bluuebunny/crossref_metadata_2025 huggingface dataset:
The predictive value of PaO2/FIO2 and additional parameters for in-hospital mortality in patients with acute pulmonary embolism: an 8-year prospective observational single-center cohort study
Authors: Wang Yan , Yang He , Qiao Lisong , Tan Zheng , Jin Jin , Yang Jingjing , Zhang Li , Fang Bao Min , Xu Xiaomao
Published: December 2019

Background

Rapid stratification and appropriate treatment on admission are critical to saving lives of patients with acute pulmonary embolism (PE). None of the clinical prediction tools perform well when applied to all patients with acute PE. It may be important to integrate respiratory features into the 2014 European Society of Cardiology model. First, we aimed to assess the relationship between the arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FIO2) ratio and in-hospital mortality, determine the optimal cutoff value of PaO2/FIO2, and determine if this value, which is quick and easy to obtain on admission, is a predictor of in-hospital mortality in this population. Second, we aimed to evaluate the potential additional determinants including laboratory parameters that may affect the in-hospital mortality.

We hypothesized that the PaO2/FiO2 ratio would be a clinical prediction tool for in-hospital mortality in patients with acute PE.

Methods

A prospective single-center observational cohort study was conducted in Beijing Hospital from January 2010 to November 2017. Arterial blood gas analysis data captured on admission, clinical characteristics, risk factors, laboratory data, imaging findings, and in-hospital mortality were compared between survivors and non-survivors. The area under the receiver operating characteristic curve (AUC) for in-hospital mortality based on the PaO2/FiO2value was determined, and the association between the parameters and in-hospital mortality was analyzed by using logistic regression analysis.

Results

Body mass index, history of cancer, PaO2/FiO2value, pulse rate, cardiac troponin I level, lactate dehydrogenase level, white blood cell count, D-dimer level, and risk stratification measurements differed between survivors and non-survivors. The optimal cutoff value of PaO2/FiO2for predicting mortality was 265 (AUC = 0.765,P < 0.001). Only a PaO2/FiO2ratio < 265 (95% confidence interval [CI] 1.823–21.483,P = 0.004), history of cancer (95% CI 1.161–15.927,P = 0.029), and risk stratification (95% CI 1.047–16.957,P = 0.043) continued to be associated with an increased risk of in-hospital mortality of acute PE.

Conclusion

A simple determination of the PaO2/FiO2ratio at <265 may provide important information on admission about patients’ in-hospital prognosis, and PaO2/FiO2ratio < 265, history of cancer, and risk stratification are predictors of in-hospital mortality of acute PE.
Determinant of time-to-first birth interval after marriage among Ethiopian women
Authors: Chernet Ayele Gebeyehu , Shebeshi Dinberu Seyoum , Banbeta Akalu
Published: December 2019

Background

Time-to-first birth after marriage has a significant role in the future life of each individual woman and has a direct relationship with fertility. This study aimed to see the determinant of time-to-first birth interval after marriage among Ethiopian women.

Methods

The data was obtained from 2011 Ethiopia Demographic and Health Survey which is the third survey. The sample was selected using a stratified; two-stage cluster sampling design and the data was analysed using parametric shared frailty model.

Results

A total of 7925 ever married women from the nine region of the country were included in this study. Of the total women, 5966 (75.3%) of them gave firstbirth. Age, residence area, employment status, contraceptive use and education of women were associated significantly to time-to-first birth.

Conclusions

Women having younger age at first marriage, urban women, contraceptive users had prolonged time to first birth interval. There is a need of teaching family for contraceptive use and improving women education to increase the length of first birth interval in Ethiopia.
Clinical evidence-guided network pharmacology analysis reveals a critical contribution of β1-adrenoreceptor upregulation to bradycardia alleviation by Shenxian-Shengmai
Authors: Gao Jiaming , Wang Taiyi , Yao Xi , Xie Weiwei , Shi Xianru , He Shuang , Zhao Tao , Wang Chunhua , Zhu Yan
Published: December 2019

Background

Shenxian-Shengmai (SXSM) Oral Liquid is a CFDA-approved patent Chinese Herbal medicine, which has been clinically used for the treatment of bradycardia. However, its active components and action mechanism remain to be established. The present study aimed to evaluate the efficacy of SXSM on bradycardia and to identify the possible active components and their pharmacological targets for this action.

Methods

A literature-based meta-analysis was performed to evaluate the clinical efficacy of SXSM on bradycardia, which was confirmed by a rat ex vivo cardiac model. Network pharmacology analysis was then conducted to reveal the potential targets of SXSM active components and their anti-arrhythmia mechanisms. Finally, the identified drug-target interaction was confirmed by immunofluorescence assay in cardiomyocyte.

Results

Meta-analysis of the available clinical study data shows that Shenxian-Shengmai Oral Liquid has a favorable effect for bradycardia. In an ex vivo bradycardia model of rat heart, SXSM restored heart rate by affecting Heart rate variability (HRV) which is associated with autonomic nervous system activity. A drug-target-pathway network analysis connecting SXSM components with arrhythmia suggested that a prominent anti-arrhythmia mechanisms of SXSM was via β1-adrenergic signaling pathway, which was subsequently validated by immunofluorescence assay showing that SXSM indeed increased the expression of ADRB1 in cultured cardiomyocytes.

Conclusion

By combining approaches of clinical evidence mining, experimental model confirmation, network pharmacology analyses and molecular mechanistic validation, we show that SXSM is an effective treatment for bradycardia and it involves multiple component interacting via multiple pathways, among which is the critical β1-adrenergic receptor upregulation. Our integrative approach could be applied to other multi-component traditional Chinese medicine investigation where ample clinical data are accumulated but advanced mechanistic studies are lacking.
Oolong tea consumption and its interactions with a novel composite index on esophageal squamous cell carcinoma
Authors: Liu Shuang , Lin Zheng , Huang Liping , Chen Huilin , Liu Yanfang , He Fei , Peng Xiane , Chen Weilin , Huang Ruigang , Lu Wanting , Yang Huimin , Xiang Zhisheng , Zhang Zhihui , Hu Zhijian
Published: December 2019

Background

No previous study has investigated the association between oolong tea consumption and esophageal squamous cell carcinoma (ESCC), we aim to elucidate the association between oolong tea consumption and ESCC and its joint effects with a novel composite index.

Methods

In a hospital-based case-control study, 646 cases of ESCC patients and 646 sex and age matched controls were recruited. A composite index was calculated to evaluate the role of demographic characteristics and life exposure factors in ESCC. Unconditional logistic regression was used to calculate the point estimates between oolong tea consumption and risk of ESCC.

Results

No statistically significant association was found between oolong tea consumption and ESCC (OR = 1.39, 95% CI: 0.94–2.05). However, drinking hot oolong tea associated with increased risk of ESCC (OR = 1.60, 95% Cl: 1.06–2.41). Furthermore, drinking hot oolong tea increased ESCC risk in the high-risk group (composite index> 0.55) (OR = 3.14, 95% CI: 1.93–5.11), but not in the low-risk group (composite index≤0.55) (OR = 1.16, 95% CI: 0.74–1.83). Drinking warm oolong tea did not influence the risk of ESCC.

Conclusions

No association between oolong tea consumption and risk of ESCC were found, however, drinking hot oolong tea significantly increased the risk of ESCC, especially in high-risk populations.
Supervised practice program guided by the Accreditation Council for Education in Nutrition and Dietetics standards improves potential employability of nutrition/dietetics graduates: perspective of employers and preceptors
Authors: Bawadi Hiba , Al-Jayyousi Ghadir Fakhri , Du Xiangyun , Ganji Vijay , Kerkadi Abdelhamid , Moawad Joyce , Abunada Taghreed
Published: December 2019

Background

This study investigated employers’ perspectives on the impact of a supervised practice program (SPP), guided by international accreditation standards on the skill development and potential employability of dietetics students.

Main body

This study was based on qualitative research. Fifteen potential employers, who also served as SPP preceptors, participated in this study. Participants were interviewed using semi-structured questionnaire. All interviews were conducted face-to-face by a trained interviewer. Participates were invited to discuss their own experiences in the current SPP, their perceptions of the impact of SPP on skills and attributes of graduates, and their overall ideas of how SPP may contribute to the employability of graduates.

This study found that the SPP program guided by international accreditation standards shaped the duties and responsibilities of preceptors/supervisors and promoted a beneficial relationship between preceptors and SPP students. The benefits to graduates include bridging the gap between classroom didactic knowledge and practice; improving workplace self-confidence; developing competencies such as critical-thinking, communication, interviewing, and counselling skills in various multidisciplinary and multicultural settings. In addition, the preceptors suggested that accreditation-guided SPP contributes to the employability of graduates. Also, they opined that it reduced the need for orientation and shortened the probation time because students were familiar with the work environment and work flow. This lead to the improved preparedness for work.

Conclusion

SPP based on set of competencies guided by international accreditation standards provides an up-to-date curriculum, improves the quality of the nutrition and dietetics services, and increases the potential employability of the graduates.
Using machine learning models to improve stroke risk level classification methods of China national stroke screening
Authors: Li Xuemeng , Bian Di , Yu Jinghui , Li Mei , Zhao Dongsheng
Published: December 2019

Background

With the character of high incidence, high prevalence and high mortality, stroke has brought a heavy burden to families and society in China. In 2009, the Ministry of Health of China launched the China national stroke screening and intervention program, which screens stroke and its risk factors and conducts high-risk population interventions for people aged above 40 years old all over China. In this program, stroke risk factors include hypertension, diabetes, dyslipidemia, smoking, lack of exercise, apparently overweight and family history of stroke. People with more than two risk factors or history of stroke or transient ischemic attack (TIA) are considered as high-risk. However, it is impossible for this criterion to classify stroke risk levels for people with unknown values in fields of risk factors. The missing of stroke risk levels results in reduced efficiency of stroke interventions and inaccuracies in statistical results at the national level. In this paper, we use 2017 national stroke screening data to develop stroke risk classification models based on machine learning algorithms to improve the classification efficiency.

Method

Firstly, we construct training set and test sets and process the imbalance training set based on oversampling and undersampling method. Then, we develop logistic regression model, Naïve Bayesian model, Bayesian network model, decision tree model, neural network model, random forest model, bagged decision tree model, voting model and boosting model with decision trees to classify stroke risk levels.

Result

The recall of the boosting model with decision trees is the highest (99.94%), and the precision of the model based on the random forest is highest (97.33%). Using the random forest model (recall: 98.44%), the recall will be increased by about 2.8% compared with the method currently used, and several thousands more people with high risk of stroke can be identified each year.

Conclusion

Models developed in this paper can improve the current screening method in the way that it can avoid the impact of unknown values, and avoid unnecessary rescreening and intervention expenditures. The national stroke screening program can choose classification models according to the practice need.
Enolase and dipeptidyl peptidase IV protein sub-unit vaccines are not protective against a lethal Streptococcus suis serotype 2 challenge in a mouse model of infection
Authors: Dumesnil Audrey , Martelet Léa , Grenier Daniel , Auger Jean-Philippe , Harel Josée , Nadeau Eric , Gottschalk Marcelo
Published: December 2019

Background

Streptococcus suis is a major swine pathogen causing arthritis, meningitis and sudden death in post-weaning piglets and is also a zoonotic agent. S. suis comprises 35 different serotypes of which the serotype 2 is the most prevalent in both pigs and humans. In the absence of commercial vaccines, bacterins (mostly autogenous), are used in the field, with controversial results. In the past years, the focus has turned towards the development of sub-unit vaccine candidates. However, published results are sometimes contradictory regarding the protective effect of a same candidate. Moreover, the adjuvant used may significantly influence the protective capacity of a given antigen. This study focused on two protective candidates, the dipeptidyl peptidase IV (DPPIV) and the enolase (SsEno). Both proteins are involved in S. suis pathogenesis, and while contradictory protection results have been obtained with SsEno in the past, no data on the protective capacity of DPPIV was available.

Results

Results showed that among all the field strains tested, 86 and 88% were positive for the expression of the SsEno and DPPIV proteins, respectively, suggesting that they are widely expressed by strains of different serotypes. However, no protection was obtained after two vaccine doses in a CD-1 mouse model of infection, regardless of the use of four different adjuvants. Even though no protection was obtained, significant amounts of antibodies were produced against both antigens, and this regardless of the adjuvant used.

Conclusions

Taken together, these results demonstrate that S. suis DPPIV and SsEno are probably not good vaccine candidates, at least not in the conditions evaluated in this study. Further studies in the natural host (pig) should still be carried out. Moreover, this work highlights the importance of confirming results obtained by different research groups.
RETRACTED ARTICLE: N6-methyladenosine induced miR-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1
Authors: Wang Hongsheng , Deng Qianqian , Lv Ziyan , Ling Yuyi , Hou Xue , Chen Zhuojia , Dinglin Xiaoxiao , Ma Shuxiang , Li Delan , Wu Yingmin , Peng Yanxi , Huang Hongbing , Chen Likun
Published: December 2019

Background

Brain metastasis (BM) is one of the principal causes of mortality for lung cancer patients. While the molecular events that govern BM of lung cancer remain frustrating cloudy.

Methods

The miRNA expression profiles are checked in the paired human BM and primary lung cancer tissues. The effect of miR-143-3p on BM of lung cancer cells and its related mechanisms are investigated.

Results

miR-143-3p is upregulated in the paired BM tissues as compared with that in primary cancer tissues. It can increase the invasion capability of in vitro blood brain barrier (BBB) model and angiogenesis of lung cancer by targeting the three binding sites of 3’UTR of vasohibin-1 (VASH1) to inhibit its expression. Mechanistically, VASH1 can increase the ubiquitylation of VEGFA to trigger the proteasome mediated degradation, further, it can endow the tubulin depolymerization through detyrosination to increase the cell motility. m6A methyltransferase Mettl3 can increase the splicing of precursor miR-143-3p to facilitate its biogenesis. Moreover, miR-143-3p/VASH1 axis acts as adverse prognosis factors for in vivo progression and overall survival (OS) rate of lung cancer.

Conclusions

Our work implicates a causal role of the miR-143-3p/VASH1 axis in BM of lung cancers and suggests their critical roles in lung cancer pathogenesis.
IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia
Authors: Rivera-Escalera Fátima , Pinney Jonathan J. , Owlett Laura , Ahmed Hoda , Thakar Juilee , Olschowka John A. , Elliott Michael R. , O’Banion M. Kerry
Published: December 2019

Background

Neuroinflammation is thought to contribute to the pathogenesis of Alzheimer’s disease (AD), yet numerous studies have demonstrated a beneficial role for neuroinflammation in amyloid plaque clearance. We have previously shown that sustained expression of IL-1β in the hippocampus of APP/PS1 mice decreases amyloid plaque burden independent of recruited CCR2+myeloid cells, suggesting resident microglia as the main phagocytic effectors of IL-1β-induced plaque clearance. To date, however, the mechanisms of IL-1β-induced plaque clearance remain poorly understood.

Methods

To determine whether microglia are involved in IL-1β-induced plaque clearance, APP/PS1 mice induced to express mature human IL-1β in the hippocampus via adenoviral transduction were treated with the Aβ fluorescent probe methoxy-X04 (MX04) and microglial internalization of fibrillar Aβ (fAβ) was analyzed by flow cytometry and immunohistochemistry. To assess microglial proliferation, APP/PS1 mice transduced with IL-1β or control were injected intraperitoneally with BrdU and hippocampal tissue was analyzed by flow cytometry. RNAseq analysis was conducted on microglia FACS sorted from the hippocampus of control or IL-1β-treated APP/PS1 mice. These microglia were also sorted based on MX04 labeling (MX04+and MX04−microglia).

Results

Resident microglia (CD45loCD11b+) constituted > 70% of the MX04+cells in both Phe- and IL-1β-treated conditions, and < 15% of MX04+cells were recruited myeloid cells (CD45hiCD11b+). However, IL-1β treatment did not augment the percentage of MX04+microglia nor the quantity of fAβ internalized by individual microglia. Instead, IL-1β increased the total number of MX04+microglia in the hippocampus due to IL-1β-induced proliferation. In addition, transcriptomic analyses revealed that IL-1β treatment was associated with large-scale changes in the expression of genes related to immune responses, proliferation, and cytokine signaling.

Conclusions

These studies show that IL-1β overexpression early in amyloid pathogenesis induces a change in the microglial gene expression profile and an expansion of microglial cells that facilitates Aβ plaque clearance.
A high-performance 8 nV/√Hz 8-channel wearable and wireless system for real-time monitoring of bioelectrical signals
Authors: Petkos Konstantinos , Koutsoftidis Simos , Guiho Thomas , Degenaar Patrick , Jackson Andrew , Greenwald Stephen E. , Brown Peter , Denison Timothy , Drakakis Emmanuel M.
Published: December 2019

Background

It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Finally, to the best of our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording electrocorticographic (ECoG) signals.

Methods

To address this problem, we designed and developed a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless instrument (55 × 80 mm2). The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments.

Results

To provide ex vivo proof-of-function, a wide variety of high-quality bioelectrical signal recordings are reported, including electroencephalographic (EEG), electromyographic (EMG), electrocardiographic (ECG), acceleration signals, and muscle fasciculations. Low-noise in vivo recordings of weak local field potentials (LFPs), which were wirelessly acquired in real time using segmented deep brain stimulation (DBS) electrodes implanted in the thalamus of a non-human primate, are also presented.

Conclusions

The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5–500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile and reliable tool to be utilized in a wide range of applications and environments.
The prevalence of burnout syndrome among resident physicians in Syria
Authors: Alhaffar Bahaa Aldin , Abbas Ghadir , Alhaffar Alaa Aldin
Published: December 2019

Introduction

Burnout syndrome is a work-related chronic stress that is described as emotional exhaustion, a decreased sense of personal accomplishment, and depersonalization. it has been considered an important problem especially among workers in the health sector.

Objectives

The aim of this research was to study the prevalence of burnout among Syrian residents during the Syrian crisis, which started 9 years ago, and to assess the factors related to burnout syndrome.

Methods

A cross-sectional study was conducted to assess the levels of burnout syndrome; data were collected from residents doing their residency in 12 different hospitals spread over 8 governorates in Syria. A web-based Arabic version of Maslach Burnout Inventory questionnaire was used. The final sample size was 3350 residents from different specialties. SPSS V.22 was used to analyses the data using descriptive and inferential statistics.

Results

(93.75%) had a high level in at least one of the three domains of the burnout index, and (19.3%) of the residents had a high level of burnout in all three domains. Significant relation was found between gender, age group and affiliated authority variables and the levels of burnout. However no significant relation was found between burnout and the specialties or geographic variables. Males, residents in Ministry of Defense, and emergency medicine residents had the highest levels of burnout.

Conclusion

High levels of burnout was found among residents during the Syrian crisis in comparison with other studies, which highlights the role of the current situation in raising workload on the Syrian residents.
Finite element analysis of two cephalomedullary nails in treatment of elderly reverse obliquity intertrochanteric fractures: zimmer natural nail and proximal femoral nail antirotation-ΙΙ
Authors: Chen Jian , Ma Jian-xiong , Wang Ying , Bai Hao-hao , Sun Lei , Wang Yan , Lu Bin , Dong Ben-chao , Tian Ai-xian , Ma Xin-long
Published: December 2019

Background

More elderly patients are suffering from intertrochanteric fractures. However, the choice of internal fixation is still controversial, especially in the treatment of unstable intertrochanteric fracture; thus, previous implants continue to be improved, and new ones are being developed. The purpose of our study was to compare the biomechanical advantages between the zimmer natural nail (ZNN) and proximal femoral nail antirotation-II (PFNA-II) in the treatment of elderly reverse obliquity intertrochanteric fractures.

Methods

A three-dimensional finite element was applied for reverse obliquity intertrochanteric fracture models (AO31-A3.1) fixed with the ZNN or PFNA-II. The distribution, peak value and position of the von Mises stress and the displacement were the criteria for comparison between the two groups.

Results

The stresses of the internal fixation and femur in the ZNN model were smaller than those in the PFNA-II model, and the peak values of the two groups were 364.8 MPa and 171.8 MPa (ZNN) and 832.3 MPa and 1795.0 MPa (PFNA-II). The maximum amount of displacement of the two groups was similar, and their locations were the same, i.e., in the femoral head vertex (3.768 mm in the ZNN model and 3.713 mm in the PFNA-II model).

Conclusions

The displacement in the two models was similar, but the stresses in the implant and bone were reduced with the ZNN. Therefore, the ZNN implant may provide biomechanical advantages over PFNA-II in reverse obliquity intertrochanteric fractures, as shown through the finite element analysis. These findings from our study may provide a reference for the perioperative selection of internal fixations.
Magnetic resonance imaging and computed tomography of equine cheek teeth and adjacent structures: comparative study of image quality in horses in vivo, post-mortem and frozen-thawed
Authors: Röttiger Christin , Hellige Maren , Ohnesorge Bernhard , Bienert-Zeit Astrid
Published: December 2019

Background

The use of cadavers for radiology research methodologies involving subjective image quality evaluation of anatomical criteria is well-documented. The purpose of this method comparison study was to evaluate the image quality of dental and adjacent structures in computed tomography (CT) and high-field (3 T) magnetic resonance (MR) images in cadaveric heads, based on an objective four-point rating scale. Whilst CT is a well-established technique, MR imaging (MRI) is rarely used for equine dental diagnostics. The use of a grading system in this study allowed an objective assessment of CT and MRI advantages in portraying equine cheek teeth. As imaging is commonly performed with cadaveric or frozen and thawed heads for dental research investigations, the second objective was to quantify the impact of the specimens’ conditions (in vivo, post-mortem, frozen-thawed) on the image quality in CT and MRI.

Results

The CT and MR images of nine horses, focused on the maxillary premolar 08s and molar 09s, were acquired post-mortem (Group A). Three observers scored the dental and adjacent tissues. Results showed that MR sequences gave an excellent depiction of endo- and periodontal structures, whereas CT produced high-quality images of the hard tooth and bony tissues. Additional CT and MRI was performed in vivo (Group B) and frozen-thawed (Group C) in three of these nine horses to specify the condition of the best specimens for further research. Assessing the impact of the specimens’ conditions on image quality, specific soft tissues of the maxillary 08s and 09s including adjacent structures (pulps, mucosa of the maxillary sinuses, periodontal ligament, soft tissue inside the infraorbital canal) were graded in group B and C and analysed for significant differences within CT and MR modalities in comparison to group A. Results showed that MRI scores in vivo were superior to the post-mortem and frozen-thawed condition.

Conclusions

On comparing the imaging performance of CT and MRI, both techniques show a huge potential for application in equine dentistry. Further studies are needed to assess the clinical suitability of MRI. For further research investigations it must be considered, that the best MR image quality is provided in live horses.
Peripheral blood metabolome predicts mood change-related activity in mouse model of bipolar disorder
Authors: Hagihara Hideo , Horikawa Tomoyasu , Irino Yasuhiro , Nakamura Hironori K. , Umemori Juzoh , Shoji Hirotaka , Yoshida Masaru , Kamitani Yukiyasu , Miyakawa Tsuyoshi
Published: December 2019

Bipolar disorder is a major mental illness characterized by severe swings in mood and activity levels which occur with variable amplitude and frequency. Attempts have been made to identify mood states and biological features associated with mood changes to compensate for current clinical diagnosis, which is mainly based on patients’ subjective reports. Here, we used infradian (a cycle > 24 h) cyclic locomotor activity in a mouse model useful for the study of bipolar disorder as a proxy for mood changes. We show that metabolome patterns in peripheral blood could retrospectively predict the locomotor activity levels. We longitudinally monitored locomotor activity in the home cage, and subsequently collected peripheral blood and performed metabolomic analyses. We then constructed cross-validated linear regression models based on blood metabolome patterns to predict locomotor activity levels of individual mice. Our analysis revealed a significant correlation between actual and predicted activity levels, indicative of successful predictions. Pathway analysis of metabolites used for successful predictions showed enrichment in mitochondria metabolism-related terms, such as “Warburg effect” and “citric acid cycle.” In addition, we found that peripheral blood metabolome patterns predicted expression levels of genes implicated in bipolar disorder in the hippocampus, a brain region responsible for mood regulation, suggesting that the brain–periphery axis is related to mood-change-associated behaviors. Our results may serve as a basis for predicting individual mood states through blood metabolomics in bipolar disorder and other mood disorders and may provide potential insight into systemic metabolic activity in relation to mood changes.
The atypical cadherin flamingo determines the competence of neurons for activity-dependent fine-scale topography
Authors: Li Ruonan , Liang Yuhua , Zheng Siyang , He Qun , Yang Limin
Published: December 2019

The topographic projection of afferent terminals into two-dimensional maps is essential for sensory systems to encode the locations of sensory stimuli. In vertebrates, guidance cues are critical for establishing a coarse topographic map, while neuronal activity directs fine-scale topography between adjacent afferent terminals. However, the molecular mechanism underlying activity-dependent fine-scale topography is not well known. Studies in the Drosophila visual system have demonstrated that cell-adhesion molecules direct fine-scale topography, but whether or not these molecules are involved in activity-dependent fine-scale topography remains to be determined. We previously reported that the nociceptors in Drosophila larvae form an activity-dependent fine-scale topographic system. The establishment of this system is instructed by the level of neuronal activity in individual nociceptors. Here, we show that the atypical cadherin Flamingo (Fmi) is required for establishing the nociceptor topographic map. We found that the topographic defect caused by loss of fmi was epistatic to the inhibition of neuronal activity and the overexpression of the activity-regulated gene Trim9. These results suggest that Fmi and neuronal activity interact to regulate fine-scale topography. This study provides a link between neuronal activity and the cell-adhesion molecule in the establishment of fine-scale topography.
OPG/RANK/RANKL signaling axis in patients with type I diabetes: Associations with parathormone and vitamin D
Authors: Karalazou Paraskevi , Ntelios Dimitrios , Chatzopoulou Fani , Fragou Aikaterini , Taousani Maria , Mouzaki Konstantina , Galli-Tsinopoulou Assimina , Kouidou Sofia , Tzimagiorgis Georgios
Published: December 2019

Background

Type 1 diabetes (T1D) has been associated with a higher fracture risk due to alterations in bone structure and metabolism. On the other hand, the important role of the RANKL/OPG/RANK signaling axis in bone physiology is well established. The aim of this study was to evaluate the levels of receptor activator of nuclear factor kappa-B ligand (RANKL), receptor activator of nuclear factor kappa-B (RANK) and plasma osteoprotegerin (OPG) levels, in T1D youngsters and to investigate factors that could influence theOPG/RANK/RANKLsignaling axis such as 25-hydroxy vitamin D [25(OH) D], parathormone (PTH) and age.

Methods

Serum RANKL, RANK, 25(OH) D, PTH levels and plasma OPG levels, were measured in 71 youngsters with T1D and 50 healthy controls matched for age and gender.

Results

Plasma OPG levels were significantly lower (p = 0.025) in T1D patients compared to controls. Serum RANKL levels were significantly higher (p = 0.037), while no differences were observed in serum RANK levels (p = 0.946) between the two groups. Serum 25(OH) D levels found significantly decreased (p < 0.001) while serum PTH levels were significantly elevated (p < 0.001) in T1D patients than in controls.

Conclusions

Our results demonstrated that OPG and RANKL may be promising biomarkers for T1D patients. However, their circulating levels were associated with several factors including PTH, 25(OH) D and therefore, may represent an integrative biomarker for a variety of endocrine signaling disturbances observed in T1D.
The Pseudomonas aeruginosa accessory genome elements influence virulence towards Caenorhabditis elegans
Authors: Vasquez-Rifo Alejandro , Veksler-Lublinsky Isana , Cheng Zhenyu , Ausubel Frederick M. , Ambros Victor
Published: December 2019

Background

Multicellular animals and bacteria frequently engage in predator-prey and host-pathogen interactions, such as the well-studied relationship betweenPseudomonas aeruginosaand the nematodeCaenorhabditis elegans. This study investigates the genomic and genetic basis of bacterial-driven variability inP. aeruginosavirulence towardsC. elegansto provide evolutionary insights into host-pathogen relationships.

Results

Natural isolates ofP. aeruginosathat exhibit diverse genomes display a broad range of virulence towardsC. elegans. Using gene association and genetic analysis, we identify accessory genome elements that correlate with virulence, including both known and novel virulence determinants. Among the novel genes, we find a viral-like mobile element, thetegblock, that impairs virulence and whose acquisition is restricted by CRISPR-Cas systems. Further genetic and genomic evidence suggests that spacer-targeted elements preferentially associate with lower virulence while the presence of CRISPR-Cas associates with higher virulence.

Conclusions

Our analysis demonstrates substantial strain variation inP. aeruginosavirulence, mediated by specific accessory genome elements that promote increased or decreased virulence. We exemplify that viral-like accessory genome elements that decrease virulence can be restricted by bacterial CRISPR-Cas immune defense systems, and suggest a positive, albeit indirect, role for host CRISPR-Cas systems in virulence maintenance.
Accuracy, robustness and scalability of dimensionality reduction methods for single-cell RNA-seq analysis
Authors: Sun Shiquan , Zhu Jiaqiang , Ma Ying , Zhou Xiang
Published: December 2019

Background

Dimensionality reduction is an indispensable analytic component for many areas of single-cell RNA sequencing (scRNA-seq) data analysis. Proper dimensionality reduction can allow for effective noise removal and facilitate many downstream analyses that include cell clustering and lineage reconstruction. Unfortunately, despite the critical importance of dimensionality reduction in scRNA-seq analysis and the vast number of dimensionality reduction methods developed for scRNA-seq studies, few comprehensive comparison studies have been performed to evaluate the effectiveness of different dimensionality reduction methods in scRNA-seq.

Results

We aim to fill this critical knowledge gap by providing a comparative evaluation of a variety of commonly used dimensionality reduction methods for scRNA-seq studies. Specifically, we compare 18 different dimensionality reduction methods on 30 publicly available scRNA-seq datasets that cover a range of sequencing techniques and sample sizes. We evaluate the performance of different dimensionality reduction methods for neighborhood preserving in terms of their ability to recover features of the original expression matrix, and for cell clustering and lineage reconstruction in terms of their accuracy and robustness. We also evaluate the computational scalability of different dimensionality reduction methods by recording their computational cost.

Conclusions

Based on the comprehensive evaluation results, we provide important guidelines for choosing dimensionality reduction methods for scRNA-seq data analysis. We also provide all analysis scripts used in the present study at www.xzlab.org/reproduce.html.
Measurement training and feedback system for implementation of evidence-based treatment for adolescent externalizing problems: protocol for a randomized trial of pragmatic clinician training
Authors: Hogue Aaron , Bobek Molly , MacLean Alexandra , Porter Nicole , Jensen-Doss Amanda , Henderson Craig E.
Published: December 2019

Background

Innovations in clinical training and support that enhance fidelity to evidence-based treatment (EBT) for adolescent behavior problems are sorely needed. This study will develop an online training system to address this gap: Measurement Training and Feedback System for Implementation (MTFS-I). Using procedures intended to be practical and sustainable, MTFS-I is designed to increase two aspects of therapist behavior that are fundamental to boosting EBT fidelity: therapist self-monitoring of EBT delivery, and therapist utilization of core techniques of EBTs in treatment sessions. This version of MTFS-I focuses on two empirically supported treatment approaches for adolescent conduct and substance use problems: family therapy and cognitive behavioral therapy (CBT).

Methods/design

MTFS-I expands on conventional measurement feedback systems for client outcomes by adding training in observational coding to promote EBT self-monitoring and focusing on implementation of EBT treatment techniques. It has two primary components. (1) The training component, delivered weekly in two connected parts, involves self-monitored learning modules containing brief clinical descriptions of core EBT techniques and mock session coding exercises based on 5–8 min video segments that illustrate delivery of core techniques. (2) The feedback component summarizes aggregated therapist-reported data on EBT techniques used with their active caseloads. MTFS-I is hosted online and requires approximately 20 min per week to complete for each treatment approach. This randomized trial will first collect data on existing delivery of family therapy and CBT techniques for youth in outpatient behavioral health sites (Baseline phase). It will then randomize site clinicians to two study conditions (Implementation phase): Training Only versus Training + Feedback + Consultation. Therapists will choose whether to train in family therapy, CBT, or both. Study aims will compare clinician performance across study phase and between study conditions on MTFS-I uptake, reliability and accuracy in EBT self-monitoring, and utilization of EBT techniques in treatment sessions (based on observer coding of audiotapes).

Discussion

Study contributions to implementation science and considerations of MTFS-I sustainability are discussed.

Trial registration

ClinicalTrials.gov, NCT03722654. Registered on 29 October 2018.
Correction to: A downstream box fusion allows stable accumulation of a bacterial cellulase in Chlamydomonas reinhardtii chloroplasts
Authors: Richter Lubna V. , Yang Huijun , Yazdani Mohammad , Hanson Maureen R. , Ahner Beth A.
Published: December 2019

In the original version of the article [1], a calculation error resulted in a 3-order of magnitude mistake for the y-axis of the data reported in Fig. 5c and d.
Overall and sex-specific associations between methylation of the ABCG1 and APOE genes and ischemic stroke or other atherosclerosis-related traits in a sibling study of Chinese population
Authors: Qin Xueying , Li Jin , Wu Tao , Wu Yiqun , Tang Xun , Gao Pei , Li Lin , Wang Mengying , Wu Yao , Wang Xiaowen , Chen Dafang , Hu Yonghua
Published: December 2019

Background

Identifying subjects with a high risk of ischemic stroke is fundamental for prevention of the disease. Both genetic and environmental risk factors contribute to ischemic stroke, but the underlying epigenetic mechanisms which mediate genetic and environmental risk effects are not fully understood. The aim of this study was to explore whether DNA methylation loci located in the ATP-binding cassette G1 (ABCG1) and apolipoprotein E (APOE) genes, both involved in the metabolism of lipids in the body, are related to ischemic stroke, using the Fangshan/Family-based Ischemic Stroke Study in China. We also tested if these CpG sites were associated with early signs of cardiovascular atherosclerosis (carotid intima–media thickness (cIMT), ankle–brachial index (ABI), and brachial–ankle pulse wave velocity (baPWV)).

Results

DNA methylation at the cg02494239 locus in ABCG1 was correlated with ischemic stroke after adjusting for gender, previous history of diabetes and hypertension, smoking, drinking, body mass index, and blood lipid levels (above vs below mean, OR = 2.416, 95% CI 1.024–5.700, P = 0.044; 75–100% percentile vs 0–25% percentile, OR = 4.461, 95% CI 1.226–16.225, P = 0.023). No statistically significant associations were observed for the cg06500161 site in ABCG1 and the cg14123992 site in APOE with ischemic stroke. The study detected that hypermethylation of the ABCG1 gene was significantly associated with cIMT, hypermethylation of the APOE gene was significantly related to ABI, and methylation of the APOE gene was statistically negatively correlated with baPWV. The above relationships demonstrated gender differences.

Conclusions

These findings suggest that epigenetic modification of ABCG1 and APOE may play a role in the pathway from disturbed blood lipid levels to the development of cardiovascular diseases. Future prospective validation of these findings is warranted.
Huge abdominal cerebrospinal fluid pseudocyst following ventriculoperitoneal shunt: a case report
Authors: Koide Yasuhiro , Osako Takaaki , Kameda Masahiro , Ihoriya Hiromi , Yamamoto Hirotsugu , Fujisaki Noritomo , Aokage Toshiyuki , Yumoto Tetsuya , Date Isao , Naito Hiromichi , Nakao Atsunori
Published: December 2019

Introduction

Abdominal pseudocysts comprising cerebrospinal fluid are an uncommon but significant complication in patients with ventriculoperitoneal shunt. We present a successfully treated 12-year-old boy with a history of ventriculoperitoneal shunting and a huge abdominal cerebrospinal fluid pseudocyst.

Case presentation

A12-year-old Japanese boy presented with a deteriorated consciousness and a palpable and elastic large lower abdominal mass. Computed tomography of his abdomen demonstrated a collection of homogenous low-density fluid near the catheter tip of the ventriculoperitoneal shunt. Cerebral computed tomography revealed an increased ventricular size. Based on the clinical diagnosis of abdominal pseudocyst, the peritoneal shunt catheter was secured and divided into two parts by cutting it on the chest; then, the proximal side of the peritoneal shunt catheter was externalized for extraventricular drainage. The cyst was percutaneously aspirated with ultrasound guidance, and the distal side of the peritoneal shunt catheter was removed. The distal side of the peritoneal shunt catheter was reinserted in another position into his abdomen after 3-week extraventricular drainage management.

Conclusion

Emergency physicians should know about this potential complication as an important differential diagnosis resulting from acute abdominal complaints in patients with ventriculoperitoneal shunts.
Psychometric properties of the Jefferson Scale of Empathy: a COSMIN systematic review protocol
Authors: Williams Brett , Beovich Bronwyn
Published: December 2019

Background

Empathy is an important characteristic to possess for healthcare professionals. It has been found to improve communication between professionals and patients and to improve clinical health outcomes. The Jefferson Scale of Empathy (JSE) was developed to measure this quality and has been used extensively, and psychometrically appraised, with a variety of cohorts and in different cultural environments. However, no study has been undertaken to systematically examine the methodological quality of studies which have assessed psychometric factors of the JSE. This systematic review will examine the quality of published papers that have reported on psychometric factors of the JSE.

Methods

A systematic review of studies which report on the psychometric properties of the JSE will be conducted. We will use a predefined search strategy to identify studies meeting the following eligibility criteria: original data is reported on for at least one of the psychometric measurement properties described in the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias checklist, examines the JSE in a healthcare cohort (using the student, physician or health profession versions of the JSE), and is published from January 2001 and in the English language. Conference abstracts, editorials and grey literature will be excluded. Six electronic databases (Medline, EMBASE, PsychInfo, PubMed, Web of Science and CINAHL) will be systematically searched for articles meeting these criteria and studies will be assessed for eligibility by two review authors. The methodological quality of included papers will be examined using the COSMIN Risk of Bias checklist.

Discussion

A narrative description of the findings will be presented along with summary tables. Recommendations for use of the JSE with various cohorts and circumstances will be offered which may inform future research in this field.

Systematic review registration

PROSPERO CRD42018111412
A perspective on graph theory-based stability analysis of impulsive stochastic recurrent neural networks with time-varying delays
Authors: Iswarya M. , Raja R. , Rajchakit G. , Cao J. , Alzabut J. , Huang C.
Published: December 2019

In this work, the exponential stability problem of impulsive recurrent neural networks is investigated; discrete time delay, continuously distributed delay and stochastic noise are simultaneously taken into consideration. In order to guarantee the exponential stability of our considered recurrent neural networks, two distinct types of sufficient conditions are derived on the basis of the Lyapunov functional and coefficient of our given system and also to construct a Lyapunov function for a large scale system a novel graph-theoretic approach is considered, which is derived by utilizing the Lyapunov functional as well as graph theory. In this approach a global Lyapunov functional is constructed which is more related to the topological structure of the given system. We present a numerical example and simulation figures to show the effectiveness of our proposed work.