bluuebunny/crossref_metadata_2025 huggingface dataset:
A Framework for Systemic Sustainable Construction Industry Development (SSCID)
Authors: Gyadu-Asiedu William , Ampadu-Asiamah Adwoa , Fokuo-Kusi Alfred
Published: December 2020

The quest by most countries to achieve sustainable construction has met with several challenges as evidenced in low goal accomplishment. This is largely due to the fact that the issues have not been addressed within the context of the CI. Using the system thinking philosophy as applied to the construction industry, it should be possible to ensure sustainable development within the entire industry which should then spearhead sustainable construction as part of its sustainable development goals (SDGs). This paper proposes a framework by which a construction industry of a country could be developed sustainably and systemically. The methodology used involved an analytic study of relevant literature, reports and other documents on the implementation and challenges in sustainable development as applied to the construction industry. It identifies the major challenges and barriers militating against the CI development which must be addressed. It also posits that the goals of sustainable CI development should be linked to the SDGs. A framework is designed by which all the development of all the systems or organisations in the CI (all firms: construction, consulting, supplying, etc.) could be achieved taking cognisance of the identifiable components of CI development. This continuous process of ensuring sustainable development of the various organisations which shall be measured, monitored and managed (The 3Ms) will provide the needed environment for sustainable construction industry among other benefits. The framework is expected to operate on a construction industry information modelling (CIIM) principle and in an environment akin to the Building information modelling (BIM).
The Effects of Beta-cell Mass and Function, Intercellular Coupling, and islet Synchrony on Ca2+ Dynamics in Patients with Type 2 Diabetes Mellitus
Authors: Saadati Maryam , Jamali Yousef
Published: December 2020

Type 2 diabetes (T2D) is a challenging metabolic disorder characterized by a substantial loss of beta-cell mass via progressive programmed cell death and alteration of beta-cell function in the islets of Langerhans, disrupting insulin secretion and glucose homeostasis. The mechanisms for deficiency in beta-cell mass and function during the hyperglycemia development and T2D pathogenesis are complex. To study the relative contribution of beta-cell mass to beta-cell function in T2D, we make use of a comprehensive electrophysiological model from human beta-cell clusters. We find that defect in beta-cell mass causes a functional decline in single beta-cell, impairment in intra-islet synchrony, and changes in the form of oscillatory patterns of membrane potential and intracellular Ca2+ concentration, which can lead to changes in insulin secretion dynamics and insulin levels. The model demonstrates good correspondence between suppression of synchronizing electrical activity and pulsatile insulin release, and published experimental measurements. We then compare the role of gap junction-mediated electrical coupling with both beta-cell synchronization and metabolic coupling in the behavior of Ca2+ concentration dynamics within human islets. Our results indicate that inter-beta-cellular electrical coupling depicts a more important factor in shaping the physiological regulation of islet function and in human T2D. We further predict that varying the conductance gating of delayed rectifier K+ channels modifies oscillatory activity patterns of the beta-cell population lacking intercellular coupling, which significantly affects Ca2+ concentration and insulin secretion.
Human Cryptochrome Mediates Oxidative Stress Responses Modulated by Static and Electromagnetic Fields in Doxorubicin-Treated Cells
Authors: Hajipour-Verdom Behnam , Alipour Mozhgan , Abdolmaleki Parviz , Hosseinkhani Saman , Khoobi Mehdi , Panjali Zahra , Alipour Mohsen , Alam Nader Riyahi
Published: December 2020

Cryptochromes (CRYs) have been suggested to involve in the magnetic sensing for navigation of migratory birds in response to Earth’s magnetic fields. Magnetic fields (MFs) through wireless penetration change the cell physiology by effect on physicochemical reactions. Here, we aimed to investigate the behavior of HEK 293T cells overexpressing human CRY-based magnetoreception complexes undergo doxorubicin (DOX) treatment and exposure to moderate intensity static magnetic field (SMF) and extremely low frequency-pulsed electromagnetic field (ELF-PEMF). The ability of this magnetosensor is depended on CRY-photoreceptor proteins that complemented with putative magnetosensor proteins (MagR). The results indicate that magnetic sensitivity of CRY-based magnetosensor can effects on the intracellular reactive oxygen species (ROS) production and cell growth, cell cycle progression and expression of DNA damage-related genes due to treatment of DOX, SMF and ELF-PEMF. Our findings show that ROS accumulation significantly decreased in the cells expressing CRY/MagR complexes in response to all treatments, and also cell viability is decreased in contrast to MFs exposure. In addition, magnetosensitive complexes mediated the upregulation of genes in the base excision repair (BER) pathway including ITPA in presence of SMF as well as MTH1 in presence of ELF-PEMF in the DOX treated-cells. Furthermore, CRY/MagR induced a remarkable cell cycle arrest at G0/G1 phase in the all treatments. These results demonstrated that CRY/MagR complexes modify the DNA damage responses during genotoxic stresses by controlling the cell cycle progression and ROS levels. Therefore, our data suggest that CRY-based magnetosensitive complexes can increase the cytotoxic effects of DOX even when SMF and/or ELF-PEMF exposure were provided, exclusively.
Pure T-cell Mediated Rejection Following Kidney Transplant According to Response to Treatment 
Authors: Kwon Hyunwook , Kim Young Hoon , Kim Dong Hyun , Ko Youngmin , Lim Seong Jun , Jung Joo Hee , Baek Chung Hee , Kim Hyosang , Park Su-Kil , Shin Sung , Cho Yong-Pil , Han Duck Jong
Published: December 2020

Over the last two decades, the focus of studies on graft survival (GS) after kidney transplantation (KT) has largely shifted from T-cell mediated rejection (TCMR) to antibody-mediated rejection (ABMR). However, there are still cases of pure acute TCMR in histological reports, even after a long time following transplant. We thus evaluated the impact of pure TCMR on GS according to treatment response. We also performed molecular diagnosis using a molecular microscope diagnostic system (MMDx) to determine the accuracy of the histologic diagnosis of pure TCMR. A total of 63 patients were included in our study and divided into non-responders (N = 22) and responders (N = 44) according to their response to rejection treatment. Molecular diagnosis and histologic diagnosis were conducted simultaneously on a separate group of 23 patients. The non-responders had a significantly longer duration between treatment and recurrent rejection than did the responders (24 vs. 11 months; P < 0.01). The cumulative incidence of recurrent rejection after treatment was significantly higher in the non-responders as well (64% vs. 29%; P < 0.01). Non-response to rejection treatment was significantly associated with the following factors: GFR at biopsy, ΔGFR (baseline GFR – GFR at biopsy), TCMR within one year, t score, and IF/TA score. We also found that non-responder vs. responder (HR = 3.31; P = 0.04) and lower GFR at biopsy per 10 mL/min/1.73m2 (HR = 0.56; P = 0.03) were independent risk factors of graft failure. The responders had a significantly superior overall GS rate compared with the non-responders (P < 0.01). Molecular assessment using MMDx showed a good correlation with histologic diagnosis in ABMR, but not in TCMR. Solitary TCMR was a significant risk factor of graft failure in patients who did not respond to rejection treatment. Molecular assessment using MMDx did not show a good correlation with histologic diagnosis in TCMR, suggesting that acute pure TCMR at one year after transplant in histologic reports should be interpreted with caution.
STK35L1 regulates Plasmodium infection and expression of cell cycle genes during liver stage of malaria
Authors: Sharma Phulwanti , Kalia Inderjeet , Kaushik Vibha , Brünnert Daniela , Quadiri Afshana , Kashif Mohammad , Chahar Kirti , Agarwal Akhil , Singh Agam Prasad , Goyal Pankaj
Published: December 2020

Protein kinases of both the parasite and host are crucial in parasite invasion and survival and might be drug targets against drug-resistant malaria. STK35L1 was among the top five hits in kinome-wide screening, suggesting a role in malaria’s liver stage. The function of STK35L1 in malaria is not known yet. We found that STK35L1 was highly upregulated during the infection of P. berghei in HepG2 cells and mice liver. Knockdown of STK35L1 remarkably suppressed the sporozoite infection in hepatocytes. STAT3 is upregulated and phosphorylated during P. berghei sporozoites infection. We found that STAT3 activation is required for both STK35L1 and STAT3 upregulation. Furthermore, ten cell cycle genes were upregulated in the sporozoite-infected hepatocytes. Knockdown of STK35L1 completely inhibited the upregulation of these genes. We identified STK35L1 as a host kinase that plays an obligatory role in malaria’s liver stage. It may be a potential drug target against drug-resistant malaria.
Artificial Intelligence in Detecting Temporomandibular Joint Osteoarthritis on Orthopantomogram
Authors: Choi Eunhye , Kim Donghyun , Lee Jeong-Yun , Park Hee-Kyung
Published: December 2020

Orthopantomogram (OPG) is still important in primary diagnosis of temporomandibular joint osteoarthritis (TMJOA), because of cost and radiation of computed tomogram (CT). The aims of this study were to develop an artificial intelligence (AI) model and compare its TMJOA diagnostic performance on OPG with that of an oromaxillofacial radiology (OMFR) expert. An AI model was developed using Karas’ ResNet model and trained to classify images into three categories: normal, indeterminate OA, and OA. This study included 1189 OPG images confirmed by cone-beam CT and evaluated the results by model (accuracy, precision, recall, and F1 score) and diagnostic performance (accuracy, sensitivity, and specificity). The model performance was unsatisfying when AI developed with 3 categories. After the indeterminate OA images were reclassified as normal, OA, or omission, the AI diagnosed TMJOA in a similar manner to the expert and was most accordant with CBCT read when the indeterminate OA was omitted (accuracy: 0.78, sensitivity: 0.73, and specificity: 0.82). Our deep learning model showed a sensitivity equivalent to that of an expert, with a better balance between sensitivity and specificity, which implies that AI can play an important role in primary diagnosis of TMJOA on OPGs in most general practice clinics where OMFR experts or CT are not available.
Patterns of Pain Location in Music Students. A Cluster Analysis 
Authors: Cruder Cinzia , Barbero Marco , Soldini Emiliano , Gleeson Nigel
Published: December 2020

Background: According to existing literature, musicians experience high rates of musculoskeletal (MSK) disorders involving different anatomical areas. The aim of the study was to identify patterns of pain location in a sample of music students enrolled in different pan-European music institutions. A further goal was to explore the association between the identified pain patterns and students’ characteristics.Methods: A total of 340 music students (mean age 23.3 years, 66.2% female) with current MSK pain completed a web-based questionnaire including both background information (i.e. lifestyle and physical activity, practice habits) and clinical features (i.e. pain characteristics, disability, pain self-efficacy, psychological distress, perfectionism and fatigue). Results: Five patterns of pain location were identified by hierarchical cluster analysis: wrist pain (WP) representing 22.6% of the total sample, widespread pain (WSP) (16.9%), right shoulder pain (RSP) (18.5%), both shoulders pain – left concentrated (LSP) (23.2%), neck and back pain (NBP) (18.8%). Amongst the identified patterns of pain location, bivariate analysis identified the WSP cluster as containing the largest number of associated variables. Participants in this cluster reported a higher percentage of women (p<.05), a higher perceived exertion (p<.01) and psychological distress (p<.001), as well as a lower level of self-efficacy (p<.01). Similarly, a higher percentage of participants included in the WSP cluster perceived their playing activity as the main cause of their MSK pain (p<.01). Additionally, a higher level of disability in relation to playing-related activity was reported by participants included in the WP and WSP clusters (p<.001). The RSP cluster was characterised by a higher percentage of participants playing an instrument in a neutral position (p<.001) and lower levels of socially prescribed perfectionism (p<.01). A higher percentage of participants playing an instrument with both arms elevated in the left quadrant position were included in the LSP cluster and a higher percentage of singers were included in the NBP cluster (p<.001).Conclusions: Five distinct patterns of pain location were identified and their associations with the students’ characteristics were explored. These findings may be helpful in the exploration of different aetiologies of MSK pain among musicians and in the development of targeted preventive strategies and treatments.
Coconut Lethal Yellowing-Like Diseases: Insights From Predicting Potential Distribution Under Different Climate Change Scenarios
Authors: Aidoo Owusu Fordjour , Cunze Sarah , Guimapi Ritter , Arhin Linda , Ablormeti Fred Komla , Tettey Elizabeth , Dampare Frank , Afram Yayra , Bonsu Osei , Obeng Joshua , Lutuf Hanif , Dickinson Matthew , Yankey Ndede
Published: December 2020

Coconut is recognized for its popularity in contributing to food and nutritional security. It generates income and helps to improve rural livelihood. However, there is a rise in the number of plant diseases due to globalization, including lethal yellowing-like diseases (LYD). A clear understanding of climate-suitable areas for disease invasion is essential for implementing quarantine measures. Therefore, we modelled in Maximum Entropy to establish habitat suitability of LYD under current and future climate change scenarios using three Shared Socioeconomic Pathways (SSPs) (1.26, 3.70 and 5.85) for three time periods (2041-2060, 2061-2080 and 2081-2100). The area under the curve value for LYD was 0.98, suggesting that the model’s performance was very good. The predictor variables that most influenced LYD projections were minimum temperature of the coldest month (88.4%) and the precipitation of the warmest quarter (7.3%). Outside its current range, the model projected climate-suitable areas of LYD in Australia, Asia and South America. Our study highlights potential climate suitable and unsuitable areas of LYD, and provides useful information for increasing quarantine measures. Also, the potential expansion of the disease into uninfected areas suggests that future research should focus on the development of resistant or tolerant coconut varieties against the disease.
Fundamental Movement Skill Proficiency and Objectively Measured Physical Activity in Children with Bronchiectasis: A Cross-Sectional Study.
Authors: Joschtel Barbara , Gomersall Sjaan , Tweedy Sean , Petsky Helen , Chang Anne , Trost Stewart
Published: December 2020

Background: Bronchiectasis is a major contributor to respiratory morbidity and healthcare utilization in children. Children with bronchiectasis exhibit low levels of physical activity (PA) and poor fundamental movement skills (FMS) may be a contributing factor. However, there are no data on FMS’s in this patient group. The current study assessed FMS proficiency in children with bronchiectasis and examined associations with objectively measured PA.Methods: Forty-six children with bronchiectasis (mean age 7.5 ± 2.6 y) were recruited from the Queensland Children’s Hospital, Brisbane. Daily time spent in sedentary activities, light-intensity activities and games, walking, running, and moderate-to-vigorous activities and games was measured objectively using the ActiGraph GT3X+ accelerometer. The raw accelerometer data were processed into PA metrics using a random forest PA classification algorithm specifically developed for children. FMS were assessed using the Test of Gross Motor Development 2nd Edition (TGMD-2).Results: Fewer than 5% of children demonstrated mastery in the run, gallop, hop, and leap; while fewer than 10% demonstrated mastery for the two-handed strike, overarm throw, and underarm throw. The mean Gross Motor Quotient of 82.7 ± 12.8 indicated that, as a group, FMS performance was well below average.Only eight of the 46 children (17.4%) achieved their age equivalency for locomotor skills, while just four (8.7%) achieved their age equivalency for object control skills. Children achieving their age equivalency for FMS exhibited significantly higher levels of PA than children not achieving their age equivalency (51.7 vs 36.7 min/day). When examined by the five activity classes predicted by the random forest PA classification algorithm, children achieving their age equivalency exhibited significantly greater participation moderate-to-vigorous intensity activities and games (22.1 vs 10.7 min/day). No significant differences were observed for sedentary activities, light-intensity activities and games, walking, and running.Conclusion: Children with bronchiectasis exhibit significant delays in their FMS development. However, those who meet their age equivalency for FMS proficiency participate in significantly more daily MVPA than children who do not meet their age-equivalency. Therapeutic exercise programs designed to improve FMS proficiency are thus likely to be beneficial in this patient group.
Design of A Multi-Epitope Protein Vaccine Against Herpes Simplex Virus, Human Papillomavirus and Chlamydia Trachomatis as the Main Causes of Sexually Transmitted Diseases
Authors: Dorosti Hesam , Eskandari Sedigheh , Zarei Mahboubeh , Nezafat Navid , Ghasemi Younes
Published: December 2020

Background: Sexually transmitted diseases (STDs) have a profound effect on reproductivity and sexual health worldwide. According to world health organization (WHO) 375 million new case of STD, including chlamydia trachomatis (chlamydia), Neisseria gonorrhoeae, HSV, HPV has been reported in 2016. More than 30 diverse pathogenesis have identified to be transmitted through sexual intercourse. Of these, viral infections (hepatitis B, herpes simplex virus (HSV or herpes), HIV, and human papillomavirus (HPV) are incurable. However, symptoms caused by the incurable viral infections can be alleviated through treatment. Antimicrobial resistance (AMR) of sexually transmitted infections (STIs) to antibiotics has increased recent years, in this regard, vaccination is proposed as an important strategy for prevention or treatment of STDs. Vaccine against HPV 16 and 18 suggests a new approach for controlling STDs but until now, there is no prophylactic or therapeutic vaccine have been approved for HSV-2 and Chlamydia trachomatis(CT); in this reason, developing an efficient vaccine is inevitable. Recently, different combinatorial forms of subunit vaccines against two or three type of bacteria have been designed. Results: In this study, to design a combinatorial vaccine against HSV, CT, and HPV, the E7 and L2 from HPV, glycoprotein D from HSV-2 and ompA from CT were selected as final antigens. Afterward, the immunodominant helper T lymphocytes (HTLs) and cytolytic T lymphocytes (CTLs) epitopes were chosen from aforesaid antigens. P30 (tetanus toxoid epitope) as universal T-helper were also added to the vaccine. Moreover, flagellin D1/D0 as TLR5 agonist and the RS09 as a TLR4 ligand were incorporated to N and C-terminals of peptide vaccine, respectively. Finally, all selected parts were fused together by appropriate linkers to enhance vaccine efficiency. The physicochemical, structural, and immunological properties of the designed vaccine protein were assessed. To achieve the best 3D model of the protein vaccine, modeling, refinement, and validation of modeled structures were also done. Docking evaluation demonstrated suitable interaction between the vaccine and TLR5. Moreover, molecular dynamics (MD) studies showed an appropriate and stable structure of protein and TLR5. Conclusion: Based on immunoinformatic analysis, our vaccine candidate could potentially incite humoral and cellular immunities, which are critical for protection against HPV, HSV-2, and chlamydia trachomatis. It should be noted that, experimental studies are needed to confirm the efficacy of the designed vaccine.
Study on the Differentially Expressed Genes and Signaling Pathways in Systemic Lupus Erythematosus Using Integrated Bioinformatics Method
Authors: Liang Jing , Zhang Xin , Zhao Wenjia
Published: December 2020

Background: Systemic lupus erythematosus (SLE) is a chronic immune connective tissue disease, which is common in women of childbearing age and easy to cause multiple organ inflammatory injury. The occurrence of prostate cancer is the result of multiple factors and genes, but we have little understanding of the mechanism involved. In this study, we deeply explored and analyzed the existing gene data in GEO database in order to find the key genes and new therapeutic targets of SLE.Results: The expression profile dataset of GDS4185, GDS4888, GDS4889 and GDS4890 containing 99 specimens, 42 cases of SLE patients and 57 cases of normal volunteers, were downloaded from the Gene Expression Omnibus (GEO) website. The differentially expressed genes (DEGs) in different tissues was analyzed by statistical hypothesis T test. The gene ontology (GO) enrichment analysis was carried out by the DAVID online tool. KEGG pathway annotation of DEGs was carried out by the KOBAS online computing database. The protein–protein interaction (PPI) networks of the DEGs were built from the STRING website and Cytoscape software. A total of 839 DEGs were calculated from the four GEO datasets. The GO and KEGG analysis indicated that the functions of DEGs mostly participated in the Osteoclast differentiation, HTLV-I infection, Measles, FoxO signaling pathway, Herpes simplex infection, Primary immunodeficiency, Jak-STAT signaling pathway. The following 14 closely related genes, HERC5, TP53, CDC20, GNB2, GNB4, PPP2R1A, GNAI2, PMCH, SOCS3, HERC6, STAT1, SOCS1, ISG15, IFIT3, were key nodes from the PPI network. These genes may have synergistic or indirect interactions with each other in the process of biological metabolism inducing the pathogenesis of SLE.Conclusion: Mining geo database has great scientific research value. In the future, scientific research must fully excavate a variety of database analysis methods. In this study, the screened candidate genes provide effective theoretical basis for the diagnosis, treatment, expected evaluation and related laboratory research of SLE, which are worthy of further experimental verification.
Visual Assessment of Commercial Drivers in the South West Region of Cameroon
Authors: Vofo Brice , Ayuk Doris , Pe'er Jacob , Chichom-Mefire Alain , Tendongfor Nicholas , Nche Eleanor
Published: December 2020

Background: Driving is a visually intensive task. In Cameroon where the burden of road traffic deaths is high, visual assessment is not universally performed before the issuance of driver’s licenses. This study assesses the visual status of commercial drivers (CDs) in the Southwest Region of Cameroon.Methods: This was a cross-sectional community-based study on CDs in Limbe and Buea. Questionnaires were used to assess socio-demographic parameters, the incidence of road traffic crashes (RTCs), and self-reported visual status. Visual acuity (VA) was measured using a standard Snellen chart at 6 meters. Statistical analysis was done using descriptive methods; frequencies, paired Student’s t-test, and Chi-square test.Results: 207 CDs were enrolled. All were male, with a mean age of 41.8 ± 12.1 years. 15.0% had undergone an eye exam prior to licensure, and 3.4% within the past 10 years. VA in the better-seeing eye was less than 6/9 and 6/12 in 14.1%, and 10.6% of CDs, respectively. 75% of CDs with self-reported poor vision and 95% of CDs with VA < 0.5 had a history of an RTC compared to 55.8% of CDs with self-reported good vision and 55.7% of CDs with VA ≥ 0.5 (p<0.05). Injuries from RTCs were more common in CDs with self-reported poor vision (81.1%) and in those with VA<0.5 (90.5%) compared to CDs who self-reported good vision (55.8%) and those with VA ≥ 0.5 (55.7%) p<0.05.Conclusion: A large proportion of CDs did not have a visual assessment before the issuance or renewal of their driver’s licenses. A considerable number had poor vision in their better-seeing eye and suffered more from RTCs and related injuries. The concerned authorities should consider making vision tests a necessary requirement for the obtention of driver’s licenses.
Grid1 Regulates the Onset of Puberty in Female Rats
Authors: Ye Jing , Qin Ping , Li Hailing , Kang Tiezhu , Si Wenyu , Yao Zhiqiu , Liu Ya , Yu Tong , Zhang Yunhai , Ling Yinghui , Cao Hongguo , Wang Juhua , Li Yunsheng , Fang Fugui
Published: December 2020

The present study aimed to investigate whether Grid1, encoding the glutamate ionotropic receptor delta type subunit 1(GluD1), influences the onset of puberty in female rats. First, we detected the expression of Grid1 mRNA and its protein in the hypothalamus from infancy to puberty. Second, we evaluated the suppression of Grid1 expression by Lentivirus-Grid1 (LV-Grid1) in primary hypothalamus cells through measuring the expression level of Grid1. Finally, LV-Grid1 was intracerebroventricular injected (ICV) into 21-day-old rats and to investigate the effect of Grid1 suppression on puberty onset in vivo. Results showed that GluD1 immunoreactivity could be detected in the arcuate nucleus (ARC), paraventricular nucleus (PVN), and periventricular nucleus (PeN). Grid1 mRNA levels were the lowest at prepuberty. Treatment of hypothalamic neurons with LV-Grid1 decreased the mRNA expression levels of Grid1 and Rfrp-3 (encoding RFamide-related peptide 3, RFRP 3), but increased that of Gnrh (encoding gonadotropin-releasing hormone, GnRH). After 7 days of ICV LV-Grid1 into rats, the Grid1 mRNA was significantly reduced (by 46%), Gnrh mRNA expression was significantly increased, but Rfrp-3 mRNA levels were decreased. The time of rat vaginal opening (VO) was earlier in the LV-Grid1 group; the concentrations of luteinizing hormone (LH), estradiol (E2), and progesterone (P4) in serum were significantly increased; and the ovaries were significantly larger. Our study revealed that Grid1 affects the onset of puberty by regulating the level of GnRH and RFRP3.
Nanoemulsion Formulation of Cold Pressed Neem Oil As a Repellent Against Anopheles Stephensi 
Authors: Taheri Mohammadreza , Iman Maryam , Khoobdel Mehdi , Dehghan Omid , Zarei Seyed Mohammad
Published: December 2020

Background: To formulate a nanoemulsion (NE) from cold pressed neem oil and to compare its repellant activity with normal cold pressed oil and N,N-Diethyl-meta-toluamide (DEET) as a standard chemical compound and to improve efficacy of repellency against Anopheles stephensi, through NE formulations.Methods: In this study, complete protection time (CPT) and failure time of samples were evaluated on human subjects using the arm in cage assay, and their values were determined against An. stephensi. The droplet size of the NE were measured with dynamic light scattering. Pseudo ternary phase diagrams were constructed consisting of an emulsion system of an active ingredient (neem oil), surfactant (Tween 80), and water. Two formulations were selected from the isotropic regions and showed particle sizes of 12.3 and 93.9 nm in diameter.Results: The results (expressed in minutes as mean±SD) showed that CPTs of neem oil NE in tween 80, and DEET 20% were 240±39 min and 360±24 respectively. Dose values for Neem oil in formulation and for DEET were 77 μg/cm2 and 308 μg/cm2, respectively. Nano neem oil in tween 80 provided significantly longer protection than normal cold pressed neem oil (P<0.01). The prepared NEs showed high kinetic stability for weeks, without phase separation, sedimentation or creaming. Nevertheless, their droplet size increased slightly over time. Compared to non-formulated neem oil, the NE significantly increased the Repellency of the tested species.Conclusions: NE of neem oil significantly increases the CPT and reduces needed dose values. Hence, neem oil NE can be a good alternative to DEET and other chemical repellents.
Community Acceptance of Reactive Focal Mass Drug Administration and Reactive Focal Vector Control Using Indoor Residual Spraying, a Mixed-Methods Study in Zambezi Region, Namibia
Authors: Roberts Kathryn W. , Gueye Cara Smith , Baltzell Kimberly , Ntuku Henry , McCreesh Patrick , Maglior Alysse , Whittemore Brooke , Uusiku Petrina , Mumbengegwi Davis , Kleinschmidt Immo , Gosling Roly , Hsiang Michelle S.
Published: December 2020

BackgroundIn Namibia, as in many malaria elimination settings, reactive case detection (RACD), or malaria testing and treatment around index cases, is a standard intervention. Reactive focal mass drug administration (rfMDA), or treatment without testing, and reactive focal vector control (RAVC) in the form of indoor residual spraying, are alternative or adjunctive interventions, but there is limited data regarding their community acceptability.MethodsA parent trial aimed to compare the effectiveness of rfMDA versus RACD, RAVC versus RAVC, and rfMDA+RAVC versus RACD only. To assess acceptability of these interventions, we conducted a mixed-methods study that included key informant interviews (KIIs) and focus group discussions (FGDs) in three rounds (pre-trial and in years 1 and 2 of the trial), and an endline survey. ResultsIn total, 17 KIIs, 49 FGDs were conducted with 449 people over three annual rounds of qualitative data collection. Pre-trial, community members more accurately predicted the level of community acceptability than key stakeholders. Throughout the trial, key participant motivators included: malaria risk perception, access to free community-based healthcare and IRS, and community education by respectful study teams. RACD or rfMDA were offered to 1,372 and 8,948 individuals in Years 1 and 2, respectively and refusal rates were low (<2%). RAVC was offered to few households (n=72) in Year 1. In year 2, RAVC was offered to more households (n=944) and refusal were <1%. In the endline survey, 94.3% of 2,147 respondents said they would participate in the same intervention again.ConclusionsCommunities found both reactive focal interventions and their combination highly acceptable. Engaging communities and centering and incorporating their perspectives and experiences during design, implementation, and evaluation of this community-based intervention was critical for optimizing study engagement.
Medication Risk Management and Health Equity in New Zealand General Practice: A Retrospective Cross-Sectional Study
Authors: Leitch Sharon , Zeng Jiaxu , Smith Alesha , Stokes Tim
Published: December 2020

BackgroundDespite an overt commitment to equity, health inequities are evident throughout Aotearoa New Zealand. A general practice electronic alert system was developed to notify clinicians about their patient’s risk of harm due to their pre-existing medical conditions or current medication. We aimed to determine whether there were any disparities in clinician action taken on the alert based on patient ethnicity or other demographic factors.MethodsSixty-six New Zealand general practices from throughout New Zealand participated. Data were available for 1611 alerts detected for 1582 patients between 1 Jan 2018 and 1 July 2019. The primary outcome was whether action was taken following an alert or not. Logistic regression was used to assess if patients of one ethnicity group were more or less likely to have action taken. Potential confounders considered in the analyses include patient age, gender, ethnicity, socio-economic deprivation, number of long term diagnoses and number of long term medications.ResultsNo evidence of a difference was found in the odds of having action taken amongst ethnicity groups, however the estimated odds for Māori and Pasifika patients were lower compared to the European group (Māori OR 0.88, 95%CI 0.63–1.22; Pasifika OR 0.88, 95%CI 0.52–1.49). Females had significantly lower odds of having action taken compared to males (OR 0.76, 95%CI 0.59–0.96).ConclusionThis analysis of data arising from a general practice electronic alert system in New Zealand found clinicians typically took action on those alerts. However, clinicians appear to take less action for women and Māori and Pasifika patients. Use of a targeted alert system has the potential to mitigate risk from medication-related harm. Recognising clinician biases may improve the equitability of health care provision.
Identification of Hub Genes and Pathways With Immune Cell Infiltration in Cholangiocarcinoma by Weighted Gene Co-expression Network Analysis
Authors: Yan Ye , Zhao Lihao , Su Huafang , Li Gang , Jiang Sujing
Published: December 2020

Background: Cholangiocarcinoma (CCA) is the most frequent tumor in biliary tract and the second most common primary tumor of the liver. However, the molecular biomarkers in tumorigenesis of CCA remain unclear. Therefore, we aim to explore the underlying mechanisms of progression and screen for novel prognostic biomarkers and therapeutic targets.Method: The genes expression sequencing of normal and CCA samples were selected from the Gene Expression Omnibus database (GEO) and the Cancer Genome Atlas (TCGA). The weighted gene co-expression network analysis (WGCNA) was used to build the co-expression network. Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied for the selected genes. The protein-protein interactions of these modules are visualized using cytoscape. Furthermore, the significance of these genes was confirmed by survival analysis. The tumor immune estimation resource (TIMER) was presented to investigate assess the relationship between the hub genes and the immune cells infiltration.Results: Ten hub genes with CCA development were identified in this study containing CDC20, CCNA2, TOP2A, AURKA, CCNB2, UBE2C, NUSAP1, PRC1, PTTG1 and MCM4. Key genes of CCNB2 and PTTG1 might be potential prognostic biomarkers for CCA. GO analysis indicated the enrichment terms of nuclear division, collagen-containing extracellular matrix and cell adhesion molecule binding. KEGG analysis demonstrated that the cell cycle pathway was the significantly altered pathway. There was a negative correlation between TOP2A, AURKA, CCNB2, PRC1 expression and the infiltration of CD4+T cell, while MCM4 expression was positively associated with the infiltration of neutrophil cells. No significant association between CDC20 levels and CD4+T cell, CD8+T cell, B cell, neutrophil, macrophage, or dendritic cell infiltration in CCA, the same as CCNA2, UBE2C, NUSAP1, PTTG1 respectively.Conclusion: These candidate genes may involve in the development of CCA. Our results offer novel insights into the etiology, prognosis, and treatment of CCA.
Effects of intraoperative fluid management on postoperative outcomes after pericardiectomy
Authors: Fang Likui , Zheng Hong , Yu Wenfeng , Chen Gang , Zhong Fangming
Published: December 2020

Background The effects of intraoperative fluid management on the patients with constrictive pericarditis undergoing pericardiectomy remain unclear. This study explored the relationship between intraoperative fluid management and postoperative outcomes in these patients.Methods We retrospectively studied 92 patients with constrictive pericarditis undergoing pericardiectomy and assigned them to the restrictive group and the liberal group according to the intraoperative total fluid infusion rate. Postoperative outcomes were compared between the two groups. Binary logistic regression analysis was performed to determine the relationship between the intraoperative total fluid infusion rate and postoperative outcomes.Results There were 46 (50.0%) cases in the restrictive group (2.68 to 7.46 ml/kg/h) and 46 (50.0%) cases in the liberal group (7.47 to 20.55 ml/kg/h). Compared with the liberal group, the restrictive group had significantly lower incidences of postoperative complications and cardiac complications (P=0.005 and P=0.006, respectively). Binary logistics regression analysis also showed the increased risks of postoperative complications (OR, 3.551; 95%CI, 1.192-10.580; P=0.023) and cardiac complications (OR, 5.083; 95%CI, 1.206-21.426; P=0.027) at the liberal group. In addition, the restrictive group had shorter postoperative hospital stay (P=0.026) in comparison to the liberal group.Conclusion In patients with constrictive pericarditis undergoing pericardiectomy the intraoperative total fluid infusion rate was significantly associated with postoperative outcomes. Restrictive fluid management strategy could exert positive effects on enhanced recovery after surgery and might be the preferred intraoperative fluid management policy.
Profile of Congenital Heart Disease and Access to Definitive Care Among Children Seen at Gulu Regional Referral Hospital in Northern Uganda: a Four-year Experience
Authors: Aliku Twalib Olega , Beaton Andrea , Lubega Sulaiman , Dewyer Alyssa , Scheel Amy , Kamarembo Jenipher , Akech Rose , Sable Craig , Lwabi Peter
Published: December 2020

Objectives: The aim of this study was to describe the profile of Congenital Heart Disease [CHD] and access to definitive surgical or catheter-based care among children attending a regional referral hospital in Northern Uganda. Methods: This was a retrospective chart review of all children aged less than 17 years attending Gulu Regional Referral Hospital Cardiac clinic from November 2013 to July 2017. Results: A total of 299 children were diagnosed with CHD during the period. The median age at diagnosis was 12 months ([QR: 4 – 48] with females representing 59.2% [n=177] of cases. Neonates comprised only 7.4% [n=22]. The commonest CHD seen was ventricular septal defect [VSD] in 19.4% [n=58] of cases, followed by atrioventricular septal defect (AVSD) in 17.1% [n=51] and patent ductus arteriosus (PDA) in 15.7% [n=47]. The commonest cyanotic CHD seen was tetralogy of Fallot [TOF] in 5% [n=15], followed by double outlet right ventricle [DORV] in 4% [n=12] and truncus arteriosus in 3.4% [n=10]. Dextro-transposition of the great arteries [D-TGA] was seen in 1.3% [n=4]. At initial evaluation, 75% [n=224] of all CHD needed definitive intervention and 14% of these children [n=32] had accessed surgical or catheter-based therapy within 2 years of diagnosis. Three quarters of the cases who had intervention [n=24] had definitive care at the UHI including all 12 cases who underwent catheter-based interventions. Conclusions: There is delayed diagnosis of most rural Ugandan Children with CHD and access to definitive care is severely limited. In-country programs offer the most feasible option to increase access to definitive care.
Multi-Center Randomized Trial of Compound Kushen Injection for Decreasing Radiation- Induced Thoracic Toxicity in Lung Cancer Patients
Authors: Yu Qingxi , Wang Jun , Wang Fan , Yin Haitao , Li Xia , Yuan Shengli , Yang Fujun , Xia Bing , Jia Zhongyao , Liu Sen , Zhang Kaixian , Jiang Xuechao , Liu Fengchun , Wang Luanqiu , Deng Junji , Tong Xu , Liu Shuyan , Lin Hongsheng , Yuan Shuanghu
Published: December 2020

Background: Thoracic radiation therapy plays an important role in the treatment of inoperable lung cancer. However, radiotherapy-induced toxicity poses an important challenge for radiation oncologists. Research has shown that Compound Kushen Injection (CKI) has anti-inflammatory activity and can reduce toxicity when given with chemotherapy. In the present trial, we investigated whether CKI also can decrease chemoradiotherapy-induced thoracic toxicity in lung cancer patients.Methods: A prospective, open, randomized, multi-center study was performed, in which a total of 296 patients were enrolled and randomly divided 1:1 into experimental and control groups. The control group received standard chemoradiotherapy including precise thoracic radiotherapy (60 Gy/30 fractions/6 weeks) plus concurrent platinum-based chemotherapy. The experimental group received standard chemoradiotherapy plus CKI via mainline treatments of 250 ml CKI (20 ml diluted in 0.9% normal saline) daily for 20 continuous days. The incidence of adverse events and severity of thoracic toxicity after treatment were observed according to version 4.0 of the Common Terminology Criteria for Adverse Events. Adverse drug reactions (ADRs) and quality of life (QLQ-C30) also were compared between the two groups.Results: Two hundred ninety-one qualifying patients were included in the statistical analysis. Symptomatic radiation-induced thoracic toxicity was lower in the experimental group than in the control group (14.1% vs 25.6%, p=0.017). According to QLQ-C30 questionnaire findings, CKI provided superior outcomes related to pain relief, relieving fatigue, social functioning and emotional functioning (p<0.05). The rates of adverse events (26.4% vs 30.8%, p>0.05) and severe adverse events (5.4% vs 2.8%, p>0.05) did not differ significantly between the experimental and control groups.Conclusion: CKI significantly alleviated symptomatic radiation-induced thoracic toxicity, as well as pain, when given with chemoradiotherapy for lung cancer treatment.
IGF2BP3 Promotes Lung Cancer Progression Through FTO Dependent m6A Modification by Stabilizing N-myc
Authors: Wang Xiaolin , Chen Yong , Min Lingfeng , Shi Hongcan , Lu Shichun , Sun Chao , Jin Weiguo , Shu Yusheng
Published: December 2020

Background: N6-methyladenosine modification has been involved in various biological processes. However, its role in non-small cell lung cancer has not been well studied. Here, we show that IGF2BP3, as an transcription factor, plays a critical oncogenic role in non-small-cell lung cancer carcinogenesis through activating FTO expression and inducing aberrant m6A modification. Methods: To evaluate the role of IGF2BP3 in non-small-cell lung cancer, we performed cell proliferation and cell cycle assays in three lung cancer cell lines. Lung cancer mouse model is used to examine the effects of IGF2BP3/FTO/N-myc on lung proliferation potentials in vivo. We analyzed the correlation between IGF2BP3 and FTO, IGF2BP3 and N-myc protein in colon cancer patients by Pearson correlation. To finally explore the relationship of IGF2BP3/FTO/N-myc, we used western blots, proliferation and cell cycle assays to confirm that IGF2BP3 may regulate lung cancer progression through FTO dependent m6A modification by stabilizing N-myc.Results: We first identified that IGF2BP3 overexpressed in non-small-cell lung cancer tissue and cells. Then, we showed that FTO was the dysregulated factor responsible for the abnormal N6-methyladenosine modification in non-small-cell lung cancer. The loss-of-function assay demonstrated that IGF2BP3 enhances FTO-mediated cell proliferation and promotes cell apoptosis, through regulating expression of target gene N-myc by reducing m6A level in mRNA transcript. Conclusion: Our study demonstrates the functional importance of IGF2BP3 and N6-methyladenosine methylation modification in the tumor progression of non-small-cell lung cancer, and provides profound insights into lung carcinogenesis and drug response.
HPV16 E7 Oncoprotein As a Predictor of Diagnosis and Prognosis in Patients with Cervical Lesions
Authors: Shuai Guangnan , Xu Junhui , Liu Meihua , Zhu Xueping , Zhang Na , Qu Pengpeng
Published: December 2020

Backgroud：The early diagnosis and treatment of HSIL is a key measure to prevent the occurrence of cervical cancer. Although the methods of cervical cancer screening are becoming more and more abundant, some patients still have unnecessary colposcopy referrals. This study aim to explore the value of human papillomavirus 16 (HPV16) E7 oncoproteinin cervical lesion screening and risk assessment of the prognosis for more effective colposcopy. Method: HPV16 E7 oncoprotein in cervical exfoliated cells was detected by using E7 Oncoprotein (HPV16) Diagnostic Kit (Magnetic Partical Chemiluminescence Method). In the first part, HPV16 E7 oncoprotein in different degrees of cervical lesions was retrospectively compared to find the best critical value; In the second part, the value of this test was verified ; In the third part, the women diagnosed as low-grade squamous intraepithelial lesions (LSIL) or normal were followed up for 3 years and the outcomes were compared. Results: In the first part, the expression of HPV16 E7 oncoprotein was positively correlated with the degree of cervical lesion; The critical value determined by ROC curve is 8.68ng/ml, which is accurate in the diagnosis of high-grade squamous intraepithelial lesions (HSIL) and invasive carcinoma of cervix (CA); In the second part, there were higher sensitivity(87.1) and specificity(70) for E7 oncoprotein; HPV16 E7 oncoprotein has higher consistency with pathological examination in detection of HSIL or cervical cancer（0.573 vs 0.369) than TCT; In the third part，HPV16 E7 oncoprotein has a high positive predictive value (82.4%) and positive likelihood ratio (4.43) for the prognosis of patients with LSIL and below. Conclusions: The status of HPV16E7 oncoprotein shows important clinical value for the detection and prediction of cervical lesions. Patients with positive HPV16 E7 oncoprotein are more likely to develop the disease and have a higher risk of disease progression.
Neuropilin 1 and Neuropilin 2 Gene Invalidation or Pharmacological Inhibition Reveals Their Relevance for the Treatment of Metastatic Renal Cell Carcinoma
Authors: Dumond Aurore , Brachet Etienne , Durivault Jérôme , Vial Valérie , Puszko Anna , Lepelletier Yves , Montemagno Christopher , Pagnuzzi-Boncompagni Marina , Hermine Olivier , Garbay Christiane , Lagarde Nathalie , Montes Matthieu , Demange Luc , Grépin Renaud , Pagès Gilles
Published: December 2020

BackgroundDespite the improvement of relapse-free survival mediated by anti-angiogenic drugs like sunitinib (Sutent ®), or by combinations of anti-angiogenic drugs with immunotherapy, metastatic clear cell Renal Cell Carcinoma (mccRCC) remain incurable. Hence, new relevant treatments are urgently needed. The VEGFs coreceptors, Neuropilins 1, 2 (NRP1, 2) are expressed on several tumor cells including ccRCC. We analyzed the role of the VEGFs/NRPs signaling in ccRCC aggressiveness and evaluated the relevance to target this pathway.MethodsWe correlated the NRP1, 2 levels to patients’ survival using online available data base. Human and mouse ccRCC cells were knocked-out for the NRP1 and NRP2 genes by a CRISPR/Cas9 method. The number of metabolically active cells was evaluated by XTT assays. Migration ability was determined by wound closure experiments and invasion ability by using Boyden chamber coated with collagen. Production of VEGFA and VEGFC was evaluated by ELISA. Experimental ccRCC were generated in immuno-competent/deficient mice. The effects of a competitive inhibitor of NRP1, 2, NRPa-308, was tested in vitro and in vivo with the above-mentioned tests and on experimental ccRCC. NRPa-308 docking was performed on both NRPs.ResultsKnock-out of the NRP1 and NRP2 genes inhibited cell metabolism and migration and stimulated the expression of VEGFA or VEGFC, respectively. NRPa-308 presented a higher affinity for NRP2 than for NRP1. It decreased cell metabolism and migration/invasion more efficiently than sunitinib and the commercially available NRP inhibitor EG00229. NRPa-308 presented a robust inhibition of experimental ccRCC growth in immunocompetent and immunodeficient mice. Such inhibition was associated with decreased expression of several pro-tumoral factors. Analysis of the TCGA database showed that the NRP2 pathway, more than the NRP1 pathway correlates with tumor aggressiveness only in metastatic patients.ConclusionsOur study strongly suggests that inhibiting NRPs is a relevant treatment for mccRCC patients in therapeutic impasses and NRPa-308 represents a relevant hit.