bluuebunny/crossref_metadata_2025 huggingface dataset:
SP600125 Enhances Temperature-Controlled Repeated Thermal Stimulation-Induced Neurite Outgrowth in PC12-P1F1 Cells
Authors: Luo You-Ran , Kudo Tada-aki , Tominami Kanako , Izumi Satoshi , Tanaka Takakuni , Hayashi Yohei , Noguchi Takuya , Matsuzawa Atsushi , Nakai Junichi , Hong Guang , Wang Hang
Published: December 2022

This study evaluated the mechanism of temperature-controlled repeated thermal stimulation (TRTS)-mediated neuronal differentiation. We assessed the effect of SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, on neuronal differentiation of rat PC12-P1F1 cells, which can differentiate into neuron-like cells by exposure to TRTS or neurotrophic factors, including bone morphogenetic protein (BMP) 4. We evaluated neuritogenesis by incubating the cells under conditions of TRTS and/or SP600125. Cotreatment with SP600125 significantly enhanced TRTS-mediated neuritogenesis, whereas that with other selective mitogen-activated protein kinase (MAPK) inhibitors did not—e.g., extracellular signal-regulated kinase (ERK)1/2 inhibitor U0126, and p38 MAPK inhibitor SB203580. We tried to clarify the mechanism of SP600125 action by testing the effect of U0126 and the BMP receptor inhibitor LDN193189 on the SP600125-mediated enhancement of intracellular signaling. SP600125-enhanced TRTS-induced neuritogenesis was significantly inhibited by U0126 or LDN193189. Gene expression analysis revealed that TRTS significantly increased β3-Tubulin, MKK3, and Smad7 gene expressions. Additionally, Smad6 and Smad7 gene expressions were substantially attenuated through SP600125 co-treatment during TRTS. Therefore, SP600125 may partly enhance TRTS-induced neuritogenesis by attenuating the negative feedback loop of BMP signaling. Further investigation of the mechanisms underlying the effect of SP600125 during TRTS-mediated neuritogenesis may contribute to the future development of regenerative neuromedicine.
Clustered DNA Damage Patterns after Proton Therapy Beam Irradiation Using Plasmid DNA
Authors: Souli Maria P. , Nikitaki Zacharenia , Puchalska Monika , Brabcová Kateřina Pachnerová , Spyratou Ellas , Kote Panagiotis , Efstathopoulos Efstathios P. , Hada Megumi , Georgakilas Alexandros G. , Sihver Lembit
Published: December 2022

Modeling ionizing radiation interaction with biological matter is a major scientific challenge, especially for protons that are nowadays widely used in cancer treatment. That presupposes a sound understanding of the mechanisms that take place from the early events of the induction of DNA damage. Herein, we present results of irradiation-induced complex DNA damage measurements using plasmid pBR322 along a typical Proton Treatment Plan at the MedAustron proton and carbon beam therapy facility (energy 137–198 MeV and Linear Energy Transfer (LET) range 1–9 keV/μm), by means of Agarose Gel Electrophoresis and DNA fragmentation using Atomic Force Microscopy (AFM). The induction rate Mbp−1 Gy−1 for each type of damage, single strand breaks (SSBs), double-strand breaks (DSBs), base lesions and non-DSB clusters was measured after irradiations in solutions with varying scavenging capacity containing 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris) and coumarin-3-carboxylic acid (C3CA) as scavengers. Our combined results reveal the determining role of LET and Reactive Oxygen Species (ROS) in DNA fragmentation. Furthermore, AFM used to measure apparent DNA lengths provided us with insights into the role of increasing LET in the induction of highly complex DNA damage.
Isogenic Human-Induced Pluripotent Stem-Cell-Derived Cardiomyocytes Reveal Activation of Wnt Signaling Pathways Underlying Intrinsic Cardiac Abnormalities in Rett Syndrome
Authors: Ng Kwong-Man , Ding Qianqian , Tse Yiu-Lam , Chou Oscar Hou-In , Lai Wing-Hon , Au Ka-Wing , Lau Yee-Man , Ji Yue , Siu Chung-Wah , Tang Clara Sze-Man , Colman Alan , Tsang Suk-Ying , Tse Hung-Fat
Published: December 2022

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by MeCP2 mutations. Nonetheless, the pathophysiological roles of MeCP2 mutations in the etiology of intrinsic cardiac abnormality and sudden death remain unclear. In this study, we performed a detailed functional studies (calcium and electrophysiological analysis) and RNA-sequencing-based transcriptome analysis of a pair of isogenic RTT female patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) that expressed either MeCP2wildtype or MeCP2mutant allele and iPSC-CMs from a non-affected female control. The observations were further confirmed by additional experiments, including Wnt signaling inhibitor treatment, siRNA-based gene silencing, and ion channel blockade. Compared with MeCP2wildtype and control iPSC-CMs, MeCP2mutant iPSC-CMs exhibited prolonged action potential and increased frequency of spontaneous early after polarization. RNA sequencing analysis revealed up-regulation of various Wnt family genes in MeCP2mutant iPSC-CMs. Treatment of MeCP2mutant iPSC-CMs with a Wnt inhibitor XAV939 significantly decreased the β-catenin protein level and CACN1AC expression and ameliorated their abnormal electrophysiological properties. In summary, our data provide novel insight into the contribution of activation of the Wnt/β-catenin signaling cascade to the cardiac abnormalities associated with MeCP2 mutations in RTT.
Selective Role of TNFα and IL10 in Regulation of Barrier Properties of the Colon in DMH-Induced Tumor and Healthy Rats
Authors: Bekusova Viktoria , Zudova Tatiana , Fatyykhov Ilyas , Fedorova Arina , Amasheh Salah , Markov Alexander G.
Published: December 2022

Recently it has been reported that the tumor adjacent colon tissues of 1,2-dymethylhydrazine induced (DMH)-rats revealed a high paracellular permeability. We hypothesized that the changes might be induced by cytokines. Colorectal cancer is accompanied by an increase in tumor necrosis factor alpha (TNFα) and interleukin 10 (IL10) that exert opposite regulatory effects on barrier properties of the colon, which is characterized by morphological and functional segmental heterogeneity. The aim of this study was to analyze the level of TNFα and IL10 in the colon segments of DMH-rats and to investigate their effects on barrier properties of the proximal and distal parts of the colon in healthy rats. Enzyme immunoassay analysis showed decreased TNFα in tumors in the distal part of the colon and increased IL10 in proximal tumors and in non-tumor tissues. Four-hour intraluminal exposure of the colon of healthy rats with cytokines showed reduced colon barrier function dependent on the cytokine: TNFα decreased it mainly in the distal part of the colon, whereas IL10 decreased it only in the proximal part. Western blot analysis revealed a more pronounced influence of IL10 on tight junction (TJ) proteins expression by down-regulation of the TJ proteins claudin-1, -2 and -4, and up-regulation of occludin only in the proximal part of the colon. These data may indicate a selective role of the cytokines in regulation of the barrier properties of the colon and a prominent role of IL10 in carcinogenesis in its proximal part.
Therapeutic Applications for Oncolytic Self-Replicating RNA Viruses
Authors: Lundstrom Kenneth
Published: December 2022

Self-replicating RNA viruses have become attractive delivery vehicles for therapeutic applications. They are easy to handle, can be rapidly produced in large quantities, and can be delivered as recombinant viral particles, naked or nanoparticle-encapsulated RNA, or plasmid DNA-based vectors. The self-replication of RNA in infected host cells provides the means for generating much higher transgene expression levels and the possibility to apply substantially reduced amounts of RNA to achieve similar expression levels or immune responses compared to conventional synthetic mRNA. Alphaviruses and flaviviruses, possessing a single-stranded RNA genome of positive polarity, as well as measles viruses and rhabdoviruses with a negative-stranded RNA genome, have frequently been utilized for therapeutic applications. Both naturally and engineered oncolytic self-replicating RNA viruses providing specific replication in tumor cells have been evaluated for cancer therapy. Therapeutic efficacy has been demonstrated in animal models. Furthermore, the safe application of oncolytic viruses has been confirmed in clinical trials. Multiple myeloma patients treated with an oncolytic measles virus (MV-NIS) resulted in increased T-cell responses against the measles virus and several tumor-associated antigen responses and complete remission in one patient. Furthermore, MV-CEA administration to patients with ovarian cancer resulted in a stable disease and more than doubled the median overall survival.
Agmatine Administration Effects on Equine Gastric Ulceration and Lameness
Authors: Taguchi Takashi , Morales Yniguez Francisco J. , Takawira Catherine , Andrews Frank M. , Lopez Mandi J.
Published: December 2022

Osteoarthritis (OA) accounts for up to 60% of equine lameness. Agmatine, a decarboxylated arginine, may be a viable option for OA management, based on reports of its analgesic properties. Six adult thoroughbred horses, with lameness attributable to thoracic limb OA, received either daily oral phenylbutazone (6.6 mg/kg), agmatine sulfate (25 mg/kg) or a control for 30 days, with 21-day washout periods between treatments. Subjective lameness, thoracic limb ground reaction forces (GRF), plasma agmatine and agmatine metabolite levels were evaluated using an established rubric, a force platform, and mass spectrometry, respectively, before, during and after each treatment period. Gastric ulceration and plasma chemistries were evaluated before and after treatments. Braking GRFs were greater after 14 and 29 days of agmatine compared to phenylbutazone administration. After 14 days of phenylbutazone administration, vertical GRFs were greater than for agmatine or the control. Glandular mucosal ulcer scores were lower after agmatine than phenylbutazone administration. Agmatine plasma levels peaked between 30 and 60 min and were largely undetectable by 24 h after oral administration. In contrast, plasma citric acid levels increased throughout agmatine administration, representing a shift in the metabolomic profile. Agmatine may be a viable option to improve thoracic limb GRFs while reducing the risk of glandular gastric ulceration in horses with OA.
HCV-HIV Chronic Coinfection Prevalence in Amazon Region
Authors: Lobo Marcio Nahum , Irias Susan Denice Flores , Neto Pedro Leão Fontes , Avelino Maria Eduarda Sousa , da Silva Torres Maria Karoliny , de Carvalho Souza Marlinda , Fonseca Ricardo Roberto Souza , Freitas Pedro Eduardo Bonfim , Nunes Heloisa Marceliano , de Araújo Júnior José Raul Rocha , de Brito Dickson Ciro Nascimento , Oliveira-Filho Aldemir Branco , Machado Luiz Fernando Almeida
Published: December 2022

Hepatitis C virus (HCV) infection is an important public health problem, especially in areas with a low human development index such as the Amazon region. This study aimed to identify the prevalence and genotypes of HCV among people living with HIV (PLWH), both neglected chronic diseases in the Amazon region. From March 2016 to June 2017, 433 PWLH were attended to at two sexually transmitted infection referral centers in the city of Belém, in the Brazilian state of Pará in the Amazon region. All individuals were submitted to testing via the rapid immunochromatographic assay (RIA) for the qualitative detection of anti-HCV antibodies. Samples with anti-HCV antibodies were evaluated by reverse transcriptase polymerase chain reaction (RT-PCR), and samples with HCV RNA were subjected to nucleotide sequencing and phylogenetic analysis. Three (0.7%) PLWH had anti-HCV antibodies, and only one (0.2%) had HCV RNA (genotype 2); of these, 31 (7.1%) self-declared to have used drugs at least one time, and 12 (2.7%) regularly use injected drugs. One participant was elderly, single, heterosexual, with a history of unprotected sex and multiple sexual partners. This study detected a low prevalence of HCV infection and recorded the presence of HCV genotype 2 for the first time among PLWH in the Brazilian Amazon.
Impact of Lactate on 30-Day All-Cause Mortality in Patients with and without Out-of-Hospital Cardiac Arrest Due to Cardiogenic Shock
Authors: Rusnak Jonas , Schupp Tobias , Weidner Kathrin , Ruka Marinela , Egner-Walter Sascha , Forner Jan , Bertsch Thomas , Kittel Maximilian , Mashayekhi Kambis , Tajti Péter , Ayoub Mohamed , Behnes Michael , Akin Ibrahim
Published: December 2022

In patients with cardiogenic shock (CS) due to myocardial infarction, elevated lactate levels are known to be negative predictors. Studies regarding the prognostic impact in patients with CS complicated by out-of-hospital cardiac arrest (OHCA) are limited. Two hundred and sixty-three consecutive patients with CS were included. The prognostic value of lactate on days 1, 2, 3, 4 and 8 was tested stratified by OHCA and non-OHCA. Statistical analyses included the univariable t-test, Spearman’s correlation, C-statistics, Kaplan–Meier analyses, as well as multivariable mixed analysis of variance (ANOVA) and Cox proportional regression analyses. The primary endpoint of all-cause mortality occurred in 49.4% of the non-OHCA group and in 63.4% of the OHCA group. Multivariable regression models showed an association of lactate values with 30-day all-cause mortality in the non-OHCA (p = 0.024) and OHCA groups (p = 0.001). In Kaplan–Meier analyses, patients with lactate levels ≥ 4 mmol/L (log-rank p = 0.001) showed the highest risk for 30-day all-cause mortality in the non-OHCA as well as in the OHCA group. However, in C-statistics lactate on days 1 and 8 had a better discrimination for 30-day all-cause mortality in the OHCA group compared to the non-OHCA group. In conclusion, patients presenting with CS lactate levels showed a good prognostic performance, with and without OHCA. Especially, lactate levels on days 1 and 8 were more accurate in the discrimination for all-cause mortality in CS-patients with OHCA.
Inflammatory Bowel Disease Patients’ Acceptance for Switching from Intravenous Infliximab or Vedolizumab to Subcutaneous Formulation: The Nancy Experience
Authors: Remy Clotilde , Caron Bénédicte , Gouynou Celia , Haghnejad Vincent , Jeanbert Elodie , Netter Patrick , Danese Silvio , Peyrin-Biroulet Laurent
Published: December 2022

Background: Subcutaneous infliximab and vedolizumab formulations have been developed for maintenance therapy in inflammatory bowel disease. The objective of this study was to explore the inflammatory bowel disease patient’s acceptance for switching from intravenous infliximab or vedolizumab to subcutaneous, as well as to describe the causes of refusal or, conversely, the factors associated with acceptance. Methods: Patients were prospectively recruited between June 2021 and March 2022 during their infusion of infliximab or vedolizumab in the Medical Day Hospital of Nancy University Hospital. Adult patients with an established diagnosis of inflammatory bowel disease in clinical remission were eligible for inclusion in this study if they had been treated with intravenous infliximab or vedolizumab for at least six months. Results: One hundred and thirty patients were included in this study. Thirty-six patients (27.7%) received vedolizumab and ninety-four patients (72.3%) received infliximab. Median duration of treatment at inclusion was 7.0 years [3.0–11.0]. In this cohort, 77.7% of patients accepted the switch from intravenous infliximab or vedolizumab to subcutaneous. The main reasons for patient’s refusal for switching from intravenous to subcutaneous formulation were fear of loss of efficacy, a more spaced-out medical follow-up, increased frequency of administration, and self-administered injection. A short duration of treatment was associated with a high switch acceptance rate (odd ratio (OR) (95% confidence interval (CI)) = 0.9 (0.8–0.9); p = 0.0002). Conclusion: A large majority of the patients included accepted the switch of their treatment with infliximab or vedolizumab from the intravenous form to the subcutaneous form. This study identified one predictor influencing the acceptance rate in inflammatory bowel disease population: short treatment duration. Subcutaneous infliximab and vedolizumab hold potential for greater patient flexibility by self-administration, reducing travel and hospital attendance for infusion.
Conventional and Pro-Inflammatory Pathways of Fibrinolytic Activation in Non-Traumatic Hyperfibrinolysis
Authors: Zipperle Johannes , Ziegler Bernhard , Schöchl Herbert , Voelckel Wolfgang , Dungel Peter , Cadamuro Janne , Osuchowski Marcin , Schlimp Christoph J. , Oberladstätter Daniel
Published: December 2022

Hyperfibrinolysis (HF) frequently occurs after severe systemic hypoperfusion during major trauma and out-of-hospital cardiac arrest (OHCA). In trauma-induced HF, hypoperfusion, the activation of protein C (APC), and the release of tissue plasminogen activator (t-PA) have been identified as the driving elements of premature clot breakdown. The APC pathway also plays a role in inflammatory responses such as neutrophil extracellular trap formation (NETosis), which might contribute to lysis through cleavage of fibrin by neutrophil elastases. We investigated whether the APC and the plasminogen pathway were general drivers of HF, even in the absence of a traumatic incident. Additionally, we were interested in inflammatory activation such as the presence of NETs as potential contributing factors to HF. A total of 41 patients with OHCA were assigned to a HF and a non-HF group based on maximum lysis (ML) in thromboelastometry. Thrombin–antithrombin (TAT)-complex, soluble thrombomodulin (sTM), APC–PC inhibitor complex, t-PA, PAI-1, t-PA–PAI-1 complex, plasmin–antiplasmin (PAP), d-dimers, neutrophil elastase, histonylated DNA (hDNA) fragments, and interleukin-6 were assessed via immunoassays in the HF group vs. non-HF. APC–PC inhibitor complex is significantly higher in HF patients. Antigen levels of t-PA and PAI-1 do not differ between groups. However, t-PA activity is significantly higher and t-PA–PAI-1 complex significantly lower in the HF group. Consistent with these results, PAP and d-dimers are significantly elevated in HF. HDNA fragments and neutrophil elastase are not elevated in HF patients, but show a high level of correlation, suggesting NETosis occurs in OHCA as part of inflammatory activation and cellular decay. Just as in trauma, hypoperfusion, the activation of protein C, and the initiation of the plasminogen pathway of fibrinolysis manifest themselves in the HF of cardiac arrest. Despite features of NETosis being detectable in OHCA patients, early pro-inflammatory responses do not appear be associated with HF in cardiac arrest.
Different Characteristics and Clinical Outcomes between Early-Onset and Late-Onset Asthma: A Prospective Cohort Study
Authors: Wu Bing-Chen , Chang Chiung-Hsin , Tsai Yun-Chen , Lin Tin-Yu , Chang Po-Jui , Lo Chun-Yu , Lin Shu-Min
Published: December 2022

Late-onset asthma (LOA) differs from early-onset asthma (EOA) in terms of prognosis and the treatment response because it has a much worse prognosis and a poorer response to standard asthma treatment. This study sought to investigate the characteristics and clinical outcomes of asthma patients with phenotypes distinguished by age at onset and atopy status. We prospectively recruited patients with asthma who were registered in a pay-for-performance program operated by Taiwan’s National Health Insurance Administration (NHIA). These patients received regular outpatient treatment for at least 1 year at every outpatient clinic visit since 2019. Baseline characteristics and clinical outcomes were compared between patients with LOA (≥40 years) and those with EOA (<40 years). Of the consecutive 101 patients with asthma, 21 patients (20.7%) had EOA and 80 (79.3%) had LOA. In the 12-month period, patients with EOA had higher declines in forced expiratory volume in one second (FEV1; −2.1 ± 8.4 vs. 6.8 ± 13.1, % of predicted value, p = 0.037) and forced vital capacity (FVC; −4.6 ± 12.0 vs. 6.1 ± 13.6, % of predicted value, p = 0.023) than patients with LOA. Patients with nonatopic EOA had a significantly higher exacerbation rate at 12 months than patients with nonatopic LOA (50% vs. 11.8%, p = 0.012). Identification of different phenotypes of asthma is important in clinical practice because treatment responses may differ.
Are We Getting It Right? A Scoping Review of Outcomes Reported in Cell Therapy Clinical Studies for Cerebral Palsy
Authors: Finch-Edmondson Megan , Paton Madison C. B. , Honan Ingrid , Karlsson Petra , Stephenson Candice , Chiu Darryl , Reedman Sarah , Griffin Alexandra R. , Morgan Catherine , Novak Iona
Published: December 2022

Cell therapies are an emergent treatment for cerebral palsy (CP) with promising evidence demonstrating efficacy for improving gross motor function. However, families value improvements in a range of domains following intervention and the non-motor symptoms, comorbidities and complications of CP can potentially be targeted by cell therapies. We conducted a scoping review to describe all outcomes that have been reported in cell therapy studies for CP to date, and to examine what instruments were used to capture these. Through a systematic search we identified 54 studies comprising 2066 participants that were treated with a range of cell therapy interventions. We categorized the reported 53 unique outcome instruments and additional descriptive measures into 10 categories and 12 sub-categories. Movement and Posture was the most frequently reported outcome category, followed by Safety, however Quality of Life, and various prevalent comorbidities and complications of CP were infrequently reported. Notably, many outcome instruments used do not have evaluative properties and thus are not suitable for measuring change following intervention. We provide a number of recommendations to ensure that future trials generate high-quality outcome data that is aligned with the priorities of the CP community.
Correction: Magallon et al. Oxidative Stress and Endoplasmic Reticulum Stress in Rare Respiratory Diseases. J. Clin. Med. 2021, 10, 1268
Authors: Magallón María , Pastor Sara , Carrión Ana Esther , Bañuls Lucía , Pellicer Daniel , Castillo Silvia , Bondía Sergio , Navarro-García María Mercedes , González Cruz , Dasí Francisco
Published: December 2022

Sara Pastor was not included as an author in the original publication [...]
Long-Term Domiciliary High-Flow Nasal Therapy in Patients with Bronchiectasis: A Preliminary Retrospective Observational Case-Control Study
Authors: Crimi Claudia , Nolasco Santi , Campisi Raffaele , Nigro Mattia , Impellizzeri Pietro , Cortegiani Andrea , Noto Alberto , Gramegna Andrea , Vancheri Carlo , Blasi Francesco , Crimi Nunzio , Aliberti Stefano , Carlucci Annalisa
Published: December 2022

High-flow nasal therapy (HFNT) provides several pathophysiological benefits in chronic respiratory disorders. We aimed to evaluate the effectiveness of long-term HFNT in patients with bronchiectasis (BE). Methods: This is a retrospective bicentric case-control study of outpatients with BE on optimized medical treatment with a severe exacerbation requiring hospitalization in the previous year. Patients on long-term home HFNT (cases) and patients on optimized medical treatment alone (controls) were matched by age, sex, bronchiectasis severity index, and exacerbations in the previous year. Data on BE exacerbations, hospitalizations/year, mucus features, respiratory symptoms, and pulmonary function were collected. The primary outcome was the change from baseline in the exacerbation rates at 12 months between groups. Results: 20 patients in the HFNT group and 20 controls were included. A significant reduction in exacerbations [−1.9 (−2.8 to −0.9), p = 0.0005] and hospitalizations [−0.7 (−1.1 to −0.3), p = 0.0006] was found in the HFNT group vs controls. A slight improvement in pulmonary function [FEV1% +6,1% (+1% to +11.3%) (p = 0.0219), FVC% +4.6% (+0.8% to +8.3%) (p = 0.0188) and FEF25–75% +13.4 (+11 to +15.9) (p = 0.0189) was also found in the HFNT group compared to controls. Conclusions: In this preliminary study, long-term domiciliary HFNT improved the clinical course of patients with BE.
Characterization of Bioactive Compounds Having Antioxidant and Anti-Inflammatory Effects of Liliaceae Family Flower Petal Extracts
Authors: Kaushik Neha , Kim June-Hyun , Nguyen Linh Nhat , Kaushik Nagendra Kumar , Choi Kyung-A
Published: December 2022

Beneficial natural products utilized in cosmetics formulation and pharmaceutical applications are of enormous interest. Lily (Lilium) serves as an essential edible and medicinal plant species with wide classification. Here, we have performed the screening of various extracts that were prepared from flower petals grown from the bulbs of eight Lilium varieties, with a viewpoint to their applicability as a viable source of natural anti-inflammatory and antioxidants agent. Interestingly, our findings indicated that all ethanol and water extracts exhibited a substantially differential spectrum of antioxidant as well as anti-inflammatory properties. Specifically, Serrano showed a close similarity among ethanol and water extracts among all tested lily petal extracts. Therefore, to obtain a detailed analysis of chemical compounds, liquid chromatography–mass spectroscopy was performed in ethanolic and water extracts of Serrano petals. Together, our preliminary results indicated that lily petals extracts used in this study could serve as a basis to develop a potential new whitening agent with powerful antioxidant and anti-inflammatory properties for medicinal, functional food, and cosmetic applications.
Surface Modification of Additively Fabricated Titanium-Based Implants by Means of Bioactive Micro-Arc Oxidation Coatings for Bone Replacement
Authors: Kozelskaya Anna I. , Rutkowski Sven , Frueh Johannes , Gogolev Aleksey S. , Chistyakov Sergei G. , Gnedenkov Sergey V. , Sinebryukhov Sergey L. , Frueh Andreas , Egorkin Vladimir S. , Choynzonov Evgeny L. , Buldakov Mikhail , Kulbakin Denis E. , Bolbasov Evgeny N. , Gryaznov Anton P. , Verzunova Ksenia N. , Apostolova Margarita D. , Tverdokhlebov Sergei I.
Published: December 2022

In this work, the micro-arc oxidation method is used to fabricate surface-modified complex-structured titanium implant coatings to improve biocompatibility. Depending on the utilized electrolyte solution and micro-arc oxidation process parameters, three different types of coatings (one of them—oxide, another two—calcium phosphates) were obtained, differing in their coating thickness, crystallite phase composition and, thus, with a significantly different biocompatibility. An analytical approach based on X-ray computed tomography utilizing software-aided coating recognition is employed in this work to reveal their structural uniformity. Electrochemical studies prove that the coatings exhibit varying levels of corrosion protection. In vitro and in vivo experiments of the three different micro-arc oxidation coatings prove high biocompatibility towards adult stem cells (investigation of cell adhesion, proliferation and osteogenic differentiation), as well as in vivo biocompatibility (including histological analysis). These results demonstrate superior biological properties compared to unmodified titanium surfaces. The ratio of calcium and phosphorus in coatings, as well as their phase composition, have a great influence on the biological response of the coatings.
Sedimentary and Diagenetic Controls across the Cretaceous—Paleogene Transition: New Paleoenvironmental Insights of the External Ionian Zone from the Pelagic Carbonates of the Gardiki Section (Epirus, Western Greece)
Authors: Moforis Leonidas , Kontakiotis George , Janjuhah Hammad Tariq , Zambetakis-Lekkas Alexandra , Galanakis Dimitrios , Paschos Panagiotis , Kanellopoulos Christos , Sboras Sotirios , Besiou Evangelia , Karakitsios Vasileios , Antonarakou Assimina
Published: December 2022

Field investigation, biostratigraphic, paleoecological, and sedimentary microfacies analyses, as well as diagenetic processes characterization, were carried out in the Epirus region (Western Ionian Basin) to define the depositional environments and further decipher the diagenetic history of the Late Cretaceous–Early Paleocene carbonate succession in western continental Greece. Planktonic foraminiferal biostratigraphy of the studied carbonates revealed that the investigated part of the Gardiki section covers the Cretaceous–Paleogene (K-Pg) transition, partly reflecting the Senonian limestone and calciturbidites formations of the Ionian zone stratigraphy. Litho-and bio-facies analyses allowed for the recognition of three distinct depositional facies: (a) the latest Maastrichtian pelagic biomicrite mudstone with in situ planktonic foraminifera, radiolarians, and filaments, (b) a pelagic biomicrite packstone with abundant planktonic foraminifera at the K-Pg boundary, and (c) an early Paleocene pelagic biomicrite wackestone with veins, micritized radiolarians, and mixed planktonic fauna in terms of in situ and reworked (aberrant or broken) planktonic foraminifera. The documented sedimentary facies characterize a relatively low to medium energy deep environment, representing the transition from the deep basin to the deep shelf and the toe of the slope crossing the K-Pg boundary. Micropaleontological and paleoecological analyses of the samples demonstrate that primary productivity collapse is a key proximate cause of this extinction event. Additional petrographic analyses showed that the petrophysical behavior and reservoir characteristics of the study deposits are controlled by the depositional environment (marine, meteoric, and burial diagenetic) and further influenced by diagenetic processes such as micritization, compaction, cementation, dissolution, and fracturing.
A Potential Beach Monitoring Based on Integrated Methods
Authors: Lapietra Isabella , Lisco Stefania , Capozzoli Luigi , De Giosa Francesco , Mastronuzzi Giuseppe , Mele Daniela , Milli Salvatore , Romano Gerardo , Sabatier François , Scardino Giovanni , Moretti Massimo
Published: December 2022

This study focuses on the analysis of sandy beaches by integrating sedimentological, geomorphological, and geophysical investigations. The beach represents an extremely variable environment where different natural processes act simultaneously with human activities, leading to the gathering of different methodologies of the Earth Sciences to study its evolution in space and time. The aim of this research is to propose a potential procedure for monitoring the morpho-sedimentary processes of sandy beaches by analyzing the textural and compositional characteristics of the sands and quantifying the volumes involved in the coastal dynamics. The study area includes two Apulian sandy beaches (Torre Guaceto and Le Dune beach) that are representative of the coastal dynamics of a large sector of the central/northern Mediterranean Sea involving the southern Adriatic Sea and the northern Ionian Sea. Sedimentological and ecological investigations allowed to describe the textural and compositional characteristics of the beach sands by interpreting their sand provenance and the physical/biological interactions within the beach. The topographic surveys carried out with a Terrestrial Laser Scanner and an Optical Total Station, aimed to quantify the variations of sediment volume over time, whereas the Delft3d software was applied to analyze the effects of the dominant wave motion on the sedimentary dynamics. Lastly, the geophysical techniques which included Sub Bottom Profiler procedures, Ground Penetrating Radar investigation, and resistivity models enabled us to calculate the sand sediment thickness above the bedrock.
Green Ports Analysis Using an End-to-End Tool Application in the Fishing Port of Vigo
Authors: Ramos Velasco Eduardo , González-Cancelas Nicoletta , Camarero Orive Alberto , Díaz-Gutiérrez David
Published: December 2022

Modern ports tend to focus on freight transport and cruise traffic. The fishing sector is often the forgotten sector in terms of sustainability and port planning, despite the fact that fishing is a sector of great importance and interest; though it is currently obsolete in many respects. Literature on sustainability and green ports in the context of fishing ports is practically non-existent; however, it is necessary in order to implement a sustainable fishing infrastructure. For this reason, the aim of this study is, within the green ports framework as outlined by the European Commission and using an innovative end-to-end tool methodology, to determine the reality of the conditions of the port environment in fishing ports. Furthermore, this study establishes a possible green ports scenario for Spanish fishing ports and carries out an analysis of a specific case study within the Spanish port system: the Port of Vigo. It is concluded that the key fishing features of the Port of Vigo should, in order to expand its sustainability strategies, are: growth expectations, closely related to the evolution of the goods unloaded in the Port of Vigo and the possible growth that this may have in the future; legislation and current trends in terms of sustainability; and diversification, the Port of Vigo has realistic options to diversify the business beyond the traditional fishing activities.
Hereditary Diffuse Gastric Cancer: A 2022 Update
Authors: Kole Christo , Charalampakis Nikolaos , Sakellariou Stratigoula , Papaxoinis George , Apostolou Konstantinos G. , Machairas Nikolaos , Papanikolaou Ioannis S. , Schizas Dimitrios
Published: December 2022

Gastric cancer is ranked fifth among the most commonly diagnosed cancers, and is the fourth leading cause of cancer-related deaths worldwide. The majority of gastric cancers are sporadic, while only a small percentage, less than 1%, are hereditary. Hereditary diffuse gastric cancer (HDGC) is a rare malignancy, characterized by early-onset, highly-penetrant autosomal dominant inheritance mainly of the germline alterations in the E-cadherin gene (CDH1) and β-catenin (CTNNA1). In the present study, we provide an overview on the molecular basis of HDGC and outline the essential elements of genetic counseling and surveillance. We further provide a practical summary of current guidelines on clinical management and treatment of individuals at risk and patients with early disease.
Novel Method to Detect Pitfalls of Intracoronary Pressure Measurements by Pressure Waveform Analysis
Authors: Jenei Csaba , Tar Balázs , Ágoston András , Sánta Péter , Sánta János , Csippa Benjámin , Wéber Richárd , Gyürki Dániel , Halász Gábor , Szabó Gábor Tamás , Czuriga Dániel , Kőszegi Zsolt
Published: December 2022

Potential pitfalls of fractional flow reserve (FFR) measurements are well-known drawbacks of invasive physiology measurement, e.g., significant drift of the distal pressure trace may lead to the misclassification of stenoses. Thus, a simultaneous waveform analysis of the pressure traces may be of help in the quality control of these measurements by online detection of such artefacts as the drift or the wedging of the catheter. In the current study, we analysed the intracoronary pressure waveform with a dedicated program. In 130 patients, 232 FFR measurements were performed and derivative pressure curves were calculated. Local amplitude around the dicrotic notch was calculated from the distal intracoronary pressure traces (δdPn/dt). A unidimensional arterial network model of blood flow was employed to simulate the intracoronary pressure traces at different flow rates. There was a strong correlation between δdPn/dt values measured during hyperaemia and FFR (r = 0.88). Diagnostic performance of distal δdPn/dt ≤ 3.52 for the prediction of FFR ≤ 0.80 was 91%. The correlation between the pressure gradient and the corresponding δdPn/dt values obtained from all measurements independently of the physiological phase was also significant (r = 0.80). During simulation, the effect of flow rate on δdPn/dt further supported the close correlation between the pressure ratios and δdPn/dt. Discordance between the FFR and the δdPn/dt can be used as an indicator of possible technical problems of FFR measurements. Hence, an online calculation of the δdPn/dt may be helpful in avoiding some pitfalls of FFR evaluation.
The Value of Early and Follow-Up Elevated Scores Based on Peripheral Complete Blood Cell Count for Predicting Adverse Outcomes in COVID-19 Patients
Authors: Chelariu Andrei-Costin , Coman Adorata , Lionte Catalina , Gorciac Victoria , Sorodoc Victorita , Haliga Raluca , Petris Ovidiu , Bologa Cristina , Puha Gabriela , Stoica Alexandra , Constantin Mihai , Sirbu Oana , Ceasovschih Alexandr , Sorodoc Laurentiu
Published: December 2022

Background: The ongoing COVID-19 pandemic has put a constant strain on hospital resources, so there is a dire need for investigation methods that are widely available and that can predict mortality and the need for critical care. Hematological indices, which can be easily calculated from a complete blood count (CBC), are useful in determining a patient’s inflammatory response to infectious diseases. Aim: This was a prospective cohort study that aimed to assess the prognostic value of scores based on CBCs in hospitalized patients with mild or moderate COVID-19 and medical comorbidities regarding the need for intensive care unit (ICU) therapy and short-term mortality. Methods: We included 607 patients with confirmed COVID-19, followed up for the need for ICU admission (15.5%) and 30 day mortality post-discharge (21.7%). CBC-derived scores were tested upon emergency department (ED) admission and after a median of 8 days. Results: In a multivariate model, elevated followed-up neutrophil-to-lymphocyte ratio (NLR) predicted increased odds for ICU admission (OR: 1.14 [95%CI: 1.06–1.22], p < 0.001) and short-term mortality (OR: 1.30 [95%CI: 1.09–1.57], p = 0.005). Monocyte-to-lymphocyte ratio (MLR) predicted 2.5-fold increased odds for ICU admission and 2.2-fold increased odds for mortality. Conclusion: NLR and MLR followed up 8 days post-admission are predictive for adverse outcomes in mild or moderate COVID-19 patients.
Quality of Life in Patients with Acute Severe Ulcerative Colitis: Long-Term Follow-Up Results from the CONSTRUCT Trial
Authors: Alrubaiy Laith , Hutchings Hayley A. , Louca Andrea , Rapport Frances , Watkins Alan , Sebastian Shaji , Williams John G.
Published: December 2022

Background: there is currently limited research examining the QoL of patients with Ulcerative colitis (UC) following treatment of acute severe colitis (ASUC). Objective: to examine the long-term QoL of ASUC patients enrolled in the CONSTRUCT trial following treatment of UC with infliximab or ciclosporin and to compare the differences in the QoL between the two drug treatments over time. Methods: The CONSTRUCT trial examined the cost and clinical effectiveness of infliximab and ciclosporin treatments for acute severe UC. We collected QoL questionnaire data from patients during the active trial period up to 36 months. Following trial completion, we contacted patients postannually for up to a maximum of 84 months. We collected QoL data using a disease-specific (CUCQ, or CUCQ+ for patients who had colectomy surgery) or generic (EQ5D-3L) questionnaire. We analysed QoL scores to determine if there was any difference over time and between treatments in generic or disease-specific QoL. Results: Following initial treatment with infliximab and ciclosporin, patients experienced a statistically significant improvement in both the generic and disease-specific QoL at three months. Generic scores remained fairly static for the whole follow-up period, reducing only slightly up to 84 months. Disease-specific scores showed a much sharper improvement up to 2 years with a gradual reduction in QoL up to 84 months. Generic and disease-specific QoL remained higher than baseline values. There was no significant difference between treatments in any of the QoL scores. Conclusions: Both infliximab and ciclosporin improve QoL following initial treatment for ASUC. QoL scores remain higher than at admission up to 84 months post-treatment.
Assessment of Physical Vulnerability and Uncertainties for Debris Flow Hazard: A Review concerning Climate Change
Authors: Khan Mudassir Ali , Mustaffa Zahiraniza , Harahap Indra Sati Hamonangan , Ibrahim Muhammad Bello , Al-Atroush Mohamed Ezzat
Published: December 2022

Global climate change has increased severe torrential hazards, particularly debris flows in mountainous regions. After floods and earthquakes, debris flows are the most devastating natural hazard in the world. The effects of debris flow on human life and built environments necessitate reconsidering current infrastructure planning, engineering, and risk management practices. Hence, the vulnerability of elements at risk is critical for effective risk reduction systems. Therefore, this article reviews the existing physical vulnerability approach of infrastructure, particularly building toward debris flow hazards in the last 20 years. Furthermore, uncertainties associated with the vulnerability assessment and their quantification techniques have also been discussed in detail. It was found that matrices, curves, and indicators have been extensively used for vulnerability assessment approaches in the last two decades. However, if aleatory and epistemic uncertainties are not quantified or conserved in the vulnerability assessment process, it makes the system inefficient and unreliable. Moreover, data requirements, strengths, and weaknesses of approaches presented herein are highlighted with case studies. Finally, a thorough discussion on future needs in the field of risk assessment methodologies is highlighted by considering uncertainties into account.
Challenges, Experience, and Prospects of Urban Renewal in High-Density Cities: A Review for Hong Kong
Authors: Wang Yidi , Fan Ying , Yang Zan
Published: December 2022

Redevelopment in Hong Kong must be accelerated in response to urban decay and land shortages. However, due to a lack of incentives and effective policy tools under Hong Kong’s floor area ratio regulations, there has been limited public–private partnerships in the urban renewal process, reducing both the public welfare and the efficiency of land use. We review the evolution of Hong Kong’s density schemes for addressing urban redevelopment issues to identify the most important barriers to private sector involvement. We also summarise the international experience and identify viable policies, compare cases in Hong Kong with successful transfer of development rights (TDRs) examples, point out TDRs’ shortcomings, and propose targeted policy optimisation strategies. On a practical level, this study has implications for the creation of targeted density policies to address Hong Kong’s ageing infrastructure and facilitate the urban transformation of Hong Kong and similar high-density cities so that they can continue to support sustainable urban growth.
The Therapeutic Role of SGLT-2 Inhibitors in Acute Heart Failure: From Pathophysiologic Mechanisms to Clinical Evidence with Pooled Analysis of Relevant Studies across Safety and Efficacy Endpoints of Interest
Authors: Patoulias Dimitrios , Fragakis Nikolaos , Rizzo Manfredi
Published: December 2022

(1) Background: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors constitute a novel drug class with remarkable cardiovascular benefits for patients with chronic heart failure (HF). Recently, this class has been utilized in acute HF as an additional treatment option to classic diuretics, which remain the cornerstone of treatment. (2) Methods: We attempted to identify those pathophysiologic mechanisms targeted by SGLT-2 inhibitors, which could be of benefit to patients with acute HF. We then conducted a comprehensive review of the literature within the PubMed database in order to identify relevant studies, both randomized controlled trials (RCTs) and observational studies, assessing the safety and efficacy of SGLT-2 inhibitors in acute HF. (3) Results: SGLT-2 inhibitors induce significant osmotic diuresis and natriuresis, decrease interstitial fluid volume and blood pressure, improve left ventricular (LV) function, ameliorate LV remodeling and prevent atrial arrhythmia occurrence, mechanisms that seem to be beneficial in acute HF. However, currently available studies, including six RCTs and two real-world studies, provide conflicting results concerning the true efficacy of SGLT-2 inhibitors, including “hard” surrogate endpoints. (4) Conclusions: Current evidence appears insufficient to substantiate the use of SGLT-2 inhibitors in acute HF. Further trials are required to shed more light on this issue.
A Pilot Study on the Use of Low Doses of CBD to Control Seizures in Rare and Severe Forms of Drug-Resistant Epilepsy
Authors: Pesántez Ríos Gabriela , Armijos Acurio Luciana , Jimbo Sotomayor Ruth , Cueva Victor , Pesántez Ríos Ximena , Navarrete Zambrano Hugo , Pascual Samuel , Pesántez Cuesta Galo
Published: December 2022

Due to its anticonvulsant properties, cannabidiol can be supportive as an adjuvant therapy in the management of drug resistant epilepsy. This retrospective observational study evaluates the intensity and frequency of the seizures of patients with drug-resistant epilepsy that have been treated with antiepileptic medication associated with CBD in low doses for at least 12 months. Thirty-four patients were included in the study. The most frequent diagnosis of epilepsy was focal symptomatic epilepsy and Lennox–Gastaut syndrome (35.2%). During the follow-up, there was a statistically significant decrease in the seizure frequency (t student p < 0.001). A high proportion of patients, 16, concluded the study with a total control of the seizures reaching a 100% improvement, 12 reported ≥ 75% improvement, 3 ≥ 50%, and 2 ≥ 25%; only 1 patient had an improvement of less than 25%. This is the first Latin American study that demonstrates that long-term CBD added to the usual drugs significantly reduces the frequency, duration, and type of seizures in the different etiologies of epilepsy, being especially effective on the seizures that are the most incapacitating, improving the quality of life of the individual and their family.
The Energetic Costs of Uphill Locomotion in Trail Running: Physiological Consequences Due to Uphill Locomotion Pattern—A Feasibility Study
Authors: Zimmermann Paul , Müller Nico , Schöffl Volker , Ehrlich Benedikt , Moser Othmar , Schöffl Isabelle
Published: December 2022

The primary aim of our feasibility reporting was to define physiological differences in trail running (TR) athletes due to different uphill locomotion patterns, uphill running versus uphill walking. In this context, a feasibility analysis of TR athletes’ cardiopulmonary exercise testing (CPET) data, which were obtained in summer 2020 at the accompanying sports medicine performance center, was performed. Fourteen TR athletes (n = 14, male = 10, female = 4, age: 36.8 ± 8.0 years) were evaluated for specific physiological demands by outdoor CPET during a short uphill TR performance. The obtained data of the participating TR athletes were compared for anthropometric data, CPET parameters, such as V˙Emaximum, V˙O2maximum, maximal breath frequency (BFmax) and peak oxygen pulse as well as energetic demands, i.e., the energy cost of running (Cr). All participating TR athletes showed excellent performance data, whereby across both different uphill locomotion strategies, significant differences were solely revealed for V˙Emaximum (p = 0.033) and time to reach mountain peak (p = 0.008). These results provide new insights and might contribute to a comprehensive understanding of cardiorespiratory consequences to short uphill locomotion strategy in TR athletes and might strengthen further scientific research in this field.