bluuebunny/crossref_metadata_2025 huggingface dataset:
Guidelines Translation for Distress Management in Cancer Patients Based on CAN-IMPLEMENT: Implementation Part
Authors: Fu Liang , Zhang Xiaoju , Hu Yan , Lu Zhenqi , Yang Yang , Huang Mingzhu , Li Yuanyuan , Zhu Fuzhong , Wang Yang , Huang Zhe
Published: August 2020

Background: Stomach cancer patients receiving chemotherapy suffered severe distress. This study aimed to align the Cancer-related Distress Management Guidelines into clinical practice among stomach cancer patients receiving chemotherapy, and to monitor the implementation process of Cancer-related Distress Management Guidelines, evaluate the effects of guidelines implementation, and maintain the guidelines implementation in clinical practice.Methods: A Guideline Adaptation and Implementation Planning Resource (CAN-IMPLEMENT) was used as the research framework, which include three phases. Here the Implementation Part (Phase 2 and Phase 3) was reported: alignment of Cancer-related Distress Management Guidelines in clinical practice among stomach cancer patients receiving chemotherapy, and process monitoring and outcome evaluation of Cancer-related Distress Management Guidelines.Results: After the guidelines implementation, the formal audit criteria, working pathways, assessment tools, multidisciplinary panels, training manual for healthcare professionals, education and handbook for patients and their caregivers of distress management were developed on institutional level, as well as the related assessment tools and record forms. The completion rate of distress management record was increased from 0.0% to 97.9% (P<0.001). The compliance of most items in the audit checklist for medical staff's distress management were improved, from 57.1% to 100.0% (P<0.001). The distress positive rate of stomach cancer patients receiving chemotherapy was decreased from 22.7% to 9.3% (P<0.05), and the distress scores were declined from 2 (0-9) to 0 (0-7) (P<0.001).Conclusions: The completion rate of distress management records increased significantly after guidelines implementation, revealing the process quality control of the distress management practice was good. At the institutional level, this guidelines implementation promoted the establishment of distress management system. To healthcare professionals, the guidelines implementation improved the distress management compliance. For stomach cancer patients receiving chemotherapy, distress management practices can effectively improve the distress of stomach cancer patients receiving chemotherapy.
Joint inference of CFC lifetimes and banks suggests previously unidentified emissions
Authors: Lickley Megan , Fletcher Sarah , Rigby Matt , Solomon Susan
Published: August 2020

Chlorofluorocarbons (CFCs) are harmful ozone depleting substances and greenhouse gases. CFC production was phased-out under the Montreal Protocol, however recent studies suggest new and unexpected emissions of CFC-11. Quantifying CFC emissions requires accurate estimates of both atmospheric lifetimes and ongoing emissions from old equipment (i.e. ‘banks’). In a Bayesian framework we simultaneously infer lifetimes, banks and emissions of CFC-11, 12 and 113 using available constraints. We find that lifetimes of all three gases are likely shorter than previous estimates, suggesting that best estimates of inferred emissions are larger than recent evaluations. Our analysis indicates that bank emissions are decreasing faster than inferred emissions, and we estimate new, unexpected emissions during 2014-2016 were 19.6, 16.2, and 7.7 Gg/yr for CFC-11, 12 and 113, respectively. While recent studies have focused on unexpected CFC-11 emissions, our results call for further investigation of potential sources of emissions of CFC-12 and CFC-113, along with CFC-11.
Loss-of-function of the NOMO1 Gene Causes Neuropsychiatric Disorder-related Phenotypes
Authors: Li Fei , Li Tingting , Lin Jia , Jian Jing , Zhang Qi , Zhang Yinglan , Liu Xiuyun , Ji Yongxia , Wang Xu , Li Qiang
Published: August 2020

Background: Clinical genome-wide analysis identified NOMO1 in human chromosome 16p13.11 as a candidate gene associated with neuropsychiatric disorders such as autism, schizophrenia and epilepsy. However, the important contributions underlying NOMO1 deficiency resulting in neuropsychiatric disorders is not understand, and the molecular and pathogenesis mechanisms of nomo1 gene are unclear. Therefore, it is necessary to construct animal models to systematically study the effects of nomo1 deficiency on neuropsychiatric system and explore pathogenic molecular mechanism of diseases.Methods: We developed a viable vertebrate model of loss-of-function of nomo1 using CRISPR/Cas9 and studied the characterization of nomo1 mutant zebrafish. Phenotypic research was performed in developing nomo1 mutant zebrafish, including morphological measurements, behavioral tests, and functional mechanism analyses.Results: The nomo1 loss-of-function zebrafish model accurately recapitulated key neuropsychiatric disorders traits. The mutant zebrafish showed decreased locomotion in the larval stage (7 dpf), increased spontaneous movement in infancy (15 dpf and 30 dpf), and social defects and repetitive behaviors in adolescence (2 mpf). More importantly, we demonstrated that these behavioral phenotypes stem from abnormal brain structure and neurotransmitter metabolism. Transcriptome analysis provided insights for studying the functional mechanism of nomo1 pathogenesis. Further results revealed that the neuroactive drug PTZ recovered the decreased locomotion phenotype in larval zebrafish, which provides functional basis for the exploration of drug sensitivity and intervention in behavioral phenotypes of nomo1 mutant zebrafish.Conclusion: This study firstly reveal the functional evidence that loss-of-function of nomo1 elicits neuropsychiatric disorders, and emphasize the relationship between nomo1 deficiency and neuropsychiatric disorders from the perspectives of behavioral phenotypes, brain development, and neurotransmitter metabolism.Limitation: The behavioral phenotype intervention of neuroactive drug in nomo1-/-zebrafish can be directly translated to the behavior of human associated diseases need further study.
Investigation of Equity in Arrival Time of Emergent Accidental Patient to Hospital in (2018-2019) in a City in North of Iran
Authors: Omidi Mohaddese , Zohrevandi Behzad , Rad Enayatollah Homaie
Published: August 2020

Background: Fairness is an important and controversial issue when allocating public resources. People need to be arrived early to the hospitals when they are injured in traffic accidents. Both the mean and equity of the time of arriving to the hospital are important. The aim of this study was to investigate of equity in arrival time of emergent accidental patient to hospital in 2018-2019 in a city in North of Iran.Methods: This study was a Descriptive-analytical study. In this study we extracted the information from Guilan province trauma system data for Poursina Hospital in Rasht in 2018 and 2019. Data included information on age, sex, level of education, place of residence, time of transfer from the scene of the accident to the hospital, type of vehicle, marriage and occupation. The Gini coefficient was used to calculate equity in access to pre-hospital emergency services and regression models were estimated for inequity in time to receive hospital services. Results: The study showed that the mean and standard deviation of patients' arrival time from the time of the accident to the time of arrival at the hospital was 64.48 ± 47.63 minutes (minimum 9 minutes and maximum 462 minutes). Gini coefficient was 0.31 (p <0.001) which shows in the Rasht city has a relative and appropriate equity when the patient arrives. The contribution of each factor using the regression model indicated the existence of a part of the inequity due to the way the patient was transferred. The transfer time of patients by car was 40 minutes longer (p-value <0.001) and by other methods (except ambulance and car) was 26 minutes longer (p = 0.036). In children, the transfer time was 42 minutes less (p = 0.003). Other variables did not explain the inequity (p> 0.05)Conclusion: According to the time of arrival of patients and Gini index, in Rasht, equity in providing services is in a good condition. This indicates that the emergency department does not systematically transport people to the hospital late.
Targeting TCTP sensitizes tumor to T cell-mediated therapy by reversing immune-refractory phenotypes
Authors: Lee Hyo-Jung , Song Kwon-Ho , Oh Se Jin , Kim Suyeon , Cho Eunho , Kim Jungwon , Park Yun gyu , Lee Kyung-Mi , Yee Cassian , Jung Sang Taek , Kim Tae Woo
Published: August 2020

The authors have requested that this preprint be removed from Research Square.
Regulation of CTGF Expression by miR-133b for the Treatment of Renal Interstitial Fibrosis in Old UUO Rats
Authors: Cao Dan , Wang Yuan , Zhang Yingjie , Zhang Yinping , Huang Qi , Yin Zhong , Cai Guangyan , Chen Xiangmei , Sun Xuefeng
Published: August 2020

Introduction: Renal interstitial fibrosis, an important pathological feature of kidney aging and chronic renal failure, is regulated by mesenchymal stem cells (MSCs). We have previously demonstrated the high expression of miR-133b in MSC-derived extracellular vesicles (MSC-EVs) from old rats, which mediated the inhibition of epithelial-mesenchymal transition (EMT) of renal tubules induced by transforming growth factor-β1 (TGF-β1). We investigated the effect of miR-133b for the treatment of geriatric renal interstitial fibrosis and evaluated its target genes.Methods: miR-133b expression induced during the EMT of HK2 cells by TGF-β1 at different concentrations (0, 6, 8, and 10 ng/mL) and time points (0, 24, 48, and 72 h) was detected using real-time polymerase chain reaction. The target genes of miR-133b were validated using a dual-luciferase reporter assay. In vitro experiments were performed to observe mRNA and protein expression of miR-133b targets, E-cadherin, α-smooth muscle actin (SMA), fibronectin, and collagen 3A1 (Col3A1), in HK2 cells transfected with miR-133b under TGF-β1 stimulation. A 24-week-old unilateral ureteral obstruction (UUO) mouse model was established and injected with transfection reagent and miR-133b into the caudal vein. miR-133b、 target gene and other indexes mentioned above mRNA and protein levels and renal interstitial fibrosis were detected at 7 and 14 days.Results: miR-133b expression gradually decreased with an increase in TGF-β1 concentration and treatment time, and miR-133b mimic downregulated connective tissue growth factor (CTGF) expression. Dual-luciferase reporter assay confirmed CTGF as a direct target of miR-133b. miR-133b mimic transfection inhibited the TGF-β1-induced EMT of HK2 cells; this effect was reversed by CTGF overexpression. miRNA-133b expression significantly increased (approximately 70-100 times) in mouse kidneys after injection of the miRNA-133b overexpression complex, significantly alleviating renal interstitial fibrosis in UUO mice.Conclusion: miR-133b exerted targeted inhibitory effects on CTGF expression, consequently reducing the TGF-β1-induced EMT of HK2 cells and renal interstitial fibrosis in old UUO mice.
Ethnobotanical Utilization of Kigelia africana (Lam.) Benth. according to Herbal Medicine Traders in Benin.
Authors: Dossou-Yovo Hubert Olivier , Vodouhè Fifanou G. , Kindomihou Valentin , Sinsin Brice
Published: August 2020

BackgroundThis research aimed at gathering knowledge on the medicinal exploitation and magic utilization of Kigelia africana in Benin. The species has received very little attention in Benin where it is widely used in traditional medicine to treat diseases and recently recorded as a threatened speciesMethodsA semi-structured questionnaire was used in different markets in Benin to gather ethnobotanical knowledge on Kigelia africana from herbal traders. Various percentages of traders were calculated, the Use Value of the most traded parts was determined and the two proportions test was performed to check for difference in Use Value.ResultsThirty-six percent of respondents obtained parts of the species both by purchase in their own markets and by travelling far. The same proportion confirmed that they travelled very far before buying parts they used to sell. None mentioned harvesting the plant parts from wild populations. A high proportion of informants (63%) reported selling fruits and bark whereas a relatively low proportion of them (37%) sell fruits, bark and leaves of the species. Bark was recorded as most sold followed by fruits. Leaves were recorded as least sold.The majority of respondents confirmed the scarcity of the species in recent years. Thirteen diseases, disorders and rituals were recorded and the majority oftraders mentioned the use of bark in treating stomach infections followed by gynecological disorders. Fruits were mainly used in magic rituals followed by treatment for stomach infections. Fruits showed a Use Value higher than bark although bark was recorded as most in demand. Five types of preparation were recorded and 54% of traders mentioned bark decoctions while 27% highlighted infusion of fruits in water.ConclusionsKigelia africana plays an important role in local ethnomedicine and bark and fruits were the most traded organs. Its fruits were relatively more important than bark in terms of uses but harvesting and trade of its parts are threats to the species. Urgent conservation tools are needed for its long-term sustainable exploitation.
Nurses’ Perceptions and Experiences of Rotating-Shift Work in Acute Hospitals: A Qualitative Study
Authors: Min Ari , Yoon Yea Seul , Lee Won
Published: August 2020

Background: An 8-hour shift system with faster rotation (e.g., shift changes every 2 to 5 days) is common for nurses at acute hospitals in Korea. However, there is a lack of information regarding nurses’ perceptions and experiences of rotating shift schedules, as well as the ways in which rotating-shift work affects patient outcomes. This study aimed to identify and describe emergent themes and offer new insights into nurses’ perceptions and experiences of rotating-shift work in Korea. Moreover, it explored the relationship between rotating-shift work and nurse and patient outcomes.Methods: A qualitative descriptive design was employed. Focus group interviews were conducted with 24 rotating-shift nurses at Korean acute care hospitals. Qualitative data were collected between January and February 2019, and conventional content analysis was employed. Results: Three themes and eight subthemes emerged. Major themes were unsatisfactory work schedules, the impact of shift work on nurses' lives, and the impact of schedule-related fatigue on overall work performance.Conclusion: Study findings highlight the importance of optimal scheduling, to reduce fatigue among rotating-shift nurses. Managers and administrators may improve nurse performance and patient safety by reviewing scheduling practices, considering the potential impact of shift schedules on nurse and patient outcomes, and addressing nurse’s scheduling issues. Furthermore, hospital authorities should consider revising schedules to include sufficient breaks between shifts. This study addressed issues that stem from rotating shift work, affecting both nurses and patients. Nurse interviews clarified these issues, which were classified according to theme. This study aimed to find practical solutions for shift planning problems, particularly in Korea, and to inform the development of scheduling guidelines for rotating-shift work in the future.
Cryogenic electro-optic interconnect for superconducting devices
Authors: Kippenberg Tobias , Youssefi Amir , Shomroni Itay , Joshi Yash , Bernier Nathan , Lukashchuk Anton , Uhrich Philipp , Qiu Liu
Published: August 2020

Encoding information onto optical fields using electro-optical modulation is the backbone of modern telecommunication networks, offering vast bandwidth and low-loss transport via optical fibers.
For these reasons, optical fibers are also replacing electrical cables for short range communications within data centers.
Compared to electrical coaxial cables, optical fibers also introduce two orders of magnitude smaller heat load from room to milli-Kelvin temperatures, making optical interconnects based on electro-optical modulation an attractive candidate for interfacing superconducting quantum circuits and hybrid superconducting devices.
Yet, little is known about optical modulation at cryogenic temperatures.
Here we demonstrate a proof-of-principle cryogenic electro-optical interconnect, showing that currently employed Ti-doped lithium niobate phase modulators are compatible with operation down to 800mK ---below the typical operation temperature of conventional microwave amplifiers based on high electron mobility transistors (HEMTs)---and maintain their room temperature Pockels coefficient.
We utilize cryogenic electro-optical modulation to perform
spectroscopy of a superconducting circuit optomechanical system, measuring optomechanically induced transparency (OMIT).
In addition, we encode thermomechanical sidebands from the microwave domain onto an optical signal processed at room temperature.
Although the currently achieved noise figure is significantly higher than that of a typical HEMT,
substantial noise reduction should be attainable by harnessing recent advances in integrated modulators, by increasing the modulator length, or by using materials with a higher electro-optic coefficient, leading to noise levels on par with HEMTs.
Our work highlights the potential of electro-optical modulators for massively parallel readout for emerging quantum computing or cryogenic classical computing platforms.
Traditional herbal healing practices for the treatment of Malaria and associated symptoms by Miju-Mishmi tribe of Lohit district, Arunachal Pradesh, Northeast India
Authors: Talukdar Simi
Published: August 2020

Background: Miju-Mishmi tribe of Lohit district have been practising traditional herbal medicine for curing various ailments including malaria. Present study investigated the traditionally used antimalarial plants and their mode of preparation by Miju-Mishmi tribe to cure malaria and associated symptoms. Also, to explore their biological relevance and phytopharmacological confirmation about the presence of secondary metabolites. Methods: The study was conducted in three villages of Lohit district of Arunachal Pradesh., viz. Karhe, ZiroBasti and Telluliang village. Semi-structured interviews and Focus Group Discussions (FGD) were conducted with purposively selected interviewees including traditional healers, herb sellers, cured patients, and elderly knowledgeable persons. To understand the popularity of each medicinal plant, systematic analysis of ethnobotanical indices, viz., Fidelity Level, Preference Ranking, Use Value, Informant Consensus Factor and Formulation Score were calculated. Qualitative phytochemical profiling was performed for the plants whose PR % scores ≥ 65 and FL scores ≥ 80%.Results: A of total 79 medicinal plants belonging to 50 families and 71 genera were used in twenty-nine ethnomedicinal formulations. Among these, twenty-four plants were reported to be newly used. Mostly leaves (30.38%) of the herbaceous species (48.10%) were used in different formulations. Maximum formulations were prescribed for internal application (83.54%) with wide utility of extraction (25.81%) followed by decoction (22.58%) mode. The highest fidelity value (≥ 80%) was reported for Aconitum heterophyllum followed by Paris polyphylla, Coptis teeta, Euphorbia neriifolia, Holarrhena pubescens, Tinospora cordifolia, Andrographis paniculata. The highest PR value (≥ 65%) was account for C. teeta, followed by T. cordifolia, A. nilagirica and P. polyphylla for curing malaria fever. The UV index ranges between 0.07 to 0.87, with highest ranking reported for C. teeta (UV=0.87). Species like A. heterophyllum, Andrographis paniculata, Artemisia nilagirica, C. teeta, Holarrhena pubescens, and P. polyphylla are in high market demand. Preliminary qualitative phytochemical profiling of selected plants has confirmed their therapeutic efficacy against malaria.Conclusion: Indigenous Miju-Mishmi people have a great knowledge of antimalarial medicinal plants, which requires a proper documentation. There is an enormous probability of getting many effective antimalarial leads from the reported indigenous plants of Mishmi hills for discovery of new drugs.
Deep Convolution Neural Network Based Artificial Intelligence Improves Diagnosis of Thyroid Scintigraphy for Thyrotoxicosis: a Dual Center Study
Authors: Yang Pei , Pi Yong , He Tao , Zhou Ke , Zhong Xiao , Liu Yemei , Sun Jiangming , Wei Jianan , Xiang Yongzhao , Jiang Lisha , Li Lin , Yi Zhang , Zhao Zhen , Cai Huawei
Published: August 2020

Background: 99mTc-pertechnetate thyroid scintigraphy is a valid avenue for distinguishing causes of thyrotoxicosis in the clinic, but the interpretation of thyroid scintigraphic images is subjected with significant variation among different inter-observers. We aim to develop an artificial intelligence (AI) system to improve the diagnosis of thyrotoxicosis.Materials and methods: We constructed an AI model based on a deep neural network with 2468 thyroid scintigraphic images collected from West China Hospital, and evaluated the diagnostic accuracy for classifying four patterns of thyrotoxicosis: ‘diffusely increased,’ ‘diffusely decreased,’ ‘focal increased,’ and ‘heterogeneous uptake.’ Then, we compared the diagnostic performance of the AI model and five physicians with 200 testing cohorts from two centers.Results: We constructed the AI model, which has the best performance in internal database validation based on four kinds of standout pre-trained networks. This AI model achieves satisfactory performance in classifying four patterns of thyrotoxicosis with an overall accuracy of 91.92% for internal and 86.75% for external data validation. In the following contrastive study, the AI model represented improved diagnostic accuracy and consistency than 5 physicians for interpreting data from West China Hospital (88% vs. 66~73%) and Panzhihua Central Hospital (83% vs. 53%~79%), respectively.Conclusion: Deep convolution neural network based AI model represented considerable performance in classifying four patterns of thyroid scintigraphic images; this may help physicians diagnose causes of thyrotoxicosis and reduced the physicians’ error rate.
Frequency and Risk Factors for Reverse Triggering in Pediatric ARDS During Synchronized Intermittent Mandatory Ventilation
Authors: Shimatani Tatsutoshi , Yoon Benjamin , Kyogoku Miyako , Kyo Michihito , Ohshimo Shinichiro , Newth Christopher JL , Hotz Justin C. , Shime Nobuaki , Khemani Robinder G.
Published: August 2020

[BACKGROUND] Reverse triggering (RT) occurs when respiratory effort begins after a mandatory breath is initiated by the ventilator. RT may exacerbate ventilator-induced lung injury and lead to breath stacking. We sought to describe the frequency and risk factors for RT amongst ARDS patients and identify risk factors for breath-stacking. [METHODS] Secondary analysis of physiologic data from children on Synchronized Intermittent Mandatory pressure control ventilation enrolled in a single center RCT for ARDS. When children had a spontaneous effort on esophageal manometry, waveforms were recorded and independently analyzed by two investigators to identify RT. [RESULTS] We included 81,990 breaths from 100 patient-days and 36 patients. Overall, 2.46% of breaths were RTs, occurring in 15/36 patients (41.6%). Higher tidal volume and a minimal difference between neural respiratory rate and set ventilator rate were independently associated with RT (p = 0.001) in multivariable modeling. Breath stacking occurred in 534 (26.5%) of 2017 RT breaths, and 14 (93.3%) of 15 RT patients. In multivariable modeling, breath stacking was more likely to occur when total airway delta pressure (Peak Inspiratory Pressure-PEEP) at the time patient effort began, Peak Inspiratory Pressure, PEEP, and Delta Pressure were lower, and when patient effort started well after the ventilator initiated breath (higher phase angle) (all p < 0.05). Together these parameters were highly predictive of breath stacking (AUC 0.979). [CONCLUSIONS] Patients with higher tidal volume and who have a set ventilator rate close to their spontaneous respiratory rate are more likely to have RT, which results in breath stacking over 25% of the time. Trial registration: NIH/NHLBI R01HL124666, Clinical Trials.gov NCT03266016, Registered 29 August 2017, https://clinicaltrials.gov/ct2/show/NCT03266016
Measurement of step surface contour based on variable sampling phase shift interference phase extraction algorithm based on selective sampling
Authors: Zhang Songsong , Huang Haisong , Xiong Qiaoqiao
Published: August 2020

Variable frequency phase shift interferometry is widely applied in optical precision measurement, with the accuracy of phase extraction’s direct impact on that of phase shift interferometry. In the variable-frequency phase-shift interferometry, the commonly used phase-shifting devices are prone to phase shift errors, because the ordinary equal-step phase extraction algorithm, which can be merely used to measure simple and smooth surface, influences the accuracy of phase extraction resulting in measuring error, and causes inefficiency led by the long time the iterative process lasts for when applied in complex stepped surfaces measurement. As a sort of step-by-step phase-shifting phase extraction algorithm based on selective sampling is used to measure the step surface contour, the interference image is firstly sampled at equal intervals to reduce the iterative calculation, and in view of the fact that the phase calibration of the test system is not required in this algorithm, the measured phase is given by using the alternating iterative method despite the unknown phase and unknown phase shift amount. The phase extraction accuracy and iteration time among traditional iterative algorithm, four-step phase shift algorithm and the variable phase shift phase interpolation algorithm based on selective sampling are compared in the simulation and experiment. It is shown that the variable frequency phase shifting interference phase extraction algorithm based on selective sampling has shorter operation time, less error and higher accuracy than traditional iterative algorithm in measuring complex step surface.
Low-dose Diosbulbin-B (DB) Regulates Tumor-Intrinsic PD-L1/NLRP3 Signaling Pathway to Increase Cisplatin-Sensitivity in Gastric Cancer (GC)
Authors: Li Chunfeng , Qiu Junqiang , Xue Yingwei
Published: August 2020

Background: Generation of cisplatin (DDP)-resistance by gastric cancer (GC) cells seriously limits the therapeutic efficacy of this drug in clinic, and recent data suggested that Diosbulbin-B (DB), the main anti-tumor compound of Dioscorea bulbifera L, was effective to improve cisplatin-sensitivity in GC cells. However, the underlying mechanisms are still largely unknown.Methods: Genes expressions were determined by Real-Time qPCR and Western Blot. Cell viability was evaluated by cell counting kit-8 and trypan blue staining assay. Annexin V-FITC/PI double staining assay was used to examine cell apoptosis. The Spheroid formation assay was used to evaluated cell stemness. Immunohistochemistry (IHC) was employed to examine the expressions and localization of Ki67 protein in mice tumor tissues.Results: Here we found that low-dose DB (12.5 μM) downregulated PD-L1 to activate NLRP3-medicated pyroptosis, and inhibited cancer stem cells (CSCs) properties, to sensitize cisplatin-resistant GC (CR-GC) cells to cisplatin. Mechanistically, the CR-GC cells were obtained, and either low-dose DB or cisplatin alone had little effects on cell viability in CR-GC cells, while low-dose DB significantly induced apoptotic cell death in cisplatin treated CR-GC cells. In addition, low-dose DB triggered cell pyroptosis in CR-GC cells stimulated with cisplatin, which were abrogated by silencing NLRP3. Next, CSCs tended to be enriched in CR-GC cells, instead of their parental cisplatin-sensitive GC (CS-GC) cells, and low-dose DB (12.5 μM) inhibited spheroid formation and stemness biomarkers (CD44, CD133, SOX2, OCT4 and Nanog) expressions to eliminate CSCs in CR-GC cells, which were reversed by upregulating programmed death ligand-1 (PD-L1). Furthermore, we proved that PD-L1 negatively regulated NLRP3 in CR-GC cells, and low-dose DB (12.5 μM) activated NLRP3-mediated pyroptotic cell death in cisplatin treated CR-GC cells by downregulating PD-L1. Also, low-dose DB aggravated the inhibiting effects of cisplatin on tumorigenesis of CR-GC cells in vivo. Conclusions: Collectively, low-dose DB (12.5 μM) regulated intrinsic PD-L1/NLRP3 pathway to improve cisplatin-sensitivity in CR-GC cells, and this study provided alternative therapy treatments for GC.
Diagnostic Value of Serum HER2 Levels in Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Shamshirian Amir , Aref Amir Reza , Yip George W. , Warkiani Majid Ebrahimi , Heydari Keyvan , Bazaz Sajad Razavi , Hamzehgardeshi Zeinab , Shamshirian Danial , Moosazadeh Mahmood , Alizadeh-Navaei Reza
Published: August 2020

Background: Measurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict of prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focusing on the diagnostic/screening value of serum HER-2 levels in comparison to routine methods.Methods: We performed a systematic search via PubMed, Scopus, Cochrane-Library, and Web of Science databases for human diagnostic studies reporting the levels of serum HER-2 in breast cancer patients, which was confirmed using the histopathological examination. Meta-analyses were carried out for sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR).Results: Fourteen studies entered into this investigation. The meta-analysis indicated the low sensitivity for serum HER2 levels (Sensitivity: 53.05, 95%CI 40.82-65.28), but reasonable specificity of 79.27 (95%CI 73.02-85.51) and accuracy 72.06 (95%CI 67.04-77.08). We also found a significant differences for PPV (PPV: 56.18, 95%CI 44.16-68.20), NPV (NPV: 76.93, 95%CI 69.56-84.31), PLR (PLR: 2.10, 95%CI 1.69-2.50) and NLR (NLR: 0.58, 95%CI 0.44-0.71).Conclusion: Our findings revealed that although serum HER-2 levels showed low sensitivity for breast cancer diagnosis, its specificity was reasonable. Hence, it seems that the measurement of serum HER-2 levels can play a significant role as a verification test for initial negative screening test results, especially in low-income regions due to its cost-effectiveness and ease of implementation.
Alteration in the immune microenvironment based on APC status in MSS/pMMR colon cancer data retrieved from TCGA
Authors: Lin Haishan , Zhen Hongchao , Shan Kun , Ma Xiaoting , Cao Bangwei
Published: August 2020

Immunotherapy is currently the most advanced anti-tumor treatment approach. The efficacy of anti-tumor immunotherapy is closely related to the tumor immune microenvironment, including immune cells, infiltration of immune factors, and expression of immune checkpoints. At present, the biomarkers for predicting the efficacy of colon cancer immunotherapy do not cover all colon cancer patients suitable for immunotherapy. In this study, TCGA database was used to identify tumor genotypes suitable for anti-tumor immunotherapy. We found that some of the MSS/pMMR populations, that were initially considered unsuitable for immunotherapy, might actually be suitable. In APC-wt/MSS colon cancer, the expression of PD-1, PD-L1, CTLA4 and CYT（GZMA and PRF1）were increased. Based on calculations done by ESTIMATE and CIBERSORT algorithms, the ImmunoScore and the proportion of CT8+ T cell infiltration is increased in these patients. Enrichment analysis was done to screen signaling pathways involved in immune response, extracellular matrix, and cell adhesion. Tumors from 42 colon cancer patients, including 22 APC-mt/MSS and 20 APC-wt/MSS, were immunohistochemically evaluated for expression of CD8 and PD-L1. And APC-wt/MSS tumors showed significantly higher expression of CD8 and PD-L1 than APC-mt/MSS tumor. Based on the results, we found that some colon cancers of APC-wt/MSS are classified by Tumor Immune Microenvironment types (TIMTs) TMIT I. So that we speculate that APC-wt/MSS colon cancer patients could benefit from anti-tumor immunotherapy.
A novel four-gene prognostic signature as a risk biomarker in cervical cancer
Authors: Wang Jun , Zheng Hua , Han Yatian , Wang Geng , Li Yanbin
Published: August 2020

Background: Cervical cancer (CC) is a major malignancy affecting women worldwide, with limited treatment options for patients with advanced disease. The aim of this study was to identify novel prognostic biomarkers for CC by a bioinformatics-based analysis using the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA)-CC cohort. Methods: RNA-Seq data from four GEO datasets (GSE5787, GSE6791, GSE26511, and GSE63514) were used to identify differentially expressed genes (DEGs) between CC and normal cervical tissues. Functional and enrichment analyses of the DEGs were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and the Database for Annotation, Visualization and Integrated Discovery (DAVID). The Oncomine database, Cytoscape software, and Kaplan–Meier survival analysis were used for in-depth screening for hub DEGs. Cox regression was then used to develop prognostic signature, which was in turn used to create a nomogram. Results: A total of 207 DEGs were identified in the tissue samples, eight of which were prognostically significant in terms of overall survival (OS). Thereafter, a novel four-gene signature consisting of DSG2, MMP1, SPP1, and MCM2 was developed and validated using stepwise Cox analysis. The area under the receiver operating characteristic (ROC) curve (AUC) values of 0.785, 0.609, and 0.686 in the training, verification, and combination groups, respectively. Moreover, the nomogram analysis showed that a combination of this four-gene signature plus lymph node metastasis (LNM) status effectively predicted the 1- and 3-year OS probabilities of CC patients with accuracies of 69.01% and 83.93%, respectively. Conclusions: We developed a four-gene signature that can accurately predict the prognosis, in terms of OS, of CC patients, and could be a valuable tool for designing treatment strategies.
Objective environmental exposures correlate differently with recreational and transportation walking: A cross-sectional national study in the Netherlands
Authors: Wang Zhiyong , Ettema Dick , Helbich Marco
Published: August 2020

Background Walking is a good and simple way to increase people’s energy expenditure, but there is limited evidence whether the neighborhood environment correlates differently with recreational and transportation walking. Aim To investigate how recreational walking and transportation walking are associated with the natural and built environmental characteristics of the living environment in the Netherlands, and examine the differences in their associations between weekdays and weekends. Method and data We extracted the total duration of daily walking (in minutes per person) for recreation and transport from the Dutch National Travel Survey 2015-2017 (N=66,880) and analyzed it as an outcome variable. Objective measures of the natural (i.e., Normalized Difference Vegetation Index (NDVI) and meteorological conditions) and built environment (i.e., crossing density, land-use mix, and residential building density) around respondents’ home addresses were determined for buffers with 300, 600, and 1,000 m radii using a geographic information system. To assess associations between recreational and transport walking and the environmental exposures separately, we fitted Tobit regression models to the walking data, adjusted for multiple confounders. Results On weekdays, people living in areas with less NDVI, higher land-use mix, higher residential building density, and higher crossing density were more likely to engage in transportation walking. While recreational walking was negatively associated with NDVI, crossing density, precipitation, and daily average temperature, it was positively associated with residential building density. At weekends, land-use mix supports both recreational and transportation walking. A negative association appeared for NDVI and transportation walking. Daily average rainfall and temperature were inversely correlated with recreational walking. Sensitivity tests indicated that some associations depend on the buffer size. Conclusions Our findings suggest that the built and natural environments have different impacts on people’s recreational and transportation walking. We also found differences in the walking–environment associations between weekdays and weekends. Place-based policies to design walking-friendly neighborhoods may have different implications for different types of walking.
A novel AXIN2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a monochorionic diamniotic twin family
Authors: Xu Jin , Yan Qing , Song Chengcheng , Liang Jingjia , Zhao Liang , Zhang Xin , Weng Zhenkun , Xu Cheng , Liu Qian , Xu Shuqin , Pang Lu , Zhang Liye , Sun Yuan , Wang Gang , Gu Aihua
Published: August 2020

Background: Craniosynostosis, the premature fusion of one or more cranial sutures, affects approximately 1 in every 2000-2500 live births. The etiology of sagittal craniosynostosis, the most prevalent form of isolated craniosynostosis, involves interplay between genetic and environmental insults, such as perinatal risk factors. However, the detailed information still remains largely unknown. Methods: The proband, a female monochorionic twin diagnosed with sagittal craniosynostosis, as well as her healthy twin sister and parents, were enrolled in our study. The obstetric medical records were retrospectively reviewed. Genetic cause was investigated by whole exome sequencing (WES) and further confirmed by Sanger sequencing.Results: We identified a novel heterozygous mutation of AXIN2 (c.1181G>A) in monochorionic twins and their father. However, only the proband presented sagittal craniosynostosis. This mutation results in the replacement of Arg at residue 394 by His (p.R394H). Arg 394 is located at the GSK3β binding domain of the AXIN2 protein, which is highly conserved across species. The obstetric medical records revealed that the proband had additional persistent breech presentation and intrauterine growth restriction, except for the perinatal risk factors shared by the twins.Conclusions: Based on the role of AXIN2 in craniosynostosis development and deleterious prediction in silico of AXIN2 (c.1181G>A: p.R394H), we speculate that this particular mutation confers susceptibility to sagittal craniosynostosis, while extra environmental insults are also involved in the pathogenesis of this case. Our findings provide a new evidence for the gene-environment interplay in understanding pathogenesis of craniosynostosis.
Relationship of Common Variants in miR-27a-3p Gene with Susceptibility and Prognosis of Oral Cancer
Authors: Wang Lili , Song Hongguang , Yang Shiming
Published: August 2020

Background: miR-27a-3p has been found dysexpressed in various cancers. The aim of the present study was to clarify the prognostic value of miR-27a-3p in patients with oral cancer.Methods: We used quantitative real-time polymerase chain reaction (qRT-PCR) assay to detect the expression of miR-27a-3p in the tissue of oral cancer and adjacent normal specimens. The association of miR-27a-3p with clinicopathological characteristics was analyzed via the Chi-square test. Kaplan-Meier survival and Cox regression analysis were performed to evaluate the prognostic value of miR-27a-3p in oral cancer patients.Results: The down-regulated expression of miR-27a-3p was found in oral cancer tissues compared with the matched noncancerous samples (P<0.05). And its expression was influenced by TNM stage (P=0.032), T stage (P=0.014) and lymph node metastasis (P=0.025). Kaplan–Meier analysis result showed that the decreased level of miR-27a-3p expression was associated with a poor overall survival of oral cancer patients. Additionally, multivariate cox regression analysis revealed that the low expression of miR-27a-3p was an independent prognostic maker in oral cancer patients (HR=0.462, 95% CI=0.223-0.957, P=0.038).Conclusions: Taken together, the expression pattern of miR-27a-3p was decreased in oral cancer tissues. The decreased expression of miR-27a-3p was a potential prognostic biomarker in patients with oral cancer.
Owning a pet is associated with changes in the composition of gut microbiota and could influence the risk of metabolic disorders in humans.
Authors: Arenas-Montes Javier , Perez-Martinez Pablo , Vals-Delgado Cristina , Romero-Cabrera Juan Luis , Cardelo Magdalena P. , Leon-Acuña Ana , Quintana-Navarro Gracia M. , Alcala-Diaz Juan F. , Lopez-Miranda Jose , Camargo Antonio , Perez-Jimenez Francisco
Published: August 2020

Background: Pet ownership positively influences clinical outcomes in cardiovascular prevention. Additionally, cardiovascular disease (CVD) have been previously linked to microbiota dysbiosis. We evaluated the influence of owning a pet and its relationship with the intestinal microbiota.Methods: We analysed the gut microbiota from 162 coronary patients from the CORDIOPREV study (NCT00924937) according to whether they owned pets (n=83) or not (n=79). The pet owner group was further divided according to whether they owned dogs only (n=28) or not (n=55). A 7-item pet-owners test score was used.Results: Patients who owned pets had less risk of metabolic syndrome (MetS) (OR=0.462) and obesity (OR=0.519) and were younger (P<0.001) than patients who did not own pets. Additionally, patients who owned dogs had less risk of MetS (OR=0.378) and obesity (OR=0.418) and were younger (P<0.001) than patients who did not own pets. A preponderance of the genera Serratia and Coprococcus was found in the group of owners, while the genera Ruminococcus, an unknown genus of Enterobacteriaceae and Anaerotruncus were preponderant in the group of non-owners. In patients who owned dogs the Methanobrevibacter and two more genera, Coprococcus and Oscillospira, were more common. Conclusions: Our study suggests that the prevalence of MetS and obesity in CVD patients is lower in pet owners, and that pet ownership could be a protective factor against MetS through the shaping of the gut microbiota. Thus, owning a pet could be considered as a protective factor against cardiometabolic diseases.
Knowledge Translation in Africa: Are The Structures in Place?
Authors: Asamani James Avoka , Nabyonga-Orem Juliet
Published: August 2020

Background: Contextualised evidence to generate local solutions on the progressive path to universal health coverage is important. However, this evidence must be translated into action. Knowledge translation (KT) experts have highlighted plausible mechanisms to foster the uptake of evidence. The objective of this study was to assess the extent to which structures are in place to foster uptake of evidence, in countries of the WHO African Region. Methods: Employing a cross sectional survey we collected data on the availability of structures to foster uptake of evidence into policy in the 35 member states of WHO African region. Data were analysed using a simple counting of the presence or absence of such structures. Results: Less than 50% of countries had evidence collation and synthesis mechanisms. The lack of such mechanisms presents a missed opportunity to identify comprehensive solutions that can respond to heath sector challenges. Close to 50% of countries had KT platforms in place. However, the availability of these was in several forms, as an institution-based platform, as an annual event to disseminate evidence and as a series of conferences at the national. In some countries, KTs were mainstreamed into routine health sector performance review processes. Several challenges impacted the functionality of the KT platforms including inadequate funding and lack of dedicated personnel. Regarding dissemination of evidence, sharing reports, scientific publications and one-off presentations in meetings were the main approaches employed. Conclusion: The availability of KT platforms in the WHO African countries can be described as suboptimal at best and non-existent at the worst. The current structures, where these exist, cannot adequately foster KT. Knowledge translation platforms need to be viewed as sector wide platforms and mainstreamed in routing health sector performance review and policy making processes. Funds for their functionality must be planned for as part of the health sector budget. Dissemination of evidence needs to be viewed differently to embrace the concept of “disseminate for impact”. Further, funding for dissemination activities needs to be planned for as part of the evidence generation plan.
Impact of Superparamagnetic Iron Oxide Nanoparticles on In Vitro and In Vivo Radiosensitisation of Cancer Cells
Authors: Russell Emily , Dunne Victoria , Russell Ben , Mohamud Hibaaq , Ghita Mihaela , McMahon Stephen , Butterworth Karl , Schettino Giuseppe , McGarry Conor , Prise Kevin
Published: August 2020

Purpose The recent implementation of MR-Linacs has highlighted theranostic opportunities of contrast agents in both imaging and radiotherapy. There is a lack of data exploring the potential of superparamagnetic iron oxide nanoparticles (SPIONs) as radiosensitisers. This study aimed to characterise the uptake and radiobiological effects of SPIONs in tumour cell models in vitro and to provide proof-of-principle application in a xenograft tumour model. Methods SPION uptake was measured using ICP-MS in 6 cancer cell lines; H460, MiaPaCa2, DU145, MCF7, U87 and HEPG2. The impact of SPIONs on radiobiological response was determined by measuring DNA damage using 53BP1 immunofluorescence and cell survival. Measured dose enhancement factors (DEFs) were with the predicted DEFs based on physical absorption estimations. In vivo efficacy was demonstrated using a subcutaneous H460 xenograft tumour model in SCID mice by following intra-tumoural injection of SPIONs. Results SPIONs significantly increased DNA damage in all cell lines with the exception of U87 cells at a dose of 1 Gy, 1 hr post-irradiation. Levels of DNA damage correlated with the cell survival, in which all cell lines except U87 cells showed an increased sensitivity (P < 0.05) in the linear quadratic curve fit for 1 hr exposure to 0.1 mM SPIONs. There was also a 30.1 % increase in the number of DNA damage foci found for HEPG2 cells at 2 Gy. No strong correlation was found between SPION uptake and DNA damage at any dose, yet the biological consequences of SPIONs on radiosensitisation were found to be much greater, with DEFs up to 1.28 ± 0.03, compared with predicted physical dose enhancement levels of 1.0001. In vivo , intra-tumoural injection of SPIONs combined with radiation showed significant tumour growth delay compared to animals treated with radiation or SPIONs alone (p < 0.05). Conclusions SPIONs showed radiosensitising effects in 5 out of 6 cancer cell lines. No correlation was found between the cell-specific uptake of SPIONs into the cells and DNA damage levels. The in vivo study found a significant decrease in the tumour growth rate.