bluuebunny/crossref_metadata_2025_split huggingface dataset:
E-cigarette-Induced Pulmonary Inflammation and Dysregulated Repair are Mediated by nAChR α7 Receptor: Role of nAChR α7 in ACE2 Covid-19 receptor regulation
Authors: Wang Qixin , Sundar Isaac , Li Dongmei , Lucas Joseph , Muthumalage Thivanka , McDonough Samantha , Rahman Irfan 
Published: May 2020

Abstract
Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanism that mediate, toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChR α7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lungs tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased the inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased ACE2 Covid-19 receptor, whereas nAChR α7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8, and MMP9 were altered both at the protein and mRNA transcript levels in female and male, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChR α7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin significantly in a sex-dependent manner, but without the direct role of nAChR α7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChR α7 in a sex-dependent manner.
Non-specific effects of rabies vaccine on the incidence of common infectious disease episodes: study protocol for a randomized controlled trial
Authors: Odita Christianah Ibironke , Conan Anne , Barry Donna , Smith-Antony Marshalette , Battice Juliet , England Shianne , Gessner Bradford D , Knobel Darryn 
Published: May 2020

Abstract
Background: Vaccines may cause non-specific effects (NSEs) on morbidity and mortality through immune-mediated mechanisms that are not explained by the prevention of the targeted disease. Much of the evidence for NSEs comes from observational studies with a high risk of bias, and there is a clear need for new data from randomised controlled trials. Recently, it was proposed that rabies vaccine has protective NSEs in people and in animals. The aim of the proposed study is to determine if rabies vaccine reduces the incidence rate of episodes of common infectious disease syndromes in a population of veterinary students on the island of St. Kitts. Methods: The trial design is a single-site, two-arm, parallel-group, participant-blinded, randomized, placebo-controlled, two-sided comparative study, with an internal pilot study for blinded sample size re-estimation. Allocation to study arm is by block randomization stratified by sex within cohort with a 1:1 allocation ratio. The primary study outcome is the number of new weekly episodes of common infectious diseases including respiratory, diarrheal, and febrile illnesses. A vaccine efficacy ancillary study is planned.Discussion: Demonstration of a non-specific protective effect of rabies vaccine against unrelated respiratory, gastrointestinal and febrile illnesses would provide supportive evidence for the design of similar studies in children in populations with a high burden of these illnesses.Trial registration: ClinicalTrials.gov, NCT03656198. Registered 24 August 2018.
The three-dimensional stable mandibular landmarks in patients between the ages of 12.5 and 17.1 years
Authors: Chen Gui , Awadi Mona Al , Chambers David William , Lagravère-Vich Manuel O , Xu Tianmin , Oh Heesoo 
Published: May 2020

Abstract
Background: With the aid of implants, Björk identified two-dimensional mandibular stable structures in cephalograms during facial growth. However, we do not know what the three-dimensional stable structures are with certainty. The purpose of this study was to identify the most stable mandibular landmarks in growing patients using three-dimensional images.Methods: The sample was comprised of two cone-beam computed tomography (CBCT) scans taken about 4.6 years apart in 20 growing patients between the ages of 12.5 (T1) and 17.1 years (T2). After head orientation, landmarks were located on the chin (Pog), internal symphysis (Points C, D and E), and mandibular canals, which included the mental foramina (MF and MFA) and mandibular foramina (MdF). The linear distance change between Point C and these landmarks was measured on each CBCT to test stability through time. The reliability of the suggested stable landmarks was also evaluated. Results: The total distance changes between Point C and points D, E, Pog, MF, and MFA were all less than 1.0 mm from T1 to T2. The reliability measures of these landmarks, which were measured by the Cronbach alpha, were above 0.94 in all three dimensions for each landmark. From T1 to T2, the distance changes from Point C to the right and left mandibular foramina were 3.39±3.29 mm and 3.03±2.83 mm, respectively. Conclusions: During a growth period that averaged 4.6 years, ranging from 11.2 to 19.8 years old, the structures that appeared relatively stable and could be used in mandibular regional superimpositions included Pog, landmarks on the inferior part of the internal symphysis, and the mental foramen. The centers of the mandibular foramina and the starting points of the mandibular canal underwent significant changes in the transverse and sagittal dimensions.
Non-Active Site Mutants of HIV-1 Protease Influence Resistance and Sensitisation Towards Protease Inhibitors
Authors: Bastys Tomas , Gapsys Vytautas , Walter Hauke , Heger Eva , Doncheva Nadezhda T , Kaiser Rolf , de Groot Bert L , Kalinina Olga V 
Published: May 2020

Abstract
Background HIV-1 can develop resistance to antiretroviral drugs, mainly through mutations within the target regions of the drugs. In HIV-1 protease, a majority of resistance-associated mutations that develop in response to therapy with protease inhibitors are found in the protease’s active site that serves also as a binding pocket for the protease inhibitors, thus directly impacting the protease-inhibitor interactions. Some resistance-associated mutations, however, are found in more distant regions, and the exact mechanisms how these mutations affect protease-inhibitor interactions are unclear. Furthermore, some of these mutations, e.g. N88S and L76V, do not only induce resistance to the currently administered drugs, but contrarily induce sensitivity towards other drugs. In this study, mutations N88S and L76V, along with three other resistance-associated mutations, M46I, I50L, and I84V, are analysed by means of molecular dynamics simulations to investigate their role in complexes of the protease with different inhibitors and in different background sequence contexts. Results Using these simulations for alchemical calculations to estimate the effects of mutations M46I, I50L, I84V, N88S, and L76V on binding free energies shows they are in general in line with the mutations’ effect on IC50 values. For the primary mutation L76V, however, the presence of a background mutation M46I in our analysis influences whether the unfavourable effect of L76V on inhibitor binding is sufficient to outweigh the accompanying reduction in catalytic activity of the protease. Finally, we show that L76V and N88S changes the hydrogen bond stability of these residues with residues D30/K45 and D30/T31/T74, respectively. Conclusions We demonstrate that estimating the effect of both binding pocket and distant mutations on inhibitor binding free energy using alchemical calculations can reproduce their effect on the experimentally measured IC50 values. We show that distant site mutations L76V and N88S affect the hydrogen bond network in the protease’s active site, which offers an explanation for the indirect effect of these mutations on inhibitor binding. This work thus provides valuable insights on interplay between primary and background mutations and mechanisms how they affect inhibitor binding.
Pediatric Outpatient Utilization by Differing Medicaid Payment Models in the United States
Authors: Canares Therese , Friedman Ari , Rodean Jonathan , Burns Rebecca R. , Berkowitz Deena , Hall Matt , Alpern Elizabeth , Montalbano Amanda 
Published: May 2020

Abstract
Background In the United States (US), medicaid capitated managed care costs are controlled by optimizing patients’ healthcare utilization. Adults in capitated plans utilize primary care providers (PCP) more than emergency departments (ED), compared to fee-for-service (FFS). Pediatric data are lacking. We aim to determine the association between US capitated and FFS Medicaid payment models and children’s outpatient utilization. Methods This retrospective cohort compared outpatient utilization between two payment models of Medicaid enrollees aged 1-18 years using Truven’s 2014 Marketscan Medicaid database. Children enrolled >11 months were included, and were excluded for eligibility due to disability/complex chronic condition, lack of outpatient utilization, or provider capitation penetration rate <5% or >95%. Negative binomial and logistic regression assessed relationships between payment model and number of visits or odds of utilization, respectively. Results Of 711,008 children, 66,980(9.4%) had FFS and 644,028(90.6%) had capitated plans. Children in capitated plans had greater odds of visits to urgent care, PCP-acute, and PCP-well-child care (aOR 1.21[95%CI 1.15-1.26]; aOR 2.07[95%CI 2.03-2.13]; aOR 1.86 [95%CI 1.82-1.91], respectively), and had lower odds of visits to EDs and specialty care (aOR 0.82 [95%CI 0.8-0.83]; aOR 0.61 [95%CI 0.59-0.62], respectively), compared to FFS. Conclusions The majority of children in this US Medicaid population had capitated plans associated with higher utilization of acute care, but increased proportion of lower-cost sites, such as PCP-acute visits and UC. Policies that improve healthcare coverage of children and programs that encourage capitated payment models with care coordination may improve access to timely acute care in lower-cost settings for non-chronically ill children.
Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway
Authors: wang zhongli , liu chao 
Published: May 2020

Abstract
Background: The expression of circRNA_100269 in gastric cancer (GC) tissues and cells, together with its regulatory roles on GC cells were investigated. Methods: The levels of circRNA_100269 in GC and matched para-carcinoma tissues, as well as in human GC cell lines and normal gastric epithelial cells were evaluated using RT-qPCR. The models with overexpression or knockdown of circRNA_100269 were generated using lentiviral vectors. Cell viability was examined using MTT assay; cell migration and invasive activity were determined by wound healing and Transwell assay. Cell cycle arrest and apoptosis were assessed; molecules involved in PI3K/Akt signaling, apoptosis and EMT were evaluated using RT-qPCR and immunoblotting. Tumour growth and expression of relevant proteins were examined in circRNA_100269 knockout mice.Results: The results indicated the expression of circRNA_100269 was dramatically decreased in GC samples compared with para-carcinoma tissues (p<0.05), while the levels of PI3K were notably increased (p<0.05). Moreover, the level of circRNA_100269 was relevant to histology grade and occurrence of metastasis in GC patients (p<0.05), where circRNA_100269 and PI3K was inversely correlated (p<0.05). Additionally, circRNA_100269 was downregulated in GC cells compared with normal gastric epithelial cells. Overexpressed circRNA_100269 remarkably suppressed the proliferation, migration, invasion and EMT of GC cells (p<0.05), induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis (p<0.05). In addition, PI3K/Akt signaling was involved in circRNA_100269-mediated proliferation, migration, invasion, EMT and apoptosis in GC cells (p<0.05). Knockdown of circRNA_100269 also significantly promoted tumor growth in vivo (p<0.05). Conclusions: the data of the present study suggested that the expression level of circRNA_100269 was decreased in GC tissues and cells. In addition, circRNA_100269 inhibited the progression of GC by suppressing PI3K/Akt signaling. Therefore, circRNA_100269/PI3K/Akt axis may be a potential therapeutic target for GC treatment.
Effect of neoadjuvant radiotherapy on survival of non-metastatic Pancreatic Ductal Adenocarcinoma: A SEER Database Analysis
Authors: Wang Dan , Liu Chongshun , Zhou Yuan , Yan Tingyu , Li Chenglong , Yang Qionghui , Xu Yang , Zhao Lilan , Pei Qian , Tan Fengbo , Güngör Cenap , Li Yuqiang 
Published: May 2020

Abstract
Background: Neoadjuvant radiotherapy has been shown to improve marginal negative resection and local control of Pancreatic Ductal Adenocarcinoma (PDAC). However, whether it improves overall survival (OS) in patients with non-metastatic PDAC remains controversial. Therefore, the purpose of this study was to analyze the benefits of only surgery, neoadjuvant radiotherapy, adjuvant radiotherapy, and surgery plus chemotherapy for OS in patients with non-metastatic PDAC. Methods: PDAC diagnosed by surgical histopathology in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016 was selected. Kaplan-Meier analysis was used to compare the prognosis of patients with different treatments. Cox proportional risk model was used to analyze independent predictors of OS.Propensity score matching (PSM) was used to analyze the tumor prognosis of different treatment methods. Results: Before PSM analysis, the OS of surgery plus chemotherapy (HRs = 0.896, 95%CIs, 0.827-0.970; P=0.007) were significantly better than the other three treatments for stage T1-3N0M0 PDAC patients. For stage T1-3N+M0 patients, adjuvant radiotherapy (HRs=0.613, 95% CIs, 0.579-0.649; P< 0.001) had significantly better OS than surgery plus chemotherapy and neoadjuvant radiotherapy. For stage T4N0M0 patients, neoadjuvant radiotherapy (HRs=0.482, 95% CIs, 0.347-0.670; P < 0.001) had significantly better OS than surgery plus chemotherapy and adjuvant radiotherapy. For stage T4N+M0 patients, neoadjuvant radiotherapy (HRs=0.338, 95% CIs, 0.215-0.532; P < 0.001) had significantly longer OS than adjuvant radiotherapy and surgery plus chemotherapy.Even after PSM, Chemotherapy plus surgery was still the best treatment for T1-3N0M0 patients. Postoperative adjuvant radiotherapy had the best prognosis among T1-3N+M0 patients, and neoadjuvant radiotherapy was the best treatment for T4 patients. Conclusions: For patients with non-metastatic PDAC, neoadjuvant radiotherapy, adjuvant radiotherapy and surgery plus chemotherapy were superior to only surgery in OS. For patients with stage T4 non-metastatic PDAC, neoadjuvant radiotherapy had the potential to be strongly recommended over adjuvant radiotherapy and surgery plus chemotherapy. However, neoadjuvant radiotherapy failed to benefit the survival of T1-3N0M0 stage patients, and surgery plus chemotherapy was preferred. For T1-3N+M0, neoadjuvant radiotherapy had no obvious advantage over adjuvant radiotherapy or surgery plus chemotherapy in OS, and adjuvant radiotherapy was more recommended.
Post-hoc analysis of changes in renal function of prostate cancer patients: Focus on androgen deprivation therapy
Authors: Miyazawa Yoshiyuki , Sekine Yoshitaka , Arai Seiji , Oka Daisuke , Nakayama Hiroshi , Syuto Takahiro , Nomura Masashi , Koike Hidekazu , Matsui Hiroshi , Shibata Yasuhiro , Suzuki Kazuhiro 
Published: May 2020

Abstract
Background To investigate the association between androgen deprivation therapy (ADT) and changes in the estimated glomerular filtration rate (eGFR) in male Japanese prostate cancer patients, based on post-hoc analysis of data from a previous prospective study.Methods From among 103 prostate cancer patients in whom renal function changes were tracked over 5 years, 88 were divided into a group who completed ADT within 3 years (short ADT group; n = 47) and a group who continued with ADT for more than 5 years (continuous ADT group; n = 41). We compared the groups in terms of the eGFR, calculated based on age and serum creatinine (mg/dL), before ADT initiation and every other year over the next 5 years. This study was approved by the Ethics Committee for Clinical Studies of Gunma University Hospital (Approval No: 8 − 5).Results The eGFR decreased by 4.91 and 2.89 ml/min in the short and continuous ATD groups, respectively, over the 5-year period following ADT initiation. The respective decreases in the eGFR were 0.98 and 0.58 ml/min/year. No significant difference in the eGFR was observed between the two groups at any measurement point.Conclusions ADT patients showed a decrease in the eGFR of 0.58–0.98 ml/min/y over a 5-year period, which is about twice as high as that of normal Japanese males. No significant difference in the eGFR by ADT duration was observed.
Navigation-assisted anchor insertion in shoulder arthroscopy: a validity study
Authors: Jung Kyunghwa , Kim Hyojune , Kholinne Erica , Park Dongjun , Choi Hyunseok , Lee Seongpung , Shin Myung-Jin , Kim Dong-Min , Hong Jaesung , Koh Kyoung-Hwan , Jeon In-Ho 
Published: May 2020

Abstract
PurposeThis study aimed to compare conventional and navigation-assisted arthroscopic rotator cuff repair in terms of anchor screw insertion.MethodsThe surgical performance of five operators were compared while using conventional system and the proposed navigation-assisted system in a phantom surgical model and cadaveric shoulders. The participating operators were divided into two groups: expert (n = 3) and novice (n = 2) groups. In phantom model, the experimental tasks included anchor insertion into the rotator cuff footprint and sutures retrieval. Motion analysis camera system was used to track surgeons’ hand movements. Surgical performance metric included total path length, count of movements, and duration of surgery. In cadaveric experiments, repeatability and reproducibility of anchor insertion angle were compared among three experts and the feasibility of the navigation-assisted anchor insertion was validated.ResultsThere was no significant difference in the total path length, the count of movements and time taken, between the conventional system and the proposed system in phantom model. In cadaveric shoulders, however, the clustering of the anchor insertion angle indicated that the proposed system enabled both novice and expert operators to reproducibly insert anchor with an angle close to the predetermined target angle, resulting in an angle error of less than two degrees (P = 0.0002).ConclusionThe proposed navigation-assisted system improved the surgical performance of novice to expert level. All experts achieved a high repeatability and reproducibility for anchor insertion. Navigation-assisted system can help to make surgeons be familiar to insertion of suture anchors in right direction easily, even in-experienced, by providing better guidance for anchor orientation.Level of EvidenceA retrospective study (level 2)
Characteristics and evaluation of the effectiveness of monitoring and control measures for the first 69 Patients with COVID-19 from 18 January 2020 to 2 March in Wuxi, China
Authors: Shi Ping , Gao Yumeng , Shen Yuan , Chen Enping , Chen Hai , Liu Juan , Chen Yujun , Xiao Yong , Shi Chao , Lu Bing 
Published: May 2020

Abstract
Background: The novel coronavirus disease 2019(COVID-19) outbreak and has caused has caused 82,830 confirmed cases and 4,633 deaths in China by 26 April 2020. We analyzed data on 69 infections in Wuxi to describe the epidemiologic characteristics and evaluate the control measures.Methods: The demographic characteristics, exposure history, and illness timelines of COVID-19 cases in Wuxi were collected.Results: Among the 69 positive infections with COVID-19, mild and normal types accounted for 75.36% (52/69), adolescents and children are mainly mild and asymptomatic. The basic reproductive number was estimated to be 1.12 (95% CI, 0.71 to 1.69). The mean incubation period was estimated to be 4.77 days (95% CI, 3.61 to 5.94), with a mean serial interval of 6.31 days (95%CI, 5.12 to 7.50). We also found that age (RR=1.57, 95%CI: 1.11-2.21) and fever (RR=4.09, 95%CI: 1.10-15.19) were risk factors for COVID-19 disease severity.Conclusions: The incidence of COVID-19 in Wuxi has turned into a lower level, suggesting that the early prevention and control measures have achieved effectiveness. The community transmission can be effectively prevented through isolation and virus detection of all the people who were exposed together and close contact with the infected people. Aging and fever are risk factors for clinical outcome, which might be useful for preventing severe transition.
Perceptions of patients with end-stage kidney disease (ESKD) and their informal caregivers on palliative care as a treatment option: a qualitative study
Authors: Sarfo-Walters Catherine , Boateng Edward Appiah 
Published: May 2020

Abstract
Background
Palliative care is increasingly becoming an accepted treatment choice for many individuals diagnosed with end-stage kidney disease (ESKD). Yet, its utilisation is non-existent in many lower- and middle-income countries (LMICs). This study explored the perceptions of individuals with ESKD and their informal caregivers on palliative care as a treatment option for the disease in Ghana.
Methods
This was a phenomenological study, with an in-depth analysis of data collected from nine individuals with ESKD and six informal caregivers through individual, face-to-face semi-structured interviews. The study was conducted in two renal centres within the Kumasi metropolis, Ghana among individuals with ESKD seeking care from both renal centres and their informal caregivers.
Results
Three main themes were derived from this study – motivation for initiating haemodialysis, facing realities of haemodialysis, and considering palliative care. Participants felt that haemodialysis (HD) was not meeting their health expectations and demonstrated a general willingness to utilise palliative care if it would reduce suffering.
Conclusions
This study has shown that individuals with ESKD or their informal caregivers would consider palliative care services, if available. It paves the way for discussions about Palliative care for ESKD to begin across renal centres within Ghana and other similar settings. Exploring perspectives of clinicians in such settings could inform strategies on how to implement Palliative care for ESKD management in such settings.