bluuebunny/crossref_metadata_2025 huggingface dataset:
A deterministic equation to predict the accuracy of multi-population genomic prediction with multiple genomic relationship matrices
Authors: Raymond Biaty , Wientjes Yvonne C. J. , Bouwman Aniek C. , Schrooten Chris , Veerkamp Roel F.
Published: April 2020

Background

A multi-population genomic prediction (GP) model in which important pre-selected single nucleotide polymorphisms (SNPs) are differentially weighted (MPMG) has been shown to result in better prediction accuracy than a multi-population, single genomic relationship matrix ($${\mathbf{GRM}}$$GRM) GP model (MPSG) in which all SNPs are weighted equally. Our objective was to underpin theoretically the advantages and limits of the MPMG model over the MPSG model, by deriving and validating a deterministic prediction equation for its accuracy.

Methods

Using selection index theory, we derived an equation to predict the accuracy of estimated total genomic values of selection candidates from population$$A$$A($$r_{{{\mathbf{EGV}}_{{A_{T} }} }}$$rEGVAT), when individuals from two populations,$$A$$Aand$$B$$B, are combined in the training population and two$${\mathbf{GRM}}$$GRM, made respectively from pre-selected and remaining SNPs, are fitted simultaneously in MPMG. We used simulations to validate the prediction equation in scenarios that differed in the level of genetic correlation between populations, heritability, and proportion of genetic variance explained by the pre-selected SNPs. Empirical accuracy of the MPMG model in each scenario was calculated and compared to the predicted accuracy from the equation.

Results

In general, the derived prediction equation resulted in accurate predictions of$$r_{{{\mathbf{EGV}}_{{A_{T} }} }}$$rEGVATfor the scenarios evaluated. Using the prediction equation, we showed that an important advantage of the MPMG model over the MPSG model is its ability to benefit from the small number of independent chromosome segments ($$M_{e}$$Me) due to the pre-selected SNPs, both within and across populations, whereas for the MPSG model, there is only a single value for$$M_{e}$$Me, calculated based on all SNPs, which is very large. However, this advantage is dependent on the pre-selected SNPs that explain some proportion of the total genetic variance for the trait.

Conclusions

We developed an equation that gives insight into why, and under which conditions the MPMG outperforms the MPSG model for GP. The equation can be used as a deterministic tool to assess the potential benefit of combining information from different populations, e.g., different breeds or lines for GP in livestock or plants, or different groups of people based on their ethnic background for prediction of disease risk scores.
A novel risk model for mortality and hospitalization following cardiac resynchronization therapy in patients with non-ischemic cardiomyopathy: the alpha-score
Authors: Yang Shengwen , Liu Zhimin , Hu Yiran , Jing Ran , Gu Min , Niu Hongxia , Ding Ligang , Xing Anlu , Zhang Shu , Hua Wei
Published: April 2020

Background

Non-ischemic cardiomyopathy (NICM) has been associated with a better left ventricle reverse remodeling response and improved clinical outcomes after cardiac resynchronization therapy (CRT). The aims of our study were to identify the predictors of mortality and heart failure hospitalization in patients treated with CRT and design a risk score for prognosis.

Methods

A cohort of 422 consecutive NICM patients with CRT was retrospectively enrolled between January 2010 and December 2017. The primary endpoint was all-cause mortality and heart transplantation.

Results

In a multivariate analysis, the predictors of all-cause death were left atrial diameter [Hazard ratio (HR): 1.056, 95% confidence interval (CI): 1.020–1.093, P = 0.002]; non-left bundle branch block [HR: 1.793, 95% CI: 1.131–2.844, P = 0.013]; high sensitivity C-reactive protein [HR: 1.081, 95% CI: 1.029–1.134 P = 0.002]; and N-terminal pro-B-type natriuretic peptide [HR: 1.018, 95% CI: 1.007–1.030, P = 0.002]; and New York Heart Association class IV [HR: 1.018, 95% CI: 1.007–1.030, P = 0.002]. The Alpha-score (Atrial diameter, non-LBBB, Pro-BNP, Hs-CRP, NYHA class IV) was derived from each independent risk factor. The novel score had good calibration (Hosmer-Lemeshow test, P > 0.05) and discrimination for both primary endpoints [c-statistics: 0.749 (95% CI: 0.694–0.804), P < 0.001] or heart failure hospitalization [c-statistics: 0.692 (95% CI: 0.639–0.745), P < 0.001].

Conclusion

The Alpha-score may enable improved discrimination and accurate prediction of long-term outcomes among NICM patients with CRT.
Mycoplasma genitalium in Singapore is associated with Chlamydia trachomatis infection and displays high macrolide and Fluoroquinolone resistance rates
Authors: Hart Tim , Tang Wen Ying , Mansoor Siti Aminah bte , Chio Martin T. W. , Barkham Timothy
Published: April 2020

Background

Mycoplasma genitaliumis an emerging sexually transmitted infection, with increasing rates of resistance to fluroquinolones and macrolides, the recommended treatments. Despite this,M. genitaliumis not part of routine screening for Sexually Transmitted Infections (STIs) in many countries and the prevalence of infection and patterns of disease remain to be determined in many populations. Such data is of particular importance in light of the reported rise in antibiotic resistance inM. genitaliumisolates.

Methods

Urine and urethral swab samples were collected from the primary public sexual health clinic in Singapore and tested forC. trachomatis (CT)orN. gonorrhoeae(NG) infection and for the presence ofM. genitalium. Antibiotic resistance inM. genitaliumstrains detected was determined by screening for genomic mutations associated with macrolide and fluroquinolone resistance.

Results

We report the results of a study intoM. genitaliumprevalence at the national sexual health clinic in Singapore.M. genitaliumwas heavily associated with CT infection (8.1% of cases), but present in only of 2.4% in CT negative cases and not independently linked to NG infection. Furthermore, we found high rates of resistance mutations to both macrolides (25%) and fluoroquinolones (37.5%) with a majority of resistant strains being dual-resistant. Resistance mutations were only found in strains from patients with CT co-infection.

Conclusions

Our results support targeted screening of CT positive patients forM. genitaliumas a cost-effective strategy to reduce the incidence ofM. genitaliumin the absence of comprehensive routine screening. The high rate of dual resistance also highlights the need to ensure the availability of alternative antibiotics for the treatment of multi-drug resistantM. genitaliumisolates.
Early maternal weight gain as a risk factor for SGA in pregnancies with hyperemesis gravidarum: a 15-year hospital cohort study
Authors: Meinich Tale , Trovik Jone
Published: April 2020

Background

Inadequate maternal weight gain increases the risk of small-for-gestational age (SGA) infants. Women with hyperemesis gravidarum (HG) are at risk of significant early pregnancy weight loss and insufficient total pregnancy weight gain. Recent studies have implied that weight gain during the first half of pregnancy is more crucial to pregnancy outcome than total weight gain.

The aim of this study was to investigate whether not regaining prepregnancy weight by 13–18 weeks of gestation contributed to not reaching minimum body mass index (BMI)-specific total pregnancy weight gain and influenced the risk of SGA outcome in HG pregnancies.

Methods

In this retrospective 15-year cohort (2002–2016) of women hospitalized due to hyperemesis gravidarum, we reviewed individual patient hospital files and corresponding outpatient maternity records to collect prepregnancy BMI and weight, pregnancy weight gain (spanning 3-week intervals), delivery weight and foetal outcomes. BMI and total pregnancy weight gain goals were categorized according to the Institute of Medicine (IOM) 2009 guidelines: BMI < 18,5 kg/m2: 12.5–18 kg, 18.5–24.9 kg/m2: 11.5–16 kg, 25–29.9 kg/m2: 7–11.5 kg and ≥ 30 kg/m2: 5–9 kg. Birth weight was categorized as SGA if less than the 10th percentile of sex- and gestational length-specific Norwegian neonatal weight charts. Nonparametric tests were used to compare weight categories, and logistic regression was used to predict the odds ratio (OR) of inadequate total pregnancy weight gain or SGA delivery.

Results

Out of 892 women hospitalized for HG during 2002–2016, 784 had a pregnancy lasting ≥ 24 weeks, of which 746 were singleton pregnancies with follow-up until delivery. Among these women, 42 were classified as underweight, 514 as normal weight, 230 as overweight and 102 as obese before pregnancy. Not regaining prepregnancy weight by week 13–18 was an independent predictor of inadequate total gestational weight gain with an OR of 7.05 (95% CI 4.24–11.71) and an independent predictor for SGA outcome with an OR of 2.66 (95% CI 1.11–6.34), even when adjusted for total pregnancy weight gain, prepregnancy BMI, parity, age and smoking status.

Conclusion

Inadequate total maternal weight gain and not regaining prepregnancy weight by week 13–18 may be considered independent risk factors for delivering a baby that is small for gestational age in pregnancies with hyperemesis gravidarum. Achieving adequate weight gain during the first trimester in HG pregnancies is important for the foetal outcome, underscoring the importance of nutritional treatment during this period.
Smokeless tobacco use: its prevalence and relationships with dental symptoms, nutritional status and blood pressure among rural women in Burkina Faso
Authors: Diendéré Jeoffray , Zeba Augustin Nawidimbasba , Nikièma Léon , Kaboré Ahmed , Savadogo Paul Windinpsidi , Tougma Somnoma Jean-Baptiste , Tinto Halidou , Ouédraogo Arouna
Published: April 2020

Background

Sub-Saharan women use smokeless tobacco (SLT) more than smoked tobacco. Among Western African countries, the estimated weighted prevalence of SLT use in rural women was found to be the highest in Burkina Faso (after Sierra Leone). This study aimed to assess the prevalence of SLT use and its associated factors among rural women in Burkina Faso by using nationally representative data.

Methods

We used data from the 2013 STEPwise approach to Surveillance (STEPS) study, which provided sociodemographic, clinical (anthropometric, systolic blood pressure [SBP], diastolic blood pressure [DBP] and dental symptoms), biological (total and high-density lipoprotein cholesterol and fasting blood sugar), and tobacco and alcohol consumption data. Data for 1730 rural women were used, and we performed Student’s chi-squared and logistic regression analyses.

Results

The prevalence of current SLT use was 13.8% (95% CI: 12.2–15.5). Significant risks for SLT use were the presence of dental symptoms (adjusted odds ratio [aOR] = 2.59; p < 0.001), undernourishment (aOR = 1.78; p < 0.01), decreased waist circumference (aOR = 0.98; p < 0.05), decreased DBP (aOR = 0.97; p < 0.01), increased SBP (aOR = 1.01; p < 0.05), and increased differential blood pressure (aOR = 1.01; p < 0.05). The co-use of alcohol was also a significant risk factor (aOR = 2.80; p < 0.001).

Conclusion

The prevalence of current SLT use was high among rural women in Burkina Faso, and significant concerns for users included alcohol co-use, the occurrence of dental symptoms, undernourishment, and an increase in differential blood pressure. National Public Health interventions are needed to reduce SLT use and its health-related concerns.
Social capital and fertility behaviors: a cross-sectional study in Iranian women health care workers
Authors: Firouzbakht Mojgan , Tirgar Aram , Hajian-Tilaki Karimollah , Bakouei Fatemeh , Riahi Mohammad Esmaeil , Nikpour Maryam
Published: April 2020

Background

Fertility, in addition to the biomedical aspect, is phenomena of social, economic and demographic changes. Social network were considered for understanding fertility behaviors and changes in the levels of fertility. This study was conducted to investigate the relationship between social capital and childbirth behaviors in Iranian women employees.

Methods

This cross-sectional study was conducted in 2017 on 536 women health care workers who randomly selected from health care setting Babol/Iran. Data were collected using demographic, childbearing behavior and social capital questionnaires. The SPSS-21 software was employed to analysis the data at a significant level of 0.05.

Results

The results of the study showed that, there was significant relationship between number of pregnancy and social capital (P = 0.039). Furthermore, social capital has a significant relationship with the time of pregnancy (P = 0.043), the time of pregnancy in women with high social capital was observed to be relatively 30% shorter compare the women with low social capital.

Conclusion

Social capital, as one of the important factors influencing childbirth behaviors, should be considered in population planning and policy making.
In vitro enzyme inhibitory and cytotoxic studies with Evolvulus alsinoides (Linn.) Linn. Leaf extract: a plant from Ayurveda recognized as Dasapushpam for the management of Alzheimer’s disease and diabetes mellitus
Authors: Mettupalayam Kaliyannan Sundaramoor Pavithra , Kilavan Packiam Kannan
Published: April 2020

Background

Evolvulus alsinoides (Linn.) Linn. (Convolvulaceae) is a therapeutic herb alleviating brain patterns associated with three categories of regulatory principles of the body, mind, and behaviour. In the current research, enzyme inhibition and cytotoxic potentials of E. alsinoides (L.) L. leaf extract has been studied validating its potential application.

Methods

The plant phenolics in the leaf extracts obtained via cold-maceration with solvents viz.: n-hexane, chloroform, ethyl acetate, methanol, and water were quantitatively analyzed. The antioxidant potency was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing Ability of Plasma (FRAP) assays at five concentrations (100–500 μg). The enzyme inhibition potential was performed with α-amylase, α-glucosidase, and acetylcholinesterase at seven concentrations (25–500 μg). The experiments were done in triplicates and statistically validated using Minitab-17 and SPSS 22.

Results

Water extract contain 45.08 ± 0.02 mg GAE/g, 49.30 ± 0.07 mg GAE/g, 211.21 ± 0.02 mg QE/g tannins, phenolics, flavonoids respectively. Its antioxidant activity was supported by IC50 52.43 ± 0.2 μg/mL (DPPH assay) and 41.58 ± 0.03 (FRAP assay). Methanolic extract inhibits α-amylase with IC50 1.33 ± 0.05 μg/mL. Water extract inhibits α-glucosidase and acetylcholinesterase with IC50 3.58 ± 0.02 μg/mL and 4.46 ± 0.03 μg/mL. Cytotoxicity studies with SH-SY5Y cell-line substantiate the inhibition potential of water extract with IC50 103.0035 μg/mL.

Discussion and conclusions

The extracts with potent antioxidant and enzyme-inhibiting activity were determined. The findings of the research are the first report about the inhibition effects of Evolvulus alsinoides (Linn.) Linn extracts against α-amylase, α-glucosidase and acetylcholinesterase. The extracts shall be examined in future studies to evaluate its pharmaceutical potential.
Life satisfaction of Taiwanese dental graduates received residencies in the U.S.: a cross-sectional study
Authors: Fu Martin M. , Chen Rebecca Y. , Kao Huan-Chen , Wang Chi-Hsien , Chan Hsun-Liang , Fu Earl , Lee Tony Szu-Hsien
Published: April 2020

Background

Each year, more than 200 international dental graduates start U.S. specialty trainings to become specialists. It is unknown if their life satisfaction is associated with any dental career-related factor before residencies (e.g. dental school class rank, research experience, or private practice experience) and after residencies (e.g. staying in the U.S., teaching status, workplace, or board certification). This cross-sectional study aimed to identify these potential factors by surveying Taiwanese dental graduates who pursued U.S. residencies.

Methods

Life satisfaction was measured with a structured questionnaire, Satisfaction With Life Scale (SWLS), which includes five statements on a 5-point Likert scale. Online surveys were sent out to 290 Taiwanese dental graduates who were known to pursue U.S. residencies. T-test, one way analysis of variance, and multivariable adjusted generalized linear model (GLM) were used to assess the differences of mean SWLS scores from different variables.

Results

Surveys were completed by 158 dentists. Mean SWLS score of 125 specialists was higher (p = 0.0007) than the score of 33 residents. For the 125 specialists, multivariable adjusted GLM demonstrated better life satisfaction was positively associated with multiple independent factors, such as having research experience, being ranked in the top 26 ~ 50% of the class in dental school, starting U.S. residency within 4 years after dental school, starting residency before year 1996, and specializing in endodontics (vs. periodontics). Life satisfaction was not associated with any factors after residency (e.g. staying in the U.S. afterwards, teaching status, or workplace), but better mean life satisfaction score was significantly associated with being American specialty board certified (p < 0.001) for the specialists in the 26 ~ 75% of their class in dental school. For the 33 residents, better mean life satisfaction score was associated with better dental school class rank in both bivariate (p = 0.020) and multivariable adjusted GLM (p = 0.004) analyses.

Conclusions

The life satisfaction of Taiwanese dental graduates pursuing U.S. residencies might be associated with some professional factors, such as research experience, dental school class rank, residency timing, specialty type, and specialty board certification. We hope our results may provide some objective information on making career decisions for international dental graduates/students who are preparing for U.S. residency.
Correction to: The International Conference on Intelligent Biology and Medicine 2019: computational methods for drug interactions
Authors: Ning Xia , Zhang Chi , Wang Kai , Zhao Zhongming , Mathé Ewy
Published: April 2020

After publication of this supplement article [1], it is requested the grant ID in the Funding section should be corrected from NSF grant IIS-7811367 to NSF grant IIS-1902617.
Caring for Africa’s sickle cell children: will we rise to the challenge?
Authors: Oron Assaf P. , Chao Dennis L. , Ezeanolue Echezona E. , Ezenwa Loveth N. , Piel Frédéric B. , Ojogun Osifo Telison , Uyoga Sophie , Williams Thomas N. , Nnodu Obiageli E.
Published: April 2020

Background

Most of the world’s sickle cell disease (SCD) burden is in Africa, where it is a major contributor to child morbidity and mortality. Despite the low cost of many preventive SCD interventions, insufficient resources have been allocated, and progress in alleviating the SCD burden has lagged behind other public-health efforts in Africa. The recent announcement of massive new funding for research into curative SCD therapies is encouraging in the long term, but over the next few decades, it is unlikely to help Africa’s SCD children substantially.

Main discussion

A major barrier to progress has been the absence of large-scale early-life screening. Most SCD deaths in Africa probably occur before cases are even diagnosed. In the last few years, novel inexpensive SCD point-of-care test kits have become widely available and have been deployed successfully in African field settings. These kits could potentially enable universal early SCD screening. Other recent developments are the expansion of the pneumococcal conjugate vaccine towards near-universal coverage, and the demonstrated safety, efficacy, and increasing availability and affordability of hydroxyurea across the continent. Most elements of standard healthcare for SCD children that are already proven to work in the West, could and should now be implemented at scale in Africa. National and continental SCD research and care networks in Africa have also made substantial progress, assembling care guidelines and enabling the deployment and scale-up of SCD public-health systems. Substantial logistical, cultural, and awareness barriers remain, but with sufficient financial and political will, similar barriers have already been overcome in efforts to control other diseases in Africa.

Conclusion and recommendations

Despite remaining challenges, several high-SCD-burden African countries have the political will and infrastructure for the rapid implementation and scale-up of comprehensive SCD childcare programs. A globally funded effort starting with these countries and expanding elsewhere in Africa and to other high-burden countries, including India, could transform the lives of SCD children worldwide and help countries to attain their Sustainable Development Goals. This endeavor would also require ongoing research focused on the unique needs and challenges of SCD patients, and children in particular, in regions of high prevalence.
Functional expression of polyethylene terephthalate-degrading enzyme (PETase) in green microalgae
Authors: Kim Ji Won , Park Su-Bin , Tran Quynh-Giao , Cho Dae-Hyun , Choi Dong-Yun , Lee Yong Jae , Kim Hee-Sik
Published: April 2020

Background

For decades, plastic has been a valuable global product due to its convenience and low price. For example, polyethylene terephthalate (PET) was one of the most popular materials for disposable bottles due to its beneficial properties, namely impact resistance, high clarity, and light weight. Increasing demand of plastic resulted in indiscriminate disposal by consumers, causing severe accumulation of plastic wastes. Because of this, scientists have made great efforts to find a way to biologically treat plastic wastes. As a result, a novel plastic degradation enzyme, PETase, which can hydrolyze PET, was discovered in Ideonella sakaiensis 201-F6 in 2016.

Results

A green algae, Chlamydomonas reinhardtii, which produces PETase, was developed for this study. Two representative strains (C. reinhardtii CC-124 and CC-503) were examined, and we found that CC-124 could express PETase well. To verify the catalytic activity of PETase produced by C. reinhardtii, cell lysate of the transformant and PET samples were co-incubated at 30 °C for up to 4 weeks. After incubation, terephthalic acid (TPA), i.e. the fully-degraded form of PET, was detected by high performance liquid chromatography analysis. Additionally, morphological changes, such as holes and dents on the surface of PET film, were observed using scanning electron microscopy.

Conclusions

A PET hydrolyzing enzyme, PETase, was successfully expressed in C. reinhardtii, and its catalytic activity was demonstrated. To the best of our knowledge, this is the first case of PETase expression in green algae.
Perinatal urinary benzophenone-3 concentrations and glucose levels among women from a fertility clinic
Authors: Wang Zifan , Mínguez-Alarcón Lidia , Williams Paige L. , Bellavia Andrea , Ford Jennifer B. , Keller Myra , Petrozza John C. , Calafat Antonia M. , Hauser Russ , James-Todd Tamarra
Published: April 2020

Background

Subfertile women have higher risk of glucose intolerance during pregnancy. Studies suggest associations between several endocrine disrupting chemicals (EDCs) and pregnancy glucose levels. However, the association between benzophenone-3 (BP-3), an EDC widely found in sunscreen, and pregnancy glucose levels remains unclear. We aimed to assess the association between perinatal exposures to BP-3 and pregnancy glucose levels in subfertile women.

Methods

We evaluated 217 women from a prospective cohort based at a fertility clinic who had urinary BP-3 concentrations measured during 3-month preconception, first and/or second trimesters, and blood glucose measured at glucose load tests (GLTs) during late pregnancy. Multivariable linear and logistic regression models were used to assess associations between time-specific BP-3 in quartiles (Q1 – Q4) and mean glucose levels, as well as odds of abnormal GLT (glucose level ≥ 140 mg/dL), adjusting for potential confounders. Effect modification was assessed by age, season, BMI, infertility diagnosis, sex of fetus (es) and physical activity.

Results

Women with higher first trimester BP-3 concentrations had lower mean glucose levels [mean glucose (95% CI) for Q4 vs Q1 = 103.4 (95.0, 112.5) vs. 114.6 (105.8, 124.2) mg/dL]. Women with higher second trimester BP-3 concentrations had lower odds of abnormal GLT [OR (95% CI) for Q3 vs. Q1 = 0.12 (0.01, 0.94)]. The associations between BP-3 and glucose levels were modified by several factors: women with female-factor infertility, urine collected during summer, older age, lower BMI, or carried female fetus (es) had the strongest inverse associations between BP-3 and glucose levels, while no associations were observed in the remaining subgroups.

Conclusions

Time-specific inverse associations between BP-3 and pregnancy glucose levels existed in subfertile women, and especially among certain subgroups of this high-risk-population.
Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles
Authors: Unal Ozlem , Akkoc Yunus , Kocak Muhammed , Nalbat Esra , Dogan-Ekici Asiye Isin , Yagci Acar Havva , Gozuacik Devrim
Published: April 2020

Nanoparticle based gene delivery systems holds great promise. Superparamagnetic iron oxide nanoparticles (SPIONs) are being heavily investigated due to good biocompatibility and added diagnostic potential, rendering such nanoparticles theranostic. Yet, commonly used cationic coatings for efficient delivery of such anionic cargos, results in significant toxicity limiting translation of the technology to the clinic. Here, we describe a highly biocompatible, small and non-cationic SPION-based theranostic nanoparticles as novel gene therapy agents. We propose for the first-time, the usage of the microRNA machinery RISC complex component Argonaute 2 (AGO2) protein as a microRNA stabilizing agent and a delivery vehicle. In this study, AGO2 protein-conjugated, anti-HER2 antibody-linked and fluorophore-tagged SPION nanoparticles were developed (SP-AH nanoparticles) and used as a carrier for an autophagy inhibitory microRNA, MIR376B. These functionalized nanoparticles selectively delivered an effective amount of the microRNA into HER2-positive breast cancer cell lines in vitro and in a xenograft nude mice model of breast cancer in vivo, and successfully blocked autophagy. Furthermore, combination of the chemotherapy agent cisplatin with MIR376B-loaded SP-AH nanoparticles increased the efficacy of the anti-cancer treatment both in vitro in cells and in vivo in the nude mice. Therefore, we propose that AGO2 protein conjugated SPIONs are a new class of theranostic nanoparticles and can be efficiently used as innovative, non-cationic, non-toxic gene therapy tools for targeted therapy of cancer.
Migraine screen questionnaire: further psychometric evidence from categorical data methods
Authors: Manzar Md. Dilshad , Hameed Unaise Abdul , Salahuddin Mohammed , Khan Mohammad Yunus Ali , Nureye Dejen , Wakene Wakuma , Alamri Majed , Albougami Abdulrhman , PandiPerumal Seithikuruppu R. , Bahammam Ahmed S.
Published: April 2020

Background

Psychometric investigations of tools used in the screening of migraine including the migraine screen questionnaire (MS-Q), using an adequate statistical approach is needed. We assessed the psychometric properties of the migraine screen questionnaire (MS-Q) using categorical data methods.

Material and methods

A total of 343 students at Mizan-Tepi University, Ethiopia, age range = 18–35 years were selected by a simple random sampling method to participate in a cross-sectional study. The respondents completed the MS-Q, a semi-structured socio-demographic questionnaire, and a visual analog scale for attention (VAS-A).

Results

The cumulative variance rule (> 40%), the Kaiser’s criteria (Eigenvalue> 1), the Scree test and, the parallel analysis (minimum rank) identified a 1-factor model for the MS-Q with the factor loadings in the range of 0.78 to 0.84. Fit indices favored a 1-factor model of the MS-Q as indicated by comparative fit index (0.993), weighted root mean square residual (0.048), root mean square error of approximation (0.067), the goodness of fit index (1.00), and non-normed fit index (0.987). The values of the Factor Determinacy Index (0.953), marginal reliability (0.909), H-latent (0.909), H-observed (0.727), explained common variance (0.906) and the mean item residual absolute loadings (0.225) further complimented finding of the 1-Factor model. McDonald’s Omega (0.903) suggested adequate internal consistency. Discriminative validity was supported by significantly higher scores for the total and all the MS-Q items except one among those with complaints of attention.

Conclusion

The categorical methods support the psychometric validity of the MS-Q in the study population.
Correction to: LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway
Authors: Shi Deyao , Wu Fashuai , Mu Shidai , Hu Binwu , Zhong Binlong , Gao Feng , Qing Xiangcheng , Liu Jianxiang , Zhang Zhicai , Shao Zengwu
Published: April 2020

In the original publication of this manuscript [1], Fig. 5a needs to be revised, and adjustments have also been made to the captions for Figs. 2, 4, 5 and S1 to improve clarity for the reader.
COVID-19: ICU delirium management during SARS-CoV-2 pandemic
Authors: Kotfis Katarzyna , Williams Roberson Shawniqua , Wilson Jo Ellen , Dabrowski Wojciech , Pun Brenda T. , Ely E. Wesley
Published: April 2020

The novel coronavirus, SARS-CoV-2-causing Coronavirus Disease 19 (COVID-19), emerged as a public health threat in December 2019 and was declared a pandemic by the World Health Organization in March 2020. Delirium, a dangerous untoward prognostic development, serves as a barometer of systemic injury in critical illness. The early reports of 25% encephalopathy from China are likely a gross underestimation, which we know occurs whenever delirium is not monitored with a valid tool. Indeed, patients with COVID-19 are at accelerated risk for delirium due to at least seven factors including (1) direct central nervous system (CNS) invasion, (2) induction of CNS inflammatory mediators, (3) secondary effect of other organ system failure, (4) effect of sedative strategies, (5) prolonged mechanical ventilation time, (6) immobilization, and (7) other needed but unfortunate environmental factors including social isolation and quarantine without family. Given early insights into the pathobiology of the virus, as well as the emerging interventions utilized to treat the critically ill patients, delirium prevention and management will prove exceedingly challenging, especially in the intensive care unit (ICU). The main focus during the COVID-19 pandemic lies within organizational issues, i.e., lack of ventilators, shortage of personal protection equipment, resource allocation, prioritization of limited mechanical ventilation options, and end-of-life care. However, the standard of care for ICU patients, including delirium management, must remain the highest quality possible with an eye towards long-term survival and minimization of issues related to post-intensive care syndrome (PICS). This article discusses how ICU professionals (e.g., physicians, nurses, physiotherapists, pharmacologists) can use our knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the pandemic.
Varlociraptor: enhancing sensitivity and controlling false discovery rate in somatic indel discovery
Authors: Köster Johannes , Dijkstra Louis J. , Marschall Tobias , Schönhuth Alexander
Published: April 2020

Accurate discovery of somatic variants is of central importance in cancer research. However, count statistics on discovered somatic insertions and deletions (indels) indicate that large amounts of discoveries are missed because of the quantification of uncertainties related to gap and alignment ambiguities, twilight zone indels, cancer heterogeneity, sample purity, sampling, and strand bias. We provide a unifying statistical model whose dependency structures enable accurate quantification of all inherent uncertainties in short time. Consequently, false discovery rate (FDR) in somatic indel discovery can now be controlled at utmost accuracy, increasing the amount of true discoveries while safely suppressing the FDR.
CircAtlas: an integrated resource of one million highly accurate circular RNAs from 1070 vertebrate transcriptomes
Authors: Wu Wanying , Ji Peifeng , Zhao Fangqing
Published: April 2020

Existing circular RNA (circRNA) databases have become essential for transcriptomics. However, most are unsuitable for mining in-depth information for candidate circRNA prioritization. To address this, we integrate circular transcript collections to develop the circAtlas database based on 1070 RNA-seq samples collected from 19 normal tissues across six vertebrate species. This database contains 1,007,087 highly reliable circRNAs, of which over 81.3% have been assembled into full-length sequences. We profile their expression pattern, conservation, and functional annotation. We describe a novel multiple conservation score, co-expression, and regulatory networks for circRNA annotation and prioritization. CircAtlas can be accessed at http://circatlas.biols.ac.cn/.
Centromeric cohesion failure invokes a conserved choreography of chromosomal mis-segregations in pancreatic neuroendocrine tumor
Authors: Quevedo Rene , Spreafico Anna , Bruce Jeff , Danesh Arnavaz , El Ghamrasni Samah , Giesler Amanda , Hanna Youstina , Have Cherry , Li Tiantian , Yang S. Y. Cindy , Zhang Tong , Asa Sylvia L. , Haibe-Kains Benjamin , Krzyzanowska Monika , Smith Adam C. , Singh Simron , Siu Lillian L. , Pugh Trevor J.
Published: April 2020

Background

Pancreatic neuroendocrine tumors (PANETs) are rare, slow growing cancers that often present with local and distant metastasis upon detection. PANETS contain distinct karyotypes, epigenetic dysregulation, and recurrent mutations in MEN1, ATRX, and DAXX (MAD+); however, the molecular basis of disease progression remains uncharacterized.

Methods

We evaluated associations between aneuploidy and the MAD+ mutational state of 532 PANETs from 11 published genomic studies and 19 new cases using a combination of exome, targeted panel, shallow WGS, or RNA-seq. We mapped the molecular timing of MAD+ PANET progression using cellular fractions corrected for inferred tumor content.

Results

In 287 PANETs with mutational data, MAD+ tumors always exhibited a highly recurrent signature of loss of heterozygosity (LOH) and copy-number alterations affecting 11 chromosomes, typically followed by genome doubling upon metastasis. These LOH chromosomes substantially overlap with those that undergo non-random mis-segregation due to ectopic CENP-A localization to flanking centromeric regions in DAXX-depleted cell lines. Using expression data from 122 PANETs, we found decreased gene expression in the regions immediately adjacent to the centromere in MAD+ PANETs. Using 43 PANETs from AACR GENIE, we inferred this signature to be preceded by mutations in MEN1, ATRX, and DAXX. We conducted a meta-analysis on 226 PANETs from 8 CGH studies to show an association of this signature with metastatic incidence. Our study shows that MAD+ tumors are a genetically diverse and aggressive subtype of PANETs that display extensive chromosomal loss after MAD+ mutation, which is followed by genome doubling.

Conclusions

We propose an evolutionary model for a subset of aggressive PANETs that is initiated by mutation of MEN1, ATRX, and DAXX, resulting in defects in centromere cohesion from ectopic CENP-A deposition that leads to selective loss of chromosomes and the LOH phenotype seen in late-stage metastatic PANETs. These insights aid in disease risk stratification and nominate potential therapeutic vulnerabilities to treat this disease.
Correction to: A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
Authors: Gawel Danuta R. , Serra-Musach Jordi , Lilja Sandra , Aagesen Jesper , Arenas Alex , Asking Bengt , Bengnér Malin , Björkander Janne , Biggs Sophie , Ernerudh Jan , Hjortswang Henrik , Karlsson Jan-Erik , Köpsen Mattias , Lee Eun Jung , Lentini Antonio , Li Xinxiu , Magnusson Mattias , Martínez-Enguita David , Matussek Andreas , Nestor Colm E. , Schäfer Samuel , Seifert Oliver , Sonmez Ceylan , Stjernman Henrik , Tjärnberg Andreas , Wu Simon , Åkesson Karin , Shalek Alex K. , Stenmarker Margaretha , Zhang Huan , Gustafsson Mika , Benson Mikael
Published: April 2020

An amendment to this paper has been published and can be accessed via the original article.
Exploratory analysis of age and sex dependent DNA methylation patterns on the X-chromosome in whole blood samples
Authors: Li Shuxia , Lund Jesper B. , Christensen Kaare , Baumbach Jan , Mengel-From Jonas , Kruse Torben , Li Weilong , Mohammadnejad Afsaneh , Pattie Alison , Marioni Riccardo E. , Deary Ian J. , Tan Qihua
Published: April 2020

Background

Large numbers of autosomal sites are found differentially methylated in the aging genome. Due to analytical difficulties in dealing with sex differences in X-chromosome content and X-inactivation (XCI) in females, this has not been explored for the X chromosome.

Methods

Using data from middle age to elderly individuals (age 55+ years) from two Danish cohorts of monozygotic twins and the Scottish Lothian Birth Cohort 1921, we conducted an X-chromosome-wide analysis of age-associated DNA methylation patterns with consideration of stably inferred XCI status.

Results

Through analysing and comparing sex-specific X-linked DNA methylation changes over age late in life, we identified 123, 293 and 55 CpG sites significant (FDR < 0.05) only in males, only in females and in both sexes of Danish twins. All findings were significantly replicated in the two Danish twin cohorts. CpG sites escaping XCI are predominantly de-methylated with increasing age across cohorts. In contrast, CpGs highly methylated in both sexes are methylated even further with increasing age. Among the replicated sites in Danish samples, 16 (13%), 24 (8.2%) and 3 (5.5%) CpGs were further validated in LBC1921 (FDR < 0.05).

Conclusions

The X-chromosome of whole blood leukocytes displays age- and sex-dependent DNA methylation patterns in relation to XCI across cohorts.
Self-reactive T cells induce and perpetuate chronic relapsing arthritis
Authors: Tuncel Jonatan , Holmberg Jens , Haag Sabrina , Hopkins Malin Hultqvist , Wester-Rosenlöf Lena , Carlsen Stefan , Olofsson Peter , Holmdahl Rikard
Published: April 2020

Background

CD4+ T cells play a central role during the early stages of rheumatoid arthritis (RA), but to which extent they are required for the perpetuation of the disease is still not fully understood. The aim of the current study was to obtain conclusive evidence that T cells drive chronic relapsing arthritis.

Methods

We used the rat pristane-induced arthritis model, which accurately portrays the chronic relapsing-remitting disease course of RA, to examine the contribution of T cells to chronic arthritis.

Results

Rats subjected to whole-body irradiation and injected with CD4+ T cells from lymph nodes of pristane-injected donors developed chronic arthritis that lasted for more than 4 months, whereas T cells from the spleen only induced acute disease. Thymectomy in combination with irradiation enhanced the severity of arthritis, suggesting that sustained lymphopenia promotes T cell-driven chronic inflammation in this model. The ability of T cells to induce chronic arthritis correlated with their expression of Th17-associated transcripts, and while depletion of T cells in rats with chronic PIA led to transient, albeit significant, reduction in disease, neutralization of IL-17 resulted in almost complete and sustained remission.

Conclusion

These findings show that, once activated, self-reactive T cells can sustain inflammatory responses for extended periods of time and suggest that such responses are promoted in the presence of IL-17.
Dysregulation of 2-oxoglutarate-dependent dioxygenases by hyperglycaemia: does this link diabetes and vascular disease?
Authors: Green Hannah L. H. , Brewer Alison C.
Published: April 2020

The clinical, social and economic burden of cardiovascular disease (CVD) associated with diabetes underscores an urgency for understanding the disease aetiology. Evidence suggests that the hyperglycaemia associated with diabetes is, of itself, causal in the development of endothelial dysfunction (ED) which is recognised to be the critical determinant in the development of CVD. It is further recognised that epigenetic modifications associated with changes in gene expression are causal in both the initiation of ED and the progression to CVD. Understanding whether and how hyperglycaemia induces epigenetic modifications therefore seems crucial in the development of preventative treatments. A mechanistic link between energy metabolism and epigenetic regulation is increasingly becoming explored as key energy metabolites typically serve as substrates or co-factors for epigenetic modifying enzymes. Intriguing examples are the ten-eleven translocation and Jumonji C proteins which facilitate the demethylation of DNA and histones respectively. These are members of the 2-oxoglutarate-dependent dioxygenase superfamily which require the tricarboxylic acid metabolite, α-ketoglutarate and molecular oxygen (O2) as substrates and Fe (II) as a co-factor. An understanding of precisely how the biochemical effects of high glucose exposure impact upon cellular metabolism, O2 availability and cellular redox in endothelial cells (ECs) may therefore elucidate (in part) the mechanistic link between hyperglycaemia and epigenetic modifications causal in ED and CVD. It would also provide significant proof of concept that dysregulation of the epigenetic landscape may be causal rather than consequential in the development of pathology.
Estimation of inbreeding and identification of regions under heavy selection based on runs of homozygosity in a Large White pig population
Authors: Shi Liangyu , Wang Ligang , Liu Jiaxin , Deng Tianyu , Yan Hua , Zhang Longchao , Liu Xin , Gao Hongmei , Hou Xinhua , Wang Lixian , Zhao Fuping
Published: April 2020

Background

Runs of homozygosity (ROHs) are homozygous segments of the genome where the two haplotypes inherited from the parents are identical. The current availability of genotypes for a very large number of single nucleotide polymorphisms (SNPs) is leading to more accurate characterization of ROHs in the whole genome. Here, we investigated the occurrence and distribution of ROHs in 3,692 Large White pigs and compared estimates of inbreeding coefficients calculated based on ROHs (FROH), homozygosity (FHOM), genomic relationship matrix (FGRM) and pedigree (FPED). Furthermore, we identified genomic regions with high ROH frequencies and annotated their candidate genes.

Results

In total, 176,182 ROHs were identified from 3,569 animals, and all individuals displayed at least one ROH longer than 1 Mb. The ROHs identified were unevenly distributed on the autosomes. The highest and lowest coverages of Sus scrofa chromosomes (SSC) by ROH were on SSC14 and SSC13, respectively. The highest pairwise correlation among the different inbreeding coefficient estimates was 0.95 between FROH_total and FHOM, while the lowest was − 0.083 between FGRM and FPED. The correlations between FPED and FROH using four classes of ROH lengths ranged from 0.18 to 0.37 and increased with increasing ROH length, except for ROH > 10 Mb. Twelve ROH islands were located on four chromosomes (SSC1, 4, 6 and 14). These ROH islands harboured genes associated with reproduction, muscular development, fat deposition and adaptation, such as SIRT1, MYPN, SETDB1 and PSMD4.

Conclusion

FROH can be used to accurately assess individual inbreeding levels compared to other inbreeding coefficient estimators. In the absence of pedigree records, FROH can provide an alternative to inbreeding estimates. Our findings can be used not only to effectively increase the response to selection by appropriately managing the rate of inbreeding and minimizing the negative effects of inbreeding depression but also to help detect genomic regions with an effect on traits under selection.
Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues
Authors: Li Meng-Yuan , Li Lin , Zhang Yue , Wang Xiao-Sheng
Published: April 2020

Background

Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.

Methods

We comparedACE2expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student’sttest. We also investigated the correlations betweenACE2expression and immune signatures in various tissues using Pearson’s correlation test.

Results

ACE2expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle.ACE2showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland.ACE2was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels,ACE2expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs,ACE2expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively.

Conclusions

Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.
Multiobjective clustering algorithm for complex data in learning management systems
Authors: Ramadan Rabie A. , Alhaisoni Majed Mohaia , Khedr Ahmed Y.
Published: April 2020

Learning Management Systems (LMS) is now an emergent technology where massive data are collected and requires handling. This data comes from different sources with multiple features which represents another complex paradigm. However, as part of business intelligence and decision support, this data needs to be classified and analyzed for the management, teachers, as well as students to make the appropriate decisions. Thus, one of the effective data analysis methods is clustering. However, LMS data encompasses multi-features, which are not sufficient to make appropriate decisions. Therefore, single feature clustering algorithms would not help LMS decision-makers. Consequently, multifeatured/multiobjective clustering algorithms could be one of the proposed solutions. Thus, looking at different multiobjective clustering algorithms as compared to the LMS nature of data, those algorithms do not satisfy the clustering purpose. In addition, the LMS data could be huge, complex, and sequential algorithms would not help as well. Thus, this paper is a step forward towards clustering LMS data for better decision making. The paper proposes a new clustering framework based upon distributed systems and a new multiobjective algorithm for the purpose of LMS clustering. The algorithm has been examined experimentally in order to answer some of the questions that help taking decision based upon LMS collected data.