bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the pediatric-centered integrated care AOK Junior: protocol for a mixed-method study
Authors: Liersch Sebastian , Krüger Kathrin , Oedingen Carina , Spreenberg Andrea , Bergemann Torben , Krauth Christian
Published: March 2020

Background

The “AOK-Junior” care program of the AOK Nordost (a German statutory health insurance) completes the primary care for children and adolescents (C&A) in the federal states of Berlin, Brandenburg and Mecklenburg-Vorpommern in Germany. The focus of this program is on prevention and early detection of illness on C&A. Furthermore, the aim is to maintain the health of C&A and to prevent, detect and treat illness on time. Elements of the program are not only the integrated care of C&A, but also, for example, weight reduction and additional medical checkups U10, U11 and J2. The evaluation of the complex intervention should provide information about the effectiveness of early disease detection and costs-effectiveness as well as of other parameters like satisfaction.

Methods

The evaluation is performed on the levels of structural-, process- and results-quality. The cost effectiveness is also assessed by means of a health economic evaluation. In addition to the collection of qualitative and quantitative primary data from participating and non-participating C&A and paediatricians, routine data from a statutory health insurance are used in the evaluation. Furthermore, a cross-sectional design is used to evaluate the structure and process quality. The effectiveness is evaluated in longitudinal section design on the basis of the secondary data. The quantitative surveys include net n = 1096 C&A and n = 340 pediatricians. For the focus groups, a sample of 72 to 96 parents as well as pediatricians will be sought by using the method of theoretical sampling.

Discussion

Around 560 pediatricians and 63,000 C&A currently participate in the AOK Nordost care program. The project provides information to what extent secondary preventive measures can lead to the early detection of diseases and on the associated cost-effectiveness. Furthermore, potentials and barriers of the program implementation are identified. The results of the evaluation study are expected not only to contribute to the further development of the care program, but also to derive recommendations for action.

Trial registration

German Clinical Trials Register (DRKS), DRKS-ID: DRKS00015280. Prospectively registered on 18 March 2019.
Is insurance instability associated with hypertension outcomes and does this vary by race/ethnicity?
Authors: Kressin Nancy R. , Terrin Norma , Hanchate Amresh D. , Price Lori Lyn , Moreno-Koehler Alejandro , LeClair Amy , Suzukida Jillian , Kher Sucharita , Freund Karen M.
Published: March 2020

Background

Stable health insurance is often associated with better chronic disease care and outcomes. Racial/ethnic health disparities in outcomes are prevalent and may be associated with insurance instability, particularly in the context of health insurance reform.

Methods

We examined whether insurance instability was associated with uncontrolled blood pressure (UBP) and whether this association varied by race/ethnicity. We used a retrospective longitudinal observational cohort study of patients diagnosed with hypertension who obtained care within two health systems in Massachusetts. We measured the UBP, insurance instability, and race of 43,785 adult primary care patients, age 21–64 with visits from 1/2005–12/2013.

Results

We found higher rates of UBP for blacks and Hispanics at each time point over the entire 9 years. Insurance instability was associated with greater rates of UBP. Always uninsured black patients fared worst, while white and Hispanic patients with consistent public insurance fared best.

Conclusions

Stable insurance of any type was associated with better hypertension control than no or unstable insurance.
Triglyceride glucose index is an independent predictor for the progression of coronary artery calcification in the absence of heavy coronary artery calcification at baseline
Authors: Won Ki-Bum , Park Eun Ji , Han Donghee , Lee Ji Hyun , Choi Su-Yeon , Chun Eun Ju , Park Sung Hak , Han Hae-Won , Sung Jidong , Jung Hae Ok , Chang Hyuk-Jae
Published: March 2020

Background

Data on the relationship between the triglyceride glucose (TyG) index and coronary artery calcification (CAC) progression is limited. This longitudinal study evaluated the association of TyG index with CAC progression in asymptomatic adults.

Methods

We enrolled 12,326 asymptomatic Korean adults who had at least two CAC evaluations. The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). CAC progression was defined as a difference ≥ 2.5 between the square roots (√) of the baseline and follow-up coronary artery calcium score (CACS) (Δ√transformed CACS). Annualized Δ√transformed CACS was defined as Δ√transformed CACS divided by the inter-scan period.

Results

During a mean 3.3 years, the overall incidence of CAC progression was 30.6%. The incidence of CAC progression (group I [lowest]: 22.7% versus [vs.] group II: 31.7% vs. group III [highest]: 37.5%, P < 0.001) and annualized Δ√transformed CACS (group I: 0.46 ± 1.44 vs. group II: 0.71 ± 2.02 vs. group III: 0.87 ± 1.75, P < 0.001) were markedly elevated with increasing TyG index tertiles. Multivariate linear regression analysis showed that TyG index was associated with annualized Δ√transformed CACS (β = 0.066, P = 0.036). In multivariate logistic regression analysis, the TyG index was significantly associated with CAC progression in baseline CACS ≤ 100.

Conclusion

The TyG index is an independent predictor of CAC progression, especially in adults without heavy baseline CAC.
Dyslipidemia and cardiovascular disease risk among the MASHAD study population
Authors: Hedayatnia Mahshad , Asadi Zahra , Zare-Feyzabadi Reza , Yaghooti-Khorasani Mahdiyeh , Ghazizadeh Hamideh , Ghaffarian-Zirak Roshanak , Nosrati-Tirkani Abolfazl , Mohammadi-Bajgiran Maryam , Rohban Mohadese , Sadabadi Fatemeh , Rahimi Hamid-Reza , Ghalandari Marzieh , Ghaffari Mohammad-Seddigh , Yousefi Asa , Pouresmaeili Elnaz , Besharatlou Mohammad-Reza , Moohebati Mohsen , Ferns Gordon A. , Esmaily Habibollah , Ghayour-Mobarhan Majid
Published: March 2020

Introduction

Dyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran.

Material and methods

This prospective cohort study comprised a population of 8698 men and women aged 35–65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence.

Results

After 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19–2; P-value< 0.01; HR: 1.53; 95% CI: 1.18–1.98; P < 0.01; HR: 1.57; 95% CI: 1.27–2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12–6.57; P-value< 0.05).

Conclusion

In the present study, TC baseline level was significantly associated with the risk of MI among men.
Impact of monocyte to high-density lipoprotein ratio on prevalent hyperuricemia: findings from a rural Chinese population
Authors: Chen Meng-Qi , Shi Wen-Rui , Shi Chu-Ning , Zhou Ya-Ping , Sun Ying-Xian
Published: March 2020

Background

Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel inflammatory marker that has been used to predict various inflammation-related diseases. This study aims to explore the association between MHR and prevalent hyperuricemia in a rural Chinese population.

Methods

8163 eligible participants (mean age: 54.13 years, males: 45.71%) from northeast China were enrolled in this cross-sectional study between 2012 to 2013. MHR was determined as blood monocyte count ratio to high-density lipoprotein cholesterol concentration.

Results

The prevalence of hyperuricemia was 12.86%. After adjusting for potential confounding factors, per SD increase of MHR caused a 25.2% additional risk for hyperuricemia, and the top quartile of MHR had an 82.9% increased risk for hyperuricemia compared with the bottom quartile. Additionally, smooth curve fitting and subgroup analyses showed a linear and robust association between MHR and prevalent hyperuricemia respectively. Finally, after introducing MHR into the established model of risk factors, the AUC displayed a significant improvement (0.718 vs 0.724, p = 0.008). Furthermore, Category-free net reclassification improvement (0.160, 95% CI: 0.096–0.224, P < 0.001) and integrated discrimination improvement (0.003, 95% CI: 0.002–0.005, P < 0.001) also demonstrated significant improvements.

Conclusions

The present study suggests that MHR was positively and independently correlated with prevalent hyperuricemia among rural Chinese adults. Our results also implicate an important value for MHR in optimizing the risk stratification of hyperuricemia.
In vitro and numerical simulation of blood removal from cerebrospinal fluid: comparison of lumbar drain to Neurapheresis therapy
Authors: Khani Mohammadreza , Sass Lucas R. , Sharp M. Keith , McCabe Aaron R. , Zitella Verbick Laura M. , Lad Shivanand P. , Martin Bryn A.
Published: March 2020

Background

Blood removal from cerebrospinal fluid (CSF) in post-subarachnoid hemorrhage patients may reduce the risk of related secondary brain injury. We formulated a computational fluid dynamics (CFD) model to investigate the impact of a dual-lumen catheter-based CSF filtration system, called Neurapheresis™ therapy, on blood removal from CSF compared to lumbar drain.

Methods

A subject-specific multiphase CFD model of CSF system-wide solute transport was constructed based on MRI measurements. The Neurapheresis catheter geometry was added to the model within the spinal subarachnoid space (SAS). Neurapheresis flow aspiration and return rate was 2.0 and 1.8 mL/min, versus 0.2 mL/min drainage for lumbar drain. Blood was modeled as a bulk fluid phase within CSF with a 10% initial tracer concentration and identical viscosity and density as CSF. Subject-specific oscillatory CSF flow was applied at the model inlet. The dura and spinal cord geometry were considered to be stationary. Spatial–temporal tracer concentration was quantified based on time-average steady-streaming velocities throughout the domain under Neurapheresis therapy and lumbar drain. To help verify CFD results, an optically clear in vitro CSF model was constructed with fluorescein used as a blood surrogate. Quantitative comparison of numerical and in vitro results was performed by linear regression of spatial–temporal tracer concentration over 24-h.

Results

After 24-h, tracer concentration was reduced to 4.9% under Neurapheresis therapy compared to 6.5% under lumbar drain. Tracer clearance was most rapid between the catheter aspiration and return ports. Neurapheresis therapy was found to have a greater impact on steady-streaming compared to lumbar drain. Steady-streaming in the cranial SAS was ~ 50× smaller than in the spinal SAS for both cases. CFD results were strongly correlated with the in vitro spatial–temporal tracer concentration under Neurapheresis therapy (R2 = 0.89 with + 2.13% and − 1.93% tracer concentration confidence interval).

Conclusion

A subject-specific CFD model of CSF system-wide solute transport was used to investigate the impact of Neurapheresis therapy on tracer removal from CSF compared to lumbar drain over a 24-h period. Neurapheresis therapy was found to substantially increase tracer clearance compared to lumbar drain. The multiphase CFD results were verified by in vitro fluorescein tracer experiments.
Gender inequality in early initiation of breastfeeding in Bangladesh: a trend analysis
Authors: Sen Kanchan Kumar , Mallick Taslim Sazzad , Bari Wasimul
Published: March 2020

Background

Early initiation of breastfeeding within 1 hour after birth is essential for newborns, because it reduces risk of neonatal mortality and hypothermia to a great extent and also helps in preventing the long-term chronic diseases and in increasing energy and immunity to newborn. In order to reach the ‘very good state’ of timely or early initiation of breastfeeding recommended by WHO, Bangladesh needs to increase the current rate of 51.24 to 100%. An attempt has been made in this study to examine how the early breastfeeding practice changes among male and female children with time controlling the factors associated with this practice.

Methods

Data from last four consecutive Bangladesh Demographic and Health Surveys (BDHS) have been used in the study. The participants were included whose child born within the last 5 years preceding the surveys of 2004, 2007 and 2011, and within the last 3 years preceding the survey of 2014 in the study and the respective selected participants were 5145, 4765, 7099 and 4370. To conduct the trend analysis, the descriptive statistics of selected variables along with prevalence of early initiation of breastfeeding have been computed by different years and a multiple logistic regression model has been fitted to the pooled dataset of 2004–2014 considering survey years as time.

Results

Rate of early initiation of breastfeeding increased as time progressed and it was faster for female child compared to male child. For example, female children were significantly 10 and 6% less likely to be initiated early than their counterparts in 2004 and 2007, respectively; whereas after 2007 both male and female children were equally treated for breastfeeding practice. It was also found that rate of early initiation significantly increased for one unit increased in survey year and this increasing rate was higher for female child compared to male child. For example, for one unit of increased in survey year, the early initiation of breastfeeding increased by 60% for male child and by 67% for female child. Besides, survey time, gender, education of parents, wanted index child, mode of delivery, antenatal care visits, wealth index, exposure to media and division were found to have potential influence on early initiation of breastfeeding.

Conclusion

Demographic and health surveys conducted in Bangladesh since 2011 have shown no evidence of gender discrimination regarding timely initiation of breastfeeding. In order to achieve the target rate of early initiation of breastfeeding recommended by WHO, it requires to take effective intervention regarding maternal and child health education.
An improved growth medium for enhanced inoculum production of the plant growth-promoting fungus Serendipita indica
Authors: Osman Mohamed , Stigloher Christian , Mueller Martin J. , Waller Frank
Published: March 2020

Background

The plant endophytic fungus Serendipita indica colonizes roots of a wide range of plant species and can enhance growth and stress resistance of these plants. Due to its ease of axenic cultivation and its broad host plant range including the model plant Arabidopsis thaliana and numerous crop plants, it is widely used as a model fungus to study beneficial fungus-root interactions. In addition, it was suggested to be utilized for commercial applications, e.g. to enhance yield in barley and other species. To produce inoculum, S. indica is mostly cultivated in a complex Hill-Käfer medium (CM medium), however, growth in this medium is slow, and yield of chlamydospores, which are often used for plant root inoculation, is relatively low.

Results

We tested and optimized a simple vegetable juice-based medium for an enhanced yield of fungal inoculum. The described vegetable juice (VJ) medium is based on commercially available vegetable juice and is easy to prepare. VJ medium was superior to the currently used CM medium with respect to biomass production in liquid medium and hyphal growth on agar plates. Using solid VJ medium supplemented with sucrose (VJS), a high amount of chlamydospores developed already after 8 days of cultivation, producing significantly more spores than on CM medium. Use of VJ medium is not restricted to S. indica, as it also supported growth of two pathogenic fungi often used in plant pathology experiments: the ascomycete Fusarium graminearum, the causal agent of Fusarium head blight disease on wheat and barley, and Verticillium longisporum, the causal agent of verticillium wilt.

Conclusions

The described VJ medium is recommended for streamlined and efficient production of inoculum for the plant endophytic fungus Serendipita indica and might prove superior for the propagation of other fungi for research purposes.
PTSD and opioid use: implications for intervention and policy
Authors: Dahlby Lucia , Kerr Thomas
Published: March 2020

Background

North America remains in the midst of an escalating opioid overdose epidemic, largely driven by the influx of synthetic opioids such a fentanyl and related analogues. High rates of mental illness among substance-using populations have been well documented; in particular, opioid-using individuals suffer from high rates of PTSD. Despite the devastating disease burden of both PTSD and OUD, especially within the context of the current opioid overdose epidemic, treatment options and outcomes remain suboptimal.

Main body

Comorbid PTSD-OUD is often complex and inextricably intertwined, thereby impeding effective diagnosis, assessment and early intervention. Best outcomes occur when treatment addresses both comorbidities simultaneously, known as parallel or integrative approaches. Despite these findings, affected individuals often do not receive adequate or equitable access to healthcare. The WHO recommends that public spending for both mental and physical aspects of healthcare be equitable to the burden of disease. Despite these recommendations mental healthcare services remain chronically underfunded in Canada. The Mental Health Parity Act is a call for the Canadian government to implement equitable public spending on all aspects of healthcare. Furthermore, prohibitory legislative practices serve to marginalize substance-using populations thereby increasing the likelihood of exposure to traumatic violence and other associated harms.

Conclusion

Efforts are now needed to address regulatory drug-use frameworks and public healthcare policies that perpetuate these inequalities. Alternative regulatory frameworks for drugs and mental health parity should be implemented and evaluated in an effort to reduce violence, trauma and ultimately opioid-related overdose deaths.
Efficacy and safety of intensity-modulated radiotherapy alone versus intensity-modulated radiotherapy plus chemotherapy for treatment of intermediate-risk nasopharyngeal carcinoma
Authors: Aftab Omer , Liao Shufang , Zhang Rongjun , Tang Nan , Luo Meiqing , Zhang Bin , Shahi Sanjeev , Rai Raju , Ali Jazib , Jiang Wei
Published: March 2020

Background

This study directs to evaluate the efficacy and safety of intensity-modulated radiotherapy (IMRT) alone versus IMRT plus chemotherapy in intermediate-risk NPC (stage II and T3N0M0).

Methods

A total of 124 patients with stage II and T3N0M0 NPC were pair-matched (1:1 ratio) to form two groups: an IMRT-alone group and an IMRT/chemotherapy group. Survival outcomes (overall survival [OS], disease–free survival [DFS], locoregional relapse–free survival [LRRFS], distant metastasis–free survival [DMFS]) and treatment-related grade 3–4 acute toxicity events were compared between the groups.

Results

Survival outcomes for patients with stage II and T3N0M0 NPC were quiet comparable between patients treated with IMRT alone versus patients treated with IMRT/chemotherapy: 5-year OS was 91.9% vs. 90.3%, respectively (P = 0.727); DFS was 87.1% vs. 88.7%, respectively (P = 0.821); LRFFS was 96.8% vs. 95.2%, respectively (P = 0.646), and DMFS was 91.9% vs. 91.5%, respectively (P = 0.955). Grade 3 acute toxicities were significantly higher with IMRT/chemotherapy than with IMRT alone: mucositis, 15% vs. 5% (P = 0.004); leukopenia/neutropenia, 8% vs. 1% (P <  0.015); and nausea/vomiting, 22% vs. 3% (P <  0.001).

Conclusion

For intermediate-risk (stage II and T3N0M0) NPC patients, the addition of chemotherapy to IMRT does not appear to provide any survival benefit. Moreover, grade 3 acute toxicities are also more common in patients receiving IMRT plus chemotherapy.
Translating traditional herbal formulas into modern drugs: a network-based analysis of Xiaoyao decoction
Authors: Zhang Daiyan , Zhang Yun , Gao Yan , Chai Xingyun , Pi Rongbiao , Chan Ging , Hu Yuanjia
Published: March 2020

Background

Traditional Chinese medicine (TCM) encompasses numerous herbal formulas which play critical therapeutic roles through “multi-components, multi-targets and multi-pathways” mechanisms. Exploring the interaction among these mechanisms can certainly help to depict the core therapeutic function of herbal formulas. Xiaoyao decoction (XYD) is one of the most well-known traditional Chinese medicine formulas which has been widely applied to treat various diseases. In this study, taking XYD as an example, we proposed a network pharmacology-based method to identify the main therapeutic targets of this herbal concoctions.

Methods

Chemical data of XYD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID) and Compound Reference Database (CRD) and screened oral bioavailability attributes from SwissADME using Veber’s filter. Targets of sample chemicals were identified using the online tool similarity ensemble approach (SEA), and pathways were enriched using STRING database. On the basis of targets–pathways interactions from the enrichment, a “targets–pathways–targets” (TPT) network was constructed. In the TPT network, the importance of each target was calculated by the declining value of network efficiency, which represents the influential strength of a specific set-off target on the whole network. Network-based predictive results were statistically validated with existing experimental evidence.

Results

The TPT network was comprised of 279 nodes and 6549 edges. The declining value of network efficiency of the sample targets was significantly correlated with their involvement frequency in existing studies of XYD using Spearman’s test (p < 0.001). The top 10% of candidate targets, such as AKT1, PIK3R1, NFKB1 and RELA, etc., were chosen as XYD’s main therapeutic targets, which further show pharmacological functions synergistically through 11 main pathways. These pathways are responsible for endocrine, nutritional or metabolic diseases, neoplasms and diseases of the nervous system, etc.

Conclusions

The network pharmacology-based approach in the present study shows promising potential for identifying the main therapeutic targets from TCM formulas. This study provides valuable information for TCM researchers and clinicians for better understanding the main therapeutic targets and therapeutic roles of herbal decoctions in clinical settings.
Premature termination codon readthrough upregulates progranulin expression and improves lysosomal function in preclinical models of GRN deficiency
Authors: Frew Jonathan , Baradaran-Heravi Alireza , Balgi Aruna D. , Wu Xiujuan , Yan Tyler D. , Arns Steve , Shidmoossavee Fahimeh S. , Tan Jason , Jaquith James B. , Jansen-West Karen R. , Lynn Francis C. , Gao Fen-Biao , Petrucelli Leonard , Feldman Howard H. , Mackenzie Ian R. , Roberge Michel , Nygaard Haakon B.
Published: March 2020

Background

Frontotemporal lobar degeneration (FTLD) is a devastating and progressive disorder, and a common cause of early onset dementia. Progranulin (PGRN) haploinsufficiency due to autosomal dominant mutations in the progranulin gene (GRN) is an important cause of FTLD (FTLD-GRN), and nearly a quarter of these genetic cases are due to a nonsense mutation. Premature termination codons (PTC) can be therapeutically targeted by compounds allowing readthrough, and aminoglycoside antibiotics are known to be potent PTC readthrough drugs. Restoring endogenous PGRN through PTC readthrough has not previously been explored as a therapeutic intervention in FTLD.

Methods

We studied whether the aminoglycoside G418 could increase PGRN expression in HEK293 and human induced pluripotent stem cell (hiPSC)-derived neurons bearing the heterozygous S116X, R418X, and R493X pathogenic GRN nonsense mutations. We further tested a novel substituted phthalimide PTC readthrough enhancer in combination with G418 in our cellular models. We next generated a homozygous R493X knock-in hiPSC isogenic line (R493X−/− KI), assessing whether combination treatment in hiPSC-derived neurons and astrocytes could increase PGRN and ameliorate lysosomal dysfunction relevant to FTLD-GRN. To provide in vivo proof-of-concept of our approach, we measured brain PGRN after intracerebroventricular administration of G418 in mice expressing the V5-tagged GRN nonsense mutation R493X.

Results

The R418X and R493X mutant GRN cell lines responded to PTC readthrough with G418, and treatments increased PGRN levels in R493X−/− KI hiPSC-derived neurons and astrocytes. Combining G418 with a PTC readthrough enhancer increased PGRN levels over G418 treatment alone in vitro. PGRN deficiency has been shown to impair lysosomal function, and the mature form of the lysosomal protease cathepsin D is overexpressed in R493X−/− KI neurons. Increasing PGRN through G418-mediated PTC readthrough normalized this abnormal lysosomal phenotype in R493X−/− KI neuronal cultures. A single intracerebroventricular injection of G418 induced GRN PTC readthrough in 6-week-old AAV-GRN-R493X-V5 mice.

Conclusions

Taken together, our findings suggest that PTC readthrough may be a potential therapeutic strategy for FTLD caused by GRN nonsense mutations.
Sex difference in synaptic plasticity in the anterior cingulate cortex of adult mice
Authors: Liu Ren-Hao , Xue Man , Li Xu-Hui , Zhuo Min
Published: March 2020

Sex differences in certain types of pain sensitivity and emotional responses have been previously reported. Synaptic plasticity is a key cellular mechanism for pain perception and emotional regulation, including long-term potentiation (LTP) and long-term depression (LTD). However, it is unclear whether there is a sex difference at synaptic level. Recent studies indicate that excitatory transmission and plasticity in the anterior cingulate cortex (ACC) are critical in chronic pain and pain related emotional responses. In the present study, we used 64-channel multielectrode (MED64) system to record synaptic plasticity in the ACC of male and female adult mice. We found that there was no significant difference in theta-burst stimulation (TBS)-induced LTP between female and male mice. Furthermore, the recruitment of inactive channels was also not different. For LTD, we found that LTD was greater in slices of ACC in male mice than female mice. Our results demonstrate that LTP in the ACC does not show any sex-related difference.
BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty
Authors: Tiberi Simone , Robinson Mark D.
Published: March 2020

Alternative splicing is a biological process during gene expression that allows a single gene to code for multiple proteins. However, splicing patterns can be altered in some conditions or diseases. Here, we present BANDITS, a R/Bioconductor package to perform differential splicing, at both gene and transcript level, based on RNA-seq data. BANDITS uses a Bayesian hierarchical structure to explicitly model the variability between samples and treats the transcript allocation of reads as latent variables. We perform an extensive benchmark across both simulated and experimental RNA-seq datasets, where BANDITS has extremely favourable performance with respect to the competitors considered.
Calcineurin signaling pathway influences Aspergillus niger biofilm formation by affecting hydrophobicity and cell wall integrity
Authors: Liu Li , Yu Bin , Sun Wenjun , Liang Caice , Ying Hanjie , Zhou Shengmin , Niu Huanqing , Wang Yibing , Liu Dong , Chen Yong
Published: March 2020

Background

Biofilms, as a kind of fixed-cell community, can greatly improve industrial fermentation efficiency in immobilized fermentation, but the regulation process is still unclear, which restricts their application. Ca2+ was reported to be a key factor affecting biofilm formation. However, the effect of Ca2+ on biofilm structure and microbiology was yet only studied in bacteria. How Ca2+-mediated calcineurin signaling pathway (CSP) alters biofilm formation in bacteria and fungi has rarely been reported. On this basis, we investigated the regulation of CSP on the formation of biofilm in Aspergillus niger.

Results

Deletion of the key genes MidA, CchA, CrzA or CnaA in the CSP lowered the Ca2+ concentration in the mycelium to a different extent, inhibited the formation of A. niger biofilm, reduced the hydrophobicity and adhesion of spores, destroyed the cell wall integrity of hyphae, and reduced the flocculation ability of hyphae. qRT-PCR results showed that the expression of spore hydrophobic protein RodA, galactosaminogalactan (GAG) biosynthesis genes (uge3, uge5, agd3, gtb3), and α-1,3-glucan biosynthesis genes (ags1, ags3) in the ∆MidA, ∆CchA, ∆CrzA, ∆CnaA strains were significantly down-regulated compared with those of the wild type (WT). In addition, the transcription levels of the chitin synthesis gene (chsB, chsD) and β-1,3-glucan synthesis gene (FksA) were consistent with the change in chitin and β-1,3-glucan contents in mutant strains.

Conclusion

These results indicated that CSP affected the hydrophobicity and adhesion of spores, the integrity of mycelial cell walls and flocculation by affecting Ca2+ levels in mycelium, which in turn affected biofilm formation. This work provides a possible explanation for how CSP changes the formation of A. niger biofilm, and reveals a pathway for controlling biofilm formation in industrial immobilized fermentation.
Biodiesel and flavor compound production using a novel promiscuous cold-adapted SGNH-type lipase (HaSGNH1) from the psychrophilic bacterium Halocynthiibacter arcticus
Authors: Le Ly Thi Huong Luu , Yoo Wanki , Jeon Sangeun , Lee Changwoo , Kim Kyeong Kyu , Lee Jun Hyuck , Kim T. Doohun
Published: March 2020

Background

Biodiesel and flavor compound production using enzymatic transesterification by microbial lipases provides mild reaction conditions and low energy cost compared to the chemical process. SGNH-type lipases are very effective catalysts for enzymatic transesterification due to their high reaction rate, great stability, relatively small size for convenient genetic manipulations, and ease of immobilization. Hence, it is highly important to identify novel SGNH-type lipases with high catalytic efficiencies and good stabilities.

Results

A promiscuous cold-adapted SGNH-type lipase (HaSGNH1) from Halocynthiibacter arcticus was catalytically characterized and functionally explored. HaSGNH1 displayed broad substrate specificity that included tert-butyl acetate, glucose pentaacetate, and p-nitrophenyl esters with excellent stability and high efficiency. Important amino acids (N83, M86, R87, F131, and I173F) around the substrate-binding pocket were shown to be responsible for catalytic activity, substrate specificity, and reaction kinetics. Moreover, immobilized HaSGNH1 was used to produce high yields of butyl and oleic esters.

Conclusions

This work provides a molecular understanding of substrate specificities, catalytic regulation, immobilization, and industrial applications of a promiscuous cold-adapted SGNH-type lipase (HaSGNH1) from H. arcticus. This is the first analysis on biodiesel and flavor synthesis using a cold-adapted halophilic SGNH-type lipase from a Halocynthiibacter species.
Parasite associations predict infection risk: incorporating co-infections in predictive models for neglected tropical diseases
Authors: Clark Nicholas J. , Owada Kei , Ruberanziza Eugene , Ortu Giuseppina , Umulisa Irenee , Bayisenge Ursin , Mbonigaba Jean Bosco , Mucaca Jean Bosco , Lancaster Warren , Fenwick Alan , Soares Magalhães Ricardo J. , Mbituyumuremyi Aimable
Published: March 2020

Background

Schistosomiasis and infection by soil-transmitted helminths are some of the world’s most prevalent neglected tropical diseases. Infection by more than one parasite (co-infection) is common and can contribute to clinical morbidity in children. Geostatistical analyses of parasite infection data are key for developing mass drug administration strategies, yet most methods ignore co-infections when estimating risk. Infection status for multiple parasites can act as a useful proxy for data-poor individual-level or environmental risk factors while avoiding regression dilution bias. Conditional random fields (CRF) is a multivariate graphical network method that opens new doors in parasite risk mapping by (i) predicting co-infections with high accuracy; (ii) isolating associations among parasites; and (iii) quantifying how these associations change across landscapes.

Methods

We built a spatial CRF to estimate infection risks forAscaris lumbricoides,Trichuris trichiura, hookworms (Ancylostoma duodenaleandNecator americanus) andSchistosoma mansoniusing data from a national survey of Rwandan schoolchildren. We used an ensemble learning approach to generate spatial predictions by simulating from the CRF’s posterior distribution with a multivariate boosted regression tree that captured non-linear relationships between predictors and covariance in infection risks. This CRF ensemble was compared against single parasite gradient boosted machines to assess each model’s performance and prediction uncertainty.

Results

Parasite co-infections were common, with 19.57% of children infected with at least two parasites. The CRF ensemble achieved higher predictive power than single-parasite models by improving estimates of co-infection prevalence at the individual level and classifying schools into World Health Organization treatment categories with greater accuracy. The CRF uncovered important environmental and demographic predictors of parasite infection probabilities. Yet even after capturing demographic and environmental risk factors, the presences or absences of other parasites were strong predictors of individual-level infection risk. Spatial predictions delineated high-risk regions in need of anthelminthic treatment interventions, including areas with higher than expected co-infection prevalence.

Conclusions

Monitoring studies routinely screen for multiple parasites, yet statistical models generally ignore this multivariate data when assessing risk factors and designing treatment guidelines. Multivariate approaches can be instrumental in the global effort to reduce and eventually eliminate neglected helminth infections in developing countries.
Culicoides species composition and molecular identification of host blood meals at two zoos in the UK
Authors: England Marion E. , Pearce-Kelly Paul , Brugman Victor A. , King Simon , Gubbins Simon , Sach Fiona , Sanders Christopher J. , Masters Nic J. , Denison Eric , Carpenter Simon
Published: March 2020

Background

Culicoidesbiting midges are biological vectors of arboviruses including bluetongue virus (BTV), Schmallenberg virus (SBV) and African horse sickness virus (AHSV). Zoos are home to a wide range of ‘at risk’ exotic and native species of animals. These animals have a high value both in monetary terms, conservation significance and breeding potential. To understand the risk these viruses pose to zoo animals, it is necessary to characterise theCulicoidesfauna at zoos and determine which potential vector species are feeding on which hosts.

Methods

Light-suction traps were used at two UK zoos: the Zoological Society of London (ZSL) London Zoo (LZ) and ZSL Whipsnade Zoo (WZ). Traps were run one night each week from June 2014 to June 2015.Culicoideswere morphologically identified to the species level and any blood-fedCulicoideswere processed for blood-meal analysis. DNA from blood meals was extracted and amplified using previously published primers. Sequencing was then carried out to determine the host species.

Results

A total of 11,648Culicoideswere trapped and identified (n = 5880 from ZSL WZ;n = 5768 from ZSL LZ), constituting 25 different species. The six putative vectors of BTV, SBV and AHSV in northern Europe were found at both zoos and made up the majority of the total catch (n = 10,701). A total of 31 host sequences were obtained from blood-fedCulicoides. Culicoides obsoletus/C. scoticus,Culicoides dewulfi,Culicoides parrotiandCulicoides punctatuswere found to be biting a wide range of mammals including Bactrian camels, Indian rhinoceros, Asian elephants and humans, withCulicoides obsoletus/C. scoticusalso biting Darwin’s rhea. The bird-biting species,Culicoides achrayi, was found to be feeding on blackbirds, blue tits, magpies and carrion crows.

Conclusions

To our knowledge, this is the first study to directly confirm blood-feeding ofCulicoideson exotic zoo animals in the UK and shows that they are able to utilise a wide range of exotic as well as native host species. Due to the susceptibility of some zoo animals toCulicoides-borne arboviruses, this study demonstrates that in the event of an outbreak of one of these viruses in the UK, preventative and mitigating measures would need to be taken.
The conserved DNMT1-dependent methylation regions in human cells are vulnerable to neurotoxicant rotenone exposure
Authors: Freeman Dana M. , Lou Dan , Li Yanqiang , Martos Suzanne N. , Wang Zhibin
Published: March 2020

Background

Allele-specific DNA methylation (ASM) describes genomic loci that maintain CpG methylation at only one inherited allele rather than having coordinated methylation across both alleles. The most prominent of these regions are germline ASMs (gASMs) that control the expression of imprinted genes in a parent of origin-dependent manner and are associated with disease. However, our recent report reveals numerous ASMs at non-imprinted genes. These non-germline ASMs are dependent on DNA methyltransferase 1 (DNMT1) and strikingly show the feature of random, switchable monoallelic methylation patterns in the mouse genome. The significance of these ASMs to human health has not been explored. Due to their shared allelicity with gASMs, herein, we propose that non-traditional ASMs are sensitive to exposures in association with human disease.

Results

We first explore their conservancy in the human genome. Our data show that our putative non-germline ASMs were in conserved regions of the human genome and located adjacent to genes vital for neuronal development and maturation. We next tested the hypothesized vulnerability of these regions by exposing human embryonic kidney cell HEK293 with the neurotoxicant rotenone for 24 h. Indeed,14 genes adjacent to our identified regions were differentially expressed from RNA-sequencing. We analyzed the base-resolution methylation patterns of the predicted non-germline ASMs at two neurological genes, HCN2 and NEFM, with potential to increase the risk of neurodegeneration. Both regions were significantly hypomethylated in response to rotenone.

Conclusions

Our data indicate that non-germline ASMs seem conserved between mouse and human genomes, overlap important regulatory factor binding motifs, and regulate the expression of genes vital to neuronal function. These results support the notion that ASMs are sensitive to environmental factors such as rotenone and may alter the risk of neurological disease later in life by disrupting neuronal development.
DNA looping by two 5-methylcytosine-binding proteins quantified using nanofluidic devices
Authors: Liu Ming , Movahed Saeid , Dangi Saroj , Pan Hai , Kaur Parminder , Bilinovich Stephanie M. , Faison Edgar M. , Leighton Gage O. , Wang Hong , Williams David C. , Riehn Robert
Published: March 2020

Background

MeCP2 and MBD2 are members of a family of proteins that possess a domain that selectively binds 5-methylcytosine in a CpG context. Members of the family interact with other proteins to modulate DNA packing. Stretching of DNA–protein complexes in nanofluidic channels with a cross-section of a few persistence lengths allows us to probe the degree of compaction by proteins.

Results

We demonstrate DNA compaction by MeCP2 while MBD2 does not affect DNA configuration. By using atomic force microscopy (AFM), we determined that the mechanism for compaction by MeCP2 is the formation of bridges between distant DNA stretches and the formation of loops.

Conclusions

Despite sharing a similar specific DNA-binding domain, the impact of full-length 5-methylcytosine-binding proteins can vary drastically between strong compaction of DNA and no discernable large-scale impact of protein binding. We demonstrate that ATTO 565-labeled MBD2 is a good candidate as a staining agent for epigenetic mapping.
The impact of peri-natal stress on psychosis risk: results from the Bo-FEP incidence study
Authors: De Matteis Tiziano , D’Andrea Giuseppe , Lal Jatin , Berardi Domenico , Tarricone Ilaria
Published: March 2020

Objective

According to the gene-environment interaction model the pathogenesis of psychosis relies on an adverse neuro-socio-developmental pathway. Perinatal stress represents an important risk factor for the development of psychosis because of the increasingly evident interference with socio-neuro-development in the earlier phases of life. We aim to investigate the correlation of perinatal risk factors with the onset of psychosis with a case–control–incidence study.

Results

Patients (and their mothers) were eligible if they presented with first-episode psychosis at the Bologna West Community Mental Health Centre (Bo-West CMHC) between 2002 and 2012. The Bo-West CMHC serves a catchment area of about 200,000 people. The controls were recruited in the same catchment area and study period. 42 patients, 26 controls and their mothers were included. We collected the history of peri-natal stress and calculated crude and adjusted Odds Ratios for onset of first-episode psychosis. Adjusted logistic regression showed that psychosis onset was significantly associated with stressful situations during pregnancy, lower level of maternal physical health before or during pregnancy, use of anti-inflammatory drugs during pregnancy, and low level of maternal education. The results of our study suggest that stress during perinatal period increases the risk of developing psychosis.
Evaluation of Allplex™ Entero-DR assay for detection of antimicrobial resistance determinants from bacterial cultures
Authors: Mojica María Fernanda , De La Cadena Elsa , Correa Adriana , Appel Tobias Manuel , Pallares Christian José , Villegas María Virginia
Published: March 2020

Objective

To evaluate the sensitivity and specificity of the Allplex™ Entero-DR, a quantitative PCR-based method, for the detection of β-lactamase-encoding genes and vancomycin-resistance determinants in 156 previously characterized Gram-negative bacilli and Enterococcus spp. from bacterial cultures.

Result

The method had 100% sensitivity and between 92 and 100% of specificity for identifying blaKPC, blaVIM, blaIMP, blaNDM, blaOXA-48-like, blaCTX-M and vanA. In nine isolates, unspecific amplifications were detected. The Ct of these false positives was above 33. The Ct of the correctly identified bla and van genes did not surpass 28 and 30, respectively. None of the clinical isolates included as negative controls yielded any amplification. Therefore, the Allplex™ Entero-DR assay is a highly accurate test for the detection of important antibiotic resistance determinants. With this assay, reliable results can be obtained within 3 h. However, according to our data, samples with Ct values greater than 33 should be considered with caution.
Evaluation of the yeast surface display system for screening of functional nanobodies
Authors: Kajiwara Kaho , Aoki Wataru , Ueda Mitsuyoshi
Published: March 2020

Yeast surface display is a powerful technology used to isolate and engineer proteins to improve their activity, specificity, and stability. In this method, gene expression is regulated by promoters, and secretion efficiency is affected by secretion signals. Furthermore, both the accessibility and activity of the displayed proteins are affected by the length of anchor proteins. The ideal promoter, secretion signal, and anchor protein combination depend on the proteins of interest. In this study, we optimized a yeast surface display suitable for nanobody evaluation. We designed five display systems that used different combinations of promoters, secretion signals, and anchor proteins. Anti-hen egg-white lysozyme nanobody was used as the model nanobody. The amount of nanobodies displayed on yeast cells, the number of antigens bound to the displayed nanobodies, and the display efficiency were quantified. Overall, we improved the yeast display system for nanobody engineering and proposed its optimization.
SARS-CoV-2 and COVID-19: The most important research questions
Authors: Yuen Kit-San , Ye Zi -Wei , Fung Sin-Yee , Chan Chi-Ping , Jin Dong-Yan
Published: March 2020

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.