bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of a sensitive and specific lead biosensor using a genetically engineered bacterial system with a luciferase gene reporter controlled by pbr and cadA promoters
Authors: Nourmohammadi Esmail , Hosseinkhani Saman , Nedaeinia Reza , Khoshdel-Sarkarizi Hoda , Nedaeinia Mozhdeh , Ranjbar Maryam , Ebrahimi Neshat , Farjami Zahra , Nourmohammadi Mohammad , Mahmoudi Ali , Goli Mohammad , A.Ferns Gordon , Sadeghizadeh Majid
Published: September 2020

Background: A bacterial biosensor refers to genetically engineered bacteria that produce an assessable signal in the presence of a physical or chemical agent in the environment. Methods: We have designed and evaluated a bacterial biosensor expressing a luciferase-reporter gene controlled by pbr and cadA promoters in Cupriavidus metallidurans (previously termed Ralstonia metallidurans) containing the CH34 and pI258 plasmids of Staphylococcus aureus, respectively, and that can be used for the detection of heavy metals. In the present study, we have produced and evaluated biosensor plasmids designated pGL3-luc/pbr-biosensor and pGL3-luc/cad-biosensor, that were based on the expression of luc+ and under the control of the cad promoter and the cadC gene of S. aureus plasmid pI258 and pbr promoter and pbrR gene from plasmid pMOL30 of Cupriavidus metallidurans. Results: We found that the pGL3-luc/pbr-biosensor may be used to measure lead concentrations between 1-100 μM in the presence of other metals, including: zinc, cadmium, tin and nickel. The latter metals did not result in any significant signal. The pGL3-luc/cad-biosensor could detect lead concentrations between 10 nM to 10 μM. Conclusions: This biosensor was found to be a specific for measuring lead ions in both environmental and biological samples.
Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction
Authors: Wang Hao , Lu Hao , Zhang Xiao-Meng , Goto Ken-ichiro , Kobayashi Eiichi , Yoshida Yoichi , Adachi Akihiko , Matsutani Tomoo , Iwadate Yasuo , Min Seiichiro , Machida Toshio , Sata Mizuki , Yamagishi Kazumasa , Iso Hiroyasu , Sawada Norie , Tsugane Shoichiro , Kamitsukasa Ikuo , Wada Takeshi , Aotsuka Akiyo , Sugimoto Kazuo , Takizawa Hirotaka , Kashiwado Koichi , Shin Hideo , Tomiyoshi Go , Nakamura Rika , Shinmen Natsuko , Kuroda Hideyuki , Xu Anding , Hiwasa Takaki
Published: September 2020

Background: Ischemic stroke, such as transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI) , are the serious problems in the aging society. Therefore, development of biomarkers for TIA and aCI are attempted. Methods: Candidate antigens recognized by IgG autoantibodies in the serum of 19 TIA patients were screened by a human aortic endothelial cell cDNA library. Serum antibody levels against the antigens were examined by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in healthy donor (HD), TIA, and aCI cohorts ( n = 285, 92 and 529). The antibody levels in the sera of the Japan Public Health Center-based Prospective Cohort Study (JPHC) from 1991 to 1993 was also examined. Results: Aldolase A, fructose-bisphosphate (ALDOA) and fumarate hydratase (FH) were identified as the candidate antigens. AlphaLISA revealed that the levels of anti-ALDOA antibodies (ALDOA-Abs) and anti-FH antibodies (FH-Abs) were both higher in patients with TIA or aCI than those in HDs ( P < 0.05). The levels of ALDOA-Abs [odds ratio (OR): 2.46, P = 0.0050] and FH-Abs (OR: 2.49, P = 0.0037) were independent predictors of TIA by multivariate logistic regression analysis. The case-control study showed the levels of ALDOA-Abs (OR: 2.50, P < 0.01) and FH-abs (OR: 2.60, P < 0.01) were associated with risk of aCI. Correlation analysis demonstrated that both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease and habitual smoking. These antibody levels were also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis. Conclusions: ALDOA-Abs and FH-Abs can serve as novel potential biomarkers for prediction of atherosclerotic TIA and aCI.
Intralipid postconditioning in patients of Cardiac surgery undergoing cardioPulmonary Bypass (iCPB): study protocol for a randomized controlled trial
Authors: Yuan Yuan , Xiong Hui , Zhang Yan , Yu Hong , Zhou Rong-Hua
Published: September 2020

Background

Intralipid is a necessary fatty acid carrier that has been safely used as an energy supplier in the clinic. It has played an important role in rescuing the cardiac arrest caused by local anesthetic toxicity. In recent years, experimental studies have shown that intralipid postconditioning (ILPC) could reduce myocardial ischemic/reperfusion (I/R) injuries. Our research group has innovatively conducted a pilot randomized controlled trial (RCT) and the results showed that ILPC could reduce the release of cTnT and CK-MB, biomarkers of myocardial I/R injury, in valve replacement surgery. However, the potential effects of ILPC on the clinical outcome of adult cardiac surgery patients are unclear. Intralipid postconditioning in patients of cardiac surgery undergoing cardiopulmonary bypass (iCPB) trial is aimed to further study whether ILPC could improve short-term and long-term clinical outcome, as well as cardiac function in adult cardiac surgery patients.

Methods

The iCPB trial is an ongoing, single-center, prospective, double blinded, large sample RCT. In total, 1000 adults undergoing cardiac surgery will be randomly allocated to either ILPC group or the control group. Intervention group received an intravenous infusion of 2 mL/kg of 20% intralipid (medium-chain and long-chain fat emulsion injection C6~C24, Pharmaceutical) within 10 minutes before aortic cross-unclamping, and the control group received an equivalent volume of normal saline. The primary endpoints are complex morbidity of major complications during hospitalization, and all-cause mortality within 30 days after surgery. The secondary endpoints include: (1) all-cause mortality 6 months and 1 year postoperatively, (2) the quality of life within 1 year after surgery,using QoR-15 questionnaire, (3) the postoperative cardiac function evaluated by LVEF, LVEDs, LVEDD, and the myocardial injury evaluated by CK-MB, cTnT, BNP, (4) short-term clinical outcomes during hospitalization and total cost are also detailed evaluated.

Discussion

The iCPB trial is the first to explore ILPC on the clinical outcome of adult cardiac surgery patients. The results are expected to provide potential evidences about whether ILPC could reduce the morbidity and mortality, improve the cardiac function and quality of life. Therefore, provide a rationale for the evaluation of the potentially clinically relevant benefit of intralipid therapy.
Safety of bronchoscopy in patients with malignant hematologic disorders
Authors: Uruga Hironori , Sato Toshitaka , Nishida Aya , Uchida Naoyuki , Tsuji Masanori , Moriguchi Shuhei , Takahashi Yui , Ogawa Kazumasa , Murase Kyoko , Hanada Shigeo , Takaya Hisashi , Miyamoto Atsushi , Morokawa Nasa , Kimura Muneyoshi , Araoka Hideki , Tsuchihashi Rumiko , Asano-Mori Yuki , Wake Atsushi , Taniguchi Shuichi , Kishi Kazuma
Published: September 2020

Background: Factors affecting the safety of bronchoscopy in patients with malignant hematologic disorders have not been well described. We evaluated the safety of bronchoscopy and describe factors affecting its complication rate in such patients.Methods: Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with malignant hematologic disorders and pulmonary infiltrates were performed at our institution. The bronchoscopic procedure used and its complications were evaluated.Results: The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Thirty-five bronchoscopies (11.1%) were complicated by hemoptysis and 7 patients developed pneumothorax, 4 of whom required thoracic drainage. Two patients (0.6%) were intubated within 48 hours of the procedure and prolonged oxygen desaturation (>48 hours) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation (hazard ratio 0.28, 95% confidence interval 0.09–0.85, p = 0.03). Transbronchial lung biopsy significantly increased the risk of hemoptysis (hazard ratio 10.40, 95% confidence interval 4.18–25.90, p = 0.00), while use of midazolam significantly reduced the risk (hazard ratio 0.31, 95% confidence interval 0.14–0.73, p = 0.01).Conclusions: Bronchoscopy is relatively safe in patients with malignant hematologic disorders. Caution and judicious use of sedatives may improve the patient's procedural tolerance and lower complications.
LncRNA SNHG10 is downregulated in non-small cell lung cancer and predicts poor survival
Authors: Liang Meng , Wang Linlin , Cao Chuanhua , Song Shimao , wu feng
Published: September 2020

Background: LncRNA SNHG10 has been reported to be an oncogenic lncRNA in liver cancer. However, its roles in non-small cell lung cancer (NSCLC) remains unknown. Methods: Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. RT-qPCR was used to detect the expression of SNHG10 and miR-21 in tissues. Overexpression experiments were used to evaluate the interaction between SNHG10 and miR-21 in NSCLC cells. CCK-8 assay was used to detect the cell proliferation. Results: We observed the expression of SNHG10 was down-regulated in non-small cell lung cancer (NSCLC) compared with that in non-tumor tissues. Moreover, we found that high expression levels of SNHG10 predicted favorable survival of NSCLC patients, and the expression of miR-21 were increased in NSCLC and inversely correlated with SNHG10 expression. In NSCLC cells, overexpression of SNHG10 resulted in increased miR-21 gene methylation and decreased miR-21 expression. Moreover, overexpression of SNHG10 attenuated the enhancing effect of miR-21 overexpression on cell proliferation. Conclusions: SNHG10 may involve in NSCLC cell proliferation by regulating the miR-21 gene methylation.
Maternal Sciatic Nerve Administered Bupivacaine Induces Hippocampal Cell Apoptosis in Offspring
Authors: Mirkheshti Alireza , Shakeri Alireza , Memary Elham , Baniasadi Mansoureh , Zaringhalam Jalal , Tajbakhsh Ardeshir , Mirzaei Marzieh , Lak Elena
Published: September 2020

Background: Bupivacaine, an amid-type local anesthetic, is widely used for clinical patients especially in pregnant women. In addition to neurotoxicity effect of bupivacaine, it can cross the placenta, accumulates in this tissue and retained in fetal tissues. Nevertheless, whether bupivacaine can cause neurotoxicity in fetus remains unclear. Hence, this study was design to investigate the effects of maternal bupivacaine use on fetus hippocampal cell apoptosis and the possible related mechanism.Methods: On day 15 of pregnancy, sciatic nerve of pregnant wistar rat (180-200 g) were exposed by lateral incision of the right thigh and 0.2 ml of bupivacaine was injected. After their delivery, we randomly selected one male offspring of every mother. On day 30 after of their birth, the rat’s hippocampi were isolated for molecular studies. Western blotting was used to examine the expression of cleaved caspase-3, caspase-8 and p-Akt in fetal hippocampus.Results: Our results showed that maternal bupivacaine use caused a significant increment of cleaved caspase-3 and caspase-8 expression in fetal hippocampus compared with the sham group. In addition, maternally administered bupivacaine could significantly decrease hippocampal P.Akt/T.Akt ratio which was concurrent with an increment of cleaved caspase-3 and caspase-8 expression. Conclusion: Our data suggest that maternal bupivacaine use increases fetal hippocampal cell apoptosis markers such as caspase 8 and cleaved caspase 3, at least in part, via inhibiting the Akt activation.
The short-term effectiveness of precise safety decompression via double percutaneous lumbar foraminoplasty and percutaneous endoscopic lumbar decompression for lumbar lateral spinal canal (LLSC) stenosis
Authors: Wang Yu , Deng Mingyan , Wu Hao , Wu Ye , Guo Chuan , Zhang Dongfeng , Kong Qingquan
Published: September 2020

Purpose: This prospective study reports on a new technique, namely precise safety decompression via double percutaneous lumbar foraminoplasty (DPLF) and percutaneous endoscopic lumbar decompression (PELD) for lateral lumbar spinal canal (LLSC) stenosis, and its short-term clinical outcomes.Methods: The study analyzed 69 patients with single-level LLSC stenosis simultaneously occurring in both zones 1 and 2 (defined as retrodiscal space and upper bony lateral recess respectively by new LLSC classification) who underwent DPLF–PELD from November 2018 to April 2019. Clinical outcomes were evaluated according to preoperative, three months postoperatively, and last follow-up, via leg pain/low back pain (LBP) visual analog scale (VAS) scores, Oswestry disability index (ODI) scores, and the Macnab criteria. The postoperative MRI and CT were used to confirm the complete decompression, and flexion-extension x-rays at the last follow-up were used to observe lumbar stability.Results: All patients successfully underwent DPLF–PELD, and the stenosis was completely decompressed, confirmed by postoperative MRI and CT. The mean follow-up duration was 13 months (range: 8–17 months). The mean preoperative leg pain VAS score is 7.05 ± 1.04 (range 5–9), which decreased to 1.03 ± 0.79(range: 0–3) at three months postoperatively and to 0.75 ± 0.63 (range: 0–2) by the last follow-up visit(p < 0.05). The mean preoperative ODI was 69.8 ± 9.05 (range: 52–85), which decreased to 20.3 ± 5.52 (range: 10–35) at the third month postoperatively and to 19.6 ± 5.21 (range: 10–34) by the final follow-up visit(p < 0.05). The satisfactory (excellent or good) results were 94.2%. There was one patient with aggravated symptoms, which were relieved after an open surgery. Two patients had a dural tear, and two patients suffered postoperative LBP. No recurrence or segmental instability was observed at the final follow-up.Conclusion: DPLF–PELD could be a good alternative for the treatment of LLSC stenosis patients whose stenosis occurred in both zones 1 and 2.
Shotgun proteomics of peach fruit reveals major metabolic pathways associated to ripening
Authors: Nilo-Poyanco Ricardo , Moraga Carol , Benedetto Gianfranco , Orellana Ariel , Almeida Andréa Miyasaka
Published: September 2020

BackgroundFruit ripening in Prunus persica melting varieties involves several physiological changes that have a direct impact on the fruit organoleptic quality and storage potential. By studying the proteomic differences between the mesocarp of mature and ripe fruit, it would be possible to highlight critical molecular processes involved in the fruit ripening.ResultsTo accomplish this goal, the proteome from mature and ripe fruit was assessed from the variety O’Henry through shotgun proteomics using 1D-gel (PAGE-SDS) as fractionation method followed by LC/MS-MS analysis. Data from the 131,435 spectra could be matched to 2,740 proteins, using the peach genome reference v1. After data pre-treatment, 1,663 proteins could be used for comparison with datasets assessed using transcriptomic approaches and for quantitative protein accumulation analysis. Close to 26% of the genes that code for the proteins assessed displayed higher expression at ripe fruit compared to other fruit developmental stages, based on published transcriptomic data. Differential accumulation analysis between mature and ripe fruit revealed that 15% of the proteins identified were modulated by the ripening process, with glycogen and isocitrate metabolism, and protein localization overrepresented in mature fruit, as well as cell wall modification in ripe fruit. Potential biomarkers for the ripening process, due to their differential accumulation and gene expression pattern, included a pectin methylesterase inhibitor, a gibbellerin 2-beta-dioxygenase, an omega-6 fatty acid desaturase, a homeobox-leucine zipper protein and an ACC oxidase. Transcription factors enriched in NAC and Myb protein domains would target preferentially the genes encoding proteins more abundant in mature and ripe fruit, respectively.ConclusionsShotgun proteomics is an unbiased approach to get deeper into the proteome allowing to detect differences in protein abundance between samples. This technique provided a resolution so that individual gene products could be identified. Many proteins likely involved in cell wall and sugar metabolism, aroma and color, change their abundance during the transition from mature to ripe fruit.
CT-Guided Hook-Wire Localization of Malignant Pulmonary Nodules for Video Assisted Thoracoscopic Surgery
Authors: Zhang Huijun , Li Ying , Yimin Nadier , He Zelai , Chen Xiaofeng
Published: September 2020

Objectives: Video assisted thoracoscopic surgery (VATS) can currently be used to diagnose and treat pulmonary nodules. However, intraoperative location of pulmonary nodules in VATS is challenging due to their small diameter and deep location in the pulmonary parenchyma. The purpose of this study was to report the clinical safety and effectiveness of CT-guided hook-wire for preoperative localization of malignant pulmonary nodules smaller than 1 cm in diameter.Methods: From February 2017 to January 2018, we collected the data of 80 patients with malignant pulmonary nodules less than 1 cm in diameter who underwent CT-guided hook-wire preoperative localization and VATS surgery. The effectiveness of preoperative localization was evaluated based on surgical duration, success rate of VATS surgery, and localization-related complications.Results: The diameter of pulmonary nodules were 0.85 ± 0.17 mm with a distance to the pleural surface of 19.66 ± 14.10 mm. The length of the hook-wire in the lung parenchyma was 29.17 ± 13.14 mm and hook-wire dislodgement occurred in 2 patients. Complications included 27 cases of minor pneumothorax and 18 cases of mild parenchymal hemorrhage. A significant correlation was observed between the length of the hook-wire in the lung parenchyma and mild parenchymal hemorrhage (P = 0.044). The average time of hook-wire localization was 9.0 ± 2.6 min and the average operation time for VATS was 89.02 ± 23.35 min without conversion thoracotomy.Conclusions: CT-guided hook-wire localization of the lesion during VATS resection is safe for malignant pulmonary nodules with diameter less than 1 cm.
Temporal dynamics of the fecal microbiota in veal calves in a 6-month field trial
Authors: Massot Méril , Haenni Marisa , Nguyen Thu Thuy , Madec Jean-Yves , Mentré France , Denamur Erick
Published: September 2020

Background Little is known about maturation of calves’ gut microbiome in veal farms, in which animals are confined under intensive-farming conditions and the administration of collective antibiotic treatment in feed is common. We conducted a field study on 45 calves starting seven days after their arrival in three veal farms. We collected monthly fecal samples over six months and performed 16S rRNA gene sequencing and quantitative PCR of Escherichia coli to follow the dynamics of their microbiota, including that of their commensal E. coli populations. We used mixed-effect models to characterize the dynamics of α-diversity indices and numbers of E. coli, and searched for an effect of collective antibiotic treatments on the estimated parameters. On two farms, we also searched for associations between recommended daily doses of milk powder and bacterial abundance. Results There was high heterogeneity between calves’ microbiota upon their arrival at the farms, followed by an increase in similarity, starting at the first month. From the second month, 16 genera were detected at each sampling in all calves, representing 67.5% (± 9.9) of their microbiota. Shannon diversity index showed a two-phase increase, an inflection occurring at the end of the first month. Calves receiving antibiotics had a lower intercept estimate for Shannon index (-0.17 CI95%[0.27; -0.06], p = 0.003) and a smaller number of E. coli/ gram of feces during the treatment and in the 15 days following it (-0.37 log10 (E. coli/g) CI95%[-0.66; -0.08], p = 0.01) than unexposed calves. There were moderate to strong positive associations between the dose of milk powder and the relative abundances of the genera Megasphaera, Enterococcus, Dialister and Mitsuokella, and the number of E. coli (rs ≥ 0.40; Bonferroni corrected p < 0.05).Conclusions This observational study shows early convergence of the developing microbiota between veal calves and associations between the dose of milk powder and members of their microbiota. It suggests that administration of collective antibiotic treatment results in a reduction of diversity and size of the E. coli population and highlights the need for additional work to fully understand the impact of antibiotic treatment in the veal industry.
CILP2 overexpression correlates with tumor progression and poor prognosis in patients with colorectal cancer in the study of The Cancer Genome Atlas (TCGA) and our cohort analysis
Authors: Huang Feng , Peng Yuanfei , Ye Qing , Chen Jinhu , Li Yangming , Liu Shengyuan , Xu Yangmei , Huang Lijie
Published: September 2020

Background: Genetic alterations play an important role in the progression of colorectal cancer. Identifying new biomarkers to assess the prognosis of patients with colorectal cancer is critical. Cartilage Intermediate Layer Protein 2 (CILP2) gene, screened from the TCGA database by bioinformatics, may be closely related to the progression of colorectal cancer. CILP2 was barely reported with clinical features of tumors.Materials and methods: Clinical information and RNA-seq data were derived from the TCGA colorectal carcinoma cohort. CILP2 expression at mRNA level was estimated by bioinformatical analysis of TCGA cases. Tissue microarray (TMA) was constructed containing paraffin-embedded 64 pairs of colorectal cancer and matched adjacent normal tissues. The expression at the protein level was detected in 64 pairs of colorectal cancer and matched adjacent normal tissues by immunohistochemical analysis. CILP2 expression level and its clinical value were estimated by bioinformatical analysis with linear and logistic regression. Survival analysis was performed between high and low groups of CILP2 expression by Cox regression analysis, and the P-value was calculated by the log-rank test. Kaplan-Meier curves were tested by the log-rank test.Results: CILP2 was statistically significantly higher expressed in the colorectal cancer tissues when compared with paired adjacent normal tissues in the TCGA cohort (P<0.001) and in the TMA cohort (P=0.001). Also, CILP2 high-expression was strongly correlated with T3/4 stage (P=0.001), N1/2/3 stage (P=0.005), M1 stage (P=0.048), and higher clinical stage (UICC 2010 stage) (P<0.001) in TCGA cohort, and also positively associated with T3/4 stage (P=0.022) and higher clinical stage (UICC 2010 stage) (P=0.03) in TMA cohort. Furthermore, CILP2 overexpression predicted poor prognosis and could be as an independent prognostic factor (P=0.003).Conclusion: We revealed that CILP2 is associated with advanced stages and could play a role as an independent predictor of poor survival in colorectal cancer.
Phase II Multicenter Randomized Controlled Clinical Trial on the Efficacy of Intra-articular Injection of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet Rich Plasma for the Treatment of Knee Osteoarthritis
Authors: Lamo-Espinosa José María , Blanco Juan F. , Sánchez Mikel , Moreno Victoria , Granero-Moltó Froilán , Sánchez-Guijo Fermín , Crespo-Cullel Íñigo , Mora Gonzalo , Vicente Diego Delgado San , Pompei-Fernández Orlando , Aquerreta Jesús Dámaso , Núñez-Córdoba Jorge María , Vitoria María , Valentí-Azcárate Andrés , Andreu Enrique J. , Cañizo María del Consuelo del , Valentí-Nin Juan Ramón , Prósper Felipe
Published: September 2020

Background: Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100x106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial.Methods: A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100x106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage.Results: No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p=0.389) and from 5.3 (1.9) to 3.5 (2.5) (p=0.01), respectively at 12 months.. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p=0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p=0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage.Conclusions: Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23
Application of OU processes to modelling temporal dynamics of the human microbiome, and calculating optimal sampling schemes.
Authors: Kenney Toby , Gao Junqiu , Gu Hong
Published: September 2020

Background:

The vast majority of microbiome research so far has focused on the structure of the microbiome at a single time-point. There have been several studies that measure the microbiome from a particular environment over time. A few models have been developed by extending time series models to accomodate specific features in microbiome data to address questions of stability and interactions of the microbime time series. Most research has observed the stability and mean reversion for some microbiomes. However, little has been done to study the mean reversion rates of these stable microbes and how sampling frequencies are related to such conclusions. In this paper, we begin to rectify this situation. We analyse two widely studied microbial time series data sets on four healthy individuals. We choose to study healthy individuals because we are interested in the baseline temporal dynamics of the microbiome.

Results:

For this analysis, we focus on the temporal dynamics of individual genera, absorbing all interactions in a stochastic term. We use a simple stochastic differential equation models to assess the following three questions. (1) Does the microbiome exhibit temporal continuity? (2) Does the microbiome have a stable state? (3) To better understand the temporal dynamics, how frequently should data be sampled in future studies?

We find that a simple Ornstein-Uhlenbeck model which incorporates both temporal continuity and reversion to a stable state fits the data for almost every genus better than a Brownian motion model that contains only temporal continuity. The Ornstein-Uhlenbeck model also fits the data better than modelling separate time points as independent. Under the Ornstein-Uhlenbeck model, we calculate the variance of the estimated mean reversion rate (the speed with which each genus returns to its stable state). Based on this calculation, we are able to determine the optimal sample schemes for studying temporal dynamics.

Conclusions:

There is evidence of temporal continuity for most genera; there is clear evidence of a stable state; and the optimal sampling frequency for studying temporal dynamics is in the range of one sample every 0.8–3.2 days.
Evaluation of the Effect of Cooled Haemodialysis on cognitive Function in Patients suffering with End-stage Kidney Disease (E-CHECKED): Feasibility Randomised Control Trial Protocol
Authors: Dasgupta Indranil , Odudu Aghogho , Baharani Jyoti , Fergusson Niall , Griffiths Helen , Harrison John , Maruff Paul , Thomas G Neil , Woodhall Gavin , Youssef Samir , Tadros George
Published: September 2020

Background: Cognitive impairment is common in haemodialysis (HD) patients and is associated independently with depression and mortality. This association is poorly understood, and no intervention is proven to slow cognitive decline. There is evidence that cooler dialysis fluid (dialysate) may slow white matter changes in the brain, but no study has investigated the effect of cooler dialysate on cognition. This study addresses whether cooler dialysate can prevent the decline in cognition and improve quality of life (QOL) in HD patients.Methods: This is a multi-site prospective randomised, double-blinded feasibility trial. Setting: Four HD units in the United Kingdom.: Participants and interventions Ninety HD patients randomised (1:1) to standard care (dialysate temperature 36.5C) or intervention (dialysate temperature 35°C) for 12 months. Primary outcome measure: Change in cognition using the Montreal Cognitive Assessment (MoCA). Secondary outcome measures: Recruitment and attrition rates, reasons for non-recruitment, frequency of intradialytic hypotension, depressive symptom scores, patient and carers burden, a detailed computerised cognitive test and QOL assessments. Analysis: mixed method approach, utilising measurement of cognition, questionnaires, physiological measurements and semi-structured interviews.Discussion: The results of this feasibility trial will inform the design of a future adequately powered substantive trial investigating the effect of dialysate cooling on prevention and/ or slowing in cognitive decline in patients undergoing haemodialysis using a computerised battery of neuro-cognitive tests. The main hypothesis that would be tested in this future trial is that patients treated with regular conventional haemodialysis will have a lesser decline in cognitive function and a better quality of life over one year by using cooler dialysis fluid at 35°C, versus a standard dialysis fluid temperature of 36.5°C. This also should reflect in improvements in their abilities for activities of daily living and therefore, reduce carers' burden. If successful, the treatment could be universally applied at no extra cost.Trial registration: ClinicalTrials.gov Identifier: NCT03645733. Registered retrospectively on August 24, 2018.
Deep Learning Accelerators: A Case Study with MAESTRO
Authors: Bolhasani Hamidreza , Jassbi Somayyeh Jafarali
Published: September 2020

In recent years, deep learning has become one of the most important topics in computer sciences. Deep learning is a growing trend in the edge of technology and its applications are now seen in many aspects of our life such as object detection, speech recognition, natural language processing, etc. Currently, almost all major sciences and technologies are benefiting from the advantages of deep learning such as high accuracy, speed and flexibility. Therefore, any efforts in improving performance of related techniques is valuable. Deep learning accelerators are considered as hardware architecture, which are designed and optimized for increasing speed, efficiency and accuracy of computers that are running deep learning algorithms. In this paper, after reviewing some backgrounds on deep learning, a well-known accelerator architecture named MAERI (Multiply-Accumulate Engine with Reconfigurable interconnects) is investigated. Performance of a deep learning task is measured and compared in two different data flow strategies: NLR (No Local Reuse) and NVDLA (NVIDIA Deep Learning Accelerator), using an open source tool called MAESTRO (Modeling Accelerator Efficiency via Spatio-Temporal Resource Occupancy). Measured performance indicators of novel optimized architecture, NVDLA shows higher L1 and L2 computation reuse, and lower total runtime (cycles) in comparison to the other one.
Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis
Authors: Florholmen Jon R. , Johnsen Kay-Martin , Renate Meyer , Olsen Trine , Moe Øystein Kittel , Tandberg Petter , Gundersen Mona D. , Kvamme Jan-Magnus , Johnsen Knut , Løitegård Terje , Raschpichler Gabriele , Vold Cecilia , Sørbye Sveinung W. , Goll Rasmus
Published: September 2020

BackgroundThere are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis. MethodsTreatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004-2014, followed by a validation study from 2014-2018. Patients were treated according to clinical guidelines following a standard step-up regime. Patients were categorized according to the treatment level necessary to achieve clinical remission: mild, moderate and severe. The biopsies were assessed by Robarts histopathology index (RHI) and TNF gene transcripts. ResultsWe included 66 patients in the calibration cohort and 89 patients in the validation. Mucosal TNF transcripts showed high test reliability for predicting severe outcome in UC . When combined with histological activity (RHI) scores the test improved its diagnostic reliability. Based on the cut-off values of mucosal TNF and RHI scores from the calibration cohort, the combined test had still high reliability in the validation cohort (specificity 0.99, sensitivity 0.44, PPV 0.89, NPV 0.87) and a diagnostic odds-ratio (DOR) of 54.ConclusionsThe combined test using TNF transcript and histological score at debut of UC can predict severe outcome and the need for anti-TNF therapy with a high level of precision. These validated data may be of great clinical utility and contribute to a personalized medical approach with the possibility of top-down treatment for selected patients.
Bioinformatic analysis reveals hub genes and pathways that promote melanoma metastasis
Authors: Su Wenxing , Guan Yi , Huang Biao , Wang Juanjuan , Wei Yuqian , Zhao Ying , Jiao Qingqing , Ji Jiiang , Yu Daojiang , Xu Longjiang
Published: September 2020

Background: Melanoma has the highest mortality rate of all skin tumors, and metastases are the major cause of death from it. The molecular mechanism leading to melanoma metastasis is currently unclear. Methods: With the goal of revealing the underlying mechanism, three data sets with accession numbers GSE8401, GSE46517 and GSE7956 were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the differentially expressed gene (DEG) of primary melanoma and metastatic melanoma, three kinds of analyses were performed, namely functional annotation, protein‐protein interaction (PPI) network and module construction, and co-expression and drug-gene interaction prediction analysis. Results: A total of 41 up-regulated genes and 79 down-regulated genes was selected for subsequent analyses. Results of pathway enrichment analysis showed that extracellular matrix organization and proteoglycans in cancer are closely related to melanoma metastasis. In addition, seven pivotal genes were identified from PPI network, including CXCL8, THBS1, COL3A1, TIMP3, KIT, DCN, and IGFBP5, which have all been verified in the TCGA database and clinical specimens, but only CXCL8, THBS1 and KIT had significant differences in expression. Conclusions: To conclude, CXCL8, THBS1 and KIT may be the hub genes in the metastasis of melanoma and thus may be regarded as therapeutic targets in the future.
Source model for the Mw 6.0 earthquake in Jiashi, China on 19 January 2020 from Sentinel-1A InSAR data
Authors: Yu Pengfei , Qiao Xuejun , Xiong Wei , Chen Wei , Nie Zhaosheng , Wang Dijin , Jia Zhige , Li Jie
Published: September 2020

On January 19, 2020, an Mw 6.0 earthquake occurred in Jiashi, Xinjiang Uygur Autonomous Region of China. The epicenter was located at the basin-mountain boundary between the southern Tian Shan and the Tarim Basin. Interferometric Synthetic Aperture Radar (InSAR) is used to obtain the coseismic deformation field from both ascending and descending Sentinel-1A satellite images of the European Space Agency. The results showed that the coseismic deformation is distributed between the Kalping fault and the Ozgertaou fault. The earthquake produced significant deformation over an area of approximately 40 km by 30 km. The maximum and minimal displacements along the line of sight (LOS) are 5.3 cm and -4.2 cm for the ascending interferogram and are 7.2 cm and -3.0 cm for the descending interferogram, respectively. The fault geometry from the Multi peak Particle Swarm Optimization computation indicates that the seismogenic fault is a shallow low-dipping planar fault that is 4.58 km depth underground. The finite slip model inverted by the Steepest Descent Method implies that the rupture is dominated by a thrust fault. The slips are concentrated in a depth of 5 ~ 7 km with a maximum slip of 0.29 m. The estimated total seismic moment is 1.688×1018 Nm, corresponding to a magnitude of Mw 6.1. The seismogenic fault is the Kalping fault which has a listric structure. The coseismic deformation only occurred on the décollement layer and did not involve the ramp segment. The coseismic Coulomb stress changes have enhanced the stress on the deep margin of the Jiashi earthquake rupture area, indicating that there is still the possibility of strong earthquakes in this region in the future.
Control of Panama disease of banana by intercropping with Chinese chive (Allium tuberosum Rottler): cultivar differences
Authors: Li Zhen-Fang , Wang Tong , He Chenlin , Cheng Kelin , Zeng Rensen , Song Yuanyuan
Published: September 2020

Panama disease (Fusarium wilt disease) caused by Fusarium oxysporum f. sp. cubense race 4 (FOC) severely threatens banana (Musa spp.) production worldwide. Intercropping of banana with Allium plants has shown a potential to reduce Panama disease. In this study, six cultivars of Chinese chive ( Allium tuberosum Rottler) were selected to compare their differences in antifungal activity and active compounds. Three cultivars Duokang Fujiu 11, Fujiuhuang 2, and Duokang Sijiqing with higher levels of antifungal compounds were further used for intercropping with banana in the pots and field to compare their effects on growth and disease incidence of banana.
The six cultivars showed significant differences in antifungal activity against FOC mycelia growth in both leaf volatiles and aqueous leachates. The aqueous leachates displayed stronger antifungal activity than the volatiles. FJH cultivar showed the best inhibitory effect among all six cultivars. Contents of three main antifungal compounds dipropyl trisulfide (DPT), dimethyl trisulfide (DMT), and 2-methyl-2-pentenal (MP) in volatiles and aqueous leachates varied considerably among cultivars. Pot and field experiments showed that intercropping with three selected Chinese chive cultivars significantly improved banana vegetative growth, increased photosynthetic characteristics and yield but decreased disease incidence of Panama disease.
Our results indicate that intercropping with Chinese chive shows potential to reduce banana Panama disease and selection of appropriate cultivars is vital for effective disease control.
Orthopaedic surgeons’ perceptions on COVID-19 related changes in practice: an international survey
Authors: Meraghni Nadhir , Bouyoucef Hichem , soal Nacim , Larbi Redouane Si , Benkaidali Riad , Kara Zoubir , Hamza Amine
Published: September 2020

Purpose The purpose of this study was to assess the orthopaedic surgeons’ perceptions on COVID-19 related changes in their practice.MethodsAn online survey was shared with orthopaedic surgeons practicing in different countries.ResultsThis study showed that orthopaedic surgery plan management was adapted to respond more effectively to the COVID-19 pandemic while maintaining the continuity of health care and ensuring protection of medical staff and patients. Among the introduced measures, elective surgery was postponed to free-up beds for suspected or COVID-19 positive patients requiring hospitalization. Additionally, the number of outpatient visits was considerably decreased and non-urgent visits were postponed to reduce the flow of patients in and out of hospitals and therefore minimize the risk of contamination. Interestingly, data revealed the willingness of orthopaedic surgeons to take care of COVID-19 positive patients and support their colleagues in intensive care units, if needed.ConclusionsThough, orthopaedic surgeons are not in the frontline, they have an important role to play to face the increasing pressure due to the COVID-19 pandemic. In addition to the changes imposed in their current practice, they have a role in providing support to other colleagues in the fight against this global crisis.
Frequent birth-and-death events throughout perforin-1 evolution
Authors: Araujo-Voces Miguel , Quesada Victor
Published: September 2020

Background Through its ability to open pores in cell membranes, perforin-1 plays a key role in the immune system. Consistent with this role, the gene encoding perforin shows hallmarks of complex evolutionary events, including amplification and pseudogenization, in multiple species. A large proportion of these events occurred in phyla for which scarce genomic data were available. However, recent large-scale genomics projects have added a wealth of information on those phyla. Using this input, we annotated perforin-1 homologs in more than eighty species including mammals, reptiles, birds, amphibians and fishes. Results We have annotated more than 400 perforin genes in all groups studied. Most mammalian species only have one perforin locus, which may contain a related pseudogene. However, we found four independent small expansions in unrelated members of this class. We could reconstruct the full-length coding sequences of only a few avian perforin genes, although we found incomplete and truncated forms of these gene in other birds. In the rest of reptilia, perforin-like genes can be found in at least three different loci containing up to twelve copies. Notably, mammals, non-avian reptiles, amphibians, and possibly teleosts share at least one perforin-1 locus as assessed by flanking genes. Finally, fish genomes contain multiple perforin loci with varying copy numbers and diverse exon/intron patterns. We have also found evidence for shorter genes with high similarity to the C2 domain of perforin in several teleosts. A preliminary analysis suggests that these genes arose at least twice during evolution from perforin-1 homologs. Conclusions The assisted annotation of new genomic assemblies shows complex patterns of birth-and-death events in the evolution of perforin. These events include duplication/pseudogenization in mammals, multiple amplifications and losses in reptiles and fishes and at least one case of partial duplication with a novel start codon in fishes.
Assessing the association between periodontitis and preterm birth : A case control study
Authors: UWAMBAYE Peace , MUNYANSHONGORE Cyprien , RULISA Stephen , Shiau Harlan J , NUHU Assuman , KERR Michael S
Published: September 2020

Background: Premature delivery is among the leading causes of perinatal mortality and morbidity in developed societies which is an important problem in obstetrics. Maternal periodontitis is a prevalent condition that has been suspected to be associated with adverse pregnancy outcomes such as preterm birth. However, there are still conflicting results which this study aims to address by examining the association between periodontitis and preterm birth. This study provides necessary information to inform decisions on the screening tool to be recommended for use by nurses and midwives to screen for periodontal diseases during antenatal consultations in order to improve mothers’ and children’s health. Methods: A case control study was conducted at 12 health facilities in the Southern Province of Rwanda from February to August 2018. A total of 555 women in the postpartum period were enrolled in the study. Cases and controls were enrolled in a ratio of 1:2, each enrolled case of preterm birth was followed by 2 control cases delivered at term gestation that were next on the register. There were 185 cases of preterm deliveries and 370 controls of term delivery. Multivariate regression analysis was done and the variables were hierarchically grouped into three groups: The first group involved demographic variables that were put in the regression model as Step 1. The second group was made up of other potential factors that were put in the regression model as the second step. The third group was periodontitis, as it was hypothesized to be a major predictor variable and this constituted the the third step of the regression model. Results: Significant association was found between periodontitis and preterm birth. Women who had periodontitis had 6 times the odds of giving birth to preterm birth babies compared to women who had no periodontitis (p<0.001) (95% CI 3.9, 10.4). Conclusion: Periodontitis is a risk factor for preterm birth and preventive solutions such as having a periodontitis screening tool for nurses and midwives during antenatal care consultations is highly recommended.
Prevalence, predictors and outcome of carotid stenosis. A sub study in the Preventive Antibiotics in Stroke Study (PASS)
Authors: Velzen Twan van , Kuhrij Laurien , Westendorp Willeke , de Beek Diederik van , Nederkoorn Paul
Published: September 2020

Background: The prevalence of carotid artery stenosis (CAS) in acute ischaemic stroke (AIS) patients is historically reported at 15-20%, but an up-to-date estimate is lacking. We hypothesise it is lower than historically reported, due to better risk management to date. The study aims to study prevalence, predictors and survival of CAS in AIS patients. Methods: We included patients with AIS from the Preventive Antibiotics in Stroke Study (PASS), a large Dutch randomized, multicentre, open-label phase III trial that included 2538 patients with acute stroke and randomised between standard care or preventive ceftriaxone. Patients with stroke in the anterior circulation that underwent diagnostic testing of the internal carotid artery (ICA) were eligible for this sub study and used in these secondary analyses. Logistic regression analyses were performed to identify predictors for CAS ≥50%. Additionally, an ordinal regression was performed to assess the association between presence of CAS at baseline and functional outcome at three months on the modified Rankin scale (mRS). Results: 1480 patients with AIS were included; 277 had CAS (18.7%; 95%CI:17.7-19.7). Age, hypertension, smoking and male gender were found as best-fit predictors for presence of CAS. Significant shift in mRS score after 90 days for CAS ≥50% towards a higher mRS score with an OR of 1.66 (95% CI 1.30-2.10) was found.Conclusions: Current prevalence of CAS is 18.7%, which is higher than we expected. Gender, smoking and hypertension are important factors associated with CAS. Patients with CAS had a significantly higher mRs score after 90 days. Clinical Trial Registration-URL: https://doi.org/10.1186/ISRCTN66140176 Unique identifier: ISRCTN66140176