bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Occupational Stress, Job Burnout and Quality of Life among Surgical nurses in Xinjiang, China
Authors: Li Xue , Jiang Ting , Sun Jian , Shi Lingyun , Liu Jiwen
Published: October 2020

Background: Nursing is a high-risk occupation that involves exposure to stress. The physical and mental health of nurses is directly related to the quality of medical services, so the quality of life of nurses cannot be ignored. Methods: This study adopted the cluster random sampling method and carried out a questionnaire survey among 488 surgical nurses from five affiliated hospitals of Xinjiang medical university from May 2019 to September 2019. The study analyzed the relationship between occupational stress, job burnout and quality of life. The Effort-Reward Imbalance questionnaire(ERI), Maslach Burnout Inventory General Survey(MBI-GS), and the 36-item Short Form Health Survey(SF-36) were used to evaluate occupational stress, job burnout and quality of life among surgical nurses. Results The results revealed that the quality of life score among surgical nurses was not high, and differences were observed in the quality of life score of patients according to gender, age, title, and frequency of night shifts (P < 0.05). Occupational stress and job burnout are risk factors for quality of life, and the interaction between high stress and high burnout seriously reduces quality of life. The structural equation model revealed that occupational stress and job burnout have a direct impact on life quality, occupational stress has a direct impact on job burnout, and job burnout is the mediating factor of occupational stress on life quality.Conclusion Occupational stress and job burnout affect quality of life, and their interaction also affects quality of life. Higher levels of stress and burnout were associated with lower quality of life scores.
Identification Method of Drought Resistance on Maize Based on qRT-PCR
Authors: Liu Xinyue , Liu Songtao , Zenda Tinashe , Wang Yafei , Li Jiao , Dong Anyi , Yang Yatong , Duan Huijun
Published: October 2020

Background: In order to reveal the mechanism of drought resistance of maize, establish the molecular identification system of drought resistance and solve the problem of difficult identification of drought resistance of maize. Taking Nongdan 476, a drought-tolerant maize hybrid cultivar, and Zhongxin 978, a drought-sensitive maize hybrid cultivar, as materials, drought stress and normal watering treatment were carried out at seedling stage, flare stage, tasseling stage and filling stage, and leaf tissue were collected for transcriptomes.Results: P-vaule < 0.05 was selected as the screening standard. There were 6281, 17191, 21790 and 15475 differentially expressed genes of each stage, respectively. At the same time, only DnaJ gene was significantly differentially expressed at the four stages. The preliminary results of qRT-PCR showed that the up regulation of DnaJ gene expression was consistent with the results of transcriptome analysis. DnaJ gene expression was further detected by using control samples with specific drought resistance index of yield. The results showed that DnaJ gene expression drought resistance index (DIE) was highly correlated with yield drought resistance index (DIP), and the 5-level criteria for DnaJ gene expression drought resistance index (DIE) were defined by their linear equations. Conclusion: Drought resistance of maize is a character controlled by multiple genes. There is a significant difference between the expression of DnaJ gene in drought resistant and non drought resistant maize, which has the potential to be used as molecular identification of drought resistance of maize, and can provide a more comprehensive and accurate technical means for drought resistance cultivation and breeding of maize.
Diagnosis and Treatment of Femoral Head Osteonecrosis: A Protocol for Development of Evidence Based Clinical Practice Guidelines
Authors: Cheng Edward , Mont Michael A. , Goodman Stuart B. , Sierra Rafael J , Cui Quanjun , Salem Hytham S , Group ARCO Clinical Practice Guidelines
Published: October 2020

Background: There are many treatment options for patients who have osteonecrosis of the femoral head (ONFH) and management strategies vary widely both among and within individual countries. Although many researchers have attempted to elucidate the optimal strategies for managing this disease, the lack of large-scale randomized control trials and the lack of agreement on disease staging have curtailed the development of clear-cut guidelines.Methods: The Association Research Circulation Osseous (ARCO) group sought to address three questions for the management of patients who have ONFH: (1) What imaging studies are most sensitive and specific for the diagnostic evaluation of patients who have ONFH?; (2)What is the best treatment strategy for preventing disease progression in patients who have pre-collapse lesions?; and (3) What is the best treatment strategy for patients who have post-collapse disease? The PICO (Patient, Intervention, Comparison, and Outcome) format was used to formulate the search strategy for each research question. A systematic review will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. ARCO participants have been allocated to three groups, each representing one of the PICO questions. After qualitative and quantitative analysis of the data extracted from studies pertaining to each of the three research questions, a set of evidence-based clinical practice guidelines will be proposed for the management of patients who have ONFH. Discussion: It is not always clear which treatment method is optimal for the management of ONFH. Thus, many surgeons have developed and performed various procedures based on various patient-specific factors. As there is no consensus on the optimal treatment for various stages of disease, it was clear that developing evidence-based clinical practice guidelines would provide more structure and uniformity to management of these patients. Therefore, the results of this systematic review will lead to the development guidelines that may improve patient-care strategies and result in better outcomes for patients who have ONFH.Systematic Review Registration: Registration with PROSPERO has been submitted and is pending.
On-chip 2D beam-steering with a liquid-crystal-tunable optical phased array
Authors: Nakamura Kazuki , Hashiya Akira , Nomura Takaiki , Yamaoka Yoshikazu , Tsukuda Masahiko , Takagi Hiroyuki , Sasaki Yoshiki , Ishikawa Atsushi , Fowler Daivid , Malhouitre Stephane , Muffato Viviane , Rabaud Wilfried , Hisada Kazuya , Hirasawa Taku , Inada Yasuhisa
Published: October 2020

Optical phased arrays (OPAs) with the ability of dynamic beam-steering hold great promise for industrial applications. Although they potentially offer high-resolution, high-speed and wide-angle beam-steering, 2D beam-steering has only been achieved by 1D OPAs with wavelength-tuning or by 2D OPAs containing enormous numbers of elements, thereby significantly increasing the system complexity and power consumption. Here we demonstrate a liquid-crystal-tunable Bragg-reflector waveguide outcoupler integrated with a 1D OPA. The output beam angle is controlled by an electric-field applied to the liquid crystal between the Bragg-mirrors, independently from steering along a second axis with the OPA. Our proof-of-concept demonstration with an 8-channel OPA shows 2D beam-steering with a 16° × 15° field-of-view and 12 ms × 14 μs time-response. Our approach opens a practical way for scalable OPAs capable of single wavelength 2D beam-steering, as well as demonstrating a strategy for the integration of liquid crystal materials with silicon photonics.
Reduced Ejection Fraction and Augmented Right Atrium are Independent Risk Factors of Deep Regional CBF in Cerebral Small Vessel Disease
Authors: Chen Xiaodong , Lu Danli , Guo Ning , Kang Zhuang , Zhang Ke , Wang Jihui , Men Xuejiao , Lu Zhengqi , Qiu Wei
Published: October 2020

Background: Systemic cardiac hypoperfusion is a well-acknowledged contributor to ischemic leukoencephalopathy. However, it has remained elusive how atherosclerosis-mediated cardiac remodelling modifies cerebral perfusion homeostasis as well as neuroimaging burden in cerebral small vessel disease (CSVD) development. Methods: This retrospective study identified 103 CSVD patients (CSVD burdenlow 0~1, n=61 and CSVD burdenhigh 2~4, n=42) from Sep. 2017 to Dec. 2019 who underwent transthoracic echocardiography(n=81), structural magnetic resonance imaging and arterial spin labelling. Total CSVD burden was graded according to the ordinal “small vessel disease” rating score (0-4). We investigated the univariate and multivariate linear regression of mean deep regional cerebral blood flow (CBF) as well as logistic regression analysis of CSVD burdenhigh. Results: Augmented right atrial diameter (B coefficient, -0.289; 95% CI, -0.578 to -0.001; P=0.049) and decreased left ventricular ejection fraction (B coefficient, 32.555; 95% CI, 7.399 to 57.711; P=0.012) were echocardiographic parameters linked with declined deep regional CBF in CSVD patients. Binary logistic regression analysis demonstrated decreased mean deep CBF (OR 0.894; 95% CI 0.811-0.985; P=0.024) was independently associated with higher CSVD burden after adjusted for clinical confounders. Multivariate receiver operating characteristics curve combing clinical risk factors, mean deep CBF and echocardiographic parameters showed predictive significance for CSVD burdenhigh diagnosis (area under curve=84.25%, 95% CI 74.86% - 93.65%, P<0.0001). Conclusion: The interrelationship of “cardiac -deep regional CBF-neuroimaging burden” reinforces the importance and prognostic significance of echocardiographic and cerebral hemodynamic assessment in CSVD early-warning.
The eukaryotic replisome requires an additional helicase to disarm dormant replication origins
Authors: Hill Jake , Eickhoff Patrik , Drury Lucy , Costa Alessandro , Diffley John
Published: October 2020

Origins of eukaryotic DNA replication are ‘licensed’ during G1 phase of the cell cycle by loading the six related minichromosome maintenance (MCM) proteins into a double hexameric ring around double-stranded DNA. In S phase, some double hexamers (MCM DHs) are converted into active CMG (Cdc45-MCM-GINS) helicases which nucleate assembly of bidirectional replication forks. The remaining unfired MCM DHs act as ‘dormant’ origins to provide backup replisomes in the event of replication fork stalling. The fate of unfired MCM DHs during replication is unknown. Here we show that active replisomes cannot remove unfired MCM DHs. Instead, they are pushed ahead of the replisome where they prevent fork convergence during replication termination and replisome progression through nucleosomes. Pif1 helicase, together with the replisome, can remove unfired MCM DHs specifically from replicating DNA, allowing efficient replication and termination. Our results provide an explanation for how excess replication license is removed during S phase.
Non-use of Contraceptive Methods Among Married: Analysis of the 2018 Guinea Demographic and Health Survey
Authors: Sidibe Sidikiba , Camara Bienvenu Salim , Dioubaté Nafissatou , Grovogui Fassou Mathias , Delamou Alexandre , Kouanda Seni
Published: October 2020

Background: Modern contraceptive prevalence in Guinea was low in 2018. This study aimed to examine current modern contraceptive non-use among 1086 married women in Guinea who have used a contraceptive method. Methods: We used the dataset of the 2018 Guinea Demographic and Health Survey (GDHS). The analysis included descriptive statistics, tests of association, and logistic regression of women who are not currently using modern contraceptive methods among ever users. Results: Among the sampled women, 454 (42%) did not use modern contraceptive methods. Three out of five non-users made the decision to not use contraceptives. The factors associated with modern contraceptive non-use included living in the administrative regions of Boké (adjusted odds ratio [AOR]: 2.87; 95% confidence interval [CI]: 1.46–5.56) and Mamou (AOR: 3.56; 95% CI: 1.38–9.19); age 25–29 years (AOR: 2.80; 95% CI: 1.25–6.30), 30–34 years (AOR: 3.10; 95% CI: 1.31–7.38), and 45–49 years (AOR: 3.49; 95% CI: 1.22–10.00); and husband’s desire for more children (AOR: 1.58; 95% CI: 1.02–2.46). Conclusions: Interventions that focus on contraceptive non-users among ever users who are currently not using any modern contraceptive method could lead to the resumption of modern contraceptive use among these women. Furthermore, community-level family planning interventions such as male or couple sensitisation or men’s involvement in reproductive issues could improve community perception about contraception and women’s rights for reproductive health.
A Study of Icariin Modulating Hippocampal Neurogenesis in Depression Based on Quantitative CSF Proteomics
Authors: Zeng Ning-Xi , Li Huizhen , Wang Han-Zhang , Liu Kai-Ge , Gong Xia-Yu , Luo Wu-Long , Yan Can , Wu Li-Li
Published: October 2020

BackgroundHippocampal neurogenesis dysfunction is one of the main pathogenesis of depression. Icariin (ICA) has significant anti-depression and anti-hippocampal damage effects but could not effectively cross the blood-brain-barrier and accumulate in brain. Based on the proteomics of cerebrospinal fluid (CSF), this study aimed to explore the mechanism of ICA against hippocampal neurogenesis dysfunction in depression.MethodsIn vivo, rats were exposed to 6-week CUMS and treated by ICA to observe the effects of ICA on depressive symptoms, cognitive functions, neurogenesis and number of neurons in DG. Tandem mass tag (TMT) proteomics were used to screen the differentially expressed proteins (DEPs) in CSF co-regulated by CUMS and ICA. Parallel reaction monitoring (PRM) was used to validate 10 DEPs that were related to cell proliferation and survival. In vitro, CSF was conducted on primary hippocampal neural stem cells (NSCs) to observe the proliferation and differentiation under high-corticosterone (CORT) concentration.Results﻿It was shown that ICA could alleviate depressive symptoms, learning-memory dysfunction, neurogenesis dysfunction and neuronal loss in DG of depression rats and ICA-CSF could effectively repair the CORT-induced damage. A total of 52 DEPs co-regulated by CUMS and ICA in CSF were screened and mainly involved in ribosome pathway, PI3K-Akt pathway and IL-17 pathway. Rps4x, Rps12, Rps14, Rps19, Hsp90b1, Hsp90aa1 and HtrA1 were validated by PRM.ConclusionsThese findings indicate that to regulate the expression of proteins in CSF may be involved in the effects of ICA against hippocampal neurogenesis dysfunction in depression.
Was Lung Computed Tomography Necessary for Patients Receiving Selective Surgery From Low-risk Areas of COVID-19?
Authors: Fu Jun , Chen Zhida , Xu Xinghua , Pan Lichao , Gu Liangyou , Xu Chi , Du Yinqiao , Ni Ming , Chen Jiying , Chai Wei , Yu Qilin , Lu Qiang
Published: October 2020

ObjectiveLung computed tomography (CT) image was considered as supplementary diagnostic criteria for COVID-19 in the newest diagnosis and treatment program; however, the diagnostic effectiveness of lung CT in patients that have a strict screening for symptoms, history and reverse transcription-polymerase chain reaction (RT-PCR) testing remain unclear. To share our experience about elective surgery during the COVID-19 pandemic and to analyze the effectiveness and necessity of lung CT for screening COVID-19 in elective surgery patients from low risk areas.MethodsBased on the database of our Hospital Information System, participants were all patients receiving elective surgery in departments of general surgery, hepatological surgery, orthopedics, neurosurgery and urology at our hospital from 11 January, 2020 to 11 May, 2020.ResultsIn total, 2375 patients (1150 females and 1225 males) were enrolled in this current study. The mean age was 52 years old, ranging from 6 to 94. All the RT-PCR results of these 2375 patients were negative, including the patients with fever. The most common features on lung CT were nodular lesions (n=624, 26.3%) and striplike lesions (n=467, 19.7%). While, there were only 120 patients (5.1%) with ground-glass opacities (GGO) and 54 patients (2.3%) with lung consolidations on the lung CT, which were ruled out the COVID-19 by the RT-PCR results, clinical manifestation, fever screen, contact history and travel history. During the hospital stay, a total number of 1085 patients were screened with temperature ≥ 37.3℃, which were ruled out COVID-19 by consultation of special fever clinic and respiratory department.ConclusionsAfter strict screening for symptoms, history (contact COVID-19 patients or travelling to high-risk areas) and RT-PCR testing, lung CT image was not recommended as routine examination in patients receiving selective surgery from the low-risk areas of COVID-19.
Diagnosis of Brain Tumor Using Nano Segmentation and Advanced-cnn Classification
Authors: V DEEPA P , S Joseph Jawhar , Geisa Mary
Published: October 2020

Background: In recent days, the field of nano-technology is becoming popular due to increased rate of accurate detection and effectiveness in clinical patients using Computer-Aided Diagnosis (CAD). The high rate of precision with accuracy and classification of brain tumor as benign or malignant can be achieved with nano-scale imaging technology. This helps to enhance the superiority of life for brain tumor diseased patients. Results: In this work, we propose the novel Semantic nano-segmentation for the detection of brain tumors even in nano scale range. Proposed Semantic Nano-segmentation based on Advanced - Convolutional Neural Networks will help the radiologists to find the brain cancer even at early stages with nodules at very smaller size. The proposed method of Advanced - Convolutional Neural Networks (A-CNN) uses ResNet-50. Here the nano-image is taken as input and tumor image is segmented using Semantic Nano-segmentation which carries an average dice and SSIM values to be 0.2133 and 0.9704 respectively. The accuracy of 93.2% and 92.7% is obtained by the proposed Semantic nano segmentation for benign and malignant tumor images respectively. A-CNN method of automatic classification has an average accuracy of 99.57% and 95.7% for benign and malignant images respectively. Conclusion: This novel nano-method is created for effective detection of tumor area in nanometers (nm) and thus evaluates the disease perfectly. Closeness of the Proposed method at ROC curve with reference to True Positive values indicates higher performance than other methods. Comparative analysis on ResNet-50 with testing and training data at rate of 90% -10%, 80%-20% and 70%-30% respectively is made which proves the effectiveness of the proposed work.
A New and Convenient Method to Get Paraffin-Embedded Sections of Tuberculous Bacteria as Positive Quality Controls for Acid-Fast Staining
Authors: Tao Lili , Yu Guangyin , Huang Chuqiang , Tan Junliang , Yin Xiaomin , Yu Hao
Published: October 2020

Background: Acid-fast staining for the detection of Mycobacterium tuberculosis has a high false negative-rate, partly due to it is hard to get a good positive control tissue of acid-fast staining. We aimed to design a simple and convenient method for making positive quality controls for acid-fast staining in paraffin-embedded sections.Methods: Three methods were used to get more tuberculous bacteria, which involving centrifugation, mixing, and culture of tubercle bacilli in pleural fluid, prior to the preparation of paraffin-embedded sections.Results: Culturing tubercle bacilli in pleural fluid proved to be, by far, the best of the three methods, with sufficient bacteria, convenient observation, clear staining, and potential for upscaled production.Conclusions: The application of this method should improve the detection rate of tuberculous bacteria, thus facilitating clinical treatment.
Prognostic Influence of Tobacco Smoking on Human Papilloma Virus-Related Oropharyngeal Cancer is Dependent Upon Treatment Modality
Authors: ITAMI Jun , KOBAYASHI Kenya , MORI Taisuke , HONMA Yoshitaka , KUBO Yuko , MURAKAMI Naoya , OMURA Go , NAKAYAMA Yuko , IGAKI Hiroshi , OKUMA Kae , INABA Koji , TAKAHASHI Kana , KASHIHARA Tairo , KANEDA Tomoya , SHIMA Satoshi , TAKAHASHI Ayaka , SHIMIZU Yuri , YOSHIMOTO Seiichi
Published: October 2020

[Purpose] Tobacco smoking has been reported to influence the prognosis of human papilloma virus (HPV)-related orophageyngeal squamous cell carcinoma (OPSCC). However, it remains to be studied whether tobacco smoking equally affects the patients treated by various modalities. [Material and Method] From 2010 through 2018, 241 patients with OPSCC were treated in a single institution, out of which 144 patients had HPV-related OPSCC. P16 immunohistochemical staining was used as a surrogate of HPV infection. Two patients was excluded because of inadequate radiation dose, and the remaining　142 patients were the subject of this study. Median age was 63.8 years and more than 80% were male. More than 70% were smokers or ex-smokers with a median pack year of 17.3. Eighty-seven patients (61.3%) were classified as stage I.[Results] For all 142 patients with HPV-related OPSCC, overall survival (OS) and disease-specific survival (DSS) were 87.0% and 93.4% in 3 years, respectively. There were no differences of OS and DSS according to the stages by 8th edition of tumor, node, and metastasis (TNM) classification and the primary sites. OS and DSS were different by the amount of tobacco smoking expressed in pack year (PY) > 30 and < 30. Also the presence of secondary cancer impacted OS. However, the influence of the amount of tobacco smoking was reduced in the patients treated by radiation therapy. [Conclusions] The impact of tobacco smoking upon the prognosis of HPV-related OPSCC seems to be dependent upon therapeutic modalities.
Comparison of Two Inverse Planning Algorithms for Cervical Cancer Brachytherapy
Authors: Fu Qi , Xu Yingjie , Zuo Jing , An Jusheng , Huang Manni , Yang Xi , Chen Jiayun , Yan Hui , Dai Jianrong
Published: October 2020

Purpose: To compare two methods, the hybrid inverse planning optimization (HIPO) algorithm and the inverse planning simulated annealing (IPSA) algorithm, for cervical cancer brachytherapy and provide suggestions for their usage.Material and methods: This study consisted of 24 cervical cancer patients treated with CT image-based high-dose-rate brachytherapy using various combinations of tandem/ovoid applicator and interstitial needles. For fixed catheter configurations, plans were retrospectively optimized with two methods: IPSA and HIPO. The dosimetric parameters with respect to target coverage, localization of high dose volume (LHDV), conformal index (COIN), and sparing of organs at risk (OARs) were evaluated. A plan assessment method which combines a graphical analysis and a scoring index was used to compare the quality of two plans for each case. The characteristics of dwell time distributions of the two plans were also analyzed.Results: Both IPSA and HIPO can produce clinically acceptable treatment plans. The rectum D2cc was slightly lower for HIPO as compared to IPSA (p=0.002). All other dosimetric parameters for targets and OARs were not significantly different between the two algorithms. The generated radar plots and scores intuitively presented the plan properties and enabled to reflect the clinical priorities for the treatment plans. Different characteristics were observed between the dwell time distributions generated by IPSA and HIPO. Conclusions: Despite significant difference in dwell time distributions, both the two algorithms could generate high-quality treatment plans. With the help of the plan assessment method, the clinical decision on the optimal plan can be made quickly and consistently for each patient.
Successfully Treatment of Application Awake Extracorporeal Membrane Oxygenation in Critical COVID-19 Patient: A Case Report
Authors: Tang Junyi , Li Wencan , Jiang Fanli , Wang Tao
Published: October 2020

Background: A newly infectious diseases named coronavirus disease 2019 (COVID-19) emerged in China and now has spread in many countries, and constituted a public health emergency of international concern. Extracorporeal membrane oxygenation (ECMO) is used as salvage therapies in critical COVID-19 patients with respiratory/cardiac failure. Case presentation: A 49-year-old female patient was diagnosed with COVID-19 and progressed to critical cases, she was successfully treated with the application of awake extracorporeal membrane oxygenation. This case is the first reported successfully treatment of application awake ECMO in critical COVID-19 patient in China.Conclusions: Here we present the first reported successfully treatment of application awake ECMO in critical COVID-19 patient, however, whether awake ECMO can be widely used in the treatment of critical COVID-19 patients need more practice.
Fenofibrate Alleviates Insulin Resistance and Hepatic Steatosis via Modulation of let-7/ SERCA2b Axis
Authors: Zhang Dan , Niu Shan-zhuang , Ma Yi-cheng , Zhou Bo , Deng Yi , Geng Zuo-tao , Wen Yu , Luo Su-feng , Shi Chun-jing , Pu Guang-yu , Zou Cheng-gang , Chen Yuan-Li , Ma Lan-qing
Published: October 2020

Background: Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist, which is widely used in clinical practice to effectively ameliorates the development of NAFLD. However, the molecular mechanism remains largely unknown, the present study aimed to investigate the role and specific mechanism of fenofibrate on lipid metabolism disorders associated diseases.Methods: The male C57BL6/J mice were divided into 3 groups, the mice in control group (n=10) were fed with normal chow diet, and the mice in HFD-fed group (n =10) were fed with a high fat diet (HFD) for 14 weeks. For the fenofibrate +HFD-fed group (n =10), the mice fed HFD were orally gavaged with fenofibrate (40 mg/kg) daily for the last 4 weeks. Body weight and hip width were measured. Macrosteatosis and fat deposition in the liver were measured by H&E staining and Oil red O staining individually. The levels of serum and hepatic triglyceride were measured, and HOMA-IR, HOMA-ISI were analyzed. The levels of SCD-1, Bip, CHOP and SERCA2b were measured by western blotting. The expression of let-7 were analyzed by qPCR, and the complementarity between the 3′-UTR of SERCA2b gene and let-7 was measured by luciferase reporter assay.Results: Fenofibrate reduces hepatic steatosis and insulin resistance in HFD-fed mice. Fnofibrate alleviates endoplasmic reticulum stress (ER stress) of mice fed a high fat diet (HFD). Fenofibrate increases the levels of Sarco-endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) which serves as a regulator of ER stress. Further, the levels of let-7 microRNA is also regulated by fenofibrate, and let-7 directly targets 3’-UTR of SERCA2b. Conclusion: The present data suggests that fenofibrate alleviates ER stress through the let-7/SERCA2b axis to protect against excessive lipid accumulation in the liver of Non-alcoholic fatty liver disease (NAFLD) mice.
Targeting STAT3 abrogates Tim-3 upregulation of adaptive resistance to PD-1 blockade on regulatory T cells of melanoma
Authors: Huang Lili , Xu Yu , Fang Juemin , Liu Weixing , Chen Jianhua , Liu Zhuqing , Xu Qing
Published: October 2020

Background Programmed cell death-1 (PD-1) blockade immunotherapies have demonstrated excellent clinical benefits in multiple cancers, but < 20% of melanoma patients respond to these treatments. Thus, it is crucial to understand for getting awareness of the dynamic changes vibrant transformations in the tumor microenvironment (TME) after PD-1 blockade, in exploring novel intervention targets as a potential therapy, for developing immunotherapy efficacy. MethodsTo ascertain the differentially expressed between PDCD1low and PDCD1high subsets and further PDCD1 related genes in skin cutaneous melanoma (SKCM) patients, a genomic analysis was conducted by The Cancer Genome Atlas (TCGA) datasets and web platform TIMER2.0 datasets. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Peripheral blood mononuclear cells (PBMCs), regulatory T (Treg) cells and B16F10 melanoma mouse were used as models. The cellular and molecular characteristics and mechanisms of Treg cells in melanoma were assessed by performing gene expression studies, immunohistochemistry, RNA sequencing, and flow cytometry.ResultsHere, we evaluate the countenance of T cell immunoglobulin and mucin-domain containing-3 (Tim-3), various immunosuppressive factors within tumor infiltrated regulatory T (Treg) cells after treated with anti-PD-1 or the indicator transduction and activator of transcription 3 (STAT3) inhibitors. Tim-3 gene is expressed differentially between PD-1low and PD-1high subsets from TCGA datasets and melanoma patients’ biopsies. Increased expression of Tim-3 is markedly observed within the tissues of the PD-1 blockade resistance of melanoma patients. Targeting STAT3 significantly boosts the response of resistant-PD-1 therapy within the melanoma mouse model. Mechanistically, the manifestation of STAT3 decreases the expression of Tim-3 and various cytokines in the purified Treg cells from individual peripheral blood mononuclear cells (PBMCs) and murine melanoma model, limiting the immunosuppression of Treg cells. ConclusionsOur findings indicate that Tim-3 expression on Treg cells within the TME is STAT3-dependent, providing support to STAT3 as a target and enhancing the immunotherapy for patients suffering from melanoma.
Development and Characterization of an Efficient Mutant Resource of the Mega Variety, Samba Mahsuri for Rice Improvement
Authors: Potupureddi Gopi , Balija Vishalakshi , Ballichatla Suneel , CG Gokulan , Awalellu Komal , Lekkala Swathi , Jallipalli Karteek , Mohammad Ershad , M Milton , Arutla Srikanth , Burka Rajender , Gouri Laha Shankar , Ayyangari Padmakumari Phani , Lella SubbaRao Venkata , Raman Sundaram Meenakshi , BC Viraktamath , Vemuri Ravindra Babu , Kranthi Brahma , Madnala Raju , Patel Hitendra Kumar , Sonti Ramesh Venkata , Madhav Maganti Sheshu
Published: October 2020

Background:Novel variants of rice (Oryza sativa L.) can be obtained from induced mutations. The objective of the present study is to induce mutations in the background of Samba Mahsuri (BPT-5204), a popular and mega rice variety of India for creating novel variants for morphological, physiological and biotic stresses through using Ethyl Methane Sulphonate (EMS).Results: A population derived from 10, 500 M1 plants and their descendants was phenotyped for a wide range of traits leading to the identification of 124 mutants having variations in key agro-morphological traits, and 106 mutants exhibited variation for physiological traits. Higher yield is the ultimate goal of crop improvement and we identified 574 mutants having higher yield compared to wild type by having better yield attributing traits. Further, a total of fifty mutants showed better panicle exsertion phenotypes as compared to Samba Mahsuri leading to enhancement of yield. Upon rigorous screening for three major biotic stresses, nine mutants showed enhanced tolerance for yellow stem borer, and thirteen different mutants each showed enhanced tolerance for sheath blight and bacterial leaf blight, respectively. On the whole, 1406 desired mutant lines identified at M2 were forwarded to an advanced generation (M5). Whole genome re-sequencing and analyses of 15 stable mutants revealed high level of similarities (99.91 to 99.99%) with the Samba Mahsuri. Conclusions:The lines showing enhanced tolerance to important biotic stresses (YSB, ShB and BLB) as well as several economically important traits are unique genetic resources which can be utilized for the identification of novel genes/alleles for different traits. The lines which have better agronomic features can be used as pre-breeding lines. The entire mutagenic population is maintained as a national resource for genetic improvement of the rice crop.
Effective Prevention of Atopic Dermatitis by Applying Fam’s Baby Moisturizer Twice Daily or Once Daily Compared with 2e Moisturizer Once Daily in High-Risk Neonates: Study Protocol for A Randomized, Blinded, Parallel, Three Group, Phase II Trial (PAF Study)
Authors: Inuzuka Yusuke , Yamamoto-Hanada Kiwako , Pak Kyongsun , Miyoshi Takekazu , Kobayashi Toru , Ohya Yukihiro
Published: October 2020

BackgroundAtopic dermatitis (AD) is a chronic and inflammatory skin disease that commonly affects young children. AD causes health-related burdens associated with pruritus and poor quality of life. The efficacy of moisturizer application shows inconsistency on primary prevention of AD according to previous randomized, controlled trials. Which moisturizer is effective and how often moisturizer should be applied to prevent development of AD in infants remain unclear. We hypothesize that twice daily application of moisturizer using Fam’s Baby is more effective than once daily application and that a sufficient amount of moisturizer application is effective for preventing development of AD in neonates and infants. Therefore, this study aimed to examine whether applying Fam’s Baby twice daily or once daily prevents AD compared with 2e moisturizer once daily in neonates and infants with at least one parent or sibling who has had atopic dermatitis.MethodsThis study is a single-center, three-parallel group, assessor-blind, superiority, individually randomized, controlled, phase II trial. A newborn with at least one parent or sibling who has had AD is randomly assigned to application of Fam’s Baby twice daily, Fam’s Baby once daily, or 2e once daily in a 1:1:1 ratio until 32 weeks old. The primary outcome is the time to the first onset of AD during administration of the moisturizer.DiscussionThis is the first phase II randomized, controlled trial in Japan to investigate whether applying moisturizer (Fam’s Baby) twice daily or once daily can prevent the incidence of AD compared with another moisturizer (2e) once daily in high-risk neonates. In this study, we will use 2e once daily as control moisturizer to confirm the efficacy for primary prevention of AD as found in our previous trial. Evaluation of application of moisturizers for preventing AD in this study is expected to contribute to a reduction in the prevalence of AD and a reduction in health care costs. Trial registrationJapan Registry of Clinical Trials (jRCT); ID: jRCTs031200070. Registered on 20 July 2020.
Daily Oral Low-Dose Vitamin A Supplementation Increases the Retinol Levels in Serum and Breast Milk of Lactating Mothers and Has No Effect on Infant Health Status: A Randomized Placebo-Controlled Trial in China
Authors: Ding Ye , Hu Ping , Yang Yue , Ye Mei , Lu Xiaolong , Jiang Wei , Xie Zhencheng , Fu Youjuan , Li Fang , Zhu Yunhua , Xu Fangping , Liu Ying , Wang Zhixu
Published: October 2020

Background: Vitamin A supplementation has been advocated as a potential strategy to improve the vitamin A status of lactating mothers and infants. In China, vitamin A supplements are readily available in the form of daily oral low doses. However, the existing clinical trials are limited to single or two high-dose maternal administration.Objective: We aimed to evaluate the effects of the daily oral low-dose vitamin A supplementation on the retinol levels in serum and breast milk of lactating mothers and the health status of infants in China.Methods: Lactating mothers who met the inclusion criteria and planned to continue exclusive breast-feeding were randomly assigned to receive either daily oral vitamin A and D drops (one soft capsule of 1800IU vitamin A and 600IU vitamin D2), or a matching placebo for 2 months. Before and after the intervention, the dietary intake was investigated by instant photography, and the retinol concentration in maternal serum and breast milk was determined by UPLC. During the trial, the health status of infants was diagnosed by pediatrician or reported by lactating mothers.Results: 245 participants completed the study with 117 in supplementation group and 128 in control group. After the 2-month intervention, maternal serum retinol concentration increased in supplementation group with no change in control group. Although breast milk retinol concentrations decreased significantly in both groups, the decrease in supplementation group was significantly less than that in the control group. However, maternal vitamin A supplementation was not associated with lower risks of infant febrile illness, respiratory tract infection, diarrhea and eczema respectively. Conclusion: Daily oral low-dose vitamin A supplementation is helpful to improve the maternal vitamin A status and can also play a positive role in vitamin A status of infants through breast milk.
Effect of Maximum Average Temperature on Suicide Rates in California, 2008-2017: Public Health Implications of Climate Change
Authors: Qamar Mavra , Cheng Sierra , Plouffe Rebecca , Nanos Stephanie , Fisman David N , Soucy Jean-Paul R
Published: October 2020

BackgroundSuicide prevention is a salient public health responsibility, as it is one of the top ten leading causes of premature mortality in the United States. Risk factors of suicide transcend the individual and societal level as risk can increase based on climatic variables. Previous studies have been country-based. Currently, studies focused solely on regions, provinces, or states, such as California, are limited. The present study holds two purposes: i) to assess the effect of maximum temperature on suicides, and ii) to evaluate the effect of number of monthly heat events on suicide rates, in California from 2008-2017.MethodsThe exposure was measured as the average Californian daily maximum temperature within each month, and the number of monthly heat events, which was calculated as a count of the days exhibiting a >15% increase from the historical monthly temperature. The outcome was measured as California’s monthly suicide rate. Negative binomial regression models assessed the relationship between maximum temperature and suicides, and heat events and suicide. A seasonal decomposition of a time series and auto-correlogram further analyzed the seasonality of suicide and the trend from 2008-2017. ResultsThere were 40,315 deaths by suicide in California between 2008-2017. Negative binomial regression indicated a 6.1% increase in suicide incidence rate ratio (IRR) per 10°F increase in maximum temperature (IRR=1.00590 per 1°F, 95% CI: 1.00387, 1.00793, p<0.0001) and a positive, non-significant association between suicide rates and number of heat events adjusted for month of occurrence (IRR 1.00148 per heat event, 95% CI: 0.99636, 1.00661, p=0.572). The time series analysis and auto-correlogram suggested seasonality of deaths by suicide.ConclusionThe present study provided preliminary evidence that will generate future directions for research. We must seek to further illuminate the relationship of interest and apply our findings to public health interventions that will lower the rates of death by suicide as we are confronted with the effects of climate change.
Effects of training podiatrists to use imagery-based motivational interviewing to improve self-care for people with diabetes-related foot disease: A mixed-methods pilot study
Authors: Kaczmarek Tracey , Netten Jaap Van , Lazzarini Peter , Kavanagh David
Published: October 2020

Background

Self-care in diabetic foot disease (DFD) is challenging and can contribute to poor outcomes. Motivational Interviewing (MI) engages people in self-care and integrating imagery may further improve its outcomes. No previous studies have trained podiatrists in using MI to address DFD self-care. This was the first study on training podiatrists to conduct imagery-based motivational interviewing (MI) when treating people with diabetes-related foot disease (DFD), and to examine impacts on MI related skills, job satisfaction and subjective experiences in a mixed-methods pilot study.

Methods

Eleven recruited podiatrists (Median age 35, 9 female) received two 4-hour training sessions and three received later mentoring. MI and imagery skills were rated using validated tools during two clinical sessions per participant at baseline, and 2- and 12-weeks post-training. Job satisfaction was assessed at baseline and 12 weeks. Semi-structured interviews at 12 weeks were analysed using the framework approach.

Results

Significant improvements over time ( p =.006-.044) with substantial effect sizes (η 2 =.50-.67) were found in three of four global MI related communication skills and two of four MI behaviours. However, effects on these indices were not sustained to 12 weeks, and imagery was rarely used. Job satisfaction was high at baseline and unchanged at follow-up ( p =0.34, η 2 =.100). In qualitative interviews, MI training and skills were valued, but significant challenges in using MI when treating people with DFD were reported.

Conclusion

Training podiatrists in MI may have potential but more training, observation and mentoring appear needed to obtain sustained communication changes in practice.
RDmap: A Map for Exploring Rare Diseases
Authors: Yang Jian , Dong Cong , Duan Huilong , Shu Qiang , Li Haomin
Published: October 2020

Background: The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases make the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases. Methods: By defining the quantitative distance among phenotypes and pathogenic genes based on corresponding ontology systems, the distance matrix of rare diseases included in Orphanet was calculated and mapped into Euclidean space. Enhanced by clustering classes and disease information, a rare disease map was developed based on ECharts. Results: The rare disease map called RDmap was published at http://rdmap.nbscn.org. The phenotype-based map comprises 3,287 rare diseases and the gene-based map comprises 3,789 rare genetic diseases and they were bridged by 1,718 overlapping diseases. RDmap works similar to the widely used Google map and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword search in an in-silico evaluation and 20 published cases of rare diseases also demonstrated that RDmap can be used by clinicians to improve diagnosis. Conclusion: RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasing complicated rare genetic diseases.
Double attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab×mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activity
Authors: Ho Kai-Wen , Chen I-Ju , Cheng Yi-An , Liao Tzu-Yi , Liu En-Shuo , Chen Huei-Jen , Lu Yun-Chi , Su Yu-Cheng , Roffler Steve R. , Huang Bo-Cheng , Liu Hui-Ju , Huang Ming-Yii , Chen Chiao-Yun , Cheng Tian-Lu
Published: October 2020

Background

Tumor-targeted nanoparticles hold great promise as new tools for therapy of liquid cancers. Furthermore, the therapeutic efficacy of nanoparticles can be improved by enhancing the cancer cellular internalization.

Methods

In this study, we developed a humanized bispecific antibody (BsAbs: CD20 Ab×mPEG scFv) which retains the clinical anti-CD20 whole antibody (Ofatumumab) and is fused with anti-mPEG single chain antibodies (scFv) that can target the systemic liquid tumor cells. This combination achieves the therapeutic function and simultaneously “grabs” PEGylated liposomal doxorubicin (PLD) to enhance the cellular internalization and anticancer activity of PLD.

Results

We successfully constructed the CD20 Ab×mPEG scFv and proved that CD20 Ab×mPEG scFv can target CD20-expressing Raji cells and simultaneously grab PEGylated liposomal DiD increasing the internalization ability up to 60% in 24 h. We further showed that the combination of CD20 Ab×mPEG scFv and PLD successfully led to a 9-fold increase in tumor cytotoxicity (LC 50 : 0.38 nM) compared to the CD20 Ab×DNS scFv and PLD (lC 50 : 3.45 nM) in vitro . Importantly, a combination of CD20 Ab×mPEG scFv and PLD had greater anti-liquid tumor efficacy ( P = 0.0005) in Raji-bearing mice than CD20 Ab×DNS scFv and PLD.

Conclusion

Our results indicate that this “double-attack” strategy using CD20 Ab×mPEG scFv and PLD can retain the tumor targeting ( first attack ) and confer PLD tumor-selectivity ( second attack ) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.
Spinal cerebrospinal fluid flow is increased in rats with elevated intracranial pressure 18 hours after cortical ischaemic stroke
Authors: Bothwell Steven William , Omileke Daniel , Pepperall Debbie-Gai , Patabendige Adjanie , Spratt Neil J
Published: October 2020

Background

A dramatic oedema-independent intracranial pressure (ICP) rise occurs 24 hours post-stroke in rats and may explain infarct expansion. Underlying mechanisms of this rise are unknown but evidence suggests cerebrospinal fluid (CSF) dynamics are involved.

Methods

We investigated how CSF flow changes post-stroke and how this relates to ICP by infusing CSF tracer into the lateral ventricles of rats and assessing transport time and total tracer transport to the spinal subarachnoid space over a 90 minute period.

Results

Stroke animals with ICP rise had faster tracer transit when compared with stroke animals without ICP rise (27.6 ± 4, n = 6, vs 48.6 ± 4.5 mins, n = 6) or animals subjected to a sham procedure (47.9 ± 4 mins, n = 8), F(2,17) = 0.1, p≤0.01. There was a correlation between tracer transit time and ΔICP (R = -0.52, p=0.02) and infarct volume (R = -0.6, p=0.04). There was no difference in total tracer observed.

Conclusions

Faster tracer transit in stroke animals may be explained by impairment of other CSF outflow pathways, whereby, spinal drainage acts as a compensatory mechanism. Investigation into the disruption of other CSF drainage routes post-stroke may offer insight into the underlying mechanisms of infarct expansion post-stroke.
High-pressure syntheses and crystal structure analyses of a new low-density CaFe2O4-related and CaTi2O4-type MgAl2O4 phases
Authors: Ishii Takayuki , Criniti Giacomo , Bykova Elena , Dubrovinsky Leonid , Katsura Tomoo , Arii Hidekazu , Kojitani Hiroshi , Akaogi Masaki
Published: October 2020

Three single crystals of CaTi2O4 (CT)-type, CaFe2O4 (CF)-type, and new low-density CaFe2O4 (LD-CF) related MgAl2O4 were synthesized at 27 GPa and 2500 °C and also CT-type MgAl2O4 at 45 GPa and 1727 °C using conventional and advanced multi-anvil technologies, respectively. The structures of CT-type and LD-CF related MgAl2O4 were analyzed by single-crystal X-ray diffraction. The lattice parameters of the CT-type phases synthesized at 27 and 45 GPa were a = 2.7903(4), b = 9.2132(10), and c = 9.3968(12) Å, and a = 2.7982(6), b = 9.2532(15), and c = 9.4461(16) Å, respectively, (Z = 4, space group: Cmcm) at ambient conditions. This phase has an AlO6 octahedral site and an MgO8 bicapped trigonal prism with two longer cation-oxygen bonds. The LD-CF related phase has a novel structure with orthorhombic symmetry (space group: Pnma), and lattice parameters of a = 9.207(2), b = 3.0118(6), and c = 9.739(2) Å (Z = 4). The structural framework comprises tunnel-shaped spaces constructed by edge- and corner-sharing of AlO6 and a 4+1 AlO5 trigonal bipyramid, in which MgO5 trigonal bipyramids are accommodated. The CF-type MgAl2O4 also has the same space group of Pnma but a slightly different atomic arrangement, with Mg and Al coordination numbers of 8 and 6, respectively. The LD-CF related phase has the lowest density of 3.50 g/cm3 among MgAl2O4 polymorphs, despite its high-pressure synthesis from the spinel-type phase (3.58 g/cm3), indicating that the LD-CF related phase formed via back-transformation from a high-pressure phase during the recovery. Combined with the previously determined phase relations, the phase transition between CF-and CT-type MgAl2O4 is expected to have a steep Clapeyron slope. Therefore, CT-type phase may be stable in basaltic- and continental-crust compositions at higher temperatures than the average mantle geotherm in the wide pressure range of the lower mantle. The LD-CF related phase could be found in shocked meteorites and used for estimating shock conditions.