bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between the home environment and child adiposity: a systematic review
Authors: Kininmonth Alice R. , Smith Andrea D. , Llewellyn Clare H. , Dye Louise , Lawton Clare L. , Fildes Alison
Published: January 2021

Background

Extensive research has demonstrated the role of the Home Environment (HE) in shaping children’s energy balance behaviours. Less is known about direct relationships with bodyweight. This review examines associations between the social and physical aspects of three pre-defined Home Environment domains (food, physical activity and media) and adiposity measures in children ≤12 years.

Methods

Six electronic databases (PubMed, Medline, EBSCO CINAHL, EMBASE, Web of Science, PsycInfo) were systematically searched up to October 2020. Studies reporting at least one physical and/or social aspect of the food, physical activity and/or media domains of the Home Environment in relation to child adiposity outcomes were included (n = 62).

Results

Most studies examined one (n = 41) or two domains (n = 16). Only five studies assessed all three domains of the Home Environment. Most consistent relationships were observed for physical aspects of the home media environment; with greater availability of electronic devices associated with higher child adiposity (21/29 studies). Findings were less consistent for the smaller number of studies examining physical aspects of the home food or physical activity environments. 8/15 studies examining physical food environments reported null associations with adiposity. Findings were similarly mixed for physical activity environments; with 4/7 reporting null associations, 2/7 reporting negative associations and 1/7 reporting positive associations between access to physical activity equipment/garden space and adiposity. Fewer studies assessed social aspects (e.g. caregiver modelling or limit setting) of the Home Environment in relation to child adiposity and findings were again mixed; 9/16 media environment, 7/11 food environment and 9/13 physical activity environment studies reported null associations with child adiposity outcomes.

Conclusions

The home media environment was most consistently associated with adiposity in childhood. Findings were less consistent for the home food and physical activity environments. Greater agreement on definitions and the measurement of the obesogenic home environment is required in order to clarify the strength and direction of relationships with child adiposity. Robust longitudinal research using comprehensive measures of the holistic home environment is needed to better identify which aspects contribute to excess weight gain in childhood.

Trial registration

PROSPERO Systematic review registration number: CRD42018115139.
Immune responses to azacytidine in animal models of inflammatory disorders: a systematic review
Authors: Landman Sija , van der Horst Chiel , van Erp Piet E. J. , Joosten Irma , de Vries Rob , Koenen Hans J. P. M.
Published: January 2021

Inflammatory disorders like diabetes, systemic lupus erythematodes, inflammatory lung diseases, rheumatoid arthritis and multiple sclerosis, but also rejection of transplanted organs and GvHD, form a major burden of disease. Current classes of immune suppressive drugs to treat these disorders are never curative and side effects are common. Therefore there is a need for new drugs with improved and more targeted modes of action. Potential candidates are the DNA methyl transferase inhibitor 5-azacytidine (Aza) and its derivative 5-aza 2′deoxycitidine (DAC). Aza and DAC have been tested in several pre-clinical in vivo studies. In order to obtain an overview of disorders for which Aza and/or DAC can be a potential treatment, and to find out where information is lacking, we systematically reviewed pre-clinical animal studies assessing Aza or DAC as a potential therapy for distinct inflammatory disorders. Also, study quality and risk of bias was systematically assessed. In the 35 identified studies, we show that both Aza and DAC do not only seem to be able to alleviate a number of inflammatory disorders, but also prevent solid organ rejection and GvHD in in vivo pre-clinical animal models. Aza/DAC are known to upregulate FOXP3, a master transcription factor for Treg, in vitro. Seventeen studies described the effect on Treg, of which 16 studies showed an increase in Treg. Increasing Treg therefore seems to be a common mechanism in preventing inflammatory disorders by Aza/DAC. We also found, however, that many essential methodological details were poorly reported leading to an unclear risk of bias. Therefore, reported effects might be an overestimation of the true effect.
Deep learning model for classifying endometrial lesions
Authors: Zhang YunZheng , Wang ZiHao , Zhang Jin , Wang CuiCui , Wang YuShan , Chen Hao , Shan LuHe , Huo JiaNing , Gu JiaHui , Ma Xiaoxin
Published: January 2021

Background

Hysteroscopy is a commonly used technique for diagnosing endometrial lesions. It is essential to develop an objective model to aid clinicians in lesion diagnosis, as each type of lesion has a distinct treatment, and judgments of hysteroscopists are relatively subjective. This study constructs a convolutional neural network model that can automatically classify endometrial lesions using hysteroscopic images as input.

Methods

All histopathologically confirmed endometrial lesion images were obtained from the Shengjing Hospital of China Medical University, including endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyps, and submucous myomas. The study included 1851 images from 454 patients. After the images were preprocessed (histogram equalization, addition of noise, rotations, and flips), a training set of 6478 images was input into a tuned VGGNet-16 model; 250 images were used as the test set to evaluate the model’s performance. Thereafter, we compared the model’s results with the diagnosis of gynecologists.

Results

The overall accuracy of the VGGNet-16 model in classifying endometrial lesions is 80.8%. Its sensitivity to endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyp, and submucous myoma is 84.0%, 68.0%, 78.0%, 94.0%, and 80.0%, respectively; for these diagnoses, the model’s specificity is 92.5%, 95.5%, 96.5%, 95.0%, and 96.5%, respectively. When classifying lesions as benign or as premalignant/malignant, the VGGNet-16 model’s accuracy, sensitivity, and specificity are 90.8%, 83.0%, and 96.0%, respectively. The diagnostic performance of the VGGNet-16 model is slightly better than that of the three gynecologists in both classification tasks. With the aid of the model, the overall accuracy of the diagnosis of endometrial lesions by gynecologists can be improved.

Conclusions

The VGGNet-16 model performs well in classifying endometrial lesions from hysteroscopic images and can provide objective diagnostic evidence for hysteroscopists.
Hypoxia and the phenomenon of immune exclusion
Authors: Pietrobon Violena , Marincola Francesco M.
Published: January 2021

Over the last few years, cancer immunotherapy experienced tremendous developments and it is nowadays considered a promising strategy against many types of cancer. However, the exclusion of lymphocytes from the tumor nest is a common phenomenon that limits the efficiency of immunotherapy in solid tumors. Despite several mechanisms proposed during the years to explain the immune excluded phenotype, at present, there is no integrated understanding about the role played by different models of immune exclusion in human cancers. Hypoxia is a hallmark of most solid tumors and, being a multifaceted and complex condition, shapes in a unique way the tumor microenvironment, affecting gene transcription and chromatin remodeling. In this review, we speculate about an upstream role for hypoxia as a common biological determinant of immune exclusion in solid tumors. We also discuss the current state of ex vivo and in vivo imaging of hypoxic determinants in relation to T cell distribution that could mechanisms of immune exclusion and discover functional-morphological tumor features that could support clinical monitoring.
Validation of a method evaluating T cell metabolic potential in compliance with ICH Q2 (R1)
Authors: Mercier-Letondal Patricia , Marton Chrystel , Godet Yann , Galaine Jeanne
Published: January 2021

Background

Metabolic cell features are able to give reliable information on cell functional state. Thus, metabolic potential assessment of T cells in malignancy setting represents a promising area, especially in adoptive cell therapy procedures. Easy to set up and convenient Seahorse technology have recently been proposed by Agilent Technologies and it could be used to monitor T cells metabolic potential. However, this method demonstrates an inter-assay variability and lacks practices standardization.

Results

We aimed to overcome these shortcomings thanks to a lymphoblastic derived JURKAT cell line seeding in each experiment to standardize the Seahorse process. We used an adapted XF Cell MitoStress Kit protocol, consisting in the evaluation of basal, stressed and maximal glycolysis and oxidative phosphorylation related parameters, through sequential addition of oligomycin and carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) to a glucose containing medium. Data were acquired and analyzed through Agilent Seahorse XFe96 analyzer. Indeed, we validated this method in the light of ICH Q2 (R1) guidelines. We were able to confirm the specificity and accuracy of the method. We also demonstrated the precision, linearity and range of the method in our experimental conditions.

Conclusion

The validation of the method consisting in a JURKAT cell line experimental incorporation as a control material contributes to improve the Seahorse technology’s robustness. These results lay the groundwork for the implementation of this technology to optimize T cell based cellular therapy products production process and monitoring.
Development of nomogram based on immune-related gene FGFR4 for advanced non-small cell lung cancer patients with sensitivity to immune checkpoint inhibitors
Authors: Wang Li , Ren Zhixuan , Yu Bentong , Tang Jian
Published: January 2021

Introduction

Immune checkpoint inhibitors (ICIs) have become a frontier in the field of clinical technology for advanced non-small cell lung cancer (NSCLC). Currently, the predictive biomarker of ICIs mainly including the expression of PD-L1, TMB, TIICs, MMR and MSI-H. However, there are no official biomarkers to guide the treatment of ICIs and to determine the prognosis. Therefore, it is essential to explore a systematic nomogram to predict the prognosis of ICIs treatment in NSCLC

Methods

In this work, we obtained gene expression and clinical data of NSCLC patients from the TCGA database. Immune-related genes (IRGs) were downloaded from the ImmPort database. The detailed clinical annotation and response data of 240 advanced NSCLC patients who received ICIs treatment were obtained from the cBioPortal for Cancer Genomics. Kaplan–Meier survival analysis was used to perform survival analyses, and selected clinical variables to develop a novel nomogram. The prognostic significance of FGFR4 was validated by another cohort in cBioPortal for Cancer Genomics.

Results

3% of the NSCLC patients harbored FGFR4 mutations. The mutation of FGFR4 were confirmed to be associated with PD-L1, and TMB. Patients harbored FGFR4 mutations were found to have a better prolonged progression-free survival (PFS) to ICIs treatment (FGFR4: P = 0.0209). Here, we built and verified a novel nomogram to predict the prognosis of ICIs treatment for NSCLC patients.

Conclusion

Our results showed that FGFR4 could serve as novel biomarkers to predict the prognosis of ICIs treatment of advanced NSCLC. Our systematic prognostic nomogram showed a great potential to predict the prognosis of ICIs for advanced NSCLC patients.
Anti-migraine agents from an immunological point of view
Authors: Assas Mushref Bakri
Published: January 2021

The new wave of anti-migraine agents is nothing less than a milestone in our battle to manage this devastating disease. However, concerns have recently increased regarding the safety of these drugs. CGRP, while known as a potent vasodilator, is also a key neural and immune modulator. The roles of CGRP in immune determination, have been studied in depth, with particular focus on its functional significance with respect to common immune challenges i.e., bacterial, viral, fungal and parasitic infections. This review discusses many potential areas of concern in regard to blocking CGRP function and its potential influence on immune milieus during infection, and the risk of adverse effects. Finally, this review recommends specific measures to be taken into consideration when administering anti-CGRP/CGRPR agents.
An analytical method for the identification of cell type-specific disease gene modules
Authors: Guan Jinting , Lin Yiping , Wang Yang , Gao Junchao , Ji Guoli
Published: January 2021

Background

Genome-wide association studies have identified genetic variants associated with the risk of brain-related diseases, such as neurological and psychiatric disorders, while the causal variants and the specific vulnerable cell types are often needed to be studied. Many disease-associated genes are expressed in multiple cell types of human brains, while the pathologic variants affect primarily specific cell types. We hypothesize a model in which what determines the manifestation of a disease in a cell type is the presence of disease module comprised of disease-associated genes, instead of individual genes. Therefore, it is essential to identify the presence/absence of disease gene modules in cells.

Methods

To characterize the cell type-specificity of brain-related diseases, we construct human brain cell type-specific gene interaction networks integrating human brain nucleus gene expression data with a referenced tissue-specific gene interaction network. Then from the cell type-specific gene interaction networks, we identify significant cell type-specific disease gene modules by performing statistical tests.

Results

Between neurons and glia cells, the constructed cell type-specific gene networks and their gene functions are distinct. Then we identify cell type-specific disease gene modules associated with autism spectrum disorder and find that different gene modules are formed and distinct gene functions may be dysregulated in different cells. We also study the similarity and dissimilarity in cell type-specific disease gene modules among autism spectrum disorder, schizophrenia and bipolar disorder. The functions of neurons-specific disease gene modules are associated with synapse for all three diseases, while those in glia cells are different. To facilitate the use of our method, we develop an R package, CtsDGM, for the identification of cell type-specific disease gene modules.

Conclusions

The results support our hypothesis that a disease manifests itself in a cell type through forming a statistically significant disease gene module. The identification of cell type-specific disease gene modules can promote the development of more targeted biomarkers and treatments for the disease. Our method can be applied for depicting the cell type heterogeneity of a given disease, and also for studying the similarity and dissimilarity between different disorders, providing new insights into the molecular mechanisms underlying the pathogenesis and progression of diseases.
Model based on five tumour immune microenvironment-related genes for predicting hepatocellular carcinoma immunotherapy outcomes
Authors: Gu Xinyu , Guan Jun , Xu Jia , Zheng Qiuxian , Chen Chao , Yang Qin , Huang Chunhong , Wang Gang , Zhou Haibo , Chen Zhi , Zhu Haihong
Published: January 2021

Background

Although the tumour immune microenvironment is known to significantly influence immunotherapy outcomes, its association with changes in gene expression patterns in hepatocellular carcinoma (HCC) during immunotherapy and its effect on prognosis have not been clarified.

Methods

A total of 365 HCC samples from The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA-LIHC) dataset were stratified into training datasets and verification datasets. In the training datasets, immune-related genes were analysed through univariate Cox regression analyses and least absolute shrinkage and selection operator (LASSO)-Cox analyses to build a prognostic model. The TCGA-LIHC, GSE14520, and Imvigor210 cohorts were subjected to time-dependent receiver operating characteristic (ROC) and Kaplan–Meier survival curve analyses to verify the reliability of the developed model. Finally, single-sample gene set enrichment analysis (ssGSEA) was used to study the underlying molecular mechanisms.

Results

Five immune-related genes (LDHA, PPAT, BFSP1, NR0B1, and PFKFB4) were identified and used to establish the prognostic model for patient response to HCC treatment. ROC curve analysis of the TCGA (training and validation sets) and GSE14520 cohorts confirmed the predictive ability of the five-gene-based model (AUC > 0.6). In addition, ROC and Kaplan–Meier analyses indicated that the model could stratify patients into a low-risk and a high-risk group, wherein the high-risk group exhibited worse prognosis and was less sensitive to immunotherapy than the low-risk group. Functional enrichment analysis predicted potential associations of the five genes with several metabolic processes and oncological signatures.

Conclusions

We established a novel five-gene-based prognostic model based on the tumour immune microenvironment that can predict immunotherapy efficacy in HCC patients.
Do geography and ethnicity play a role in juvenile Spondyloarthritis? A multi-center binational retrospective study
Authors: Ghantous Nassem , Heshin-Bekenstein Merav , Dequattro Kimberly , Lakovsky Yaniv , Hendel Amir Moshe , Rappoport Nadav , Aviel Yonatan Butbul , Tirosh Irit , Harel Liora , Weiss Pamela F. , Gensler Lianne , Mackenzie John , Amarilyo Gil
Published: January 2021

Background

Observations among Israeli pediatric rheumatologists reveal that pediatric Juvenile Spondyloarthritis (JSpA) may present differently compared to patients from the United States (US). This study is aimed to compare the demographic and clinical variables of Israeli and US JSpA patients upon presentation.

Methods

We performed a retrospective, cross-sectional, multicenter comparison of JSpA patients among 3 large Israeli pediatric rheumatology centers and a large US pediatric rheumatology center. Patients with diagnosis of Juvenile Ankylosing Spondylitis (JAS) and/or Enthesitis-related Arthritis (ERA) were included. The demographic, clinical and radiologic features were compared.

Results

Overall 87 patients were included (39 Israeli, 48 US patients). Upon presentation, inflammatory back pain, sacroiliac joint tenderness and abnormal modified Schober test, were significantly more prevalent among Israeli patients (59% vs. 35.4, 48.7% vs. 16.7, and 41.2% vs. 21.5%, respectively, all p < 0.05), whereas peripheral arthritis and enthesitis were significantly more prevalent among US patients (43.6% vs. 91.7 and 7.7% vs. 39.6% in Israeli patients vs. US patients, p < 0.05). In addition, 96.7% of the Israeli patients versus 29.7% of the US patients demonstrated sacroiliitis on MRI (p < 0.001, N = 67). Less than one-third of the Israeli patients (32%) were HLA-B27 positive vs. 66.7% of US patients (p = 0.007).

Conclusion

Israeli children with JSpA presented almost exclusively with axial disease compared to US patients who were more likely to present with peripheral symptoms. HLA B27 prevalence was significantly lower in the Israeli cohort compared to the US cohort. Further studies are needed to unravel the genetic and possibly environmental factors associated with these findings.
Microglial inflammation after chronic spinal cord injury is enhanced by reactive astrocytes via the fibronectin/β1 integrin pathway
Authors: Yoshizaki Shingo , Tamaru Tetsuya , Hara Masamitsu , Kijima Ken , Tanaka Masatake , Konno Dai-jiro , Matsumoto Yoshihiro , Nakashima Yasuharu , Okada Seiji
Published: January 2021

Background

After spinal cord injury (SCI), glial scarring is mainly formed around the lesion and inhibits axon regeneration. Recently, we reported that anti-β1 integrin antibody (β1Ab) had a therapeutic effect on astrocytes by preventing the induction of glial scar formation. However, the cellular components within the glial scar are not only astrocytes but also microglia, and whether or not β1Ab treatment has any influence on microglia within the glial scar remains unclear.

Methods

To evaluate the effects of β1Ab treatment on microglia within the glial scar after SCI, we applied thoracic contusion SCI to C57BL/6N mice, administered β1Ab in the sub-acute phase, and analyzed the injured spinal cords with immunohistochemistry in the chronic phase. To examine the gene expression in microglia and glial scars, we selectively collected microglia with fluorescence-activated cell sorting and isolated the glial scars using laser-captured microdissection (LMD). To examine the interaction between microglia and astrocytes within the glial scar, we stimulated BV-2 microglia with conditioned medium of reactive astrocytes (RACM) in vitro, and the gene expression of TNFα (pro-inflammatory M1 marker) was analyzed via quantitative polymerase chain reaction. We also isolated both naïve astrocytes (NAs) and reactive astrocytes (RAs) with LMD and examined their expression of the ligands for β1 integrin receptors. Statistical analyses were performed using Wilcoxon’s rank-sum test.

Results

After performing β1Ab treatment, the microglia were scattered within the glial scar and the expression of TNFα in both the microglia and the glial scar were significantly suppressed after SCI. This in vivo alteration was attributed to fibronectin, a ligand of β1 integrin receptors. Furthermore, the microglial expression of TNFα was shown to be regulated by RACM as well as fibronectin in vitro. We also confirmed that fibronectin was secreted by RAs both in vitro and in vivo. These results highlighted the interaction mediated by fibronectin between RAs and microglia within the glial scar.

Conclusion

Microglial inflammation was enhanced by RAs via the fibronectin/β1 integrin pathway within the glial scar after SCI. Our results suggested that β1Ab administration had therapeutic potential for ameliorating both glial scar formation and persistent neuroinflammation in the chronic phase after SCI.
Statistical field theory of the transmission of nerve impulses
Authors: Zangari del Balzo Gianluigi
Published: January 2021

Background

Stochastic processes leading voltage-gated ion channel dynamics on the nerve cell membrane are a sufficient condition to describe membrane conductance through statistical mechanics of disordered and complex systems.

Results

Voltage-gated ion channels in the nerve cell membrane are described by the Ising model. Stochastic circuit elements called “Ising Neural Machines” are introduced. Action potentials are described as quasi-particles of a statistical field theory for the Ising system.

Conclusions

The particle description of action potentials is a new point of view and a powerful tool to describe the generation and propagation of nerve impulses, especially when classical electrophysiological models break down.

The particle description of action potentials allows us to develop a new generation of devices to study neurodegenerative and demyelinating diseases as Multiple Sclerosis and Alzheimer’s disease, even integrated by connectomes. It is also suitable for the study of complex networks, quantum computing, artificial intelligence, machine and deep learning, cryptography, ultra-fast lines for entanglement experiments and many other applications of medical, physical and engineering interest.
A numerical simulation of air flow in the human respiratory system for various environmental conditions
Authors: Issakhov Alibek , Zhandaulet Yeldos , Abylkassymova Aizhan , Issakhov Assylbek
Published: January 2021

The functions of the nasal cavity are very important for maintaining the internal environment of the lungs since the inner walls of the nasal cavity control the temperature and saturation of the inhaled air with water vapor until the nasopharynx is reached. In this paper, three-dimensional computational studies of airflow transport in the models of the nasal cavity were carried out for the usual inspiratory velocity in various environmental conditions. Three-dimensional numerical results are compared with experimental data and calculations of other authors. Numerical results show that during normal breathing, the human nose copes with heat and relative moisture metabolism in order to balance the intra-alveolar conditions. It is also shown in this paper that a normal nose can maintain balance even in extreme conditions, for example, in cold and hot weather. The nasal cavity accelerates heat transfer by narrowing the air passages and swirls from the nasal concha walls of the inner cavity.
Potential challenges to sustained viral load suppression in the HIV treatment programme in South Africa: a narrative overview
Authors: Bessong Pascal O. , Matume Nontokozo D. , Tebit Denis M.
Published: January 2021

Background

South Africa, with one of the highest HIV prevalences in the world, introduced the universal test and treat (UTT) programme in September 2016. Barriers to sustained viral suppression may include drug resistance in the pre-treated population, non-adherence, acquired resistance; pharmacokinetics and pharmacodynamics, and concurrent use of alternative treatments.

Objective

The purpose of this review is to highlight potential challenges to achieving sustained viral load suppression in South Africa (SA), a major expectation of the UTT initiative.

Methodology

Through the PRISMA approach, published articles from South Africa on transmitted drug resistance; adherence to ARV; host genetic factors in drug pharmacokinetics and pharmacodynamics, and interactions between ARV and herbal medicine were searched and reviewed.

Results

The level of drug resistance in the pre-treated population in South Africa has increased over the years, although it is heterogeneous across and within Provinces. At least one study has documented a pre-treated population with moderate (> 5%) or high (> 15%) levels of drug resistance in eight of the nine Provinces. The concurrent use of ARV and medicinal herbal preparation is fairly common in SA, and may be impacting negatively on adherence to ARV. Only few studies have investigated the association between the genetically diverse South African population and pharmacokinetics and pharmacodynamics of ARVs.

Conclusion

The increasing levels of drug resistant viruses in the pre-treated population poses a threat to viral load suppression and the sustainability of first line regimens. Drug resistance surveillance systems to track the emergence of resistant viruses, study the burden of prior exposure to ARV and the parallel use of alternative medicines, with the goal of minimizing resistance development and virologic failure are proposed for all the Provinces of South Africa. Optimal management of the different drivers of drug resistance in the pre-treated population, non-adherence, and acquired drug resistance will be beneficial in ensuring sustained viral suppression in at least 90% of those on treatment, a key component of the 90-90-90 strategy.
Combined Lycium barbarum polysaccharides and C-phycocyanin increase gastric Bifidobacterium relative abundance and protect against gastric ulcer caused by aspirin in rats
Authors: Hsieh Shu-Yu , Lian Yu Zhi , Lin I-Hsuan , Yang Yu-Chen , Tinkov Alexey A. , Skalny Anatoly V. , Chao Jane C.-J.
Published: January 2021

Background

Non-steroidal anti-inflammatory drugs such as aspirin are used for the treatment of cardiovascular disease. Chronic use of low-dose aspirin is associated with the occurrence of gastric ulcer. The aim of this study was to investigate the healing potential of Lycium barbarum polysaccharides (LBP) from Chinese Goji berry and C-phycocyanin (CPC) from Spirulina platensis on gastric ulcer in rats.

Methods

Male Sprague–Dawley rats were divided into five groups: normal, aspirin (700 mg/kg bw), LBP (aspirin + 100 mg/kg bw/d LBP), CPC (aspirin + 50 mg/kg bw/d CPC), and MIX (aspirin + 50 mg/kg bw/d LBP + 25 mg/kg bw/d CPC) groups. Gastric ulcer was developed by daily oral feeding of aspirin for 8 weeks. Treatments were given orally a week before ulcer induction for 9 weeks.

Results

The MIX group elevated gastric cyclooxygenase-1, prostaglandin E2, and total nitrite and nitrate levels by 139%, 86%, and 66%, respectively, compared with the aspirin group (p < 0.05). Moreover, the MIX group reduced lipid peroxides malondialdehyde levels by 78% (p < 0.05). The treatment of LBP and/or CPC increased gastric Bifidobacterium relative abundance by 2.5–4.0 times compared with the aspirin group (p < 0.05).

Conclusions

We conclude that combined LBP and CPC enhance gastroprotective factors, inhibit lipid peroxidation, and increase gastric Bifidobacterium relative abundance. Combined LBP and CPC have protective potential against gastric ulcer caused by aspirin in rats.
New field wind manipulation methodology reveals adaptive responses of steppe plants to increased and reduced wind speed
Authors: Zhang Shudong , Liu Guofang , Cui Qingguo , Huang Zhenying , Ye Xuehua , Cornelissen Johannes H. C.
Published: January 2021

Background

Wind strongly impacts plant growth, leaf traits, biomass allocation, and stem mechanical properties. However, whether there are common whole-plant wind responses among different plant species is still unclear. We tested this null hypothesis by exposing four eudicot steppe species to three different wind treatments in a field experiment: reduced wind velocity using windbreaks, ambient wind velocity, and enhanced wind velocity through a novel methodology using wind-funneling baffles.

Results

Across the four species, wind generally decreased plant height, projected crown area, and stepwise bifurcation ratio, and increased root length and stem base diameter. In contrast, the response patterns of shoot traits, especially mechanical properties, to wind velocity were idiosyncratic among species. There was no significant difference in total biomass among different treatments; this might be because the negative effects on heat dissipation and photosynthesis of low wind speed during hot periods, could counteract positive effects during favorable cooler periods.

Conclusions

There are common wind response patterns in plant-size-related traits across different steppe species, while the response patterns in shoot traits vary among species. This indicates the species-specific ways by which plants balance growth and mechanical support facing wind stress. Our new field wind manipulation methodology was effective in altering wind speed with the intended magnitude. Especially, our field wind-funneling baffle system showed a great potential for use in future field wind velocity enhancement. Further experiments are needed to reveal how negative and positive effects play out on whole-plant performance in response to different wind regimes, which is important as ongoing global climatic changes involve big changes in wind regimes.
Commercial and public payer opioid analgesic prescribing policies: a case study
Authors: Arfken Cynthia L. , Tutag Lehr Victoria
Published: January 2021

Background

One strategy to address the high number of U.S. opioid-related deaths is to restrict high-risk or inappropriate opioid analgesic prescribing and dispensing. Federal and state laws and regulations have implemented restrictions but less is known about commercial and public payers’ policies aside from clinician anecdotal reports that these policies are increasing. To assess the number and types of policies with temporal trends, we examined commercial and public (Medicaid) payer policies in one state, Michigan, that has high opioid-related deaths and implemented opioid analgesic prescribing laws.

Methods

Policies for seven large commercial payers and the public payer for 2012–2018 were reviewed and categorized by actions. Joinpoint regression was used to summarize temporal trends on number of policies for all payers and subgroups.

Results

Across the 7 years, there were 529 action policies (75.57 (95% confidence intervals (CI) 35.93, 115.22) actions per year) with a range of 36 to 103 actions by payer. Limitations on number of days for initial prescriptions and prior authorizations were the most frequently implemented policy. The temporal trend showed a decline in new policies from 2012 to 2013 but a steady increase from 2014 to 2018 (average annual percent change or AAPC=29.6% (95% confidence intervals 13.2, 48.5%)). The public payer (n=47 policies) showed no increase in number of policies over time (AAPC=2.9% (95% CI -41.6, 61.6%).

Conclusions

The eight commercial and public payers implemented many new policies to restrict opioid analgesic prescribing with a steady increase in the number of such policies implemented from 2014 to 2018. This case study documented that at least in one state with high opioid-related deaths and multiple commercial payers, new and different policies were increasingly implemented creating barriers to patient care. The impact of these policies is understudied, complicating recommendation of best practices.
Surgical spacer placement for proton radiotherapy in locally advanced pancreatic body and tail cancers: initial clinical results
Authors: Lee Dongha , Komatsu Shohei , Terashima Kazuki , Toyama Hirochika , Matsuo Yoshiro , Takahashi Daiki , Suga Masaki , Nishimura Naoko , Tai Kentaro , Kido Masahiro , Demizu Yusuke , Tokumaru Sunao , Okimoto Tomoaki , Sasaki Ryohei , Fukumoto Takumi
Published: January 2021

Background

Particle radiotherapy has increasingly gained acceptance for locally advanced pancreatic cancers owing to superior tumor conformity and dosimetry compared to conventional photon radiotherapy. However, the close proximity of the pancreas to the stomach and duodenum leads to radiation-induced gastrointestinal toxicities, which hinder the delivery of curative doses to the tumor. To overcome this problem, a surgical spacer was placed between the tumor and gastrointestinal tract, and subsequent proton radiotherapy was performed in this study.

Methods

Data from 9 patients who underwent surgical spacer placement and subsequent proton radiotherapy were analyzed. The safety and feasibility of the spacer placement surgery were evaluated; the impact of the spacer on dosimetry was also assessed using dose volume histogram (DVH) analyses, before and after surgical spacer placement.

Results

Surgical spacer placement and subsequent proton radiotherapy were successfully completed in all cases. Surgical spacer placement significantly improved the dose intensity covering 95%, mean, and minimum doses for the gross tumor volume, and the clinical and planning target volume based on the DVH, while respecting the dose constraints of the gastrointestinal tract. Based on the Common Terminology Criteria for Adverse Events, two patients (22.2%) developed gastrointestinal ulcer (Grade 2) at 1 and 35 months, and one patient (11.1%) developed gastric perforation (Grade 4) at 4 months after proton radiotherapy.

Conclusions

Surgical spacer placement in the locally advanced pancreatic body and tail cancers is relatively safe and technically feasible. Comparing radiation plans, surgical spacer placement seems to improve the dose distribution in the locally advanced pancreatic body and tail cancers, which are close to the gastrointestinal tract.
Efficacy of mesenchymal stromal cells for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials
Authors: Qu Huazheng , Sun Shui
Published: January 2021

Background

Mesenchymal stromal cells (MSCs) are used as an emerging new option for the treatment of knee osteoarthritis (OA). However, their efficacy remains controversial across studies with different doses of MSCs and cell processing methods. We conducted this meta-analysis to assess the efficacy of MSCs in the treatment of knee OA.

Methods

Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China), and CNKI (National Knowledge Infrastructure, China) databases were systematically reviewed. The pain level and function improvements were evaluated using visual analog scale (VAS), McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC). The pooled estimate was calculated with weighted mean difference (WMD) with 95% confidence intervals (95%CIs).

Results

Nine RCTs involving 476 patients were included in this meta-analysis. The pooled estimate showed that the treatment of MSCs significantly reduced VAS, WOMAC pain, WOMAC stiffness, and WOMAC function scores at a long-term follow-up (12 or 24 months). However, for the IKDC and WOMAC total scores, MSCs also showed significant improvement in these outcomes, although this was not statistically significant when compared to the control.

Conclusion

Based on the current studies, our results suggested that MSCs were a promising option for the treatment of patients with knee OA. However, considering the potential limitations, more well-performed, large-scale RCTs are needed to verify our findings.
The impact of different artificial disc heights during total cervical disc replacement: an in vitro biomechanical study
Authors: Wang Xiao-Fei , Meng Yang , Liu Hao , Wang Bei-Yu , Hong Ying
Published: January 2021

Background

The principles of choosing an appropriate implant height remain controversial in total cervical disc replacement (TDR). By performing an in vitro biomechanical study and exploring the biomechanical impact of implant height on facet joint and motion function, the study aimed to offer valid proposals regarding implant height selection during TDR.

Methods

A total of 6 fresh-frozen male cadaveric cervical spines (C2–C7) with 5 mm intervertebral disc height at C5/6 level were enrolled in the study. Specimens with the intact condition and with different height artificial discs were tested. Facet joint pressures and range of motion under each condition were recorded using a specialized machine.

Results

The artificial disc heights that were involved in this study were 5 mm, 6 mm, and 7 mm. The range of motion decreased along with the increment of implant height, while facet joint pressure showed an opposite trend. Specimens with a 5 mm implant height could provide a similar range of motion (11.8° vs. 12.2° in flexion-extension, 8.7° vs. 9.0° in rotation, 7.9° vs. 8.2° in lateral bending) and facet joint pressure (27.8 psi vs. 25.2 psi in flexion, 59.7 psi vs. 58.9 psi in extension, 24.0 psi vs. 22.7 psi in rotation, 32.0 psi vs. 28.8 psi in lateral bending) compared with intact specimens. Facet joint pressure of specimens with 6 mm implant height (≥ 1 mm in height) increased during flexion at the C5–6 segment (30.4 psi vs. 25.2 psi, P = 0.076). However, specimens with 7 mm implant height (≥ 2 mm in height) showed a significant reduction in motion (9.5° vs. 12.2° in flexion-extension, P < 0.001) and increment of facet joint pressure at C5–6 segment (44.6 psi vs. 25.2 psi in flexion, 90.3 psi vs. 58.9 psi in extension, P < 0.0001) and adjacent segments.

Conclusions

This study suggested that an appropriate artificial disc height can achieve near-normal biomechanical properties and is recommended. We should be very cautious when using artificial discs ≥ 1 mm in height compared to normal. However, implants ≥ 2 mm in height compared to normal significantly increased the facet joint pressure and decreased the range of motion; therefore, it should not be used in clinical practice.
Application of bilateral internal mammary artery with different configurations in coronary artery bypass grafting
Authors: Han Zengqiang , Zhang Guodong , Chen Shenglong , Liu Gang , Chen Yu
Published: January 2021

Background

A large number of studies have shown that BIMA grafting is superior to single internal mammary artery grafting in cardiac function protection and long-term survival after surgery. While, there is still no consensus on how is the best configuration to use BIMA. This study aims to compare intraoperative blood flow, early clinical results and early postoperative patency of different configurations of BIMA.

Methods

There were 74 patients who underwent CABGs with bilateral internal mammary artery with different configurations we included. According to the different target territories that RIMA grafted to, the patients were divided into bilateral group (group I) with 20 cases and left group (group II) with 54 cases. Intraoperative blood flow, early clinical results and early postoperative patency of different configurations of BIMA were compared.

Results

There was no difference in the early postoperative death and major complications between group I and Group II(P>0.05). Compared with the LIMA in group II, the LIMA in group I had a slightly higher DF value (76.7 ± 6.2 vs 73.1 ± 6.8, P = 0.040). Compared with the RIMA in group II, the RIMA in group I had a slightly higher MGF (51.7 ± 34.4 ml/min vs 31.4 ± 21.4 ml/min, P = 0.024). There was no difference in the other TTFM parameters of LIMA and RIMA between group I and Group II(P>0.05). Further subgroup analysis revealed that compared with free RIMA in group II, in situ RIMA had a higher DF value (71.4 ± 7.8 vs 61.8 ± 18.1,P = 0.025). The PI of LIMA in free RIMA subgroup was higher than the PI of LIMA in in-situ RIMA subgroup (3.0 ± 1.6 vs 2.1 ± 1.0,P = 0.018). The results of early postoperative CTA examination showed that all IMAs grafts were completely patent.

Conclusions

The use of BIMA for CABG is safe and efficacious, RIMA used in right coronary artery received more satisfactory graft flow. BIMA with no stenosis and occlusion in the early stage, therefore is the ideal and stable coronary bypass graft.
Rare and low frequency genomic variants impacting neuronal functions modify the Dup7q11.23 phenotype
Authors: Qaiser Farah , Yin Yue , Mervis Carolyn B. , Morris Colleen A. , Klein-Tasman Bonita P. , Tam Elaine , Osborne Lucy R. , Yuen Ryan K. C.
Published: January 2021

Background

7q11.23 duplication (Dup7) is one of the most frequent recurrent copy number variants (CNVs) in individuals with autism spectrum disorder (ASD), but based on gold-standard assessments, only 19% of Dup7 carriers have ASD, suggesting that additional genetic factors are necessary to manifest the ASD phenotype. To assess the contribution of additional genetic variants to the Dup7 phenotype, we conducted whole-genome sequencing analysis of 20 Dup7 carriers: nine with ASD (Dup7-ASD) and 11 without ASD (Dup7-non-ASD).

Results

We identified three rare variants of potential clinical relevance for ASD: a 1q21.1 microdeletion (Dup7-non-ASD) and two deletions which disrupted IMMP2L (one Dup7-ASD, one Dup7-non-ASD). There were no significant differences in gene-set or pathway variant burden between the Dup7-ASD and Dup7-non-ASD groups. However, overall intellectual ability negatively correlated with the number of rare loss-of-function variants present in nervous system development and membrane component pathways, and adaptive behaviour standard scores negatively correlated with the number of low-frequency likely-damaging missense variants found in genes expressed in the prenatal human brain. ASD severity positively correlated with the number of low frequency loss-of-function variants impacting genes expressed at low levels in the brain, and genes with a low level of intolerance.

Conclusions

Our study suggests that in the presence of the same pathogenic Dup7 variant, rare and low frequency genetic variants act additively to contribute to components of the overall Dup7 phenotype.
Fingolimod in children with Rett syndrome: the FINGORETT study
Authors: Naegelin Yvonne , Kuhle Jens , Schädelin Sabine , Datta Alexandre N. , Magon Stefano , Amann Michael , Barro Christian , Ramelli Gian Paolo , Heesom Kate , Barde Yves-Alain , Weber Peter , Kappos Ludwig
Published: January 2021

Background

Rett syndrome (RS) is a severe neurodevelopmental disorder for which there is no approved therapy.
This study aimed to assess safety and efficacy of oral fingolimod in children with RS using a pre-post and case–control design.

Methods

At the University of Basel Children’s Hospital, Basel, Switzerland, children with RS were included if they were older than 6 years and met the established diagnostic criteria of RS, including a positive MeCP2 mutation. Participants were observed 6 months before and after treatment and received 12 months of fingolimod treatment. Serum samples of 50 children without RS served as reference for brain-derived neurotrophic factor (BDNF) measurements. Primary outcome measures were safety and efficacy, the latter measured by change in levels of BDNF in serum/CSF (cerebrospinal fluid) and change in deep gray matter volumes measured by magnetic resonance imaging (MRI). Secondary outcome measure was efficacy measured by change in clinical scores [Vineland Adaptive Behaviour Scale (VABS), Rett Severity Scale (RSSS) and Hand Apraxia Scale (HAS)].

Results

Six children with RS (all girls, mean and SD age 11.3 ± 3.1 years) were included. Serum samples of 50 children without RS (25 females, mean and SD age 13.5 ± 3.9 years) served as reference for BDNF measurements. No serious adverse events occurred. Primary and secondary outcome measures were not met. CSF BDNF levels were associated with all clinical scores: RSSS (estimate − 0.04, mult.effect 0.96, CI [0.94; 0.98], p = 0.03), HAS (estimate − 0.09, mult.effect 0.91, CI [0.89; 0.94], p <  0.01) and VABS (communication: estimate 0.03, mult.effect 1.03, CI [1.02; 1.04], p < 0.01/daily living: estimate 0.03, mult.effect 1.03, CI [1.02; 1.04], p < 0.01/social skills: estimate 0.07, mult.effect 1.08, CI [1.05; 1.11], p < 0.01/motoric skills: estimate 0.04, mult.effect 1.04, CI [1.03; 1.06], p = 0.02).

Conclusions

In children with RS, treatment with fingolimod was safe. The study did not provide supportive evidence for an effect of fingolimod on clinical, laboratory, and imaging measures. CSF BDNF levels were associated with clinical scores, indicating a need to further evaluate its potential as a biomarker for RS. This finding should be further validated in independent patient groups.

Trial Registration

Clinical Trials.gov NCT02061137, registered on August 27th 2013, https://clinicaltrials.gov/ct2/show/study/NCT02061137.