bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning Algorithm for Delay Prediction in IoT and Tactile Internet
Authors: Abdellah Ali R. , Mahmood Omar Abdulkareem , Kirichek Ruslan , Paramonov Alexander , Koucheryavy Andrey
Published: November 2021

The next-generation cellular systems, including fifth-generation cellular systems (5G), are empowered with the recent advances in artificial intelligence (AI) and other recent paradigms. The internet of things (IoT) and the tactile internet are paradigms that can be empowered with AI solutions and integrated with 5G systems to deliver novel services that impact the future. Machine learning technologies (ML) can understand examples of nonlinearity from the environment and are suitable for network traffic prediction. Network traffic prediction is one of the most active research areas that integrates AI with information networks. Traffic prediction is an integral approach to ensure security, reliability, and quality of service (QoS) requirements. Nowadays, it can be used in various applications, such as network monitoring, resource management, congestion control, network bandwidth allocation, network intrusion detection, etc. This paper performs time series prediction for IoT and tactile internet delays, using the k-step-ahead prediction approach with nonlinear autoregressive with external input (NARX)-enabled recurrent neural network (RNN). The ML was trained with four different training functions: Bayesian regularization backpropagation (Trainbr), Levenberg–Marquardt backpropagation (Trainlm), conjugate gradient backpropagation with Fletcher–Reeves updates (Traincgf), and the resilient backpropagation algorithm (Trainrp). The accuracy of the predicted delay was measured using three functions based on ML: mean square error (MSE), root mean square error (RMSE), and mean absolute percentage error (MAPE).
Stability and Consolidation of Sediment Tailings Incorporating Unsaturated Soil Mechanics
Authors: Satyanaga Alfrendo , Wijaya Martin , Zhai Qian , Moon Sung-Woo , Pu Jaan , Kim Jong R.
Published: November 2021

Tailing dams are commonly used to safely store tailings without damaging the environment. Sand tailings (also called Sediment tailings) usually have a high water content and hence undergo consolidation during their placement. As the sediment tailings are usually placed above the ground water level, the degree of saturation and permeability of the sediment tailing is associated with the unsaturated condition due to the presence of negative pore-water pressure or suction. Current practices normally focus on the analyses saturated conditions. However, this consolidation process requires the flow of water between saturated and unsaturated zones to be considered. The objective of this study is to investigate the stability and consolidation of sediment tailings for the construction of road pillars considering the water flow between saturated and unsaturated zones. The scope of this study includes the unsaturated laboratory testing of sediments and numerical analyses of the road pillar. The results show that the analyses based on saturated conditions overestimate the time required to achieve a 90% degree of consolidation. The incorporation of the unsaturated soil properties is able to optimize the design of slopes for road pillars into steeper slope angles.
Glycidol Fatty Acid Ester and 3-Monochloropropane-1,2-Diol Fatty Acid Ester in Commercially Prepared Foods
Authors: Shimamura Yuko , Inagaki Ryo , Oike Minami , Dong Beibei , Gong Wan , Masuda Shuichi
Published: November 2021

Glycidyl fatty acid esters (GEs), which are the main pollutant in processed oils, are potential mutagens or carcinogens. 3-Monochloropropane-1,2-diol fatty acid esters (3-MCPDEs) are also well-known food processing contaminants. 3-MCPDEs are believed to be a precursor to GEs in foodstuffs. In vivo, lipase breaks down the phosphate ester of GEs and 3-MCPDEs to produce glycidol and 3-MCPD, respectively, which are genotoxic carcinogens. Thus, it is important to determine human exposure to GEs and 3-MCPDEs through foodstuffs. There are only reports on the amount of GE and 3-MCPDE in cooking oils and cooked foods. The content in multiple types of foods that are actually on the market was not clarified. In this study, 48 commercially prepared foods were analyzed to identify other sources of exposure to GE and 3-MCPDE. All of them contained relatively high amounts of GEs and 3-MCPDEs. The correlation between GEs and 3-MCPDEs in individual foods was examined. There was a correlation between the amounts of GEs and 3-MCPDEs in the food products (r = 0.422, p < 0.005). This is the first report on the content in multiple types of commercially prepared foods that are actually on the market was clarified.
Stability of Bioactive Compounds in Olive-Pomace Oil at Frying Temperature and Incorporation into Fried Foods
Authors: Ruiz-Méndez María-Victoria , Márquez-Ruiz Gloria , Holgado Francisca , Velasco Joaquín
Published: November 2021

The stability of minor bioactive compounds in olive-pomace oils (OPOs) was evaluated at frying temperature under the conditions of a thermoxidation test. Bioactive compounds analyzed included squalene, tocopherols, sterols, triterpenic acids and alcohols, and aliphatic alcohols. In order to determine the amount of OPO bioactive compounds incorporated into foods after frying, three different kinds of frozen products were selected, i.e., pre-fried potatoes (French fries), pre-fried battered chicken nuggets, and chicken croquettes (breaded patties), and were used in discontinuous frying experiments. Results obtained in both the thermoxidation and frying studies showed high stability of triterpenic alcohols (erythrodiol and uvaol), oleanolic acid, and aliphatic alcohols, naturally present in OPOs. In all fried foods, the content of lipids increased after frying, as expected, although the extent of absorption of OPOs into fried foods and the exchange with food lipids depended on the food characteristics. Overall, frying with OPOs improved the nutritional properties of all products tested by increasing the level of oleic acid and by the incorporation of squalene, triterpenic acids and alcohols, and aliphatic alcohols, in significant quantities.
Effects of Long-Term Bottle Storage on Red and Rosé Wines Sealed with Different Types of Closures
Authors: Tchouakeu Betnga Prudence Fleur , Longo Edoardo , Merkytė Vakarė , Dupas de Matos Amanda , Rossetti Fabrizio , Boselli Emanuele
Published: November 2021

Volatile and non-volatile chemical profiles, free and total SO2 and dissolved oxygen content were studied in three red (Merlot, Lagrein red, St. Magdalener) and one rosé (Lagrein rosé) wine after 30 months of storage in bottles. Each wine was sealed with closures made of a ‘blend’ (B) of natural cork microgranules and polymers without glue and was compared with wines closed with other types of corks (C; a technical cork 1 + 1, or an agglomerated natural cork or a natural one-piece cork). Glutathionyl caftaric acid (GRP) was inversely correlated with total SO2 content and was higher in all three red wines closed with B compared to C, whereas epicatechin was higher in three wines closed with C compared to B. Three volatile compounds formed by fermentation (ethyl butanoate, isoamyl lactate, and octanol) were inversely correlated with both free and total SO2. In terms of their volatile profiles, ethyl octanoate and 2,3-butanediol were significantly higher in the Lagrein red wines closed with C closures, whereas no significant difference was observed in Merlot, Lagrein rosé and St. Magdalener wines. Small differences in some phenolic compounds due to the type of closure were found: GRP, syringic acid, (+)-catechin, and (−)-epicatechin differentiated the Merlot wines closed with B from the C closures. Protocatechuic acid and GRP levels differentiated the Lagrein red wines according to their closure type, whereas only (−)-epicatechin differentiated the Lagrein rosé wines. GRP, caffeic acid, (−)-epicatechin, and anthocyanin content differentiated the St. Magdalener wines according to their closure type. Even though St. Magdalener and Lagrein rosé closed with C could be distinguished from those closed with B by using the (sensory) triangle test (α = 0.05), these differences appeared to be relative as it did not include all the wines in a systematic manner.
Application and Effects of Ohmic-Vacuum Combination Heating on the Quality Factors of Tomato Paste
Authors: Alkanan Zina T. , Altemimi Ammar B. , Al-Hilphy Asaad R. S. , Cacciola Francesco , Ibrahim Salam A.
Published: November 2021

Ohmic-vacuum combination heating is a common method used in the food industry as a concentration process. In the present study, an OH-VC combination heating system was developed for producing tomato paste at temperatures of 70, 80, and 90 °C and pressure of 0.3, 0.5, and 0.7 bar and electric field of 1.82, 2.73, and 3.64 V/cm using a central composite design. The effects of heating conditions on the quality and sensory evaluation of tomato paste were also evaluated. Each combination of temperature, pressure, and the electric field was quantified for specific energy consumption, energy efficiency, and productivity. A decrease of 35.08% in the amount of acid ascorbic and lycopene content 19.01%, using conventional heating compared to ohmic-vacuum heating under optimized conditions, was attained. The results also highlighted an increase in the amount of HMF (69.79%) and PME (24.33%) using conventional heating compared to ohmic-vacuum heating under optimized conditions. Ascorbic acid, lycopene, titratable acidity, productivity, energy efficiency was higher than conventional heating; on the other hand, HMF, PME, pH, SEC were lower than conventional heating at the applied OH-VC process. No significant effects between OH-VC and conventional heating on the TSS were observed. In addition, OH-VC heating was highly efficient in the inhibition of bacterial growth. Further, a minor effect on the sensory properties of tomato paste with OH-VC heating compared to the conventional treatment. The obtained results indicate a strong potential for an OH-VC combination heating system as a rapid-heating, high-efficiency alternative for saving electrical energy consumption and preserving nutritional value.
Genome-Wide RNA-Sequencing Reveals Massive Circular RNA Expression Changes of the Neurotransmission Genes in the Rat Brain after Ischemia–Reperfusion
Authors: Filippenkov Ivan B. , Stavchansky Vasily V. , Denisova Alina E. , Valieva Liya V. , Remizova Julia A. , Mozgovoy Ivan V. , Zaytceva Elizaveta I. , Gubsky Leonid V. , Limborska Svetlana A. , Dergunova Lyudmila V.
Published: November 2021

Ischemic brain stroke is one of the most serious and socially significant diseases. In addition to messenger RNAs (mRNAs), encoding protein, the study of regulatory RNAs in ischemic has exceptional importance for the development of new strategies for neuroprotection. Circular RNAs (circRNAs) have a closed structure, predominantly brain-specific expression, and remain highly promising targets of research. They can interact with microRNAs (miRNAs), diminish their activity and thereby inhibit miRNA-mediated repression of mRNA. Genome-wide RNA-Seq analysis of the subcortical structures of the rat brain containing an ischemic damage focus and penumbra area revealed 395 circRNAs changed their expression significantly at 24 h after transient middle cerebral artery occlusion model (tMCAO) conditions. Furthermore, functional annotation revealed their association with neuroactive signaling pathways. It was found that about a third of the differentially expressed circRNAs (DECs) originate from genes whose mRNA levels also changed at 24 h after tMCAO. The other DECs originate from genes encoding non-regulated mRNAs under tMCAO conditions. In addition, bioinformatic analysis predicted a circRNA–miRNA–mRNA network which was associated with the neurotransmission signaling regulation. Our results show that such circRNAs can persist as potential miRNA sponges for the protection of mRNAs of neurotransmitter genes. The results expanded our views about the neurotransmission regulation in the rat brain after ischemia–reperfusion with circRNA action.
Chromosome Genome Assembly of Cromileptes altivelis Reveals Loss of Genome Fragment in Cromileptes Compared with Epinephelus Species
Authors: Yang Yang , Wu Lina , Weng Zhuoying , Wu Xi , Wang Xi , Xia Junhong , Meng Zining , Liu Xiaochun
Published: November 2021

The humpback grouper (Cromileptes altivelis), an Epinephelidae species, is patchily distributed in the reef habitats of Western Pacific water. This grouper possesses a remarkably different body shape and notably low growth rate compared with closely related grouper species. For promoting further research of the grouper, in the present study, a high-quality chromosome-level genome of humpback grouper was assembled using PacBio sequencing and high-throughput chromatin conformation capture (Hi-C) technology. The assembled genome was 1.013 Gb in size with 283 contigs, of which, a total of 143 contigs with 1.011 Gb in size were correctly anchored into 24 chromosomes. Moreover, a total of 26,037 protein-coding genes were predicted, of them, 25,243 (96.95%) genes could be functionally annotated. The high-quality chromosome-level genome assembly will provide pivotal genomic information for future research of the speciation, evolution and molecular-assisted breeding in humpback groupers. In addition, phylogenetic analysis based on shared single-copy orthologues of the grouper species showed that the humpback grouper is included in the Epinephelus genus and clustered with the giant grouper in one clade with a divergence time of 9.86 Myr. In addition, based on the results of collinearity analysis, a gap in chromosome 6 of the humpback grouper was detected; the missed genes were mainly associated with immunity, substance metabolism and the MAPK signal pathway. The loss of the parts of genes involved in these biological processes might affect the disease resistance, stress tolerance and growth traits in humpback groupers. The present research will provide new insight into the evolution and origin of the humpback grouper.
Detection of Sepsis in Platelets Using MicroRNAs and Membrane Antigens
Authors: Vieira Corrêa Priscilla Cristina Moura , Carneiro Débora Monteiro , da Silva Valente Luciana do Socorro , Diogo Fabíola Marques , Lamarão Leticia Martins , da Silva Maués Jersey Heitor , Moreira-Nunes Caroline Aquino , Burbano Rommel Mario Rodríguez
Published: November 2021

The present study proposes to legitimize in sepsis a characteristic found in platelets that suffer storage lesions in blood banks, which is the increased expression of miRNA miR-320a in relation to miR-127. Under physiologically normal conditions, an inverse relationship is observed. The aim of this study was to verify whether the analysis of miR-320a and miR-127 expression in platelets could detect a decrease in their viability and function due to the presence of pathogens in the blood of patients hospitalized in the Intensive Care Unit. We also investigated the expression of membrane antigens sensitive to platelet activation. Of the 200 patients analyzed, only those who developed sepsis (140) were found to have a higher relative quantity of miR-320a than that of miR-127. This characteristic and the increased expression of membrane antigens P2Y12, CD62P, CD41, and CD61 showed a significant association (p < 0.01) with all types of sepsis evaluated in this study. Additionally, 40% of patients hospitalized for sepsis had negative results for the first cultures. We conclude that analysis of miR-127 and miR-320a expression combined with membrane antigens evaluation, in association with the available clinical and diagnostic parameters, are important tools to detect the onset of sepsis.
Next Generation Sequencing Identifies the HLA-DQA1*03:03 Allele in the Type 1 Diabetes Risk-Associated HLA-DQ8 Serotype
Authors: Enczmann Jürgen , Balz Vera , Hoffmann Maximilian , Kummer Sebastian , Reinauer Christina , Döing Carsten , Förtsch Katharina , Welters Alena , Mayatepek Ertan , Meissner Thomas , Jacobsen Marc , Seyfarth Julia
Published: November 2021

The highest genetic type 1 diabetes risk is conferred by HLA class II haplotypes defined by alleles at the HLA-DR and -DQ loci. The combination of HLA-DQA1*03:01 and DQB1*03:02 alleles (summarized as ‘HLA-DQ8′) is reported to be among the two most prevalent HLA class II haplotypes in Caucasian type 1 diabetes patients. This classification is based on conventional genotyping of exon 2 of the DQ gene locus and excludes exon 3. In this study, HLA genotyping on the type 1 diabetes susceptibility loci HLA-DRB1, DQA1 and DQB1 was performed using a high-resolution next generation sequencing method. In addition to the routinely examined exon 2, exon 3 was also sequenced. Samples from 229 children with type 1 diabetes were included and compared to a cohort of 9,786 controls. In addition to previously described HLA-DQ haplotypes in type 1 diabetes patients, we found that as well as HLA-DQA1*03:01,HLA-DQA1*03:03 also contributed to HLA-DQ8. HLA-DQA1*03:03 differs from HLA-DQA1*03:01 by one nucleotide substitution in exon 3 at position 160, leading to a single amino acid replacement. DRB1*04:05 was exclusively associated with DQA1*03:03 whereas the DRB1*04:01 haplotype comprised either DQA1*03:01 or DQA1*03:03. Significantly increased type 1 diabetes risk was confirmed for all these haplotypes with only minor differences between DQA1*03:01 and DQA1*03:03 alleles. This study identified the HLA-DQA1*03:03 allele as an addition to the already known type 1 diabetes risk haplotypes, and can contribute to more precise HLA genotyping approaches.
The Persistence of Staphylococcus aureus in Pressure Ulcers: A Colonising Role
Authors: Fayolle Martin , Morsli Madjid , Gelis Anthony , Chateauraynaud Marion , Yahiaoui-Martinez Alex , Sotto Albert , Lavigne Jean-Philippe , Dunyach-Remy Catherine
Published: November 2021

Decubitus pressure ulcers (PU) are a major complication of immobilised patients. Staphylococcus aureus is one of the most frequently detected microorganisms in PU samples; however, its persistence and role in the evolution of these wounds is unknown. In this study, we analysed S. aureus strains isolated from PU biopsies at inclusion and day 28. Eleven S. aureus (21.1%) were detected in 52 patients at inclusion. Only six PUs (11.5%) continued to harbour this bacterium at day 28. Using a whole genome sequencing approach (Miseq®, Illumina), we confirmed that these six S. aureus samples isolated at D28 were the same strain as that isolated at inclusion, with less than 83 bp difference. Phenotypical studies evaluating the growth profiles (Infinite M Mano, Tecan®) and biofilm formation (Biofilm Ring Test®) did not detect any significant difference in the fitness of the pairs of S. aureus. However, using the Caenorhabditis elegans killing assay, a clear decrease of virulence was observed between strains isolated at D28 compared with those isolated at inclusion, regardless of the clinical evolution of the PU. Moreover, all strains at inclusion were less virulent than a control S. aureus strain, i.e., NSA739. An analysis of polymicrobial communities of PU (by metabarcoding approach), in which S. aureus persisted, demonstrated no impact of Staphylococcus genus on PU evolution. Our study suggested that S. aureus presented a colonising profile on PU with no influence on wound evolution.
Evaluation of Genome-Enabled Prediction for Carcass Primal Cut Yields Using Single-Step Genomic Best Linear Unbiased Prediction in Hanwoo Cattle
Authors: Naserkheil Masoumeh , Mehrban Hossein , Lee Deukmin , Park Mi Na
Published: November 2021

There is a growing interest worldwide in genetically selecting high-value cut carcass weights, which allows for increased profitability in the beef cattle industry. Primal cut yields have been proposed as a potential indicator of cutability and overall carcass merit, and it is worthwhile to assess the prediction accuracies of genomic selection for these traits. This study was performed to compare the prediction accuracy obtained from a conventional pedigree-based BLUP (PBLUP) and a single-step genomic BLUP (ssGBLUP) method for 10 primal cut traits—bottom round, brisket, chuck, flank, rib, shank, sirloin, striploin, tenderloin, and top round—in Hanwoo cattle with the estimators of the linear regression method. The dataset comprised 3467 phenotypic observations for the studied traits and 3745 genotyped individuals with 43,987 single-nucleotide polymorphisms. In the partial dataset, the accuracies ranged from 0.22 to 0.30 and from 0.37 to 0.54 as evaluated using the PBLUP and ssGBLUP models, respectively. The accuracies of PBLUP and ssGBLUP with the whole dataset varied from 0.45 to 0.75 (average 0.62) and from 0.52 to 0.83 (average 0.71), respectively. The results demonstrate that ssGBLUP performed better than PBLUP averaged over the 10 traits, in terms of prediction accuracy, regardless of considering a partial or whole dataset. Moreover, ssGBLUP generally showed less biased prediction and a value of dispersion closer to 1 than PBLUP across the studied traits. Thus, the ssGBLUP seems to be more suitable for improving the accuracy of predictions for primal cut yields, which can be considered a starting point in future genomic evaluation for these traits in Hanwoo breeding practice.
Familial Dilated Cardiomyopathy and Sudden Cardiac Arrest: New Association with a SCN5A Mutation
Authors: Rico Yolanda , Ramis Maria Francisca , Massot Montse , Torres-Juan Laura , Pons Jaume , Fortuny Elena , Ripoll-Vera Tomas , González Rosa , Peral Vicente , Rossello Xavier , Heine Suñer Damià
Published: November 2021

Dilated cardiomyopathy (DCM) has significant morbidity and mortality. Familial transmission is reported in 20–35% of cases, highlighting the role of genetics in this disorder. We present an interesting family in which the index case is a 64-year-old woman who survived a sudden cardiac arrest. She presented left ventricular dilatation and dysfunction, which indicated the presence of DCM, as well as a history of DCM and sudden arrest in her family (mother and sister). Genetic testing identified a heterozygous mutation c.74A > G missense change that causes an amino acid, p.Glu25Gly, change in the N-terminal domain of the SCN5A protein. After performing an exhaustive family medical history, we found that this previously not described mutation segregated within the family. All relatives with the DCM phenotype were carriers, whereas none of the noncarriers showed signs of heart disease, so this mutation is the most likely cause of the disease. This is the first time that a variant in the N-terminal domain of SCN5A has been associated with DCM.
Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing
Authors: De Falco Luigia , Piscopo Carmelo , D’Angelo Rossana , Evangelista Eloisa , Suero Teresa , Sirica Roberto , Ruggiero Raffaella , Savarese Giovanni , Di Carlo Antonella , Furino Giulia , Scarpato Ciro , Fico Antonio
Published: November 2021

Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46, XY Disorders of Sex Development (46, XY DSD). The diagnosis of 46, XY DSD is very challenging and not rarely is confirmed only at older ages, when an affected XY female presents with primary amenorrhea or develops progressive virilization. The patient described in this paper represents a case of discrepancies between non-invasive prenatal testing (NIPT) and ultrasound based fetal sex determination detected during prenatal screening. Exome sequencing was performed on the cell free fetal DNA (cffDNA), amniotic fluid, and the parents. Libraries were generated according to the manufacturer’s protocols using TruSight One Kits (Illumina Inc., San Diego, CA, USA). Sequencing was carried out on NEXT Seq 500 (Illumina) to mean sequencing depth of at least 100×. A panel of sexual disease genes was used in order to search for a causative variant. The finding of a mutation (c.645 A>T, p.Glu215Asp) in HSD17B3 gene in amniotic fluid as well as in cffDNA and both parents supported the hypothesis of the HSD17B3 deficiency. In conclusion, we used clinical exome sequencing and non-invasive prenatal detection, providing a solution for NIPT of a single-gene disorder. Early genetic diagnoses are useful for patients and clinicians, contribute to clinical knowledge of DSD, and are invaluable for genetic counseling of couples contemplating future pregnancies.
Overexpression of Orange Gene (OsOr-R115H) Enhances Heat Tolerance and Defense-Related Gene Expression in Rice (Oryza sativa L.)
Authors: Jung Yu Jin , Go Ji Yun , Lee Hyo Ju , Park Jung Soon , Kim Jin Young , Lee Ye Ji , Ahn Mi-Jeong , Kim Me-Sun , Cho Yong-Gu , Kwak Sang-Soo , Kim Ho Soo , Kang Kwon Kyoo
Published: November 2021

In plants, the orange (Or) gene plays roles in regulating carotenoid biosynthesis and responses to environmental stress. The present study investigated whether the expression of rice Or (OsOr) gene could enhance rice tolerance to heat stress conditions. The OsOr gene was cloned and constructed with OsOr or OsOr-R115H (leading to Arg to His substitution at position 115 on the OsOr protein), and transformed into rice plants. The chlorophyll contents and proline contents of transgenic lines were significantly higher than those of non-transgenic (NT) plants under heat stress conditions. However, we found that the levels of electrolyte leakage and malondialdehyde in transgenic lines were significantly reduced compared to NT plants under heat stress conditions. In addition, the levels of expression of four genes related to reactive oxygen species (ROS) scavenging enzymes (OsAPX2, OsCATA, OsCATB, OsSOD-Cu/Zn) and five genes (OsLEA3, OsDREB2A, OsDREB1A, OsP5CS, SNAC1) responded to abiotic stress was showed significantly higher in the transgenic lines than NT plants under heat stress conditions. Therefore, OsOr-R115H could be exploited as a promising strategy for developing new rice cultivars with improved heat stress tolerance.
Fertility of Cryptorchid Testis—An Unsolved Mistery
Authors: Ciongradi Carmen Iulia , Sârbu Ioan , Iliescu Halițchi Codruța Olimpiada , Benchia Diana , Sârbu Klara
Published: November 2021

Cryptorchidism (undescended testis) is one of the most common diagnoses in the pediatric urologist office. Even in the modern era, there still are a lot of debates regarding the optimal time for surgery related to the expected results in relation with the testicular function, including fertility. The review below intends to clarify issues regarding the impact of cryptorchidism on testicular histology and function, semen analysis, the relation between hormonal and surgical treatment, future fertility, and paternity rate.
LEAFY COTYLEDON 2: A Regulatory Factor of Plant Growth and Seed Development
Authors: Liu Boling , Sun Ge , Liu Changju , Liu Shijuan
Published: November 2021

Transcription factors are key molecules in the regulation of gene expression in all organisms. The transcription factor LEAFY COTYLEDON 2 (LEC2), which belongs to the DNA-binding protein family, contains a B3 domain. The transcription factor is involved in the regulation of important plant biological processes such as embryogenesis, somatic embryo formation, seed storage protein synthesis, fatty acid metabolism, and other important biological processes. Recent studies have shown that LEC2 regulates the formation of lateral roots and influences the embryonic resetting of the parental vernalization state. The orthologs of LEC2 and their regulatory effects have also been identified in some crops; however, their regulatory mechanism requires further investigation. Here, we summarize the most recent findings concerning the effects of LEC2 on plant growth and seed development. In addition, we discuss the potential molecular mechanisms of the action of the LEC2 gene during plant development.
Rare Pathogenic Variants in Genes Implicated in Glutamatergic Neurotransmission Pathway Segregate with Schizophrenia in Pakistani Families
Authors: Fatima Ambrin , Abdullah Uzma , Farooq Muhammad , Mang Yuan , Mehrjouy Mana M. , Asif Maria , Ali Zafar , Tommerup Niels , Baig Shahid M.
Published: November 2021

Schizophrenia is a disabling neuropsychiatric disorder of adulthood onset with high heritability. Worldwide collaborations have identified an association of ~270 common loci, with small individual effects and hence weak clinical implications. The recent technological feasibility of exome sequencing enables the identification of rare variants of high penetrance that refine previous findings and improve risk assessment and prognosis. We recruited two multiplex Pakistani families, having 11 patients and 19 unaffected individuals in three generations. We performed genome-wide SNP genotyping, next-generation mate pairing and whole-exome sequencing of selected members to unveil genetic components. Candidate variants were screened in unrelated cohorts of 508 cases, 300 controls and fifteen families (with 51 affected and 47 unaffected individuals) of Pakistani origin. The structural impact of substituted residues was assessed through in silico modeling using iTASSER. In one family, we identified a rare novel microduplication (5q14.1_q14.2) encompassing critical genes involved in glutamate signaling, such as CMYA5, HOMER and RasGRF2. The second family segregates two ultra-rare, predicted pathogenic variants in the GRIN2A (NM_001134407.3: c.3505C>T, (p.R1169W) and in the NRG3 NM_001010848.4: c.1951G>A, (p.E651K). These genes encode for parts of AMPA and NMDA receptors of glutamatergic neurotransmission, respectively, and the variants are predicted to compromise protein function by destabilizing their structures. The variants were absent in the aforementioned cohorts. Our findings suggest that rare, highly penetrant variants of genes involved in glutamatergic neurotransmission are contributing to the etiology of schizophrenia in these families. It also highlights that genetic investigations of multiplex, multigenerational families could be a powerful approach to identify rare genetic variants involved in complex disorders.
In Silico Analysis of Pathogenic CRB1 Single Nucleotide Variants and Their Amenability to Base Editing as a Potential Lead for Therapeutic Intervention
Authors: Bellingrath Julia-Sophia , McClements Michelle E. , Kaukonen Maria , Fischer Manuel Dominik , MacLaren Robert E.
Published: November 2021

Mutations in the Crumbs homolog 1 (CRB1) gene cause both autosomal recessive retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). Since three separate CRB1 isoforms are expressed at meaningful levels in the human retina, base editing shows promise as a therapeutic approach. This retrospective analysis aims to summarise the reported pathogenic CRB1 variants and investigate their amenability to treatment with currently available DNA base editors. Pathogenic single nucleotide variants (SNVs) were extracted from the Leiden open-source variation database (LOVD) and ClinVar database and coded by mutational consequence. They were then analyzed for their amenability to currently available DNA base editors and available PAM sites from a selection of different Cas proteins. Of a total of 1115 unique CRB1 variants, 69% were classified as pathogenic SNVs. Of these, 62% were amenable to currently available DNA BEs. Adenine base editors (ABEs) alone have the potential of targeting 34% of pathogenic SNVs; 19% were amenable to a CBE while GBEs could target an additional 9%. Of the pathogenic SNVs targetable with a DNA BE, 87% had a PAM site for a Cas protein. Of the 33 most frequently reported pathogenic SNVs, 70% were targetable with a base editor. The most common pathogenic variant was c.2843G>A, p.Cys948Arg, which is targetable with an ABE. Since 62% of pathogenic CRB1 SNVs are amenable to correction with a base editor and 87% of these mutations had a suitable PAM site, gene editing represents a promising therapeutic avenue for CRB1-associated retinal degenerations.
Co-Occurrence of Fragile X Syndrome with a Second Genetic Condition: Three Independent Cases of Double Diagnosis
Authors: Tabolacci Elisabetta , Pomponi Maria Grazia , Remondini Laura , Pietrobono Roberta , Orteschi Daniela , Nobile Veronica , Pucci Cecilia , Musto Elisa , Pane Marika , Mercuri Eugenio M. , Neri Giovanni , Genuardi Maurizio , Chiurazzi Pietro , Zollino Marcella
Published: November 2021

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism caused by the instability of a CGG trinucleotide repeat in exon 1 of the FMR1 gene. The co-occurrence of FXS with other genetic disorders has only been occasionally reported. Here, we describe three independent cases of FXS co-segregation with three different genetic conditions, consisting of Duchenne muscular dystrophy (DMD), PPP2R5D--related neurodevelopmental disorder, and 2p25.3 deletion. The co-occurrence of DMD and FXS has been reported only once in a young boy, while in an independent family two affected boys were described, the elder diagnosed with FXS and the younger with DMD. This represents the second case in which both conditions coexist in a 5-year-old boy, inherited from his heterozygous mother. The next double diagnosis had never been reported before: through exome sequencing, a girl with FXS who was of 7 years of age with macrocephaly and severe psychomotor delay was found to carry a de novo variant in the PPP2R5D gene. Finally, a maternally inherited 2p25.3 deletion associated with a decreased level of the MYT1L transcript, only in the patient, was observed in a 33-year-old FXS male with severe seizures compared to his mother and two sex- and age-matched controls. All of these patients represent very rare instances of genetic conditions with clinical features that can be modified by FXS and vice versa.
Exome Sequencing Identifies a Novel FBN1 Variant in a Pakistani Family with Marfan Syndrome That Includes Left Ventricle Diastolic Dysfunction
Authors: Farooqi Nadia , Metherell Louise A. , Schrauwen Isabelle , Acharya Anushree , Khan Qayum , Nouel Saied Liz M. , Ali Yasir , El-Serehy Hamed A. , Jalil Fazal , Leal Suzanne M.
Published: November 2021

Introduction: Cardiomyopathies are diseases of the heart muscle and are important causes of heart failure. Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy that can be acquired, syndromic or non-syndromic. The current study was conducted to explore the genetic defects in a Pakistani family with cardiac disease and features of Marfan’s syndrome (MFS). Methods: A family with left ventricle (LV) diastolic dysfunction and MFS phenotype was assessed in Pakistan. The clinical information and blood samples from the patients were collected after physical, cardiovascular, and ophthalmologic examinations. An affected individual (proband) was subjected to whole-exome sequencing (WES). The findings were further validated through Sanger sequencing in the family. Results: Through WES and sanger validation, we identified a novel variant NM_000138.4; c.1402A>G in the Fibrillin-1 (FBN1) gene that segregates with LV diastolic dysfunction and MFS. Furthermore, bioinformatic evaluation suggested that the novel variant is deleterious and disease-causing. Conclusions: This study identified for the first time a novel FBN1 variant in a family with LV diastolic dysfunction and MFS in Pakistan.
The Decisive Case-Control Study Elaborates the Null Association between ADAMTS5 rs226794 and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis
Authors: Kao Chung-Cheng , Hsu Hsiang-En , Chen Yi-Chou , Tu Ming-Yu , Chuang Su-Wen , Su Sui-Lung
Published: November 2021

Background: Osteoarthritis is an important health issue for the elderly. Many studies indicate that genetics is an important risk factor for osteoarthritis, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is one gene that is most frequently implicated. Many recent studies have examined the relationship between a polymorphism in the ADAMTS5 gene (rs226794) and the risk for developing osteoarthritis without definitive results. Objective: In this case-control study, we examined the correlation between the ADAMTS5 gene polymorphism, rs226794, and knee osteoarthritis. We used a meta-analysis and trial sequential analysis to determine whether ADAMTS5 rs226794 expression increases susceptibility to osteoarthritis. Methods: This study consisted of two parts: a case-control study and a meta-analysis. The case-control study included subjects who underwent knee radiography at the Health Examination Center of the Tri Service General Hospital from 2015 to 2019. The Kellgren–Lawrence (KL) grading system was used as diagnostic criteria. Patients with unsuccessful gene sequencing were excluded. There were 606 subjects in the knee osteoarthritis group (KL ≥ 2) and 564 in the control group (KL < 2). Gene sequencing was performed using iPLEX Gold to determine the association between the gene polymorphism of ADAMTS5 rs226794 and knee osteoarthritis. For the meta-analysis, databases such as PubMed, Embase, and Cochrane were queried to identify studies that examined the relationship between ADAMTS5 rs226794 and osteoarthritis. Next, the findings of the meta-analysis were incorporated with the results of the case-control study and samples from the published studies to estimate the association between the genetic polymorphism and osteoarthritis using an odds ratio and a 95% confidence interval. Results: We found a non-significant association between the G allele and knee OA (crude-OR: 0.93 (95% CI: 0.79–1.10) and adjusted-OR: 1.02 (95% CI: 0.76–1.36) in the allele model) in the present study, and the analysis of other genetic models revealed a similar trend. After including five published studies and our case-control study, the results with 2866 Asians indicated a conclusively null association between ADAMTS5 rs226794 and knee OA) OR: 1.09 (95% CI: 0.93–1.26). The results for Caucasians also revealed a null association (OR: 1.21 (95% CI: 0.81–1.82)). Conclusions: This study indicates that the gene polymorphism, ADAMTS5 rs226794, is not significantly associated with knee osteoarthritis. Additionally, assuming that the cumulative sample size in the allele model is sufficient, we confirmed that the G allele is not a risk factor for osteoarthritis. This study integrated all available evidence to arrive at this conclusion, and it suggests that no additional studies are necessary.
Analysis of Fear Post COVID in First-Year Students after the Incorporation to the Classroom: Descriptive Study in University Students of Health Sciences
Authors: Cantero-Garlito Pablo A. , Rodríguez-Hernández Marta , Moraleda-Sepúlveda Esther , Polonio-López Begoña , Marcos-Tejedor Félix
Published: November 2021

Background: After the onset of the COVID-19 pandemic, social restriction measures were implemented, among them, the adaptation of university teaching to online modality until the end of the 2019–2020 school year in order to stop the spread of the SARS-CoV-2 virus. At the beginning of the 2020–2021 school year, the Spanish universities opted for face-to-face teaching. To that end, different special measures and adaptations were implemented in higher education facilities, aimed at minimizing the risk of infection and ensuring safe face-to-face learning. The objective was to explore and describe the level of fear of first-year students after the start of in-person classes in the context of the COVID-19 pandemic. Methods: The sample was 185 first-year students who were evaluated on the first day of class. For that purpose, an ad-hoc questionnaire was administered to collect demographic information and to find the level of fear and concern. The Fear of COVID-19 Scale was used to assess the severity of the participants’ fear of the pandemic situation. Results: The results indicate that participating university population does not report fear of the virus, but they describe various psychosomatic characteristics, such as increased pulse rate and heart palpitations (p = 0.008) and insomnia (p = 0.05) when they think about infection with coronavirus. Nevertheless, when data are disaggregated by gender, we observe differences specifically in women (83.2%), such as fear (p = 0.006) and sweaty hands when they think of the virus (p = 0.023). Conclusions: Incoming university freshmen do not express concern or fear of potential infection with COVID-19, but they are concerned about family transmission after beginning face-to-face classes.
Opportunities and Problems of the Consensus Conferences in the Care Robotics
Authors: Maccioni Giovanni , Ruscitto Selene , Gulino Rosario Alfio , Giansanti Daniele
Published: November 2021

Care robots represent an opportunity for the health domain. The use of these devices has important implications. They can be used in surgical operating rooms in important and delicate clinical interventions, in motion, in training-and-simulation, and cognitive and rehabilitation processes. They are involved in continuous processes of evolution in technology and clinical practice. Therefore, the introduction into routine clinical practice is difficult because this needs the stability and the standardization of processes. The agreement tools, in this case, are of primary importance for the clinical acceptance and introduction. The opinion focuses on the Consensus Conference tool and: (a) highlights its potential in the field; (b) explores the state of use; (c) detects the peculiarities and problems (d) expresses ideas on how improve its diffusion.
Comparison of Activity in Scapular Stabilizing Muscles during Knee Push-Up Plus and Modified Vojta’s 3-Point Support Exercises
Authors: Lim Hyoungwon
Published: November 2021

Selective serratus anterior (SA) strengthening without compensatory movement of the shoulder stabilizers is essential for shoulder stability and functional movement without causing shoulder injury and dysfunction. The purpose of this study was to compare electromyographic (EMG) activity between the SA, upper trapezius (UT), lower trapezius (LT), and pectoralis major (PM) during the knee push-up plus (KPUP) and modified Vojta’s 3-point support (MV3PS) exercises. Scapular stabilizer muscle activity (UT, LT, SA, and PM) was investigated during the KPUP and MV3PS exercises in 40 healthy adults (19 males, 21 females) using surface EMG. Muscle activity of the SA was significantly higher during the MV3PS exercise than during the KPUP (p < 0.05). However, muscle activity in the PM was significantly lower during the MV3PS exercise (p < 0.05). In addition, the LT and UT showed less muscle activity during the MV3PS exercise, although the difference was not statistically significant (p > 0.05). These findings suggest that the MV3PS exercise better activates the SA than KPUP.
Higher Order Aberrations following Scleral Buckling Surgery in Patients with Rhegmatogenous Retinal Detachment
Authors: Lee Chia-Yi , Wu Wei-Chi , Yeung Ling , Chen Hung-Chi , Chen Kuan-Jen , Chen Yen-Po , Hwang Yih-Shiou , Lai Chi-Chun
Published: November 2021

We aim to evaluate magnitudes of higher order aberrations (HOAs) from 3rd–6th order after scleral buckling (SB) for rhegmatogenous retinal detachment (RRD). A retrospective cross-sectional study of 19 patients with RRD who received SB (six receiving encircling SB, thirteen receiving segmental SB) was conducted. A wavefront analysis for surveying HOAs and other ophthalmic parameters were collected. Data between operated and fellow eyes, and a subgroup analysis of operated eyes, were analyzed by the Mann–Whitney U test, while a generalized linear model was applied to evaluate the correlation of HOAs to best-corrected visual acuity (BCVA) and optical symptoms. BCVA in the operated eyes was significantly worse (LogMAR: 0.18 ± 0.23 versus 0.05 ± 0.07, p = 0.001). Tilt (0.32 ± 0.14 versus 0.13 ± 0.08, p = 0.004), defocus (1.78 ± 0.47 versus 1.05 ± 0.17, p = 0.019) and coma (0.43 ± 0.11 versus 0.27 ± 0.09, p = 0.016) were significantly increased after SB. All root mean square (RMS), including RMS-3, RMS-4 and total RMS, were higher in operated eyes (all p < 0.05). Regarding Zernike terms, a significant elevation of vertical coma in the operated eyes was found (p = 0.038). In addition, tilt (0.41 ± 0.10 versus 0.17 ± 0.12, p = 0.007), defocus (2.27 ± 0.58 versus 0.82 ± 0.39, p = 0.001) and coma (0.59 ± 0.17 versus 0.11 ± 0.10, p = 0.015) were higher in the segmental subgroup, whereas spherical aberration (SA) was higher in the encircling subgroup (0.22 ± 0.04 versus 0.40 ± 0.15, p = 0.024) and RMS-4 and total RMS were increased in the segmental subgroup (both p < 0.05). Besides, tilt was correlated to worse BCVA (p = 0.036), whereas all four HOAs were correlated to the presence of optical symptoms (all p < 0.05). In conclusion, SB may increase HOAs, which could be associated with unfavorable postoperative visual outcomes and subject symptoms.
Structural Barriers Associated with the Intersection of Traumatic Stress and Gun Violence: A Case Example of New Orleans
Authors: Bailey Rahn Kennedy , Barker Chikira H. , Grover Amit
Published: November 2021

Gun violence drastically increased in urban cities following the ease of shutdown restrictions associated with the Coronavirus Pandemic. The association of gun violence and COVID-19 has highlighted the importance of taking a public health perspective, particularly as it relates to impacts on the Black community. In this article we discuss macro-level factors and community traumas in the city of New Orleans, an area that has had longstanding issues related to gun violence. Community structural issues, traumatic stress from disasters, and recommendations to address disparities in social determinants of health are discussed.
Factors Affecting Pharmacy Students’ Decision to Study in Pharmacy Colleges in Saudi Arabia: A Cross-Sectional Questionnaire-Based Analysis
Authors: Alshehri Ahmed M. , Elsawaf Lara A. , Alzaid Shaikah F. , Almogbel Yasser S. , Alminggash Mohammed A. , Almalki Ziyad S. , Algarni Majed A.
Published: November 2021

(1) Background: Many factors may play a role in deciding to opt for pharmacy as a major. However, no previous studies have been conducted in Saudi Arabia to explore these factors. This study aims to identify the potential factors that prompted students to join the pharmacy program. (2) Methods: A cross-sectional questionnaire was distributed among undergraduate pharmacy students in Saudi Arabia, addressing areas such as reasons that encourage them to choose pharmacy as a major, and students’ socio-demographic characteristics. Descriptive statistics were used to describe the study variables, and a simple logistic regression analysis was performed to identify the potential factors. (3) Results: A total of 491 students completed the questionnaire. Around 40% of them had chosen to study pharmacy as their first choice. Only gender, current GPA, and reasons related to the pharmacy field were found to have a statistically significant association with students selecting pharmacy as their first choice. (4) Conclusions: This study shows that pharmacy students have a future-oriented outlook and selected pharmacy as their first choice because it will develop them professionally, financially, and intellectually. Educating high school students about the characteristic of pharmacy would help attract more talented students to the pharmacy carrier.