bluuebunny/crossref_metadata_2025 huggingface dataset:
Methodology for assessment of public health emergency preparedness and response synergies between institutional authorities and communities
Authors: de Vries Daniel H. , Kinsman John , Takacs Judit , Tsolova Svetla , Ciotti Massimo
Published: May 2020

Background

This paper describes a participatory methodology that supports investigation of the synergistic collaboration between communities affected by infectious disease outbreak events and relevant official institutions. The core principle underlying the methodology is the recognition that synergistic relationships, characterised by mutual trust and respect, between affected communities and official institutions provide the most effective means of addressing outbreak situations.

Methods

The methodological approach and lessons learned were derived from four qualitative case studies including (i) two tick-borne disease events (Crimean-Congo haemorrhagic fever in Spain, 2016, and tick-borne encephalitis in the Netherlands, 2016); and (ii) two outbreaks of acute gastroenteritis (norovirus in Iceland, 2017, and verocytotoxin-producing Escherichia coli [VTEC] in Ireland, 2018). An after-event qualitative case study approach was taken using mixed methods. The studies were conducted in collaboration with the respective national public health authorities in the affected countries by the European Centre for Disease Prevention and Control (ECDC). The analysis focused on the specific actions undertaken by the participating countries’ public health and other authorities in relation to community engagement, as well as the view from the perspective of affected communities.

Results

Lessons highlight the critical importance of collaborating with ECDC National Focal Points during preparation and planning and with anthropological experts. Field work for each case study was conducted over one working week, which although limiting the number of individuals and institutions involved, still allowed for rich data collection due to the close collaboration with local authorities. The methodology enabled efficient extraction of synergies between authorities and communities. Implementing the methodology required a reflexivity among fieldworkers that ackowledges that different versions of reality can co-exist in the social domain. The method allowed for potential generalisability across studies. Issues of extra attention included insider-outsider perspectives, politically sensitivity of findings, and how to deal with ethical and language issues.

Conclusions

The overall objective of the assessment is to identify synergies between institutional decision-making bodies and community actors and networks before, during and after an outbreak response to a given public health emergency. The methodology is generic and could be applied to a range of public health emergencies, zoonotic or otherwise.
Predicting the risk of childhood overweight and obesity at 4–5 years using population-level pregnancy and early-life healthcare data
Authors: Ziauddeen Nida , Wilding Sam , Roderick Paul J. , Macklon Nicholas S. , Smith Dianna , Chase Debbie , Alwan Nisreen A.
Published: May 2020

Background

Nearly a third of children in the UK are overweight, with the prevalence in the most deprived areas more than twice that in the least deprived. The aim was to develop a risk identification model for childhood overweight/obesity applied during pregnancy and early life using routinely collected population-level healthcare data.

Methods

A population-based anonymised linked cohort of maternal antenatal records (January 2003 to September 2013) and birth/early-life data for their children with linked body mass index (BMI) measurements at 4–5 years (n = 29,060 children) in Hampshire, UK was used. Childhood age- and sex-adjusted BMI at 4–5 years, measured between September 2007 and November 2018, using a clinical cut-off of ≥ 91st centile for overweight/obesity. Logistic regression models together with multivariable fractional polynomials were used to select model predictors and to identify transformations of continuous predictors that best predict the outcome.

Results

Fifteen percent of children had a BMI ≥ 91st centile. Models were developed in stages, incorporating data collected at first antenatal booking appointment, later pregnancy/birth, and early-life predictors (1 and 2 years). The area under the curve (AUC) was lowest (0.64) for the model only incorporating maternal predictors from early pregnancy and highest for the model incorporating all factors up to weight at 2 years for predicting outcome at 4–5 years (0.83). The models were well calibrated. The prediction models identify 21% (at booking) to 24% (at ~ 2 years) of children as being at high risk of overweight or obese by the age of 4–5 years (as defined by a ≥ 20% risk score). Early pregnancy predictors included maternal BMI, smoking status, maternal age, and ethnicity. Early-life predictors included birthweight, baby’s sex, and weight at 1 or 2 years of age.

Conclusions

Although predictive ability was lower for the early pregnancy models, maternal predictors remained consistent across the models; thus, high-risk groups could be identified at an early stage with more precise estimation as the child grows. A tool based on these models can be used to quantify clustering of risk for childhood obesity as early as the first trimester of pregnancy, and can strengthen the long-term preventive element of antenatal and early years care.
MyoMiner: explore gene co-expression in normal and pathological muscle
Authors: Malatras Apostolos , Michalopoulos Ioannis , Duguez Stéphanie , Butler-Browne Gillian , Spuler Simone , Duddy William J.
Published: May 2020

Background

High-throughput transcriptomics measures mRNA levels for thousands of genes in a biological sample. Most gene expression studies aim to identify genes that are differentially expressed between different biological conditions, such as between healthy and diseased states. However, these data can also be used to identify genes that are co-expressed within a biological condition. Gene co-expression is used in a guilt-by-association approach to prioritize candidate genes that could be involved in disease, and to gain insights into the functions of genes, protein relations, and signaling pathways. Most existing gene co-expression databases are generic, amalgamating data for a given organism regardless of tissue-type.

Methods

To study muscle-specific gene co-expression in both normal and pathological states, publicly available gene expression data were acquired for 2376 mouse and 2228 human striated muscle samples, and separated into 142 categories based on species (human or mouse), tissue origin, age, gender, anatomic part, and experimental condition. Co-expression values were calculated for each category to create the MyoMiner database.

Results

Within each category, users can select a gene of interest, and the MyoMiner web interface will return all correlated genes. For each co-expressed gene pair, adjustedp-value and confidence intervals are provided as measures of expression correlation strength. A standardized expression-level scatterplot is available for every gene pair r-value. MyoMiner has two extra functions: (a) a network interface for creating a 2-shell correlation network, based either on the most highly correlated genes or from a list of genes provided by the user with the option to include linked genes from the database and (b) a comparison tool from which the users can test whether any two correlation coefficients from different conditions are significantly different.

Conclusions

These co-expression analyses will help investigators to delineate the tissue-, cell-, and pathology-specific elements of muscle protein interactions, cell signaling and gene regulation. Changes in co-expression between pathologic and healthy tissue may suggest new disease mechanisms and help define novel therapeutic targets. Thus, MyoMiner is a powerful muscle-specific database for the discovery of genes that are associated with related functions based on their co-expression.

MyoMiner is freely available athttps://www.sys-myo.com/myominer
Mesenchymal stem/stromal cells: the therapeutic effects in animal models of acute pulmonary diseases
Authors: Sadeghian Chaleshtori Sirous , Mokhber Dezfouli Mohammad Reza , Jabbari Fakhr Massoumeh
Published: May 2020

The pulmonary diseases are one of the most important causes of death in the world. The successful therapies in the field of lung diseases are very limited and the medical treatments available are ineffective in many of the lung diseases. Many studies have evaluated the new therapies in the acute pulmonary diseases, and the transplantation of mesenchymal stem/stromal cells (MSCs), which is a branch of cell therapy, has a special place among the new medical techniques. The MSCs are present throughout the body and are thought to play a role in tissue regeneration and inflammation control. In the event of injury, the local MSCs traverse the shortest possible distance from the tissue or blood vessels to reach the affected site. But, there are few undifferentiated cells in the tissues. The exogenous MSCs are used to immunity modify or regenerative treatments in preclinical models of acute pulmonary diseases. Several studies have shown the positive effects of MSCs replacement in the acute lung disorders. The effection mechanism of the MSCs include the differentiation ability and the secretion of paracrine agents such as the anti-inflammatory mediators. Many studies suggest that this treatment method is safe and is probably to be widely used in future clinical trials. This review will describe the therapeutic effects of the MSCs in the experimental models of the acute pulmonary diseases for use as a method of treatment in clinical trials in future.
Association of the insulin resistance marker TyG index with the severity and mortality of COVID-19
Authors: Ren Huihui , Yang Yan , Wang Fen , Yan Yongli , Shi Xiaoli , Dong Kun , Yu Xuefeng , Zhang Shujun
Published: May 2020

Background

The triglyceride and glucose index (TyG) has been proposed as a marker of insulin resistance. This study aims to evaluate the association of the TyG index with the severity and mortality of coronavirus disease 2019 (COVID-19).

Methods

The study included a cohort of 151 patients with COVID-19 admitted in a tertiary teaching hospital in Wuhan. Regression models were used to investigate the association between TyG with severity and mortality of COVID-19.

Results

In this cohort, 39 (25.8%) patients had diabetes, 62 (41.1%) patients were severe cases, while 33 (22.0%) patients died in hospital. The TyG index levels were significantly higher in the severe cases and death group (mild vs. severe 8.7 ± 0.6 vs. 9.2 ± 0.6, P < 0.001; survivor vs. deceased 8.8 ± 0.6 vs. 9.3 ± 0.7, P < 0.001), respectively. The TyG index was significantly associated with an increased risk of severe case and mortality, after controlling for potential confounders (OR for severe case, 2.9, 95% CI 1.2–6.3, P = 0.007; OR for mortality, 2.9, 95% CI 1.2–6.7, P = 0.016). The associations were not statistically significant for further adjustment of inflammatory factors.

Conclusion

TyG index was closely associated with the severity and morbidity in COVID-19 patients, thus it may be a valuable marker for identifying poor outcome of COVID-19.
Electrochemical modeling and evaluation for textile electrodes to skin
Authors: Song Jinzhong , Zhang Yu , Yang Yijing , Liu Hao , Zhou Tianshu , Zhang Kui , Li Fan , Xu Zhi , Liu Qingjun , Li Jingsong
Published: May 2020

Background

With the development of wearable health-monitoring technologies, a variety of textile electrodes have been produced and applied by researchers. However, there are no universal and effective methods even testing platforms for evaluating the skin–electrode electrochemical interface for textile electrodes because different human bodies have different skin characteristics.

Methods

An electrochemical modeling and evaluation for textile electrodes to skin was proposed, and two electrochemical evaluation platforms (EEP) were set up based on two simulated skin models (SSM). First, skin–electrode electrochemical interface (SEEI) models for traditional wet electrodes and textile electrodes were analyzed. Based on the SEEI models and YY/T 0196-2005 (Chinese YY/T pharmaceutical industry standard for disposable ECG electrode), three skin–electrode electrochemical characteristics (SEEC), including skin–electrode static impedance (SESI), skin–electrode alternating current impedance (SEAI), and skin–electrode polarization voltage (SEPV), were proposed. Then, three electrochemical evaluation methods for textile electrodes to skin were proposed and analyzed, which were the correlation between SEEC and skin–electrode contact pressure (SECP), skin–electrode relative movement (SERM), and conduction loss of active signals (CLAS). Finally, an electrochemical evaluation platform was set up based on an active simulated skin model (ASSM) and passive simulated skin model (PSSM).

Results

9 feature parameters based on the passive electrochemical evaluation platform (PEEP) and 11 feature parameters based on the active electrochemical evaluation platform (AEEP) were obtained for evaluating textile electrodes. And four kinds of textile electrode characteristics including SEEC, SECP, SERM, and CLAS were quantitatively measured based on the electrochemical evaluation platform, and the testing accuracy and range for these characteristics were measured separately. Finally, correlation between SEEC and SECP for 10 kinds of textile electrode samples was studied, and 14 electrochemical characteristics and four skin–electrode contact pressure characteristics were extracted. Experimental results showed that significant correlations were found between six SEEC characteristics and SECP characteristics, and the correlation coefficient between ACI_3 and USECP was the highest. And the polarization voltages of most dry electrode samples showed a downward trend with the increase of contact pressure.

Conclusions

The electrochemical evaluation platform yielded effective experimental data and could provide strong support for the evaluation and application of textile electrodes, which was also effective in evaluating other bioelectric electrodes such as 3M electrode, stainless steel electrode, dry electrode and microneedle electrode.
Postural control learning dynamics in Parkinson’s disease: early improvement with plateau in stability, and continuous progression in flexibility and mobility
Authors: Rahmati Zahra , Behzadipour Saeed , Schouten Alfred C. , Taghizadeh Ghorban , Firoozbakhsh Keikhosrow
Published: May 2020

Background

Balance training improves postural control in Parkinson’s disease (PD). However, a systematic approach for the development of individualized, optimal training programs is still lacking, as the learning dynamics of the postural control in PD, over a training program, are poorly understood.

Objectives

We investigated the learning dynamics of the postural control in PD, during a balance-training program, in terms of the clinical, posturographic, and novel model-based measures.

Methods

Twenty patients with PD participated in a balance-training program, 3 days a week, for 6 weeks. Clinical tests assessed functional balance and mobility pre-training, mid-training, and post-training. Center-of-pressure (COP) was recorded at four time-points during the training (pre-, week 2, week 4, and post-training). COP was used to calculate the sway measures and to identify the parameters of a patient-specific postural control model, at each time-point. The posturographic and model-based measures constituted the two sets of stability- and flexibility-related measures.

Results

Mobility- and flexibility-related measures showed a continuous improvement during the balance-training program. In particular, mobility improved at mid-training and continued to improve to the end of the training, whereas flexibility-related measures reached significance only at the end. The progression in the balance- and stability-related measures was characterized by early improvements over the first 3 to 4 weeks of training, and reached a plateau for the rest of the training.

Conclusions

The progression in balance and postural stability is achieved earlier and susceptible to plateau out, while mobility and flexibility continue to improve during the balance training.
Secondary surgical cytoreduction needs to be assessed taking into account surgical technique, completeness of cytoreduction, and extent of disease
Authors: Segura-Sampedro Juan José , Morales-Soriano Rafael , Arjona-Sánchez Álvaro , Cascales-Campos Pedro
Published: May 2020

Recent evidence suggested that secondary surgical cytoreduction followed by chemotherapy does not result in longer overall survival in patients with platinum-sensitive recurrent ovarian cancer.

This statement is based on a phase III multicenter, randomized clinical trial that lacks a description of the surgical protocol, the surgical technique, and the surgical variables. In a study that evaluates surgical cytoreduction, it is mandatory to assess the grade of cytoreductive surgery achieved (Sugarbaker PH, Langenbeck’s Arch Surg 384:576–87, 1999), the extent of disease using PCI (Peritoneal Cancer Index), the technique itself, and the existence of a multidisciplinary approach with extensive upper abdominal procedures in experienced centers (Ren et al, BMC Cancer 15:1-12, 2015). There is evidence proving that the quality of cytoreduction (Al Rawahi et al, Cochrane Database Syst Rev 2013, 2013), the measurement of the amount of disease by PCI (Elzarkaa et al, J Gynecol Oncol 29, 2018), and a multidisciplinary approach with supramesocolic procedures (Ren et al, BMC Cancer 15:1-12, 2015) impact overall survival.

This study fails to compare chemotherapy with secondary cytoreductive surgery since, due to the lack of variables, we can assess neither the performed surgery nor its criteria. This study should not be taken into account to recommend chemotherapy alone over a surgical approach in this group of patients.
Prostaglandin E2 affects in vitro maturation of bovine oocytes
Authors: Boruszewska Dorota , Kowalczyk-Zieba Ilona , Suwik Katarzyna , Staszkiewicz-Chodor Joanna , Jaworska Joanna , Lukaszuk Krzysztof , Woclawek-Potocka Izabela
Published: May 2020

The role of prostaglandin E2 (PGE2) in the successful resumption of oocyte meiosis and cumulus expansion has been well-documented. However, there remains very little information available on the influence of PGE2 on other processes that occur during oocyte maturation. In this study, we supplemented a maturation medium with PGE2 and monitored oocyte quality markers, glucose metabolism, mitochondrial status, oxidative stress, and apoptosis in the cumulus-oocyte complexes (COCs), using a well-established in vitro model of embryo production in cattle. We found that this increased availability of PGE2 during maturation led to an increase in the expression of genes associated with oocyte competence and improved the quality of blastocysts produced. Prostaglandin E2 also appeared to stimulate glucose uptake and lactate production in the COCs, both influencing the expression of enzymes involved in glycolysis and the hexosamine biosynthetic pathway. We found that PGE2 reduced intracellular reactive oxygen species levels, and simultaneously increased glutathione concentration and stimulated antioxidant gene expression in the oocyte. These results indicate that PGE2 has an important role in the protection of oocytes against oxidative stress. Mitochondrial membrane potential was also improved in PGE2-treated oocytes, and there was a reduction in the occurrence of apoptosis in the COCs. Promotion of an anti-apoptotic balance in transcription of genes involved in apoptosis was present in both oocytes and the cumulus cells. In summary, PGE2 could represent a novel autocrine/paracrine player in the mechanisms that can facilitate successful oocyte maturation and oocyte survival in the cow.
Effects of co-exposure to CS2 and noise on hearing and balance in rats: continuous versus intermittent CS2 exposures
Authors: Chalansonnet Monique , Carreres-Pons Maria , Venet Thomas , Thomas Aurélie , Merlen Lise , Boucard Stéphane , Cosnier Frédéric , Nunge Hervé , Bonfanti Elodie , Llorens Jordi , Campo Pierre , Pouyatos Benoît
Published: May 2020

Background

Carbon disulfide (CS2) exacerbates the effect of noise on hearing, and disrupts the vestibular system. The goal of this study was to determine whether these effects are also observed with intermittent CS2 exposure.

Methods

Rats were exposed for 4 weeks (5 days/week, 6 h/day) to a band noise at 106 dB SPL either alone or combined with continuous (63 ppm or 250 ppm) or intermittent (15 min/h or 2 × 15 min/h at 250 ppm) CS2. Hearing function was assessed by measuring distortion product otoacoustic emissions (DPOAEs); balance was monitored based on the vestibulo-ocular reflex (VOR). Functional measurements were performed before, at the end of exposure and 4 weeks later. Histological analyses of the inner ear were also performed following exposure and after the 4-week recovery period.

Results

The results obtained here confirmed that CS2 exposure exerts two differential temporary effects on hearing: (1) it attenuates the noise-induced DPOAE decrease below 6 kHz probably through action on the middle ear reflex when exposure lasts 15 min per hour, and (2) continuous exposure to 250 ppm for 6 h extends the frequency range affected by noise up to 9.6 kHz (instead of 6 kHz with noise alone). With regard to balance, the VOR was reversibly disrupted at the two highest doses of CS2 (2 × 15 min/h and continuous 250 ppm). No morphological alterations to the inner ear were observed.

Conclusion

These results reveal that short periods of CS2 exposure can alter the sensitivity of the cochlea to noise at a dose equivalent to only 10 times the short-term occupational limit value, and intermittent exposure to CS2 (2 × 15 min/h) can alter the function of the vestibular system.
Clinical implementation of MRI-based organs-at-risk auto-segmentation with convolutional networks for prostate radiotherapy
Authors: Savenije Mark H. F. , Maspero Matteo , Sikkes Gonda G. , van der Voort van Zyp Jochem R. N. , T. J. Kotte Alexis N. , Bol Gijsbert H. , T. van den Berg Cornelis A.
Published: May 2020

Background

Structure delineation is a necessary, yet time-consuming manual procedure in radiotherapy. Recently, convolutional neural networks have been proposed to speed-up and automatise this procedure, obtaining promising results. With the advent of magnetic resonance imaging (MRI)-guided radiotherapy, MR-based segmentation is becoming increasingly relevant. However, the majority of the studies investigated automatic contouring based on computed tomography (CT).

Purpose

In this study, we investigate the feasibility of clinical use of deep learning-based automatic OARs delineation on MRI.

Materials and methods

We included 150 patients diagnosed with prostate cancer who underwent MR-only radiotherapy. A three-dimensional (3D) T1-weighted dual spoiled gradient-recalled echo sequence was acquired with 3T MRI for the generation of the synthetic-CT. The first 48 patients were included in a feasibility study training two 3D convolutional networks called DeepMedic and dense V-net (dV-net) to segment bladder, rectum and femurs. A research version of an atlas-based software was considered for comparison. Dice similarity coefficient, 95% Hausdorff distances (HD95), and mean distances were calculated against clinical delineations. For eight patients, an expert RTT scored the quality of the contouring for all the three methods. A choice among the three approaches was made, and the chosen approach was retrained on 97 patients and implemented for automatic use in the clinical workflow. For the successive 53 patients, Dice, HD95 and mean distances were calculated against the clinically used delineations.

Results

DeepMedic, dV-net and the atlas-based software generated contours in 60 s, 4 s and 10-15 min, respectively. Performances were higher for both the networks compared to the atlas-based software. The qualitative analysis demonstrated that delineation from DeepMedic required fewer adaptations, followed by dV-net and the atlas-based software. DeepMedic was clinically implemented. After retraining DeepMedic and testing on the successive patients, the performances slightly improved.

Conclusion

High conformality for OARs delineation was achieved with two in-house trained networks, obtaining a significant speed-up of the delineation procedure. Comparison of different approaches has been performed leading to the succesful adoption of one of the neural networks, DeepMedic, in the clinical workflow. DeepMedic maintained in a clinical setting the accuracy obtained in the feasibility study.
EVI5 is an oncogene that regulates the proliferation and metastasis of NSCLC cells
Authors: Cai Tingting , Zhou Jieqi , Zeng Yuanyuan , Du Wenwen , Zhang Yang , Liu Ting , Fu Yulong , Huang Jian-an , Qian Qian , Zhu Jianjie , Ling Chunhua , Liu Zeyi
Published: May 2020

Background

The Ecotropic viral integration site 5 (EVI5), an important protein in regulating cell cycle, cytokinesis and cellular membrane traffic, functions as a stabilizing factor maintaining anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 in S/G2 phase. However, the mechanism by which EVI5 promotes malignant transformation of non-small cell lung cancer (NSCLC) remains unknown. In the present study, we addressed the role of EVI5 in NSCLC by regulating tumor growth, migration and invasion.

Methods

The expression levels of EVI5 and miR-486-5p in NSCLC tissues and cells were measured by real-time PCR. Meanwhile, EVI5 and its associated protein expression were analyzed by western blot and co-immunoprecipitation assay. Flow cytometry was performed to determine cell proliferation and apoptosis. CCK-8 and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of EVI5 in vivo, lung carcinoma xenograft mouse model was applied..

Results

EVI5 was upregulated in NSCLC tissues and cell lines when compared with that in normal tissues and cell line. Knockdown of EVI5 in vitro inhibited tumor cell proliferation, migration and invasion in NSCLC cells. Further, inoculation of EVI5-deficient tumor cells into nude mice suppressed tumor proliferation and metastasis compared to control mice inoculated with unmanipulated tumor cells. These data indicated that EVI5 promote the proliferation of NSCLC cells which was consistent with our previous results. Additionally, we showed that EVI5 was directly regulated by miR-486-5p, and miR-486-5p-EVI5 axis affected the NSCLC migration and invasion through TGF-β/Smad signaling pathway by interacting with TGF-β receptor II and TGF-β receptor I.

Conclusions

Based on these results, we demonstrated a new post-transcriptional mechanism of EVI5 regulation via miR-486-5p and the protumoral function of EVI5 in NSCLC by interacting with Emi1 and/or TGF-β receptors, which provides a new insight into the targeted therapy of NSCLC.
MOFA+: a statistical framework for comprehensive integration of multi-modal single-cell data
Authors: Argelaguet Ricard , Arnol Damien , Bredikhin Danila , Deloro Yonatan , Velten Britta , Marioni John C. , Stegle Oliver
Published: May 2020

Technological advances have enabled the profiling of multiple molecular layers at single-cell resolution, assaying cells from multiple samples or conditions. Consequently, there is a growing need for computational strategies to analyze data from complex experimental designs that include multiple data modalities and multiple groups of samples. We present Multi-Omics Factor Analysis v2 (MOFA+), a statistical framework for the comprehensive and scalable integration of single-cell multi-modal data. MOFA+ reconstructs a low-dimensional representation of the data using computationally efficient variational inference and supports flexible sparsity constraints, allowing to jointly model variation across multiple sample groups and data modalities.
Usual care including home exercise with versus without spa therapy for chronic low back pain: protocol for the LOMBATHERM’ study, a multicentric randomised controlled trial
Authors: Forestier Romain , Suehs Carey , Françon Alain , Marty Marc , Genevay Stéphane , Sellam Jérémie , Chauveton Claire , Erol Forestier Fatma Begüm , Molinari Nicolas
Published: May 2020

Background

Low back pain is highly prevalent and a major source of disability worldwide. Spa therapy is frequently used to treat low back pain, but the associated level of evidence for efficacy is insufficient. To fill this knowledge gap, this protocol proposes an appropriately powered, prospective, evaluator-blinded, multi-centre, two-parallel-arm, randomised (1:1), controlled trial that will compare spa therapy in addition to usual care including home exercise (UCHE) versus UCHE alone for the treatment of chronic low back pain.

Methods

Eligible patients (anticipated sample size of 358) will have had low back pain for more than 3 months and scores for pain greater than 40 mm on a visual analogue scale (VAS). Following initial consent for UCHE and baseline evaluations, patients are randomised (1:1) to UCHE alone, or UCHE plus spa therapy (18 days of mud packs, underwater massages, showers and water exercises under medical supervision). Patients in the latter arm will be requested to sign an additional consent form as per Zelen randomisation. Follow-up visits will occur at approximately months 1, 6 and 12 and (along with baseline assessments) will cover changes over time in VAS pain scores, the impact of lower back pain on daily life (the Rolland and Morris Disability Questionnaire (RMDQ)), inappropriate fears and beliefs about lower back pain (the fear, avoidance, belief questionnaire (FABQ)), general quality of life (the Euroqol Group 5 dimension, 5 level questionnaire (EQ-5D-5 L)), Patient Acceptable Symptom State (PASS), consumption of analgesic drugs and nonsteroidal anti-inflammatory drugs (NSAIDs), and overall state of health. Health resource use and days of sick leave (and subsequently the associated costs) will also be recorded. The primary outcome is the presence/absence of a clinically relevant change (improvement of at least 30%) in the VAS score for pain at 6 months.

Discussion

Despite the fact that previous, rather dated recommendations encourage spa therapy for the treatment of low back pain, the current literary corpus is methodologically poor. This protocol has been designed to provide results spanning a thorough range of outcomes at the highest evidence level possible.

Trial registration

ClinicalTrials.gov: NCT03910023. Registered on 10 April 2019.
Australian Aedes aegypti mosquitoes are susceptible to infection with a highly divergent and sylvatic strain of dengue virus type 2 but are unlikely to transmit it
Authors: Pickering Paul , Hugo Leon E. , Devine Gregor J. , Aaskov John G. , Liu Wenjun
Published: May 2020

Background

Humans are the primary hosts of dengue viruses (DENV). However, sylvatic cycles of transmission can occur among non-human primates and human encroachment into forested regions can be a source of emergence of new strains such as the highly divergent and sylvatic strain of DENV2, QML22, recovered from a dengue fever patient returning to Australia from Borneo. The objective of the present study was to evaluate the vector competence of Australian Aedes aegypti mosquitoes for this virus.

Methods

Four- to five-day-old mosquitoes from two strains of Ae. aegypti from Queensland, Australia, were fed a meal of sheep blood containing 108 50% cell culture infectious dose per ml (CCID50/ml) of either QML22 or an epidemic strain of DENV serotype 2 (QML16) isolated from a dengue fever patient in Australia in 2015. Mosquitoes were maintained at 28 °C, 75% relative humidity and sampled 7, 10 and 14 days post-infection (dpi). Live virions in mosquito bodies (abdomen/thorax), legs and wings and saliva expectorates from individual mosquitoes were quantified using a cell culture enzyme-linked immunosorbent assay (CCELISA) to determine infection, dissemination and transmission rates.

Results

The infection and dissemination rates of the sylvatic DENV2 strain, QML22, were significantly lower than that for QML16. While the titres of virus in the bodies of mosquitoes infected with either of these viruses were similar, titres in legs and wings were significantly lower in mosquitoes infected with QML22 at most time points although they reached similar levels by 14 dpi. QML16 was detected in 16% (n = 25) and 28% (n = 25) of saliva expectorates at 10 and 14 dpi, respectively. In contrast, no virus was detected in the saliva expectorates of QML22 infected mosquitoes.

Conclusions

Australia urban/peri-urban Ae. aegypti species are susceptible to infection by the sylvatic and highly divergent DENV 2 QML22 but replication of QML22 is attenuated relative to the contemporary strain, QML16. A salivary gland infection or escape barrier may be acting to prevent infection of saliva and would prevent onward transmission of this highly divergent virus in Australia.
Reliability and validity of a novel Kinect-based software program for measuring a single leg squat
Authors: Ressman John , Rasmussen-Barr Eva , Grooten Wilhelmus Johannes Andreas
Published: May 2020

Background

The Single leg squat (SLS) is a movement screening test widely used in clinical settings. The SLS is highly subjective in its nature. Objective measures, such as 3D-motion analyses, are seldom used in daily clinical work. An interactive, Kinect-based 3D-movement analysis system, the Qinematic™, is proposed to be easily used in clinical settings to assess the SLS. The aim of this study was to establish the test-retest reliability and construct validity of Qinematic™ for assessing the SLS. A further aim was to identify angles of medial knee displacement, to summarise the discriminative ability of the SLS measured by Qinematic™.

Methods

We performed a test-retest reliability study (n = 37) of the SLS using Qinematic™ and a construct validity study, in which Qinematic™ data were compared with visual assessment of video-recorded SLS.

Results

Three variables (left knee down, right knee up and down) reached “substantial reliability” (ICC = 0.64–0.69). One variable, “left knee up”, showed a significant difference between the two test occasions (T1–6.34°, T2 0.66°, p = 0.013, ICC = 0.50), and “poor absolute reliability” was seen for all variables (SEM = 9.04–10.66, SDC = 25.06–29.55). A moderate agreement between the visual assessment and Qinematic™ data for various knee angles was shown (Kappa = 0.45–0.58). The best discriminative ability of the SLS was found at a knee angle of 6° (AUC = 0.82, sensitivity = 0.86, specificity = 0.78, PPV = 0.58, NPV = 0.94).

Conclusions

Qinematic™ shows a poor absolute reliability, and a substantial relative reliability, in measuring a SLS at the way down. This indicates that Qinematic™ should not be recommended for the use on an individual level, but it can possibly be used on a group level. The merged results of the construct validity study indicate that Qinematic™ at 6° of medial displacement can identify subjects with a knee over foot position. In summary, the use of the Qinematic™ net trajectory angle, which estimates the “line of best fit” cannot be recommended to assess a knee medial to foot position and should be reconsidered.
Automated recognition of spontaneous facial expression in individuals with autism spectrum disorder: parsing response variability
Authors: Bangerter Abigail , Chatterjee Meenakshi , Manfredonia Joseph , Manyakov Nikolay V. , Ness Seth , Boice Matthew A. , Skalkin Andrew , Goodwin Matthew S. , Dawson Geraldine , Hendren Robert , Leventhal Bennett , Shic Frederick , Pandina Gahan
Published: May 2020

Background

Reduction or differences in facial expression are a core diagnostic feature of autism spectrum disorder (ASD), yet evidence regarding the extent of this discrepancy is limited and inconsistent. Use of automated facial expression detection technology enables accurate and efficient tracking of facial expressions that has potential to identify individual response differences.

Methods

Children and adults with ASD (N= 124) and typically developing (TD,N= 41) were shown short clips of “funny videos.” Using automated facial analysis software, we investigated differences between ASD and TD groups and within the ASD group in evidence of facial action unit (AU) activation related to the expression of positive facial expression, in particular, a smile.

Results

Individuals with ASD on average showed less evidence of facial AUs (AU12, AU6) relating to positive facial expression, compared to the TD group (p< .05,r= − 0.17). Using Gaussian mixture model for clustering, we identified two distinct distributions within the ASD group, which were then compared to the TD group. One subgroup (n= 35), termed “over-responsive,” expressed more intense positive facial expressions in response to the videos than the TD group (p< .001,r= 0.31). The second subgroup (n= 89), (“under-responsive”), displayed fewer, less intense positive facial expressions in response to videos than the TD group (p< .001;r= − 0.36). The over-responsive subgroup differed from the under-responsive subgroup in age and caregiver-reported impulsivity (p< .05,r= 0.21). Reduced expression in the under-responsive, but not the over-responsive group, was related to caregiver-reported social withdrawal (p< .01,r= − 0.3).

Limitations

This exploratory study does not account for multiple comparisons, and future work will have to ascertain the strength and reproducibility of all results. Reduced displays of positive facial expressions do not mean individuals with ASD do not experience positive emotions.

Conclusions

Individuals with ASD differed from the TD group in their facial expressions of positive emotion in response to “funny videos.” Identification of subgroups based on response may help in parsing heterogeneity in ASD and enable targeting of treatment based on subtypes.

Trial registration

ClinicalTrials.gov,NCT02299700. Registration date: November 24, 2014
The diatomic molecular spectroscopy database
Authors: Liu Xiangyue , Truppe Stefan , Meijer Gerard , Pérez-Ríos Jesús
Published: May 2020

Motivation

The spectroscopy of diatomic molecules is an important research area in chemical physics due to its relevance in astrochemistry, combustion chemistry, and ultracold physics. However, there is currently no database where the user can easily retrieve, in a useful format, the spectroscopic constants of a given molecule. A similar situation appears concerning the vibrational Franck–Condon factors for diatomic molecules, a crucial parameter to infer laser cooling prospects for molecules. To address this problem, and inspired by the idea that data should be open and freely accessible, we have developed a user-friendly website (https://rios.mp.fhi.mpg.de) where the user can retrieve spectroscopic constants and Franck–Condon factors in useful formats.

Implementation

In this database, the spectroscopic constants of the ground states and first excited states of the diatomic molecules are accessible from the website and can be retrieved in readable formats. The website is implemented within the LAMP web service stacks. In particular, using Linux as the operative system, Apache as the HTTP Server, MySQL as the database management system, and PHP as the programming language for the web. Furthermore, the user can register and upload new data. This project is licensed under the Free-Libre/Open Source Software (FLOSS) license Apache License 2.0 which allows free and open access to the codes as well as efficient collaboration in the maintenance of the software.

Conclusions and impact

The present data-driven website presents essential information in a user-friendly manner and may help the chemical physics community to identify molecules that should be explored through spectroscopic techniques.
Biotransformation of 5-hydroxymethylfurfural into 2,5-dihydroxymethylfuran by Ganoderma sessile and toxicological assessment of both compounds
Authors: Hou Ya-nan , Wang Ya-rong , Zheng Chun-hui , Feng Kun
Published: May 2020

Biotransformation has the advantages of low cost and environmental protection and is a preferred method for production of compounds. At present, most 2,5-dihydroxymethylfuran (DHMF) is synthesized by chemical methods. In this study, 12.008 μg/mL DHMF was produced from 9.045 μg/mL 5-hydroxymethylfurfural (5-HMF) with a yield of 1.33 g/g using the crude enzymes from fungus Ganoderma sessile. To elucidate the toxic potential for both compounds, cytotoxicity tests and acute toxicity were evaluated respectively. 5-HMF induced weak cytotoxicity in HCT-8, A549 and SGC-7901 cells and DHMF exerted no cytotoxicity on HCT-8 while induced inhibition proliferation of A549 and SGC-7901 cells. The acute toxicity study showed no mortality happened in any group even at the single dose of 2000 mg/kg body weight. These results suggest it is feasible to convert 5-HMF to DHMF via crude enzymes from fungus G. sessile under mild condition, and that DHMF displays a potential effect of antitumor in vitro with little acute toxicity.
Thenar oxygen saturation (StO2) alterations during a spontaneous breathing trial predict extubation failure
Authors: Mesquida Jaume , Gruartmoner Guillem , Espinal Cristina , Masip Jordi , Sabatier Caroline , Villagrá Ana , Gómez Hernando , Pinsky Michael , Baigorri Francisco , Artigas Antonio
Published: May 2020

Background

Weaning from mechanical ventilation (MV) is a cardiovascular stress test. Monitoring the regional oxygenation status has shown promising results in predicting the tolerance to spontaneously breathe in the process of weaning from MV. Our aim was to determine whether changes in skeletal muscle oxygen saturation (StO2) measured by near-infrared spectroscopy (NIRS) on the thenar eminence during a vascular occlusion test (VOT) can be used to predict extubation failure from mechanical ventilation.

Methods

We prospectively studied 206 adult patients with acute respiratory failure receiving MV for at least 48 h from a 30-bed mixed ICU, who were deemed ready to wean by their physicians. Patients underwent a 30-min spontaneous breathing trial (SBT), and were extubated according to the local protocol. Continuous StO2 was measured non-invasively on the thenar eminence. A VOT was performed prior to and at 30 min of the SBT (SBT30). The rate of StO2 deoxygenation (DeO2), StO2 reoxygenation (ReO2) rate and StO2 hyperemic response to ischemia (HAUC) were calculated.

Results

Thirty-six of the 206 patients (17%) failed their SBT. The remainder 170 patients (83%) were extubated. Twenty-three of these patients (13.5%) needed reinstitution of MV within 24 h. Reintubated patients displayed a lower HAUC at baseline, and higher relative changes in their StO2 deoxygenation rate between baseline and SBT30 (DeO2 Ratio). A logistic regression-derived StO2 score, combining baseline StO2, HAUC and DeO2 ratio, showed an AUC of 0.84 (95% CI 0.74–0.91) for prediction of extubation failure.

Conclusions

Extubation failure was associated to baseline and dynamic StO2 alterations during the SBT. Monitoring StO2-derived parameters might be useful in predicting extubation outcome.
On Grüss inequalities within generalized K-fractional integrals
Authors: Rashid Saima , Jarad Fahd , Noor Muhammad Aslam , Noor Khalida Inayat , Baleanu Dumitru , Liu Jia-Bao
Published: May 2020

In this paper, we introduce the generalized $\mathcal{K}$K-fractional integral in the frame of a new parameter $\mathcal{K}>0$K>0. This paper offers some new important inequalities of Grüss type using the generalized $\mathcal{K}$K-fractional integral and associated integral inequalities. Our results with this new integral operator have the abilities to be implemented for the evaluation of many mathematical problems related to the real world applications.
Women in household decision-making and implications for dietary quality in Bhutan
Authors: Sariyev Orkhan , Loos Tim K. , Zeller Manfred , Gurung Tulsi
Published: May 2020

Despite the wide range of literature supporting the linkages between women’s empowerment and food security, it is not examined in social contexts where females historically enjoy equality and even favoritism, for instance where there is female succession and/or polyandry. This study was done in the Kingdom of Bhutan where matrilineal succession and polyandry were prevalent during the twentieth century.

Both quantitative and qualitative survey methods were employed with the objectives of (i) investigating women’s participation in crucial domestic decision-making processes and (ii) identifying the implications of female involvement in domestic decision-making on household-level dietary quality.

While descriptive analyses and qualitative interviews revealed that women do not lack significant participation in domestic decision-making, the estimations indicate that the relationship between women’s participation in decision-making and dietary diversity is non-linear. Further analyses indicate a positive association between (perfect) gender equal decision-making regarding household livelihoods and household-level dietary quality.
Biomarkers in individualized management of chimeric antigen receptor T cell therapy
Authors: Du Mengyi , Hari Parameswaran , Hu Yu , Mei Heng
Published: May 2020

The development of chimeric antigen receptor (CAR) T cell immunotherapy has achieved promising results, both in clinical studies and in commercial products for patients with hematologic malignancies. Despite high remission rates of CAR-T cell therapy in previously untreatable, refractory and/or relapsed patients, several challenges in CAR-T therapy remain to be overcome, especially in integrating such therapies into personalized disease management approaches. Given the unique characteristics of CAR-T therapy, it is particularly urgent to identify biomarkers to maximize their clinical benefits. This systematic review summarizes clinically relevant biomarkers that may help individualized disease management in patients receiving CAR-T cell therapy in terms of toxicity warning, efficacy prediction and relapse monitoring. We summarize data from 18 clinical trials, including traditional indicators like cytokines, biochemical proteins, tumor burden, as well as potential novel indicators such as CAR-T cell expansion and persistency. The establishment of a biomarker-based system aimed at individualized management is recommended to guide better clinical application of CAR-T products.
On K-means clustering-based approach for DDBSs design
Authors: Amer Ali A.
Published: May 2020

In Distributed Database Systems (DDBS), communication costs and response time have long been open-ended challenges. Nevertheless, when DDBS is carefully designed, the desired reduction in communication costs will be achieved. Data fragmentation (data clustering) and data allocation are on popularity as the prime strategies in constant use to design DDBS. Based on these strategies, on the other hand, several design techniques have been presented in the literature to improve DDBS performance using either empirical results or data statistics, making most of them imperfect or invalid particularly, at least, at the initial stage of DDBSs design. In this paper, thus, a heuristic k-means approach for vertical fragmentation and allocation is introduced. This approach is primarily focused on DDBS design at the initial stage. Many techniques are being joined in a step to make a promising work. A brief yet effective experimental study, on both artificially-created and real datasets, has been conducted to demonstrate the optimality of the proposed approach, comparing with its counterparts, as the obtained results has been shown encouraging.