bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI-based Radiomics of Rectal Cancer: Preoperative Assessment of the Pathological Features
Authors: Ma Xiaolu , Shen Fu , Jia Yan , Xia Yuwei , Li Qihua , Lu Jianping
Published: October 2019

[EXSCINDED]
Abstract
Abstract
Abstract

Background
This study aimed to evaluate the significance of MRI-based radiomics model derived from high-resolution T2-weighted images (T2WIs) in predicting tumor pathological features of rectal cancer.Methods

A total of 152 patients with rectal cancer who underwent surgery without any neoadjuvant therapy between March 2017 and September 2018 were included retrospectively. The patients were scanned using a 3-tesla magnetic resonance imaging, and high-resolution T2WIs were obtained. Lesions were delineated, and 1029 radiomics features were extracted. Least absolute shrinkage and selection operator was used to select features, and multilayer perceptron (MLP), logistic regression, support vector machine (SVM), decision tree, random forest (RF), and K-nearest neighbor were trained using fivefold cross-validation to build a prediction model. The diagnostic performance of the prediction models was assessed using the receiver operating characteristic curves.Results

A total of 1029 features were extracted, and 15, 11, and 11 features were selected to predict the degree of differentiation, T stage, and N stage, respectively. The best performance of the radiomics model for the degree of differentiation, T stage, and N stage was obtained by SVM [area under the curve (AUC), 0.862; 95% confidence interval (CI), 0.750–0.967; sensitivity, 83.3%; specificity, 85.0%], MLP (AUC, 0.809; 95% CI, 0.690–0.905; sensitivity, 76.2%; specificity, 74.1%), and RF (AUC, 0.809; 95% CI, 0.690–0.905; sensitivity, 76.2%; specificity, 74.1%).Conclusion

This study demonstrated that the high-resolution T2WI–based radiomics model could serve as pretreatment biomarkers in predicting pathological features of rectal cancer.
Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats
Authors: Sepehrinezhad Ali , Dehghanian Amirreza , Rafati Ali , Ketabchi Farzaneh
Published: October 2019

Background : Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases.
Methods: Female Sprague Dawley rats were assigned into four groups of Sham (n=7), portal vein ligation (PPVL, n=7), common bile duct ligation (CBDL, n=7), and combination of them (CBDL+ PPVL, n=7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O 2 50%) and hypoxia (O 2 10%). Besides, we assessed blood parameters and liver histology.
Results: Liver histology score, liver enzymes, WBC and malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group.
Conclusion: Severe liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.
Spatial phylogenetics of the Chinese angiosperm flora provides insights into endemism and conservation
Authors: Zhang Xiao-Xia , Ye Jian-Fei , Laffan Shawn W. , Mishler Brent D. , Thornhill Andrew H. , Lu Li-Min , Mao Ling-Feng , Liu Bing , Chen You-Hua , Lu An-Ming , Miller Joseph T. , Chen Zhi-Duan
Published: October 2019

Background The flora of China is well known for its high endemism. Identifying centers of endemism and designating conservation priorities for the Chinese flora are essential goals for biodiversity studies. We used a phylogeny that included 2,909 Chinese angiosperm genera and 1.39 million spatial distribution records to conduct spatial phylogenetics analyses. Then, we identified centers of neo- and paleo-endemism in the Chinese angiosperm flora using spatial phylogenetic methods. Phylogenetic endemism centers were compared with taxonomic endemism centers, and their implications for conservation were examined. Results (1) The majority of grid cells with significant phylogenetic endemism (PE) were dominated by mixed- or super-endemism in China, but only one grid cell dominated by neo-endemism was located in the Qinghai–Tibet Plateau. (2) Ten geographic centers of grid cells with high PE were identified. Four of these found in northern China are recognized for the first time here. (3) Arid and semiarid regions were commonly linked to PE centers in both our study and other spatial phylogenetics studies worldwide. (4) Five priority conservation gaps were detected by overlaying the boundaries of China’s nature reserves on these centers of endemism. Conclusions The spatial phylogenetics approach provides an evolutionary perspective to understanding the diversity and endemism patterns. These integrated methods are necessary for broad-scale conservation planning, especially when aiming to conserve evolutionary history.
An analysis of the current demand of senior citizens in underdeveloped areas of Western China for the combination of medical and elderly care and the corresponding influencing factors: a case study of Lanzhou
Authors: Wang Jiancheng , Wang Yunhua , Cai Hui , Zhang Juxia , Pan Bei , Bao Guoxian , Guo Tiankang
Published: October 2019

Background: This study aims to understand the current demand of senior citizens in Lanzhou, China for the combination of medical and elderly care services and discuss its influencing factors. Methods: 7500 participants aged 60 or above living in Lanzhou, China were recruited, A uniform and self-designed questionnaire survey was conducted on these subjects. Then, two methods, namely, single factor chi-square test and multi-factor binomial logistic regression were used to analyze. Results: Among 7,320 senior citizens, 3,772 have demand for the combination of medical and elderly care with a demand rate of 53.15%. The differences between genders, marital status, education background, occupation before retirement, number of children, monthly income, self-assessment of health, type of endowment insurance, type of medical insurance, current elderly care model, elderly care demand, self-care ability, awareness of the combination of medical and elderly care and willingness to pay for the combination of medical and elderly care and the demand of senior citizens in Lanzhou for the combination of medical and elderly care are all of statistical significance ( P ＜0.05), while the differences between age, mode of living and chronic diseases and the demand of senior citizens in Lanzhou for the combination of medical and elderly care are all of no statistical significance ( P ＞0.05). Conclusions: The factors that influence the demand for the combination of medical and elderly care by senior citizens in Lanzhou are complicated, among which, the number of children, type of medical insurance and willingness to pay for the combination of medical and elderly care are main factors that influence their demand. The awareness of and the demand for the combination of medical and elderly care among senior citizens in Lanzhou are at a low level, and the number of children, type of medical insurance and willingness to pay for the combination of medical and elderly care have great influence on the demand rate.
The timing of symptomatic pulmonary embolism in patients with non-warfarin following elective primary total joint arthroplasty
Authors: HU CHUAN , LIU CHUAN , WANG YUAN-HE , DING TAO , SUN KANG , YANG XU , ZENG GUO-BO , TIAN Shao-qi
Published: October 2019

Background: The purpose of this study was to investigate the incidence and timing of postoperative symptomatic pulmonary embolism (PE) in patients receiving non-warfarin following primary total joint arthroplasty (TJA), to clarify the appropriate duration of postoperative VTE prophylaxis. Methods: We retrospectively reviewed the medical records of 11148 patients who underwent primary TJA, including total knee arthroplasty (TKA) and total hip arthroplasty (THA) at our institution from January 2012 to March 2019. The median postoperative day of diagnosis of symptomatic PE and interquartile range for day of diagnosis were determined. Multivariate Cox proportional hazards modeling was used to test the difference of timing for PE based on demographics and comorbidities. Results: The overall 90-day rate of symptomatic PE was 0.71%. The median day of diagnosis for symptomatic PE was 3 day postoperatively (interquartile: 2–7 day). Factors that showed statistical significance on multivariate analysis in association with earlier timing of PE occurrence in patients with atrial fibrillation, diabetes mellitus, coronary heart disease and history of stroke. Conclusion: The vast majority symptomatic PE occurs in the early postoperative period after TJA, and atrial fibrillation, diabetes mellitus, coronary heart disease and history of stroke were independent factors affecting the timing of symptomatic PE.
System Reliability Analysis of the Scoliosis Disorder
Authors: Nouri Fatemeh , Ghasemi Seyed Hooman
Published: October 2019

Background: Scoliosis is a spine abnormal deviation, which is an idiopathic disorder among children and adolescents. As a matter of the fact, distribution of loads on the patient's spine and load carrying capacity of the vertebral column are both random variables. Therefore, the probabilistic approach may consider as a sophisticated method to deal with this problem. Method: Reliability analysis is a probabilistic-based approach to consider the uncertainties of load and resistance of the vertebral column. The main contribution of this paper is to compare the reliability level of a normal and scoliosis spinal. To do so, the numerical analyses associated with the inherent random parameters of bones and applied load are performed. Then, the reliability indices for all vertebrae and discs are determined. Accordingly, as the main innovation of this paper, the system reliability indices of the spinal column for both normal and damaged backbone system are represented. Results: Based on the required reliability index for normal spinal curvature the target system reliability level for scoliosis disorder is proposed. Conclusion: Since the proposed target reliability index is based on the strength limit state of the vertebral column, it can be considered as a reliability level for any proposed treatment approaches.
Identification and comparison of the porcine H1, U6, and 7SK RNA polymerase III promoters for short hairpin RNA expression
Authors: Yin Hai chang , Chen Xin yu , wei wang , MENG QING
Published: October 2019

Background RNA polymerase III is an essential enzyme in eukaryotes for synthesis of tRNA, 5S rRNA, and other small nuclear and cytoplasmic RNAs. Thus, RNA polymerase III promoters are often used in small hairpin RNA (shRNA) expression. In this study, the porcine H1, U6, and 7SK RNA polymerase III type promoters were cloned into a pcDNA3.1(+) expression vector containing a shRNA sequence targeting enhanced green fluorescent protein (EGFP). PK and DF-1 cells were cotransfected with the construction of recombinant interference expression vector and the EGFP expression vector, pEGFP-N1. The average fluorescence intensity of EGFP in transfected cells was measured by fluorescence microscopy and flow cytometry. Real-time PCR was used to detect expressed shRNAs and the relative expression of EGFP, to confirm the activity of the promoters.Results The results showed that the activity of porcine 7SK promoter is stronger than the U6 promoter, which is in turn stronger than porcine H1.Conclusions This study confirms that the porcine H1 promoter is effective for expression of shRNA, and may be an excellent tool to knock down gene expression in pigs for functional genomics studies. The results also lay a foundation for the development of porcine RNAi technology and genetically modified porcine research.
Water, Sanitation and Hygiene Practices Associated with Intestinal Parasitic Infections, Diarrhoea, Undernutrition and Clinical Signs of Nutritional Deficiencies among Children in Surkhet, Dailekh and Achham districts, Nepal: a cross-sectional study
Authors: Shrestha Akina , Six Jeanne , Dahal Dikshya , Shrestha Rubika , Bhatta Madan , Marks Sara , Meierhofer Regula
Published: October 2019

Background: Providing universal access to safe water, sanitation and hygiene (WASH) in remote Nepal remains challenging. Efforts to improve WASH access in these areas are impeded by a dearth of information on the status of WASH conditions and its association with health and nutritional status of children in Nepal. Methods: We investigated WASH practices, nutritional status, and their association with intestinal parasitic infections, diarrhoea, undernutrition and clinical signs of nutritional deficiencies (hereafter health outcomes) during March to May 2018. Data was collected through cross-sectional survey of 1427 households, including questionnaires, observations, stool analysis, anthropometry, water quality measurements and assessment of clinical signs of nutritional deficiencies. Results: We found that 51.1% of children were suffering from intestinal parasitic infections and 55.5% had undernutrition; 52.2% had waterborne illnesses; and 63.9% had clinical signs of nutritional deficiencies. Multivariate mixed logistic regression analysis revealed significant associations between health outcomes and intermittent water supply (adjusted odds ratio (AOR)=2.72, 95% confidence intervals (CI)=1.18-6.31, P =0.02), washing hands when they look dirty (AOR=0.47, 95% CI=0.32-0.71, P =0.01), handwashing after going to toilet (AOR=0.37, 95% CI=0.13-1.02, P =0.06), cleanliness of the toilet (AOR=0.68, 95% CI=0.47-0.98, P =0.04), presence of earthen floor (AOR=2.29, 95% CI=1.20-4.37, P =0.01), caregivers who can read (AOR=4.07, 95% CI=1.00-16.55, P =0.05), no toilet (AOR=6.12, 95% CI=1.08-14.25, P =0.04), cleanliness of caregivers hand (AOR=0.61, 95% CI=0.41-0.89, P =0.01), regular deworming (AOR=0.44, 95% CI=0.20-0.94, P =0.03), own food production (AOR=0.67, 95% CI=0.46-0.97, P =0.03), animals inside the house overnight (AOR=1.71, 95% CI=1.17-2.51, P =0.01), source water quality (AOR=10.44, 95% CI=1.61-67.4, P =0.01), better socioeconomic status (AOR=0.43, 95% CI=0.25-0.75, P =0.01), and food supplements (AOR=0.57, 95% CI=0.38-0.84, P =0.01). Conclusions: Findings suggest improvements in WASH services, along with household hygiene and nutritional interventions, may together reduce child morbidity and mortality in Nepal.
Advocating an attack against severe malaria: a cost-effectiveness analysis
Authors: Greenhalgh Scott , Chandwani Veda
Published: October 2019

Background: Recently a study found that the gut microbiota, Lactobacillus and Bifidobacterium, have the ability to modulate the severity of malaria. The modulation of the severity of malaria is not however, the typical focal point of most widespread interventions. Thus, an essential element of information required before serious consideration of any intervention that targets reducing severe malaria incidence is a prediction of the health benefits and costs required to be cost-effective. Methods: Here, we developed a mathematical model of malaria transmission to evaluate an intervention that targets reducing severe malaria incidence. We consider intervention scenarios of a 2-, 7-, and 14-fold reduction in severe malaria incidence, based on the potential reduction in severe malaria incidence caused by gut microbiota, under entomological inoculation rates occurring in 41 countries in sub-Saharan Africa. For each intervention scenario, disability-adjusted life years averted and incremental cost-effectiveness ratios were estimated using country specific data, including the reported proportions of severe malaria incidence in healthcare settings. Results. Our results show that an intervention that targets reducing severe malaria incidence with annual costs between $23.6 to $34.2 USD per person and causes a 14-fold reduction in severe malaria incidence would be cost-effective in 14-17 countries and very cost-effective in 1-7 countries respectively. Furthermore, if model predictions are based on the distribution of gut microbiota through a freeze-dried yogurt that cost $0.20 per serving, a 2- to 14-fold reduction in severe malaria incidence would be cost-effective in 25 countries and very cost-effective in 19 countries. Conclusion: Our findings indicate interventions that target severe malaria can be cost-effective, in conjunction with standard interventions, for reducing the health burden and costs attributed to malaria. While our results illustrate a stronger cost-effectiveness for greater reductions, they consistently show that even a limited reduction in severe malaria provides substantial health benefits, and could be economically viable. Therefore, we suggest that interventions that target severe malaria are worthy of consideration, and merit further empirical and clinical investigation.
Primary caregivers’s provision of a healthy diet in a resource constrained environment in South Africa.
Authors: Brown Melissa Judith , Roman Nicolette
Published: October 2019

Background: Primary caregivers are frequently hearing mixed messages about healthy eating therefore, making it essential for these caregivers to have a clear understanding of what healthy eating is. The lack of understanding of what constituents healthy and nutritionally dense eating has not been investigated in low income families South Africa. Methods: A qualitative, cross-sectional study involving 10 in-depth interviews. Participants were purposefully selected. Data was analyzed manually using the thematic framework analysis method. The data was analyzed by means of thematic framework analysis Results: Primary caregivers struggled to provide daily access to food for their children, and at times would turn to family and friends for assistance in meal provision either through actual food or short-term financial assistance. For caregivers, limited resources impacted the ability of being able to provide a healthy diet. However, it was indicated that while shopping, caregivers looked for foods that were stated to be healthy and low in fat as well as for vitamins. These items were only accessible if they were cheap. Unemployment of fathers as well as absent fathers placed a great burden on mothers and grandmothers in the study group as this meant they needed to provide the nutritional, financial, emotional and physical care of the family. Conclusion: Primary caregivers’ food choices were based on the availability of resources, the cost, as well as access to quality food in the surrounding areas. It was also limited to what they were able to carry. Based on the reflection of primary caregivers, it was indicated that the consumption of processed foods and refined carbohydrates was high, while that of fruits and vegetables was low. Primary caregivers wanted the opportunity to learn about what a healthy diet is and how to be able to provide one for their family with their limited financial resources.
Spatial distribution and Determinants of Optimal ANC visit among pregnant women in Ethiopia: Further analysis of 2016 Ethiopia demographic Health Survey
Authors: Tadesse Zemenu Tessema , Babel Yaregal Animut
Published: October 2019

Background Antenatal care (ANC) is essential to improve maternal and newborn health and wellbeing. Antenatal care coverage is improving in Africa, since over two-thirds of pregnant women have at least one ANC contact. However, to realize the complete life-saving potential that ANC guarantees for mothers and babies, four visits providing essential proof based mostly interventions square measure neededObjective The aim of this study was to identify determinants for Optimal ANC visit and its spatial distribution among pregnant women in Ethiopia.Method This study was based on 2016 Ethiopia Demography and Health Survey. Individual women record (IR) file was used to extract the data and 8,025 pregnant women were included in the final analysis. The binary response variable considered in this study indicated whether women completed an optimal ANC visit or not from skilled health care provider and coded as 1/0. Sata14 and ArcGIS10.1 software’s were used for analysis. Generalized estimating equation (GEE) model was fitted to identify factors associated with an optimal ANC visit. Crude and Adjusted odds ratio with a 95% CI computed to assess the strength of association between independent and outcome variables.Results This study revealed that rural residence (AOR=0.59, 95%CI: 0.45-0.77),male partners educational status[secondary school (AOR=1.33, 95%CI: 1.05-1.67)], distance to the health institutions[not a big problem (AOR=1.21, 95%CI: 1.04-1.39)], community level literacy(AOR=1.07, 95%CI: 1.03-1.12), and community level service utilization(AOR=2.67,95%CI:2.21-3.24) were significantly associated with optimal ANC visits. Hot spot areas are observed in Addis Ababa, Tigray Region Harari and Dire Dawa, which means an optimal ANC visit well in these regions and cold spot area.Conclusion Living in peripheral regions of the country and in rural areas, lower educational status of male partners, and distance to health institutions were prohibiting factors for adequate number of visits. In this study community level literacy and community level service utilizations were also affect women’s’ ANC utilization which implies community level interventions should be considered for improving antenatal care utilization and better health outcomes. The government should be should give spatial attention regions like Afar, Amhara, Oromia Benishangul, SNNP and Somalia which had low optimal ANC visit
Small Incision Lenticule Extraction (SMILE) for Moderate and High Myopia: Seven-Year Outcomes of Refraction, Corneal tomography and Wavefront Aberrations
Authors: Xia Fei , Shen Yang , Han Tian , Zhao Jing , Xu Hai-Peng , Zhou Xingtao
Published: October 2019

Background To investigate the long-term corneal stability and wavefront aberrations after small incision lenticule extraction (SMILE) for moderate and high myopia.Methods Prospective, non-consecutive case series. A total of 26 patients (42 eyes) who underwent SMILE from May 2010 to March 2013 at the Fudan University Eye and ENT Hospital (Shanghai, China) were enrolled. The periods of follow-up were 1 month, 1 year, 5 years and 7 years after surgery. The routine eye examinations included uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), manifest refraction and corneal topography.Results All surgeries were executed without any complications. At the final visit, a UDVA of 20/20 or better was achieved in 42 eyes (100%), 21 eyes (50%) exhibited no change in CDVA. 15 eyes (36%) gained one line, 6 eyes (14%) gained two lines, and no eyes lost CDVA lines. 93% and 100% of eyes were within ±0.5 D and ±1.00 D of the target refraction, respectively. A mean refractive regression of -0.17 D was observed between 1 month and 7 years postoperatively. Mean corneal front curvature (KMF) were significantly increased between pre- and post-SMILE surgery (P<0.0001). Higher-order aberrations (HOAs) and vertical coma were significantly increased after SMILE compared to those measured before surgery (all P<0.001). There were no significant differences in horizontal coma, trefoil and spherical aberration between pre- and post-SMILE surgery (all P>0.05).Conclusions SMILE is an effective, safe and stable procedure for myopia correction, with relatively constant corneal stability and wavefront aberrations.
Investigating the biomechanics function of the plate-type external fixator in the treatment of tibial fractures: a biomechanical study
Authors: Shi Di , Liu Kaiyuan , Zhang Haomeng , Wang Xinli , Li Guochen , Zheng Lianhe
Published: October 2019

Background People have been pursuing to design an external fixator with the optimal biomechanics function and the lowest profile, since the fracture healing is dependent on the stability and durability of fixation and a low profile is more acceptable to patients. The plate-type external fixator, a novel prototype of an external tibial fixation device, is a low profile construct. However, the biomechanical properties remained unclear. The objective of the study was to investigate stiffness and strength of the plate-type external fixator and the unilateral external fixator. We hypothesized that the plate-type external fixator could provide higher stiffness, while retaining sufficient strength. Methods Fifty-four cadaver tibias underwent a standardized midshaft osteotomy to create a fracture gap model to simulate a comminuted diaphyseal fracture. All specimens were randomly divided into three groups of eighteen specimens each and stabilized with either the unilateral external fixator or the two configurations of the plate-type external fixator. Six specimens of each configuration were tested to determine fixation stiffness in axial compression, four-point bending, and torsion, respectively. Afterwards, dynamically loading until failure was performed in each load mode to determine construct strength and failure modes. Results The plate-type external fixator provided higher stiffness and strength compared with the traditional unilateral external fixator. The highest biomechanics was observed for the classical plate-type external fixator, with the extended plate-type external fixator close behind. Conclusions The plate-type external fixator is stiffer and stronger than the traditional unilateral external fixator under axial compression, four-point bending and torsion loading conditions.
Path analysis of skin cancer preventive behaviors in rural women based on protection motivation theory
Authors: Kaviani Abdol-Hossain , Khorsandi Mahboobeh , Roozbahani Nasrin
Published: October 2019

Background: Determining factors affecting adopting preventive behaviors of skin cancer is helpful in designing interventions promoting these behaviors. The present study was conducted aimed to analyze preventive behaviors’ path of skin cancer in rural women based on protection motivation theory.
Methods: In this cross-sectional study, 230 rural women in the west of Iran were selected randomly. Data were collected by a valid and reliable questionnaire including demographic information and structures of protection motivation theory by interview with rural women and then analyzed using SPSS 22 and LISREL8.8.
Results: In relation with skin cancer preventive behaviors, 27.8% of women were dressed up when working under the sun, 21.7% used sunscreen cream, 5.7% wore cap and 4.8 wore gloves and sunglasses. Protection motivation theory and per capita income explained 76% of motivation variance and 25% of the variance of skin cancer preventive behaviors. Response efficacy structure was the strongest predictor of the motivation of protection (0/001> p, ß= -0.44) and per capita income (0/001> p, ß= -0.34) and motivation (0/001> p, ß= -0.33) were the strongest predictors of these behaviors.
Conclusions: This study showed that protection motivation theory is efficient in predicting preventive behaviors of skin cancer and promoting interventions of the behaviors can be designed and implemented by this theory. It is also necessary to perform proper planning in promoting these behaviors in people with low per capita income.
Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment
Authors: Chen Wenli , Hua Xiaoxiao , Yu Weiguang , Liu Jun , Xiao Li , Han Guowei
Published: October 2019

Background

The purpose of this study was to compare the efficacy of osimertinib (OSI) versus afatinib (AFA) in patients with T790M-positive, non-small-cell lung cancer (NSCLC) and multiple central nervous system (CNS) metastases after failure of initial epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment.

Methods

The cohort consisting of 124 patients (OSI: n=60, median age=64.24 years [range, 51.91 to 76.57]; AFA: n=64, median age=64.13 years [range, 50.41 to 77.85]) with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment were consecutively identified at the Cancer Medical Center, Sun Yat-Sen University between March 2017 and July 2017; patients underwent either oral OSI (80 mg/day) or oral AFA (40 mg/day) until the occurrence of disease progression, intolerable adverse events (AEs), or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS).

Results

After a median follow-up of 24 months (range, 6 to 26), a significant improvement in OS was observed in the OSI group compared with the AFA group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.23 - 0.41; p = 0.009; median, 13.0 versus 9.2 months). The median duration of PFS was significantly longer with OSI than with AFA (HR 0.25, 95% CI 0.11 - 0.34; p = 0.001; median, 5.4 versus 4.3 months). The proportion of grade 3 or higher AEs was lower with OSI (22.4%) than with AFA (39.4%).

Conclusion

In patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment, OSI was associated with significantly improved survival benefit compared with AFA, and OSI exhibited a controllable tolerability profile.
The development and external validation of a nomogram predicting overall survival for gastric cancer patients with inadequate lymph nodes based on an international database
Authors: Li Shuangxi , Desiderio Jacopo , Li Ziyu , Tozzi Federico , Ji Jiafu , Parisi Amilcare
Published: October 2019

Background The inadequate lymph nodes could lead to stage migration and indicate a poor prognosis for gastric cancer after curative surgery. Some emerging novel predictors and the methodology of nomogram could increase the accuracy of survival prediction.Methods An international database regarding gastric cancer was employed as the primary cohort. The patients with inadequate (<30) lymph nodes (LN) were analyzed by Cox proportional hazards regression. Based on the selected model, a nomogram was plotted and calibrated by the external validation database.Results A total of 1109 patients were included in the primary cohort, and 6584 patients in the validation cohort. There were significant differences regarding the clinical characteristics between the two cohorts. The model containing age, T stages, N stages, metastatic lymph nodes (mLN), and the number of total LN retrieved (TLN) showed superiority over the conventional TNM stages. The Harrell's concordance index of the nomogram and TNM stages was 0.744 and 0.717 respectively. The external validation demonstrated a good concordance with the nomogram-predicted survival.Conclusions The nomogram containing age, T stages, N stages, mLN, and TLN had a better accuracy than the conventional TNM staging system in predicting overall survival for gastric cancer patients with inadequate (<30) LNs.
COESA - Sustainable, healthy cities: Protocol of a mixed methods evaluation of a cluster randomized controlled trial for Aedes control in Brazil using a community mobilization approach
Authors: Zinszer Kate , Caprara Andrea , Lima Antonio , Degroote Stéphanie , Zahreddine Monica , Abreu Kellyanne , Carabali Mabel , Charland Katia , Dantas Mayana Azevedo , Wellington José , Parra Beatriz , Fournet Florence , Bonnet Emmanuel , Pérez Denis , Robert Emilie , Dagenais Christian , Benmarhnia Tarik , Andersson Neil , Ridde Valéry
Published: October 2019

Background: Dengue is increasing in its global presence with an estimated 4 billion people at-risk of infection in at least 128 countries. Despite the promising results of EcoHealth and community mobilization approaches to Aedes reduction, more evidence of their efficacy on reducing dengue risk is needed. The principal research question is to determine if interventions based upon community mobilization reduce the risk of dengue virus infection among children 3 to 9 years old compared to usual dengue control practice in Fortaleza, Brazil. Methods: The present study will follow a pragmatic cluster randomized controlled trial (cRCT) design with randomization at the census tract level with equal allocation to the two arms. In each arm, there will be 34 clusters of 86 children between 3 to 9 years old for an expected total of 5,848 children enrolled in the study, assuming a risk reduction of 29.5% based upon findings from a previous multi-site cRCT. The primary outcomes are rates of anti-dengue Immunoglobulin G (IgG) seroconversion and adult female Aedes density. The intervention is based upon a participatory health research approach, Socializing Evidence for Participatory Action (SEPA), where the research evidence is used to foster community engagement and ownership of the health issue and solution. Following allocation, intervention communities will develop and implement their own solutions that will likely include a wide variety of collective events and media approaches. Data collection activities over a period of three years include household visits for blood collection, household surveys, and entomological surveys; and qualitative activities including focus groups, indepth interviews, and document analysis to evaluate the process, acceptability, fidelity, and sustainability of the intervention. Study participants will be aware of their assignment and all research staff will be blinded although the intervention assignment will likely be revealed to field staff through interaction with participants. Discussion: The results of our study will provide evidence on community mobilization as an intervention for dengue control. We anticipate that if community mobilization is effective in Fortaleza, the results of this study will help develop evidence-based vector control programs in Brazil, and also in other countries struggling with Aedes-transmitted diseases.
Diagnosis of EBV-Associated Inflammatory Pseudotumor in the Spleen: A Case Report
Authors: Chebotarev Dmitrii Il'ich , Kovrigina A.M. , Korzhova S.M. , Danishyan K.I. , Sabirov K.R.
Published: October 2019

The paper focuses on Epstein-Barr virus (EBV)-associated inflammatory pseudotumor in the spleen, an extremely rare disease which so far remained undefined in the Russian literature. The morphology of it is not characterized by any specific features and is represented by a spindlecell component with pronounced inflammatory infiltration which complicates differential diagnosis. Previously this nosology was regarded within a group of the so-called inflammatory pseudotumors due to the similarity of the clinical course and radiological presentation with tumor processes. Today the term “inflammatory pseudotumor” is considered obsolete, since as pathogenesis was being studied within this disease group, the individual forms with similar morphology and different histogenesis were identified. Differential diagnosis in the context of additional diagnostic techniques is based in such cases on a wide range of reactive states, benign and malignant tumors.
Role of Biochemical Inflammatory Markers in Patients with Chemotherapy-Induced Neutropenia
Authors: Dubinina Yuliya Nikolaevna , Sarzhevskii V.O. , Melnichenko V.Ya.
Published: October 2019

The growing number of autologous and allogeneic transplantations of bone marrow and hematopoietic stem cells as well as their technological effectiveness give rise to drug antineoplastic therapies with increased toxicity leading to development of complications. The most serious among this sort of complications are infections. Probability of infections in patients with chemotherapy-induced neutropenia reaches 90 %. In this context the search for an optimal marker of infectious complications becomes more and more important. The present review deals with basic biochemical inflammatory markers and the analysis of trials assessing diagnostic and prognostic value of C-reactive protein, procalcitonin, and presepsin.
Critical colored-RVB states in the frustrated quantum Heisenberg model on the square lattice
Authors: Poilblanc Didier , Mambrini Matthieu , Capponi Sylvain
Published: October 2019

We consider a family of SU(2)-symmetric Projected Entangled Paired
States (PEPS) on the square lattice, defining colored-Resonating Valence
Bond (RVB) states, to describe the quantum disordered phase of the
J_1-J_2J1−J2
frustrated Heisenberg model. For J_2/J_1\sim 0.55J2/J1∼0.55
we show the emergence of critical (algebraic) dimer-dimer correlations –
typical of Rokhsar-Kivelson (RK) points of quantum dimer models on
bipartite lattices – while, simultaneously, the spin-spin correlation
length remains short. Our findings are consistent with a spin liquid or
a weak Valence Bond Crystal in the neighborhood of an RK point.
Economic assessment of the accidental risk of natural emergencies for train traffic
Authors: Popov V. G. , Sukhov F. I. , Bolandova Yu. K.
Published: October 2019

Aim. The paper is dedicated to the evaluation of the risk of transportation accidents caused by natural emergencies affecting train traffic on a specific line. The ever-growing anthropogenic burden on the environment inevitably causes climate change that, in turn, gives rise to higher numbers of extreme weather events. The latter usually cause industrial accidents and disasters. The assessment of the factors of climate-related risk that quantitatively characterize their effect on the railway infrastructure is the starting point of calamity risk management and adaptation of human activities to the ever-changing climate.

Methods. The authors propose a method of risk assessment that takes into consideration the effect of various natural emergencies that affect rolling stock in motion. The method is based on elements of the probability theory and mathematical statistics. The developed method enables the assessment of the risk of a transportation accident caused by natural emergencies specific to not only a line, but a route on a railway network.

Results. For the Nevinnomysskaya – Tuapse line that includes 6 sections of the North Caucasus Railway, one of which was damaged due to abundant precipitations on October 24 and 25, 2018, the risk of transportation accident caused by the effects of three types of natural emergencies on the sociotechnical system of this line has been calculated:

– flood,

– hurricane with wind strength of over 22 mps,

– heavy rain.

The parameters of such emergencies are characterized by the following factors:

– frequency as compared to other types of emergencies,

– average annual number of natural emergencies,

– characteristic spatial scale of the natural emergency,

– characteristic duration of the natural emergency.

The conditional probabilities of the effects on the railway sociotechnical system of an event that has characteristic spatial scale and duration and has caused a transportation accident involving a train were estimated based on the assumption that a train flow in space follows the normal Erlang distribution of the k-th kind. The risk of transportation accident involving up and down trains travelling along the i-th line of the j-th railway caused by a hazardous effect of a natural emergency of the m-th type is identified subject to the jointness of events. Using the discounting method, an equation was obtained for estimating the mathematical expectation of economic damage by traffic safety disturbances, which allowed estimating the economic component of the risk.

Conclusions. As the result, a method is proposed for estimation of the risk of transportation accidents caused by natural emergencies, an example is provided of such risk estimation, including the economic component, for the Nevinnomysskaya – Tuapse line.
Nglyc: A Random Forest Method for Prediction of N-Glycosylation Sites in Eukaryotic Protein Sequence
Authors: Pugalenthi Ganesan , Nithya Varadharaju , Chou Kuo-Chen , Archunan Govindaraju
Published: October 2019

Background:

N-Glycosylation is one of the most important post-translational mechanisms in eukaryotes. N-glycosylation predominantly occurs in N-X-[S/T] sequon where X is any amino acid other than proline. However, not all N-X-[S/T] sequons in proteins are glycosylated. Therefore, accurate prediction of N-glycosylation sites is essential to understand Nglycosylation mechanism.

Objective:

In this article, our motivation is to develop a computational method to predict Nglycosylation sites in eukaryotic protein sequences.

Methods:

In this article, we report a random forest method, Nglyc, to predict N-glycosylation site from protein sequence, using 315 sequence features. The method was trained using a dataset of 600 N-glycosylation sites and 600 non-glycosylation sites and tested on the dataset containing 295 Nglycosylation sites and 253 non-glycosylation sites. Nglyc prediction was compared with NetNGlyc, EnsembleGly and GPP methods. Further, the performance of Nglyc was evaluated using human and mouse N-glycosylation sites.

Results:

Nglyc method achieved an overall training accuracy of 0.8033 with all 315 features. Performance comparison with NetNGlyc, EnsembleGly and GPP methods shows that Nglyc performs better than the other methods with high sensitivity and specificity rate.

Conclusion:

Our method achieved an overall accuracy of 0.8248 with 0.8305 sensitivity and 0.8182 specificity. Comparison study shows that our method performs better than the other methods. Applicability and success of our method was further evaluated using human and mouse N-glycosylation sites. Nglyc method is freely available at https://github.com/bioinformaticsML/ Ngly.
Correlation between the Activity of Aldehyde Dehydrogenase and Oxidative Stress Markers in the Saliva of Diabetic Patients
Authors: Younus Hina , Ahmad Sumbul , Alam Md. Fazle
Published: October 2019

Background:

Reactive aldehydes are involved in diseases associated with oxidative stress, including diabetes. Human salivary aldehyde dehydrogenase (hsALDH) presumably protects us from many toxic ingredient/contaminant aldehydes present in food.

Objective:

This study aimed to probe the activity of hsALDH in patients with diabetes and than to correlate it with various oxidative stress markers in the saliva.

Methods:

The saliva samples were collected from total 161 diabetic patients from Rajiv Gandhi Centre for Diabetes, Jawaharlal Nehru Medical College (JNMC), AMU, Aligarh, (India). HsALDH activity and markers of oxidative stress [8-hydroxydeoxyguanosine (8-OHDG), malondialdehyde (MDA) and advanced glycation end products (AGEs)] were measured in the saliva samples.

Results:

Patients with early stage of diabetes had higher activity of hsALDH when compared with the control group. As the history of diabetes increases, the activity of the enzyme decreases and also higher oxidative stress markers (8-OHDG, MDA and AGEs) are detected in the saliva samples. Negative significant correlation between hsALDH activity and oxidative stress markers were observed (p <0.0001).

Conclusion:

The activity of hsALDH increases in early stages of diabetes most probably to counter the increased oxidative stress associated with diabetes. However, in later stages of diabetes, the activity of the enzyme decreases, possibly due to its inactivation resulting from glycation.
Multivariate Optimization of the Refolding Process of an Incorrectly Folded Fc-Fusion Protein in a Cell Culture Broth
Authors: Behrouz Hossein , Molavi Behnaz , Tavakoli Ata , Askari Mansoureh , Maleknia Shayan , Mahboudi Fereidoun , Khodadadian Mehdi
Published: October 2019

Background:

Protein misfolding is a common problem in large-scale production of recombinant proteins, which can significantly reduce the yield of the process.

Objective:

In this work, we aimed at treating a cell culture broth containing high levels (>45%) of incorrectly folded Fc-fusion proteins by a simple redox buffer system in order to increase the proportion of the protein with correct conformation.

Methods:

Multi-variable process optimization was firstly conducted at a small scale (25 mL), employing an experimental design methodology. After identifying the key variables using a resolution IV Fractional Factorial Design (FFD), the process was then optimized by the Central Composite Design (CCD).

Results:

The optimal conditions for the refolding reaction were 340 mM Tris-base, 6.0 mM L-cysteine, 0.5 mM L-cystine, a buffer pH of 9.0, a reaction temperature of 8.5ºC and a reaction time of 24 h. Based on the treatment conditions obtained at a small scale, the process was further scaled up to 4500- L. The misfolded content was always less than 20%. The reaction can proceed well in the absence of chemical additives, such as chaotropic agents, aggregation suppressors, stabilizers and chelators.

Conclusion:

The refolding process increases the fraction of active protein in the original broth reducing the burden on downstream purification steps markedly.
Characterizations and Fibrinolytic Activity of Serine Protease from Bacillus subtilis C10
Authors: Thu Nguyen T.A. , Khue Nguyen T.M. , Huy Nguyen D. , Tien Nguyen Q.D. , Loc Nguyen H.
Published: October 2019

Background:

Fibrinolytic enzymes, such as Nattokinases from Bacillus species are known
to degrade the fibrin blood clots. They belong to serine protease group having commercial applications,
such as therapeutic agents and functional food formulation.

Objective:

The present study reports some characteristics and fibrinolytic activity of serine protease
from B. subtilis C10 strain that was isolated from shrimp shell.

Method:

Extracellular enzyme from B. subtilis C10 culture was harvested and partially purified by
ammonium sulphate precipitation. Fibrinolytic activity of the enzyme was determined by zymography
and measured by spectrophotometry with fibrinogen and thrombin used as substrates. The optimal
temperature and pH for fibrinolytic activity were studied in the range of 31-43ºC and 5-10, respectively.
The thermal and pH stability of enzyme was studied by incubating enzyme for 30 min in the same
range of temperature and pH as above. The effect of some metal ions and reagents on fibrinolytic activity
of enzyme was evaluated by concentrations of 5 mM and 5%, respectively.

Results:

Zymogram analysis indicated the presence of four fibrinolytic enzymes with molecular
weights of approximately 69, 67, 39 and 36 kDa. The optimal temperature and pH for enzyme activity
were 37°C and 9, respectively. The thermal and pH stability ranged from 35-39°C and 8-10, respectively.
Fibrinolytic activity reached a maximum value of about 400 U/mg protein after 16 h of C10
strain culture. Enzyme has been drastically inhibited by PMSF and SDS, and partially inhibited by
EDTA, while Triton X-100 has significantly increased enzyme activity. Effects of ions such as Mg2+,
Ca2+ and Mn2+ on enzyme were negligible, except Cu2+ and Zn2+ have strongly decreased its activity.

Conclusion:

Results from the present study suggested that enzyme obtained from B. subtilis C10 could
be serine protease that has a high fibrinolytic activity up to about 400 U/mg protein at the most appropriate
temperature and pH of 37ºC and 9. This activity can be improved up to 142% by incubating enzyme
with 5% Triton X-100 for 30 min.