bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal Effect of Na+/K+ ATPase Blocker Ouabain on the Tumor Microenvironment and Malignant Cells
Authors: Harich Octavia-Oana , Gavriliuc Oana-Isabella , Ordodi Valentin-Laurentiu , Tirziu Alexandru , Paunescu Virgil , Panaitescu Carmen , Bojin Maria-Florina
Published: May 2023

The Na+/K+ ATPase is a protein involved in the active transport of ions across the cellular membrane. Ouabain is a cardiotonic glycoside that, by inhibiting the Na+/K+ pump, interferes with cell processes mediated directly by the pump, but also indirectly influences other cellular processes, such as cellular cycle and proliferation, growth, cell differentiation, angiogenesis, migration, adhesion and invasion. We used the SK-BR-3 breast cancer cell line, mesenchymal stem cells (MSCs), and tumor-associated fibroblasts (TAFs) in vitro for determining the changes induced by Ouabain in concentration of 10-5 M, 10-6 M, 10-8 M, 10-9 M on these cellular types, employing specific methods: SEM for morphological evaluation; immunocytochemistry, flowcytometry to assess immunophenotypical markers expression, cell cycle and Annexin V/PI assay for cellular proliferation and viability testing; flowchamber assay to evaluate functional adhesion behavior; RT-PCR for Na+/K+ ATPase subunits molecular expression. Being indicative of the pro-apoptotic and inhibitory effect of Ouabain on tumor invasion and metastasis, the results support the addition of Ouabain to the oncological therapeutic arsenal, trailing the “repurposing drugs” approach.
Superconducting Gravimeters: A Novel Tool for Validating Remote Sensing Evapotranspiration Products
Authors: Pendiuk Jonatan , Degano María Florencia , Guarracino Luis , Rivas Raúl Eduardo
Published: May 2023

The practical utility of remote sensing techniques relies on validating them with ground-truth data. Validation requires similar spatial-temporal scales for ground measurements and remote sensing resolution. Evapotranspiration (ET) estimates are commonly compared to weighing lysimeter data, which provide precise but localized measurements. To address this limitation, we propose using superconducting gravimeters (SG) to obtain ground-truth ET data at larger spatial scales. SG measure gravity acceleration with high resolution (tenths of nm/s2) within a few hundred meters. Similar to lysimeters, gravimeters provide direct estimates of water mass changes for determining ET without soil disturbance. To demonstrate the practical applicability of SG data, we conducted a case study in Buenos Aires Province, Argentina (-34.87, -58.14). We estimated cumulative ET values for 8-day and monthly intervals using gravity and precipitation data from the study site. Comparing these values with MODIS-based ET products (MOD16A2), we found a very good agreement at the monthly scale, with an RMSE of 32.6 mm/month (1.1 mm/day). This study represents progress in using SG for hydrogeological applications. The future development of lighter and smaller gravimeters is expected to further expand their use.
Climate Change, Ecological Modernization, and Disaster Management: The Coastal Embankment Project in Southwestern Bangladesh
Authors: Kais Shaikh Mohammad , Islam Md Saidul
Published: May 2023

Climate change, one of the severest environmental threats to humankind, disproportionately affects low-income developing countries in the global South. Having no feasible mitigation alternatives, these countries resort to adaptation efforts in addressing the climate perturbations. Climate change adaptation (or resilience) is primarily a localized course of action that depends on individuals, social networks, economies, ecologies, political structures, and the capabilities of all those to work collectively to absorb, learn from and transform in the face of new realities. With a view to controlling the floods that shattered the life and economy of the then East Pakistan, which is Bangladesh now, during the mid-twentieth century, the coastal embankment project (CEP) was instituted as an adaptation strategy to natural disasters in southwestern Bangladesh. Based on the qualitative analysis of primary and secondary data, this paper seeks to critically evaluate the efficacy of the CEP in terms of the space for feasible action and ecological modernization. The findings of this research indicate that the CEP has become an unrealistic venture that hinders the growing economic activity of shrimp aquaculture in the area. This paper is expected to contribute to generate further theoretical and empirical discourse on evaluating similar development projects around the globe.
Reduction of Power Losses and Voltage Improvement in a Smart Grid Incorporated with Electric Vehicles
Authors: Ntombela Mlungisi , Musasa Kabeya
Published: May 2023

Concern about the planet's future has motivated governments around the world to adopt policies that promote more responsible energy consumption. Reducing emissions of the principal cause of climate change man-made greenhouse gases requires greater system efficiency and the utilization of renewable energy sources. The generation of electricity is the single largest source of hazardous pollutants, followed by the transportation sector. This is true due to the extreme reliance on petroleum and its derivatives that these industries have. Electric mobility is receiving more attention from businesses, governments, and academic institutions as a means to reduce the negative impacts of current energy consumption. Without measures to address common technical issues, electric vehicles would strain electrical infrastructure. In order to determine the best strategy for switching operations and feeder reconfiguration, this research presents a helpful hybrid genetic algorithm particle swarm optimization (HGAPSO) method. Meet transmission limits while decreasing real power losses and enhancing the system's bus voltage profile. The effects of HGAPSO on power losses and voltage distributions in the network are analyzed. Then, a report is produced contrasting GA and PSO. This cross-breeding of GA and PSO led to HGAPSO. This important problem can be solved more effectively with the use of new or improved algorithms. To find the optimal reconfiguration and properly rearrange transmission network interconnection, it employs a plethora of heuristic optimization algorithms. The objective is to limit bus voltage variations while maintaining the system's radial topology and minimizing power usage. The reliability and performance of the procedure were evaluated using MATLAB's IEEE 33-bus communication network. The outcomes demonstrate the effectiveness of the proposed technique, which cuts down on power waste during standalone runs and speeds up the processing time.
Recommended Interventions to Improve Human Papillomavirus Vaccination Uptake among Adolescents: A Review of Quality Improvement Methodologies
Authors: Khalid Karniza , Lee Kun Yun , Mukhtar Nur Farihan , Warijo Othman
Published: May 2023

Background: Routine human papillomavirus (HPV) vaccine uptake continues to be suboptimal since its recommendation in 2006 for girls and in 2011 for boys. This paper aims to review published quality improvement (QI) methodologies on interventions to improve HPV vaccine uptake among adolescents; Methods: Science Direct and Scopus databases were searched for QI initiatives evaluating the effect of multimodal interventions to improve HPV vaccination rates (initiation and/or completion of series) among adolescents. Studies that included an outcome of interest among adolescents aged 10 to 18 years old were included. Two investigators worked independently to screen for potential articles and a designated investigator extracted data on study characteristics and evaluated the outcomes; Results: Preliminary search yielded a total of 523 articles and 13 were included in the final analysis. Common strategies were provider-specific and patient- and/or parent-specific interventions, with an emphasis on education and knowledge empowerment. System-level interventions such as policy changes and revised protocol were less commonly prescribed despite being associated with more significant weight on the overall outcome; Conclusions: Creative, sustainable, and economical multilevel interventions that focus not only on provider training and public education but also incorporate local policy and system enhancement can substantially improve HPV vaccination coverage among adolescents.
Conferring High Iaa Productivity on Low-Iaa-Producing Organisms With PonAAS2, an Aromatic Aldehyde Synthase of a Galling Sawfly, and Identification of Its Inhibitor
Authors: Hiura Takeshi , Yoshida Hibiki , Miyata Umi , Asami Tadao , Suzuki Yoshihito
Published: May 2023

Gall-inducing insects often contain high concentrations of phytohormones, such as auxin and cytokinin, which are suggested to be involved in gall induction, but no conclusive evidence has been obtained. There are two possible approaches to investigating the importance of phytohormones in gall induction: demonstrating either that high phytohormone productivity can induce gall-inducing ability in non-gall-inducing insects, or that gall-inducing ability is inhibited when phytohormone productivity in galling insects is suppressed. In this study, we show that the overexpression of PonAAS2, which encodes an aromatic aldehyde synthase (AAS) responsible for the rate-limiting step in indoleacetic acid (IAA) biosynthesis in a galling sawfly (Pontania sp.) that contains high levels of endogenous IAA, conferred high IAA productivity on Caenorhabditis elegans, as the model system. This result strongly suggests that PonAAS2 can also confer high IAA productivity on low-IAA-producing insects. We also successfully identified an inhibitor of PonAAS2 in a chemical library. This highly selective inhibitor showed stronger inhibitory activity against AAS than against aromatic amino acid decarboxylase, which belongs to the same superfamily as AAS. We also confirm that this inhibitor clearly inhibited IAA productivity in the high-IAA-producing C. elegans engineered here.
End-to-End PQC Encryption Protocol for GPKI-based Video Conferencing System
Authors: Park Yeongjae , Yoo Hyeondo , Ryu Jieun , Choi Young-Rak , Kang Ju-Sung , Yeom Yongjin
Published: May 2023

Owing to the expansion of non-face-to-face activities, security issues in video conferencing systems are becoming more critical. In this paper, we focus on the end-to-end encryption (E2EE) function among security services of video conferencing systems. First, the E2EE-related protocols of Zoom and Secure Frame (SFrame), which are representative video conferencing systems, are thoroughly investigated, and the two systems are compared and analyzed overall. Next, the E2EE protocol in the Government Public Key Infrastructure (GPKI)-based video conferencing system, in which the user authentication mechanism is fundamentally different from those used in private sector systems, such as Zoom or SFrame, will be considered. In particular, among E2EE-related protocols, we propose a detailed mechanism in which the post-quantum cryptography (PQC) key encapsulation mechanism (KEM) is applied to the user key exchange process. As the session key is not disclosed to the central server even in futuristic quantum computers, the mechanism to which the PQC KEM method proposed in this study is applied satisfies the E2EE security requirements and can be applied to domestic GPKI-based systems. It is expected to contribute in strengthening the safety of the next-generation video conferencing system.
Capturing the Kidney Transcriptome by Urinary Extracellular Vesicles – from Preanalytical Obstacles to Biomarker Research
Authors: Barreiro Karina , Dwivedi Om Prakash , Rannikko Antti , Holthofer Harry , Tuomi Tiinamaija , Groop Per-Henrik , Puhka Maija
Published: May 2023

Urinary extracellular vesicles (uEV) hold non-invasive RNA biomarkers for genitourinary tract diseases. However, missing knowledge about reference genes and effects of pre-analytical choices hinder biomarker studies. We aimed to assess how pre-analytical variables (urine storage temperature, isolation workflow) affect diabetic kidney disease (DKD) -linked miRNAs or kidney -linked miRNAs and mRNAs (kidney-RNAs) in uEV isolates and to discover stable reference mRNAs across diverse uEV datasets. We studied nine raw and normalized sequencing datasets including healthy controls and individuals with prostate cancer or type 1 diabetes with or without albuminuria. We focused on kidney-RNAs reviewing literature for DKD-linked miRNAs from kidney tissue, cell culture and uEV/urine experiments. RNAs were analyzed by expression heatmaps, hierarchical clustering and selecting stable mRNAs with normalized counts (>200) and minimal coefficient of variation. Kidney-RNAs were decreased after urine storage at -20°C vs -80°C. Isolation workflows captured kidney-RNAs with different efficiencies. Ultracentrifugation captured DKD -linked miRNAs that separated healthy and diabetic macroalbuminuria groups. Eleven mRNAs were stably expressed across the datasets. Hence, preanalytical choices had variable effects on kidney-RNAs – analyzing kidney-RNAs complemented global correlation, which could fade differences in some relevant RNAs. Replicating prior DKD-marker results and discovery of candidate reference mRNAs encourages further uEV biomarker studies.
Tribocorrosion Susceptibility and Cell Viability Study of 316L Stainless Steel and Ti6Al4V Titanium Alloy With and Without DLC Coatings
Authors: Sene Ana Claudia Alves , Da Silva Michely Glenda Pereira , Macário Paulo Fabrício , Vieira Angela Aparecida , Leite Priscila Maria Sarmeiro Correa Marciano , Da Silva Newton Soares , Marques Francisco Das Chagas , Vieira Lúcia
Published: May 2023

Stainless steel 316L (SS316L) and titanium-alloy Ti6AL4V exhibit properties for bio-medical applications; however their tribocorrosion associated with metallosis is still a major concern. Therefore smoothing DLC coatings aiming for the improvement of tri-bocorrosion and cell viability of stainless steel 316L (SS316L) and titanium-alloy Ti6AL4V with and without DLC coatings were compared. The motivation was due to many papers detailing metallosis caused by metal debris in the body's soft tissues. Nowadays, metallosis is responsible for almost of prosthesis replacement surgeries. DLC coatings were produced using the Plasma Enhanced Chemical Vapor Deposition (PECVD) technique; acetylene gas was used as a carbon precursor, and silane gas produced an amorphous silicon interface between the DLC coating and metal substrate. A combined setup of techniques thoroughly evaluated the coatings considering chemical composition, coatings adhesion at a metallic substrate, scratch resistance, and tribocorrosion susceptibility. The cytotoxicity and genotoxicity of metallic samples with and without DLC coatings were analyzed, considering cell viability and its correlation with coatings’ chemical composition
Dog Assisted Therapy Is Hypothesized to Lower Stress in Children With Autism Spectrum Disorder (ASD) And Children With Down Syndrome (DS), Which May Be Visible on a Physiological Level. In This Study, We Measured Heart Rate Variability (HRV) And Salivary
Authors: Griffioen Richard Eric , Van Boxtel Geert J.M. , Verheggen Theo , Enders-Slegers Marie-Jose , Van der Steen Steffie
Published: May 2023

Dog Assisted Therapy is hypothesized to lower stress in children with Autism Spectrum Disorder (ASD) and children with Down Syndrome (DS), which may be visible on a physiological level. In this study, we measured Heart Rate Variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of 6 weekly sessions of Dog-Assisted Therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after 6 sessions (6 weeks). The effect of Dog Assisted Therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.
The Real-World Evidence on the Fragility and Its Impact on the Choice of Treatment Regimen in Newly Diagnosed Patients With Multiple Myeloma Over 75 Years of Age
Authors: Tyczyńska Agata , Krzemek Marcela Krzysława , Cortez Alexander Jorge , Jurczyszyn Artur , Godlewska Katarzyna , Ciepłuch Hanna , Subocz Edyta , Hałka Janusz , Kulikowska de Nałęcz Anna , Wiśniewska Anna , Swiderska Alina , Waszczuk-Gajda Anna , Drozd-Sokołowska Joanna , Guzicka-Kazimierczak Renata , Porowska Agnieszka , Wiśniewski Kamil , Knopińska-Posłuszny Wanda , Kłoczko Janusz , Rzepecki Piotr , Woszczyk Dariusz , Symonowicz Hanna , Basak Grzegorz Władysław , Zdziarska Barbara , Jamroziak Krzysztof , Zaucha Jan M.
Published: May 2023

Fragility scales are intended to help in therapeutic decisions. Here we asked if the fragility as-sessment in MM patients ≥75 years old qualified for treatment by the local physician correlates with the choice of treatment: a 2- or 3-drug regimen. Between 7/2018 to 12/2019 we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in com-pletely dependent. Patients with more than 3 comorbidities were 26.9% (53 patients). Thus, ac-cording to the Palumbo calculator, 43 patients were in the intermediate-fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received 3-drug regimens and 20.3% (40) received 2-drug regimens. In each ECOG group, more than 3/4 of patients received 3-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received 3-drug regimens. Out of 53 pa-tients with at least 4 comorbidities, 71.7% received 3-drug regimens, and the rest 2-drug regi-mens. Three-drugs regimens received 34 patients from the intermediate-fit group (79.0%), and 123 (79.9%) from the frail group. Early mortality occurred in 25 patients (12.7%). No one discon-tinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with tri-ple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations which questions the clinical utility of current fragility scales in everyday practice.
Survival, Development, and Fecundity of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) on Various Host Plant Species and Their Implication for the Pest Management
Authors: Nurkomar Ihsan , Trisnawati Dina Wahyu , Fahmi Fajrin , Buchori Damayanti
Published: May 2023

Spodoptera frugiperda is a relatively new invasive polyphagous insect pest in Indonesia. So far, S. frugiperda infestation has only been reported in corn, however in other countries S. frugiperda has been known to attack many commercial crops. To date, information on biological parameters of S. frugiperda is limited in Indonesian ecologies. Since host plants are a critical factor for insect life-history and has the potential to be used for pest control strategies, it is important to study the biology and survival of S. frugiperda on different host plants. This research was aimed to study the survival, life cycle, and fecundity of S. frugiperda on different host plants and how it affects pest management. The study was conducted by rearing S. frugiperda on 14 common cultivated host plant species in Indonesia. Survival rate, development time, fecundity, and potential attack rate of S. frugiperda on various tested host plants were analyzed in this study. The findings re-vealed that corn was the main host for S. frugiperda. The ability of S. frugiperda to survive on pa-paya, water spinach, banana, spinach, cucumber, and coco grass indicates that these plants are potential alternate host for S. frugiperda. Long beans, bok choy, choy sum, and beans might be in-dicated as a shelter for S. frugiperda. Meanwhile, inappropriate hosts for S. frugiperda include cabbage, broccoli, and cauliflower due to their low survival rate on these plants. This research implies that these plants have the potential to be used as a hedge, trap, or bunker plant in S. frugi-perda management strategies. However, to prevent a detrimental damage, control methods are needed in integrated manner, including monitoring pest populations, environmental engineering, and conservation of natural enemies.
Budesonide Analogues Preserve Stem Cell Pluripotency and Delay 3D Gastruloid Development
Authors: Amoroso Filomena , Ibello Eduardo , Saracino Federica , Cermola Federica , Ponticelli Giovanna , Scalera Enrica , Ricci Francesca , Villetti Gino , Cobellis Gilda , Minchiotti Gabriella , Patriarca Eduardo Jorge , De Cesare Dario , D'Aniello Cristina
Published: May 2023

Small molecules that can modulate or stabilize cell-cell interactions are valuable tools for investigating the impact of collective cell behavior on various biological processes such as development/morphogenesis, tissue regeneration and cancer progression. Recently, we showed that budesonide, a glucocorticoid widely used as anti-asthmatic drug, is a potent regulator of stem cell pluripotency. Here we tested the effect of different budesonide derivatives and identified CHD-030498 as a more effective analogue of budesonide. CHD-030498 was able to prevent stem cell pluripotency exit in different cell-based models, including embryonic stem-to-mesenchymal transition, spontaneous differentiation and 3D gastruloid development, and at lower doses compared to budesonide.
IL-23/IL-17 axis in the Chronic Hepatitis C and Nonalcoholic Steatohepatitis – New Insight Into Immunohepatotoxicity of Different Chronic Liver Diseases
Authors: Vujovic Ankica , Isakovic Andjelka M , Misirlic-Dencic Sonja , Juloski Jovan , Mirkovic Milan , Djelic Marina , Milošević Ivana
Published: June 2023

Considering the relevance of the pathogenesis research of different liver diseases, in our study we investigated the possible activity of IL-23/IL-17 axis on the im-munohepatotoxicity of two etiologically different CLD. A total of patients with CHC infection, 19 with NASH and 20 healthy controls (CG) were recruited. After histological verification from liver tissue obtain by liver biopsy, patients with CHC were divided into two groups: CHC-NSF (F0/F1/F2)-non-significant fibrosis, 20 patients, and CHC-SF (F3/F4)-significant fibrosis/cirrhosis, 16 patients. All anthropometric, biochemical, immunological cytokines (IL-6, IL-10, IL-17 and IL-23) tests were performed accordance to standard procedure. The plasma levels of IL-6, Il-17A and IL-23 were significantly higher in CHC-SF and NASH in compared with CG. Also, plasma levels of IL-23/IL-17A were significantly higher in NASH in compared to CHC-SF. In CHC-SF we had significantly lowest IL-10 level in compared with all three groups. Liver tissue levels of IL-17A and IL-23 in CHC-NSF were significantly lower in compared with NASH. IN CHC-SF and NASH, IL17-A and IL-23 in liver tissue were significantly higher in compare to plasma levels. In conclusan, proinflammatory response of IL-23/17A axis is dominant in plasma and liver tissue in CHC with higher levels of liver fibrosis and in NASH patients.
The Importance of Neutrophils in Osteoarthritis:
Current Concepts and Therapeutic Perspectives
Authors: Mehrani Yeganeh , Rahimi Rasool , Morovati Solmaz , Mehrani Hossein , Karimi Negar , Ghasemi Samaneh
Published: June 2023

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in osteoarthritis pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating some protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with osteoarthritis, and possible therapeutic approaches to target neutrophils for the treatment of osteoarthritis are described. Understanding neutrophil heterogeneity and their mechanisms of action in joint inflammation, provides a potential strategy for OA management.
Chronic Fatigue Syndrome and Multiple Sclerosis have Reduced Craniospinal Compliance and Dilated Pressurized Bridging Cortical Veins: A Hypothesis Illustrated with Two Case Studies
Authors: Bateman Grant , Bateman Alexander
Published: June 2023

Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) share similarities regarding their epidemiology, symptomatology and craniospinal physiology. Indeed, the cardinal feature of CFS, fatigue, is also a major factor in the symptomatology of the majority of MS patients. Recently, we have found that there is a significant reduction in the craniospinal compliance in MS which affects both the stiffness of the walls of the spinal canal and the walls of the cerebral venous system. This change in compliance brings about an alteration in the effectiveness of the pulse wave dampening in the craniospinal system. The result is an impedance mismatch between the cortical veins and their draining sinuses, leading to dilatation of these upstream veins. We deduce this dilatation can only be brought about by an increase in the pressure gradient between the vein lumen and the subarachnoid space (i.e. the transmural pressure gradient). We hypothesise that given the similarities between MS and CFS, a similar mechanism underlies the physiology of CFS. We present two case studies to highlight the expected findings in CFS patients if this hypothesis were proven to be correct.
Coordination Polymers With the Pyrazine-2,5-Diyldimethanol Linker – Supramolecular Networks Through Robust Hydrogen and Halogen Bonds
Authors: Armaghan Mahsa , Stürzer Tobias , Janiak Christoph
Published: June 2023

The synthesis and crystal structure of pyrazine-2,5-diyldimethanol (pzydmH2, C8H8N2O2) a new symmetric water-soluble N,O-chelating tetra-dentate organic ligand is reported and an environmentally friendly method was used to synthesize coordination compounds in water under ambient conditions from the reaction of pzydmH2 with the halide salts of Cu(II), Zn(II), Hg(II) and Cd(II): {[Cu(pzydmH2)0.5(µ-Br)(Br)(H2O)]·H2O}n 1, {[Zn2(pzydmH2)(µ-Cl)(Cl)3(H2O)]·H2O}n 2, [Hg2(pzydmH2)0.5(µ-Cl)2(Cl)2]n 3, {[Cd2(pzydmH2)(µ-Cl)4]·H2O}n 4, and {[Cd2(pzydmH2)(µ-Br)4]·H2O}n 5. Single-crystal X-ray diffraction analysis revealed that 1-3 are 1D coordination polymers and 4 and 5 are 3D coordination networks, all constructed by bridging pyrazine-2,5-diyldimethanol and halogen ions. The hydroxyl groups in the organic linker extend the 1D chains to non-covalent 3D networks. In all non-covalent and covalent 3D networks water molecules were trapped by strong hydrogen bond interactions. Supramolecular analysis revealed strong O-H···O, O-H···N, O-H···X and week of C-H···O, C-H···X (X = Cl, Br) hydrogen bonds, as well as π-π(pyrazine ring), metal-halogen···π(pyrazine ring) and O-H···ring(5-membered chelate ring) interactions. Also X···O weak halogen bonds are present in 1-5 (X = Cl and Br).
CoVigator – a Knowledge Base for Navigating SARS-CoV-2 Genomic Variants
Authors: Bukur Thomas , Riesgo-Ferreiro Pablo , Sorn Patrick , Gudimella Ranganath , Hausmann Johannes , Rösler Thomas , Löwer Martin , Schrörs Barbara , Sahin Ugur
Published: June 2023

Background: The outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in the global COVID-19 pandemic. The urgency for an effective SARS-CoV-2 vaccine has led to the development of a first series of vaccines at unprecedented speed. The discovery of SARS-CoV-2 spike-glycoprotein mutants, however, and consequentially the potential to escape vaccine-induced protection and increased infectivity, demonstrates the persisting importance of monitoring SARS-CoV-2 mutations to enable early detection and tracking of genomic variants of concern.
Results: We developed the CoVigator tool with three components: 1) a knowledge base that collects new SARS-CoV-2 genomic data, processes it and stores its results; 2) a comprehensive variant calling pipeline; 3) an interactive dashboard highlighting the most relevant findings. The knowledge base routinely downloads and processes virus genome assemblies or raw sequenc-ing data from the COVID-19 Data Portal (C19DP) and the European Nucleotide Archive (ENA), respectively. The results of the variant calling pipeline are visualized through the dashboard in the form of tables and customizable graphs, making it a versatile tool for tracking SARS-CoV-2 variants. We put a special emphasis on the identification of intrahost mutations and make available to the community what is, to the best of our knowledge, the largest dataset on SARS-CoV-2 intrahost mutations. In the spirit of open data, all CoVigator results are available for download. The CoVigator dashboard is accessible via covigator.tron-mainz.de.
Conclusion: With increasing demand worldwide in genome surveillance for tracking the spread of SARS-CoV-2, CoVigator will be a valuable resource of up-to-date list of mutations, which can be incorporated into global efforts to sustainably prevent or treat infections.
The Effects of Tricalcium Silicate Nanoparticle-containing Cement: In Vitro and In Vivo Studies
Authors: Ezawa Naho , Akashi Yoshihiko , Nakajima Kei , Kokubun Katsutoshi , Furusawa Masahiro , Matsuzaka Kenichi
Published: June 2023

A tricalcium silicate nanoparticle-containing cement (NPC) was developed to overcome the disadvantages of existing mineral trioxide aggregate (MTA) dental materials. This study aimed at evaluating the effects of NPC on the osteogenic differentiation of human periodontal ligament fibroblasts (HPLFs) in vitro, and on the healing of furcal perforations created experimentally in rat molars in vivo, in comparison to MTA. The in vitro studies performed the following assays; pH measurement using a pH meter, the release of calcium ions using a calcium assay kit, cell attachment and morphology using SEM, cell proliferation using a coulter counter, marker expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and cell mineralized deposit formation using Alizarin Red S (ARS) staining. In the in vivo studies, MTA and NPC were used to fill the rat molar perforations. Rat molars were processed at 7, 14 and 28 days for analysis of inflammatory processes using hematoxylin and eosin (HE) staining, immunohistochemical staining of Runx2 and tartrate-resistant acid phosphate (TRAP) staining. The results demonstrate that the nanoparticle size distribution of NPC is critical for osteogenic potential at an earlier stage compared to MTA. Further studies are required to elucidate the mechanism of action of NPC in osteogenic differentiation.
Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD)
Authors: Stancioiu Felician , Bogdan Raluca , Dumitrescu Radu
Published: June 2023

Autistic spectrum disease (ASD) is an increasingly common diagnosis nowadays with a prevalence of 1-2% in most countries. Its complex causality – a combination of genetic, immune, metabolic and environmental factors - is translated into pleiomorphic developmental disorders of various severity, which have in common two main aspects: repetitive, restrictive behaviors, and difficulties in social interaction varying from awkward habits and verbalization to complete lack of interest from the ASD child for the outside world. The wide variety of ASD causes also makes it very difficult to find a common denominator – a disease biomarker and medication – and currently there is no commonly used diagnostic and therapeutic strategy besides clinical evaluation and psychotherapy.It is known that inflammation is present in a majority of ASD children, and blood inflammatory markers, together with metabolic, electrophysiological markers and imagistics are useful for ASD diagnostic validation and treatment; however, they tend to leave out a sizeable proportion of ASD kids who do not have such modifications. Genetic testing – whole exome sequencing or targeted profiling on about 500 ASD-linked genes- may also provide good insight into pathophysiology, however many times its results are more restrictive rather than offering additional therapeutic options.Here we describe a new biomarker for ASD - the neuron-specific enolase (NSE) - which was elevated above the normal clinical range (less than 16.3 ng/mL) in the vast majority of ASD kids tested in our study (40 of 41, or 97.5%). This finding opens up a new direction for diagnostic confirmation, dynamic evaluation and therapeutic intervention for ASD kids.
Remdesivir-Nirmatrelvir Combination: In Vitro Activity and a Case Report
Authors: Gidari Anna , Sabbatini Samuele , Schiaroli Elisabetta , Bastianelli Sabrina , Pierucci Sara , Busti Chiara , Saraca Lavinia Maria , Capogrossi Luca , Pasticci Maria Bruna , Francisci Daniela
Published: June 2023

Introduction: This study aims to investigate the activity of the remdesivir-nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and to report a case of Coronavirus Disease 2019 (COVID-19) cured with this combination.
Methods: A Vero E6 cell-based infection assay was used to investigate the in vitro activity of the remdesivir-nirmatrelvir combination. The SARS-CoV-2 strains tested were 20A.EU1, BA.1 and BA.5. After incubation, a viability assay was performed. The supernatants were collected and used for viral titration.
The Highest Single Agent (HSA) reference model was calculated. An HSA score >10 is considered synergic.
Results: Remdesivir and nirmatrelvir showed synergistic activity at 48 and 72 h with an HSA score of 52.8 and 28.6, respectively (p<0.0001). This data has been confirmed performing supernatant titration and against the omicron variants: the combination reduced the viral titer better than the more active compound alone.
An immunocompromised patient with prolonged and critical COVID-19 was successfully treated with remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab, and dexamethasone, with an excellent clinical-radiological response. However, she required further off-label prolonged therapy with nirmatrelvir/ritonavir up to the negativization.
Conclusion: Remdesivir-nirmatrelvir combination has synergic activity in vitro. This combination may have a role in immunosuppressed patients with severe COVID-19 and prolonged viral shedding.
Complex Analysis of Endothelial Markers as Potential Prognostic Indicators in Luminal Invasive Breast Carcinoma Patients: Outcomes of a Six-Year Observational Study
Authors: Kwiatkowska Katarzyna , Rhone Piotr , Koziorzemska Paulina , Formanowicz Dorota , Ruszkowska-Ciastek Barbara
Published: June 2023

(1) Background: Metastasis is a complex process in which the primary cancer cells spread to a distant organ or organs, creating a secondary tumour location, which in many patients leads to treatment failure and death. The aim of the present study was to assess the association of endothelial markers (i.e., sP-selectin, sE-selectin and von Willebrand factor) with the leptin-to-adiponectin ratio (LAR) and to perform an analysis of the predictive value on the survival of patients with luminal A and B invasive breast cancer (IBrC). (2) Methods: The trial included 70 previously untreated women with a median age of 54.5 years and a median tumour size of 1.5 cm. The concentrations of pre- and post-treatment endothelial markers, leptin, and adiponectin were evaluated with specific ELISA kits. The median duration of follow-up was 68.5 months (interquartile range (IQR) = 59–72 months) with a recurrence rate of 15.71%. (3) Results: Regardless of the treatment pattern, endothelial marker concentrations and the LAR increased after treatment. The follow-up showed a significantly higher relapse rate in patients with IBrC who had higher pre-treatment sP-selectin and post-treatment LAR levels. A post-treatment LAR of 0.83 ng/mL with a sensitivity of 88.9% and specificity of 57.9% was established as the optimal cut-off value for distinguishing patients with or without disease recurrence. Additionally, a higher risk of breast cancer relapse was associated with a lower post-treatment sP-selectin concentration. (4) Conclusions: Our results showed mainly that pre-treatment sP-selectin levels and post-treatment LAR may have a value as prognostic indicators and may contribute to predicting the future outcome in patients with early-stage IBrC.
Assessment of Site Amplification Factors in Southern Lima, Peru Based on Microtremor H/V Spectral Ratios and Deep Neural Network
Authors: Miura Hiroyuki , Gonzales Carlos , Diaz Miguel , Estrada Miguel , Lazares Fernando , Aguilar Zenon , Pan Da , Matsuoka Masashi
Published: May 2023

Evaluation of site amplification factors (SAFs) of seismic waves has been one of the important issues for evaluating seismic hazards. The authors have proposed a deep neural network (DNN) model in order to cost-effectively and accurately estimate SAF from microtremor horizontal-to-vertical spectral ratio (MHVR). In this study, we assessed the SAFs in southern Lima, Peru by estimating from MHVRs and DNN. First, we validated the applicability of the DNN model to Lima by estimating the SAFs from the MHVRs observed at seismic stations in Lima. From the comparison with the observed SAFs derived from spectral inversion technique, we confirmed that the SAFs in Lima were accurately estimated by the DNN model. The SAFs in the southern Lima including Chorrillos and Villa El Salvador districts were evaluated by applying the DNN model to the observed MHVRs at approximately 250 sites. We found that large amplifications at low frequency around 1 Hz were expected in the southeastern coastal areas formed by eolian sands whereas smaller amplification were estimated in the northwestern areas mainly located on alluvial deposits.
Extraction and analysis of per- and polyfluoroalkyl Substances (PFAS) from Meals Ready-to-Eat (MRE) films using GC-MS and LC-MS/MS
Authors: Kimble Ashley , Muensterman Derek , Cahuas Liliana , Titaley Ivan , Field Jennifer , Bednar Anthony , Moores Lee
Published: May 2023

This work was in response to the Defense Logistic Agency’s (DLA) Subsistence Network Broad Agency Announcement, BAA-0003-16 addressing 2019 NDAA Section 329 that states packaging materials used for Meals Ready-to-Eat (MRE) that contact food products must be free of per- and polyfluoroalkyl substances (PFAS). This was addressed by determining the presence or absence of PFAS on MREs by extraction followed by gas chromatography mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Any samples positive for PFAS were quantitated using LC triple quadrupole (QqQ) MS at the US Army Engineering and Research Development Center (ERDC) and by high resolution quadrupole time-of-flight (qTOF) MS and GC-MS at Oregon State University (OSU).
Atypical Mycobacterial Infection in Post Abdomino-Thoracic Trauma: A Case Report
Authors:   Junior resident, Department of General and GI surgery, PSG Institute of Medical Sciences & Research, Coimbatore 641004, Tamil Nadu, India., Joseph Jenny , Bhat Sunay N ,   Associate Professor, Department of General and GI surgery, PSG Institute of Medical Sciences & Research, Coimbatore 641004, Tamil Nadu, India.
Published: June 2023

Objective/Background: SSIs remain a significant cause of morbidity and mortality after surgery. One in eight patients develop SSI after exploratory laparotomies making it one of the major factors responsible for post-operative mortality and morbidity. Atypical mycobacteria are responsible for a spectrum of diseases ranging from superficial skin infections to widely disseminated systemic infections. Health care associated infections due to non-tuberculous mycobacteria is on the rise due to contaminated hospital water supplies, solutions, improperly sterilized instruments and devices. Our case is of an atypical mycobacterial infection in a patient with abdomino-thoracic trauma who underwent multiple surgeries. Case presentation: A 24 year old gentleman presented with a penetrating stab injury to the abdomen and left hemi-thorax following an assault. Patient underwent an emergency exploratory laparotomy which revealed a 4 x 4 cm defect in the left hemi-diaphragm, through which the stomach was herniating into the left thoracic cavity. During the 2nd post-operative week, patient developed empyema thorax, for which pigtail drain was placed initially and later thoracotomy with decortication and intercostal drainage were performed. Following discharge after 2 weeks, he presented with fever, body pain and pus discharge from the previously inserted intercostal drain site. Pus obtained was positive for acid fast bacilli and gene expert was negative. Atypical mycobacterial infection was diagnosed based on high index of suspicion and he received treatment for 6 months. Conclusion: This case highlights that identification of atypical mycobacterial infections in post-operative patients require a high index of suspicion. Management requires multi-drug approach and surgical intervention wherever necessary. Even with the existing sterilization techniques and preventive measure, atypical mycobacterial infection cannot be completely eliminated from a hospital set-up and hence must be considered in all nosocomial infections.
Structure of a 10-23 Deoxyribozyme Exhibiting a Homodimer Conformation
Authors: Cramer Evan , Starcovic Sarah , Avey Rebekah , Kaya Ali , Robart Aaron
Published: May 2023

Deoxyribozymes (DNAzymes) are in vitro evolved DNA sequences capable of catalyzing chemical reactions. The RNA cleaving 10–23 DNAzyme was the first DNAzyme to be evolved and possesses clinical and biotechnical applications as a biosensor and a knockdown agent. DNAzymes do not require the recruitment of other components to cleave RNA and can turnover, thus they have a distinct advantage over other knockdown methods (siRNA, CRISPR, morpholinos). Despite this, a lack of structural and mechanistic information has hindered the optimization and application of the 10–23 DNAzyme. Here, we report a 2.7 Å crystal structure of the RNA cleaving 10–23 DNAzyme in a homodimer conformation. Although proper coordination of the DNAzyme to substrate is observed along with intriguing patterns of bound magnesium ions, the dimer conformation likely does not capture the true catalytic form of the 10–23 DNAzyme.
Deterministic switching of antiferromagnetic spin textures by chaotic magnons
Authors: Yu Haiming , Chen Jilei , Wang Jinlong , Sheng Lutong , Jia Hao , Wei Weiwei , Zhang Han , Zhang Yuelin , Wang Hanchen , Yuan Rundong , Liu Song , Chen Tingyong , Grundler Dirk , Yu Dapeng , Ansermet Jean-Philippe
Published: May 2023

Topological spin textures such as magnetic skyrmions1-7 are promising candidates as information carriers for next-generation memory-in-logic devices8. Antiferromagnetic spin textures9-12, compared to their ferromagnetic counterparts, innately possess high stability with respect to external disturbance13,14 and high-frequency dynamics15-18 compatible with ultrafast information processing. However, deterministic creation and reconfigurable switching of different antiferromagnetic spin textures have not been realized so far. Here, we demonstrate room-temperature deterministic switching between antiferromagnetic domain walls, Bloch bimerons and Néel bimerons in single-crystal hematite (α-Fe2O3)12,19-22. All three topological states are found to be remarkably stable and fully controllable, as confirmed by 1’000 switching cycles. Their dynamics exhibit distinct resonance frequencies and magnetic field dependences. The switching from domain walls to Bloch bimerons requires only one microwave pulse (100 ns) with ultralow energy consumption (1 nJ). When the dynamic excitation wavevector approaches that of static spin textures, and the power lies beyond a threshold, chaotic magnons23-26 are excited, which subsequently nucleate bimerons and finally lead to a deterministic switching, as unveiled by micromagnetic simulations. The progressive switching from Bloch-type to Néel-type bimerons imitates the weighted sum operation in neuromorphic computing27,28. Thus, our work points to the possibility of using spin textures in antiferromagnets for information processing.
Convergent approach of double intermediates in flow microreactor: flash irreversible carbocations generation enables direct cross–coupling
Authors: Soutome Hiroki , Yamashita Hiroki , Ashikari Yosuke , Takumi Masahiro , Shimizu Yutaka , Nagaki Aiichiro
Published: May 2023

In biosynthesis multiple kinds of reactive intermediates are generated, transported, and reacted across different parts of organisms, enabling highly sophisticated synthetic reactions. Inspired by such ideal reaction conditions, herein we report a convergent synthetic approach using double intermediates, carbocations and carbanions, at once. By reactions of unsaturated precursors, such as enamines, with a superacid in a flow microreactor, carbocations were generated rapidly and irreversibly, and before decomposition, they were transported to react with rapidly and independently generated carbanions, enabling direct C–C bond formation. Taking advantage of the reactivity of these double reactive intermediates, the reaction took place within a few seconds, enabling synthetic reactions which are not applicable in conventional reactions.
Construction of New Urbanization and Economic Growth of Resource-Based Cities: Evidence from China
Authors: Yang Zhiliang , Cao Ying , Du Junhong
Published: May 2023

development of a resource-based city economy. Using data from prefecture-level cities between 2011 and 2017, this study employs a double difference approach to assess the impact of the new urbanization comprehensive pilot policy on the economic growth of resource-based cities. According to the research findings, the new urbanization construction has promoted the growth of GDP per capita in resource-based cities, and has passed the robustness test; heterogeneity analysis shows that the policy effect of new urbanization construction in resource-rich cities is stronger than the policy effect of new urbanization construction in resource-poor cities, and the policy effect in energy resource-based cities is significant, but the policy effect of metal and other resource-based cities is not significant. The policy effect of resource-based cities in the eastern and western regions is significant, while that in the central regions is not significant.