bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of the Magnitude of People Who Inject Drugs in Hawassa, Ethiopia: A Descriptive Study
Authors: Deyessa Negussie , Senbete Bekele , Abdo Aman , Mundia Bernard M.
Published: August 2021

Background: - Injecting drug use contributes substantially to developing the HIV pandemic in many developing countries. Due to the hidden nature and stigma of the issue, it didn’t prove easy to investigate using regular surveys. Therefore, this research pursues to determine the magnitude of individuals who inject drugs in Hawassa and explain the epidemiological and social condition of HIV among people who inject drugs.Methods: - The study used rapid assessment methods and the combined method of estimating population, by nomination and multiplier methods, using two datasets. The first was the proportion of people who use service within a year as a multiplier. The second was a list of individuals with a condition who utilized a particular health service within a year as a benchmark. The rapid assessment included qualitative methods to extract information relevant to enumeration cites, selection of first seeds as data sources. The study made a simple description of the study subjects to yield socio-demographics and behaviours related to HIV and other health-related problems.Results: - The study estimated a total of estimated 688 (95% CI; 502, 991) people who inject drugs, with a prevalence of 266 per 100,000 people. The study found that people who inject drugs were more young age, male gender. They also lived in lower educational status, were unmarried, and living in small clerk businesses. People who inject drugs and have taken part in the study were more likely to use additional substances like alcohol, khat, and other hard substances like cannabis. The most common form of drug used was Cocaine (83.3%). Most of the PWIDs were sexually active with regular (50.3%) and casual partners (884.6%). They claimed to involve in risky sexual behavior. Conclusion and recommendation:- A significant number of people who inject drugs are available in Hawassa. Lack of assistance in harm reduction in the city has rendered PWIDs vulnerable and at greater risk for HIV/ AIDS. Therefore, the Ministry of Health and other relevant authorities have to start implementing the WHO’s nine key harm reduction measures provided by the World Health Organization.
Reversibility of Historical and Future Climate Change with a Complex Earth System Model
Authors: Yang Shili , Tian Di , Chou JieMing , Wei Ting , Zhu Xian , Dong WenJie
Published: August 2021

The reversibility of a wide range of components of the earth system was investigated by comparing forward and time-reversed historical and future simulations of a coupled earth system model known as the Beijing Normal University earth system model. Many characteristics of the climate system, including the surface temperature, ocean heat content (OHC), convective precipitation, total runoff, ground evaporation, soil moisture, sea ice extent and Atlantic Meridional Overturning Circulation, did not fully return to their initial values when the historical or future natural and anthropogenic forcing agents were reversed. The surface temperature and OHC declines lagged behind the decline in greenhouse gases (GHGs). Reverses in other variables occurred in direct response to the decline in GHGs. The sea level increased, even after all of the forces returned to the original values. Furthermore, most of the climate variables did not return to their original values because of thermal inertial. The end states of variables, other than those related to thermal storage, mainly depended on the original state of the natural and anthropogenic forces, and were unaffected by the future growth rate of the GHGs. The climate policy implication of this study is that climate change cannot be completely reversed even if all the external forces are returned to their initial values.
Endoscopic Resection of Esophageal Granular Cell Tumors: A Single Center Experience
Authors: Liu Kaipeng , Zhou Yangyang , Zheng Qingfen , Liu Dan , Yang Huiyu , Liu Bingrong
Published: August 2021

Background: Granular cell tumors (GCTs) are rare tumors probably originating from neurogenic Schwann cells. The aim was to evaluate the safety and feasibility of endoscopic resection for esophageal GCTs. Methods: The study retrospectively analyzed patients with pathologically diagnosed esophageal GCTs in our center from February 2012 to December 2020. Clinicopathological characteristics, endoscopic features and clinical outcomes were collected and analyzed. Results: 12 males and 10 females were identified. Lesions were located in the upper, middle and lower esophagus in three, six and thirteen cases respectively. 14 lesions (63.6%) exhibited white-to-yellow discoloration. The mean maximum diameter of these lesions was 5.7±2.2 mm (range 2-11.6 mm). The most lesions (91%) were located in the mucosa or submucosa layer, and 2 lesions (9.0%) were in the muscularis propria layer. Endoscopic mucosal resection (n=17), endoscopic submucosal dissection (n=4) and endoscopic submucosal excavation (n=1) were performed. En bloc resection was achieved in 20 lesions (90.9%). The R0 resection was achieved in 20 lesions (90.9%). No patients experienced intraoperative perforation or delayed bleeding in the mean length of postoperative hospital stay of 4.2±2.1 days (range 1-9 days). All patients had no recurrence or metastasis during the mean follow-up period of 48.1±27.2 months (range 2-102 months). Conclusion: Endoscopic resection is safe and effective for management of esophageal GCTs. Clinically, the appropriate approach of endoscopic resection should be selected according to the origin and size of the lesion.
Endovascular Revascularization Strategies Using Catheter-Based Thrombectomy Versus Conventional Catheter-Directed Thrombolysis for Acute Limb Ischemia
Authors: Gong Maofeng , He Xu , Zhao Boxiang , Kong Jie , Gu Jianping , Chen Guoping
Published: August 2021

Background
Acute limb ischemia (ALI) is an important clinical event threatening both life and the affected limbs, but the optimal treatment for ALI remains undefined. The aim of this study was to compare the safety and effectiveness of thrombectomy approaches via either catheter-based thrombectomy (CBT) or catheter-directed thrombolysis (CDT).
Methods
A total of 98 patients (mean age 69.7 years, 60 male) who underwent endovascular intervention for ALI from January 2015 to August 2018 were included. Of these, 57 were treated with primary CBT via a large-bore catheter, an AngioJet catheter or Rotarex catheter, and/or underwent low-dose CDT, and 41 were treated with primary CDT. The safety and effectiveness of CBT compared to conventional CDT and other various endovascular techniques were evaluated.
Results
More Rutherford IIb patients were treated with primary CBT (68.4%) than CDT (26.8%; P < .001). Patients who underwent primary CBT achieved a higher technical success rate than those who underwent primary CDT in a shorter procedure time (P < .001), whereas 42.1% of patients who underwent CBT did not need adjunctive CDT. The duration and dosage of adjunctive CDT in the CBT group were significantly decreased compared with those in the primary CDT group (both P < .001), and the CBT group achieved a shorter in-hospital length of stay (P < .001). Subgroup analysis revealed that patients treated with AngioJet and Rotarex catheters achieved slightly lower dosages, shorter CDT durations and shorter in-hospital stay lengths than those treated with large-bore catheters (P > .05). Clinical success was estimated to be achieved in 98.2% of patients who underwent CBT, which is similar to the 97.6% estimated in those who underwent primary CDT (P = 1.000), and this finding was similar among the CBT subgroups. Patients who underwent primary CBT had slightly fewer complications than those who underwent primary CDT (P = .059), especially minor complications (P = .036). The freedom from amputation at 6 and 12 months for CBT and CDT was assessed (93.0% vs 90.2% respectively, P = .625; 89.5% vs 82.5%, respectively, P = .34,). Comparable limb salvage was found for different techniques of large bore catheters, AngioJet catheters and Rotarex catheters. The Kaplan-Meier table analysis also showed similar limb salvage rates between groups.
Conclusions
Endovascular treatment of ALI with the use of catheter-based therapies is a safe and effective modality with similar safety and clinical outcome to conventional CDT alone, and this treatment modality overcomes the common shortcomings of CDT alone. Different CBT techniques have comparable efficacy but different adverse event profiles.
SnoRNA ENST00000391318 Suppressed Endometrial Receptivity by Competitively Binding To miRNA-3928-5p To Regulate CDH11 in Women in a GnRH Antagonist Stimulation Protocol
Authors: Ji Xiaowei , Liu Suying , Wang Lin , Xu Jun , Zou Xutong , He Liying , Chen Wei , Liu Miao , Dong Xi
Published: August 2021

Background

To determine the small nucleolar RNA (snoRNA) expression profiles in the endometrium during the implantation phase and identify their potential biological functions.
Methods

We used RNA sequencing to analyze the expression changes of snoRNAs in the endometrium of women during the implantation phase of the natural cycle and in the GnRH antagonist stimulation protocol. The expression of snoRNA ENST00000391318 was manipulated in endometrial cells by lentivirus. CCK-8, clone formation, flow cytometry, scratch and Transwell assays were used to detect the effects of ENST00000391318 on the proliferation, apoptosis, migration and invasion of endometrial cells. RNA pulldown and luciferase reporter gene experiments were used to detect the binding of ENST00000391318 to miRNA.
Results

Endometrial SNORNA ENST00000391318 was upregulated in the GnRH antagonist stimulation protocol. SNORNA ENST00000391318 overexpression inhibited cell proliferation and the cell cycle in Ishikawa cells, and SNORNA ENST00000391318 knockdown promoted cell proliferation and the cell cycle in Ishikawa cells. SNORNA ENST00000391318 overexpression inhibited cell migration and invasion in Ishikawa cells. SNORNA ENST00000391318 inhibited the expression of endometrium receptivity factor. miRNA-3928-5p is a target of SNORNA ENST00000391318 in Ishikawa cells. SNORNA ENST00000391318 regulates the expression of CDH11 through interaction with miRNA-3928-5p in Ishikawa cells.
Conclusions

The ENST00000391318/miR-3928-5p/CDH11 signaling pathway can regulate the receptivity of the endometrium for patients in the GnRH antagonist stimulation protocol. SNORNA ENST00000391318 downregulates the function of miR-3928-5p through a ceRNA mechanism to upregulate the expression of CDH11. SNORNA ENST00000391318 downregulates the receptivity of the endometrium by upregulating the expression of CDH11.
Patient-Reported Outcomes of Upadacitinib Versus Abatacept in Patients with Rheumatoid Arthritis and an Inadequate Response to Biologic Disease-Modifying Antirheumatic Drugs: 12-Week Results of a Phase 3 Trial
Authors: Bergman Martin , Tundia Namita , Martin Naomi , Suboticki Jessica L , Goldschmidt Debbie , Song Yan , Wright Grace C
Published: August 2021

Background In previous clinical trials, patients with active rheumatoid arthritis (RA) treated with upadacitinib (UPA) have improved patient-reported outcomes (PROs). This post hoc analysis of SELECT-CHOICE, a phase 3, double-blind, randomized clinical trial evaluated the impact of UPA vs abatacept (ABA) with background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on PROs in patients with RA who have inadequate response or intolerance to biologic DMARDs (bDMARD-IR).Methods: Patients in SELECT-CHOICE received UPA (oral 15 mg once daily) or ABA (intravenous). PROs evaluated included Patient Global Assessment of Disease Activity (PtGA) by visual analog scale (VAS), patient’s assessment of pain by VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), duration and severity of morning stiffness, 36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Impairment (WPAI), and EQ-5D 5-Level (EQ-5D-5L) index score. Least squares mean (LSM) changes from baseline to week 12 were based on an analysis of covariance model. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) were compared using chi-square tests.Results: Data from 612 patients were analyzed (UPA, n=303; ABA, n=309). Mean age was 56 years and mean disease duration was 12 years. Thirty-two percent received >1 bDMARD and 72% received concomitant methotrexate at baseline. At week 12, UPA treatment showed significantly greater improvements than ABA treatment in PtGA, pain, HAQ-DI, morning stiffness severity, EQ-5D-5L, WPAI activity impairment domain, and 3/8 SF-36 domains and physical component summary (PCS) scores (P<0.05). Significantly more UPA- vs ABA-treated patients reported improvements ≥ MCID in HAQ-DI (74% vs 64%) and SF-36 PCS (79% vs 66%) and 4/8 domain scores (P<0.05). The proportions of patients achieving MCID in the remaining PROs were similar between groups.Conclusions: In this study, treatment with UPA or ABA resulted in clinically meaningful improvements in PROs at week 12 in patients with active RA. UPA treatment elicited greater improvements in key domains of physical functioning, pain, and general health, and earlier improvements in HAQ-DI compared with ABA.Trial registration: NCT03086343, March 22, 2017
Tourism Demand Forecasting Using Stacking Ensemble Model With Adaptive Fuzzy Combiner
Authors: Cankurt Selcuk , Subasi Abdulhamit
Published: August 2021

Over the last decades, several soft computing techniques have been applied to tourism demand forecasting. Among these techniques, a neuro-fuzzy model, Adaptive neuro fuzzy inference system (ANFIS) has started to emerge. A conventional ANFIS model cannot deal with the large dimension of a dataset, and cannot work with our dataset, which is a composed of a 62 time-series, as well. This study attempts to develop an ensemble model by incorporating neural networks with ANFIS to deal with the large number of input variables for multivariate forecasting. Our proposed approach is a collaboration of two base learners, which are types of the neural network models and a meta-learner of ANFIS in the framework of the stacking ensemble. The results show that the stacking ensemble of ANFIS (meta-learner) and ANN models (base learners) outperforms its stand-alone counterparts of base learners. Numerical results indicate that the proposed ensemble model achieved a MAPE of 7.26% compared to its single-instance ANN models with MAPEs of 8.50% and 9.18% respectively. Finally, this study which is a novel application of the ensemble systems in the context of tourism demand forecasting has shown better results compared to those of the single expert systems based on the artificial neural networks.
LSH-GAN: in-silico generation of cells for small
sample high dimensional scRNA-seq data
Authors: Lall Snehalika , Ray Sumanta , Bandyopadhyay Sanghamitra
Published: August 2021

A fundamental problem of downstream analysis of scRNA-seq data is the unavailability of enough cell samples compare to the feature size. This is mostly due to the budgetary constraint of single cell experiments or simply because of the small number of available patient samples. Here, we present an improved version of generative adversarial network (GAN) called LSH-GAN to address this issue by producing new realistic cell samples. We update the training procedure of the generator of GAN using locality sensitive hashing which speeds up the sample generation, thus maintains the feasibility of applying the standard procedures of downstream analysis. LSH-GAN outperforms the benchmarks for realistic generation of quality cell samples. Experimental results show that generated samples of LSH-GAN improves the performance of the downstream analysis such as feature (gene) selection and cell clustering.
A Prefix Based Approach for Joint Doppler and Channel Estimation in Underwater Communication
Authors: Bhadouria Vijay Singh , Agrawal Monika , Kumar Ritesh
Published: August 2021

Developing a reliable and robust underwater acoustic communication system is a difficult task, due to the complicated nature of the underwater channel, non-stationary noise, and a number of other factors. Indeed, channel estimation or equalization presents numerous challenges in this non-stationary, highly Doppler, multipath environment; as a result, traditional equalizers and PLL-based methods have limited performance. Generally, communication over such time-varying channels is accomplished via packets that contain a prefix/preamble signal for training, a payload containing the actual data, and a silent period for proper alignment. The prefix signal must be designed properly because it is used to estimate the channel and also to determine the start of packet. This paper proposes a novel prefix signal based on the hyperbolic chirp signal, where its Doppler invariance properties enable the extraction of the entire packet even when Doppler and severe multipath are present. Additionally, this proposed prefix enables an efficient and accurate method for fully characterising an underwater channel. The proposed prefix signal is used to estimate the multipath delay and amplitude, and different Doppler scales. Extensive simulations using various channel models are used to determine the proposed method robustness and efficacy under a wide range of conditions. Additionally, the proposed algorithm has been validated on a real-world channel.
High-Speed Joining of Tubes To Panel Sheets Using Electro-Hydraulic Forming
Authors: Babalo Vahid , Hossein Mohammad Reza Mirza , Fazli Ali , Solanpour Mehdi
Published: August 2021

This study presents a new method for high-speed joining of the sheet to the end of a tube without the need for any additional processes. Joining of the AA3105 sheets to the AA1170 tube is carried out with a thickness of 0.5 mm. The process is performed using electro-hydraulic forming which is a local deformation of the tube and sheet. In this method, the mechanical force is transmitted by working media in a very short time. The shock wave accelerates the panel sheet towards the die and tube to create a form-fit joint. To avoid friction between the mandrel and the flat sheet, the panel sheet is pre-drilled. The experimental tests were performed to show the effect of process parameters including; washer housing angle, sheet hole diameter, and the gap between the mandrel and top of the sheet. In addition, pull-out test is utilized to determine the strength of the joints in different conditions. Accordingly, the usage of electro-hydraulic forming on joining thin tubular parts to flat sheets was successful and the feasibility of this technique as an advanced joining approach was verified.
Ranking based RPL for Multipoint-to-Point Multi-modal Data Communication in IoT Network.
Authors: Bhat Archana , V Geetha
Published: August 2021

IPv6 Routing Protocol for low power and lossy networks (RPL) is a standardized and default routing protocol for low power lossy networks. However, this is basically designed for sensor networks with scalar data and not optimised for the networks with multi-modal sensors. The data rate of each multi-modal sensor varies based on various applications. RPL suffers from packet drops and re-transmissions which results in packet loss and energy consumption in case of multi-modal data transmission. Hence, the routing strategy implemented in RPL needs better scheduling strategy at parent node for forwarding packets based on various parameters. In this paper, relevant Objective Functions for multi-modal sensor data communication is proposed based on various parameters identified and a weighted ranking based scheduling strategy is proposed for multi-modal data communication called R-RPL. The goal of proposed ranking based RPL (R-RPL) is to increase the throughput and reduce the loss in terms of energy and delay based on proposed scheduling strategy for parent selection. The performance of the proposed R-RPL is evaluated in the contiki based Cooja simulator and compared with RPL protocol. The analysis shows that the R-RPL performs better compared to RPL with respect to packet delivery ratio and energy consumption.
Clinical validation, implementation, and reporting of polygenic risk scores for common diseases
Authors: Vassy Jason , Hao Limin , Kraft Peter , Berriz Gabriel , Hynes Elizabeth , Koch Christopher , Kumar Prathik , Parpattedar Shruti , Steeves Marcie , Yu Wanfeng , Antwi Ashley , Brunette Charles , Danowski Morgan , Gala Manish , Green Robert , Jones Natalie , Lewis Anna , Lubitz Steven , Natajaran Pradeep , Lebo Matthew
Published: August 2021

Implementation of polygenic risk scores (PRS) may improve disease prevention and management but requires the construction and validation of clinical assays, interpretation, and reporting pipelines. We developed a clinical genotype array-based assay for published PRS for 6 common diseases. First, we calculated PRS for 36,423 Mass General Brigham Biobank (MGBB) participants. Finding significant variation in the PRS distributions by race, we implemented adjustment for population structure with ancestry-informative principal components. We replicated published thresholds for odds ratio (OR)>2 in MGBB overall [ranging from 1.75 (1.57, 1.95) for Type 2 diabetes to 2.38 (2.07, 2.73) for breast cancer]. After confirming the high performance and robustness of the pipeline for use as a clinical assay, we analyzed the first 141 prospective samples from the Genomic Medicine at VA Study; frequency of PRS corresponding to published OR>2 ranged from 5/141 (3.6%) for colorectal cancer to 8/48 (16.7%) for breast cancer. Our development of a clinical PRS assay for multiple conditions illustrates the generalizability of this process and necessary technical and reporting decisions for meaningful clinical PRS implementation.
In situ grown bifacial graphene stabilizes composite electrode for efficient perovskite solar cells
Authors: Han Liyuan , Lin Xuesong , Su Hongzhen , He Sifan , Song Yenan , Wang Yanbo , Qin Zhenzhen , Wu Yongzhen , Yang Xudong , Han Qifeng , Fang Junfeng , Graetzel Michael
Published: August 2021

Instability of rear electrodes undermines the long-term operational durability of efficient perovskite solar cells (PSCs). Here, a composite electrode of copper-nickel (Cu-Ni) alloy stabilized by in situ grown bifacial graphene is designed. The alloying makes the work function of Cu suitable for regular PSCs and Cu-Ni is the ideal substrate for preparing high-quality graphene via chemical vapor deposition, which simultaneously protects the device from oxygen, water and internal components reaction. To rivet the composite electrode with semi-device, a thermoplastic copolymer is employed as an adhesive layer during hot pressing. The resultant device achieved power conversion efficiency of 24.34% with significantly improved stability; the devices without encapsulation retained 97% of their initial efficiency after the damp heat test at 85oC with relative humidity of 85% for 1440 hours and the encapsulated devices maintained 95% of their initial efficiencies after maximum power point tracking under continuous 1 sun illumination for 5000 hours.
Rheumatoid Arthritis, as a Clinical Disease, but Not Rheumatoid Arthritis-associated Autoimmunity is Linked to Cardiovascular Events
Authors: Gouze Helene , Aegerter Philippe , Said-Nahal Roula , Zins Marie , Goldberg Marcel , Morelle Guillaume , Schett Georg , Breban Maxime , D’Agostino Maria-Antonietta
Published: August 2021

Background: Rheumatoid Arthritis (RA) is characterized by increased cardiovascular (CV) mortality. CV events are particularly high in patients with RA-specific autoimmunity, including rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), raising the question whether RA-specific autoimmunity itself is associated with CV events.Methods: New CV events (myocardial infarction, stroke or death by CV cause) were recorded in 20,625 subjects of the Electricité de France – Gaz de France (GAZEL) cohort. Self-reported RA cases in the GAZEL cohort were validated by phone interview on the basis of a specific questionnaire. In 1,618 subjects, in whom serum was available, RF and ACPA were measured. A piecewise exponential Poisson regression was used to analyze the association of CV events with presence of RA as well as RA-specific autoimmunity (without RA).Results: CV events in GAZEL were associated with age, male sex, smoking, hypertension, hyperlipidemia and diabetes mellitus (HR from 1.06 to 1.87, p < 0.05). Forty-two confirmed RA cases were identified. Confirmed RA was significantly associated with CV risk increase (HR of 3.03; 95% CI: 1.13-8.11, p=0.03) independently of conventional CV risk factors. One hundred seventy-eight subjects showed RF or ACPA positivity without presence of RA. CV events were not associated with ACPA positivity (HR: 1.52, 95% CI: 0.47-4.84, p= 0.48) or RF positivity (HR: 1.15, 95% CI: 0.55-2.40, p= 0.70) in the absence of RA.Conclusions: RA, as a clinical chronic inflammatory disease, but not mere positivity for RF or ACPA in the absence of clinical disease is associated with increased CV risk.
Factors Affecting Drug Retention of Janus kinase Inhibitors in Patients with Rheumatoid Arthritis: The ANSWER Cohort Study
Authors: Ebina Kosuke , Hirano Toru , Maeda Yuichi , Yamamoto Wataru , Hashimoto Motomu , Murata Koichi , Onishi Akira , Jinno Sadao , Hara Ryota , Son Yonsu , Amuro Hideki , Takeuchi Tohru , Yoshikawa Ayaka , Katayama Masaki , Yamamoto Keiichi , Okita Yasutaka , Hirao Makoto , Etani Yuki , Kumanogoh Atsushi , Okada Seiji , Nakata Ken
Published: August 2021

Background: This multi-center, retrospective study aimed to clarify the factors affecting drug retention of the Janus kinase inhibitors (JAKi) baricitinib (BAR) and tofacitinib (TOF) in patients with RA.Methods: Patients were included as follows: females, 80.6%; age, 60.5 years; DAS28-ESR, 4.3; treated with either BAR (n = 166) or TOF (n = 185) and concomitant glucocorticoid (prednisolone [PSL] equivalent) 5.3 mg/day (46.7%) or methotrexate (MTX) 8.9 mg/week (60.7%); bDMARDs- or JAKi-switched cases (76.6%). The reasons for drug discontinuation were classified into four major categories: lack of effectiveness, toxic adverse events, non-toxic reasons and remission. The drug retention rate was estimated at 24 months using the Kaplan–Meier method and adjusted for potential confounders using multivariate Cox proportional hazards modelling.Results: Adjusted discontinuation rates for the corresponding reasons were as follows: lack of effectiveness (22.3%), toxic adverse events (13.3%), non-toxic reasons (7.2%) and remission (0.0%). Prior use of anti-interleukin-6 receptor antibody (aIL-6R) was significantly associated with discontinuation due to lack of effectiveness (P = 0.021). Ageing (P = 0.015), usage of PSL ≥5 mg/day (P = 0.017) and female sex (P = 0.041) were significantly associated with discontinuation due to toxic adverse events. Factors not associated with treatment discontinuation were: number of prior bDMARDs or JAKi, concomitant MTX usage, different JAKi and prior use of TNF inhibitor, CTLA4-Ig or other JAKi.Conclusions: Prior use of aIL-6R was associated with discontinuation due to lack of effectiveness, while ageing (≥75 years), PSL usage ≥5 mg/day, and female sex were associated with discontinuation due to toxic adverse events.
Regulation of Osteoblast Autophagy based on PI3K/AKT/mTOR Signaling Pathway Study on the Effect of β-ecdysterone on Fracture Healing
Authors: Tang Yanghua , Mo Yafeng , Xin Dawei , Xiong Zhenfei , Zeng Linru , Luo Gan , Cao Yanguang
Published: August 2021

Objectives: To investigate the effects of β-ecdysterone on fracture healing and the underlying mechanism.Methods: MTT assay was used to detect the cell viability. AO/PI and flow cytometry assays were used to determine the apoptotic rate. The expression level of RunX2, ATG7 and LC3 was evaluated by qRT-PCR and Western blot assays. X-ray and HE staining were conducted on the fractured femur. Immunohistochemical assay was used to detect the expression level of Beclin-1 and immunofluorescence assay was used to measure the expression level of LC3 in the fractured femurs. Western blot was utilized to determine the expression level of PI3K, p-AKT1, AKT1, p-mTOR, mTOR, p-p70S6K, and p70S6K.Results: The ALP activity and the expression of RunX2 in fractured osteoblasts were significantly elevated, the apoptotic rate was suppressed by rapamycin, 60, and 80 μM β-ecdysterone. The state of autophagy both in fractured osteoblasts and femurs was facilitated by rapamycin and β-ecdysterone. Compared to control, Garrett score was significantly promoted in rapamycin and β-ecdysterone groups, accompanied by ameliorated pathological state. Lastly, the PI3K/AKT/mTOR pathway both in fractured osteoblasts and femurs was inhibited by rapamycin and β-ecdysterone.Conclusion: β-ecdysterone might facilitate fracture healing by activating autophagy through suppressing PI3K/AKT/mTOR signal pathway.
A GAN-based dimensionality reduction technique for aerodynamic shape optimization
Authors: Zhang Jun , Wang Wenzheng , Wu Qiuyu , Hu Liwei
Published: August 2021

Aerodynamic shape optimization (ASO) based on computational fluid dynamics simulations is extremely computationally demanding because a search needs to be performed in a high-dimensional design space. One solution to this problem is to reduce the dimensionality of the design space for aircraft optimization. Hence, in this study, a dimensionality reduction technique is designed based on a generative adversarial network (GAN) to facilitate ASO. The novel GAN model is developed by combining the GAN with airfoil curve parameterization and can directly produce realistic and highly accurate airfoil curves from input data of aerodynamic shapes. In addition, the respective interpretable characteristic airfoil variables can be obtained by extracting latent codes with physical meaning, while reducing the dimensionality of the airfoil design space. The results of simulation experiments show that the proposed technique can significantly improve the optimization convergence rate of the ASO process.
3D Printed Templates Improve the Accuracy and Safety of Pedicle Screw Placement in the Treatment of Pediatric Congenital Scoliosis
Authors: Cao Jun , Zhang Xuejun , Liu Haonan , Yao Ziming , Bai Yunsong , Guo Dong , Feng Lei
Published: August 2021

Background: Three-dimensional (3-D) printed guidance templates are being increasingly used in spine surgery. The purpose of this study was to determine if 3D printed navigation templates can improve the accuracy of pedicle screw placement and decrease the complication rate compared to freehand screw placement in the treatment of children with congenital scoliosis. Methods: The records of pediatric patients with congenital scoliosis treated at our hospital from January 2017 to January 2019 were retrospectively reviewed. Patients were divided into those where a 3D printed guidance templated was used and those in which the freehand method was used for pedicle screw placement. The accuracy rate of pedicle screw placement, surgical outcomes, and complications were compared between groups.Results: A total of 67 children with congenital scoliosis were included (43 males and 24 females; mean age of 4.13 ± 2.66 years; range, 2-15 years). There were 34 children in the template-assisted group and 33 in the freehand group. The excellent accuracy rate of pedicle screw placement was significantly higher in the template-assisted group (96.10% vs. 88.64%, P = 0.007). The main Cobb angle and kyphosis angle were similar between the 2 groups preoperatively and postoperatively (all, P > 0.05), and in both groups both angles were significantly decreased after surgery as compared to the preoperative values (all, P < 0.001). The degree of change of the Cobb angle of the main curve and kyphosis angle were not significantly different between the 2 groups. There were no postoperative complications in the template group and 4 in the freehand group (0% vs. 12.12%; P = 0.009). All 4 patients with complications required revision surgery.
An Application of PRECIS-2 to Evaluate Trial Design in a Pilot Cluster Randomised Controlled Trial of a Community-based Smoking Cessation Intervention for Women Living in Disadvantaged Areas of Ireland
Authors: Darker Catherine , Loudon Kirsty , O'Connell Nicola , Castello Stefania , Burke Emma , Vance Joanne , Reynolds Caitriona , Buggy Aine , Dougall Nadine , Williams Pauline , Dobbie Fiona , Bauld Linda , Hayes Catherine B
Published: August 2021

Background “We Can Quit2” (WCQ2) was a pilot cluster randomised controlled trial with an embedded process evaluation assessing the feasibility and acceptability of ‘We Can Quit’ (WCQ), a peer-delivered community-based stop-smoking programme for women in disadvantaged communities. The control group comprised ‘enhanced usual care’ offered by the Irish Health Service Executive (HSE). The PRagmatic Explanatory Continuum Indicator Summary (PRECIS-2) is a tool to assess whether a trial design is more explanatory (working under ideal conditions) or pragmatic (working under ‘real world’ conditions). The aim of this paper was to retrospectively evaluate the WCQ2 pilot trial using PRECIS-2 to inform the decision-making process on progression to a future definitive trial (DT).Methods The WCQ2 trial protocol and HSE standard stop-smoking service were described across the nine PRECIS-2 domains: Eligibility, Recruitment, Setting, Organisation, Flexibility-Delivery, Flexibility-Adherence, Follow-up, Primary Outcome. Team members scored the domains as pragmatic or explanatory for each arm in a half-day workshop. Results Seven team members (practitioners and researchers) assessed the overall trial design as more explanatory than pragmatic. Important differences emerged between the two arms. WCQ targeted adult women from disadvantaged communities whereas HSE run a limited enhanced service for all quitters. Recruitment to trial was challenging, intense efforts were needed as the trial proceeded. WCQ was delivered in a non-clinical community setting, HSE services in a clinical setting. WCQ organisation was co-designed with community partners and comprises peer-to-peer group support delivered by trained lay community facilitators, whereas HSE one-to-one support is delivered by Smoking Cessation Officers with a clinical background. Only WCQ allowed flexibility in delivery and adherence. Follow-up was more intensive in WCQ. Greater efforts to improve participant retention will be required in a future DT. Conclusions PRECIS-2 allowed the reflection of practitioners and researchers on similarities and differences between intervention and control arms. Results will inform the decision on progression to an effectiveness DT, which will require more a pragmatic and less explanatory design. This novel use of PRECIS-2 to retrospectively evaluate a complex community-based pilot trial in advance of a full DT will also support learning for those undertaking hybrid trials of implementation and effectiveness. Trial registration: This trial is registered with the ISRCTN registry (No. 74721694), available at https://doi.org/10.1186/ISRCTN74721694
Echinacoside Exhibits Antidepressant-like Effects Through AMPAR–Akt/ERK–mTOR Pathway Stimulation and BDNF Expression in Mice
Authors: Chuang Han-Wen , Wang Tse-Yen , Huang Chih-Chia , Wei I-Hua
Published: August 2021

Background: Several natural products have been demonstrated to be effective in the treatment of depressive disorders. Echinacoside, a naturally occurring phenol extracted from Cistanche tubulosa, Echinacea angustifolia, and Cistanche spp, has a wide range of physiological effects, such as antioxidation, neuroprotection, anti-inflammatory, and immunoregulation, which are closely related to depression. In addition, echinacoside can activate protein kinase B (Akt), extracellular signal–regulated kinase (ERK), and brain-derived neurotrophic factor (BDNF) in the brain. A key downstream event of the Akt, ERK, and BDNF signaling pathways, namely mechanistic target of rapamycin (mTOR) signaling, plays a crucial role in generating an antidepressant effect. Thus, echinacoside is a promising therapeutic agent for depression. However, research regarding the role of echinacoside in brain mTOR activation and antidepressant effect remains lacking. Materials and methods: The forced swimming test in C57BL/6 mice was used to investigate the antidepressant-like activities of echinacoside and the underlying mechanism involved in glutamatergic signaling. Results: We confirmed the suggestions by previous reports that echinacoside activates Akt/ERK signaling and further demonstrated that echinacoside triggers mTOR signaling and α-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation in the Akt/ERK signaling pathway downstream and upstream, respectively, and upregulates BDNF in the hippocampus of mice to exhibit antidepressant-like activities. Conclusion: To the best of our knowledge, our study is the first to reveal that echinacoside is a potential treatment for depressive disorders. Moreover, the present study suggests a mechanism for the neuroprotective effect of echinacoside.
COVID-19 Experiences Predicting High Anxiety and Depression Among a Sample of BRCA1/BRCA2-positive Women in the US
Authors: Dibble Kate E , Connor Avonne E
Published: August 2021

Purpose. During the COVID-19 pandemic, breast and ovarian cancer survivors experienced more anxiety and depression than before the pandemic. Studies have not investigated the similarities of this trend among BRCA1/2-positive women who are considered high risk for these cancers. The current study examines the impact of COVID-19 experiences on anxiety and depression in a sample of BRCA1/2-positive women in the U.S.Methods. 211 BRCA1/2-positive women from medically underserved backgrounds completed an online survey. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression for associations between COVID-19 experiences and self-reported anxiety and depression stratified by demographic factors. Results. Overall, women who reported quarantining/isolation (aOR, 0.46, 95% CI, 0.24-0.88) experienced significantly fewer depressive symptoms than women who did not report this experience. Racial/ethnic minority women caring for someone at home during COVID-19 were 3.78 times more likely (95% CI, 1.04-13.6) to report high anxiety while non-Hispanic white women were less likely (aOR, 0.36, 95% CI, 0.10-1.33, p-interaction=0.011). Conclusions. To date, this is the first study to analyze anxiety and depression considering several COVID-19 predictors among BRCA1/2-positive women. Our findings can be used to inform future research and advise COVID-19-related mental health resources specific to these women.
Solvent Effect on the Efficiency of Triphenylamine-Based Dye-Sensitized Solar Cells, Molecular Approach
Authors: Pakravesh Faezeh , Izadyar Mohammad
Published: August 2021

In this research, dynamics, and kinetics of some metal-free organic dyes based on triphenylamine having a D-π-A type structure were investigated in the gas phase and solvent (ethanol, dichloromethane, toluene, tetrahydrofuran, chloroform, and dimethylformamide) using the quantum chemistry calculations. These structures consist of triphenylamine as the donor linked to the acceptor units of cyanoacrylic acid and benzoic acid via different π-conjugated systems. The obtained results show that TC601 dye having the ethynyl anthracene phenyl π-conjugated system has the preferred charge/hole transfer properties (ΔG inj/ ΔG reg ), which in ethanol as the solvent, the lowest values of ΔG inj and ΔG reg were evaluated. Molecular spectroscopic properties of the studied dyes reveal that H-P and F-P dyes have favorable molar absorption coefficients in all media. Also, the behaviors of the light-harvesting efficiency (LHE) and incident photon to current efficiency (IPCE) as the functions of the wavelength were analyzed, which show that the presence of solvent increases the values of IPCE and LHE for most studied dyes in comparison with the gas phase. Finally, based on different analyses, TC601 as the dye and ethanol as the solvent are proposed as the preferred candidates to be applied in the DSSCs.
Novel Design of Amine and Metal Hydroxide Functional Group Modified Onto Sludge Biochar for Arsenic Removal
Authors: Chen Chih-Kuei , Nguyen Nhat-Thien , Le Thuy-Trang , Duong Cong-Chinh , Nguyen Cong-Nguyen , Truong Duc-Toan
Published: August 2021

Among the arsenic removal technologies, the adsorption method is found to be an efficient, inexpensive and simple method with obvious advantages and application value for arsenic removal in water. While, each method has its limitations, the traditional adsorption method used for arsenic removal due to its high operating cost and low adsorption efficiency. Consequently, this study explicitly designed sludge biochar (SB) adsorbed for arsenic removal with lower operation costs and higher adsorption efficiency properties. Generally, biochar only relies on micropores for pollutant adsorption, but physical adsorption is not highly efficient for arsenic removal. Therefore, in order to improve the removal efficiency of arsenic by SB, diethylenetriamine (DETA) and FeCl3 were used in this study to modify the surface of SB by an immersion method. The modified SB has not only pore adsorption characteristics but also electrostatic adsorption, oxidation-reduction and complexation characteristics. The objectives of this research are to obtain optimum operation conditions by assessing the effect of different Fe content, pH and initial concentration on adsorbing arsenic. The arsenic adsorption mechanism on SB was studied using Density Functional Theory (DFT) to understand the functional effect on arsenic adsorption. Results showed the presence of amine and iron oxyhydroxides functional greatly promoted SB surface activity and its arsenic adsorption potential. DFT model result is the same as the result of arsenic adsorption performance with the high adsorption energy. The reaction mechanism is divided into four pathways, including oxidation-reduction, complexation, electrostatic adsorption and pore adsorption.
Heparin-binding Proteins in Amniotic Fluid: Predicter for Histological Chorioamnionitis?
Authors: Wang Yixiao , Yu Xiang , Wu Chengqian , Li Ting , Jia Ruizhe , Ding Hongjuan
Published: August 2021

Background: Histological chorioamnionitis (HCA) is a serious threat to fetal health during pregnancy, which is not easily detected due to the lack of clinical symptoms, and there is still a lack of effective predictors and diagnostic indicators. Heparin-binding protein (HBP), an antimicrobial protein secreted by neutrophils, is highly valuable in predicting a variety of infectious diseases and is expected to be an effective predictor of histological chorioamnionitis.Methods: A total of 100 full-term healthy pregnant women delivered by cesarean section (control group) and 51 randomly enrolled pregnant women (pathology group) were included in this study. Amniotic fluid was extracted at delivery for HBP concentration, and postpartum placental pathology was performed in the pathology group to clarify the diagnosis of HCA. The predictive value of HBP in amniotic fluid for HCA was determined by establishing the reference interval for HBP in normal population and the receiver operating characteristic (ROC) curve.Results: The 95% confidence interval (95% CI) for HBP concentration in the amniotic fluid of normal pregnant women was 0- 87.08 ng/ml, with a median of 6.41 ng/ml; HBP concentration in the amniotic fluid of pregnant women with HCA was significantly higher than that of controls (P < 0.001) and non-HCA pregnant women (P < 0.001). The ROC curve showed that when the cut-off value of HBP in amniotic fluid was 82.67 ng/ml, the corresponding sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) were 84.20%, 96.90%, 94.12%, 91.18% and 0.86 (P < 0.001, 95% CI 0.715-1.000), respectively. Discussion: HBP in amniotic fluid is a potential, good predictor of HCA. We will further to explore its clinical application value.
Cutting force prediction considering force-deflection coupling in five-axis milling with fillet-end cutter
Authors: Duan Xianyin , Li Lantao , Chen Chen , Yu Sheng , Zhu Zerun , Peng Fangyu
Published: August 2021

With the increasing demand for higher quality and performance of equipment and assembly in aerospace, shipbuilding, medical and other fields, the machining accuracy of parts is facing higher requirements. It is particularly important to predict the cutting force accurately, which is the main physical quantity in the machining process and basis of process inspection and quality control. In this paper, the cutting force model in five-axis milling with fillet-end cutter is proposed, which reveals the law of force-deflection coupling. Firstly, the initial cutter deflection model induced by the ideal cutting force ignoring the effect of deflection is built based on analysis of the geometric characteristics of fillet-end cutter. Then the undeformed chip thickness model is educed considering the cutter posture and cutter deflection. Further, the iterative method is utilized to resolve the coupling relationship between cutter deflection and cutting force. Finally, the cutting force model under force-deflection coupling is established for achieving more accurate prediction. To verify the effectiveness of the proposed cutting force model, the milling experiment is carried out on a five-axis milling center. The measured cutting force values are utilized to inspect the accuracy of prediction models considering and not considering force-deflection coupling respectively. The results show that the proposed method could improve the prediction accuracy of cutting force, which show the effectiveness of taking force-deflection coupling law into consideration clearly. The influence of cutter posture on cutting force is analyzed using the proposed cutting force model. The cutting force decreases with the increasing of lead angle or tilt angle, and the influence of tilt angle is greater than that of lead angle under experimental conditions of five-axis milling using the set process parameters.
T-type Calcium Channel Inhibitors Induce Apoptosis in Medulloblastoma Cells Associated With Altered Metabolic Activity
Authors: Sedeeq Mohammed , Maklad Ahmed , Feng Zikai , Wilson Richard , Gueven Nuri , Azimi Iman
Published: August 2021

Medulloblastoma (MB) is the most common malignant paediatric brain tumour. In our previous studies, we developed a novel 3D assay for MB cells and screened of plasma membrane calcium channel modulators. These studies identified T-type (CaV3) channel inhibitors, mibefradil and NNC-55-0396 (NNC) as selective inhibitors of MB cell growth. Mibefradil was originally approved for treatment of hypertension and angina pectoris, and recently successfully completed a Phase I trial for recurrent high-grade glioma. NNC is an analogue of mibefradil with multiple advantages compared to mibefradil that makes it attractive for potential future clinical trials. In this study, we aimed to characterise the effect of mibefradil and NNC on MB cells and elucidate their mechanism of action. This study demonstrates that the induction of toxicity in MB cells is selective to T-type but not to L-type Ca2+ channel inhibitors. Addition of CaV3 inhibitors to vincristine sensitised MB cells to this MB chemotherapeutic agent, suggesting a synergistic effect. Furthermore, CaV3 inhibitors induced cell death in MB cells via apoptosis. Supported by proteomics data and cellular assays, apoptotic cell death was associated with reduced mitochondrial membrane potential and reduced ATP levels, which suggests that both compounds alter the metabolism of MB cells. This study offers new insights into the action of mibefradil and NNC and will pave the way to test these molecules or their analogues in pre-clinical MB models alone and in combination with vincristine to assess their suitability as a potential MB therapy.