bluuebunny/crossref_metadata_2025 huggingface dataset:
Range and niche expansion through multiple interspecific hybridization - a Genotyping by Sequencing analysis of Cherleria (Caryophyllaceae)
Authors: Moore Abigail Jane , Messick Jennifer A. , Kadereit Joachim W.
Published: May 2020

Background
Cherleria (Caryophyllaceae) is a circumboreal genus that also occurs in the high mountains of the northern hemisphere. In this study, we focus on a clade that diversified in the European High Mountains, which was identified using nuclear ribosomal (nrDNA) sequence data in a previous study. With the nrDNA data, all but one species was monophyletic, with little sequence variation within most species. Here, we use genotyping by sequencing (GBS) data to determine whether the nrDNA data showed the full picture of the evolution in the genomes of these species.
Results
The overall relationships found with the GBS data were congruent with those from the nrDNA study. Most of the species were still monophyletic and many of the same subclades were recovered, including a clade of three narrow endemic species from Greece and a clade of largely calcifuge species. The GBS data provided additional resolution within the two species with the best sampling, C. langii and C. laricifolia, with structure that was congruent with geography. In addition, the GBS data showed significant hybridization between several species, including species whose ranges did not currently overlap.
Conclusions
The hybridization led us to hypothesize that lineages came in contact on the Balkan Peninsula after they diverged, even when those lineages are no longer present on the Balkan Peninsula. Hybridization may also have helped lineages expand their niches to colonize new substrates and different areas. Not only do genome-wide data provide increased phylogenetic resolution of difficult nodes, they also give evidence for a more complex evolutionary history than what can be depicted by a simple, branching phylogeny.
Preliminary result of carbon-ion radiotherapy using the spot scanning method for prostate cancer
Authors: Takakusagi Yosuke , Kato Hiroyuki , Kano Kio , Anno Wataru , Tsuchida Keisuke , Mizoguchi Nobutaka , Serizawa Itsuko , Yoshida Daisaku , Kamada Tadashi
Published: May 2020

Background: Carbon-ion radiotherapy (CIRT) for prostate cancer was initiated at Kanagawa Cancer Center in 2015. The present study analyzed the preliminary clinical outcomes of CIRT for prostate cancer. Methods: The clinical outcomes of 253 patients with prostate cancer who were treated with CIRT delivered using the spot scanning method between December 2015 and December 2017 were retrospectively analyzed. The irradiation dose was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. Biochemical relapse was defined using the Phoenix definition. Toxicities were assessed according to CTCAE version 4.0. Results: The median patient age was 70 (47–86) years. The median follow-up duration was 35.3 (4.1–52.9) months. According to the D’Amico classification system, 8, 88, and 157 patients were classified as having low, intermediate, and high risks, respectively. Androgen deprivation therapy was administered in 244 patients. The biochemical relapse-free rate in the low-, intermediate-, and high-risk groups at 3 years was 87.5%, 88.0%, and 97.5%, respectively (P = 0.036). Grade 2 acute urinary toxicity was observed in 12 (4.7%) patients. Grade 2 acute rectal toxicity was not observed. Grade 2 late urinary toxicity and grade 2 late rectal toxicity were observed in 17 (6.7%) and 3 patients (1.2%), respectively. Previous transurethral resection of the prostate was significantly associated with late grade 2 toxicity in univariate analysis. The predictive factor for late rectal toxicity was not detected.Conclusion: The present study demonstrated that CIRT using the spot scanning method for prostate cancer produces favorable outcomes.
The Association between dietary total antioxidant capacity with the risk of helicobacter pylori infection among adult: a case–control study
Authors: Sohouli Mohammadhassan , Haghshenas Niloufar , Fatahi Somaye
Published: May 2020

Background Dietary total antioxidant capacity (DTAC) has been assumed as a useful tool to assess the relationship between the cumulative antioxidant food capacity and several chronic disorders. The aim of this study was to evaluate the association between DTAC and risk of Helicobacter pylori in a case-control study.Methods This case-control study was carried out among 150 patients with Helicobacter pylori and 302 healthy subjects aged 18–55 years. Dietary data were collected using a validated 168- items quantitative food frequency questionnaire. DTAC was calculated based on the ferric reducing-antioxidant power (FRAP) values that reported by US Department of Agriculture. Results The mean age and BMI of the study participants were 38.70 years and 25.86, respectively. Compared with control subjects, participants with H pylori significantly were older and had higher BMI and smoking use. Patients with H pylori compared with control individuals had also lower intake of total fiber, vitamin E, vitamin C, vitamin D, total dairy, whole grain and vegetables. Compared with participants in the lowest tertile of DTAC, those in the highest terrtile had a significantly lower OR for H pylori after further adjustment for potential confounders (Model 2: OR, 0.20; 95% CI, 0.10 – 0.40; P for trend, < 0.001).Conclusions Our findings showed that a high DTAC was associated with a reduced risk of Helicobacter pylori in adult, which reflects the increased intake of natural dietary antioxidants to prevent the progression of Helicobacter pylori. However, further studies are needed to investigate the t relation between DTAC and risk of Helicobacter pylori.
Detection of Speaker De-identification Disguise Based on Dense Convolutional Network
Authors: Wang Yong , Su Zhuoyi , Zhu Zhengyu
Published: May 2020

Nowadays, speaker disguise is a common operation that presents a great challenge to social security. Therefore, it is important to recognize the authenticity of speech. Most of the current researches focus on speech spoofing, which simulates a target speaker to break through the state-of-art ASV systems by increasing false acceptance rate. Meanwhile, there is another type of disguise, i.e. de-identification, which transforms a speech signal without a target to increase the false rejection rate in order not to be recognized. It has received far less attention. Therefore, in this paper, we investigate the de-identification model and propose a method to detect de-identification speeches from genuine speeches by using a very deep dense convolutional network with 135 layers. The experimental results show that the average accuracy of the proposed method outperforms the reported state-of-the-art methods.
DNMT1 facilitates proliferation and metastasis of breast cancer cells by promoting MEG3 promoter methylation in MEG3/miR-494-3p/OTUD4 regulatory axis
Authors: Zhu Xiaotao , Lv Lin , Wang Mingzheng , Fan Chen , Lu Xiaofeng , Jin Miaomiao , Li Shuguang , Wang Fan
Published: May 2020

Background

To explore the mechanism of DNMT1 facilitating proliferation and metastasis of breast cancer cells by promoting MEG3 promoter methylation in MEG3/miR-494-3p/OTUD4 regulatory axis.
Methods

Human breast cancer cell lines (MCF-7, MDA-MB-231, SKBR3) and human breast epithelial cell line MCF10A were selected for the experiments. The expressions of DNMT1, MEG3, miR-494-3p and OTUD4 were detected by qRT-PCR. Western blot was used to detect the protein expressions of DNMT1 and OTUD4. ChIP assay verified the binding relationship of DNMT1 and MEG3 promoter region. MEG3 methylation and its level were test by MethPrimer software and MSP, respectively. The targeted binding sites of miR-494-3p and MEG3/OTUD4 were predicted by bioinformatics. RIP and dual-luciferase reporter gene assays verified the combination of miR-494-3p and MEG3/OTUD4. Cell proliferation, migration and invasion abilities were detected by CCK-8, wound healing and Transwell assays.
Results

DNMT1 was highly expressed while MEG3 was poorly expressed in breast cancer cells. Silencing DNMT1 inhibited the proliferation, migration and invasion of breast cancer cells by promoting the expression of lncRNA MEG3 through demethylation. MEG3 as a ceRNA regulated the expression of miR-494-3p in breast cancer. In addition, miR-494-3p could bind to the 3’-UTR of OTUD4, thus negatively regulating the expression of OTUD4 and forming the MEG3/miR-494-3p/OTUD4 regulatory axis that affected the proliferation, invasion and migration of breast cancer. Overexpression of MEG3 could inhibit breast cancer tumor growth in vivo.
Conclusion

Silencing DNMT1 promoted the expression of MEG3 through demethylation, which inhibited the expression of miR-494-3p to promote the expression of downstream target OTUD4, thus inhibiting the proliferation, migration and invasion abilities of breast cancer cells.
Sleep states detection using halfwave and Franklin transformation
Authors: Paul Yash , Fridli S.
Published: May 2020

Sleep is a physiological phenomenon and a sufficient amount of sleep is mandatory for a human for his/her health. Three biomedical signals namely Blood, EEG and Nasal are used to identify various sleep stages. The discrete version of these signals is piecewise linear function and applied two piecewise linear data reduction techniques namely a new Halfwave method in time domain and Franklin transformation in frequency domain on the discrete versions of these selected signals. As a result we obtained two piecewise linear functions with low complexity that still preserve the characteristics of the stages of the sleep in the signals. The components of the feature vector are generated from the parameters of the two reduced piece wise linear functions. Algorithm is tested on MIT-BIH Polysomnographic Database having more than 70 hours long term EEG, Blood and Nasal signals with six different sleep classes. Proposed method shows better performance so far on such long duration data in terms of Sensitivity, Specificity, Accuracy and False Alarm Rate/hour. Algorithm achieved an average sensitivity, specificity accuracy and false alarm rate of 98.35% and 97.32%, 96.96%, 0.029 respectively for two classes, 96.62% and 97.10%, 93.94%, 0.030 for 4 classes, 96.13% and 98.33%, 93.84%, 0.016 for all (six) classes.
Toward developing a metastatic or neoadjuvant breast cancer treatment strategy that incorporates history of response to previous treatments
Authors: Olow Aleksandra K. , Veer Laura J. van't , Wolf Denise M.
Published: May 2020

Background: Information regarding response to past treatments may provide clues concerning the classes of drugs most or least likely to work for a particular metastatic or neoadjuvant early stage breast cancer patient. However, currently there is no systematized knowledge base that would support clinical treatment decision-making that takes response history into account.Methods: To model history-dependent response data we leveraged a published in vitro breast cancer viability dataset (84 cell lines, 90 therapeutic compounds) to calculate the odds ratios (log(OR)) of responding to each drug given knowledge of (intrinsic/prior) response to all other agents. This OR matrix is assuming (1) response is based on intrinsic rather than acquired characteristics, and (2) intrinsic sensitivity remains unchanged at the time of the next decision point. Fisher’s exact test is used to identify predictive pairs and groups of agents (BH p<0.05). Recommendation systems are used to make further drug recommendations based on past ‘history’ of response.Results: Of the 90 compounds, 57 have sensitivity profiles significantly associated with those of at least one other agent, mostly targeted drugs. Nearly all associations are positive, with (intrinsic/prior) sensitivity to one agent predicting sensitivity to others in the same or a related class (OR>1). In vitro conditional response patterns clustered compounds into five predictive classes: (1) DNA damaging agents, (2) Aurora A kinase and cell cycle checkpoint inhibitors; (3) microtubule poisons; (4) HER2/EGFR inhibitors; and (5) PIK3C catalytic subunit inhibitors. The apriori algorithm implementation made further predictions including a directional association between resistance to HER2 inhibition and sensitivity to proteasome inhibitors.Conclusions: Investigating drug sensitivity conditioned on observed sensitivity or resistance to prior drugs may be pivotal in informing clinicians deciding on the next line of breast cancer treatments for patients who have progressed on their current treatment. This study supports a strategy of treating patients with different agents in the same class where sensitivity was previously observed.
Community midwifery model’s effect on availability, utilization and outcomes of maternal and newborn health services in hard-to-reach communities of Busia Kenya: a Quasi-experimental study
Authors: Shikuku Duncan Ndombi , Tanui Geofrey , Wabomba Mercy , Wanjala Dennis , Friday Josephine , Peru Taphroze , Atamba Evelyne , Sisimwo Kenneth
Published: May 2020

Background
Globally, poor women in hard-to-reach areas are least likely to receive healthcare and carry the burden of maternal and neonatal mortality related to complications of childbirth. Midwifery can avert 83% of all maternal & neonatal deaths and stillbirths. This study evaluated the effect of an enhanced community midwifery model (CMM) on skilled attendance during pregnancy and childbirth and maternal and perinatal outcomes against the background of protracted healthcare workers' strikes in rural Kenya.
Methods
A quasi-experimental (one-group pretest-posttest) designed. Six-months pretest period: December’2016-May’2017. Between Dec’2016-Feb’2017 (period 1) - a doctors’ strike and March-May’2017 (period 2), normal healthcare services resumed. An enhanced CMM (using 10 CMs linked to 6 health facilities) was implemented in the proceeding 5-months posttest period (period 3) – June-October’2017 during the national nurses/midwives’ strike. Differences in performance means for MNH variables of interest between the three periods were computed by ANOVA. Two-groups test of proportions for before and during/after the enhanced CMM computed.
Results
There were differences in mean monthly attendance for community midwifery services for the three periods: 1st ANC (1.8-2.3-9.9, P = 0.0087), 4th ANC (1.4-1.0-7.1, P = 0.0212), skilled births (1.5-1.7-13.1, P < 0.0001). Mean attendance at facility were: 1st ANC (55.7-70.8-4.0), 4th ANC (29.6-38.1-1.2) and skilled births (63.1-87.4-5.6), P ≤ 0.05. No differences in attendance between the doctors’ strike and normalcy period for both CMs and health facilities’ MNH services (P ≥ 0.05). However, significant increases for CMs MNH services during the nurses/midwives strike and significant reductions at the facility level during the same period (P ≤ 0.05). An increase of 68%, 74.5%, 67.8% and 33.3% in the proportion of 1st and 4th ANC, skilled births and PNC conducted by CMs during/after the CMM respectively (P ≤ 0.0001). A double and triple reduction in macerated stillbirths (0.70%-0.36%) and neonatal deaths (0.54%-0.18%) respectively and an increase in babies discharged alive (98.05%-100%) with no change in maternal deaths during/post intervention.
Conclusions
There was improvement in access/utilization of pregnancy and childbirth services from CMs. There is a golden opportunity to integrate the CMs to primary health care system to improve uptake of MNH care services through an enhanced CMM strategy in hard-to-reach communities.
Changes in the Spectrum of Dental Emergencies Under the Influence of SARS-COV-2
Authors: Wu Kan , Li Chunjie , Yang Zheng , Yang Shangchun , Yang Wenbin , Hua Chengge
Published: May 2020

BackgroundTo master the distribution and changing characteristics of dental diseases is of great significance for the dental emergency center in order to strengthen the treatment abilities of medical staff and the effective use of emergency resources in the face of public health emergencies of highly infectious respiratory diseases.MethodsThe medical records of 4260 cases of dental emergency patients from December 2019 to March 2020 were retrospectively analyzed, with patients being divided into the pre- Corona Virus Disease 2019 (SARS-COV-2) group and the during SARS-COV-2 group according to the date of their admittance to the dental emergency department. The patient demographics, occurrence of dental emergencies and treatment approaches were compared before and during the pandemic.ResultsDuring the pandemic period, the number of dental emergency visits increased by 25.56% compared with those before the pandemic. From the view of demographic, the proportion of patients aged 0 –17 years decreased by 10.6%, while the proportion of patients aged 46 – 65 years increased by 6.9%. The emergency patient amount reduced during the week and increased at the weekend, the distribution of the peak time of patient visits was 13:00 – 18:00, and the emergency patient amount at night decreased obviously compared with that before the outbreak of the epidemic.A major change is acute pulpitis/root periarthritis ratio increased by 9.2%, fell 17.9%, before the outbreak on dental and maxillofacial trauma stitch, the residual roots and residual crowns and other non-emergency diseases increased by 3.2%. Among the treatment methods, dental local drug irrigation, dental local hemostasis, and local treatment of pericoronitis were the main treatment approaches, accounting for 63.1% of the total cases. The use of local anesthesia decreased and the use of painkillers increased during the SARS-COV-2 pandemic.ConclusionSARS-COV-2 led to changes in the spectrum of dental emergency cases. The dental emergency department should optimize the treatment procedures, optimize the staffing and reasonably allocate materials according to the changes, to improve the on-site treatment capacity and provide adequate dental emergency care.
Mapping and Territorial Risk Analysis of Hospital Admissions due to Community-Acquired Pneumonia in Children (Brazil)
Authors: Pina Juliana Coelho , Alves Luana Seles , Furtado Maria Cândida de Carvalho , Arcêncio Ricardo Arcêncio , Gondim Ellen Cristina , de Mello Débora Falleiros
Published: May 2020

Background
The concentration of child morbidity and mortality due to pneumonia in developing countries reflects the social inequities, which lead to greater exposure to risk factors and make access to prevention, diagnosis and treatment of the disease more difficult. This study aimed to map and assess the territorial risk for hospitalization due to Community-Acquired Pneumonia in children under 5 years of age.
Methods
Ecological study, carried out in the city of Ribeirão Preto, state of São Paulo, Brazil. The study population consisted of hospitalized children under the age of five, diagnosed with community-acquired pneumonia, in Ribeirão Preto-São Paulo-Brazil, from 2012 to 2013. Data were collected in different databases, by a trained team, between March 2012 and August 2013 and from the 2010 Demographic Census of the Brazilian Institute of Geography and Statistics. The 956 urban census tracts were considered as the units of analysis. Descriptive statistics were performed for the sociodemographic characteristics, with the calculation of measures of absolute frequency and proportions for the categorical variables, using the Statistica software (12.0). The incidence of cases per 10,000 inhabitants was calculated by census tracts during the study period. For the identification of the spatial risk clusters, the Kernel density estimator and the Getis-Ord Gi* technique were measured from the Radius of the distance of 7,589 km, with p < .01, found using the Incremental Spatial Autocorrelation tool.
Results
The study included 265 children under the age of five, hospitalized due to community-acquired pneumonia. A concentration of cases was identified in the regions with greater social vulnerability (low income, poor housing conditions and homelessness), as well as a lower occurrence of cases in the most developed and economically privileged area of the city. The majority of the children lived in territories served by traditional primary healthcare units, in which the health surveillance and family and community focus are limited.
Conclusions
The results contribute to the comprehension of the social factors involved in child hospitalization due to pneumonia, based on the analysis of the spatial distribution, and address the interface with individual and institutional factors.
Early or delayed sigmoid resection in complicated diverticular disease? A single center experience
Authors: Tschann Peter , Lechner Daniel , Feurstein Benedikt , Adler Stephanie , Girotti Paolo , Fleischmann Isabella , Hufschmidt Martin , Königsrainer Ingmar
Published: May 2020

Background:Diverticular disease appears to be one of the most common conditions in the western world. The standard approach in treatment of diverticular disease is a laparoscopic resection, usually after an inflammation free time of 4 to 6 weeks. The aim of this study was to evaluate the timing of operation.Methods:61 patients underwent left-sided colonic resection because of diverticular disease between January 2017 and February 2020. 37 patients were treated because of complicated diverticulitis (CDD stage 2a or 2b) either early within 7 days after first symptoms (group A: n = 17) or delayed about 6 weeks after the first contact and conservative therapy (group B: n = 20).Results:Overall mortality was 0%. The average operation time was shorter in the early elective group (Group A: 140,4 min vs. Group B: 151,2 min (p = 0,29). The hospital stay (group A: 9,9 d vs. group B: 16,9 d) and the postoperative stay (group A: 4,8 d vs. group B: 8,1 d) was significantly longer in group B (p = 0,01). We observed – although not reliable due to low number of patients - more postoperative complications in the delayed group (group A: 5,9% vs. group B: 15,0%) (p = 0,61).Conclusion:The data in this study confirm the early operation as safe and efficient due to lower costs. We can recommend an early approach in selected cases with the first episode of a complicated diverticulitis.
A Crisis within a Crisis: COVID-19 Knowledge and Awareness among the Syrian Population—A National Survey Assessment
Authors: Mohsen Fatema , Bakkar Batoul , Armashi Humam , Aldaher Nizar
Published: May 2020

Background: COVID-19 is an infectious respiratory disease that emerged from a wet market in Wuhan China and quickly exploded into a global pandemic. This coronavirus has overwhelmed public health systems worldwide, and forced governments to impose draconian lockdowns of entire populations. With no vaccine or treatment to date, it is of paramount importance to assess the public’s awareness about COVID-19 so that knowledge gaps among the population can be targeted with prevention-focused educational campaigns. The aim of this study is to examine the Syrian public’s awareness and knowledge regarding COVID-19. Methods: This web-based cross-sectional study was distributed randomly in March 2020, nearly 10 year into the Syrian war crisis. The survey consists of a series of questions about socio-demographic characteristics, knowledge of the causative agent, incubation period, treatment, transmission pathways, clinical features, and prevention methods. Data was analysed using the statistical Package for Social Sciences version 25.0.Results: Of the 3586 participants, 68.2% were females, 50.8% were unemployed, and 79.2% were at college-educated. The study revealed good awareness regarding COVID-19 (mean 75.6%, SD±9.4%). Multiple linear regression analysis correlated knowledge scores with gender, education level, occupation, economic status, and the number of household members.Conclusion: This study revealed some potentially troubling knowledge gaps which underscore the need for a vigorous public education campaign. This campaign must reinforce the public's awareness, knowledge, and vigilance towards precautionary measures against COVID-19 and, most importantly aid in controlling the worldwide spread of the disease.
Impacts and lessons learned from the local production of WHO-Recommended Alcohol-Based Hand Rub during Covid-19 Pandemic in Uganda.
Authors: Fred Tusabe , Otita Morgan , Kesande Maureen , Fred Twinomugisha
Published: May 2020

In January 2020, the World Health Organization (WHO) declared the outbreak of a new coronavirus disease, COVID-19. The WHO and the Centers for Disease Control and Prevention (CDC) recommend using an alcohol-based hand rub (ABHR) as one of the measures to combat the spread of COVID-19. Objective To assess the impacts and lessons learned from the local production of WHO-recommended alcohol-based hand rub during the COVID-19 Pandemic in Uganda. Method Space for local production was identified at a health facility in Central Uganda that was air-conditioned and well ventilated. Volunteers were trained on the local production of ABHR. The volunteers were trained theoretically and practically for Four days; and each was able to produce at least a batch of ABHR. Logistical support for supplying the raw materials needed for production was from the Infectious Diseases Institute. There were also already established ABHR production units and trained staff on local production of ABHR in 2019 in the Kabarole and Kasese districts, respectively in Western Uganda. These districts were threatened by several outbreaks, including Ebola virus disease, and were monitored for ABHR production during the COVID-19 Pandemic. Result Two production units were set up during the Ebola outbreak, in awake of COVID-19, a production unit in Kasese, was able to produce 3020 litres, and the Kabarole unit produced 2020 litres respectively. A new production unit was set up at Kasangati HCIV in central Uganda and eight laboratory technologists trained on Local Production of ABHR, and within Eleven days they were able to produce 2300ltrs. Conclusion The initiative to produce WHO-recommended hand rub locally during an outbreak is feasible, especially in a resource-limited country like Uganda. There is a need to rapidly scale-up the production capacity of ABHR and to ensure and maintain quality assurance at each production unit.
Synthesis of a novel green carbon dots as a bioimaging agent and a drug delivery system for enhanced antioxidant and antibacterial efficacy
Authors: Tejwan Neeraj , Kundu Mousumi , Sharma Anirudh , Das Joydeep , Sil Parames C
Published: May 2020

Background

Now-a-days, synthesis of carbon dots (CDs) from renewable sources has attracted considerable attention due to their wide spread availability, lower cost, higher aqueous solubility and more biocompatibility. Here, we have synthesized water soluble CDs from the root extract of red Korean ginseng via simple microwave irradiation. The CDs were further loaded with a natural flavonoid, rutin, to check its efficacy as a drug delivery system.
Result

The CDs showed a size distribution between 1–4 nm and excitation-dependent fluorescence emission, and could be used as a bio-imaging agent.The CDs showed a drug loading content of 14% and a sustained drug release behavior at physiological conditions. CDs showed excellent free radical scavenging activity both in cell free systems and intra-cellular conditions. Besides, loading with the drug further improved the intra-cellular radical scavenging activity. The CDs and the nanohybrids also showed very little toxicity upto the concentration of 100 µg/mL in normal kidney epithelial cells. The CDs and the nanohybrids also showed a dose-dependent antibacterial effect against both gram negative as well as gram positive bacteria.
Conclusion

Our synthesized green CDs can be considered as a promising candidate for the biomedical applications due to its facile synthesis, low cytotoxicity, excellent fluorescent properties and potential as drug delivery systems.
Discovery of Vanoxerine Dihydrochloride as a CDK2/4/6 Triple-Inhibitor for the Treatment of Human Hepatocellular Carcinoma
Authors: Zhu Ying , Shi Xi-Nan , Xia Zhong-Kun , Li Hong-Jian , Su Rong , Ke Kun-Bin , Dong Chao , Zhou Feng-Mei , Wang Lin , Chen Rong , Wu Shi-Guo , Zhao Hui , Gu Peng , Leung Kwong-Sak , Wong Man-Hon , Lu Gang , Zhang Jian-Ying , Jiang Bing-Hua , Qiu Jian-Ge , Lin Marie Chia-mi
Published: May 2020

Background Cyclin-dependent kinases 2/4/6 (CDK2/4/6) play critical roles in cell cycle progression, and their deregulations are hallmarks of hepatocellular carcinoma (HCC).Methods Here we combined computational and experimental approaches to discover a CDK2/4/6 triple-inhibitor from FDA approved small-molecule drugs for the treatment of HCC.Results Based on molecular docking results, vanoxerine dihydrochloride was found to exhibit strongest cytotoxic effect on human HCC QGY7703 and Huh7 cells (IC50: 3.79 µM for QGY7703and 4.04 µM for Huh7 cells). Vanoxerine dihydrochloride treatment caused G1arrest, induced apoptosis, and reduced the expressions of CDK2/4/6, cyclin D/E, retinoblastoma protein (Rb), as well as the phosphorylation of CDK2/4/6 and Rb in QGY7703 and Huh7 cells. In addition, combined vanoxerine dihydrochloride and 5-Fu produced synergistic cytotoxicity in Huh7 cells. Finally, in vivo studies in preclinical animal model of BALB/C mice subcutaneously xenografted with Huh7 cells, we showed that injection of vanoxerine dihydrochloride (40 mg/kg, i.p.) produced significant antitumor activity (p < 0.05), comparable to that achieved by 5-Fu (10 mg/kg, i.p.), with the combination treatment resulted in strongest effect.Conclusions The present study is the first to identify a CDK2/4/6 triple inhibitor vanoxerine dihydrochloride, and demonstrate that it represents a novel therapeutic strategy for HCC treatment alone or in combination with 5-Fu.
Combination Therapy of CDK4/CDK6 Inhibitor Palbociclib and Irradiation in non-Malign and Malign Cells
Authors: Jost Tina , Hecht Markus , Kapfer Paula , Heinzerling Lucie , Fietkau Rainer , Distel Luitpold
Published: May 2020

Background: The CDK 4/6 kinase inhibitor palbociclib is approved for first line treatment of metastatic breast cancer in combination with hormonal therapy and investigated within clinical trials for melanoma. In metastatic disease frequently palliative radiation treatment is necessary. Due to recent findings of radiosensitizing effects of palbociclib in HNSCC and HCC, a possible influence of palbociclib on radiosensitivity was studied in malign and non-malign cells. Methods: Different tumor cells and primary fibroblasts were treated with palbociclib and ionizing radiation (IR) in 2D and 3D cell cultures. Clonogenic assays were performed to study the sensitizing effect of palbociclib on irradiation induced cytotoxicity. Apoptosis, necrosis and cell cycle distribution was analyzed by flow cytometry. Cell migration was studied with scratch assays. Results: The effect of irradiation on skin cancer cells could be slightly decreased by palbociclib in four out of eight cells comparing 2 Gy vs. 2 Gy + 1 µmol/L in the 2D cell culture model. The 3D cell culture model detected differences in cell death more sensitive than the 2D model. Necrosis was increased in primary fibroblasts (0.2 µmol/L + IR vs. IR; p = 0.0041), whereas apoptosis was decreased in skin cancer cells ICNI (0.2 µmol/L + IR vs. IR with p = 0.0005 // 2 µmol/L + IR vs. IR with p = 0.0072). Overall palbociclib attenuated radiation induced cell death in skin and breast cancer cells. In malign cells combination therapy seems to rise senescence in clonogenic assays, whereas healthy controls showed more cell death. Palbociclib did not influence cell cycle distribution in the fibroblasts but led to an accumulation of the tumor cells in G0/G1 cell cycle phase. Additionally, palbociclib decreased migration behavior of the malign and non-malign cells, but without influence on e-cadherin expression during inhibitor treatment.Conclusions: Palbociclib increases the radiosensitivity of primary fibroblasts. In cancer cells palbociclib seems to be radioprotective. This effect in cancer cells is probably based on the accumulation of cells in the less radiosensitive G0/G1 cell cycle phase. Further studies are needed to assess whether a combined therapy of palbociclib and radiation is appropriate.
Safety risk assessment model based on comprehensive weight - set pair analysis theory for heritage buildings adjacent to metro construction
Authors: Wang Qian , Yang Changming , Tian Lin , Lu Jiguang , Wu Fengwen , An Jianyong
Published: May 2020

With the rapid development of urban rail transit systems, the safety of nearby heritage buildings and historic sites is threatened. To better protect these heritage buildings and sites, it is crucial to be able to rapidly and accurately evaluate these threats, especially when a rail project has a potential impact upon numerous heritage buildings and sites in an old city. Based on set pair analysis (SPA) theory, this paper presents a risk assessment model to assess the safety of heritage buildings adjacent to metro construction. First, the risk level of adjacent heritage buildings is graded. Second, this study establishes an assessment index system comprising 16 single indexes among four categories related to heritage building, metro, soil, and management, and determines the threshold for the level of corresponding risk for each evaluation factor. To improve the reliability of the index weighting, a linear weighting method is adopted, which comprehensively considers subjective weights calculated by the analytic hierarchy process and objective weights calculated by the clustering weight method. Finally, the proposed SPA model is verified by using it to assess the structural safety risk of a heritage building adjacent to the Zhengzhou Metro Line Three. By extracting the field measured data at different survey points on the metro line, the risk levels of the heritage building in the shield tunneling process are evaluated, and the results verify the feasibility of the SPA model. The proposed SPA method can provide decision-making support for controlling risk on similar projects.
Assessing the Intrinsic and Extrinsic Drivers and Targeting the Observed Resilience of Malaria in Northwestern and Southern Tanzania: A Protocol for a Cross-Sectional Exploratory Study
Authors: Chiduo Mercy G , Mandara Celine I. , Rumisha Susan F. , Chaky Frank , Francis Filbert T. , Mmbando Bruno P. , Seth Misago D. , Challe Daniel P. , Ndekuka Leah , Massawe Isolide S. , Liheluka Edwin , Makunde Williams H. , Mhina Athanas D. , Baraka Vito , Segeja Method D. , Derua Yahya A. , Batengana Berndard M. , Hayuma Paul M. , Nkya Gineson , Madebe Rashid A. , Malimi Masunga C. , Mandike Renata , Mkude Sigsbert , Molteni Fabrizio , Njau Ritha , Mohamed Ally , Ishengoma Deus S.
Published: May 2020

Background Despite high coverage and successes in malaria control strategies, some areas of Tanzania have indicated stagnantion or revesal of malaria burden. In malaria research, most studies are designed to assess drivers of malaria transmission focusing only on one dimension, single location while very few studies assess multiple components and their interactions. This article describes the protocol used to assess intrinsic and extrinsic drivers of persistent malaria transmission (hotsposts) in four regions from northwestern (Geita and Kigoma) and southern (Ruvuma and Mtwara) Tanzania.Results: Preliminary results show that 6,297 HHs and 28,361 individuals with median age of 16yrs (IQR= 7-35yrs) were registered from the 16 villages. Over 49% of individuals used bed-nets in the previous night before the survey and 43.9% of HHs had bed-nets covering two members per household. For parasitological survey, 25.8% of registered individuals (n=7,313) were selected from 2,527 HHs (40.1%) and invited for assessment and sampling. The positivity rate (PR) by mRDTs was 33.3% (range = 21.9% to 41.1%); while by microscopy, the PR was 20.6% and varied from 8.0% to 29.0%. Socio-anthropology interviews were conducted with a total of 1,687 heads/representatives of HHs. For qualitative surveys 32 Focus group discussion (two from each village) and 16 key informant interviews (two per district) were conducted. Thirty-one health facilities were visited for health system survey; 19.4% (n=6) were hospitals; 41.9% (n=13) health centres and 38.7% (n=12) dispensaries. For entomological survey, 8,891 adult mosquitoes were collected, whereby Anopheles gambiae complex, An. funestus group and other mosquitoes accounted for 12.0%, 49.7% and 38.3%, respectively.Conclusion: An analysis plan using data from the five components surveyed has been proposed and results from this study are expected to determine factors potentially responsible for persistence of malaria (hotspots) in the study areas. Rather than the traditional methodology of focusing on one metric, the approach will triangulate observations from all five components, highlighting understanding of potential drivers while studying their complex interactions and map spatial heterogeneity. This study will provide an important framework and data which will guide future studies and malaria surveillance in Tanzania and other malaria endemic countries.
Impact of career choice motivation on academic burnout in senior dental students
Authors: Mohebbi Simin Z. , Gholami Mahdia , Chegini Mostafa , Ghoreyshi Younes , Gorter Ronald C. , Bahramian Hoda
Published: May 2020

Background
Motivation is the basis of many activities including learning, and lack of career motivation can lead to decreased efficiency. This study assessed the association between academic burnout and career choice motivation in senior dental students.
Methods
This cross-sectional study evaluated senior dental students of all four dental schools in Tehran, in 2017. Dental students voluntarily filled-out a 33-question questionnaire with three parts. The first part of the questionnaire included the Burnout Clinical Subtype Questionnaire (BCSQ-SS) with 12 questions regarding academic burnout. The second part included 8 questions regarding career choice motivations and the third part included 13 questions regarding demographics. The individual scores of each domain and the total score were reported. The factor analysis of 8 questions regarding dental career choice motivation yielded 3 factors of social status and security, altruism, and others’ advice motivations. Data were analyzed using the regression test.
Results
Totally, 131 students filled out the questionnaire (response rate = 86%). The total score of academic burnout was 38.89% ± 1.13%. The highest and the lowest burnout scores belonged to domains of “overload” (46.69%± 1.46%) and “neglect” (31.98%± 1.32%), respectively. The most and the least frequent motivations of students for choosing dentistry were high income and failing to enter other fields, respectively. The burnout score was higher in students with altruism motivations (P = 0.007) and lower in students with others’ advice motivations (P = 0.004). The burnout score was higher in students with inadequate or moderate financial support from the family and lower in students whose mothers’ educational level was equal or lower than high-school diploma.
Conclusion
Senior dental students in Tehran were involved with different levels of academic burnout. Low financial support and altruism as study motivations in career choice were associated with higher level of academic burnout.
A Critical Role for Immune System-released Activating Agent (Israa) in the Ontogenetic Development of the Brain
Authors: Al-Awadi Aminah M. I. , AlJawder Abdulaziz Isa , Mousa Alyaa , Taha Safa , Bakhiet Moiz
Published: May 2020

Background: The Immune System-Released Activating Agent (ISRAA) was discovered as a novel molecule that functions as a mediator between the nervous and immune systems in response to a nervous stimulus following an immune challenge. Thisresearch investigated the role ofISRAA)in promoting the ontogeny of the mouse brain. Methods: Astrocyte cultures were prepared from two-month-old BALB/c mice. Recombinant ISRAA protein was used to stimulate astrocyte cultures. Immunohistochemistry and ELISA were utilized to measure ISRAA andIFN-g levels, IFN-gR expression and STAT1 nuclear translocation. MTT-assay was used to evaluate cellular survival and proliferation. To assess astrocyte cell lysates and tyrosine-phosphorylated proteins, SDS-PAGE and western blot were used.Results: ISRAA was highly expressed in mouse embryonic astrocytes,depending on cell age. Astrocytes agedseven days (E7) showed increased proliferation and diminisheddifferentiation, while 21-day-old (E21)astrocytes depictedreversed effects. ISRAAstimulated the tyrosine phosphorylation of numerous cellular proteins and thenuclear translocation of STAT1. IFN-g was vital for ISRAAactionas ISRAA induced IFN-gin both age groups, but only E21 astrocytes expressed IFN-gR. Conclusion: The results suggest that ISRAA is cruciallyinvolved in mouse brain development through the cytokine network involving IFN-g.
What’s the “Secret Sauce”? How Implementation Variation Affects the Success of Colorectal Cancer Screening Outreach
Authors: Coury Jennifer , Miech Edward J. , Styer Patricia , Petrik Amanda F. , Coates Kelly E. , Green Beverly B. , Baldwin Laura-Mae , Shapiro Jean A. , Coronado Gloria
Published: May 2020

Background Mailed fecal immunochemical testing (FIT) programs can improve colorectal cancer (CRC) screening rates, but health systems often vary implementation (i.e., adapt) these programs for their organizations. A health insurance plan implemented a mailed FIT program (named BeneFIT) and allowed participating health systems to adapt the program. This mixed-methods study explored which program adaptations might have achieved higher screening rates.Methods We used a multi-method approach. First, we conducted a descriptive analysis of CRC screening rates by key health system characteristics and program adaptations. Second, we applied Configurational Comparative Methods (CCMs) to determine potential explanatory factors consistent with higher screening rates. The main outcome measure was CRC screening rates.Results Seventeen health systems took part in at least one year of BeneFIT. The overall screening completion rate was 20% (4–28%) in Year 1, and 25% (12–35%) in Year 2 of the program. Health systems that used two or more adaptations had higher screening rates, and no single adaptation clearly led to higher screening rates. In Year 1, smaller systems (having < 2 clinics) with phone reminders (n = 2) met the implementation success threshold (≥ 19% screening rate) while larger systems were successful when offering a patient incentive (n = 4), scrubbing mailing lists (n = 4), or allowing mailed FIT returns with no other adaptations (n = 1). In Year 2, large systems (> 2 clinics) were successful with a phone reminder (n = 4) or a patient incentive (n = 3). Of the 10 systems that implemented BeneFIT in both years, seven improved in Year 2.Conclusions Health systems can choose between many adaptations and successfully implement a health plan’s mailed FIT program. Screening completion rates are positively associated with the number of adaptations implemented by a health system. Health system size emerged as an important contextual factor, with different solutions for larger than smaller health systems.Contributions to the Literature· Our paper analyzes adaptations that enable health care providers to implement mailed fecal immunochemical testing (FIT) programs in delivery systems.· Our results explore which adaptations made by health systems to mailed FIT programs are related to screening rate improvements. Our analysis shows that a health system’s organizational characteristics in combination with the adaptations themselves may affect resulting CRC screening rates and implementation.· Our paper describes different pathways that health care organizations can use to implement CRC screening outreach to improve the health of their populations. We show results of implementation flexibility and customizing CRC screening outreach to particular clinic environments.
A Risk Signature with Immune and Inflammatory Cells Infiltration in Gastric Cancer Predicts Survival and Efficiency of Chemotherapy
Authors: Li Sen , Wang Wenpeng , Ma Pengfei , Zhang Junli , Cao Yanghui , Liu Chenyu , Zhang Xijie , Chen Li , Song Shubing , Li Zhiguo , Zhao Yuzhou
Published: May 2020

Background In order to accurately predict outcomes of gastric cancer (GC), we developed a risk signature with tumor infiltration immune and inflammatory cells for prognosis.Methods A risk signature model in combination with CD66b + neutrophils, CD3 + T, CD8 + T lymphocytes, and FOXP3 + regulatory T cells was developed in a training cohort of 327 GC patients undergoing surgical resection between 2011 and 2012, and validated in a validation cohort of 285 patients from 2012 to 2013.Results High CD66b expression predicted poor disease-special survival (DSS) as well as inversely correlated with CD8 (P < 0.05) and FOXP3 expression (P < 0.05) in the training cohort, comparable disease-free survival (DFS) findings were observed in the validation cohort.Furthermore, a risk stratification was developed from integration of CD66b + neutrophils and T immune cells. In both DFS and DSS, the high-risk group all demonstrated worse prognosis than low-risk group in both the training cohort and the validation cohort (all P < 0.05). In addition, the high-risk group was associated with post-operative relapses. Furthermore, this risk signature model increase the predictive accuracy and efficiency for post-operative relapses. At last, the high-risk group identified a subgroup of GC patients who tend to not benefit from adjuvant chemotherapy.Conclusions Incorporation of neutrophils into T lymphocytes could provide more accurate prognostic information in GC, and this risk stratification predicted survival benefit from post-operative adjuvant chemotherapy in GC.
Development and psychometric properties of the HBM- based Substance Abuse Prevention Questionnaire (HBM-SAPQA) among Afghanian students
Authors: Mohammadi Kanali , Tavafian Sedigheh sadat , Tavousi Mahmoud
Published: May 2020

Background
In Afghanistan, adolescents and young people are the most important at risk groups for substance abuse. Considering the importance of model-based interventions, this study aims to design and validate a questionnaire based on the Health Belief Model (HBM) for assessing the beliefs of Afghan students regarding substance abuse prevention behavior.
Methods
This study was conducted in two stages. Firstly, the items of the questionnaire were designed by conducting a combined documentary literature review and qualitative study. In the next step, its psychometric properties were evaluated through qualitative and quantitative formal validity (calculation of impact score), qualitative and quantitative content validity - Content Validity Ratio (CVR) and Content Validity Index (CVI)- and structural validity through Factor Explanatory Analysis (FEA). Finally, consistency compatibility through Cronbach’s alpha as well as reliability (internal correlation) test re-test were assessed. To above steps, the SPSS version 18 was applied.
R esults
74 items were obtained for the questionnaire by performing a qualitative study and using existing scientific sources for literature review. In the study of formal validity of quantitative items, the effect coefficient of all above 1.5 was calculated. The CVR of each item was more than 0.8 (mean 0.93), and their CVI was more than 0.79. In this stage, 12 items related to cues to action hanged to 1 item with 12 options so all 63 remained items were retained in the questionnaire. In FEA 40 items related to main constructs of HBM were assessed by which, by eliminating 2 items, structural validity was confirmed for 38 items in 5 factors and covering about 40% of the variance for EFA 408 students with average age of 23 years old were assessed. In the internal compatibility process, the acceptable values ​​of Cronbach's alpha between 0.71 and 0.81 were calculated for all factors. Test re test approved to assess reliability of the instrument.
Conclusion
The HBM-SAPQA tool obtained the acceptable validity/reliability to apply the beliefs of Afghan students regarding substance abuse preventive behavior. Although the result of this study showed, this questionnaire has good validity and reliability, but this result should be confirmed in future studies.