bluuebunny/crossref_metadata_2025 huggingface dataset:
Early upregulation of AR and steroidogenesis enzyme expression after 3 months of androgen-deprivation therapy.
Authors: Hamid Agus Rizal A.H. , Putra Harun Kusuma , Sari Ningrum Paramita , Diana Putri , Sesari Saras Serani , Novita Eka , Gultom Fajar Lamhot , Saraswati Meilania , Tanurahardja Budiana , Asmarinah Asmarinah , Umbas Rainy , Mochtar Chaidir Arief
Published: May 2020

Background: Androgen deprivation therapy (ADT) is a standard treatment for advanced prostate cancer (PCa). However, PCa recurrence and progression rates during ADT are high. Until now, there has been no evidence regarding when progression begins. This study evaluated the gene expression of intraprostatic androgen receptor (AR) and steroidogenic enzymes in the early stages of ADT. Methods: Prostate tissue samples were taken from PCa patients with urinary retention who received ADT (ADT-PCa; n=10) and were further subgrouped into ADT ≤12 months (n=4) and ADT >12 months (n=6). The ADT-PCa tissues were then compared with BPH (n=12) and primary (no treatment) PCa tissues (n=16). mRNA for gene expression analysis of AR and steroidogenic enzymes was extracted from formalin-fixed paraffin embedded (FFPE) tissues and analyzed by real-time PCR. Protein expression was evaluated by immunohistochemistry with specific antibodies. Results: AR gene expression was higher in the ADT-PCa group than in the BPH or primary PCa group. Both the ADT ≤12 and > 12 months subgroups had significantly higher relative gene expression levels of AR (p<0.01 and 0.03, respectively) than the primary PCa group. In the ADT-PCa group, AR protein expression showed an increasing trend in the ADT ≤12 months subgroup and was significantly elevated in the ADT >12 months subgroup compared with the PCa group (100%; p <0.01). Half (50%) of the patients in the ADT ≤12 months subgroup were found to have upregulation of AR, and one showed upregulation beginning at 3 months of ADT. A trend toward elevated relative gene expression of SRD5A3 was also apparent in the ADT groups. Conclusion: AR and steroidogenic enzymes are upregulated in ADT-PCa patients as early as 3 months, without PSA elevation. Steroidogenic enzymes, particularly SRD5A3, were also upregulated before PSA rose.
Risk Factors of Metachronous Brain Metastasis in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer
Authors: Ouyang Wen , Yu Jing , Zhou Yan , Hu Jing , Huang Zhao , Zhang Junhong , Xie Conghua
Published: May 2020

Background NSCLC patients with EGFR mutation were at a higher incidence of developing brain metastasis (BM). Patients with BM are associated with high mortality. Reducing BM incidence becomes increasingly significant for NSCLC patients to achieve prolonged survival. The aim of the study was to explore the possible risk factors of developing metachronous BM during EGFR-TKIs treatment, and to identify the potential candidates for prophylactic cranial irradiation (PCI ) or the first-line osimertinib treatment. Methods A total of 157 consecutive EGFR-mutated advanced NSCLC patients without BM at initial diagnosis in our institution from 2012 and 2018 were retrospectively reviewed . Comparisons of OS were performed based on BM status. The cumulative incidence of metachronous BM was calculated by the Kaplan-Meier method, and the independent risk factors of metachronous BM were investigated by multivariate analysis. Results Patients developing metachronous BM had worse survival (mOS: 22.1 months) than patients not-developing BM (mOS: 44.8 months). Moreover, the multivariate analysis indicated that age ≤ 49 years ( P =0.035), number of extracranial metastases ( P =0.013), and malignant pleural effusion ( P =0.002) were independent risk factors of metachronous BM. Furthermore, the 1-year actuarial incidence of developing metachronous BM in patients with no risk factor (n =101), 1 risk factor (n =46), and 2 risk factors (n =10) were 7.01%, 14.61%, and 43.75%, respectively ( P <0.001). Conclusions Patients developing metachronous BM during EGFR-TKIs treatment have worse outcomes. Our results suggested that EGFR-mutated advanced NSCLC patients with ≥ 1 risk factors were candidates for PCI or the first-line Osimertinib treatment.
Evaluation of a Rapid Immunochromatographic test kit to the Gold Standard Fluorescent Antibody test for diagnosis of rabies in animals in Bhutan
Authors: Tenzin Tenzin , Lhamo Kelzang , Rai Purna B , Tshering Dawa , Jamtsho Pema , Namgyal Jamyang , Wangdi Thrinang , Letho Sangay , Rai Tuku , Jamtsho Sonam , Dorji Chendu , Rinchen Sangay , Lungten Lungten , Wangmo Karma , Lungten Lungten , Wangchuk Pema , Gempo Tshewang , Jigme Kezang , Phuntshok Karma , Tenzinla Tenzinla , Gurung Ratna B , Dukpa Kinzang
Published: May 2020

Background: Rabies kills approximately 59,000 people in the world each year worldwide. Rapid and accurate diagnosis of rabies is important for instituting rapid containment measures and for advising the exposed people for postexposure treatment. The application of a rapid diagnostic tests in the field can greatly enhance disease surveillance and diagnostic activities, especially in resource poor settings. In this study, a total of 179 brain tissue samples collected from different rabies suspect animal species (113 dogs, 50 cattle, 10 cats, 3 goats, 2 horses, and 1 bear) were selected and tested using both rapid immunochromatographic kit and the reference standard fluorescent antibody test (FAT). We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a rapid antigen detection test kit produced by BioNote, Inc. (Hwaseong-si, Korea) relative to a FAT for its fit-for-purpose for confirmation of clinical cases of rabies for early response and enhancing rabies surveillance. Results: Among 179 samples examined in this study, there was a concordance in results by the rapid test and FAT in 115 positive samples and 54 negative samples. Test results were discordant in 10 samples which were positive by FAT, but negative (false negative) by rapid kit. The rapid test kit showed a sensitivity of 92% (95% CI: 85.9 – 95.6) and specificity of 100% (95% CI: 93.4 – 100) using FAT as the reference standard. The positive and negative predictive values were found to be 100% (95% CI:96.7 – 100) and 84.4% (95% CI: 73.6 – 91.3), respectively. Overall, there was 94.4% (95% CI: 90 – 96.9) test agreement between rapid test and FAT (Kappa value = 0.874) with a positive percent agreement and negative percent agreement of 92 and 100%, respectively. Conclusions: Our finding demonstrated that the rapid test kit (BioNote) can be used for rabies surveillance and confirming clinical case of rabies in animals for making rapid decisions particularly controlling rabies outbreaks in resource poor settings.
The role of text messaging intervention in Inner Mongolia among patients with type 2 diabetes mellitus: a randomized controlled trial
Authors: Wang Xuemei , Liu Dan , Du Maolin , Hao Ruiqi , Zheng Huiqiu , Yan Chaoli
Published: May 2020

Background: Short messages service (SMS) provides a practical medium for delivering content to address patients to adherence to self-management. The aim of study was to design some patient-centered health education messages, evaluate the feasibility of messages, and explore the effect of this model. Methods: The messages were designed by a panel of experts, and SMS Quality Evaluation Questionnaire was used to evaluate their quality. A two-arm randomized controlled trial was conducted to evaluate the effectiveness of this management model. Participants were randomly divided into an intervention group (IG) who received evaluated messages and a control group (CG) who received regular education. The primary outcomes were changes in plasma glucose and control rates, and the secondary outcomes were improvements in diet control, physical activities, weight control, etc. Results: A total of 42 messages covering five main domains: health awareness, diet control, physical activities, living habits and weight control were designed, and the average scores of the messages were 8.0 (SD 0.7), 8.5 (SD 0.6), 7.9 (SD 1.0), 8.0 (SD 0.7), and 8.4 (SD 0.9), respectively. In the SMS intervention, 171 patients with an average age of 55.1 years were involved, including 86 in the CG and 85 in the IG. At 12 months, compared with the control group (CG), the decrease of fasting plasma glucose (FPG) (1.5 vs. 0.4, P = 0.011) and control rate (49.4% vs. 33.3%, P = 0.034), the postprandial glucose (PPG) (5.8 vs. 4.2, P = 0.009) and control rate (57.8% vs. 33.7%, P = 0.002) were better in the intervention group (IG). In terms of self-management, improvements in weight control (49.3% vs. 28.2%, P=0.031), vegetables consumption (87.3% vs. 29.0%, P<0.001), fruits consumption (27.5% vs. 7.4%, P=0.022), and physical activities (84.7% vs. 70.0%, P=0.036) were better in the IG than in the CG. Conclusions: The overall quality of the messages was high. It was effective and feasible to carry out an SMS intervention to improve the behavioral habits of patients with chronic diseases in remote and undeveloped areas. Keywords: type 2 diabetes mellitus; mHealth; randomized controlled trialTrial registration: Clinicaltrials.gov, ChiCTR1900023445. Registered May 28, 2019--Retrospectively registered, http://www.chictr.org.cn/index.aspx
Magnitude of Home Delivery and Associated Factors Among Child Bearing Age Mothers in Sherkole District, Benishangul Gumuz Regional State-Western-Ethiopia.
Authors: Gebremariam Resom Berhe , Nigusie Adane
Published: May 2020

Background: The World Health Organization estimates that globally only 43 percent of women have access to skilled care during deliveries and the rest are exposed to unskilled delivery service. A recent Ethiopian Demographic and Health Survey report stated that maternal death was 412 per 100,000 in 2016.This still indicates that maternal health remains a major public health problem in Ethiopia irrespective of the government’s measure to institutional delivery. Therefore, the aim of this study was to assess the magnitude of home delivery and associated factors among women of child bearing age in Sherkole district, Western Ethiopia.Methods: - A community based cross sectional study was conducted among women aged 15-49 years in Sherkole district, Benishangul Gumuz region from January to June 2018. A total of 451 randomly selected women were included in the study. Stratified sampling followed by simple random sampling technique was used to select the study participants. Data were collected using pretested and structured questionnaires. Bivariate and multivariate logistic regression models were fitted to identify factors associated with home delivery among women in the child bearing age. An adjusted odds ratio with a 95% confidence interval was computed to determine the level of significance. Results: The magnitude of home delivery was 353 (80%) and were assisted by non-skilled birth attendants. Mothers whose husband chooses the place of delivery [AOR: 5.6, 95% CI (2.1-15.2), Mothers’ occupation ([AOR: 0.21 95% C I (0.08-0.57), ANC visit [AOR: 95 CI: 5.1(1.6-15.8), decision making [AOR: 95 CI: 0.3(0.01-0.7)] and traditional remedies [AOR: 95%CI: 0.03 (0.01-0.09)] were significantly associated with home delivery.Conclusions: Based on the findings of the survey, it was concluded that the overall magnitude of home delivery was found to be high. Therefore, it is recommended that the promotion of antenatal care follow-up with maternal and child health information particularly on delivery complications or danger signs needs due attention and remedial actions. In addition, it is empirical to study the need and the feasibility of introducing defaulter tracing mechanisms in ANC services, by learning from experiences of settings that have already adopted it.
Predicting Non-elective hospital readmission or Death using a Composite Assessment of Cognitive and Physical Frailty in Elderly inpatients with Cardiovascular Disease
Authors: Yao Simin , Zheng Peipei , Liang Yaodan , Wan Yuhao , Sun Ning , Luo Yao , Yang Jiefu , Wang Hua
Published: May 2020

Background: We aimed to assess the utility of the combination of the mini-mental state examination (MMSE) + clock drawing test (CDT) and the Fried phenotype for predicting non-elective hospital readmission or death within six months in elderly inpatients with cardiovascular disease (CVD).Methods: A single-center prospective cohort was conducted from September 2018 to February 2019. Inpatients ≥65 years old were recruited. Predictive validity was tested using a Cox proportional hazards regression model analysis, and the discriminative ability was evaluated by the receiver operating characteristic (ROC) curve. Results: A total of 542 patients were included. Overall, 12% (64/542) screened positive for cognitive impairment, 16% (86/542) were physically frail and 8% (44/542) had cognitive impairment combined with physical frailty, showing an older age (P<0.001) and a lower education level (P<0.001) than physically frail patients. A total of 113 patients (20.9%) died or were readmitted at six months. Frail participants with a normal (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.06-2.82, P=0.028) or impaired cognition (HR: 2.50, 95% CI: 1.27-4.91, P=0.008) had a higher risk of non-elective hospital readmission or death than robust patients after adjusting for the age, sex, education level, marital status, the presence of diabetes mellitus, heart failure, and history of stroke. The area under the ROC curve (AUC) showed that the discriminative ability in relation to six months readmission and death for the MMSE + CDT + Fried phenotype was 0.65 (95% CI: 0.60-0.71), and the AUC for men was 0.71 (95% CI: 0.63-0.78), while that for women was 0.60 (95% CI: 0.51-0.69).Conclusions: Accounting for cognitive impairment in the frailty phenotype may allow for the better prediction of non-elective hospital readmission or death in elderly inpatients with CVD in the short term.Trial registration: ChiCTR1800017204; date of registration: 07/18/2018.
Intra-carotid arterial transfusion of circulatory-derived autologous endothelial progenitor cells in rodent after ischemic stroke — evaluating the impact of therapeutic time points on prognostic outcomes
Authors: Lin Kun-Chen , Chai Han-Tan , Chen Kuan-Hung , Sung Pei‐Hsun , Chiang John Y. , Shao Pei-Lin , Huang Chi-Ruei , Li Yi-Chen , Ko Sheung-Fat , Yip Hon-Kan
Published: May 2020

Background: This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and Results: Adult-male SD rats (n=70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2x10 6 cells/by LICA administration 3h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS) and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain-infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2 and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all p<0.0001). By day 60, the endothelial cell markers at protein and cellular levels, and number of small vessels exhibited an opposite pattern of BIV among the groups (all p<0.0001). The protein and cellular levels of inflammation, and protein levels of oxidative stress, autophagy and apoptosis, were highest in group 2, lowest in group 1 and progressively increased from groups 3 to 7 (all p<0.0001). The angiogenesis biomarkers at protein and cellular levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 4 to 7 (all p<0.0001). Conclusion: Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.
Variability in blood lipids affects the neutrophil to lymphocyte ratio in patients undergoing elective percutaneous coronary intervention: A retrospective study
Authors: Zhao Liding , Xu Tian , Li Ya , Luan Yi , Lv Qingbo , Fu Guosheng , Zhang Wenbin
Published: May 2020

Background: Atherosclerosis is associated with chronic inflammation and lipid metabolism. The neutrophil to lymphocyte ratio (NLR) as an indicator of inflammation has been confirmed to be associated with cardiovascular disease prognosis. However, few studies have explored the effects of blood lipid variability on NLR. The aim of this study was to explore the relationship between variability in blood lipid levels and NLR. Methods: The association between variability in blood lipids and NLR was assessed with both univariate and multivariate linear regression. Multivariate linear regression was also performed for a subgroup analysis. Results: The variability of high-density lipoprotein cholesterol (HDL-C) (regression coefficients [β] 4.008, standard error (SE) 0.503, P-value<0.001) and low-density lipoprotein cholesterol (LDL-C) ([β] 0.626, SE 0.164, P-value<0.001) were risk factors for the NLR value, although baseline LDL-C and HDL-C were not risk factors for NLR values. Variability of HDL-C ([β] 4.328, SE 0.578, P-value<0.001) and LDL-C ([β] 0.660, SE 0.183, P-value<0.001) were risk factors for NLR variability. Subgroup analysis demonstrated that the relationship between variability of LDL-C and NLR was consistent with the trend of the total sample for those with diabetes mellitus, controlled blood lipid, statins, atorvastatin. The relationship between the variability of HDL-C and NLR was consistent with the trend of the total sample in all subgroups. Conclusion: The variability of HDL-C and LDL-C are risk factors for the value and variability of NLR, while the relationship between variability of HDL-C and NLR is more stable than the variability of LDL-C in the subgroup analysis, which provides a new perspective for controlling inflammation in patients undergoing PCI.
“Combined Sodium Dimercaptopropanesulfonate and Zinc versus D-penicillamine as First-line Therapy for Neurological Wilson’s disease”
Authors: Zhang Jing , Xiao Lulu , Yang Wenming
Published: May 2020

Background: Even though recent research has achieved significant advancement in the development of therapeutic approaches for Wilson’s diseases (WD), the current treatment options available for WD are still limited, expecially for WD patients with neurological symptoms. Objective: The aim of this study was to compare the course of treatment for WD patients with neurological symptoms receiving either combined sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) and zinc treatment or D-penicillamine (DPA) monotherapy as first-line therapy. Methods: The case records of 158 patients diagnosed with neurological WD were retrospectively analyzed. These patients were treated with intravenous DMPS+Zinc and in combination with oral Zinc as a maintenance therapy (Group 1) or DPA alone (Group 2) for 1 year. During the period of treatment, the neurological symptoms of the patients were assessed using the Global Assessment Scale (GAS). The key hematological and biochemical parameters of the patients (such as the levels of aminotransferase, serum ceruloplasmin, 24-h urine copper excretion), as well as adverse effects were recorded and analyzed. Results: 93 patients in Group 1, displayed decreased GAS scores consistently in comparison to the baseline (P < 0.01). Among them, 82(88.2%) patients displayed a significant improvement in their neurological status after 1 year, while 8 patients (8.6%) experienced neurological deterioration. Among the 65 patients in Group 2, 37 patients (58.5%) displayed neurological improvements, while 17 patients (26.2%) experienced neurological deterioration at 1-year follow up. 6 patients discontinued their treatment midway due to their exacerbating neurological symptoms. A comprehensive comparison of the effectiveness of the two courses of treatment revealed that patients in group 1 demonstrated a higher improvement ratio ( P < 0.01) and lower worsening ratio of the neurological symptoms of the patients ( P < 0.01) in comparison to the patients in group 2. Meanwhile, renal function, liver enzyme and the blood cell counts remained stabilized in group1. Conclusions: This study suggests that the combined therapeutic approach of treatment with DPMS and zinc should be the preferred first-line therapy in treating the neurological symptoms of WD, in comparison to the treatment with DPA, as the experimental data demonstrates that it is significantly more efficient.
Doing exercise or sport together with one’s child is positively associated with mothers’ momentary affect in daily life, but not with higher levels of overall physical activity
Authors: Kanning Martina , Do Bridgette , Mason Tyler B. , Belcher Britni R. , Yang Chih-Hsiang , Dunton Genevieve F.
Published: May 2020

Background Physical inactivity is a widespread problem with a great need for innovative intervention concepts to overcome it. Epidemiological studies have identified working women in high-income Western countries to be at greater risk for physical inactivity. The current study included working mothers and examined within-subject associations between doing exercise/sport together with one’s child and five different affective states, and with light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA).Method: During one week, mothers (N = 192) completed up to eight ecological momentary assessment (EMA) surveys a day to assess momentary affect and certain situational circumstances (e.g., doing exercise/sport, being together with child). Physical activity was assessed objectively with waist-worn accelerometers. Results Multilevel analysis showed that doing exercise/sport together with one’s child was associated with higher positive affect and lower negative affect compared to being active alone. However, greater frequency of doing exercise/sport together with children was negatively associated with MVPA. Discussion Due to the positive effect on momentary affect, combining spending time together with one’s child and simultaneously doing exercise/sport might be a good strategy of pairing two relevant personal goals. However, this strategy was not associated with sufficient MVPA.
Exercise training improves adipocyte accumulation and muscle fibrosis by TGF-β1 and α-SMA reduction after botulinum toxin type A administration in mice
Authors: Na Jungtae , Lee Esther , Im Song I , Kim Yu-jin , Kim Su Young , Kim Beom Joon
Published: May 2020

Background: We aimed to investigate the effect of treadmill exercise on functional recovery of the murine gastrocnemius muscle and nerve after botulinum toxin type A (BoNT-A) administration. Methods: After the injection of 0.5 units of BoNT-A into the gastrocnemius muscle of ICR mice, treadmill exercise was conducted for a 6-week period, after which the muscle volume, weight, and sciatic functional index (SFI) was determined and a nerve conduction study (NCS) and histological evaluation were performed. Results: After exercise, there was no change in the gastrocnemius weight and volume, but NCS and SFI increased. Exercise prevented induced adipocyte accumulation and muscle fibrosis. Moreover, transforming growth factor-β1 and α-smooth muscle actin expressions decreased and CD34, brain-derived neurotrophic factor, and synaptosomal nerve-associated protein 25 expressions increased when treadmill exercise was performed after BoNT-A administration. Conclusions: Exercise can effectively recover the nerve function and would aid in muscle function recovery by preventing fat cell accumulation and muscle fibrosis after BoNT-A administration.
Impact of sublethal pyrethroid exposure on resistant Anopheles gambiae mosquitoes’ fitness
Authors: Kropf Alida , Fodjo Behi K , Zoh Marius G , Sadia Chistabelle G , Kouadio Affoué FP , Mouhamadou Chouaibou
Published: May 2020

Background : There is increasing evidence of insecticide resistance spreading among wild mosquito populations, which is widely believed to compromise vector control once it reaches a threshold that enables mosquitoes to survive exposure to long lasting treated bed-net (LLIN) or indoor residual spraying (IRS). However, very little is known about the long-term impact of insecticide resistance on malaria transmission, which makes the consequence of insecticide resistance spreading difficult to predict. Methods: To gain more clarity, we have assessed five life-history traits of a resistant Anopheles gambiae laboratory strain that was repeatedly exposed to a LLIN and compared with individuals issued from the same strain but exposed to an untreated bed-net. Results: The non-parametric Kruskal-Wallis test did not show any significant impact of gonotrophic cycle on the five traits. However, the Kolmogorov-Smirnov non-parametric test revealed a significant (i) drop in blood feeding mean rates (D = 0.800; P< 0.0001), (ii) increase in 24-hours post-exposure (D = 0.600; P< 0.001) and (iii) end of gonotrophic cycle mortality (D = 0.611; P <0.006), and (iv) drop in egg laying rate (D = 0.730, P< 0.0001) when mosquitoes were exposed. Surprisingly, there was rather an upward trend in the number of L3 larvae/female mosquito for the exposed group comparing to the unexposed one, although the difference was not significant (D = 0.417, P> 0.05). Conclusion: Our study shows that in a context of widespread of resistance to insecticides, current pyrethroid-based vector control tools can still confer protection against malaria.
Lung ultrasound in patients with rheumatoid arthritis and the definition of significant interstitial lung disease
Authors: Carlo Marco Di , Tardella Marika , Filippucci Emilio , Carotti Marina , Salaffi Fausto
Published: May 2020

Background. In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. However, in patients with RA it is not yet clear how to interpret, in quantitative terms, the presence of B-lines, the LUS artifact indicative of ILD. The aim of this study was to determine the cut-off number of LUS B-lines that identifies a significant RA-ILD.Methods. A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence.Patients underwent LUS (carried out in 14 defined intercostal spaces), chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of chest HRCT using a computer-aided method (CaM). The discriminative validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis.Results. 72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years). The mean estimate of pulmonary fibrosis using the CaM was 11.20% (SD 7.48) at chest HRCT, while at LUS the mean number of B-lines was 10.65 (SD 15.11). A significant RA-ILD, as measured by the CaM at HRCT, was detected in 25 patients (34.7%). The presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant RA-ILD with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4.Conclusion. The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.
Expression of FAM83H and ZNF16 are associated with shorter survival of patients with gallbladder carcinoma
Authors: Ahn Sung Woo , Ahn Ae-Ri , Ha Sang Hoon , Hussein Usama Khamis , Yang Jae Do , Kim Kyoung Min , Park Ho Sung , Park See-Hyoung , Yu Hee Chul , Jang Kyu Yun
Published: May 2020

Background: Recently, FAM83H was reported to have roles in cancer progression in conjunction with oncogenic molecules such as MYC and b-catenin. Moreover, the data from the public database indicates a molecular relationship between FAM83H and zinc finger proteins, especially between FAM83H and ZNF16. However, studies on FAM83H and ZNF16 in gallbladder cancer have been limited. Methods: This study investigated the expression of FAM83H and ZNF16 in 105 gallbladder carcinomas. Results: In human gallbladder carcinomas, immunohistochemical expression of FAM83H was significantly associated with ZNF16 expression. In univariate analysis, nuclear and cytoplasmic expression of FAM83H or ZNF16 were significantly associated with shorter survival of gallbladder carcinoma patients. Multivariate analysis revealed the nuclear expression of FAM83H as an independent indicator of poor prognosis of overall survival (p = 0.005) and relapse-free survival (p = 0.005) of gallbladder carcinoma patients. Moreover, co-expression patterns of nuclear FAM83H and ZNF16 were also independent indicators of shorter survival of gallbladder carcinoma patients (overall survival; p < 0.001, relapse-free survival; p < 0.001). Conclusions: This study suggests FAM83H and ZNF16 are associated with the progression of gallbladder carcinoma, and the expressions of FAM83H and ZNF16 might be novel prognostic indicators of gallbladder carcinoma patients.
LncRNA MEG3 affects cell proliferation, apoptosis and migration by targeting miR-9-5p/MDK axis and activating PDK/AKT pathway in hepatocellular carcinoma
Authors: Wu Dezhi , Ma Zheng , Ma Deyu , Li Qiquan
Published: May 2020

The authors have withdrawn this preprint due to erroneous posting.
Using Caputo-Fabrizio Derivative For The Transmission of Mathematical Model Epidemic Corona Virus
Authors: Tahir Muhammad , Zaman Gul , Shah Syed Inayat Ali
Published: May 2020

In just a matter of weeks, a rapidly spreading corona virus that originated in Wuhan, China, has infected more than 20,000 people and killed at least 427 worldwide. The virus is capable of spreading from person to person, and Chinese authorities are scrambling to treat a flood of new patients successfully. The virus has spread from an initial outbreak in Wuhan, China, to 25 other countries, and has resulted in the quarantine of at least 16 Chinese cities. In this article, we considered the mathematical model [1] in which Bats-Hosts-Reservoir-People and their transmission was taken, while we introduced the population of susceptible Bats and visitors to Wuhan city or any country in same mathematical model. Now two types of population are: first in [1] introducing susceptible Bats and second visitors to Wuhan city, china or any country. We used Caputo-Fabrizio derivative with provided result that the addition of susceptible Bats and visitors are not responsible in spread of infection. The numerical result also supposed our model.
Increased Vδ1 γδT cells Predominantly Contributed to IL-17 Production in the Development of Adult Human Post-infectious Irritable Bowel Syndrome
Authors: dong liwei , sun xiaoning , ma zhichao , fu jiao , liu fujin , huang baili , liang dongchun , sun deming , lan cheng
Published: May 2020

Background: gdT cells play an important role in the mucosa inflammation and immunity-associated disorders. Our previous study reported that gd T cells producing IL-17 were involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, their subset characteristic profile in this kind of disease remains unclear. Thus the current study’s aim is to investigate the functionally predominant subset and its role in PI-IBS. Methods: The total T cells were collected from the peripheral blood of patients with PI-IBS. The peripheral proportion of Vδ1 and Vδ2 subset was detected by FACS after stained with anti δ1-PE and anti δ2-APC. The local colonic proportion of this two subsets were measured under laser confocal fluorescence microscope. Vδ1 gd T cells were enriched from the total peripheral T cells by minoantibody-immuno-microbeads (MACS) method. and cultured, functionally evaluated by CCK-8 assay (proliferation), CD69/CD62L molecules expression assay (activation) and ELISA (IL-17 production) respectively.Results: 1. Vδ1 gd T cells significantly increased while Vδ2 gd T cells remained unchanged in both the peripheral blood and local colonic tissue from PI-IBS patients (P<0.05). 2. When cultured in vitro, the Vδ1 gd T cells remarkably proliferated, activated and produced IL-17 (P<0.05).Conclusions: Our results suggest that Vδ1 gd T cells was the predominant gd T cells subset in both peripheral and intestinal tissue, and was the major IL-17 producing gd T cells in PI-IBS.
Association Between Harm Reduction Strategies and Healthcare Utilization and Outcomes in Patients on Long-term Prescribed Opioid Therapy Presenting to Acute Healthcare Settings: A Systematic Review and Meta-analysis
Authors: Deschamps Jean , Gilbertson James , Straube Sebastian , Dong Kathryn , MacMaster Frank P. , Korownyk Christina , Montgomery Lori , Mahaffey Ryan , Downar James , Clarke Hance , Muscedere John , Rittenbach Katherine , Featherstone Robin , Sebastianski Meghan , Vandermeer Ben , Lynam Deborah , Magnussen Ryan , Bagshaw Sean M , Rewa Oleksa G
Published: May 2020

BackgroundLong-term prescription of opioids by healthcare professionals has been linked to poor individual patient outcomes and high resource utilization. Harm reduction strategies in this population in regard to acute healthcare settings may have substantial impact.MethodsWe performed a systematic review and meta-analysis of primary studies. The studies were included according to the following criteria: 1) age 18 and older; 2) long-term/chronic prescribed opioid therapy; 3) acute healthcare setting presentation from a complication of opioid therapy; 4) evaluating a harm reduction strategy; 5) comparing the effectiveness of different interventions; 6) addressing patient or healthcare related outcomes. We performed a qualitative analysis of harm reduction strategies identified. We pooled patient and system related outcome data for each harm reduction strategy.ResultsA total of 5664 studies were screened and 21 studies were included. A total of 11 broad categories of harm reduction strategies were identified. Meta-analysis was performed for the “supports for patients in pain” harm reduction strategy on two system-related outcomes using a ratio of means. The number of emergency department (ED) visits were significantly reduced for cohort studies (n=6, 0.36, 95% CI [0.20-0.62], I2 = 87%) and randomized controlled trials (RCTs) (n=3, 0.71, 95% CI [0.61-0.82], I2 = 0%). The number of opioid prescriptions at ED discharge was significantly reduced for RCTs (n=3, 0.34, 95% CI [0.14-0.82], I2 = 78%).InterpretationFor patients presenting to acute healthcare settings with complications related to long-term opioid therapy, the intervention with the most robust data is “supports for patients in pain”.Study registrationCRD42018088962
TGF-β gene polimorphisms as risk factors for asthma control among clinic patients.
Authors: Panek Michał Gabriel , Stawiski Konrad , Kuna Piotr Bolesław
Published: May 2020

Background:

TGF-β and its receptors play a key role in asthma pathogenesis, bronchial hyperreactivity and bronchial remodeling. Expression of isoforms 1–3 of TGFβ cytokine is influenced by tagging polymorphisms in the TGFβ1, TGFβ2 and TGFβ3 gene, and these SNPs may be associated with the risk of asthma development and severity as well as with other diseases. Polymorphic forms of TGF-β1, TGF-β2 and TGF-β3 genes regulate the degree of bronchial inflammation, deterioration of lung functional parameters in spirometry and elevated level of total IgE. All this results in intensification of disease symptoms. According to current GINA 2020 guidelines, the Asthma Control Test (ACT™) should be applied to assess asthma symptoms.
Methods:

An analysis of polymorphisms localized in TGF-β1, TGF-β2 and TGF-β3 genes was conducted on 652 DNA samples with an application of the MassARRAY® system using the mass spectrometry technique MALDI TOF MS. The degree of asthma control was evaluated with ACT™.
Results:

The occurrence of the T / C genotype in rs8109627 (p = 0.0171) in the TGF-β1 gene is significantly associated with a higher ACT result (controlled asthma) in a multivariate linear regression analysis model after using backward stepwise selection of variables. In addition, in the linear model for prediction of ACT score we showed SNP rs8109627 (p = 0.0497) in the TGF-β1 gene (improvement of the disease control - controlled asthma) and rs2796822 (p = 0.0454) in the TGF-β2 gene (deterioration of the diseases control - uncontrolled asthma) significantly modify the degree of asthma control.
Discussion:

We described clinical significance of two SNPs in two genes TGF-β1 and TGF-β2, as yet unknown. We proved that the use of both genotypes and MAC allows to create a moderately correct prognostic model which is about 70% efficient on the entire set of analyzed SNPs in TGF-β1, TGF-β2, and TGF-β3 genes.
Cost-effectiveness analysis of traditional Chinese medicine combined with antiviral drugs for hepatitis B cirrhosis based on Markov model
Authors: Wang Zhiheng , Zhang Mengpei , Zhang Haoxiang , Zuo Kaini , Pan Jie , Wang Xiaomei , Wentao Zhu
Published: May 2020

Background Hepatitis B cirrhosis brings a heavy burden to the health care system all over the world, and traditional Chinese medicine had a good effect in the treatment of hepatitis B cirrhosis. To correctly understand the clinical effect of Chinese medicine combined with antiviral drugs in the treatment of hepatitis B cirrhosis, the long-term therapeutic effect of traditional Chinese medicine combined with antiviral drugs in the treatment of hepatitis B cirrhosis was simulated using Markov model analysis.Methods We used four-state Markov modelling with a probabilistic cohort analysis to calculate the cost per quality-adjusted life year (QALY) gained. A one-year cycle length was applied. The best available evidence provided the model with data on the state of hepatitis B cirrhosis, risk of mortality, utility weight, and probability of transition between disease costs. A 3% discount rate was used for costs and QALYs. Cost-effectiveness acceptability curves were presented to assist decision makers.Results The model indicated that the combination of traditional Chinese medicine and antiviral therapy was cost-effective, and the result showed that there was some uncertainty. In the treatment of hepatitis B cirrhosis simulated by Markov model for 20 years, the combination of traditional Chinese medicine and anti-virus drugs increased 1.48 QALYs per patient compared with the use of antiviral drugs alone, and the total cost saved was 45,551.61 yuan. The total cost saving was mainly due to the reduction of number of hospitalizations caused by serious complications.Conclusion The combination of traditional Chinese medicine and antiviral in the treatment of hepatitis B cirrhosis could save the cost of hospitalization and improve the health output, which was a better outcome evaluated by pharmacoeconomics.
YTHDC2 Promotes the Apoptosis of Colorectal Cancer Cells Through the p38MAPK Signaling Pathway
Authors: Yu Tao , Xu YanYan , Sun Tao , Huang Di , Cao Feng , Gao Xin , Liu Gang
Published: May 2020

Background

The role of the m6A-binding protein YTHDC2 in the occurrence and development of colorectal cancer (CRC) is unclear. We aimed to explore the molecular mechanisms underlying this process and clarify the signaling pathway involved.
Methods

Firstly, the relationship between YTHDC2 and CRC in TCGA database was analyzed to identify relevant signaling pathways and biological processes. Then, western blot was used to analyze expression of YTHDC2 in HCT116 and Caco2 cells. After knockdown or overexpression of YTHDC2 in the above cells, RT-PCR and western blot were used to analyze p38MAPK, p-p38MAPK, and downstream apoptosis-related proteins in the MAPK signaling pathway. Flow cytometry was performed to detect changes in apoptosis.
Results

And the results were shown that the expression of YTHDC2 was significantly lower in tumor tissues than in normal tissues. Increased expression of YTHDC2 was associated with better overall survival among patients with CRC. Gene set enrichment analysis revealed that YTHDC2 regulates the MAPK signaling pathway. Flow cytometry revealed apoptosis was significantly reduced and enhanced in response to YTHDC2 knockdown and overexpression, respectively. There was no significant change in the expression of p38MAPK, while p-p38MAPK was significantly increased in response to overexpression and decreased in response to knockdown. Gene Expression Profiling Interactive Analysis showed apoptotic protein expression to be positively correlated with YTHDC2 expression, consistent with the results of RT-PCR and western blot.
Conclusion

In general, apoptosis of CRC cells is promoted by YTHDC2 via activation of the exogenous death receptor and endogenous mitochondrial apoptosis-related pathways in the p38MAPK signaling pathway.
Ratio of the Medial Hip Joint Space as a Predictor for Collapse of the Femoral Head in Non-traumatic Osteonecrosis: A Retrospective Study and Finite Element Analysis
Authors: Lin Tianye , Yang Peng , Li Hongzhu , Xu Jingli , Xiong Binglang , Chen Zhenqiu , He Wei , Wei Qiushi , Zhang Qing-Wen
Published: May 2020

Background: There has been no indicators that can effectively predict femoral head collapse in ONFH so far. The aim of this study is to retrospectively analyze the first-visit medial space ratio of the hip joint to evaluate its efficacy in predicting ONFH-induced collapse and impacts on the mechanical environment of necrotic femoral head.Methods: In this retrospective analysis for traditional Chinese medicine (TCM), non-traumatic osteonecrosis of femoral head (NONFH) patients from January 2010 to December 2016 were selected. The medial space ratio at their first visit and and collapse of the femoral head during the follow-up were recorded. Patients were divided into group A, B, C, D, and E according to the grading of the medial space ratio at the first visit. A total of 14 hip joint models with distinct medial space ratios were established. The maximum stress intensities of the cartilage, cortical bone and the necrotic area (N-unit area) of the femoral head in the models were quantitated using a finite element analysis.Results: One hundred twenty-eight patients (142 hips) were included in this study. The average follow-up time was 5.4±1.5 years.The Kaplan-Meier survival analysis showed that survival rates of the first-visit medial space ratios in group C and D were significantly higher (exceeding 45.76%) than that in group E (22.73%). There was no significant difference in the survival rates between group C and D (P > 0.05). The finite element analysis showed that in either the necrosis or non-necrosis group, the maximum stress in cartilage, cortical bone and the N-unit area of the femoral head increased with the medial space ratio decreasing. Conclusion: The medial space ratio shows clinical implications of predicting the collapse of NONFH except for assessing the relationship between the femoral head and the acetabulum. The stress concentrations of cartilage, cortical bone, and the necrotic area of the femoral head are enhanced with the medial space radio decreasing. Once the medial space ratio falls below 4 and continues to decline, the risk of necrotic collapse will become higher.
YAP Overexpression in Breast Cancer Cells Promotes Angiogenesis Through Activating Yap Signaling in Vascular Endothelial Cells
Authors: Yan Yu , Song Qiang , Yao Li , Zhao Liang , Cai Hui
Published: May 2020

Background:The YAP signaling pathway is altered and implicated as oncogenic in human mammary cancers.However, roles of YAP signaling that regulate the breast tumor angiogenesis have remained elusive. Tumor angiogenesis is coordinated by the activation of both cancer cells and vascular endothelial cells. Whether the YAP signalingpathway can regulate the intercellular interaction between cancer cells and endothelial cellsis essentially unknown.Results: We showed here that conditioned media from YAP overexpressed breast cancer cells (CM-YAP+) could promote angiogenesis, accompanied byincreased tube formation, migration, and proliferation of human umbilical vein endothelial cells (HUVECs). Down regulation of YAP in HUVECs reversed CM-YAP+ induced angiogenesis.CM-YAP+ time-dependently activated YAP inHUVECs by dephosphorylating YAP and increasing nuclear translocation.We also identified that both G13-RhoA and PI3K/Akt signaling pathway were necessary for CM-YAP+ induced activation of YAP.Besides, connective tissue growth factor (CTGF) and angiopoietin-2 (ANG-2)actedas down-stream of YAP in HUVECs to promote angiogenesis.In addition, subcutaneous tumors nude mice model demonstrated that tumors overexpressed YAP revealed moreneovascularization in vivo.Conclusions: YAP-YAP interaction between breastcancer cells and endothelial cellscould promote tumor angiogenesis, supporting that YAP is a potential marker and target fordeveloping novel therapeutic strategies against breast cancer.
Twin-Chain Polymer Networks Loaded With Nanostructured Fluids for the Selective Removal of A Non-Original Varnish From A 20th Century Oil Painting At The Peggy Guggenheim Collection, Venice
Authors: Buemi Luciano Pensabene , Petruzzellis Maria Laura , Chelazzi David , Baglioni Michele , Mastrangelo Rosangela , Giorgi Rodorico , Baglioni Piero
Published: May 2020

This paper reports on the evaluation of a polyvinyl alcohol (PVA) “twin-chain” polymer network (TC-PN) combined with an oil-in-water nanostructured fluid (NSF) for the removal of a polyvinyl acetate (PVAc) varnish. Small Angle X-ray Scattering, Confocal Laser Scanning Microscopy, and Fluorescence Correlation Spectroscopy showed that the structure of the gel and the NSF are only minimally altered by loading the fluid into the gel. The NSF is partially free to diffuse through the network, but also interacts with the gel walls. During the cleaning, the dynamics of the fluid at the gel-substrate interface are controlled by the osmotic balance taking place among the interconnected pores. These features grant effective and controlled cleaning performances. The case study identified for this research is Pablo Picasso’s The Studio (L’Atelier, 1928), one of the masterpieces in the Peggy Guggenheim Collection, Venice (PGC). In 1969 the oil painting, originally unprotected, was wax-lined and then varnished using a PVAc varnish. Over the years, the white shades of the painting have been compromised by the yellowing of the varnish and soiling of deposits. On painting mock-ups, the NSF-loaded hydrogels allowed the swelling and softening of PVAc varnish and wax layers, which were then removed with gentle mechanical action. Effective varnish and wax removal at the micron scale, and the absence of residues from the cleaning system (gel and NSF), were confirmed by Fourier Transform Infrared Spectroscopy (FTIR) 2D imaging. The effective and safe removal of the aged PVAc varnish and wax layer from the surface of the painting was then carried out using the same cleaning protocol successfully tested on the mock-ups, setting the NSF-loaded PVA TC-PNs as robust and reliable tools for the cleaning of sensitive works of art.