bluuebunny/crossref_metadata_2025 huggingface dataset:
The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles
Authors: Khan Shibbir Ahmed , Ilies Marc A.
Published: January 2023

The phospholipase A2 (PLA2) superfamily of phospholipase enzymes hydrolyzes the ester bond at the sn-2 position of the phospholipids, generating a free fatty acid and a lysophospholipid. The PLA2s are amphiphilic in nature and work only at the water/lipid interface, acting on phospholipid assemblies rather than on isolated single phospholipids. The superfamily of PLA2 comprises at least six big families of isoenzymes, based on their structure, location, substrate specificity and physiologic roles. We are reviewing the secreted PLA2 (sPLA2), cytosolic PLA2 (cPLA2), Ca2+-independent PLA2 (iPLA2), lipoprotein-associated PLA2 (LpPLA2), lysosomal PLA2 (LPLA2) and adipose-tissue-specific PLA2 (AdPLA2), focusing on the differences in their structure, mechanism of action, substrate specificity, interfacial kinetics and tissue distribution. The PLA2s play important roles both physiologically and pathologically, with their expression increasing significantly in diseases such as sepsis, inflammation, different cancers, glaucoma, obesity and Alzheimer’s disease, which are also detailed in this review.
α-Synuclein Aggregates in the Nigro-Striatal Dopaminergic Pathway Impair Fine Movement: Partial Reversal by the Adenosine A2A Receptor Antagonist
Authors: Cai Qionghui , Xu Na , He Yan , Zhu Jiamin , Ye Fenfen , Luo Zhi , Lu Ruojun , Huang Linshan , Zhang Feiyang , Chen Jiang-Fan , Li Yan
Published: January 2023

Parkinson’s disease (PD) is characterized pathologically by abnormal aggregation of alpha-synuclein (α-Syn) in the brain and clinically by fine movement deficits at the early stage, but the roles of α-Syn and associated neural circuits and neuromodulator bases in the development of fine movement deficits in PD are poorly understood, in part due to the lack of appropriate behavioral testing paradigms and PD models without motor confounding effects. Here, we coupled two unique behavioral paradigms with two PD models to reveal the following: (i) Focally injecting α-Syn fibrils into the dorsolateral striatum (DLS) and the transgenic expression of A53T-α-Syn in the dopaminergic neurons in the substantia nigra (SN, PITX3-IRES2-tTA/tetO-A53T mice) selectively impaired forelimb fine movements induced by the single-pellet reaching task. (ii) Injecting α-Syn fibers into the SN suppressed the coordination of cranial and forelimb fine movements induced by the sunflower seed opening test. (iii) Treatments with the adenosine A2A receptor (A2AR) antagonist KW6002 reversed the impairment of forelimb and cranial fine movements induced by α-Syn aggregates in the SN. These findings established a causal role of α-Syn in the SNc-DLS dopaminergic pathway in the development of forelimb and cranial fine movement deficits and suggest a novel therapeutic strategy to improve fine movements in PD by A2AR antagonists.
AaCaMKs Positively Regulate Development, Infection Structure Differentiation and Pathogenicity in Alternaria alternata, Causal Agent of Pear Black Spot
Authors: Jiang Qianqian , Li Yongcai , Mao Renyan , Bi Yang , Liu Yongxiang , Zhang Miao , Li Rong , Yang Yangyang , Prusky Dov B.
Published: January 2023

Calcium/calmodulin-dependent protein kinase (CaMK), a key downstream target protein in the Ca2+ signaling pathway of eukaryotes, plays an important regulatory role in the growth, development and pathogenicity of plant fungi. Three AaCaMKs (AaCaMK1, AaCaMK2 and AaCaMK3) with conserved PKC_like superfamily domains, ATP binding sites and ACT sites have been cloned from Alternaria alternata, However, their regulatory mechanism in A. alternata remains unclear. In this study, the function of the AaCaMKs in the development, infection structure differentiation and pathogenicity of A. alternata was elucidated through targeted gene disruption. The single disruption of AaCaMKs had no impact on the vegetative growth and spore morphology but significantly influenced hyphae growth, sporulation, biomass accumulation and melanin biosynthesis. Further expression analysis revealed that the AaCaMKs were up-regulated during the infection structure differentiation of A. alternata on hydrophobic and pear wax substrates. In vitro and in vivo analysis further revealed that the deletion of a single AaCaMKs gene significantly reduced the A. alternata conidial germination, appressorium formation and infection hyphae formation. In addition, pharmacological analysis confirmed that the CaMK specific inhibitor, KN93, inhibited conidial germination and appressorium formation in A. alternata. Meanwhile, the AaCaMKs genes deficiency significantly reduced the A. alternata pathogenicity. These results demonstrate that AaCaMKs regulate the development, infection structure differentiation and pathogenicity of A. alternata and provide potential targets for new effective fungicides.
Calmodulin and Amyloid Beta as Coregulators of Critical Events during the Onset and Progression of Alzheimer’s Disease
Authors: O’Day Danton H.
Published: January 2023

Calmodulin (CaM) and a diversity of CaM-binding proteins (CaMBPs) are involved in the onset and progression of Alzheimer’s disease (AD). In the amyloidogenic pathway, AβPP1, BACE1 and PSEN-1 are all calcium-dependent CaMBPs as are the risk factor proteins BIN1 and TREM2. Ca2+/CaM-dependent protein kinase II (CaMKII) and calcineurin (CaN) are classic CaMBPs involved in memory and plasticity, two events impacted by AD. Coupled with these events is the production of amyloid beta monomers (Aβ) and oligomers (Aβo). The recent revelations that Aβ and Aβo each bind to both CaM and to a host of Aβ receptors that are also CaMBPs adds a new level of complexity to our understanding of the onset and progression of AD. Multiple Aβ receptors that are proven CaMBPs (e.g., NMDAR, PMCA) are involved in calcium homeostasis an early event in AD and other neurodegenerative diseases. Other CaMBPs that are Aβ receptors are AD risk factors while still others are involved in the amyloidogenic pathway. Aβ binding to receptors not only serves to control CaM’s ability to regulate critical proteins, but it is also implicated in Aβ turnover. The complexity of the Aβ/CaM/CaMBP interactions is analyzed using two events: Aβ generation and NMDAR function. The interactions between Aβ, CaM and CaMBPs reveals a new level of complexity to critical events associated with the onset and progression of AD and may help to explain the failure to develop successful therapeutic treatments for the disease.
Angiogenic Modification of Microfibrous Polycaprolactone by pCMV-VEGF165 Plasmid Promotes Local Vascular Growth after Implantation in Rats
Authors: Klabukov Ilya , Balyasin Maksim , Krasilnikova Olga , Tenchurin Timur , Titov Alexander , Krasheninnikov Mikhail , Mudryak Daniil , Sulina Yana , Shepelev Alexey , Chvalun Sergei , Dyuzheva Tatiana , Yakimova Anna , Sosin Dmitry , Lyundup Alexey , Baranovskii Denis , Shegay Peter , Kaprin Andrey
Published: January 2023

Insufficient vascular growth in the area of artificial-material implantation contributes to ischemia, fibrosis, the development of bacterial infections, and tissue necrosis around the graft. The purpose of this study was to evaluate angiogenesis after implantation of polycaprolactone microfiber scaffolds modified by a pCMV-VEGF165-plasmid in rats. Influence of vascularization on scaffold degradation was also examined. We investigated flat microfibrous scaffolds obtained by electrospinning polycaprolactone with incorporation of the pCMV-VEGF-165 plasmid into the microfibers at concentrations of 0.005 ng of plasmid per 1 mg of polycaprolactone (0.005 ng/mg) (LCGroup) and 0.05 ng/mg (HCGroup). The samples were subcutaneously implanted in the interscapular area of rats. On days 7, 16, 33, 46, and 64, the scaffolds were removed, and a histological study with a morphometric evaluation of the density and diameter of the vessels and microfiber diameter was performed. The number of vessels was increased in all groups, as well as the resorption of the scaffold. On day 33, the vascular density in the HCGroup was 42% higher compared to the control group (p = 0.0344). The dose-dependent effect of the pCMV-VEGF165-plasmid was confirmed by enhanced angiogenesis in the HCGroup compared to the LCGroup on day 33 (p-value = 0.0259). We did not find a statistically significant correlation between scaffold degradation rate and vessel growth (the Pearson correlation coefficient was ρ = 0.20, p-value = 0.6134). Functionalization of polycaprolactone by incorporation of the pCMV-VEGF165 plasmid provided improved vascularization within 33 days after implantation, however, vessel growth did not seem to correlate with scaffold degradation rate.
METTL3 Regulates Osteoclast Biological Behaviors via iNOS/NO-Mediated Mitochondrial Dysfunction in Inflammatory Conditions
Authors: Li Di , He Jinlin , Fang Caihong , Zhang Yiwen , He Mingli , Zhang Zhanqi , Hou Jinsong , Xu Qiong
Published: January 2023

Excessive differentiation of osteoclasts contributes to the disruption of bone homeostasis in inflammatory bone diseases. Methyltransferase-like 3 (METTL3), the core methyltransferase that installs an N6-methyladenosine (m6A) modification on RNA, has been reported to participate in bone pathophysiology. However, whether METTL3-mediated m6A affects osteoclast differentiation in inflammatory conditions remains unelucidated. In this study, we observed that the total m6A content and METTL3 expression decreased during LPS-induced osteoclastogenesis. After knocking down METTL3, we found reduced levels of the number of osteoclasts, osteoclast-related gene expression and bone resorption area. A METTL3 deficiency increased osteoclast apoptosis and pro-apoptotic protein expression. RNA sequencing analysis showed that differentially expressed genes in METTL3-deficient cells were mainly associated with the mitochondrial function. The expression of the mitochondrial function-related genes, ATP production and mitochondrial membrane potential decreased after METTL3 knockdown. Moreover, the most obviously upregulated gene in RNA-Seq was Nos2, which encoded the iNOS protein to induce nitric oxide (NO) synthesis. METTL3 knockdown increased the levels of Nos2 mRNA, iNOS protein and NO content. NOS inhibitor L-NAME rescued the inhibited mitochondrial function and osteoclast formation while suppressing osteoclast apoptosis in METTL3-silenced cells. Mechanistically, a METTL3 deficiency promoted the stability and expression of Nos2 mRNA, and similar results were observed after m6A-binding protein YTHDF1 knockdown. Further in vivo evidence revealed that METTL3 knockdown attenuated the inflammatory osteolysis of the murine calvaria and suppressed osteoclast formation. In conclusion, these data suggested that METTL3 knockdown exacerbated iNOS/NO-mediated mitochondrial dysfunction by promoting a Nos2 mRNA stability in a YTHDF1-dependent manner and further inhibited osteoclast differentiation and increased osteoclast apoptosis in inflammatory conditions.
Light Pollution Disrupts Seasonal Differences in the Daily Activity and Metabolic Profiles of the Northern House Mosquito, Culex pipiens
Authors: Wolkoff Matthew , Fyie Lydia , Meuti Megan
Published: January 2023

The Northern House mosquito, Culex pipiens, is an important disease vector, and females are capable of surviving the winter in a state of overwintering diapause. This species’ diapause response has been extensively studied, and recent evidence suggests that the circadian clock is involved in measuring seasonal changes in daylength to initiate the diapause response. However, differences in the circadian activity of diapausing and non-diapausing Cx. pipiens have not been thoroughly investigated. Additionally, recent findings indicate that artificial light at night (ALAN) can disrupt mosquito diapause, potentially prolonging the mosquito biting season. We compared the circadian locomotor activity of mosquitoes reared in diapause-averting, long-day conditions and diapause-inducing, short-day conditions with and without ALAN to elucidate the interplay between circadian activity, diapause, and light pollution. We also uncovered metabolic differences between mosquitoes reared under diapausing and non-diapausing photoperiods with and without ALAN by measuring the concentration of protein, fructose, glycogen, water-soluble carbohydrates, and lipids. We found that ALAN exposure altered several diapause-associated phenotypes including slightly, but not significantly, increasing activity levels in short day-reared mosquitoes; and preventing some short day-reared mosquitoes from accumulating lipids. ALAN also significantly reduced glycogen and water-soluble carbohydrate levels in long day-reared mosquitoes. Based on our findings, light pollution may decrease insect fitness by perturbing metabolism, and may also impact several phenotypes associated with insect diapause, potentially extending the mosquito biting season and preventing insects in urban environments from overwintering successfully.
Weeds Enhance Insect Diversity and Abundance and May Improve Soil Conditions in Mango Cultivation of South Florida
Authors: Kleiman Blaire , Koptur Suzanne
Published: January 2023

This study examined if weeds could serve as insectary plants to increase beneficial insect abundance and diversity in mango cultivation in southern Florida. Additionally, we examined how weed presence affects mango tree soil health. We found that weeds significantly increased pollinating and parasitoid insect abundance and diversity. Eight insect orders and eighteen families were significantly more abundant on mango trees with weeds growing beneath them than those where weeds were removed. There was no difference in predatory insects between treatments, and slightly more herbivorous insects on weedy mango trees. Pollinating insects visiting mango flowers in the weed treatment were significantly greater, as well as spiders on weedy mango trees. However, there were more lacewings (Neuroptera) observed on the mango trees without weeds, and leaf chlorophyll in the old and new mango leaves was significantly greater, in the weed-free treatment. Soil conditions, however, significantly improved in soil carbon and a greater pH reduction in the presence of weeds, though weeds affected neither soil nitrogen, phosphorous, nor chlorophyll in productive green leaves. These results show that a tolerable level of selective weed species’ presence may benefit insect, plant, and soil biodiversity in farms. This is important in increasing production, sustainability, and biodiversity in agriculture, which otherwise may be deficient in non-crop life.
Detection of Arthropod-Borne Bacteria and Assessment of MALDI-TOF MS for the Identification of Field-Collected Immature Bed Bugs from Mauritania
Authors: Sevestre Jacques , Lemrabott Mohamed Aly Ould , Bérenger Jean-Michel , Zan Diarra Adama , Ould Mohamed Salem Boukhary Ali , Parola Philippe
Published: January 2023

Human infestations by bed bugs have upsurged globally in recent decades, including in African countries, where recent reports pointed out an increase in infestation. Sympatric dwelling has been described for two species of bed bug parasitizing humans: Cimex hemipterus (the tropical bed bug) and C. lectularius. Identification of these two species is based on morphological characteristics, and gene sequencing, and may also rely on Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS). The present work aimed to assess whether MALDI-TOF MS was applicable for species level identification of immature stages of Cimex. Arthropods were collected in domestic settings in Nouakchott, Mauritania. Identification used morphological keys and MALDI-TOF MS identification was assessed for immature stages. Quantitative PCR and sequencing assays were used to detect arthropod-associated bacteria in each specimen. A total of 92 arthropods were collected, all morphologically identified as C. hemipterus (32 males, 14 females and 45 immature stages). A total of 35/45 specimens produced good quality MALDI-TOF MS spectra. Analysis allowed species level identification of all immature C. hemipterus after their spectra were entered into our in-house MALDI-TOF MS arthropod spectra database. Molecular screening allowed detection of Wolbachia DNA in each specimen. These results suggested that MALDI-TOF MS is a reliable tool for species level identification of Cimex specimens, including immature specimens. Future studies should assess this approach on larger panels of immature specimens for different Cimex species and focus on the precise staging of their different immature developmental stages.
Increased Proteoglycanases in Pulmonary Valves after Birth Correlate with Extracellular Matrix Maturation and Valve Sculpting
Authors: Dupuis Loren E. , Evins Sarah E. , Abell Morgan C. , Blakley Morgan E. , Horkey Samuel L. , Barth Jeremy L. , Kern Christine B.
Published: January 2023

Increased mechanical forces on developing cardiac valves drive formation of the highly organized extracellular matrix (ECM) providing tissue integrity and promoting cell behavior and signaling. However, the ability to investigate the response of cardiac valve cells to increased mechanical forces is challenging and remains poorly understood. The developmental window from birth (P0) to postnatal day 7 (P7) when biomechanical forces on the pulmonary valve (PV) are altered due to the initiation of blood flow to the lungs was evaluated in this study. Grossly enlarged PV, in mice deficient in the proteoglycan protease ADAMTS5, exhibited a transient phenotypic rescue from postnatal day 0 (P0) to P7; the Adamts5−/− aortic valves (AV) did not exhibit a phenotypic correction. We hypothesized that blood flow, initiated to the lungs at birth, alters mechanical load on the PV and promotes ECM maturation. In the Adamts5−/− PV, there was an increase in localization of the proteoglycan proteases ADAMTS1, MMP2, and MMP9 that correlated with reduced Versican (VCAN). At birth, Decorin (DCN), a Collagen I binding, small leucine-rich proteoglycan, exhibited complementary stratified localization to VCAN in the wild type at P0 but colocalized with VCAN in Adamts5−/− PV; concomitant with the phenotypic rescue at P7, the PVs in Adamts5−/− mice exhibited stratification of VCAN and DCN similar to wild type. This study indicates that increased mechanical forces on the PV at birth may activate ECM proteases to organize specialized ECM layers during cardiac valve maturation.
Prediction Models of Primary Membranous Nephropathy: A Systematic Review and Meta-Analysis
Authors: Geng Chanyu , Huang Liming , Li Yi , Wang Amanda Ying , Li Guisen , Feng Yunlin
Published: January 2023

Background: Several statistical models for predicting prognosis of primary membranous nephropathy (PMN) have been proposed, most of which have not been as widely accepted in clinical practice. Methods: A systematic search was performed in MEDLINE and EMBASE. English studies that developed any prediction models including two or more than two predictive variables were eligible for inclusion. The study population was limited to adult patients with pathologically confirmed PMN. The outcomes in eligible studies should be events relevant to prognosis of PMN, either disease progression or response profile after treatments. The risk of bias was assessed according to the PROBAST. Results: In all, eight studies with 1237 patients were included. The pooled AUC value of the seven studies with renal function deterioration and/or ESRD as the predicted outcomes was 0.88 (95% CI: 0.85 to 0.90; I2 = 77%, p = 0.006). The paired forest plots for sensitivity and specificity with corresponding 95% CIs for each of these seven studies indicated the combined sensitivity and specificity were 0.76 (95% CI: 0.64 to 0.85) and 0.84 (95% CI: 0.80 to 0.88), respectively. All seven studies included in the meta-analysis were assessed as high risk of bias according to the PROBAST tool. Conclusions: The reported discrimination ability of included models was good; however, the insufficient calibration assessment and lack of validation studies precluded drawing a definitive conclusion on the performance of these prediction models. High-grade evidence from well-designed studies is needed in this field.
REVersal of nEuromusculAr bLocking Agents in Patients Undergoing General Anaesthesia (REVEAL Study)
Authors: Greco Massimiliano , Caruso Pier Francesco , Angelotti Giovanni , Aceto Romina , Coppalini Giacomo , Martinetti Nicolò , Albini Marco , Bash Lori D. , Carvello Michele , Piccioni Federico , Monzani Roberta , Montorsi Marco , Cecconi Maurizio
Published: January 2023

Background: Neuromuscular blocking agent (NMBA) monitoring and reversals are key to avoiding residual curarization and improving patient outcomes. Sugammadex is a NMBA reversal with favorable pharmacological properties. There is a lack of real-world data detailing how the diffusion of sugammadex affects anesthetic monitoring and practice. Methods: We conducted an electronic health record analysis study, including all adult surgical patients undergoing general anesthesia with orotracheal intubation, from January 2016 to December 2019, to describe changes and temporal trends of NMBAs and NMBA reversals administration. Results: From an initial population of 115,046 surgeries, we included 37,882 procedures, with 24,583 (64.9%) treated with spontaneous recovery from neuromuscular block and 13,299 (35.1%) with NMBA reversals. NMBA reversals use doubled over 4 years from 25.5% to 42.5%, mainly driven by sugammadex use, which increased from 17.8% to 38.3%. Rocuronium increased from 58.6% (2016) to 94.5% (2019). Factors associated with NMBA reversal use in the multivariable analysis were severe obesity (OR 3.33 for class II and OR 11.4 for class III obesity, p-value < 0.001), and high ASA score (OR 1.47 for ASA III). Among comorbidities, OSAS, asthma, and other respiratory diseases showed the strongest association with NMBA reversal administration. Conclusions: Unrestricted availability of sugammadex led to a considerable increase in pharmacological NMBA reversal, with rocuronium use also rising. More research is needed to determine how unrestricted and safer NMBA reversal affects anesthesia intraoperative monitoring and practice.
Diagnostic Value of Multi-Mode Ultrasonic Flow Imaging Examination in Solid Renal Tumors of Different Sizes
Authors: Zhang Dai , Wang Ying , Yang Fan , Mao Yiran , Mu Jie , Zhao Lihui , Xu Wengui
Published: January 2023

Purposes: To explore the value of Microflow Imaging (MFI) in renal solid tumors. Methods: A total of 195 patients with 199 lesions pathologically confirmed masses were retrospectively analyzed. The 199 masses were divided into the tumor ≤ 4 cm group (n = 104) and tumor > 4 cm group (n = 95). The diagnostic efficacy of Color Doppler Flow Imaging (CDFI), Power Doppler Imaging (PDI) and MFI in renal tumors sizes were compared by determining the Adler grade, vascular morphology and peripheral blood flow. Results: Among 199 tumors, 161 lesions were malignant and 38 lesions were benign. MFI in malignant tumor ≤ 4 cm demonstrated statistically significant differences in Adler grade and vascular morphology as compared to CDFI and PDI (p < 0.05). In malignant tumor > 4 cm group, MFI showed significant difference in vascular morphology compared with CDFI (p < 0.05). MFI showed a significant difference in the peripheral annular blood flow of malignant tumors when compared to CDFI and PDI (p < 0.05). In addition, the malignant tumors of the two sizes by MFI in peripheral annular blood flow detection showed significant difference (p < 0.05). The area under the curve of ROC by MFI in the tumor ≤ 4 cm was 0.771, which was higher than CDFI and PDI (p < 0.05), but no obvious difference among the tumor > 4 cm (p > 0.05). Conclusion: MFI provides a new method for the differential diagnosis of small renal carcinoma. Based on the convenience and non-radiation of MFI, we can choose MFI as an imaging diagnostic tool for patients who need long-term active surveillance (AS) follow-up.
The Impact of Tissue Preparation on Salivary Gland Tumors Investigated by Fourier-Transform Infrared Microspectroscopy
Authors: Stefanakis Mona , Bassler Miriam C. , Walczuch Tobias R. , Gerhard-Hartmann Elena , Youssef Almoatazbellah , Scherzad Agmal , Stöth Manuel Bernd , Ostertag Edwin , Hagen Rudolf , Steinke Maria R. , Hackenberg Stephan , Brecht Marc , Meyer Till Jasper
Published: January 2023

Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows.
Factors Associating with Non-Dipping Pattern of Nocturnal Blood Pressure in Patients with Essential Hypertension
Authors: Koike Tsutomu , Imamura Teruhiko , Tomoda Fumihiro , Ohara Maiko , Fujioka Hayato , Kakeshita Kota , Yamazaki Hidenori , Kinugawa Koichiro
Published: January 2023

Background: In patients with essential hypertension, a non-dipping blood pressure pattern is a strong risk factor for cardiovascular diseases. However, background factors associating with such a blood pressure pattern remain unknown. Methods: Untreated essential hypertensive patients without chronic kidney diseases who were admitted to our outpatient clinic were included. Blood sampling and 24 h ambulatory blood pressure monitoring were mandatorily performed. Non-dipper status was defined as a maximum decrease in nocturnal systolic blood pressure within 10%. Clinical factors associating with non-dipper status were investigated. Results: A total of 154 patients (56 ± 12 years old, 86 men) were included. Among baseline characteristics, a higher serum uric acid level was independently associated with non-dipper status (odds ratio 1.03, 95% confidence interval 1.00–1.05, p < 0.05). Among those with non-dipper status, a higher high-sensitivity C-reactive protein level tended to be associated with incremental nighttime systolic blood pressure levels (p = 0.065). Conclusions: Hyperuricemia and micro-inflammation might be associated with attenuated nocturnal blood pressure dipping and incremental nighttime systolic blood pressure levels.
Extracorporeal Life Support for Cardiogenic Shock in Octogenarians: Single Center Experience
Authors: Scupakova Nadezda , Urbonas Karolis , Jankuviene Agne , Puodziukaite Lina , Andrijauskas Povilas , Janusauskas Vilius , Zorinas Aleksejus , Laurusonis Kestutis , Serpytis Pranas , Samalavicius Robertas
Published: January 2023

Background: The age limit for the use of extracorporeal membrane oxygenation (ECMO) support for post-cardiotomy cardiac failure is not defined. The aim of the study was to evaluate the outcomes of octogenarians supported with ECMO due to cardiogenic shock. Methods: A retrospective review of consecutive elderly patients supported with ECMO during a 13-year period in a tertiary care center. Patient’s demographic variables, comorbidities, perioperative data and outcomes were collected from patient medical records. Data of octogenarian patients were compared with the septuagenarian group. The main outcomes of the study was in hospital mortality, 6-month survival and 1-year survival after hospital discharge and discharge options. Multivariate logistic regression analysis was performed to identify the factors associated with hospital survival. Results: Eleven patients (18.3%) in the elderly group were octogenarians (aged 80 years or above), and forty-nine (81.7%) were septuagenarians (aged 70–79 years). There were no differences except age in demographic and preoperative variables between groups. Pre ECMO SAVE, SOFA, SAPS—II and inotropic scores were significantly higher in septuagenarians than octogenarians. There was no statistically significant difference in hospital mortality, 6-month survival, 1 year survival or discharge options between groups. Conclusions: ECMO could be successfully used in selected octogenarian patients undergoing cardiac surgery to support a failing heart. An early decision to initiate ECMO therapy in elderly post-cardiotomy shock patients is associated with favorable outcomes.
Additive Manufacturing of Polyhydroxyalkanoate-Based Blends Using Fused Deposition Modelling for the Development of Biomedical Devices
Authors: Gregory David Alexander , Fricker Annabelle T. R. , Mitrev Peter , Ray Meghna , Asare Emmanuel , Sim Daniel , Larpnimitchai Soponvit , Zhang Zixuan , Ma Jinge , Tetali Santosh S. V. , Roy Ipsita
Published: January 2023

In the last few decades Additive Manufacturing has advanced and is becoming important for biomedical applications. In this study we look at a variety of biomedical devices including, bone implants, tooth implants, osteochondral tissue repair patches, general tissue repair patches, nerve guidance conduits (NGCs) and coronary artery stents to which fused deposition modelling (FDM) can be applied. We have proposed CAD designs for these devices and employed a cost-effective 3D printer to fabricate proof-of-concept prototypes. We highlight issues with current CAD design and slicing and suggest optimisations of more complex designs targeted towards biomedical applications. We demonstrate the ability to print patient specific implants from real CT scans and reconstruct missing structures by means of mirroring and mesh mixing. A blend of Polyhydroxyalkanoates (PHAs), a family of biocompatible and bioresorbable natural polymers and Poly(L-lactic acid) (PLLA), a known bioresorbable medical polymer is used. Our characterisation of the PLA/PHA filament suggest that its tensile properties might be useful to applications such as stents, NGCs, and bone scaffolds. In addition to this, the proof-of-concept work for other applications shows that FDM is very useful for a large variety of other soft tissue applications, however other more elastomeric MCL-PHAs need to be used.
Chronotype, Time of Day, and Performance on Intelligence Tests in the School Setting
Authors: Jankowski Konrad S. , Díaz-Morales Juan Francisco , Vollmer Christian
Published: January 2023

Research suggests the existence of an association between chronotype and intellectual performance, but the nature of this link remains unclear. Studies conducted in a laboratory setting point to the synchrony effect (better performance at a person’s preferred time of day) for fluid intelligence, but not for crystallized intelligence, whereas studies that have analyzed students’ grades suggest that the effect exists for both. In the present study, we aimed to verify the synchrony effect by applying direct measures of crystallized intelligence, fluid intelligence, and subjective sleepiness–alertness in a sample of high school students during their morning or afternoon class. The results revealed a synchrony effect for crystallized, but not for fluid intelligence. During morning class, students with a morning chronotype performed better than evening chronotypes on a test of crystallized intelligence, whereas during afternoon class there was no difference between chronotypes. The association resulted from decreased performance during morning class in evening chronotypes that improved during afternoon class and constant performance in morning chronotypes. These effects were independent of sleepiness–alertness levels. The results suggest that individual differences between chronotypes may be important for tasks performed during morning classes, but not during afternoon ones, and that performance across school days may depend on time of day in evening chronotypes.
Electromigration-Aware Architecture for Modern Microprocessors
Authors: Gabbay Freddy , Mendelson Avi
Published: January 2023

Reliability is a fundamental requirement in microprocessors that guarantees correct execution over their lifetimes. The reliability-related design rules depend on the process technology and device operating conditions. To meet reliability requirements, advanced process nodes impose challenging design rules, which place a major burden on the VLSI implementation flow because they impose severe physical constraints. This paper focuses on electromigration (EM), one of the critical factors affecting semiconductor reliability. EM is the aging process of on-die wires in integrated circuits (ICs). Traditionally, EM issues have been handled at the physical design level, which enforces reliability rules using worst-case scenario analysis to detect and solve violations. In this paper, we offer solutions that exploit architectural characteristics to reduce EM impact. The use of architectural methods can simplify EM solutions, and such methods can be incorporated with standard physical-design-based solutions to enhance current methods. Our comprehensive physical simulation results show that, with minimal area, power, and performance overhead, the proposed solution can relax EM design efforts and significantly extend a microprocessor’s lifetime.
Fine Structure of Vertical Density Distribution in the Black Sea and Its Relationship with Vertical Turbulent Exchange
Authors: Podymov Oleg I. , Zatsepin Andrei G. , Ostrovskii Alexander G.
Published: January 2023

This paper is concerned with the analysis of the long-term regular time series of current velocity and conductivity, temperature, and depth (CTD) profiles, measured with the moored autonomous profiler Aqualog over the upper part of the continental slope at a fixed geographical location in the Northeastern Black Sea. This study focuses on the fine structure of the density profiles to show that the fine-structure Cox number (C) is a power function of the Richardson number (Ri). A similar inverse power relationship with the same exponent was found earlier for the coefficient of vertical turbulent mass exchange (Kρ) and Ri. Based on those results, the analysis indicated a statistically significant correlation between C and Kρ, which suggests that the estimations of Kρ could be conducted from the CTD data only.
Uncertainty in the Estimation of Partial Safety Factors for Different Steel-Grade Corroded Pipelines
Authors: Bhardwaj Utkarsh , Teixeira Angelo Palos , Guedes Soares C.
Published: January 2023

This paper assesses the uncertainty of the partial safety factors for the design of corroded pipelines against burst failure due to the variability associated with the strength model selection. First, 10 calibrated burst pressure prediction models for corroded pipelines are adopted and duly categorised under low-, medium- and high-grade steel classes. The probabilistic characteristics of the pipe burst strength are studied using Monte Carlo simulation for the selected models. Model uncertainty factors are used to correct the burst pressure predictions by the design equations. Model strength factors are derived for models in each category that will provide coherent reliability. The first-order reliability method is employed to estimate the partial safety factors and their uncertainty as a function of operational time. Finally, the influence of the corrosion growth model on the evaluation of partial safety factors is assessed. The results obtained in this study can provide vital guidance regarding the design and maintenance of different steel-grade pipelines.
A Field Theory-Based Novel Algorithm for Navigational Hazard Index
Authors: Liu Yihua , Ma Yu
Published: January 2023

Collision risk assessment is crucial for autonomous ships to identify risks and make decisions for collision avoidance. In this paper, a field theory-based navel algorithm is proposed to define and describe the risk of ship collision. Based on the field theory and the asymmetric Gaussian function, the ship collision risk field is constructed, and the field potential is used to characterize the navigational hazard index. The effectiveness and superiority of the algorithm are verified through study cases. The results show that the proposed algorithm can obtain the index continuously, reflect the risk level accurately, and provide reliable basis for the navigation of autonomous ships. Therefore, it has important application potential in the development of intelligence navigation.
Verification of the Ekman Upwelling Criterion with In Situ Temperature Measurements in the Southeastern Baltic Sea
Authors: Myslenkov Stanislav , Silvestrova Ksenia , Krechik Viktor , Kapustina Mariia
Published: January 2023

Upwelling leads to a sharp and strong decrease in water temperature in the coastal zone of the southeastern Baltic Sea. The quality of existing hydrodynamic models cannot fully meet the requirements of accurate upwelling forecasts. This study provides insight into the applicability of the simplified Ekman upwelling criterion method for the southeastern Baltic Sea. The upwelling criterion is the ratio of the vertical velocity and the duration of the upwelling wind to the mixed layer density. The vertical velocity was determined by the divergence of the integral Ekman transport in the transverse direction. Calculation of the criterion was based on wind data from NCEP/CFSR reanalysis. The upwelling criterion was compared with in situ temperatures from direct measurements near the D-6 oil platform taken in 2015–2017. Only 46% of calculated upwelling cases were confirmed by temperature decreases in the sub-surface. It was found that more than half of the cases of strong temperature decreases were caused by a northern wind (Ekman upwelling), when the criterion exceeded the threshold value. Comparison of the hydrodynamic model results and direct measurements shows that the model’s quality is far from perfect, and the simplified methods can be used as alternatives to models. Some recommendations were made for future upwelling research.
Primary Structure and Conformation of a Tetrodotoxin-Binding Protein in the Hemolymph of Non-Toxic Shore Crab Hemigrapsus sanguineus
Authors: Nagashima Yuji , Fujimoto Kenta , Okai Masahiko , Kitani Yoichiro , Yoshinaga-Kiriake Aya , Ishizaki Shoichiro
Published: January 2023

Tetrodotoxin (TTX)-binding proteins are present in toxic TTX-bearing animals, such as pufferfish and gastropods. These may prevent autotoxicity. However, TTX-binding proteins are also found in the nontoxic marine shore crab, Hemigrapsus sanguineus. Here, we isolated the TTX-binding protein, HSTBP (Hemigrapsus sanguineus TTX-binding protein), from the hemolymph of H. sanguineus and elucidated its primary structure using cDNA cloning. HSTBP, a 400 kDa acidic glycoprotein by gel filtration high-performance liquid chromatography, comprises 3 subunits, 88 kDa (subunit-1), 65 kDa (subunit-2), and 26 kDa (subunit-3) via sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reduced conditions. The open reading frame of the cDNA comprises 5049 base pairs encoding 1683 amino acid residues, and the mature protein contains 1650 amino acid residues from Arg34 to Ser1683. The three subunits are arranged in tandem in the following order: subunit-3 (Arg34-Gln261), subunit-1 (Asp262-Phe1138), and subunit-2 (Val1139-Ser1683). A BLAST homology search showed weak similarity of HSTBP to clotting proteins of crustaceans (29–40%). SMART analysis revealed a von Willebrand factor (vWF)-type (⇒delete hyphen) D domain at Phe1387-Gly1544. We confirmed that the recombinant protein of HSTBP subunit-2 containing the vWF-type (⇒delete hyphen) D domain bound to TTX at a molecular ratio of 1:1.
Imaging Features of Main Hepatic Resections: The Radiologist Challenging
Authors: Cutolo Carmen , Fusco Roberta , Simonetti Igino , De Muzio Federica , Grassi Francesca , Trovato Piero , Palumbo Pierpaolo , Bruno Federico , Maggialetti Nicola , Borgheresi Alessandra , Bruno Alessandra , Chiti Giuditta , Bicci Eleonora , Brunese Maria Chiara , Giovagnoni Andrea , Miele Vittorio , Barile Antonio , Izzo Francesco , Granata Vincenza
Published: January 2023

Liver resection is still the most effective treatment of primary liver malignancies, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), and of metastatic disease, such as colorectal liver metastases. The type of liver resection (anatomic versus non anatomic resection) depends on different features, mainly on the type of malignancy (primary liver neoplasm versus metastatic lesion), size of tumor, its relation with blood and biliary vessels, and the volume of future liver remnant (FLT). Imaging plays a critical role in postoperative assessment, offering the possibility to recognize normal postoperative findings and potential complications. Ultrasonography (US) is the first-line diagnostic tool to use in post-surgical phase. However, computed tomography (CT), due to its comprehensive assessment, allows for a more accurate evaluation and more normal findings than the possible postoperative complications. Magnetic resonance imaging (MRI) with cholangiopancreatography (MRCP) and/or hepatospecific contrast agents remains the best tool for bile duct injuries diagnosis and for ischemic cholangitis evaluation. Consequently, radiologists should be familiar with the surgical approaches for a better comprehension of normal postoperative findings and of postoperative complications.
Practical Aspects of Esophageal Pressure Monitoring in Patients with Acute Respiratory Distress Syndrome
Authors: Dostal Pavel , Dostalova Vlasta
Published: January 2023

Esophageal pressure (Pes) monitoring is a minimally invasive advanced respiratory monitoring method with the potential to guide ventilation support management. Pes monitoring enables the separation of lung and chest wall mechanics and estimation of transpulmonary pressure, which is recognized as an important risk factor for lung injury during both spontaneous breathing and mechanical ventilation. Appropriate balloon positioning, calibration, and measurement techniques are important to avoid inaccurate results. Both the approach of using absolute expiratory Pes values and the approach based on tidal Pes difference have shown promising results for ventilation adjustments, with the potential to decrease the risk of ventilator-induced lung injury.
Management of Hyponatremia in Heart Failure: Practical Considerations
Authors: Şorodoc Victoriţa , Asaftei Andreea , Puha Gabriela , Ceasovschih Alexandr , Lionte Cătălina , Sîrbu Oana , Bologa Cristina , Haliga Raluca Ecaterina , Constantin Mihai , Coman Adorata Elena , Petriș Ovidiu Rusalim , Stoica Alexandra , Şorodoc Laurenţiu
Published: January 2023

Hyponatremia is commonly encountered in the setting of heart failure, especially in decompensated, fluid-overloaded patients. The pathophysiology of hyponatremia in patients with heart failure is complex, including numerous mechanisms: increased activity of the sympathetic nervous system and the renin–angiotensin–aldosterone system, high levels of arginine vasopressin and diuretic use. Symptoms are usually mild but hyponatremic encephalopathy can occur if there is an acute decrease in serum sodium levels. It is crucial to differentiate between dilutional hyponatremia, where free water excretion should be promoted, and depletional hyponatremia, where administration of saline is needed. An inappropriate correction of hyponatremia may lead to osmotic demyelination syndrome which can cause severe neurological symptoms. Treatment options for hyponatremia in heart failure, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. The aim of this review is to summarize the principal mechanisms involved in the occurrence of hyponatremia, to present the main guidelines for the treatment of hyponatremia, and to collect and analyze data from studies which target new treatment options, such as vaptans.
Trustful Blockchain-Based Framework for Privacy Enabling Voting in a University
Authors: Diaconita Vlad , Belciu Anda , Stoica Maria Georgiana
Published: January 2023

In this study, we explore the challenges and potential solutions to blockchain-based voting. As a first step, we present a comparison of the relevant platforms for implementing smart contracts in decentralized applications (dApps). We analyze the top platforms, highlighting their advantages and disadvantages, their architecture, and which are more reliable for developing smart contracts. The goal is to find a technology that offers various facilities to the developer and multiple functionalities and performance in the development of smart contracts in a field that has seen an incredible pace of innovation. Based on the findings from our research, we propose a framework based on blockchain technology and smart contracts for university-level voting based on blockchains.
Identification of Wetland Conservation Gaps in Rapidly Urbanizing Areas: A Case Study in Zhengzhou, China
Authors: Liu Chang , Hu Yongge , Taukenova Assemgul , Tian Guohang , Mu Bo
Published: January 2023

Exploring protected area (PA) siting from a biodiversity perspective is critical in mitigating human impacts on ecosystems. This paper used the MaxEnt model to predict the geographic distribution patterns of wetland species in Zhengzhou and the environmental factors affecting species’ habitat selection. Environmental variables were screened by correlation analysis to avoid affecting the prediction results due to overfitting of the model. The AUC value of the training set of the model ROC curve was above 0.8, and the prediction accuracy was high. The prediction results showed that the only nature reserve in Zhengzhou, Yellow River Wetland Nature Reserve, currently covers only 10.25% of the total area of the high suitability areas for plants and 17.54% of the high suitability habitat areas for waterfowl in the whole area of Zhengzhou. The potential suitability areas of wetland species outside the reserve can provide a basis for site selection for wetland conservation planning in Zhengzhou. It was found that the geographic distribution of wetland species in Zhengzhou is constrained by the distribution of water bodies, bioclimatic variables, land cover, and population density.