bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial Toxicity Associated with Imatinib and Sorafenib in Isolated Rat Heart Fibers and the Cardiomyoblast H9c2 Cell Line
Authors: Bouitbir Jamal , Panajatovic Miljenko V. , Krähenbühl Stephan
Published: February 2022

Tyrosine kinase inhibitors (TKIs) are associated with cardiac toxicity, which may be caused by mitochondrial toxicity. The underlying mechanisms are currently unclear and require further investigation. In the present study, we aimed to investigate in more detail the role of the enzyme complexes of the electron transfer system (ETS), mitochondrial oxidative stress, and mechanisms of cell death in cardiac toxicity associated with imatinib and sorafenib. Cardiac myoblast H9c2 cells were exposed to imatinib and sorafenib (1 to 100 µM) for 24 h. Permeabilized rat cardiac fibers were treated with both drugs for 15 min. H9c2 cells exposed to sorafenib for 24 h showed a higher membrane toxicity and ATP depletion in the presence of galactose (favoring mitochondrial metabolism) compared to glucose (favoring glycolysis) but not when exposed to imatinib. Both TKIs resulted in a higher dissipation of the mitochondrial membrane potential in galactose compared to glucose media. Imatinib inhibited Complex I (CI)- and CIII- linked respiration under both conditions. Sorafenib impaired CI-, CII-, and CIII-linked respiration in H9c2 cells cultured with glucose, whereas it inhibited all ETS complexes with galactose. In permeabilized rat cardiac myofibers, acute exposure to imatinib and sorafenib decreased CI- and CIV-linked respiration in the presence of the drugs. Electron microscopy showed enlarged mitochondria with disorganized cristae. In addition, both TKIs caused mitochondrial superoxide accumulation and decreased the cellular GSH pool. Both TKIs induced caspase 3/7 activation, suggesting apoptosis as a mechanism of cell death. Imatinib and sorafenib impaired the function of cardiac mitochondria in isolated rat cardiac fibers and in H9c2 cells at plasma concentrations reached in humans. Both imatinib and sorafenib impaired the function of enzyme complexes of the ETS, which was associated with mitochondrial ROS accumulation and cell death by apoptosis.
PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer
Authors: Karim Shahid , Burzangi Abdulhadi S. , Ahmad Aftab , Siddiqui Nasir Ali , Ibrahim Ibrahim M. , Sharma Priyanka , Abualsunun Walaa A. , Gabr Gamal A.
Published: February 2022

Colorectal cancer (CRC) is the third leading cause of death in men and the fourth in women worldwide and is characterized by deranged cellular energetics. Thymoquinone, an active component from Nigella sativa, has been extensively studied against cancer, however, its role in affecting deregulated cancer metabolism is largely unknown. Further, the phosphoinositide 3-kinase (PI3K) pathway is one of the most activated pathways in cancer and its activation is central to most deregulated metabolic pathways for supporting the anabolic needs of growing cancer cells. Herein, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines. Further, we show that such an abrogation of deranged cell metabolism was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2), via modulating the PI3/AKT axis. While overexpression of HK2 showed that it is essential for fueling glycolytic metabolism as well as sustaining tumorigenicity, its pharmacologic and/or genetic inhibition led to a reduction in the observed effects. The results decipher HK2 mediated inhibitory effects of thymoquinone in modulating its glycolytic metabolism and antitumor effects. In conclusion, we provide evidence of metabolic perturbation by thymoquinone in CRC cells, highlighting its potential to be used/repurposed as an antimetabolite drug, though the latter needs further validation utilizing other suitable cell and/or preclinical animal models.
The Unitary Micro-Immunotherapy Medicine Interferon-γ (4 CH) Displays Similar Immunostimulatory and Immunomodulatory Effects than Those of Biologically Active Human Interferon-γ on Various Cell Types
Authors: Jacques Camille , Chatelais Mathias , Fekir Karim , Brulefert Adrien , Floris Ilaria
Published: February 2022

As a cytokine, gamma-interferon (IFN-γ) is considered a key player in the fine-tuned orchestration of immune responses. The extreme cellular sensitivity to cytokines is attested by the fact that very few of these bioactive molecules per cell are enough to trigger cellular functions. These findings can, at least partially, explain how/why homeopathically-prepared cytokines, and especially micro-immunotherapy (MI) medicines, are able to drive cellular responses. We focused our fundamental research on a unitary MI preparation of IFN-γ, specifically employed at 4 CH, manufactured and impregnated onto sucrose-lactose pillules as all other MI medicines. We assessed the IFN-γ concentration in the medium after dilution of the IFN-γ (4 CH)-bearing pillules and we evaluated in vitro drug responses in a wide range of immune cells, and in endothelial cells. Our results showed that IFN-γ (4 CH) stimulated the proliferation, the activation and the phagocytic capabilities of primary immune cells, as well as modulated their cytokine-secretion and immunity-related markers’ expression in a trend that is quite comparable with the well-recognized biological effects induced by IFN-γ. Altogether, these data provide novel and additional evidences on MI medicines, and specifically when active substances are prepared at 4 CH, thus suggesting the need for more investigations.
Genome-Wide Identification of MYB Transcription Factors and Screening of Members Involved in Stress Response in Actinidia
Authors: Xia Hui , Liu Xinling , Lin Zhiyi , Zhang Xuefeng , Wu Meijing , Wang Tong , Deng Honghong , Wang Jin , Lin Lijin , Deng Qunxian , Lv Xiulan , Xu Kunfu , Liang Dong
Published: February 2022

MYB transcription factors (TFs) play an active role in plant responses to abiotic stresses, but they have not been systematically studied in kiwifruit (Actinidia chinensis). In this study, 181 AcMYB TFs were identified from the kiwifruit genome, unevenly distributed on 29 chromosomes. The high proportion (97.53%) of segmental duplication events (Ka/Ks values less than 1) indicated that AcMYB TFs underwent strong purification selection during evolution. According to the conservative structure, 91 AcR2R3-MYB TFs could be divided into 34 subgroups. A combination of transcriptomic data under drought and high temperature from four AcMYB TFs (AcMYB2, AcMYB60, AcMYB61 and AcMYB102) was screened out in response to stress and involvement in the phenylpropanoid pathway. They were highly correlated with the expression of genes related to lignin biosynthesis. qRT-PCR analysis showed that they were highly correlated with the expression of genes related to lignin biosynthesis in different tissues or under stress, which was consistent with the results of lignin fluorescence detection. The above results laid a foundation for further clarifying the role of MYB in stress.
Heterodimer of A2A and Oxytocin Receptors Regulating Glutamate Release in Adult Striatal Astrocytes
Authors: Amato Sarah , Averna Monica , Guidolin Diego , Pedrazzi Marco , Pelassa Simone , Capraro Michela , Passalacqua Mario , Bozzo Matteo , Gatta Elena , Anderlini Deanna , Maura Guido , Agnati Luigi F. , Cervetto Chiara , Marcoli Manuela
Published: February 2022

Background: Roles of astrocytes in the modulatory effects of oxytocin (OT) in central nervous system are increasingly considered. Nevertheless, OT effects on gliotransmitter release have been neglected. Methods: In purified astrocyte processes from adult rat striatum, we assessed OT receptor (OTR) and adenosine A2A receptor expression by confocal analysis. The effects of receptors activation on glutamate release from the processes were evaluated; A2A-OTR heteromerization was assessed by co-immunoprecipitation and PLA. Structure of the possible heterodimer of A2A and OT receptors was estimated by a bioinformatic approach. Results: Both A2A and OT receptors were expressed on the same astrocyte processes. Evidence for A2A-OTR receptor-receptor interaction was obtained by measuring the release of glutamate: OT inhibited the evoked glutamate release, while activation of A2A receptors, per se ineffective, abolished the OT effect. Biochemical and biophysical evidence for A2A-OTR heterodimers on striatal astrocytes was also obtained. The residues in the transmembrane domains 4 and 5 of both receptors are predicted to be mainly involved in the heteromerization. Conclusions: When considering effects of OT in striatum, modulation of glutamate release from the astrocyte processes and of glutamatergic synapse functioning, and the interaction with A2A receptors on the astrocyte processes should be taken into consideration.
Robust Segmentation Based on Salient Region Detection Coupled Gaussian Mixture Model
Authors: Pan Xiaoyan , Zheng Yuhui , Jeon Byeungwoo
Published: February 2022

The impressive progress on image segmentation has been witnessed recently. In this paper, an improved model introducing frequency-tuned salient region detection into Gaussian mixture model (GMM) is proposed, which is named FTGMM. Frequency-tuned salient region detection is added to achieve the saliency map of the original image, which is combined with the original image, and the value of the saliency map is added into the Gaussian mixture model in the form of spatial information weight. The proposed method (FTGMM) calculates the model parameters by the expectation maximization (EM) algorithm with low computational complexity. In the qualitative and quantitative analysis of the experiment, the subjective visual effect and the value of the evaluation index are found to be better than other methods. Therefore, the proposed method (FTGMM) is proven to have high precision and better robustness.
The Phylogenetic Relationships of the Fanniidae within the Muscoid Grade (Diptera: Calyptrata) Based on the Musculature of the Male Terminalia
Authors: Sorokina Vera S. , Ovtshinnikova Olga G.
Published: February 2022

The abdominal and pregenital segments and the genitalia were studied in males of Fannia subpellucens (Zetterstedt, 1845), Fannia canicularis (Linnaeus, 1761) and Fannia incisurata (Zetterstedt, 1838). In comparison with the remaining members of the muscoid grade, in addition to the symmetry of the pregenital segments, significant reductions of the sclerites and musculature of the male terminalia have been observed in Fanniidae. The muscular structure of pregenital segments confirms that the fused pregenital ring is syntergosternite VI + VII + VIII. Symmetry and fusion, as well as the lower number of the sclerites and muscles of the pregenital segments and male genitalia of the Fanniidae, can be considered apomorphic character states. The presence of the lateral bacilliform sclerite, as well as the presence and position of the epandrial muscles M 26, three pairs of muscles M 19 and paired muscles M 18, can be considered as a plesiomorphic character state of the Fanniidae. The structure of the sclerites and muscles of the male abdominal segments and terminalia place the Fanniidae at the base of the muscoid grade and Oestroidea, as has been confirmed by recent molecular studies.
A Novel Echocardiographic-Based Classification for the Prediction of Peri-Device Leakage following Left Atrial Appendage Occluder Implantation
Authors: Hamadanchi Ali , Ijuin Shun , Haertel Franz , Bekfani Tarek , Westphal Julian , Franz Marcus , Moebius-Winkler Sven , Schulze P. Christian
Published: February 2022

(1) Background: The assessment of residual peri-device leakages (PDL) after left atrial appendage occlusion (LAAO) remains crucial for post-procedural management. Our study aimed to verify a novel echocardiographic classification for the prediction of PDL. (2) Methods: Echocardiographic data of 72 patients who underwent percutaneous LAAO were evaluated. All echo images were analyzed by two independent investigators using standard analysis software (Image-Arena IA-4.6.4.44 by TomTec®, Munich, Germany). A total number of 127 studies was evaluated. Forty-four patients had baseline studies, at 45 days and at 6 months post-implantation. We propose a morphological classification of LAA devices based on the amount of echodensity inside the devices into three types: type A showing complete homogenous thrombosis, type B incompletely thrombosed device with inhomogeneous echo-free space <50% of device, and type C with partially thrombosed device in which the echo free space was >50% of device in various planes, which we called the “ice-cream cone” sign. Each type was matched to the degree of PDL and clinical outcome parameters. (3) Results: Patients with type C had the highest percentage of PDL at 45 days follow-up (type A: 24%, type B: 31%, type C 100% PDL, p < 0.001) and at 6 months follow-up (type A: 7%, type B: 33%, type C 100% PDL, p < 0.001). Notably, device size in patients with PDL was larger than that in patients without PDL at 6 months follow-up (25.6 ± 3.5 mm vs. 28.7 ± 3.4 mm, p = 0.004). Device size in patients with type C appearance was the largest of the three types (type A: 25.9 ± 3.6 mm, type B: 25.8 ± 3.4 mm, type C 29.8 ± 3.0 mm, type A vs. C; p = 0.019; type B vs. C, p = 0.007). (4) Conclusions: In conclusion, PDL are common post-LAAO, and their frequency is underestimated and under-recognized. PDL are much more common in patients with larger LAA ostial sizes and likely lower longitudinal compression. Type C appearance of the LAAO devices (“ice-cream cone sign”) has a high positive predictive value for PDL. Further studies are needed for better delineation of the clinical importance of this proposed classification.
Prevalence of Ocular Anomalies in Craniosynostosis: A Systematic Review and Meta-Analysis
Authors: Rostamzad Parinaz , Arslan Zehra , Mathijssen Irene , Koudstaal Maarten , Pleumeekers Mieke , Versnel Sarah , Loudon Sjoukje
Published: February 2022

Background: The aim of this study was to describe the ophthalmic abnormalities and their prevalence in craniosynostosis prior to craniofacial surgery. Methods: A systematic search was conducted on Medline OVID, Embase, Cochrane, Google Scholar, Web of Science Core Collection. Inclusion criteria were English papers, children aged <18 years with non-syndromic and syndromic craniosynostosis, case reports, case series, and case-control studies. A system of domains was established consisting of an anatomic and functional ophthalmic domain. A meta-analysis of single proportions was carried out using random effects model and pooled mean proportions with 95% confidence intervals (CI) were calculated. Results: Thirty-two papers analyzing 2027 patients were included. Strabismus was the most common anomaly in non-syndromic craniosynostosis: Horizontal strabismus was highest prevalent in unicoronal craniosynostosis (UCS) 19% (95% CI 9–32), followed by vertical strabismus 17% (95% CI 5–33). In syndromic craniosynostosis, horizontal strabismus was most prevalent in Crouzon syndrome 52% (95 CI 26–76), followed by Apert syndrome 50% (95% CI 42–58). Vertical strabismus was most prevalent in Saethre-Chotzen 60% followed by Muenke’s syndrome 36%. Furthermore, astigmatism was the second most reported outcome in non-syndromic craniosynostosis and highest prevalent in UCS 35% (95% CI 21–51). In syndromic craniosynostosis, astigmatism was most frequently seen in Crouzon syndrome 43% (95% CI 22–65), followed by Apert syndrome 34% (95% CI 14–58). Moreover, in syndromic craniosynostosis, 5–40% had a decrease in visual acuity (VA) ≤ 0.3 LogMAR in the better eye and 11–65% had a VA ≤ 0.3 LogMAR in at least one eye. Discussion: This review demonstrates the high prevalence of ocular anomalies in non-syndromic and syndromic craniosynostosis. A multidisciplinary and systematic approach is needed for the screening and optimal treatment of these conditions in a timely manner.
Influence of Guided Tissue Regeneration Techniques on the Success Rate of Healing of Surgical Endodontic Treatment: A Systematic Review and Network Meta-Analysis
Authors: Zubizarreta-Macho Álvaro , Tosin Roberta , Tosin Fabio , Velasco Bohórquez Pilar , San Hipólito Marín Lara , Montiel-Company José María , Mena-Álvarez Jesús , Hernández Montero Sofía
Published: February 2022

Several regeneration techniques and materials have been proposed for the healing of bone defects after surgical endodontic treatment; however, the existing literature does not provide evidence on the most recommended techniques or materials. The aim of the present systematic review and network meta-analysis (NMA) is to summarize the clinical evidence on the efficacy of guided tissue regeneration techniques (GRTs). The PRISMA recommendations were followed. Four databases were searched up to December 2021. Randomized clinical trials (RCTs) with a minimum follow-up of 6 months were included. The risk of bias was assessed using the Cochrane Collaboration tool. A fixed effects model and frequentist approach were used in the NMA. Direct GRT technique comparisons were combined to estimate indirect comparisons, and the estimated effect size of the comparisons was analyzed using the odds ratio (OR). Inconsistency was assessed with the Q test, with a significance level of p < 0.01, and a net heat plot. A total of 274 articles was identified, and 11 RCTs (6 direct comparisons of 15 techniques) were included in the NMA, which examined 6 GRT techniques: control, Os, PL, MB, MB + Os, and MB + PL. The MB + Os group compared to the control (OR = 3.67, 95% CI: 1.36–9.90) and to the MB group (OR = 3.47, 95% CI: 1.07–11.3) showed statistically significant ORs (p ˂ 0.05). The MB + Os group presented the highest degree of certainly (P-score = 0.93).
Acute Kidney Injury in Patients with Severe ARDS Requiring Extracorporeal Membrane Oxygenation: Incidence, Prognostic Impact and Risk Factors
Authors: Pilarczyk Kevin , Huenges Katharina , Bewig Burkhard , Balke Lorenz , Cremer Jochen , Haneya Assad , Panholzer Bernd
Published: February 2022

(1) Background: Acute kidney injury (AKI) is a common but under-investigated complication in patients receiving extracorporeal membrane oxygenation (ECMO). We aimed to define the incidence and clinical course, as well as the predictors of AKI in adults receiving ECMO support. (2) Materials and Methods: This is a retrospective analysis of all patients undergoing veno-venous ECMO treatment in a tertiary care center between December 2008 and December 2017. The primary endpoint was the new occurrence of an AKI of stage 2 or 3 according to the Kidney Disease: Improving Global Outcomes (KDIGO) classification after ECMO implantation. (3) Results: During the observation period, 103 patients underwent veno-venous ECMO implantation. In total, 59 patients (57.3%) met the primary endpoint with an AKI of stage 2 or 3 and 55 patients (53.4%) required renal replacement therapy. Patients with an AKI of 2 or 3 suffered from more bleeding and infectious complications. Whereas weaning failure from ECMO (30/59 (50.8%) vs. 15/44 (34.1%), p = 0.08) and 30-day mortality (35/59 (59.3%) vs. 17/44 (38.6%), p = 0.06) only tended to be higher in the group with an AKI of stage 2 or 3, long-term survival of up to five years was significantly lower in the group with an AKI of stage 2 or 3 (p = 0.015). High lactate, serum creatinine, and ECMO pump-speed levels, and low platelets, a low base excess, and a low hematocrit level before ECMO were independent predictors of moderate to severe AKI. Primary hypercapnic acidosis was more common in AKI non-survivors (12 (32.4%) vs. 0 (0.0%), p < 0.01). Accordingly, pCO2-levels prior to ECMO implantation tended to be higher in AKI non-survivors (76.12 ± 27.90 mmHg vs. 64.44 ± 44.31 mmHg, p = 0.08). In addition, the duration of mechanical ventilation prior to ECMO-implantation tended to be longer (91.14 ± 108.16 h vs. 75.90 ± 86.81 h, p = 0.078), while serum creatinine (180.92 ± 115.72 mmol/L vs. 124.95 ± 77.77 mmol/L, p = 0.03) and bicarbonate levels were significantly higher in non-survivors (28.22 ± 8.44 mmol/L vs. 23.36 ± 4.19 mmol/L, p = 0.04). (4) Conclusion: Two-thirds of adult patients receiving ECMO suffered from moderate to severe AKI, with a significantly increased morbidity and long-term mortality.
Effect of Transcutaneous Vagus Nerve Stimulation in Erosive Hand Osteoarthritis: Results from a Pilot Trial
Authors: Courties Alice , Deprouw Camille , Maheu Emmanuel , Gibert Eric , Gottenberg Jacques-Eric , Champey Julien , Banneville Béatrice , Chesnel Camille , Amarenco Gérard , Rousseau Alexandra , Berenbaum Francis , Sellam Jérémie
Published: February 2022

Beyond its effect on vegetative functions, the activation of the vagus nerve inhibits inflammation and reduces pain signaling. The aim of this open-label pilot study was to determine the efficacy and tolerance of transcutaneous auricular VNS (taVNS) on erosive hand osteoarthritis (EHOA) symptoms. Symptomatic EHOA patients with hand pain VAS ≥ 40/100 mm and ≥1 interphalangeal swollen joint(s) were included. The taVNS was performed for 4 weeks using an auricular electrode applied one hour per day and connected to a TENS device with pre-established settings. Clinical efficacy was evaluated by changes between baseline and at 4 weeks with hand pain VAS and the functional index FIHOA score, using a Wilcoxon t-test. The treatment tolerance was also evaluated. Eighteen patients (median age 69 years old, 83% women) were analyzed. At baseline, hand pain VAS was 60 mm [IQR 50; 78.2] and FIHOA 15 [10.7; 20.2]. After 4 weeks, taVNS significantly reduced hand pain VAS, with a median decrease of 23.5 mm [7.7; 37.2] (p = 0.001), as well as FIHOA, with a median decrease of 2 points [0.75; 5.2] (p = 0.01). No serious adverse events were reported. One patient stopped taVNS because of auricular discomfort. This first proof-of-concept trial indicated that taVNS is feasible and may decrease joint inflammation and clinical symptoms in EHOA, arguing for a randomized controlled study versus sham stimulation.
Oral Manifestations and Maxillo-Facial Features in the Acromegalic Patient: A Literature Review
Authors: De Stefani Alberto , Dassie Francesca , Wennberg Alexandra , Preo Giorgia , Muneratto Alice , Fabris Roberto , Maffei Pietro , Gracco Antonio , Bruno Giovanni
Published: February 2022

Background: Acromegaly is a chronic disease caused by an abnormal secretion of growth hormone (GH) by a pituitary adenoma, resulting in an increased circulating concentration of insulin-like growth factor 1 (IGF-1). The main characteristics are a slow progression of signs and symptoms, with multisystemic involvement, leading to acral overgrowth, progressive somatic changes, and a complex range of comorbidities. Most of these comorbidities can be controlled with treatment. The literature reveals that the most evident and early signs are those related to soft tissue thickening and skeletal growth, especially in the head and neck region. Methods: The authors reviewed the available literature on the clinical oro-dental features of acromegaly, selecting articles from PubMed and Google Scholar. The aim of this review was to summarize all the reported clinical oro-dental features of acromegalic patients. Results: The most common facial dimorphisms involved the maxillo-facial district, with hypertrophy of the paranasal sinuses, thickening of the frontal bones, and protruding glabella, which may be associated with joint pain and clicks. Regarding the oro-dental signs, the most frequent are dental diastema (40–43%), mandibular overgrowth (22–24%), mandibular prognathism (20–22%), and macroglossia (54–58%). These signs of acromegaly can be significantly reduced with adequate treatment, which is more effective when initiated early. Conclusions: Increased awareness of acromegaly among dentists and maxillo-facial surgeons, along with the early identification of oro-facial changes, could lead to an earlier diagnosis and treatment, thereby improving patients’ quality of life and prognosis.
Association of Neuroretinal Thinning and Microvascular Changes with Hypertension in an Older Population in Southern Italy
Authors: Niro Alfredo , Sborgia Giancarlo , Lampignano Luisa , Giuliani Gianluigi , Castellana Fabio , Zupo Roberta , Bortone Ilaria , Puzo Pasquale , Pascale Angelo , Pastore Valentina , Buonamassa Rosa , Galati Roberta , Bordinone Marco , Cassano Flavio , Griseta Chiara , Tirelli Sarah , Lozupone Madia , Bevilacqua Vitoantonio , Panza Francesco , Sardone Rodolfo , Alessio Giovanni , Boscia Francesco
Published: February 2022

Background: Retinal microvasculature assessment at capillary level may potentially aid the evaluation of early microvascular changes due to hypertension. We aimed to investigate associations between the measures obtained using optical coherence tomography (OCT) and OCT-angiography (OCT-A) and hypertension, in a southern Italian older population. Methods: We performed a cross-sectional analysis from a population-based study on 731 participants aged 65 years+ subdivided into two groups according to the presence or absence of blood hypertension without hypertensive retinopathy. The average thickness of the ganglion cell complex (GCC) and the retinal nerve fiber layer (RNFL) were measured. The foveal avascular zone area, vascular density (VD) at the macular site and of the optic nerve head (ONH) and radial peripapillary capillary (RPC) plexi were evaluated. Logistic regression was applied to assess the association of ocular measurements with hypertension. Results: GCC thickness was inversely associated with hypertension (odds ratio (OR): 0.98, 95% confidence interval (CI): 0.97–1). A rarefaction of VD of the ONH plexus at the inferior temporal sector (OR: 0.95, 95% CI: 0.91–0.99) and, conversely, a higher VD of the ONH and RPC plexi inside optic disc (OR: 1.07, 95% CI: 1.04–1.10; OR: 1.04, 95% CI: 1.02–1.06, respectively) were significantly associated with hypertension. Conclusion: A neuroretinal thinning involving GCC and a change in capillary density at the peripapillary network were related to the hypertension in older patients without hypertensive retinopathy. Assessing peripapillary retinal microvasculature using OCT-A may be a useful non-invasive approach to detect early microvascular changes due to hypertension.
Analysis of Preventable Risk Factors for Toxoplasma gondii Infection in Pregnant Women: Case-Control Study
Authors: Bieńkowski Carlo , Aniszewska Małgorzata , Kowalczyk Monika , Popielska Jolanta , Zawadka Konrad , Ołdakowska Agnieszka , Pokorska-Śpiewak Maria
Published: February 2022

Background: Toxoplasma gondii (TG) is a parasitic protozoon that may cause miscarriages or birth defects if the infection occurs during pregnancy. The study’s aim was to evaluate the risk factors associated with TG infection in pregnant women. Materials: Medical charts for all 273 pregnant women with suspected TG infection consecutively admitted to the Hospital of Warsaw between 2019 and 2020 were retrospectively analyzed. The presumptive TG diagnosis was verified by a serologic assessment of IgM and IgG titers, and IgG affinity tests. Results: The median age was 32 years (range: 19–42 years). The diagnosis of primary TG infection was confirmed in 74/273 (27.1%) women. In 114/273 (41.8%) there was evidence of past infection. In 71/273 (26%) women, an infection was excluded. In 172/273 (62%) women the recommended testing for other infectious diseases putting fetus development at risk was performed correctly. Logistic regression model analysis revealed that living in rural areas and eating raw meat were independent factors associated with increased risk of TG infection during pregnancy (OR 2.89, 95% CI: 1.42–5.9, p = 0.004; and OR 2.07, 95% CI: 1.03–4.18, p = 0.04, respectively). Conclusions: The independent risk factors for TG infection during pregnancy include living in rural areas and eating raw meat. The physician’s educational role here is crucial for the efficient prevention of congenital toxoplasmosis.
Towards Risk Assessments of Microplastics in Bivalve Mollusks Globally
Authors: Ding Jinfeng , Sun Yunmei , He Changfei , Li Jingxi , Li Fengmin
Published: February 2022

The ubiquitous presence of microplastics in bivalve mollusks and related risks have raised particular concerns. In this study, the available data on the abundance and polymer type of microplastics in bivalves from twenty-two countries were extracted to comprehensively understand the risks of microplastics in bivalves. Following the data from 52 peer-reviewed papers, the abundance, chemical composition, and human exposure risks of microplastics of bivalves among countries were initially assessed. Abundance risk results indicated that bivalves from 22 countries presented a low pollution load index, showing a lower risk level (level I). The polymer risk index (H) of bivalves from Portugal (Hcountry = 1335, level IV) and India (Hcountry = 1187, level IV) were higher than the other countries due to the occurrence of hazardous microplastics, such as polyvinyl chloride. For the human exposure risks, the global mean value of microplastic exposure to humans via mollusk consumption is estimated to be 751 microplastics/capita/year, with the maximum intake by the Chinese. This study suggests that abundance risk may be a fundamental indicator for assessing the potential hazard to humans until the chemical composition risks are confirmed. This study is the first attempt to assess the potential risks of microplastics in bivalves using three evaluation models based on microplastic abundances and polymer types, which will contribute to establishing future human health risk assessment frameworks. These findings will also assist efforts in policy-making to minimize microplastic risks in seafood.
Zonal Distribution Characteristics of Microplastics in the Southern Indian Ocean and the Influence of Ocean Current
Authors: Li Jingxi , Gao Fenglei , Zhang Di , Cao Wei , Zhao Chang
Published: February 2022

As a new type of pollutant, microplastics widely exist in the marine environment and have attracted a lot of attention from the international community. In order to study the distribution of microplastics and the influence of ocean current, microplastic samples in seawater of the southern Indian Ocean were collected using a peristaltic pump equipped on-board and concentrated on site. Qualitative and quantitative analyses of microplastics were performed using a stereo-microscope and a micro-Fourier transform infrared spectroscope attenuated total reflection. The results showed that the average abundance of microplastics in seawater of the southern Indian Ocean was 2.3 ± 2.1 items/m3, which was consistent with that in other oceans. Polyethylene terephthalate (PET), polyethylene (PE), Rayon, polyamide (PA), and polyvinylidene chloride (PVDC) were the main polymers of microplastics in the southern Indian Ocean. The size range of all detected microplastics was 108.2–4703.0 µm. All microplastics had different colors, such as black, red, yellow, gray, blue, green, purple, and transparent. Fiber was the dominant shape of microplastics. The abundance distribution of microplastics fluctuated in the latitudinal direction. The abundance of microplastics from the present study area was higher in the coastal region of the South Africa continent and the Indian Ocean garbage patch, with an average abundance of 4.0 items/m3. The average abundance of microplastics was relatively high in the convergence area of the circulation, which revealed that the ocean current facilitated the agglomeration and transportation of microplastics.
Regulation of the Leucine Metabolism in Mortierella alpina
Authors: Sonnabend Robin , Seiler Lucas , Gressler Markus
Published: February 2022

The oleaginous fungus Mortierella alpina is a safe source of polyunsaturated fatty acids (PUFA) in industrial food and feed production. Besides PUFA production, pharmaceutically relevant surface-active and antimicrobial oligopeptides were isolated from this basal fungus. Both production of fatty acids and oligopeptides rely on the biosynthesis and high turnover of branched-chain-amino acids (BCAA), especially l-leucine. However, the regulation of BCAA biosynthesis in basal fungi is largely unknown. Here, we report on the regulation of the leucine, isoleucine, and valine metabolism in M. alpina. In contrast to higher fungi, the biosynthetic genes for BCAA are hardly transcriptionally regulated, as shown by qRT-PCR analysis, which suggests a constant production of BCAAs. However, the enzymes of the leucine metabolism are tightly metabolically regulated. Three enzymes of the leucine metabolism were heterologously produced in Escherichia coli, one of which is inhibited by allosteric feedback loops: The key regulator is the α-isopropylmalate synthase LeuA1, which is strongly disabled by l-leucine, α-ketoisocaproate, and propionyl-CoA, the precursor of the odd-chain fatty acid catabolism. Its gene is not related to homologs from higher fungi, but it has been inherited from a phototrophic ancestor by horizontal gene transfer.
COVID-19 Detection in CT/X-ray Imagery Using Vision Transformers
Authors: Al Rahhal Mohamad Mahmoud , Bazi Yakoub , Jomaa Rami M. , AlShibli Ahmad , Alajlan Naif , Mekhalfi Mohamed Lamine , Melgani Farid
Published: February 2022

The steady spread of the 2019 Coronavirus disease has brought about human and economic losses, imposing a new lifestyle across the world. On this point, medical imaging tests such as computed tomography (CT) and X-ray have demonstrated a sound screening potential. Deep learning methodologies have evidenced superior image analysis capabilities with respect to prior handcrafted counterparts. In this paper, we propose a novel deep learning framework for Coronavirus detection using CT and X-ray images. In particular, a Vision Transformer architecture is adopted as a backbone in the proposed network, in which a Siamese encoder is utilized. The latter is composed of two branches: one for processing the original image and another for processing an augmented view of the original image. The input images are divided into patches and fed through the encoder. The proposed framework is evaluated on public CT and X-ray datasets. The proposed system confirms its superiority over state-of-the-art methods on CT and X-ray data in terms of accuracy, precision, recall, specificity, and F1 score. Furthermore, the proposed system also exhibits good robustness when a small portion of training data is allocated.
Pharmacogenomics-Guided Pharmacotherapy in Patients with Major Depressive Disorder or Bipolar Disorder Affected by Treatment-Resistant Depressive Episodes: A Long-Term Follow-Up Study
Authors: Del Casale Antonio , Pomes Leda Marina , Bonanni Luca , Fiaschè Federica , Zocchi Clarissa , Padovano Alessio , De Luca Ottavia , Angeletti Gloria , Brugnoli Roberto , Girardi Paolo , Preissner Robert , Borro Marina , Gentile Giovanna , Pompili Maurizio , Simmaco Maurizio
Published: February 2022

Treatment-resistant depression (TRD) reduces affected patients’ quality of life and leads to important social health care costs. Pharmacogenomics-guided treatment (PGT) may be effective in the cure of TRD. The main aim of this study was to evaluate the clinical changes after PGT in patients with TRD (two or more recent failed psychopharmacological trials) affected by bipolar disorder (BD) or major depressive disorder (MDD) compared to a control group with treatment as usual (TAU). We based the PGT on assessing different gene polymorphisms involved in the pharmacodynamics and pharmacokinetics of drugs. We analyzed, with a repeated-measure ANOVA, the changes between the baseline and a 6 month follow-up of the efficacy index assessed through the Clinical Global Impression (CGI) scale, and depressive symptoms through the Hamilton Depression Rating Scale (HDRS). The PGT sample included 53 patients (26 BD and 27 MDD), and the TAU group included 52 patients (31 BD and 21 MDD). We found a significant within-subject effect of treatment time on symptoms and efficacy index for the whole sample, with significant improvements in the efficacy index (F = 8.544; partial η² = 0.077, p < 0.004) and clinical global impression of severity of illness (F = 6.818; partial η² = 0.062, p < 0.01) in the PGT vs. the TAU group. We also found a significantly better follow-up response (χ² = 5.479; p = 0.019) and remission (χ² = 10.351; p = 0.001) rates in the PGT vs. the TAU group. PGT may be an important option for the long-term treatment of patients with TRD affected by mood disorders, providing information that can better define drug treatment strategies and increase therapeutic improvement.
An Assessment of the Impact of Legal Regulation on Financial Security in OECD Countries
Authors: Vaitkus Robertas , Vasiliauskaitė Asta
Published: February 2022

The recurrent economic and financial crises expose the state, enterprises, and households to a range of financial risks and negative financial consequences. As a result, governments are seeking the most efficient measures of legal regulation and other measures ensuring financial security in order to address financial insecurity. The financial security can be considered from a variety of perspectives, and this research proposes that microeconomic and macroeconomic indicators be taken into account when assessing the financial security situation. The results of this research confirmed that legal regulation has a significant positive impact on financial security in OECD countries during the analysis period. Based on the results of the study, it can be argued that legal regulation, including anti-corruption measures, must be an essential part of the financial security strategies being developed. The studies carried out provide a platform for further research, which will allow identification of regulatory measures that would most effectively contribute to financial security needs in individual OECD countries.
Cultural Tourism Weakens Seasonality: Empirical Analysis of Chinese Tourism Cities
Authors: Zhang Jing , Yu Zhonglei , Miao Changhong , Li Yuting , Qiao Shuai
Published: February 2022

Cultural tourism is less seasonal than nature tourism. However, previous studies have mainly compared the tourist flow of scenic spots, and it is still unclear how cultural tourism affects regional tourism seasonality. This study investigated the seasonal patterns by analyzing the monthly inbound tourist flow of the 28 typical Chinese tourist cities from 2001 to 2012, and examined the effect of cultural tourism on weakening seasonality by using the random-response panel Tobit model. It was found that the seasonal patterns of inbound tourists present non-peak, one-peak, two-double, and three-peak regular fluctuations, and also have irregular fluctuations affected by emergencies and festivals. Cultural tourism can weaken the seasonality of regional tourism, while nature tourism products enhance tourism seasonality. Suitable travel times throughout the year and destination reception industry levels, locations, and external connections have a significant impact on the regional tourism seasonality, but climate comfort, foreign direct investment, and simply the number of hotels and international travel agencies are not significant for tourism seasonality.
Typing Colonial Perceptions of Carrum Carrum Swamp: The Expected and the Surprising
Authors: Dobbie Meredith Frances
Published: February 2022

Carrum Carrum Swamp was a vast wetland to the south-east of Melbourne, Victoria, Australia, at the time that it was first sighted by white colonists in 1803. By 1878, the colonists had commenced converting the swamp to dry land for agricultural and horticultural pursuits, and 100 years later it was predominantly residential land. Shifting values in the 1970s led to environmental concerns about water quality in local creeks and Port Phillip Bay and subsequent residential development on the former swamp included the construction of stormwater treatment wetlands. Perceptions of wetlands are now diverse, including positive perceptions that support their presence in urban settings. In contrast, traditionally, wetlands have been perceived negatively, as waste lands, leading to their drainage. Nevertheless, alternative, perhaps positive, perceptions could have existed, only to be overwhelmed by the negative perceptions driving drainage. Understanding the full range of past perceptions is important to ensure that the historical record is correct and to provide historical context to contemporary perceptions of wetlands. It will better equip natural resource managers and designers and managers of constructed wetlands in urban locations to ensure that wetlands are healthy, functioning and appreciated by their local and wider communities. Thus, the perceptions of Carrum Carrum Swamp by colonists from 1803 to 1878 were examined through qualitative content analysis of historical documents, and a typology was developed. Seven different perceptions were identified: scientific, premodern, exploitative, romantic, aesthetic, medico-mythic and ecological. Most could be traced to the colonists’ predominantly British heritage, but one perception arose in the colony in response to the specific environmental conditions that the colonists encountered. This ecological perception valued wetlands as places of predictable water supply in a land of unpredictable rainfall. It recognised wetlands as part of a broader hydrological system, with influences on the local climate. Its proponents promoted the need for a different approach to the management of wetlands than in Britain and Europe. Nevertheless, a dominant exploitative perception prevailed, leading to the drainage of Carrum Carrum Swamp. The typology developed in this study will be useful for exploring perceptions of other wetlands, both colonial and contemporary.
Influence Analysis of the Antifriction Layer Materials and Thickness on the Contact Interaction of Spherical Bearings Elements
Authors: Adamov Anatoliy A. , Kamenskikh Anna A. , Pankova Anastasia P.
Published: February 2022

Bearings are the supporting elements of bridges. They perceive vertical and horizontal loads from the bridge span. Spherical bearings are one of the construction common types. The material and configuration of the anti-friction layers determine the bearing performance. The paper performed the contact deformation analysis of spherical bearing elements at a nominal vertical load of 1000 kN. The six types of the spherical sliding layer material are considered: ultra-high molecular weight polyethylene (UHMWPE) from three different manufacturers, modified polytetrafluoroethylene (PTFE), and composite materials by PTFE with two different forms of reinforcing bronze inclusions. Young’s modulus, Poisson’s ratio, and strain curve are obtained experimentally for spherical sliding layer materials. Paper considered the influence of the sliding layer material on the contact parameters and deformation characteristics of the structure with a standard interlayer thickness by 4 mm. Research observed significant the composite interlayer deformation and the appearance of “no contact” zones on the mating surfaces. The option of increasing the sliding layer thickness up to 6–8 mm is considered. A decrease is observed in the maximum level of contact parameters by increase of the sliding layer thickness. The influence of the anti-friction layer materials becomes insignificant on the bearing deformation with an increase of the spherical sliding layer thickness.
Characteristics of Friction Plug Joints for AA2219-T87 FSW Welds
Authors: Sun Zhuanping , Yang Xinqi , Li Shuxin
Published: February 2022

In this study, Friction plug welding (FPW) for 8 mm thickness AA2219-T87 sheets were carried out, and defect-free joints were obtained. The geometric size of plug and plate hole, rotational speed and welding force exhibit significant effects on the weld formation. Meanwhile, it is concluded that significant inhomogeneity of microstructure and mechanical properties exists in FPW joints. The recrystallization zone has the highest mechanical properties owing to the fine equiaxed grains and uniformly distributed θ precipitates. The entire plug, thermo-mechanically affected zone and nugget thermo-mechanically affected zone closed to the bonding interface are significantly softened due to the deformation of the grains and θ’ precipitate dissolution. The ultimate tensile strength (UTS) and elongation of the FPW joints can reach 359 MPa and 7.3% at 77 K and 305 MPa and 5% at 298 K, respectively.
Carbon Nanotube Devices for Quantum Technology
Authors: Baydin Andrey , Tay Fuyang , Fan Jichao , Manjappa Manukumara , Gao Weilu , Kono Junichiro
Published: February 2022

Carbon nanotubes, quintessentially one-dimensional quantum objects, possess a variety of electrical, optical, and mechanical properties that are suited for developing devices that operate on quantum mechanical principles. The states of one-dimensional electrons, excitons, and phonons in carbon nanotubes with exceptionally large quantization energies are promising for high-operating-temperature quantum devices. Here, we discuss recent progress in the development of carbon-nanotube-based devices for quantum technology, i.e., quantum mechanical strategies for revolutionizing computation, sensing, and communication. We cover fundamental properties of carbon nanotubes, their growth and purification methods, and methodologies for assembling them into architectures of ordered nanotubes that manifest macroscopic quantum properties. Most importantly, recent developments and proposals for quantum information processing devices based on individual and assembled nanotubes are reviewed.
Analysis of Experimental Results Regarding the Selection of Spring Elements in the Front Suspension of a Four-Axle Truck
Authors: Stańco Mariusz , Kowalczyk Marcin
Published: February 2022

Most special vehicles on public roads and off-road are equipped with various suspension systems. The suspensions used in trucks are designed to absorb the energy that results from overcoming uneven ground. These suspensions are divided into dependent and independent ones. Knowledge of the loads that occur while driving a vehicle, mainly off-road, is critical from the point of view of the adhesion and fatigue life of the suspension system. In the case of four-axle cars with 2 + 2 axles, in which the first two axles are equipped with a dependent suspension based on leaf springs, only one axle may carry the load. This paper attempts to analyze the results of experimental tests carried out on a vehicle in the conditions of roads with an unstable surface such as dirt roads, gravel roads, and roadless tracks. An analysis of fatigue life estimation is presented using equivalent stress values. It was also determined how the use of front axles load equalizing elements in the tested car influences their fatigue life.
Interaction of Lipopolysaccharide-Spiked Blood with Anti-Fouling Polymyxin B-Modified Glass
Authors: Wong Hoi Ting , Romaschin Alexander , Bjelobrk Sara , De La Franier Brian , Thompson Michael
Published: February 2022

Bacterial endotoxin, also known as lipopolysaccharide (LPS), plays a major role in the initiation of sepsis, a severe inflammatory condition. Removal of the toxin from blood is one accepted method of patient treatment. Polymyxin B (PMB)-modified columns have been employed successfully for this purpose via extra-corporeal blood-flow systems that incorporate a cartridge for toxin removal. Herein we demonstrate that PMB-modified glass beads are able to reduce the presence of LPS competitively with the equivalent fiber column used in a commercial cartridge. Analysis by gas chromatography-mass spectrometry and ELISA of released fatty acids from the toxin indicates that PMB does not physically capture or significantly remove LPS from the blood samples. In reality, interaction between the surface-bound PMB and the toxin may lead to disaggregation or monomerization of LPS aggregates. As aggregates are the bioactive form of LPS, it is possible that the monomerization of these entities may be the mechanism by which their toxicity is reduced. Moreover, this work indicates that LPS monomers are stabilized subsequent to disaggregation induced by PMB.