bluuebunny/crossref_metadata_2025 huggingface dataset:
The Candidate Genes Underlying a Stably Expressed QTL for Low Temperature Germinability in Rice (Oryza sativa L.)
Authors: Yang Tifeng , Zhou Lian , Zhao Junliang , Dong Jingfang , Liu Qing , Fu Hua , Mao Xingxue , Yang Wu , Ma Yamei , Chen Luo , Wang Jian , Bai Song , Zhang Shaohong , Liu Bin
Published: October 2020

Background

Direct seeding is an efficient cultivation technique in rice. However, poor low temperature germinability (LTG) of modern rice cultivars limits its application. Identifying the genes associated with LTG and performing molecular breeding is the fundamental way to address this issue. However, few LTG QTLs have been fine mapped and cloned so far.

Results

In the present study, the LTG evaluation of 375 rice accessions selected from the Rice Diversity Panel 2 showed that there were large LTG variations within the population, and the LTG of Indica group was significantly higher than that of Japonica and Aus groups (p < 0.01). In total, eleven QTLs for LTG were identified through genome-wide association study (GWAS). Among them, qLTG_sRDP2–3/qLTG_JAP-3, qLTG_AUS-3 and qLTG_sRDP2–12 are first reported in the present study. The QTL on chromosome 10, qLTG_sRDP2–10a had the largest contribution to LTG variations in 375 rice accessions, and was further validated using single segment substitution line (SSSL). The presence of qLTG_sRDP2–10a could result in 59.8% increase in LTG under 15 °C low temperature. The expression analysis of the genes within qLTG_sRDP2–10a region indicated that LOC_Os10g22520 and LOC_Os10g22484 exhibited differential expression between the high and low LTG lines. Further sequence comparisons revealed that there were insertion and deletion sequence differences in the promoter and intron region of LOC_Os10g22520, and an about 6 kb variation at the 3′ end of LOC_Os10g22484 between the high and low LTG lines, suggesting that the sequence variations of the two genes could be the cause for their differential expression in high and low LTG lines.

Conclusion

Among the 11 QTLs identified in this study, qLTG_sRDP2–10a could also be detected in other three studies using different germplasm under different cold environments. Its large effect and stable expression make qLTG_sRDP2–10a particularly valuable in rice breeding. The two genes, LOC_Os10g22484 and LOC_Os10g22520, were considered as the candidate genes underlying qLTG_sRDP2–10a. Our results suggest that integrating GWAS and SSSL can facilitate identification of QTL for complex traits in rice. The identification of qLTG_sRDP2–10a and its candidate genes provide a promising source for gene cloning of LTG and molecular breeding for LTG in rice.
Effect of rTMS on Parkinson’s cognitive function: a systematic review and meta-analysis
Authors: Jiang Yi , Guo Zhiwei , McClure Morgan A. , He Lin , Mu Qiwen
Published: October 2020

Background

To evaluate the effects and optimal parameters of repetitive transcranial magnetic stimulation (rTMS) on cognition function of patients with Parkinson’s disease (PD) and to estimate which cognitive function may obtain more benefits from rTMS.

Method

The articles dealing with rTMS on cognitive function of PD patients were retrieved from the databases until April 2019. Outcomes of global cognitive function and different cognitive domains were extracted. The standardized mean differences (SMDs) with 95% confidence interval (CI) of cognitive outcome for different parameters, scales, and cognitive functions were estimated.

Results

Fourteen studies involving 173 subjects were included in this meta-analysis. A significant effect size was observed with the mini-mental state examination (MMSE) for the global cognitive outcome based on the evidence of four published articles. Further subtests for different cognitive domains demonstrated prominent effect for the executive function. The significant effect sizes for executive function were found with multiple sessions of high-frequency rTMS over frontal cortex; especially over dorsolateral prefrontal cortex (DLPFC). All of the other cognitive domains, which included memory, attention, and language ability, did not obtain significant effects.

Conclusions

Multiple sessions of high-frequency rTMS over the DLPFC may have positive effect on executive function in PD patients. Further well designed studies with large sample sizes are needed to verify our results and ascertain the long-term effects of rTMS.
Pilot study of ziv-aflibercept in myopic choroidal neovascularisation patients
Authors: Nawar Amin E. , Shafik Heba M.
Published: October 2020

Background

Myopic choroidal neovascularization (CNV) is the most common sight-threatening complication associated with high myopia. The present study evaluated the efficacy and safety of the intravitreal injection of ziv-aflibercept in patients with myopic CNV.

Methods

This prospective interventional study was conducted on 20 eyes of 20 patients with active myopic CNV. Twelve patients were 40 years or older. This study was performed in the Ophthalmology Department of Tanta University Eye Hospital, Tanta University, Egypt. Optical coherence tomography (OCT) was performed for all patients at baseline and monthly after injection during the 6-month follow up period. The main outcome measures were changes in BCVA and CMT. The exploratory outcome measures were CNV size, IOP and the number of injections needed in each age group during the study period.

Results

Patients with myopic CNV younger than 40 years needed fewer injections (2.00 ± 0.76) than patients older than 40 years (2.50 ± 1.00), with no statistical significance detected between the two groups (p-value 0.246). CNV was smaller in the younger age group (p-value 0.209), best corrected visual acuity (BCVA) improved significantly in the younger and older age groups (p-values 0.001 and 0.028, respectively), and central macular thickness (CMT) decreased significantly after 6 months, from 242.88 ± 23.83 μm to 191.13 ± 13.83 μm in the younger age group and from 251.33 ± 26.60 μm to 197.08 ± 17.64 μm in the older age group (p = 0.001). No significant correlation was found between the final BCVA and either the spherical equivalent or central macular thickness after 6 months, with p-values of 0.135 and 0.145, respectively. No significant changes in IOP were detected in either group after the intravitreal injection.

Conclusion

Ziv-aflibercept is a highly effective and safe drug in cases of active myopic CNV; however, a larger number of patients and a longer follow-up period are needed to confirm our results.

This study was retrospectively registered at clinicaltrials.gov (ID: NCT04290195) on 26-2-2020.
Isolation, characterization and in vitro anti-salmonellal activity of compounds from stem bark extract of Canarium schweinfurthii
Authors: SOKOUDJOU Jean Baptiste , ATOLANI Olubunmi , NJATENG Guy Sedar Singor , KHAN Afsar , TAGOUSOP Cyrille Ngoufack , BITOMBO André Nehemie , KODJIO Norbert , GATSING Donatien
Published: October 2020

Background

Bacteria belonging to theSalmonellagenus are major concern for health, as they are widely reported in many cases of food poisoning. The use of antibiotics remains a main stream control strategy for avian salmonellosis as well as typhoid and paratyphoid fevers in humans. Due to the growing awareness about drug resistance and toxicities, the use of antibiotics is being discouraged in many countries whilst advocating potent benign alternatives such as phyto-based medicine. The objective of this work was to isolate, characterise the bioactive compounds ofCanarium schweinfurthii; and evaluate their anti-salmonellal activity.

Methods

The hydro-ethanolic extract ofCanarium schweinfurthiiwas fractionated and tested for their anti-salmonellal activity. The most active fractions (i.e. chloroform and ethyl acetate partition fractions) were then explored for their phytochemical constituents. Fractionation on normal phase silica gel column chromatography and size exclusion chromatography on Sephadex LH-20 led to the isolation of four compounds (maniladiol, scopoletin, ethyl gallate and gallic acid) reported for the first time inCanarium schweinfurthii.

Results

Result indicated that scopoletin and gallic acid had greater activity than the crude extracts and partition fractions. Among the isolated compounds, scopoletin showed the highest inhibitory activity with a MIC of 16 μg/ml againstSalmonellaTyphimurium andSalmonellaEnteritidis.

Conclusions

The overall results of this study indicates that the hydro-ethanolic extract as well as some of isolated compounds have interesting anti-salmonellal activities that could be further explored for the development of potent therapy for salmonellosis. Furthermore, the study adds credence to the folkloric applications of the plant.
Endothelial dysfunction in neuroprogressive disorders—causes and suggested treatments
Authors: Morris Gerwyn , Puri Basant K. , Olive Lisa , Carvalho Andre , Berk Michael , Walder Ken , Gustad Lise Tuset , Maes Michael
Published: October 2020

Background

Potential routes whereby systemic inflammation, oxidative stress and mitochondrial dysfunction may drive the development of endothelial dysfunction and atherosclerosis, even in an environment of low cholesterol, are examined.

Main text

Key molecular players involved in the regulation of endothelial cell function are described, including PECAM-1, VE-cadherin, VEGFRs, SFK, Rho GEF TRIO, RAC-1, ITAM, SHP-2, MAPK/ERK, STAT-3, NF-κB, PI3K/AKT, eNOS, nitric oxide, miRNAs, KLF-4 and KLF-2. The key roles of platelet activation, xanthene oxidase and myeloperoxidase in the genesis of endothelial cell dysfunction and activation are detailed. The following roles of circulating reactive oxygen species (ROS), reactive nitrogen species and pro-inflammatory cytokines in the development of endothelial cell dysfunction are then described: paracrine signalling by circulating hydrogen peroxide, inhibition of eNOS and increased levels of mitochondrial ROS, including compromised mitochondrial dynamics, loss of calcium ion homeostasis and inactivation of SIRT-1-mediated signalling pathways. Next, loss of cellular redox homeostasis is considered, including further aspects of the roles of hydrogen peroxide signalling, the pathological consequences of elevated NF-κB, compromised S-nitrosylation and the development of hypernitrosylation and increased transcription of atherogenic miRNAs. These molecular aspects are then applied to neuroprogressive disorders by considering the following potential generators of endothelial dysfunction and activation in major depressive disorder, bipolar disorder and schizophrenia: NF-κB; platelet activation; atherogenic miRs; myeloperoxidase; xanthene oxidase and uric acid; and inflammation, oxidative stress, nitrosative stress and mitochondrial dysfunction.

Conclusions

Finally, on the basis of the above molecular mechanisms, details are given of potential treatment options for mitigating endothelial cell dysfunction and activation in neuroprogressive disorders.
Variability of forced vital capacity in progressive interstitial lung disease: a prospective observational study
Authors: Veit Tobias , Barnikel Michaela , Crispin Alexander , Kneidinger Nikolaus , Ceelen Felix , Arnold Paola , Munker Dieter , Schmitzer Magdalena , Barton Jürgen , Schiopu Sanziana , Schiller Herbert B. , Frankenberger Marion , Milger Katrin , Behr Jürgen , Neurohr Claus , Leuschner Gabriela
Published: October 2020

Background

Fibrotic interstitial lung disease (ILD) is often associated with poor outcomes, but has few predictors of progression. Daily home spirometry has been proposed to provide important information about the clinical course of idiopathic pulmonary disease (IPF). However, experience is limited, and home spirometry is not a routine component of patient care in ILD. Using home spirometry, we aimed to investigate the predictive potential of daily measurements of forced vital capacity (FVC) in fibrotic ILD.

Methods

In this prospective observational study, patients with fibrotic ILD and clinical progression were provided with home spirometers for daily measurements over 6 months. Hospital based spirometry was performed after three and 6 months. Disease progression, defined as death, lung transplantation, acute exacerbation or FVC decline > 10% relative was assessed in the cohort.

Results

From May 2017 until August 2018, we included 47 patients (IPF n = 20; non-IPF n = 27). Sufficient daily measurements were performed by 85.1% of the study cohort. Among these 40 patients (IPF n = 17; non-IPF n = 23), who had a mean ± SD age of 60.7 ± 11.3 years and FVC 64.7 ± 21.7% predicted (2.4 ± 0.8 L), 12 patients experienced disease progression (death: n = 2; lung transplantation: n = 3; acute exacerbation: n = 1; FVC decline > 10%: n = 6). Within the first 28 days, a group of patients had high daily variability in FVC, with 60.0% having a variation ≥5%. Patients with disease progression had significantly higher FVC variability than those in the stable group (median variability 8.6% vs. 4.8%; p = 0.002). Cox regression identified FVC variability as independently associated with disease progression when controlling for multiple confounding variables (hazard ratio: 1.203; 95% CI:1.050–1.378; p = 0.0076).

Conclusions

Daily home spirometry is feasible in IPF and non-IPF ILD and facilitates the identification of FVC variability, which was associated with disease progression.
The role of Allied Health Professions and Nursing Research Internships in developing a research culture: a mixed-methods exploration of stakeholder perspectives
Authors: Nightingale J. , Fowler-Davis S. , Grafton K. , Kelly S. , Langham C. , Lewis R. , Bianco B. , Harrop D.
Published: October 2020

Background

Developing research capability and capacity within the healthcare professions is a challenge throughout diverse international settings. Within England, the National Institute for Health Research aimed to address these challenges through the Integrated Clinical Academic (ICA) research careers escalator for nurses, midwives and allied health professionals. Poor academic progression has been identified in the advanced stages of the pathway, though progression from the earlier entry point (Internship) has not previously been investigated. A national evaluation of four completed Internship cohorts was undertaken to explore stakeholder perspectives and progression beyond the Internship programme.

Methods

A mixed methods project used sequential qualitative and quantitative data collection phases commencing with two stakeholder focus groups (n = 10); the findings informed the development of an online survey distributed to previous cohorts of interns (n = 104), their managers (n = 12) and academic mentors (n = 36). Eight semi-structured interviews subsequently explored the challenges and opportunities afforded by the internships. Thematic analysis was used to review qualitative data from focus groups and interviews, with survey data analysed and displayed using descriptive statistics. Synthesis of data from each phase is displayed within the four level evaluation framework outlined within the New World Kirkpatrick® Training Evaluation Model.

Results

Important regional differences exist yet the internships are highly valued by all stakeholders. Representation varied between different professions, with nursing and some service-based professions poorly represented. All interns successfully completed the programme (n = 104), with evidence of positive impacts on interns, colleagues and patient care. Balancing research commitments with clinical activity was challenging; middle managers were seen as gatekeepers to programme success. Progression to the next stage of the ICA pathway is highly competitive and was achieved by only a quarter of interns; access to mentors outside of the funded programme is vital for a successful transition.

Conclusions

The Internship programme succeeds in providing a range of important early experiences in research, though progression beyond the programme is challenging due, in part, to a widening gap between Internship and the next level of the ICA framework. Vital mentorship support to bridge this gap is threatened by a lack of time and funding; therefore, the pursuit of a clinical-academic career will continue to be elusive for many nurses and allied health professionals. A partnership approach to clinical academic support at institutional level is needed with several international models offering alternative strategies for consideration.
How much the Iranian government spent on disasters in the last 100 years? A critical policy analysis
Authors: Seddighi Hamed , Seddighi Sadegh
Published: October 2020

Background

During the past 20 years, Iran has been experiencing a significant increase in the occurrence of disasters mainly due to the emergence of anthropogenic climate change. This paper aims at analyzing the trend of national budget allocation in Iran over the last 100 years to evaluate the focus of the Iranian state on the four phases of Preparedness, Mitigation, Response, and Recovery and propose modifications.

Methods

It is used a critical policy analysis with what’s the problem represented approach. In this approach is focused on problematization and policy gaps. The most important policy statement in any government is the budget. During the first screening, 1028 regulations and laws were found from 1910 to 2020. After full text screening, 494 regulations and laws related to budget allocation to disasters were analyzed.

Results

The Iranian government has spent around 29 billion USD on disasters during the last 100 years. Droughts, earthquake and flood have costs the government more than other disasters, accounting for more than 14, 6.9, and 6.1 billion USD, respectively, in the allocated budget. Most of the Iranian government expenditure during the last 100 years on various disasters such as drought, flood, earthquake, and COVID-19 has been spent on involuntary costs including Response and Recovery. Mitigation and Preparedness are the two critical disaster management phases with very small shares of national budgeting.

Conclusions

From policy audit and policy gaps it is concluded that Iranian governments during last 100 years, problematized the issue of “disasters strike” and not “disasters’ risks”. In time of disasters, governments tried to solve the issues or impacts of disasters with budgeting to response and recovery. Nevertheless, disasters’ prevention or mitigation or preparedness was not a problem for Iranian governments from 1920 to 2020.
Social network-based measurement of abortion incidence: promising findings from population-based surveys in Nigeria, Cote d’Ivoire, and Rajasthan, India
Authors: Bell Suzanne O. , Shankar Mridula , Omoluabi Elizabeth , Khanna Anoop , Andoh Hyacinthe Kouakou , OlaOlorun Funmilola , Ahmad Danish , Guiella Georges , Ahmed Saifuddin , Moreau Caroline
Published: October 2020

Background

Monitoring abortion rates is highly relevant for demographic and public health considerations, yet its reliable estimation is fraught with uncertainty due to lack of complete national health facility service statistics and bias in self-reported survey data. In this study, we aim to test the confidante methodology for estimating abortion incidence rates in Nigeria, Cote d’Ivoire, and Rajasthan, India, and develop methods to adjust for violations of assumptions.

Methods

In population-based surveys in each setting, female respondents of reproductive age reported separately on their two closest confidantes’ experience with abortion, in addition to reporting about their own experiences. We used descriptive analyses and design-based F tests to test for violations of method assumptions. Using post hoc analytical techniques, we corrected for biases in the confidante sample to improve the validity and precision of the abortion incidence estimates produced from these data.

Results

Results indicate incomplete transmission of confidante abortion knowledge, a biased confidante sample, but reduced social desirability bias when reporting on confidantes' abortion incidences once adjust for assumption violations. The extent to which the assumptions were met differed across the three contexts. The respondent 1-year pregnancy removal rate was 18.7 (95% confidence interval (CI) 14.9–22.5) abortions per 1000 women of reproductive age in Nigeria, 18.8 (95% CI 11.8–25.8) in Cote d’Ivoire, and 7.0 (95% CI 4.6–9.5) in India. The 1-year adjusted abortion incidence rates for the first confidantes were 35.1 (95% CI 31.1–39.1) in Nigeria, 31.5 (95% CI 24.8–38.1) in Cote d’Ivoire, and 15.2 (95% CI 6.1–24.4) in Rajasthan, India. Confidante two’s rates were closer to confidante one incidences than respondent incidences. The adjusted confidante one and two incidence estimates were significantly higher than respondent incidences in all three countries.

Conclusions

Findings suggest that the confidante approach may present an opportunity to address some abortion-related data deficiencies but require modeling approaches to correct for biases due to violations of social network-based method assumptions. The performance of these methodologies varied based on geographical and social context, indicating that performance may be better in settings where abortion is legally and socially restricted.
High Smad7 in the early post-operative recurrence of Crohn’s disease
Authors: Zorzi Francesca , Calabrese Emma , Di Fusco Davide , De Cristofaro Elena , Biancone Livia , Casella Sara , Palmieri Giampiero , Monteleone Giovanni
Published: October 2020

Background

In Crohn’s disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-β1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD.

Methods

Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Smad7 was examined by immunohistochemistry and cytokine expression was analysed by flow-cytometry.

Results

Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of Smad7-expressing cells in both the epithelial and lamina propria compartments. Transition from this stage to endoscopic recurrence was marked by persistence of high number of Smad7-positive cells, which reduced significantly in the late stages of the disease, where Smad7 expression remained, however, greater than that seen in normal controls. In samples with early lesions, Smad7 expression positively correlated with the number of interferon-γ-secreting cells.

Conclusions

Smad7 induction is an early event in the inflammatory sequence occurring in CD, thus suggesting that knockdown of Smad7 can help prevent post-operative recurrence.
Commentary on human pluripotent stem cell-based blood–brain barrier models
Authors: Lippmann Ethan S. , Azarin Samira M. , Palecek Sean P. , Shusta Eric V.
Published: October 2020

In 2012, we provided the first published evidence that human pluripotent stem cells could be differentiated to cells exhibiting markers and phenotypes characteristic of the blood–brain barrier (BBB). In the ensuing years, the initial protocols have been refined, and the research community has identified both positive and negative attributes of this stem cell-based BBB model system. Here, we give our perspective on the current status of these models and their use in the BBB community, as well as highlight key attributes that would benefit from improvement moving forward.
Prediction of the treatment response in ovarian cancer: a ctDNA approach
Authors: Sharbatoghli Mina , Vafaei Somayeh , Aboulkheyr Es Hamidreza , Asadi-Lari Mohsen , Totonchi Mehdi , Madjd Zahra
Published: October 2020

Ovarian cancer is the eighth most commonly occurring cancer in women. Clinically, the limitation of conventional screening and monitoring approaches inhibits high throughput analysis of the tumor molecular markers toward prediction of treatment response. Recently, analysis of liquid biopsies including circulating tumor DNA (ctDNA) open new way toward cancer diagnosis and treatment in a personalized manner in various types of solid tumors. In the case of ovarian carcinoma, growing pre-clinical and clinical studies underscored promising application of ctDNA in diagnosis, prognosis, and prediction of treatment response. In this review, we accumulate and highlight recent molecular findings of ctDNA analysis and its associations with treatment response and patient outcome. Additionally, we discussed the potential application of ctDNA in the personalized treatment of ovarian carcinoma.

Graphical abstract

ctDNA-monitoring usage during the ovarian cancer treatments procedures.
What is the optimal time-response window for the use of photobiomodulation therapy combined with static magnetic field (PBMT-sMF) for the improvement of exercise performance and recovery, and for how long the effects last? A randomized, triple-blinded, placebo-controlled trial
Authors: Leal-Junior Ernesto Cesar Pinto , de Oliveira Marcelo Ferreira Duarte , Joensen Jon , Stausholm Martin Bjørn , Bjordal Jan Magnus , Tomazoni Shaiane Silva
Published: October 2020

Background

The optimal time-response window for photobiomodulation therapy (PBMT) using low-level laser therapy (LLLT) and/or light emitting diodes therapy (LEDT) combined with static magnetic fields (sMF) before physical activity still was not fully investigated. The aim of the present study was to investigate the better of four time-response windows for PBMT combined with sMF (PBMT-sMF) use before exercise in humans.

Methods

A prospectively registered, randomized, triple-blinded (volunteers, therapists and assessors) placebo-controlled trial was carried out. Sixty healthy untrained male subjects were randomly allocated to six experimental groups (n = 10 per group): PBMT-sMF 5 mins, PBMT-sMF 3 h, PBMT-sMF 6 h, PBMT-sMF 1-day, placebo, and control. The control group performed all procedures, however did not receive any kind of intervention. PBMT-sMF active or PBMT-sMF placebo was applied precisely in different time points after baseline MVC test to ensure that both MVC tests and eccentric exercise protocol would occur at the same hour of the day in all groups. Then, after five minutes, 3 h, 6 h or 1-day (24 h) of PBMT-sMF treatment (active or placebo) the eccentric exercise protocol was performed. The primary outcome was peak torque obtained from maximum voluntary contraction (MVC). The secondary outcomes were creatine kinase (CK), and delayed onset muscle soreness (DOMS). The primary and secondary outcomes were measured at baseline, immediately after, 1 h, 24 h and 48 h after the eccentric exercise protocol.

Results

Sixty patients were randomized and analyzed to each sequence. The outcomes in absolute values show that all active PBMT-sMF groups increased (p < 0.05) MVC from immediately after to 1 h after eccentric exercise, and decreased (p < 0.05) CK activity at all time points. However, PBMT-sMF 5 mins, 3 h and 6 h groups showed better results in MVC and CK analysis from 24 h to 48 h, and also to DOMS (p < 0.05) at all time points. Participants did not report any adverse events.

Conclusions

PBMT-sMF can be used from 5 min to 6 h before exercise, and the effects can last up to 54 h after treatment. However, the effects start to decrease when a 1-day (24 h) time-response window is used.

Trial registration

NCT03420391. Registered 05 February 2018.
Molecular characteristics of rotavirus genotypes circulating in the south of Benin, 2016–2018
Authors: Agbla Jijoho Michel , Esona Mathew D. , Agbankpe Alidehou Jerrold , Capo-Chichi Annick , Gautam Rashi , Dougnon Tamegnon Victorien , Razack Osseni , Bowen Michael D. , Bankole Honore Sourou
Published: October 2020

Objective

Rotavirus remains the main causative agent of gastroenteritis in young children in countries that have not yet introduced the vaccine. In Benin, rotavirus vaccine was introduced late December 2019 into the EPI. This study aims to provide pre-vaccination era rotavirus genotyping data in Benin. These data can supplement data from the surveillance system of Ministry of Health of Benin which is supported by the World Health Organization (WHO).

Results

Of the 420 diarrheal stool samples, actively collected in southern Benin from July 2016 through November 2018 from children under 5 years old and suffering from gastroenteritis, 167 (39.8%) samples were rotavirus EIA positive. 186 (44.3%) samples contained amplifiable rotavirus RNA detected by qRT-PCR method and were genotyped using one-step RT-PCR multiplex genotyping method. G1P[8] represents the predominant genotype (32%) followed by the G2P[4] (26%), G3P[6] (16%), G12P[8] (13%) and mixed G and P types (1%). Four samples (2%) could not be assigned both G and P type specificity.
Serious neonatal morbidities are associated with differences in DNA methylation among very preterm infants
Authors: Everson Todd M. , O’Shea T. Michael , Burt Amber , Hermetz Karen , Carter Brian S. , Helderman Jennifer , Hofheimer Julie A. , McGowan Elisabeth C. , Neal Charles R. , Pastyrnak Steven L. , Smith Lynne M. , Soliman Antoine , DellaGrotta Sheri A. , Dansereau Lynne M. , Padbury James F. , Lester Barry M. , Marsit Carmen J.
Published: October 2020

Background

Infants born very preterm are more likely to experience neonatal morbidities compared to their term peers. Variations in DNA methylation (DNAm) associated with these morbidities may yield novel information about the processes impacted by these morbidities.

Methods

This study included 532 infants born < 30 weeks gestation, participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants study. We used a neonatal morbidity risk score, which was an additive index of the number of morbidities experienced during the NICU stay, including bronchopulmonary dysplasia (BPD), severe brain injury, serious neonatal infections, and severe retinopathy of prematurity. DNA was collected from buccal cells at discharge from the NICU, and DNAm was measured using the Illumina MethylationEPIC. We tested for differential methylation in association with the neonatal morbidity risk score then tested for differentially methylated regions (DMRs) and overrepresentation of biological pathways.

Results

We identified ten differentially methylated CpGs (α Bonferroni-adjusted for 706,278 tests) that were associated with increasing neonatal morbidity risk scores at three intergenic regions and at HPS4, SRRD, FGFR1OP, TNS3, TMEM266, LRRC3B, ZNF780A, and TENM2. These mostly followed dose–response patterns, for 8 CpGs increasing DNAm associated with increased numbers of morbidities, while for 2 CpGs the risk score was associated with decreasing DNAm. BPD was the most substantial contributor to differential methylation. We also identified seven potential DMRs and over-representation of genes involved in Wnt signaling; however, these results were not significant after Bonferroni adjustment for multiple testing.

Conclusions

Neonatal DNAm, within genes involved in fibroblast growth factor activities, cellular invasion and migration, and neuronal signaling and development, are sensitive to the neonatal health complications of prematurity. We hypothesize that these epigenetic features may be representative of an integrated marker of neonatal health and development and are promising candidates to integrate with clinical information for studying developmental impairments in childhood.
A survey on data analysis on large-Scale wireless networks: online stream processing, trends, and challenges
Authors: Medeiros Dianne S. V. , Cunha Neto Helio N. , Lopez Martin Andreoni , S. Magalhães Luiz Claudio , Fernandes Natalia C. , Vieira Alex B. , Silva Edelberto F. , F. Mattos Diogo M.
Published: October 2020

In this paper we focus on knowledge extraction from large-scale wireless networks through stream processing. We present the primary methods for sampling, data collection, and monitoring of wireless networks and we characterize knowledge extraction as a machine learning problem on big data stream processing. We show the main trends in big data stream processing frameworks. Additionally, we explore the data preprocessing, feature engineering, and the machine learning algorithms applied to the scenario of wireless network analytics. We address challenges and present research projects in wireless network monitoring and stream processing. Finally, future perspectives, such as deep learning and reinforcement learning in stream processing, are anticipated.
The impact of a multi-domain intervention on cerebral glucose metabolism: analysis from the randomized ancillary FDG PET MAPT trial
Authors: Delrieu Julien , Voisin Thierry , Saint-Aubert Laure , Carrie Isabelle , Cantet Christelle , Vellas Bruno , Payoux Pierre , Andrieu Sandrine
Published: October 2020

Background

The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the efficacy of omega-3 fatty acid supplementation, multidomain intervention (MI), or a combination of both on cognition. Although the MAPT study was negative, an effect of MI in maintaining cognitive functions compared to placebo group was showed in positive amyloid subjects. A FDG PET study (MAPT-NI) was implemented to test the impact of MI on brain glucose metabolism.

Methods

MAPT-NI was a randomized, controlled parallel-group single-center study, exploring the effect of MI on brain glucose metabolism. Participants were non-demented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. Participants were randomly assigned (1:1) to “MI group” or “No MI group.” The MI consisted of group sessions focusing on 3 domains: cognitive stimulation, physical activity, nutrition, and a preventive consultation. [18F]FDG PET scans were performed at baseline, 6 months, and 12 months, and cerebral magnetic resonance imaging scans at baseline. The primary objective was to evaluate the MI effect on brain glucose metabolism assessed by [18F]FDG PET imaging at 6 months. The primary outcome was the quantification of regional metabolism rate for glucose in cerebral regions involved early in Alzheimer disease by relative semi-quantitative SUVr (FDG-based AD biomarker). An exploratory voxel-wise analysis was performed to assess the effect of MI on brain glucose metabolism without anatomical hypothesis.

Results

The intention-to-treat population included 67 subjects (34 in the MI group and 33 in the No MI group. No significant MI effect was observed on primary outcome at 6 months. In the exploratory voxel-wise analysis, we observed a difference in favor of MI group on the change of cerebral glucose metabolism in limbic lobe (right hippocampus, right posterior cingulate, left posterior parahippocampal gyrus) at 6 months.

Conclusions

MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism. This finding could suggest a delay effect of MI on AD progression.

Trial registration

ClinicalTrials.gov Identifier, NCT01513252.
FDG-PET hypermetabolism is associated with higher tau-PET in mild cognitive impairment at low amyloid-PET levels
Authors: Rubinski Anna , Franzmeier Nicolai , Neitzel Julia , Ewers Michael ,   the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: October 2020

Background

FDG-PET hypermetabolism can be observed in mild cognitive impairment (MCI), but the link to primary pathologies of Alzheimer’s diseases (AD) including amyloid and tau is unclear.

Methods

Using voxel-based regression, we assessed local interactions between amyloid- and tau-PET on spatially matched FDG-PET in 72 MCI patients. Control groups included cerebrospinal fluid biomarker characterized cognitively normal (CN,n = 70) and AD dementia subjects (n = 95).

Results

In MCI, significant amyloid-PET by tau-PET interactions were found in frontal, lateral temporal, and posterior parietal regions, where higher local tau-PET was associated with higher spatially corresponding FDG-PET at low levels of local amyloid-PET. FDG-PET in brain regions with a significant local amyloid- by tau-PET interaction was higher compared to that in CN and AD dementia and associated with lower episodic memory.

Conclusion

Higher tau-PET in the presence of low amyloid-PET is associated with abnormally increased glucose metabolism that is accompanied by episodic memory impairment.
Social attention to activities in children and adults with autism spectrum disorder: effects of context and age
Authors: Kaliukhovich Dzmitry A. , Manyakov Nikolay V. , Bangerter Abigail , Ness Seth , Skalkin Andrew , Goodwin Matthew S. , Dawson Geraldine , Hendren Robert L. , Leventhal Bennett , Hudac Caitlin M. , Bradshaw Jessica , Shic Frederick , Pandina Gahan
Published: October 2020

Background

Diminished visual monitoring of faces and activities of others is an early feature of autism spectrum disorder (ASD). It is uncertain whether deficits in activity monitoring, identified using a homogeneous set of stimuli, persist throughout the lifespan in ASD, and thus, whether they could serve as a biological indicator (“biomarker”) of ASD. We investigated differences in visual attention during activity monitoring in children and adult participants with autism compared to a control group of participants without autism.

Methods

Eye movements of participants with autism (n = 122; mean age [SD] = 14.5 [8.0] years) and typically developing (TD) controls (n = 40, age = 16.4 [13.3] years) were recorded while they viewed a series of videos depicting two female actors conversing while interacting with their hands over a shared task. Actors either continuously focused their gaze on each other’s face (mutual gaze) or on the shared activity area (shared focus). Mean percentage looking time was computed for the activity area, actors’ heads, and their bodies.

Results

Compared to TD participants, participants with ASD looked longer at the activity area (mean % looking time: 58.5% vs. 53.8%, p < 0.005) but less at the heads (15.2% vs. 23.7%, p < 0.0001). Additionally, within-group differences in looking time were observed between the mutual gaze and shared focus conditions in both participants without ASD (activity: Δ = − 6.4%, p < 0.004; heads: Δ = + 3.5%, p < 0.02) and participants with ASD (bodies: Δ = + 1.6%, p < 0.002).

Limitations

The TD participants were not as well characterized as the participants with ASD. Inclusion criteria regarding the cognitive ability [intelligence quotient (IQ) > 60] limited the ability to include individuals with substantial intellectual disability.

Conclusions

Differences in attention to faces could constitute a feature discriminative between individuals with and without ASD across the lifespan, whereas between-group differences in looking at activities may shift with development. These findings may have applications in the search for underlying biological indicators specific to ASD.

Trial registration ClinicalTrials.gov identifier NCT02668991.
Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation
Authors: Alsaqati Mouhamed , Heine Vivi M. , Harwood Adrian J.
Published: October 2020

Background

Tuberous sclerosis complex (TSC) is a rare genetic multisystemic disorder resulting from autosomal dominant mutations in the TSC1 or TSC2 genes. It is characterised by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway and has severe neurodevelopmental and neurological components including autism, intellectual disability and epilepsy. In human and rodent models, loss of the TSC proteins causes neuronal hyperexcitability and synaptic dysfunction, although the consequences of these changes for the developing central nervous system are currently unclear.

Methods

Here we apply multi-electrode array-based assays to study the effects of TSC2 loss on neuronal network activity using autism spectrum disorder (ASD) patient-derived iPSCs. We examine both temporal synchronisation of neuronal bursting and spatial connectivity between electrodes across the network.

Results

We find that ASD patient-derived neurons with a functional loss of TSC2, in addition to possessing neuronal hyperactivity, develop a dysfunctional neuronal network with reduced synchronisation of neuronal bursting and lower spatial connectivity. These deficits of network function are associated with elevated expression of genes for inhibitory GABA signalling and glutamate signalling, indicating a potential abnormality of synaptic inhibitory–excitatory signalling. mTORC1 activity functions within a homeostatic triad of protein kinases, mTOR, AMP-dependent protein Kinase 1 (AMPK) and Unc-51 like Autophagy Activating Kinase 1 (ULK1) that orchestrate the interplay of anabolic cell growth and catabolic autophagy while balancing energy and nutrient homeostasis. The mTOR inhibitor rapamycin suppresses neuronal hyperactivity, but does not increase synchronised network activity, whereas activation of AMPK restores some aspects of network activity. In contrast, the ULK1 activator, LYN-1604, increases the network behaviour, shortens the network burst lengths and reduces the number of uncorrelated spikes.

Limitations

Although a robust and consistent phenotype is observed across multiple independent iPSC cultures, the results are based on one patient. There may be more subtle differences between patients with different TSC2 mutations or differences of polygenic background within their genomes. This may affect the severity of the network deficit or the pharmacological response between TSC2 patients.

Conclusions

Our observations suggest that there is a reduction in the network connectivity of the in vitro neuronal network associated with ASD patients with TSC2 mutation, which may arise via an excitatory/inhibitory imbalance due to increased GABA-signalling at inhibitory synapses. This abnormality can be effectively suppressed via activation of ULK1.
Synergistic interaction of eugenol and antimicrobial drugs in eradication of single and mixed biofilms of Candida albicans and Streptococcus mutans
Authors: Jafri Huma , Banerjee Gopa , Khan Mohd Sajjad Ahmad , Ahmad Iqbal , Abulreesh Hussein Hasan , Althubiani Abdullah Safar
Published: October 2020

In vitro eradication of the C. albicans and S. mutans mixed biofilms by eugenol alone and in combination with the antimicrobial drugs. Previously characterized strains of C. albicans (CAJ-01 and CAJ-12) and S. mutans MTCC497 were used to evaluate the eradication of biofilms using XTT reduction assay, viability assay, time dependent killing assay and scanning electron microscopy (SEM). Synergistic interaction was assessed by checkerboard method. Sessile MIC (SMIC) of eugenol was equivalent to the planktonic MIC (PMIC) against C. albicans and S. mutans mixed biofilms. SMIC of fluconazole and azithromycin was increased upto 1000-folds over PMIC. Eradication of single or mixed biofilms was evident from the viability assay and SEM. At 1 × MIC of eugenol, log10CFU count of C. albicans cells were decreased from 6.3 to 4.2 and 3.8 (p < 0.05) in single and mixed biofilms, respectively. SEM studies revealed the eradication of C. albicans and S. mutans cells from glass surface at 800 µg/mL concentration of eugenol. Time dependent killing assay showed dose dependent effect of eugenol on pre-formed CAJ-01, CAJ-12 and S. mutans biofilm cells. Eugenol was highly synergistic with fluconazole (FICI = 0.156) against CAJ-12 single biofilms. However, the combination of eugenol and azithromycin showed maximum synergy (FICI = 0.140) against pre-formed C. albicans and S. mutans mixed biofilms. These findings highlighted the promising efficacy of eugenol in the eradication of biofilms of two oral pathogens (C. albicans and S. mutans) in vitro and could also be exploited in synergy with fluconazole and azithromycin in controlling oral infections.
rSodC is a potential antigen to diagnose Corynebacterium pseudotuberculosis by enzyme-linked immunoassay
Authors: Farias Antonio Pedro Fróes de , Rocha Filho José Tadeu Raynal , Marchioro Silvana Beutinger , Moreira Luan Santana , Marques Andressa Souza , Sá Maria da Conceição Aquino de , Oliveira Antonio Anderson dos Santos , Alcântara Maria Emília , Mariutti Ricardo Barros , Arni Raghuvir Krishnaswamy , Trindade Soraya Castro , Meyer Roberto
Published: October 2020

Caseous lymphadenitis (CL) is a chronic infectious disease that affects sheep and goats. Many serological tests have been developed to detect the disease; one of the most widely used is the enzyme-linked immunosorbent assay (ELISA), due to its advantages, which include acceptable cost-effectiveness, applicability, sensitivity and specificity. ELISA formulations using recombinant proteins can exhibit significant sensitivity and specificity when using a single purified antigen. DTxR, Trx, TrxR, LexA, SodC, SpaC, NanH, and PknG recombinant proteins can be considered target proteins for ELISA development due to its extracellular or on the cell surface location, which allows a better recognition by the immune system. Therefore, the objectives of this study were to evaluate the antigenic reactivity of Corynebacterium pseudotuberculosis recombinant proteins in goat and sheep serum. Of eight proteins evaluated, rSodC was selected for validation assays with small ruminant serum samples from the semiarid region of the state of Bahia, Brazil. Validation assays with goat serum samples showed that ELISA-rSodC presented sensitivity and specificity of 96% and 94%, respectively. Validation assays with sheep serum showed that ELISA-rSodC exhibited sensitivity and specificity of 95% and 98%, respectively. Analysis of 756 field serum samples showed that rSodC identified 95 positive samples (23%) in goats and 75 positive samples (21%) in sheep. The ELISA with recombinant SodC protein developed in this study discriminated positive and negative serum samples with high levels of sensitivity and specificity. This formulation is promising for epidemiological surveys and CL control programs.

Trial registration AEC No 4958051018. 12/18/2018, retrospectively registered
Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury
Authors: Mao Ling , Zhou Ya , Chen Longqing , Hu Lin , Liu Shiming , Zheng Wen , Zhao Juanjuan , Guo Mengmeng , Chen Chao , He Zhixu , Xu Lin
Published: October 2020

Background

Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model.

Results

We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4−/− mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge.

Conclusions

Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.