bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic and Predictive Biomarkers in Gliomas
Authors: Śledzińska Paulina , Bebyn Marek G. , Furtak Jacek , Kowalewski Janusz , Lewandowska Marzena A.
Published: September 2021

Gliomas are the most common central nervous system tumors. New technologies, including genetic research and advanced statistical methods, revolutionize the therapeutic approach to the patient and reveal new points of treatment options. Moreover, the 2021 World Health Organization Classification of Tumors of the Central Nervous System has fundamentally changed the classification of gliomas and incorporated many molecular biomarkers. Given the rapid progress in neuro-oncology, here we compile the latest research on prognostic and predictive biomarkers in gliomas. In adult patients, IDH mutations are positive prognostic markers and have the greatest prognostic significance. However, CDKN2A deletion, in IDH-mutant astrocytomas, is a marker of the highest malignancy grade. Moreover, the presence of TERT promoter mutations, EGFR alterations, or a combination of chromosome 7 gain and 10 loss upgrade IDH-wildtype astrocytoma to glioblastoma. In pediatric patients, H3F3A alterations are the most important markers which predict the worse outcome. MGMT promoter methylation has the greatest clinical significance in predicting responses to temozolomide (TMZ). Conversely, mismatch repair defects cause hypermutation phenotype predicting poor response to TMZ. Finally, we discussed liquid biopsies, which are promising diagnostic, prognostic, and predictive techniques, but further work is needed to implement these novel technologies in clinical practice.
A Secreted Chorismate Mutase from Xanthomonas arboricola pv. juglandis Attenuates Virulence and Walnut Blight Symptoms
Authors: Assis Renata de A. B. , Sagawa Cíntia H. D. , Zaini Paulo A. , Saxe Houston J. , Wilmarth Phillip A. , Phinney Brett S. , Salemi Michelle , Moreira Leandro M. , Dandekar Abhaya M.
Published: September 2021

Walnut blight is a significant above-ground disease of walnuts caused by Xanthomonas arboricola pv. juglandis (Xaj). The secreted form of chorismate mutase (CM), a key enzyme of the shikimate pathway regulating plant immunity, is highly conserved between plant-associated beta and gamma proteobacteria including phytopathogens belonging to the Xanthomonadaceae family. To define its role in walnut blight disease, a dysfunctional mutant of chorismate mutase was created in a copper resistant strain Xaj417 (XajCM). Infections of immature walnut Juglans regia (Jr) fruit with XajCM were hypervirulent compared with infections with the wildtype Xaj417 strain. The in vitro growth rate, size and cellular morphology were similar between the wild-type and XajCM mutant strains, however the quantification of bacterial cells by dPCR within walnut hull tissues showed a 27% increase in XajCM seven days post-infection. To define the mechanism of hypervirulence, proteome analysis was conducted to compare walnut hull tissues inoculated with the wild type to those inoculated with the XajCM mutant strain. Proteome analysis revealed 3296 Jr proteins (five decreased and ten increased with FDR ≤ 0.05) and 676 Xaj417 proteins (235 increased in XajCM with FDR ≤ 0.05). Interestingly, the most abundant protein in Xaj was a polygalacturonase, while in Jr it was a polygalacturonase inhibitor. These results suggest that this secreted chorismate mutase may be an important virulence suppressor gene that regulates Xaj417 virulence response, allowing for improved bacterial survival in the plant tissues.
Genome-Wide Identification and Expression Profiling of the BZR Transcription Factor Gene Family in Nicotiana benthamiana
Authors: Chen Xuwei , Wu Xinyang , Qiu Shiyou , Zheng Hongying , Lu Yuwen , Peng Jiejun , Wu Guanwei , Chen Jianping , Rao Shaofei , Yan Fei
Published: September 2021

Brassinazole-resistant (BZR) family genes encode plant-specific transcription factors (TFs), play essential roles in the regulation of plant growth and development, and have multiple stress-resistance functions. Nicotiana benthamiana is a model plant widely used in basic research. However, members of the BZR family in N. benthamiana have not been identified, and little is known about their function in abiotic stress. In this study, a total of 14 BZR members were identified in the N. benthamiana genome, which could be divided into four groups according to a phylogenetic tree. NbBZRs have similar exon-intron structures and conserved motifs, and may be regulated by cis-acting elements such as STRE, TCA, and ARE, etc. Organ-specific expression analysis showed that NbBZR members have different and diverse expression patterns in different tissues, and most of the members are expressed in roots, stems, and leaves. The analysis of the expression patterns in response to different abiotic stresses showed that all the tested NbBZR members showed a significant down-regulation after drought treatment. Many NbBZR genes also responded in various ways to cold, heat and salt stress treatments. The results imply that NbBZRs have multiple functions related to stress resistance.
FISH and Chimps: Insights into Frequency and Distribution of Sperm Aneuploidy in Chimpanzees (Pan troglodytes)
Authors: Guyot Charlotte , Gandula Marlène , Noordermeer Wendy , François-Brazier Céline , Moigno Rosemary , Bessonnat Julien , Brouillet Sophie , Dhellemmes Magali , Bidart Marie , Arnoult Christophe , Satre Véronique , Coutton Charles , Martinez Guillaume
Published: September 2021

Numerical chromosomal aberrations in sperm are considered to be a major factor in infertility, early pregnancy loss and syndromes with developmental and cognitive disabilities in mammals, including primates. Despite numerous studies in human and farm animals, the incidence and importance of sperm aneuploidies in non-human primate remains mostly undetermined. Here we investigated the incidence and distribution of sperm aneuploidy in chimpanzees (Pan troglodytes), the species closest to human. We identify evolutionary conserved DNA sequences in human and chimpanzee and selected homologous sub-telomeric regions for all chromosomes to build custom probes and perform sperm-FISH analysis on more than 10,000 sperm nuclei per chromosome. Chimpanzee mean autosomal disomy rate was 0.057 ± 0.02%, gonosomes disomy rate was 0.198% and the total disomy rate was 1.497%. The proportion of X or Y gametes was respectively 49.94% and 50.06% for a ratio of 1.002 and diploidy rate was 0.053%. Our data provide for the first time an overview of aneuploidy in non-human primate sperm and shed new insights into the issues of aneuploidy origins and mechanisms.
Role of Neutrophils on the Ocular Surface
Authors: Mun Yongseok , Hwang Jin Sun , Shin Young Joo
Published: September 2021

The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.
A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers
Authors: Hosseinkhani Negar , Shadbad Mahdi Abdoli , Asghari Jafarabadi Mohammad , Karim Ahangar Noora , Asadzadeh Zahra , Mohammadi Seyede Momeneh , Lotfinejad Parisa , Alizadeh Nazila , Brunetti Oronzo , Fasano Rossella , Silvestris Nicola , Baradaran Behzad
Published: September 2021

Preclinical studies have indicated that T-cell immunoglobulin and ITIM domain (TIGIT) can substantially attenuate anti-tumoral immune responses. Although multiple clinical studies have evaluated the significance of TIGIT in patients with solid cancers, their results remain inconclusive. Thus, we conducted the current systematic review and meta-analysis based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) to determine its significance in patients with solid cancers. We systematically searched the Web of Science, Embase, PubMed, and Scopus databases to obtain peer-reviewed studies published before September 20, 2020. Our results have shown that increased TIGIT expression has been significantly associated with inferior overall survival (OS) (HR = 1.42, 95% CI: 1.11–1.82, and p-value = 0.01). Besides, the level of tumor-infiltrating TIGIT+CD8+ T-cells have been remarkably associated inferior OS and relapse-free survival (RFS) of affected patients (HR = 2.17, 95% CI: 1.43–3.29, and p-value < 0.001, and HR = 1.89, 95% CI: 1.36–2.63, and p-value < 0.001, respectively). Also, there is a strong positive association between TIGIT expression with programmed cell death-1 (PD-1) expression in these patients (OR = 1.71, 95% CI: 1.10–2.68, and p-value = 0.02). In summary, increased TIGIT expression and increased infiltration of TIGIT+CD8+ T-cells can substantially worsen the prognosis of patients with solid cancers. Besides, concerning the observed strong association between TIGIT and PD-1, ongoing clinical trials, and promising preclinical results, PD-1/TIGIT dual blockade can potentially help overcome the immune-resistance state seen following monotherapy with a single immune checkpoint inhibitor in patients with solid cancers.
Butyric and Citric Acids and Their Salts in Poultry Nutrition: Effects on Gut Health and Intestinal Microbiota
Authors: Melaku Mebratu , Zhong Ruqing , Han Hui , Wan Fan , Yi Bao , Zhang Hongfu
Published: September 2021

Intestinal dysfunction of farm animals, such as intestinal inflammation and altered gut microbiota, is the critical problem affecting animal welfare, performance and farm profitability. China has prohibited the use of antibiotics to improve feed efficiency and growth performance for farm animals, including poultry, in 2020. With the advantages of maintaining gut homeostasis, enhancing digestion, and absorption and modulating gut microbiota, organic acids are regarded as promising antibiotic alternatives. Butyric and citric acids as presentative organic acids positively impact growth performance, welfare, and intestinal health of livestock mainly by reducing pathogenic bacteria and maintaining the gastrointestinal tract (GIT) pH. This review summarizes the discovery of butyric acid (BA), citric acid (CA) and their salt forms, molecular structure and properties, metabolism, biological functions and their applications in poultry nutrition. The research findings about BA, CA and their salts on rats, pigs and humans are also briefly reviewed. Therefore, this review will fill the knowledge gaps of the scientific community and may be of great interest for poultry nutritionists, researchers and feed manufacturers about these two weak organic acids and their effects on intestinal health and gut microbiota community, with the hope of providing safe, healthy and nutrient-rich poultry products to consumers.
Relationships between Mitochondrial Function, AMPK, and TORC1 Signaling in Lymphoblasts with Premutation Alleles of the FMR1 Gene
Authors: Fisher Paul R. , Allan Claire Y. , Sanislav Oana , Atkinson Anna , Ngoei Kevin R. W. , Kemp Bruce E. , Storey Elsdon , Loesch Danuta Z. , Annesley Sarah J.
Published: September 2021

The X-linked FMR1 gene contains a non-coding trinucleotide repeat in its 5’ region that, in normal, healthy individuals contains 20–44 copies. Large expansions of this region (>200 copies) cause fragile X syndrome (FXS), but expansions of 55–199 copies (referred to as premutation alleles) predispose carriers to a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). The cytopathological mechanisms underlying FXTAS are poorly understood, but abnormalities in mitochondrial function are believed to play a role. We previously reported that lymphoblastoid cell lines (LCLs, or lymphoblasts) of premutation carriers have elevated mitochondrial respiratory activities. In the carriers, especially those not clinically affected with FXTAS, AMP-activated protein kinase (AMPK) activity was shown to be elevated. In the FXTAS patients, however, it was negatively correlated with brain white matter lesions, suggesting a protective role in the molecular mechanisms. Here, we report an enlarged and extended study of mitochondrial function and associated cellular stress-signaling pathways in lymphoblasts isolated from male and female premutation carriers, regardless of their clinical status, and healthy controls. The results confirmed the elevation of AMPK and mitochondrial respiratory activities and reduction in reactive O2 species (ROS) levels in premutation cells and revealed for the first time that target of rapamycin complex I (TORC1) activities are reduced. Extensive correlation, multiple regression, and principal components analysis revealed the best fitting statistical explanations of these changes in terms of the other variables measured. These suggested which variables might be the most “proximal” regulators of the others in the extensive network of known causal interactions amongst the measured parameters of mitochondrial function and cellular stress signaling. In the resulting model, the premutation alleles activate AMPK and inhibit both TORC1 and ROS production, the reduced TORC1 activity contributes to activation of AMPK and of nonmitochondrial metabolism, and the higher AMPK activity results in elevated catabolic metabolism, mitochondrial respiration, and ATP steady state levels. In addition, the results suggest a separate CGG repeat number-dependent elevation of TORC1 activity that is insufficient to overcome the inhibition of TORC1 in premutation cells but may presage the previously reported activation of TORC1 in FXS cells.
Design, Synthesis, Biological Evaluation, 2D-QSAR Modeling, and Molecular Docking Studies of Novel 1H-3-Indolyl Derivatives as Significant Antioxidants
Authors: Aziz Maged A. , Shehab Wesam S. , Al-Karmalawy Ahmed A. , EL-Farargy Ahmed F. , Abdellattif Magda H.
Published: September 2021

Novel candidates of 3-(4-(thiophen-2-yl)-pyridin/pyran/pyrimidin/pyrazol-2-yl)-1H-indole derivatives (2–12) were designed by pairing the pyridine/pyrane/pyrimidine/pyrazole heterocycles with indole and thiophene to investigate their potential activities as (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) inhibitors. The purpose of these derivatives’ modification is to create high-efficiency antioxidants, especially against ABTS, as a result of the efficiency of this set of key heterocycles in the inhibition of ROS. Herein, 2D QSAR modeling was performed to recommend the most promising members for further in vitro investigations. Furthermore, the pharmacological assay for antioxidant activity evaluation of the yielded indole-based heterocycles was tested against ABTS (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); by utilizing ascorbic acid as the standard. Candidate 10 showed higher antioxidant activity (IC50 = 28.23 μg/mL) than ascorbic acid itself which achieved (IC50 = 30.03 μg/mL). Moreover, molecular docking studies were performed for the newly designed and synthesized drug candidates to propose their mechanism of action as promising cytochrome c peroxidase inhibitors compared to ascorbic acid as a reference standard. Our findings could be promising in the medicinal chemistry scope for further optimization of the newly designed and synthesized compounds regarding the introduced structure-activity relationship study (SAR) in order to get a superior antioxidant lead compound in the near future.
Interleukin-9 Facilitates Osteoclastogenesis in Rheumatoid Arthritis
Authors: Kar Santanu , Gupta Ranjan , Malhotra Rajesh , Sharma Vijay , Farooque Kamran , Kumar Vijay , Chakraborty Sushmita , Mitra Dipendra Kumar
Published: September 2021

In rheumatoid arthritis (RA), inflammatory cytokines play a pivotal role in triggering abnormal osteoclastogenesis leading to articular destruction. Recent studies have demonstrated enhanced levels of interleukin-9 (IL-9) in the serum and synovial fluid of patients with RA. In RA, strong correlation has been observed between tissue inflammation and IL-9 expression in synovial tissue. Therefore, we investigated whether IL-9 influences osteoclastogenesis in patients with RA. We conducted the study in active RA patients. For inducing osteoclast differentiation, mononuclear cells were stimulated with soluble receptor activator of NF-kB ligand (sRANKL) and macrophage-colony-stimulating factor (M-CSF) in the presence or absence of recombinant (r) IL-9. IL-9 stimulation significantly enhanced M-CSF/sRANKL-mediated osteoclast formation and function. Transcriptome analysis revealed differential gene expression induced with IL-9 stimulation in the process of osteoclast differentiation. IL-9 mainly modulates the expression of genes, which are involved in the metabolic pathway. Moreover, we observed that IL-9 modulates the expression of matrix metalloproteinases (MMPs), which are critical players in bone degradation. Our results indicate that IL-9 has the potential to influence the structural damage in the RA by promoting osteoclastogenesis and modulating the expression of MMPs. Thus, blocking IL-9 pathways might be an attractive immunotherapeutic target for preventing bone degradation in RA.
Adjustment of K+ Fluxes and Grapevine Defense in the Face of Climate Change
Authors: Monder Houssein , Maillard Morgan , Chérel Isabelle , Zimmermann Sabine Dagmar , Paris Nadine , Cuéllar Teresa , Gaillard Isabelle
Published: September 2021

Grapevine is one of the most economically important fruit crops due to the high value of its fruit and its importance in winemaking. The current decrease in grape berry quality and production can be seen as the consequence of various abiotic constraints imposed by climate changes. Specifically, produced wines have become too sweet, with a stronger impression of alcohol and fewer aromatic qualities. Potassium is known to play a major role in grapevine growth, as well as grape composition and wine quality. Importantly, potassium ions (K+) are involved in the initiation and maintenance of the berry loading process during ripening. Moreover, K+ has also been implicated in various defense mechanisms against abiotic stress. The first part of this review discusses the main negative consequences of the current climate, how they disturb the quality of grape berries at harvest and thus ultimately compromise the potential to obtain a great wine. In the second part, the essential electrical and osmotic functions of K+, which are intimately dependent on K+ transport systems, membrane energization, and cell K+ homeostasis, are presented. This knowledge will help to select crops that are better adapted to adverse environmental conditions.
Interaction of 9-Methoxyluminarine with Different G-Quadruplex Topologies: Fluorescence and Circular Dichroism Studies
Authors: Nowak-Karnowska Joanna , Głuszyńska Agata , Kosman Joanna , Neunert Grażyna , Dembska Anna
Published: September 2021

The interactions of G–quadruplexes of different topologies with highly fluorescent 9-methoxyluminarine ligand 9-MeLM were investigated by fluorescence and circular dichroism spectroscopy. The results showed that 9-methoxyluminarine was able to interact and did not destabilize any investigated molecular targets. The studied compound was selectively quenched by parallel c-MYC G-quadruplex DNA, whereas hybrid and antiparallel G4 topology caused only a negligible decrease in the fluorescence of the ligand. A high decrease of fluorescence of the ligand after binding with c-MYC G-quadruplex suggests that this molecule can be used as a selective probe for parallel G-quadruplexes.
Genetic Testing in Patients with Hypertrophic Cardiomyopathy
Authors: Bonaventura Jiri , Polakova Eva , Vejtasova Veronika , Veselka Josef
Published: September 2021

Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with an estimated prevalence of up to 1 in 200 individuals. In the majority of cases, HCM is considered a Mendelian disease, with mainly autosomal dominant inheritance. Most pathogenic variants are usually detected in genes for sarcomeric proteins. Nowadays, the genetic basis of HCM is believed to be rather complex. Thousands of mutations in more than 60 genes have been described in association with HCM. Nevertheless, screening large numbers of genes results in the identification of many genetic variants of uncertain significance and makes the interpretation of the results difficult. Patients lacking a pathogenic variant are now believed to have non-Mendelian HCM and probably have a better prognosis than patients with sarcomeric pathogenic mutations. Identifying the genetic basis of HCM creates remarkable opportunities to understand how the disease develops, and by extension, how to disrupt the disease progression in the future. The aim of this review is to discuss the brief history and recent advances in the genetics of HCM and the application of molecular genetic testing into common clinical practice.
MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma
Authors: Zhou Yuchuan , Liu Hongxia , Zheng Wang , Chen Qianping , Hu Songling , Pan Yan , Bai Yang , Zhang Jianghong , Shao Chunlin
Published: September 2021

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Radiotherapy has long been an important treatment method of GBM. However, the intrinsic radioresistance of GBM cells is a key reason of poor therapeutic efficiency. Recently, many studies have shown that using the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) in radiotherapy may improve the prognosis of GBM patients, but the underlying molecular mechanisms remain unclear. In this study, Gene Expression Omnibus (GEO) datasets GSE153982 and GSE131956 were analyzed to evaluate radiation-induced changes of gene expression in GBM without or with SAHA treatment, respectively. Additionally, the survival-associated genes of GBM patients were screened using the Chinese Glioma Genome Atlas (CGGA) database. Taking the intersection of these three datasets, 11 survival-associated genes were discovered to be activated by irradiation and regulated by SAHA. The expressions of these genes were further verified in human GBM cell lines U251, T98G, and U251 homologous radioresistant cells (U251R) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). It was found that MMP14 mRNA was considerably highly expressed in the radioresistant cell lines and was reduced by SAHA treatment. Transfection of MMP14 siRNA (siMMP14) suppressed cell survivals of these GBM cells after irradiation. Taken together, our results reveal for the first time that the MMP14 gene contributed to SAHA-induced radiosensitization of GBM.
Peptide Location Fingerprinting Reveals Tissue Region-Specific Differences in Protein Structures in an Ageing Human Organ
Authors: Eckersley Alexander , Ozols Matiss , Chen Peikai , Tam Vivian , Hoyland Judith A. , Trafford Andrew , Chan Danny , Sherratt Michael J.
Published: September 2021

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural differences in complex proteomes. PLF applied to published young and aged intervertebral disc (IVD) MS datasets (posterior, lateral and anterior regions of the annulus fibrosus) identified 268 proteins with age-associated structural differences. For several ECM assemblies (collagens I, II and V and aggrecan), these differences were markedly conserved between degeneration-prone (posterior and lateral) and -resistant (anterior) regions. Significant differences in peptide yields, observed within collagen I α2, collagen II α1 and collagen V α1, were located within their triple-helical regions and/or cleaved C-terminal propeptides, indicating potential accumulation of damage and impaired maintenance. Several proteins (collagen V α1, collagen II α1 and aggrecan) also exhibited tissue region (lateral)-specific differences in structure between aged and young samples, suggesting that some ageing mechanisms may act locally within tissues. This study not only reveals possible age-associated differences in ECM protein structures which are tissue-region specific, but also highlights the ability of PLF as a proteomic tool to aid in biomarker discovery.
LED-Induced Microglial Activation and Rise in Caspase3 Suggest a Reorganization in the Retina
Authors: Balogh Boglárka , Szarka Gergely , Tengölics Ádám J. , Hoffmann Gyula , Völgyi Béla , Kovács-Öller Tamás
Published: September 2021

Vision is our primary sense as the human eye is the gateway for more than 65% of information reaching the human brain. Today’s increased exposure to different wavelengths and intensities of light from light emitting diode (LED) sources could induce retinal degeneration and accompanying neuronal cell death. Damage induced by chronic phototoxic reactions occurring in the retina accumulates over years and it has been suggested as being responsible for the etiology of many debilitating ocular conditions. In this work, we examined how LED stimulation affects vision by monitoring changes in the expression of death and survival factors as well as microglial activation in LED-induced damage (LID) of the retinal tissue. We found an LED-exposure-induced increase in the mRNA levels of major apoptosis-related markers BAX, Bcl-2, and Caspase-3 and accompanying widespread microglial and Caspase-3 activation. Everyday LED light exposure was accounted for in all the described changes in the retinal tissue of mice in this study, indicating that overuse of non-filtered direct LED light can have detrimental effects on the human retina as well.
Synthesis of Oxidized 3β,3′β-Disteryl Ethers and Search after High-Temperature Treatment of Sterol-Rich Samples
Authors: Zmysłowski Adam , Sitkowski Jerzy , Bus Katarzyna , Michalska Katarzyna , Szterk Arkadiusz
Published: September 2021

It was proven that sterols subjected to high-temperature treatment can be concatenated, which results in polymeric structures, e.g., 3β,3′β-disteryl ethers. However, it was also proven that due to increased temperature in oxygen-containing conditions, sterols can undergo various oxidation reactions. This study aimed to prove the existence and perform quantitative analysis of oxidized 3β,3′β-disteryl ethers, which could form during high-temperature treatment of sterol-rich samples. Samples were heated at 180, 200 and 220 °C for 0.5 to 4 h. Quantitative analyses of the oxidized 3β,3′β-disteryl ethers were performed with liquid extraction, solid-phase extraction and liquid chromatography coupled with mass spectrometry. Additionally, to perform this analysis, the appropriate standards of all oxidized 3β,3′β-disteryl ethers were prepared. Eighteen various oxidized 3β,3′β-disteryl ethers (derivatives of 3β,3′β-dicholesteryl ether, 3β,3′β-disitosteryl ether and 3β,3′β-distigmasteryl ether) were prepared. Additionally, the influence of metal compounds on the mechanism of ether formation at high temperatures was investigated.
Detecting and Mitigating Adversarial Examples in Regression Tasks: A Photovoltaic Power Generation Forecasting Case Study
Authors: Santana Everton Jose , Silva Ricardo Petri , Zarpelão Bruno Bogaz , Barbon Junior Sylvio
Published: September 2021

With data collected by Internet of Things sensors, deep learning (DL) models can forecast the generation capacity of photovoltaic (PV) power plants. This functionality is especially relevant for PV power operators and users as PV plants exhibit irregular behavior related to environmental conditions. However, DL models are vulnerable to adversarial examples, which may lead to increased predictive error and wrong operational decisions. This work proposes a new scheme to detect adversarial examples and mitigate their impact on DL forecasting models. This approach is based on one-class classifiers and features extracted from the data inputted to the forecasting models. Tests were performed using data collected from a real-world PV power plant along with adversarial samples generated by the Fast Gradient Sign Method under multiple attack patterns and magnitudes. One-class Support Vector Machine and Local Outlier Factor were evaluated as detectors of attacks to Long-Short Term Memory and Temporal Convolutional Network forecasting models. According to the results, the proposed scheme showed a high capability of detecting adversarial samples with an average F1-score close to 90%. Moreover, the detection and mitigation approach strongly reduced the prediction error increase caused by adversarial samples.
Tool for Measuring Productivity in Software Development Teams
Authors: Mota Jhemeson Silva , Tives Heloise Acco , Canedo Edna Dias
Published: September 2021

Despite efforts to define productivity, there is no consensus in the software industry regarding what the term productivity means and, instead of having only one metric or factor that describes productivity, it is defined by a set of aspects. Our objective is to develop a tool that supports the productivity measurement of software development teams according to the factors found in the literature. We divided these factors into four groups: People, Product, Organization, and Open Source Software Projects. We developed a web system containing the factors that influence productivity identified in this work, called Productive, to support software development teams in measuring their productivity. After developed the tool, we monitored its use over eight weeks with two small software development teams. From the results, we found that software development companies can use the system to support monitoring team productivity. The results also point to an improvement in productivity while using the system, and a survey applied to users demonstrates the users’ positive perception regarding the results obtained. In future work, we will monitor the use of the tool and investigate the users’ perceptions in other project contexts.
Small-Scale Production of Amblyseius tamatavensis with Thyreophagus cracentiseta (Acari: Phytoseiidae, Acaridae)
Authors: Massaro Marcela , Montrazi Matheus , Melo José Wagner S. , de Moraes Gilberto J.
Published: September 2021

Amblyseius tamatavensis, a predatory mite, has been mentioned as potentially useful for the control of Bemisia tabaci. The objective of this work was to compare the production rates of A. tamatavensis in closed units containing T. cracentiseta as food, at different combinations of numbers of predator inoculated, periods of production and volumes of rearing units. Final predator densities increased with increasing production periods up to 30–45 days, reducing afterward. Likewise, maximum final densities increased with increasing predator inoculation levels, up to 200 predators per rearing unit. The results led us to select the proportion of 150 predators per unit for a production period of 30 days to evaluate the effect of the size of the experimental unit. Then, in the second part of the study, a direct relationship was observed between volume and final predator density (y = 8610.25x + 2166.04; R2 = 0.99; p < 0.0001). It was also calculated that ri value was quite stable (0113–0.119), with a calculated value of 0.115 at all volumes of rearing units. It can be concluded that progressively larger numbers of predators can be obtained with progressively larger rearing units.
Gryllus bimaculatus Extract Protects against Lipopolysaccharide-Derived Inflammatory Response in Human Colon Epithelial Caco-2 Cells
Authors: Kim Kyong , Park Eun-Young , Baek Dong-Jae , Jang Se-Eun , Oh Yoon-Sin
Published: September 2021

Increased tight junction permeability and overproduction of proinflammatory cytokines are crucial pathophysiological mechanisms in inflammatory bowel disease (IBD). This study evaluated anti-inflammatory effects of aqueous ethanolic Gryllus bimaculatus extract (AE-GBE) against intestinal permeability on lipopolysaccharide (LPS)-treated Caco-2 cells. Treatment with AE-GBE increased cell viability and significantly reduced inflammatory mediators such as nitric oxide and LPS-induced reactive oxidative stress. LPS increased the expression levels of iNOS, Cox-2, and 4-hydroxylnonenal; however, these levels were attenuated by AE-GBE treatment. Moreover, the mRNA and protein expression levels of the inflammatory cytokines TNFα, IL-6, IL-1β, and IFNγ were increased by LPS, but were significantly reduced by AE-GBE treatment. Intestinal epithelial permeability and the related expression of the proteins Zoula ocludence-1, occludin, and claudin-1 was increased by LPS treatment, and this effect was significantly reduced by AE-GBE treatment. The reduction in AMPK phosphorylation in LPS-treated Caco-2 cells was reversed in activation by co-treatment with AE-GBE. In conclusion, AE-GBE can protect epithelial cells from LPS-induced impaired barrier integrity by increasing tight junction proteins and preventing various inflammatory mediators. Thus, AE-GBE has the potential to improve inflammation-related diseases, including IBD, by inhibiting excessive production of inflammation-inducing mediators.
Distribution and Molecular Diversity of Whitefly Species Colonizing Cassava in Kenya
Authors: Munguti Florence M. , Kilalo Dora C. , Nyaboga Evans N. , Wosula Everlyne N. , Macharia Isaac , Mwango’mbe Agnes W.
Published: September 2021

The whitefly, Bemisia tabaci (Gennadium, Hemiptera) has been reported to transmit viruses that cause cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) in many parts of sub-Saharan Africa (SSA). Currently, there is limited information on the distribution, species and haplotype composition of the whitefly populations colonizing cassava in Kenya. A study was conducted in the major cassava growing regions of Kenya to address this gap. Analyses of mitochondrial DNA cytochrome oxidase 1 (mtCO1) sequences revealed the presence of four distinct whitefly species: Bemisia tabaci, Bemisia afer, Aleurodicus dispersus and Paraleyrodes bondari in Kenya. The B. tabaci haplotypes were further resolved into SSA1, SSA2 and Indian Ocean (IO) putative species. The SSA1 population had three haplogroups of SSA1-SG1, SSA-SG2 and SSA1-SG3. Application of KASP genotyping grouped the Bemisia tabaci into two haplogroups namely sub-Saharan Africa East and Southern Africa (SSA-ESA) and sub-Saharan Africa East and Central Africa (SSA-ECA). The study presents the first report of P. bondari (Bondar’s nesting whitefly) on cassava in Kenya. Bemisia tabaci was widely distributed in all the major cassava growing regions in Kenya. The increased detection of different whitefly species on cassava and genetically diverse B. tabaci mitotypes indicates a significant influence on the dynamics of cassava virus epidemics in the field. The study highlights the need for continuous monitoring of invasive whitefly species population on cassava for timely application of management practices to reduce the impact of cassava viral diseases and prevent potential yield losses.
Clinical Impact of Preoperative Relief of Jaundice Following Endoscopic Retrograde Cholangiopancreatography on Determining Optimal Timing of Laparoscopic Cholecystectomy in Patients with Cholangitis
Authors: Paik Kyu-Hyun , Lee Yoon Suk , Park Won-Suk , Shin Yong Chan , Paik Woo Hyun
Published: September 2021

Background: About 10% of patients with gallbladder (GB) stones also have concurrent common bile duct (CBD) stones. Laparoscopic cholecystectomy (LC) after removal of CBD stones using endoscopic retrograde cholangiopancreatography (ERCP) is the most widely used method for treating coexisting gallbladder and common bile duct stones. We evaluated the optimal timing of LC after ERCP according to clinical factors, focusing on preoperative relief of jaundice. Methods: A total of 281 patients who underwent elective LC after ERCP because of choledocholithiasis and cholecystolithiasis from January 2010 to April 2018 were retrospectively reviewed. We compared the hospital stay, perioperative morbidity, and rate of surgical conversion to open cholecystectomy according to the relief of jaundice before surgery. These enrolled patients were divided into two groups: relief of jaundice before surgery (group 1, n = 125) or not (group 2, n = 156). Results: The initial total bilirubin level was higher in group 1; however, there were no significant differences in the other baseline characteristics including age, sex, American Society of Anesthesiologists score, previous surgical history, white blood cell count, C-reactive protein, and operative time between the two groups. There was also no significant difference in postoperative hospital stay between the two groups (4.5 ± 3.3 vs. 5.5 ± 5.6 days, p = 0.087). However, after ERCP, the waiting time until LC was significantly longer in group 1 (5.0 ± 4.9 vs. 3.5 ± 2.4 days, p < 0.001). There were no statistical differences in the conversion rate (3.2% vs. 3.8%, p = 0.518) or perioperative morbidity (4.0% vs. 5.8%, p = 0.348), either. Conclusions: LC would not be delayed until the relief of jaundice after ERCP since there were no significant differences in perioperative morbidity or surgical conversion rate to open cholecystectomy. Early LC after ERCP may be feasible and safe in patients with cholangitis and cholecystolithiasis.
Different Impact of Beta-Blockers on Long-Term Mortality in Heart Failure Patients with and without Chronic Obstructive Pulmonary Disease
Authors: Higuchi Satoshi , Kohno Takashi , Kohsaka Shun , Shiraishi Yasuyuki , Takei Makoto , Goda Ayumi , Shoji Satoshi , Nagatomo Yuji , Yoshikawa Tsutomu
Published: September 2021

The administration of beta-blockers is challenging and their efficacy is unclear in heart failure (HF) patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the association of beta-blockers with mortality in such patients. This multicenter observational cohort study included hospitalized HF patients with a left ventricular ejection fraction <50% and evaluated them retrospectively. COPD was diagnosed based on medical records and/or the clinical judgment of each investigator. The study endpoints were two-year all-cause, cardiac, and non-cardiac mortality. This study included 83 patients with COPD and 1760 patients without. Two-year all-cause, cardiac, and non-cardiac mortality were observed in 315 (17%), 149 (8%), and 166 (9%) patients, respectively. Beta-blockers were associated with lower all-cause mortality regardless of COPD (COPD: hazard ratio [HR] 0.39, 95% CI 0.16–0.98, p = 0.044; non-COPD: HR 0.62, 95% CI 0.46–0.83, p = 0.001). This association in HF patients with COPD persisted after multivariate analysis and inverse probability weighting and was due to lower non-cardiac mortality (HR 0.40, 95% CI 0.14–1.18. p = 0.098), not cardiac mortality (HR 0.37, 95% CI 0.07–2.01, p = 0.248). Beta-blockers were associated with lower all-cause mortality in HF patients with COPD due to lower non-cardiac mortality. This may reflect selection biases in beta-blocker prescription.
The Two-Step Treatment for Giant Hepatic Hemangiomas
Authors: Della Corte Angelo , Marino Rebecca , Ratti Francesca , Palumbo Diego , Guazzarotti Giorgia , Gusmini Simone , Augello Luigi , Cipriani Federica , Fiorentini Guido , Venturini Massimo , Aldrighetti Luca , De Cobelli Francesco
Published: September 2021

The aim of the present study is to analyze the feasibility and the impact of a two-step approach in the treatment of giant hemangiomas (GH) i.e., exceeding 10 cm in maximum diameter, consisting of transarterial embolization (TAE) followed by laparoscopic liver resection (LLR). Ten patients with 11 GH were treated with TAE and subsequent LLR between 2017 and 2020 (Group A). A matched cohort of 10 patients with GH treated with upfront LLR between 2014 and 2017 was identified for comparison (Group B). Data were analyzed regarding intraoperative and postoperative outcomes, including successful completion of LLR, morbidity, and mortality. Successful microparticle embolization of the GH-feeding arteries was performed in all patients in group A. In three cases a liquid embolic agent (Squid-18) was also injected to obtain complete embolization. No complications were observed after TAE. Successful surgery was performed after a mean time interval of 2.2 days from TAE without any case of conversion to laparotomy. Statistically significant differences between group A and group B were found in intraoperative blood loss (250 ± 200 vs. 400 ± 300 mL, p = 0.039), operative time (245 ± 60 vs. 420 ± 60 min, p = 0.027), and length of stay (5 ± 1 vs. 8 ± 2 days, p = 0.046). Our data suggest that two-step TAE + LLR might be a safe and effective option for surgical treatment of GH >10 cm.
Conservative Management of Uterine Fibroid-Related Heavy Menstrual Bleeding and Infertility: Time for a Deeper Mechanistic Understanding and an Individualized Approach
Authors: Dolmans Marie-Madeleine , Cacciottola Luciana , Donnez Jacques
Published: September 2021

(1) Background: Uterine fibroids are the most common form of benign uterine tumors, causing heavy menstrual bleeding (HMB), pelvic pain, infertility and pressure symptoms. Almost a third of women with uterine fibroids seek treatment. The objective of this review is to understand the mechanisms linking fibroids to these symptoms and evaluate different options for their management, particularly the place of gonadotropin-releasing hormone (GnRH) antagonist. (2) Methods: We gathered the most recent and relevant papers on the main fibroid-related symptoms and medical and surgical therapy for their treatment. Those reporting use of oral GnRH antagonists were investigated in detail. (3) Results: The mechanisms explaining myoma-related HMB and infertility were reviewed, as they are essential to a deeper mechanistic understanding and oriented approach. The choice of treatment depends on the number, size, and location of fibroids, and is guided by the patient’s age and desire to preserve her fertility. Economic impacts of myomas in terms of direct costs, lost workdays, and complications were found to be significant. Medical, surgical, and non-surgical strategies were analyzed in this context. Novel medical approaches with GnRH antagonist were explored and found to represent an effective new option. (4) Conclusion: The need for alternatives to surgical intervention is very real, especially for women seeking to preserve their fertility. New options now exist, with GnRH antagonists proven to treat fibroid symptoms effectively, opening the door to novel strategies for the management of myomas.
Contemporary Pillars of Heart Failure with Reduced Ejection Fraction Medical Therapy
Authors: Rahamim Eldad , Nachman Dean , Yagel Oren , Yarkoni Merav , Elbaz-Greener Gabby , Amir Offer , Asleh Rabea
Published: September 2021

Heart failure with reduced ejection fraction (HFrEF) is a clinical condition associated with cardiac contractility impairment. HFrEF is a significant public health issue with a high morbidity and mortality burden. Pathological left ventricular (LV) remodeling and progressive dilatation are hallmarks of HFrEF pathogenesis, ultimately leading to adverse clinical outcomes. Therefore, cardiac remodeling attenuation has become a treatment goal and a standard of care over the last three decades. Guideline-directed medical therapy mainly targeting the sympathetic nervous system and the renin–angiotensin–aldosterone system (RAAS) has led to improved survival and a reduction in HF hospitalization in this population. More recently, novel pharmacological therapies targeting other pathways implicated in the pathophysiology of HFrEF have emerged at an exciting rate, with landmark clinical trials demonstrating additive clinical benefits in patients with HFrEF. Among these novel therapies, angiotensin receptor–neprilysin inhibitors (ARNI), sodium–glucose cotransporter-2 inhibitors (SGLT2i), vericiguat (a novel oral guanylate cyclase stimulator), and omecamtiv mecarbil (a selective cardiac myosin activator) have shown improved clinical benefit when added to the traditional standard-of-care medical therapy in HFrEF. These new comprehensive data have led to a remarkable change in the medical therapy paradigm in the setting of HFrEF. This article will review the pivotal studies involving these novel agents and present a suggestive paradigm of pharmacological therapy representing the 2021 European Society of Cardiology (ESC) guidelines for the treatment of chronic HFrEF.
Reduction Mammoplasty: A Ten-Year Retrospective Review of the Omega Resection Pattern Technique
Authors: Viscardi Juan A. , Oranges Carlo M. , Schaefer Dirk J. , Kalbermatten Daniel F.
Published: September 2021

Reduction mammoplasty is the gold standard procedure for symptomatic breast hypertrophy and it is also used for contralateral breast symmetrisation following breast cancer surgery. We aim at introducing a new procedure, which uses an omega resection pattern to simplify the inferior pedicle breast resection technique. A retrospective review of all patients who underwent the omega resection reduction mammoplasty at the University Hospital of Basel between 2010 and 2020 was carried out. We collected patient demographics, surgical outcomes, operation time, type and frequency of complications at 12 months follow-up. Outcomes were compared with the most commonly used techniques. Additionally, we assessed if patients’ and clinical characteristics augmented/diminished the complication rate. During the study period, 67 reduction mammaplasties were performed by a senior plastic surgeon (Mage = 42.5, SDage = 15.6; MBMI = 27.28, SDBMI = 3.4; 20% smokers). The average tissue removed was 826 g (ranging from 15 to 2307 g). In 10 breasts (15%) occurred minor complications. No major complications were reported. Operation time (M = 149 min; ranging from 87 to 270 min) was significantly shorter than the inferior, superomedial, and superior pedicle techniques. Univariate Odd Ratios showed that no-smoker status, a BMI in a normal range, resection weight between 500 g to 1500 g, NTN distance < 30 cm, removal of drains one day after the operation, ASA index of 2, inpatient clinic hospitalisation, and not undergoing other concomitant surgical operations were protective factors against the risk to develop complications. The omega resection pattern technique demonstrated to be an effective, safe, and fast mammoplasty reduction procedure for bilateral macromastia and unilateral symmetrizing procedures, even for large breasts, able to be adopted as a new valid alternative to the existing ones.