bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Magnetic Treatment On Seedling Growth, Nitrogen Metabolism, And Mineral Nutrient Contents In Populus×Euramericana 'Neva' Under Cadmium Stress
Authors: Liu Xiumei , Ma Fengyun , Wang Lu , Zhu Hong , Meng Shiyuan , Bi Sisheng , Guo Jianyao , Wang Huatian
Published: August 2021

Background: The potted experiment was carried out to investigate the mechanism of nutrient metabolism and seedling growth caused by magnetic treatment (MT) following exposure to cadmium (Cd) stress. One-year-old seedlings of Populus×euramericana 'Neva' were treated with different Cd(NO3)2 solutions for 30 days. Properties of seedling growth and root morphology were promoted by MT under Cd exposure.Results: Contents of ammonium (NH4+-N), nitrate (NO3--N), and total nitrogen (TN) in leaves, also NH4+-N and TN in roots, were increased by MT combined with Cd-stress, although NO3--N content was decreased. Activities of nitrate reductase (NR), nitrite reductase (NiR), glutathione reductase (GR), and glutamate synthase (GOGAT) in leaves and activities of NR, GS and GOGAT in roots were stimulated by MT; conversely, NiR activity in roots was inhibited. MT improved the synthesis of cysteine (Cys) and glutamine (Gln) in leaves and reduced the contents of glutamic acid (Glu) and glycine (Gly), while contents of Cys, Glu, Gln, and Gly were increased in roots. (4) The contents of Ca, Mg, Fe, Mn, Zn and Cu were increased by MT under Cd stress in leaves, whereas content of K was reduced. In roots, contents of K, Ca, and Fe were increased by MT under Cd-stress, but the contents of Na, Mg, Mn, Zn, and Cu were decreased.Conclusions: Magnetization could regulate the uptake of mineral nutrients by roots and translocation from the roots to aboveground parts by affecting the root morphology. MT could also improve nitrogen assimilation and the synthesis of free amino acids by stimulating the activities of key enzymes.
Web-Based Software Applications for Frailty Assessment in Older Adults: Current Status and Insights Into Future Development
Authors: Chang Riley , Low Hilary , McDonald Andrew , Park Grace , Song Xiaowei
Published: August 2021

Background: A crucial aspect of continued senior care is the early detection and management of frailty. Developing reliable and secure electronic frailty assessment tools can benefit virtual appointments, a need especially apparent since the COVID-19 pandemic. An emerging effort has targeted web-based software applications to improve accessibility and usage. Methods: We conducted an environmental scan through MEDLINE and Google searches (last updated on June 1st, 2021) to identify currently available web applications, each of which was evaluated and assigned a rating score based on eight featured categories.Results: Twelve web-based frailty assessment applications were found, chiefly provided by the USA (50%) or European countries (42%) and focused on frailty grading and outcome prediction for specific patient groups (58%). The categories that scored well among the applications included the User Interface (2.67/3) and the Cost (2.75/3). Other categories had a mean score of 1.5 or lower. The least developed features in the existing web applications included Data Saving.Conclusions: This is the first study that has compiled a comprehensive list of frailty assessments available online, described their usage and evaluated their advantages and limitations. The study emphasized several essential features with future web application development to support early detection and management of frailty with virtual care.
Interleukin 7 Inhibit Autophagy via P53 Regulated AMPK/mTOR Signaling Pathway in Non-small Cell Lung Cancer
Authors: Zhu Yunjia , Jiang Xi , Ding Zhiying , Ming Jian
Published: August 2021

Interleukin 7(IL-7) has been demonstrated regulating lymphangiogenesis, apoptosis, and proliferation. Whether IL-7 induce or inhibit autophagy in non-small cell lung cancer(NSCLC) are unknown. Methods In this study, Western blot was used to detect cytoplasmic and nuclear protein of p53, total protein of AMP-activated protein kinase(AMPK) and mammalian target of rapamycin (mTOR). Quantitative Real-Time PCR(qRT-PCR) was used to detect p53 mRNA level after treated with IL-7. Then using transmission electron microscopy (TEM) to observe the morphological change of autophagosome. 123 cases of NSCLC were collected for survival analysis, immunohistochemistry staining and cox regression multivariate analysis. Results We find that IL-7 induce the p53 translocation from nucleus to cytoplasm, then IL-7 down-regulate phosphorylation of AMPK and up-regulate phosphorylation of mTOR. The expression of AMPK and p53 were associated with IL-7/IL-7R and mTOR expression. Clinically, AMPK and p53 were well correlated with stage and survival of lung cancer patients. IL-7R, mTOR and tumor stage were the strongest predictors of survival. Conclusion In conclusion, IL-7 inhibit autophagy in NSCLC via P53 regulated AMPK/mTOR signaling pathway. AMPK and p53 are correlated with patients’ survival. IL-7R, mTOR and tumor stage are the strongest predictor of survival.
An Optical Clearing Technique to Visualize Internal Root Structure
Authors: HE YUNXIAO , Yan Qingqing , Yang Dongyong , Li Min , Xiao Youli
Published: August 2021

BackgroundRoots play an important role in the foraging and uptake of nutrients and water from soil to support sessile plant growth. Research on root growth and development in plants is very limited due to the thickness and opacity of roots. We developed a tissue clearing technique that enables visualization of crop internal root structure.ResultsThe application of methyl salicylate reduced the time taken for root clearing and accelerated the dye permeation into the tissue; the whole procedure for root clearing was performed within 3 days. We applied our technique on the roots of monocotyledonous plants, such as rice (Oryza sativa L.), wheat (Triticum aestivum L.), and maize (Zea mays L.), and dicotyledonous plants, such as rape (Brassica napus L. var oleifera), tomato (Solanum lycopersicum), and soybean (Glycine max (Linn.) Merr.), and obtained clear root structure. It not only shortens the time for root tissue clearing but also keeps the cell structure of intact roots. The transparent sample can be preserved for more than one year without any structural deformation.Conclusions﻿Our technique can create a 3-D reconstruction of the entire root structure. In summary, this method is a useful tool for visualizing the structures of thick root tissues and will be a valuable tool for research on root growth and development in plants.
Epidemiological Characteristics of COVID-19 Deaths in China: An Analysis of Environmental Factors
Authors: Feng Xixi , Du Peipei , Li Guobao , Cao Peihua , Luo Jiaohua , Yan Xiaodong , Luo Jiawei , He Daihai , Yang Lin , Wang Xiaohui , Fu Yang , Yang Shu , Chen Yaolong
Published: August 2021

Background
Since December 2019, China has carried out dramatic containment measures to control the spread of COVID-19. As of April 6, 2020, most of the confirmed cases outside Hubei province have been cured or confirmed dead. In this study, we aimed to understand environmental factors leading to COVID-19-related mortality outside of Hubei province, in mainland China.
Methods
We collected spatial-temporal and environmental data of 99 cases of COVID-19-related deaths outside of Hubei province in Mainland China between January 22, 2020 and April 6, 2020. A descriptive analysis, including a spatial-temporal distribution of daily reported diagnosed cases and related deaths, was conducted. We analyzed the possible environmental factors that affect the provincial-level CFR of COVID-19 outside Hubei, China.
Results
Among the 99 reported deaths, 59 (59.6%) were male and 40 (40.4%) were female. The mean age at death was 71.30 (SD 12.98) years and 74 deaths were among those 65 years or older. The CFR was negatively correlated with temperature (r=-0.679, P < 0.001) and humidity (r=-0.607, P = 0.002), while latitude was positively correlated with the CFR (r = 0.636, P = 0.001). There were no statistically significant associations between CFR and the social environment factors.
Conclusion
Higher CFR of COVID-19 was associated with lower temperature, lower humidity, and higher latitude. Continual analysis of daily reported diagnoses and mortality data can help healthcare professionals and policy makers understand the trends within a country in order to better prepare nationwide prevention and care guidelines, along with adequately appropriate funds accordingly.
Five-Level Unilateral Laminectomy Bilateral Decompression (ULBD) by Two-Stage Unilateral Biportal Endoscopy (UBE)
Authors: Wang Wenlong , Liu Zheng
Published: August 2021

Background Unilateral biportal endoscopy (UBE) is a relatively new yet common minimally invasive procedure in spine surgery, capable of achieving adequate decompression for lumbar spinal stenosis through unilateral laminectomy bilateral decompression (ULBD). Neither additional fusion nor rigid fixation is required, as UBE-ULBD rarely causes iatrogenic lumbar instability. However, to our knowledge, five-level ULBD via two-stage UBE without lumbar fusion has been yet to be reported in the treatment of multilevel lumbar spinal stenosis.Case description We present a case of an 80-year-old female patient who developed progressive paralysis of the lower extremities. Radiographic examinations showed multilevel degenerative lumbar spinal stenosis and extensive compression of the dural sac and nerve roots from L1-2 to L5-S1. The patient underwent five-level ULBD through two-stage UBE without lumbar fusion or fixation. One week after the final procedure, the patient could ambulate with walking aids and braces. Moreover, no back pain or limited lumbar motion was observed at the 6-month follow-up.Conclusions Multilevel ULBD through UBE may provide elderly patients with an alternative, minimally invasive procedure for treating spinal stenosis. This procedure could be achieved by staging surgeries. In this case, we reported complaints of little back pain, despite not needing to perform lumbar fusion or fixation.
Comparison Effect of Nebulized Milrinone and Intravenous Milrinone in Patients With Pulmonary Hypertension Who Candidate of Open-heart Surgery: a Double Blind Randomized Clinical Trial
Authors: Joreirahmadi Sara , zadeh Fatemeh Javaherforoosh , Babazadehdezfuli Marziyeh , Gholizadeh Behnam , Bakhtiari Nima
Published: August 2021

Objective: This study was aimed to compare the effect of nebulized milrinone versus intravenous administration of milrinone in pulmonary hypertension patients who are candidates for open-heart surgeryMethod: A total of 32 patients candidates for open-heart surgery complicated by pulmonary hypertension were involved in this study and were arbitrarily classified into the nebulized milrinone group (n=16) and intravenous milrinone group (n=16) that they received drug after the opening of the cross-clamp of the aorta and before weaning off CPB. Heart rate (HR), cardiac output (CO), cardiac index (CI), stork volume (SV), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (mPAP), Systemic vascular resistance (SVR) pulmonary vascular resistance(PVR) and MAP/mPAP ratio, Extubation time, ICU stay and hospital stay were collected. Results: MAP and MAP/mPAP ratio increased significantly, however, mPAP was significantly lower in the nebulized milrinone group than in the intravenous milrinone group. Extubation time, ICU stay and hospital stays decreased significantly in the nebulized milrinone group than in the intravenous milrinone group.Conclusion: the administration of the nebulized milrinone before weaning off from CPB, accelerated and facilitated separation from CPB as it significantly decreases mPAP and preserves MAP.Trial registry: Registered under No. IRCT20201104049266N1
The Appropriate Acquisition Time Interval Following Injection of 99mTc-Sestamibi with Water Protocol in Single Photon Emission Computed Tomography Myocardial Perfusion Imaging: First Experience in Indonesia
Authors: Prasetyo Nora Anggun , Soeriadi Erwin Affandi , Budiawan Hendra , Kartamihardja Achmad Hussein Sundawa
Published: August 2021

BackgroundAccording to EANM/ESC guideline, image acquisitions in stress test should be begun at 30-60 minutes after tracer administration. Our center is a referral hospital for nuclear medicine imaging with many patients but limited number of gamma camera. The shorter time between injection of radiopharmaceutical and imaging acquisition will lead to more examination can be done.The aim of this study was to evaluate the appropriate acquisition time interval with water protocol in 99mTc-Sestamibi SPECT myocardial perfusion imaging.MethodsPatients who were referred to undergo stress MPI between October 2020 to December 2020 were included in this study. Cardiac stress procedure was performed using treadmill with modified Bruce Protocol. Subjects should drink a total of 330 mL water following 99mTc-Sestamibi injection. Image acquisitions were performed 10 and 30 minutes afterwards. Quantitative assessment was done by calculated target background ratio (TBR). Statistical analysis was performed using student t-test with Microsoft Excel version 2019. P-value < 0.05 was considered to be statistically significance.ResultsThirty out of 35 subjects were included in this study. Sixteen of them are male and 14 are female with mean of age was 48.7 years old (28 – 80). Mean target background uptake ratio (TBR) in 10- and 30-minutes images were 0.67 (0.44 – 1.11) and 0.76 (0.43 – 1.18) respectively (p-value = 0.15).ConclusionThere was no significant difference of target to background ratio between acquisition time 10- and 30-minutes following injection of 99mTc-Sestamibi with water protocol in myocardial perfusion imaging.Trial registrationNot applicable.
Temporal Trend and Spatial Analysis of the HIV Epidemic in Young Men who have Sex with Men in the Second Largest Brazilian Amazonian Province
Authors: Seabra Iaron Leal , Pedroso Andrey Oeiras , Rodrigues Taymara Barbosa , Ferreira Glenda Roberta Oliveira Naiff , Ferreira Ana Lucia Silva , Arcêncio Ricardo Alexandre , Gomes Dulce , Silva Richardson Augusto Rosendo , Botelho Eliã Pinheiro
Published: August 2021

Background: In the last decade, young men who have sex with men (MSM) have been highly affectedimpacted by the HIV. Much more than attributing the risk behavior to HIV uniquely to the individual, behaviors are shaped by social determinants of health (SDHs). Despite of the problem, there is a scarcity of studies evaluating the SHDs impact on HIV among young MSN. Therefore, . Iin this study,paper we analyzed the HIV epidemic among Amazonian young MSM byin employing temporal trendstrend and spatial analysis. The Brazilian Amazon region has the highest HIV/AIDS detection rate among all the other Brazilian regions. Methods: We conducted an ecologicalEcological study using reported cases of HIV/AIDS in young MSM living in Pará, the second largestlarger Brazilian Amazonian province, between 2007 and 2018. Data were obtained from the Information System for Notifiable Diseases. ForTo the temporal analysis, we employed autoregressive integrated moving average models, and seasonality and trend decomposition using locally weighted polynomial regression. To the spatial analysis, Moran’s spatial autocorrelation, spatial scan, and spatial regression techniques were used for spatial analysis.. Results: A total of 2,192 notifications were included in the study. Greater variabilityvariabilities in HIV/AIDS incidence rates waswere found in the festive months. The HIV/AIDS incidence rates exhibitedpresented an upward trend from 2013. This, and this trend is forecasted to continue until 2022. Belém, the capital of Pará, presented the highest spatial risk for HIV/AIDS and was the only city to present spatiotemporal risk from, 2014 to 2018. The geographic variation of the epidemic was associated with the number of men with formal jobs, the average salary of men, and the percentage of people over 18 years old with elementary education. Conclusion: The upward trend of HIV/AIDS incidence forecasted until 2022 and the variability of the epidemic promoted by the social determinants of health signalsbrings an alert and subsidies to health authorities. Policies Subsidies to reinforce the policies to controlagainst HIV among young MSM are urgently required.
A Transcriptome Profile Reveals The Regulatory Mechanism of Verticillium Dahliae Against Bacillus
Authors: Tian Wenhui , Cheng Zhenrui , Wang Junxia , Cheng Fengfeng , Li Luping , Huo Chunxiao , Li Wenxuan , Han Shouyan , Guo Xinyong , Wang Aiying
Published: August 2021

Background: Verticillium dahliae, the causal agent of Verticillium wilt, is notoriously invasive in many crops and has been involved in numerous epidemics worldwide. Bacillus species, as representatives of biocontrol bacteria, produce a variety of lipopeptides (LPs), which are useful as biofungicides to many pathogenic fungi, including Verticillium dahliae. This study will explore the mechanism of resistance of V. dahliae to Bacillus and biocontrol bacteria.Results: By using in vitro confrontation bioassays, we found that under the stress induced by Bacillus, the spore vitality of V. dahliae with larger colonies was higher, and more abundant microsclerotia were formed. Then, according to the RNA-Seq analysis, the target of rapamycin (TOR) and mitophagy pathways were enriched among the significantly upregulated 542 genes observed in two co-culture groups with different colony sizes. In addition, in the group of V. dahliae with large colonies, the pathways related to cell wall synthesis, microsclerotia formation and the clearance of reactive oxygen species were regulated, and the expression of genes was up-regulated.Conclusion: This study found that the larger colonies of V. dahliae were more resistant to the antagonistic actions of Bacillus and the likelihood of the formation of homeostasis. Therefore, the prevention of Verticillium wilt by Bacillus is more effective than the treatment of an active fungal infection. These transcriptomic insights provide direction for the use of fungicides in the prevention and treatment of diseases such as Verticillium wilt.
Improving Hybrid Models For Precipitation Forecasting By Combining Nonlinear Machine Learning Methods
Authors: Parviz Laleh , Rasouli Kabir , Torabi Ali
Published: August 2021

Precipitation forecast, especially on monthly and annual scales, is a key for optimal water resources management and planning, especially in semiarid climates with scarce water. The traditional hybrid models, in which two statistical models are used to separate and simulate linear and nonlinear components of precipitation time series, are still unable to provide accurate precipitation forecasts. This research aims to improve hybrid forecast models by combining one linear model and three nonlinear models with two preprocessing configurations: 1) using residuals of a linear model, representing the nonlinear component with different time steps and 2) using original time series of observations with different time steps, linear model simulations and residuals. Gene Expression Programming (GEP), Support Vector Regression (SVR) and Group Method of Data Handling (GMDH) models were used individually as in the traditional hybrid models and combinedly as in the proposed hybrid models in this study. The performance of the hybrid models was improved by different methods such as inverse variance (Iv) as an error-based method, least square regression, genetic algorithm and SVR. Two weather stations of Tabriz (annual) and Rasht (monthly) in Iran were selected to test the developed models. The results showed that Theil’s coefficient, UII, decreased in configuration one for the Tabriz station by 9% and 15% for SVR and GMDH relative to GEP, suggesting that these two models performed better than GEP in the precipitation forecast. The error criteria used in developing the proposed hybrid models with all forecast combination methods better represent observations than the hybrid model. MSE decreased by 67% and Nash Sutcliffe increased by 5% in the Rasht station in configuration two when we combined the three models using GA to obtain the improved hybrid model relative to the hybrid model combined with SVR. Generally, the hybrid models when SVR, the error based methods and GA were incorporated showed better performance than traditional hybrid models. The developed models have implications for modeling highly nonlinear systems using full advantages of machine learning methods.
Loss of The Phloem-Expressed Sugar Transporter VST1 Reduces Aphid Performance In Watermelon
Authors: Li Maoying , Guo Shaogui , Zhang Jie , Sun Honghe , Tian Shouwei , Wang Jinfang , Zuo Yi , Yu Yongtao , Gong Guoyi , Zhang Haiying , Ren Yi , Xu Yong
Published: August 2021

Aphids can damage plants through sugar withdrawal by hijacking sugar metabolism and transport genes to increase their sugar sucking ability. Blocking plant diseases and pest access to nutrients has emerged as an exciting strategy for improving disease and insect resistance in plants. Our previous work identified a shift in the localization of the vacuolar sugar transporter (VST1) that contributes to sucrose (Suc) and glucose (Glc) unloading in the phloem of sweet watermelons. In this study, the potential role of VST1 in the response to aphid infestation was investigated. Loss of VST1 function adversely impacted aphid settling and honeydew production. The vst1 mutant displayed less aphid-induced hydrogen peroxide accumulation and cell death than wild-type (WT) plants. Additionally, the expression of the VST1 gene was induced by aphids. The mutation of VST1 reduced Suc and Glc accumulation in the phloem, indicating that Suc and Glc are important carbohydrate substrates in phloem sap that are transported by VST1 to support aphid propagation and infestation. Taken together, our results demonstrated that the mutation of VST1 by genome editing can decrease aphid performance in watermelon by blocking the sugar supply obtained from phloem sap.
Alterations of Genetic Variants and Transcriptomic Features of Response to Tamoxifen in the Breast Cancer Cell Line
Authors: Nezamivand-Chegini Mahnaz , Kharrati-Koopaee Hamed , Heydari seyed taghi , Giahi Hasan , Dehshahri Ali , Dianatpour Mehdi , Lankarani Kamran Bagheri
Published: August 2021

Background

Breast cancer is one of the most important causes of mortality in the world, and Tamoxifen therapy is known as a medication strategy for estrogen receptor-positive breast cancer. In current study, two hypotheses of Tamoxifen consumption in breast cancer cell line (MCF7) were investigated. First, the effect of Tamoxifen on genes expression profile at transcriptome level was evaluated between the control and treated samples. Second, due to the fact that Tamoxifen is known as a mutagenic factor, there may be an association between the alterations of genetic variants and Tamoxifen treatment, which can impact on the drug response.
Methods

In current study, the whole-transcriptome (RNA-seq) dataset of four investigations (19 samples) were derived from European Bioinformatics Institute (EBI). At transcriptome level, the effect of Tamoxifen was investigated on gene expression profile between control and treatment samples. Moreover, Tamoxifen is known as a mutagenic factor, therefore, its contribution to alterations of genetic variants and drug response were examined.
Results

Results achieved from RNA-seq analysis indicated the contribution of several candidate genes to tumor suppression process and consequently, the achievement of an effective treatment. For instance, XIAP-associated factor 1 (XAF1) was reported as an up-regulated gene under Tamoxifen therapy. XAF1 is a tumor suppressor that contributes to the apoptosis induction and tumor growth inhibition along with TP53. Results of gene ontology enrichment analysis of differential gene expressions indicated that most of them could considerably lead to the cell death, apoptosis, and negative regulation of proteolysis process. Findings achieved from evaluating Tamoxifen mutagenicity effect on drug response was not confirmed perfectly. The most reported candidate genes, which were related to differential genetic variants between control and treated samples, played the oncogene and tumor suppressor dual roles and also their exact roles in breast cancer were not investigated precisely.
Conclusion

At transcriptome level, Tamoxifen consumption in MCF7 cell line could be associated with candidate genes and biological pathways that contribute to the apoptosis, proteolysis, and tumor suppression. The mutagenicity effect of Tamoxifen and its contribution to drug response was not confirmed perfectly.
Utilization of Long Acting and Permanent Contraceptive Method and Associated Factor Among Women of Reproductive Age in West Guji Zone, Southern Ethiopia, 2018.
Authors: Zeleke Eden Dagnachew , Assefa Dawit Getachew , Woldesenbet Tigist Tekle , Gido Rediet
Published: August 2021

Background: Increasing access to family planning helps to ensure the reproductive right, decrease unintended pregnancy, improve health and nutritional status of children, reduction of maternal mortality and enhance longer birth spacing . There is continually low utilization of long acting and permanent contraceptive method among low and middle income countries. The aim of this study was to assess the Utilization of Long Acting and permanent Contraceptive methods and associated factor among Women of Reproductive Age in west Guji Zone.Methods: Mixed study design was conducted among women of reproductive age in West Guji Zone. Systematic random sampling method was used to select study subjects for the survey with sample size of 507. Descriptive was utilized to summarize the data while logistic regression to assess factors influencing the utilization of Long Acting and permanent Contraceptive methods use. Statistical significance was declared for variables outcomes of the P-value less than 0.05.Result: Current utilization of Long Acting And permanent Contraceptive methods at West Guji zone among reproductive aged group was 51.1%. More than median of participants had negative altitude (72.4%) and poor knowledge (57%) towards long acting and permanent contraceptive method. Educational status of women, number of alive children, acceptance of utilization of Long Acting And permanent Contraceptive methods , how treated by other staff and waiting time during service delivery are significant determinant factor of long acting and permanent family planning method. According to qualitative data, Myths and misconceptions about utilization of intrauterine contraceptive device and implants and negative altitude to ward Long Acting And permanent Contraceptive methods were major barriers to the use of Long Acting And permanent Contraceptive methods.Conclusion: Educational status, number of alive children ( Parity) , acceptance of Long Acting And permanent Contraceptive methods , how treated by other staff and waiting time to get the service are statistically significant predictors of utilization of long acting and permanent family planning methods. More than half of women had negative altitude and poor knowledge on Long Acting And permanent Contraceptive methods. Myths and misconception might affect the utilization of long acting and permanent family planning method.
Understanding the Factors that Impact Effective Uptake and Integration of Health Programs in South African Primary Health Care Clinics
Authors: Heerden Alastair , Ntinga Xolani , Lippman Sheri A. , Leslie Hannah H. , Steward Wayne T.
Published: August 2021

Introduction: There is an increasingly urgent gap in knowledge regarding the translation of effective HIV prevention and care programming into scaled clinical policy and practice. Challenges limiting the translation of efficacious programming into national policy include both the paucity of proven efficacious programs that are reasonable for clinics to implement and the difficulty in moving a successful program from research trial to scaled programming. This study aims to bridge the divide between science and practice by exploring health care providers’ views on what is needed to integrate of HIV programming into clinic systems.Methods: We conducted 20 in-depth interviews with clinic managers and clinic program implementing staff and 5 key informant interviews with district health managers overseeing programming in the uMgungundlovu District of KwaZulu-Natal Province, South Africa. Qualitative data were analyzed using a template approach. A priori themes were used to construct templates of relevance including current care context for HIV and past predictors of successful implementation. Data were coded and analyzed in accordance with these templates.Results: Heath care providers identified three main factors that impact integration of HIV programming into general clinical care: perceived benefits, resource availability, and clear communication. The perceived benefits of HIV programs hinged on the social validation of the program by early adopters. Wide program availability and improved convenience for providers and patients increased perceived benefit. Limited staffing capacity and a shortage of space were noted as resource constraints. Programs that specifically tackled these constraints through, for example clinic decongestion, were reported as being the most successful. Clear communication with all entities involved in clinic-based programs, some of which include external partners, was noted as central to maximizing program function and provider uptake. Conclusions: Amid the COVID-19 pandemic, new programs are already being developed for implementation at the primary health care level. A better understanding of the factors which both facilitate and prevent programmatic success will improve public health outcomes. Implementation is likely to be most successful when programs capitalize on endorsements from early adopters, tackle resource constraints, and foster greater communication among partners responsible for implementation.
Risk Factors for Lymph Node Metastasis of Soft Tissue Sarcomas of the Head, Neck and Extremities, And the Clinical Significance of Negative Lymph Node Dissection
Authors: Liu Qikun , Yu Xiaojun , Li Mengwei , Li Zhiwei , Jiang Yongqiao , Kang Hao
Published: August 2021

Background: To determine the risk factors for lymph node metastasis (LNM) of soft tissue sarcomas (STS) of the head, neck, and extremities, and the clinical outcome of negative lymph node dissection (NLND). Methods: We pooled patients of STS using the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2015. Logistics regression analysis to identify risk factors for LNM, the Cox proportional hazards model and Fine-Grey’s model were used for survival analysis, Propensity score matching analysis (PSM) was further used to clarify the impact of NLND on patient prognosis.Results: A total of 3,276 patients were enrolled in our study, of whom 283 (8.6%) developed LNM. Rhabdomyosarcoma had the highest rate of LNM (25.3%), followed by clear cell sarcoma (16.8%) and epithelioid sarcoma (12.4%), while leiomyosarcoma had the lowest rate of LNM (1.3%). Sex, tumor size, grade, histology, and site were significantly associated with LNM. Age, tumor size, grade, stage, histology, and marital status were independent prognostic factors for the cancer-specific survival for patients without LNM. For specific histologic subtypes of STS, NLND significantly improves overall survival (HR: 0.718, 95%CI, 0.535-0.962; P=0.026) and cancer-specific survival (HR: 0.699, 95%CI, 0.506-0.967; P=0.031) and reduces cancer-specific mortality (Gray’s test, P=0.017). However, for patients with leiomyosarcoma, NLND did not improve overall survival (P=0.46) or reduce cancer-specific mortality (Gray’s test, P=0.772).Conclusions: We identified the rate of LNM and risk factors for LNM in STS of the head, neck and extremities. In addition, prophylactic NLND treatment is necessary and has a clinical benefit for patients with STS who are at high risk for LNM, but has no significant impact on the prognosis of patients with leiomyosarcoma.
Training Associated Alterations in Equine Respiratory Immunity Using a Multiomics Comparative Approach
Authors: Karagianni Anna Eleonora , Kurian Dominic , Cillán-Garcia Eugenio , Eaton Samantha L. , Wishart Thomas M. , Pirie R. Scott
Published: August 2021

Neutrophilic airway inflammation is highly prevalent in racehorses in training, with the term mild to moderate equine asthma (MMEA) being applied to the majority of such cases. Our proposed study is largely derived from the strong association between MMEA in racehorses and their entry into a race training program. The objectives of this study are to characterise the effect of training on the local pulmonary immune system by defining the gene and protein expression of tracheal wash (TW) derived samples from Thoroughbred racehorses prior to and following commencement of race training. Multiomics analysis detected 2,138 differentially expressed genes and 260 proteins during the training period. Gene and protein sets were enriched for biological processes related to acute phase response, oxidative stress, haemopoietic processes, as well as to immune response and inflammation. This study demonstrated TW samples to represent a rich source of airway cells, protein and RNA to study airway immunity in the horse and highlighted the benefits of a multiomics methodological approach to studying the dynamics of equine airway immunity. Findings likely reflect the known associations between race-training and both airway inflammation and bleeding, offering further insight into the potential mechanisms which underpin training associated airway inflammation.
Influence of Planting Xanthoceras Sorbifolia Bunge on Bacteria and Fungi Diversity of Fly Ash
Authors: Liu Zehui L. , Chen Zhiwen , Huo Jinxian , Zhao Jianguo , Ma Hongfang , Bai Xiuli , Qiao Jun , Li Weijia , Li Jingwei , Ge Sai
Published: August 2021

Background: Fly ash is the product of coal combustion, and a large amount of fly ash accumulation is of great harm to the environment. The yellow horn (Xanthoceras sorbifolia Bunge) is a unique edible oil tree species in China. Yellow horn has developed root system and can survive in soil contaminated with heavy metals. Thus, it could be used for phytoremediation in fly ash. Results: In this study, high-throughput 16S rRNA and ITS rDNA gene Illumina sequencing technology was used to analyze the microbial community diversity in fly ash before (CK group) and after (S group) planting yellow horn. The abundance and diversity of microorganisms in fly ash were changed by planting yellow horn. The dominant bacterial phyla: Proteobacteria (CK-24% vs S-42%), Firmicutes (CK-23% vs S-10%), Actinobacteria (CK-15% vs S-11%). The dominant phyla in fungi: Ascomycota (72% for CK, 69% for S), Mortierellomycota (4% for CK, 3% for S).Some beneficial bacteria that could degrade heavy metals increased in proportion, including Betaproteobacteriales (4% for CK vs 10% for S group), Burkholderiacae (1% for CK vs 6% for S groups), Nitrospirae (0.3% for CK vs 0.8% for S groups), Rhizobiales (3% for CK vs 6% for S groups) and Sphingomonadaceae (2% for CK vs 4% for S groups). Conclusion: These results indicate that the planting of yellow horn can increase the abundance of heavy metal-degrading bacteria in rhizosphere fly ash, which is of great significance for the biological remediation of fly ash.
Why Using Bed Nets is a Challenge amongst Minority Populations in Central Vietnam
Authors: Nguyen Thuan Thi , Nguyen Xa Xuan , Wilson-Barthes Marta , Sawada Ikumi , Muela Joan , Hausmann-Muela Susanna , Pham Thanh Vinh , Nguyen Hong Van , Nguyen Van Van , Tran Duong Thanh , D’Alessandro Umberto , Grietens Koen Peeters , Erhart Annette
Published: August 2021

Background: Despite free distribution of insecticidal-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) to populations at-risk, malaria transmission persists in forested areas in Vietnam especially amongst ethnic minority communities. A study was conducted between April 2009 and December 2010 in four villages of Ca Dong and M’nong ethnicity located in Central Vietnam with persistent malaria transmission. The objective was to assess the feasibility of bed net use in forest settings with a specific emphasis on contrasting people’s willingness/choice to use nets versus structural limitations to the uptake of the intervention. Methods: The study used an exploratory mixed-method design for complementarity. The qualitative strand included participant observation, informal interviews, in-depth interviews, and group discussions to explore contextual barriers to bednet use. The quantitative strand consisted of a cross sectional household survey (n=141) in a selected village with direct access to bed nets and the health centre. The main outcome was bednet use and related risk factors (using survey logistic regression), and secondary outcomes included the quantification of contextual factors identified during the qualitative strand. Results: Despite self-reported bednet coverage (72.5% of households had sufficient net coverage) and appropriate betnet use the night before the survey (82.2% of HHMs), only 18.4% of HHMs were effectively protected by nets in both the village home and the forest field. The distribution of LLINs and ITNs was not accounted for multiple residency and sleeping places linked to slash-and-burn agriculture, and contextual factors including open-housing structured, high poverty, and animistic beliefs contributing to inappropriate use and shorter lifespan of nets. Health messages promoting bednet use were provided to the population but only 19.8% of respondents considered mosquito bites as the sole cause of malaria. The multi-variable logistic regression showed the effect of four significant factors to appropriate bednet use: being female (AOR=8.08; p=0.009); having knowledge of mosquito bites and malaria link (AOR=7.43; p=0.008); not sleeping in the kitchen (AOR=24.57; p=0.001); and, having sufficient number of bednets in the household (AOR=21.69; p=0.001). Conclusion: This study identified contextual factors that constrains effective bednet use amongst ethnic minority populations living in forested areas of Central Vietnam and calls for multi-sectoral interventions to address the complexity of residual malaria transmission and reach the malaria elimination goal of 2030.
Verification of Genetic Differences and Immune Cell Infiltration Subtypes in Neuroblastoma Tumor Microenvironment for Immunotherapy
Authors: Qian Bo , Sun Jing , Zuo Pengcheng , Da Min , Mo Xuming , Fang Yongjun
Published: August 2021

Background: The tumor microenvironment (TME) has achieved remarkable results in the research of cancer progression in the past few years. it is crucial to understand the nature and function of TME in tumors because of precise treatment strategies for individual cancers having received widespread attention, including immunotherapy. The immune infiltrative profiles of neuroblastoma (NB) have not yet been completely illustrated. The purpose of this research is to analyses tumor immune cell infiltration (ICI) in the microenvironment of NB.Methods: We applied CIBERSORT and ESTIMATE algorithms to evaluate the ICI status of 438 NB samples. Three ICI models were selected and ICI scores were acquired. Subgroups with high ICI scores based on immune activation signaling pathways have better overall survival. Results: The genes of immunosuppressive glycosaminoglycan biosynthesis heparan sulfate signaling pathway were markedly enriched in the low ICI score subgroup. It was inferred that compared with low ICI NB subtypes, patients with high ICI NB subtypes were more likely to respond to immunotherapy and a better prognosis. Conclusion: Notably, our ICI scores not only provided new clinical and theoretical basis for mining NB prognostic markers related to the microenvironment, but also aided new ideas for the development of new NB precision immunotherapy methods.
Soluble Programmed Cell Death-1 Predicts Hepatocellular Carcinoma Development During Nucleoside Analogue Treatment
Authors: Kozuka Ritsuzo , Enomoto Masaru , Dong Minh Phuong , Hai Hoang , Thuy Le Thi Thanh , Odagiri Naoshi , Yoshida Kanako , Kotani Kohei , Motoyama Hiroyuki , Kawamura Etsushi , Hagihara Atsushi , Fujii Hideki , Uchida-Kobayashi Sawako , Tamori Akihiro , Kawada Norifumi
Published: August 2021

Soluble immune checkpoint molecules are emerging novel mediators of immune regulation. However, it is unclear whether soluble immune checkpoint proteins affect the development of hepatocellular carcinoma (HCC) during nucleos(t)ide analogue (NA) treatment in patients with chronic hepatitis B virus infection. This study included 122 NA-naïve patients who received NA therapy. We assessed the associations of clinical factors, including soluble immune checkpoint proteins, with HCC development during NA treatment. The baseline serum concentrations of 16 soluble immune checkpoint proteins were measured using multiplexed fluorescent bead-based immunoassay. In total, 13 patients developed HCC during the follow-up period (median duration, 4.3 years). Of the 16 proteins, soluble inducible T-cell co-stimulator (≥ 164.71 pg/mL; p = 0.014), soluble programmed cell death-1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031), soluble CD40 (≤ 493.68 pg/mL; p = 0.032), and soluble herpes virus entry mediator (≤ 2,470.83 pg/mL; p = 0.038) were significantly associated with HCC development (log-rank test). In a multivariate analysis, an sPD-1 level ≤ 447.27 pg/mL (p = 0.014; hazard ratio [HR], 4.537) and α-fetoprotein level ≥ 6.4 ng/mL (p = 0.040; HR, 5.524) were independently and significantly associated with HCC development. sPD-1 is a novel predictive biomarker for HCC development during NA treatment.
Phase II Prospective Study of Trastuzumab in Combination with S-1 and Oxaliplatin (SOX100) Therapy for HER2-Positive Advanced Gastric Cancer
Authors: Mori Yoshinori , Kataoka Hiromi , Ebi Masahide , Adachi Kazunori , Yamaguchi Yoshiharu , Hayashi Noriyuki , Hirata Yoshikazu , Sobue Satoshi , Ishihara Ryo , Suzuki Yuta , Mizushima Takashi , Inoue Yusuke , Hasegawa Izumi , Ono Satoshi , Hirano Atsuyuki , Kimura Yoshihide , Seno Kyoji , Ozeki Keiji , Shimura Takaya , Kubota Eiji
Published: August 2021

Purpose The standard first-line treatment for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer (AGC) is trastuzumab in combination with cisplatin and fluoropyrimidines. We evaluated the efficacy and safety of S-1 and oxaliplatin (100 mg/m2) (SOX100) combined with trastuzumab, a monoclonal antibody against HER2 for HER2-positive AGC.Methods In this single-arm, multicenter phase II study, patients with HER2-positive AGC received S-1 (80–120 mg per day) orally on days 1–14, oxaliplatin (100 mg/m2) intravenously on day 1, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety. Results A total of 25 patients from six centers were enrolled from December 2015 to March 2020. In the 25 patients evaluable for analysis, the 1-year survival rate was 70.8% [90% confidence interval (CI) = 55.5%–86.1%], whereas the median OS, PFS, and ORR were 17.8 (95% CI 10.5–22.9) months, 7.6 (95% CI 5.0–10.9) months, and 75.0 (95% CI 53.3–90.2) %, respectively. Major grade 3/4 adverse events included anorexia (20%), anemia (16%), peripheral sensory neuropathy (16%), and diarrhea (15%). Conclusion SOX100 combined with trastuzumab was effective with a favorable safety profile in patients with HER2-positive AGC.
CRISPR/Cas9 Mediated-Disruption of ZNF543 Gene: An Approach Towards Discovering Its Relation to TRIM28 Gene in Parkinson's Disease
Authors: Hashemabadi Mohammad , Sasan Hosseinali , Amandadi Mojdeh , Esmaeilzadeh-Salestani Keyvan , Esmaeili-Mahani Saeed , Ravan Hadi
Published: August 2021

Genetic studies of familial forms of Parkinson’s disease (PD) have shown that the ZNF543 gene is a candidate gene that operates relevant to this disease. However, until now there is no evidence for ZNF543 gene function in PD, and mechanisms resulting from its mutation had not been elucidated. Given the same genetic location of the ZNF543 gene with TRIM28 and effects of both of them on PD pathogenesis, we surmised that ZNF543 may act as a transcription factor for TRIM28 gene expression. By knocking out the ZNF543 gene via the CRISPR/Cas9 editing platform, we assessed the functional effect of loss of expression of this gene on TRIM28 gene expression. Four sgRNAs with different PAM sequences were designed against two parts of the regulatory region of ZNF543 gene, and highly efficient disruption of ZNF543 expression in human neuroblastoma cell line was evaluated by polymerase chain reaction and T7 endonuclease assay. Moreover, evaluation of TRIM28 gene expression in ZNF543-knocked-out cells indicated a significant increase of TRIM28 gene expression, suggesting that ZNF543 probably regulates the expression of TRIM28. This approach offers a window into pinpointing the mechanism by which ZNF543 gene mutations mediate PD pathogenicity.
Novel lipid nanoparticle provides potent SARS-CoV-2 mRNA vaccine at low dose with low local reactogenicity, high thermostability and limited systemic biodistribution
Authors: Alishetty Suman , Carrasco Manuel , Alameh Mohamad-Gabriel , Paige Mikell , Said Hooda , Wright Lacey , Narayanan Aarthi , Alem Farhang , Hernandez Keziah , Gillevet Patrick , Soliman Ousamah , Hicks Philip , Manzoni Tomaz , Bates Paul , Stephens-Shields Alisa , Cleveland Thomas , Grishaev Alexander , Weissman Drew , Buschmann Michael
Published: August 2021

Concerns with current mRNA Lipid Nanoparticle (LNP) systems include dose-limiting reactogenicity, adverse events that may be partly due to systemic off target expression of the immunogen, and a very limited understanding of the mechanisms responsible for the frozen storage requirement. We applied a new rational design process to identify a novel multiprotic ionizable lipid, called C24, as the key component of the mRNA LNP delivery system. We show that the resulting C24 LNP has a multistage protonation behavior resulting in greater endosomal protonation and greater translation of an mRNA-encoded luciferase reporter after intramuscular (IM) administration compared to the standard reference MC3 LNP. Off-target expression in liver after IM administration was reduced 6 fold for the C24 LNP compared to MC3. Neutralizing titers in immunogenicity studies delivering a nucleoside-modified mRNA encoding for the diproline stabilized spike protein immunogen were 10 fold higher for the C24 LNP versus MC3, and protection against viral challenge in a SARS-CoV-2 mouse model occurred at a very low 0.25 µg prime/boost dose of the same immunogen in the C24 LNP. Injection site inflammation was notably reduced for C24 compared to MC3. In addition, we found the C24 LNP to be entirely stable in bioactivity and mRNA integrity when stored at 4 ºC for at least 19 days. Storage at higher temperatures reduced both bioactivity and mRNA integrity, but less so for C24 than MC3, and in a manner consistent with the phosphodiester transesterification reaction mechanism of mRNA cleavage. The higher potency, lower injection site inflammation, and higher stability of the C24 LNP present important advancements in the evolution mRNA vaccine delivery.