bluuebunny/crossref_metadata_2025 huggingface dataset:
The Expanding Role of Alternative Splicing in Vascular Smooth Muscle Cell Plasticity
Authors: Green Immanuel D. , Liu Renjing , Wong Justin J. L.
Published: September 2021

Vascular smooth muscle cells (VSMCs) display extraordinary phenotypic plasticity. This allows them to differentiate or dedifferentiate, depending on environmental cues. The ability to ‘switch’ between a quiescent contractile phenotype to a highly proliferative synthetic state renders VSMCs as primary mediators of vascular repair and remodelling. When their plasticity is pathological, it can lead to cardiovascular diseases such as atherosclerosis and restenosis. Coinciding with significant technological and conceptual innovations in RNA biology, there has been a growing focus on the role of alternative splicing in VSMC gene expression regulation. Herein, we review how alternative splicing and its regulatory factors are involved in generating protein diversity and altering gene expression levels in VSMC plasticity. Moreover, we explore how recent advancements in the development of splicing-modulating therapies may be applied to VSMC-related pathologies.
MiR-125a-3p and MiR-320b Differentially Expressed in Patients with Chronic Myeloid Leukemia Treated with Allogeneic Hematopoietic Stem Cell Transplantation and Imatinib Mesylate
Authors: Martins Juliana R. B. , Moraes Leonardo N. , Cury Sarah S. , Capannacci Juliana , Carvalho Robson Francisco , Nogueira Célia Regina , Hokama Newton Key , Hokama Paula O. M.
Published: September 2021

Chronic myeloid leukemia (CML), a hematopoietic neoplasm arising from the fusion of BCR (breakpoint cluster region) gene on chromosome 22 to the ABL (Abelson leukemia virus) gene on chromosome 9 (BCR-ABL1 oncogene), originates from a small population of leukemic stem cells with extensive capacity for self-renewal and an inflammatory microenvironment. Currently, CML treatment is based on tyrosine kinase inhibitors (TKIs). However, allogeneic hematopoietic stem cell transplantation (HSCT-allo) is currently the only effective treatment of CML. The difficulty of finding a compatible donor and high rates of morbidity and mortality limit transplantation treatment. Despite the safety and efficacy of TKIs, patients can develop resistance. Thus, microRNAs (miRNAs) play a prominent role as biomarkers and post-transcriptional regulators of gene expression. The aim of this study was to analyze the miRNA profile in CML patients who achieved cytogenetic remission after treatment with both HSCT-allo and TKI. Expression analyses of the 758 miRNAs were performed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Bioinformatics tools were used for data analysis. We detected miRNA profiles using their possible target genes and target pathways. MiR-125a-3p stood out among the downregulated miRNAs, showing an interaction network with 52 target genes. MiR-320b was the only upregulated miRNA, with an interaction network of 26 genes. The results are expected to aid future studies of miRNAs, residual leukemic cells, and prognosis in CML.
Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma
Authors: Hafezi Shirin , Saber-Ayad Maha , Abdel-Rahman Wael M.
Published: September 2021

The most frequent mutated oncogene family in the history of human cancer is the RAS gene family, including NRAS, HRAS, and, most importantly, KRAS. A hallmark of pancreatic cancer, recalcitrant cancer with a very low survival rate, is the prevalence of oncogenic mutations in the KRAS gene. Due to this fact, studying the function of KRAS and the impact of its mutations on the tumor microenvironment (TME) is a priority for understanding pancreatic cancer progression and designing novel therapeutic strategies for the treatment of the dismal disease. Despite some recent enlightening studies, there is still a wide gap in our knowledge regarding the impact of KRAS mutations on different components of the pancreatic TME. In this review, we will present an updated summary of mutant KRAS role in the initiation, progression, and modulation of the TME of pancreatic ductal adenocarcinoma (PDAC). This review will highlight the intriguing link between diabetes mellitus and PDAC, as well as vitamin D as an adjuvant effective therapy via TME modulation of PDAC. We will also discuss different ongoing clinical trials that use KRAS oncogene signaling network as therapeutic targets.
Comparative Analysis of Genome Editors Efficiency on a Model of Mice Zygotes Microinjection
Authors: Averina Olga A. , Permyakov Oleg A. , Grigorieva Olga O. , Starshin Alexey S. , Mazur Alexander M. , Prokhortchouk Egor B. , Dontsova Olga A. , Sergiev Petr V.
Published: September 2021

Genome editing is an indispensable tool for functional genomics. The caveat of the genome-editing pipeline is a prevalence of error-prone non-homologous end joining over homologous recombination, while only the latter is suitable to introduce particularly desired genetic variants. To overcome this problem, a toolbox of genome engineering was appended by a variety of improved instruments. In this work, we compared the efficiency of a number of recently suggested improved systems for genome editing applied to the same genome regions on a murine zygote model via microinjection. As a result, we observed that homologous recombination utilizing an ssDNA template following sgRNA directed Cas9 cleavage is still the method of choice for the creation of animals with precise genome alterations.
Sex-Specific Differences in Lysine, 3-Hydroxybutyric Acid and Acetic Acid in Offspring Exposed to Maternal and Postnatal High Linoleic Acid Diet, Independent of Diet
Authors: Shrestha Nirajan , Melvin Steven D , McKeating Daniel R. , Holland Olivia J. , Cuffe James S. M. , Perkins Anthony V. , McAinch Andrew J. , Hryciw Deanne H.
Published: September 2021

Background: Linoleic acid (LA) is an essential polyunsaturated fatty acid (PUFA) that is required for foetal growth and development. Excess intake of LA can be detrimental for metabolic health due to its pro-inflammatory properties; however, the effect of a diet high in LA on offspring metabolites is unknown. In this study, we aimed to determine the role of maternal or postnatal high linoleic acid (HLA) diet on plasma metabolites in adult offspring. Methods: Female Wistar Kyoto (WKY) rats were fed with either low LA (LLA) or HLA diet for 10 weeks prior to conception and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), treated with either LLA or HLA diets and sacrificed at PN180. Metabolite analysis was performed in plasma samples using Nuclear Magnetic Resonance. Results: Maternal and postnatal HLA diet did not alter plasma metabolites in male and female adult offspring. There was no specific clustering among different treatment groups as demonstrated by principal component analysis. Interestingly, there was clustering among male and female offspring independent of maternal and postnatal dietary intervention. Lysine was higher in female offspring, while 3-hydroxybutyric acid and acetic acid were significantly higher in male offspring. Conclusion: In summary, maternal or postnatal HLA diet did not alter the plasma metabolites in the adult rat offspring; however, differences in metabolites between male and female offspring occurred independently of dietary intervention.
Biodegradability of Novel Polylactide and Polycaprolactone Materials with Bacteriostatic Properties Due to Embedded Birch Tar in Different Environments
Authors: Richert Agnieszka , Kalwasińska Agnieszka , Brzezinska Maria Swiontek , Dąbrowska Grażyna B.
Published: September 2021

The microbial biodegradation of new PLA and PCL materials containing birch tar (1–10% v/v) was investigated. Product of dry distillation of birch bark (Betula pendula Roth) was added to polymeric materials to obtain films with antimicrobial properties. The subject of the study was the course of enzymatic degradation of a biodegradable polymer with antibacterial properties. The results show that the type of the material, tar concentration, and the environment influenced the hydrolytic activity of potential biofilm degraders. In the presence of PCL films, the enzyme activities were higher (except for α-D-glucosidase) compared to PLA films. The highest concentration of birch tar (10% v/v) decreased the activity of hydrolases produced by microorganisms to the most significant extent; however, SEM analysis showed the presence of a biofilm even on plastics with the highest tar content. Based on the results of the biological oxygen demand (BOD), the new materials can be classified as biodegradable but, the biodegradation process was less efficient when compared to plastics without the addition of birch tar.
Ganoderic Acids Prevent Renal Ischemia Reperfusion Injury by Inhibiting Inflammation and Apoptosis
Authors: Shao Guangying , He Jinzhao , Meng Jia , Ma Ang , Geng Xiaoqiang , Zhang Shun , Qiu Zhiwei , Lin Dongmei , Li Min , Zhou Hong , Lin Shuqian , Yang Baoxue
Published: September 2021

Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury (AKI), which can lead to acute renal failure. The development of RIRI is so complicated that it involves many factors such as inflammatory response, oxidative stress and cell apoptosis. Ganoderic acids (GAs), as one of the main pharmacological components of Ganoderma lucidum, have been reported to possess anti-inflammatory, antioxidant, and other pharmacological effects. The study is aimed to investigate the protective effect of GAs on RIRI and explore related underlying mechanisms. The mechanisms involved were assessed by a mouse RIRI model and a hypoxia/reoxygenation model. Compared with sham-operated group, renal dysfunction and morphological damages were relieved markedly in GAs-pretreatment group. GAs pretreatment could reduce the production of pro-inflammatory factors such as IL-6, COX-2 and iNOS induced by RIRI through inhibiting TLR4/MyD88/NF-kB signaling pathway. Furthermore, GAs reduced cell apoptosis via the decrease of the ratios of cleaved caspase-8 and cleaved caspase-3. The experimental results suggest that GAs prevent RIRI by alleviating tissue inflammation and apoptosis and might be developed as a candidate drug for preventing RIRI-induced AKI.
Recent Advances in the Discovery and Function of Antimicrobial Molecules in Platelets
Authors: Aquino-Domínguez Alba S. , Romero-Tlalolini María de los A. , Torres-Aguilar Honorio , Aguilar-Ruiz Sergio R.
Published: September 2021

The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a crucial role in responding against microorganisms. Activated platelets release molecules with antimicrobial activity. This ability was first demonstrated in rabbit serum after coagulation and later in rabbit platelets stimulated with thrombin. Currently, multiple discoveries have allowed the identification and characterization of PMPs (platelet microbicidal proteins) and opened the way to identify kinocidins and CHDPs (cationic host defense peptides) in human platelets. These molecules are endowed with microbicidal activity through different mechanisms that broaden the platelet participation in normal and pathologic conditions. Therefore, this review aims to integrate the currently described platelet molecules with antimicrobial properties by summarizing the pathways towards their identification, characterization, and functional evaluation that have promoted new avenues for studying platelets based on kinocidins and CHDPs secretion.
Regulation of ER Composition and Extent, and Putative Action in Protein Networks by ER/NE Protein TMEM147
Authors: Maimaris Giannis , Christodoulou Andri , Santama Niovi , Lederer Carsten Werner
Published: September 2021

Nuclear envelope (NE) and endoplasmic reticulum (ER) collaborate to control a multitude of nuclear and cytoplasmic actions. In this context, the transmembrane protein TMEM147 localizes to both NE and ER, and through direct and indirect interactions regulates processes as varied as production and transport of multipass membrane proteins, neuronal signaling, nuclear-shape, lamina and chromatin dynamics and cholesterol synthesis. Aiming to delineate the emerging multifunctionality of TMEM147 more comprehensively, we set as objectives, first, to assess potentially more fundamental effects of TMEM147 on the ER and, second, to identify significantly TMEM147-associated cell-wide protein networks and pathways. Quantifying curved and flat ER markers RTN4 and CLIMP63/CKAP4, respectively, we found that TMEM147 silencing causes area and intensity increases for both RTN4 and CLIMP63, and the ER in general, with a profound shift toward flat areas, concurrent with reduction in DNA condensation. Protein network and pathway analyses based on comprehensive compilation of TMEM147 interactors, targets and co-factors then served to manifest novel and established roles for TMEM147. Thus, algorithmically simplified significant pathways reflect TMEM147 function in ribosome binding, oxidoreductase activity, G protein-coupled receptor activity and transmembrane transport, while analysis of protein factors and networks identifies hub proteins and corresponding pathways as potential targets of TMEM147 action and of future functional studies.
Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome
Authors: Lee Paul , Yim Rita , Yung Yammy , Chu Hiu-Tung , Yip Pui-Kwan , Gill Harinder
Published: September 2021

Myelodysplastic syndrome (MDS) is a heterogeneous, clonal hematological disorder characterized by ineffective hematopoiesis, cytopenia, morphologic dysplasia, and predisposition to acute myeloid leukemia (AML). Stem cell genomic instability, microenvironmental aberrations, and somatic mutations contribute to leukemic transformation. The hypomethylating agents (HMAs), azacitidine and decitabine are the standard of care for patients with higher-risk MDS. Although these agents induce responses in up to 40–60% of patients, primary or secondary drug resistance is relatively common. To improve the treatment outcome, combinational therapies comprising HMA with targeted therapy or immunotherapy are being evaluated and are under continuous development. This review provides a comprehensive update of the molecular pathogenesis and immune-dysregulations involved in MDS, mechanisms of resistance to HMA, and strategies to overcome HMA resistance.
Current Biomaterial-Based Bone Tissue Engineering and Translational Medicine
Authors: Qi Jingqi , Yu Tianqi , Hu Bangyan , Wu Hongwei , Ouyang Hongwei
Published: September 2021

Bone defects cause significant socio-economic costs worldwide, while the clinical “gold standard” of bone repair, the autologous bone graft, has limitations including limited graft supply, secondary injury, chronic pain and infection. Therefore, to reduce surgical complexity and speed up bone healing, innovative therapies are needed. Bone tissue engineering (BTE), a new cross-disciplinary science arisen in the 21st century, creates artificial environments specially constructed to facilitate bone regeneration and growth. By combining stem cells, scaffolds and growth factors, BTE fabricates biological substitutes to restore the functions of injured bone. Although BTE has made many valuable achievements, there remain some unsolved challenges. In this review, the latest research and application of stem cells, scaffolds, and growth factors in BTE are summarized with the aim of providing references for the clinical application of BTE.
The Combination of Abscisic Acid (ABA) and Water Stress Regulates the Epicuticular Wax Metabolism and Cuticle Properties of Detached Citrus Fruit
Authors: Romero Paco , Lafuente María Teresa
Published: September 2021

The phytohormone abscisic acid (ABA) is a major regulator of fruit response to water stress, and may influence cuticle properties and wax layer composition during fruit ripening. This study investigates the effects of ABA on epicuticular wax metabolism regulation in a citrus fruit cultivar with low ABA levels, called Pinalate (Citrus sinensis L. Osbeck), and how this relationship is influenced by water stress after detachment. Harvested ABA-treated fruit were exposed to water stress by storing them at low (30–35%) relative humidity. The total epicuticular wax load rose after fruit detachment, which ABA application decreased earlier and more markedly during fruit-dehydrating storage. ABA treatment changed the abundance of the separated wax fractions and the contents of most individual components, which reveals dependence on the exposure to postharvest water stress and different trends depending on storage duration. A correlation analysis supported these responses, which mostly fitted the expression patterns of the key genes involved in wax biosynthesis and transport. A cluster analysis indicated that storage duration is an important factor for the exogenous ABA influence and the postharvest environment on epicuticular wax composition, cuticle properties and fruit physiology. Dynamic ABA-mediated reconfiguration of wax metabolism is influenced by fruit exposure to water stress conditions.
Retinal Organoid Technology: Where Are We Now?
Authors: Zhang Zuming , Xu Zihui , Yuan Fa , Jin Kangxin , Xiang Mengqing
Published: September 2021

It is difficult to regenerate mammalian retinal cells once the adult retina is damaged, and current clinical approaches to retinal damages are very limited. The introduction of the retinal organoid technique empowers researchers to study the molecular mechanisms controlling retinal development, explore the pathogenesis of retinal diseases, develop novel treatment options, and pursue cell/tissue transplantation under a certain genetic background. Here, we revisit the historical background of retinal organoid technology, categorize current methods of organoid induction, and outline the obstacles and potential solutions to next-generation retinal organoids. Meanwhile, we recapitulate recent research progress in cell/tissue transplantation to treat retinal diseases, and discuss the pros and cons of transplanting single-cell suspension versus retinal organoid sheet for cell therapies.
Transgenic Expression of Bmp3b in Mesenchymal Progenitors Mitigates Age-Related Muscle Mass Loss and Neuromuscular Junction Degeneration
Authors: Kurosawa Tamaki , Minato Keitaro , Ikemoto-Uezumi Madoka , Hino Jun , Tsuchida Kunihiro , Uezumi Akiyoshi
Published: September 2021

Skeletal muscle is a vital organ for a healthy life, but its mass and function decline with aging, resulting in a condition termed sarcopenia. The etiology of sarcopenia remains unclear. We recently demonstrated that interstitial mesenchymal progenitors are essential for homeostatic muscle maintenance, and a diminished expression of the mesenchymal-specific gene Bmp3b is associated with sarcopenia. Here, we assessed the protective function of Bmp3b against sarcopenia by generating conditional transgenic (Tg) mice that enable a forced expression of Bmp3b specifically in mesenchymal progenitors. The mice were grown until they reached the geriatric stage, and the age-related muscle phenotypes were examined. The Tg mice had significantly heavier muscles compared to control mice, and the type IIB myofiber cross-sectional areas were preserved in Tg mice. The composition of the myofiber types did not differ between the genotypes. The Tg mice showed a decreasing trend of fibrosis, but the degree of fat infiltration was as low as that in the control mice. Finally, we observed the preservation of innervated neuromuscular junctions (NMJs) in the Tg muscle in contrast to the control muscle, where the NMJ degeneration was conspicuous. Thus, our results indicate that the transgenic expression of Bmp3b in mesenchymal progenitors alleviates age-related muscle deterioration. Collectively, this study strengthens the beneficial role of mesenchymal Bmp3b against sarcopenia and suggests that preserving the youthfulness of mesenchymal progenitors may be an effective means of combating sarcopenia.
The E3 Ubiquitin Ligase NEDD4-1 Mediates Temozolomide-Resistant Glioblastoma through PTEN Attenuation and Redox Imbalance in Nrf2–HO-1 Axis
Authors: Chuang Hao-Yu , Hsu Li-Yun , Pan Chih-Ming , Pikatan Narpati Wesa , Yadav Vijesh Kumar , Fong Iat-Hang , Chen Chao-Hsuan , Yeh Chi-Tai , Chiu Shao-Chih
Published: September 2021

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. It is highly resistant to chemotherapy, and tumor recurrence is common. Neuronal precursor cell-expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ligase that controls embryonic development and animal growth. NEDD4-1 regulates the tumor suppressor phosphatase and tensin homolog (PTEN), one of the major regulators of the PI3K/AKT/mTOR signaling axis, as well as the response to oxidative stress. Methods: The expression levels of NEDD4-1 in GBM tissues and different cell lines were determined by quantitative real-time polymerase chain reaction and immunohistochemistry. In vitro and in vivo assays were performed to explore the biological effects of NEDD4-1 on GBM cells. Temozolomide (TMZ)-resistant U87MG and U251 cell lines were specifically established to determine NEDD4-1 upregulation and its effects on the tumorigenicity of GBM cells. Subsequently, miRNA expression in TMZ-resistant cell lines was investigated to determine the dysregulated miRNA underlying the overexpression of NEDD4-1. Indole-3-carbinol (I3C) was used to inhibit NEDD4-1 activity, and its effect on chemoresistance to TMZ was verified. Results: NEDD4-1 was significantly overexpressed in the GBM and TMZ-resistant cells and clinical samples. NEDD4-1 was demonstrated to be a key oncoprotein associated with TMZ resistance, inducing oncogenicity and tumorigenesis of TMZ-resistant GBM cells compared with TMZ-responsive cells. Mechanistically, TMZ-resistant cells exhibited dysregulated expression of miR-3129-5p and miR-199b-3p, resulting in the induced NEDD4-1 mRNA-expression level. The upregulation of NEDD4-1 attenuated PTEN expression and promoted the AKT/NRF2/HO-1 oxidative stress signaling axis, which in turn conferred amplified defense against reactive oxygen species (ROS) and eventually higher resistance against TMZ treatment. The combination treatment of I3C, a known inhibitor of NEDD4-1, with TMZ resulted in a synergistic effect and re-sensitized TMZ-resistant tumor cells both in vitro and in vivo. Conclusions: These findings demonstrate the critical role of NEDD4-1 in regulating the redox imbalance in TMZ-resistant GBM cells via the degradation of PTEN and the upregulation of the AKT/NRF2/HO-1 signaling pathway. Targeting this regulatory axis may help eliminate TMZ-resistant glioblastoma.
Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders
Authors: Sukhorukov Vladimir , Voronkov Dmitry , Baranich Tatiana , Mudzhiri Natalia , Magnaeva Alina , Illarioshkin Sergey
Published: September 2021

Aging is associated with a decline in cognitive function, which can partly be explained by the accumulation of damage to the brain cells over time. Neurons and glia undergo morphological and ultrastructure changes during aging. Over the past several years, it has become evident that at the cellular level, various hallmarks of an aging brain are closely related to mitophagy. The importance of mitochondria quality and quantity control through mitophagy is highlighted by the contribution that defects in mitochondria–autophagy crosstalk make to aging and age-related diseases. In this review, we analyze some of the more recent findings regarding the study of brain aging and neurodegeneration in the context of mitophagy. We discuss the data on the dynamics of selective autophagy in neurons and glial cells during aging and in the course of neurodegeneration, focusing on three mechanisms of mitophagy: non-receptor-mediated mitophagy, receptor-mediated mitophagy, and transcellular mitophagy. We review the role of mitophagy in neuronal/glial homeostasis and in the molecular pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and other disorders. Common mechanisms of aging and neurodegeneration that are related to different mitophagy pathways provide a number of promising targets for potential therapeutic agents.
Leveraging Aviation Risk Models to Combat Cybersecurity Threats in Vehicular Networks
Authors: Ebert Jonathan , Newton Ohad , O’Rear Jeffery , Riley Scott , Park Jaehong , Gupta Maanak
Published: September 2021

The rapidly developing technology and lack of standards in the transportation industry for the proposed Vehicle-to-Vehicle (V2V), Vehicle-to-Infrastructure (V2I), and Vehicle-to-Everything (V2X) networks, which all vehicles will operate under, drives concern about information validity and authenticity due to the risk of erroneous or malicious information being injected into a vehicular network (VN). In this paper, we apply a risk management process to a vehicular network that will identify hazards and possible controls that can lower their risk. After researching and reviewing various technologies along with several risk models, we have developed a basic framework for assessing and assigning risk through a phased method that leads to input for our developed model.
Information Content Measurement of ESG Factors via Entropy and Its Impact on Society and Security
Authors: Hassani Hossein , Unger Stephan , Entezarian Mohammad Reza
Published: September 2021

We conducted a singular and sectoral vulnerability assessment of ESG factors of Dow-30-listed companies by applying the entropy weight method and analyzing each ESG factor’s information contribution to the overall ESG disclosure score. By reducing information entropy information, weaknesses in the structure of a socio-technological system can be identified and improved. The relative information gain of each indicator improves proportionally to the reduction in entropy. The social pillar contains the most crucial information, followed by the environmental and governance pillars, relative to each other. The difference between the social and economic pillars was found to be statistically not significant, while the differences between the social pillar, respective to the economic and governance pillars were statistically significant. This suggests noisy information content of the governance pillar, indicating improvement potential in governance messaging. Moreover, we found that companies with lean and flexible governance structures are more likely to convey information content better. We also discuss the impact of ESG measures on society and security.
Anatomy and Ultrastructure of Galls Induced by Neuroterus quercusbaccarum (Hymenoptera: Cynipidae) on Oak Leaves (Quercus robur)
Authors: Jankiewicz Leszek Stanisław , Guzicka Marzenna , Marasek-Ciolakowska Agnieszka
Published: September 2021

The structure and ultrastructure of two developmental stages of the spangle gall induced by Neuroterus quercusbaccarum (Hymenoptera, Cynipidae) were investigated using light microscopy (LM), fluorescence microscopy (FM), and transmission (TEM) and scanning (SEM) electron microscopy. The general design of the gall structure was typical of Cynipidae, but some structural features distinguished the spangle gall. Previously undescribed, characteristic multicellular epidermal protuberances with large openings were observed in autumn on the surface of galls. These may facilitate the gas exchange between the atmosphere and the inside of the gall, thus assisting larval respiration. The larval chamber is surrounded by both a sclerenchymatous capsule and numerous cells containing calcium oxalate crystals that may both serve as protective barriers. In young galls, the nutritive tissue is a wall-less protoplasmic mass, potentially easily accessible to young larvae with delicate mandibles. Cell walls only develop at a later stage. The nutritive tissue was found to be rich in proteins and lipids, but starch grains were not observed. Cellular topology suggests that spangle galls grow by anticlinal division of marginal epidermal cells and periclinal division of subepidermal cells. Cellular proliferation (hyperplasia) also occurs in the leaf tissue near the connection with the gall peduncle, which eventually lignifies.
Characterizing the Spatiotemporal Distribution of Three Native Stink Bugs (Hemiptera: Pentatomidae) across an Agricultural Landscape
Authors: Grabarczyk Erin E. , Cottrell Ted E. , Tillman Glynn
Published: September 2021

Stink bugs (Hemiptera: Pentatomidae) are polyphagous pests that cause significant economic losses to a variety of crops. Although many species have been documented to aggregate within agricultural fields, much less is known regarding the timing and distribution of adults and nymphs within and between surrounding non-crop habitat. Therefore, we explored the spatiotemporal distribution of Euschistus servus (Say), Euschistus tristigmus (Say), and Chinavia hilaris (Say), three species of North American origin, and examined whether distribution patterns varied between species according to habitat. Stink bugs were monitored weekly for three years within an 18 km2 grid of pheromone-baited traps. We tested whether habitat affected distribution patterns, used spatial analysis by distance indices (SADIE) to identify aggregations, and visualized distributions with interpolated maps. Overall, E. servus adults were captured in crops, whereas E. tristigmus adults and nymphs were mainly captured in forests. Accordingly, distribution patterns of E. tristigmus were relatively stable over time, whereas aggregations of adult E. servus varied over space, and the timing of aggregations reflected the phenology of major crops. Chinavia hilaris was most often captured in forest, followed by crop habitat. Pest management strategies for stink bugs may require an area-based management approach that accounts for movement in agricultural fields and surrounding habitat.
Effects of Constant versus Fluctuating Temperatures on Fitness Indicators of the Aphid Dysaphis plantaginea and the Parasitoid Aphidius matricariae
Authors: Tougeron Kévin , Ferrais Louise , Renard Marie-Eve , Hance Thierry
Published: September 2021

Testing fluctuating rather than constant temperatures is likely to produce more realistic datasets, as they are ecologically more similar to what arthropods experience in nature. In this study, we evaluated the impact of three constant thermal regimes (7, 12, and 17 °C) and one fluctuating thermal regime (7–17 °C with a mean of 12 °C) on fitness indicators in the rosy apple aphid Dysaphis plantaginea, a major pest of apple orchards, and the parasitoid Aphidius matricariae, one of its natural enemies used in mass release biological control strategies. For some—but not all—traits, the fluctuating 7–17 °C regime was beneficial to insects compared to the constant 12 °C regime. Both aphid and parasitoid development times were shortened under the fluctuating regime, and there was a clear trend towards an increased longevity under the fluctuating regime. The fecundity, mass, and size were affected by the mean temperature, but only the mass of aphids was higher at 7–17 °C than at a constant 12 °C. Parasitism rates, but not emergence rates, were higher under the fluctuating regime than under the constant 12 °C regime. Results are discussed within the framework of insect thermal ecology and Jensen’s inequality. We conclude that incorporating thermal fluctuations in ecological studies could allow for the more accurate consideration of how temperature affects host–parasitoid interactions and insect responses to temperature change over time.
Pollination in the Rainforest: Scarce Visitors and Low Effective Pollinators Limit the Fruiting Success of Tropical Orchids
Authors: Reyes Hortensia Cabrera , Draper David , Marques Isabel
Published: September 2021

A single plant might be visited by many flower visitors but not all might act as pollinators. Legitimate pollinators might also differ considerably in their efficiency, limiting pollination success. Unsuitable climatic conditions such as rain also affect pollinator activity. However, in the evergreen rainforest there is no prolonged dry season and flowering occurs usually under rain. Here, we explore the dependence on pollinators and the efficiency of flower visitors for the fruiting success of 10 Andean rainforest orchids. All species were self-compatible but strictly pollinator-dependent. Overall, we found low levels of fruit set in control flowers while experimental geitonogamous and cross-pollinations increased fruit set, revealing extensive pollination limitation in all populations. Seed viability dropped considerably after self and geitonogamous pollinations suggesting the possibility of early-acting inbreeding depression. Even though we monitored flower visitors on an extensive survey, few visitors were seen in these species and even fewer acted as legitimate pollinators. Thus, even though orchid pollination might be extremely diversified, these results show that few visitors are pollinating these species, explaining the low levels of fruit set recorded in the area studied.
Improvement in Metabolic Co-Morbidities after Implantation of CardioMEMS in Patients with Heart Failure with Preserved Ejection Fraction Phenotype
Authors: Alam Amit , Van Zyl Johanna , Nayyar Navdeep , Hall Shelley , Jermyn Rita
Published: September 2021

Background: Heart failure with preserved ejection fraction (HFpEF) patients often have other comorbidities, including obesity, dyslipidemia, hypertension, and diabetes, comprising the metabolic syndrome. The impacts of hemodynamic monitoring via CardioMEMS on these co-morbidities remain unknown. Methods: A retrospective analysis of 29 patients with HFpEF (EF 45% or greater) and CardioMEMS was performed at a single center. Weight, body mass index (BMI), systolic blood pressures (SBP), high-density lipoprotein (HDL), triglycerides (TGL), hemoglobin A1C (HbA1c), and pulmonary artery diastolic pressures (PADP) were assessed at baseline and six months post-implant. Paired t-tests and the Wilcoxon signed-rank test were used, as appropriate, to test differences between time points. Results: These patients were 69% female, with a mean age of 73 years, and 62% had non-ischaemic cardiomyopathies (NICM). At the time of CardioMEMS implantation, average PADP was 20.1 mmHg ± 5.7, weight was 102.6 kg ± 22.7, BMI was 38.0 kg/m2 ± 8.3, SBP was 135 mmHg ± 19, HDL was 42.4 mg/dL ± 11.3, and median TGL was 130 mg/dL (100, 180). At six months we witnessed a decrease by 20.9% in PADP to 15.9 mmHg ± 5.8, (p < 0.001). In addition, the following was noted: weight decreased by 2.5% to 100.0 kg ± 23.2, (p = 0.006), BMI reduced by 2.6% to 37.0 ± 8.2, (p = 0.002), SBP decreased by 6.7% to 126 mmHg ± 16 (p < 0.001), HDL increased by 10.8% to 47 mg/dL ± 11.9 (p < 0.001), and TGL decreased by 15.4% to 110 mg/dL (105, 135) (p = 0.001). 62% of patients were diabetic with no significant improvements in HbA1C values at the 6-month follow-up. Conclusion: The utilization of CardioMEMS to optimize PADP results in an improvement in the comorbidities associated with the metabolic syndrome. Further studies are warranted to validate these findings and delineate clinical significance.
Treatment of Meatal Strictures by Dorsal Inlay Oral Mucosa Graft Urethroplasty: A Single-Center Experience
Authors: Wirtz Michel , Claeys Wietse , Francois Philippe , Waterloos Marjan , Waterschoot Mieke , Lumen Nicolaas
Published: September 2021

Background: To report on the use of oral mucosa graft urethroplasty for meatal strictures using the dorsal inlay technique. Methods: Patients who underwent a single-stage dorsal inlay oral mucosal graft urethroplasty between January 2000 and May 2021 were included in this study. A follow-up of a minimum of 12 months was necessary for inclusion. Exclusion criteria were stricture extension into the penile urethra, concomitant stricture at another location, flap urethroplasty for a meatal stricture, dorsal inlay urethroplasty with another type of graft, ventral onlay graft urethroplasty or staged urethroplasty. Recurrence was defined by the inability to pass a 14F metal sound through the reconstructed meatus irrespective of patients’ complaints. Results: Our study cohort included 40 patients. Buccal mucosal graft (BMG) urethroplasty was used in 25 patients and 15 patients were treated with the aid of lingual mucosal graft (LMG). The median follow-up was 85 (IQR: 69–110) months. Seven (17.5%) patients suffered a stricture recurrence of which four (10%) needed re-intervention. The median 5-y recurrent free survival (RFS) for the entire cohort was 85 (±6)%. The median 5-y RFS was 96 (±4)% versus 65 (±13)% for respectively BMG and LMG (p = 0.03). Post-operative complications were identified in 11 (27.5%) patients with only one (2.5%) patient who had a grade 3a complication. Conclusions: Dorsal inlay oral mucosa graft urethroplasty is a safe and feasible technique for selected patients with meatal stenosis.
Non-Sentinel Lymph Node Detection during Sentinel Lymph Node Biopsy in Not-Complete-Lymph-Node-Dissection Era: A New Technique for Better Staging and Treating Melanoma Patients
Authors: Picciotto Franco , Avallone Gianluca , Castellengo Federico , Merli Martina , Caliendo Virginia , Senetta Rebecca , Lesca Adriana , Deandreis Désirée , Fierro Maria Teresa , Quaglino Pietro , Ribero Simone
Published: September 2021

Sentinel lymph node biopsy has been demonstrated to be an effective staging procedure since its introduction in 1992. The new American Joint Committee on Cancer (AJCC) classification did not consider the lack of information that would result from the less usage of the complete lymph node dissection as for a diagnostic purpose. Thus, this makes it difficult the correct staging and would leave about 20% of the further positive non-sentinel lymph nodes in the lymph node basin. In this paper, we aim to describe a new surgical technique that, combined with single-photon emission computed tomography-computed tomography (SPECT-CT), allows for better staging of melanoma patients. This is a prospective study that includes 104 patients with cutaneous melanoma. Sentinel lymph node biopsy was offered according to the AJCC guideline. Planar lymphoscintigraphy was performed in association with SPECT-CT, identifying and removing all non-biologically “excluded” lymph nodes, guiding the surgeon’s hand in detection and removal of lymph nodes. Even if identification and removal of non-sentinel lymph nodes is unable to increase overall survival, it definitely gives better disease control in the basin. With a “classic” setting, the risk of leaving further lymph nodes out of the sentinel lymph node procedure is around 20%, thus, basically, the surgical sentinel lymph node of first and second lymph nodes would have therapeutic value and complete lymph node dissection classically performed.
Efficacy of Empiric Antibiotic Coverage in Community-Acquired Pneumonia Associated with Each Atypical Bacteria: A Meta-Analysis
Authors: Eljaaly Khalid , Aljabri Ahmed , Rabaan Ali A. , Aljuhani Ohoud , Thabit Abrar K. , Alshibani Mohannad , Almangour Thamer A.
Published: September 2021

The benefit of empiric coverage for community-acquired pneumonia (CAP) for atypical bacteria is controversial. This meta-analysis purpose was to compare the clinical failure rate between adults who empirically received atypical coverage versus those who did not. We searched PubMed and EMBASE for randomized controlled trials (RCTs), comparing the clinical failure rate of CAP associated with individual atypical bacteria between adults who received empiric atypical coverage versus those who did not. Risk differences (RDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Eight double-blind RCTs (65 patients with Legionella spp., 176 patients with M. pneumoniae, and 78 patients with C. pneumoniae) were included in the meta-analysis. The rate of clinical failure was significantly lower with empiric atypical coverage in CAP associated with Legionella spp. (RD, −42.6%; 95% CI, −69.8% to −15.4%; p-value = 0.002; I2 = 0%) and Mycoplasma pneumoniae (RD, −9.5%; 95% CI, −18.9% to −0.1%; p-value = 0.048; I2 = 0%), but not with Chlamydia pneumoniae (RD, 7.1%; 95% CI, −9.0% to 23.1%; p-value = 0.390; I2 = 0%). This meta-analysis of RCTs found that empiric atypical coverage decreased the clinical failure rate of CAP associated with Legionella spp. and M. pneumoniae, but not with C. pneumoniae.
Effect of SSRIs on Resting-State Functional Brain Networks in Adolescents with Major Depressive Disorder
Authors: Chu Shu-Hsien , Parhi Keshab K. , Westlund Schreiner Melinda , Lenglet Christophe , Mueller Bryon A. , Klimes-Dougan Bonnie , Cullen Kathryn R.
Published: September 2021

Investigation of brain changes in functional connectivity and functional network topology from receiving 8-week selective serotonin reuptake inhibitor (SSRI) treatments is conducted in 12 unmedicated adolescents with major depressive disorder (MDD) by using wavelet-filtered resting-state functional magnetic resonance imaging (fMRI). Changes are observed in frontal-limbic, temporal, and default mode networks. In particular, topological analysis shows, at the global scale and in the 0.12–0.25 Hz band, that the normalized clustering coefficient and smallworldness of brain networks decreased after treatment. Regional changes in clustering coefficient and efficiency were observed in the bilateral caudal middle frontal gyrus, rostral middle frontal gyrus, superior temporal gyrus, left pars triangularis, putamen, and right superior frontal gyrus. Furthermore, changes of nodal centrality and changes of connectivity associated with these frontal and temporal regions confirm the global topological alternations. Moreover, frequency dependence is observed from FDR-controlled subnetworks for the limbic-cortical connectivity change. In the high-frequency band, the altered connections involve mostly frontal regions, while the altered connections in the low-frequency bands spread to parietal and temporal areas. Due to the limitation of small sample sizes and lack of placebo control, these preliminary findings require confirmation with future work using larger samples. Confirmation of biomarkers associated with treatment could suggest potential avenues for clinical applications such as tracking treatment response and neurobiologically informed treatment optimization.
Looking for a Tailored Therapy for Heart Failure: Are We Capable of Treating the Patient Instead of the Disease?
Authors: Fucili Alessandro , Cimaglia Paolo , Severi Paolo , Giannini Francesco , Boccadoro Alberto , Micillo Marco , Rapezzi Claudio , Tavazzi Luigi , Ferrari Roberto
Published: September 2021

After almost a decade of stagnation in clinical research for HF treatment, five large randomized trials recently published have supported the use of four new classes of drugs, namely: angiotensin receptor/neprilysin inhibitor, sodium–glucose co-transporters 2 inhibitors, soluble guanylate cyclase modulators, and myosin activators. Each treatment has proved to be beneficial for both long-term outcomes and quality of life. Beside their clinical relevance, all these novel treatments have a different mechanism of action beyond the usual neuro-hormonal blockage. These different pathways, together with the unquestionable clinical evidence, advocate a re-thinking of HF treatment and of the appropriate drug to integrate with the existing standard therapy, according to different characteristics of HFrEF patients. This study aimed to offer a synthetic overview of the mechanisms of action of the new drugs and to propose a more personalized approach, considering patients’ characteristics and safety profiles. To this end, we have identified seven profiles for patients with chronic heart failure with reduced ejection fraction and two for pre-discharge patients.
Association between Serum Osteoprotegerin Levels and Severity of Coronary Artery Disease in Patients with Acute Myocardial Infarction
Authors: Cottin Yves , Issa Rany , Benalia Mourad , Mouhat Basile , Meloux Alexandre , Tribouillard Laura , Bichat Florence , Rochette Luc , Vergely Catherine , Zeller Marianne
Published: September 2021

Background. Osteoprotegerin (OPG), a glycoprotein of the tumour necrosis factor (TNF) superfamily, is one of the main biomarkers for vascular calcification. Aim. We aimed to evaluate the association between serum OPG levels and extent of coronary lesions in patients with acute myocardial infarction (MI). Methods. Consecutive patients hospitalized for an acute MI who underwent coronary angiography were included. SYNTAX score was calculated to assess the severity of coronary artery disease. The population was analysed in low (5 (3–6)), medium (11 (9–13)) and high (20 (18–23)) tertiles of SYNTAX score. Results. Among the 378 patients included, there was a gradual increase in age, rate of diabetes, anterior wall location, and a reduction in left ventricular ejection fraction across the SYNTAX tertiles. OPG levels significantly increased across the tertiles (962 (782–1497), 1240 (870–1707), and 1464 (1011–2129) pg/mL, respectively (p < 0.001)). In multivariate analysis, OPG [OR(CI95%): 2.10 (1.29–3.49) 0.003], were associated with the high SYNTAX group, beyond hypercholesterolemia, CV history and reduced glomerular filtration rate. Conclusion. We found an association between OPG levels and coronary lesions complexity patients with acute MI.
Vascular Protective Effects of New Oral Anticoagulants in Patients with Atrial Fibrillation
Authors: Jang Gyeong-Won , Lee Jung Myung , Choi Seung Woo , Kim Joan , Lee Young Shin , Kim Hyung Oh , Chung Hyemoon , Woo Jong Shin , Kim Jin Bae , Kim Woo-Shik , Kim Weon
Published: September 2021

This study was designed to determine the efficacy of a new oral anticoagulant (NOAC) therapy for the prevention of endothelial dysfunction and atherosclerosis progression in patients with atrial fibrillation (AF). Sixty-five AF patients with a CHA2DS2-VASc score ≥2 without previous history of cardiovascular disease were registered and randomly assigned to either an NOAC group (dabigatran or rivaroxaban) or the warfarin group. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were taken using Endo-PAT2000. Carotid intima–media thickness (IMT) was measured at baseline, 12 months, and 24 months, and several biomarkers were also analyzed. For the primary end point, the reactive hyperemia index (RHI) for the NOAC group was 1.5 ± 0.4 and that for the warfarin group was 1.6 ± 0.5. The left and right carotid IMT was 0.7 mm in the NOAC groups and 0.8 mm in the warfarin group. At 12 months, RHI was 1.6 ± 0.3 for the dabigatran group, 1.6 ± 0.5 for the rivaroxaban group, and 1.6 ± 0.3 for the warfarin group. The three groups did not differ statistically with respect to change in left and right carotid IMT at 12 and 24 months, respectively. The biomarkers for endothelial function and atherosclerosis were not significantly different. There was a trend of reduced P-selectin levels in the NOAC group compared to the warfarin group. In patients with AF, there were no significant differences in the prevention of endothelial dysfunction and atherosclerosis progression between the NOAC and warfarin groups.