bluuebunny/crossref_metadata_2025 huggingface dataset:
Morbimortality Associated with Liver Cirrhosis in Peru: An Ecological Analysis for the Period of 2004–2016
Authors: Rojas-Acuña Daniela , Polo-Samillan Nilo , Vasquez-Chavesta Angie Z. , Escalante-Arias Crist , Rios-Perez Cristhian J. , Toro-Huamanchumo Carlos J.
Published: July 2022

Liver cirrhosis (LC) is an irreversible, chronic disease and constitutes the last clinical stage of many different liver diseases. The main cause of death is upper gastrointestinal bleeding caused by esophageal variceal rupture. We aim to depict the trend and estimate the morbimortality. For this, we conducted an ecological study and analyzed data from 2004–2016 using the public information provided by the Peruvian Ministry of Health (Ministerio de Salud del Perú, MINSA). Morbidity and mortality were presented according to 5-year groups. Regions were divided according to age quintiles for each studied year, and standardized morbidity and mortality rates were calculated for each natural geographic region; we found that LC-related morbidity per 100,000 people was 52.3 in 2004 and 117.9 in 2016. LC-related mortality had increased from 13.6 deaths per 100,000 people in 2004–2005 to 16.8 deaths per 100,000 people in 2015–2016. Morbidity showed an upward trend in Peru, especially in the departments of Callao, Ica, and Tumbes, whereas mortality showed an upward trend in the departments of Lambayeque, Ica, and Callao.
Changes in Elements and Relationships among Elements in Intervertebral Disc Degeneration
Authors: Staszkiewicz Rafał , Bryś Kamil , Gładysz Dorian , Gralewski Marcin , Garczarek Michał , Gadzieliński Marcin , Wieczorek Jerzy , Marcol Wiesław , Ostenda Aleksander , Grabarek Beniamin Oskar
Published: July 2022

Intervertebral disc degeneration (IVDD) is a complex and progressive process of disc aging. One of the most important causes of changes in the internal environment, leading to IVDD, can be changes in the concentration of individual metal elements. This study aimed to analyze the concentrations of copper, iron, manganese, lead, zinc, sodium, potassium, phosphorus, and calcium in the degenerated intervertebral discs of the lumbosacral spine, compared to healthy intervertebral discs. The study group (S) consisted of 113 Caucasian patients, qualified by a specialist surgeon for IVDD of the lumbosacral spine. The control group (C) consisted of 81 individuals. The biological material was obtained from Caucasian human cadavers during post-mortem examination. The concentrations of individual elements were assessed using inductively coupled plasma–optical emission spectroscopy (ICP-OES). Statistically significant differences in the concentrations of microelements, depending on the degree of pain intensity, were noted for only potassium (p < 0.05). Statistically significant differences in the concentrations of the assessed microelements, depending on the degree of radiological advancement of the lesions, were noted for copper and iron (p < 0.05). In the degenerated intervertebral discs, the strongest relationships were noted between the concentrations of zinc and lead (r = 0.67; p < 0.05), zinc and phosphorus (r = 0.74; p < 0.05), and zinc and calcium (r = 0.77; p < 0.05). It has been indicated that, above all, the concentrations of copper and iron depend on the advancement of radiological changes, according to the Pfirrmann scale; however, no influence on the pain intensity, depending on the concentration of the assessed elements, was found.
Scale of Operation, Financial Support, and Agricultural Green Total Factor Productivity: Evidence from China
Authors: Wang Li , Tang Jinyang , Tang Mengqian , Su Mengying , Guo Lili
Published: July 2022

Large-scale agricultural operations number among the ways to promote the green development of the agricultural sector, which can not only encourage farmers to adopt green innovative technology, reduce the input of chemical fertilizers and pesticides, and achieve environmental protection, but it also enables production with a high efficiency through an economy of scale and an improvement in farmers’ income. Based on the agricultural panel data of 30 provincial administrative regions in China from 2000 to 2019, the panel autoregressive distribution lag model was used to explore the dynamic relationship between a business’ scale, financial support, and agricultural green total factor productivity (AGTFP). The empirical outcomes indicate that there is a significant cross-sectional dependence, cointegration relationship, and long-run relationship between the scale of agricultural operations, financial support for agriculture, and AGTFP. Strengthening the intensity of financial support for agriculture is not conducive to improving AGTFP. On the contrary, increasing the scale of agricultural operations could promote AGTFP. In addition, the panel Granger causality test results indicate that financial support for agriculture has a unidirectional causal relationship with the scale of agricultural operations and AGTFP. The impulse response results demonstrate that reducing part of the financial support for agriculture or increasing the scale of operation can promote AGTFP. These conclusions have a long-term practical significance for agricultural departments and decision-making regarding financial distribution.
Perfluorooctanoic Acid Affects Thyroid Follicles in Common Carp (Cyprinus carpio)
Authors: Manera Maurizio , Castaldelli Giuseppe , Giari Luisa
Published: July 2022

Carp kidney is comprised of nephrons, hemopoietic tissue, and also hormonally-active thyroid follicles. Given this anatomical trait, it has been used to assess the thyroid disrupting potential of perfluorooctanoic acid (PFOA), a widespread and feared per- poly-fluoroalkyl substance and a persistent organic pollutant capable of interfering with the endocrine system in animals and humans. The occurrence and morphology of thyroid follicles in kidneys of carp experimentally exposed to 200 ng L−1 or 2 mg L−1 waterborne PFOA for 56 days were studied. The abundance of thyroid follicles was significantly higher and vesiculation increased in exposed fish as compared to controls. The number of vesiculated follicles/total number of follicles was positively correlated with PFOA blood concentration in fish exposed to the highest dose (2 mg L−1). The structure and ultrastructure of thyroid follicles were affected by PFOA also at the lower, environmentally relevant, concentration (200 ng L−1). Increased cellular projections, enhanced colloid endocytosis, rough endoplasmic reticulum enlargement and fragmentation and cytoplasm vacuolation were the main features displayed by PFOA-exposed carp. These results show that PFOA affects the occurrence and status of follicles and suggest the utility of fish kidney as a multipurpose biomarker organ in environmental pathology research, according to the One Health approach.
Attachment Stories in Middle Childhood: Reliability and Validity of Clinical and Nonclinical Children’s Narratives in a Structured Setting
Authors: Zevalkink Jolien , Ankone Elle
Published: July 2022

Middle childhood is one of the most understudied periods of development and lacks a gold standard for measuring attachment representations. We investigated the reliability and validity of a Dutch version of the Story-Stem Battery coded using the Little Piggy Narrative (LPN) Coding System in a clinical (N = 162) and a nonclinical group (N = 98) of 4–10-year-old children. Their attachment stories were furthermore coded using the coherence scale. Factor analyses showed that the items of the LPN system formed four attachment scales and a separate scale reflecting distress/anxiety, with sufficient internal consistency for the scales and high interrater reliability (n = 20). Furthermore, we studied construct and discriminatory validity. The attachment scores correlated with coherence and child behavioral problems in the expected direction. Results showed age and gender differences, indicating that separate norm groups are necessary. In particular, disorganized attachment, coherence and distress/anxiety differ between clinical and nonclinical children across age and gender. Results for the other three organized attachment scales were more complex. For instance, older boys from the nonclinical group had higher scores on secure attachment than their clinical peers, while girls from the clinical and nonclinical groups did not differ, even though girls in the nonclinical group had higher secure attachment scores than boys. Results are discussed in light of attachment theory and developmental pathways in middle childhood, as well as their clinical implications.
Influence of Rehabilitation Aid with Biofeedback on the Rehabilitation Process during Remote Home-Based Rehabilitation
Authors: Zadrapova Mariana , Mrázková Eva , Janura Miroslav , Strycek Michal , Cerny Martin
Published: July 2022

Ensuring the regularity and correctness of rehabilitation exercises in the home environment is a prerequisite for successful treatment. This clinical study compares balance therapy in the home environment on a conventional balance mat and an instrumented wobble board, with biofeedback supported by a rehabilitation scheme realized as web-based software that controls the course of rehabilitation remotely. The study included 55 patients with knee injuries. The control group consisted of 25 patients (12 females and 13 males, mean age 39 ± 12 years) and the study group of 30 patients (19 females and 11 males, mean age 40 ± 12 years). Treatment effects were compared using the ICS Balance Platform measurement system. Measurements showed significant differences in the change in ICS Balance platform parameters representing the dynamic stability of the patients. The dynamic stability improved more with the instrumented wobble board. The study did not show an influence of different methods of communication with patients during home-based rehabilitation.
Bidirectional Causality between Spreading COVID-19 and Individual Mobilisation with Consumption Motives across Prefectural Borders in Japan
Authors: Kawano Yasuhiro , Matsumoto Ryusuke , Motomura Eishi , Shiroyama Takashi , Okada Motohiro
Published: July 2022

A combination of pharmaceutical and non-pharmaceutical interventions as well as social restrictions has been recommended to prevent the spread of coronavirus disease 2019 (COVID-19). Therefore, social contact surveys play an essential role as the basis for more effective measures. This study attempts to explore the fundamental basis of the expansion of COVID-19. Temporal bidirectional causalities between the numbers of newly confirmed COVID-19 cases (NCCC) and individual mobilisations with consumption motives across prefecture borders in three metropolitan regions in Japan were analysed using vector autoregression models. Mobilisation with consumption in pubs from Kanto to Tokai contributed to the spread of COVID-19 in both regions. Meanwhile, causal mobilisation with consumption motives in Kansai also contributed to the expansion of COVID-19; however, the pattern was dependent on the industrial characteristics of each prefecture in Kansai. Furthermore, the number of pub visitors in Kanto immediately decreased when NCCC increased in Kanto. In contrast, the causal mobilisations for the expansion of COVID-19 in the Tokai and Kansai regions were unaffected by the increasing NCCC. These findings partially proved the validity of the conventional governmental measures to suppress pub visitors across prefectural borders. Nevertheless, the individual causal mobilisations with consumption motives that contributed to the increasing COVID-19 cases are not identical nationwide, and thus, regional characteristics should be considered when devising preventive strategies.
Estimating the Economic Values of Restricted Monoculture Eucalyptus Plantations: A Choice Modeling Approach
Authors: Tesfaw Amare , Senbeta Feyera , Alemu Dawit , Teferi Ermias
Published: July 2022

Today, evaluating ecological wellbeing and ecosystem services is becoming a great concern towards conserving the natural resource base. Healthy functioning ecosystems have fundamental roles for aiding humankind to lead a healthy life and ensure an improved social welfare. Estimating the non-market benefits of ecosystem services can help experts and the public frame policy directions designed for landscape development. The ecosystem of the Eucalyptus hotspot highlands of northwestern Ethiopia, where this study was carried out, provides services that are essential to changes in the life of the society and biodiversity. However, in recent years, the ecosystem is facing a serious threat from intensive monoculture plantations of Eucalyptus. This has resulted in transformation of the cultural landscapes and a loss of biodiversity. The problem in turn calls for designing appropriate ecological improvement programs. Thus, the current study examined the preferences of residents concerning this area and estimated their willingness to pay (WTP) for the proposed ecosystem improvement programs using a Choice Experiment approach. Data were aggregated from 388 residents using a questionnaire survey in January 2020. The survey contained ecological improvement schemes and a hypothetical event by which respondents expressed their willingness to pay a yearly utility fee as a compensation for the improvement programs. Results showed significant differences in resident preferences towards the proposed ecological improvement attributes. The findings also indicated that the socioeconomic backgrounds of residents contributed for the heterogeneity in their WTP for ecological improvement schemes. Accordingly, the marginal willingness to pay of residents was USD 205/person/year for the respective ecological improvement attributes. The findings suggest that policy makers should consider such attribute-based public preferences while planning landscape development and conservation programs. This study can provide vital policy implications and contribute to knowledge as it presents how the non-market valuations of ecosystems help maximize social welfare.
Refined Urban Functional Zone Mapping by Integrating Open-Source Data
Authors: Deng Yue , He Rixing
Published: July 2022

The determination of a reasonable spatial analysis unit is an essential step in urban functional zone (UFZ) division, which significantly affects the results. However, most studies on the division of functional zones are based on excessively large spatial units, such as blocks or traffic analysis zones (TAZs), which easily overlook the detailed characteristics of urban regions and introduce bias to the research conclusion. To address this issue, a refined zone segmentation method, namely, the Voronoi diagram for the polygon method, was proposed to generate refined spatial analysis units. Afterward, the functional topics of the spatial analysis unit were classified by a multiclass support vector machine (SVM) to produce the final UFZ map, where the functional topics of each spatial unit were obtained by coupling latent Dirichlet allocation (LDA). To verify the effectiveness of the proposed method, experiments were conducted in Beijing, China. The results indicated that the proposed segmentation method can generate fine-scale spatial units and provide fine-grained and higher accuracy UFZs (overall accuracy = 84%; kappa = 0.82).
AaZFP3, a Novel CCCH-Type Zinc Finger Protein from Adonis amurensis, Promotes Early Flowering in Arabidopsis by Regulating the Expression of Flowering-Related Genes
Authors: Wang Meiqi , Zhang Haizhen , Dai Shengyue , Feng Shuang , Gong Shufang , Wang Jingang , Zhou Aimin
Published: July 2022

CCCH-type zinc finger proteins (ZFP) are a large family of proteins that play various important roles in plant growth and development; however, the functions of most proteins in this family are uncharacterized. In this study, a CCCH-type ZFP, AaZFP3, was identified in the floral organ of Adonis amurensis. Quantitative real-time PCR (qPCR) analysis revealed that AaZFP3 was widely expressed in the flowers of A.amurensis. Subcellular localization analysis showed that the AaZFP3 protein was mainly localized to the cytoplasm in tobacco and Arabidopsis. Furthermore, the overexpression of AaZFP3 promoted early flowering in Arabidopsis under both normal and relatively low-temperature conditions. RNA-sequencing and qPCR analyses revealed that the expression of multiple key flowering-time genes was altered in transgenic Arabidopsis overexpressing AaZFP3 compared to wild-type. Of these genes, FLOWERING LOCUS T (AtFT) expression was most significantly up-regulated, whereas FLOWERING LOCUS C (AtFLC) was significantly down-regulated. These results suggest that the overexpression of AaZFP3 promotes early flowering in Arabidopsis by affecting the expression of flowering-time genes. Overall, our study indicates that AaZFP3 may be involved in flowering regulation in A.amurensis and may represent an important genetic resource for improving flowering-time control in other ornamental plants or crops.
SaRCC1, a Regulator of Chromosome Condensation 1 (RCC1) Family Protein Gene from Spartina alterniflora, Negatively Regulates Salinity Stress Tolerance in Transgenic Arabidopsis
Authors: Li Wanchang , Wen Jian , Song Yueyi , Yuan Huiyan , Sun Bin , Wang Ren , Xu Sheng
Published: July 2022

A regulator of chromosome condensation 1 (RCC1) family protein has been functionally characterized to be involved in various cellular processes. In this study, one RCC1 gene named SaRCC1 was cloned from the full-length cDNA library of Spartinaalterniflora. The open reading frame (ORF) of SaRCC1 was 1440 bp, and it encoded 479 amino acids with a calculated molecular mass of 51.65 kDa. Multiple amino acid sequence alignments showed that SaRCC1 had high identity with other plant RCC1s, and the phylogenetic analysis indicated that SaRCC1 had a closer affinity to Zea mays RCC1 family protein (ZmRCC1). SaRCC1 gene was induced under salt stress conditions, and its encoded protein was located in peroxisome. In order to further investigate the function of SaRCC1, transgenic Arabidopsis plants ectopically both sense-overexpressing and antisense-overexpressing SaRCC1 were generated. SaRCC1-overexpressing lines exhibited an increased salt and ABA hypersensitivity and reduced resistance to salinity stress. On the other hand, the transcripts of some stress-responsive genes in the SaRCC1 transgenic plants were affected in response to salinity stress. Our results provide evidence for the involvement of SaRCC1, negatively regulating salt stress responses by affecting stress-related gene expression in Arabidopsis.
Roles of microRNAs and Long Non-Coding RNAs Encoded by Parasitic Helminths in Human Carcinogenesis
Authors: Leija-Montoya Ana Gabriela , González-Ramírez Javier , Martínez-Coronilla Gustavo , Mejía-León María Esther , Isiordia-Espinoza Mario , Sánchez-Muñoz Fausto , Chávez-Cortez Elda Georgina , Pitones-Rubio Viviana , Serafín-Higuera Nicolas
Published: July 2022

Infectious agents such as viruses, bacteria, and parasites can lead to cancer development. Infection with the helminthic parasite Schistosoma haematobium can cause cancer of the urinary bladder in humans, and infection with the parasites Clonorchis sinensis and Opisthorchis viverrini can promote cholangiocarcinoma. These three pathogens have been categorized as “group 1: carcinogenic to humans” by the International Agency for Research on Cancer (IARC). Additionally, the parasite Schistosoma japonicum has been associated with liver and colorectal cancer and classified as “group 2B: possibly carcinogenic to humans”. These parasites express regulatory non-coding RNAs as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which modulate genic expression in different biological processes. In this review, we discuss the potential roles of miRNAS and lncRNAs encoded by helminthic parasites that are classified by the IARC as carcinogenic and possibly carcinogenic to humans. The miRNAs of these parasites may be involved in carcinogenesis by modulating the biological functions of the pathogen and the host and by altering microenvironments prone to tumor growth. miRNAs were identified in different host fluids. Additionally, some miRNAs showed direct antitumoral effects. Together, these miRNAs show potential for use in future therapeutic and diagnostic applications. LncRNAs have been less studied in these parasites, and their biological effects in the parasite–host interaction are largely unknown.
Characterization of SARS-CoV-2 Escape Mutants to a Pair of Neutralizing Antibodies Targeting the RBD and the NTD
Authors: Peter Antonia Sophia , Grüner Eva , Socher Eileen , Fraedrich Kirsten , Richel Elie , Mueller-Schmucker Sandra , Cordsmeier Arne , Ensser Armin , Sticht Heinrich , Überla Klaus
Published: July 2022

Mutations in the spike protein of SARS-CoV-2 can lead to evasion from neutralizing antibodies and affect the efficacy of passive and active immunization strategies. Immunization of mice harboring an entire set of human immunoglobulin variable region gene segments allowed to identify nine neutralizing monoclonal antibodies, which either belong to a cluster of clonally related RBD or NTD binding antibodies. To better understand the genetic barrier to emergence of SARS-CoV-2 variants resistant to these antibodies, escape mutants were selected in cell culture to one antibody from each cluster and a combination of the two antibodies. Three independently derived escape mutants to the RBD antibody harbored mutations in the RBD at the position T478 or S477. These mutations impaired the binding of the RBD antibodies to the spike protein and conferred resistance in a pseudotype neutralization assay. Although the binding of the NTD cluster antibodies were not affected by the RBD mutations, the RBD mutations also reduced the neutralization efficacy of the NTD cluster antibodies. The mutations found in the escape variants to the NTD antibody conferred resistance to the NTD, but not to the RBD cluster antibodies. A variant resistant to both antibodies was more difficult to select and only emerged after longer passages and higher inoculation volumes. VOC carrying the same mutations as the ones identified in the escape variants were also resistant to neutralization. This study further underlines the rapid emergence of escape mutants to neutralizing monoclonal antibodies in cell culture and indicates the need for thorough investigation of escape mutations to select the most potent combination of monoclonal antibodies for clinical use.
Nanodiamonds as Possible Tools for Improved Management of Bladder Cancer and Bacterial Cystitis
Authors: Zupančič Daša , Veranič Peter
Published: July 2022

Nanodiamonds (NDs) are a class of carbon nanomaterials with sizes ranging from a few nm to micrometres. Due to their excellent physical, chemical and optical properties, they have recently attracted much attention in biomedicine. In addition, their exceptional biocompatibility and the possibility of precise surface functionalisation offer promising opportunities for biological applications such as cell labelling and imaging, as well as targeted drug delivery. However, using NDs for selective targeting of desired biomolecules within a complex biological system remains challenging. Urinary bladder cancer and bacterial cystitis are major diseases of the bladder with high incidence and poor treatment options. In this review, we present: (i) the synthesis, properties and functionalisation of NDs; (ii) recent advances in the study of various NDs used for better treatment of bladder cancer and (iii) bacterial cystitis; and (iv) the use of NDs in theranostics of these diseases.
DNA Damage Response Regulation by Histone Ubiquitination
Authors: Sekiguchi Miyu , Matsushita Nobuko
Published: July 2022

Cells are constantly exposed to numerous genotoxic stresses that induce DNA damage. DNA double-strand breaks (DSBs) are among the most serious damages and should be systematically repaired to preserve genomic integrity. The efficiency of repair is closely associated with chromatin structure, which is regulated by posttranslational modifications of histones, including ubiquitination. Recent evidence shows crosstalk between histone ubiquitination and DNA damage responses, suggesting an integrated model for the systematic regulation of DNA repair. There are two major pathways for DSB repair, viz., nonhomologous end joining and homologous recombination, and the choice of the pathway is partially controlled by posttranslational modifications of histones, including ubiquitination. Histone ubiquitination changes chromatin structure in the vicinity of DSBs and serves as a platform to select and recruit repair proteins; the removal of these modifications by deubiquitinating enzymes suppresses the recruitment of repair proteins and promotes the convergence of repair reactions. This article provides a comprehensive overview of the DNA damage response regulated by histone ubiquitination in response to DSBs.
Adipose Tissue Dysfunction and Obesity-Related Male Hypogonadism
Authors: Genchi Valentina Annamaria , Rossi Erica , Lauriola Celeste , D’Oria Rossella , Palma Giuseppe , Borrelli Anna , Caccioppoli Cristina , Giorgino Francesco , Cignarelli Angelo
Published: July 2022

Obesity is a chronic illness associated with several metabolic derangements and comorbidities (i.e., insulin resistance, leptin resistance, diabetes, etc.) and often leads to impaired testicular function and male subfertility. Several mechanisms may indeed negatively affect the hypothalamic–pituitary–gonadal health, such as higher testosterone conversion to estradiol by aromatase activity in the adipose tissue, increased ROS production, and the release of several endocrine molecules affecting the hypothalamus–pituitary–testis axis by both direct and indirect mechanisms. In addition, androgen deficiency could further accelerate adipose tissue expansion and therefore exacerbate obesity, which in turn enhances hypogonadism, thus inducing a vicious cycle. Based on these considerations, we propose an overview on the relationship of adipose tissue dysfunction and male hypogonadism, highlighting the main biological pathways involved and the current therapeutic options to counteract this condition.
Immunomodulation of Mesenchymal Stem Cells in Acute Lung Injury: From Preclinical Animal Models to Treatment of Severe COVID-19
Authors: Li Ju-Pi , Wu Kang-Hsi , Chao Wan-Ru , Lee Yi-Ju , Yang Shun-Fa , Chao Yu-Hua
Published: July 2022

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health challenge worldwide. Owing to the emergence of novel viral variants, the risks of reinfections and vaccine breakthrough infections has increased considerably despite a mass of vaccination. The formation of cytokine storm, which subsequently leads to acute respiratory distress syndrome, is the major cause of mortality in patients with COVID-19. Based on results of preclinical animal models and clinical trials of acute lung injury and acute respiratory distress syndrome, the immunomodulatory, tissue repair, and antiviral properties of MSCs highlight their potential to treat COVID-19. This review article summarizes the potential mechanisms and outcomes of MSC therapy in COVID-19, along with the pathogenesis of the SARS-CoV-2 infection. The properties of MSCs and lessons from preclinical animal models of acute lung injury are mentioned ahead. Important issues related to the use of MSCs in COVID-19 are discussed finally.
Reorganization of the Brain Extracellular Matrix in Hippocampal Sclerosis
Authors: Sitaš Barbara , Bobić-Rasonja Mihaela , Mrak Goran , Trnski Sara , Krbot Skorić Magdalena , Orešković Darko , Knezović Vinka , Petelin Gadže Željka , Petanjek Zdravko , Šimić Goran , Kolenc Danijela , Jovanov Milošević Nataša
Published: July 2022

The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE in correlation to clinical findings. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic episodes had a less intense diffuse WFA staining in Cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein, and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons’ excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy.
Mitochondrial RNAs as Potential Biomarkers of Functional Impairment in Diabetic Kidney Disease
Authors: Di Mauro Stefania , Scamporrino Alessandra , Filippello Agnese , Di Marco Maurizio , Di Martino Maria Teresa , Scionti Francesca , Di Pino Antonino , Scicali Roberto , Malaguarnera Roberta , Purrello Francesco , Piro Salvatore
Published: July 2022

Type 2 diabetes and renal damage are strictly linked. The progressive increase in T2D incidence has stimulated the interest in novel biomarkers to improve the diagnostic performance of the commonly utilized markers such as albuminuria and eGFR. Through microarray method, we analyzed the entire transcriptome expressed in 12 serum samples of diabetic patients, six without DKD and six with DKD; the downregulation of the most dysregulated transcripts was validated in a wider cohort of 69 patients by qPCRs. We identified a total of 33 downregulated transcripts. The downregulation of four mitochondrial messenger RNAs (MT-ATP6, MT-ATP8, MT-COX3, MT-ND1) and other two transcripts (seysnoy, skerdo) was validated in patients with eGFR stage G3 versus G2 and G1. The four messenger RNAs correlated with creatinine and eGFR stages, while seysnoy and skerdo were associated with white blood cell values. All transcripts correlated also with Blood Urea Nitrogen. The four mitochondrial messenger RNAs had a high diagnostic performance in G3 versus G2 discrimination, with AUC values above 0.8. The most performant transcript was MT-ATP6, with an AUC of 0.846; sensitivity = 90%, specificity = 76%, p-value = 7.8 × 10−5. This study led to the identification of a specific molecular signature of DKD, proposing the dosage of RNAs, especially mitochondrial RNAs, as noninvasive biomarkers of diabetes complication.
Uncovering Hierarchical Regulation among MYB-bHLH-WD40 Proteins and Manipulating Anthocyanin Pigmentation in Rice
Authors: Sun Xingming , Zhang Zhanying , Li Jinjie , Zhang Hongliang , Peng Youliang , Li Zichao
Published: July 2022

Anthocyanins accumulate in various organs of rice, and the regulatory genes involved in pigmentation of specific organs, such as pericarp, hull, leaf, apiculus, and stigma have been elucidated. However, the corresponding gene for rice culm pigmentation has not been clarified. The well-known MYB-bHLH-WD40 (MBW) complex plays vital role in regulating the anthocyanin biosynthesis pathway in plants. However, the core members of MBW and the hierarchical regulation between these members are not fully elucidated in rice. Here, by map-based cloning, we identified the culm-specific pigmentation gene S1 whose alleles are also known for hull/pericarp pigmentation. We also clarified that one WD40 protein encoding gene, WA1, is indispensable for anthocyanin biosynthesis in rice. In the cascading regulation among MBW members, S1 (bHLH) acts as the master gene by activating the expression of C1 (MYB), and then C1 activates the expression of WA1 (WD40), which is unique in plant species. This enables MBW members to be coordinated in a common way to efficiently regulate anthocyanin biosynthesis genes. Based on these studies, we explored the minimal gene set required for anthocyanin biosynthesis in rice. These findings will help us design new rice varieties with anthocyanin accumulation in specific organs as needed.
An Attention-Refined Light-Weight High-Resolution Network for Macaque Monkey Pose Estimation
Authors: Liu Sicong , Fan Qingcheng , Liu Shanghao , Li Shuqin , Zhao Chunjiang
Published: July 2022

Macaque monkey is a rare substitute which plays an important role for human beings in relation to psychological and spiritual science research. It is essential for these studies to accurately estimate the pose information of macaque monkeys. Many large-scale models have achieved state-of-the-art results in pose macaque estimation. However, it is difficult to deploy when computing resources are limited. Combining the structure of high-resolution network and the design principle of light-weight network, we propose the attention-refined light-weight high-resolution network for macaque monkey pose estimation (HR-MPE). The multi-branch parallel structure is adopted to maintain high-resolution representation throughout the process. Moreover, a novel basic block is designed by a powerful transformer structure and polarized self-attention, where there is a simple structure and fewer parameters. Two attention refined blocks are added at the end of the parallel structure, which are composed of light-weight asymmetric convolutions and a triplet attention with almost no parameter, obtaining richer representation information. An unbiased data processing method is also utilized to obtain an accurate flipping result. The experiment is conducted on a macaque dataset containing more than 13,000 pictures. Our network has reached a 77.0 AP score, surpassing HRFormer with fewer parameters by 1.8 AP.
Deletion of the Serotonin Receptor 7 Gene Changed the Development and Behavior of the Mosquito, Aedes aegypti
Authors: Li Miaozhen , Zhang Lei , Wu Yuchen , Li Yixun , Chen Xin , Chen Jing , Wang Qiuhui , Liao Chenghong , Han Qian
Published: July 2022

Serotonin (5-HT) plays a vital role in many physiological processes in insects, regulating physiological activities such as growth and movement through multiple 5-HT receptors (5-HTRs), which were potential targets for some new insecticides. However, the specific function of individual 5-HTRs in Ae. aegypti is still unclear. In this study, we investigated the function of the 5-HT7A receptor during Ae. aegypti development. 5-HTR7A transcripts were detected at all stages of development by real-time PCR. The results indicated that the gene expression was highest in the limbs (p < 0.01). We also generated 5-HTR7A mutant mosquitoes using CRISPR-mediated gene editing. The mutants had an abnormal phenotype at the larval stage, including an aberrant head-to-chest ratio and decreased motor activity. The mutant pupae developed abnormally, and most died (56.67%) (p < 0.0001). Using external stimuli to larvae and pupae with abnormal phenotypes, we found the mutant G1 and G2 generations responded to external stimuli in a longer time than the wild-type (WT) mosquitoes, and most of the mutants were 2 to 3 s slower than the WTs to respond to external stimuli (p < 0.01). Due to higher mortality, mutant larvae and pupae had fewer numbers than the WTs. The egg hatching rate of mutant G1 and G2 generations was lower than that of the WTs (p < 0.01). The expression level of 5-HTR7A in the mutants decreased by about 65% compared with the control group using real-time PCR (p < 0.05). In all, the 5-HT7A receptor plays an important role in the metamorphosis, development and motor function of Aedes aegypti.
Physiological Effects of Training in Elite German Winter Sport Athletes: Sport Specific Remodeling Determined Using Echocardiographic Data and CPET Performance Parameters
Authors: Zimmermann Paul , Schöffl Isabelle , Schöffl Volker , Zimmermann Lukas , Eckstein Max L. , Moser Othmar , Wüstenfeld Jan
Published: July 2022

Nine ski mountaineering (Ski-Mo), ten Nordic-cross country (NCC), and twelve world elite biathlon (Bia) athletes were evaluated for cardiopulmonary exercise test (CPET) performance and pronounced echocardiographic physiological cardiac remodeling as a primary aim of our descriptive preliminary report. In this context, a multicenter retrospective analysis of two-dimensional echocardiographic data including speckle tracking of the left ventricle (LV-GLS) and CPET performance analysis was performed in 31 elite world winter sports athletes, which were obtained during the annual sports medicine examination between 2020 and 2021. The matched data of the elite winter sports athletes (14 women, 17 male athletes, age: 18–32 years) were compared for different CPET and echocardiographic parameters, anthropometric data, and sport-specific training schedules. Significant differences could be revealed for left atrial (LA) remodeling by LA volume index (LAVI, p = 0.0052), LV-GLS (p = 0.0003), and LV mass index (LV Mass index, p = 0.0078) between the participating disciplines. All participating athletes showed excellent performance data in the CPET analyses, whereby significant differences were revealed for highest maximum respiratory minute volume (VE maximum) and the maximum oxygen pulse level across the participating athletes. This study on sport specific physiological demands in elite winter sport athletes provides new evidence that significant differences in CPET and cardiac remodeling of the left heart can be identified based on the individual athlete’s training schedule, frequency, and physique.
Lymphocyte Population Changes at Two Time Points during the Acute Period of COVID-19 Infection
Authors: Scalia Giulia , Raia Maddalena , Gelzo Monica , Cacciapuoti Sara , Rosa Annunziata De , Pinchera Biagio , Scotto Riccardo , Tripodi Lorella , Mormile Mauro , Fabbrocini Gabriella , Gentile Ivan , Parrella Roberto , Castaldo Giuseppe , Scialò Filippo
Published: July 2022

We previously observed an increase of serum interleukins (IL) and a reduction of most lymphocyte subpopulations in hospitalized COVID-19 patients. Herein, we aimed to evaluate the changes in serum IL-6, IL-10, and IL-17A levels and cytometric lymphocyte profiles in 144 COVID-19 patients at admission and after one week, also in relation to steroid treatment before hospitalization. After one week of hospitalization, we found that: (i) total lymphocytes were increased in all patients; (ii) neutrophils and IL-6 were reduced in mild/moderate patients; (iii) B lymphocytes were increased in severe patients; (iv) T lymphocyte populations increased in mild/moderate patients. In the eight patients that died during hospitalization, total leukocytes increased while T, T helper, T cytotoxic, T regulatory, and NK lymphocytes showed a reducing trend in five of the eight patients. Even if seven days are too few to evaluate the adaptive immunity of patients, we found that the steroid therapy was associated with a reduced COVID-19 inflammation and cytokine activation only in patients with severe disease, while in patients with less severe disease, the steroid therapy seems to have immunosuppressive effects on lymphocyte populations, and this could hamper the antiviral response. A better knowledge of cytokine and lymphocyte alterations in each COVID-19 patient could be useful to plan better treatment with steroids or cytokine targeting.
Effects of Elevated Progesterone Levels on the Day of hCG on the Quality of Oocyte and Embryo
Authors: Woo Jeesoo , Kwon Hwang , Choi Donghee , Park Chan , Kim Jihyang , Shin Jieun , Kim Jeehyun , Kang Youn-Jung , Koo Hwaseon
Published: July 2022

This study is designed to investigate the effects of increased progesterone (P4) levels on the quality of retrieved oocytes and embryos during IVF. This retrospective analysis included 982 all-freezing in vitro fertilization (IVF) cycles (conducted between November 2019 and June 2020 at CHA Fertility Center Bundang, South Korea) in which serum P4 levels were measured on the day of human chorionic gonadotropin (hCG) administration. Our study revealed that the serum P4 levels on the day of hCG administration are strongly associated with the rates of oocyte maturation, displaying a positive correlation in patients with serum P4 < 2.25 ng/mL (p = 0.025). Moreover, patients with serum P4 < 1.25 ng/mL showed relatively low fertilization rates (p = 0.037), and the rates of good embryo retrieval were significantly increased with the serum P4 level < 1.5 ng/mL (p = 0.001). Interestingly, serum P4 level on the day of hCG administration affects the rate of good-quality embryo development, especially at the cleavage stage, and is associated with the status of ovarian responses. Our current study suggests that serum P4 level on the day of hCG administration negatively affects the rates of oocyte maturation, fertilization, and the development of good embryos.
Exercise Limitation after Critical versus Mild COVID-19 Infection: A Metabolic Perspective
Authors: Joris Maurice , Pincemail Joël , Colson Camille , Joris Jean , Calmes Doriane , Cavalier Etienne , Misset Benoit , Guiot Julien , Minguet Grégory , Rousseau Anne-Françoise
Published: July 2022

Exercise limitation in COVID-19 survivors is poorly explained. In this retrospective study, cardiopulmonary exercise testing (CPET) was coupled with an oxidative stress assessment in COVID-19 critically ill survivors (ICU group). Thirty-one patients were included in this group. At rest, their oxygen uptake (VO2) was elevated (8 [5.6–9.7] mL/min/kg). The maximum effort was reached at low values of workload and VO2 (66 [40.9–79.2]% and 74.5 [62.6–102.8]% of the respective predicted values). The ventilatory equivalent for carbon dioxide remained within normal ranges. Their metabolic efficiency was low: 15.2 [12.9–17.8]%. The 50% decrease in VO2 after maximum effort was delayed, at 130 [120–170] s, with a still-high respiratory exchange ratio (1.13 [1–1.2]). The blood myeloperoxidase was elevated (92 [75.5–106.5] ng/mL), and the OSS was altered. The CPET profile of the ICU group was compared with long COVID patients after mid-disease (MLC group) and obese patients (OB group). The MLC patients (n = 23) reached peak workload and predicted VO2 values, but their resting VO2, metabolic efficiency, and recovery profiles were similar to the ICU group to a lesser extent. In the OB group (n = 15), no hypermetabolism at rest was observed. In conclusion, the exercise limitation after a critical COVID-19 bout resulted from an altered metabolic profile in the context of persistent inflammation and oxidative stress. Altered exercise and metabolic profiles were also observed in the MLC group. The contribution of obesity on the physiopathology of exercise limitation after a critical bout of COVID-19 did not seem relevant.
Application of the UNIFAC Model for the Low-Sulfur Residue Marine Fuel Asphaltenes Solubility Calculation
Authors: Povarov Vladimir G. , Efimov Ignaty , Smyshlyaeva Ksenia I. , Rudko Viacheslav A.
Published: July 2022

Since 2020, 0.5% limits on the sulfur content of marine fuels have been in effect worldwide. One way to achieve this value is to mix the residual sulfur and distillate low sulfur components. The main problem with this method is the possibility of sedimentation instability of the compounded residual marine fuel due to sedimentation of asphaltenes. In this paper, the application of the UNIFAC group solution model for calculating the solubility of asphaltenes in hydrocarbons is considered. This model makes it possible to represent organic compounds as a set of functional groups (ACH, AC, CH2, CH3), the qualitative and quantitative composition of which determines the thermodynamic properties of the solution. According to the asphaltene composition, average molecular weight (450–2500 mol/L) and group theories of solutions, a method for predicting the sedimentation stability of compounded residual marine fuels was proposed. The effect of the heat of fusion, temperature of fusion, molecular weight, and group composition on the solubility of asphaltenes in marine fuel has been evaluated. The comparison of the model approach with the data obtained experimentally is carried out. The results obtained make it possible to predict the sedimentation stability of the fuel system depending on the structure and composition of asphaltenes.
Morphological and Phylogenetic Analyses Reveal Four New Species of Gnomoniopsis (Gnomoniaceae, Diaporthales) from China
Authors: Wang Shi , Zhang Zhaoxue , Liu Rongyu , Liu Shubin , Liu Xiaoyong , Zhang Xiuguo
Published: July 2022

The fungal genus Gnomoniopsis (Gnomoniaceae, Diaporthales) has been reported all around the world and isolated from multiple plant hosts. Based on multilocus phylogenies from a combined dataset of internal transcribed spacer (ITS) region, the ribosomal RNA gene cluster, and partial regions of translation elongation factor 1 alpha (tef1) and partial beta-tubulin (tub2), in conjunction with morphological characteristics, we describe and illustrate herein four new species, including Gnomoniopsisdiaoluoshanensis sp. Nov., G. lithocarpi sp. Nov., G. mengyinensis sp. Nov. and G.yunnanensis sp. Nov. Alongside this, their similarity and dissimilarity to morphologically-allied and phylogenetically-related species are annotated and discussed. For facilitating future identification, we update the key to all species currently recognized in this genus.
Initial Results of the International Efforts in Screening New Agents against Candida auris
Authors: Poester Vanice Rodrigues , Munhoz Lívia Silveira , Benelli Jéssica Louise , Melo Aryse Martins , Al-Hatmi Abdullah M. S. , Larwood David J. , Martinez Marife , Stevens David A. , Xavier Melissa Orzechowski
Published: July 2022

Background: Candida auris is an emergent fungal pathogen and a global concern, mostly due to its resistance to many currently available antifungal drugs. Objective: Thus, in response to this challenge, we evaluated the in vitro activity of potential new drugs, diphenyl diselenide (PhSe)2 and nikkomycin Z (nikZ), alone and in association with currently available antifungals (azoles, echinocandins, and polyenes) against Candida auris. Methods: Clinical isolates of C. auris were tested in vitro. (PhSe)2 and nikZ activities were tested alone and in combination with amphotericin B, fluconazole, or the echinocandins, micafungin and caspofungin. Results: (PhSe)2 alone was unable to inhibit C. auris, and antagonism or indifferent effects were observed in the combination of this compound with the antifungals tested. NikZ appeared not active alone either, but frequently acted cooperatively with conventional antifungals. Conclusion: Our data show that (PhSe)2 appears to not have a good potential to be a candidate in the development of new drugs to treat C. auris, but that nikZ is worthy of further study.