bluuebunny/crossref_metadata_2025 huggingface dataset:
Availability, prices, and affordability of selected essential cancer medicines in a middle-income country – the case of Mexico
Authors: Moye-Holz Daniela , Ewen Margaret , Dreser Anahi , Bautista-Arredondo Sergio , Soria-Saucedo Rene , Dijk Jitse P. van , Reijneveld Sijmen A. , Hogerzeil Hans V.
Published: February 2020

Background: More alternatives have become available for the diagnosis and treatment of cancer in low- and middle-income countries. Because of increasing demands, governments are now facing a problem of limited affordability and availability of essential cancer medicines. Yet, precise information about the access to these medicines is limited, and the methodology is not very well developed.
Objective: To assess the availability and affordability of essential cancer medicines in Mexico, and compare their prices against those in other countries of the region.
Methods: We surveyed 21 public hospitals and 19 private pharmacies in 8 states of Mexico. Data were collected on the availability and prices of 49 essential cancer medicines. Prices were compared against those in Chile, Peru, Brazil, Colombia and PAHO’s Strategic Fund.
Results: Of the various medicines, mean availability in public and private sector outlets was 61.2% and 67.5%, respectively. In the public sector, medicines covered by the public health insurance “People’s Health Insurance” were more available. Only seven (public sector) and five (private sector) out of the 49 medicines were considered affordable. Public sector procurement prices were 41% lower than in other countries of the region.
Conclusions: The availability of essential cancer medicines, in the public and private sector, falls below World Health Organization’s 80% target. The affordability remains suboptimal as well. A national health insurance scheme could serve as a mechanism to improve access to cancer medicines in the public sector. Comprehensive pricing policies are warranted to improve the affordability of cancer medicines in the private sector.
Relationship between Internet addiction and sleep disturbance in high school students: a cross-sectional study
Authors: Tokiya Mikiko , Itani Osamu , Otsuka Yuichiro , Kaneita Yoshitaka
Published: February 2020

Background: Worldwide, the increase in the number of Internet users has increased Internet dependence. In adolescents, this dependence interferes with sleep, which is important for the development of psychophysiological capabilities. However, few large-scale surveys have descriptively examined the relationship between Internet addiction (IA) and sleep disturbance using standardized questionnaires. We conducted this study to determine the relationship between sleep disturbance in adolescents and IA based on the categories of the Young Diagnostic Questionnaire (YDQ) through a complete survey of one prefecture in Japan. Methods: In 2016, a self-report questionnaire was used to survey high school students (n=10,405, age range: 15–16 years) in all 54 day-boarding high schools in the selected prefecture. We defined “sleep disturbance” by scores greater than 5.5 points on the Japanese version of the Pittsburgh Sleep Quality Index. IA was evaluated using the YDQ: “IA,” when 5 of the 8 YDQ items were present; “at-risk,” when either 3 or 4 YDQ items were reported; and “non-IA,” when less than 2 YDQ items were positive. Multiple logistic regression analysis was undertaken with sleep disturbance as the dependent variable, IA as the explanatory variable, and adjustments for 8 items. Results: High YDQ scores were associated with high prevalence rates of sleep disturbance in both male and female participants. These findings persisted after controlling for other factors in the multiple regression model. Conclusions: Among Japanese adolescents, there exists a significant independent relationship between IA and sleep disturbances.
Expanding the Role of Paralegals: Supporting Realization of the Right to Health for Vulnerable Communities
Authors: Wirya Albert , Larasati Ajeng , Gruskin Sofia , Ferguson Laura
Published: February 2020

Background
All around the world, the paralegal program prepares members of marginalized communities to face the legal system. Having a common background with their clients and being capable of conducting flexible work, paralegals’ role moves beyond enlarging the beneficiaries of legal aid to addressing intersectional issues around health-related rights. This study assesses the health and other impacts of paralegals recruited by Lembaga Bantuan Hukum Masyarakat (LBHM), a human rights organization which provides legal assistance and operates in Jakarta, Indonesia. The positive results these paralegals can bring in the specific context can contribute to the development of community-based paralegals elsewhere.

Methods
This mixed methods research was carried out in 2016-2018. In 2016, a quantitative survey was administered to LBHM-trained paralegals and a sub-set of paralegals who completed the survey were then also interviewed. Quantitative data were analysed using SPSS, and, for the qualitative data, thematic analysis was conducted.

Results
The paralegals make important contributions to health-related rights in four distinct ways. Firstly, most of the paralegals checked their clients’ health in all stages of detention, especially regarding their drug dependency status and checking for signs of torture. Secondly, paralegals help clients to be more aware of their health-related rights, especially regarding their rights to obtain health services inside detention. Thirdly, paralegals can ensure that their clients obtain health services by taking medicines directly to the clients or encouraging the law enforcement agencies to refer the clients to health services. Lastly, in drug cases, paralegals help their clients to obtain alternative sentences besides imprisonment.

Conclusions
These four contributions verify the positive impacts paralegals, recruited from marginalized communities, can deliver for community members facing criminal justice processes. The shifting role of paralegals from merely an intermediary between clients and lawyers to champions of the health-related rights of their clients can happen as a result of adequate training, support, and networks with other agents in criminal justice system.
Difference in autonomic nervous effect of blue light depending on the angle of incidence on the eye
Authors: Yuda Emi , Yoshida Yutaka , Ueda Norihiro , Hayano Junichiro
Published: February 2020

Objective: Blue light has been attributed to the adverse biological effects caused by the use of smartphones and tablet devices at night. However, it is not realistic to immediately avoid nighttime exposure to blue light in the lifestyle of modern society, so other effective methods to reduce the unwanted influences should be investigated. Earlier studies reported that inferior retinal light exposure causes greater melatonin suppression than superior retinal exposure. We examined whether the autonomic responses to blue light depends on the angle of incidence on the eye. Results: In eight healthy subjects, blue light from organic electroluminescent lighting device (15.4 lx at subjects’ eye) was exposed from 6 angles (0º, 30º, 45º, 135º, 150º, and 180º) for 5 min each with a 10-min interval of darkness. After adjusting the order effect of angles, however, no significant difference was detected in autonomic indices of heart rate variability with the angle of incidence, except that the exposure from 45º caused lower heart rate than exposures from 0º, 150º, and 180º. Further researches on the physiological properties of the biological effects of blue light are needed to control and reduce the health risks of using blue-light-emitting devices.
Treatment success and mortality among adults with tuberculosis in rural eastern Uganda: a retrospective cohort study
Authors: Izudi Jonathan , Tamwesigire Imelda K. , Bajunirwe Francis
Published: February 2020

Background

Successful treatment of tuberculosis leads to clinical and public health benefits such as reduction in transmission, complications, and mortality among patients. However, data are limited on treatment outcomes and the associated factors among persons with bacteriologically confirmed pulmonary (BC-PTB) in rural areas of high tuberculosis and Human Immunodeficiency Virus (HIV) burden countries such as Uganda. We investigated factors associated with successful treatment of tuberculosis and mortality among adult persons with BC-PTB in rural eastern Uganda.

Methods

We constructed a retrospective cohort of patients with BC-PTB from a routine tuberculosis clinic database in eastern Uganda. We performed bivariate and multivariate analysis. Using a 5% level of significance, we used the modified Poisson regression analysis to determine factors independently associated with treatment success and mortality.

Results

We retrieved 1,123 patient records. Of these, 477(42.5%) had a cure, 323 (28.0%) had treatment completion, 17(1.5%) had failed treatment, 81(7.2%) had died, 89(7.9%) were lost to follow-up, and 136(12.1%) had missing treatment outcome. Overall, 800 (81.1%) of the 987 persons with BC-PTB that had an outcome, were successfully treated. Successful treatment of tuberculosis was less likely to occur among those with HIV infection (Adjusted risk ratio (aRR), 0.88; 95% Confidence Interval (CI), 0.82-0.95), older than 50 years (aRR, 0.89; 95% CI, 0.81-0.97), or male (aRR, 0.92; 95% CI, 0.87-0.98). Mortality was associated with HIV infection (aRR, 4.48; 95% CI, 2.95-6.79), older than 50 years (aRR, 2.93; 95% CI, 1.74-4.92), year of enrollment into treatment from 2015 (aRR, 0.80; 95% CI, 0.66-0.97), and Community-Based Directly Observed Therapy Short Course (aRR, 0.26; 95% CI, 0.13-0.50).

Conclusions

Treatment success rate among adult persons with BC-PTB in rural eastern Uganda is suboptimal and mortality is high. HIV infection and older age reduce the chance of successful treatment of tuberculosis, and increase risk of mortality. Older and HIV infected persons with BC-PTB will require special consideration to optimize treatment success and reduce risk of mortality.
Real-world questions and concerns about disease-modifying antirheumatic drugs (DMARDs): a retrospective analysis of questions to a medicine call center
Authors: Masri Hiba EL , Hollingworth Samantha , Driel Mieke van , Benham Helen , McGuire Treasure
Published: February 2020

Background Disease modifying antirheumatic drugs (DMARDs) have transformed the treatment of numerous autoimmune and inflammatory diseases but their perceived risk of harm be a barrier to use.Methods In a retrospective mixed-methods study, we analysed conventional (c) and biologic (b) DMARDs-related calls and compared them with rest of calls (ROC) from consumers to an Australian national medicine call center operated by clinical pharmacists from September 2002 to June 2010. This includes the period where bDMARDs became available on the Pharmaceutical Benefits Scheme, the government-subsidized prescription medicines formulary. We compared caller and patient demographics, enquiry types and motivation to information-seek for both cDMARDs and bDMARDs with ROC, using a t-test for continuous data and a chi-square test for categorical data. We explored call narratives to identify common themes.Results There were 1,547 calls involving at least one DMARD. The top three cDMARD enquiry types were side effects (27.2%), interactions (21.9%), and risk versus benefit (11.7%). For bDMARDs, the most common queries involved availability and subsidized access (18%), mechanism and profile (15.8%), and side effects (15.1%). The main consumer motivations to information-seek were largely independent of medicines type and included: inadequate information (44%), wanting a second opinion (23.6%), concern about a worrying symptom (18.8%), conflicting information (6.9%), or information overload (2.3%). Question themes common to conventional and biological DMARDs were caller overemphasis on medication risk and the need for reassurance. Callers seeking information about bDMARDs generally overestimated effectiveness and focused their attention on availability, cost, storage, and medicine handling.Conclusion Consumers have considerable uncertainty regarding DMARDs and may overemphasise risk. Patients cautiously assess the benefits and risks of their DMARDs but when new treatments emerge, they tend to overestimate their effectiveness.
Histone deacetylase inhibitors Induce Expression of Chromosomally Tagged Variant-Specific Surface Protein Genes in Giardia lamblia
Authors: Orozco Daniel Roberto , Garlapati Srinivas
Published: February 2020

Objective RNA interference and miRNA mediated mechanisms have been proposed to explain the expression of a specific variant of VSP at a time on the surface of Giardia lamblia. Recently, epigenetic mechanisms involving histone acetylations have been proposed to explain the process of antigenic switching in Giardia lamblia. However, due to the limited availability of specific antibodies for all the vsp variants present in the genome, it was difficult to monitor vsp gene switching. In this study, we have used an endogenous tagging method to tag specific vsp genes vsp1267 and vsp9B10A with a sequence encoding hemagglutinin (HA) epitope at the 3’end of the coding sequences without altering the 5’ upstream elements. With this method, we have monitored the expression of the tagged vsp genes in cells treated with histone deacetylase inhibitors using RT-PCR. Results Our results show that vsp1267-3XHA can be induced by treatment with sodium 4-phenylbutyrate, M344 and splitomicin but not by apicidin and Trichostatin A, while vsp9B10A-3XHA expression can be induced by Trichostatin A and splitomicin but not by sodium 4-phenylbutyrate, M344 and apicidin. The induced expression of these variants was not due to growth inhibition. These results support the role of histone acetylations in vsp expression.
Reducing Suicidal Ideation among Turkish Migrants in the Netherlands and in the UK A Pilot RCT of a guided Online Intervention
Authors: Eylem Ozlem , Straten Annemieke van , de Wit Leonore , Rathod Shanaya , Bhui Kamaldeep , Kerkhof Ad J.F.M.
Published: February 2020

Background: The evidence for the effectiveness of e-mental health interventions among ethnic minorities is still preliminary. This mixed methods study investigates the feasibility of a culturally adapted, guided online intervention with the intention to understand how it works and for whom to inform refinement. It also examines indications for its effectiveness in reducing suicidal ideation when compared with the treatment as usual. Methods: Turkish migrants (first and second generation) with mild to moderate suicidal thoughts were recruited from the general population using social media and newspaper advertisements. The intervention group obtained direct access to a 6 weeks guided online intervention while participants in the waiting list condition had to wait for 6 weeks. The intervention is based on an existing online intervention and was culturally adapted. Participants in both conditions completed baseline, post-test, and follow up questionnaires on suicidal ideation (primary outcome), depression, worrying, hopelessness, suicide attempt and self-harm, acculturation, quality of life, and usability. In addition, participants were interviewed to examine the feasibility and mechanisms of action in more depth. The responses were analysed by inductive thematic analysis. Results: A total of 85 people signed up via the study website and 18 (10 intervention, 8 waitlist control) were included. While the therapeutic benefits were emphasised (e.g. feeling connected with the intervention), the feasibility was judged to be low. The main reasons given were: not having severe suicidal thoughts and not being represented by the culturally adapted intervention. No suicide attempts were recorded during the study. The suicidal ideation, depression and hopelessness scores were improved in both groups. Conclusion: The online intervention, as might be expected in a small feasibility study, was not superior to the control condition. Future studies need to attend the implementation issues raised including measures of stigma, acculturation, careful cultural adaptations alongside more attention to coaching and relational support. They should also consider how to improve engagement alongside selection of those who are motivated to use online interventions and offer alternatives for those who are not. Trial registration: NTR5028. Registered 1 March 2015, https://www.trialregister.nl/trial/4926
Supervisors’ intention to observe clinical task performance: an exploratory study using the Theory of Planned Behaviour during postgraduate medical training
Authors: de Jonge Laury PJWM , Mesters Ilse , Govaerts Marjan JB , Timmerman Angelique A , Muris Jean WM , Kramer Anneke WM , Vleuten Cees PM van der
Published: February 2020

Background Direct observation of clinical task performance plays a pivotal role in competency-based medical education. Although formal guidelines require supervisors to engage in direct observations, research demonstrates that trainees are infrequently observed. Supervisors may not only experience practical and socio-cultural barriers to direct observations in healthcare settings, they may also question usefulness or have low perceived self-efficacy in performing direct observations. A better understanding of how these multiple factors interact to influence supervisors’ intention to perform direct observations may help us to more effectively implement the aforementioned guidelines and increase the frequency of direct observations. Methods We conducted an exploratory quantitative study, using the Theory of Planned Behaviour (TPB) as our theoretical framework. In applying the TPB, we transfer a psychological theory to medical education to get insight in the influence of cognitive and emotional processes on intentions to use direct observations in workplace based learning and assessment. We developed an instrument to investigate supervisors intention to perform direct observations. The relationships between the TPB measures of our questionnaire were explored by computing bivariate correlations using Pearson’s R tests. Hierarchical regression analysis was performed in order to assess the impact of the respective TPB measures as predictors on the intention to perform direct observations. Results In our study 82 GP supervisors completed our TPB questionnaire. We found that supervisors had a positive attitude towards direct observations. Our TPB model explained 45% of the variance in supervisors’ intentions to perform them. Normative beliefs and past behaviour were significant determinants of this intention. Conclusion Our study suggests that supervisors use their past experiences to form intentions to perform direct observations in a careful, thoughtful manner and, in doing so, also take the preferences of the learner and other stakeholders potentially engaged in direct observations into consideration. These findings have potential implications for research into work-based assessments and the development of training interventions to foster a shared mental model on the use of direct observations.
Overdose-Associated Admissions Among People Who Inject Opioids at a County Safety-Net Hospital Following Implementation of a Syringe Services Program
Authors: Bornstein Kasha , Coye Austin , Onge Joan St. , Li Hua , Muller Amanda , Bartholomew Tyler , Tookes Hansel
Published: February 2020

Background Syringe service programs (SSPs) are an evidence-based harm reduction strategy that reduce dangerous sequelae of injection drug use among people who inject drugs (PWID) such as overdose. SSP services include safer injection education and community-based naloxone distribution programs. This study evaluates differences in overdose-associated hospital admissions following implementation of the first legal SSP in Florida, based in Miami-Dade County. Methods We performed a retrospective analysis of hospitalizations for injection drug-related sequelae at a county hospital before and after the implementation of the SSP. An algorithm utilizing ICD-10 codes for opioid use and sequelae was used to identify people who inject opioids (PWIO). Florida Department of Law Enforcement Medical Examiners Commission Report data was used to analyze concurrent overdose death trends in Florida counties. Results Over the 25-month study period, 302 PWIO admissions were identified; 146 in the pre-index vs. 156 in post-index. A total of 26 admissions with PWIO overdose were found; 20 pre-index and 6 post-index (p=0.0034). Conclusions Declining overdose-associated admissions among PWIO suggests early impacts following SSP implementation.
The efficacy of Bifidobacterium quadruple viable tablet in the treatment of diarrhea predominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled, multicenter trial.
Authors: Bai Tao , Zeng Haoyu , Long Yanqin , Li Xiaoqing , Sun Xiaohong , Lan Yu , Gao Lingling , Zhang Lu , Feng Zenghui , Hou Xiaohua
Published: February 2020

Background: Irritable bowel syndrome (IBS) is one of the most acommon functional gastrointestinal disorders characterized by recurrent abdominal pain associated with defecation or a change in bowel habits. Leading to significant negative effect on patients’ quality of life and huge financial burden to health system, the management of IBS is a great challenge. Probiotics are considered as an effective therapy, however, in a lack of high-quality evidence of efficacy, no specific strain- and dose-probiotics were recommended in clinical guidelines. This study aims to evaluate the efficacy of the bifidobacterium quadruple viable tablet in the treatment of IBS-D.Methods/design: A multicenter randomized controlled trial will be performed in fourteen hospitals. A total of three hundred patients fulfill the eligible criteria will be stratified divided into an experimental group and a control group randomly in a ratio of 1:1. The experimental group is treated with the bifidobacterium quadruple viable tablet while the control group is treated with placebo. All the patients will receive a 4-week treatment and a 2-week follow-up. The primary outcome is the effectiveness in improving abdominal pain and stool consistency, the secondary outcome include evaluation of overall symptom relief, frequency of defecation, bloating, urgency of defecation, remedial medication, score of IBS-QOL and changes of microbiota and metabonomics. Physical examination, vital signs, laboratory tests, adverse events and concomitant medication will be taken into account for intervention safety assessment during the trial.Discussion: This multicenter randomized controlled trial may provide high-quality evidence on the efficacy of the bifidobacterium quadruple viable tablet for IBS-D on both physical and mental dimensions in China. To fill the gap of previous probiotics intervention studies, in addition, this study will also present safety assessment which will be a significant emphasis.Trial registration: Chinese Clinical Trial Registry, ID: ChiCTR1800017721 ( http://www.chictr.org.cn/showproj.aspx?proj=29440 ). Registered on 10 August 2018.
The rescue intervention strategy for asthma patients under severe air pollution: a protocol for a single-center prospective randomized controlled trial
Authors: Yang Xiaoyu , Huang Junjun , Hu Yan , Guo Cuiyan , Wang Xi , Yang Zhao , Zhou Tianyu , Wang Guangfa
Published: February 2020

Background Asthma is a common chronic airway inflammatory disease. Exacerbation of asthma not only accelerates the progression of the disease, but also increases the incidence of hospitalization and death. Studies have shown that air pollution is a high-risk factor of exacerbation of asthma. However, there are rare treatment strategies recommended to reduce severe air pollution related exacerbation of asthma. Methods/design This is a single-center, prospective, randomized and standard treatment parallel control clinical trial. Seventy-two asthma patients in non-exacerbation stage according to GINA guidelines 2017 will be recruited and equally assigned to Rescue Intervention Strategy (RIS) group or the control group. Original treatments for participants include unused inhaled drug, use short-acting β-agonists (SABA) on demand or use Budesonide/Formoterol (160μg/4.5μg/ dose, 1-2 dose / time, b.i.d). The rescue intervention strategy for RIS group is Budesonide / Formoterol plus the original treatment until the end of severe pollution (air quality index, AQI<200). Control group will maintain the original treatment. The intervention will last for one year. Primary outcome is the frequency of exacerbation asthma per year. And the secondary outcomes include the number of unplanned outpatient visits, emergency visits, hospitalization, medical cost and mortality caused by exacerbation asthma per year. Discussion The rescue intervention strategy is a novel strategy for asthma management under severe air pollution. Results of the study will provide reference information to guide clinical practice in reducing the air pollution related exacerbation of asthma.
18F-FDG PET/CT Metabolic Parameters and HER2 Expression in Colorectal Cancer
Authors: Yang Ziyi , Liu Shuai , Sun Yuyun , Xu Junyan , Jiang Jinjin , Ma Xiaoxi , Zhang Yingjian , Song Shaoli
Published: February 2020

Purpose: The relationship between 18F-FDG uptake and HER2 expression in colorectal cancer has not been investigated yet. This study aimed to investigate the predictive efficiency of preoperative 18F-FDG PET/CT for HER2 expression and prognosis in colorectal cancer.Results: Over all 131 colorectal cancer patients, there were 27 (20.6%) patients were HER2 positive. SUVmax of primary tumor (Mean ± SD) in HER2-positive and HER2-negative group was 18.238 ± 8.912 and 14.455 ± 6.531, respectively. SUVmax in HER2-positive group were higher than in negative group (p = 0.034). When the cutoff was based on 5cm, tumor size demonstrated significant positive correlations with SUVmax (p = 0.012) and HER2 expression (p = 0.014). Multivariate analysis showed that both SUVmax and tumor size had significant correlation with HER2 expression (p = 0.049 vs p = 0.043, respectively). In addition, statistical analysis showed that patients with higher SUVmax had better PFS (p = 0.029). There was no statistical difference of PFS between HER2-positive and HER2-negative group (p = 0.28).Conclusion: 18F-FDG metabolic parameters had significant correlation with HER2 expression in colorectal cancer. SUVmax combined with primary tumor size were better for predicting the HER2 status of colorectal cancer.
Indocyanine green fluorescence imaging to assess bowel perfusion during totally laparoscopic surgery for colon cancer
Authors: Su Hao , Wu Hongliang , Mandula Bao , Luo Shou , Wang Xuewei , Zhao Chuanduo , Liu Qian , Wang Xishan , Zhou Zhixiang , Zhou Haitao
Published: February 2020

Aim: To retrospectively evaluate the feasibility and safety of intraoperative assessment of bowel perfusion in totally laparoscopic surgery for colon cancer using indocyanine green fluorescence imaging (IGFI).
Methods: From October 2017 to June 2019, consecutive patients with colon cancer who underwent totally laparoscopic surgery were enrolled retrospectively and grouped into the IGFI group (n=84) and control group (n=105). In the IGFI group, indocyanine green (ICG) was injected intravenously, and the bowel perfusion was observed using a fluorescence camera system prior to and after completion of the anastomosis.
Results: The two groups were demographically comparable. The IGFI group exhibited a significantly shorter operative time (p=0.0374) while intraoperative blood loss did not significantly differ among the groups (p=0.062). In the IGFI group, average time to perfusion fluorescence was 48.4±14.0 s after ICG injection, and four patients (4.8%) were required to choose a more proximal point of resection due to the lack of adequate fluorescence at the point previously selected. There were no differences in terms of pathological outcomes, postoperative recovery and the postoperative complication rates between the groups (p＞0.05).
Conclusion: IGFI shows promise as a safe and feasible tool to assess bowel perfusion during a totally laparoscopic surgery for colon cancer and may reduce the operative time.
High-throughput analysis suggests differences in journal false discovery rate by subject area and impact factor but not open access status
Authors: Hall Lauren , Hendricks Audrey E
Published: February 2020

Background: A low replication rate has been reported in some scientific areas motivating the creation of resource-intensive collaborations to estimate the replication rate by repeating individual studies. The substantial resources required by these projects limits the number of studies that can be repeated and consequently the generalizability of the findings. We extend the use of a method from Jager and Leek to estimate the false discovery rate (FDR) for 94 journals over a five-year period using p-values from 30,000 abstracts enabling the study of how the FDR varies by journal characteristics. Results: We find that the empirical FDR is higher for cancer vs. general medicine journals (p = 5.14E-6), especially for those with lower journal impact factors. Conversely, we find no significant evidence of a higher FDR, on average, for Open Access vs. closed access journals (p = 0.256, 95% CI: -0.014, 0.051). Conclusions: Our results identify areas of research that may need additional scrutiny and support to facilitate replicable science. Given our publicly available R code and data, others can complete a broad assessment of the empirical FDR across other subject areas and characteristics of published research.
NIPT technique based on the use of long chimeric DNA reads
Authors: Belova Vera , Plakhina Daria , Evfratov Sergey , Tsukanov Kirill , Khvorykh Gennady , Rakitko Alexander , Konoplyannikov Alexander , Ilinsky Valery , Rebrikov Denis , Korostin Dmitriy
Published: February 2020

Background: Non-invasive prenatal testing for aneuploidy on chromosomes 21, 18 and 13 is actively used in clinical practice around the world. One of the limitations of the wider implementation of this test is the high cost of the analysis itself, as the high throughput sequencing is still relatively expensive. At the same time, there is a trend of increase of the length of reads yielded by sequencers. Since extracellular DNA is short, in the order of 140-160 bp, it is not possible to effectively use long reads.Results: The authors used high-performance sequencing of cfDNA libraries that went through additional stages of enzymatic fragmentation and random ligation of the resulting products to create long chimeric reads. The authors used a controlled set of samples to analyze a set of cfDNA samples of pregnant women with a high risk of fetus aneuploidy according to the results of the first trimester screening and confirmed by invasive karyotyping of the fetus using laboratory and analytical approaches developed by the authors. They evaluated the sensitivity, specificity, PPV and NPV of the results.Conclusions: The authors developed a technique for constructing long chimeric reads from short cfDNA fragments and validated the test using a control set of extracellular DNA samples obtained from pregnant women. The obtained sensitivity and specificity parameters of the NIPT developed by the authors corresponded to the approaches proposed earlier (99, 93% and 99.14% for 21 trisomy; 100% and 98.34% for 18 trisomy; 100% and 99.17% for 13 trisomy, respectively).
The Epidemiology of Moebius Syndrome
Authors: carta arturo , favilla stefania , Mora Paolo , Calzetti Giacomo , Casalini Maria Cristina , Ferrari Pier Francesco , Bianchi Berrnardo , simonelli maria beatrice , farci roberta , gandolfi Stefano
Published: February 2020

Background: The epidemiology of Moebius Syndrome is actually unknown. In the present study we have investigated the epidemiology of MBS in a well defined population over a precise geographical area. Materials and Methods: Our University Hospital is the only national referral centre for the diagnosis and treatment of MBS. Participants to this cross sectional study are patients affected by MBS which have been periodically followed by our medical staff since 1998. Most of the patients were referred to our hospital by the Italian Association of Moebius Syndrome (AISMO). Demographic data necessary for our purposes were made available by AISMO database updated to April 2018. Subjects were assigned to the geographical macro-areas which are the ones conventionally used for surveys and epidemiological investigations by the Italian National Institute of Statistics. Rates and prevalence of the MBS cases were calculated referring to the last survey of the Italian population of 2018. Every study parameter was then calculated by reference to the whole country and to macro-area partition. Gender rate and the corresponding prevalence were calculated with respect to the weighted whole population and to the respective gender population. Chi-square (c 2 ) analysis was adopted to investigate possible differences among geographical regions and/or gender. A p value <0.05 was considered statistically significant. Results: 164 out of 212 MBS patients satisfied our inclusion criteria. All cases were Caucasian and sporadic. The median age at diagnosis was 3.6 years (range: 0-55); this range was significantly reduced to 0-5 years (median age at diagnosis: 2.2 years) for patients evaluated after 2007. The birth prevalence calculated was 0.06 cases per 10,000 live births with an overall prevalence of 0.27/100000 without any gender or geographical predisposition. Conclusions: The rate of MBS prevalence herein observed, rounded for possible underestimation, is 0.3/100000 people without any geographical difference in the distribution of the cases. According to our data, MBS must be considered a rare disease but not so rare as previously postulated by researchers on their personal basis.
Pelvic asymmetry as a risk factor for nonspecific chronic low back pain
Authors: Yu Qiuhua , Huang Huanjie , Zhang Zhou , Hu Xiaoqian , Li Wenfeng , Li Le , Chen Min , Liang Zhenwen , Lo Wai Leung Ambrose , Wang Chuhuai
Published: February 2020

Background Empirical evidence that identifies the pelvic asymmetry in which movement plane that contribute to non-specific chronic low back pain (NCLBP) is currently lacking. Objective To establish the reliability of the Global Postural System (GPS) in assessing pelvic asymmetry and identify the association between pelvic asymmetry parameters and the occurrence of NCLBP in young adults. Design A cross-sectional, regression study. Methods People who aged between 18 and 30 and were diagnosed with NCLBP were recruited. Healthy individuals who were matched for age, gender, and education level were recruited as controls and for the reliability analysis. Reliability was assessed by the ICC (3, k), standard error and minimal detectable difference. Bivariate correlation analysis and logistic regression analysis were used to determine the risk factors. Results Twenty-eight healthy participants and 28 people with NCLBP were recruited. Moderate to excellent ICCs were observed for the inter-rater and intra-rater reliability of most postural parameters. The bivariate correlation analysis indicated that age, body mass index and pelvic asymmetry parameters were related to the occurrence of NCLBP. Pelvic angle asymmetry (odd ratio=1.17), and asymmetry of the distance between the posterior superior iliac spine and the floor (odd ratio=1.21) were significant risk factors of NCLBP. Limitation This study did not explore the causal relationship between pelvic asymmetry in the sagittal plane/pelvic asymmetry in the transverse plane and the occurrence of NCLBP. The interpretation of the results may not be generalized beyond the sample population. Conclusions The GPS is a reliable method to assess pelvic asymmetry in a clinical setting. The pelvic asymmetry parameters obtained from the GPS are likely to assist in the early identification of the potential occurrence of NCLBP.
The mutational burden and oligogenic inheritance in Klippel-Feil Syndrome
Authors: Li Ziquan , Zhao Sen , Cai Siyi , Zhang Yuanqiang , Wang Lianlei , Niu Yuchen , Li Xiaoxin , Hu Jianhua , Chen Jingdan , Wang Shengru , Wang Huizi , Liu Gang , Tian Ye , Wu Zhihong , Zhang Jianguo , Wang Yipeng , Wu Nan
Published: February 2020

Background: Klippel-Feil syndrome (KFS) represents a rare anomaly characterized by congenital fusion of cervical vertebrae. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. Methods: We consecutively recruited a Chinese cohort of 37 patients with KFS. The clinical manifestations and radiological assessments were analyzed and whole-exome sequencing (WES) was performed. Additionally, rare variants in KFS cases and controls were compared using genetic burden analysis. Results: We primarily examined rare variants in five reported genes (GDF6, MEOX1, GDF3, MYO18B and RIPPLY2) associated with KFS and detected three variants of uncertain significance in MYO18B. Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS, followed by FREM2, SUFU, VANGL1 and KMT2D. In addition, seven patients were proposed to show potential oligogenic inheritance involving more than one candidate gene, the frequency of which was significantly higher than that in the in-house controls. Conclusions: Our study presents an exome-sequenced cohort and identifies five novel genes potentially associated with KFS, extending the spectrum of known mutations contributing to this syndrome. Furthermore, the genetic burden analysis provides further evidence for potential oligogenic inheritance of KFS.
Anti-tumor effects of LncRNA-CR594175 silenceing on hepatocellular carcinoma cell line HepG2 in vivo and in vitro
Authors: Liu Quan , Yu Xuxu , Yang Minjie , Li Xiangke , Zhai Xuejia , Lian Yujin , Chen Zhong , Fan Qingxia , Song Lijie , Li Wencai
Published: February 2020

Background Hepatocellular carcinoma (HCC) is one of the cancers of highest incidence and mortality worldwide. Methods High-throughput screening was applied to find the most varied expressed LncRNA in primary hepatocellular carcinoma and explore the interaction network of it. Results We found that lncRNA-CR594175 was the lncRNA of most varied expression, which was lower in adjacent noncancerous tissues than in primary HCC, and was lower in primary HCC than in its metastases. Knockdown of CR594175 inhibited the proliferation and invasion of HCC cells HepG2. The mechanism study revealed that CR594175, as a RNA sponge, broke the negative regulation of CTNNB1 (Catenin, beta-1) by hsa-miR142-3p, and once CR594175 was silenced, the highly expressed hsa-miR142-3p regained its regulation on CTNNB1 and inhibited the proliferation and invasion through Wnt signaling pathway. Conclusions Our present study demonstrates for the first time that CR594175 silencing suppressed proliferation and invasion of HCC cells HepG2 in vivo and in vitro by restoring the negative regulation of CTNNB1 by hsa-miR142-3p, laying a solid theoretic base for using lncRNA-CR594175 as genetic therapy target for HCC and offering a reasonable explanation for inactivation of miRNA in difference tumors or tumor of different stages.
Diversity of plant assemblages dampens the variability of the growing season phenology of wetland ecosystems
Authors: Rheault Guillaume , Lévesque Esther , Proulx Raphaël
Published: February 2020

Background: The functioning of ecosystems is highly variable through space and time. Climatic and edaphic factors are forcing ecological communities to converge, whereas the diversity of plant assemblages dampens these effects by allowing communities’ dynamics to diverge. This study evaluated whether the growing season phenology of plant communities within wetland ecosystems is determined by the climatic/edaphic factors of contrasted regions, by the species richness of plant communities, or by the diversity of plant assemblages. From 2013 to 2016, we monitored the phenology and floristic composition of 118 plant communities across five wetland ecosystems distributed along a gradient of edaphic and climatic conditions in the Province of Quebec, Canada. Results: Growing season phenology of wetlands was driven by differences among plant assemblage within ecosystems, and not by the species richness of each individual community (<1% of the explained variation). Variation in the growing season length of wetlands reflected a balance between the effects of climatic and edaphic factors on green-up dates and the dampening effects of plant assemblage diversity on green-down dates. Conclusions: The latter dampening effect may be particularly important in the context of increasing anthropogenic activities, which are predicted to impair the ability of wetlands to adapt to fluctuating environmental conditions. Our findings suggest that stakeholders should not necessarily consider local monospecific plant communities of lower conservation value to the global functioning of wetland ecosystems.
Validation of Androgen Receptor loss as a risk factor for the development of brain metastases from ovarian cancers
Authors: Mittica Gloria , Goia Margherita , Gambino Angela , Scotto Giulia , Fonte Mattia , Senetta Rebecca , Aglietta Massimo , Borella Fulvio , Sapino Anna , Katsaros Dionyssios , Maggiorotto Furio , Ghisoni Eleonora , Giannone Gaia , Tuninetti Valentina , Genta Sofia , Eusebi Chiara , Momi Marina , Cassoni Paola , Valabrega Giorgio
Published: February 2020

Background Central nervous system (CNS) spreading from epithelial ovarian carcinoma (EOC) is an uncommon but increasing phenomenon. We previously reported in a small series of 11 patients a correlation between Androgen Receptor (AR) loss and localization to CNS. Aims of this study were: to confirm predictive role of AR loss in an independent validation cohort; to evaluate if AR status impacts on EOC survival. Results We collected other 29 cases and 19 controls as validation cohort. In this independent cohort at univariate analysis, cases exhibited lower expression of AR, considered both as continuous ( p <0.001) and as discrete variable (10% cut-off: p <0.003; Immunoreactive score: p <0.001). AR negative EOC showed an odds ratio (OR) = 8.33 for CNS dissemination compared with AR positive EOC. Kaplan-Meier curves of the whole dataset showed that AR<10% significantly correlates with worse outcomes (p=0.005 for PFS and p=0.002 for brain PFS (bPFS) respectively). Comparison of AR expression between primary tissue and paired brain metastases in the whole dataset did not show any statistically significant difference. Conclusions AR’s deficiency confirms its predictive role for CNS involvement from EOC in an independent cohort of cases and controls. Early assessment of AR status could improve clinical management and patients’ prognosis.
Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome
Authors: Li You , Xiong Guohui , Tan Jun , Wang Shudi , Zhang Ziyu , Wu Qiongfang , Wan Lei , Huang Ouping
Published: February 2020

The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells(GCs) is one of the causes of PCOS. Herein, we carried out RNA-seq to detect the different gene expression levels in ovarian GCs between 3 patients with PCOS and 4 normal controls, and found that Hedgehog signaling pathway(Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PCOS group. To further verify the above results, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysis. The qPCR results also indicated that the expression levels of other Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PCOS group were significantly higher than those in the control group. These results suggest that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.
Long non-coding RNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression by sponging miR-655-3p
Authors: Zhao Yuxin , Wang Zhaoxia , Gao Meili , Wang Xuehong , Feng Hui , Cui Yuanyuan , Tian Xia
Published: February 2020

Background: Long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported as an oncogene in many tumors including retinoblastoma (RB). This research mainly focused on the functions and mechanism of MALAT1 in RB.Methods: The levels of MALAT1, microRNA-655-3p (miR-655-3p), and ATPase family AAA domain containing 2 (ATAD2) in RB tissues and cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and apoptotic rate were monitored via cell counting kit 8 (CCK8) assay and flow cytometry, respectively. The protein levels of p21, CyclinD1, B-cell lymphoma-2 (Bcl-2), cleaved-casp-3, E-cadherin, Ncadherin, Vimentin, and ATAD2 were detected by Western blot assay. Transwell assay was performed to estimate the abilities of migration and invasion. The interactions between miR-655-3p and MALAT1 or ATAD2 were predicted by starBase. Dual-luciferase reporter assay was constructed to verify these interactions. The mice model experiments were established to validate the effects of MALAT1 in vivo.Results: MALAT1and ATAD2 were significantly increased while the level of miR-655-3p was remarkably decreased in RB tissues and cells. MALAT1 knockdown inhibited cell proliferation, metastasis, and epithelial-mesenchymal transition (EMT) but promoted apoptosis via miR-655-3p in vitro, and blocked xenograft tumor growth in vivo. MALAT1 was validated to sponge miR-655-3p and ATAD2 was verified as a candidate of miR-655-3p. MiR-655-3p overexpression inhibited cell proliferation but promoted apoptosis by targeting ATAD2. MALAT1 silencing affected cell behaviors by regulating ATAD2. MALAT1 depletion down-regulated ATAD2 expression via miR-655-3p in RB cells.Conclusion: MALAT1 positively regulated ATAD2 to accelerate cell proliferation but retard apoptosis by sponging miR-655-3p in RB cells.