bluuebunny/crossref_metadata_2025 huggingface dataset:
Narrow Genetic Diversity of Wolbachia Symbionts in Acrididae Grasshopper Hosts (Insecta, Orthoptera)
Authors: Ilinsky Yury , Demenkova Mary , Bykov Roman , Bugrov Alexander
Published: January 2022

Bacteria of the Wolbachia genus are maternally inherited symbionts of Nematoda and numerous Arthropoda hosts. There are approximately 20 lineages of Wolbachia, which are called supergroups, and they are designated alphabetically. Wolbachia strains of the supergroups A and B are predominant in arthropods, especially in insects, and supergroup F seems to rank third. Host taxa have been studied very unevenly for Wolbachia symbionts, and here, we turn to one of largely unexplored insect families: Acrididae. On the basis of five genes subject to multilocus sequence typing, we investigated the incidence and genetic diversity of Wolbachia in 41 species belonging three subfamilies (Gomphocerinae, Oedipodinae, and Podisminae) collected in Turkey, Kazakhstan, Tajikistan, Russia, and Japan, making 501 specimens in total. Our results revealed a high incidence and very narrow genetic diversity of Wolbachia. Although only the strains belonging to supergroups A and B are commonly present in present, the Acrididae hosts here proved to be infected with supergroups B and F without A-supergroup variants. The only trace of an A-supergroup lineage was noted in one case of an inter-supergroup recombinant haplotype, where the ftsZ gene came from supergroup A, and the others from supergroup B. Variation in the Wolbachia haplotypes in Acrididae hosts within supergroups B and F was extremely low. A comprehensive genetic analysis of Wolbachia diversity confirmed specific features of the Wolbachia allelic set in Acrididae hosts. This result can help to elucidate the crucial issue of Wolbachia biology: the route(s) and mechanism(s) of Wolbachia horizontal transmission.
Diet Prevents Social Stress-Induced Maladaptive Neurobehavioural and Gut Microbiota Changes in a Histamine-Dependent Manner
Authors: Costa Alessia , Rani Barbara , Bastiaanssen Thomaz F. S. , Bonfiglio Francesco , Gunnigle Eoin , Provensi Gustavo , Rossitto Moira , Boehme Marcus , Strain Conall , Martínez Clara S. , Blandina Patrizio , Cryan John F. , Layé Sophie , Corradetti Renato , Passani Maria Beatrice
Published: January 2022

Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protective effects against the insults of chronic stress afforded by a healthy diet. By using C57BL/6J male mice that do not synthesize histamine (Hdc−/−) and their wild type (Hdc+/+) congeners we evaluated if the histaminergic system participates in the protective action of a diet enriched with polyunsaturated fatty acids and vitamin A on the deleterious effect of chronic stress. Behavioural tests across domains relevant to cognition and anxiety were performed. Hippocampal synaptic plasticity, cytokine expression, hippocampal fatty acids, oxylipins and microbiota composition were also assessed. Chronic stress induced social avoidance, poor recognition memory, affected hippocampal long-term potentiation, changed the microbiota profile, brain cytokines, fatty acid and oxylipins composition of both Hdc−/− and Hdc+/+ mice. Dietary enrichment counteracted stress-induced deficits only in Hdc+/+ mice as histamine deficiency prevented almost all the diet-related beneficial effects. Interpretation: Our results reveal a previously unexplored and novel role for brain histamine as a mediator of many favorable effects of the enriched diet. These data present long-reaching perspectives in the field of nutritional neuropsychopharmacology.
Chalcogen···Chalcogen Bonding in Molybdenum Disulfide, Molybdenum Diselenide and Molybdenum Ditelluride Dimers as Prototypes for a Basic Understanding of the Local Interfacial Chemical Bonding Environment in 2D Layered Transition Metal Dichalcogenides
Authors: Varadwaj Pradeep , Marques Helder , Varadwaj Arpita , Yamashita Koichi
Published: January 2022

An attempt was made, using computational methods, to understand whether the intermolecular interactions in the dimers of molybdenum dichalcogenides MoCh2 (Ch = chalcogen, element of group 16, especially S, Se and Te) and similar mixed-chalcogenide derivatives resemble the room temperature experimentally observed interactions in the interfacial regions of molybdenites and their other mixed-chalcogen derivatives. To this end, MP2(Full)/def2-TVZPPD level electronic structure calculations on nine dimer systems, including (MoCh2)2 and (MoChCh′2)2 (Ch, Ch′ = S, Se and Te), were carried out not only to demonstrate the energetic stability of these systems in the gas phase, but also to reproduce the intermolecular geometrical properties that resemble the interfacial geometries of 2D layered MoCh2 systems reported in the crystalline phase. Among the six DFT functionals (single and double hybrids) benchmarked against MP2(full), it was found that the double hybrid functional B2PLYPD3 has some ability to reproduce the intermolecular geometries and binding energies. The intermolecular geometries and binding energies of all nine dimers are discussed, together with the charge density topological aspects of the chemical bonding interactions that emerge from the application of the quantum theory of atoms in molecules (QTAIM), the isosurface topology of the reduced density gradient noncovalent index, interaction region indicator and independent gradient model (IGM) approaches. While the electrostatic surface potential model fails to explain the origin of the S···S interaction in the (MoS2)2 dimer, we show that the intermolecular bonding interactions in all nine dimers examined are a result of hyperconjugative charge transfer delocalizations between the lone-pair on (Ch/Ch′) and/or the π-orbitals of a Mo–Ch/Ch′ bond of one monomer and the dπ* anti-bonding orbitals of the same Mo–Ch/Ch′ bond in the second monomer during dimer formation, and vice versa. The HOMO–LUMO gaps calculated with the MN12-L functional were 0.9, 1.0, and 1.1 eV for MoTe2, MoSe2 and MoS2, respectively, which match very well with the solid-state theoretical (SCAN-rVV10)/experimental band gaps of 0.75/0.88, 0.90/1.09 and 0.93/1.23 eV of the corresponding systems, respectively. We observed that the gas phase dimers examined are perhaps prototypical for a basic understanding of the interfacial/inter-layer interactions in molybdenum-based dichalcogenides and their derivatives.
Bidimensional Polyiodide Netting Stabilized by a Cu(II) Macrocyclic Complex
Authors: Savastano Matteo , Monini Valeria , Bazzicalupi Carla , Bianchi Antonio
Published: January 2022

Iodine-dense polyiodide phases are interesting materials for a number of potential uses, including batteries and solid-state conductors. The incorporation of transition metal cations is considered a promising way to enhance the stability, tune the properties, and influence the architecture of polyiodides. However, several interesting metals, including Cu(II), may suffer redox processes, which generally make them not compatible with the I2/I− redox couple. Herein L, a simple derivative of cyclen, is proposed as a Cu(II) ligand capable of protecting the +2 oxidation state of the metal even in the presence of polyiodides. With a step by step approach, we report the crystal structure of free L; then we present spectrophotometric verification of Cu(II) complex stability, stoichiometry, and formation kinetic in DMF solution, together with Cu(II) binding mode elucidation via XRD analysis of [Cu(L)Cl]ClO4∙CH3CN crystals; afterwards, the stability of the CuL complex in the presence of I− is demonstrated in DMF solution, where the formation of a Cu:L:I− ternary complex, rather than reduction to Cu(I), is observed; lastly, polyiodide crystals are prepared, affording the [Cu(L)I]2I3I5 crystal structure. This layered structure is highly peculiar due to its chiral arrangement, opening further perspective for the crystal engineering of polyiodide phases.
Schizophrenia and Hospital Admissions for Cardiovascular Events in a Large Population: The APNA Study
Authors: Guillen-Aguinaga Sara , Brugos-Larumbe Antonio , Guillen-Aguinaga Laura , Ortuño Felipe , Guillen-Grima Francisco , Forga Luis , Aguinaga-Ontoso Ines
Published: January 2022

(1) Background: Patients with schizophrenia have higher mortality, with cardiovascular diseases being the first cause of mortality. This study aims to estimate the excess risk of hospital admission for cardiovascular events in schizophrenic patients, adjusting for comorbidity and risk factors. (2) Methods: The APNA study is a dynamic prospective cohort of all residents in Navarra, Spain. A total of 505,889 people over 18 years old were followed for five years. The endpoint was hospital admissions for a cardiovascular event. Direct Acyclic Graphs (DAG) and Cox regression were used. (3) Results: Schizophrenic patients had a Hazard Ratio (HR) of 1.414 (95% CI 1.031–1.938) of hospital admission for a cardiovascular event after adjusting for age, sex, hypertension, type 2 diabetes, dyslipidemia, smoking, low income, obesity, antecedents of cardiovascular disease, and smoking. In non-adherent to antipsychotic treatment schizophrenia patients, the HR was 2.232 (95% CI 1.267–3.933). (4) Conclusions: Patients with schizophrenia have a higher risk of hospital admission for cardiovascular events than persons with the same risk factors without schizophrenia. Primary care nursing interventions should monitor these patients and reduce cardiovascular risk factors.
Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level
Authors: Leonardi Benedetta , Gentili Federica , Perrone Marco Alfonso , Sollazzo Fabrizio , Cocomello Lucia , Silva Kikina Stefani , Wald Rachel M. , Palmieri Vincenzo , Secinaro Aurelio , Gagliardi Maria Giulia , Parisi Attilio , Turchetta Attilio , Galletti Lorenzo , Bianco Massimiliano , Drago Fabrizio
Published: January 2022

Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical compromise. Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity, and the International Physical Activity Questionnaire (IPAQ) can provide additional data on physical activity (PA) achieved. Our aim was to assess the association between CPET values, IPAQ measures, and MRI parameters. All rToF patients who had both an MRI and CPET performed within one year between March 2019 and June 2021 were selected. Clinical data were extracted from electronic records (including demographic, surgical history, New York Heart Association (NYHA) functional class, QRS duration, arrhythmia, MRI parameters, and CPET data). PA level, based on the IPAQ, was assessed at the time of CPET. Eighty-four patients (22.8 ± 8.4 years) showed a reduction in exercise capacity (median peak VO2 30 mL/kg/min (range 25–33); median percent predicted peak VO2 68% (range 61–78)). Peak VO2, correlated with biventricular stroke volumes (RVSV: β = 6.11 (95%CI, 2.38 to 9.85), p = 0.002; LVSV: β = 15.69 (95% CI 10.16 to 21.21), p < 0.0001) and LVEDVi (β = 8.74 (95%CI, 0.66 to 16.83), p = 0.04) on multivariate analysis adjusted for age, gender, and PA level. Other parameters which correlated with stroke volumes included oxygen uptake efficiency slope (OUES) (RVSV: β = 6.88 (95%CI, 1.93 to 11.84), p = 0.008; LVSV: β = 17.86 (95% CI 10.31 to 25.42), p < 0.0001) and peak O2 pulse (RVSV: β = 0.03 (95%CI, 0.01 to 0.05), p = 0.007; LVSV: β = 0.08 (95% CI 0.05 to 0.11), p < 0.0001). On multivariate analysis adjusted for age and gender, PA level correlated significantly with peak VO2/kg (β = 0.02, 95% CI 0.003 to 0.04; p = 0.019). We observed a reduction in objective exercise tolerance in rToF patients. Biventricular stroke volumes and LVEDVi were associated with peak VO2 irrespective of RV size. OUES and peak O2 pulse were also associated with biventricular stroke volumes. While PA level was associated with peak VO2, the incremental value of this parameter should be the focus of future studies.
Vitamin D Inhibits IL-6 Pro-Atherothrombotic Effects in Human Endothelial Cells: A Potential Mechanism for Protection against COVID-19 Infection?
Authors: Cimmino Giovanni , Conte Stefano , Morello Mariarosaria , Pellegrino Grazia , Marra Laura , Morello Andrea , Nicoletti Giuseppe , De Rosa Gennaro , Golino Paolo , Cirillo Plinio
Published: January 2022

Background: Thrombosis with cardiovascular involvement is a crucial complication in COVID-19 infection. COVID-19 infects the host by the angiotensin converting enzyme-2 receptor (ACE2r), which is expressed in endothelial cells too. Thus, COVID-related thrombotic events might be due to endothelial dysfunction. IL-6 is one of the main cytokines involved in the COVID-19 inflammatory storm. Some evidence indicates that Vitamin D (VitD) has a protective role in COVID-19 patients, but the molecular mechanisms involved are still debated. Thus, we investigated the effect of VitD on Tissue Factor and adhesion molecules (CAMs) in IL-6-stimulated endothelial cells (HUVEC). Moreover, we evaluated levels of the ACE2r gene and proteins. Finally, we studied the modulation of NF-kB and STAT3 pathways. Methods: HUVEC cultivated in VitD-enriched medium were stimulated with IL-6 (0.5 ng/mL). The TF gene (RT-PCR), protein (Western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. Similarly, CAMs soluble values (ELISA) and ACE2r (RT-PCR and Western blot) levels were assessed. NF-kB and STAT3 modulation (Western blot) were also investigated. Results: VitD significantly reduced TF expression at both gene and protein levels as well as TF-procoagulant activity in IL-6-treated HUVEC. Similar effects were observed for CAMs and ACE2r expression. IL-6 modulates these effects by regulating NF-κB and STAT3 pathways. Conclusions: IL-6 induces endothelial dysfunction with TF and CAMs expression via upregulation of ACE2r. VitD prevented these IL-6 deleterious effects. Thus, it might be speculated that this is one of the hypothetical mechanism(s) by which VitD exerts its beneficial effects in COVID-19 infection.
Adherence to Eye Drops Usage in Dry Eye Patients and Reasons for Non-Compliance: A Web-Based Survey
Authors: Uchino Miki , Yokoi Norihiko , Shimazaki Jun , Hori Yuichi , Tsubota Kazuo ,   on behalf of the Japan Dry Eye Society
Published: January 2022

This study aimed to investigate the actual use of eye drops for dry eye disease (DED), the reasons for instillation behavior, and the relationship between instillation behavior and subjective symptoms. This web-based cross-sectional study collected data on instillation behavior, medication instruction, reasons for instillation behavior, and subjective symptoms. In total, 2645 participants were enrolled. The proportion of participants who instilled at the frequency specified in the package insert (the specified frequency) was 10.2%. The most common reason for not instilling at the prescribed frequency was as-needed instillation to alleviate subjective symptoms, and 61.3% of participants instilled when feeling symptoms. The improvement in the subjective symptoms score was significantly greater in the group that regularly instilled at the specified frequency than the other group (p = 0.0027), and patients in the other group were younger and had a higher rate of contact lens use and over-the-counter eye drops use. In conclusion, most participants did not instill the DED eye drops at the specified frequency to alleviate symptoms. In order to obtain the appropriate effect of eye drops, ophthalmologists need to impress upon patients the importance of regular instillation at the frequency specified in the package insert, while taking into account patient characteristics.
The Impact of Modifying Sunitinib Treatment Scheduling on Renal Cancer Tumor Biology and Resistance
Authors: Lin Harrison Sicheng , Ding Qiang , Lichner Zsuzsanna , Kim Sung Sun , Saleeb Rola , Farag Mina , Di Meo Ashley , Plant Pamela , Kaldas Mirit , Bjarnason Georg Arnold , Yousef George Makram
Published: January 2022

With sunitinib treatment of metastatic renal cell carcinoma, most patients end up developing resistance over time. Recent clinical trials have shown that individualizing treatment protocols could delay resistance and result in better outcomes. We developed an in vivo xenograft tumor model and compared tumor growth rate, morphological, and transcriptomic differences between alternative and traditional treatment schedules. Our results show that the alternative treatment regime could delay/postpone cancer progression. Additionally, we identified distinct morphological changes in the tumor with alternative and traditional treatments, likely due to the significantly dysregulated signaling pathways between the protocols. Further investigation of the signaling pathways underlying these morphological changes may lead potential therapeutic targets to be used in a combined treatment with sunitinib, which offers promise in postponing/reversing the resistance of sunitinib.
Are Oropharyngeal Dysphagia Screening Tests Effective in Preventing Pneumonia?
Authors: Okuni Ikuko , Ebihara Satoru
Published: January 2022

Oropharyngeal dysphagia, a clinical condition that indicates difficulty in moving food and liquid from the oral cavity to the esophagus, has a markedly high prevalence in the elderly. The number of elderly people with oropharyngeal dysphagia is expected to increase due to the aging of the world’s population. Understanding the current situation of dysphagia screening is crucial when considering future countermeasures. We report findings from a literature review including citations on current objective dysphagia screening tests: the Water Swallowing Test, Mann Assessment of Swallowing Ability, and the Gugging Swallowing Screen. Pneumonia can be predicted using the results of the screening tests discussed in this review, and the response after the screening tests is important for prevention. In addition, although interdisciplinary team approaches prevent and reduce aspiration, optimal treatment is a challenging. Intervention studies with multiple factors focusing on the elderly are needed.
Failure Analysis in Multiple TKA Revisions—Periprosthetic Infections Remain Surgeons’ Nemesis
Authors: Kirschbaum Stephanie , Erhart Sarah , Perka Carsten , Hube Robert , Thiele Kathi
Published: January 2022

Background: The aim of this study was to categorize reasons for failure and to analyze the survivorship of multiple total knee arthroplasty (TKA) revisions. Methods: The study retrospectively evaluated all multiple TKA revisions performed between 2005 and 2015 at the authors’ institutions. Sixty-three patients (35 female, 28 male, age 64 ± 10 years, follow-up 55 ± 36 months) underwent a total of 157 re-revision TKA surgeries (range 2–5). The revision indications were divided up into main diagnoses. Survivorship was evaluated by mixed model analysis. Results: The main overall reason for re-revision was periprosthetic joint infection (PJI) (48%), followed by instability (12%), polyethylene wear (11%), malpositioning (8%), and aseptic loosening (8%). Survivorship shortened with an increasing number of revision surgeries (p = 0.003). While PJI was in 38% of all cases, the reason for the first revision, incidence increased constantly with the number of revisions (48% at second revision, 55% at third revision, 86% at fourth revision, and 100% at fifth revision, p = 0.022). If periprosthetic infection caused the first revision, patients showed an average of two more septic revisions at follow-up than patients with an aseptic first revision indication (p < 0.001). In 36% of cases, the reason for follow-up surgery in case of periprosthetic infection was again PJI. Conclusion: The probability of survival of the implanted knee arthroplasty is significantly reduced with each subsequent revision. Periprosthetic infection is the main cause of multiple revisions.
Serum C18:1-Cer as a Potential Biomarker for Early Detection of Gestational Diabetes
Authors: Juchnicka Ilona , Kuźmicki Mariusz , Zabielski Piotr , Krętowski Adam , Błachnio-Zabielska Agnieszka , Szamatowicz Jacek
Published: January 2022

We hypothesized that sphingolipids may be early biomarkers of gestational diabetes mellitus (GDM). Here, 520 women with normal fasting plasma glucose levels were recruited in the first trimester and tested with a 75 g oral glucose tolerance test in the 24th–28th week of pregnancy. Serum sphingolipids concentrations were measured in the first and the second trimester by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/MS/MS) in 53 patients who were diagnosed with GDM, as well as 82 pregnant women with normal glucose tolerance (NGT) and 32 non-pregnant women. In the first trimester, pregnant women showed higher concentrations of C16:0, C18:1, C22:0, C24:1, and C24:0-Cer and lower levels of sphinganine (SPA) and sphingosine-1-phosphate (S1P) compared to non-pregnant women. During pregnancy, we observed significant changes in C16:0, C18:0, C18:1, and C24:1-Cer levels in the GDM group and C18:1 and C24:0-Cer in NGT. The GDM (pre-conversion) and NGT groups in the first trimester differed solely in the levels of C18:1-Cer (AUC = 0.702 p = 0.008), also considering glycemia. Thus, C18:1-Cer revealed its potential as a GDM biomarker. Sphingolipids are known to be a modulator of insulin resistance, and our results indicate that ceramide measurements in early pregnancy may help with GDM screening.
Rethinking the Body in the Brain after Spinal Cord Injury
Authors: Leemhuis Erik , Giuffrida Valentina , De Martino Maria Luisa , Forte Giuseppe , Pecchinenda Anna , De Gennaro Luigi , Giannini Anna Maria , Pazzaglia Mariella
Published: January 2022

Spinal cord injuries (SCI) are disruptive neurological events that severly affect the body leading to the interruption of sensorimotor and autonomic pathways. Recent research highlighted SCI-related alterations extend beyond than the expected network, involving most of the central nervous system and goes far beyond primary sensorimotor cortices. The present perspective offers an alternative, useful way to interpret conflicting findings by focusing on the deafferented and deefferented body as the central object of interest. After an introduction to the main processes involved in reorganization according to SCI, we will focus separately on the body regions of the head, upper limbs, and lower limbs in complete, incomplete, and deafferent SCI participants. On one hand, the imprinting of the body’s spatial organization is entrenched in the brain such that its representation likely lasts for the entire lifetime of patients, independent of the severity of the SCI. However, neural activity is extremely adaptable, even over short time scales, and is modulated by changing conditions or different compensative strategies. Therefore, a better understanding of both aspects is an invaluable clinical resource for rehabilitation and the successful use of modern robotic technologies.
A Prognostic Merit of Statins in Patients with Chronic Hemodialysis after Percutaneous Coronary Intervention—A 10-Year Follow-Up Study
Authors: Funamizu Takehiro , Iwata Hiroshi , Chikata Yuichi , Doi Shinichiro , Endo Hirohisa , Wada Hideki , Naito Ryo , Ogita Manabu , Kato Yoshiteru , Okai Iwao , Dohi Tomotaka , Kasai Takatoshi , Isoda Kikuo , Okazaki Shinya , Miyauchi Katsumi , Minamino Tohru
Published: January 2022

Background: Patients with end-stage renal disease (ESRD) on chronic hemodialysis who are complicated by coronary artery disease (CAD) are at very high risk of cardiovascular (CV) events and mortality. However, the prognostic benefit of statins, which is firmly established in the general population, is still under debate in this particular population. Methods: As a part of a prospective single-center percutaneous coronary intervention (PCI) registry database, this study included consecutive patients on chronic hemodialysis who underwent PCI for the first time between 2000 and 2016 (n = 201). Participants were divided into 2 groups by following 2 factors, such as (1) with or without statin, and (2) with or without high LDL-C (> and ≤LDL-C = 93 mg/dL, median) at the time of PCI. The primary endpoint was defined as CV death, and the secondary endpoints included all-cause and non-CV death, and 3 point major cardiovascular adverse events (3P-MACE) which is the composite of CV death, non-fatal myocardial infarction and stroke. The median and range of the follow-up period were 2.8, 0–15.2 years, respectively. Results: Kaplan–Meier analyses showed significantly lower cumulative incidences of primary and secondary endpoints other than non-CV deaths in patients receiving statins. Conversely, no difference was observed when patients were divided by the median LDL-C at the time of PCI (p = 0.11). Multivariate Cox proportional hazard analysis identified statins as an independent predictor of reduced risk of CV death (Hazard ratio of statin use: 0.43, 95% confidence interval 0.18–0.88, p = 0.02), all-cause death (HR: 0.50, 95%CI 0.29–0.84, p = 0.007) and 3P-MACE (HR: 0.50, 95%CI 0.25–0.93, p = 0.03). Conclusions: Statins were associated with reduced risk of adverse outcomes in patients with ESRD following PCI.
Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis
Authors: Schmid Benedikt , Griesel Mirko , Fischer Anna-Lena , Romero Carolina S. , Metzendorf Maria-Inti , Weibel Stephanie , Fichtner Falk
Published: January 2022

Background: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. Methods: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Results: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65–1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03–1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71–0.96) but may have little or no effect on mortality (RR: 1.08, 0.51–2.31). Conclusions: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.
Downregulation of the LncRNA MEG3 Promotes Osteogenic Differentiation of BMSCs and Bone Repairing by Activating Wnt/β-Catenin Signaling Pathway
Authors: Liu Juan , Qi Xin , Wang Xiao-Hong , Miao Hong-Sheng , Xue Zi-Chao , Zhang Le-Le , Zhao San-Hu , Wu Liang-Hao , Gao Guo-Yi , Lou Mei-Qing , Yi Cheng-Qing
Published: January 2022

Background: Previous studies have demonstrated that long non-coding RNA maternally expressed gene 3 (MEG3) emerged as a key regulator in development and tumorigenesis. This study aims to investigate the function and mechanism of MEG3 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explores the use of MEG3 in skull defects bone repairing. Methods: Endogenous expression of MEG3 during BMSCs osteogenic differentiation was detected by quantitative real-time polymerase chain reaction (qPCR). MEG3 was knockdown in BMSCs by lentiviral transduction. The proliferation, osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs were assessed by Cell Counting Kit-8 (CCK-8) assay, qPCR, alizarin red and alkaline phosphatase staining. Western blot was used to detect β-catenin expression in MEG3 knockdown BMSCs. Dickkopf 1 (DKK1) was used to block wnt/β-catenin pathway. The osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs after wnt/β-catenin inhibition were assessed by qPCR, alizarin red and alkaline phosphatase staining. MEG3 knockdown BMSCs scaffold with PHMG were implanted in a critical-sized skull defects of rat model. Micro-computed tomography(micro-CT), hematoxylin and eosin staining and immunohistochemistry were performed to evaluate the bone repairing. Results: Endogenous expression of MEG3 was increased during osteogenic differentiation of BMSCs. Downregulation of MEG3 could promote osteogenic differentiation of BMSCs in vitro. Notably, a further mechanism study revealed that MEG3 knockdown could activate Wnt/β-catenin signaling pathway in BMSCs. Wnt/β-catenin inhibition would impair MEG3-induced osteogenic differentiation of BMSCs. By using poly (3-hydroxybutyrate-co-3-hydroxyhexanoate, PHBHHx)-mesoporous bioactive glass (PHMG) scaffold with MEG3 knockdown BMSCs, we found that downregulation of MEG3 in BMSCs could accelerate bone repairing in a critical-sized skull defects rat model. Conclusions: Our study reveals the important role of MEG3 during osteogenic differentiation and bone regeneration. Thus, MEG3 engineered BMSCs may be effective potential therapeutic targets for skull defects.
Regular Intake of Green Tea Polyphenols Suppresses the Development of Nonmelanoma Skin Cancer through miR-29-Mediated Epigenetic Modifications
Authors: Kansal Vikash , Agarwal Anshu , Harbour Angela , Farooqi Humaira , Singh Vijay Kumar , Prasad Ram
Published: January 2022

Previously, we and others have shown that the regular intake of green tea polyphenols (GTPs) reduces ultraviolet B (UVB) radiation-induced skin cancer by targeting multiple signaling pathways, including DNA damage, DNA repair, immunosuppression, and inflammation. Here, we determine the effect of GTPs on UVB-induced epigenetic changes, emphasizing DNA hypermethylation in UV-exposed skin and tumors and their association with miR-29, a key regulator of DNA methyltransferases (DNMTs). Skin cancer was induced in SKH-1 hairless mice following repeated exposures of UVB radiation (180 mJ/cm2, three times/week, 24 weeks) with or without GTPs supplementation (0.2%) in drinking water. Regular intake of GTPs inhibited tumor growth by hindering the cascade of DNA hypermethylation events. GTPs supplementation significantly blocked UVB-induced DNA hypermethylation in the skin (up to 35%; p < 0.0001) and in tumors (up to 50%; p < 0.0001). Experimental results showed that the levels of DNA hypermethylation were higher in GTPs-treated mice than in the control group. The expressions of miR-29a, miR-29b, and miR-29c were markedly decreased in UV-induced skin tumors, and GTPs administration blocked UVB-induced miR-29s depletion. Furthermore, these observations were verified using the in vitro approach in human skin cancer cells (A431) followed by treatment with GTPs or mimics of miR-29c. Increased levels of miR-29 were observed in GTPs-treated A431 cells, resulting in increased TET activity and decreased DNA hypermethylation. In conclusion, UVB-mediated miR-29 depletion promotes DNA hypermethylation and leads to enhanced tumor growth by silencing tumor suppressors. Regular intake of GTPs rescued UVB-induced miR-29 depletion and prevented tumor growth by maintaining reduced DNA hypermethylation and activating tumor suppressors. Our observations suggest that miR-based strategies and regular consumption of GTPs could minimize the risk of UVB-induced skin cancers and contribute to better management of NMSCs.
Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach
Authors: Rigato Matteo , Carraro Gianni , Cirella Irene , Dian Silvia , Di Vico Valentina , Stefanelli Lucia Federica , Ravarotto Verdiana , Bertoldi Giovanni , Nalesso Federico , Calò Lorenzo A.
Published: January 2022

Autosomal dominant polycystic disease (ADPKD) is the most frequent monogenic kidney disease. It causes progressive renal failure, endothelial dysfunction, and hypertension, all of which are strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is known to slow the renal deterioration rate, but not all the molecular mechanisms involved in this effect are well-established. We evaluated the OxSt state in untreated ADPKD patients compared to that in tolvaptan-treated ADPKD patients and healthy subjects. OxSt was assessed in nine patients for each group in terms of mononuclear cell p22phox protein expression, NADPH oxidase key subunit, MYPT-1 phosphorylation state, marker of Rho kinase activity (Western blot) and heme oxygenase (HO)-1, induced and protective against OxSt (ELISA). p22phox protein expression was higher in untreated ADPKD patients compared to treated patients and controls: 1.42 ± 0.11 vs. 0.86 ± 0.15 d.u., p = 0.015, vs. 0.53 ± 0.11 d.u., p < 0.001, respectively. The same was observed for phosphorylated MYPT-1: 0.96 ± 0.28 vs. 0.68 ± 0.09 d.u., p = 0.013 and vs. 0.47 ± 0.13 d.u., p < 0.001, respectively, while the HO-1 expression of untreated patients was significantly lower compared to that of treated patients and controls: 5.33 ± 3.34 vs. 2.08 ± 0.79 ng/mL, p = 0.012, vs. 1.97 ± 1.22 ng/mL, p = 0.012, respectively. Tolvaptan-treated ADPKD patients have reduced OxSt levels compared to untreated patients. This effect may contribute to the slowing of renal function loss observed with tolvaptan treatment.
Bathymetric Survey of the St. Anthony Channel (Croatia) Using Multibeam Echosounders (MBES)—A New Methodological Semi-Automatic Approach of Point Cloud Post-Processing
Authors: Šiljeg Ante , Marić Ivan , Domazetović Fran , Cukrov Neven , Lovrić Marin , Panđa Lovre
Published: January 2022

Multibeam echosounders (MBES) have become a valuable tool for underwater floor mapping. However, MBES data are often loaded with different measurement errors. This study presents a new user-friendly and methodological semi-automatic approach of point cloud post-processing error removal. The St. Anthony Channel (Croatia) was selected as the research area because it is regarded as one of the most demanding sea or river passages in the world and it is protected as a significant landscape by the Šibenik-Knin County. The two main objectives of this study, conducted within the Interreg Italy–Croatia PEPSEA project, were to: (a) propose a methodological framework that would enable the easier and user-friendly identification and removal of the errors in MBES data; (b) create a high-resolution integral model (MBES and UAV data) of the St. Anthony Channel for maritime safety and tourism promotion purposes. A hydrographic survey of the channel was carried out using WASSP S3 MBES while UAV photogrammetry was performed using Matrice 210 RTK V2. The proposed semi-automatic post-processing of the MBES acquired point cloud was completed in the Open Source CloudCompare software following five steps in which various point filtering methods were used. The reduction percentage in points after the denoising process was 14.11%. Our results provided: (a) a new user-friendly methodological framework for MBES point filtering; (b) a detailed bathymetric map of the St. Anthony Channel with a spatial resolution of 50 cm; and (c) the first integral (MBES and UAV) high-resolution model of the St. Anthony Channel. The generated models can primarily be used for maritime safety and tourism promotion purposes. In future research, ground-truthing methods (e.g., ROVs) will be used to validate the generated models.
Methods for Fitting the Limit State Function of the Residual Strength of Damaged Ships
Authors: Zhu Zhiyao , Ren Huilong , Wang Xiuhuan , Zhao Nan , Li Chenfeng
Published: January 2022

The limit state function is important for the assessment of the longitudinal strength of damaged ships under combined bending moments in severe waves. As the limit state function cannot be obtained directly, the common approach is to calculate the results for the residual strength and approximate the limit state function by fitting, for which various methods have been proposed. In this study, four commonly used fitting methods are investigated: namely, the least-squares method, the moving least-squares method, the radial basis function neural network method, and the weighted piecewise fitting method. These fitting methods are adopted to fit the limit state functions of four typically sample distribution models as well as a damaged tanker and damaged bulk carrier. The residual strength of a damaged ship is obtained by an improved Smith method that accounts for the rotation of the neutral axis. Analysis of the results shows the accuracy of the linear least-squares method and nonlinear least-squares method, which are most commonly used by researchers, is relatively poor, while the weighted piecewise fitting method is the better choice for all investigated combined-bending conditions.
Study on the Vortex in a Pump Sump and Its Influence on the Pump Unit
Authors: Song Xijie , Liu Chao , Wang Zhengwei
Published: January 2022

The vortex in a pump sump is a negative problem for the pump unit, which can lead to the decline of pump performance. Focusing on the internal pressure characteristics of the floor-attached vortex (FAV) and its influence on the pump unit, the FAV was analyzed adopting the previously verified numerical simulation method and experiment. The results show that the pressure in the vortex core gradually decreases with time, drops to a negative pressure at the development stage, and then reaches the lowest pressure during the continuance stage. When the negative pressure of the vortex tube is around the vaporization pressure of the continuance stage, it can cause a local cavitation at the impeller inlet. The evolution of the FAV is accompanied by a change of pressure gradient in the vortex core which is discussed in detail. This research provides theoretical guidance for a better understanding of the vortex characteristics and the optimal design for the pump.
Protective Pathways: Connecting Environmental and Human Security at Local and Landscape Level with NLP and Geospatial Analysis of a Novel Database of 1500 Project Evaluations
Authors: Morrow Nathan , Mock Nancy B. , Gatto Andrea , LeMense Julia , Hudson Margaret
Published: January 2022

Localized actionable evidence for addressing threats to the environment and human security lacks a comprehensive conceptual frame that incorporates challenges associated with active conflicts. Protective pathways linking previously disciplinarily-divided literatures on environmental security, human security and resilience in a coherent conceptual frame that identifies key relationships is used to analyze a novel, unstructured data set of Global Environment Fund (GEF) programmatic documents. Sub-national geospatial analysis of GEF documentation relating to projects in Africa finds 73% of districts with GEF land degradation projects were co-located with active conflict events. This study utilizes Natural Language Processing on a unique data set of 1500 GEF evaluations to identify text entities associated with conflict. Additional project case studies explore the sequence and relationships of environmental and human security concepts that lead to project success or failure. Differences between biodiversity and climate change projects are discussed but political crisis, poverty and disaster emerged as the most frequently extracted entities associated with conflict in environmental protection projects. Insecurity weakened institutions and fractured communities leading both directly and indirectly to conflict-related damage to environmental programming and desired outcomes. Simple causal explanations found to be inconsistent in previous large-scale statistical associations also inadequately describe dynamics and relationships found in the extracted text entities or case summaries. Emergent protective pathways that emphasized poverty and conflict reduction facilitated by institutional strengthening and inclusion present promising possibilities. Future research with innovative machine learning and other techniques of working with unstructured data may provide additional evidence for implementing actions that address climate change and environmental degradation while strengthening resilience and human security. Resilient, participatory and polycentric governance is key to foster this process.
Does Polycentric Development Improve Green Utilization Efficiency of Urban Land? An Empirical Study Based on Panel Threshold Model Approach
Authors: Yan Siqi , Wang Jian
Published: January 2022

In the context of increasing resource and environmental constraints, measurement and determinants of green utilization efficiency of urban land (GUEUL) is currently the subject of a rapidly expanding literature. Previous research concerning determinants of GUEUL focuses primarily on effects of socio-economic conditions on GUEUL, and little attention has been devoted to impacts of spatial structure and urban development patterns. This research explores impacts of polycentric development on GUEUL of urban agglomeration (UA), using data for major UAs in China covering the period 2005–2019. GUEUL and the extent of polycentricity is measured by employing an improved directional slack-based measure (SBM) model and the rank-size distribution-based approach, respectively. The linkage between polycentric development and GUEUL is explored by estimating models of determinants of GUEUL, and the nonlinear characteristics of the relationship are investigated by employing the panel threshold model approach. The results suggest that polycentric development positively impacts GUEUL of UAs, and such effect rises with economic development levels. In addition, degree of agglomeration, economic development level and intensity of government investment in science and technology is found to be positively related to GUEUL. The empirical results have significant implications for improving GUEUL through formulating and implementing regional and urban policies.
Satisfaction Factors That Predict Loyalty in Ecotourism: A Study of Foreign Tourism in Costa Rica
Authors: Carvache-Franco Mauricio , Carvache-Franco Wilmer , Pérez-Orozco Allan , Víquez-Paniagua Ana Gabriela , Carvache-Franco Orly
Published: January 2022

Recently, foreign tourists have revealed a growing interest for natural environment enjoyment. This study aimed to: (a) identify the service satisfaction factors and (b) analyze the influence that satisfaction factors exert on the loyalty of ecotourists. The empirical analysis was carried out in Arenal National Park and Caño Negro Wildlife Refuge in Costa Rica, a country with international prominence in ecotourism due to the wealth of resources in its protected areas. A factorial analysis and the stepwise multiple regression method were performed for the data analysis of 246 surveys made in situ. Results show three satisfaction factors in ecotourism: “nature and culture”, “infrastructure”, and “service”, where “nature and culture” was the most influential predictor of tourists’ loyalty. The study also found a positive correlation between satisfaction and loyalty in ecotourism. This research will provide relevant insights to public institutions and private companies efficient planning and benefit the community and protected areas.
Evaluation and Comparison of the Common Land Model and the Community Land Model by Using In Situ Soil Moisture Observations from the Soil Climate Analysis Network
Authors: Ou Minzhuo , Zhang Shupeng
Published: January 2022

Soil moisture is a key state variable in land surface processes. Since field measurements of soil moisture are generally sparse and remote sensing is limited in terms of observation depth, land surface model simulations are usually used to continuously obtain soil moisture data in time and space. Therefore, it is crucial to evaluate the performance of models that simulate soil moisture under various land surface conditions. In this work, we evaluated and compared two land surface models, the Common Land Model version 2014 (CoLM2014) and the Community Land Model Version 5 (CLM5), using in situ soil moisture observations from the Soil Climate Analysis Network (SCAN). The meteorological and soil attribute data used to drive the models were obtained from SCAN station observations, as were the soil moisture data used to validate the simulation results. The validation results revealed that the correlation coefficients between the simulations by CLM5 (0.38) and observations are generally higher than those by CoLM2014 (0.11), especially in shallow soil (0–0.1016 m). The simulation results by CoLM2014 have smaller bias than those by CLM5 . Both models could simulate diurnal and seasonal variations of soil moisture at seven sites, but we found a large bias, which may be due to the two models’ representation of infiltration and lateral flow processes. The bias of the simulated infiltration rate can affect the soil moisture simulation, and the lack of a lateral flow scheme can affect the models’ division of saturated and unsaturated areas within the soil column. The parameterization schemes in land surface models still need to be improved, especially for soil simulations at small scales.
Paradigmatic Uniformity: Evidence from Heritage Speakers of Spanish
Authors: Camacho José
Published: January 2022

Subject-verb agreement mismatches have been reported in the L2 and heritage literature, usually involving infinitives, analyzed as default morphological forms for fully specified T-heads. This article explores the mechanisms behind these mismatches, testing two hypotheses: the default form and the surface-similarity hypotheses. It compares non-finite and finite S-V mismatches with subjects with different persons, testing whether similarity with other paradigmatic forms makes them more acceptable, controlling for the role of verb frequency. Participants were asked to rate sentences on a Likert scale that included (a) infinitive forms with first, second and third person subjects, and (b) third person verbal forms with first, second and third person subjects. Two stem-stressed verbs (e.g., tra.j-o ‘brought.3p.past’) and two affix-stressed verbs (e.g., me.ti-o ‘introduced.3p.past’), varying in frequency were tested. Inflectional affixes of stem-stressed verbs are similar to other forms of the paradigm both phonologically and in being unstressed (tra.j-o ‘brought.3p.past’ vs. trai.g-o ‘bring.1 p.pres’), whereas affixes of affix-stressed verbs have dissimilar stress patterns (me.ti-o ´introduced.3p.past’ vs. me.t-o ‘introduce.1p.pres’). Results show significantly higher acceptability for finite vs. non-finite non-matching, and for 1st vs. 2nd person subjects. Stem-stressed verbs showed higher acceptability ratings than affix-stressed ones, suggesting a role for surface-form correspondence, partially confirming previous findings.