bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian fibrosarcoma: A single-institution experience and a review of the literature
Authors: Sun Tingting , Cheng Ning-Hai , Cao Dong-Yan , Peng Peng
Published: October 2020

Ovarian fibrosarcoma is an extremely rare and malignant sex cord-stromal tumor. Due to its low incidence and poor prognosis, until now, very few cases have been reported, and most of the reported cases have been sporadic. Therefore, the treatments and prognostic factors of ovarian fibrosarcoma are still debatable. Here, we report 5 cases of ovarian fibrosarcoma that presented at Peking Union Medical College Hospital over the past 20 years. The 5 patients were 41, 51, 54, 76, and 76 years of age when initial symptoms of pelvic mass or pain appeared. On ultrasound, this disease usually manifests as unilateral pelvic masses, within which uneven echo enhancement and some blood flow signals are observed. No significant increase was observed in the levels of preoperative tumor markers, such as serum CA125 and sex hormones. The final diagnosis depends on postoperative histopathological results since these tumors are easily misdiagnosed when intraoperative frozen sections are used for examination. Pathologic examinations showed that the tumor cells were spindle-shaped with moderate to severe atypia and high mitotic counts. The immunohistochemistry profile is not specific, but the positive rate of Ki-67 was consistent with the degree of malignancy and the prognosis of patients with this tumor. In addition, the tumor may also be positive for Vimentin, α-inhibin, SMA, estrogen receptor and progesterone receptor. Significant differences were observed in the surgical methods used, and no unified chemotherapy regimen has been established. The overall survival was >15, >7, >6, <1, and <1 year for each patient. After reviewing the literature, evidence-based large-scale case studies were lacking. For treatments, complete cytoreductive surgery plus regimens typically used against malignant sex cord-stromal tumors, as described in the NCCN guidelines, are recommended. Due to its low incidence, both multicenter clinical studies and molecular studies are required to provide gynecologists with a better understanding and guidance for future management of patients with ovarian fibrosarcoma.
Identification and biochemical characterisation of Acanthamoeba castellanii cysteine protease 3
Authors: Wang Zhixin , Wu Duo , Tachibana Hiroshi , Feng Meng , Cheng Xunjia
Published: October 2020

Background: Acanthamoeba spp. are free-living amoeba that are ubiquitously distributed in the environment. This study examines pathogenic Acanthamoeba cysteine proteases (AcCPs) belonging to the cathepsin L-family and explores the mechanism of AcCP3 interaction with host cells.Methods: Six AcCP genes were amplified by polymerase chain reaction (PCR). Quantitative real-time PCR was used to analyse the relative mRNA expression of AcCPs during the encystation process, and between pre- and post-reactivated trophozoites. To further verify the role of AcCP3 in these processes, AcCP3 recombinant proteins were expressed in Escherichia coli, and the hydrolytic activity of AcCP3 was determined. The influence of the AcCP3 on the hydrolytic activity of trophozoites and the toxicity of trophozoites to human corneal epithelial cells (HCECs) was examined by inhibiting AcCP3 expression using siRNA. Further, the levels of p-Raf and p-Erk were examined in HCECs following coculture with AcCP3 gene knockdown trophozoites by western blotting.Results: During encystation, five out of six AcCPs exhibited decreased expression, and only AcCP6 was substantially up-regulated at the mRNA level, indicating that most AcCPs were not directly correlated to encystation. Further, six AcCPs exhibited increased expression level following trophozoite reactivation with HEp-2 cells, particularly AcCP3, indicating that these AcCPs might be virulent factors. After refolding of recombinant AcCP3 protein, the 27 kDa mature protein from the 34 kDa pro-protein hydrolysed host haemoglobin, collagen and albumin, and showed high activity in an acidic environment. After AcCP3 knockdown, the hydrolytic activity of trophozoite crude protein against gelatin was decreased, suggesting that these trophozoite had decreased toxicity. Compared with untreated trophozoites or negative control siRNA-treated trophozoites, AcCP3-knockdown trophozoites were less able to penetrate and damage monolayers of HCECs. Western blot analysis showed that the activation levels of the Ras/Raf/Erk/p53 signalling pathways in HCECs decreased after inhibiting the expression of trophozoite AcCP3.Conclusions: AcCP6 was correlated to encystation. Further, AcCP3 was a virulent factor in trophozoites, and participated in the activation of the Ras/Raf/Erk/p53 signalling pathways of host cells.
A Comprehensive Scheme for the Objective Upper Body Assessments of Subjects with Cerebellar Ataxia
Authors: Tran Ha , Nguyen Khoa , Pathirana Pubudu , Horne Malcolm , Power Laura , Szmulewicz David
Published: October 2020

BackgroundCerebellar Ataxia refers to the disturbance in movement resulting from cerebellar dysfunction. It manifests as inaccurate movements with delayed onset and overshoot, especially when movements are repetitive or rhythmic. Identification of ataxia is integral to the diagnosis and assessment of severity, and is important in monitoring progression and improvement. Ataxia is identified and assessed by clinicians observing subjects perform standardised movement tasks that emphasise ataxic movements. Our aim in this paper was to use data recorded from motion sensors worn while subjects performed these tasks, in order to make an objective assessment of ataxia that accurately modelled the clinical assessment.MethodsInertial measurement units and a Kinect system were used to record motion data while control and ataxic subjects performed four instrumented version of upper extremities tests, i.e. Finger Chase Test (FCT), Finger Tapping Test (FTT), Finger to Nose Test (FNT) and Dysdiadochokinesia Test (DDKT). Kinematic features were extracted from this data and correlated with clinical ratings of severity of ataxia using the Scale for the Assessment and Rating of Ataxia (SARA). These features were refined using Feed Backward feature Elimination (the best performing method of four). Using several different learning models, including Linear Discrimination, Quadratic Discrimination Analysis, Support Vector Machine and K-Nearest Neighbour these extracted features were used to accurately discriminate between ataxics and control subjects. Leave-One-Out cross validation estimated the generalised performance of the diagnostic model as well as the severity predicting regression model.ResultsThe selected model accurately (96.4%) predicted the clinical scores for ataxia and correlated well with clinical scores of the severity of ataxia (rho = 0.8, p < 0.001). The severity estimation was also considered in a 4-level scale to provide a rating that is familiar to the current clinically-used rating of upper limb impairments. The combination of FCT and FTT performed as well as all four test combined in predicting the presence and severity of ataxia.ConclusionIndividual bedside tests can be emulated using features derived from sensors worn while bedside tests of cerebellar ataxia were being performed. Each test emphasises different aspects of stability, timing, accuracy and rhythmicity of movements. Using the current models it is possible to model the clinician in identifying ataxia and assessing severity but also to identify those test which provide the optimum set of data.Trial registrationHuman Research and Ethics Committee, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia (HREC Reference Number: 11/994H/16).
Oral beta-lactam step down in bacteremic E. coli urinary tract infections
Authors: Saad Stephan , Mina Neil , Lee Colin , Afra Kevin
Published: October 2020

Background. Literature is scarce regarding oral step down to beta-lactams in bacteremic urinary tract infections. Oral fluoroquinolones are an accepted and common step down for bacteremic urinary tract infections; however, their use is associated with mounting safety concerns. We compared clinical cure in patients with E. coli bacteremic urinary tract infections who were stepped down to oral beta-lactams compared to oral fluoroquinolones.Methods. This multicentre retrospective cohort study included patients with first positive concurrent urine and blood cultures from January 2016 to December 2016. Patients were included if they received empiric intravenous beta-lactam therapy with step down to either oral beta-lactam or fluoroquinolone for treatment completion. The primary outcome was clinical cure. Secondary outcomes were length of hospitalization, all-cause mortality and C. difficile infection. Multivariate analysis and propensity score were used to control for confounding.Results. A total of 207 patients were identified with bacteremic E.coli urinary tract infections. Clinical cure was achieved in 72/77 (94%) in the oral beta-lactam group versus 127/130 (98%) in the oral fluoroquinolone group (absolute difference -4.2%, 95% confidence interval [CI] -10.3% to 1.9%, p=0.13). The adjusted odds ratio (OR) for clinical cure with oral beta-lactams was 0.31 (95% CI 0.05 – 1.90, p=0.21); propensity score adjusted analysis showed a similar result. There was no statistically significant difference in secondary outcomes.Conclusions. Oral beta-lactams appear to be a safe and effective step down option in bacteremic E. coli urinary tract infections compared to oral fluoroquinolones.
Head phantoms for bioelectromagnetic applications: a material study
Authors: Hunold Alexander , Machts René , Haueisen Jens
Published: October 2020

Background: Assessments of source reconstruction procedures in electroencephalography and computations of transcranial electrical stimulation profiles require verification and validation with the help of ground truth configurations as implemented by physical head phantoms.. For these phantoms, synthetic materials are needed, which are mechanically and electrochemically stable and possess conductivity values similar to the modeled human head tissues. Typical three-compartment head models comprise a scalp layer with a conductivity range from 0.137 S/m to 2.1 S/m, a skull layer with conductivity values between 0.066 S/m and 0.00275 S/m, and an intracranial volume with an often-used average conductivity value of 0.33 S/m. To establish a realistically shaped physical head phantom with a well-defined volume conduction configuration we here characterize the electrical conductivity of synthetic materials for modeling head compartments. We analyze agarose hydrogel, gypsum, and sodium chloride (NaCl) solution as surrogate materials for scalp, skull, and intracranial volume. We measure the impedance of all materials when immersed in NaCl solution using a four-electrode setup. The measured impedance values, temperature compensated to 25°C, were used to calculate the electrical conductivity values of each material. Further, the conductivities in the longitudinal and transversal directions of reed sticks immersed in NaCl solution were measured to test their suitability for mimicking the anisotropic conductivity of white matter tracts.Results: We obtained conductivities of 0.314 S/m, 0.30 S/m, 0.311 S/m (2 %, 3 %, 4 % agarose), 0.0425 S/m and 0.0017 S/m (gypsum with and without NaCl in the compound), and 0.332 S/m (0.17 % NaCl solution). These values are within the range of the conductivity values used for EEG and TES modeling. The reed sticks showed anisotropic conductivity with a ratio of 1:2.8. Conclusion: We conclude that the tested materials agarose, gypsum, and NaCl solution can serve as stable representations of the three main conductivity compartments of the head scalp, skull, and intracranial volume. An anisotropic conductivity structure such as a fiber track in white matter can be modeled using tailored reed sticks inside a volume conductor.
Hemopneumothorax Detection Through the Process of Artificial Evolution - A Feasibility Study
Authors: Sommer Adir , Mark Noy , Gerasi Rafi , Avraham Linn Wagnert , Fan-Marko Ruth , Eisenkraft Arik , Nachman Dean
Published: October 2020

Background : Tension pneumothorax is one of the leading causes of preventable death on the battlefield. Current prehospital diagnosis relies on a subjective clinical impression complemented by a manual thoracic and respiratory examination. These techniques are not fully applicable in field conditions and on the battlefield, where situational and environmental factors may impair clinical capabilities. We aimed to assemble a device able to sample, analyze, and classify the unique acoustic signatures of pneumothorax and hemothorax. Methods : Tested on an ex-vivo porcine model, we have assembled a device consisting of two sensitive digital stethoscopes and sampled 12 seconds of mechanical ventilation breathing sounds over the animals’ thorax. The thoracic cavity was injected with increasing volumes of 200, 400, 600, 800, and 1000 ml of air and saline to simulate pneumothorax and hemothorax, respectively. The data was analyzed using a multi-objective genetic algorithm that was used to develop an optimal mathematical detector through the process of artificial evolution, a cutting-edge approach in the artificial intelligence discipline. Results : The algorithm was able to classify the signals according to their distinctive characteristics and to accurately predict, in up to 80% of cases, the presence of pneumothorax and hemothorax, starting from 400 ml, and regardless of background noise. Conclusions : We present a potential objective and rapid diagnosis modality that can overcome independent and subjective factors that may delay diagnosis and treatment of potentially lethal thoracic injuries, with emphasis on field conditions. A future diagnostic device could be embedded with the algorithm and provide real-time detection and monitoring of pneumothorax and hemothorax.
Diversified crop rotations enhance groundwater and economic sustainability of food production
Authors: Yang Xiaolin , Steenhuis Tammo , Davis Kyle , Werf Wopke van der , Ritsema Coen , Chen Yuanquan , Pacenka Steven , Zhang Fusuo , Siddique Kadambot
Published: October 2020

Earth’s water resources are critical for supporting livelihoods and food security but are being
increasingly overexploited to support global agriculture. Diversifying cropping systems could potentially resolve unsustainable water use but trade-offs with other aspects of sustainability and food security have not yet been assessed. We perform a detailed meta-analysis to systematically compare 31 different crop rotations in China– in terms of actual evapotranspiration (ETa), effect on groundwater depth, grain yield, economic output, and water use efficiency (WUE) – and identify configurations that can achieve co-benefits across multiple dimensions. We find that a combination of lowering the cropping index (i.e., harvest frequency), incorporating fallow periods, and introducing higher value crops into the currently dominant winter wheat-summer maize double cropping system can reduce growing season ETa by as much as 31%, mitigate groundwater decline by 19% or more, and increased economic output and economic WUE by more than 11% and 3%, respectively. We also find that multiple diversified wheat-maize–based rotations– all with rotation lengths greater than two years– achieve co-benefits across all evaluated dimensions. This study provides new empirical evidence of the opportunities for diversified crop rotations to balance the multiple objectives of food production, sustainable groundwater use and farmer profitability. Extending this solution to other water-stressed agricultural regions could be an effective strategy in achieving more sustainable food production globally.
Comparison of Irinotecan and Oxaliplatin as the First-Line Therapies for Metastatic Colorectal Cancer: A Meta-analysis
Authors: Kawai Sadayuki , Takeshima Nozomi , Hayasaka Yu , Notsu Akifumi , Yamazaki Mutsumi , Kawabata Takanori , Yamazaki Kentaro , Mori Keita , Yasui Hirofumi
Published: October 2020

BackgroundIrinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC). Previous meta-analyses of randomized controlled trials (RCTs) showed that treatment with Ox-based compared with IRI-based regimens was associated with better overall survival (OS). However, these reports did not include trials of molecular targeting agents and did not take methods for the administration of concomitant drugs, such as bolus or continuous infusion of 5-fluorouracil, into account. A systematic literature review was performed to compare the efficacy and toxicity profiles between IRI- and Ox-based regimens as the first-line treatments for mCRC.MethodsThis meta-analysis used data from the Cochrane Central Register of Controlled Trials, PubMed, and SCOPUS. The primary endpoint was OS, and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).ResultsNineteen trials involving 4,571 patients were included in the analysis. No statistically significant difference was observed between the two groups in terms of OS, PFS, and ORR. There was no significant heterogeneity. Regarding ≥ grade 3 AEs, IRI-based regimens were associated with a high incidence of leukopenia, febrile neutropenia, and diarrhea. Moreover, there was a high incidence of thrombocytopenia and peripheral sensory neuropathy in patients who received Ox-based regimens. In a subgroup analysis, IRI combined with bevacizumab was correlated with a better PFS (HR = 0.90, 95% CI = 0.82–0.98, P = 0.02), but not with OS.ConclusionAlthough the safety profiles of IRI- and Ox-based regimens varied, their efficacy did not significantly differ. Therefore, both regimens could be used as the first-line treatments for mCRC with consideration of the patients’ condition or toxicity profiles.
“The Health Equity Curse”: Ethical Tensions in Promoting Health Equity
Authors: Pauly Bernie , Revai Tina , Marcellus Lenora , Martin Wanda , Easton Kathy , MacDonald Marjorie
Published: October 2020

Background: Public health (PH) practitioners have a strong moral commitment to health equity and social justice. However, PH values often do not align with health systems values, making it challenging for PH practitioners to promote health equity. In spite of a growing range of PH ethics frameworks and theories, little is known about ethical concerns related to promotion of health equity in PH practice. The purpose of this paper is to examine the ethical concerns of PH practitioners in promoting health equity in the context of mental health promotion and prevention of harms of substance use.Methods: As part of a broader program of public health systems and services research, we interviewed 32 PH practitioners. Results: Using constant comparative analysis, we identified four systemic ethical tensions: [1] biomedical versus social determinants of health agenda; [2] systems driven agendas versus situational care; [3] stigma and discrimination versus respect for persons; and [4] trust and autonomy versus surveillance and social control.Conclusions: Naming these tensions provides insights into the daily ethical challenges of PH practitioners and an opportunity to reflect on the relevance of PH frameworks. These findings highlight the value of relational ethics as a promising approach for developing ethical frameworks for PH practice.
Phospholipid Composition of APOE Lipoproteins Affects Microglia Activation in an Isoform-specific Manner
Authors: Fitz Nicholas , Nam KyongNyon , Wolfe Cody , Letronne Florent , Playso Brittany , Iordanova Bistra , Kozai Takashi , Biedrzycki Richard , Kagan Valerian , Tyurina Yulia , Han Xianlin , Lefterov Iliya , Koldamova Rada
Published: October 2020

Apolipoprotein E4 (APOE) is the strongest genetic risk factor for Alzheimer’s disease (AD). Our lipidomic analysis identified a common phospholipid signature with a high level of correlation between APOEε3/3 and APOEε4/4 AD postmortem brain samples and native lipoproteins isolated from astrocyte conditioned media of mice expressing human APOE3 or APOE4. Behavioral testing demonstrated that native E3 lipoproteins were more effective than E4 at ameliorating the harmful effects of Aβ on cognition. We posit that APOE isoform-specific differences in the phospholipid composition of native lipoproteins prompt a differential microglial response. Using time-lapse in vivo two-photon imaging we compared the effect of E3 or E4 infused with Aβ and determined that E3 lipoproteins induced a faster microglial migration towards Aβ. To determine how E3 and E4 lipoproteins affect microglial transcriptome in response to Aβ we performed bulk and single cell RNA-seq of WT and Trem2ko mice. We show that compared to E4, cortical infusion of E3 lipoproteins upregulated a higher proportion of genes associated with an activated immune response accompanied by a downregulation of homeostatic genes. scRNA-seq identified microglia-specific clusters affected by Trem2 deficiency suggesting that lack of Trem2 impairs the transition of microglia from homeostatic to an activated state. Compared to E3, E4-expressing microglia showed a reduced Aβ uptake that was additionally aggravated by Trem2 deficiency. Together, our findings have elucidated unique phenotypic and transcriptional differences in the microglial response to Aβ in the presence of E3 or E4 lipoproteins which could impact AD pathogenesis.
Evaporating Potential
Authors: Fang Sunmiao , Li Jidong , Xu Yin , Shen Chun , Guo Wanlin
Published: October 2020

Evaporation induced electric potential in functional materials has been promoting the emergence of a new discipline, hydrovoltaics1,2, but the phenomena have been widely ascribed to streaming potential related classic electrokinetic effects3,4. Here we show that evaporation in ambient environment can directly generate a sustainable voltage of up to 1 V with a current density of around 20 nA cm-2 from a porous carbon black film without contribution from streaming potential. Multi-electrode measurements confirm that the evaporating potential is generated mainly within the precursor ahead of the main capillary front. Detailed theoretical and experimental analyses indicate that the evaporating potential following the quadratic distribution arises from molecule evaporation induced carrier transfer in the precursor film. This new finding should lay a solid foundation for the emerging hydrovoltaics.
Longevity factor klotho and resistance to cognitive deficits in a transgenic mouse model and in individuals with Parkinson’s disease
Authors: Moreno Arturo , Luthra Nijee , Bonham Luke , Lin Jonathan , Broestl Lauren , Betourne Alexandre , Sehgal Rohan , Wang Dan , Lesne Sylvain , Ostrem Jill , Yokoyama Jennifer , Dubal Dena
Published: October 2020

Aging is the primary risk factor for Parkinson’s disease (PD) and cognitive impairment from PD is a major and unmet biomedical challenge. Klotho, a pleiotropic protein, extends lifespan and enhances cognition. Whether longevity factors such as klotho can counteract PD-related mortality and deficits in mice or associate with resistance to PD in humans is unknown. Here we show that transgenic elevation of klotho increased lifespan, improved synaptic and cognitive, but not motor, functions in mice, and decreased steady state α-synuclein levels in the brains of mice that express wildtype human α-synuclein. In humans, a genetic variant of KLOTHO that increases circulating klotho levels associated with better executive cognition and less CSF abnormalities of α-synuclein in individuals with PD. Thus, klotho can counteract cognitive deficits related to PD, possibly modulating α-synuclein levels – and these findings may be relevant to new therapeutic pathways for human PD.
Study on the Mechanism of Tiaogan Yunpi Decoction in Treating Diarrhea-Irritable Bowel Syndrome Based on Network Pharmacology
Authors: Yan Jing , Ge Fei , Miao Zhi-wei , Liu Li-na , Lu Jun , Liu Feng , Shang Wen-bin , Zhao Juan , Yu Xi-zhong , Sun Zhi-guang , Ning Li-qin , Lu Dong-xue
Published: October 2020

Tiaogan Yunpi Decoction (TGYPD) is a clinical experience commonly used by tutors to treat diarrhea-irritable bowel syndrome (D-IBS); it has been commonly employed to treat ulcerative colitis and chemotherapy-induced intestinal mucositis. However, the mechanism of TGYPD in D-IBS treatment remains unclear. In the present study, the potential mechanism of TGYPD for irritable bowel syndrome was tested by network pharmacology combined with the IBS rat model. On the whole, 56 active ingredients were screened out, and 238 assessed targets were identified; 1934 known disease targets regarding the occurrence and development of irritable bowel syndrome were successfully searched from the disease database. GO biological processes primarily impact cytokine receptor binding, transcription factor activity, cytokine activity, antioxidant activity, biosynthesis regulation, cell cycle regulation and other cellular active sites of irritable bowel syndrome. Besides, the mentioned processes are involved in AGE- RAGE signaling pathway, TNF and IL-17 signaling pathway, Toll-like receptor (TLRs) signaling pathway, multiple cancer signaling pathways, and viral key signaling pathways of infection, hepatitis and endocrine resistance. As reported by the protein interaction network (PPI), IL-6, CXCL8, VEGFR, JUN, MAPK3 and AKT1 are likely to act as the critical targets for TGYPD to treat IBS. Moreover, in the model of IBS-D rats, TGYPD is capable of significantly reducing stool Bristol type and AWR scores, as well as effectively decreasing TNF-αand IFN-γ. As revealed from colon pathological section, TGYPD can relieve intestinal damage and mitigate intestinal mucosal immune inflammation. As suggested from the results of the Western blotting assay, TGYPD is capable of suppressing the expression of TLR4-MYD88-NF-kB signaling pathway in intestines. In brief, the results achieved in this study suggest that TGYPD can significantly mitigate immune inflammation and protect against intestinal mucosal barrier in the intestines of the IBS-D rat model. This study provides novel insights that can be referenced by other TCM studies.
The Effect of 0.01% Atropine Eye Drops Combined with Auricular Acupoint Stimulation on Myopia Progression and Choroidal Thickness: The Preliminary Results from a Randomized Controlled Trial
Authors: Kong Xie-He , Zhao Yue , Chen Zhi , Zeng Li , Han Rong , Dong Xiao-Qing , Guo Xiao-Cong , Shi Zheng , Yang Guang , Yang Yan-Ting , Zhang Dan , Zhou Xing-Tao , Ma Xiao-Peng
Published: October 2020

Background: Use of 0.01% atropine eye drops (0.01%A) is one of the most common treatments for myopia control for children in Asia. Auricular acupoint stimulation (AAS) was reported to enhance the effect of higher-concentration atropine (0.25%, 0.125%) on myopia control. This study was designed to compare the effect of 0.01%A combined with AAS and 0.01%A alone on myopia progression and choroidal thickness in children.Methods: A total of 104 children were stratified by age and randomly assigned at 1:1 to receive 0.01%A or 0.01%A+AAS treatment for 6 months. Repeated measurements of cycloplegic spherical equivalent (SE) autorefraction, axial length (AL), and choroidal thickness were performed at baseline, 1 month, 3 months and 6 months.Results: The adjusted mean SE change over the 6 months was −0.38 ± 0.04 D in the 0.01%A group (n = 50) and −0.25 ± 0.04 D in the 0.01%A+AAS group (n = 50), demonstrating a significant between-group difference (P = 0.02). There was no statistically significant difference in the change of AL or choroidal thickness between the two groups (both P > 0.05).Conclusion: Compared with 0.01%A monotherapy, AAS as adjunctive treatment slowed myopic progression in Chinese children by a small, statistically amount during this 6-month observation. Future follow-up study is needed to verify its effects on axial elongation or choroidal thickness.Trial registration: Trial registration: Chinese Clinical Trial Registry, ChiCTR1900021316. Registered 13 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35435
Exploration of the Potential Mechanisms of Lingqihuangban Granule for Treating Diabetic Retinopathy Based on Network Pharmacology
Authors: He Shuai , Gu Chufeng , Su Tong , Zhou Chuandi , Lhamo Thashi , Draga Deji , Yin Lili , Qiu Qinghua
Published: October 2020

Background: The Lingqihuangban Granule (LQHBG), a remarkable Chinese herbal compound, has been used for decades to treat diabetic retinopathy (DR) in Department of Ophthalmology, Shanghai General Hospital (National Clinical Research Center for Eye Diseases) with obvious effects. Through the method of network pharmacology, the present study constructed bioactive component-relative targets and protein-protein interaction network of the LQHBG and implemented gene function analysis and pathway enrichment of targets, discussing the mechanisms of traditional Chinese medicine LQHBG in treating DR. Materials and methods: The bioactive ingredients of LQHBG were screened and obtained using TCMSP and ETCM databases, while the potential targets of bioactive ingredients were predicted by SwissTargetPrediction and ETCM databases. Compared with the disease target databases of TTD, Drugbank, OMIM and DisGeNET, the therapeutic targets of LQHBG for DR were extracted. Based on DAVID platform, GO annotation and KEGG pathway analyses of key targets were explored, combined with the screening of core pathways on Omicshare database and pathway annotation on Reactome database. Results: A total of 357 bioactive components were screened from LQHBG, involving 86 possible targets of LQHBG treating DR. In PPI network, INS and ALB were identified as key genes. The effective targets were enriched in multiple signaling pathways, such as PI3K/Akt and MAPK pathways. Conclusion: This study revealed the possible targets and pathways of LQHBG treating DR, reflecting the characteristics of multicomponent, multitarget and multipathway treatment of a Chinese herbal compound, and provided new ideas for further discussion.
Value of serum sTREM-1,D-lactate and I-FABP in diagnosis and prognosis evaluation in liver cirrhotic patients with sepsis
Authors: Yang Danhong , Zhang Qiang , Wang Weiping , Huang Yicheng , Pan Hongying , Wu Miaomiao
Published: October 2020

BackgroundSepsis is can cause serious negative effects among patients with cirrhosis.Finding reliable biomarker in early diagnose and prognosis in septic patients with liver cirrhosis is very important.We assessed value of serumsoluble triggering receptor expressed on myeloid cells-1 ( sTREM-1),D-lactate and Intestinal fatty acid binding protein(I-FABP) in diagnosis and prognosis evaluation in liver cirrhotic patients with sepsis.MethodsA prospective observational study of 158 cirrhosis patients was conducted. A total of 158cirrhosis patients were enrolled, 83 of whom were diagnosed with sepsis and 75 patients without sepsis during hospitalization.We evaluated value of early diagnostic and prognosis of cells-1(sTREM-1),D-lactate and I-FABP in cirrhotic patients with sepsis.Receiver operating characteristic curves (ROCs) were used to assess the ability of tested biomarkers to diagnose and prognosis cirrhotic patients with sepsis.ResultsOur results showed the CRP，PCT，sTREM-1, D-lactate and I-FABP were significantly higher in the sepsis group than in the no-sepsis group.,but only levels of serum sTREM-1 showed increasing trend with the severity of the cirrhotic patients with sepsis. The cutoff value of sTREM-1was 123.62 pg/mL and showed 84.3% sensitivity and 92.0% specificity and high accuracy in the early diagnosis for cirrhotic patients with sepsis.The AUC of sTREM-1 was 0.959(95%CI: 0.934–0. 985) and higher than that of CRP,PCT,D-lactate and I-FABP( P <0.001, P =0.002, P <0.001, P <0.001 respectively).Total 31(37.35%) cirrhotic patients with sepsis cases died during 90-day follow-up.Only sTREM-1 level had significance between survivors and non-survivors(263.99±213.79 vs 672.24±191.44,P=0.031).The AUCs of sTREM-1 for predicting 90-day mortality was 0.904( 95% CI:0.836-.971 ) and higher than that of CRP,PCT,D-lactate (P=0.001,p=0.003, P <0.001 respectively) The AUCs of I-FABP is only 0.482 and had no value of predicting prognosis.ConclusionSerum sTREM-1 is a valuable new biomarker for early diagnosis and prognosis in cirrhosis with sepsis, proving more accurate than CRP,PCT, D - lactate and I - FABP.Serum D-lactate and I-FABP levels can identify early cirrhosis with sepsis, but they is little relationship with the prognosis of patients.
A Network-Based Model to Explore the Role of Testing in Epidemic Control
Authors: Cui Yapeng , Ni Shunjiang , Shen Shifei
Published: October 2020

Background: Testing is one of the most effective means to deal with epidemics. However, there is an upper bound on daily testing volume due to the limited healthcare staff and working hours, and different testing methods may also be adopted such as random testing and contact-tracking testing. Methods: In this paper, a network-based epidemic transmission model combined with testing mechanism is proposed to study the role of testing in epidemic control. We simulate the epidemic spread process on complex networks and introduce testing preference to describe different testing strategies. Results: Through a series of numerical simulations, we find that testing can flatten the infection curve and delay the outbreak of epidemics. In addition, the higher the priority for testing individuals in close contacts with confirmed cases, the smaller the infection scale. Compared with the increase speed of daily testing volume, the upper bound of daily testing volume plays a more important role in epidemic control. We also discover that when testing combined with other measures is adopted, the daily testing volume required to control epidemics (i.e., control infection scale below 5%) will be reduced by more than 40% even if other measures only reduce individuals’ infection probability by 10%. Conclusions: In short, although testing can effectively inhibit the spread of infectious diseases, it requires a huge amount of daily testing volume. It is highly recommended that testing be adopted combined with other measures such as wearing masks and social distancing to deal with infectious diseases. Our research contributes to understanding the role of testing in epidemic control and provides useful suggestions for the government and individuals in response to epidemics.
Scale-up and Sustainability of a Personalized End-of-Life Care Intervention: A Longitudinal Mixed-Methods Study
Authors: Takaoka Alyson , Tam Benjamin , Vanstone Meredith , Clarke France J. , Hoad Neala , Swinton Marilyn , Toledo Feli , Boyle Anne , Woods Anne , Duan Erick H. , Heels-Ansdell Diane , Waugh Lily , Soth Mark , Rudkowski Jill , Alhazzani Waleed , Perri Dan , Ligori Tania , Jaeschke Roman , Zytaruk Nicole , Cook Deborah J.
Published: October 2020

Background: Scaling-up and sustaining healthcare interventions can be challenging. Our objective was to describe how the 3 Wishes Project (3WP), a personalized end-of-life intervention, was scaled-up and sustained in an intensive care unit (ICU).Methods: In a longitudinal mixed-methods study from January 1,2013 - December 31, 2018, dying patients and families were invited to participate if the probability of patient death was >95% or after a decision to withdraw life support. A research team member or bedside clinician learned more about each of the patients and their family, then elicited and implemented <3 personalized wishes for patients and/or family members. We used a qualitative descriptive approach to analyze interviews and focus groups conducted with 25 clinicians who cared for patients enrolled in the project. We used descriptive statistics to summarize patient, wish, and clinician characteristics, and analyzed outcome data in quarters using Statistical Process Control charts. The primary outcome was enrollment of terminally ill patients and respective families; the secondary outcome was the number of wishes per patient; tertiary outcomes included wish features and stakeholder involvement. Results: Both qualitative and quantitative analyses suggested a three-phase approach to the scale-up of this intervention during which 369 dying patients were enrolled, having 2039 terminal wishes implemented. From a research project to clinical program to an approach to practice, we documented a three-fold increase in enrolment with a five-fold increase in total wishes implemented, without a change in cost. Beginning as a study, the protocol provided structure; starting gradually enabled frontline staff to experience and recognize the value of acts of compassion for patients, families, and clinicians. The transition to a clinical program was marked by handover from the research staff to bedside staff, whereby project catalysts mentored project champions to create staff partnerships, and family engagement became more intentional. The final transition involved empowering staff to integrate the program as an approach to care, expanding it within and beyond the organization. Conclusions: The 3WP is an end-of-life intervention which was implemented as a study, scaled-up into a clinical program, and sustained by becoming integrated into practice as an approach to care.
Deletion of the transcriptional regulator GntR affects apoptosis and autophagy in Brucella abortus-infected RAW 264.7 cells
Authors: Li Zhiqiang , Wei Shujuan , Wang Shuli , Xi Li , Cui Yanyan , Zhang Jinliang , Hao Junfang , Zhang Huan , Zhang Hui
Published: October 2020

Background: Brucellosis is an important zoonotic disease caused by the pathogen Brucella. Regulating apoptosis and autophagy is the prerequisite for the intracellular survival of Brucella. GntR is an important transcriptional regulator of Brucella that can regulate the expression of many target genes, and then play a regulatory role in many cell processes, including regulation apoptosis and autophagy. Therefore, understanding the relationship between GntR and apoptosis and autophagy is crucial to comprehending the pathogenic mechanism of Brucella. Methods: In the present study, we described the influence of GntR on apoptosis and autophagy after the infection of RAW 264.7 cells with Brucella. We constructed the GntR mutant strain (2308ΔGntR) of Brucella abortus 2308 (S2308). Following the infection of the RAW 264.7 cells with S2308 and 2308ΔGntR, apoptosis and autophagy were detected. Results: Western blot analysis and flow cytometry analysis indicated that the apoptosis rate of the 2308ΔGntR-infected group was remarkably higher than that of the S2308-infected group. Confocal laser microscopy experiments indicated the presence of the P62 protein as punctate aggregates in the 2308ΔGntR group. Conclusion: These results showed that 2308ΔGntR promoted apoptosis and inhibited autophagy in the RAW 264.7 cells during Brucella infection.
Effects of Short Chain Fatty Acids (SCFAs) Modulation on Potentially Diarrhea Causing Pathogens in Yaks Through Metagenomics Sequencing
Authors: Li Kun , Zeng Zhibo , Liu Juanjuan , Pei Lulu , Wang Yaping , Li Aoyun , Kulyar Muhammad Fakhar-e-Alam , Shahzad Muhammad , Qi Desheng , LI JIAKUI
Published: October 2020

Yaks are of great importance on the plateau; however, an emerging endemic diarrheal disease during the last few years is posing a great threat to the health of these animals. Yaks have special gut microbiotal community and short-chain fatty acids (SCFAs) which are not only the principle nutrient substrates of intestinal epithelial cells but can also regulate the epithelial barrier. Until now, metagenomics sequencing has not been reported in diarrheal yaks. A scarce information is available regarding the levels of fecal SCFAs and diarrhea in yaks. The purpose of our study was to identify the potential pathogens that cause the emerging diarrhea and also to explore the potential relationship of short-chain fatty acids in this issue. We estimated diarrhea rate in yaks after collecting the equal number of fecal samples from affected animals. Metagenomics sequencing and quantitative analysis of SCFAs were performed which revealed 15-25% and 5-10% prevalence in diarrheal yak’s calves and adults yaks respectively. Significant difference was observed in GC contents (44.69%~46.08% vs 46.12%~46.38%) under two reference groups (p<0.05). Violin box plot also showed the higher degree of dispersion in gene abundance distribution of diarrhea yaks, while genes of normal yaks were relatively gathered. We found 366163 significant differential abundance genes in diarrheal yaks, with 141305 up-regulated and 224858 down-regulated genes as compared with normal yaks via DESeq analysis. Metagenomic binning analysis indicated the higher significant of bin 33 (Bacteroidales) (p<0.05) in diarrheal animals, while bin 10 (p<0.0001), bin 30 (Clostridiales) (p<0.05), bin 51 (Lactobacillales) (p<0.05), bin 8 (Lachnospiraceae) (p<0.05) and bin 47 (Bacteria) (p<0.05) were obviously higher in normal animals. At different levels, an obviously difference in Phylum, Class, Oder, Family, Genus and Species was noticed as 4, 8, 8, 16, 17 and 30 respectively. Compared with healthy yaks, Acetic acid (p<0.01), Propionic acid (p<0.01), Butyric acid (p<0.01), Isobutyric acid, Isovaleric acid (p<0.05) and Caproic acid (p<0.01) were all observed obviously at lower rate in diarrheal yaks. In conclusion, besides the increased pathogens level of Staphylococcus aureus, Babesia ovata, Anaplasma phagocytophilum, Bacteroides fluxus, viruses, Klebsiella pneumonia, and inflammation-related bacteria; the decreased of SCFAs caused by the imbalance of intestinal microbiota may potentially leads to emergence of diarrhea in yaks.
Lower Normal Thyroid Function is Associated With a Higher Risk of Metabolic Syndrome: A Retrospective Cohort on Chinese Population
Authors: Ding Xi , Zhu Chunying , Li Rui , Wu Liping , Wang Yue , Hu Shiqian , Zhao Fengyi , Zhao Yang , Zhang Meng , He Mingqian , Chen Ziyi , Shi Bingyin
Published: October 2020

BackgroundRecently, the relationship between thyroid hormones (THs) across the euthyroid ranges and metabolic syndrome (MetS) has been widely discussed. This study aimed to present specific cutoff values of THs to assess the association between THs and MetS in a euthyroid cohort.MethodsData of 2694 subjects, aged 18-80 years, who attended health examination in Xi’an Electric Power Central Hospital from April 2011 to December 2015 were collected and analyzed. The basic cohort enrolled 929 participants (followed up by 2221 person-years totally) to assess correlations between serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4) levels and MetS. The second cohort included 698 participants (followed up by 1709 person-years totally) to evaluate relationships between serum free triiodothyronine (FT3), free thyroxine (FT4) levels and MetS. MetS was defined according to the criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) scientific statements of 2009. Euthyroidism was defined as serum TSH, FT3 and FT4 levels within the reference ranges without taking any thyroid medication.ResultsThe cutoff values for TSH, T3, T4, FT3 and FT4 were 2.0mIU/L, 1.9nmol/L, 117nmol/L, 4.3pmol/L and 16pmol/L, respectively. Participants were categorized into two groups according to cutoff values: the lower-THs group and the higher-THs group. There was no significant difference in the risk of MetS between two groups in TSH, T3, T4 and FT3. The incidence of MetS was significantly higher in lower-FT4 group than higher-FT4 group (1.00 vs 0.622 (0.458, 0.846), P=0.002). The lower-FT4/higher-TSH group had the highest hazard ratios of MetS. (2.131vs 1.0 (1.380,3.291), P=0.006)ConclusionsLower normal FT4 (FT4≤16.0 pmol/L) is an independent risk factor for MetS, and lower normal thyroid function (TSH>2.0 mIU/L and FT4≤16.0 pmol/L) is associated with a higher risk of developing MetS.
Engineered Whole Cut Meats Assembled of Cell Fibers Constructed by Tendon-Gel Integrated Bioprinting
Authors: Kang Dong-Hee , Louis Fiona , Liu Hao , Shimoda Hiroshi , Nishiyama Yasutaka , Nozawa Hajime , Kakitani Makoto , Takagi Daisuke , Kasa Daijiro , Nagamori Eiji , Irie Shinji , Kitano Shiro , Matsusaki Michiya
Published: October 2020

With the current interest in artificial meat, mammalian cell-based cultured meat has mostly been in minced form. There is thus still a high demand for artificial steak-like meat. Herein, we demonstrate in vitro construction of engineered steak-like meat assembled of three types of edible bovine cell fibers, such as skeletal muscle, adipose, and blood capillary fabricated by tendon-gel integrated printing (TIP) technology. Because actual meat is an anisotropically aligned assembly of the fibers connected to tendon for the actions of contraction and relaxation, TIP was discovered to construct the fiber assembly connecting tendon gels with engineered structures. In this study, a total of 72 fibers comprising 42 muscle, 28 adipose, and 2 blood capillary were constructed by TIP and subsequently assembled to fabricate a steak-like meat with a diameter of 5 mm and a length of 10 mm by consulting histological images of actual Wagyu beef steak. The TIP discovered here could be a powerful manufacturing technology for fabrication of the desired types of steak-like cultured meats.
Neural Response to Trauma-Related and Trauma-Unrelated Negative Stimuli in Remitted and Persistent Pediatric Posttraumatic Stress Disorder
Authors: Wang Peng , Peng Zulai , Liu Lu , An Li , Liu Yuxin , Cao Qingjiu , Sun Li , Ji Ning , Chen Yun , Yang Binrang , Wang Yufeng
Published: October 2020

Background: Most youths who suffer from posttraumatic stress disorder (PTSD) lose their diagnosis in the first 1-2 years. However, there are few studies on this brain mechanism, and the heterogeneity of the findings is partially due to the different stimuli applied and the mixed trauma history. Therefore, the use of trauma-related/unrelated stimuli to study the remittance mechanism of earthquake-induced PTSD could advance our knowledge of PTSD and inspire future treatment.Methods: Thirteen youths with PTSD, 18 remitted participants and 18 control participants underwent functional magnetic resonance imaging (fMRI) while viewing trauma-related pictures, trauma-unrelated negative pictures and scrambled pictures.Results: Under trauma-unrelated condition, the neural activity of the left hippocampus in the remitted group was in the middle between the two other groups. Under trauma-related condition, the PTSD and the remitted group exhibited higher neural activity in the right middle occipital gyrus than controls. The remitted group showed higher neural activity in the right parahippocampal gyrus and right lingual gyrus under trauma-related condition than trauma-unrelated condition, while no significant difference was found in PTSD group.Conclusion: PTSD symptom-related group difference is mainly reflected in the left hippocampus under the trauma-unrelated condition, while the hyperactivity in the right middle occipital gyrus under trauma related condition could be an endophenotype for PTSD.