bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering Pichia pastoris with surface-display minicellulosomes for carboxymethyl cellulose hydrolysis and ethanol production
Authors: Dong Ce , Qiao Jie , Wang Xinping , Sun Wenli , Chen Lixia , Li Shuntang , Wu Ke , Ma Lixin , liu yi
Published: May 2020

Backgrounds: Engineering yeast as a consolidated bioprocessing (CBP) microorganism by surface assembly of cellulosomes has been aggressively utilized for cellulosic ethanol production. However, most of the previous studies focused on Saccharomyces cerevisiae, achieving efficient conversion of phosphoric acid-swollen cellulose (PASC) or microcrystalline cellulose (Avicel) but not carboxymethyl cellulose (CMC) to ethanol, with an average titer below 2 g/L. Results: Harnessing an ultra-high-affinity IM7/CL7 protein pair, here we describe a method to engineer Pichia pastoris with minicellulosomes by in vitro assembly of three recombinant cellulases including an endoglucanase (EG), an exoglucanase (CBH) and a β-glucosidase (BGL), as well as a carbohydrate binding module (CBM) on the cell surface. For the first time, the engineered yeasts enable efficient and direct conversion of CMC to bioethanol, observing an impressive ethanol titer of 5.1 g/L. Conclusions: The research promotes the application of P. pastoris as a CBP cell factory in cellulosic ethanol production and provides a promising platform for screening the cellulases from different species to construct surface-assembly celluosome.
Accommodating conscientious objection in the midwifery workforce: a ratio-data analysis of midwives, birth and late abortions in 18 European countries in 2016
Authors: Fleming Valerie , Maxwell Clare , Ramsayer Beate
Published: May 2020

Background In recent years the role of a midwife has expanded to include the provision of abortion related care. The laws on abortion in many European countries allow for those who hold a conscientious objection to participating to refrain from such participation. However, some writers have expressed concerns that this may have a detrimental effect on the workforce and limit women’s access to the service. Method The aim of this study was to provide a picture of the potential exposure midwives in Europe have to late abortions, an important factor in the integration of accommodation of conscientious objection to abortion by midwives into workload planning. We collected data from Ministries of Health or government statistical departments in 32 European countries on numbers of: births, abortions, late abortions and midwives in 2016. We conducted a ratio-data analysis in those countries that met the inclusion criteria. Results 18 of the 32 countries provided full data thus our calculations are based on a total of 4,036,633 live births, 49,834 late abortions and a total of 132,071 midwives. The calculated ratios of live births to midwife, abortions to midwife and late abortions to midwife illustrate the wide variations between countries in relation to ratios of midwives to live births (15.22 - 53.99) and late abortions, (0.17-1.47) Conclusions This study provides the first comprehensive insight to ratios relating to birth and abortion, especially late abortion services, with regard to the midwifery workforce. It is essential to improve the reporting of abortion data and access to it within Europe to support evidence-informed decisions on optimising the contribution of the midwifery workforce especially within highly contentious fields such as abortion services. The study’s findings suggest that there should be neither be any difficulty for those who are responsible for workload allocation nor compromises to a women’s right to abortion services.
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

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

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.
Nanodelivery of Triamcinolone Acetonide using PLGA-Chitosan Nanoparticles for the Treatment of Inflammation-related Ocular Cataract
Authors: Xing Yi , Zhu Lijuan , Zhang Ke , Li Teng , Huang Shaohua
Published: May 2020

This preprint has been removed from Research Square.
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

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

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

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

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

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

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

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

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

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.
Morphological Markers of Pathological Changes in Bitches Endometrium Affected by a Cystic Endometrial Hyperplasia - Pyometra Complex (CEH-P)
Authors: Woźna-Wysocka Magdalena , Rybska Marta , Błaszak Beata , Jaśkowski Bartłomiej Maria , Kulus Magdalena , Jaśkowski Jędrzej Maria
Published: May 2020

Background The aim of the analysis was to designate the morphological symptoms that appear during the Cystic Endometrial Hyperplasia - Pyometra complex (CEH-P), diagnosed by microscopic examination. The investigation were conducted on the uteri of 120 bitches in age between 1–16. The microscopic examinations were based on histological stainings. The aim of examinations was to find the differences in morphology of endometrium in the specimens of the uteri wall (H&E stain). All of the uteri were divided into three pathological groups (GI – GIII), created on the basis of clinically symptoms of analyzed diseases. Uteri without symptoms were classified as a control group (C).Results Histopathological analysis that were conducted have confirmed preliminary macroscopic evaluation for control group with unchanged uteri, group GII with cystic endometrial hyperplasia of uteri (CEH), and group GIII with uteri with pyometra. The confirmation of compatibility of both macroscopic and microscopic evaluation of the uteri were observed in groups GII and GIII. In the uteri of the group GI a severe congestion of endometrium have been observed – it is typical for the inflammation – which was not confirmed during histopathological examinations. Those examinations revealed only endometrial haemorrhage.Conclusions The results are showing that during classification of research material microscopic examinations are required. The diagnose based on the macroscopic changes in typical for CEH-P symptoms might be incorrect, if it is not supported by detailed research. More than that, in all uteri with the closed pyometra the CEH was also observed. It suggest that pyometra may occur as a consequence of cystic endometrial hyperplasia and bacterial infections ended with inflammation. The results obtained can be used to create a basis for pathologic classification of endometrial hyperplasia, including CEH-P complex in bitches.
Identification and Verification of Candidate Genes Regulating Human Umbilical Vein Endothelial Cells Behavior Under Hyperglycemia
Authors: MA XIAOYE , ZHOU YUCHEN , XIE JUNCHAO , MENG GUILIN , ZHAO YICHEN , ZHAO YANXIN , Liu Xueyuan
Published: May 2020

Background: Diabetes is a metabolic disease that has been widely demonstrated to be correlated with many microvascular and macrovascular diseases that seriously damage the patient’s life quality. This study intended to investigate the underlying molecular mechanisms of endothelial dysfunction under hyperglycemia. Methods: The gene expression profile of GSE49524 was downloaded and differentially expressed genes (DEGs) in hyperglycemia human umbilical cord endothelial cells (HUVECs) samples compared with normoglycemia HUVECs samples were identified by R software. Afterward, we analyzed the data by applying a combination of the bioinformatics method and used the microRNAs (miRNAs) databases to predict microRNAs that target key genes. The expression of the top 10 differentially expressed genes was validated through quantitative real-time PCR (qRT-PCR). Results: A total of 65 genes were distinguished as DEGs. The dominant GO (gene ontology) terms and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways which were significantly overrepresented in the hyperglycemia HUVECs were identified. The results of the protein-protein interaction networks demonstrated that fibronectin 1 (FN1) is of the highest degree. In addition, several predicted miRNAs that target FN1 were obtained too. The further verification of the top 10 DEGs through qRT-PCR illustrated that nine of the up-regulated DEGs were up-regulated significantly in the hyperglycemia group when compared to the control group. Conclusions:This exploratory study may help to prompt an understanding of the underlying molecular mechanisms of the effect of hyperglycemia on the behavior of HUVECs and contribute to the production of effective therapeutic interventions.
Let-7d inhibits intratumoral macrophage M2 polarization and subsequent tumor angiogenesis by targeting IL-13 and IL-10
Authors: Su Boxing , Han Haibo , Gong Yanqing , Li Xuesong , Ji Chaoyue , Yao Jingjing , Yang Jianghui , Hu Weiguo , Zhao Wei , Li Jianxing , Zhang Gang , Zhou Liqun
Published: May 2020

Background: The microRNA let-7d has been reported to be a tumor suppressor in many types of cancer, including renal cell carcinoma (RCC). Tumor-associated macrophages are M2-polarized macrophages that can enhance tumor growth and angiogenesis in many human cancers. However, the role of let-7d in TAM-associated RCC tumor progression remains elusive.Methods: Human macrophage cell line THP-1 cells pretreated with phorbol myristate acetate were co-cultured with let-7d overexpressing RCC cells, the conditioned medium were obtained and its effect on human umbilical vein endothelial cells (HUVECs) was accessed in vitro. The phenotype of cocultured macrophages and macrophages in mouse models bearing let-7d overexpressing RCC cell derived xenograft were analyzed in vitro and in vivo using flow cytometry and quantitative real-time PCR.Results: First, we observed a strongly inverse correlation between let-7d expression and microvessel density in RCC tissues. Furthermore, the proliferation, migration, and tube formation of HUVECs was significantly inhibited by conditioned medium from a coculture system of the human macrophage THP-1 cell line with let-7d-overexpressing RCC cells. Moreover, the proportion of M2 macrophages was significantly lower in the group that was cocultured with let-7d-overexpressing RCC cells. Subcutaneous xenografts formed by the injection of let-7d-overexpressing RCC cells together with THP-1 cells resulted in a significant decrease in the M2 macrophage ratio and microvessel density compared with those formed by the injection of control RCC cells with THP-1 cells. In silico analysis revealed interleukin-10 (IL-10) and IL-13 as potential let-7d target genes. Consistently, the activities of the luciferase reporters containing the 3’-UTRs of the IL-10 and IL-13 genes were significantly inhibited by let-7d. Importantly, the addition of IL-10 and IL-13 counteracted the inhibitory effects of the conditioned medium from the coculture system of let-7d-overexpressing RCC cells in vitro. Additionally, the overexpression of IL-10 and IL-13 reversed the effects of let-7d on macrophage M2 polarization and tumor angiogenesis in vivo. Finally, the expression of IL-10 and IL-13 were inversely correlated with the expression of let-7d in RCC clinical specimens.Conclusions: These results suggest that let-7d may inhibit intratumoral macrophage M2 polarization and subsequent tumor angiogenesis at least in part by targeting IL-10 and IL-13.
Modelling of Seismicity in Southern Pakistan using GIS Techniques
Authors: Khan Muhammad
Published: May 2020

This study was aimed to expound spatial association between tectonic earthquakes and individual faults in southern Pakistan. A population of fault lines are exposed to the onshore region located to the north of active Makran subduction zone and within Indus Basin where geophysical prospecting reported neotectonic deformation and faulting. A catalog of earthquakes has been compiled considering the seismic events originated from southern Pakistan and neighboring southeastern Iran, southern Afghanistan and frontal offshore areas. Since, the faulty blocks are extending beyond the international borders, a wide region was outlined for cataloging and thorough screening of fault lines. The catalog has been thoroughly processed by standard procedures necessary for magnitude coherency, main shocks decluttering, magnitude completeness and removal of spatially outlier events etc. GIS-based vectors of fault lines were abstracted by the digitization of regional tectonic lineaments and structural maps. A rigorous effort was made to review available literature to gather updated data of plate kinematics, GPS constraints, relative blocks movement across the faults and rate of fault mechanics (slip-sense) during major events. The weights of evidence method was used to judge the spatial associations between seismic events and populations of faults lines to ascribe ‘seismicity index’ which ranked the potential faults from I (least active level) to V (highly active level). The SI helped to compare each fault response e.g. seismicity yield, released seismic stresses collinear to the fault line, active or aseismic segments and probabilistic estimate for future sizeable earthquake. Kernel density maps were prepared to allure the vulnerable pockets of the elongated faults for specific magnitude windows. The spatial patterns of earthquakes in southern Pakistan were significant to study the seismogenic potential associated with the active tectonic lineaments and faulted blocks. Spatial analysis of data sets for seismic events suggest stronger spatial associations between earthquake epicenters and faults oriented N-S, and weaker spatial associations of epicenters with some -unknown faults in the plains of Indus Basin.
The Effect of Bone Cement Distribution on the Outcome of Percutaneous Vertebroplasty: A Case Cohort Study
Authors: Tan Lei , Wen Bingtao , Guo Zhaoqing , Chen Zhongqiang
Published: May 2020

Background: To analyze the effect of different types of bone cement distribution after percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compression fracture (OVCF). Methods: 137 patients withsinglelevelOVCF who underwent PVP were retrospectively analyzed. The patients were divided into two groups according to bone cementdistribution. Group A:bone cement contacted both upper and lower endplates; Group B: bone cement missed at least one endplate. Group Bwas divided into 3 subgroups. Group B1: bone cement only contacted the upper endplates; Group B2: bone cement only contacted the lower endplates; Group B3: bone cement only located in the middle of vertebral body. The visual analogue scale (VAS) scoreat 24 hours post operation and last follow-up, anterior vertebral height restoration ratio (AVHRR), anterior vertebral height loss ratio (AVHLR) and vertebral body recompression ratewere compared. Results: 24 hours post operation, the pain of all groups were significantly improved. At the last follow-up, the VAS score of group A was lower than that of group B. There were 9 cases (6.6%) of cement leakage, 4 cases (6.9%) in group A and 5 cases (6.3%) in group B. At the last follow-up, there were 16 cases (11.7%) of vertebral body recompression, including 3 cases (5.2%) in group A and 13 cases (16.5%) in group B. There was no significant difference in AVHRR between two groups. At the last follow-up, AVHLR in group B was higher than that in group A. In subgroup analysis, there was no significant difference in VAS score,vertebral recompression rate, AVHRR or AVHLR.Conclusions: If the bone cement fully contacted both the upper and lower endplates, it can better restore the strength of the vertebral bodyand maintain the height of the vertebral body, reduce the risk of the vertebral body recompression and long term pain.
Mechanism of lncRNA H19 in the Regulation of Lipid Accumulation and Inflammatory Response in Macrophages
Authors: Wang Xue-Mei , Gao Xiao-Ming , Liu Fen , Cao Ying , Wang Jie-Ying , Xing Yuan
Published: May 2020

Background and aims: Lipid accumulation of macrophages caused by oxidative stress is the key reason for the early pathological changes of atherosclerosis. LncRNA H19 repression downregulated NF-κB activation, upregulated ABCA1 expression, intracellular lipid accumulation increased, but the role of lncRNA H19 in atherogenesis and the molecular mechanisms have not been defined. We aimed to explore if and how lncRNA H19 affects lipid accumulation of macrophages by regulating lipid metabolism and inflammatory response.Methods and results: THP-1 macrophages were cultured with ox-LDL to form foam cells. THP-1-derived macrophages were incubated with H19 siRNA or not. Oil Red O staining was used for the determination lipid accumulation in macrophages. Enzymatic methods were performed to analyze cholesterol concentration. Both western blot and qRT-PCR were applied to detect target gene expression. ELISA was used to examine the levels of oxidative and inflammatory mediators. We found that lncRNA H19 repression reduced lipid accumulation by elevating efficiency of RCT and via upregulation of ABCA1 and PPARα expression in THP-1 derived macrophages. Further, lncRNA H19 repression upregulated PGC-1α and downregulated NF-κB signaling pathway.Conclusion: These results suggest that lncRNA H19 repression inhibits atherosclerosis by promoting RCT process and reducing inflammatory response via PGC-1α and NF-κB pathways, respectively.
Mesangial IgM Deposition predicts renal outcome in patients with IgA nephropathy: A multicenter, prospective, observational study
Authors: Tan Li , Tang Yi , Pei Gai-Qin , Zhong Zheng-Xia , Tan Jia-Xing , Ma Ya , Wang Dong-Guang , Zhou Ling , Sheikh-Hamad David , Qin Wei
Published: May 2020

BackgroundMesangial IgM deposition is commonly found in patients with immunoglobulin A nephropathy (IgAN). This study aims to investigate the relationships between mesangial IgM deposition and disease progression in IgAN patients.MethodsA total of 1239 patients with biopsy-proven primary IgAN were enrolled in this multicenter, prospective, observational study between January 2013 and August 2017. According to the degree of IgM deposition, 1239 patients were divided into three groups: Grade 0 (no or trace; n = 713, 57.55%), Grade 1 (mild; n = 414, 33.41%), Grades 2 + 3 (moderate and marked; n = 112, 9.04%). Using a 1: 1 propensity score matching (PSM) method identifying age, gender, and treatment modality to minimize confounding factors, 1042 matched patients (out of 1239) with different degrees of IgM deposition were enrolled to evaluate the severity of baseline clinicopathological features and renal outcome: Grade 0 (n = 521, 50.00%), Grade 1 (n = 409, 39.25%), Grades 2 + 3 (n = 112, 10.75%). Kaplan–Meier and Cox proportional hazards analyses were performed to determine whether different degrees of mesangial IgM deposition are associated with varying renal outcomes in IgAN.ResultsDuring a mean follow-up of 48.90 ± 23.86 and 49.01 ± 23.73 months, before and after adjusting for propensity scores respectively, the rate of complete remission (CR) was progressively lower with increased IgM deposition in both unmatched (63.39%, 46.14%, 45.54%) and matched cohort (61.80%, 46.45%, 45.54%), whereas the proportion of patients progressing to end stage renal disease (ESRD) showed reverse correlation (P < 0.001). Kaplan–Meier analysis indicated negative correlation between the intensity of mesangial IgM deposits and cumulative renal survival (all P < 0.05). Moreover, Cox regression analysis revealed that the degree of mesangial IgM deposition predicted renal outcome independent of MESTC score and clinical variables in the unmatched (Grade 1, HR, 1.59; 95% CI, 1.11–2.29; P = 0.01; Grades 2 + 3, HR, 1.69; 95% CI, 1.02–2.08; P = 0.04) and matched cohort (Grade 1, HR, 1.84; 95% CI, 1.19–2.85; P = 0.01; Grades 2 + 3, HR, 1.91; 95% CI, 1.01–3.24; P = 0.04).ConclusionsMesangial IgM deposition plays an important role in renal prognosis and is independently associated with worse renal outcomes in patients with IgAN.Trial registration TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074
Identification of Protective Peptides of Fasciola Hepatica-Derived Cathepsin L1 (FhCL1) in Vaccinated Sheep by a Linear B-cell Epitope Mapping Approach
Authors: Perazzo Leandro Buffoni , Garza-Cuartero Laura , Pérez-Caballero Raúl , Zafra Rafael , Martínez-Moreno F. Javier , Molina-Hernández Verónica , Pérez José , Martínez-Moreno Álvaro , Mulcahy Grace
Published: May 2020

The authors have withdrawn this preprint due to erroneous posting.
Dual-source CT in Diagnosis of Coronary Artery Fistula and its Value
Authors: WANG Cheng , LI Yaying , LIU Jiangyong
Published: May 2020

Background: Coronary artery fistula refers to the symptom that the coronary artery trunk or branch connects with the heart cavity or the pulmonary circulation blood vessels in a congenital or an acquired manner. As early detection and diagnosis of CAF was necessary for the prevention and management of late symptoms and complications, we are supposed to master the imaging performance of CAFs so as to make a correct diagnosis. This paper seeks to investigate the imaging manifestations and application value of CT diagnosis of coronary fistula and its application value. Methods: To retrospectively analyze the clinical data and DSCT image data of 62 patients with coronary fistula, and summarize, analyze and summarize their image manifestations and types.Results: 62 CAFs originate from 58 LCA vessels, 32 RCA vessels. The distribution frequency of drainage site from high to low was as follows: 40 cases (63%) of the main pulmonary artery, 10 cases (16%) of the right atrium, 7 cases (11%) of the right ventricle, 3 cases (5%) of the left ventricle, 1 case (2%) of the left atrium, and 1 case of coronary sinus (2%), 1 case of the right lower pulmonary vein (2%). There were 39 cases (63%) of single fistula vessel, and 23 cases (37%) of multiple fistula vessel, including 21 cases of left and right coronary arteries. Coronary artery-pulmonary fistulae were the most common with a total of 40 cases. Conclusion: The popularization of CT improved the detection rate of CAFs. Coronary pulmonary-artery fistula was probably the most common seen type of CAFs. ECG-gating coronary artery CTA can accurately assess the origin of CAFs, the course of fistula vessels, and the drainage site, thereby providing important information for clinicians to treat coronary fistula.Trial registration: retrospectively registered
The Effect of Acromioplasty or Bursectomy on the Results of Arthroscopic Repair of Full Thickness Rotator Cuff Tears: Does the Acromion Type Affect These Results?
Authors: Karakus Ozgun , Sari Ahmet Sinan
Published: May 2020

Introduction: The aim of this study was to investigate the effect of subacromial decompression on the results of full thickness rotator cuff repair applied arthroscopically. Examination was also made of the effect of acromion type on the subacromial decompression procedure in patients applied with arthroscopic rotator cuff repair. Materials and Methods: The study included a total of 150 patients, comprising 102 (68%) females and 48 (32%) males with a full thickness rotator cuff tear repaired arthroscopically. The patients were separated into 3 groups of 50. Group A comprised those with acromioplasty and bursectomy applied additional to the repair. In Group B, only bursectomy was performed additional to the repair and in Group C, only rotator cuff repair was applied. Evaluation was made of the postoperative long-term pain and functional results. Results: The mean age of the cases was 65.63±9.22 years (range, 46-86 years). The affected side was right side in 95 (63.3%) cases and left side in 55 (36.7%). No statistically significant difference was determined between the groups according to the postoperative Constant Murley and ASES scores (p>0.05). In the paired comparisons, the postoperative VAS scores of Group C were higher than those of Groups A and B (p=0.018, p=0.029, p<0.05). No statistically significant difference was determined between Group A and Group B in respect of the postoperative VAS scores (p>0.05). Conclusions: In the arthroscopic repair of full thickness rotator cuff tears, neither acromioplasty, coraco-acromial ligament loosening nor bursectomy were determined to have any positive effect on the results. Whatever the acromion type, there is no need for an additional subacromial decompression procedure after rotator cuff repair, in respect of pain and functional outcomes. Only acromial spurs should be gently removed paying attention to the coraco-acromial ligament.