bluuebunny/crossref_metadata_2025 huggingface dataset:
Seroprevalence and some Demographic Factors Associated with Toxoplasma gondii Infection among Male Population in Duhok Province/Iraq
Authors: Eassa et al. Souzan
Published: June 2020

The present study aims to investigate the seroprevalence rate of Toxoplasma gondii infection and its relation to some demographic factors among males in Duhok province/Iraq. A total of 424 random blood samples were collected from the male population of different ages (18-60) years and different social-economic classes. Out of 424 samples examined, 108 (25.47%) were seropositive to the anti- T. gondii antibodies; 88 (20.75%) were found seropositive for IgG, while 20 (4.72%) samples were seropositive for IgM. Regarding occupation, the highest percentage for chronic toxoplasmosis was reported in workers followed by policemen and pensioners at rates of 23.96%, 23.6%, and 23.07%, respectively. The age group 18-30 years showed the highest seropositive rate which was 26.6%; the seropositivity rate decreased with the increase of age. Regarding the blood groups, the highest percentage of IgG was reported in both O+ and B- groups, which were 23.2% and 23.1%, respectively. The higher rate of seropositivity was observed among married males (21.32%) as compared to unmarried males (19.05%) and fertile (22.3%) versus sterile males (12.5%). Concerning IgM antibodies, the highest seropositivity (9.4%) was reported in infertile males. The results of this study showed the importance of demographic factors to the epidemiology of T. gondii in males, which support the role of public health in the control of infectious diseases.
Characterization and Biological Activity of Some New Derivatives Derived from Sulfamethoxazole Compound
Authors: Alsahib Sanaa abdul
Published: June 2020

A new series of Sulfamethoxazole derivatives was prepared and examined for antifibrinolytic and antimicrobial activities. Sulfamethoxazole derivatives bear heterocyclic moieties such as 1,3,4-thiadiazine {3},  pyrazolidine-3,5-diol {4} 6-hydroxy-1,3,4-thiadiazinane-2-thione {5} and [(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)diazenyl] {8}. Their structures were elucidated by spectral methods (FT-IR, H1-NMR). Physical properties are also determined for all compound derivatives.  Recently prepared compounds were tested for their antimicrobial activity in the laboratory. Each screened compound showed good tendency to moderate antimicrobial activity.
Strong Subordination for E -valent Functions Involving the Operator Generalized Srivastava-Attiya
Authors: Al-Khafaji Thamer Khalil MS. Al
Published: June 2020

Some relations of inclusion and their properties are investigated for functions of type " -valent that involves the generalized operator of Srivastava-Attiya by using the principle of strong differential subordination.
The Jacobson Radical of the Endomorphism Semiring of P.Q.- Principal Injective Semimodules
Authors: Aljebory et al. Khitam
Published: June 2020

In this work, we introduced the Jacobson radical (shortly Rad (Ș)) of the endomorphism semiring Ș =  ( ), provided that  is principal P.Q.- injective semimodule and some related concepts, we studied some properties and added conditions that we needed. The most prominent result is obtained in section three

-If   is a principal self-generator semimodule, then (ȘȘ) = W(Ș).

Subject Classification: 16y60
On the Growth of Solutions of Second Order Linear Complex Differential Equations whose Coefficients Satisfy Certain Conditions
Authors: Alkhalidy Ayad , Hussein Eman
Published: June 2020

In this paper, we study the growth of solutions of the second order linear complex differential equations  insuring that any nontrivial solutions are of infinite order. It is assumed that the coefficients satisfy the extremal condition for Yang’s inequality and the extremal condition for Denjoy’s conjecture. The other condition is that one of the coefficients itself is a solution of the differential equation .
بعض خواص الفضاءات الخطية ضد المعيارية الضبابية المنتهية الابعاد
Authors: Hussein et al. Esraa
Published: June 2020

في هذا البحث تعريف الفضاءات الخطية ضد المعيارية وافضل خواصها تم استخدامها لبرهان بعض الخواص للفضاءات الخطية ضد المعيارية الضبابية المنتهية الابعاد
Comparison of Various Particle-Size Distribution-Measurement Methods
Authors: Roostaei Morteza , Hosseini Seyed Abolhassan , Soroush Mohammad , Velayati Arian , Alkouh Ahmad , Mahmoudi Mahdi , Ghalambor Ali , Fattahpour Vahidoddin
Published: June 2020

Sieve analysis, sedimentation, and laser diffraction (LD) have been the methods of choice in determining particle-size distribution (PSD) for sand control design. However, these methods do not provide any information regarding the particle shape. In this study, we introduce the application of dynamic image analysis (DIA) to characterize particle sizes and shape descriptors of sand-bearing formations.

DIA, which is an advanced method of particle size and shape characterization, along with other PSD measurement methods, including sieving, sedimentation, and LD, were used to study size and shape variations of 372 unconsolidated formation sand samples from North America, Latin America, and the Middle East. Different methods were compared in the estimation of PSD and fines content, which are the primary factors important in sand-control design.

Through minimizing the sampling and measurement errors, the deviation between different PSD measurement techniques was attributed solely to the shape of the particles and the amount of fine fraction. For fines-content measurement, the values obtained through Feret min parameter values (the minimum size of a particle along all directions) calculated by DIA and sieving measurement are comparable within a 5% confidence band. The deviation between the results of different methods becomes more significant by increasing fines content. Moreover, this deviation increases for less isodiametric grains. The fines and clay content show higher values when measured by any wet analysis. LD also tends to overestimate the fines fraction and underestimate silt/sand fraction compared with other dry techniques. By comparing the deviation of the DIA and sieving at standard mesh sizes, an algorithm has been developed that chooses the equivalent sphere sizes of DIA with minimum deviation from sieving.

This study performs several measurements on formation sands to illustrate the real advantage of the new methods over traditional measurement techniques. Furthermore, particle-shape descriptors were used to explain the deviation between the results of different PSD measurement methods.
A preliminary assessment of vital-signs-integrated patient-assisted intravenous opioid analgesia (VPIA) for postsurgical pain
Authors: SNG Ban Leong , Tan Daryl Jian'an , TAN Chin Wen , HAN Nian-Lin Reena , SULTANA Rehena , SIA Alex Tiong Heng
Published: June 2020

Background: We developed a Vital-signs-integrated Patient-assisted Intravenous opioid Analgesia (VPIA) analgesic infusion pump, a closed-loop vital signs monitoring and drug delivery system which embodied in a novel algorithm that took into account patients’ vital signs (oxygen saturation, heart rate). The system aimed to allow responsive titration of personalized pain relief to optimize pain relief and reduce the risk of respiratory depression. Moreover, the system would be important to enable continuous monitoring of patients during delivery of opioid analgesia.Methods: Nineteen patients who underwent elective gynecological surgery with postoperative patient controlled analgesia (PCA) with morphine were recruited. The subjects were followed up from their admission to the recovery room/ ward for at least 24 hours until assessment of patient satisfaction on the VPIA analgesic infusion pump.Results: The primary outcome measure of incidence of oxygen desaturation showed all patients had at least one episode of oxygen desaturation (<95%) during the study period. Only 6 (31.6%) patients had oxygen desaturation that persisted for more than 5 minutes. The median percentage time spent during treatment that oxygen saturation fell below 95% was 1.9%. Fourteen (73.7%) out of 19 patients encountered safety pause, due to transient oxygen desaturation or bradycardia. The patients’ median [IQR] pain scores at rest and at movement after post-op 24 hours were 0.0 [2.0] and 3.0 [2.0], respectively. The average morphine consumption in the first 24 hours was 12.5 ± 7.1mg. All patients were satisfied with their experience with the VPIA analgesic infusion pump. Conclusions: The use of VPIA analgesic infusion pump, when integrated with continuous vital sign monitor and variable lockout algorithm, was able to provide pain relief with good patient satisfaction.Keywords: infusion pump, postoperative pain, vital sign monitoring, oxygen desaturation.Trial registration: This study was registered on clinicaltrials.gov registry (NCT02804022) on 28 Feb 2016.
Six-minute walking distance in healthy Chinese people older than 60 years
Authors: Zou He , Zhang Jia , Zou Yingying , Chen Xiaoshu , Wang Yi , Shiwei Huang , Ye Fanhao , Yu Haizhu
Published: June 2020

Introduction: The six-minute walking test (6MWT) is a tool that plays a key role in evaluating the functional exercise capacity, prognosis and evaluation of treatment response of patients with various cardiopulmonary diseases. However, standard reference equations are currently unavailable for the six-minute walking distance (6MWD) for people aged 60-85 years in China. The purpose of this study was to 1) measure the 6MWD of healthy Chinese people aged 60-85 years, 2) establish reference equations for predicting the 6MWD, and 3) compare our reference equations with equations reported in previously published studies.Method: We obtained informed consent from each participant prior to the test, and the research design was approved by the Ethics Committee of Wenzhou People’s Hospital. The demographic and anthropometric data and the 6MWD of healthy Chinese subjects aged 60-85 years old were measured using a standardized protocol. Every subject completed two 6MWTs, and the longest 6MWD further analyzed.Results: Two hundred sixty-six subjects (128 males and 138 females) completed the 6MWT, and the mean walking distance was 518±72 m. Males achieved a longer walking distance than females (518±72 m vs. 487±70m; p<0.0001), and active subjects achieved a longer walking distance than nonactive subjects (512±76 m vs. 485±63 m; p<0.0001). According to the univariate analysis, the 6MWD was significantly associated with age, height, body mass index (BMI), heart rate and blood pressure after exercise and changes in heart rate before and after exercise. The stepwise multivariate regression analysis identified age, height and BMI as independent predictors of the 6MWD. The reference equations for Caucasians and South Americans tended to overestimate the 6MWD of our subjects, while the equations for Asian and African populations tended to underestimate the 6MWD.Conclusions: This study is the first to describe the 6MWD of healthy Chinese people aged 60-85 years, and reference prediction equations were proposed. These findings will help to improve the evaluation of Chinese patients with diseases that affect exercise capacity.
PS4DR: A multimodal workflow for identification and prioritization of drugs based on pathway signatures
Authors: Emon Mhammad Asif , Domingo-Fernández Daniel , Hoyt Charles Tapley , Hofmann-Apitius Martin
Published: June 2020

Background: During the last decade, there has been a surge towards computational drug repositioning owing to constantly increasing -omics data in the biomedical research field. While numerous existing methods focus on the integration of heterogeneous data to propose candidate drugs, it is still challenging to substantiate their results with mechanistic insights of these candidate drugs. Therefore, there is a need for more innovative and efficient methods which can enable better integration of data and knowledge for drug repositioning. Results: Here, we present a customizable workflow ( PS4DR) which not only integrates high-throughput data such as genome-wide association study (GWAS) data and gene expression signatures from disease and drug perturbations but also takes pathway knowledge into consideration to predict drug candidates for repositioning. We have collected and integrated publicly available GWAS data and gene expression signatures for several diseases and hundreds of FDA-approved drugs or those under clinical trial in this study. Additionally, different pathway databases were used for mechanistic knowledge integration in the workflow. Using this systematic consolidation of data and knowledge, the workflow computes pathway signatures that assist in the prediction of new indications for approved and investigational drugs. Conclusion: We showcase PS4DR with applications demonstrating how this tool can be used for repositioning and identifying new drugs as well as proposing drugs that can simulate disease dysregulations. We were able to validate our workflow by demonstrating its capability to predict FDA-approved drugs for their known indications for several diseases. Further, PS4DR returned many potential drug candidates for repositioning that were backed up by epidemiological evidence extracted from scientific literature. Source code is freely available at https://github.com/ps4dr/ps4dr .
Epidemiology, vaccine effectiveness, and risk factors for mortality for pneumococcal disease among hospitalised adults in Singapore: a case-control study
Authors: Chan Tyson , Tay Min Zhi , Kyaw Win Mar , Chow Angela , Ho Hanley J
Published: June 2020

Background: Streptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore. Methods: Retrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015-2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design. Results: We identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1±15.4yrs, and 65.5% were male. Compared with controls (N=9,181), IPD patients were younger (mean age 61.5±16.3yrs, vs 72.2±16.1yrs in controls; p<0.001) and with less co-morbidities [median Charlson’s score 1 (IQR 0-4), vs 3 (1-5) in controls; p<0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8-17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio=0.20, 95%CI 0.06–0.69; p=0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥85yrs and Charlson’s score >3.Conclusion: Patients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.
A three-arm, multicenter, open-label randomized controlled trial of hydroxychloroquine and low-dose prednisone to treat recurrent pregnancy loss in women with undifferentiated connective tissue diseases: Protocol for the immunosuppressant regimens for Living FEtuses (ILIFE) Trial
Authors: Yang Shaoying , Ni Ruoning , Lu Yikang , Wang Suli , Xie Feng , Zhang Chunyan , Lu Liangjing
Published: June 2020

Background: Undifferentiated connective tissue disease (UCTD) is known to induce adverse pregnancy outcomes, and even recurrent spontaneous abortion (RSA) by placental vascular damage and inflammation activation. Anticoagulation can prevent pregnancy morbidities. However, it is unknown whether the addition of immune suppressant to anticoagulation can prevent spontaneous pregnancy loss in UCTD patients. The purpose of this study is to evaluate the efficacy of hydroxychloroquine (HCQ) and low-dose prednisone on recurrent pregnancy loss for women with UCTD.Methods: The Immunosuppressant for Living Fetuses (ILIFE) Trial is a three-arm, multicenter, open-label randomized controlled trial with the primary objective of comparing hydroxychloroquine combined with low-dose prednisone and anticoagulation with anticoagulation alone in treating UCTD women with recurrent spontaneous abortion. The third arm of using hydroxychloroquine combined with anticoagulant for secondary comparison. A total of 426 eligible patients will be randomly assigned to each of the three arms with a 1:1:1 allocation ratio. The primary outcome is the rate of live births. Secondary outcomes include adverse pregnancy outcomes and progression of UCTD.Discussion: This is the first multi-center, open-label, randomized controlled trial which evaluates the efficacy of immunosuppressant regimens on pregnancy outcomes and UCTD progression. It will provide evidence on whether the immunosuppressant ameliorates the pregnancy prognosis in UCTD patients with RSA and the progression into defined connective tissue disease. Trial registration: ClinicalTrials.gov, NCT03671174. Registered on 14 September 2018. https://www.clinicaltrials.gov/ct2/show/NCT03671174
Self- Care Practices and Associated Factors among Adult Diabetic Patients in Public Hospitals of Dire Dawa Administration, Eastern Ethiopia
Authors: Getie Asmare , Geda Biftu , Alemayhu Tadesse , Bante Agenehu , Aschalew Zeleke , Alemu Biresaw wassihun
Published: June 2020

Background: Diabetes is a huge growing problem, and causes high and escalating costs to the society. Self- care practice for adults with diabetes is not well addressed in sub-Saharan Africa including Ethiopia. To prevent serious morbidity and mortality, diabetes treatment requires commitment to demanding self-care practice. The aim of this study was to assess self- care practices and its associated factors among adults with diabetes in Dire Dawa public hospitals of Eastern, Ethiopia.METHODS: Cross-sectional study was conducted among 513 adults with diabetes. The study participants were selected through systematic random sampling. Data was collected from February 1st to March 1st, 2018. Patients were interviewed using a structured questionnaire. Data were entered into Epi-data version 3.3.1 and exported to SPSS version 22.0 for analysis. Bivariable and multivariable logistic regression with crude and adjusted odds ratios along with the 95% confidence interval was computed and interpreted accordingly. Good self-care was defined based on mean calculation; a result above the mean value had a good self-care practice, and a P-value of <0.05 was considered to declare a result as statistically significant.RESULT: The result of the study showed that 55.9 %, (95% CI: 51.4, 60.3) of participants had good self-care practices. Good self-care practice was associated with having family support, treatment satisfaction, diabetes education, having glucometer, higher educational status, duration of the disease, high economic status and having good knowledge. There were statistical association between good diabetes knowledge (AOR= 2.14 , 95% CI :1.37, 3.35), family support system (AOR= 2.69, 95% CI:1.56, 4.62), treatment satisfaction (AOR= 2.07, 95% CI:1.18, 3.62), diabetes education (AOR= 2.21, 95% CI: 1.35, 3.63), high economic status (AOR= 1.89, 95% CI: 1.01, 3.48), having glucometer,(AOR=2.69, 95% CI:1.57, 4.63),higher educational status (AOR= 2.68 , 95% CI: 1.31, 5.49), and duration of disease greater than 10 years AOR=2.70, 95% CI: 1.17, 6.26) with good self-care practice.Conclusion: In this study a substantial number of the patients had poor self-care practices especially dietary practice and self-monitoring of blood glucose which have critical roles in controlling diabetes. Provision of diabetes self-care education and counseling especially on importance of self-monitoring of blood glucose, and dietary practice should be considered by responsible bodies.
Mobile X-ray outside the Hospital: a scoping review
Authors: Toppenberg Maria Dietz , Christiansen Thomas Erik Møller , Rasmussen Finn , Nielsen Camilla Palmhøj , Damsgaard Else Marie
Published: June 2020

Background: For several years mobile X-ray equipment has been routinely used for imaging in patients too unwell within the hospital, when transportation to the radiology department was inadvisable. Now, mobile X-ray examinations are also used outside the hospital. Objective: The literature describes that fragile patients may benefit from mobile X-ray, but we need to know if it is an evident alternative to hospital-based examination and in what populations.Data sources: To conduct this scoping review, we searched PubMed, Cinahl, Embase, EconLit and Health Technology Assessment. Study eligibility criteria: English-, Danish-, Norwegian-, German-, Italian-, French- and Swedish-language studies, published 1.1.2009- 1.5.2020 about mobile X-ray outside the hospital were included. Participants and interventions: Participants were patients examined using mobile X-ray as the intervention.Study appraisal and synthesis methods: PRISMA was used when eligible to build up the review. To extract data from the selected articles, we used a structured summary table. Results: We included 12 studies in this scoping review. The results were divided into four topics: 1. Target population 2. Population health 3. Experience of care and 4. Cost effectiveness.The conclusions is that target population could be larger, population health may be improved, image quality seems to be good and mobile X-ray may be cost effective. Limitations: Limitations of language, databases and grey literature may have resulted in studies outside western countries being missed. Conclusions: Mobile X-ray may be used outside hospital. There seems to be potential benefits to both patients and health care staff. Based on the published studies it is not possible to draw a final conclusion if mobile X-ray examination is a relevant diagnostic offer and for whom. Further studies are needed to assess the feasibility of use in fragile patients, also regarding staff, relatives and society.
Risk literacy assessment of general practitioners and medical students using the Berlin Numeracy Test
Authors: Friederichs Hendrik , Birkenstein Roman , Becker Jan C. , Marschall Bernhard , Weissenstein Anne
Published: June 2020

Background: The responsibility for helping patients understand potential health benefits and risks, especially regarding screening tests, falls largely to general practitioners (GPs). The Berlin Numeracy Test (BNT) specifically measures risk literacy (i.e., the ability to understand different aspects of statistical numeracy associated with accurate interpretation of information about risks). This study explored the association between risk literacy levels and clinical experience in GPs vs. medical students. Additionally, the effect of GP risk literacy on evaluation of the predictive value of screening tests was examined.Methods: The participants were 84 GPs and 92 third-year medical students who completed the BNT (total score range 0–4 points). The GPs received an additional case scenario on mammography screening as a simple measure of performance in applying numeracy skills.Results: Despite having an average of 25.9 years of clinical experience, GPs scored no better than medical students on risk literacy (GPs: 2.33 points, 95% confidence interval [CI] 2.08–2.59; students: 2.34, 95% CI 2.07–2.61; P = .983). Of all GPs, 71.6% (n = 58) greatly overestimated the real predictive value.Conclusions: In this study, we found no difference in risk literacy between current students and current GPs. GPs lack risk literacy and consequently do not fully understand numeric estimates of probability in routine screening procedures.
Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in the microglia.
Authors: Lin Shao-Peng , Wei Jue-Xian , Ye Shan , Hu Jiasong , Bu Jingyi , Zhu Lidong , Li Qi , Liao Haojun , Wu Yi , Lin Pei-Yi , Chen Sheng-Qiang , Chen Xiao-Hui
Published: June 2020

Background and purpose: Artemisinin has been in use as an anti-malarial drug for almost half a century in the world. There is growing evidence that artemisinin also possesses potent anti-inflammatory and immunoregulatory properties. However, the efficacy of artemisinin treatment in neurocognitive deficits associated with sepsis remains unknown. Here, we evaluate the possible protective effects and explore the underlying mechanism of artemisinin on cognitive impairment resulting from sepsis.Methods: Male C57BL/6 mice were pretreated with either vehicle or artemisinin, and then injected with LPS to establish an animal model of sepsis. The cognitive function was then assessed using the Morris water maze. Neuronal damage and neuroinflammation in the hippocampus were evaluated by immunohistochemical and ELISA analysis. Additionally, the protective mechanism of artemisinin was determined in vitro.Results: The results showed that artemisinin preconditioning attenuated LPS-induced cognitive impairment, neural damage, and microglial activation in the mouse brain. The in vitro experiment revealed that artemisinin could reduce the production of pro-inflammatory cytokines and suppress the microglial migration in the BV2 microglia cells. Meanwhile, western blot demonstrated that artemisinin suppressed nuclear translocation of nuclear factor kappa-B and the expression of pro-inflammatory cytokines (i.e. tumor necrosis factor alpha, interleukin-6) by activating adenosine monophosphate-activated protein kinaseα1 (AMPKα1) pathway. Furthermore, knock-down of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin.Conclusion: Artemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect was probably mediated by the activation of AMPKα1 signalling pathway in microglia.
Determinants of self-paid rotavirus vaccination status in Kanazawa, Japan, including socioeconomic factors, parents’ perception, and children’s characteristics
Authors: Hara Megumi , Koshida Rie , Araki Kaoru , Kondo Masahide , Hirota Yoshio
Published: June 2020

Background: Japan’s National Immunization Program does not cover rotavirus vaccine and no government subsidies are available. This study aimed to measure the uptake of and determinants that influenced self-paid rotavirus vaccination, including socioeconomic status and relative poverty.Methods: We conducted a cross-sectional study at health check-ups for all children aged 18 months in Kanazawa, Japan, between December 2017 and July 2018. Community nurses collected information on self-paid vaccination history, parents’ perceptions of and recommendations for rotavirus vaccine, and socioeconomic status in interviews using a unified questionnaire. We used multivariable logistic regression to assess vaccine uptake and possible determinants.Results: In total, 1,282 participants were enrolled. The estimated rotavirus vaccine coverage was 72.9%. Rotavirus vaccine uptake was positively correlated with: parents’ perceptions that rotavirus gastroenteritis is serious and that the rotavirus vaccine is effective; pediatricians’ recommendations; information from the city office, articles in magazines and on the Internet; and parents’ education level. Lower household income was negatively correlated with rotavirus vaccination. Vaccine expense, fear of adverse reactions to the vaccine, number of household members and siblings, and children’s characteristics were not correlated with rotavirus vaccination. Poverty was negatively correlated with rotavirus vaccination, even after adjustment for other determinants (adjusted odds ratio 0.49, 95% confidence interval: 0.26–0.90).Conclusion: Parents’ perceptions, socioeconomic status, relative poverty, and pediatricians’ recommendations are determinants of vaccination. This study suggests that appropriate information about rotavirus vaccine, subsidies for those of lower socioeconomic status, and national recommendations are necessary to achieve higher coverage.
Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds
Authors: Teklemichael Awet Alem , Mizukami Shusaku , Toume Kazufumi , Mosaddeque Farhana , Kamel Mohamed Gomaa , Kaneko Osamu , Komatsu Katsuko , Karbwang Juntra , Huy Nguyen Tien , Hirayama Kenji
Published: June 2020

Background: The herbal medicine has been a rich source of new drugs exemplified by quinine and artemisinin. In this study, examined a variety of Japanese traditional herbal medicine (Kampo) for their potential antimalarial activities. Methods: We designed a comprehensive screening to identify novel antimalarial drugs from a library of Kampo herbal extracts (n = 120) and related compounds (n=96). The antimalarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and -resistant (Dd2) strains of Plasmodium falciparum . The cytotoxicity was also evaluated using primary Adult Mouse Brain cells. After being selected through the first in vitro assay, positive extracts and compounds were examined for possible in vivo antimalarial activity. Results: Out of 120 herbal extracts, Coptis Rhizome showed the highest antimalarial activity (IC 50 1.9 µg/mL of 3D7 and 4.85 µg/mL of Dd2) with a high selectivity index (SI) > 263 (3D7) and > 103 (Dd2). Three major chlorinated compounds (coptisine, berberine, and palmatine) related to Coptis Rhizome also showed antimalarial activities with IC 50 1.1, 2.6, and 6.0 µM (against 3D7) and 3.1, 6.3, and 11.8 µM (against Dd2), respectively. Among them, coptisine chloride exhibited the highest antimalarial activity (IC 50 1.1 µM against 3D7 and 3.1 µM against Dd2) with SI of 37.8 and 13.2, respectively. . Finally, the herbal extract of Coptis Rhizome and its major active compound coptisine chloride exhibited significant antimalarial activity in mice infected with P. yoelii 17X strain with respect to its activity on parasite suppression consistently from day 3 to day 7 post-challenge. The effect ranged from 50.38 to 72.13% (P <.05) for Coptis Rhizome and from 81 to 89% (P <.01) for coptisine chloride. Conclusion: Coptis Rhizome and its major active compound coptisine chloride showed promising antimalarial activity against chloroquine-sensitive (3D7) and -resistant (Dd2) strains in vitro as well as in vivo mouse malaria model. Thus Kampo herbal medicine is a potential natural resource for novel antipathogenic agents.
Multivariate Network Meta-Analysis Incorporating Class Effects
Authors: Owen Rhiannon Kate , Bujkiewicz Sylwia , Tincello Douglas G , Abrams Keith R
Published: June 2020

Background: Network meta-analysis synthesises data from a number of clinical trials in order to assess the comparative efficacy of multiple healthcare interventions in similar patient populations. In situations where clinical trial data are heterogeneously reported i.e. data are missing for one or more outcomes of interest, synthesising such data can lead to disconnected networks of evidence, increased uncertainty, and potentially biased estimates which can have severe implications for decision-making. To overcome this issue, strength can be borrowed between outcomes of interest in multivariate network meta-analyses. Furthermore, in situations where there are relatively few trials informing each treatment comparison, there is a potential issue with the sparsity of data in the treatment networks, which can lead to substantial parameter uncertainty. A multivariate network meta-analysis approach can be further extended to borrow strength between interventions of the same class using hierarchical models. Methods: We extend the trivariate network meta-analysis model to incorporate the exchangeability between treatment effects belonging to the same class of intervention to increase precision in treatment effect estimates. We further incorporate a missing data framework to estimate uncertainty in trials that fail to report measures of variability in order to maximise the use of all available information for healthcare decision-making. The methods are applied to a motivating dataset in overactive bladder syndrome. The outcomes of interest were mean change from baseline in incontinence, voiding and urgency episodes. All models were tted using Bayesian Markov Chain Monte Carlo (MCMC) methods in WinBUGS. Results: All models (univariate, multivariate, and multivariate models incorporating class effects) produced similar point estimates for all treatment effects. Incorporating class effects in multivariate models often increased precision in treatment effect estimates. Conclusions: Multivariate network meta-analysis incorporating class effects allowed for the comparison of all interventions across all outcome measures to ameliorate the potential impact of outcome reporting bias, and further borrowed strength between interventions belonging to the same class of treatment to increase the precision in treatment effect estimates for healthcare policy and decision-making. Keywords: multivariate; network meta-analysis; mixed treatment comparisons; meta-analysis; class effect
Comparison of hierarchical EMAX and NDLM models in dose-response for early phase clinical trials
Authors: Huang Xiaqing , Gajewski Byron
Published: June 2020

Background: Phase II clinical trials primarily aim to find the optimal dose and investigate the relationship between dose and efficacy relative to standard of care (control). Therefore, before moving forward to a phase III confirmatory trial, the most effective dose is needed to be identified. Methods: The primary endpoint of a phase II trial is typically a binary endpoint of success or failure. The EMAX model, ubiquitous in pharmacology research, was fit for many compounds and described the data well, except for a single compound, which had nonmonotone dose–response (Thomas et al., 2014). To mitigate the risk of nonmonotone dose response one of the alternative options is a Bayesian hierarchical EMAX model (Gajewski et al., 2019). The hierarchical EMAX adapts to its environment. Results: When the dose-response curve is monotonic it enjoys the efficiency of EMAX. When the dose-response curve is non-monotonic the additional random effect hyperprior makes the hierarchical EMAX model more adjustable and flexible. However, the normal dynamic linear model (NDLM) is a useful model to explore dose-response relationships in that the efficacy at the current dose depends on the efficacy of the previous dose(s). Previous research has compared the EMAX to the hierarchical EMAX (Gajewski et al., 2019) and the EMAX to the NDLM (Liu et al., 2017), however, the hierarchical EMAX has not been directly compared to the NDLM. Conclusions: The focus of this paper is to compare these models and discuss the relative merit for each of their uses for an ongoing early phase dose selection study.
14-type HPV mRNA test in triage of HPV DNA positive postmenopausal women with normal cytology
Authors: Asciutto Katrin Christine , Borgfeldt Christer , Forslund Ola
Published: June 2020

Background: During 2013 and 2016 the Region of Skåne, Sweden, started to analyse human papillomavirus (HPV) and cytology in postmenopausal women 60-65 years of age. Our aim was to evaluate high-risk (HR) HPV mRNA testing for the triage of HPV DNA positive postmenopausal women with normal cytology. Methods: A total of 271 women, 60-65 years of age, underwent liquid based cytology (LBC) and HPV testing by using the HR-HPV DNA MGP-PCR-Luminex assay. HR-HPV DNA-positive women with normal cytology underwent complimentary HPV mRNA testing (Aptima, Hologic Inc.). Over a period of 49 months (SD 11.0) the women received regular follow-up at intervals of 12-18 months. Women with abnormal cytology and/or a positive HR-HPV DNA and/or mRNA result at two subsequent visits were scheduled for colposcopy and clinical examination. Results: Over the surveillance period, 3.6% (10/271) of the HR-HPV DNA positive women developed histologically confirmed high-grade squamous intraepithelial lesions (HSILs) or worse. The cumulative incidence rates (CIR) were 29.7% (CI 24.8-30.1) for HSIL or worse among HPV mRNA-positive women at enrolment (39.5% 107/271) and 0% among HPV mRNA negative women (60.5%, 164/271), (p=0.002). Conclusions : Postmenopausal women with normal cytology along with the presence of HR-HPV mRNA are at increased risk for development of severe cervical dysplasia, in contrast to those women with negative HR-HPV mRNA. The HR-HPV mRNA APTIMA assay detecting 14 HR-HPV types may be a useful triage method among HPV DNA positive postmenopausal women with normal cytology.
Hepatocyte growth factor (HGF) and stem cell factor (SCF) maintained the stemness of human bone marrow mesenchymal stem cells (hBMSCs) during long-term expansion by preserving mitochondrial function via the PI3K/AKT, ERK1/2, and STAT3 signaling pathways
Authors: Cao Zeyuan , Xie Yunyi , Yu Le , Li Yi , Wang Yan
Published: June 2020

Background: Mesenchymal stem cells (MSCs) have a limited self-renewal ability, impaired multi-differentiation potential, and undetermined cell senescence during in vitro series expansion. To address this concern, we investigated the effects of the microenvironment provided by stem cells from human exfoliated deciduous teeth (SHED) in maintaining the stemness of human bone marrow mesenchymal stem cells (hBMSCs) and identified the key factors and possible mechanisms responsible for maintaining the stemness of MSCs during long-term expansion in vitro.Methods: The passage 3 (P3) to passage 8 (P8) hBMSCs were cultured in the conditioned medium from SHED (SHED-CM). The percentage of senescent cells was evaluated by β-galactosidase staining. In addition, the osteogenic differentiation potential was analyzed by reverse transcription quantitative PCR (RT-qPCR), Western blot, alizarin red and alkaline phosphatase (ALP) staining. Furthermore, RT-qPCR results identified hepatocyte growth factor (HGF) and stem cell factor (SCF) as key factors. Thus, the effects of HGF and SCF on mitochondrial function were assessed by measuring the ROS and mitochondrial membrane potential levels. Finally, selected mitochondrial-related proteins associated with the PI3K/AKT, ERK1/2, and STAT3 signaling pathways were investigated to determine the effects of HGF and SCF in preserving the mitochondrial function of hBMSCs during long-term expansion. Results: SHED-CM had significantly enhanced the cell proliferation, reduced the senescent cells, and maintained the osteogenesis and pro-angiogenic capacity in P8 hBMSCs during long-term expansion. In addition, hBMSCs treated with 100 ng/ml HGF and 10 ng/ml SCF had reduced ROS levels, and preserved mitochondrial membrane potential compared with P8 hBMSCs during long-term expansion. Furthermore, HGF and SCF upregulated the expression of mitochondrial-related proteins associated with the PI3K/AKT, ERK1/2, and STAT3 signaling pathways, possibly contributing to the maintenance of hBMSCs stemness by preserving mitochondrial function. Conclusion: Both HGF and SCF are key factors in maintaining the stemness of hBMSCs by preserving mitochondrial function through the expression of proteins associated with the PI3K/AKT, ERK1/2, and STAT3 signaling pathways. This study provides new insights into the anti-senescence capability of HGF and SCF, as well as new evidence for their potential application in optimizing the long-term culture of MSCs.
Translational Outcomes Relevant to Neurodevelopmental Disorders Following Early Life Exposure of Rats to Chlorpyrifos
Authors: Berg Elizabeth L , Ching Tianna M , Bruun Donald A , Rivera Josef K , Careaga Milo , Ellegood Jacob , Lerch Jason P , Wöhr Markus , Lein Pamela J , Silverman Jill
Published: June 2020

Background: Neurodevelopmental disorders (NDDs), including intellectual disability, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are pervasive, lifelong disorders for which pharmacological interventions are not readily available. Substantial increases in the prevalence of NDDs over a relatively short period cannot be attributed solely to genetic factors and/or improved diagnostic criteria. There is now a consensus that multiple genetic loci combined with exposure(s) to environmental risk factors during critical periods of neurodevelopment influence NDD susceptibility and symptom severity. Organophosphorus (OP) pesticides have been identified as potential environmental risk factors. Epidemiological studies suggest children exposed prenatally to the OP pesticide chlorpyrifos (CPF) have significant mental and motor delays and strong positive associations for the development of a clinical diagnosis of developmental delay, ADHD, or ASD. Methods: We tested the hypothesis that developmental CPF exposure impairs behavior relevant to NDD phenotypes, i.e., deficits in social communication and repetitive, restricted behavior. Male and female rat pups were exposed to CPF at 0.1, 1.0, or 3.0 mg/kg (s.c.) from postnatal days 1-4. Results: These CPF doses did not significantly inhibit acetylcholinesterase activity in the blood or brain but significantly impaired pup ultrasonic vocalizations (USV) in both sexes. Social communication in juveniles via positive affiliative 50-kHz USV playback was absent in females exposed to CPF at 0.3 mg/kg and 1.0 mg/kg. In contrast, this CPF exposure paradigm had no significant effect on gross locomotor abilities or contextual and cued fear memory. Ex vivo magnetic resonance imaging largely found no differences between the CPF rats and the corresponding vehicle controls; however there were some interesting trends in females at a dosage of 0.3 mg/kg. Conclusions: This work characterizes a rat model of developmental CPF exposure that exhibits adverse behavioral phenotypes resulting from perinatal exposures at levels that did not significantly inhibit acetylcholinesterase activity in brain or blood. These data suggest that current regulations regarding safe levels of CPF need to be reconsidered.
Community-Based Cluster Randomized Controlled Trial: Empowering Households to Identify and Provide Appropriate Care for Low-Birthweight Newborns in Nepal
Authors: Hodgins Stephen , Rajbhandari Binamra , Joshi Deepak , Ban Bharat , Khatry Subarna , Mullany Luke C
Published: June 2020

Background: Most newborn deaths occur among those of low birthweight (LBWt), due to prematurity &/or impaired fetal growth. Simple practices can substantially mitigate this risk. In low-income country settings where many births occur at home, strategies are needed that empower mothers to determine if their babies are higher risk and take measures to reduce risk. Earlier studies suggest that foot-length may be a good proxy for birthweight. An earlier Nepal study found a 6.9cm cut-off performed relatively well, differentiating normal from low birthweight.Methods: Community-based, cluster-randomized controlled trial. Objective: to determine whether family-administered screening, associated with targeted messages improves care practices known to mitigate LBWt-associated risks. Participants: women participating in a parent trial in rural Nepal, recruited late in pregnancy. Women were given a 6.9cm card to assess whether the baby’s foot is small; if so, to call a number on the card for advice. Follow-up visits were made over the 2 weeks following the birth, assessing for 2 behavioral outcomes: reported skin-to-skin thermal care, and care-seeking outside the home; assessed restricting to low birthweight (using 2 cutoffs: 2,500g and 2,000g). Randomization: 17 clusters intervention, 17 control.The study also documented performance along the presumed causal chain from intervention through behavioral impact.Results: 2,022 intervention, 2,432 control. Intervention arm: 519 had birthweight <2,500g (vs. 663 among controls), of which 503 were available for analysis (vs. 649 among controls). No significant difference found on care-seeking; for those <2,500g RR 1.13 (95%CI: 0.97-1.131). A higher proportion of those in the intervention arm reported skin-to-skin thermal care than among controls; for those <2,500g RR 2.50 (95%CI: 2.01-3.1). However, process measures suggest this apparent effect cannot be attributed to the intervention; the card performed poorly as a proxy for LBWt, misclassifying 84.5% of those <2,000 as normal.Conclusions: Although the trial found an apparent effect on one of the behavioral outcomes, this cannot be attributed to the intervention; most likely it was a result of pure chance. Other approaches are needed for identifying small, at-risk babies in such settings, and targeting them for appropriate care messaging.Trial registration: https://clinicaltrials.gov/ct2/show/NCT02802332, registered 6/16/2016.
The geno-spatio analysis of Mycobacterium tuberculosis complex in hot and cold spots of Guangxi, China
Authors: Lin Dingwen , Cui Zhezhe , Virasakdi Virasakdi , Palittapongarnpim Prasit , Chaiprasert Angkana , Ruangchai Wuthiwat , Ou Jing , Huang Liwen
Published: June 2020

Background At present, there are few studies on polymorphism of Mycobacterium tuberculosis (Mtb) gene and how it affects the TB epidemic. This study aimed to document the differences of polymorphisms between tuberculosis hot and cold spot areas of Guangxi Zhuang Autonomous Region, China. Methods The cold and hot spot areas, each with 3 counties, had been pre-identified by TB incidence for 5 years from the surveillance database. Whole genome sequencing analysis was performed on all sputum Mtb isolates from the detected cases during January and June 2018. Single nucleotide polymorphism (SNP) of each isolate compared to the H37Rv strain were called and used for lineage and sub-lineage identification. Pairwise SNP differences between every pair of isolates were computed. Analyses of Molecular Variance (AMOVA) across counties of the same hot or cold spot area and between the two areas were performed. Results As a whole, 59.8% (57.7% sub-lineage 2.2 and 2.1% sub-lineage 2.1) and 39.8% (17.8% sub-lineage 4.4, 6.5% sub-lineage 4.2 and 15.5% sub-lineage 4.5) of the Mtb strains were Lineage 2 and Lineage 4 respectively. The percentages of sub-lineage 2.2 (Beijing family strains) are significantly higher in hot spots. Through the MDS dimension reduction, the genomic population structure in the three hot spot counties is significantly different from those three cold spot counties (T-test p = 0.05). The median of SNPs distances among Mtb isolates in cold spots was greater than that in hot spots (897 vs 746, Rank-sum test p < 0.001). Three genomic clusters, each with genomic distance ≤ 12 SNPs, were identified with 2, 3 and 4 consanguineous strains. Two clusters were from hot spots and one was from cold spots. Conclusion Narrower genotype diversity in the hot area may indicate higher transmissibility of the Mtb strains in the area compared to those in the cold spot area.