bluuebunny/crossref_metadata_2025 huggingface dataset:
miRNA-1246 in Extracellular Vesicles Secreted from Metastatic Tumor Induces Drug Resistance in Tumor Endothelial Cells
Authors: Torii Chisaho , Maishi Nako , Kawamoto Taisuke , Morimoto Masahiro , Akiyama Kosuke , Yoshioka Yusuke , Minami Takashi , Tsumita Takuya , Alam Mohammad Towfik , Ochiya Takahiro , Hida Yasuhiro , Hida Kyoko
Published: August 2020

Background: Tumor endothelial cells (TECs) reportedly exhibit altered phenotypes. We have demonstrated that TECs acquire drug resistance with the upregulation of p-glycoprotein (p-gp, ABCB1), contrary to traditional assumptions. Furthermore, p-gp expression was higher in TECs of highly metastatic tumors than in those of low metastatic tumors. However, the detailed mechanism of differential p-gp expression in TECs remains unclear. Methods: miRNA was identified in highly metastatic tumor extracellular vesicles (EVs) and the roles of miRNA in endothelial cell resistance were analyzed in vitro and in vivo. Results: In the present study, we found that treatment of highly metastatic tumor-conditioned medium induced resistance to 5-fluorouracil (5-FU) with interleukin-6 (IL-6) upregulation in endothelial cells (ECs). Among the soluble factors secreted from highly metastatic tumors, we focused on extracellular vesicles (EVs) and determined that miR-1246 was contained at a higher level in highly metastatic tumor EVs than in low metastatic tumor EVs. Furthermore, miR-1246 was transported via the EVs into ECs and induced IL-6 expression. Upregulated IL-6 induced resistance to 5-FU with STAT3 and Akt activation in ECs in an autocrine manner. Conclusions: These results suggested that highly metastatic tumors induce drug resistance in ECs by transporting miR-1246 through EVs.
3D Holographic Visualization for Pre-procedural Planning of Spatially Complex Brain Aneurysm Treatment
Authors: Weunski Crew Joseph , Hanlon Aydan , Al-Nimer Sara , Yanof Jeffrey , Hussain Shazam
Published: August 2020

The purpose of this study was to develop and demonstrate a novel imaging platform that post-processes volumetric imaging data (e.g. Computed Tomography (CT) or Magnetic Resonance angiography) to provide holographic visualization for pre-procedural treatment planning of a morphologically complex brain aneurysm. Digital CT images were segmented, using the Materialise Mimics software, into three-dimensional digital models that were imported into a prototype application for the Microsoft HoloLens. Feedback from testing the prototype indicated potential for augmented reality to assist an interventionalist in spatial understanding and depth perception of spatially complex anatomy and could increase confidence in pre-procedural planning. Future studies will be conducted with additional cases to further validate the utility of the platform in surgical planning decisions and to expand the platform for patient/resident education, telemedicine, and intra-operative use.
Predicting Incidence of Long-term Care Insurance Certification in Japan with the Kihon Checklist for Frailty Screening Tool: Analysis of Local Government Survey Data
Authors: Ito Kumiko , Kawai Hisashi , Tsuruta Harukazu , Obuchi Shuichi
Published: August 2020

Background
Predicting incidence of long-term care insurance (LTCI) certification in the short term is of increasing importance in Japan. The present study examined whether the Kihon Checklist (KCL) can be used to predict incidence of LTCI certification (care level 1 or higher) in the short term among older Japanese persons.
Methods
In 2015, the local government in Tokyo, Japan, distributed the KCL to all individuals older than 65 years who had not been certified as having a disability or who had already been certified as requiring support level 1–2 according to LTCI system. We also collected LTCI certification data within the 3 months after collecting the KCL data. The data of 17785 respondents were analyzed. First, we selected KCL items strongly associated with incidence of LTCI certification, using stepwise forward-selection multiple logistic regression. Second, we conducted receiver operating characteristic (ROC) analyses for three conditions (1: Selected KCL items, 2: The main 20 KCL items (nos. 1–20), 3: All 25 KCL items). Third, we estimated specificity and sensitivity for each condition.
Results
During a 3-month follow-up, 81 (0.5%) individuals required new LTCI certification. Eight KCL items were selected by multiple logistic regression as predictive of certification. The area under the ROC curve in the three conditions was 0.92–0.93, and specificity and sensitivity for all conditions were greater than 80%.
Conclusions
Three KCL conditions predicted short-term incidence of LTCI certification. This suggests that KCL items may be used to screen for the risk of incident LTCI certification.
Fetal Sex-Dependent Associations Between Gestational Hormone Concentrations and Adverse Birth Outcomes: A Cohort Study
Authors: Cathey Amber L , Watkins Deborah J , Rosario Zaira Y , Vega Carmen M Vélez , Mukherjee Bhramar , O'Neill Marie S , Loch-Caruso Rita , Alshawabkeh Akram N , Cordero José F , Meeker John D
Published: August 2020

Background: Adverse birth outcomes remain significant public health problems that can have long-lasting impacts on mother and child. Understanding biological mechanisms underlying these outcomes, including altered endocrine function, can inform prevention efforts. Thus, we aimed to explore associations between repeated gestational hormone measurements and birth outcomes. Secondarily, we assessed impacts of fetal sex and timing of hormone measurement on these associations. Methods: We explored associations between repeated gestational hormone measurements and birth outcomes among 976 women in PROTECT, a longitudinal prospective birth cohort in northern Puerto Rico. Birth outcomes assessed included preterm and spontaneous preterm birth (PTB), preeclampsia, gestational diabetes mellitus (GDM), small/large for gestational age (SGA, LGA), birth weight z-score, and gestational age at birth. Multivariate logistic and linear regressions were fit using pregnancy average concentrations of hormones. We also conducted sensitivity analyses assessing impacts of fetal sex and timing of hormone measurement on observed associations. Results: Among male fetuses, spontaneous PTB was associated with increased average corticotropin releasing hormone (CRH) (OR: 2.50, 95% CI: 1.19, 5.24), increased total triiodothyronine (T3) (OR: 1.80, 95% CI: 1.02, 3.16) and decreased testosterone (OR: 0.34, 95% CI: 0.15, 0.74). Odds of GDM increased with average free thyroxine (fT4) (OR: 2.80, 95% CI: 1.06, 7.41), and decreased with average testosterone (OR: 0.23, 95% CI: 0.06, 0.86). Progesterone/estriol ratio was inversely associated with birth weight z-score (b: -0.14, 95% CI: -0.27, -0.01) and gestational age (b: -0.39 weeks, 95% CI: -0.66 , -0.12), and positively associated with odds of SGA (OR: 2.08, 95% CI: 1.36, 3.19). Among females, birth weight z-score was inversely associated with progesterone (b: -0.17, 95% CI: -0.31, -0.02) and total thyroxine (T4) (b: -0.16, 95% CI: -0.30, -0.02), and GDM was inversely associated with progesterone/estriol (OR: 0.34, 95% CI: 0.12, 0.99). Conclusions: Associations between hormones and birth outcomes vary based on timing of hormone measurement and fetal sex. Future studies are needed to understand mechanisms involved in adverse birth outcomes and fetal sex differences.
Measuring Body Condition of Lizards: A Comparison Between Non-Invasive Dual-Energy X-ray Absorptiometry, Chemical Fat Extraction and Calculated Indices
Authors: Sion Guy , Watson Maggie J. , Bouskila Amos
Published: August 2020

BackgroundCondition indices (CIs) are used in ecological studies as a way of measuring an individual animal’s health and fitness. Noninvasive CIs are estimations of a relative score of fat content or rely on a ratio of body mass compared to some measure of size, usually a linear dimension such as tarsus or snout-vent length. CIs are generally measured invasively by lethal fat extraction as in a seasonal sample of individuals in a population. Many alternatives to lethal fat extraction are costly or time consuming. As an alternative, dual-energy X-ray absorptiometry (DXA) allows for non-destructive analysis of body composition and enables multiple measurements during an animal's life time. DXA has never been used for ecological studies in a small, free-ranging lizard before, therefore we calibrated this method against a chemical extraction of fat from a sample of 6 geckos (Israeli fan toed gecko Ptyodactylus guttatus) ranging in body mass between 4.2–11.5 g. ResultsWe found that fat mass measured with DXA was significantly correlated with the mass of chemically extracted fat for specimens more than 4.8g (N=5, R2=0.995, P<0.001). Fat percentage regressed with body mass significantly predicted the DXA fat percentage (N=30, R2adj.=0.875, P<0.001). Live wet mass was significantly correlated with calculated fat mass (N=30, R2=0.984, P<0.001) for specimens more than 4.8g. Among the other calculated non-invasive CIs that we tested, the best was mass/SVL (N=30, rMass/SVL= 0.83, PTwo-tailed<0.001). ConclusionsWe recommend that in situations where DXA cannot be used, that the most accurate of the body condition estimators for both males and females in this species is mass/SVL (snout-vent length) for both sexes.
The Combination of Trehalose and Glycerin: An Effective and Non-Toxic Recipe for Clinical Cryopreservation of Human Adipose-Derived Stem Cells
Authors: Zhang Tian-Yu , Tan Poh-Ching , Xie Yun , Zhang Xiao-Jie , Zhang Pei-Qi , Gao Ying-Ming , Zhou Shuang-Bai , Li Qing-Feng
Published: August 2020

Background: Adipose-derived stem cells (ADSCs) promote tissue regeneration and repair. Cryoprotective agents (CPA) protect cells from cryodamage in the process of cryopreservation. Safe and efficient cryopreservation of ADSCs is critical in the clinical application of cell-based therapy. However, most CPAs contain toxic concentrations limiting the possibility of their clinical application. Objective: The aim of this study is to develop a non-toxic xeno-free CPA for ADSCs to achieve high-efficiency and low-risk cryopreservation. Methods: We explored the most efficient concentrations in different concentrations of trehalose (0.3M, 0.6M, 1.0M, and 1.25M) and glycerol (10%, 20%, 30% v/v); then evaluated the outcome of the combination of trehalose and glycerol in ADSC cryopreservation, compared to the commonly used CPA, DMSO (10%) + FBS (90%). All samples were slowly freezed and stored in liquid nitrox for 30 days. The effectiveness was evaluated by the cell viability, proliferation, migration and multi-potential differentiation of ADSCs after thawing. Results: Compared to the CPAs with single reagent, 1.0M Tre + 20%Gly group showed significantly higher efficiency in preserving ADSCs activities after thawing, with better outcome in both cell viability and proliferating capacity. Compared to 10%DMSO+90%FBS, ADSCs preserved in 1.0M Tre + 20%Gly group showed similar cell viability, surface markers and multi-potential differentiation but significantly higher migration capability, indicating that better cell function preservation can be achieved by 1.0M Tre + 20%Gly. Conclusions: 1.0M Tre + 20%Gly can preserve ADSCs with high migration capability and cell viability compared to 10%DMSO+90%FBS and maintain similar stemness and multi-potential differentiation as fresh cells. Our results demonstrate that 1.0M Tre + 20%Gly can achieve highly efficient cryopreservation of ADSCs and is suitable for clinical applications.
Deep Brain Stimulation of the Cuneiform Nucleus for Levodopa-Resistant Freezing of Gait in Parkinson’s Disease: Study Protocol for a Prospective, Pilot Trial
Authors: Chang Stephano , Cajigas Iahn , Guest James D. , Noga Brian R. , Luca Corneliu C. , Jagid Jonathan R.
Published: August 2020

Background: Freezing of gait (FOG) is a particularly debilitating motor deficit seen in a subset of Parkinson’s Disease (PD) patients that is poorly responsive to standard levodopa therapy or deep brain stimulation (DBS) of established PD targets such as the subthalamic nucleus and the globus pallidus interna. The proposal of a DBS target in the midbrain, known as the pedunculopontine nucleus (PPN) to address FOG was based on its observed pathology in PD and its hypothesized involvement in locomotor control as a part of the mesencephalic locomotor region, a functionally defined area of the midbrain that elicits locomotion in both intact animals and decerebrate animal preparations with electrical stimulation. Initial reports of PPN DBS were met with much enthusiasm; however, subsequent studies produced mixed results, and recent meta-analysis results have been far less convincing than initially expected. A closer review of the extensive MLR preclinical literature, including recent optogenetics studies, strongly suggests that the closely related cuneiform nucleus (CnF), just dorsal to the PPN, may be a superior target to promote gait initiation.Methods: We will conduct a prospective, open-label, single-arm pilot study to assess safety and feasibility of CnF DBS in PD patients with levodopa-refractory FOG. Four patients will receive CnF DBS and have gait assessments with and without DBS during a 6-month follow up.Discussion: This paper presents the study design and rationale for a pilot study investigating a novel DBS target for gait dysfunction, including targeting considerations. This pilot study is intended to support future larger scale clinical trials investigating this target.Trial Registration: Clinicaltrials.gov Identifier: NCT04218526 (registered January 6, 2020), https://www.clinicaltrials.gov/ct2/show/NCT04218526
High Incidence of Venous Thromboembolism in Patients with Coronavirus Disease 2019: A Call for Improved Awareness and Prevention
Authors: Zhang Yun-xia , Zhang Meng , Wang Yimin , Qin Wei , Zhang Zhu , Li Chenghong , Zhai Zhenguo
Published: August 2020

Background: An increased risk of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID-19) has been reported. We performed a meta-analysis to evaluate the prevalence of VTE in COVID-19 patients.Methods: The PubMed and Embase databases were searched for studies reporting VTE in COVID-19 patients up to June 27, 2020. The selected studies were predefined into the “suspected screening group” and the “routine screening group.” The VTE prevalence was calculated using random-effect models.Results: We selected 20 studies including a total of 2763 COVID-19 patients. In 2203 COVID-19 patients from the suspected screening group, the pool VTE incidence was 15.2% (95% confidence interval [CI]: 10.5–21.6%). In 560 COVID-19 patients from the routine screening group, the VTE prevalence was 40.8% (95% CI: 20.6–64.7%). Furthermore, the VTE incidence of critically ill COVID-19 patients from the two groups was 19.6% and 61.4%, respectively, which indicates that critically ill COVID-19 patients were more susceptible to VTE.Conclusions: A high incidence of VTE was observed in COVID-19 patients, especially in severe cases. The incidence of VTE in COVID-19 patients from the routine screening group was higher than that in patients from the suspected screening group. This indicates that a lower threshold of suspicion to perform VTE imaging tests may be reasonable and there is an urgent need to adapt a regular screening strategy for VTE.
Quasi-Optical Design Of A Millimeter Wave Imaging System
Authors: Jadidi Faeze , Eslamimajd Abdollah , Erfaniyan Alireza , Armaki Seyed Hossein Mohseni
Published: August 2020

In this paper, we report complete design and simulation of a quasi-optical millimeter wave imaging system with Fresnel lens and horn Antenna using ZEMAX and FEKO softwares, respectively. It is much easier to make a Fresnel lens at millimeter wavelengths compared to spherical and aspherical lenses. The use of Fresnel lens to focus millimeter wave radiation greatly reduces the thickness and also the weight of the focusing element from 25 Kg to 4.5 Kg. A horn antenna with Gaussian profile and corrugated walls at the central frequency of 94 GHz for feeding this system is designed. The symmetry of the designed corrugated Gaussian horn radiation pattern in E and H orthogonal planes, its wide bandwidth as well as its low side lobe levels make it a good candidate for feeding a W band millimeter-wave imaging system. The designed quasi-optical imaging system has low weight with high resolution and can be used to detect hidden objects within a distance of 5 meters with 30 mm resolution in W band at 94 GHz central frequency.
Evaluation of Post-tracheostomy`s Scars and Its Impact on Persons Quality of Life: A Case Control Study
Authors: Poghosyan Anna , Shahparonyan Rafik G. , Minasyan Armen M. , Bablumyan Aren Yu. , Malkhasyan Irina E. , Matosyan Khachatur H. , Sargsyan Ani M. , Tadevosyan Artashes E. , Muradyan Armen A.
Published: August 2020

Background: Tracheostomy is one of the more commonly performed procedures in critically ill patients. Postoperative scarring is one of the bothersome sequelae of tracheostomies. Scars distorted the physical appearance, especially when found on the head and neck, which could cause a negative impact on quality of life. The aim of this study was to evaluate and assess the impact on quality of life of post-tracheostomy`s scars, depending on the method of tracheostomy.Methods: The prospective, single-center observational study was conducted. One hundred and fifty-six persons with more than four months of post-tracheostomy surgical scars presence were observed using the Patient and Observer Scar Assessment Scale and Dermatology Life Quality index questionnaire. Persons were divided on two groups depending on method of performed tracheostomy, and duration of cannulated period was considered in both groups. Statistical analyses were performed by using SPSS ver. 16.0 (SPSS Inc., Chicago, IL, USA) and p-values of <0.05 were considered significant.Results: The patients who had a tracheostomic tube cannulation period of less than 15 days had better cosmetic results than those who had tracheostomic tubes for more than 15 days, regardless of the method of tracheostomy 6.64± 0.082 vs. 16.15± 0.096 (p<0.05) in surgical tracheostomy group and 7.26± 0.211 vs.14.17± 0.379 (p<00.05) in percutaneous dilatational group. The Dermatology Life Quality index scores have shown a mean value of 0.6 ±0.013, which means that post-tracheostomy scarring in the presented study, had no effect on the person's quality of life.Conclusions: Aesthetic outcomes of post-tracheostomy`s scars after the open surgical tracheostomy technique, performed using a minimally invasive approach, did not statistically differ from those of the percutaneous dilatational technique. Persons with a long duration of tracheostomic tube ventilation showed worse aesthetic outcomes compared with short-term tracheostomic cannulation, not dependent on the tracheostomy performing technique.The Dermatology Life Quality index have shown that post-tracheostomy`s scarring in the presented study had no effect on the person's quality of life.Trial registration: ISRCTN24668317 (IRB no.YSMU №7/18-19). Date of registration 23/04/2019
Exosomes Derived From Stem Cells From Apical Papilla Promote Craniofacial Soft Tissue Regeneration Through Enhancing Cdc42-Mediated Vascularization
Authors: Liu Yao , Zhuang Xueying , Yu Si , Yang Ning , Zeng Jianhong , Chen Xu
Published: August 2020

Background: Reconstruction of complex critical-size defects (CSD) in craniofacial region is a major challenge, and the soft tissue regeneration is crucial in determining the therapeutic outcome of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) which are homologous to craniofacial tissue, and represent a promising source for craniofacial tissue regeneration. Exosomes, which contained compound bioactive contents, are the key factors of stem cell paracrine action. However, the roles of exosomes derived from SCAP (SCAP-Exo) in tissue regeneration are not fully understood. Here, we explored the effects and underlying mechanisms of SCAP-Exo on CSD in maxillofacial soft tissue.Methods: SCAP-Exo were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis. The effects of SCAP-Exo on wound healing and vascularisation were detected by measuring wound area, histological and immunofluorescence analysis in the palate gingiva CSD of mice. Real-time live cell imaging and functional assays were used to assess the effects of SCAP-Exo on the biological functions of endothelial cells (ECs). Furthermore, the molecular mechanisms of SCAP-Exo mediated ECs angiogenesis in vitro was tested by immunofluorescence staining, Western blot and Pull-Down assays. Finally, in vivo experiments were carried out to verify whether SCAP-Exo could affect the vascularisation and wound healing through Cdc42.Results: We showed that SCAP-Exo promoted tissue regeneration of palatal gingiva CSD by enhancing vascularisation in the early phase in vivo, and also indicated SCAP-Exo improved the angiogenic capacity of endothelial cells (ECs) in vitro. Mechanistically, SCAP-Exo elevated cell migration by improving cytoskeletal reorganization of ECs via cell division cycle 42 (Cdc42) signalling. Furthermore, we revealed that SCAP-Exo transferred Cdc42 into the cytoplasm of ECs, and the Cdc42 protein could be reused directly by the recipient ECs, which resulted in the activation of Cdc42 dependent filopodia formation and elevation of cell migration of ECs.Conclusion: This study demonstrated that SCAP-Exo had a superior effect on angiogenesis and effectively promoted craniofacial soft tissue regeneration. These data provide a new option for SCAP-Exo to be used as a cell-free approach to optimize tissue regeneration in the clinic.
Predictors of Delirium Incidence, Time to Onset, and Recurrence in a Mixed Medical-surgical ICU Population: A Secondary Analysis Using Cox and CHIAD Decision Tree Modeling
Authors: Moghadam Keivan Gohari , Miller Andrew C , Rahimibashar Farshid , Salesi Mahmood , Ashtari Sara , Vahedian-Azimi Amir
Published: August 2020

Background: To address whether in intensive care unit (ICU) patients, which factors correlate with development of delirium (primary outcome), as well as more rapid delirium onset and recurrence (secondary outcomes).Methods: A retrospective secondary analysis of 4,200 patients was collected from two academic medical centers. Delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in all patients. Univariate and multivariate Cox models, logistic regression analysis, and Chi-square Automatic Interaction Detector (CHAID) decision tree modeling were used to explore delirium risk factors.Results: Increased delirium risk as associated with exposed only to artificial light (AL) hazard ratio (HR) 1.84 (95% CI: 1.66-2.044, P<0.001), physical restraint application 1.11 (95% CI: 1.001-1.226, P=0.049), and high nursing care requirements (>8 hours per 8-hour shift) 1.18 (95% CI: 1.048-1.338, P=0.007). Delirium incidence was inversely associated with greater family engagement 0.092 (95% CI: 0.014-0.596, P=0.012), low staff burnout and anticipated turnover scores 0.093 (95% CI: 0.014-0.600, P=0.013), non-ICU length-of-stay (LOS)<15 days 0.725 (95% CI: 0.655-0.804, P<0.001), and ICU LOS ≤15 days 0.509 (95% CI: 0.456-0.567, P<0.001). CHAID modelling indicated that AL exposure and age <65 years conveyed a high risk of delirium incidence, whereas SOFA score ≤11, APACHE IV score >15 and natural light (NL) exposure were associated with moderate risk, and female sex were associated with low risk. More rapid time to delirium onset correlated with baseline sleep disturbance (P=0.049), high nursing care requirements (P=0.019), and prolonged ICU and non-ICU hospital LOS (P<0.001). Delirium recurrence correlated with age>65 years (HR 2.198; %95 CI: 1.101-4.388, P=0.026) and high nursing care requirements (HR 1.978, 95% CI: 1.096-3.569), with CHAID modeling identifying AL exposure (P<0.001) and age >65 years (P=0.032) as predictive variables.Conclusion: Development of ICU delirium correlated with application of physical restraints, high nursing care requirements, prolonged ICU and non-ICU LOS, exposure exclusively to AL (rather than natural), less family engagement, and greater staff burnout and anticipated turnover scores. ICU delirium occurred more rapidly in patients with baseline sleep disturbance, and recurrence correlated with presence of delirium on ICU admission, exclusive AL exposure, and high nursing care requirements.
Prevalence of Oral Human Papillomavirus Infection among Indian HIV-Positive Men Who Have Sex With Men: A Cross-Sectional Study
Authors: Hernandez Alexandra Lydia , Karthik Rajiv , Sivasubramanian Murugesan , Raghavendran Anantharam , Lensing Shelly , Lee Jeannette Y , Abraham Priya , Mathai Dilip , Palefsky Joel M
Published: August 2020

Background: Oral human papillomavirus (HPV) infection has been causally linked to a subset of oropharyngeal cancers in Western populations15-20, and both oropharyngeal cancer and oral HPV infection are increased among HIV-positive individuals24,41. India has high incidences of oral and oropharyngeal cancers, and Indian HIV-positive men who have sex with men (MSM) may be at increased risk of developing oropharyngeal cancers. However, there is little information available on the prevalence of oral HPV in this population.Methods: We tested 302 HIV-positive Indian MSM for oral HPV infection using L1 HPV DNA PCR with probes specific for 29 types and a mixture of 10 additional types. CD4+ level and plasma HIV viral load (VL) were measured. Participants completed an interviewer-administered questionnaire including a sexual history.Results: The prevalence of oral HPV was 23.7% (95% CI: 19-29%) and 2.4% of participants had oncogenic HPV types. No participants had oral HPV type 16 (HPV-16) and the prevalence of other anogenital HPV types was low. Participants with higher CD4+ levels had reduced odds of having any oral HPV infection (OR: 3.1 [1.4-6.9]) in multivariable analyses.Conclusions: This is the first report of oral HPV among Indian HIV-positive MSM. Our results show a high prevalence of oral HPV infection consistent with studies from Western populations. However, oncogenic anogenital HPV types were relatively uncommon in our study population. It is unknown what the impact of this distribution of oral HPV will be on oropharyngeal cancers. HIV-positive MSM in India should be monitored closely for oral and oropharyngeal pre-cancer and cancer.
Predicting the Willingness of Nurses to Work with COVID-19 Patients: The Impact of Knowledge and Attitude
Authors: Nashwan Abdulqadir J. , Abujaber Ahmad A. , Mohamed Ahmed S. , Villar Ralph C. , Al-Jabry Mahmood M.
Published: August 2020

Aim: This study aims to assess the impact of nurses’ knowledge and attitude toward Coronavirus Disease 2019 (COVID-19) as a predictor for their willingness to work with patients diagnosed with COVID-19 in Qatar. Design: A cross-sectional study.Methods: A self-administered, 35-item online survey was circulated to the registered nurses and midwives working in Hamad Medical Corporation; the principle healthcare provider in Qatar. Results: A total of 580 attempts to complete the survey. Of them, 377 completed surveys with a response rate of 65%. Logistic regression was used to predict nurses’ willingness to work with patients with COVID-19. Two main factors were found to be significant predictors for nurses’ willingness; knowledge level and the expected remuneration that is associated with the level of exposure to risk. The findings of this study may help nursing leaders design educational programs and remuneration models that may help boost nurses’ willingness to work with high-risk patient groups, especially during crisis situations.
What do Service Providers in Southern Ethiopia Think About Barriers to using Youth-Friendly Sexual and Reproductive Health Services for Adolescents?: Qualitative Study
Authors: Habtu Yitagesu , Kaba Mirgissa , Mekonnen Hussen
Published: August 2020

Background: In Ethiopia, lowest utilization of adolescent friendly sexual and reproductive health services (AFSRHs) is recorded among Sub-Saharan African countries. Little is known why adolescents were not accessing the existing services to the side of healthcare providers. Objective: The aim of this study is to explore contextual perceived and actual barriers to accessing AFSRHs by adolescents in Southern Ethiopia.Methods: Phenomenological study design supplemented with observation was used to explore perceived and actual barriers to accessing AFSRHs in 2020. Criterion sampling was used to select study participants. In-depth interviews with key healthcare providers and non-specialist sexual and reproductive health providers were conducted. Transcribed interviews and observation were imported to Open Code 4.02 for coding, categorizing codes, and creating themes. Finally, barriers to assessing the services were explained using thematic analysis. Results: The study explores contextual barriers to accessing sexual and reproductive health services in five emergent themes. According to providers’ view, barriers include ranging from providers (e.g poor providers’ competency), health facility (e.g. supply constraints and unsupportive environment), adolescents (e.g perceived lack of information and attitude towards SRHs), community (e.g. lack of parental and social support), and broader health system (e.g. poor implementation and multi-sectorial engagement). Conclusion: As to providers, adolescents face multiple barriers to accessing youth friendly sexual and reproductive health services. Healthcare facilities and the health systems should implement varieties of approaches to increase access to the services for adolescents. The existing strategies should be re-evaluated and new interventions at all levels of the healthcare system are needed. Moreover, implementation research is required at system level factors.
The recombinant subunit vaccine RBD-Fc, consisting of SARS-CoV-2 RBD and human IgG Fc as an immunopotentiator, elicits robust neutralizing antibody responses against SARS-CoV-2 infection
Authors: Liu Zezhong , Xu Wei , Xia Shuai , Gu Chenjian , Wang Xinling , Wang Qian , Zhou Jie , Wu Yanling , Cai Xia , Qu Di , Ying Tianlei , Xie Youhua , Lu Lu , Yuan Zhenghong , Jiang Shibo
Published: August 2020

The pandemic of COVID-19 caused by SARS-CoV-2 has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to ACE2 receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.
Expression of HYOU1 via reciprocal crosstalk between NSCLC cells and HUVECs control cancer progression and chemoresistance in multicellular tumor spheroids
Authors: Lee Minji , Song Yeonhwa , Choi Inhee , Lee Su-Yeon , Kim Sanghwa , Kim Se-Hyuk , Kim Jiho , Seo Haengran
Published: August 2020

Background

Among all cancer types, lung cancer ranks highest worldwide in terms of both incidence and mortality. The crosstalk between lung cancer cells and their tumor microenvironment (TME) has begun to emerge as the “Achilles heel” of the disease and thus constitutes an attractive target for anticancer therapy. We previously revealed that crosstalk between lung cancer cells and endothelial cells (ECs) induces chemoresistance in multicellular tumor spheroids (MCTSs).
Methods

In this study, we idientified that factors secreted in response to crosstalk between ECs and lung cancer cells play pivotal roles in the development of chemoresistance in lung cancer spheroids.
Results

We determined that the expression of hypoxia up-regulated protein 1 (HYOU1) in lung cancer spheroids was increased by factors secreted in response to crosstalk between ECs and lung cancer cells. Direct interaction between lung cancer cells and ECs also caused an elevation in the expression of HYOU1 in MCTSs. Inhibition of HYOU1 expression not only suppressed stemness and malignancy, but also facilitated apoptosis and chemosensitivity in lung cancer MCTSs. Inhibition of HYOU1 expression also significantly increased the expression of interferon signaling components in lung cancer cells. Moreover, the activation of the PI3K/AKT/mTOR pathway was involved in the HYOU1-induced aggression of lung cancer cells.
Conclusion

Taken together, our results identify HYOU1, which is induced in response to crosstalk between ECs and lung cancer cells within the TME, as a potential therapeutic target for combating the aggressive behavior of cancer cells.
miR-766-3p suppressed tumorigenesis, epithelial-mesenchymal transition, and metastasis by targeting BCL9L via β -catenin signaling pathway in osteosarcoma cells
Authors: Zhang Sheng , Chen Hongtao , Liu Wanshun , Fang Le , Qian Zhanyang , Kong Renyi , Zhang Qi , Li Juming , Cao Xiaojian
Published: August 2020

Background

Emerging evidence has indicated that abnormal microRNAs (miRNAs) play critical roles in carcinogenesis and progression of osteosarcoma (OS). The aim of this study was to clarify the relationship between miR-766-3p expression and osteosarcoma development and to explore its potential mechanism.
Methods

miR-766-3p was the most downregulated miRNA by analyzing GSE65071 from the GEO database. RT-PCR and western blot was performed to determine miR-766-3p expression and its specific target gene in human OS samples and cell lines. CCK-8 proliferation, colony formation, EdU, wound-healing, and transwell assays were used respectively to evaluate the influences of miR-766-3p depletion or ectopic expression on OS proliferation, migration and invasion in vitro. And a mouse tumorigenicity model was conducted to investigate effects of miR-766-3p in vivo. Moreover, we identified directly interactions between miR-766-3p and its specific target gene using luciferase reporter assays.
Results

miR-766-3p expression was overexpressed in OS tissues and cell lines, and ectopic miR-766-3p expression repressed the malignant level of OS, including cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in vitro and in vivo. B-Cell Lymphoma 9-Like Protein (BCL9L) was negatively correlated with miR-766-3p expression in human OS tissue, and was validated as a downstream target of miR-766-3p by the luciferase reporter assay and Western blotting. Rescue experiment indicated that BCL9L could restore the effects of miR-766-3p on OS migration and invasion. The β-Catenin signaling pathway was demonstrated as being implicated in the miR-766-3p/BCL9L axis.
Conclusions

In conclusion, miR-766-3p is a negative regulator of BCL9L and a risk factor for tumor metastasis in OS progression.
Modulation of RAS and PI3-AKT pathway by Stavudine (d4T) in PBMC of Alzheimer’s Disease Patients
Authors: Rosa Francesca La , Zoia Chiara Paola , Bazzini Chiara , Bolognini Alessandra , Saresella Marina , Conti Elisa , Ferrarese Carlo , Piancone Federica , Marventano Ivana , Galimberti Daniela , Fenoglio Chiara , Scarpini Elio , Clerici Mario
Published: August 2020

Background: Aβ42-deposition plays a pivotal role in AD-pathogenesis by inducing the activation of microglial cells and neuroinflammation. This process is antagonized by microglia-mediated clearance of Aβ plaques. Activation of the NLRP3 inflammasome is involved in neuroinflammation and in the impairments of Aβ-plaques clearance. Stavudine (d4T) on the other hand down-regulates the NLRP3 inflammasome and stimulates autophagy-mediated Aβ-clearing in a TPH-1 cell line model.We explored the effect of d4T on Aβ-autophagy using PBMC of AD patients that were primed with LPS and stimulated with Aβ in the absence/presence of d4T. We analyzed the NLRP3 activity by measuring NLRP3-ASC complexes formation by AMNIS Flow-sight and pro-inflammatory cytokines (IL-1β, IL-18 and Caspase-1) production by ELISA. Western blot analyses were used to measure phosphorylation and protein expression of p38, CREB, ERK and AKT, p70, LAMP 2A, Beclin-1 and Bax.Results: Data showed that d4T: 1) down regulates NLRP3 inflammasome activation and the production of down-stream proinflammatory cytokines even in PBMC; 2) stimulates the phosphorylation of AKT, ERK, p70 as well as LAMP2A production, but does modulate beclin-1, suggesting a selective effect of this compound on chaperone-mediated autophagy (CMA); 3) up regulates p-CREB and BAX, possibly diminishing Aβ-mediated cytotoxicity; and 4) reduces the phosphorylation of p-38, a protein involved in the production of pro-inflammatory cytokines.Conclusions: d4T reduces the activation of the NLRP3 inflammasome and stimulates CMA autophagy as well as molecular mechanisms that modulate cytotoxicity and reduce inflammation in cells of AD patients. It might be interesting to verify the possibly beneficial effects of d4T in the clinical scenario.
Involving People Affected by a Rare Condition in Shaping Future Genomic Research
Authors: Gwynne Kylie , Gray Sarah , Lacaze Paul , Nunn Jack S
Published: August 2020

Background There is evidence that involving potential participants and the public in co-designing research can improve the quality of the study design, recruitment and acceptability of the research, but appropriate methodologies for doing this are not always clear. In this study we co-designed a way of involving people affected by a rare genomic disease in shaping future genomic research about the condition. The aim was to report the process, experiences and outcomes of involving people in genomic research in a standardised way, in order to inform future methods of involvement in research co-production. Method Participants were recruited from an online community hosted by an Australian-based rare disease charity and were over the age 18 years. Once people gave consent, we shared learning resources with participants and invited them to complete an online survey before joining a two-week facilitated online discussion, followed by a second online survey. We used ‘Standardised Data on Initiatives (STARDIT)’ to map preferences, plan involvement and report any outcomes from the process, with quantitative data analysed descriptively and qualitative data thematically analysed. Results Of the 26 people who gave consent and completed the initial survey, 15 participated in the online discussion and 12 completed the follow-up survey. STARDIT was used to report six outcomes from the process, including 60% of participants’ responses showing a change towards ‘widening’ their view of who should be involved in research to include more people. Outcomes also included an improved understanding of research and how to be involved. Participants enjoyed online discussions, found learning resources useful and asked to stay involved in the research process. The partner organisation reported that a similar online discussion will be used in future research prioritisation processes. Conclusion Involving people in co-designing the process improved the study design, ensuring it met the needs of participants. Whilst the study includes participants from only one disease group, using STARDIT allowed us to map people’s preferences and report the methods and outcomes from involving people, providing a way for learning from this case study to inform future research studies beyond the discipline of public health genomics.
Bioinformatics analysis of single-cell mRNA-seq of SARS-CoV-1 and SARS-CoV-2 infection compared to MERS-CoV from Sequence Read Archive (SRA) database reveals novel targets for therapies
Authors: Wang Mengyao , Lu Peng
Published: August 2020

The global pandemic of COVID-19 caused by SARS-CoV-2 is still threatening the world. By May 13, 2020, more than 40 million people have been infected by SARS-CoV-2 and almost 300 thousand deaths were reported. The discovery and development of anti-viral drugs and vaccines are being conducted worldwide and the understanding of the molecular responses of a single cell to SARS-CoV-2 is in urgent need. The comparative analysis of gene expression in SARS-CoVs and MERS-CoV infected Calu-3 cells reveals that although the coronaviruses cause similar acute respiratory distress syndromes, the molecular responses of Calu-3 cells to SARS-CoVs infections showed a unique signature. A total of 64 correlated differentially expressed genes (DEGs) were identified in this study. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that the DEGs were significantly involved in biological process of ‘Response to interferon-γ’, ‘Viral life cycle’, ‘Phagosome’ and ‘Epstein-Barr virus infection’. STRING analysis showed that the DEGs that were up-regulated after SARS-CoVs infections but down-regulated after MERS-CoV infections showed a strong interaction network. Molecular Complex Detection (MCODE) analysis further refined a unique network consisted of eight hub genes out of 64 DEGs, which are involved in cytokine response (CXCL8, CCL20, and CSF2), ISGylation (ISG15), macrophage activation (ITGAM), complement system (C3), and NFκB signaling pathway (TRAF1 and NFκB2). The unique network identified here will be a potential fingerprint for distinguishing SARS-CoVs infections from MERS-CoV infection. The identification of the eight hub genes will lead to the discovery of new possible therapeutic targets for fighting COVID-19.
Upregulation of SIRT1 and FOXO3a Contributes to The Protective Role of Estrogen on HPH in Rats
Authors: Wang Li , Yuan Yadong , Gong Xiaowei , Mao Jianjun
Published: August 2020

Background: SIRT1 has anti-proliferation effects on cells through regulating the expression and activity of FOXOs. Estrogen (E2) has protective effects against hypoxic pulmonary hypertension (HPH), but the involvement of SIRT1 and FOXOs in the proliferation of pulmonary artery smooth muscle cells (PASMCs) and contribution to the effects of E2 on HPH are poorly understood. To use E2 to explore the roles of SIRT1 and FOXO3a in the pathogenesis and progression of HPH and pulmonary vascular remodeling (PVR) in vivo and in vitro.Methods: Female Sprague-Dawley rats with bilateral ovariectomy were randomized to normoxia, normoxia+E2, hypoxia, and hypoxia+E2. Serum E2 levels, hemodynamic, and pulmonary vascular pathomorphology were assessed. The anti-proliferation effect of E2 was determined in human PASMCs under hypoxia/normoxia. Immunohistochemistry, western blotting, and real-time PCR were used to assess SIRT1, FOXO3a, and PCNA in rat pulmonary artery and hPASMCs. SIRT1 activity was assayed.Results: Hypoxia increased mean pulmonary artery pressure (mPAP), medial width of pulmonary arterioles, right ventricular hypertrophy index (RVHI), decreased expression SIRT1 and FOXO3a and increased PCNA expression in rats; E2 alleviated these changes. In vitro, E2 significantly inhibited hypoxia-induced hPASMCs proliferation, associated with improvements in SIRT1 and FOXO3a expression, consistent with the in vivo results. SIRT1 inhibition attenuated the effects of E2 on hPASMCs proliferation and the expression of FOXO3a. A SIRT1 activator mimicked the effects of E2 on hPASMCs proliferation and the expression of FOXO3a.Conclusions: Upregulation of SIRT1 and FOXO3a contributes to the protective role of estrogen on HPH in rats, as supported by in vitro results using hPASMCs.
Performance of a reed bed system for faecal wastewater treatment: case study
Authors: Kabir Md Imran , Hoque Muhammad Azizul , Banik Bijit Kumar
Published: August 2020

Reed bed systems (RBS) have potential to treat wastewater, and being interested in such green wastewater infrastructures, an RBS has been installed for the first time in Bangladesh to treat faecal wastewater, which comes from a low-cost community latrine at a refugee camp in Cox's Bazar area. An anaerobic baffle reactor was set followed by the RBS, which was operated continuously for four months at five different retention times (3–7 days). The RBS was found to retain, on average, about 92% of 5-day biochemical oxygen demand (BOD5) and chemical oxygen demand (COD), 69% of and 52% of . Importantly, the effluent concentration met the national environmental standard for all except for . Thus the optimum hydraulic retention time in RBS has been selected to be 3 days when the ion has been reduced at maximum rate. High positive correlation () was observed between and concentrations in effluent water as well. The results of this study, thus, partly support the RBS as an effective green solution for faecal wastewater treatment.
Designing key parameters of bubble plumes to restore water quality by using conceptual models: a case study in a sub-deep reservoir
Authors: Lan Chen , Chen Jingan , Guo Jianyang , Wang Jingfu
Published: August 2020

Bubble plumes are a popular hypolimnetic reaeration technique in deep-water reservoirs since they have the advantage of delivering direct reaeration to the hypolimnion. Improving the understanding of the integrated reaeration processes is beneficial to optimize the reaeration capacity of the aeration or oxygenation system. In this study, the discrete bubble model was first employed to design an oxygenation system for a sub-deep reservoir (the Aha Reservoir, southwest China, with water depths of 10–30 m). A new approach involving the discrete bubble model was used to determine the initial bubble size of the bubble plume applied. The intrusion models were demonstrated to be useful for designing the gas flow rate of the reaeration system. Using the intrusion models, we predicted the intrusion thickness and intrusion distance during operation for the first time. Subsequently, we verified the predictions and produced more realistic empirical formulas. At present, reports about recommendations on initial bubble size and gas flow rate are rare, and practical verification is absent. Taking the Aha Reservoir as an example, the initial bubble radius of 1 mm and the gas flow rate of 20 m3·h−1 were recommended for bubble plume oxygenation and were found to be successful in the field. Our understanding of the reaeration processes during the operation of the bubble plume system is far from comprehensive, but this study serves to highlight the potential of the discrete bubble model and the intrusion models for designing a bubble plume system in an individual lake.
COMPARISON OF FLUTAMIDE DEGRADATION VIA UV/TIO2, UV/H2O2 AND UV/H2O2/TIO2 SYSTEMS
Authors: Constantin Lucian Alexandru , Constantin Mirela Alina , Nitoi Ines , Galaon Toma , Badescu Valeriu Robert , Cristea Nicolae Ionut
Published: August 2020

Synthetic solutions of flutamide were subject to degradation using three advanced oxidation systems, namely UV/TiO2, UV/H2O2 and UV/H2O2/TiO2. Optimum conditions and degradation kinetics has been established for all three systems. The experimental results showed that all three systems can be successfully used for flutamide degradation with efficiencies higher than 99% and that advanced oxidation processes are showing
good potential for degradation of organic pollutants that cannot be suitable removed/degraded using conventional wastewater treatment processes.