keller box method (KBM) against the various parameters. The findings are elaborated through tables and diagrams of velocity, temperature, skin friction, Nusselt number, streamlines, and heat lines. The percentage increase in Nusselt number and coefficient of skin friction over the flat and wavy surface is calculated which leads to the conclusion that the copper (Cu) nanoparticles are better selected as compared to the silver (Ag) for heat transfer enhancement. It is also evident from sketches that the current analysis can be used to enhance the surface drag force by means of nanoparticles. It is a matter of interest that the magnetic field can be used to manage the heat transfer rate in such a complicated surface flow. The current readings have been found accurate and valid when compared with the existing literature.
Tidal Volume in Pediatric Ventilation: Do You Get What You See?
Authors: Koomen Erik , Nijman Joppe , Nieuwenstein Ben , Kappen Teus
Published: December 2021

Mechanical ventilators are increasingly evolving into computer-driven devices. These technical advancements have impact on clinical decisions in pediatric intensive care units (PICUs). A good understanding of the design of mechanical ventilators can improve clinical care. Tidal volume (TV) is one of the corner stones of ventilation: multiple technical factors influence the TV and, thus, influence clinical decision making. Ventilator manufacturers make various design choices regarding the phase, site and conditions of TV measurement as well as algorithmic processing choices. Such choice may impact the measurement and subsequent display of TV. A software change of the TV measuring algorithm of the SERVO-i® (Getinge, Solna, Sweden) at the PICU of the University Medical Centre Utrecht was studied in a prospective cohort. It showed, as example, a clinically significant impact of 8% difference in reported TV. Design choices in both the hardware and software of mechanical ventilators can have a clinically relevant impact on the measurement of tidal volume. In our search for the optimal TV for lung-protective ventilation, such choices should be taken into account.
Osteopathic Manipulation of the Sphenopalatine Ganglia Versus Sham Manipulation, in Obstructive Sleep Apnoea Syndrom: A Randomised Controlled Trial
Authors: Attali Valérie , Jacq Olivier , Martin Karine , Arnulf Isabelle , Similowski Thomas
Published: December 2021

(1) Background: osteopathic manipulation of the sphenopalatine ganglia (SPG) blocks the action of postganglionic sensory fibres. This neuromodulation can reduce nasal obstruction and enhance upper airway stability. We investigated the manipulation of the SPG in 31 patients with obstructive sleep apnoea syndrome (OSAS); (2) Methods: Randomised, controlled, double-blind, crossover study. Participants received active (AM), then sham manipulation (SM), or vice versa. The primary endpoint was apnoea-hypopnoea index (AHI). Secondary endpoints were variation of nasal obstruction evaluated by peak nasal inspiratory flow (PNIF) and upper airways stability evaluated by awake critical closing pressure [awake Pcrit]), at 30 min and 24 h. Schirmer’s test and pain were assessed immediately post-manipulation. Tactile/gustatory/olfactory/auditory/nociceptive/visual sensations were recorded. Adverse events were collected throughout. (3) Results: SPG manipulation did not reduce AHI (p = 0.670). PNIF increased post-AM but not post-SM at 30 min (AM-SM: 18 [10; 38] L/min, p = 0.0001) and 24 h (23 [10; 30] L/min, p = 0.001). There was no significant difference on awake Pcrit (AM-SM) at 30 min or 24 h). Sensations were more commonly reported post-AM (100% of patients) than post-SM (37%). Few adverse events and no serious adverse events were reported. (4) Conclusions: SPG manipulation is not supported as a treatment for OSAS but reduced nasal obstruction. This effect remains to be confirmed in a larger sample before using this approach to reduce nasal congestion in CPAP-treated patients or in mild OSAS.
Non-Surgical Strategies for Assisting Closure of Pharyngocutaneous Fistula after Total Laryngectomy: A Systematic Review of the Literature
Authors: Locatello Luca Giovanni , Licci Giuseppe , Maggiore Giandomenico , Gallo Oreste
Published: December 2021

Background: Pharyngocutaneous fistula (PCF) is a frequent complication after total laryngectomy, with an incidence of up to 65%. Many conservative or invasive approaches are available and the choice among them is usually made on a case-by-case basis. The aim of the present review is to critically summarize the available evidence of the effectiveness of the non-surgical management of PCF. Methods: A systematic review and a meta-analysis of the literature were conducted, according to the PRISMA guidelines. Studies investigating botulinum toxin therapy, scopolamine transdermal patch, hyperbaric oxygen therapy (HBOT), and negative pressure wound therapy (NPWT) were assessed. Complete fistula closure after the initiation of non-surgical treatment was the main outcome. Results: After the application of selection criteria, a total of seven articles and 27 patients were included in the present review. All the eligible studies were descriptive case series, while only one article used a standard group as a comparison. The mean age was 63.3 and 14 patients (51.9%) had previously received RT. The reported comorbidities were diabetes, ischemic heart disease, hypertension, dyslipidemia, COPD, and atrial fibrillation. With a mean healing time of 25.0 days, the overall success rate was 92.6%. Conclusions: Non-surgical treatment of PCF is only based on the experience of small series. Although success rates seem promising, the absence of properly designed comparative studies does not allow us, at present, to identify ideal candidates for these non-invasive management strategies for PCF.
Virtual Bronchoscopy Planner and Radial-EBUS Guided Biopsy for Organizing Pneumonia Diagnosis
Authors: Lachkar Samy , Salaün Mathieu , Perrot Loic , Gervereau Diane , De Marchi Marielle , Le Bouar Gurvan , Morisse-Pradier Helene , Dominique Stephane , Piton Nicolas , Guisier Florian , Thiberville Luc
Published: December 2021

Background: The diagnosis of organizing pneumonia (OP) often requires histological confirmation. The aim of this retrospective study was to evaluate the diagnostic yield and complication rate of radial endobronchial ultrasound (r-EBUS) for OP. Methods: All patients who had r-EBUS as a first diagnostic procedure for a peripheral pulmonary lesion at Rouen University Hospital, France, between April 2008 and December 2020 were included. Cases without a final diagnosis of OP or follow-up were excluded. Patients, lesions, and r-EBUS characteristics were retrospectively analyzed. Results: 2735 r-EBUS procedures were performed, and 33 cases with final OP could be analyzed. Procedures were performed under local anesthesia in 28/33 cases (85%). Among the 33 final OP cases, 17 were considered cryptogenic, and 16 secondary. The lesions were patchy alveolar opacities in 23 cases (70%), masses or pulmonary nodules in 8 cases (24%), and diffuse infiltrative opacities in 2 cases (6%). A bronchus sign on CT scan was found in all cases. In 22 cases (67%), a histopathological diagnosis was obtained from the r-EBUS samples. In 4 cases (12%), histopathological diagnosis was made by surgery, and in 7 cases (21%) the diagnosis was made based on clinical, radiological, and evolution features. An ultrasound image was found in 100% (22/22) of cases in the r-EBUS positive (r-EBUS+) group vs. 60% (6/10) in the r-EBUS negative (r-EBUS-) group, respectively (p < 0.002). The diagnostic yield of r-EBUS for OP was 67% and increased to 79% (22/28) when an ultrasound image was obtained. The median time between CT scan and r-EBUS procedure was 14 days (3–94): 11.5 days in the r-EBUS+ group and 22 days in the r-EBUS- group (p < 0.0001). No severe complications were reported. Conclusion: r-EBUS, when performed shortly after a CT scan showing a bronchus sign, is an efficient and safe technique for OP diagnosis.
Changes in Inflammatory Markers after Administration of Tocilizumab in COVID-19: A Single-Center Retrospective Study
Authors: Olewicz-Gawlik Anna , Ginter-Matuszewska Barbara , Kamiński Mikołaj , Adamek Agnieszka , Bura Maciej , Mozer-Lisewska Iwona , Kowala-Piaskowska Arleta
Published: December 2021

The COVID-19 pandemic requires the development of effective methods for the treatment of severe cases. We aimed to describe clinical outcomes and changes in inflammatory markers in Polish patients treated with tocilizumab. The medical charts of SARS-CoV-2-positive patients treated in the Department of Infectious Diseases between 4 March and 2 September 2020 were retrospectively analyzed. The patients who received tocilizumab according to the Polish Association of Epidemiologists and Infectiologists guidelines were selected for the study. We identified 29 individuals who received tocilizumab, out of whom 11 (37.9%) died. The individuals who died had significantly higher maximal interleukin-6 (IL-6) and lactate dehydrogenase (LDH) serum levels than survivors. After administration of tocilizumab, further increase in LDH and IL-6 was a prognostic factor for unfavorable outcomes. Among inflammatory markers, 7-day mean of IL-6 serum concentration was the best predictor of death (cut-off: ≥417 pg/mL; area under ROC curve = 0.81 [95% Confidence Interval: 0.63–0.98]). The serum concentrations of inflammatory markers before administration of tocilizumab did not predict the outcome, whereas IL-6 and LDH measurements after administration of tocilizumab seemed to be of predictive value.
An Unprecedented Challenge: The North Italian Gastroenterologist Response to COVID-19
Authors: Tontini Gian Eugenio , Aldinio Giovanni , Nandi Nicoletta , Rimondi Alessandro , Consonni Dario , Iavarone Massimo , Cantù Paolo , Sangiovanni Angelo , Lampertico Pietro , Vecchi Maurizio
Published: December 2021

Background: COVID-19 pandemic has profoundly changed the activities and daily clinical scenarios, subverting organizational requirements of our Gastroenterology Units. AIM: to evaluate the clinical needs and outcomes of the gastroenterological ward metamorphosis during the COVID-19 outbreaks in a high incidence scenario. Methods: we compared the pertinence of gastroenterological hospitalization, modality of access, mortality rate, days of hospitalization, diagnostic and interventional procedures, age, Charlson comorbidity index, and frequency of SARS-CoV-2 infections in patients and healthcare personnel across the first and the second COVID-19 outbreaks in a COVID-free gastroenterological ward in the metropolitan area of Milan, that was hit first and hardest during the first COVID-19 outbreak since March 2020. Results: pertinence of gastroenterological hospitalization decreased both during the first and, to a lesser degree, the second SARS-CoV2 waves as compared to the pre-COVID era (43.6, 85.4, and 96.2%, respectively), as occurred to the admissions from domicile, while age, comorbidities, length of stay and mortality increased. Endoscopic and interventional radiology procedures declined only during the first wave. Hospitalized patients resulted positive to a SARS-CoV-2 nasopharyngeal swab in 10.2% of cases during the first COVID-19 outbreak after a median of 7 days since admission (range 1–15 days) and only 1 out of 318 patients during the second wave (6 days after admission). During the first wave, 19.5% of healthcare workers tested positive for SARS-CoV-2. Conclusions: a sudden metamorphosis of the gastroenterological ward was observed during the first COVID-19 outbreak with a marked reduction in the gastroenterological pertinence at the admission, together with an increase in patients’ age and multidisciplinary complexity, hospital stays, and mortality, and a substantial risk of developing a SARS-CoV-2 test positivity. This lesson paved the way for the efficiency of hospital safety protocols and admission management, which contributed to the improved outcomes recorded during the second COVID-19 wave.
Pretreatment Serum Levels of IL-1 Receptor Antagonist and IL-4 Are Predictors of Overall Survival in Multiple Myeloma Patients Treated with Bortezomib
Authors: Mikulski Damian , Robak Paweł , Perdas Ewelina , Węgłowska Edyta , Łosiewicz Aleksandra , Dróżdż Izabela , Jarych Dariusz , Misiewicz Małgorzata , Szemraj Janusz , Fendler Wojciech , Robak Tadeusz
Published: December 2021

Multiple myeloma (MM) is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow with an elevation in monoclonal paraprotein, renal impairment, hypercalcemia, lytic bony lesions, and anemia. Immune cells and associated cytokines play a significant role in MM growth, progression, and dissemination. While some cytokines and their clinical significance are well described in MM biology, others remain relatively unknown. The present study examines the influence on progression-free survival (PFS) and overall survival (OS) by the serum levels of 27 selected cytokines in 61 newly diagnosed MM patients receiving first-line therapy with bortezomib-based regimens. The measurements were performed using a Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay and a MAGPIX Multiplex Reader, based on the Bio-Plex® 200 System (Bio-Rad). The following levels were determined: IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF. Most patients received a VCD chemotherapy regimen (bortezomib, cyclophosphamide, and dexamethasone). In the final multivariate model, IL-13 cytokine level (HR 0.1411, 95% CI: 0.0240–0.8291, p = 0.0302) and ASCT (HR 0.3722, 95% CI: 0.1826–0.7585, p = 0.0065) significantly impacted PFS. Furthermore, ASCT (HR 0.142, 95% CI: 0.046–0.438, p = 0.0007), presence of bone disease at diagnosis (HR 3.826, 95% CI: 1.471–9.949, p = 0.0059), and two cytokine levels—IL-1Ra (HR 1.017, 95% CI: 1.004–1.030, p = 0.0091) and IL-4 (HR 0.161, 95% CI: 0.037–0.698, p = 0.0147)—were independent predictors of OS. Three clusters of MM patients were identified with different cytokine profiles. In conclusion, serum pretreatment levels of IL-13 and IL-4 are predictors of better PFS and OS, respectively, whereas IL-1Ra pretreatment levels negatively impact OS in MM patients treated with bortezomib-based chemotherapy. Cytokine signature profile may have a potential influence on the outcome of patients treated with bortezomib.
Are Markers of Allergic Inflammation in Grass Pollen Allergy Influenced by H1 Antihistamines?
Authors: Bocsan Ioana Corina , Muntean Ioana Adriana , Miron Nicolae , Pintea Irena , Dobrican Carmen Teodora , Ureche Corina , Buzoianu Anca Dana , Deleanu Diana
Published: December 2021

Soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular adhesion molecule-1 (VCAM-1) play important roles in allergic rhinitis (AR). Treatment with H1 antihistamines improves AR symptoms and in vitro reduces the levels of adhesion molecules. The aim of the study was to evaluate serum levels of ICAM-1 and VCAM-1 in patients with AR to grass pollen and their response to different H1 antihistamines. Material and methods: A total of 50 patients with grass pollen AR were clinically and biologically evaluated. ICAM-1 and VCAM-1 serum levels were evaluated during pollen season before and after treatment with levocetirizine and desloratadine through the ELISA method. Results: ICAM-1, VCAM-1, eosinophils, and total IgE were elevated in patients with AR, compared with healthy subjects. Both antihistamines improved specific symptoms of AR and increased patients’ quality of life during pollen season after one month of treatment. H1 antihistamines reduced VCAM-1, ICAM-1, and total IgE after one-month treatment but not significantly. Patients with increased baseline values tend to remain with increased values after one-month AH1 treatment. Conclusions: ICAM-1 and sVCAM-1 levels are higher in patients with grass pollen-induced AR than healthy controls during pollen exposure. Their serum levels tend to remain at high values during pollen season despite antihistaminic therapy.
Hemiarch Versus Arch Replacement in Acute Type A Aortic Dissection: Is the Occam’s Razor Principle Applicable?
Authors: Vendramin Igor , Piani Daniela , Lechiancole Andrea , Sponga Sandro , Di Nora Concetta , Londero Francesco , Muser Daniele , Onorati Francesco , Bortolotti Uberto , Livi Ugolino
Published: December 2021

Background and aim of the study: In patients with acute Type A aortic dissection (A-AAD) whether repair should be limited to ascending aorta/hemiarch replacement or extended to include the aortic arch is still debated. We have analyzed our experience to compare outcomes of patients with A-AAD treated with these 2 different surgical strategies. Methods: From 2006 to 2020, a total of 213 patients have undergone repair of A-AAD at our Center; in 163 of them ascending aorta/hemiarch replacement (Group 1) and in 75 ascending aorta and arch replacement (Group 2) were performed. The primary endpoint was early survival and secondary endpoints late survival, freedom from late complications and reoperations. Patients were compared according to era of operation: 2006 to 2013 (Era 1) and 2014 to 2020 (Era 2). Results: Overall hospital mortality was 12% and 5% in Group 1 and 2; mortality remained stable in Era 1 and 2 for Group 1 (15%), while it decreased from 8% to 1% in Group 2 patients (p = 0.24). Actuarial survival at 5 and 10 years is 72 ± 4% and 49 ± 5% in Group 1 and 77 ± 6% and 66 ± 9% in Group 2 (p = 0.073). Actuarial freedom from reoperation in the entire series is 94 ± 2% and 92 ± 3% at 5 and 10 years. Freedom from reoperation at 5 and 10 years is 92 ± 2% and 89 ± 3% in Group 1 and 98 ± 1% at all intervals in Group 2 (p = 0.068). Conclusions: An aggressive approach to A-AAD provides superior long-term results without increasing mortality. Furthermore, arch replacement during A-AAD repair represents a more stable solution with lower incidence of late aortic-related complications. Immediate aortic arch replacement should be considered in the treatment of A-AAD especially in experienced centers.
Association between Nafamostat Mesylate and In-Hospital Mortality in Patients with Coronavirus Disease 2019: A Multicenter Observational Study
Authors: Inokuchi Ryota , Kuno Toshiki , Komiyama Jun , Uda Kazuaki , Miyamoto Yoshihisa , Taniguchi Yuta , Abe Toshikazu , Ishimaru Miho , Adomi Motohiko , Tamiya Nanako , Iwagami Masao
Published: December 2021

Nafamostat mesylate may be effective against coronavirus disease 2019 (COVID-19). However, it is not known whether its use is associated with reduced in-hospital mortality in clinical practice. We conducted a retrospective observational study to evaluate the effect of nafamostat mesylate in patients with COVID-19 using the Medical Data Vision Co. Ltd. hospital-based database in Japan. We compared patients with COVID-19 who were (n = 121) and were not (n = 15,738) administered nafamostat mesylate within 2 days of admission between January and December 2020. We conducted a 1:4 propensity score matching with multiple imputations for smoking status and body mass index and combined the 20 imputed propensity score-matched datasets to obtain the adjusted odds ratio for in-hospital mortality. Crude in-hospital mortality was 13.2% (16/121) and 5.0% (790/15,738), respectively. In the propensity score-matched analysis with multiple imputations, the adjusted odds ratio (use vs. no use of nafamostat mesylate) for in-hospital mortality was 1.27 (95% confidence interval: 0.61–2.64; p = 0.52). Sensitivity analyses showed similar results. The results of this retrospective observational study did not support an association between nafamostat mesylate and improved in-hospital outcomes in patients with COVID-19, although further studies with larger sample sizes are warranted to assess the generalizability of our findings.
Demographic and Clinical Overview of Hospitalized COVID-19 Patients during the First 17 Months of the Pandemic in Poland
Authors: Flisiak Robert , Rzymski Piotr , Zarębska-Michaluk Dorota , Rogalska Magdalena , Rorat Marta , Czupryna Piotr , Lorenc Beata , Ciechanowski Przemysław , Kozielewicz Dorota , Piekarska Anna , Pokorska-Śpiewak Maria , Sikorska Katarzyna , Tudrujek Magdalena , Bolewska Beata , Angielski Grzegorz , Kowalska Justyna , Podlasin Regina , Mazur Włodzimierz , Oczko-Grzesik Barbara , Zaleska Izabela , Szymczak Aleksandra , Frańczak-Chmura Paulina , Sobolewska-Pilarczyk Małgorzata , Kłos Krzysztof , Figlerowicz Magdalena , Leszczyński Piotr , Kucharek Izabela , Grabowski Hubert
Published: December 2021

Long-term analyses of demographical and clinical characteristics of COVID-19 patients can provide a better overview of the clinical course of the disease. They can also help understand whether changes in infection symptomatology, disease severity, and outcome occur over time. We aimed to analyze the demographics, early symptoms of infection, laboratory parameters, and clinical manifestation of COVID-19 patients hospitalized during the first 17 months of the pandemic in Poland (March 2020–June 2021). The patients’ demographical and clinical data (n = 5199) were extracted from the national SARSTer database encompassing 30 medical centers in Poland and statistically assessed. Patients aged 50–64 were most commonly hospitalized due to COVID-19 regardless of the pandemic period. There was no shift in the age of admitted patients and patients who died throughout the studied period. Men had higher C-reactive protein and interleukin-6 levels and required oxygenation and mechanical ventilation more often. No gender difference in fatality rate was seen, although the age of males who died was significantly lower. A share of patients with baseline SpO2 < 91%, presenting respiratory, systemic and gastrointestinal symptoms was higher in the later phase of a pandemic than in the first three months. Cough, dyspnea and fever were more often presented in men, while women had a higher frequency of anosmia, diarrhea, nausea and vomiting. This study shows some shifts in SARS-CoV-2 pathogenicity between March 2020 and July 2021 in the Polish cohort of hospitalized patients and documents various gender-differences in this regard. The results represent a reference point for further analyses conducted under the dominance of different SARS-CoV-2 variants.
Effectiveness of Sodium Acetate Treatment on the Mechanical Properties and Morphology of Natural Fiber-Reinforced Composites
Authors: Badagliacco Dionisio , Fiore Vincenzo , Sanfilippo Carmelo , Valenza Antonino
Published: December 2021

This paper aims to investigate the ability of an eco-friendly and cheap treatment based on sodium acetate solutions to improve the mechanical properties of flax fiber-reinforced composites. Flax fibers were treated for 5 days (i.e., 120 h) at 25 °C with mildly alkaline solutions at 5%, 10% and 20% weight content of the sodium salt. Quasi-static tensile and flexural tests, Charpy impact tests and dynamical mechanical thermal (DMTA) tests were carried out to evaluate the mechanical properties of the resulting composites. Fourier transform infrared analysis (FTIR) was used to evaluate the chemical modification on the fibers surface due to the proposed treatment, whereas scanning electron microscope (SEM) and helium pycnometry were used to get useful information about the morphology of composites. It was found that the treatment with 5% solution of sodium acetate leads to the best mechanical performance and morphology of flax fiber-reinforced composites. SEM analysis confirmed these findings highlighting that composites reinforced with flax fibers treated in 5% sodium acetate solution show an improved morphology compared to the untreated ones. On the contrary, detrimental effects on the morphology as well as on the mechanical performance of composites were achieved by increasing the salt concentration of the treating solution.
Sarcodia suieae Acetyl-Xylogalactan Regulates Nile Tilapia (Oreochromis niloticus) Tissue Phagocytotic Activity and Serum Indices
Authors: Pan Po-Kai , Wu Tsung-Meng , Wen Chiu-Ming , Chen Yin-Yu , Wu Yu-Sheng
Published: December 2021

Sarcodia suieae acetyl-xylogalactan was reported to induce macrophage polarisation, and could positively regulate macrophage activation. In this study, we evaluated the effect of Sarcodia suieae acetyl-xylogalactan on the Nile tilapia. First, we assessed the influence of acetyl-xylogalactan on the survival, glucose uptake, and phagocytic activity of tilapia head kidney (THK) melanomacrophage, and observed increased proliferation of these cells in the MTT assay after 12 and 24 h of treatment. Glucose uptake increased in THK melanomacrophage treated with 20 and 30 μg acetyl-xylogalactan for 24 h. Their phagocytic activity was positively enhanced following exposure to acetyl-xylogalactan. Nile tilapia were fed with acetyl-xylogalactan for 4 weeks. At the end of the experiment, Nile tilapia were sacrificed, and the lipopolysaccharide-induced liver and head-kidney apoptosis was examined under reducing conditions in comparison with controls. The phagocytic activities of liver and head-kidney cells were enhanced after 4 weeks of feeding. Blood biochemical analysis revealed a reduction in glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels after 4 weeks of feeding. Combined with in vitro and in vivo experiments results, the extracted S. suieae acetyl-xylogalactan could directly induce THK melanomacrophage proliferation, glucose uptake, and phagocytic activity. Acetyl-xylogalactan was able to induce Nile tilapia liver and head-kidney resident macrophage activity, and reduced LPS-induced liver and head-kidney cell apoptosis. S. suieae acetyl-xylogalactan may modulate Nile tilapia macrophage activation by polarising them into M1 macrophages to improve the Nile tilapia nonspecific immune response.
All-In-One: Microbial Response to Natural and Anthropogenic Forcings in a Coastal Mediterranean Ecosystem, the Syracuse Bay (Ionian Sea, Italy)
Authors: Caruso Gabriella , Giacobbe Maria Grazia , Azzaro Filippo , Decembrini Franco , Leonardi Marcella , Miserocchi Stefano , Cao Xiuyun , Song Chunlei , Zhou Yiyong
Published: December 2021

Bacterial and phytoplankton communities are known to be in close relationships, but how natural and anthropogenic stressors can affect their dynamics is not fully understood. To study the response of microbial communities to environmental and human-induced perturbations, phytoplankton and bacterial communities were seasonally monitored in a Mediterranean coastal ecosystem, Syracuse Bay, where multiple conflicts co-exist. Quali-quantitative, seasonal surveys of the phytoplankton communities (diatoms, dinoflagellates and other taxa), the potential microbial enzymatic activity rates (leucine aminopeptidase, beta-glucosidase and alkaline phosphatase) and heterotrophic culturable bacterial abundance, together with the thermohaline structure and trophic status in terms of nutrient concentrations, phytoplankton biomass (as Chlorophyll-a), and total suspended and particulate organic matter, were carried out. The aim was to integrate microbial community dynamics in the context of the environmental characterization and disentangle microbial patterns related to natural changes from those driven by the anthropic impact on this ecosystem. In spite of the complex relationships between the habitat characteristics, microbial community abundance and metabolic potential, in Syracuse Bay, the availability of organic substrates differently originated by the local conditions appeared to drive the distribution and activity of microbial assemblage. A seasonal pattern of microbial abundances was observed, with the highest concentrations of phytoplankton in spring and low values in winter, whereas heterotrophic bacteria were more abundant during the autumn period. The autumn peaks of the rates of enzymatic activities suggested that not only phytoplankton-derived but also allochthonous organic polymers strongly stimulated microbial metabolism. Increased microbial response in terms of abundance and metabolic activities was detected especially at the sites directly affected by organic matter inputs related to agriculture or aquaculture activities. Nitrogen salts such as nitrate, rather than orthophosphate, were primary drivers of phytoplankton growth. This study also provides insights on the different seasonal scenarios of water quality in Syracuse Bay, which could be helpful for management plans of this Mediterranean coastal environment.
Reconstruction of the Long-Term Dynamics of Particulate Concentrations and Solid–Liquid Distribution of Radiocesium in Three Severely Contaminated Water Bodies of the Chernobyl Exclusion Zone Based on Current Depth Distribution in Bottom Sediments
Authors: Konoplev Alexei , Laptev Gennady , Igarashi Yasunori , Derkach Hrigoryi , Protsak Valentin , Lisovyi Hlib , Korychenskyi Kyrylo , Kirieiev Serhii , Samoilov Dmitry , Nanba Kenji
Published: December 2021

Given the importance of understanding long-term dynamics of radionuclides in the environment in general, and major gaps in the knowledge of 137Cs particulate forms in Chernobyl exclusion zone water bodies, three heavily contaminated water bodies (Lakes Glubokoe, Azbuchin, and Chernobyl NPP Cooling Pond) were studied to reconstruct time changes in particulate concentrations of 137Cs and its apparent distribution coefficient Kd, based on 137Cs depth distributions in bottom sediments. Bottom sediment cores collected from deep-water sites of the above water bodies were sliced into 2 cm layers to obtain 137Cs vertical profile. Assuming negligible sediment mixing and allowing for 137Cs strong binding to sediment, each layer of the core was attributed to a specific year of profile formation. Using this method, temporal trends for particulate 137Cs concentrations in the studied water bodies were derived for the first time and they were generally consistent with the semiempirical diffusional model. Based on the back-calculated particulate 137Cs concentrations, and the available long-term monitoring data for dissolved 137Cs, the dynamics of 137Cs solid–liquid distribution were reconstructed. Importantly, just a single sediment core collected from a lake or pond many years after a nuclear accident seems to be sufficient to retrieve long-term dynamics of contamination.
The Mechanisms of the Transportation Land Transfer Impact on Economic Growth: Evidence from China
Authors: Zhang Mingzhi , Li Zhaocheng , Wang Xinpei , Li Jiajia , Liu Hongyu , Zhang Ying
Published: December 2021

Accessibility to transportation is a crucial factor for economic growth. Transportation land, defined as the land used to support transportation infrastructure, such as city and inter-city rail, ports, and air travel, is a critical element for constructing transportation facilities and has attracted increasing attention from researchers and policy makers. Transportation land transfer (TLT) is defined as the act by which the state transfers transportation land-use rights to a land user (collective or individual) within a certain period of time as the land owner (all land in China is owned by the state). The land user pays a land-use right transfer fee to the state. This article first reveals the multidimensional effect between TLT and economic growth based on data from China’s 30 provinces for 2007–2019. The study found the following. (1) A continuous increase in the availability of transportation land is vital to ensure sustainable economic growth, and the construction of transportation land between adjacent areas has positive spatial spillover effects. (2) These positive effects work through three mechanisms, i.e., increased employment, industrial interactions, and improvements in economic operational efficiency, with a time lag. (3) The positive effects of TLT on economic growth have significant heterogeneous moderating effects on the differences in the economic development stage, the level of industrial structure, and urbanization rate. The study expands the front-end to back-end analysis of land use, provides a reference for countries and regions at different stages of development to promote economic growth using transportation land construction, and presents beneficial insights for governments to efficiently avoid the mismatch of transportation land resources.
Exploring Development Trends of Terrestrial Ecosystem Health—A Case Study from China
Authors: Li Yingchao , Fan Zhiyuan , Li Zhenhao , Zhang Xuefang , Du Ruyu , Li Minghui
Published: December 2021

Terrestrial ecosystem health (TEH) is the basis of regional sustainability development. The state of TEH is an important research direction in the land science field. The purpose of this paper was to explore the development trends and influencing factors of the. By using the radial basis function (RBF), neural network model, geographic information system (GIS), and the comprehensive index method, this paper predicted the land ecological changes of Henan Province from 2007 to 2025 based on a comprehensive evaluation of the system. The results show that the TEH of Henan Province exhibited a general trend of improvement from 2007 to 2025. The predictions exhibited a tendency to fluctuate and increase, from “severe warning” to “moderate warning” and even to “no warning” state. The early warning index of the subsystem showed a fluctuating upward trend except for the press subsystem, which fluctuated between “extraordinary warning” and “heavy warning” states. The overall TEH level is improving but is largely dependent on effective corresponding measures. The health status of the land ecosystem in Henan Province is guaranteed to be stable due to improvements in rural residential incomes, mechanization levels of cultivated land, domestic sewage treatment rates, and the numbers of scientific and technological personnel per unit of land. The TEH is mainly restricted by the population densities, urbanization levels, inputs of fertilizers and pesticides, and average wastewater load factors of the land. To improve the health level of the land ecosystem, it is necessary to reduce the use of fertilizers and pesticides and to control the urbanization rate. At the same time, improving the level of forest coverage and the effective irrigation rate play a positive role in improving ecosystem health. The results provide a reference for land-use planning and management decisions.
Value and Quality in the Dialectics between Human and Urban Capital of the City Networks on the Land District Scale
Authors: Nasca Ludovica , Giuffrida Salvatore , Trovato Maria Rosa
Published: December 2021

This contribution proposes an inter-scalar and multi-polar analysis evaluation model of the territory of the Enna district, aimed at providing a robust axiological representation of the salient aspects of the general issue of internal areas, and therefore of the set of criticalities affecting them from the perspective of the human and urban capital they express. In the prospect of investigating the relations between urban and life quality—corresponding to the “city effect”—in the territorial context of each of the 20 municipalities of the Enna district, a hierarchical descriptive-valuation model was created, which coordinates a relevant amount of information units (data) and the corresponding attributes, indicators and indices that have been turned in aggregate value judgments attributed to each administrative land unit, from the perspectives of the criteria referred to as the main forms of the territorial capital. This is a multi-dimensional valuation model based on the Multi-Attribute Value Theory. Each survey and processing is mapped with different levels of detail at the scale of municipalities, census sections and cadastral land units. The outcome of this complex process of analysis and assessment provides multiple comparisons, revealing unexpected and sometimes counter-intuitive aspects in several municipalities, some of which are characterised by innovative prospects and opportunities for redevelopment of their historic centers. Correlations between information units at the different levels of the dendrogram have also indicated interesting trends and attitudes, whose comparisons can address territorial policies on both a local and provincial scale. Furthermore, the focus on the “cities network” is here assumed and proposed as the privileged point of observation of territory and the related aspects of the quality of life.
High Resolution Land Cover Integrating Copernicus Products: A 2012–2020 Map of Italy
Authors: De Fioravante Paolo , Strollo Andrea , Assennato Francesca , Marinosci Ines , Congedo Luca , Munafò Michele
Published: December 2021

The study involved an in-depth analysis of the main land cover and land use data available nationwide for the Italian territory, in order to produce a reliable cartography for the evaluation of ecosystem services. In detail, data from the land monitoring service of the Copernicus Programme were taken into consideration, while at national level the National Land Consumption Map and some regional land cover and land use maps were analysed. The classification systems were standardized with respect to the European specifications of the EAGLE Group and the data were integrated to produce a land cover map in raster format with a spatial resolution of 10 m. The map was validated and compared with the CORINE Land Cover, showing a significant geometric and thematic improvement, useful for a more detailed and reliable evaluation of ecosystem services. In detail, the map was used to estimate the variation in carbon storage capacity in Italy for the period 2012–2020, linked to the increase in land consumption
Comparison of Dosimetry Protocols for Electron Beam Radiotherapy Calibrations and Measurement Uncertainties
Authors: Elbashir Fawzia E. M. , Ksouri Wassim , Eisa Mohamed Hassan , Alanazi Sitah , Habbani Farouk , Sulieman Abdelmoneim , Bradley David A. , Suliman Ibrahim I.
Published: December 2021

This paper presents guidelines for the calibration of radiation beams that were issued by the International Atomic Energy Agency (IAEA TRS 398), the American Association of Physicists in Medicine (AAPM TG 51) and the German task group (DIN 6800-2). These protocols are based on the use of an ionization chamber calibrated in terms of absorbed dose to water in a standard laboratory’s reference quality beam, where the previous protocols were based on air kerma standards. This study aims to determine uncertainties in dosimetry for electron beam radiotherapy using internationally established high-energy radiotherapy beam calibration standards. Methods: Dw was determined in 6-, 12- and 18 MeV electron energies under reference conditions using three cylindrical and two plane-parallel ion chambers in concert with the IAEA TRS 398, AAPM TG 51 and DIN 6800-2 absorbed dose protocols. From mean measured Dw values, the ratio TRS 398/TG 51 was found to vary between 0.988 and 1.004, while for the counterpart TRS 398/DIN 6800-2 and TG 51/DIN 6800-2, the variation ranges were 0.991–1.003 and 0.997–1.005, respectively. For the cylindrical chambers, the relative combined uncertainty (k = 1) in absorbed dose measurements was 1.44%, while for the plane-parallel chambers, it ranged from 1.53 to 1.88%. Conclusions: A high degree of consistency was demonstrated among the three protocols. It is suggested that in the use of the presently determined dose conversion factors across the three protocols, dose intercomparisons can be facilitated between radiotherapy centres.
Amelioration of Alzheimer’s Disease by Gut-Pancreas-Liver-Brain Interaction in an App Knock-In Mouse Model
Authors: Minamisawa Mayumi , Sato Yuma , Ishiguro Eitarou , Taniai Tetsuyuki , Sakamoto Taiichi , Kawai Gota , Saito Takashi , Saido Takaomi C.
Published: December 2021

In this study, we observed disease progression, changes in the gut microbiota, and interactions among the brain, liver, pancreas, and intestine in a mouse model of Alzheimer’s disease (AD), in addition to attempting to inhibit disease progression through the dietary supplementation of L-arginine and limonoids. Wild-type mice (WC) and AD mice were fed a normal diet (AC), a diet supplemented with L-arginine and limonoids (ALA), or a diet containing only limonoids (AL) for 12–64 weeks. The normal diet-fed WC and AC mice showed a decrease in the diversity of the gut microbiota, with an increase in the Firmicutes/Bacteroidetes ratio, and bacterial translocation. Considerable bacterial translocation to the pancreas and intense inflammation of the pancreas, liver, brain, and intestinal tissues were observed in the AC mice from alterations in the gut microbiota. The ALA diet or AL diet-fed mice showed increased diversity of the bacterial flora and suppressed oxidative stress and inflammatory responses in hepatocytes and pancreatic cells, bacterial translocation, and neurodegeneration of the brain. These findings suggest that L-arginine and limonoids help in maintaining the homeostasis of the gut microbiota, pancreas, liver, brain, and gut in AD mice.