bluuebunny/crossref_metadata_2025 huggingface dataset:
TO THE ACTUALIZATION OF STIMULATION OF ACTIVITIES IN THE FIELD OF CLIMATE STUDY ON THE EXAMPLE OF ENSURING THE CAREER GROWTH OF THE CARETAKERS OF THE EKATERINBURG MAGNETIC AND METEOROLOGICAL OBSERVATORY (BY THE 185TH ANNIVERSARY OF OBSERVATORY OBSERVATIONS IN THE URALS)
Authors:   Institute of Economics, Ural Branch, Russian Academy of Sciences, Yekaterinburg, Russian Federation, LITOVSKIY VLADIMIR
Published: January 2022

For the first time for the 185th anniversary of the environmental observations in the Urals, information about the first caretakers Ekaterinburg Magnetic and Meteorological Observatory (EMMO) is presented. This is based on domestic and foreign archival data currently available on the world Internet. It is shown that the first caretakers have passed a wonderful way of life. All have made a great track record in the Mining Department, to which EMMO was originally attributed. They reached the general's ranks in the Rank Tables. On the scientific side, some of them became professors of the Mining Institute and members of the Scientific Committee of the Corps of Mountain Engineers. Some gaps have been restored in the biographies of Julius Reinke, Ivan Avdeev, Vasily Rozhkov and Konstantin Shugaev. It is shown that thanks to their activities, the Ekaterinburg Magnetic and Meteorological Observatory has become a reliable outpost of scientific research in the Urals. Now its successor The Ural Hydrometeorological Center has the longest range of continuous data. It is one of the key centers of global environmental monitoring as well.
ПРЕДСТАВЛЕНИЯ О РОЛИ СВЯТЫНЬ В ОСВЯЩЕНИИ И ЗАЩИТЕ ЖИЛИЩА И ПРАКТИКА ФОРМИРОВАНИЯ БЛАГОПРИЯТНОЙ ДУХОВНОЙ АТМОСФЕРЫ В ДОМЕ В РУССКИХ ПРАВОСЛАВНЫХ СЕМЬЯХ КОНЦА XX - НАЧАЛА XXI ВЕКОВ
Authors: Шляхтина Наталья Валерьевна
Published: January 2022

В статье на современных этнографических материалах раскрывается тема православных святынь в доме и их влияния на духовную атмосферу в семье.
РОССИЙСКОЕ ЦИВИЛИЗАЦИОННОЕ ПОГРАНИЧЬЕ
Authors: Кириченко Олег Викторович
Published: January 2022

Статья обращена к теме малоизученной и имеющей общетеоретический характер. Речь идет о рассмотрении «цивилизационного механизма», созданного русской государственной властью, церковью и народом на пограничье, что позволяло политической границе быть и границей цивилизационной, не разъединяющей, но связывающей страну и народ с другими народами и странами.
ОТНОШЕНИЕ К БОГАТСТВУ В РУССКОЙ ПРАВОСЛАВНОЙ ТРАДИЦИИ: ПОЗИТИВНЫЕ И НЕГАТИВНЫЕ ТЕНДЕНЦИИ (XVIII - НАЧАЛО XX ВЕКА)
Authors: Кириченко Олег Викторович
Published: January 2022

Статья посвящена теме конвертации богатства. Автор обращается к исследованию социальной формы конвертации. Публикации по данной теме начаты автором в 13 и продолжены в 17, 18 и 19 номерах журнала.
НАРОДНЫЙ МОНАРХИЗМ В XIX И В НАЧАЛЕ XX В.
Authors: Кириченко Олег Викторович
Published: January 2022

Статья обращает внимание на особенности народного монархизма, которые существовали в имперской России и были связаны с сужением народного тела до границ простого народа, крестьянства.
Transient Changes in Defence Gene Expression and Phytohormone Content Induced by Acibenzolar-S-Methyl in Glasshouse and Orchard Grown Kiwifruit
Authors: Reglinski Tony , Wurms Kirstin , Vanneste Joel , Ah Chee Annette , Yu Janet , Oldham Jenny , Cornish Deirdre , Cooney Janine , Jensen Dwayne , Trower Tania , Taylor Joseph , Schipper Magan , Alavi Maryam , McKenzie Catherine
Published: January 2022

Acibenzolar-S-methyl (ASM), the active ingredient in Actigard® (Syngenta), is a plant defence elicitor used for the management of bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) in kiwifruit. We examined changes in gene expression and phytohormone content in two kiwifruit cultivars, ‘Hayward’ (Actinidia chinensis var. deliciosa) and ‘Zesy002’ (A. chinensis var. chinensis), following ASM application. In glasshouse studies, ASM-induced resistance to stem inoculation with Psa was accompanied by upregulation of salicylic acid (SA) defence pathway genes (PR1, PR2, and PR5) in stems and leaves. The expression of PR1 in ASM-treated plants increased by c. 5-fold in ‘Hayward’ and by over 15-fold in ‘Zesy002,’ relative to the untreated controls, whereas PR2 and PR5 increased by up to 4-fold in both cultivars. Orchard studies over three seasons confirmed the utility of PR1, PR2, and PR5 for monitoring ASM-induced responses in mature vines. PR1 and PR5 were more strongly induced by ASM than PR2 and gene upregulation in ‘Hayward,’ was accompanied by a reduction in Psa leaf spotting; no such relationship was measurable for ‘Zesy002’ because leaf spot symptoms are rarely expressed. In the third season, six additional gene candidates, BAD, Gluc2, Class IV Chit, EDS1A, NPR3, and NIMIN2, were responsive to ASM in ‘Hayward’ and ‘Zesy002.’ Gene upregulation was transient, with expression levels increasing by 1 d after ASM application and declining to control levels between 7 and 14 days. Moreover, the amplitude of gene upregulation depended on leaf developmental stage and was greater in the first true leaf and the youngest mature leaves than in immature leaves along the same shoot. Phytohormone content did not show a repeatable response pattern to ASM in potted plants or in vines possibly as a consequence of their wider role in regulating plant growth and mediating environmental responses. In conclusion, this study demonstrates that defence gene expression can be used to monitor responsiveness to ASM in two genetically distinct mature kiwifruit cultivars (‘Hayward’ and ‘Zesy002’) under orchard conditions. The use of defence marker genes could be of broader utility across kiwifruit species and could be used to guide ASM application schedules in the orchard.
Singularity Containers Improve Reproducibility and Ease of Use in Computational Image Analysis Workflows
Authors: Mitra-Behura Shilpita , Fiolka Reto Paul , Daetwyler Stephan
Published: January 2022

Reproducing computational workflows in image analysis and microscopy can be a daunting task due to different software versions and dependencies. This is especially true for users with little specific knowledge of scientific computation. To overcome these challenges, we introduce Singularity containers as a useful tool to run and share image analysis workflows among many users, even years later after establishing them. Unfortunately, containers are rarely used so far in the image analysis field. To address this lack of use, we provide a detailed step-by-step protocol to package a state-of-the-art segmentation algorithm into a container on a local Windows machine to run the container on a high-performance cluster computer.
RecruitPlotEasy: An Advanced Read Recruitment Plot Tool for Assessing Metagenomic Population Abundance and Genetic Diversity
Authors: Gerhardt Kenji , Ruiz-Perez Carlos A. , Rodriguez-R Luis M. , Conrad Roth E. , Konstantinidis Konstantinos T.
Published: January 2022

Mapping of short metagenomic (or metatranscriptomic) read data to reference isolate or single-cell genomes or metagenome-assembled genomes (MAGs) to assess microbial population relative abundance and/or structure represents an essential task of many studies across environmental and clinical settings. The filtering for the quality of the read match and assessment of read mapping results are frequently performed without visual aids or with the assistance of visualizations produced through ad-hoc, in-house approaches. Here, we introduce RecruitPlotEasy, a fully automated, user-friendly pipeline for these purposes that integrates statistical approaches to quantify intra-population sequence and gene-content diversity and identify co-occurring relative populations in the sample. Hence, RecruitPlotEasy should also greatly facilitate population genetics studies.

RecruitPlotEasy is implemented in Python and R languages and is freely available open source software under the Artistic License 2.0 from https://github.com/KGerhardt/RecruitPlotEasy.
Interpreting Functional Impact of Genetic Variations by Network QTL for Genotype–Phenotype Association Study
Authors: Yuan Kai , Zeng Tao , Chen Luonan
Published: January 2022

An enormous challenge in the post-genome era is to annotate and resolve the consequences of genetic variation on diverse phenotypes. The genome-wide association study (GWAS) is a well-known method to identify potential genetic loci for complex traits from huge genetic variations, following which it is crucial to identify expression quantitative trait loci (eQTL). However, the conventional eQTL methods usually disregard the systematical role of single-nucleotide polymorphisms (SNPs) or genes, thereby overlooking many network-associated phenotypic determinates. Such a problem motivates us to recognize the network-based quantitative trait loci (QTL), i.e., network QTL (nQTL), which is to detect the cascade association as genotype → network → phenotype rather than conventional genotype → expression → phenotype in eQTL. Specifically, we develop the nQTL framework on the theory and approach of single-sample networks, which can identify not only network traits (e.g., the gene subnetwork associated with genotype) for analyzing complex biological processes but also network signatures (e.g., the interactive gene biomarker candidates screened from network traits) for characterizing targeted phenotype and corresponding subtypes. Our results show that the nQTL framework can efficiently capture associations between SNPs and network traits (i.e., edge traits) in various simulated data scenarios, compared with traditional eQTL methods. Furthermore, we have carried out nQTL analysis on diverse biological and biomedical datasets. Our analysis is effective in detecting network traits for various biological problems and can discover many network signatures for discriminating phenotypes, which can help interpret the influence of nQTL on disease subtyping, disease prognosis, drug response, and pathogen factor association. Particularly, in contrast to the conventional approaches, the nQTL framework could also identify many network traits from human bulk expression data, validated by matched single-cell RNA-seq data in an independent or unsupervised manner. All these results strongly support that nQTL and its detection framework can simultaneously explore the global genotype–network–phenotype associations and the underlying network traits or network signatures with functional impact and importance.
Identification of Novel Lung Cancer Driver Genes Connecting Different Omics Levels With a Heat Diffusion Algorithm
Authors: Yuan Fei , Cao Xiaoyu , Zhang Yu-Hang , Chen Lei , Huang Tao , Li ZhanDong , Cai Yu-Dong
Published: January 2022

Cancer driver gene is a type of gene with abnormal alterations that initiate or promote tumorigenesis. Driver genes can be used to reveal the fundamental pathological mechanisms of tumorigenesis. These genes may have pathological changes at different omics levels. Thus, identifying cancer driver genes involving two or more omics levels is essential. In this study, a computational investigation was conducted on lung cancer driver genes. Four omics levels, namely, epigenomics, genomics, transcriptomics, and post-transcriptomics, were involved. From the driver genes at each level, the Laplacian heat diffusion algorithm was executed on a protein–protein interaction network for discovering latent driver genes at this level. A following screen procedure was performed to extract essential driver genes, which contained three tests: permutation, association, and function tests, which can exclude false-positive genes and screen essential ones. Finally, the intersection operation was performed to obtain novel driver genes involving two omic levels. The analyses on obtained genes indicated that they were associated with fundamental pathological mechanisms of lung cancer at two corresponding omics levels.
Bicuspid Valve Sizing for Transcatheter Aortic Valve Implantation: The Missing Link
Authors: Costa Giulia , Angelillis Marco , Petronio Anna Sonia
Published: January 2022

Transcatheter aortic valve implantation (TAVI) is a well-recognized and established therapy for severe aortic stenosis, with expanding indications toward younger patients with low surgical risk profile. As bicuspid aortic valve (BAV) affects ~1–2% of the population, it may be speculated that an increasing number of patients with degenerated BAV may eventually need TAVI during the course of the disease. On the other hand, BAV represents a challenge due to its peculiar anatomical features and the lack of consensus on the optimal sizing strategy. The aim of this paper is to review the peculiar aspects of BAV and to discuss and compare the currently available sizing methods. Special attention is given to the role of pre-procedural imaging, mostly with multislice computed tomography, and to the aspects that operators should evaluate in order to ensure an optimal procedural planning and avoid procedural-related complications.
Concurrent Takayasu Arteritis and Vascular Ehlers–Danlos Syndrome: A Case Report
Authors: Hashimoto Kyota , Sakai Ryota , Shibata Akiko , Okada Yusuke , Yoshinaga Syoichi , Kurasawa Takahiko , Kondo Tsuneo , Amano Koichi
Published: January 2022

Takayasu arteritis (TAK) is a rare primary systemic inflammatory vasculopathy. It is classified as a large-vessel vasculitis and is known to cause inflammatory aneurysms and vascular stenosis. Vascular Ehlers–Danlos syndrome (vEDS) is an autosomal dominant condition known to cause multiple aneurysms and arterial dissection at a young age owing to a mutation in the gene for type III collagen, COL3A1. Here, we present a case of TAK associated with vEDS with the development of multi-organ infarction of the brain, kidney, and spleen owing to multiple arterial aneurysms and stenosis of the internal carotid artery. The patient was successfully treated using anti-inflammatory agents, glucocorticoids, and tocilizumab with the addition of interventional radiology. In our case, a high inflammatory response led to vasculitis being the main cause of the disease with concurrent vEDS. When patients develop multiple aneurysms, stenosis, and dissections leading to multiple organ infarctions, a systemic differential diagnosis to consider concurrent vasculitis syndrome and non-inflammatory vasculopathy, including hereditary disorders, is important even with time constraints.
Is a Little Enough? Paucity of Immune Proteins in Serum of Precocial Neonates of a Marine Carnivoran—the Atlantic Grey Seal
Authors: McGill Suzanne , Burchmore Richard J. S. , Pomeroy Patrick P. , Kennedy Malcolm W.
Published: January 2022

Mammalian mothers usually provide their offspring with large quantities of immunoglobulins (antibodies) for circulation in blood, either trans-placentally before birth,viacolostrum briefly thereafter, or, less commonly, from milk. Neonates of true, phocid seals, however, are peculiarly impoverished in serum immunoglobulins, the levels of which slowly increase but do not reach adult levels by the time of weaning. We investigated whether grey seal (Halichoerus grypus) neonates compensate through an elevation or rapid maturation in levels of serum innate immune factors, namely acute phase and complement proteins. Instead, their sera contained remarkably low levels of acute phase proteins (including C-reactive protein, haptoglobin, hemopexin, ceruloplasmin, orosomucoid), compared to their mothers, that barely increased to adult levels by weaning. For complement, there was a strong demarcation between the early activation and amplification cascade components (present at normal adult levels in pups) and the late lytic membrane attack complex and regulatory proteins (consistently at low relative levels). Phocid neonates therefore differ dramatically from land Carnivorans, such as dogs and cats, in early life immune protection. That neonatal phocids survive this apparent vulnerability to infections between birth and weaning prompts questions as to what other mechanisms protect them, and the adaptive value of their seeming vulnerability.
Homologous Cloning of Potassium Channel Genes From the Superior Apple Rootstock Line 12-2, Which is Tolerant to Apple Replant Disease
Authors: Mao Yunfei , Yin Yijun , Cui Xueli , Wang Haiyan , Su XiaFei , Qin Xin , Liu Yangbo , Hu Yanli , Shen Xiang
Published: January 2022

Potassium channels are important ion channels that are responsible for the absorption of potassium in the plant nutrient uptake system. In this study, we used homologous molecular cloning to obtain 8 K+ channel genes from the superior apple rootstock line 12-2 (self-named): MsAKT1-1, MsKAT3-2, MsKAT1-3, MsK2P3-4, MsK2P3-5, MsK2P5-6, MsK2P3-7, and MsK2P3-8. Their lengths varied from 942 bp (MsK2P5-6) to 2625 bp (MsAKT1-1), and the number of encoded amino acids varied from 314 (MsK2P5-6) to 874 (MsAKT1-1). Subcellular localization predictions showed that MsAKT1-1, MsKAT3-2, and MsKAT1-3 were localized on the plasma membrane, and MsK2P3-4, MsK2P3-5, MsK2P5-6, MsK2P3-7, and MsK2P3-8 were localized on the vacuole and plasma membrane. The 8 K+ channel proteins contained α helices, extended strands, β turns, and random coils. MsKAT1-3 had four transmembrane structures, MsKAT3-2 had six, and the other six K+ channel genes had five. Protein structure domain analysis showed that MsAKT1-1 contained nine protein domains, followed by MsKAT3-2 with four, MsKAT1-3 with three, and the other five two-pore domain K+ channel proteins with two. Semi-quantitative RT-PCR detection of the K+ channel genes showed that their expression levels were high in roots. qRT-PCR analysis showed that the relative expression levels of the 8 genes changed after exposure to ARD stress. The above results provide a theoretical basis for further research on the functions of potassium channel genes in 12-2 and a scientific basis for the breeding of ARD-resistant rootstock.
Impact of COVID-19 on Gender-Based Violence Prevention and Response Services in Kenya, Uganda, Nigeria, and South Africa: A Cross-Sectional Survey
Authors: Roy Charlotte M. , Bukuluki Paul , Casey Sara E. , Jagun Moriam O. , John Neetu A. , Mabhena Nicoletta , Mwangi Mary , McGovern Terry
Published: January 2022

Background

Epidemics and other complex emergencies historically have had a disproportionate impact on women and girls, increasing their vulnerability to gender-based violence (GBV). The COVID-19 pandemic has been no different, with reports of rising cases of GBV emerging worldwide. Already a significant problem in Kenya, Uganda, Nigeria, and South Africa, GBV in these countries has been exacerbated by government restrictions intended to contain the spread of COVID-19. The purpose of this study was to understand how the COVID-19 pandemic affected the availability of GBV prevention and response services from the perspective of the organizations that provide them.

Methods

A cross-sectional online survey of people who work in GBV prevention and response in Kenya, Uganda, Nigeria, and South Africa was administered from July to October 2020. A convenience sample was identified through web search, contacts of in-country consultants, and relevant listservs and technical working groups. Descriptive analyses were completed using SPSS.

Results

A total of 187 respondents completed the survey. Nearly all (98.9%) survey respondents reported that COVID-19 impacted their work. The majority (77.9%) stated that work decreased due to government restrictions or GBV services being deemed non-essential. The types of service most impacted were community-based prevention, shelters, and legal services. Survey respondents overwhelmingly agreed (99.3%) that COVID-19 impacted GBV prevalence and identified adolescents and women with disabilities as particularly vulnerable groups.

Conclusions

GBV prevention and response services in Kenya, Uganda, Nigeria, and South Africa were highly impacted by the COVID-19 pandemic, largely due to government restrictions and the failure of governments to deem GBV services as essential. Preparedness for future crises should ensure that GBV is adequately prioritized in the initial response in order to maintain service availability with special attention paid to at-risk populations.
Interleukin-1 Inhibitors and Vaccination Including COVID-19 in Inflammatory Rheumatic Diseases: A Nonsystematic Review
Authors: Atagündüz Pamir , Keser Gökhan , Soy Mehmet
Published: January 2022

Newly emerging variants of coronavirus 2 (SARS-CoV-2) raise concerns about the spread of the disease, and with the rising case numbers, the Coronavirus disease 2019 (COVID-19) remains a challenging medical emergency towards the end of the year 2021. Swiftly developed novel vaccines aid in the prevention of the spread, and it seems that a specific cure will not be at hand soon. The prognosis of COVID-19 in patients with autoimmune/autoinflammatory rheumatic diseases (AIIRD) is more severe when compared to the otherwise healthy population, and vaccination is essential. Evidence for both the efficacy and safety of COVID-19 vaccination in AIIRD under immunosuppression is accumulating, but the effect of Interleukin-1 on vaccination in general and in AIIRD patients is rarely addressed in the current literature. In light of the current literature, it seems that the level of agreement on the timing of COVID-19 vaccination is moderate in patients using IL-1 blockers, and expert opinions may vary. Generally, it may be recommended that patients under IL-1 blockade can be vaccinated without interrupting the anti-cytokine therapy, especially in patients with ongoing high disease activity to avoid disease relapses. However, in selected cases, after balancing for disease activity and risk of relapses, vaccination may be given seven days after the drug levels have returned to baseline, especially for IL-1 blocking agents with long half-lives such as canakinumab and rilonacept. This may help to ensure an ideal vaccine response in the face of the possibility that AIIRD patients may develop a more pronounced and severe COVID-19 disease course.
Purine-Induced IFN-γ Promotes Uric Acid Production by Upregulating Xanthine Oxidoreductase Expression
Authors: Wang Huanhuan , Xie Lingzhu , Song Xuhong , Wang Jing , Li Xinyan , Lin Zhike , Su Ting , Liang Bin , Huang Dongyang
Published: January 2022

Objective

Limiting purine intake, inhibiting xanthine oxidoreductase (XOR) and inhibiting urate reabsorption in proximal tubule by uricosuric drugs, to reduce serum uric acid (UA) levels, are recognized treatments for gout. However, the mechanism of increased how XOR expression and activity in hyperuricemia and gout remains unclear. This study aims to explore whether exogenous purines are responsible for increased XOR expression and activity.

Methods

HepG2 and Bel-7402 human hepatoma cells were stimulated with exogenous purine, or were exposed to conditioned growth medium of purine-stimulated Jurkat cells, followed by measurement of XOR expression and UA production to determine the effect of lymphocyte-secreted cytokines on XOR expression in hepatocytes. The expression of STAT1, IRF1 and CBP and their binding on theXDHpromoter were detected by western blotting and ChIP-qPCR. The level of DNA methylation was determined by bisulfite sequencing PCR. Blood samples from 117 hyperuricemia patients and 119 healthy individuals were collected to analyze the correlation between purine, UA and IFN-γ concentrations.

Results

Excess of purine was metabolized to UA in hepatocyte metabolism by XOR that was induced by IFN-γ secreted in the conditioned growth medium of Jurkat cells in response to exogenous purine, but it did not directly induce XOR expression. IFN-γ upregulated XOR expression due to the enhanced binding of STAT1 to IRF1 to further recruit CBP to theXDHpromoter. Clinical data showed positive correlation of serum IFN‐γ with both purine and UA, and associated risk of hyperuricemia.

Conclusion

Purine not only acts as a metabolic substrate of XOR for UA production, but it induces inflammation through IFN-γ secretion that stimulates UA production through elevation of XOR expression.
CD19 CAR-T Cell Therapy Induced Immunotherapy Associated Interstitial Pneumonitis: A Case Report
Authors: Sun Zhuanyi , Xie Caiqin , Liu Hui , Yuan Xianggui
Published: January 2022

Background

Chimeric antigen receptor-modified T cells (CAR-T) targeting CD19 has produced a high durable response in refractory or relapsed diffuse large B-cell lymphoma. Besides well-known cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome during CAR-T cell therapy, there were several rarely encountered fatal complications.

Case Report

A 63-year-old male patient with refractory EBV-positive diffuse large B-cell lymphoma, developed interstitial pneumonitis with prolonged hypoxemia at 16 weeks after CD19 CAR-T cell therapy. There was no evidence of CRS and any infections. The patient recovered after intravenous immunoglobulin without tocilizumab or glucocorticoid administration. Now he is still in remission without interstitial pneumonitis 3 years after CAR-T cell therapy.

Conclusion

This is the first report of immunotherapy-associated interstitial pneumonitis after CAR-T cell therapy. Our finding suggested the importance of careful follow-up and proper treatments for immunotherapy-associated pneumonitis in the CAR-T cell therapy schedule.
Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation
Authors: Liu Hailin , Hu Jialing , Zheng Qingcui , Feng Xiaojin , Zhan Fenfang , Wang Xifeng , Xu Guohai , Hua Fuzhou
Published: January 2022

Mechanical damage is one of the predisposing factors of inflammation, and it runs through the entire inflammatory pathological process. Repeated or persistent damaging mechanical irritation leads to chronic inflammatory diseases. The mechanism of how mechanical forces induce inflammation is not fully understood. Piezo1 is a newly discovered mechanically sensitive ion channel. The Piezo1 channel opens in response to mechanical stimuli, transducing mechanical signals into an inflammatory cascade in the cell leading to tissue inflammation. A large amount of evidence shows that Piezo1 plays a vital role in the occurrence and progression of chronic inflammatory diseases. This mini-review briefly presents new evidence that Piezo1 responds to different mechanical stresses to trigger inflammation in various tissues. The discovery of Piezo1 provides new insights for the treatment of chronic inflammatory diseases related to mechanical stress. Inhibiting the transduction of damaging mechanical signals into inflammatory signals can inhibit inflammation and improve the outcome of inflammation at an early stage. The pharmacology of Piezo1 has shown bright prospects. The development of tissue-specific Piezo1 drugs for clinical use may be a new target for treating chronic inflammation.
Interaction of Insecticides and Fungicides in Bees
Authors: Schuhmann Antonia , Schmid Anna Paulina , Manzer Sarah , Schulte Janna , Scheiner Ricarda
Published: January 2022

Honeybees and wild bees are among the most important pollinators of both wild and cultivated landscapes. In recent years, however, a significant decline in these pollinators has been recorded. This decrease can have many causes including the heavy use of biocidal plant protection products in agriculture. The most frequent residues in bee products originate from fungicides, while neonicotinoids and, to a lesser extent, pyrethroids are among the most popular insecticides detected in bee products. There is abundant evidence of toxic side effects on honeybees and wild bees produced by neonicotinoids, but only few studies have investigated side effects of fungicides, because they are generally regarded as not being harmful for bees. In the field, a variety of substances are taken up by bees including mixtures of insecticides and fungicides, and their combinations can be lethal for these pollinators, depending on the specific group of insecticide or fungicide. This review discusses the different combinations of major insecticide and fungicide classes and their effects on honeybees and wild bees. Fungicides inhibiting the sterol biosynthesis pathway can strongly increase the toxicity of neonicotinoids and pyrethroids. Other fungicides, in contrast, do not appear to enhance toxicity when combined with neonicotinoid or pyrethroid insecticides. But the knowledge on possible interactions of fungicides not inhibiting the sterol biosynthesis pathway and insecticides is poor, particularly in wild bees, emphasizing the need for further studies on possible effects of insecticide-fungicide interactions in bees.
Roles of Bacterial Symbionts in Transmission of Plant Virus by Hemipteran Vectors
Authors: Wu Wei , Shan Hong-Wei , Li Jun-Min , Zhang Chuan-Xi , Chen Jian-Ping , Mao Qianzhuo
Published: January 2022

The majority of plant viruses are transmitted by hemipteran insects. Bacterial symbionts in hemipteran hosts have a significant impact on the host life, physiology and ecology. Recently, the involvement of bacterial symbionts in hemipteran vector-virus and vector-plant interactions has been documented. Thus, the exploitation and manipulation of bacterial symbionts have great potential for plant viral disease control. Herein, we review the studies performed on the impact of symbiotic bacteria on plant virus transmission, including insect-bacterial symbiont associations, the role of these bacterial symbionts in viral acquisition, stability and release during viral circulation in insect bodies, and in viral vertical transmission. Besides, we prospect further studies aimed to understand tripartite interactions of the virus-symbiotic microorganisms-insect vector.
USF1 Transcriptionally Regulates UGT1A3 and Promotes Lung Adenocarcinoma Progression by Regulating Neurotrophin Signaling Pathway
Authors: Wang Yu , Zhao Yun-Xia , Zhang Xiang-Wei , Jiang Yuan-Zhu , Ma Wei , Zhang Lin , Dong Wei
Published: January 2022

Background: Lung cancer remains the leading cause of oncological death. There is an urgent need to discover new molecular targets and to develop new treatments. Our previous study showed that one of the UDP-glucuronosyltransferases (UGTs) family, UGT1A3, is an important prognostic factor for lung adenocarcinoma (LUAD), inhibiting UGT1A3 could significantly improve the efficacy of anti-tumor drugs. In this study, we aimed to explore the upstream transcriptional factor (USF1) of UGT1A3 and its way of playing a role in LUAD.

Methods: The UGT1A3 promoter region was analyzed and dual-luciferase assay was involved to explore whether USF1 could bind to this region, and the possible regulation effects of USF1 to UGT1A3 was indicated by siRNA and recovery experiment. Then, the Cancer Genome Atlas database was used to analyze USF1 clinical features. The expression level of USF1 was detected by immunohistochemical assay and Western blotting. Cellular viability, proliferation, migration and invasion potential were also investigated. Meanwhile, the effect of USF1 in LUAD progression was detected in a mouse model. The downstream signaling pathway was analyzed by bioinformatic analysis and the expression of all related proteins was detected.

Results: UGT1A3 was transcriptionally regulated by USF1, which was highly expressed in all investigated samples including patients’ tissues, studied cells lines, and mouse models. The knockdown of USF1 inhibited cells viability, proliferation, migration and invasion, and reduced the tumor volume. Moreover, USF1 promoted the progress of LUAD by regulating the neurotrophin signaling pathway.

Conclusion: As an important transcriptional regulator of UGT1A3, USF1 was highly expressed in LUAD and promoted LUAD progression by regulating the neurotrophin signaling pathway. These findings provide a new theoretical data that could serve as a good foundation for the treatment of LUAD.
Random and Systematic Variation in Nanoscale Hf0.5Zr0.5O2 Ferroelectric FinFETs: Physical Origin and Neuromorphic Circuit Implications
Authors: De Sourav , Baig Md. Aftab , Qiu Bo-Han , Müller Franz , Le Hoang-Hiep , Lederer Maximilian , Kämpfe Thomas , Ali Tarek , Sung Po-Jung , Su Chun-Jung , Lee Yao-Jen , Lu Darsen D.
Published: January 2022

This work presents 2-bits/cell operation in deeply scaled ferroelectric finFETs (Fe-finFET) with a 1 µs write pulse of maximum ±5 V amplitude and WRITE endurance above 109 cycles. Fe-finFET devices with single and multiple fins have been fabricated on an SOI wafer using a gate first process, with gate lengths down to 70 nm and fin width 20 nm. Extrapolated retention above 10 years also ensures stable inference operation for 10 years without any need for re-training. Statistical modeling of device-to-device and cycle-to-cycle variation is performed based on measured data and applied to neural network simulations using the CIMulator software platform. Stochastic device-to-device variation is mainly compensated during online training and has virtually no impact on training accuracy. On the other hand, stochastic cycle-to-cycle threshold voltage variation up to 400 mV can be tolerated for MNIST handwritten digits recognition. A substantial inference accuracy drop with systematic retention degradation was observed in analog neural networks. However, quaternary neural networks (QNNs) and binary neural networks (BNNs) with Fe-finFETs as synaptic devices demonstrated excellent immunity toward the cumulative impact of stochastic and systematic variations.
Delays in the Reticulospinal System Are Associated With a Reduced Capacity to Learn a Simulated Feeding Task in Older Adults
Authors: Rangarajan Vishvak , Schreiber Joseph J. , Barragan Beatriz , Schaefer Sydney Y. , Honeycutt Claire F.
Published: January 2022

Learning declines with age. Recent evidence indicates that the brainstem may play an important role in learning and motor skill acquisition. Our objective was to determine if delays in the reticular formation, measured via the startle reflex, correspond to age-related deficits in learning and retention. We hypothesized that delays in the startle reflex would be linearly correlated to learning and retention deficits in older adults. To determine if associations were unique to the reticulospinal system, we also evaluated corticospinal contributions with transcranial magnetic stimulation. Our results showed a linear relationship between startle onset latency and percent learning and retention but no relationship between active or passive motor-evoked potential onsets or peak-to-peak amplitude. These results lay the foundation for further study to evaluate if (1) the reticular formation is a subcortical facilitator of skill acquisition and (2) processing delays in the reticular formation contribute to age-related learning deficits.
Efficacy and Toxicity of Whole Pelvic Radiotherapy Versus Prostate-Only Radiotherapy in Localized Prostate Cancer: A Systematic Review and Meta-Analysis
Authors: Wang Shilin , Tang Wen , Luo Huanli , Jin Fu , Wang Ying
Published: January 2022

Background

There is little level 1 evidence regarding the relative efficacy and toxicity of whole pelvic radiotherapy (WPRT) compared with prostate-only radiotherapy (PORT) for localized prostate cancer.

Methods

We used Cochrane, PubMed, Embase, Medline databases, and ClinicalTrials.gov to systematically search for all relevant clinical studies. The data on efficacy and toxicity were extracted for quality assessment and meta-analysis to quantify the effect of WPRT on biochemical failure-free survival (BFFS), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), gastrointestinal (GI) toxicity, and genitourinary (GU) toxicity compared with PORT. The review is registered on PROSPERO, number: CRD42021254752.

Results

The results revealed that compared with PORT, WPRT significantly improved 5-year BFFS and PFS, and it was irrelevant to whether the patients had undergone radical prostatectomy (RP). In addition, for the patients who did not receive RP, the 5-year DMFS of WPRT was better than that of PORT. However, WPRT significantly increased not only the grade 2 or worse (G2+) acute GI toxicity of non-RP studies and RP studies, but also the G2+ late GI toxicity of non-RP studies. Subgroup analysis of non-RP studies found that, when the pelvic radiation dose was >49 Gy (equivalent-doses-in-2-Gy-fractions, EQD-2), WPRT was more beneficial to PFS than PORT, but significantly increased the risk of G2+ acute and late GU toxicity.

Conclusions

Meta-analysis demonstrates that WPRT can significantly improve BFFS and PFS for localized prostate cancer than PORT, but the increased risk of G2+ acute and late GI toxicity must be considered.

Systematic Review Registration

PROSPERO CRD42021254752.
Semaphorins as Potential Immune Therapeutic Targets for Cancer
Authors: Jiang Jun , Zhang Fang , Wan Yi , Fang Ke , Yan Ze-dong , Ren Xin-ling , Zhang Rui
Published: January 2022

Semaphorins are a large class of secreted or membrane-bound molecules. It has been reported that semaphorins play important roles in regulating several hallmarks of cancer, including angiogenesis, metastasis, and immune evasion. Semaphorins and their receptors are widely expressed on tumor cells and immune cells. However, the biological role of semaphorins in tumor immune microenvironment is intricate. The dysregulation of semaphorins influences the recruitment and infiltration of immune cells, leading to abnormal anti-tumor effect. Although the underlying mechanisms of semaphorins on regulating tumor-infiltrating immune cell activation and functions are not fully understood, semaphorins can notably be promising immunotherapy targets for cancer.
How Can a High-Performance Screening Strategy Be Determined for Cervical Cancer Prevention? Evidence From a Hierarchical Clustering Analysis of a Multicentric Clinical Study
Authors: Bao Heling , Zhang Xiaosong , Bi Hui , Zhao Yun , Fang Liwen , Wang Haijun , Wang Linhong
Published: January 2022

Background

This study aimed to explore the cluster patterns of cervical cancer screening strategies for detecting high-grade precancerous lesions in terms of benefits, costs, and efficiency.

Methods

A total of 2,065 referral women aged 25–64 years were recruited and underwent human papillomavirus (HPV) testing, liquid-based cytology with manual reading, and cytology with artificial intelligence (AI)-assisted reading. All women were assessed by colposcopy and histological examination. We formed 14 screening strategies based on primary cytology screening, primary HPV screening incorporating HPV-16/18 genotyping triage, cytology triage, or both, and co-testing. The primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+). The hierarchical clustering method was applied to multifaceted indicators, and then, the resulting clusters were described in terms of benefits, costs, efficiency, and their interaction. This study was registered (No. ChiCTR2000034131).

Results

The relative sensitivity of HPV-based strategies compared with cytology alone with the threshold of LSIL+ ranged from 0.68 to 1.19 for CIN2+ detection and from 0.72 to 1.11 for CIN3+ detection, whereas the relative specificity ranged from 0.55 to 1.43 for CIN2+ detection and from 0.51 to 1.51 for CIN3+ detection. Five significant clusters according to the trade-off among benefits, costs, and efficiency were identified. The cluster including four primary HPV screening strategies showed the optimal balance. HPV testing with HPV-16/18 genotyping and AI-based cytology triage presented the optimal trade-off for CIN3+ detection relative to cytology alone in terms of relative sensitivity (1.06), relative specificity (0.72), colposcopies for 1 CIN3+ (3.7 vs. 3.1), a load of follow-up for women with HPV-positive and normal cytology (7.0% vs. 22.3%), and the work of manual cytology reading (35.1% vs. 100%).

Conclusions

Our study provided clinical and methodological evidence on the choice of HPV-based screening strategies. The cluster including primary HPV screening with genotyping and cytology triage showed an optimal balance among benefit, cost, and efficiency.
Predictors of Spontaneous Rupture of Hepatocellular Carcinoma and Clinical Outcomes Following Hepatectomy
Authors: Chen Yiran , Guo Deliang , Li Xinyi , Xu Chang , Zhu Qian
Published: January 2022

Objective

To explore the independent predictive factors of spontaneous tumor rupture (STR) in patients undergoing curative resection of hepatocellular carcinoma (HCC), and to evaluate the impact of STRHCC on long-term survival after hepatectomy.

Methods

The clinicopathological parameters of 106 patients with STRHCC and 201 patients with non-ruptured HCC who underwent hepatectomy from January 2007 to November 2011 at the Eastern Hepatobiliary Surgery Hospital and Zhongnan Hospital of Wuhan University were analyzed using propensity score matching (PSM) and a logistic regression model.

Results

Factors including hypertension, cirrhosis, total bilirubin (TB), tumor size, and ascites were independent predictors of STR. For all 307 HCC patients, the 1-, 3- and 5-year overall survival (OS) rates were 54.0%, 37.3% and 33.8%, respectively. After PSM, the 1-, 3-, and 5-year OS rates in the ruptured group remained significantly lower at 41.5%, 23.5%, and 17.5% when compared with the non-ruptured group at 70.8%, 47.1%, and 37.6%, respectively, while the 1-, 3-, and 5-year disease-free survival (DFS) rates between the groups did not differ significantly (50.4%, 35.1%, 27.1% vs 55.4%, 38.2%, 27.4%). STRHCC was significantly associated with increased risk of OS, but not of shorter DFS. No significant difference in postoperative morbidity or hospital death was observed between the groups.

Conclusion

Factors including hypertension, liver cirrhosis, higher TB levels, tumor size > 5cm, and ascites are significant predictors of STR. The recurrence rate of patients in the ruptured group was significantly higher than that of patients in the non-ruptured group. STR results in poorer OS but not DFS in patients undergoing curative resection for HCC. STRHCC has no impact on postoperative morbidity and mortality after hepatectomy.
Development of the ICF-CY Set for Cardiac Rehabilitation After Pediatric Congenital Heart Surgery
Authors: Luo Wen-Yi , Ni Ping , Chen Lin , Pan Qian-Qian , Zhang Hao , Zhang Ya-Qing
Published: January 2022

Background

Most children with congenital heart disease (CHD) require surgical repair, and postoperative rehabilitation is an essential step to restore the quality of life. The present study constructs and confirms the International Classification of Functioning, Disability, and Health for Children and Youth core set for children with congenital heart disease 1 year after surgery (ICF-CY-CHDS).

Methods

From February 2021 to August 2021, 340 children aged 3–6 years after CHD surgery were evaluated using the ICF-CY-CHDS and analyzed using the Rasch model.

Results

The final ICF-CY-CHDS contained 22 categories; it exhibited a nonsignificant χ2 test result for the item-trait interaction (χ2 = 6736.37, p = 0.8660, Bonferroni-adjusted p = 0.0023). The average severity of children was less than the average difficulty of categories (−2.26 logit <0 logit). The weighted k of all the categories was 0.964 (p < 0.001), and the item separation index was 0.96. The area under the ROC curve of children with a diagnosis result of heart failure was 0.866 (95% CI: 0.801 ~0.931) with good sensitivity (0.875) and specificity (0.759).

Conclusion

The ICF-CY-CHDS presents a preliminary practical direction during early cardiac rehabilitation after pediatric CHD surgery, and thus provides a basis and scope for clinical evaluation and intervention program formulation.
Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal the Protective Effect of Salvianolic Acid C in a Rat Model of Ischemic Stroke
Authors: Yang Yuting , He Yu , Wei Xiaoyu , Wan Haitong , Ding Zhishan , Yang Jiehong , Zhou Huifen
Published: January 2022

Salvianolic acid C (SAC) is a major bioactive component of Salvia miltiorrhiza Bunge (Danshen), a Chinese herb for treating ischemic stroke (IS). However, the mechanism by which SAC affects the IS has not yet been evaluated, thus a network pharmacology integrated molecular docking strategy was performed to systematically evaluate its pharmacological mechanisms, which were further validated in rats with cerebral ischemia. A total of 361 potential SAC-related targets were predicted by SwissTargetPrediction and PharmMapper, and a total of 443 IS-related targets were obtained from DisGeNET, DrugBank, OMIM, and Therapeutic Target database (TTD) databases. SAC-related targets were hit by the 60 targets associated with IS. By Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment combined with the protein-protein interaction (PPI) network and cytoHubba plug-ins, nine related signaling pathways (proteoglycans in cancer, pathways in cancer, PI3K-Akt signaling pathway, Focal adhesion, etc.), and 20 hub genes were identified. Consequently, molecular docking indicated that SAC may interact with the nine targets (F2, MMP7, KDR, IGF1, REN, PPARG, PLG, ACE and MMP1). Four of the target proteins (VEGFR2, MMP1, PPARγ and IGF1) were verified using western blot. This study comprehensively analyzed pathways and targets related to the treatment of IS by SAC. The results of western blot also confirmed that the SAC against IS is mainly related to anti-inflammatory and angiogenesis, which provides a reference for us to find and explore the effective anti-IS drugs.
Transmembrane 4 L Six Family Member 1 Suppresses Hormone Receptor-–Positive, HER2-Negative Breast Cancer Cell Proliferation
Authors: Chen Jie , Zhu Jin , Xu Shuai-Jun , Zhou Jun , Ding Xiao-Fei , Liang Yong , Chen Guang , Lu Hong-Sheng
Published: January 2022

Background: The prognosis of breast cancer varies according to the molecular subtype. Transmembrane 4 L six family 1 (TM4SF1) exhibits different expression patterns among the molecular subtypes of breast cancer. However, the expression profile of TM4SF1 in hormone receptor HR+HER2- breast cancer remains unclear.

Methods: TM4SF1 mRNA levels were examined in major subclasses of breast cancer by analyzing The Cancer Genome Atlas (TCGA) datasets. In addition, TM4SF1 protein and mRNA levels in HR+HER2- breast cancer tissue samples were determined by immunohistochemistry and Western blot assay. The effect of TM4SF1 on cell proliferation was evaluated using MTT, colony formation, 3D organoid, and xenograft models, following the TM4SF1 overexpression or knockdown.

Results: TCGA database analysis demonstrated that TM4SF1 was downregulated in breast cancer compared with the healthy adjacent breast tissue. In addition, the expression of TM4SF1 in basal-like one and the mesenchymal TNBC tissue was higher than that of the healthy adjacent breast tissue. Other types, including the luminal androgen receptor–positive TNBC tissue, expressed lower levels of TM4SF1. Immunohistochemistry and real-time quantitative PCR assays demonstrated that the TM4SF1 protein and mRNA levels were downregulated in the HR+HER2- breast cancer tissue compared with the healthy adjacent tissue. Moreover, the TM4SF1 overexpression reduced the viability of MCF-7 and ZR-75-1 breast cancer cells, whilst reducing the number of colonies and 3D-organoids formed by these cell lines. By contrast, TM4SF1 knockdown led to an increased MCF-7 cell proliferation. However, in the TNBC cell line, MDA-MB-231, TM4SF1 silencing reduced cell proliferation. In vivo, the TM4SF1 overexpression inhibited MCF-7 xenograft growth in a nude mouse model, which was associated with the downregulation of the Ki-67 expression, apoptosis induction, and inhibition of the mTOR pathway.

Conclusion: TM4SF1 is downregulated in HR + HER2-breast cancer, and the overexpression of TM4SF1 suppresses cell proliferation in this cancer subtype.