bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of prebiotic (Lacto-N-neotetraose) and probiotic (B. infantis EVC001) supplementation on gut inflammation and fecal pH in young infants suffering from severe acute malnutrition: findings from a randomized controlled trial
Authors: Palit Parag , Nuzhat Sharika , Gazi Md Amran , Islam Md Ridwan , Mahfuz Mustafa , Islam M Munirul , Alam Md Ashraful , Flannery Robin L , Kyle David J , Sarker Shafiqul A , Ahmed Tahmeed
Published: September 2020

BackgroundSevere acute malnutrition (SAM) is associated with high levels of gamma Proteobacteria chronic gut inflammation and poor gut health. In this study, we aimed to assess the effects of probiotic and/or prebiotic supplementation on gut inflammation and fecal pH in young infants with SAM.MethodsThis study was a single-blind RCT where infants aged between 2 and 6 months were randomized to receive either: probiotic (B. infantis EVC001), synbiotic (prebiotic, Lacto-N-neotetraose [LNnT] plus probiotic [B. infantis EVC001]), or placebo (Lactose) for 28 days followed by 28 days of post-supplementation follow up. Stool samples were collected at baseline and at day 10, day 28 and day 56. Fecal myeloperoxidase (MPO), as an indicator of gut inflammation and fecal pH were measured and the change in the levels of these biochemical parameters between the sample collection time points were calculated and denoted as ∆MPO and ∆pH. Kruskal-Wallis test was done to assess the effect of the supplementations on ∆MPO and ∆pH. Multivariate quantile regression analysis was performed to analyze the association of the supplements with ∆MPO and ∆pH.ResultsIn comparison to the placebo group at day 10, a significant decrease in ∆MPO was found for the probiotic group (β-coefficient: -18.44; 95% CI: -31.62 µg/ml, -52.47 µg/ml; p = 0.007) and for the synbiotic group (β-coefficient: -17.24; 95% CI: -30.94 µg/ml, -35.36 µg/ml; p = 0.015). This reduction in ∆MPO in comparison to the placebo group was sustained only in the synbiotic group at other time points. Decrease in ∆pH was observed only in the synbiotic group at day 10 and day 28, but not at day 56 in comparison to the placebo group.ConclusionOur findings demonstrate that the use of this synbiotic supplementation may result in sustained effects in reduction of gut inflammation in young infants with SAM. However, further studies are required to fully evaluate the role of this synbiotic intervention for sustained reduction in fecal pH in this study population.Trial registrationThe trial is registered at ClinicalTrials.gov (NCT0366657). Registered on 12 September, 2018 (https://clinicaltrials.gov/ct2/show/NCT03666572)
Low Noise Moving Target Detection In High Resolution Radar Using Binary Codes
Authors: Algethami Majid
Published: September 2020

Now-a-days, entire nations need securities against warfare equipment’s to save their nation, and improve the battle field surveillance. Radar, alone is the major equipment that fulfills these requirements. However the radar technology possesses certain challenges to detect targets when they are moving with high speed as static and slow moving targets can be easily detected. In this connection the research community tried to improve the radar technology to detect fast moving targets in presence of Doppler noise. In this paper various binary codes have been designed to minimize the noise peaks below the radar threshold limit, which creates multiple windows and gives precise information of the moving targets. These sequences also have good autocorrelation property to get higher range resolution and compression ratio. The validation of the paper is done by Matlab.
Network pharmacology reveals hub bio-active ingredients and possible mechanisms of a Chinese herbal prescription Ru-kang-yin against breast cancer
Authors: Chu Shirun , Chen Fang , Li Jun , Yang Mei , Xu Delin
Published: September 2020

Background

Ru-kang-yin (RKY), a traditional Chinese herbal prescription, has been clinically used as adjuvant therapy for breast cancer via inhibiting cell invasion, proliferation, and promoting apoptosis. However, its anti-breast cancer bio-active ingredients and possible mechanisms are still unclear. In the present study, the hub bio-active compounds and underlying mechanisms of RKY in treatment of breast cancer were systematically elucidated by the approach of network pharmacology.
Methods

By using network pharmacology approach, a total of 53 nonredundant bio-active components met the drug screening criteria and 155 putative targets of RKY in treatment of breast cancer were identified. Besides, 381 potential breast cancer-related targets were obtained. Among of the targets, 56 shared targets of RKY and breast cancer were acquired.
Results

Based on topological network analysis of PPI network of shared targets, 19 hub therapeutic targets of RKY against breast cancer were obtained. GO and KEGG pathway enrichment analysis of core therapeutic targets showed that the core targets remarkably involved in multiple biological functions and KEGG pathways which mainly participated in inflammatory response, cell proliferation, and apoptosis.
Conclusions

These findings uncover the hub bio-active compounds and underlying mechanisms of RKY against breast cancer and provide crucial information regarding using RKY as a promising candidate for treating breast cancer.
Gastrointestinal symptoms in coronavirus disease 2019: a cross-sectional study in Wuhan, China
Authors: Zhang Yong , Lu Zuneng , Wang Bo , Chang Jinxing , Ma Yonggang
Published: September 2020

Background

To investigate the clinical symptoms of coronavirus disease 2019 (COVID-19), particularly the prevalence, time of symptom onset, and duration of gastrointestinal (GI) symptoms.
Methods

This was a cross-sectional study using paper questionnaires. COVID-19 patients in a temporary hospital in Wuhan voluntarily completed surveys collecting data on COVID-19 symptoms and investigation results.
Results

A total of 212 adults were enrolled in this study, of whom 127 (59.9%) were female, mean age was 48.50 ± 13.15 years. Concerning symptoms, 78.8% (167/212) had fever, and 66% (140/212) had cough. Diarrhoea occurred in 43.8% (93/212) of patients. Nausea and vomiting were also common (20.7%). Fever and cough were frequently the initial symptoms of COVID-19, and they lasted for 5.00 [interquartile range (IQR): 3.00–10.00] days and 10.00 (IQR: 5.00–24.00) days, respectively. Most patients developed nausea and vomiting 2.00 (IQR: 0–9.00) days and diarrhoea 5.00 (IQR: 0.25–11.00) days after the onset of initial symptoms, respectively. There was a median duration of 4.00 (IQR: 2.00–8.75) days with diarrhoea, and 6.00 (IQR: 4.00–10.00) days with nausea and vomiting. The patients with diarrhoea were younger [45.85 ± 13.28 years vs 50.61 ± 12.82 years, P = 0.009] and were more likely to have an abnormal chest CT (95.7% vs 82.4%, P = 0.001) than those without diarrhoea.
Conclusions

In our cohort of patients, GI symptoms were common in COVID-19, occurred mostly during the middle stage of the disease, and lasted for a short duration. GI symptoms may not be associated with COVID-19 related treatment.
Primary mantle cell lymphoma complicated with cutaneous diffuse large B-cell lymphoma, leg type: a rare case report of composite non-Hodgkin lymphoma in different organs
Authors: Jiang Yanfeng , Zeng Zhiming , Yang Lihua , Zeng Jie , Qin Fengyan , Du Lihua , Ma Jie
Published: September 2020

Background

Composite lymphomas (CLs) are a kind of rare disease that two distinct categories of lymphomas occur in the same patient. Histologically, composite lymphomas can be composed of a Hodgkin’s lymphoma and a non-Hodgkin lymphoma or two distinct non-Hodgkin lymphomas. So far, most of the cases have been reported to occur in a single anatomical site or mass.
Case presentation:

A 61-year-old man without any B-type symptoms complained of an enlarging mass in the abdomen for one month. A 10 × 10 cm abdominal mass could be touched in the hypogastric region. Through pathological biopsy, mantle cell lymphoma can be diagnosed. After one cycle chemotherapy regimen of FCD, red rashes and blisters came out on the patient's right lower extremity. Cutaneous diffuse large B-cell lymphoma (DLBCL) was diagnosed by skin biopsy. In this report, we describe a case of composite lymphoma occurring in different organs, which consisted of primary mantle cell lymphoma (MCL) and cutaneous DLBCL, leg type. The patient then received a series of chemotherapy regimens without rituximab then achieved partial response (PR).
Conclusions

To our knowledge, this is a rare case of CLs occurring in different anatomic sites that were treated by chemotherapy and achieved PR. As we learn more about the mechanisms and treatment of CLs, we look forward to more treatment options in the future for patients to give them a better prognosis.
Mapping the Spatial and Temporal Variation of Agricultural and Metrological Drought Using Geospatial Techniques, Ethiopia
Authors: Senamaw Abebe , Addisu Solomon , Suryabhagavan K.V.
Published: September 2020

Background Geographic Information System (GIS) and Remote Sensing play an important role for near real time monitoring of drought condition over large areas. The objective of this study was to assess spatial and temporal variation of agricultural and metrological drought using temporal image of eMODIS NDVI based vegetation condition index (VCI) and standard precipitation index (SPI). To validate the strength of drought indices correlation analysis was made between VCI and crop yield anomaly as well as SPI and crop yield anomaly. The results revealed that the year 2009 and 2015 were drought years while the 2001 and 2007 were wet years. There was also a good correlation between NDVI and rainfall (r=0.71), VCI and crop yield anomaly (0.72), SPI and crop yield anomaly (0.74). Frequency of metrological and agricultural drought was compiled by using historical drought intensity map. ResultThe result shows that there was complex and local scale variation in frequency of drought events in the study period. There was also no year without drought in many parts of the study area. Combined drought risk map also showed that 8%, 56%, 35% and 8% of study area were vulnerable to very severe, severe and moderate drought condition respectively. Conclusion In conclusion, the study area is highly vulnerable to agricultural and meteorological drought. Thus besides mapping drought vulnerable areas, integrating socioeconomic data for better understand other vulnerable factors were recommended.
Structure Parameters and Displacement Equations of Goldberg Mechanisms With the Rank More Than sixStructure Parameters and Displacement Equations of Goldberg Mechanisms With the Rank More Than Six
Authors: Zhang Yitong , Lu Ling , Liu Wenlan , Li Yanwen , Hu Bo , Mu Dejun , Lu Wenjuan
Published: September 2020

An infinite number of N-bar Goldberg mechanisms with the rank more than six are proposed. A single closed-loop eight-bar mechanism is first developed by removing the common side links of adjacent loops from the five-loop Bennett mechanism in which all loop frames are collinear. An analysis of trajectory circles of the links shows that the mechanism developed maintains the original constraint conditions and kinematic characteristics, and that its degree of freedom (DOF) is also one. This novel single-loop mechanism is named the eight-bar Goldberg mechanism because of its similar constraint characteristics with the five-bar and six-bar Goldberg mechanisms. The eight displacement parameters of this mechanism are analyzed by using the interior angles of adjacent links, and the five cosine equations for the tangent product of the stagger angles between adjacent links are established in together with one angular displacement equation of odd links and one angular displacement equation of even links. This novel mechanism has one DOF, eight displacement parameters and seven independent displacement equations. The loop rank of the eight-bar Goldberg mechanism is seven, which revises the existing mechanism theory of single closed-loop mechanisms with the rank no more than six. Similarly, a nine-bar Goldberg mechanism is constructed, and its nine displacement parameters are analyzed. This mechanism has eight independent displacement equations and the loop rank is eight, proving that the mechanisms with the rank more than six are not rare. Then, according to the characteristics of the independent displacement equations of the eight-bar and nine-bar Goldberg mechanisms, the N (N>7) displacement parameters of N-bar Goldberg mechanisms are analyzed, and the (N–1) independent displacement equations are deduced with odd and even Ns. It is proved that the loop rank of N-bar Goldberg mechanisms is (N–1), so there exist an infinite number of mechanisms with the rank more than six
Synthesis and accumulation of amylase-trypsin inhibitors and FODMAPs in bread wheat (Triticum aestivum L.) during grain development
Authors: Call Lisa , Haider Elisabeth , D’Amico Stefano , Reiter Elisabeth , Grausgruber Heinrich
Published: September 2020

Background
Recent gastroenterology studies assume that amylase-trypsin inhibitors (ATIs) and FODMAPs (fermentable oligo-, di-, monosaccharides and polyols) play an important role in promoting wheat sensitivity. Hitherto, no study has investigated the formation of ATIs during the development of the wheat caryopsis. We collected caryopses of common wheat cv. ‘Arnold’ at eight different grain developmental stages to study compositional changes in ATI and FODMAP content.
Results
The harvested caryopses were analysed for their size, protein and carbohydrate concentrations. ATIs were further characterized by MALDI-TOF MS, and their trypsin inhibition was evaluated by an enzymatic assay. The results showed that ATI accumulation started about one week after anthesis and subsequently increased steadily until physiological maturity. However, the biological activity of ATIs in terms of enzyme inhibition was not detectable before about four weeks after anthesis. Carbohydrate analysis revealed the abundance of short-chain fructans in early stages of grain development, whereas non water soluble carbohydrates increased during later developmental stages.
Conclusions
The compositional changes of ATIs and FODMAPs during the development of wheat grains were characterized by qualitative and quantitative approaches. The results provide new insights into the complex metabolisms during grain filling and maturation, with particular emphasis on the ATI content as well as the inhibitory potential towards trypsin. The time lag between ATI accumulation and development of their biological activity is supposed to be attributed to the assembling of ATIs to dimers and tetramers, which seems to be crucial for their inhibitory potential.
Stored Whole Blood Transfusion Initiate Serum Amyloid A Activation Monitored by Real-Time Dynamic Imaging
Authors: Zhang Yulong , Wang Zhengjun , Liu Lei , Zhou Qianqian , Sun Sujing , Ma Ping , Lv Liping , Wang Xiaohui , Zhan Linsheng
Published: September 2020

BACKGROUND: Transfusion of stored whole blood (SWB) is increasingly routine practice to resuscitate severe traumatic hemorrhage patients in military operations and civilian emergency centers. It has been well established that transfusion of red blood cells (RBCs) after prolonged storage exerts harmful effects that are mainly mediated by inflammation. Whether the storage lesion that related to inflammation will happen in SWB remains unclear.METHODS: A hepatocyte SAA (serum amyloid A) specific reporter mouse that facilitated non-invasive imaging of hepatocyte SAA expression was used for the evaluation of acute inflammation and acute-phase reaction after the transfusion of SWB or components separated from end-stage whole blood. Donor C57BL/6 mouse whole blood was used to model an allogeneic transfusion in Balb/C mouse recipients. RESULTS: End-stage whole blood (14 days of storage) transfusion induced the most significant SAA expression, while 10-day-storage evoked much weaker signal compared to their fresh and 5-day-storage counterparts. It was RBCs rather than white blood cells and plasma-containing platelets that should be responsible for the systemic inflammatory and SAA activation during end-stage whole blood transfusion. Circulatory and hepatic pro-inflammatory cytokines induced the SAA expression in hepatocyte. The macrophage M1 polarization aroused by SWB activated SAA through nuclear transcription factor NF-κB. CONCLUSION: Storage lesion will also happen during the storage of whole blood, which is related to the change of RBCs after prolonged storage. The side effect induced by systemic inflammation and acute-phase reaction should be taken into consideration before resuscitation by long-term storage whole blood transfusion.
Mimecan Regulates Corticosterone Secretion and Plays A Critical Role in Adrenal Responses to Stress
Authors: Su Bin , Zhang Qianyue , Li Xuesong , Yu Huimin , Li Ping , Ma Junhua , Cao Huangming , Sun Fei , Zhao Shuangxia , Zheng Cuixia , Ru Ying , Song Huaidong
Published: September 2020

Background: A functional hypothalamic-pituitary-adrenal (HPA) axis is critical for host defenses to outside stimuli. The adrenal cortex is seemingly endowed with distinct functional units that are regulated by adrenocorticotropic hormone (ACTH). We have found that mimecan, a small leucine-rich proteoglycan expressed in the adrenal gland, has yet to be characterized in functional terms.Results: Herein, we have demonstrated the following properties: 1) adrenal mimecan expression in mouse models is significantly downregulated under hypoglycemia and scalded stress; 2) expression of mimecan in adrenal cells may be downregulated through ACTH or upregulated by glucocorticoid via related receptors (GRs); and 3) mimecan stimulates corticosterone secretion in adrenal tissues. The latter was proven using in vivo and in vitro studies to confirm the ACTH-independent activity of mimecan-maltose-binding protein (-MBP). Relative to litter-mate mice, the basal-state diurnal rhythm of corticosterone secretion is disrupted in mimecan knockout mice, and corticosterone secretion is increased under restraint stress conditions. Conclusions: These findings offer the first evidence that mimecan is key in regulating the HPA axis, assuming a critical role in adrenal responses to stress.
Single cell transcriptomics of human PINK1 iPSC differentiation dynamics reveal a core network of Parkinson’s disease
Authors: Novak Gabriela , Kyriakis Dimitrios , Grzyb Kamil , Bernini Michela , Finkbeiner Steven , Skupin Alexander
Published: September 2020

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The heterogenous pathology and complex underlying mechanisms are only partly understood and there is no treatment able to reverse PD progression. Here, we targeted the disease mechanisms by focusing on the ILE368ASN mutation within the PINK1 (PARK6) gene and systematically characterized midbrain dopaminergic neurons obtained from human induced pluripotent stem cells (iPSCs). Single-cell RNA sequencing (RNAseq) and pairwise analysis of gene expression identified genes consistently differentially expressed during the mDA neuron differentiation process. Subsequent network analysis revealed that these genes form a core network, which interacts with all known 19 protein-coding Parkinson’s disease-associated genes and includes ubiquitination, mitochondrial, protein processing, RNA metabolism, and secretory pathways as important subnetworks. Our findings indicate a unified network underlying PD pathology and offers new interpretation of the phenotypic heterogeneity of PD.
Neuronal signature of an antipsychotic response
Authors: Parrilla-Carrero Jeffrey , Kruyer Anna , Chalhoub Reda M. , Powell Courtney , Resendez Shanna , Amato Davide
Published: September 2020

D2 receptor blockade has been cited as a principal mechanism of action of all antipsychotic medications, but is poorly predictive of symptom improvement or neurophysiological responses recorded using human brain imaging. A potential hurdle in interpreting such human imaging studies arises from the inability to distinguish activity within neuronal subcircuits. We used single cell resolution imaging to record activity in distinct populations of medium spiny neurons in vivo within the mouse ventral striatum, a structure associated with schizophrenia symptoms and antipsychotic therapeutic efficacy. While we expected the antipsychotic haloperidol to excite D2 receptor expressing neurons, we report a strong cellular depression mediated by the hypofunctional NMDA channel, which may be mediated in part by the action of haloperidol on the sigma1 receptor. Altogether, the impact of haloperidol on Ca2+ events in D2 receptor expressing neurons predicted psychomotor inhibition. Our results elucidate mechanisms by which antipsychotics act rapidly in the brain to impact psychomotor outputs.
Long-Term Prognosis of Short QT Interval in Asian Patients: Multicenter Retrospective Cohort Study
Authors: Kim Dae-Young , Uhm Jae-Sun , Kim Min , Kim In-Soo , Jin Moo-Nyun , Yu Hee Tae , Kim Tae-Hoon , Kim Jong-Youn , Joung Boyoung , Pak Hui-Nam , Lee Moon-Hyoung
Published: September 2020

Background: Short QT syndrome is a rare, inherited channelopathy associated with sudden cardiac arrest (SCA) but characteristics and prognosis of short QT interval (SQTI) in Asian patients remain unclear. This study aimed to determine clinical characteristics of and outcomes in patients with SQTI in an Asian population.Methods: Consecutive patients with SQTI were recruited. SQTI was defined as a Bazett’s formula-corrected QT interval (QTc) ≤340 ms in serial electrocardiograms. Age- and sex-matched patients with a normal QTc and without overt cardiovascular disease were included at a 1:4 ratio. Clinical and ECG features and outcomes were compared between patients with and without SQTI. Results: Thirty-four patients with SQTI [age, 23.5 (21–30.5) years; 31 male] were followed up for 4.8 (2.0–7.8) years. Early repolarization, tall T wave, and U wave were significantly more frequent in patients with SQTI than the patients without SQTI. QT dispersion [44.0 (28.0–73.0) vs. 20.0 (12.0–35.0) ms, P<0.001] was significantly wider and heart rate [52.0 (47.0–58.0) vs. 70.0 (62.3–84.0) /min, P<0.001] was significantly slower in patients with SQTI than patients without SQTI. Atrial fibrillation (AF, 11.8% vs. 2.2%, P=0.030) and ventricular arrhythmia (VA)/SCA (8.7% vs 0%, P=0.007) were significantly more frequent in patients with SQTI than patients without SQTI. SQTI was significantly associated with AF [odds ratio, 5.911; 95% confidence interval, 1.257–27.808; P=0.025] and VA/SCA.Conclusions: In this Asian population, SQTI was associated with AF and VA/SCA.
Comparative physicochemical and evolutionary study of SARS-CoV-2 and SARS with special reference to salt bridge and their microenvironment: A plausible explanation for divergency, stability and severity of SARS-CoV-2
Authors: Mitra Debanjan , Pal Aditya K. , Mohapatra Pradeep Kumar Das
Published: September 2020

The occurrence of concentrated pneumonia cases in Wuhan city, Hubei province of China was first reported on December 30, 2019. Currently, it is known as COVID 19 and now it is a nightmare for the whole world. SARS CoV first reported in 2002, but not spread worldwide. After 18 years, in 2020 it reappears and spread worldwide as SARS-CoV-2 (COVID 19), the most dangerous virus creating disease in the world. Is it possible to create a favorable evolution within this short time? If possible, then what are those properties that are changed in SARS-CoV-2 to make it undefeated? What are the basic differences between SARS-CoV-2 and SARS? This study will find all those queries. Here, all protein sequences of SARS-CoV-2 and SARS are retrieved from the database to check their physicochemical, evolutionary and structural properties. Results showed that, charged residues are playing a key role in SARS-CoV-2 evolution. SARS-CoV-2 increases its polarity by the help of charged residues, not by the polar residues. Their divergence is also strictly restricted. Induction of salt bridges with their high energies makes it very stable in any extreme conditions. Microenvironment residues also play a very crucial role in its stability. Mostly residues are favorable and contribute high energies. These microenvironment residues help in protein engineering to reduce its stability and make them week. This comparative study will help to understand the evolution from SARS to SARS-CoV-2.
Hybrid Carcinoma of The Parotid Gland: A Report of Three Extremely Rare Cases with An Immunohistochemical Analysis and A Review of The Literature
Authors: Kusafuka Kimihide , Yamashita Masaru , Yamanaka Shoji , HIrata Kazuki , Kubota Aki , Murakami Akinori , Muramatsu Aya , Arai Kazumori , Suzuki Makoto
Published: September 2020

Background: Hybrid carcinoma (HC) of the salivary glands is defined as when two or more kinds of carcinoma exist at the same location in a single mass. Herein, we report 3 rare cases of salivary gland HC. Case Presentation: Case 1 involved an 86-year-old Japanese male. Case 2 involved a 70-year-old Japanese female. Case 3 involved a 66-year-old Japanese male. Histologically, case 1 involved a combination of salivary duct carcinoma (SDC) and squamous cell carcinoma (SqCC). Immunostaining indicated that the former was positive for gross cystic disease fluid protein (GCDFP)-15 and androgen receptor (AR), whereas the latter expressed cytokeratin (CK) 5/6 and p63. Case 2 involved a combination of SqCC and neuroendocrine carcinoma (NEC). Immunostaining indicated that the former was positive for CK5/6 and p40, whereas the latter was positive for synaptophysin and neural cell adhesion molecule. Case 3 involved a combination of SDC and epithelial-myoepithelial carcinoma (EMC). Immunostaining indicated that the former was positive for GCDFP-15 and AR, whereas the inner cells of the latter were positive for CK7, and the outer cells of the latter were positive for alpha-smooth muscle actin and p40. A transitional zone between the SDC and EMC existed in case 3. Conclusions: Therefore, we diagnosed them as parotid gland HC. This is the first report of a case of HC involving a combination of NEC and SqCC. In case 3, it was speculated that high-grade SDC arose from low-grade EMC. However, as HC is different from carcinoma with high-grade transformation, HC should be diagnosed carefully.
Identification and Validation of RNA Binding Protein-associated Prognostic Model for Neuroblastoma
Authors: YANG JUN , Zhou Jiaying , Li Cuili , Wang Shaohua
Published: September 2020

Background: The abnormal expression of RNA binding protein (RBP) may be related to the development and progress of cancer. However, little is known about the mechanism of RBP in neuroblastoma (NB). Methods: We downloaded the RNA expression data of NB and normal nervous tissues from the (TARGET) database and GTEx database, and determined the differential expression of RBP between normal and cancerous tissues. Then the function and prognostic value of these RBPs were systematically studied. Results: A total of 348 differentially expressed RBPs were identified, together with 166 up-regulated RBPs and 182 down-regulated RBPs. Two hub RBPs (CPEB3 and CTU1) were identified as prognostic-related genes and chose to build prognostic risk score models. Further analysis showed that based on this model, the overall survival rate of patients in the high-risk subgroup was lower (P=2.152e-04). The area under the curve(AUC) of the receiver-operator characteristic curve(ROC) of the prognostic model is 0.720 in the TARGET cohort. There is a significant difference in the survival rate of patients in the high and low risk subgroups in the validation data set GSE85047 (P = 0.1237e-08), the AUC is 0.730. Conclusions: RNA binding protein (CPEB3 and CTU1) can be used as molecular markers of NB.
USP39 Promotes Malignant Proliferation and Angiogenesis of Renal Cell Carcinoma by Inhibiting VEGF-A Alternative Splicing
Authors: Pan Xiu-wu , Xu Da , Chen Wenjin , Chen Jia-xin , Ye Jian-qing , Gan Si-shun , Zhou Wang , Xu Song , Shi Lei , Cui Xingang
Published: September 2020

Objective: To investigate the function and mechanism of USP39 in promoting malignant proliferation and angiogenesis of RCC.Methods: We applied ONCOMINE database to analyze the correlation between USP39 expression level and the clinical characteristics of RCC. The effect of USP39 on RCC was evaluated by MTT assay, cell cycle analysis, colony formation assay and tubule formation assay. The interaction between USP39 and VEGF-A alternative splicing was assessed by co-immunoprecipitation and Western blot assays. Results: The mRNA expression level of USP39 in RCC was significantly higher than that in normal renal tissue (P<0.001), and negatively correlated with the survival rate of RCC patients (P<0.01). Silencing of USP39 in 786-O and ACHN cells obviously inhibited cell proliferation and colony formation, and induced S phase arrest. USP39 overexpression significantly increased the number of tubules (P<0.05) and branches (P<0.01) formed by HUVEC cells, and USP39 knockdown produced an opposite effect (P<0.05). The USP39 (101-565) fragment directly mediated its binding to SRSF1 and SRPK1, and promoted the phosphorylation of SRSF1 to regulate VEGF-A alternative splicing. USP39 knockdown upregulated the expression of VEGF-A165b, and USP39 overexpression downregulated the expression of VEGF-A165b significantly (both P<0.05).Conclusion: USP39 acted as a pro-tumor factor by motivating the malignant biological processes of RCC, probably through promoting VEGF-A alternative splicing and regulating SRSF1 and SRPK1. USP39 may prove to be a potential therapeutic target for RCC.
Radiomics Model Based on Shear-Wave Elastography Can Predict the Axillary Lymph Node Status in Early-Stage Breast Cancer
Authors: Jiang Meng , Li Chang-Li , Chen Rui-Xue , Tang Shi-Chu , Luo Xiao-Mao , Chuan Zhi-Rui , Lv Wen-Zhi , Cui Xin-Wu , Dietrich Christoph F.
Published: September 2020

Background: Accurate prediction of axillary lymph node (ALN) involvement in early-stage breast cancer is important for determining appropriate axillary treatment and therefore avoiding unnecessary axillary surgery and complications. This study aimed to develop and validate an ultrasound radiomics nomogram for preoperative evaluation of the ALN burden. Methods: Data of 303 patients from Wuhan Tongji Hospital (training cohort) and 130 cases from Hunan Provincial Tumour Hospital (external validation cohort) between Jun 2016 and May 2019 were enrolled. Radiomic features were extracted from shear-wave elastography (SWE) and corresponding B-mode ultrasound (BMUS) images. Then, the minimum redundancy maximum relevance (MRMR) and least absolute shrinkage and selection operator (LASSO) algorithm were used to select ALN status-related features and construct the SWE and BMUS radiomic signatures. Proportional odds ordinal logistic regression was performed using the radiomic signature together with clinical data, and an ordinal nomogram was subsequently developed. We evaluated the performance of the nomogram using C-index, calibration, and compared it with clinical model.Results: Multivariate analysis indicated that SWE signature, US-reported LN status and molecular subtype were independent risk factors associated with ALN status. The radiomics nomogram based on these variables showed good calibration and discrimination in the training set (overall C-index: 0.842; 95%CI, 0.773–0.879) and the validation set (overall C-index: 0.822; 95%CI, 0.765–0.838). For discriminating between disease-free axilla (N0) and any axillary metastasis (N + (≥1)), it achieved C-index of 0.845 (95%CI, 0.777–0.914) for the training cohort and 0.817 (95%CI, 0.769–0.865) for the validation cohort. The tool could also discriminate between low (N + (1–2)) and heavy metastatic burden of ALN (N + (≥3)), with C-index of 0.827 (95%CI, 0.742–0.913) for the training cohort and 0.810 (95%CI, 0.755–0.864) for the validation cohort. Conclusions: The presented radiomics nomogram shows favourable predictive ability for ALN staging in patients with early-stage breast cancer, which could provide incremental information for preoperative decision-making.
MiR-24-3p Attenuates IL-1β-Induced Chondrocyte Injury Associated With Osteoarthritis by Targeting BCL2L12
Authors: Xu Jin , Qian Xiaozhong , Ding Ren
Published: September 2020

Background: Osteoarthritis (OA) is a chronic and degenerative joint disease prevalent in the elderly. MiR-24-3p has been reported to be involved in an OA-resembling environment. However, the functional role and underlying mechanism of miR-24-3p in chondrocyte injury associated with OA remains unknown. Methods: The expression of miR-24-3p was determined in OA cases and control patients, as well as IL-1β-stimulated chondrocyte cell line CHON-001 using reverse transcription quantitative PCR analysis. Cell viability was analyzed by CCK-8 assay. Apoptosis status was assessed by caspase-3 activity detection. The pro-inflammatory cytokines (TNF-α and IL-18) were determined using ELISA assay. The association between miR-24-3p and BCL2L12 was confirmed by luciferase reporter assay.Results: We first observed that miR-24-3p expression level was lower in the OA cases than in the control patients and IL-1β decreased the expression of miR-24-3p in the chondrocyte CHON-001. Functionally, overexpression of miR-24-3p significantly attenuated IL-1β-induced chondrocyte injury, as reflected by increased cell viability, decreased caspase-3 activity, pro-inflammatory cytokines (TNF-α and IL-18). Western blot analysis showed that overexpression of miR-24-3p weakened IL-1β-induced cartilage degradation, as reflected by reduction of MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs-5) protein expression, as well as markedly elevation of COL2A1 (collagen type II). Importantly, BCL2L12 was demonstrated to be a target of miR-24-3p. BCL2L12 knockdown imitated, while overexpression significantly abrogated the protective effects of miR-24-3p against IL-1β-induced chondrocyte injury.Conclusions: In conclusion, our work provides important insight into targeting miR-24-3p/BCL2L12 axis in OA therapy.
Effects of Neonicotinoid Seed Treatments on Phyllosphere and Soil Bacterial Communities Over Time
Authors: Parizadeh Mona , Mimee Benjamin , Kembel Steven W.
Published: September 2020

BackgroundThe phyllosphere and soil are dynamic habitats for microbial communities. Non-pathogenic microbiota, including leaf and soil beneficial bacteria, plays a crucial role in plant growth and health, as well as in soil fertility and organic matter production. In sustainable agriculture, it is important to understand the composition of these bacterial communities, their changes in response to disturbances, and their resilience to agricultural practices. Widespread pesticide application may have had non-target impacts on these beneficial microorganisms. Neonicotinoids are a family of systemic insecticides being vastly used to control soil and foliar pests in recent decades. A few studies have demonstrated the long-term and non-target effects of neonicotinoids on agroecosystem microbiota, but the generality of these findings remains unclear. In this study, we used 16S rRNA gene amplicon sequencing to characterize the effects of neonicotinoid seed treatment on soil and phyllosphere bacterial community diversity, composition and temporal dynamics in a three-year soybean/corn rotation in Quebec, Canada. Results We found that habitat, host species and time are stronger drivers of variation in bacterial composition than neonicotinoid application. They respectively explained 37.3%, 3.2% and 2.9% of the community variation. However, neonicotinoids did have an impact on bacterial community structure, especially on the taxonomic composition of soil communities (2.6%) and over time (2.4%). They also caused a decrease in soil alpha diversity in the middle of the growing season. While the neonicotinoid treatment favored some bacterial genera known as neonicotinoid biodegraders, there was a decline in the relative abundance of some potentially beneficial soil bacteria, such as the plant growth-promoting rhizobacteria and the bacteria involved in the nitrogen cycle, in response to the pesticide application.ConclusionsOur results indicate that neonicotinoids have non-target effects on phyllosphere and soil bacterial communities in a soybean-corn agroecosystem, especially potentially beneficial bacteria that are vital for plant growth and improve soil fertility. Exploring the interactions among bacteria and other organisms, as well as the bacterial functional responses to the pesticide treatment, may enhance our understanding of these non-target effects and help us adapt agricultural practices to control these impacts.
Inter-Rater Agreement and Test-Retest Reliability of the Performance and Fitness (PERF-FIT) Test Battery for Children: A Test for Motor Skill Related Fitness.
Authors: Smits-Engelsman Bouwien , Smit Eline , Doe-Asinyo Rosemary Xorlanyo , Lawerteh Stella Elikplim , Aertssen Wendy , Ferguson Gillian , Jelsma Dorothee L
Published: September 2020

Background: The Performance and Fitness (PERF-FIT) test battery for children is a recently developed, valid assessment tool for measuring motor skill-related physical fitness in 5 to 12-year-old children living in low-income settings. The aim of this study was to determine: (1) inter-rater agreement and (2) test-retest reliability of the PERF-FIT in children from 3 different countries (Ghana, South Africa and the Netherlands). Method: For inter-rater reliability 29 children, (16 boys and 13 girls, 6-10 years) were scored by 2 raters simultaneously. For test–retest reliability 72 children, (33 boys and 39 girls, 5-12 years) performed the test twice, minimally one week and maximally two weeks apart. Relative and absolute reliability indices were calculated. ANOVA was used to examine differences between the three assessor teams in the three countries.Results: The PERF-FIT demonstrated excellent inter-rater reliability (ICC, 0.99) and good test-retest reliability (ICC, ≥ 0.80) for 11 of the 12 tasks. a poor ICC was found for the Jumping item only, due to low spread in values. Overall, measurement error, Limits of Agreement and Coefficient of Variation had acceptable levels to support clinical use. No systematic differences were found between first and second measurement between the three countries but for one item (Overhead throw). Conclusions: The PERF-FIT can reliably measure motor skill related fitness in 5 to 12-year-old children in different settings and help clinicians monitor levels of power and agility, and fundamental motor skills (throwing, bouncing, catching, jumping, hopping and balance).
Impact of Host Genetics on Caecal Microbiota Composition and on Salmonella Carriage in Chicken
Authors: Cazals Anaïs , ESTELLÉ Jordi , BRUNEAU Nicolas , COVILLE Jean-Luc , MENANTEAU Pierrette , ROSSIGNOL Marie-Noëlle , JARDET Deborah , BEVILACQUA Claudia , RAU Andrea , BED’HOM Bertrand , VELGE Philippe , CALENGE Fanny
Published: September 2020

Background Salmonella Enteritidis (SE) is one of the major causes of human foodborne intoxication through the consumption of contaminated poultry products. Genetic selection of animals more resistant to Salmonella carriage and the modulation of gut microbiota are two promising ways of decreasing individual Salmonella carriage. This study aims to identify the main genetic and microbial factors controlling the individual levels of Salmonella carriage in chickens (Gallus gallus) in controlled experimental conditions. Two-hundred and forty animals from the White Leghorn inbred lines, N and 61, were infected by SE at 7 days of age. After infection, animals were kept in isolators to reduce the recontamination of birds by Salmonella. Caecal contents were sampled at 12 days post-infection and used for DNA extraction. Microbiota DNA was used to measure individual counts of SE by digital PCR and to determine the bacterial taxonomic composition through a 16S rRNA gene high-throughput sequencing approach. Results Results confirmed that the N line is more resistant to Salmonella carriage than the 61 line, and that intra-line variability is higher for the 61 line. Furthermore, the 16S analysis showed strong significant differences in microbiota taxonomic composition between the two lines. Out of 617 Operational Taxonomic Units (OTUs), over 390 were differentially abundant between the two lines. Furthermore, within the 61 line, we found a difference in the microbiota taxonomic composition between high and low Salmonella carriers, with 39 differentially abundant OTUs. Finally, via metagenome functional prediction based on 16S data, we identified several metabolic pathways potentially associated to microbiota taxonomic differences (e.g. butyrate metabolism) between high and low carriers. Conclusions Overall, this study demonstrates that the caecal microbiota composition of the N and 61 lines is influenced by the host genetics, which could be one of the reasons why these lines differ for their Salmonella carriage in experimental infection conditions.
The Study of Diagnostic Value of Bipolarity Index for Bipolar Disorder in China: Meta-analysis of Sensitivity and Specificity
Authors: Sun Fengli , Jianfeng Zhu , Hejian Tao , Weidong Jin
Published: September 2020

BackgroundThe diagnosis of bipolar disorder is still one of the key problems in psychiatric clinic. Although DSM-5 has made some important changes, it has not completely changed the missed diagnosis and misdiagnosis of bipolar disorder.It was very important that diagnostic scale was used in clinic.But the study results of assist diagnostic scale for bipolar disorder should been concluded and analyzed.Bipolarity index was one of assist diagnostic scale,which should be analyzed comprehensively.MethodsWe searched CBM, CNKI , WANFANG and CSSCI in Chinese to find literature from Julyr 31 2004 to July 31 2020 related to Bipolarity Index in diagnosis for bipolar disorder ,among which results such as comments, letters, reviews and case reports were excluded. The rate of sensitivity,specificity,accuracy,positive predictive value and negative predictive value in diagnosis was synthesized and discussed.ResultsA total of 1237 subjects were included in 5 studies. Random effect model is used to account for the data by Revman 5.2. The results showed that the sensitivity of BI in diagnostic was 0.93 (95% CI: 0.93–1.00), the specificity was 85% (95% CI: 0.69–0.96). the positive predict value was 74% (95% CI: 0.53–0.91).the negative predict value was 95% (95% CI: 0.81–1.00).and accuracy was 86% (95% CI: 0.77–0.93). Significant heterogeneity was detected across studies regarding these incidence estimates. ConclusionThe idea diagnostic value of BI was found. although the significant heterogeneity detected in studies.We must interpret the results with caution and also put attention to this result,which include comparison to other diagnostic scale,perfecting sue of BI in clinical psychiatry.
WITHDRAWN: Angelica Sinensis Extract Protects Against Memory Deficits by Promoting P38 MAPK–mediated Hippocampal Neurogenesis and Neuronal Survival in the Chronic Phase of Transient Global Cerebral Ischemia in Rats
Authors: Lee Yu-Chen , Huang Hui-Chi , Kao Shung-Te , Cheng Chin-Yi
Published: September 2020

Background: Reversible cardiac arrest and diseases related to reduced blood flow to the brain cause transient global cerebral ischemia (GCI), which may induce long-term cognitive deficits. In addition, hippocampal cornu ammonis 1 (CA1) pyramidal neurons are selectively vulnerable to ischemic insults and play an important role in memory. This study aimed to determine the effects of the Angelica sinensis (Oliv.) Diels (ASD) extract on ischemia-induced memory deficits at 28 d after transient global cerebral ischemia (GCI) and to investigate the precise mechanisms underlying the p38 mitogen-activated protein kinase (MAPK)-related signaling pathway’s involvement in hippocampal neurogenesis. Rats underwent 25 min of four-vessel occlusion. The ASD extract was intragastrically administered at doses of 0.25 g/kg (ASD-0.25 g), 0.5 g/kg (ASD-0.5 g), 1 g/kg (ASD-1 g), 1 g/kg after dimethyl sulfoxide administration (D+ASD-1 g), or 1 g/kg after SB203580 (a p38 MAPK inhibitor) administration (SB+ASD-1 g) at 1, 3, 7, 10, 14, 17, 21, and 24 d after transient GCI. Results: ASD-0.5 g, ASD-1 g, and D+ASD-1 g treatments effectively attenuated memory deficits and had the following effects: upregulation of bromodeoxyuridine (BrdU) and Ki67 expression, and BrdU/neuronal nuclei (NeuN) co-expression in the hippocampal dentate gyrus (DG); upregulation of microtubule-associated protein 2 /NeuN co-expression in the hippocampal CA1 region; upregulation of phospho-p38 MAPK (p-p38 MAPK), phospho-cAMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor A (VEGF-A) expression in the hippocampus. Furthermore, most BrdU-positive cells colocalized with NeuN and Ki67 in the hippocampal DG. SB+ASD-1 g treatment abrogated the effects of ASD-1 g on the expression of these proteins and exacerbated memory deficits. Conclusion: ASD-0.5 g and ASD-1 g treatments provided neuroprotective effects against memory deficits by enhancing hippocampal neurogenesis and dendritic stability. The effects of the ASD extract on hippocampal neurogenesis and neuronal survival are caused by the activation of p38 MAPK–mediated CREB/BDNF, GDNF, and VEGF-A signaling pathways in the hippocampus at 28 d after transient GCI.
Factors Associated With Bone Health Status of Malaysian Pre-adolescent Children in the PREBONE-kids Study
Authors: Chang Chung Yuan , Arasu Kanimolli , Wong Soon Yee , Ong Shu Hwa , Yang Wai Yew , Chong Megan Hueh Zan , Mavinkurve Meenal , Khoo Erwin Jiayuan , Chinna Karuthan , Weaver Connie M. , Chee Winnie Siew Swee
Published: September 2020

Background: Modifiable lifestyle factors and body composition can affect the attainment of peak bone mass during childhood. This study performed a cross-sectional analysis of the determinants of bone health among pre-adolescent Malaysian children with habitually low calcium intakes and vitamin D status in Kuala Lumpur (PREBONE-Kids Study). Methods: Body composition, bone mineral density (BMD), and bone mineral content (BMC) at the lumbar spine (LS) and total body (TB) were assessed using dual-energy X-ray absorptiometry (DXA). Calcium intake was assessed using 1-week diet history, MET (metabolic equivalent of task) score using cPAQ questionnaire, and serum 25(OH) vitamin D using LC-MS/MS. Results: The mean calcium intake was 348.8 ± 180.1 mg/day and mean serum 25-OH vitamin D level was 43.9 ± 14.5nmol/L. In boys, lean mass (LM) was significantly associated with LSBMC (β = 0.539, p<0.001), LSBMD (β=0.607, p<0.001), TBBMC (β=0.675, p<0.001) and TBBMD (β= 0.481, p<0.01). Height was significantly associated with LSBMC (β =0.346, p<0.001) and TBBMC (β =0.282, p<0.001) while fat mass (FM) (β=0.261, p=0.034) and MET score (β =0.163, p=0.026) were significant predictors of TBBMD. Among girls, LM was significantly associated with LSBMC (β = 0.620, p<0.001), LSBMD (β=0.700, p<0.001), TBBMC (β=0.542, p<0.001) and TBBMD (β= 0.747, p<0.001). Calcium intake was a significant predictor of LSBMC (β=0.102, p=0.034), TBBMC (β=0.122, p<0.001) and TBBMD (β=0.196, p=0.002) in girls. Lean mass (LM) was weakly correlated with MET scores (r = 0.205, p = 0.001) but not protein (r = 0.055, p = 0.393) or energy intake (r = 0.101, p = 0.117). MET score (β = 0.207, p = 0.043) was a significant predictor of LM in boys but no factor was found to predict LM in girls. Conclusion: LM is the major determinant of BMC and BMD among pre-adolescent Malaysian children and physical activity is a significant predictor of LM in boys. Encouraging physical activity, calcium intake and optimum diets that build lean body mass should be the focus for developing public health guidance to ensure optimal bone health status during rapid growth.