bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Aldh1a1 in Contributing to Breast Tumour Aggressiveness: a Study Conducted in an African Population
Authors: Gyan Eric , Green Andrew , Ahenkorah-Fondjo Linda , Jackson Andrew , Toss Micheal Shawky , Akakpo Patrick Kafui , Derkyi-Kwarteng Leonard , Rahman Ganiyu A. , Owiredu William K. B. A
Published: August 2020

Aldehyde dehydrogenase 1 member A1 (ALDH1A1) is one of the most well studied breast cancer stem cells. Its expression has been associated with poor clinicopathological features and clinical outcomes in several studies. This paper studies the expression of ALDH1A1 and its combination with CD44+/CD24−/low breast cancer stem cell and their association with clinicopathological parameters and molecular subtypes. METHOD: Tissue Microarray was constructed from 222 Formalin Fixed Paraffin Embedded (FFPE) breast cancer tissues. The expression of ALDH1A1, CD44 and CD24 were assessed by Immunohistochemistry (IHC). The association of ALDH1A1 and its association with clinicopathological parameters, molecular subtypes, CD44 and CD24 were studied in an African population. The association between CD44+/CD24−/low/ALDH1+ and the clinicopathological phenotypes were also studied. RESULTS: A high ALDH1A1 expression of 90% was recorded in this study. No association was found between ALDH1A1 and clinicopathological parameters. ALDH1A1 was positively associated with CD24 (r = 0.228, OR-4.599 95% CI- 1.751–12.076, p = 0.001) and CD44 (r = 0.228, OR-5.538 95%CI- 1.841–16.662, p = 0.001) but not associated with CD44+/CD24−/low (r = 0.134, OR- 2.720 95%CI- 0.959–7.710, p = 0.052). CD44+/CD24−/ALDH1+ however had significant associations with Age (p- 0.020, r = 0.161, OR- 2.771, 95%CI 1.147–6.697), Gender (p = 0.004, OR- 15.333 95%CI 1.339–175.54) ), Tumour grade(p = 0.005, r = 0.197, OR-3.913 95%CI 1.421–10.776) and clinical prognostic staging (p = 0.014, r = 0.182, OR-3.028 95%CI- 1.217–7.536). There was no association between CD44+/CD24−/ALDH1+ and the molecular subtypes. CONCLUSION: The high expression of ALDH1A1 in breast cancer makes it an important target for targeted therapy. This study further confirms the increased tumourigenicity of CD44+/CD24−/ALDH1+ combination phenotype and its association with increased tumour grade and clinical prognostic stage. Survival studies of ALDH1A1 and other breast cancer stem cells in African populations is strongly recommended to help further understand their effect on tumour aggressiveness.
Ultrasound Activated Nano TiO2 Loaded With Temozolomide Paves the Way for Resection of Chemo-resistant Glioblastoma Multiforme
Authors: Rehman Fawad Ur , Rauf Mohd Ahmar , Shaikh Sana , Qambrani Aqsa , Muhammad Pir , Hanif Sumaira
Published: August 2020

Background

Glioblastoma Multiforme (GBM) is one the most daunting issue to modern therapeutics, with a higher mortality rate post-diagnosis. Temozolomide (TMZ) is the only available treatment; however, the frequent resistance leaves the oncologists at the dead end. Therefore, new approaches to circumvent the GBM are highly desired. In this contribution, we have employed TiO2 nanosticks loaded with TMZ as nanomedicine for TMZ resistant GBM resection.
Results

The ultrasonication triple action effect could highly facilitate the tumor ablation by enhancing the TiO2 nanosticks traversing across BBB, releasing the TMZ payload from TiO2 nanosticks and Reactive Oxygen Species (ROS) generation from TiO2 nanosticks within GBM milieu. The tumor ablation was confirmed by MTT and Annexin(v)-PI assays, apoptotic proteins expression via western blot and ROS level detection in vitro, whereas tumor volume, weight, survival rate, and relative photon flux in the xenograft and orthoptic TMZ resistant GBM murine models as in vivo.
Conclusion

We found this nanomedicine-based ultrasound modality highly efficient in GBM treatment and is of future clinical application value due to employment of already FDA approved techniques and nanomedicine.
The complexity of scaling up an mHealth intervention. SMS for Life: A Case Study from a Health Systems Integration Perspective
Authors: Fruchtman Carmen Sant , Mbuyita Selemani , Mwanyika-Sando Mary , Braun Marcel , Savigny Don de , Cobos Daniel
Published: August 2020

Background The objective of this study was to apply systems thinking to examine the opportunities and challenges of scaling up and integrating a new electronic health technology into a complex health system. We used the implementation cycle of the supply chain management solution (SMS for Life 1.0) in Tanzania as a case study. SMS for Life was one of the earliest large-scale implementations of mHealth innovations worldwide. It aimed to bring visibility to antimalarial stock-outs through the use of SMS technology.Methods A qualitative case-study approach was used. This included a literature review, a document review of 61 project documents, a timeline of key events and the collection and analysis of 28 interviews with key stakeholders involved in or affected by the SMS for Life programme. Using the WHO mHealth Assessment and Planning for Scale (MAPS) Toolkit as a framework, we carried out a joint thematic analysis and identified the key reasons for the discontinuation of the programme.Results SMS for Life was reliable at scale and raised awareness of stock-outs with real-time monitoring. However, it was discontinued in 2015 after four years of a national rollout. The main reasons identified for the discontinuation were the programme’s failure to adapt to the continuous changes in Tanzania’s health system, the focus on stock-outs rather than ensuring appropriate stock management, and that it was perceived as costly by policy-makers.
GABAergic Neuron-Specific Whole-Brain Transduction by AAV-PHP.eB Incorporated with a New GAD65 Promoter
Authors: Hoshino Chiaki , Konno Ayumu , Kaneko Ryosuke , Hirai Hirokazu
Published: August 2020

GABAergic interneurons play a critical role in tuning neural networks in the central nervous system, and their defects cause neuropsychiatric disorders. Currently, the mDlx enhancer is solely used for adeno-associated virus (AAV) vector-mediated transgene delivery into cortical interneurons. Here, we developed a new inhibitory neuron-specific promoter of a 2.5-kb length from a genomic region of a mouse upstream of exon 1 of a gene encoding glutamic acid decarboxylase (GAD) 65 (mGAD65 promoter). Intravenous infusion of blood-brain barrier-penetrating AAV-PHPB expressing an enhanced green fluorescent protein under the control of the mGAD65 promoter transduced the whole brain in an inhibitory neuron-specific manner. The specificity and efficiency of the mGAD65 promoter for GABAergic interneurons, which was assessed at the motor cortex, were almost identical to or slightly higher than those of the mDlx enhancer. Immunohistochemical analysis revealed that the mGAD65 promoter preferentially transduced parvalbumin (PV)-expressing interneurons. Notably, the mGAD65 promoter transduced chandelier cells more efficiently than the mDlx enhancer and robustly labeled their synaptic boutons, called the cartridge, targeting the axon initial segments of excitatory pyramidal neurons. These results suggest that the mGAD65 promoter is useful for AAV-mediated targeting and the manipulation of GABAergic neurons with the dominance of cortical PV-expressing neurons, including chandelier cells.
Prevalence of Asymptomatic Visceral Leishmaniasis in Human and Dog, Benishangul Gumuz Regional State, Western Ethiopia
Authors: Bejano Shibabaw , Shumie Girma , Kumar Ashwani , Asemahagn Eyuel , Damte Demekech , Wolde Sinkinesh , Mulugeta Abate , Manaye Nigus , Bayih Abebe Genetu , Gadisa Endalamaw , Mamo Gezahegn
Published: August 2020

Background
Benishangul-Gumuz region is an important development corridor in Ethiopia. The large-scale projects; the great renaissance dam, mining and agriculture entailed huge environmental modification and settlement pattern changes. Detail epidemiological information of VL in the region is unknown.
Materials and Methods
A cross sectional study to assess the epidemiology and risk factors associated with asymptomatic VL. Leishmanin skin test (LST) was done for 1342 participants, and for 253 of them rK39 and DAT were done. Thirty-six dogs owned by households with LST positive member(s) were rK39 and DAT tested. A pretested questionnaire was used to capture individual and household characteristics.
Results
Of the 89.2% (1197/1342) who availed themselves for LST reading 6.0% were positive. The rk39 and DAT positivity among the 253 tested were 3.2% and 5.9% respectively. In dogs, positivity rates by rK39 and DAT were 13.9% and 5.6% respectively. Of the household and individual risk factors presence of dog in household (P = 0.005), male sex (0.003), residence woreda (0.000) and occupation (0.023) showed a strong positive association with LST positivity. Individuals who lived in household who owned dogs were 2.6 times more likely to be LST positive (AOR = 2.6; 95%CI = 1.54, 4.40). Being female decreased by 0.38 times the probability of being LST positive (AOR = 0.38; 95%CI = 0.20, 0.72). Living in Guba and Kurmuk has 4.7 (AOR = 4.74, 95% CI 1.83, 12.31) and 5.9 (AOR = 5.85, 95%CI 2.27, 15.09) times more risk of being infected.
Conclusions
We demonstrated presence of active VL transmission in the areas. Thus, we underline the need to establish the responsible vector(s) and reservoir(s) for comprehensive early containment plan to prevent potentially harmful public health and economic consequence.
Individualized Generation of Appropriate Assistance Timings for Active Lower Limb Robots via Machine Learning
Authors: Huang Guowei , Zhou Zikang , Liang Binghong , Nong Jinjin , Liu Youwei , Xie Longhan
Published: August 2020

Background: Obtaining appropriate assistance timings for individual users of active lower limb assistant robots (ALLARs) is one of the major challenges that limit the practical application of robots since very small assistance timing errors greatly affect the robot's assistance effect. However, neither theoretical nor experimental methods can currently generate appropriate assistance timings due to their respective availability or accuracy limitations. Method: In this paper, we proposed a new method to generate appropriate assistance timings for individual users of ALLARs via machine learning. The method has the accuracy of theoretical methods and the availability of experimental methods. We established a database of ten static physiological parameters, three dynamic parameters, and theoretical appropriate assistance timings, and mapped the static physiological parameters and the dynamic parameters to the theoretical assistance timings using multilayer neuron networks. Fold-cross validation and determination efficient were used to test the fit of the model. The root mean square error between generated values and true values of each subject was compared to that between the mean of the sample and the true values of each subject to evaluate the data accuracy of our method. We also set ±2% error as the boundary of the practical accuracy and compared the practical accuracy when using our method to that when using the mean generally. Result: The model achieved a small standard deviation of the square root error in the 10-fold cross-validation experiment and a large determination coefficient. We reduced the data error of starting and ending assistance timing from 0.0265 and 0.0172 to 0.014±0.000429 and 0.0079±0.000875, respectively, and improved the practical accuracy of starting and ending assistance timing from 54.93% and 75.49% to 89.54% and 99.95%, respectively.Conclusion: The proposed method can generate an appropriate assistance timings for different users of ALLARs walking at different speeds. Moreover, a new reference for ending assistance timings is provided and the database can be used as a reference for futer research. The practical effect of the method will be tested in future work.
Comparative Analysis of Postoperative Sexual Dysfunction and Quality of Life in Type A Aortic Dissection Patients of Different Ages
Authors: Luo Zeng-Rong , Chen Liang-Wan , Liao Dong-Shan
Published: August 2020

Background: To compare postoperative sexual dysfunction (SD) and quality of life (QOL) in Type A Aortic Dissection (AAD) Patients of Different Ages. Methods: From January 2018 to December 2019, 204 AAD postoperative survivors in Union Hospital of Fujian Medical University were selected and were divided into youth group (less than 50 years old) and elderly group (more than 50 years old). We evaluated SD according to the male International Erectile Dysfunction Index (IIEF-5) and female sexual function index (FSFI) . The Short Form 12 Health Survey Questionnaire (SF-12) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) were used to investigate the QOL, Quick Inventory Depressive Symptomatology-Self Report (QIDS-SR) and the Beck Depression Inventory-II (BDI-II) to investigate depressive symptoms. Results: 175 patients completed all the questionnaire (85.8%). The total SD prevalence rate was 38.9% (68 cases), with 27.4% of the youth (20 cases) and 47.1% of the elderly (48 cases). The age of non-SD and SD patients was 49.0±11.5 and 56.9±10.8 years, respectively (P=0.03). Compared with non-SD patients, the total physical health of SD patients was significantly worse (P=0.04), however, the mental health was not significantly worse (P=0.77); the depressive symptoms did not expressed a significant difference between the SD and non-SD groups (QIDS-SR P=0.15, BDI-Ⅱ P=0.06) . Total physical health in the youth SD group did not show significant better (P = 0.24), however, total mental health showed significantly worse (P=0.04), depressive symptoms scores were significantly higher (QIDS-SR P=0.03, BDI-Ⅱ P=0.04). Conclusion: The postoperative AAD SD prevalence of elderly is higher than that of youth, and the total physical health of SD patients is poorer than those without SD patients. The youth SD patients did not show a significant higher scores than the elderly SD patients, instead, the youth SD patients were more psychologically affected than the elderly SD patients, whose mental health was worse, and depression symptoms were more obvious, suggesting that the factors affecting the QOL of postoperative SD patients are related to physical factors, but the youth postoperative SD patients mainly affected by psychological factors.
A Genomic Blueprint of the Chicken Gut Microbiome
Authors: Gilroy Rachel , Ravi Anuradha , Getino Maria , Pursley Isabella , Horton Daniel , Alikhan Nabil-Fareed , Baker David , Gharbi Karim , Hall Neil , Watson Mick , Adriaenssens Evelien M. , Foster-Nyarko Ebenezer , Jarju Sheikh , Secka Arss , Antonio Martin , Oren Aharon , Chaudhuri Roy , Hildebrand Falk , Pallen Mark
Published: August 2020

Background: The chicken is the most abundant food animal in the world. However, despite its importance, the chicken gut microbiome remains largely undefined. Here, we exploit culture-independent and culture-dependent approaches to deliver a genomic blueprint of this complex microbial community. Results: We performed metagenomic sequencing of fifty chicken faecal samples from two breeds and analysed these, alongside all (n=582) relevant publicly available chicken metagenomes, to cluster over 20 million non-redundant genes and to construct over 5,500 metagenome-assembled bacterial genomes. In addition, we recovered nearly 600 bacteriophage genomes This represents the most comprehensive view of the chicken gut associated microbiome to date, encompassing dozens of novel candidate bacterial genera and hundreds of novel candidate species. Keen to provide a stable, clear and memorable nomenclature for novel species, we devised a scalable combinatorial system for the creation of hundreds of well-formed Latin binomials. We cultured bacterial isolates from faeces to deliver 282 whole genome sequences, incorporating thirty novel species, together with three species from the genus Escherichia, including the newly named species Escherichia whittamii.Conclusions: Our metagenomic and culture-based analyses provide new insights into the bacterial, archaeal and bacteriophage components of the chicken gut microbiome. The resulting datasets expand the known diversity of the chicken gut microbiome and provides a key resource for future high-resolution taxonomic and functional studies on the chicken gut microbiome.
Early Higher Achieved Mean Arterial Pressure Is Not Associated with Clinical Outcomes after Cardiac Arrest: A systematic Review and Meta-analysis
Authors: Wang Wen Jie , Feng Shun Yi , Zhang Su Li , Li Yong
Published: August 2020

Purpose: This study investigated the effect of early higher achieved mean arterial pressure (MAP) on clinical outcomes after cardiac arrest (CA).Methods: PubMed, ScienceDirect, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched for relevant articles until May 2020. The meta-analysis produced pooled effect size represented by odds ratios (ORs) and corresponding 95% confidence intervals (CIs).Results: Nine studies that enrolled 1337 participants were considered eligible for this meta-analysis. Early higher achieved MAP was associated with similar mortality (OR 0.54, 95% CI 0.26 – 1.12; p = 0.10), neurologic outcome (OR 1.30, 95% CI 0.65 – 2.58; p = 0.46), length of ICU stay (OR -0.06, 95% CI -0.31 – 0.19; p = 0.46), mechanical ventilation time (OR -0.14, 95% CI -0.90 – 0.62; p = 0.72), and bleeding (OR 0.57, 95% CI 0.23 – 1.40; p = 0.22) compared with low MAP. Sensitivity analysis demonstrated that the result was solid. No publication bias across the studies was observed using Begg's and Egger’ funnel plot plot. Conclusion: Based on current evidence, this meta-analysis confirmed that early higher achieved MAP does not improve the clinical outcomes after CA.REGISTRATION: (PROSPERO: CRD42020189875)
Serum S100A8 as an early diagnostic biomarker in patients with community-acquired pneumonia
Authors: Zheng Ling , Fei Jun , Xu Zheng , Feng Chun-Mei , Li Se-Ruo , Fu Lin , Zhao Hui
Published: August 2020

Background and Objectives Limited studies suggested that calprotectin may take part in the pathophysiology of community-acquired pneumonia (CAP). Nevertheless, there is no clinical study to analyze the role of S100A8 in CAP patients. The objective of this study was to analyze the association of serum S100A8 with the severity of CAP based on a cross-sectional study. Methods Entire 200 CAP patients and 100 normal subjects were recruited. Demographic data, clinical information and serum were collected on admission. Serum S100A8 and inflammatory cytokines were detected. Results Serum S100A8 was increased in CAP patients on admission. Serum S100A8 was gradually increased in parallel with the CAP severity scores. Serum S100A8 was positively correlated with CAP severity scores (CURB-65, CRB-65, PSI, CURXO and SMART-COP), blood routine parameters (WBC, neutrophil-lymphocyte ratio and monocyte-lymphocyte ratio) and inflammatory cytokines (TNFα, IL-1β and CRP). Furtherly, univariate and multivariate logistical regression analysis revealed that there was a positive association between serum S100A8 with CRB-65, PSI and CURXO. Moreover, the predictive capacity of serum S100A8 was performed by receiver operating characteristic area under the curve (AUC) analysis. The AUCs of S100A8 for CAP and CAP severity were 0.855 and 0.893, respectively. Mechanistic analysis found that S100A8 knockdown alleviated streptococcus pneumoniae-evoked inflammatory cytokines in A549 cells. Conclusion Serum S100A8 on admission was positively associated with the severity of CAP. S100A8 knockdown alleviates streptococcus pneumoniae- evoked inflammatory cytokines in A549 cells, indicating that S100A8 may exert an important role in the pathophysiology of CAP and be an early serum diagnostic biomarker for CAP.
What is the Clinical Impact of an Analytic Tool for Predicting the Fall Risk in Inpatients on Nursing Sensitive Outcomes?
Authors: Cho Insook , Jin Insun , Park Hyunchul , Dykes Patricia C.
Published: August 2020

Objectives
Patient falls remain a common cause of harm in acute-care hospitals worldwide. The purpose of this study was to explore whether an electronic analytic tool for predicting fall risk can improve clinical outcomes, including reducing inpatient falls in an acute-care setting.
Methods
We performed a double-blind experimental study that included a nonequivalent control group in 12 medical-surgical nursing units at a public hospital between May 2017 and April 2019. The intervention was the provision of risk prediction information generated by an analytic tool using nursing data obtained from the hospital’s electronic health record system. The primary outcome was the rate of falls, and secondary outcomes included fall-related injuries, the daily frequencies of nursing activities provided to patients and predefined process indicators.
Results
During the study there were 42,476 admissions, while 707 falls and 134 fall injuries occurred. The fall rate differed significantly between the two groups (1.79 vs. 2.11, t = 2.13, P = 0.0383), considering the interrupted time series analysis, a significant absolute reduction of 29.73% was noted in the intervention group (z = − 2.06, P = 0.0391), versus a 16.58% reduction in the control group (z = − 1.28, P = 0.2000). The injury rates were not significantly different (0.42 vs. 0.31, t = − 1.54, P = 0.1306). Patient-level-adjusted logistic regression showed a significant group effect on falls. Process outcomes on universal precautions were significantly better at the control units from baseline, while risk-targeted interventions increased slowly and more in the intervention group over time.
Conclusion
The introduction of an electronic analytic tool demonstrated the potential to contribute to improvement of patient outcomes, leading to positive, qualitative changes in process outcomes. Multihospital studies and combining this type of tool with efficient intervention strategies are needed to reduce both falls and fall-related injuries.
Trial registration:
Korean National Research Institute of Health, KCT0005286, Registered 4 August 2020 - Retrospectively registered, https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=16984
Extended interbody fusion using cortical bone trajectory screws vs. traditional pedicle screws in the treatment of adjacent segment disease after transforaminal lumbar interbody fusion with pedicle screws: a retrospective case control study
Authors: Song Xin , Ren Dong lin , Han Shuai , Zhang Feng , Wang Jian
Published: August 2020

Background

To present two minimally invasive surgical techniques using cortical bone trajectory screws with posterior lumbar interbody fusion (CBT-PLIF) and traditional pedicle screws and a domino system with transforaminal lumbar interbody fusion (TPS-Domino-TLIF) for adjacent segment disease (ASD) after lumbar fusion surgery, and compare the postoperative radiographic and clinical outcomes between the two techniques for ASD.
Methods

Of the 36 patients included in this study, 16 patients received CBT-PLIF and the other 20 patients received TPS-Domino-TLIF. Patient demographics, surgical data, complications, radiologic and clinical outcomes were evaluated and compared between the two groups.
Results

The surgical duration of TPS-Domino-TLIF was significantly shorter than that of CBT-PLIF (p < 0.001). There was less estimated blood loss (EBL) and a lower frequency of intra-operative fluoroscopy in TPS-Domino-TLIF as compared with CBT-PLIF (p < 0.001). The lumbar lordotic angle was improved both at immediate post-operation (p = 0.006) and the last follow-up (p = 0.007) in TPS-Domino-TLIF group as compared with CBT-PLIF group. The mean inter-vertebral height in TPS-Domino-TLIF group was significantly larger than that in CBT-PLIF group at immediate post-operation (p = 0.007) and the last follow-up (p = 0.005). The clinical outcomes in terms of the mean VAS-back, VAS-leg and ODI were improved significantly postoperatively in both groups.
Conclusions

As a more minimally invasive surgical technique for ASD, TPS-Domino-TLIF could be considered a viable alternative to the midline fusion technique using CBT.
Vaccination timeliness and associated factors among children aged 12-23 months in northwest Ethiopia: community-based study
Authors: Endalew Bekalu , Debie Ayal , Yazachew Lake
Published: August 2020

Background: vaccines are the most effective preventive and success of public health to control and eradicate serious childhood diseases. Timely childhood vaccination can help for children to develop antibody against vaccine preventable diseases. Evidences on childhood vaccination timeliness, however, there are limited in developing countries including Ethiopia. Therefore, this study was aimed at assessing vaccination timeliness and associated factors among children aged 12 to 23 months in Jabitehnan district, northwest Ethiopia.Methods: A community based cross-sectional study was conducted in Jabitehnan district from February to March 2020. A total of 548 children aged 12-23 months were included using multi-stage and simple random sampling technique. Binary logistic regression model was fitted to identify factors associated with vaccination timeliness. Adjusted odd ratio (AOR) with 95% CI and p-value less than 0.05 were used to declare statistically significant variables. Results: A total of 13.1% (95 % CI: 10.1-15.8) of children were received childhood vaccines in the recommended time interval. Higher level of maternal education (AOR: 2.73; 95% CI: 1.14-6.50), history of abortion (AOR: 3.45; 95%CI: 1.54-7.74), knowledge (AOR: 1.79; 95%CI: 1.10-3.18) and favorable attitude (AOR: 3.38; 95%CI: 1.83-6.24) were positively associated with vaccination timeliness. While home delivery (AOR: O.35; 95%CI: 0.18-0.68) and rural residence (AOR: 0.31; 95%CI: 0.14-0.65) were negatively associated. Conclusion: The overall childhood vaccination timeliness status was low in the study area. Children were received the first dose of vaccines within the recommended time relatively higher than the other doses/vaccines. Moreover, children were received measles vaccine earlier and BCG vaccine later than the acceptable time interval. Variables such as residence, maternal level of education, having history of abortion, place of delivery, knowledge and attitudes were affecting vaccination timeliness. Therefore, the policy planners and managers should give emphasis and incorporate vaccination timeliness in the childhood vaccination plan, and better to monitor and evaluate as one potential indicator to enhance the immune status of children. Health planners and managers should also improve women’s awareness to enhance their attitude towards childhood vaccination. Furthermore, it is better to promote institutional delivery service utilization to enhance childhood vaccination timeliness.
Integrated Analysis of Differentially Expressed Genes and Construction of a Competing Endogenous RNA Network in Human Huntington Neural Progenitor Cells
Authors: Tan Xiaoping , Cong Shuyan , Liu Yang , Zhang Taiming
Published: August 2020

Background Huntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking. Results Here, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using CRISPR-Cas9 approach at the HTT locus, and we identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein-protein interaction (PPI) network for mRNAs interacting with these lncRNAs. It is suggested that the function of DE lncRNAs mainly correlated with transcriptional regulation demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors. Conclusions Our research provides new clues for uncovering the mechanism of lncRNAs in HD and can be used as the focus for further investigation.
mTOR-dependent dysregulation of autophagy contributes to the retinal ganglion cell loss in streptozotocin-induced diabetic retinopathy
Authors: Madrakhimov Sanjar Batirovich , Yang Jin Young , Kim Jin Ha , Han Jung Woo , Park Tae Kwann
Published: August 2020

Background: Neurodegeneration, an early event in the pathogenesis of diabetic retinopathy (DR), precedes clinically detectable microvascular damage. Autophagy dysregulation is considered a potential cause of neuronal cell loss, however underlying mechanisms remain unclear. The mechanistic target of rapamycin (mTOR) integrates diverse environmental signals to coordinate biological processes, including autophagy. Here, we investigated the role of mTOR signaling in neuronal cell death in diabetic retinopathy. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin and tissue samples were harvested at 1, 2, 3, 4, and 6 months of diabetes. Early-stage of diabetic retinopathy was investigated in 1-month-diabetic mice treated with phlorizin or rapamycin. The effect of autophagy modulation on retinal ganglion cells was investigated in 3-months-diabetic mice treated with phlorizin or MHY1485. Tissue samples obtained from treated/untreated diabetic mice and age-matched controls were used for Western blot and histologic analysis.Results: mTOR-related proteins and glucose transporter 1 (GLUT1) was upregulated at 1 month and downregulated in the following period up to 6 months. Diabetes-induced neurodegeneration was characterized by an increase of apoptotic marker – cleaved caspase 3, a decrease of the total number of cells, and NeuN immunoreactivity in the ganglion cell layer (GCL), as well as an increase of autophagic protein. Insulin-independent glycemic control restored the mTOR pathway activity and GLUT1 expression, along with a decrease of autophagic and apoptotic proteins in 3-months-diabetic mice neuroretina. However, blockade of autophagy using MHY1485 resulted in a more protective effect on ganglion cells compared with phlorizin treatment. Conclusion: Collectively, our study describes the mechanisms of neurodegeneration through the hyperglycemia/ mTOR/ autophagy/ apoptosis pathway.
Unveiling role of Sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer
Authors: Petti Luciana , Rizzo Giulia , Rubbino Federica , Elangovan Sudharshan , Colombo Piergiuseppe , Silvia Restelli , Piontini Andrea , Arena Vincenzo , Carvello Michele , Romano Barbara , Cavalleri Tommaso , Anselmo Achille , Ungaro Federica , D’Alessio Silvia , Spinelli Antonino , Stifter Sanja , Grizzi Fabio , Sgambato Alessandro , Danese Silvio , Laghi Luigi , Malesci Alberto , VETRANO STEFANIA
Published: August 2020

BackgroundSphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information onto whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap.MethodsWe screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2−/−) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013, and characterized intestinal epithelial stem cells isolated from S1PR2−/−Lgr5-EGFP- mice.ResultsS1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/min mouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2−/− mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN.ConclusionsIn normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5.
Large-area display textiles integrated with functional systems
Authors: Peng Huisheng , Shi Xiang , Zuo Yong , Zhai Peng , Shen Jiahao , Yang Yangyiwei , Gao Zhen , Liao Meng , Wang Jiawei , Xu Xiaojie , Tong Qi , Zhang Bo , Sun Xuemei , Zhang Lihua , Pei Qibing , Jin Dayong , Chen Peining
Published: August 2020

Displays are basic building blocks of modern electronics1,2. Integrating displays into textiles offers exciting opportunities for smart electronic textiles – the ultimate form of wearables poised to change the way we interact with electronic devices3-6. Display textiles serve to bridge human-machine interactions7-9, offering for instance, a real-time communication tool for individuals with voice or speech disorders. Electronic textiles capable of communicating10, sensing11,12 and supplying electricity13,14 have been reported previously. However, textiles with functional, large-area displays have not been achieved so far because obtaining small illuminating units that are both durable and easy to assemble over a wide area is challenging. Here, we report a 6 m (L) * 25 cm (W) display textile containing 500000 electroluminescent (EL) units narrowly spaced to ~800 μm. Weaving conductive weft and luminescent warp fibres forms micron-scale EL units at the weft-warp contact points. Brightness between EL units deviates by < 6.3% and remains stable even when the textile is bent, stretched or pressed. We attribute this uniform and stable lighting to the smooth luminescent coating around the warp fibres and homogenous electric field distribution at the contact points. Our display textile is flexible and breathable and withstands repeatable machine-washing, making them suitable for practical applications. We show an integrated textile system consisting of display, keyboard and power supply can serve as a communication tool, which could potentially drive the Internet of Things in various areas including healthcare. Our approach unifies the fabrication and function of electronic devices with textiles, and we expect weaving fibre materials to shape the next-generation electronics.
CooC11 and CooC7: The Development and Validation of Age Appropriate Children’s Perceived Cooking Competence Measures
Authors: Dean Moira , Issartel Johann , Benson Tony , McCloat Amanda , Mooney Elaine , McKernan Claire , Dunne Laura , Brennan Sarah F , Moore Sarah E , McCarthy Danielle , Woodside Jayne V , Lavelle Fiona
Published: August 2020

Background
Learning cooking skills during childhood and adolescence is associated with positive dietary outcomes in adulthood as well as being tracked from adolescence to adulthood. In addition studies have found that perceived competence to be a greater motivator to perform a behaviour than actual competence. However, a lack of validated tools that effectively measure behavioural and dietary changes and other related measures in children is a limitation. Therefore, this research aimed to develop and validate age-appropriate perceived cooking competence measures for younger and older primary school aged children.
Methods
Two measures of perceived Cooking Competence (CooC11 and CooC7) for older (8–12 years) and younger (6–7 years) children were developed from a critical evaluation of publically available recommendations and expert consultation. The cooking skills within the measures were illustrated by a graphic designer in consultation with a chef and reviewed in an iterative manner by the research team. The measures were piloted for clarity, ease of use and initial face validity. Multiple studies were used for both CooC11 and CooC7 to establish psychometric properties of the measures, temporal stability, internal consistency reliability, construct validity, as well as responsiveness to change for CooC11. Analysis included Exploratory Factor Analysis, Confirmatory Factor Analysis, Intraclass Correlation Coefficients, Pearson’s Correlations, ANOVAs and Cronbach’s Alphas.
Results
Both measures had high levels of face validity and received positive user feedback. Two factors were shown in both measures with the measures showing excellent temporal stability (ICC > 0.9) and good internal consistency (Cronbach’s Alphas > 0.7). Both measures showed initial discriminant validity, with significant differences (P < 0.001) between those who reported assisting their parents with dinner preparation and those who did not. Additionally, CooC11 was significantly correlated with an adult cooking measure and had a significant responsiveness to change (P < 0.01).
Conclusions
The CooC11 and CooC7 are the first validated age-appropriate measures for assessing children’s perceived Cooking Competence for ages 8–12 and 6–7 years respectively. They can be used to evaluate the efficacy of children’s cooking intervention studies or school nutrition education programmes.
Elevated liver fibrosis index FIB-4 is associated with poor clinical outcomes in patients with sepsis, an observational cohort study
Authors: Zhu Xiaodan , Qin Xiaoyi , Pan Jingye , Hu Xiang , Zhou Wei
Published: August 2020

Background: No study for investigating the association between sub-clinical hepatic fibrosis and the outcomes of sepsis was performed before. Therefore, the purpose is to explore the association of liver fibrosis indexes with the outcomes of septic patients without overt chronic liver disease. Methods: We performed a cohort study using data extracted from the Medical Information Mart for Intensive Care Ⅲ database (v1.4). The patient records of additional external validation were obtained from the First Affiliated Hospital of Wenzhou Medical University. Aspartate aminotransferase-platelet ratio index (APRI), fibrosis-4 (FIB-4) score and non-alcoholic fatty liver disease fibrosis score (NFS) were calculated with previous formulas. The primary outcome was 28-day mortality. The secondary outcomes were 90-day mortality, in-hospital mortality and renal replacement therapy (RRT). We assessed the associations of three indexes with primary and secondary outcomes using logistic regression analysis. Furthermore, we performed multivariable analysis, sensitivity analysis and additional external validation to verify the true strength of the results.Results: In the FIB-4-sepsis cohort (N = 1560), there was a statistically significant stepwise increase from Quartile 1 to Quartile 4 in the risk of 28-day mortality (Quartile 1: reference; Quartile 2: OR = 1.570, P = 0.061, 95%CI = 0.980–2.515; Quartile 3: OR = 2.363, P < 0.001, 95%CI = 1.512–3.692; Quartile 4: OR = 2.933, P < 0.001, 95%CI = 1.895–4.538). Similarly, the increased trends could also be found in all secondary outcomes for the FIB-4-sepsis cohort. However, no significant trends were observed in the APRI-sepsis and NFS-sepsis cohorts. The results of multivariable logistic regression analysis, Kaplan-Meier analysis, Cox regression analysis and additional external validation showed good consistency.Conclusions: FIB-4 index was associated with 28-day mortality, 90-day mortality, in-hospital mortality and RRT in the septic patients without overt chronic liver disease. In other words, the high stage of sub-clinical hepatic fibrosis represented by FIB-4 could reflect the poor outcomes of patients with sepsis.
Global Impairment of Cerebral Perfusion Measured using Dynamic Susceptibility Contrast Perfusion-Weighted Imaging in Out-of-Hospital Cardiac Arrest Survivors: A Prospectively Preliminary Study
Authors: Kang Changshin , Lee In Ho , Park Jung Soo , You Yeonho , Yoo Insool , Cho Yong Chul , Jeong Wonjoon , Ahn Hong Joon , Kang Chan
Published: August 2020

Background: Dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) is useful for measuring cerebral perfusion (CP). This study aimed to assess global impairment and the prognostic performance of CP parameters measured by DSC-PWI in out-of-hospital cardiac arrest (OHCA) survivors.Methods: This is a single-centre, prospective observational study. OHCA survivors who underwent DSC-PWI within 6 h after restoration of spontaneous circulation were enrolled. CP parameters (cerebral blood volume [CBV], cerebral blood flow [CBF], mean transit time [MTT], time to peak [TTP], and time to the maximum of the residue function [Tmax]) were quantified by normalisation + leakage correction (LC) or by arterial input function (AIF) + LC. The primary outcome was survival to discharge; subjects who died due to withdrawal of life-sustaining therapy or who were diagnosed with brain death (BD) were included in non-survival. The secondary outcome was 6-months neurological outcome. CP parameters were compared across groups, and receiver operating characteristic (ROC) curves were constructed to assess prognostic performances.Results: Thirty-one subjects (male, 20; 64.5%) participated. Relative CBV (rCBV) and CBF (rCBF) quantified by normalisation + LC were significantly higher in the non-survival group (p=0.02 and p=0.03, respectively). The area under the ROC curves (AUROCs) and 100% specific sensitivities for non-survival were 0.75/31.3% and 0.73/25.0%, respectively. MTT and Tmax quantified by AIF + LC were significantly higher in non-survival (p=0.01 and p=0.01, respectively). Their AUROCs and 100% specific sensitivities were 0.77/56.3% and 0.76/43.8%, respectively. rCBV and rCBF quantified by normalisation + LC were significantly higher in the poor neurological outcome group (p<0.01 and p=0.02, respectively). The AUROCs and 100% specific sensitivities for poor neurological outcome were 0.81/23.8% and 0.77/19.1%, respectively. Tmax quantified by AIF + LC was significantly higher in poor neurological outcome (p=0.04). Its AUROC and 100% specific sensitivity were 0.74/33.3%.Conclusion: Hyperaemia and delayed CP were present in the non-survival and poor neurological outcome groups. MTT quantified by AIF + LC could be the most powerful parameter for predicting mortality or BD in OHCA survivors at an early stage of post cardiac arrest care. AIF may be more appropriate as quantifying method for CP in OHCA survivors than normalisation.
The Use of Internet Platforms for Oral Health Information and Associated Factors Among Adolescents From Jakarta: A Cross Sectional Study
Authors: Maharani Diah Ayu , Tantawi Maha El , Yoseph Marsha Griselda , Rahardjo Anton
Published: August 2020

Objective: The growth of the internet has increased its use to obtain health information including oral health information (OHI). This study assessed Indonesian adolescents’ use of different internet platforms to obtain OHI and factors associated with this use.Materials and methods: A cross-sectional study surveyed middle school students in five regions in Jakarta in 2019. Participants completed a questionnaire that assessed demographics, oral health practices (toothbrushing and dental visits), the presence of dental pain, using internet platform to obtain OHI and type of information searched for. Multinomial logistic regression was used to assess the association between using the internet for OHI (Google, Social Media (SM), both or none) and the independent factors: demographics, oral health practice, dental pain and whether participants search for causes, symptoms, prevention or treatment of oral diseases (ODs). Results: Most of the 521 participants were female (55.7%) with mean age= 13.4 years. Almost all of them (93.7%) searched the internet for OHI through Google (40.7%) or Google with SM (36.1%). Searching for OHI over SM was significantly associated with toothbrushing (OR= 4.12, 95%CI= 1.43, 11.89) and less dental visits (OR= 0.16, 95%CI= 0.05, 0.60). Searching Google for OHI was significantly associated with looking for information about causes (OR= 3.69, 95%CI= 1.33, 10.26) and treatment (OR= 6.17, 95%CI= 2.23, 17.03) of ODs. Conclusions: Most adolescents used Google to seek OHI. Oral health practices and types of OHI searched for differed by internet platform. Dental health professionals should consider using internet-based interventions to promote oral health to this age group.
Acupuncture Protects Against Cerebral Ischemia-Reperfusion Injury Via Suppressing Endoplasmic Reticulum Stress-Mediated Autophagy and Apoptosis
Authors: Sun Xiaowei , Liu Hao , Sun Zhongren , Zhang Beng , Wang Xinyu , Liu Tingting , Pan Tingting , Gao Ying , Jiang Xicheng , Li Hongtao
Published: August 2020

Background: Acupuncture treatment possesses the neuroprotection potential to attenuate cerebral ischemia-reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress has been suggested to be involved in the pathogenic mechanism of cerebral I/R injury. Whether acupuncture protects against cerebral I/R injury via regulating ER stress remains unclear. This study aimed to evaluate the role of ER stress in the neuroprotection of acupuncture against cerebral I/R injury and its underlying mechanisms. Methods: Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO) in rats. Acupuncture was carried out at Baihui (GV 20), Hegu (L14), and Taichong (Liv3) acupoints in rats immediately after reperfusion. The infarct volumes, neurological score, ER stress, autophagy and apoptosis were determined. Results: Acupuncture treatment decreased infarct volume, neurological score and suppressed ER stress via inactivation of ATF-6, PERK, and IRE1 pathways in MCAO rats. Attributing to ER stress suppression, 4-PBA (ER stress inhibitor) promoted the beneficial effect of acupuncture against cerebral I/R injury. Whereas, ER stress activator tunicamycin significantly counteracted the neuroprotective effects of acupuncture. In addition, acupuncture restrained autophagy via regulating ER stress in MCAO rats. Finally, ER stress took part in the neuroprotective effect of acupuncture against apoptosis in cerebral I/R injury. Conclusions: Our findings suggest that acupuncture offers neuroprotection against cerebral I/R injury, which is attributed to repressing ER stress-mediated autophagy and apoptosis.