bluuebunny/crossref_metadata_2025 huggingface dataset:
HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles
Authors: Sironval Violaine , Palmai-Pallag Mihaly , Vanbever Rita , Huaux François , Mejia Jorge , Lucas Stéphane , Lison Dominique , van den Brule Sybille
Published: September 2019

Background

Li-ion batteries (LIB) are increasingly used worldwide. They are made of low solubility micrometric particles, implying a potential for inhalation toxicity in occupational settings and possibly for consumers. LiCoO2(LCO), one of the most used cathode material, induces inflammatory and fibrotic lung responses in mice. LCO also stabilizes hypoxia-inducible factor (HIF) -1α, a factor implicated in inflammation, fibrosis and carcinogenicity. Here, we investigated the role of cobalt, nickel and HIF-1α as determinants of toxicity, and evaluated their predictive value for the lung toxicity of LIB particles in in vitro assays.

Results

By testing a set of 5 selected LIB particles (LCO, LiNiMnCoO2, LiNiCoAlO2) with different cobalt and nickel contents, we found a positive correlation between their in vivo lung inflammatory activity, and (i) Co and Ni particle content and their bioaccessibility and (ii) the stabilization of HIF-1α in the lung. Inhibition of HIF-1α with chetomin or PX-478 blunted the lung inflammatory response to LCO in mice. In IL-1β deficient mice, HIF-1α was the upstream signal of the inflammatory lung response to LCO. In vitro, the level of HIF-1α stabilization induced by LIB particles in BEAS-2B cells correlated with the intensity of lung inflammation induced by the same particles in vivo.

Conclusions

We conclude that HIF-1α, stabilized in lung cells by released Co and Ni ions, is a mechanism-based biomarker of lung inflammatory responses induced by LIB particles containing Co/Ni. Documenting the Co/Ni content of LIB particles, their bioaccessibility and their capacity to stabilize HIF-1α in vitro can be used to predict the lung inflammatory potential of LIB particles.
Preoperative serum C-reactive protein levels and postoperative survival in patients with esophageal squamous cell carcinoma: a propensity score matching analysis
Authors: Huang Wei , Wu Leilei , Liu Xuan , Long Hao , Rong Tiehua , Ma Guowei
Published: September 2019

Objectives

This study tested the relationship between preoperative serum C-reactive protein (CRP) levels and cancer-specific prognosis in patients with esophageal squamous cell carcinoma who have undergone curative resection.

Methods

We conducted a retrospective study on 961 patients with esophageal squamous cell cancer who underwent curative esophagectomy from 2006 to 2012 at the Sun Yat-sen University Cancer Center. Preoperative serum CRP levels were determined, and a cutoff value of 5.0 mg/mL was established. Propensity score matching (PSM) was performed to reduce the selection bias between patients with low CRP (≤ 5.0 mg/mL) and those with high CRP (> 5.0 mg/mL) levels based on age, tumor-lymph node-metastasis (TNM) stage, and tumor grade. The prognostic value of preoperative CRP levels was determined using life table, Kaplan–Meier, and Cox proportional hazards analyzes.

Results

In the unmatched cohort, the 3-year and 5-year survival rates were 57 and 53%, respectively, in patients with high preoperative CRP levels (> 5.0 mg/mL) and 68 and 56%, respectively, in those with low preoperative CRP levels (≤ 5.0 mg/mL). The difference in the survival rates of the 2 groups was significant (p = 0.004). Univariate survival analysis revealed that the preoperative CRP levels, TNM stage, tumor grade, drinking history, and anastomosis method were prognostic factors for overall survival (OS). Before conducting PSM, the low-CRP group had a lower age (p = 0.001), lower histological grade (p = 0.086), and lower TNM stage (p = 0.254).

After PSM, 176 patients with low CRP levels and 176 of those with high CRP levels were enrolled in the analysis. In the matched cohort, the 3-year and 5-year survival rates were 56 and 50%, respectively, in patients with high preoperative CRP levels (> 5.0 mg/mL) and 68 and 56%, respectively, in those with low preoperative CRP levels (≤ 5.0 mg/mL). The difference in the survival rates between the low- and high-CRP groups was significant (p = 0.044). Multivariate analysis of the matched patients revealed that the TNM stage and preoperative CRP level were independent prognostic factors for OS.

Conclusions

A high preoperative CRP level (> 5.0 mg/mL) predicts worse survival prognosis in patients who have undergone curative resection for esophageal squamous cell cancer.
Recent drug approvals for acute myeloid leukemia
Authors: Lai Catherine , Doucette Kimberley , Norsworthy Kelly
Published: September 2019

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, with an incidence that increases with age, and a generally poor prognosis. The disease is clinically and genetically heterogeneous, and recent advances have improved our understanding of the cytogenetic abnormalities and molecular mutations, aiding in prognostication and risk stratification. Until recently, however, therapeutic options were mostly limited to cytotoxic chemotherapy. Since 2017, there has been an explosion of newly approved treatment options both nationally and internationally, with the majority of new drugs targeting specific gene mutations and/or pivotal cell survival pathways. In this review article, we will discuss these new agents approved for the treatment of AML within the last 2 years, and will outline the mechanistic features and clinical trials that led to their approvals.
Myocardial ischemia during ventilator weaning: a prospective multicenter cohort study
Authors: Bedet Alexandre , Tomberli Françoise , Prat Gwenael , Bailly Pierre , Kouatchet Achille , Mortaza Sater , Vivier Emmanuel , Rosselli Sylvene , Lipskaia Larissa , Carteaux Guillaume , Razazi Keyvan , Mekontso Dessap Armand
Published: September 2019

Background

Weaning-induced cardiac pulmonary edema (WiPO) is one of the main mechanisms of weaning failure during mechanical ventilation. We hypothesized that weaning-induced cardiac ischemia (WiCI) may contribute to weaning failure from cardiac origin.

Methods

A prospective cohort study of patients mechanically ventilated for at least 24 h who failed a first spontaneous breathing trial (SBT) was conducted in four intensive care units. Patients were explored during a second SBT using multiple tools (echocardiography, continuous 12-lead ST monitoring, biomarkers) to scrutinize the mechanisms of weaning failure. WiPO definition was based on three criteria (echocardiographic signs of increased left atrial pressure, increase in B-type natriuretic peptides, or increase in protein concentration during SBT) according to a conservative definition (at least two criteria) and a liberal definition (at least one criterion). WiCI was diagnosed according to the third universal definition of myocardial infarction proposed by the European Society of Cardiology (ESC) and the American Heart Association (AHA) statement for exercise testing.

Results

Among patients who failed a first SBT, WiPO occurred in 124/208 (59.6%) and 44/208 (21.2%) patients, according to the liberal and conservative definition, respectively. Among patients with ST monitoring, WiCI was diagnosed in 36/177 (20.3%) and 12/177 (6.8%) of them, according to the ESC and AHA definitions, respectively. WiCI was not associated with WiPO and was not associated with weaning outcomes. Only two patients of the cohort were treated for an acute coronary syndrome after the second SBT, and seven other patients required coronary angiography during the weaning period.

Conclusions

This observational study showed the common occurrence of pulmonary edema in mechanically ventilated patients who failed a first SBT, but the association with cardiac ischemia and weaning outcomes was weak.
Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols
Authors: Park Jay J. H , Siden Ellie , Zoratti Michael J. , Dron Louis , Harari Ofir , Singer Joel , Lester Richard T. , Thorlund Kristian , Mills Edward J.
Published: September 2019

Background

Master protocols, classified as basket trials, umbrella trials, and platform trials, are novel designs that investigate multiple hypotheses through concurrent sub-studies (e.g., multiple treatments or populations or that allow adding/removing arms during the trial), offering enhanced efficiency and a more ethical approach to trial evaluation. Despite the many advantages of these designs, they are infrequently used.

Methods

We conducted a landscape analysis of master protocols using a systematic literature search to determine what trials have been conducted and proposed for an overall goal of improving the literacy in this emerging concept. On July 8, 2019, English-language studies were identified from MEDLINE, EMBASE, and CENTRAL databases and hand searches of published reviews and registries.

Results

We identified 83 master protocols (49 basket, 18 umbrella, and 16 platform trials). The number of master protocols has increased rapidly over the last five years. Most have been conducted in the US (n = 44/83) and investigated experimental drugs (n = 82/83) in the field of oncology (n = 76/83). The majority of basket trials were exploratory (i.e., phase I/II; n = 47/49) and not randomized (n = 44/49), and more than half (n = 28/48) investigated only a single intervention. The median sample size of basket trials was 205 participants (interquartile range, Q3-Q1 [IQR]: 500–90 = 410), and the median study duration was 22.3 (IQR: 74.1–42.9 = 31.1) months. Similar to basket trials, most umbrella trials were exploratory (n = 16/18), but the use of randomization was more common (n = 8/18). The median sample size of umbrella trials was 346 participants (IQR: 565–252 = 313), and the median study duration was 60.9 (IQR: 81.3–46.9 = 34.4) months. The median number of interventions investigated in umbrella trials was 5 (IQR: 6–4 = 2). The majority of platform trials were randomized (n = 15/16), and phase III investigation (n = 7/15; one did not report information on phase) was more common in platform trials with four of them using seamless II/III design. The median sample size was 892 (IQR: 1835–255 = 1580), and the median study duration was 58.9 (IQR: 101.3–36.9 = 64.4) months.

Conclusions

We anticipate that the number of master protocols will continue to increase at a rapid pace over the upcoming decades. More efforts to improve awareness and training are needed to apply these innovative trial design methods to fields outside of oncology.
Fluorescence optical imaging for treatment monitoring in patients with early and active rheumatoid arthritis in a 1-year follow-up period
Authors: Glimm Anne-Marie , Sprenger Lisa Ines , Haugen Ida Kristin , Mansmann Ulrich , Hermann Sandra , Häupl Thomas , Hoff Paula , Burmester Gerd-Rüdiger , Backhaus Marina , Le Lien , Ohrndorf Sarah
Published: September 2019

Background

Fluorescence optical imaging (FOI) enables visualization of inflammation in the hands in rheumatic joint diseases with currently a lack of long-term follow-up studies.

Objective

To investigate FOI for treatment monitoring in a homogenous cohort of patients with early (disease duration < 2 years) and active (DAS28 > 3.2) RA over a period of 12 months.

Methods

Thirty-five RA patients (24 (68.6%) females, mean age 53.3 years (SD 13.6)) were investigated clinically by DAS28, tender joint count (TJC) and swollen joint count (SJC) and by FOI in phases 1–3 and PrimaVistaMode (PVM) before therapy change and after 12 months. The FOI activity score (FOIAS) was calculated based on individual joint scores from 0 to 3 in 30 joints per patient, adding up to a sum score (0–90).

Results

We found a statistically significant reduction of FOIAS in phase 1 from baseline (median 5.0, IQR 24.96) to follow-up (median 1.0, IQR 4.0) in all patients (p = 0.0045), both in responders and non-responders according to EULAR response criteria by DAS28. Statistically significant reductions over 12 months were found for median DAS28(ESR) 5.61 to 3.31, TJC 7.0 to 1.0, and SJC 5.0 to 1.0 (each p <  0.001). No statistically significant correlations were detected between the FOIAS change in phase 1 and DAS28(ESR), TJC, or SJC. Correlations between the other phases and clinical outcomes were weak to moderate.

Conclusion

Reduced early enhancement in FOI phase 1 can be observed in clinically responding and non-responding early RA patients under treatment. Regarding potential marker performance, FOI probably shows a reduction of inflammation more objectively.
Novel causes and consequences of overtraining syndrome: the EROS-DISRUPTORS study
Authors: Cadegiani Flavio A. , Kater Claudio E.
Published: September 2019

Background

Hormonal physiology in athletes, dysfunctional paths leading to overtraining syndrome (OTS), and clinical and biochemical behaviors that are independently modified by the presence of OTS remain unclear. Although multiple markers of OTS have recently been identified, the independent influence of OTS on hormones and metabolism have not been assessed. Hence, the objective of the present study was to uncover the previously unrecognized independent predictors of OTS and understand how OTS independently modifies the behaviors of clinical and biochemical parameters.

Methods

In a total of 39 athletes (OTS-affected athletes (OTS) = 14 and healthy athletes (ATL) = 25), we performed two clusters of statistical analyses using the full data of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, in a total of 117 markers. We first used logistic regression to analyze five modifiable parameters (carbohydrate, protein, and overall caloric intake, sleep quality, and concurrent cognitive effort) as potential additional independent risk factors for OTS, and OTS as the outcome. We then used multivariate linear regression to analyze OTS as the independent variable and 38 dependent variables. Training patterns were found to be similar between OTS and ATL, and therefore excessive training was not a risk, and consequently not a predictor, for OTS.

Results

Each of the three dietary patterns (daily carbohydrate, daily protein, and daily overall calorie intake) were found to be the independent triggers of OTS, while sleeping, social, and training characteristics depended on other factors to induce OTS. Once triggered, OTS independently induced multiple changes, including reductions of cortisol, late growth hormone and adrenocorticotropic hormone responses to stimulations, testosterone-to-estradiol ratio, neutrophils, neutrophil-to-lymphocyte ratio, vigor levels, hydration status, and muscle mass, while increase of tension levels and visceral fat.

Conclusions

OTS can be independently triggered by eating patterns, regardless of training patterns, while the occurrence of OTS reduced late hormonal responses and the testosterone-to-estradiol ratio, worsened mood, and affected the immunology panel. These novel findings may explain underperformance, which is the key characteristic of OTS.
Chronic toxicity of low dose monosodium glutamate in albino Wistar rats
Authors: Nnadozie Josiah Okwudili , Chijioke Udunma Olive , Okafor Okechukwu Charles , Olusina Daniel Bankole , Oli Angus Nnamdi , Nwonu Patience Chiebonam , Mbagwu Herbert Orji , Chijioke Chioli Pascal
Published: September 2019

Objective

The objective of this study was to observe the effects of chronic dosing with monosodium glutamate on mortality, fertility, major organ functions and histology in albino Wistar rats.

Results

6 male and 6 female rats (age 6 weeks) were bred in a cage, feeding on standard growers’ mash, with monosodium glutamate added (120 mg/kg/day). 12 corresponding breeding rats (on standard feed without MSG) were controls. Chronic dosing with monosodium glutamate in albino Wistar rats (at a dose consistent with the human ADI) led to increased mortality, fertility impairment, and significant changes in major organ function tests and histology. 23 deaths were recorded in the rats fed with MSG additive, while mortality was zero in the control animals. Fertility was lower in rats on MSG (48 births) than in controls (117 births). The weight gain of the MSG rats was higher than in controls. Biochemical parameters and organ histology remained normal in control animals. In MSG-treated rats however, liver/renal function tests, fasting serum cholesterol and triglyceride, serum uric acid showed a significant rise at trimestrial time-points. Histology showed mild portal inflammation in MSG rats, with periglomerular fibrosis and interstitial nephritis in two rats, at 6–12 months.
Obstetric violence and its associated factors among postnatal women in a Specialized Comprehensive Hospital, Amhara Region, Northwest Ethiopia
Authors: Mihret Muhabaw Shumye
Published: September 2019

Objective

Obstetric violence is an often overlooked obstacle to quality maternal health care service utilization. In the study setting, there was limited evidence on obstetric violence. Hence, this study aimed at assessing the prevalence and associated factors of obstetric violence among women who gave birth in Gondar University Specialized Comprehensive Hospital, Northwest Ethiopia.

Results

A total of 409 women had been participated in the study with a response rate of 100%. Three in four (75.1%) women reported that they had been subjected to at least one form of obstetric violence during labor and delivery with 95% CI (70.9–79.0). The reported forms of obstetric violence include non-consented care—260 (63.6%), non-dignified care—226 (55.3%), physical abuse—192 (46.9%), non-confidential care—132 (32.3%, neglected care—52 (12.7%) and discriminated care—38 (9.3%). On the contrary, none of the respondent had reported detention for failure to pay in the hospital. The multivariable logistic regression analysis demonstrated that urban residents (AOR = 1.89; 95% CI 1.11, 3.22) and primary school attendants (AOR = 0.49; 95% CI 0.27, 0.91) were significantly associated with experiencing obstetric violence. This study indicated the high prevalence of obstetric violence. Thus, interventions need to be undertaken by taking the reported forms of obstetric violence and participants’ sociodemographic status in to account.
Patterns and predictive factors of unhealthy practice among mothers during pregnancy, childbirth, postnatal and newborn care in Southern Ethiopia: a community based cross-sectional study
Authors: Kassahun Getinet , Wakgari Negash , Abrham Ribka
Published: September 2019

Objective

The aim of this study was to assess the magnitude, patterns and predictive factors of unhealthy practice among mothers during pregnancy, childbirth, postnatal and newborn care in Southern Ethiopia.

Results

Among the total participants, 29.0% mothers performed at least one unhealthy practice during pregnancy, childbirth, postnatal period and newborn care. This study identified the following harmful practices such as food prohibition (53.2%), home delivery (41.5%), discarding colostrum (18.6%), application of substance on the cord stump (12.1%), delayed breast feeding (28.4%), prelacteal feeding (43.0%) and early bathing (49.3%). Being grand multiparous (AOR = 2.528, 95% CI 1.037–6.166), being illiterate (AOR = 7.611, 95% CI 2.375–24.396) and lack of awareness on the effect of unhealthy practice (OR = 4.673, 95% CI 1.163–18.774) were independent predictors of outcome variable.
Knowledge, beliefs and practices on antibiotic use and resistance among a group of trainee nurses in Sri Lanka
Authors: Jayaweerasingham Mathanki , Angulmaduwa Sacheera , Liyanapathirana Veranja
Published: September 2019

Objectives

Nurses are the main communication link for healthcare messages to hospitalized patients and also play a crucial role in preventing the emergence and spread antibiotic resistant bacteria through antibiotic stewardship and infection control programmes. This requires them to possess correct knowledge and attitudes towards antibiotic use and resistance. This study was carried out to identify the level of knowledge, attitude and practices on antibiotic use and antibiotic resistance among student nurses.

Results

A descriptive cross-sectional study was conducted using a pre-validated, self-administered questionnaire with closed and open ended questions, among 199 student nurses at a government nurses training school in Sri Lanka. Scores and proportions were analysed with non-parametric methods and thematic analysis was done for the qualitative data. The study cohort had a mean knowledge score of 71.9% (SD 14). However, close to 40% believed that taking antibiotics will help to prevent cold from worsening and make recovery faster. Infection control was identified as the main method that nurses can engage in preventing antibiotic resistance. While the knowledge among our study cohort appeared to be good, some misbeliefs were present. Our findings can be used in developing the nursing curricula on antibiotic use and resistance.
Haemopoietic stem cell transplantation in Systemic lupus erythematosus: a systematic review
Authors: de Silva Nipun Lakshitha , Seneviratne Suranjith L.
Published: September 2019

Despite advances in treating Systemic lupus erythematosus (SLE), a proportion of patients continue to face significant morbidity and mortality. Haemopoietic stem cell transplant (HSCT) has been recognized as an option for such patients. We analysed the evidence on efficacy and safety of HSCT in patients with SLE. A database search was done for articles on HSCT in SLE up to July 2017 in PUBMED, Cochrane library, LILACS and clinical trial registration databases to select prospective or retrospective studies with 8 or more patients. Of the 732 search results from the PUBMED, Cochrane and LILACS database search, following duplicate removal, 15 studies were eligible for detailed assessment. Findings of an additional trial were obtained from the clinical trial registration database. Data were extracted on study design, patient characteristics, nature of intervention, outcomes, complications and study quality. Case reports and small case series were summarised without detailed qualitative analysis. Most of the studies showed remission in the majority of patients. Relapse of the original disease increased with longer follow-up. Common adverse effects included: infections and secondary autoimmune disorders. Short follow up period and lack of randomised controlled trials were the main limitations restricting the generalizability of study results. A meta-analysis was not performed due to heterogeneity of studies. Although HSCT is a viable option in SLE, its exact clinical utility needs to be further evaluated in well-designed studies.
Disseminated neurocysticercosis with bilateral papilledema: a case report
Authors: Shrestha Ruchi , Shrestha Amin Kumar
Published: September 2019

Background

Ocular cysticercosis is a disease which rarely involves cutaneous skin and the optic nerve. Patients with clinical presentation of subcutaneous nodules and papilledema should always be evaluated for cysticercosis.

Case presentation

We report a rare case of ocular cysticercosis with multiple disseminated subcutaneous nodules and papilledema in both eyes. A 22-year-old Brahmin man presented with complaints of gradual loss of vision in both eyes and multiple small masses all over his body. On clinical evaluation, multiple subcutaneous nodules were seen on his face, mandibular area, elbow, arm, and abdomen. A fundus evaluation showed bilateral blurred disc margin. The case was managed with steroids and anti-parasitic drugs.

Conclusion

This case report highlights the importance of ruling out neurocysticercosis in cases with multiple disseminated subcutaneous nodules and papilledema.
Open-source QSAR models for pKa prediction using multiple machine learning approaches
Authors: Mansouri Kamel , Cariello Neal F. , Korotcov Alexandru , Tkachenko Valery , Grulke Chris M. , Sprankle Catherine S. , Allen David , Casey Warren M. , Kleinstreuer Nicole C. , Williams Antony J.
Published: September 2019

Background

The logarithmic acid dissociation constant pKa reflects the ionization of a chemical, which affects lipophilicity, solubility, protein binding, and ability to pass through the plasma membrane. Thus, pKa affects chemical absorption, distribution, metabolism, excretion, and toxicity properties. Multiple proprietary software packages exist for the prediction of pKa, but to the best of our knowledge no free and open-source programs exist for this purpose. Using a freely available data set and three machine learning approaches, we developed open-source models for pKa prediction.

Methods

The experimental strongest acidic and strongest basic pKa values in water for 7912 chemicals were obtained from DataWarrior, a freely available software package. Chemical structures were curated and standardized for quantitative structure–activity relationship (QSAR) modeling using KNIME, and a subset comprising 79% of the initial set was used for modeling. To evaluate different approaches to modeling, several datasets were constructed based on different processing of chemical structures with acidic and/or basic pKas. Continuous molecular descriptors, binary fingerprints, and fragment counts were generated using PaDEL, and pKa prediction models were created using three machine learning methods, (1) support vector machines (SVM) combined with k-nearest neighbors (kNN), (2) extreme gradient boosting (XGB) and (3) deep neural networks (DNN).

Results

The three methods delivered comparable performances on the training and test sets with a root-mean-squared error (RMSE) around 1.5 and a coefficient of determination (R2) around 0.80. Two commercial pKa predictors from ACD/Labs and ChemAxon were used to benchmark the three best models developed in this work, and performance of our models compared favorably to the commercial products.

Conclusions

This work provides multiple QSAR models to predict the strongest acidic and strongest basic pKas of chemicals, built using publicly available data, and provided as free and open-source software on GitHub.
The immunomodulatory functions and molecular mechanism of a new bursal heptapeptide (BP7) in immune responses and immature B cells
Authors: Feng Xiu Li , Zheng Yang , Zong Man Man , Hao Shan Shan , Zhou Guang Fang , Cao Rui Bing , Chen Pu Yan , Liu Qing Tao
Published: September 2019

The bursa of Fabricius (BF) is the acknowledged central humoural immune organ unique to birds and plays a vital role in B lymphocyte development. In addition, the unique molecular immune features of bursal-derived biological peptides involved in B cell development are rarely reported. In this paper, a novel bursal heptapeptide (BP7) with the sequence GGCDGAA was isolated from the BF and was shown to enhance the monoclonal antibody production of a hybridoma. A mouse immunization experiment showed that mice immunized with an AIV antigen and BP7 produced strong antibody responses and cell-mediated immune responses. Additionally, BP7 stimulated increased mRNA levels of sIgM in immature mouse WEHI-231 B cells. Gene microarray results confirmed that BP7 regulated 2465 differentially expressed genes in BP7-treated WEHI-231 cells and induced 13 signalling pathways and various immune-related functional processes. Furthermore, we found that BP7 stimulated WEHI-231 cell autophagy and AMPK-ULK1 phosphorylation and regulated Bcl-2 protein expression. Finally, chicken immunization showed that BP7 enhanced the potential antibody and cytokine responses to the AIV antigen. These results suggested that BP7 might be an active biological factor that functions as a potential immunopotentiator, which provided some novel insights into the molecular mechanisms of the effects of bursal peptides on immune functions and B cell differentiation.
Construction and characterization of immunoliposomes targeting fibroblast growth factor receptor 3
Authors: Zheng Zhong , Ji Haotian , Zong Wenbo , Ran Qiuju , Wang Xinxin , Yang Xi , Zhao Zhuo , Yang Chengjun , Xiao Yechen
Published: September 2019

Fibroblast growth factor receptor 3 (FGFR3) plays an important regulatory role in tumor cell proliferation and drug resistance. FGFR3 is often constitutively active in many tumors. To deliver drugs into tumor cells by targeting FGFR3 will be a promising and potential strategy for cancer therapy. In this study, a novel fusion protein, ScFv-Cys containing a single chain variable fragment (ScFv) and an additional C-terminal cysteine residue, was generated at a rate of 10 mg/L of bacterial culture and purified at 95% by Ni-NTA chromatography. Subsequently, the recombinant ScFv-Cys was coupled with malPEG2000-DSPE and incorporated into liposomes to generate the immunoliposomes. The results indicated that immunoliposomes can specifically deliver the fluorescent molecules, Dio into bladder cancer cells highly expressing FGFR3. In conclusion, we successfully generated FGFR3-specific immunoliposomes, and proved its targeting effect and delivering ability.
BabaoDan attenuates high-fat diet-induced non-alcoholic fatty liver disease via activation of AMPK signaling
Authors: Sheng Dandan , Zhao Shanmin , Gao Lu , Zheng Huifei , Liu Wenting , Hou Jing , Jin Yuxiang , Ye Fei , Zhao Qiudong , Li Rong , Zhao Naping , Zhang Li , Han Zhipeng , Wei Lixin
Published: September 2019

Background

Babaodan (BBD), a traditional Chinese medicine, has been shown to have protective effects during liver injury and ameliorate liver disease progression, but little is known about its effect on non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the effects of BBD on obesity-induced NAFLD.

Methods

C57BL/6 J mice were fed with normal diet, high fat diet (HFD) or HFD + BBD for 8 weeks. Weights of all mice were recorded every 3 days. At the end of the experiments, the level of livers, kidneys and adipose tissues of each animal was weighed. Blood serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) cholesterol, low density lipoprotein cholesterol (LDL-C), glucose and leptin were detected with appropriate test kits. Haematoxylin–eosin (HE), Masson trichrome and Oil Red O staining of the liver were performed. We applied immunohistochemical analysis to investigate the expression of TNF-α, IL-6 and leptin in liver tissue. The expression of genes related lipid anabolism (SREBP1-c, ACC, SCD-1, LXRα and CD36) and ß-oxidation (CPT-1 and PPARα) in liver and adipose tissues was determined by RT-PCR. The expression of AMPK and p-AMPK was determined by western blot analysis.

Results

We found the weight of bodies and tissues (retroperitoneal fat pads, kidneys and livers) of mice fed with HFD + BBD were significantly lower than that of HFD-fed mice. And liver injury induced by HFD was relieved in mice treated with BBD, accompanied with significant reduction were observed in serum ALT/AST activities and alleviated pathological damage. The levels of glucose, TG, TC, HDL-C and LDL-C in the liver or serum were significantly decreased on HFD + BBD group compared with HFD group. Furthermore, BBD treatment reduced the level of TNF-α and IL-6 induced by HFD. The level of leptin in the liver and serum were reduced in mice fed with HFD + BBD than that of HFD-fed mice. Several lipid synthesis genes (SREBP1-c, ACC, SCD-1, LXRα and CD36) were down-regulated and that of ß-oxidation (CPT-1 and PPARα) up-regulated in HFD + BBD group compared with HFD group. In addition, BBD increased the expression of p-AMPK compared with untreated HFD group, which suggested BBD improved the activation of AMPK pathway.

Conclusion

In summary, our results indicate that BBD has potential applications in the prevention and treatment of NAFLD, which may be closely related to its effect on lipid metabolism via activation of AMPK signaling.
SMYD2 promotes cervical cancer growth by stimulating cell proliferation
Authors: Sun Jun-Jie , Li Hong-Lin , Ma Hui , Shi Yang , Yin Li-Rong , Guo Su-Jie
Published: September 2019

Background

Cervical cancer is the most common gynecological malignancy with low terminal cure rate, and therefore new therapeutic targets are urgently needed to combat this disease. SMYD2, as an oncogene, is abnormal highly expressed in multiple types of tumors and further affects the occurrence and development, but the potential correlations between SMYD2 expression and cervical cancer progression is still unclear.

Methods

We first used the bioinformatics website to screen the data of cervical cancer in (The Cancer Genome Atlas) TCGA and survival analysis was used to find the different survival rates in the SMYD2 high expression group and low expression group. Through immunohistochemistry, the association between SMYD2 expression and clinical-pathological features of cervical cancer patients was further evaluated. Quantitative PCR and Immunoblot were applied to investigate the relative mRNA and protein expression levels, respectively. In vivo and in vitro experiments were performed to explore the function of SMYD2 in cancer progression.

Results

We first found a high expression of SMYD2 in cervical cancer, and survival analysis found that the poorer survival rate in the SMYD2 high expression group than that in the low expression group. Herein, our study demonstrated that the expression of SMYD2 in patients with cervical cancer was associated with FIGO stage, tumor size and further correlated with poor prognosis. Our data further showed that the inhibition of SMYD2 expression in cervical cancer cell line Caski and Siha could dramatically block the proliferation of cervical cancer cells. Additionally, SMYD2-shRNA lentivirus infected remarkably inhibited tumorigenesis in mice compared with the scramble group.

Conclusions

Taken together, this study provides strong evidence of the involvement of SMYD2 in cervical cancer growth and indicates that it could have high potential as a therapeutic target of cervical cancer.
Identification and authentication for wireless transmission security based on RF-DNA fingerprint
Authors: Wang Xueli , Zhang Yufeng , Zhang Hongxin , Wei Xiaofeng , Wang Guangyuan
Published: September 2019

For wireless transmission, radio-frequency device anti-cloning has become a major security issue. Radio-frequency distinct native attribute (RF-DNA) fingerprint is a developing technology to find the difference among RF devices and identify them. Comparing with previous research, (1) this paper proposed that mean (μ) feature should be added into RF-DNA fingerprint. Thus, totally four statistics (mean, standard deviation, skewness, and kurtosis) were calculated on instantaneous amplitude, phase, and frequency generated by Hilbert transform. (2) We first proposed using the logistic regression (LR) and support vector machine (SVM) to recognize such extracted fingerprint at different signal-to-noise ratio (SNR) environment. We compared their performance with traditional multiple discriminant analysis (MDA). (3) In addition, this paper also proposed to extract three sub-features (amplitude, phase, and frequency) separately to recognize extracted fingerprint under MDA. In order to make our results more universal, additive white Gaussian noise was adopted to simulate the real environment. The results show that (1) mean feature conducts an improvement in the classification accuracy, especially in low SNR environment. (2) MDA and SVM could successfully identify these RF devices, and the classification accuracy could reach 94%. Although the classification accuracy of LR is 89.2%, it could get the probability of each class. After adding a different noise, the recognition accuracy is more than 80% when SNR≥5 dB using MDA or SVM. (3) Frequency feature has more discriminant information. Phase and amplitude play an auxiliary but also pivotal role in classification recognition.
A conjugate gradient algorithm and its application in large-scale optimization problems and image restoration
Authors: Yuan Gonglin , Li Tingting , Hu Wujie
Published: September 2019

To solve large-scale unconstrained optimization problems, a modified PRP conjugate gradient algorithm is proposed and is found to be interesting because it combines the steepest descent algorithm with the conjugate gradient method and successfully fully utilizes their excellent properties. For smooth functions, the objective algorithm sufficiently utilizes information about the gradient function and the previous direction to determine the next search direction. For nonsmooth functions, a Moreau–Yosida regularization is introduced into the proposed algorithm, which simplifies the process in addressing complex problems. The proposed algorithm has the following characteristics: (i) a sufficient descent feature as well as a trust region trait; (ii) the ability to achieve global convergence; (iii) numerical results for large-scale smooth/nonsmooth functions prove that the proposed algorithm is outstanding compared to other similar optimization methods; (iv) image restoration problems are done to turn out that the given algorithm is successful.
On classical solutions of Rayleigh–Taylor instability in inhomogeneous viscoelastic fluids
Authors: Tan Zhidan , Wang Weiwei
Published: September 2019

We study the nonlinear Rayleigh–Taylor (RT) instability of an inhomogeneous incompressible viscoelastic fluid in a bounded domain. It is well known that there exist strong solutions of RT instability in$H^{2}$H2-norm in inhomogeneous incompressible viscoelastic fluids, when the elasticity coefficientκis less than some threshold$\kappa _{\mathrm{C}}$κC. In this paper, we prove the existence of classical solutions of RT instability in$L^{1}$L1-norm in Lagrangian coordinates based on a bootstrap instability method with finer analysis, if$\kappa <\kappa _{\mathrm{C}}$κ<κC. Moreover, we also get classical solutions of RT instability in$L^{1}$L1-norm in Eulerian coordinates by further applying an inverse transformation of Lagrangian coordinates.
A stabilized coupled method and its optimal error estimates for elliptic interface problems
Authors: Yu Jiaping , Shi Feng , Zhao Jianping
Published: September 2019

In this paper, we present a stabilized coupled algorithm for solving elliptic interface problems, mainly by introducing the jump of the solutions along the interface. A framework of theoretical proofs is provided to show the optimal error estimates of this stabilized method. Several numerical experiments are carried out to demonstrate the computational stability and effectiveness of the method.
A recurrent and transesophageal echocardiography–associated outbreak of extended-spectrum β-lactamase–producing Enterobacter cloacae complex in cardiac surgery patients
Authors: Van Maerken Tom , De Brabandere Els , Noël Audrey , Coorevits Liselotte , De Waegemaeker Pascal , Ablorh Raina , Bouchez Stefaan , Herck Ingrid , Peperstraete Harlinde , Bogaerts Pierre , Verhasselt Bruno , Glupczynski Youri , Boelens Jerina , Leroux-Roels Isabel
Published: September 2019

Background

We report a recurrent outbreak of postoperative infections with extended-spectrum β-lactamase (ESBL)–producing E. cloacae complex in cardiac surgery patients, describe the outbreak investigation and highlight the infection control measures.

Methods

Cases were defined as cardiac surgery patients in Ghent University Hospital who were not known preoperatively to carry ESBL-producing E. cloacae complex and who postoperatively had a positive culture for this multiresistant organism between May 2017 and January 2018. An epidemiological investigation, including a case-control study, and environmental investigation were conducted to identify the source of the outbreak. Clonal relatedness of ESBL-producing E. cloacae complex isolates collected from case patients was assessed using whole-genome sequencing–based studies.

Results

Three separate outbreak episodes occurred over the course of 9 months. A total of 8, 4 and 6 patients met the case definition, respectively. All but one patients developed a clinical infection with ESBL-producing E. cloacae complex, most typically postoperative pneumonia. Overall mortality was 22% (4/18). Environmental cultures were negative, but epidemiological investigation pointed to transesophageal echocardiography (TEE) as the outbreak source. Of note, four TEE probes showed a similar pattern of damage, which very likely impeded adequate disinfection. The first and second outbreak episode were caused by the same clone, whereas a different strain was responsible for the third episode.

Conclusions

Health professionals caring for cardiac surgery patients and infection control specialists should be aware of TEE as possible infection source. Caution must be exercised to prevent and detect damage of TEE probes.
Developing financial competence about mortgage loans by informal learning using banks’ online calculators
Authors: Fürstenau Bärbel , Hommel Mandy
Published: September 2019

Background and aim

Financial literacy (or financial competence) has become an internationally relevant and highly regarded topic. Since people often lack sufficient financial competence, in many countries efforts have been made to foster formal financial education. Less attention, however, has been paid to whether informal learning using information available on the Internet can also support the development of financial competence. However, this seems to be an important question because the Internet has expanded the opportunities for informal learning. In addition, people need to acquire financial competence on their own because not every financial topic relevant in one’s lifetime is covered in formal education syllabi. Against this background, in this study we tested whether people are able to develop financial competence by learning informally using information available on the Internet. We focused on mortgage loans, as they are comparatively complex financial products. Mortgage loans have the potential to significantly influence an individual’s financial situation. In addition, society might carry the burdens of risky and uninformed decisions about mortgage loans—as the financial and real estate crisis has shown.

Method

45 students of economics and business studies in their final undergraduate year participated. They were randomly assigned to an experimental or a control group. The experimental group explored information about mortgage loans using the loan calculator of a German bank. The control group did not explore webpages. Before the intervention, students from both groups completed knowledge tests and self-assessed their financial knowledge and behaviour. After the intervention, students had to work on a case and to decide whether a small family should take out a mortgage loan for financing a house. The decision had to be justified. In addition, students were administered an immediate and delayed knowledge test.

Results and conclusions

Students of both groups did not differ in knowledge acquisition, decision making about taking a mortgage loan and argumentation quality. However, prior knowledge can be referred to in order to explain the results. Therefore, informal learning using the Internet did not seem to be effective if people did not have sufficient prior knowledge. This result underlines, on the one hand, the necessity of financial education—be it prior to informal learning or in the course of informal learning. On the other hand, the results can be interpreted as a hint to consider how to improve informal learning activities, e.g. by supporting self-regulation or by improving information material.
Personalized adaptive learning: an emerging pedagogical approach enabled by a smart learning environment
Authors: Peng Hongchao , Ma Shanshan , Spector Jonathan Michael
Published: September 2019

Smart devices and intelligent technologies are enabling a smart learning environment to effectively promote the development of personalized learning and adaptive learning, in line with the trend of accelerating the integration of both. In this regard, we introduce a new teaching method enabled by a smart learning environment, which is a form of personalized adaptive learning. In order to clearly explain this approach, we have deeply analyzed its two pillars: personalized learning and adaptive learning. The core elements of personalized adaptive learning and its core concept are explored as well. The elements are four: individual characteristics, individual performance, personal development, and adaptive adjustment. And the core concept is referred to a technology-empowered effective pedagogy which can adaptively adjust teaching strategies timely based on real-time monitoring (enabled by smart technology) learners’ differences and changes in individual characteristics, individual performance, and personal development. On this basis, A framework of personalized adaptive learning is also constructed. Besides, we further explored a recommendation model of the personalized learning path. To be specific, personalized adaptive learning could be constructed from the following four aspects, namely, learner profiles, competency-based progression, personal learning, and flexible learning environments. Last, we explored a form of learning profiles model and a generative paths recommendation pattern of personal learning. This paper provides a clear understanding of personalized adaptive learning and serves as an endeavor to contribute to future studies and practices.
RETRACTED ARTICLE: Estimation of the source process and forward simulation of long-period ground motion of the 2018 Hokkaido Eastern Iburi, Japan, earthquake
Authors: Kubo Hisahiko , Iwaki Asako , Suzuki Wataru , Aoi Shin , Sekiguchi Haruko
Published: September 2019

In this study, we investigate the source rupture process of the 2018 Hokkaido Eastern Iburi earthquake in Japan (MJMA6.7) and how the ground motion can be reproduced using available source and velocity models. First, we conduct a multiple-time-window kinematic waveform inversion using strong-motion waveforms, which indicates that a large-slip area located at a depth of 25–30 km in the up-dip direction from the hypocenter was caused by a rupture propagating upward 6–12 s after its initiation. Moreover, the high-seismicity area of aftershocks did not overlap with the large-slip area. Subsequently, using the obtained source model and a three-dimensional velocity structure model, we conduct a forward long-period (< 0.5 Hz) ground-motion simulation. The simulation was able to reproduce the overall ground-motion characteristics in the sedimentary layers of the Ishikari Lowland.