bluuebunny/crossref_metadata_2025 huggingface dataset:
Commuting Analysis of the Budapest Metropolitan Area Using Mobile Network Data
Authors: Pintér Gergő , Felde Imre
Published: August 2022

The analysis of human movement patterns based on mobile network data makes it possible to examine a very large population cost-effectively and has led to several discoveries about human dynamics. However, the application of this data source is still not common practice. The goal of this study was to analyze the commuting tendencies of the Budapest Metropolitan Area using mobile network data as a case study and propose an automatized alternative approach to the current, questionnaire-based method, as commuting is predominantly analyzed by the census, which is performed only once in a decade in Hungary. To analyze commuting, the home and work locations of cell phone subscribers were determined based on their appearances during and outside working hours. The detected home locations of the subscribers were compared to census data at a settlement level. Then, the settlement and district level commuting tendencies were identified and compared to the findings of census-based sociological studies. It was found that the commuting analysis based on mobile network data strongly correlated with the census-based findings, even though home and work locations were estimated by statistical methods. All the examined aspects, including commuting from sectors of the agglomeration to the districts of Budapest and the age-group-based distribution of the commuters, showed that mobile network data could be an automatized, fast, cost-effective, and relatively accurate way of analyzing commuting, that could provide a powerful tool for sociologists interested in commuting.
Diverse Effects of Cilostazol on Proprotein Convertase Subtilisin/Kexin Type 9 between Obesity and Non-Obesity
Authors: Chen Po-Wei , Tseng Shih-Ya , Chang Hsien-Yuan , Lee Cheng-Han , Chao Ting-Hsing
Published: August 2022

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis. Cilostazol exerts favorable cellular and metabolic effects; however, the effect of cilostazol on the expression of PCSK9 has not been previously reported. Our study aimed to investigate the potential mechanisms of action of cilostazol on the expression of PCSK9 and lipid homeostasis. We evaluated the effects of cilostazol on the expression of PCSK9 in HepG2 cells and evaluated potential molecular mechanisms by measuring signaling molecules in the liver and serum lipid profiles in high-fat diet-induced obese mice and normal chow-fed mice. Cilostazol treatment significantly induced the messenger RNA and protein expression of PCSK9 in HepG2 cells and enhanced PCSK9 promoter activity. Chromatin immunoprecipitation assays confirmed that cilostazol treatment enhanced PCSK9 transcription by binding to peroxisome proliferator-activated receptor-γ (PPARγ) via the PPARγ DNA response element. PPARγ knockdown attenuated the stimulatory effect of cilostazol on PCSK9. In vitro, cilostazol treatment increased PCSK9 expression in vehicle-treated HepG2 cells but decreased PCSK9 expression in palmitic acid-treated HepG2 cells. In vivo, cilostazol treatment increased the serum levels of PCSK9 in normal mice but significantly reduced PCSK9 levels in obese mice. The expressions of PCSK9-relevant microRNAs also showed similar results. Clinical data showed that cilostazol treatment significantly reduced serum PCSK9 levels in patients with obesity. The obesity-dependent effects of cilostazol on PCSK9 expression observed from bench to bedside demonstrates the therapeutic potential of cilostazol in clinical settings.
Immune Function of Endothelial Cells: Evolutionary Aspects, Molecular Biology and Role in Atherogenesis
Authors: Kotlyarov Stanislav
Published: August 2022

Atherosclerosis is one of the key problems of modern medicine, which is due to the high prevalence of atherosclerotic cardiovascular diseases and their significant share in the structure of morbidity and mortality in many countries. Atherogenesis is a complex chain of events that proceeds over many years in the vascular wall with the participation of various cells. Endothelial cells are key participants in vascular function. They demonstrate involvement in the regulation of vascular hemodynamics, metabolism, and innate immunity, which act as leading links in the pathogenesis of atherosclerosis. These endothelial functions have close connections and deep evolutionary roots, a better understanding of which will improve the prospects of early diagnosis and effective treatment.
Comparison of Enzyme Activity in Order to Describe the Metabolic Profile of Dairy Cows during Early Lactation
Authors: Puppel Kamila , Slósarz Jan , Grodkowski Grzegorz , Solarczyk Paweł , Kostusiak Piotr , Kunowska-Slósarz Małgorzata , Grodkowska Kinga , Zalewska Anna , Kuczyńska Beata , Gołębiewski Marcin
Published: August 2022

Enzymatic diagnostics have practical applications in diseases of the liver, heart, pancreas, muscles, blood, and neoplastic diseases. This study aimed to compare enzyme activity to describe dairy cows’ metabolism during early lactation. Based on their general health symptoms, the cows were assigned to one of three groups: acidotic, healthy and ketotic. Samples of milk, blood and rumen fluid were collected at 12 ± 5 days postpartum. Ketotic cows were characterized by the highest malondialdehyde (MDA, 76.098 nM/mL), glutathione reductase (GluRed, 109.852 U/L), superoxide dismutase (SOD, 294.22 U/L) and gamma-glutamyltranspeptidase (GGTP, 71.175 U/L) activity. In comparing ketotic and acidotic cows, MDA, GluRed, SOD and GGTP activity were higher by a factor of almost: 1.85, 1.89, 0.79 and 2.50, respectively. Acidotic cows were characterized by the highest aspartate aminotransferase activity (AspAT, 125.914 U/L). In comparing acidotic and ketotic cows, AspAT activity was higher by a factor of almost 1.90. The use of enzymatic markers could limit the frequency of sampling for laboratory analyses and may result in a faster diagnosis of metabolic disorders. AspAT activity in blood serum seems to be a good indicator of acidosis; GGTP may participate in the pathogenesis of ketosis.
Shared Risk Factors between Dementia and Atherosclerotic Cardiovascular Disease
Authors: Nordestgaard Liv Tybjærg , Christoffersen Mette , Frikke-Schmidt Ruth
Published: August 2022

Alzheimer’s disease is the most common form of dementia, and the prodromal phases of Alzheimer’s disease can last for decades. Vascular dementia is the second most common form of dementia and is distinguished from Alzheimer’s disease by evidence of previous stroke or hemorrhage and current cerebrovascular disease. A compiled group of vascular-related dementias (vascular dementia and unspecified dementia) is often referred to as non-Alzheimer dementia. Recent evidence indicates that preventing dementia by lifestyle interventions early in life with a focus on reducing cardiovascular risk factors is a promising strategy for reducing future risk. Approximately 40% of dementia cases is estimated to be preventable by targeting modifiable, primarily cardiovascular risk factors. The aim of this review is to describe the association between risk factors for atherosclerotic cardiovascular disease and the risk of Alzheimer’s disease and non-Alzheimer dementia by providing an overview of the current evidence and to shed light on possible shared pathogenic pathways between dementia and cardiovascular disease. The included risk factors are body mass index (BMI); plasma triglyceride-, high-density lipoprotein (HDL) cholesterol-, low-density lipoprotein (LDL) cholesterol-, and total cholesterol concentrations; hypertension; diabetes; non-alcoholic fatty liver disease (NAFLD); physical inactivity; smoking; diet; the gut microbiome; and genetics. Furthermore, we aim to disentangle the difference between associations of risk factors in midlife as compared with in late life.
GNB3 c.825C>T (rs5443) Polymorphism and Risk of Acute Cardiovascular Events after Renal Allograft Transplant
Authors: Peitz Tobias , Möhlendick Birte , Siffert Winfried , Heinemann Falko Markus , Kribben Andreas , Eisenberger Ute , Friebus-Kardash Justa
Published: August 2022

The c.825C>T single-nucleotide polymorphism (rs5443) of the guanine nucleotide-binding protein subunit β3 (GNB3) results in increased intracellular signal transduction via G-proteins. The present study investigated the effect of the GNB3 c.825C>T polymorphism on cardiovascular events among renal allograft recipients posttransplant. Our retrospective study involved 436 renal allograft recipients who were followed up for up to 8 years after transplant. The GNB3 c.825C>T polymorphism was detected with restriction fragment length polymorphism (RFLP) polymerase chain reaction (PCR). The GNB3 TT genotype was detected in 43 (10%) of 436 recipients. Death due to an acute cardiovascular event occurred more frequently among recipients with the TT genotype (4 [9%]) than among those with the CC/CT genotypes (7 [2%]; p = 0.003). The rates of myocardial infarction (MI)–free survival (p = 0.003) and acute peripheral artery occlusive disease (PAOD)–free survival (p = 0.004) were significantly lower among T-homozygous patients. A multivariate analysis showed that homozygous GNB3 c.825C>T polymorphism exerted only a mild effect for the occurrence of myocardial infarction (relative risk, 2.2; p = 0.065) or acute PAOD (relative risk, 2.4; p = 0.05) after renal transplant. Our results suggest that the homozygous GNB3 T allele exerts noticeable effects on the risk of MI and acute PAOD only in the presence of additional nonheritable risk factors.
Phospholipid Scramblase 4 (PLSCR4) Regulates Adipocyte Differentiation via PIP3-Mediated AKT Activation
Authors: Barth Lisa A. G. , Nebe Michèle , Kalwa Hermann , Velluva Akhil , Kehr Stephanie , Kolbig Florentien , Prabutzki Patricia , Kiess Wieland , Le Duc Diana , Garten Antje , Kirstein Anna S.
Published: August 2022

Phospholipid scramblase 4 (PLSCR4) is a member of a conserved enzyme family with high relevance for the remodeling of phospholipid distribution in the plasma membrane and the regulation of cellular signaling. While PLSCR1 and -3 are involved in the regulation of adipose-tissue expansion, the role of PLSCR4 is so far unknown. PLSCR4 is significantly downregulated in an adipose-progenitor-cell model of deficiency for phosphatase and tensin homolog (PTEN). PTEN acts as a tumor suppressor and antagonist of the growth and survival signaling phosphoinositide 3-kinase (PI3K)/AKT cascade by dephosphorylating phosphatidylinositol-3,4,5-trisphosphate (PIP3). Patients with PTEN germline deletion frequently develop lipomas. The underlying mechanism for this aberrant adipose-tissue growth is incompletely understood. PLSCR4 is most highly expressed in human adipose tissue, compared with other phospholipid scramblases, suggesting a specific role of PLSCR4 in adipose-tissue biology. In cell and mouse models of lipid accumulation, we found PLSCR4 to be downregulated. We observed increased adipogenesis in PLSCR4-knockdown adipose progenitor cells, while PLSCR4 overexpression attenuated lipid accumulation. PLSCR4 knockdown was associated with increased PIP3 levels and the activation of AKT. Our results indicated that PLSCR4 is a regulator of PI3K/AKT signaling and adipogenesis and may play a role in PTEN-associated adipose-tissue overgrowth and lipoma formation.
Proliferating Lymphatic Endothelial Cells as a Prognostic Marker in Head and Neck Squamous Cell Carcinoma
Authors: Dumitru Cristina Stefania , Ceausu Amalia Raluca , Gaje Nela Pusa , Suciu Cristian Silviu , Raica Marius
Published: August 2022

Podoplanin and Ki-67 are two important markers of cancer progression. The aim of this study is to evaluate double immunostaining for Ki-67 and podoplanin in head and neck squamous cell carcinoma (HNSCC), and to observe the involvement of lymphagiogenesis in tumoral and peritumoral areas, as well as the density of tumor proliferation correlated with histopathological grading. A total of 50 patients with HNSCC were included in this study. We carried out a morphological evaluation of tissue samples, after that, cases were selected for double Ki-67 and podoplanin immunostaining. Podoplanin expression was significantly correlated with histopathological grade (p < 0.05; p = 0.037) and expression of Ki-67 (p < 0.05; p = 0.050). A high expression of podoplanin, as well as of the proliferation factor Ki-67, was observed in histopathological grade G3 and the correlation between these (p < 0.05; p = 0.028), and implication of LMVD and LVI was not significant (LMVD p = 0.577; LVI p = 0.976). This study demonstrated the importance of double immunolabeling in assessing lymphagiogenesis and tumor proliferation in correlation with histopathological grades in HNSCC.
Proteases and Their Potential Role as Biomarkers and Drug Targets in Dry Eye Disease and Ocular Surface Dysfunction
Authors: Ramos-Llorca Alba , Scarpellini Camilla , Augustyns Koen
Published: August 2022

Dry eye disease (DED) is a multifactorial disorder that leads to ocular discomfort, visual disturbance, and tear film instability. DED is accompanied by an increase in tear osmolarity and ocular surface inflammation. The diagnosis and treatment of DED still present significant challenges. Therefore, novel biomarkers and treatments are of great interest. Proteases are present in different tissues on the ocular surface. In a healthy eye, proteases are highly regulated. However, dysregulation occurs in various pathologies, including DED. With this review, we provide an overview of the implications of different families of proteases in the development and severity of DED, along with studies involving protease inhibitors as potential therapeutic tools. Even though further research is needed, this review aims to give suggestions for identifying novel biomarkers and developing new protease inhibitors.
Characterization of a Novel Fe2+ Activated Non-Blue Laccase from Methylobacterium extorquens
Authors: Ainiwaer Abidan , Liang Yue , Ye Xiao , Gao Renjun
Published: August 2022

Herein, a novel laccase gene, Melac13220, was amplified from Methylobacterium extorquens and successfully expressed in Escherichia coli with a molecular weight of approximately 50 kDa. The purified Melac13220 had no absorption peak at 610 nm and remained silent within electron paramagnetic resonance spectra, suggesting that Melac13220 belongs to the non-blue laccase group. Both inductively coupled plasma spectroscopy/optical emission spectrometry (ICP-OES) and isothermal titration calorimetry (ITC) indicated that one molecule of Melac13220 can interact with two iron ions. Furthermore, the optimal temperature of Melac13220 was 65 °C. It also showed a high thermolability, and its half-life at 65 °C was 80 min. Melac13220 showed a very good acid environment tolerance; its optimal pH was 1.5. Cu2+ and Co2+ can slightly increase enzyme activity, whereas Fe2+ could increase Melac13220′s activity five-fold. Differential scanning calorimetry (DSC) indicated that Fe2+ could also stabilize Melac13220. Unlike most laccases, Melac13220 can efficiently decolorize Congo Red and Indigo Carmine dyes even in the absence of a redox mediator. Thus, the non-blue laccase from Methylobacterium extorquens shows potential application value and may be valuable for environmental protection, especially in the degradation of dyes at low pH.
Serum Ceramide Species Are Associated with Liver Cirrhosis and Viral Genotype in Patients with Hepatitis C Infection
Authors: Höring Marcus , Peschel Georg , Grimm Jonathan , Krautbauer Sabrina , Müller Martina , Weigand Kilian , Liebisch Gerhard , Buechler Christa
Published: August 2022

Hepatitis C virus (HCV) infection affects ceramide metabolism, and, here, we have evaluated associations of eight serum ceramide species with viral load, viral genotype, and disease markers in 178 patients with chronic HCV. In this cohort, ceramide d18:1;O2/16:0 was higher in the serum of the 20 diabetic patients compared to the patients without this complication. Moreover, ceramide d18:1;O2/24:0 was negatively correlated with age. Of note, all but ceramide d18:1;O2/16:0 and 26:0 were diminished in the serum of patients with liver cirrhosis and, with the exception of ceramide d18:1;O2/16:0, were negatively correlated with the model for end-stage liver disease (MELD) score. Most of the serum ceramides are carried in low-density lipoprotein (LDL), which rises following effective direct-acting antiviral (DAA) therapy. Ceramide d18:1;O2/24:0 recovered in parallel with LDL, whereas ceramide d18:1;O2/18:0 declined. Genotype-3-infected patients had the lowest ceramide levels, which were comparable to other genotypes after DAA treatment. Notably, ceramide d18:1;O2/23:0 and 24:0 were negatively correlated with the MELD score in patients with liver cirrhosis at the end of DAA therapy. Long-chain (LC) ceramides show adverse effects, whereas very-long-chain (VL) species have protective functions in the liver. The ratio of VL/LC ceramides was higher in non-cirrhosis patients than cirrhosis patients and further increased at the end of therapy in this subgroup. In summary, our study shows that serum ceramide levels are related to liver cirrhosis and viral genotype. Whether the more favorable serum ceramide profile in non-cirrhosis patients, before and after DAA therapy, is of pathophysiological importance needs further investigation.
Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis
Authors: Alves Raquel , Gonçalves Ana Cristina , Jorge Joana , Marques Gilberto , Ribeiro André B. , Tenreiro Rita , Coucelo Margarida , Diamond Joana , Oliveiros Bárbara , Pereira Amélia , Freitas-Tavares Paulo , Almeida António M. , Sarmento-Ribeiro Ana Bela
Published: August 2022

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants—SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters’ SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.
Comorbidity of Novel CRHR2 Gene Variants in Type 2 Diabetes and Depression
Authors: Amin Mutaz , Ott Jurg , Gordon Derek , Wu Rongling , Postolache Teodor T. , Vergare Michael , Gragnoli Claudia
Published: August 2022

The corticotropin-releasing hormone receptor 2 (CRHR2) gene encodes CRHR2, contributing to the hypothalamic–pituitary–adrenal stress response and to hyperglycemia and insulin resistance. CRHR2−/− mice are hypersensitive to stress, and the CRHR2 locus has been linked to type 2 diabetes and depression. While CRHR2 variants confer risk for mood disorders, MDD, and type 2 diabetes, they have not been investigated in familial T2D and MDD. In 212 Italian families with type 2 diabetes and depression, we tested 17 CRHR2 single nucleotide polymorphisms (SNPs), using two-point parametric-linkage and linkage-disequilibrium (i.e., association) analysis (models: dominant-complete-penetrance-D1, dominant-incomplete-penetrance-D2, recessive-complete-penetrance-R1, recessive-incomplete-penetrance-R2). We detected novel linkage/linkage-disequilibrium/association to/with depression (3 SNPs/D1, 2 SNPs/D2, 3 SNPs/R1, 3 SNPs/R2) and type 2 diabetes (3 SNPs/D1, 2 SNPs/D2, 2 SNPs/R1, 1 SNP/R2). All detected risk variants are novel. Two depression-risk variants within one linkage-disequilibrium block replicate each other. Two independent novel SNPs were comorbid while the most significant conferred either depression- or type 2 diabetes-risk. Although the families were primarily ascertained for type 2 diabetes, depression-risk variants showed higher significance than type 2 diabetes-risk variants, implying CRHR2 has a stronger role in depression-risk than type 2 diabetes-risk. In silico analysis predicted variants’ dysfunction. CRHR2 is for the first time linked to/in linkage-disequilibrium/association with depression-type 2 diabetes comorbidity and may underlie the shared genetic pathogenesis via pleiotropy.
Dysregulated Metabolic Pathways in Subjects with Obesity and Metabolic Syndrome
Authors: Mir Fayaz Ahmad , Ullah Ehsan , Mall Raghvendra , Iskandarani Ahmad , Samra Tareq A. , Cyprian Farhan , Parray Aijaz , Alkasem Meis , Abdalhakam Ibrahem , Farooq Faisal , Abou-Samra Abdul-Badi
Published: August 2022

Background: Obesity coexists with variable features of metabolic syndrome, which is associated with dysregulated metabolic pathways. We assessed potential associations between serum metabolites and features of metabolic syndrome in Arabic subjects with obesity. Methods: We analyzed a dataset of 39 subjects with obesity only (OBO, n = 18) age-matched to subjects with obesity and metabolic syndrome (OBM, n = 21). We measured 1069 serum metabolites and correlated them to clinical features. Results: A total of 83 metabolites, mostly lipids, were significantly different (p < 0.05) between the two groups. Among lipids, 22 sphingomyelins were decreased in OBM compared to OBO. Among non-lipids, quinolinate, kynurenine, and tryptophan were also decreased in OBM compared to OBO. Sphingomyelin is negatively correlated with glucose, HbA1C, insulin, and triglycerides but positively correlated with HDL, LDL, and cholesterol. Differentially enriched pathways include lysine degradation, amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, fructose and mannose metabolism, and galactose metabolism. Conclusions: Metabolites and pathways associated with chronic inflammation are differentially expressed in subjects with obesity and metabolic syndrome compared to subjects with obesity but without the clinical features of metabolic syndrome.
Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury
Authors: Hippchen Yanick , Tewary Gargi , Jung Daniela , Schmal Zoé , Meessen Stephan , Palm Jan , Rübe Claudia E.
Published: August 2022

Purpose: Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA-damaging insults, such as ionizing radiation (IR). Using ex vivo irradiated cultured foreskin, H2A.J was analyzed as a biomarker of radiation-induced senescence, potentially initiating the inflammatory cascade of radiation-induced skin injury. Methods: Human foreskin explants were collected from young donors, irradiated ex vivo with 10 Gy, and cultured in air-liquid interphase for up to 72 h. At different time-points after ex vivo IR exposure, the foreskin epidermis was analyzed for proliferation and senescence markers by immunofluorescence and immunohistochemical staining of sectioned tissue. Secretion of cytokines was measured in supernatants by ELISA. Using our mouse model with fractionated in vivo irradiation, H2A.J expression was analyzed in epidermal stem/progenitor cell populations localized in different regions of murine hair follicles (HF). Results: Non-vascularized foreskin explants preserved their tissue homeostasis up to 72 h (even after IR exposure), but already non-irradiated foreskin epithelium expressed high levels of H2A.J in all epidermal layers and secreted high amounts of cytokines. Unexpectedly, no further increase in H2A.J expression and no obvious upregulation of cytokine secretion was observed in the foreskin epidermis after ex vivo IR. Undifferentiated keratinocytes in murine HF regions, by contrast, revealed low H2A.J expression in non-irradiated skin and significant radiation-induced H2A.J upregulations at different time-points after IR exposure. Based on its staining characteristics, we presume that H2A.J may have previously underestimated the importance of the epigenetic regulation of keratinocyte maturation. Conclusions: Cultured foreskin characterized by highly keratinized epithelium and specific immunological features is not an appropriate model for studying H2A.J-associated tissue reactions during radiation-induced dermatitis.
Genome Analyses of Ten New Ape Adenoviruses with Similarity to Human Mastadenovirus C
Authors: Bots Selas T. F. , Kemp Vera , Dautzenberg Iris J. C. , Hoeben Rob C.
Published: August 2022

The adenoviruses (AdVs) isolated from humans are taxonomically grouped in seven different species in the Mastadenovirus genus (HAdV-A through G). AdVs isolated from apes are often included in one of the human AdV species. Here we describe the sequence analyses of ten new AdVs that are related to the HAdV-C species and that were isolated from healthy western lowland gorillas, bonobos, chimpanzees, and orangutans kept in Dutch zoos. We analyzed these viruses and compared their genome sequences to those of human- and ape-derived AdV sequences in the NCBI GenBank database. Our data demonstrated that the ape-derived viruses clustering to HAdV-C are markedly distinct from the human HAdV-C species in the size and nucleotide composition (%GC) of their genome, differ in the amino-acid sequence of AdV proteins, and have longer RGD-loops in their penton-base proteins. The viruses form three well-separated clades (the human, the gorilla, and the combined group of the bonobo and chimpanzee viruses), and we propose that these should each be given species-level ranks. The Ad-lumc005 AdV isolated from orangutans was found to be very similar to the gorilla AdVs, and bootstrap inference provided evidence of recombination between the orangutan AdV and the gorilla AdVs. This suggests that this virus may not be a genuine orangutan AdV but may have been transferred from a gorilla to an orangutan host.
dbRUSP: An Interactive Database to Investigate Inborn Metabolic Differences for Improved Genetic Disease Screening
Authors: Peng Gang , Zhang Yunxuan , Zhao Hongyu , Scharfe Curt
Published: August 2022

The Recommended Uniform Screening Panel (RUSP) contains more than forty metabolic disorders recommended for inclusion in universal newborn screening (NBS). Tandem-mass-spectrometry-based screening of metabolic analytes in dried blood spot samples identifies most affected newborns, along with a number of false positive results. Due to their influence on blood metabolite levels, continuous and categorical covariates such as gestational age, birth weight, age at blood collection, sex, parent-reported ethnicity, and parenteral nutrition status have been shown to reduce the accuracy of screening. Here, we developed a database and web-based tools (dbRUSP) for the analysis of 41 NBS metabolites and six variables for a cohort of 500,539 screen-negative newborns reported by the California NBS program. The interactive database, built using the R shiny package, contains separate modules to study the influence of single variables and joint effects of multiple variables on metabolite levels. Users can input an individual’s variables to obtain metabolite level reference ranges and utilize dbRUSP to select new candidate markers for the detection of metabolic conditions. The open-source format facilitates the development of data mining algorithms that incorporate the influence of covariates on metabolism to increase accuracy in genetic disease screening.
Recent Development of Biomaterials Combined with Mesenchymal Stem Cells as a Strategy in Cartilage Regeneration
Authors: Chen Jishizhan
Published: August 2022

Osteoarthritis leads to the progressive decay of articular cartilage. Due to its intrinsic avascular character, cartilage shows an inadequate capacity for regeneration. Cartilage loss may result in chronic pain, movement disorder and morbidity, which lack effective treatments except for joint replacement for late-stage osteoarthritis. To overcome this challenge, tissue engineering has emerged as a promising method. Scaffolds provide mechanical and biochemical support to stem cells that undergo differentiation and secrete a cartilage-specific matrix, and this strategy has been proven to have positive results. However, there is still a gap between the current strategy and perfection. Researchers are confronted with difficulties such as poor cell survival, insufficient differentiation, hypertrophy and endochondral calcification of neocartilage, and inadequate integration into the host tissue. The current research focuses on modifying scaffold parameters, including composition, stiffness, pore size, surface morphology, hydrophilicity and electric charge. On the other hand, cell regulation is another focus, including predifferentiation, gene editing, dynamic mechanical stimulus, and hypoxia. This review aims to provide a comprehensive discussion of existing challenges, scaffold types and properties, practical methods to improve chondrogenic potential and an outlook on future trends in cartilage bioengineering.
Sensitivity Differences and Biochemical Characteristics of Laodelphax striatellus (Fallén) to Seven Insecticides in Different Areas of Shandong, China
Authors: Xue Yannan , Liu Chang , Liu Dongmei , Ding Wenjuan , Li Zhaoge , Cao Junli , Xia Xiaoming
Published: August 2022

Laodelphax striatellus Fallén is one of the main pests that can severely harm rice, corn, and wheat. Insecticides acting on the nicotinic acetylcholine receptor (nAChR) are the main type of pesticides used for the control of L. striatellus in Shandong Province, a major grain-producing region in China. In this study, the rice seedling dipping method was used to determine the sensitivities of six field L. striatellus populations in Shandong to seven insecticides acting on nAChR. The results showed that all the field populations were sensitive to clothianidin, nitenpyram, and triflumezopyrim, and the Jiaxiang population exhibited the lowest resistance ratio (RR) to imidacloprid, dinotefuran, sulfoxaflor, and thiamethoxam. The Donggang population showed a medium-level resistance to imidacloprid, with the highest RR of 17.48-fold. The Yutai population showed low-level resistance to imidacloprid and thiamethoxam, with RRs of 7.23- and 7.02-fold, respectively. The contents of cytochrome P450 monooxygenase (P450s), carboxylesterase (CarE), and glutathione S-transferase (GST) were the highest in the Donggang population and the lowest in the Jiaxiang population. The P450 gene CYP314A1 and the CarE gene LsCarE12 were highly up-regulated in all populations. No mutations of V62I, R81T, and K265E in the nAChR β1 subunit were found in any of the populations. These results provide valuable information for the strategies of resistance management of L. striatellus in the field.
In Silico Characterization and Gene Expression Analysis of Toll Signaling Pathway-Related Genes in Diaphorina citri
Authors: Rashidi Mahnaz , Killiny Nabil
Published: August 2022

The Asian citrus psyllid, Diaphorina citri is the main vector of citrus greening disease, also known as Huanglongbing (HLB). Currently, mitigating HLB depends on the control of D. citri using insecticides. To design innovative control strategies, we should investigate various biological aspects of D. citri at the molecular level. Herein we explored the Toll signaling system-related proteins in D. citri using in silico analyzes. Additionally, the transcripts of the identified genes were determined in all life stages from eggs to adults. Our findings reveal that D. citri genome possesses Toll signaling pathway-related genes similar to the insect model, Drosophila melanogaster, with slight differences. These genes include cact, TI, Myd88, Dif/DI, pll, tub, and spz encoding Cactus, Toll, Myeloid differentiation factor 88, Dorsal related immunity factor/Dorsal, Pelle, Tube, and Spaetzle, respectively. Unlike D. melanogaster, in D. citri Dorsal, immunity factor and Dorsal are the same protein. In addition, in D. citri, Pelle protein possesses a kinase domain, which is absent in Pelle of D. melanogaster. Gene expression analysis showed the transcript for cact, TI, Myd88, pll, tub, and spz are maximum in adults, suggesting the immunity increases with maturity. Instead, Dif/DI transcripts were maximal in eggs and adults and minimal in nymphal stages, indicating its role in embryonic development. The overall findings will help in designing pioneering control strategies of D. citri based on repressing its immunity by RNAi or CRISPR and combining that with biological control.
Consistency among Office, Home, and Ambulatory Blood Pressure Values in Women with Chronic Hypertension and History of Eclampsia or Preeclampsia
Authors: Wojciechowska Ewa , Sobieraj Piotr , Siński Maciej , Zaborska-Dworak Maria Anna , Gryglas Piotr , Lewandowski Jacek
Published: August 2022

Adequate control of blood pressure (BP) is essential to prevent complications in pregnant women with a history of eclampsia or pre-eclampsia. However, the importance of office (OBPM), home (HBPM), and ambulatory (ABPM) BP measurements for proper control and prognosis in high-risk pregnancy is unknown. The present study aimed to compare BP values obtained during these three different BP measurements in women with a history of eclampsia or pre-eclampsia. This study included 79 pregnant women with chronic hypertension and a documented history of eclampsia or pre-eclampsia in previous pregnancy/pregnancies. Every fifth week of the study, all participants underwent ABPM, HBPM and OBPM. BP values from the 10th, 25th, and 37th weeks of pregnancy were evaluated. Therapy was intended to meet the ABPM treatment goal of <130/80 mmHg. Day, night, and 24 h ABPM systolic BP values were lower than HBPM and OBPM values at each study visit. Night and 24 h ABPM diastolic BP values were lower than HBPM and OBPM values, while day 24 h ABPM values were slightly higher than HBPM and OBPM values. ABPM provides different BP values than OBPM and HBPM. Target BP for ABPM in high-risk pregnancy hypertension should be estimated based on the predictive value of adverse pregnancy outcomes.
Safety and Feasibility of a Discharge within 23 Hours after Colorectal Laparoscopic Surgery
Authors: Popeskou Sotirios Georgios , Christou Niki , Panteleimonitis Sofoklis , Langford Ed , Qureshi Tahseen , Parvaiz Amjad
Published: August 2022

Background: Enhanced or accelerating recovery programs have significantly reduced hospital length stay after elective colorectal interventions. Our work aims at reporting an initial experience with ambulatory laparoscopic colectomy (ALC) to assess the criteria of discharge and outcomes. Methods: Between 2006 and 2016, data regarding patients having benefited from elective laparoscopic colorectal resections in two main centres in the United Kingdom have been analysed. Both benign and malignant pathologies were included. A standardised enhanced recovery program was performed for each patient, except epidural analgesia was replaced with single shot spinal infiltration. Patients were followed up through a telephone call system by a nurse. Short-term clinical outcomes were analysed. Results: A total of 833 patients were included and 51 (6.1%) were discharged within 24 h following surgery. Of these, 4 out of 51 (7.8%) patients came back hospital within 30 days of discharge; 2 (3.9%) required reoperation (Small bowel obstruction and wound abscess drainage). Conclusions: This study highlights that a 24-h discharge following elective laparoscopic colorectal interventions seems safe and feasible in selected patients. Although challenging to achieve, a standardised approach to laparoscopic surgery in combination with strict adherence to an enhanced recovery protocol are the fundamental elements of this path.
Development of an Innovative Soft Piezoresistive Biomaterial Based on the Interconnection of Elastomeric PDMS Networks and Electrically-Conductive PEDOT:PSS Sponges
Authors: Cassa Maria Antonia , Maselli Martina , Zoso Alice , Chiono Valeria , Fracchia Letizia , Ceresa Chiara , Ciardelli Gianluca , Cianchetti Matteo , Carmagnola Irene
Published: August 2022

A deeply interconnected flexible transducer of polydimethylsiloxane (PDMS) and poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) was obtained as a material for the application of soft robotics. Firstly, transducers were developed by crosslinking PEDOT:PSS with 3-glycidyloxypropryl-trimethoxysilane (GPTMS) (1, 2 and 3% v/v) and using freeze-drying to obtain porous sponges. The PEDOT:PSS sponges were morphologically characterized, showing porosities mainly between 200 and 600 µm2; such surface area dimensions tend to decrease with increasing degrees of crosslinking. A stability test confirmed a good endurance for up to 28 days for the higher concentrations of the crosslinker tested. Consecutively, the sponges were electromechanically characterized, showing a repeatable and linear resistance variation by the pressure triggers within the limits of their working range (∆RR0  max = 80% for 1–2% v/v of GPTMS). The sponges containing 1% v/v of GPTMS were intertwined with a silicon elastomer to increase their elasticity and water stability. The flexible transducer obtained with this method exhibited moderately lower sensibility and repeatability than the PEDOT:PSS sponges, but the piezoresistive response remained stable under mechanical compression. Furthermore, the transducer displayed a linear behavior when stressed within the limits of its working range. Therefore, it is still valid for pressure sensing and contact detection applications. Lastly, the flexible transducer was submitted to preliminary biological tests that indicate a potential for safe, in vivo sensing applications.
Automatic Classification of Simulated Breast Tomosynthesis Whole Images for the Presence of Microcalcification Clusters Using Deep CNNs
Authors: Mota Ana M. , Clarkson Matthew J. , Almeida Pedro , Matela Nuno
Published: August 2022

Microcalcification clusters (MCs) are among the most important biomarkers for breast cancer, especially in cases of nonpalpable lesions. The vast majority of deep learning studies on digital breast tomosynthesis (DBT) are focused on detecting and classifying lesions, especially soft-tissue lesions, in small regions of interest previously selected. Only about 25% of the studies are specific to MCs, and all of them are based on the classification of small preselected regions. Classifying the whole image according to the presence or absence of MCs is a difficult task due to the size of MCs and all the information present in an entire image. A completely automatic and direct classification, which receives the entire image, without prior identification of any regions, is crucial for the usefulness of these techniques in a real clinical and screening environment. The main purpose of this work is to implement and evaluate the performance of convolutional neural networks (CNNs) regarding an automatic classification of a complete DBT image for the presence or absence of MCs (without any prior identification of regions). In this work, four popular deep CNNs are trained and compared with a new architecture proposed by us. The main task of these trainings was the classification of DBT cases by absence or presence of MCs. A public database of realistic simulated data was used, and the whole DBT image was taken into account as input. DBT data were considered without and with preprocessing (to study the impact of noise reduction and contrast enhancement methods on the evaluation of MCs with CNNs). The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance. Very promising results were achieved with a maximum AUC of 94.19% for the GoogLeNet. The second-best AUC value was obtained with a new implemented network, CNN-a, with 91.17%. This CNN had the particularity of also being the fastest, thus becoming a very interesting model to be considered in other studies. With this work, encouraging outcomes were achieved in this regard, obtaining similar results to other studies for the detection of larger lesions such as masses. Moreover, given the difficulty of visualizing the MCs, which are often spread over several slices, this work may have an important impact on the clinical analysis of DBT images.
Nonlinear Innovation-Based Maneuverability Prediction for Marine Vehicles Using an Improved Forgetting Mechanism
Authors: Song Chunyu , Zhang Xianku , Zhang Guoqing
Published: August 2022

This paper carries out marine vehicle maneuverability prediction based on nonlinear innovation. An improved Extended Kalman Filter (EKF) algorithm combined with a forgetting factor is developed by virtue of nonlinear innovation for ship maneuverability using full-scale data. Compared with existing algorithms, the proposed algorithm has high prediction consistency, a good prediction effect, and takes a shorter time to reach the agreement. Furthermore, the real-time prediction data are more than 95% consistent with the actual ship navigation. The forgetting factor is introduced to reduce the cumulative impact of historical interference data. Then, the tangent function is used to process errors; this can solve the problem of inaccurate maneuvering prediction of traditional identification algorithms, making up for the limitations of existing methods. The real-time prediction results are compared with the full-scale data, showing that the proposed ship prediction model has significant prediction accuracy and that the algorithm is reliable. This parameter identification method can be used to establish ship maneuvering prediction models.
Fusarium spp. Associated with Dendrobium officinale Dieback Disease in China
Authors: Mirghasempour Seyed Ali , Michailides Themis , Chen Weiliang , Mao Bizeng
Published: August 2022

A rare plant species of the Orchidaceae family, Dendrobium officinale is considered among the top ten Chinese medicinal herbs for its polysaccharide. Since 2021, when the dieback disease of D. officinale was first reported in Yueqing City, Zhejiang Province, China, Fusarium isolates (number = 152) were obtained from 70 plants in commercial greenhouses. The disease incidence ranged from 40% to 60% in the surveyed areas. Multilocus sequence analysis (MLSA) coupled with morphological characterization revealed that the collected isolates belonged to five species (sp.), viz., Fusarium concentricum, F. fujikuroi, F. nirenbergiae, F. curvatum, and F. stilboides, with isolation frequencies of 34.6%, 22.3%, 18.4%, 13.8%, and 10.5%, respectively. Notably, at least two Fusarium species were simultaneously isolated and identified from the infected plants. Finally, the pathogenicity test results demonstrated that such species were responsible for the dieback disease of D. officinale. However, F. concentricum and F. fujikuroi were more invasive compared to the other species in this study. To the best of the authors’ knowledge, this study was the first report of F. concentricum, F. curvatum, F. fujikuroi, F. nirenbergiae, and F. stilboides causing the dieback disease of D. officinale in China and worldwide. This work provides valuable data about the diversity and pathogenicity of Fusarium populations, which will help in formulating effective strategies and policies for better control of the dieback disease.
Functional Neuroimaging in Dissociative Disorders: A Systematic Review
Authors: Modesti Martina Nicole , Rapisarda Ludovica , Capriotti Gabriela , Del Casale Antonio
Published: August 2022

Background: Dissociative disorders encompass loss of integration in essential functions such as memory, consciousness, perception, motor control, and identity. Nevertheless, neuroimaging studies, albeit scarce, have suggested the existence of particular brain activation patterns in patients belonging to this diagnostic category. The aim of this review is to identify the main functional neuroimaging correlates of dissociative disorders. Methods: we searched the PubMed database to identify functional neuroimaging studies conducted on subjects with a diagnosis of a dissociative disorder, following the PRISMA guidelines. In the end, we included 13 studies in this systematic review, conducted on 51 patients with dissociative identity disorder (DID), 28 subjects affected by depersonalization disorder, 24 with dissociative amnesia, and 6 with other or not specified dissociative disorders. Results: Prefrontal cortex dysfunction seems prominent. In addition, changes in the functional neural network of the caudate are related to alterations of identity state and maintenance of an altered mental status in DID. Another role in DID seems to be played by a dysfunction of the anterior cingulate gyrus. Other regions, including parietal, temporal, and insular cortices, and subcortical areas were reported to be dysfunctional in dissociative disorders. Conclusions: Prefrontal dysfunction is frequently reported in dissociative disorders. Functional changes in other cortical and subcortical areas can be correlated with these diagnoses. Further studies are needed to clarify the neurofunctional correlations of each dissociative disorder in affected patients, in order to identify better tailored treatments.
Excessive Sagittal Slope of the Tibia Component during Kinematic Alignment—Safety and Functionality at a Minimum 2-Year Follow-Up
Authors: Bar Ziv Yaron , Livshits Gilad , Lamykin Konstantin , Khatib Salah , Ben Sira Yuval , Rabau Oded , Shohat Noam , Essa Ahmad
Published: August 2022

The aim of this study was to assess the safety and functional outcomes of excessive sagittal alignment in the unrestricted kinematic alignment technique for total knee arthroplasty (TKA). A retrospective, single-center study was conducted between 2018 and 2020, including patients undergoing primary TKA with a minimum 2-year follow-up. EOS imaging conducted before and after surgery was reviewed for overall alignment, and a number of measurements were taken, including sagittal tibial slope and other tibia and femur component positioning. Patients were interviewed and asked to fill out several questionnaires including a visual analog scale, the Oxford Knee Score, and the Knee Injury and Osteoarthritis Outcome Score. Overall, 225 patients (66.7%) had a sagittal tibial slope angle above 5° (excessive) and 112 (33.3%) patients had an angle under 5° (moderate). A significant improvement in pain and function scores was observed in both groups following the surgery (p < 0.001). There were no significant differences between the moderate and excessive groups in the average VAS, OKS or the various subtypes of the KOOS score. However, there was a slight but significant difference in the number of patients achieving MCID in KOOS symptoms. There were no cases of early failure or loosening. Unrestricted KA and the excessive sagittal alignment of the tibial component seem to be reliable and safe in terms of restoring daily function and alleviating pain after a minimum of 2 years following the surgery.