bluuebunny/crossref_metadata_2025 huggingface dataset:
Met-enkephalin modulation of age-related changes in red cell antioxidant status
Authors: Sobočanec S , Balog T , Šverko V , Marotti T
Published: May 2022

Opioid peptides have been recognized as modulators of reactive oxygen species (ROS) in mouse macrophages and human neutrophils. Since the effect cannot be ascribed to its direct scavenger properties, in this study, we tested the hypothesis that methionine-enkephalin (MENK) modulates ROS by alteration of antioxidant enzyme activity (AOE). For this purpose superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) are measured in red blood cells of 1, 4, 10, and 18-month-old CBA mice of both sexes injected with 10 mg/kg MENK. The results indicate that MENK-affected antioxidant enzyme activity of red blood cells is age- but not sex-related. The most abundant effects were observed at the reproductive stage. Increased sensitivity to oxidative stress by opioid peptides was in both sexes mainly due to increased SOD activity followed by GPX decrease. Thus, the damage ascribed to opioid peptides might be, at least partly, ascribed to deleterious effects of accumulated hydrogen peroxide (H2O2).
Temporal relationship between lens protein oxidation and cataract development in streptozotocin-induced diabetic rats
Authors: Kyselová Z , Garcia SJ , Gajdošíková A , Gajdošík A , Štefek M
Published: May 2022

We compared the progression of lens opacification with the time course of oxidation of lens proteins under conditions of streptozotocin-induced experimental diabetes in rats. By the end of the 17th week, approx. 50% of the diabetic animals developed mature cataracts. During the following month, 95% of the eyes in the diabetic group became cataractous. In the course of lens opacification we observed a time-dependent increase in the content of protein carbonyls and decrease in the concentration of protein sulfhydryls in the lenses of diabetic animals. Significantly higher protein carbonyl (p<0.01) and lower protein sulfhydryl (p<0.001) content was found in lenses with the advanced stage of cataract when compared with the diabetic lenses still transparent. We showed that the values of protein carbonyls exceeding 1.2 nmol/mg protein and of sulfhydryls falling below 60 nmol/mg protein corresponded to an approximately 50% incidence of mature cataract development. At the end of the 34th week, when all lenses of diabetic rats became cataractous, the corresponding values of protein carbonyls and sulfhydryls were 2.5 nmol/mg protein and 27 nmol/mg protein, respectively. The main finding of this study is the disclosure of quantitative relationship between the degree of protein oxidation and the rate of advanced cataract development in the widely used model of streptozotocin-induced experimental diabetes in rats.
A Theoretical Framework for Synchronous Remote Teaching? Reshaping the Pedagogical Triangle
Authors: Skog Simon
Published: May 2022

This paper explores synchronous remote teaching as a pedagogical practice and elaborates upon a framework with which to understand the practice theoretically. The empirical backdrop comprises remote teaching practice in Sweden, where this practice is implemented via digital technology and with an onsite facilitator who is present with the students. The pedagogical triangle is revisited, examined, and explored in relation to remote teaching as a new pedagogical practice. In the theoretical elaboration, the pedagogical triangle is reshaped into a pyramid due to the onsite facilitator’s participation in the remote teaching. This elaboration is a first step to establishing a theoretical understanding of remote teaching practice on its own terms.
Book Review: Indigenous Efflorescence. Beyond revitalisation in Sápmi and Ainu Mosir
Authors: Parfa Koskinen Katarina
Published: May 2022

This is a book review of an anthropological anthology, Indigenous Efflorescence. Beyond revitalisation in Sápmi and Ainu Mosiredited by Gerhard Roche, Hiroshi Maruyama and Åsa Virdi Kråik (2018). The volume acknowledge ongoing efforts around the globe to revtalise languages and cultures, defining Indigenous efflorescence as a slow revolution occurring almost unnoticeably. Examples from two Indigenous peoples are provided, Sámi and Ainu, giving voice to thirty contributors who describe contexts and practices of ´Indigenous efflorescence´ in a broad variety of settings. The review focusses on the merits of the concept of Indigenous efflorescence with a special emphasis on three of the chapters where digital contexts are provided. (Indigenous) efflorescence is an interesting theoretical concept to investigate in relation to theory and practice in remote teaching, online learning, and distance education for K-12 schools as it stresses the aim with any educational practice, which is the growth and flourishing of those involved. It also offers leverage against simplistic narratives of both decline and progress. This volume does what it sets out to do: offer hope and stimulate projects for supporting Indigenous efflorescence.
Special Issue: Theory and Practice in Remote Teaching, Online Learning, and Distance Education for K-12
Authors: Pettersson Fanny , From Jörgen , Lindberg J Ola
Published: May 2022

There are many situations where digital technology has served as the lifeline or salvation for society. Unexpected and unpredictable situations like catastrophic floods, blizzards, earthquakes, and more recently the Covid-19 pandemic have forced families to stay home, meaning that digital technologies have become important tools for people to work and learn. Other examples are societal and regional challenges such as lack of qualified teachers, diminishing birth rates, and difficulties in filling classrooms that force digital and educational development. The symposium held in May 2021, which resulted in this special issue, was intended to explore possibilities for ensuring equal access to education in rural schools using remote teaching. At the symposium, different strategies to increase access to education in the context of K-12 using digital technologies was presented and discussed. It brought together researchers from Europe and North America, all represented in this issue.
Continuous Synthesis of Monodisperse Spherical Silica Powder Using Tubular Reaction System
Authors: Cho Young-Sang , Hwang Chiyeop , Kim Seong-Jun , Park U-Hyeon
Published: May 2022

In the present study, monodisperse silica nanospheres were synthesized using a tubular reaction system in a continuous way. Screw-type blades were inserted inside a T-mixer for static mixing of the reactant streams which consisted of TEOS and NH4OH/H2O diluted with ethanol, for the continuous synthesis of the silica suspension. The diameter of the silica powder was monitored as a function of production time using dynamic light scattering to determine the optimum retention time and tube length, which were found to be 125 minutes and 7.5 m, respectively. The effects of reactant compositions on particle size were investigated by adjusting the amount of ammonia and water in the sol-gel reaction, which were then compared with the results from a batch reactor. Both the particle size and polydispersity index (PDI) of the silica suspension were measured to be comparable to nanospheres synthesized using a batch reactor. This implies that the tubular reaction system is more beneficial for potential industrial production applications in the size range from 115 to 310 nm, due to its continuous powder synthesis. The effect of the reaction medium was also studied, by replacing ethanol with methanol or propanol, indicating that the deviation in particle size with production time was not a serious issue in alcohols with lower molecular weight, such as methanol and ethanol.
Siyasette Bir Cumhuriyet Kadını: Fatma Feriha Öztürk | A Republican Woman in Politics: Fatma Feriha Öztürk
Authors: ÖZTAN Meltem , ŞAHİNOĞLU Serap
Published: May 2022

Fatma Feriha Öztürk 1928 yılında Keçiören’de doğmuştur. 1961 yılında Keçiören muhtarı iken aynı yıl Türk Kadınlar Birliği Genel Başkanı olmuştur. 1961 ve 1964 yılında CHP’den milletvekili aday adayı olmuş ancak aday olamamıştır. Fatma Feriha Öztürk tabandan gelerek 1973 yılında birinci sıradan aday gösterilerek milletvekili seçilmiştir. Milletvekilliği döneminde kadın sorunlarına odaklanarak genelev kadınlarının genel çalışma koşullarının düzenlenmesi, sağlık olanaklarının iyileştirilmesi ve sigortalanmasına yönelik mağduriyetlerinin giderilmesi çalışmalarının merkezinde bulunmuştur. Bu çalışma onunla birebir yapılan özyaşam öyküsünden hareketle, onun siyasi yaşamdaki rolünü, toplumsal cinsiyet temelli ele almayı amaçlamıştır.
A Photo-Crosslinking Approach to Identify Class II SUMO-1 Binders
Authors: Brüninghoff Kira , Wulff Stephanie , Dörner Wolfgang , Geiss-Friedlander Ruth , Mootz Henning D.
Published: May 2022

The small ubiquitin-like modifier (SUMO) is involved in various cellular processes and mediates known non-covalent protein-protein interactions by three distinct binding surfaces, whose interactions are termed class I to class III. While interactors for the class I interaction, which involves binding of a SUMO-interacting motif (SIM) to a hydrophobic groove in SUMO-1 and SUMO-2/3, are widely abundant, only a couple of examples have been reported for the other two types of interactions. Class II binding is conveyed by the E67 loop region on SUMO-1. Many previous studies to identify SUMO binders using pull-down or microarray approaches did not strategize on the SUMO binding mode. Identification of SUMO binding partners is further complicated due to the typically transient and low affinity interactions with the modifier. Here we aimed to identify SUMO-1 binders selectively enriched for class II binding. Using a genetically encoded photo-crosslinker approach, we have designed SUMO-1 probes to covalently capture class II SUMO-1 interactors by strategically positioning the photo-crosslinking moiety on the SUMO-1 surface. The probes were validated using known class II and class I binding partners. We utilized the probe with p-benzoyl-phenylalanine (BzF, also termed BpF or Bpa) at the position of Gln69 to identify binding proteins from mammalian cell extracts using mass spectrometry. By comparison with results obtained with a similarly designed SUMO-1 probe to target SIM-mediated binders of the class I type, we identified 192 and 96 proteins specifically enriched by either probe, respectively. The implicated preferential class I or class II binding modes of these proteins will further contribute to unveiling the complex interplay of SUMO-1-mediated interactions.
Case Report: Pulmonary Vein Isolation as a Tailored Treatment for Recurrent Ventricular Tachycardia During Hemodialysis in a Patient With Right Coronary Artery Chronic Total Occlusion
Authors: Cojocaru Cosmin , Pupăză Adelina , Iorgulescu Corneliu , Onciul Sebastian , Câlmâc Lucian , Vătăşescu Radu
Published: May 2022

Background

Catheter ablation of the ventricular substrate can reduce ventricular tachycardia (VT) recurrence and mortality in an electrical storm (ES). However, identification and specific treatment of plausible triggers is mandatory and may lead to the resolution of ES.

Objective

This case presentation seeks to exemplify how pulmonary vein isolation (PVI) may represent a tailored treatment of ES in cases of ventricular substrate, which only becomes arrhythmogenic during high-rate episodes of paroxysmal atrial fibrillation (PAF).

Results

A 54-year-old male with a history of inferior myocardial infarction (MI) and long-term hemodialysis was referred for repetitive implantable cardioverter-defibrillator (ICD) shocks for apparently scar-related monomorphic VT episodes preceded by PAF initiation strictly during hemodialysis. He had recently undergone ICD implantation for similar episodes of ES preceded by the rapid-ventricular response (RVR) PAF during hemodialysis. The patient had no other history of VTs. Electrocardiogram (EKG) changes occurred exclusively during PAF and suggested functional myocardial ischemia. Coronary angiography demonstrated isolated right coronary artery (RCA) chronic total occlusion (CTO). Cardiac magnetic resonance demonstrated RCA-territory residual myocardial viability and mild LV systolic dysfunction. Surgical revascularization was not feasible due to a history of bilateral above-the-knee post-traumatic amputation and severe calcification of internal mammary (IMA) and radial arteries. Subsequent CTO-percutaneous coronary intervention attempt was unsuccessful. The difficulty of assessing LV-substrate ablation end-points due to the “functional” character of the substrate, which only became arrhythmogenic during hemodialysis-related PAF, was considered. Consequently, PVI was performed rather than VT/VF substrate ablation. Twelve months after PVI, the patient remains free of PAF and VT/VF despite chronic hemodialysis sessions.

Conclusion

The ES episodes can be triggered by situational factors, such as RVR-PAF and functional ischemia, during hemodialysis in patients with CTO with otherwise no episodes of VT. Tailored treatment of such factors may lead to long-term VT freedom.
Research on Proppant Optimization and Field Test of Ultra-Deep Tight Conglomerate Sandstone Reservoir
Authors: Wu Baocheng , Xiao Fengchao , Kong Mingwei , Wang Bin , Zhang Shicheng
Published: May 2022

Efficient development of deep tight reservoirs in the southern margin of the Junggar Basin requires stimulation technology, and effective propped hydraulic fractures are the key to successful stimulation. To optimize the proppant selected for reservoir stimulation, the important parameters of proppant selection were determined through the proppant conductivity evaluation experimental study and field test, considering the influences of high temperature and high closure pressure. The results show that closure pressure, temperature, and sand concentration have a great influence on the conductivity of the proppant pack. The conductivity of the proppant pack decreases by about 10% at high temperatures, which is because the high temperature will rupture more proppant and thus reduce proppant pack permeability. In the long term, the Scenario B placement pattern can maintain high conductivity, and the long-term conductivity is increased by 6–26% compared with the Scenario C placement pattern. Furthermore, increasing the proppant placement concentration is conducive to the long-term conductivity of the fracture. During the operation of the test well, the treatment pressure was stable, and the fractures were effectively propped. No proppant flowing back occurred in the test production after the fracturing treatment, which achieved the purpose of the evaluation well, provided support for the large-scale development of subsequent development wells, and ensured orderly development.
The Role of Payment Technology Innovation in Environmental Sustainability: Mediation Effect From Consumers’ Awareness to Practice
Authors: An Jiaji , Di He , Yao Meifang , Jin Shuaiqi
Published: May 2022

Based on the traditional internal factor model, high environmental awareness should bring higher engagement in environmental practices. In reality, however, many studies have found no significant correlation between the two. To explain this, frontier research is focusing on what external factors influence environmental sustainability. As a typical example of such external factors, this article focuses on the innovation of Internet payment technology. Based on a survey of 623 individuals living across mainland China, we conduct path analysis, stepwise regression analysis, and a mediation test on Internet payment technology, environmental awareness, environmental protection practices, and demographics such as age, income, and sex. We find that Internet payment technology plays a significant mediator role between environmental awareness and environmental behaviors, and that demographics also affect sustainability. Internet payment technology can expand the range of ways in which consumers participate in environmental protection and encourage them to put more green practices through emotional and physical incentives. We thus demonstrate the positive impact of technological innovation on environmental sustainability and unfold the underlying mechanism. Besides providing a reference for other researchers, our study also proposes some applications relevant to the scientific community.
Effect of Swimming on the Induction of Vitellogenin in Conger Eel (Conger myriaster)
Authors: Liu Rucong , Li Kang , Wang Guixiang , Jiang Zhixin , Ba Xubing , Liu Liping
Published: May 2022

Vitellogenin (VTG) plays a very important role in the development of oocytes. This study aims to explore the effect of swimming on the VTG synthesis of conger eel (Conger myriaster). Circulating water flow and hormone injection regimen were two factors set in the following trials: A1 (no injection, no water flow), A2 (no injection, water flow), B1 (injection, no water flow), and B2 (injection, water flow). The flow velocity of the flowing water was 0.4 m/s (12 h, 60 days). We examined VTG, estrogen receptor (Er) gene expression, and VTG content in the liver and serum on the 30th and 60th days. VTG gene expression in A1 and A2 gradually decreased and was not significantly different between the two groups. The expression of Er gene in A1 was significantly higher than that in A2. The expression of VTG gene in group B1 was significantly higher than that in group B2, whereas the expression level of Er gene in group B1 was slightly higher than that in group B1. The VTG content in the liver in group B1 reached 1,396.93 μg/L, which was significantly higher than that in group B2 (1,302.06 μg/L). Results showed that the flowing water factor can inhibit the expression of VTG and Er genes in the liver and reduce the synthesis of VTG in the liver. Stimulation of flowing water can inhibit the yolk accumulation during the ovarian development of conger eel.
Enabling Allogeneic T Cell-Based Therapies: Scalable Stirred-Tank Bioreactor Mediated Manufacturing
Authors: Gatla Himavanth , Uth Nicholas , Levinson Yonatan , Navaei Ali , Sargent Alex , Ramaswamy Senthil , Friedrich Ben-Nun Inbar
Published: May 2022

Allogeneic T cells are key immune therapeutic cells to fight cancer and other clinical indications. High T cell dose per patient and increasing patient numbers result in clinical demand for a large number of allogeneic T cells. This necessitates a manufacturing platform that can be scaled up while retaining cell quality. Here we present a closed and scalable platform for T cell manufacturing to meet clinical demand. Upstream manufacturing steps of T cell activation and expansion are done in-vessel, in a stirred-tank bioreactor. T cell selection, which is necessary for CAR-T-based therapy, is done in the bioreactor itself, thus maintaining optimal culture conditions through the selection step. Platform's attributes of automation and performing the steps of T cell activation, expansion, and selection in-vessel, greatly contribute to enhancing process control, cell quality, and to the reduction of manual labor and contamination risk. In addition, the viability of integrating a closed, automated, downstream process of cell concentration, is demonstrated. The presented T cell manufacturing platform has scale-up capabilities while preserving key factors of cell quality and process control.
Naturalized Escherichia coli in Wastewater and the Co-evolution of Bacterial Resistance to Water Treatment and Antibiotics
Authors: Yu Daniel , Ryu Kanghee , Zhi Shuai , Otto Simon J. G. , Neumann Norman F.
Published: May 2022

Antibiotic resistance represents one of the most pressing concerns facing public health today. While the current antibiotic resistance crisis has been driven primarily by the anthropogenic overuse of antibiotics in human and animal health, recent efforts have revealed several important environmental dimensions underlying this public health issue. Antibiotic resistant (AR) microbes, AR genes, and antibiotics have all been found widespread in natural environments, reflecting the ancient origins of this phenomenon. In addition, modern societal advancements in sanitation engineering (i.e., sewage treatment) have also contributed to the dissemination of resistance, and concerningly, may also be promoting the evolution of resistance to water treatment. This is reflected in the recent characterization of naturalized wastewater strains of Escherichia coli—strains that appear to be adapted to live in wastewater (and meat packing plants). These strains carry a plethora of stress-resistance genes against common treatment processes, such as chlorination, heat, UV light, and advanced oxidation, mechanisms which potentially facilitate their survival during sewage treatment. These strains also carry an abundance of common antibiotic resistance genes, and evidence suggests that resistance to some antibiotics is linked to resistance to treatment (e.g., tetracycline resistance and chlorine resistance). As such, these naturalized E. coli populations may be co-evolving resistance against both antibiotics and water treatment. Recently, extraintestinal pathogenic strains of E. coli (ExPEC) have also been shown to exhibit phenotypic resistance to water treatment, seemingly associated with the presence of various shared genetic elements with naturalized wastewater E. coli. Consequently, some pathogenic microbes may also be evolving resistance to the two most important public health interventions for controlling infectious disease in modern society—antibiotic therapy and water treatment.
Response of Soil Microbial Community Structure Mediated by Sulfur-Induced Resistance Against Kiwifruit Bacterial Canker
Authors: Yang Sen , Shu Ran , Yin Xianhui , Long Youhua , Yuan Jun
Published: May 2022

Kiwifruit bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) is a major threat to kiwifruit worldwide, and effective control measures are still lacking. Sulfur, as a mineral, has been proved to improve plants' resistance to pathogens. It is of great significance to study the effect of sulfur on rhizosphere microorganisms in kiwifruit planting areas infected by Psa for controlling kiwifruit canker. In this study, the sulfur powder and organic fertilizer were mixed as base fertilizer to treat the soil in the area where kiwifruit bacterial canker occurs. We investigated the incidence of kiwifruit bacterial canker in 2018 and 2019 after sulfur application and the changes in microbial characteristics and community composition structure in the kiwifruit rhizosphere by using the plate-counting method and high-throughput sequencing technology. Fertilization treatments of kiwifruit roots with sulfur and organic fertilizer reduced kiwifruit bacterial canker severity. The diversity of soil microbial communities increased significantly after sulfur application in the range of 1.0~2.0 kg/m3. In particular, the bacterial genera level showed a high diversity after 2 years of sulfur application, reaching more than 516 genera. Furthermore, sulfur treatment resulted in a significant increase in specific microbial taxa, including members of the Acidothermus, norank_f__HSB_OF53-F07, and norank_f __Acidobacteriaceae__Subgroup_1. Moreover, the proportion of the dominant bacteria Acidothermus in the population showed an increasing trend. Altogether, the sulfur application is the key factor leading to microbial differences in kiwifruit rhizosphere soil. Appropriate sulfur can improve microbial structure characteristics of kiwifruit rhizosphere soil, increase bacterial diversity index, and change bacterial community composition structure.
Folding and Evolution of a Repeat Protein on the Ribosome
Authors: León-González José Alberto , Flatet Perline , Juárez-Ramírez María Soledad , Farías-Rico José Arcadio
Published: May 2022

Life on earth is the result of the work of proteins, the cellular nanomachines that fold into elaborated 3D structures to perform their functions. The ribosome synthesizes all the proteins of the biosphere, and many of them begin to fold during translation in a process known as cotranslational folding. In this work we discuss current advances of this field and provide computational and experimental data that highlight the role of ribosome in the evolution of protein structures. First, we used the sequence of the Ankyrin domain from the Drosophila Notch receptor to launch a deep sequence-based search. With this strategy, we found a conserved 33-residue motif shared by different protein folds. Then, to see how the vectorial addition of the motif would generate a full structure we measured the folding on the ribosome of the Ankyrin repeat protein. Not only the on-ribosome folding data is in full agreement with classical in vitro biophysical measurements but also it provides experimental evidence on how folded proteins could have evolved by duplication and fusion of smaller fragments in the RNA world. Overall, we discuss how the ribosomal exit tunnel could be conceptualized as an active site that is under evolutionary pressure to influence protein folding.
Uncovering the Mechanism of Drug Resistance Caused by the T790M Mutation in EGFR Kinase From Absolute Binding Free Energy Calculations
Authors: Zhou Huaxin , Fu Haohao , Liu Han , Shao Xueguang , Cai Wensheng
Published: May 2022

The emergence of drug resistance may increase the death rates in advanced non-small cell lung cancer (NSCLC) patients. The resistance of erlotinib, the effective first-line antitumor drug for NSCLC with the L858R mutation of epidermal growth factor receptor (EGFR), happens after the T790M mutation of EGFR, because this mutation causes the binding of adenosine triphosphate (ATP) to EGFR more favorable than erlotinib. However, the mechanism of the enhancement of the binding affinity of ATP to EGFR, which is of paramount importance for the development of new inhibitors, is still unclear. In this work, to explore the detailed mechanism of the drug resistance due to the T790M mutation, molecular dynamics simulations and absolute binding free energy calculations have been performed. The results show that the binding affinity of ATP with respect to the L858R/T790M mutant is higher compared with the L858R mutant, in good agreement with experiments. Further analysis demonstrates that the T790M mutation significantly changes the van der Waals interaction of ATP and the binding site. We also find that the favorable binding of ATP to the L858R/T790M mutant, compared with the L858R mutant, is due to a conformational change of the αC-helix, the A-loop and the P-loop of the latter induced by the T790M mutation. This change makes the interaction of ATP and P-loop, αC-helix in the L858R/T790M mutant higher than that in the L858R mutant, therefore increasing the binding affinity of ATP to EGFR. We believe the drug-resistance mechanism proposed in this study will provide valuable guidance for the design of drugs for NSCLC.
Brain Responses to Peer Feedback in Social Media Are Modulated by Valence in Late Adolescence
Authors: Wikman Patrik , Moisala Mona , Ylinen Artturi , Lindblom Jallu , Leikas Sointu , Salmela-Aro Katariina , Lonka Kirsti , Güroğlu Berna , Alho Kimmo
Published: May 2022

Previous studies have examined the neural correlates of receiving negative feedback from peers during virtual social interaction in young people. However, there is a lack of studies applying platforms adolescents use in daily life. In the present study, 92 late-adolescent participants performed a task that involved receiving positive and negative feedback to their opinions from peers in a Facebook-like platform, while brain activity was measured using functional magnetic resonance imaging (fMRI). Peer feedback was shown to activate clusters in the ventrolateral prefrontal cortex (VLPFC), medial prefrontal cortex (MPFC), superior temporal gyrus and sulcus (STG/STS), and occipital cortex (OC). Negative feedback was related to greater activity in the VLPFC, MPFC, and anterior insula than positive feedback, replicating previous findings on peer feedback and social rejection. Real-life habits of social media use did not correlate with brain responses to negative feedback.
A Set of Reliable Samples for the Study of Biomarkers for the Early Diagnosis of Parkinson's Disease
Authors: Konjevod Marcela , Sáiz Jorge , Barbas Coral , Bergareche Alberto , Ardanaz Eva , Huerta José Ma , Vinagre-Aragón Ana , Erro Ma Elena , Chirlaque Ma Dolores , Abilleira Eunate , Ibarluzea Jesús Ma , Amiano Pilar
Published: May 2022

Background

Parkinson's disease (PD) is a progressive neurodegenerative disorder, diagnosed according to the clinical criteria that occur in already advanced stages of PD. The definition of biomarkers for the early diagnosis of PD represents a challenge that might improve treatment and avoid complications in this disease. Therefore, we propose a set of reliable samples for the identification of altered metabolites to find potential prognostic biomarkers for early PD.

Methods

This case–control study included plasma samples of 12 patients with PD and 21 control subjects, from the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC)-Navarra cohort, part of the EPIC-Spain study. All the case samples were provided by healthy volunteers who were followed-up for 15.9 (±4.1) years and developed PD disease later on, after the sample collection. Liquid chromatography coupled to tandem mass spectrometry was used for the analysis of samples.

Results

Out of 40 that were selected and studied due to their involvement in established cases of PD, seven significantly different metabolites between PD cases and healthy control subjects were obtained in this study (benzoic acid, palmitic acid, oleic acid, stearic acid, myo-inositol, sorbitol, and quinolinic acid). These metabolites are related to mitochondrial dysfunction, the oxidative stress, and the mechanisms of energy production.

Conclusion

We propose the samples from the EPIC study as reliable and invaluable samples for the search of early biomarkers of PD. Likewise, this study might also be a starting point in the establishment of a well-founded panel of metabolites that can be used for the early detection of this disease.
Real-World Data on Access to Standards of Care for People With Spinal Muscular Atrophy in the UK
Authors: Muni-Lofra Robert , Murphy Lindsay B. , Adcock Kate , Farrugia Maria E. , Irwin Joseph , Lilleker James B. , McConville John , Merrison Andria , Parton Matt , Ryburn Liz , Scoto Mariacristina , Marini-Bettolo Chiara , Mayhew Anna
Published: May 2022

Spinal Muscular Atrophy (SMA) is characterized by muscle atrophy and weakness and has an incidence of 1:11. 000 live births which projects an estimated population in the UK of 650–1,300 affected patients. Standards of Care (SoC) were updated in 2017 and they have been widely adopted as a reference for implementation of care in SMA across the globe. The effectiveness of implementation and adherence to these standards across different countries is unclear. The aim of this study is to describe the experience of individuals with SMA regarding their care in the UK. An online anonymised survey was sent out via patient organizations, the UK SMA Patient Registry, professional networks, and social media to reach across the UK. The survey captured demographic profile, professionals involved in a patient's care, Interventions and access to mobility aids and home adaptations. Participants responded about their access to services and to rate how important each professional and intervention was for their health and wellbeing. One hundred and twenty-eight responses were collected with a median age of 34 years (1–81). Seventy-three percent of participants were adults and 60% men. Overall good access to neurologist (>90%) but limited to nurse specialist (48%) and physiotherapist (57%). Good access to respiratory support was reported but limited for interventions for positioning and bracing and exercise. This survey highlights that access to certain professionals for people with SMA is limited in the UK. Striking differences were noted between pediatric and adult populations. Limited access to care were regularly reported, with half of the study population consistently not accessing full multidisciplinary care. Access to interventions for contracture management were recorded to have significant limitations. Mobility aids and home adaptations are widely available and were also reported as the most valued interventions. Access to nutritional support or speech and language therapy appears only to be available for a small proportion of the participants. Access to respiratory care was good especially in severe forms of SMA. We found pockets of good practice in the UK that align with the SoC. However, access is not equal for adults and children and access to certain professionals is significantly limited.
Association of IL-1B rs16944 Polymorphism With Acute Encephalopathy With Biphasic Seizures and Late Reduced Diffusion Is Opposite to That of Febrile Seizures
Authors: Shibata Akiko , Kasai Mariko , Hoshino Ai , Mizuguchi Masashi
Published: May 2022

Objective

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a severe neurologic complication of febrile infectious diseases in children. At the onset, AESD is clinically manifested as febrile status epilepticus. Subsequent damage to the cerebral cortex is ascribed to neurotoxicity. The incidence of AESD is remarkably high in Japan, suggesting the involvement of genetic factors. The expression of interleukin 1 beta (IL-1β), a member of the cytokine family involved in the inflammatory response, is reportedly associated with rs16944, a polymorphism in the upstream region of the IL-1B gene, being higher in TT genotype. Previous association studies of rs16944 with febrile seizures (FS) have demonstrated a significant excess in the TT vs. CC + CT genotype in the Asian population. Here, we conducted a case-control association study of rs16944 in AESD.

Methods

We genotyped rs16944 by Sanger sequencing on 283 patients with AESD. As controls, we used genotyping data of 104 Japanese individuals obtained from the 1,000 Genomes Project. Then, we performed a case-control association study using the chi-square test.

Results

The ratio of individuals with TT vs. those with CC+CT genotype was significantly lower in AESD than in the controls [p-value 0.021, Odds Ratio (OR) 0.52]. This finding was opposite to that of a previously reported FS.

Conclusion

The AESD has a genetic background distinct from FS and is not a severe type of FS.
Cutaneous Breast Cancer Metastasis Is Effectively Treated With Intralesional Interleukin-2 and Imiquimod: A Case Report and Brief Literature Review
Authors: Drohan Ashley , Vidovic Dejan , Barnes Penelope Jane , Giacomantonio Carman Anthony , Helyer Lucy Kathryn
Published: May 2022

Breast cancer is the most common non-cutaneous cancer affecting women worldwide and is a major cause of cancer-related morbidity and mortality in females. While many women are diagnosed with early-stage disease, a subset of women may present with isolated cutaneous metastases or recurrent locoregional cutaneous metastatic disease. There is a paucity of evidence for effective treatments for cutaneous breast cancer metastases. Herein, we present a case of hormone receptor negative, HER2 positive cutaneous breast cancer metastasis treated with intralesional IL-2 and topical imiquimod, which was well tolerated with only minor low grade side effects. We also present a brief literature review of immunotherapy for cutaneous breast cancer metastasis to frame the discussion around using minimally invasive local therapies for this disease. Together, this limited data suggests that intralesional IL-2 and imiquimod may be considered as a safe option when treating a patient with cutaneous breast cancer metastases.
A Comparison Study Between CNN-Based Deformed Planning CT and CycleGAN-Based Synthetic CT Methods for Improving iCBCT Image Quality
Authors: Yang Bo , Chang Yankui , Liang Yongguang , Wang Zhiqun , Pei Xi , Xu Xie George , Qiu Jie
Published: May 2022

Purpose

The aim of this study is to compare two methods for improving the image quality of the Varian Halcyon cone-beam CT (iCBCT) system through the deformed planning CT (dpCT) based on the convolutional neural network (CNN) and the synthetic CT (sCT) generation based on the cycle-consistent generative adversarial network (CycleGAN).

Methods

A total of 190 paired pelvic CT and iCBCT image datasets were included in the study, out of which 150 were used for model training and the remaining 40 were used for model testing. For the registration network, we proposed a 3D multi-stage registration network (MSnet) to deform planning CT images to agree with iCBCT images, and the contours from CT images were propagated to the corresponding iCBCT images through a deformation matrix. The overlap between the deformed contours (dpCT) and the fixed contours (iCBCT) was calculated for purposes of evaluating the registration accuracy. For the sCT generation, we trained the 2D CycleGAN using the deformation-registered CT-iCBCT slicers and generated the sCT with corresponding iCBCT image data. Then, on sCT images, physicians re-delineated the contours that were compared with contours of manually delineated iCBCT images. The organs for contour comparison included the bladder, spinal cord, femoral head left, femoral head right, and bone marrow. The dice similarity coefficient (DSC) was used to evaluate the accuracy of registration and the accuracy of sCT generation.

Results

The DSC values of the registration and sCT generation were found to be 0.769 and 0.884 for the bladder (p < 0.05), 0.765 and 0.850 for the spinal cord (p < 0.05), 0.918 and 0.923 for the femoral head left (p > 0.05), 0.916 and 0.921 for the femoral head right (p > 0.05), and 0.878 and 0.916 for the bone marrow (p < 0.05), respectively. When the bladder volume difference in planning CT and iCBCT scans was more than double, the accuracy of sCT generation was significantly better than that of registration (DSC of bladder: 0.859 vs. 0.596, p < 0.05).

Conclusion

The registration and sCT generation could both improve the iCBCT image quality effectively, and the sCT generation could achieve higher accuracy when the difference in planning CT and iCBCT was large.
Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Lung Adenocarcinoma by Comprehensive Bioinformatics Analysis and In Vitro Study
Authors: Li Xinyan , Chen Xi , Yuan Yixiao , Zhai RuiQing , Cho William C. , Jiang Xiulin
Published: May 2022

Family with sequence similarity 72B (FAM72B) has been characterized in the regulation of neuronal development. Nevertheless, the prognostic value of FAM72B expression and its function in the immune microenvironment of lung adenocarcinoma (LUAD) currently remains elusive. In this study, by adopting bioinformatics methodology and experimental verification, we found that FAM72B was upregulated in lung cancer tissues and cell lines, and a higher FAM72B level predicted an unfavorable clinical outcome in LUAD patients. The knockdown of FAM72B significantly inhibited cell proliferation, cell migration, and induced cell apoptosis in LUAD. The receiver operating characteristic curve suggested that FAM72B had a high predictive accuracy for the outcomes of LUAD. Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analyses confirmed that FAM72B-related genes were involved in cell proliferation and immune-response signaling pathway. Moreover, upregulated FAM72B expression was significantly associated with immune cell infiltration in the LUAD tumor microenvironment. Meanwhile, a potential ceRNA network was constructed to identify the lncRNA-AL360270.2/TMPO-AS1/AC125807.2/has-let-7a/7b/7c/7e/7f/FAM72B regulatory axis that regulates FAM72B overexpression in LUAD and is associated with a poor prognosis. We also confirmed that AL360270.2, TMPO-AS1, and AC125807.2 were significantly upregulated in LUAD cell lines than in human bronchial epithelial cells. In conclusion, FAM72B may serve as a novel biomarker in predicting the clinical prognosis and immune status for lung adenocarcinoma.
Molecular and Biochemical Analysis of Duplicated Cytosolic CuZn Superoxide Dismutases of Rice and in silico Analysis in Plants
Authors: Sanyal Ravi Prakash , Prashar Vishal , Jawali Narendra , Sunkar Ramanjulu , Misra Hari Sharan , Saini Ajay
Published: May 2022

Superoxide dismutases (SODs, EC 1.15.1.1) are ubiquitous antioxidant metalloenzymes important for oxidative stress tolerance and cellular redox environment. Multiple factors have contributed toward the origin and diversity of SOD isoforms among different organisms. In plants, the genome duplication events, responsible for the generation of multiple gene copies/gene families, have also contributed toward the SOD diversity. However, the importance of such molecular events on the characteristics of SODs has not been studied well. This study investigated the effects of divergence on important characteristics of two block-duplicated rice cytosolic CuZn SODs (OsCSD1, OsCSD4), along with in silico assessment of similar events in other plants. The analysis revealed heterogeneity in gene length, regulatory regions, untranslated regions (UTRs), and coding regions of two OsCSDs. An inconsistency in the database-predicted OsCSD1 gene structure was also identified and validated experimentally. Transcript analysis showed differences in the basal levels and stress responsiveness of OsCSD1 and OsCSD4, and indicated the presence of two transcription start sites in the OsCSD1. At the amino acid level, the two OsCSDs showed differences at 18 sites; however, both exist as a homodimer, displaying typical CuZn SOD characteristics, and enhancing the oxidative stress tolerance of Escherichia coli cells. However, OsCSD4 showed higher specific activity as well as stability. The comparison of the two OsCSDs with reported thermostable CSDs from other plants identified regions likely to be associated with stability, while the homology modeling and superposition highlighted structural differences. The two OsCSDs displayed heteromeric interaction capability and forms an enzymatically active heterodimer (OsCSD1:OsCSD4) on co-expression, which may have significance as both are cytosolic. In silico analysis of 74 plant genomes revealed the prevalence of block duplications for multiple CSD copies (mostly cytosolic). The divergence and clustering analysis of CSDs suggested the possibility of an ancestral duplication event in monocots. Conserved SOD features indicating retention of SOD function among CSD duplicates were evident in few monocots and dicots. In most other species, the CSD copies lacked critical features and may not harbor SOD function; however, other feature-associated functions or novel functions might be present. These aspects of divergent CSD copies encoding co-localized CSDs may have implications in plant SOD functions in the cytosol and other organelles.
Recent Advances for Drought Stress Tolerance in Maize (Zea mays L.): Present Status and Future Prospects
Authors: Sheoran Seema , Kaur Yashmeet , Kumar Sushil , Shukla Shanu , Rakshit Sujay , Kumar Ramesh
Published: May 2022

Drought stress has severely hampered maize production, affecting the livelihood and economics of millions of people worldwide. In the future, as a result of climate change, unpredictable weather events will become more frequent hence the implementation of adaptive strategies will be inevitable. Through utilizing different genetic and breeding approaches, efforts are in progress to develop the drought tolerance in maize. The recent approaches of genomics-assisted breeding, transcriptomics, proteomics, transgenics, and genome editing have fast-tracked enhancement for drought stress tolerance under laboratory and field conditions. Drought stress tolerance in maize could be considerably improved by combining omics technologies with novel breeding methods and high-throughput phenotyping (HTP). This review focuses on maize responses against drought, as well as novel breeding and system biology approaches applied to better understand drought tolerance mechanisms and the development of drought-tolerant maize cultivars. Researchers must disentangle the molecular and physiological bases of drought tolerance features in order to increase maize yield. Therefore, the integrated investments in field-based HTP, system biology, and sophisticated breeding methodologies are expected to help increase and stabilize maize production in the face of climate change.
The Association Between Life Events and Incidence of Hypertension Among Government Employees in China: A Prospective Cohort Study
Authors: Ouyang Feiyun , He Jun , Cheng Xunjie , Qiu Dan , Li Ling , Bangura Joseph Benjamin , Duan Yanyin , Luo Dan , Xiao Shuiyuan
Published: May 2022

Background

Hypertension (HTN) is a global public health concern. However, the association between life events (LEs) and HTN is complex. Thus, we conducted a prospective cohort study to explore this complex association.

Methods

A total of 8,077 government employees without HTN were recruited through cluster sampling between 2018 and 2019 in Hunan Province, China. At baseline, information regarding sociodemographic characteristics, LEs, and behavioral factors was collected. After the 1-year follow-up, the participants were revisited to obtain the HTN diagnosis. Crude and adjusted Poisson regression models were constructed to calculate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Cubic regression spline models were used to visualize the trends between LEs and HTN IRRs. Interactive and subgroup analyses were also performed.

Results

The 1-year HTN incidence rate among government employees in Hunan province was 4.30% (95% CI: 3.86–4.74%). LEs were associated with a higher HTN risk (IRR, 1.02; 95% CI, 1.00–1.04). When calculating positive and negative LEs scores separately, only the latter was a risk factor for HTN incidence (IRR, 1.04; 95% CI, 1.03–1.06); conversely, positive LEs reduced the risk (IRR, 0.90; 95% CI, 0.85–0.96). Compared with patients in the lowest quartile of LEs score, those in quartiles two (IRR, 1.28; 95% CI, 0.96–1.71), three (IRR, 1.43; 95% CI, 1.04–1.96), and four (IRR, 1.73; 95% CI, 1.26–2.37) were at progressively higher risk. In restricted spline curves, a non-linear association was noted between LEs and HTN risk. Regarding the subcategories of LEs, work-related LEs, personal LEs, and all subcategories of negative LEs were associated with an increased risk of HTN. However, among positive LEs, only the family-related cases were associated with a lower risk of HTN.

Conclusion

LEs had a non-linear association with an increased risk of HTN. Negative LEs were risk factors for HTN incidence, whereas positive LEs reduced the risk of HTN. Thus, the importance of LEs should be highlighted in the development of HTN prevention strategies and initiatives.