bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Fhb1, Fhb2 and Fhb5 on Fusarium Head Blight Resistance and the Development of Promising Lines in Winter Wheat
Authors: Dai Xuran , Huang Yiwen , Xue Xinhui , Yu Shuo , Li Teng , Liu Hongwei , Yang Li , Zhou Yang , Li Hongjie , Zhang Hongjun
Published: December 2022

The development of Fusarium head blight (FHB)-resistant winter wheat cultivars using the gene Fhb1 has been conducted in northern China. Sumai 3, a Chinese FHB-resistant spring wheat cultivar, carries three FHB resistance genes: Fhb1, Fhb2 and Fhb5. To better use these genes for increasing FHB resistance in northern China, it is necessary to elucidate the pyramiding effects of Fhb1, Fhb2 and Fhb5 in winter wheat backgrounds. Eight gene combinations involving Fhb1, Fhb2 and Fhb5 were identified in a double haploid (DH) population, and the effects on FHB resistance were evaluated in six tests. At the single gene level, Fhb1 was more efficient than the other two genes in single-floret inoculation tests, whereas Fhb5 showed better resistance than Fhb1 and Fhb2 under a natural infection test. Pyramiding Fhb1, Fhb2 and Fhb5 showed better FHB resistance than the other gene combinations. Forty-nine DH lines showing consistently better resistance than the moderately susceptible control Huaimai 20 in multiple tests were evaluated for main agronomic traits, and no difference in grain yield was found between the mean values of DH lines and the recipient parents Lunxuan 136 and Lunxuan 6, which are higher than those of recipient parent Zhoumai 16 and the donor parent Sumai 3 (p < 0.05). Based on the phenotypic and genomic composition analyses, five promising DH lines fully combined the FHB resistance of donor Sumai 3 and the elite agronomic traits from the recipient parents. This study elucidates the pyramiding effects of three FHB resistance genes and that the promising DH lines with resistance to FHB can be directly applied in wheat production or as parents in winter wheat breeding programs.
Microbe–Immune–Stress Interactions Impact Behaviour during Postnatal Development
Authors: Francella Cassandra , Green Miranda , Caspani Giorgia , Lai Jonathan K. Y. , Rilett Kelly C. , Foster Jane A.
Published: December 2022

Decades of research have established the role of microbiota–brain communication in behaviour and brain function. Studies have shown that microbiota composition and diversity are influenced by a variety of factors including host genetics, diet, and other environmental exposures, with implications for the immunological and neurobiological development of the host organism. To further understand early-life interactions between environment, genetic factors, the microbiome and the central nervous system, we investigated the impact of postnatal stress in C57Bl/6 wild type and T-cell deficient mice on microbe–brain interactions and behaviour. Mice were exposed to immune challenge with lipopolysaccharide (LPS) at postnatal day (P) 3 and maternal separation at P9 (16 h overnight). Behavioural assessment of growth and development as well as behaviour (righting reflex, ultrasonic vocalizations in response to brief maternal separation, open field, sociability, and grooming) was conducted. Microbiota diversity and composition of fecal samples collected at P24 revealed reduced alpha diversity in T-cell-deficient mice as well as genotype- and stress-related taxa. Notably, integrated analyses of microbiota and behaviour in the context of immunocompromise revealed key behavioural related taxa that may be important to brain development. These findings are important to determining the influence of genetic and environmental factors on gut microbiota and advances our understanding microbiome–brain signaling pathways on neurodevelopment and behaviour.
Cyclic Adenosine Monophosphate: A Central Player in Gamete Development and Fertilization, and Possible Target for Infertility Therapies
Authors: Tesarik Jan , Mendoza-Tesarik Raquel
Published: December 2022

Human infertility, of both male and female origin, is often caused by the deficient response of the testis and the ovary to hormonal stimuli that govern sperm and oocyte development and fertilization. The effects of hormones and other extracellular ligands involved in these events are often mediated by G-protein-coupled receptors that employ cyclic adenosine monophosphate (cAMP) as the principal second messenger transducing the receptor-generated signal to downstream elements. This opinion article summarizes the actions of cAMP in sperm and oocyte development and fertilization, leading to therapeutic actions targeting cAMP metabolism to alleviate human male and female infertility.
An Integration of Linkage Mapping and GWAS Reveals the Key Genes for Ear Shank Length in Maize
Authors: Liang Zhenjuan , Xi Na , Liu Hao , Liu Peng , Xiang Chenchaoyang , Zhang Chen , Zou Chaoying , Cheng Xuyujuan , Yu Hong , Zhang Minyan , Chen Zhong , Pan Guangtang , Yuan Guangsheng , Gao Shibin , Ma Langlang , Shen Yaou
Published: December 2022

Ear shank length (ESL) has significant effects on grain yield and kernel dehydration rate in maize. Herein, linkage mapping and genome-wide association study were combined to reveal the genetic architecture of maize ESL. Sixteen quantitative trait loci (QTL) were identified in the segregation population, among which five were repeatedly detected across multiple environments. Meanwhile, 23 single nucleotide polymorphisms were associated with the ESL in the association panel, of which four were located in the QTL identified by linkage mapping and were designated as the population-common loci. A total of 42 genes residing in the linkage disequilibrium regions of these common variants and 12 of them were responsive to ear shank elongation. Of the 12 genes, five encode leucine-rich repeat receptor-like protein kinases, proline-rich proteins, and cyclin11, respectively, which were previously shown to regulate cell division, expansion, and elongation. Gene-based association analyses revealed that the variant located in Cyclin11 promoter affected the ESL among different lines. Cyclin11 showed the highest expression in the ear shank 15 days after silking among diverse tissues of maize, suggesting its role in modulating ESL. Our study contributes to the understanding of the genetic mechanism underlying maize ESL and genetic modification of maize dehydration rate and kernel yield.
Glutathione Depletion and MicroRNA Dysregulation in Multiple System Atrophy: A Review
Authors: Kinoshita Chisato , Kubota Noriko , Aoyama Koji
Published: December 2022

Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by parkinsonism, cerebellar impairment, and autonomic failure. Although the causes of MSA onset and progression remain uncertain, its pathogenesis may involve oxidative stress via the generation of excess reactive oxygen species and/or destruction of the antioxidant system. One of the most powerful antioxidants is glutathione, which plays essential roles as an antioxidant enzyme cofactor, cysteine-storage molecule, major redox buffer, and neuromodulator, in addition to being a key antioxidant in the central nervous system. Glutathione levels are known to be reduced in neurodegenerative diseases. In addition, genes regulating redox states have been shown to be post-transcriptionally modified by microRNA (miRNA), one of the most important types of non-coding RNA. miRNAs have been reported to be dysregulated in several diseases, including MSA. In this review, we focused on the relation between glutathione deficiency, miRNA dysregulation and oxidative stress and their close relation with MSA pathology.
Mesenchymal Stem Cells and Psoriasis: Systematic Review
Authors: Diotallevi Federico , Di Vincenzo Mariangela , Martina Emanuela , Radi Giulia , Lariccia Vincenzo , Offidani Annamaria , Orciani Monia , Campanati Anna
Published: December 2022

Mesenchymal Stem Cells (MSCs) are multipotent non-hematopoietic stromal cells found in different body tissues such as bone marrow, adipose tissue, periosteum, Wharton’s jelly, umbilical cord, blood, placenta, amniotic fluid, and skin. The biological behavior of MSCs depends mainly on their interaction with the microenvironment in which they are found, whose quality deeply influences the regenerative and immunomodulatory properties of these cells. Several studies confirm the interaction between MSCs and inflammatory microenvironment in the pathogenesis of psoriasis, designating MSCs as an important factor driving psoriasis development. This review aims to describe the most recent evidence on how the inflammatory microenvironment that characterizes psoriasis influences the homeostasis of MSCs and how they can be used to treat the disease.
IL-5 Serum and Appendicular Lavage Fluid Concentrations Correlate with Eosinophilic Infiltration in the Appendicular Wall Supporting a Role for a Hypersensitivity Type I Reaction in Acute Appendicitis
Authors: Carvalho Nuno , Carolino Elisabete , Coelho Hélder , Cóias Ana , Trindade Madalena , Vaz João , Cismasiu Brigitta , Moita Catarina , Moita Luis , Costa Paulo Matos
Published: December 2022

Appendicitis is the most common abdominal surgical emergency, but its aetiology is not fully understood. We and others have proposed that allergic responses play significant roles in its pathophysiology. Eosinophils and Interleukin (IL)-5 are involved in a hypersensitivity type I reaction. Eosinophil infiltration is common in the allergic target organ and is dependent on IL-5. In the presence of an allergic component, it is expected that the eosinophil count and IL-5 local and systemic concentrations become elevated. To address this hypothesis, we designed a prospective study that included 65 patients with acute appendicitis (grouped as acute phlegmonous or gangrenous according to the histological definition) and 18 patients with the clinical diagnosis of acute appendicitis, but with normal histological findings (control group) were enrolled. Eosinophil blood counts and appendicular wall eosinophil infiltration were determined. IL-5 levels in blood and appendicular lavage fluid were evaluated. Appendicular lavage fluid was collected by a new methodology developed and standardized by our group. Appendicular wall eosinophil infiltration was higher in acute phlegmonous appendicitis than in gangrenous appendicitis (p = 0.000). IL-5 blood levels were similar in both pathologic and control groups (p > 0.05). In the appendicular lavage fluid, the higher levels of IL-5 were observed in the phlegmonous appendicitis group (p = 0.056). We found a positive correlation between the appendicular wall eosinophilic infiltration and the IL-5 concentrations, in both the blood and the appendicular lavage fluid, supporting the IL-5 reliance in eosinophil local infiltration. We observed the highest presence of eosinophils at phlegmonous appendicitis walls. In conclusion, the present data are compatible with a hypersensitivity type I allergic reaction in the target organ, the appendix, during the phlegmonous phase of appendicitis.
The Upregulation of Regenerative Activity for Extracellular Vesicles with Melatonin Modulation in Chemically Defined Media
Authors: Kim Jun Yong , Rhim Won-Kyu , Woo Jiwon , Cha Seung-Gyu , Park Chun Gwon , Han Dong Keun
Published: December 2022

Extracellular vesicles (EVs) derived from human mesenchymal stem cells (hMSCs) have been widely known to have therapeutic effects by representing characteristics of the origin cells as an alternative for cell-based therapeutics. Major limitations of EVs for clinical applications include low production yields, unknown effects from serum impurities, and relatively low bioactivities against dose. In this study, we proposed a cell modulation method with melatonin for human umbilical cord MSCs (hUCMSCs) cultured in serum-free chemically defined media (CDM) to eliminate the effects of serum-derived impurities and promote regeneration-related activities. miRNAs highly associated with regeneration were selected and the expression levels of them were comparatively analyzed among various types of EVs depending on culture conditions. The EVs derived from melatonin-stimulated hUCMSCs in CDM (CDM mEVs) showed the highest expression levels of regeneration-related miRNAs, and 7 times more hsa-let-7b-5p, 5.6 times more hsa-miR-23a-3p, and 5.7 times more hsa-miR-100-5p than others, respectively. In addition, the upregulation of various functionalities, such as wound healing, angiogenesis, anti-inflammation, ROS scavenging, and anti-apoptosis, were proven using in vitro assays by simulating the characteristics of EVs with bioinformatics analysis. The present results suggest that the highly regenerative properties of hUCMSC-derived EVs were accomplished with melatonin stimulation in CDM and provided the potential for clinical uses of EVs.
LoSWEET14, a Sugar Transporter in Lily, Is Regulated by Transcription Factor LoABF2 to Participate in the ABA Signaling Pathway and Enhance Tolerance to Multiple Abiotic Stresses in Tobacco
Authors: Zeng Zhen , Lyu Tong , Lyu Yingmin
Published: December 2022

Sugar transport and distribution plays an important role in lily bulb development and resistance to abiotic stresses. In this study, a member of the Sugar Will Eventually be Exported Transporters (SWEET) gene family, LoSWEET14, from Oriental hybrid lily ‘Sorbonne’ was identified. LoSWEET14 encodes a protein of 278 amino acids and is capable of transporting sucrose and some types of hexoses. The transcript level of the LoSWEET14 gene was significantly increased under various stress conditions including drought, cold, salt stresses, and abscisic acid (ABA) treatment. Overexpression of LoSWEET14 in tobacco (Nicotiana tabacum) showed that the transgenic lines had larger leaves, accumulated more soluble sugars, and were more resistant to drought, cold, and salt stresses, while becoming more sensitive to ABA compared with wild-type lines. Promoter analysis revealed that multiple stress-related cis-acting elements were found in the promoter of LoSWEET14. According to the distribution of cis-acting elements, different lengths of 5′-deletion fragments were constructed and the LoSWEET14-pro3(-540 bp) was found to be able to drive GUS gene expression in response to abiotic stresses and ABA treatment. Furthermore, a yeast one hybrid (Y1H) assay proved that the AREB/ABF (ABRE-binding protein/ABRE-binding factor) from lilies (LoABF2) could bind to the promoter of LoSWEET14. These findings indicated that LoSWEET14 is induced by LoABF2 to participate in the ABA signaling pathway to promote soluble sugar accumulation in response to multiple abiotic stresses.
SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells
Authors: Truong Xuan T. , Lee Young-Seung , Nguyen Thuy T. P. , Kim Hyun-Jin , Kim Sung-Hak , Moon Changjong , Kim Don-Kyu , Choi Hueng-Sik , Jeon Tae-Il
Published: December 2022

SMILE (small heterodimer partner-interacting leucine zipper protein) is a transcriptional corepressor that potently regulates various cellular processes such as metabolism and growth in numerous tissues. However, its regulatory role in skin tissue remains uncharacterized. Here, we demonstrated that SMILE expression markedly decreased in human melanoma biopsy specimens and was inversely correlated with that of microphthalmia-associated transcription factor (MITF). During melanogenesis, α-melanocyte-stimulating hormone (α-MSH) induction of MITF was mediated by a decrease in SMILE expression in B16F10 mouse melanoma cells. Mechanistically, SMILE was regulated by α-MSH/cAMP/protein kinase A signaling and suppressed MITF promoter activity via corepressing transcriptional activity of the cAMP response element-binding protein. Moreover, SMILE overexpression significantly reduced α-MSH-induced MITF and melanogenic genes, thereby inhibiting melanin production in melanocytes. Conversely, SMILE inhibition increased the transcription of melanogenic genes and melanin contents. These results indicate that SMILE is a downstream effector of cAMP-mediated signaling and is a critical factor in the regulation of melanogenic transcription; in addition, they suggest a potential role of SMILE as a corepressor in skin pigmentation.
Cuticle Modifications and Over-Expression of the Chitin-Synthase Gene in Diflubenzuron-Resistant Phenotype
Authors: Lucchesi Valentina , Grimaldi Lorenzo , Mastrantonio Valentina , Porretta Daniele , Di Bella Letizia , Ruspandini Tania , Di Salvo Martino Luigi , Vontas John , Bellini Romeo , Negri Agata , Epis Sara , Caccia Silvia , Bandi Claudio , Urbanelli Sandra
Published: December 2022

Insecticide resistance is a major threat challenging the control of harmful insect species. The study of resistant phenotypes is, therefore, pivotal to understand molecular mechanisms underpinning insecticide resistance and plan effective control and resistance management strategies. Here, we further analysed the diflubenzuron (DFB)-resistant phenotype due to the point-mutation I1043M in the chitin-synthase 1 gene (chs1) in the mosquito Culex pipiens. By comparing susceptible and resistant strains of Cx. pipiens through DFB bioassays, molecular analyses and scanning electron microscopy, we showed that the I1043M-resistant mosquitoes have: (i) a striking level of DFB resistance (i.e., resistance ratio: 9006); (ii) a constitutive 11-fold over-expression of the chs1 gene; (iii) enhanced cuticle thickness and cuticular chitin content. Culex pipiens is one of the most important vector species in Europe and the rapid spread of DFB resistance can threaten its control. Our results, by adding new data about the DFB-resistant phenotype, provide important information for the control and management of insecticide resistance.
Molecular Phylogeny and Taxonomy of the Butterfly Subtribe Scolitantidina with Special Focus on the Genera Pseudophilotes, Glaucopsyche and Iolana (Lepidoptera, Lycaenidae)
Authors: Lukhtanov Vladimir A. , Gagarina Anastasia V.
Published: December 2022

The Palearctic blue butterfly genus Pseudophilotes Beuret, 1958 is not homogenous regarding the morphology of its genital structures. For this reason, some of its species have been considered to be representatives of other genera of the subtribe Scolitantidina (subfamily Polyommatinae). Here, we address these taxonomic problems by analyzing the phylogenetic relationships between the genera, subgenera, and species of this subtribe inferred via the analysis of five nuclear and two mitochondrial DNA sequences. We demonstrate that the enigmatic Asian species P. panope (Eversmann, 1851) belongs to the genus Pseudophilotes but not to Praephilotes Forster, 1938 or Palaeophilotes Forster, 1938 and does not represent the independent genus Inderskia Korshunov, 2000, as hypothesized previously. We synonymize P. svetlana Yakovlev, 2003 (syn. nov.) and P. marina Zhdanko, 2004 (syn. nov.) with P. panope. We demonstrate a deep genetic divergence between lineages that were previously considered as subspecies of the single species Iolana iolas (Ochsenheimer, 1816). As a result, we confirm the multispecies concept of the genus Iolana Bethune-Baker, 1914. We show that the Holarctic genus Glaucopsyche can be divided into four subgenera: Glaucopsyche Scudder, 1872 (=Shijimiaeoides Beuret, 1958), Apelles Hemming, 1931, Bajluana Korshunov and Ivonin, 1990, and Phaedrotes Scudder, 1876.
Left Ventricular Diastolic Function in Subjects Conceived through Assisted Reproductive Technologies
Authors: Sciuk Franziska , Vilsmaier Theresa , Kramer Marie , Langer Magdalena , Kolbinger Brenda , Li Pengzhu , Jakob André , Rogenhofer Nina , Dalla-Pozza Robert , Thaler Christian , Haas Nikolaus Alexander , Oberhoffer Felix Sebastian
Published: December 2022

Subjects conceived through assisted reproductive technologies (ART) potentially suffer from impaired left ventricular (LV) function due to premature vascular aging. This study aimed to evaluate whether subtle differences in LV diastolic function can be observed echocardiographically between young ART subjects and their spontaneously conceived peers. The echocardiographic assessment included the measurement of LV dimensions, mitral inflow velocities, and myocardial velocity at early diastole (E’, cm/s) at the LV wall and the interventricular septum (IVS). An average from E/E’LV and E/E’IVS (E/E’AVG) was derived. In total, 66 ART subjects and 83 controls (12.85 ± 5.80 years vs. 13.25 ± 5.89 years, p = 0.677) were included. The ART subjects demonstrated a significantly lower E’LV (19.29 ± 3.29 cm/s vs. 20.67 ± 3.78 cm/s, p = 0.020) compared to their spontaneously conceived peers. Study participants of ≥ 10 years of age displayed a significantly higher E/E’AVG (6.50 ± 0.97 vs. 6.05 ± 0.99, p = 0.035) within the ART cohort. The results of this study demonstrate a significantly lower LV diastolic function in the ART subjects. However, no significant changes in LV diastolic function were observed between the two groups when the results were adjusted for age, birth weight percentile, and gestational age. Those ART subjects born preterm might have an elevated risk of developing LV diastolic alterations and could therefore profit from close echocardiographic monitoring.
BDNF and proBDNF Serum Protein Levels in Obstructive Sleep Apnea Patients and Their Involvement in Insomnia and Depression Symptoms
Authors: Gabryelska Agata , Turkiewicz Szymon , Ditmer Marta , Karuga Filip Franciszek , Strzelecki Dominik , Białasiewicz Piotr , Sochal Marcin
Published: December 2022

Introduction: Obstructive sleep apnea (OSA) is a disorder that, apart from somatic sequelae, increases the risk of developing psychiatric conditions. Brain-derived neurotrophic factor (BDNF) signaling pathway is involved in the pathophysiology of depression and insomnia. Therefore, the study aimed to investigate differences in concentrations of BDNF and proBDNF in patients with OSA and healthy individuals, to evaluate diurnal changes of these proteins, and to assess the correlations with psychiatric symptoms. Methods: Sixty individuals following polysomnography (PSG) were divided into two groups based on the apnea-hypopnea index (AHI): OSA patients (AHI ≥ 30; n = 30) and control group (AHI < 5; n = 30). Participants filled out questionnaires: Beck Depression Inventory (BDI), Athens Insomnia Scale (AIS), and Pittsburgh Sleep Quality Index (PSQI). Peripheral blood was collected before and after PSG. Protein concentrations were measured using ELISA. OSA group was divided into subgroups: AIS (−)/AIS (+) (AIS > 5), PSQI (−)/PSQI (+) (PSQI > 5), and BDI (−)/BDI (+) (BDI > 19). Results: No differences in BDNF and proBDNF protein levels were observed between OSA and the control groups. However, BDNF and proBDNF evening protein concentrations were higher in the AIS (+) and PSQI (+) groups (p < 0.001 for all). The BDI (+) group was characterized by lower morning levels of both proteins (p = 0.047 and p = 0.003, respectively). Conclusions: BDNF signaling pathway might be involved in the pathophysiology of depression and insomnia in patients with OSA. BDNF and proBDNF protein levels might be useful in defining OSA phenotypes.
Towards the Validation of Executive Functioning Assessments: A Clinical Study
Authors: Faber Daniel , Grosse Gerrit M. , Klietz Martin , Petri Susanne , Schwenkenbecher Philipp , Sühs Kurt-Wolfram , Kopp Bruno
Published: December 2022

Neuropsychological assessment needs a more profound grounding in psychometric theory. Specifically, psychometrically reliable and valid tools are required, both in patient care and in scientific research. The present study examined convergent and discriminant validity of some of the most popular indicators of executive functioning (EF). A sample of 96 neurological inpatients (aged 18–68 years) completed a battery of standardized cognitive tests (Raven’s matrices, vocabulary test, Wisconsin Card Sorting Test, verbal fluency test, figural fluency test). Convergent validity of indicators of intelligence (Raven’s matrices, vocabulary test) and of indicators of EF (Wisconsin Card Sorting Test, verbal fluency test, figural fluency) were calculated. Discriminant validity of indicators of EF against indicators of intelligence was also calculated. Convergent validity of indicators of intelligence (Raven’s matrices, vocabulary test) was good (rxtyt = 0.727; R2 = 0.53). Convergent validity of fluency indicators of EF against executive cognition as indicated by performance on the Wisconsin Card Sorting Test was poor (0.087 ≤ rxtyt ≤ 0.304; 0.008 ≤ R2 ≤ 0.092). Discriminant validity of indicators of EF against indicators of intelligence was good (0.106 ≤ rxtyt ≤ 0.548; 0.011 ≤ R2 ≤ 0.300). Our conclusions from these data are clear-cut: apparently dissimilar indicators of intelligence converge on general intellectual ability. Apparently dissimilar indicators of EF (mental fluency, executive cognition) do not converge on general executive ability. Executive abilities, although non-unitary, can be reasonably well distinguished from intellectual ability. The present data contribute to the hitherto meager evidence base regarding the validity of popular indicators of EF.
The Predictive Power of the 14–51 Ng/L High Sensitive Troponin T (hsTnT) Values for Predicting Cardiac Revascularization in a Clinical Setting
Authors: De Jongh Frank W. , Pouwels Sjaak , De Jongh Marjolein C. , Dubois Eric A. , van Schaik Ron H. N.
Published: December 2022

Background: high sensitive Troponin T (hsTnT) values between 14–50 ng/L represent a challenge in diagnosing acute coronary syndrome (ACS) at the Emergency Department (ED). The European Society for Cardiology (ESC) recommends a second hsTnT measurement 3 h later to distinguish between ACS and other causes depending on the Δ hsTnT. Our study aims to evaluate the predictive power this approach in a clinical setting by following patients presenting at the ED with hsTnT values 14–51 ng/L. Materials and methods: patients presenting with chest pain or dyspnea and a hsTnT value between 14 and 50 ng/L at the Erasmus MC ED in 2012–2013 were included and retrospectively monitored for 90 days after initial presentation for the occurrence of a cardiac revascularization. Patient records were reviewed according to the standing protocol, which depended on the Δ hsTnT. The “event-group” consists of patients receiving cardiac revascularization within 90 days after the ED visit, whereas the “no event-group” consisted of patients without revascularization. Results: a total of 889 patients patient records were reviewed. After excluding out-of-hospital-cardia-arrests (60), non-cardiological chest pain (373) and incomplete follow-up (100), 356 patients remained for final analysis. In 207 patients, a second hsTnT was actually performed (58%). From these 207 patients, 68 (33%) had a Δ hsTnT ≥7 ng/L. In these patients, 37 (54%) experienced an event within 90 days. In the 139 patients with a Δ hsTnT < 7 ng/L, 23 (17%) presented with an event within 90 days. Conclusion: our study demonstrated a sensitivity of 62%, a specificity of 79%, a positive predicted value (PPV) of 54% and a negative predictive value (NPV) of 83% for using a 3-h Δ hsTnT ≥7 ng/L cut-off, related to risk of an event in 90 days following ED presentation.
The Association of uPA, uPAR, and suPAR System with Inflammation and Joint Damage in Rheumatoid Arthritis: suPAR as a Biomarker in the Light of a Personalized Medicine Perspective
Authors: Benucci Maurizio , Damiani Arianna , Russo Edda , Guiducci Serena , Li Gobbi Francesca , Fusi Paola , Grossi Valentina , Amedei Amedeo , Manfredi Mariangela , Infantino Maria
Published: December 2022

Background: In recent years, the involvement of the soluble urokinase Plasminogen Activator Receptor (suPAR) in the pathophysiological modulation of Rheumatoid Arthritis (RA) has been documented, resulting in the activation of several intracellular inflammatory pathways. Methods: We investigated the correlation of urokinase Plasminogen Activator (uPA)/urokinase Plasminogen Activator Receptor (uPAR) expression and suPAR with inflammation and joint damage in RA, evaluating their potential role in a precision medicine context. Results: Currently, suPAR has been shown to be a potential biomarker for the monitoring of Systemic Chronic Inflammation (SCI) and COVID-19. However, the effects due to suPAR interaction in immune cells are also involved in both RA onset and progression. To date, the literature data on suPAR in RA endorse its potential application as a biomarker of inflammation and subsequent joint damage. Conclusion: Available evidence about suPAR utility in the RA field is promising, and future research should further investigate its use in clinical practice, resulting in a big step forward for precision medicine. As it is elevated in different types of inflammation, suPAR could potentially work as an adjunctive tool for the screening of RA patients. In addition, a suPAR system has been shown to be involved in RA pathogenesis, so new data about the therapeutic response to Jak inhibitors can represent a possible way to develop further studies.
Association of TYR SNP rs1042602 with Melanoma Risk and Prognosis
Authors: Sevilla Arrate , Sánchez-Diez Ana , Cobo Sofía , Izagirre Neskuts , Martinez-Cadenas Conrado , Martí Rosa M. , Puértolas Teresa , de Unamuno Blanca , Bañuls José , Izu Rosa , Gardeazabal Jesús , Asumendi Aintzane , Boyano María D. , Alonso Santos
Published: December 2022

Cutaneous melanoma is the most aggressive of skin tumors. In order to discover new biomarkers that could help us improve prognostic prediction in melanoma patients, we have searched for germline DNA variants associated with melanoma progression. Thus, after exome sequencing of a set of melanoma patients and healthy control individuals, we identified rs1042602, an SNP within TYR, as a good candidate. After genotyping rs1042602 in 1025 patients and 773 healthy donors, we found that the rs1042602-A allele was significantly associated with susceptibility to melanoma (CATT test: p = 0.0035). Interestingly, we also observed significant differences between patients with good and bad prognosis (5 years of follow-up) (n = 664) (CATT test for all samples p = 0.0384 and for men alone p = 0.0054). Disease-free-survival (DFS) analyses also showed that patients with the A allele had shorter DFS periods. In men, the association remained significant even in a multivariate Cox Proportional-hazards model, which was adjusted for age at diagnosis, Breslow thickness, ulceration and melanoma subtype (HR 0.4; 95% confidence interval (CI) 0.20–0.83; p = 0.0139). Based on our results, we propose that rs1042602-A is a risk allele for melanoma, which also seems to be responsible for a poorer prognosis of the disease, particularly in men.
Anti-Metastatic Activity of Tagitinin C from Tithonia diversifolia in a Xenograft Mouse Model of Hepatocellular Carcinoma
Authors: Lin Chuan-Yi , Liao May-Hua , Yang Chi-Yu , Chang Chao-Kai , Hsu Shih-Mei , Juang Chi-Long , Wen Hsiao-Chuan
Published: December 2022

Sesquiterpenoid tagitinin C, present in Tithonia diversifolia leaves, has been known to have anti-hepatoma properties. Therefore, we investigated the anti-metastatic potential of tagitinin C in xenograft models of hepatocellular carcinoma (HCC). We isolated tagitinin C from a methanolic extract of the leaves of T. diversifolia. HepG-2 and Huh 7 hepatoma cells were treated with tagitinin C, and cell viability, migration, and matrix metalloproteinase (MPP) activity were assessed using the 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide assay, scratch migration assay, and MMP activity assay, respectively. We used magnetic resonance spectroscopy to determine the tumorigenicity of xenografts inoculated with Hep-G2 and Huh 7 cells. Tagitinin C was cytotoxic against Hep-G2 and Huh 7 cells, with IC50 values of 2.0 ± 0.1 µg/mL and 1.2 ± 0.1 µg/mL, respectively, and it showed an anti-metastatic effect in vitro. Additionally, MRS assays revealed that tagitinin C (15 g/mouse/day) reduced the tumorigenicity of Hep-G2 and Huh 7 cell xenografts. Tagitinin C demonstrated significant antitumor and anti-metastatic activity in the two human hepatoma cell lines. Tagitinin C might be used as an alternative or auxiliary therapy for the treatment of HCC, and its effect should be further investigated in clinical settings.
2-Furanylmethyl N-(2-propenyl)carbamate
Authors: Baker Noah C. , Mock Abby L. , Nguyen Ivy B. , Patel Savan D. , Forbes David C.
Published: December 2022

The overexpression of protein phosphatase 5 (PP5) has been correlated to tumor cell reproduction, making it a candidate for small molecule drug therapy. Prior work has focused on functionalized and decorated scaffolds that maximize contacts within and around the active site. The assembly and testing of cantharidin derivatives decorated with functionalized attachments has been our focus in order to affect the optimal binding of PP5. Condensation of 2-hydroxymethylfuran with allyl isocyanate meets the metrics of the rapid installment of functionality, as part of the core scaffold. Once condensed, cycloaddition followed by hydrogenation produces the desired derivative of norcantharidin in three synthetic steps.
6,6′-((Ethane-1,2-diylbis(azanediyl))bis(methylene))bis(2,4-bis(2-phenylpropan-2-yl)phenolate)zirconium(IV) Dichlorido
Authors: Hipólito Joana , Martins Ana M. , Alves Luis G.
Published: December 2022

The salan zirconium complex of formula [(H2N2O2)ZrCl2] (H2N2O2H2 = HOPh’CH2NH(CH2)2NHCH2Ph’OH, where Ph’ = 2,4-(CMe2Ph)C6H2) was synthesized and fully characterized by NMR and single-crystal X-ray diffraction. The solid-state molecular structure of [(H2N2O2)ZrCl2] shows distorted octahedral geometry around the zirconium center with the salan ligand adopting a β-Λ-cis conformation.
Energetic and Protective Coating via Chemical and Physical Synergism for High Water-Reactive Aluminum Powder
Authors: Zhang Lichen , Wang Shuo , Zhu Lixiang , Li Xiaodong , Su Xing , Zou Meishuai
Published: December 2022

Aluminum powder plays important role in the field of energetic materials. However, it is often vulnerable to oxygen and water due to the high reactivity of aluminum, and it is challenging to build up uniform and passivated coating via existing means. In this work, (Heptadecafluoro-1,1,2,2-tetradecyl) trimethoxysilane (FAS-17) and glycidyl azide polymer (GAP) were used to coat the surface of high water-reactive aluminum powder (w-Al) to form inactivated w-Al@FAS-17@GAP energetic materials, via the synergy of chemical bonding and physical attraction. Thermal reaction tests showed that the exothermic enthalpy of w-Al@FAS-17@GAP was 5.26 times that of w-Al. Ignition tests showed that w-Al@FAS-17@GAP burnt violently at 760 °C, while w-Al could not be ignited even at 950 °C. In addition, the combined coating of FAS-17 and GAP could effectively improve the hydrophobicity and long-term stability of w-Al, which helped to overcome the poor compatibility of w-Al with explosive components. Our work not only displayed an effective routine to synthesize O2/H2O proof Al energetic materials, but also pointed out a synergistically chemical and physical strategy for constructing intact high-performance surfaces.
A Novel Deep Learning-Based Pose Estimation Method for Robotic Grasping of Axisymmetric Bodies in Industrial Stacked Scenarios
Authors: Li Yaowei , Guo Fei , Zhang Miaotian , Suo Shuangfu , An Qi , Li Jinlin , Wang Yang
Published: December 2022

A vision-based intelligent robotic grasping system is essential for realizing unmanned operations in industrial manufacturing, and pose estimation plays an import role in this system. In this study, deep learning was used to obtain the 6D pose of an axisymmetric body which was optimal for robotic grasping in industrial stacked scenarios. We propose a method to obtain the 6D pose of an axisymmetric body by detecting the pre-defined keypoints on the side surface. To realize this method and solve other challenges in industrial stacked scenarios, we propose a multitask real-time convolutional neural network (CNN), named Key-Yolact, which involves object detection, instance segmentation, and multiobject 2D keypoint detection. A small CNN as a decision-making subsystem was designed to score multiple predictions of Key-Yolact, and the body with the highest score is considered the best for grasping. Experiments on a self-built stacked dataset showed that Key-Yolact has a practical tradeoff between inference speed and precision. The inference speed of Key-Yolact is higher by 10 FPS, whereas its precision is decreased by only 7% when compared with the classical multitask Keypoint R-CNN. Robotic grasping experiments showed that the proposed design is effective and can be directly applied to industrial scenarios.
Estimation of Critical Collapse Solutions to Black Holes with Nonlinear Statistical Models
Authors: Hatefi Ehsan , Hatefi Armin
Published: December 2022

The self-similar gravitational collapse solutions to the Einstein-axion–dilaton system have already been discovered. Those solutions become invariants after combining the spacetime dilation with the transformations of internal SL(2, R). We apply nonlinear statistical models to estimate the functions that appear in the physics of Black Holes of the axion–dilaton system in four dimensions. These statistical models include parametric polynomial regression, nonparametric kernel regression and semi-parametric local polynomial regression models. Through various numerical studies, we reached accurate numerical and closed-form continuously differentiable estimates for the functions appearing in the metric and equations of motion.
Tan-Type BLF-Based Attitude Tracking Control Design for Rigid Spacecraft with Arbitrary Disturbances
Authors: Xuan-Mung Nguyen , Golestani Mehdi , Hong Sung-Kyung
Published: December 2022

This study deals with the problem of disturbances in observer-based attitude tracking control for spacecraft in the presence of inertia-matrix uncertainty and arbitrary disturbance. Following the backstepping control, a tan-type barrier Lyapunov function (BLF)-based attitude tracking control method with prescribed settling time and performance is systematically developed. The proposed control framework possesses three advantages over the existing attitude controllers. Firstly, the singularity problem associated with the use of fractional power in fixed-time control is effectively resolved without employing any command filter or piece-wise continuous function. Secondly, inspired by the concept of the tan-type BLF approach, any desired performance for the attitude tracking error is satisfied. Lastly, the total disturbance, including the system’s uncertainty, external disturbances, and time-derivative of the virtual control, is precisely reconstructed during a predefined time, even if the initial estimation error tends to infinity. Moreover, this time is determined as a tunable gain in the observer. The numerical simulations confirm the superior performance of the proposed control strategy in comparison with the existing pertinent works.
Estimation and Hypothesis Test for Mean Curve with Functional Data by Reproducing Kernel Hilbert Space Methods, with Applications in Biostatistics
Authors: Xiong Ming , Yuan Ao , Fang Hong-Bin , Wu Colin O. , Tan Ming T.
Published: December 2022

Functional data analysis has important applications in biomedical, health studies and other areas. In this paper, we develop a general framework for a mean curve estimation for functional data using a reproducing kernel Hilbert space (RKHS) and derive its asymptotic distribution theory. We also propose two statistics for testing the equality of mean curves from two populations and a mean curve belonging to some subspace, respectively. Simulation studies are conducted to evaluate the performance of the proposed method and are compared with the major existing methods, which shows that the proposed method has a better performance than the existing ones. The method is then illustrated with an analysis of the growth data from the National Growth and Health Study (NGHS) project sponsored by the NIH.
Model Selection for High Dimensional Nonparametric Additive Models via Ridge Estimation
Authors: Wang Haofeng , Jin Hongxia , Jiang Xuejun , Li Jingzhi
Published: December 2022

In ultrahigh dimensional data analysis, to keep computational performance well and good statistical properties still working, nonparametric additive models face increasing challenges. To overcome them, we introduce a methodology of model selection for high dimensional nonparametric additive models. Our approach is to propose a novel group screening procedure via nonparametric smoothing ridge estimation (GRIE) to find the importance of each covariate. It is then combined with the sure screening property of GRIE and the model selection property of extended Bayesian information criteria (EBIC) to select the suitable sub-models in nonparametric additive models. Theoretically, we establish the strong consistency of model selection for the proposed method. Extensive simulations and two real datasets illustrate the outstanding performance of the GRIE-EBIC method.
Flexible Parametric Accelerated Hazard Model: Simulation and Application to Censored Lifetime Data with Crossing Survival Curves
Authors: Muse Abdisalam Hassan , Chesneau Christophe , Ngesa Oscar , Mwalili Samuel
Published: December 2022

This study aims to propose a flexible, fully parametric hazard-based regression model for censored time-to-event data with crossing survival curves. We call it the accelerated hazard (AH) model. The AH model can be written with or without a baseline distribution for lifetimes. The former assumption results in parametric regression models, whereas the latter results in semi-parametric regression models, which are by far the most commonly used in time-to-event analysis. However, under certain conditions, a parametric hazard-based regression model may produce more efficient estimates than a semi-parametric model. The parametric AH model, on the other hand, is inappropriate when the baseline distribution is exponential because it is constant over time; similarly, when the baseline distribution is the Weibull distribution, the AH model coincides with the accelerated failure time (AFT) and proportional hazard (PH) models. The use of a versatile parametric baseline distribution (generalized log-logistic distribution) for modeling the baseline hazard rate function is investigated. For the parameters of the proposed AH model, the classical (via maximum likelihood estimation) and Bayesian approaches using noninformative priors are discussed. A comprehensive simulation study was conducted to assess the performance of the proposed model’s estimators. A real-life right-censored gastric cancer dataset with crossover survival curves is used to demonstrate the tractability and utility of the proposed fully parametric AH model. The study concluded that the parametric AH model is effective and could be useful for assessing a variety of survival data types with crossover survival curves.
Intact Fish Skin Graft vs. Standard of Care in Patients with Neuroischaemic Diabetic Foot Ulcers (KereFish Study): An International, Multicentre, Double-Blind, Randomised, Controlled Trial Study Design and Rationale
Authors: Dardari Dured , Potier Louis , Sultan Ariane , Francois Maude , M’Bemba Jocelyne , Bouillet Benjamin , Chaillous Lucy , Kessler Laurence , Carlier Aurelie , Jalek Abdulkader , Sbaa Ayoub , Orlando Laurent , Bobony Elise , Detournay Bruno , Kjartansson Hilmar , Bjorg Arsaelsdottir Ragna , Baldursson Baldur Tumi , Charpentier Guillaume
Published: December 2022

Background: Cell and/or tissue-based wound care products have slowly advanced in the treatment of non-healing ulcers, however, few studies have evaluated the effectiveness of these devices in the management of severe diabetic foot ulcers. Method: This study (KereFish) is part of a multi-national, multi-centre, randomised, controlled clinical investigation (Odin) with patients suffering from deep diabetic wounds, allowing peripheral artery disease as evaluated by an ankle brachial index equal or higher than 0.6. The study has parallel treatment groups: Group 1 treatment with Kerecis® Omega3 Wound™ versus Group 2 treatment with standard of care. The primary objective is to test the hypothesis that a larger number of severe diabetic ulcers and amputation wounds, including those with moderate arterial disease, will heal in 16 weeks when treated with Kerecis® Omega3 Wound™ than with standard of care. Conclusion: This study has received the ethics committee approval of each participating country. Inclusion of participants began in March 2020 and ended in July 2022. The first results will be presented in March 2023. The study is registered in ClinicalTrials.gov as Identifier: NCT04537520.
Comparative Study of 4-Aminophenol Removal from Aqueous Solutions by Emulsion Liquid Membranes Using Acid and Basic Type 1 Facilitations: Optimisation and Kinetics
Authors: León Gerardo , Otón Juliana , Hidalgo Asunción María , Saavedra María Isabel , Miguel Beatriz
Published: December 2022

The molecule 4-aminophenol (4AP) is recognised as a serious environmental pollutant that enters the environment during the manufacture and processing of a variety of industrial processes and through the degradation of some pharmaceutical products. This paper describes a comparative study of 4AP removal from aqueous solutions by emulsion liquid membranes using acid and basic type 1-facilitated transports. The results are explained by analysing the stripping process through both the different relative acid/basic strength of the hydroxyl and amine groups of the 4AP molecule and the hydrogen-bonding capacity with water of the ionisation products generated by the reaction of 4AP with HCl or NaOH. To optimize the 4AP removal process, the influence of different experimental conditions (stripping agent concentration in the product phase, surfactant concentration in the membrane phase, stirring rate, feed phase/emulsion phase volume ratio, product phase/membrane phase volume ratio and emulsification rate and time) were studied. The kinetics of the removal process has been analysed by fitting the experimental results to first order, second order and the Behnajady and Avrami models. The Behnajady model presents an excellent fit, allowing to calculate both the initial removal rate and the maximal removal conversion. Optimal conditions of the removal process obtained through these parameters are in full agreement with those obtained from the experimental study.
Study of Microstructure and Properties of Aluminum/Steel Inertia Radial Friction Welding
Authors: Li Zhongsheng , Liu Zhengtao , Chen Dajun , Mo Fei , Fu Yangfan , Dai Ye , Wu Xia , Cong Dalong
Published: December 2022

In this paper, 6061-T6 aluminum alloy and 30CrMnSiA steel are bonded by inertia radial friction welding (IRFW). The formation mechanism of the aluminum/steel friction welded joints and the effect of the welding parameters on the mechanical properties are investigated through the microstructure, microzone composition, and mechanical property analysis. The results show that no visible intermetallic compound layers (IMCs) are detected on the aluminum/steel welding interface, which may be due to Si element aggregating in the welding interface and then forming a Al−Fe−Si phase, preventing the formation and growth of an Al−Fe IMCs. Eventually, a micron ultrathin interface reaction layer composed of Al0.7Fe3Si0.3, FeAl, and Fe3Al phases is formed at the aluminum/steel welding interface. The maximum average shear strength of the joint is 176 MPa. The shear fracture is a typical ductile fracture. Properly reducing the friction speed and increasing the upsetting pressure can improve the bonding strength of aluminum/steel joints.