bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular expression of arginine deiminase activates the mitochondrial apoptosis pathway by inhibiting cytosolic ferritin and inducing chromatin autophagy
Authors: Feng Qingyuan , Bian Xuzhao , Liu Xuan , Wang Ying , Zhou Huiting , Ma Xiaojing , Quan Chunju , Yao Yi , Zheng Zhongliang
Published: July 2020

Background: Based on its low toxicity, arginine starvation therapy has the potential to cure malignant tumors that cannot be treated surgically. The Arginine deiminase (ADI) gene has been identified to be an ideal cancer-suppressor gene. ADI expressed in the cytosol displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000). However, it is still unknown whether cytosolic ADI has the same mechanism of action as ADI-PEG20 or other underlying cellular mechanisms. Methods: The interactions of ADI with other protein factors were screened by yeast hybrids, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting the ferritin light-chain domain (FTL) in mitochondrial damage was evaluated by site-directed mutation and flow cytometry. Control of the mitochondrial apoptosis pathway was analyzed by Western Blotting and real-time PCR experiments. The effect of p53 expression on cancer cells death was assessed by siTP53 transfection. Chromatin autophagy was explored by immunofluorescent staining and Western Blotting. Results: ADI expressed in the cytosol inhibited the activity of cytosolic ferritin by interacting with FTL. The inactive mutant of ADI still induced apoptosis in certain cell lines of ASS- through mitochondrial damage. Arginine starvation also generated an increase in the expression of p53 and p53AIP1, which aggravated the cellular mitochondrial damage. Chromatin autophagy appeared at a later stage of arginine starvation. DNA damage occurred along with the entire arginine starvation process. Histone 3 (H3) was found in autophagosomes, which implies that cancer cells attempted to utilize the arginine present in histones to survive during arginine starvation. Conclusions: Mitochondrial damage is the major mechanism of cell death induced by cytosolic ADI. The process of chromatophagy does not only stimulate cancer cells to utilize histone arginine but also speeds up cancer cell death at a later stage of arginine starvation.
Bile cholesterol and viscosity, the keys to discriminating adenomatous polyps from cholesterol polyps by a novel predictive scoring model.
Authors: Kim Eun Young , Hong Tae Ho
Published: July 2020

Background: Adenomatous gallbladder polyps, premalignant lesions of the gallbladder, have fatal outcomes, whereas cholesterol polyps have benign features. Herein, we proposed a novel, predictive scoring model of adenomatous polyps to distinguish them from cholesterol polyps, by analyzing bile components and bile viscosity. Methods: Patients with gallbladder polyp pathologically confirmed after cholecystectomies were analyzed. After dividing patients into two groups (adenomatous or cholesterol polyps), the clinicopathologic profiles and bile nature, including components and viscosity were compared and a predictive scoring model for adenomatous polyps was assessed. Results: 11 adenomatous polyps and 96 cholesterol polyps were analyzed. The variables significantly associated with adenomatous polyps were age>55years (OR=23.550, p=0.020 ), bile viscosity<7.5sec -1 (OR=22.539, p=0.012 ), and bile cholesterol<414.5mg/dl (OR=10.004, p=0.023 ) and the points for each variable in the predictive scoring model were allocated as 3, 3, and 2, respectively. Final scores ranged from 0 to 8 points and the best performance of model at a cutoff of ≥6 points had 90.9% of sensitivity and 80.2% of specificity. Conclusions: Bile viscosity and bile cholesterol accompanied by age were revealed as significant predictors of adenomatous polyps, distinguishing them from cholesterol polyps of gallbladder. It can be the cornerstone for creating accurate guidelines for preoperatively determining treatment strategies of gallbladder polyps.
The relationship between personality dimensions, spirituality, coping strategies and clinical clerkship satisfaction among intern nursing students: A cross-sectional study
Authors: Rezapour-Mirsaleh Yasser , Aghabagheri Mahdi
Published: July 2020

Background : The clinical clerkship is a crucial stage in nursing training, yet a dissatisfaction at this stage may cause a nurse quit in future. This study aimed to investigate the relationship among personality dimensions, spirituality, coping strategies and clinical clerkship satisfaction among intern nursing students. Methods: This was a correlational, cross-sectional study. A total of 293 Iranian nursing students, who were fulfilling their clinical clerkship at university-affiliated hospitals in Tehran, were selected using cluster random sampling. All participants were provided with standard questionnaires including personality dimensions (NEO_FFI), spirituality, coping strategies (WoCQ), and satisfaction with clinical clerkship. Data were analyzed using Pearson correlation and hierarchical multiple regression. Results : The results showed that spirituality (β=0.32, p<0.001), problem-focused coping (β=0.26, p<0.001) and extraversion (of personality dimensions, β=0.22, p<0.001) played significant roles in predicting clinical clerkship satisfaction among intern nursing students. Regression analysis showed openness (β=0.14, p<0.01), extraversion (β=0.16, p<0.01), and spirituality (β=0.23, p<0.001) could significantly predict problem-focused coping style among intern nursing students. However, personality dimensions and spirituality were not good predictors for emotion-focused coping among these students (p>0.05). Conclusion : Personality dimensions, coping strategies and, in particular, spirituality are good predictors of clinical clerkship satisfaction among intern nursing students. Therefore, paying attention to spiritual needs in nursing students, improving their problem solving skills in dealing with clinical stress and training extraversion characteristics can be effective in enhancing their satisfaction with clinical clerkship.
Sagittal Abdominal Diameter and its Socioeconomic Correlates: Perspective of Sex Differences
Authors: Li Chang , Harris Marcelline , Tsilimingras Dennis , Liu Sophia , Sheng Ying , Liu Xuefeng
Published: July 2020

Background Sagittal abdominal diameter (SAD) is an anthropometric index associated with visceral adiposity. It remains unclear whether SAD and its socio-economic correlates differ in women and men, which limits the epidemiological and clinical applications of the SAD measurement. The aims of this study are to examine the sex differences in SAD and its socio-economic correlates.Methods A complex stratified multistage clustered sampling design was used to select 6,975 men and 7,079 women aged 18 years or more from the National Health Nutrition and Examination Survey 2011-2016, representative of the US civilian non-institutionalized population. SAD was measured in accordance to the standard protocols using a two-arm abdominal caliper. The sex differences in SAD and its socio-economic correlates were evaluated by performing weighted independent t tests and weighted multiple regression. Results SAD was lower in women than in men in the entire sample, as well as in all subgroups characterized by age, race, body mass index, birth place, and household income except for non-Hispanic blacks and those with household income < $20,000. Adjusted for other characteristics, SAD increased with age and body mass index for both women and men (p<.0001). Compared to white women, Asian women were associated with lower SAD (p=.018), and black women with higher SAD (p<.0001). Compared to white men, Hispanic and Asian men were associated with lower SAD (both p<.0001). Women born in other countries were more likely to have lower SAD than women born in the US (p<.0001), and so were men (p=.0118). Both women and men with a household income of <$75,000 had higher SAD than those with an income of over $75,000.Conclusion SAD is lower in women than in men, in the general population as well as in the most socio-economic subgroups. Socio-economic correlates of SAD were similar in women and men.
Pre-hospital delay in patients with myocardial infarction: an observational study in a tertiary care hospital of northern Bangladesh
Authors: Rafi Md. Abdur , Sayeed Md. Zahidus , Sultana Papia , Aik Saw , Hossain Golam
Published: July 2020

Background: Delayed hospital presentation is a hindrance to the optimum clinical outcome of modern therapies of Myocardial infarction (MI). This study aimed to investigate the significant factors associated with prolonged pre-hospital delay and the impact of this delay on in-hospital mortality among patients with MI in Northern Bangladesh.Methods: This cross sectional study was conducted in December 2019 in cardiology ward of a 1000-bed tertiary care hospital of Bangladesh. Patients admitted in the ward with the diagnosis of myocardial infarction were included in the study. Socio demographic data, clinical features and patients’ health seeking behavior was collected in a structured questionnaire from the patients. Median with interquartile range (IQR) of pre hospital delay were calculated and compared between different groups. Chi-square (χ²) test and binary logistic regression were used to estimate the determinants of pre-hospital delay and effect of pre-hospital delay on in-hospital mortality.Results: 337 patients was enrolled in the study and their median (IQR) pre-hospital delay was 9.0 (13.0) hours. 39.5% patients admitted in the specialized hospital within 6 hours. In logistic regression, determinants of pre-hospital delay were patients age (for <40 years aOR 2.43, 95% CI 0.73-8.12; for 40 to 60 years aOR 0.44, 95% CI 0.21-0.93), family income (for lower income aOR 5.74, 95% CI 0.89-37.06; for middle income aOR 14.22, 95% CI 2.15-94.17), distance from primary care center £5 km (aOR 0.42, 95% CI 0.12-0.90), predominant chest pain (aOR 0.15, 95% CI 0.05-0.48), considering symptoms as non-significant (aOR 17.81, 95% CI 5.92-53.48), referral from primary care center (for government hospital aOR 4.45, 95% CI 2.03-9.74; for private hospital OR 98.67, 95% CI 11.87-820.34); (R2= 0.528) and not having family history of MI (aOR 2.65, 95% CI 1.24-5.71). Risk of in-hospital mortality was almost four times higher who admitted after 6 hours compared to their counterpart (aOR 0.28, 95% CI 0.12-0.66); (R2 =0.303).Conclusion: Some modifiable factors contribute to higher pre-hospital delay of MI patients, resulting in increased in-hospital mortality. Patients’ awareness about cardiovascular diseases and improved referral pathway of the existing health care system may reduce this unexpected delay.
Nasal carriage of Staphylococcus aureus in farm animals and breeders in North of Morocco
Authors: Mourabit Nadira , Arakrak Abdelhay , Bakkali Mohammed , Zian Zeineb , Bakkach Joaira , Laglaoui Amin
Published: July 2020

Background: The objectives of this study were to determine for the first time, in Morocco, the nasal carriage rate, antimicrobial susceptibility profiles and virulence genes of S. aureus isolated from animals and breeders in close contact.Methods: From 2015 to 2016, 421 nasal swab samples were collected from 26 different Livestock areas in Tangier. Antimicrobial susceptibility phenotypes were determined by disk diffusion according to EUCAST 2015. The presence of nuc, mecA, mecC, lukS/F-PV, and tst genes were determined by Polymerase Chain Reaction (PCR) for all isolates. Results: The overall S. aureus nasal carriage rate was low in animals (9.97%) and high in breeders (60%) with a statistically significant difference, (OR= 13.536; 95% CI = 7.070- 25.912; p< 0.001). In general, S. aureus strains were susceptible to the majority of antibiotics and the highest resistance rates were found against tetracycline (16.7% in animals and 10% in breeders). No Methicillin-Resistant S. aureus (MRSA) was detected in animals and breeders. A high rate of tst and lukS/F-PV genes has been recovered only from animals (11.9% and 16.7%, respectively).Conclusion: Despite the lower rate of nasal carriage of S. aureus and the absence of MRSA strains in our study, S. aureus strains harbored a higher frequency of tst and lukS/F-PV of virulence genes, which is associated to an increased risk of infection dissemination in humans. This highlights the need for further larger and multi-center studies to better define the transmission of the pathogenic S. aureus between livestock, environment, and humans.
Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome.
Authors: Accarie Alison , L'homme Bruno , Benadjaoud Mohamedamine , Lim Sai Kiang , Guha Chadan , Benderitter Marc , Tamarat Radia , SEMONT Alexandra
Published: July 2020

Background: Human exposure to high doses of radiation resulting in acute radiation syndrome and death can rapidly escalate to a mass casualty catastrophe in the event of nuclear accidents or terrorism. The primary reason is that there is presently no effective treatment option, especially for radiation-induced gastrointestinal syndrome. This syndrome results from disruption of mucosal barrier integrity leading to severe dehydration, blood loss and sepsis. In this study, we tested whether extracellular vesicles derived from mesenchymal stromal cells (MSC) could reduce radiation-related mucosal barrier damage and reduce radiation-induced animal mortality. Methods: Human MSC-derived extracellular vesicles were intravenously administered to NUDE mice, 3, 24 and 48 hours after lethal whole-body irradiation (10 Grays). Integrity of the small intestine epithelial barrier was assessed by morphologic analysis, immunostaining for tight junction protein (claudin-3) and in vivo permeability to 4 kDa FITC-labeled dextran. Renewal of the small intestinal epithelium was determined by quantifying epithelial cell apoptosis (TUNEL staining) and proliferation (Ki67 immunostaining). Statistical analyses were performed using one-way ANOVA followed by a Tukey test. Statistical analyses of mouse survival were performed using Kaplan-Meier and Cox methods. Results: We demonstrated that MSC-derived extracellular vesicles treatment reduced by 85% the instantaneous mortality risk in mice subjected to 10 Grays whole-body irradiation and so increased their survival time. This effect could be attributed to the efficacy of MSC-derived extracellular vesicles in reducing mucosal barrier disruption. We showed that the MSC-derived extracellular vesicles improved the renewal of the small intestinal epithelium by stimulating proliferation and inhibiting apoptosis of the epithelial crypt cells. The MSC-derived extracellular vesicles also reduced radiation-induced mucosal permeability as evidenced by the preservation of claudin-3 immunostaining at the tight junctions of the epithelium.Conclusions: MSC-derived extracellular vesicles promote epithelial repair and regeneration and preserve structural integrity of the intestinal epithelium in mice exposed to radiation-induced gastrointestinal toxicity. Our results suggest that the administration of MSC-derived extracellular vesicles could be an effective therapy for limiting acute radiation syndrome.
Autoantibodies directed against α1-adrenergic receptor and endothelin receptor A in patients with prostate cancer
Authors: Wallukat Gerd , Jandrig Burkhard , Becker Niels-Peter , Wendler Johann J. , Göttel Peter , Müller Johannes , Schostak Martin , Schimke Ingolf
Published: July 2020

Background: For prostate cancer, signaling pathways induced by over-boarding stimulation of G-protein coupled receptors (GPCR) such as the endothelin, α1- and β-adrenergic, muscarinic and angiotensin 1 receptors were accused to support the carcinogenesis. However, excessive receptor stimulation by physiological receptor ligands is minimized by a control system that induces receptor sensitization and down-regulation. This system is missing when so-called "functional autoantibodies" bind to the GPCR (GPCR-AAB). If GPCR-AAB were found in patients with prostate cancer, uncontrolled GPCR stimulation could make these autoantibodies an additional supporter in prostate cancer. Methods: Using the bioassay of spontaneously beating cultured rat neonatal cardiomyocytes, GPCR-AAB were identified, quantified and characterized in the serum of 25 patients (aged 56-78 years, median 70 years) with prostate cancer compared to 10 male patients (aged 48-82 years, median 64) with urinary stone disorders (controls). Results: Of the cancer patients, 24 (96%) and 17 (68%), respectively, carried autoantibodies directed against the α1-adrenergic receptor (α1-AAB) and endothelin receptor A (ETA-AAB). No patient was negative for both GPCR-AAB. In contrast, ETA-AAB and α1-AAB were absent in all (100%) and 9 (90%) of the 10 control patients, respectively. While α1-AAB targeted a specific epitope of the first extracellular loop of the α1-adrenergic receptor subtype A, an epitope of the second extracellular loop of the ETA receptor was identified as a target of ETA-AAB. As demonstrated in vitro, the functional activity of both autoantibodies found in prostate cancer can be neutralized by the aptamer BC007.Conclusions: We hypothesized that α1-AAB and ETA-AAB, which are highly present in prostate cancer patients, could by their functional activity support carcinogenesis by excessive receptor stimulation. The in vitro demonstrated neutralization of α1- and ETA-AAB by the aptamer BC007 could open the door to complement the treatments already available for prostate cancer.
The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells
Authors: Li Xiaoyu , Zhang Bowen , Wang Hong , Zhao Xiaolu , Zhang Zijie , Ding Gang , Wei Fulan
Published: July 2020

Background: Periodontal ligament stem cells (PDLSCs) have many applications in the field of cytotherapy, tissue engineering, and regenerative medicine. However, the effect of age on the biological and immunological characteristics of PDLSCs remains unclear. Methods: In this study, we compared PDLSCs isolated from young and adult individuals. PDLSCs proliferation was analyzed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining, and apoptosis level was detected by Annexin V-PE/7-ADD staining. PDLSCs osteogenic/adipogenic/chondrogenic differentiation potentials were assessed by alkaline phosphatase (ALP), Alizarin Red, Oil Red O, Alcian Blue staining and related quantitative analysis. PDLSCs immunosuppressive capacity was determined by EdU and Annexin V-PE/7-ADD staining. To explore its underlying mechanism, microarray, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and western blot analyses were performed to detect differentially expressed genes and proteins in PDLSCs. Results: Our results demonstrated that with aging, the proliferation and osteogenic/adipogenic/chondrogenic differentiation potential of PDLSCs decreased, whereas apoptosis of PDLSCs increased. Moreover, the immunosuppressive ability of PDLSCs decreased with aging. Compared with PDLSCs from young subjects, analysis of mRNA expression revealed an upregulation of CCND3 and RC3H2, and a downregulation of Runx2, ALP, COL1A1, PPARγ2, CXCL12, FKBP1A, FKBP1B, NCSTN, P2RX7, PPP3CB, RIPK2, SLC11A1, and TP53 in those from adult individuals. Furthermore, protein expression levels of Runx2, ALP, COL1A1, and PPARγ2 in the adult group was decreased, whereas that of CCND3 increased. Conclusions: Taken together, aging influences biological and immunological characteristics of PDLSCs, and thus it is more appropriate to utilized PDLSCs from young individuals for tissue regeneration, post-aging treatment, and allotransplantation.
A co-production approach guided by the Behaviour Change Wheel to develop an intervention for reducing sedentary behaviour after stroke
Authors: Hall Jennifer , Morton Sarah , Hall Jessica , Clarke David J , Fitzsimons Claire F , English Coralie , Forster Anne , Mead Gillian E , Lawton Rebecca
Published: July 2020

Background: Stroke survivors are highly sedentary; thus, breaking up long uninterrupted bouts of sedentary behaviour could have substantial health benefit. However, there are no intervention strategies specifically aimed at reducing sedentary behaviour tailored for stroke survivors. The purpose of this study was to use co-production approaches to develop an intervention to reduce sedentary behaviour after stroke.Methods: A series of five co-production workshops with stroke survivors, their caregivers, stroke service staff, exercise professionals, and researchers were conducted in parallel in two stroke services (England and Scotland). Workshop format was informed by the Behaviour Change Wheel (BCW) framework for developing interventions and incorporated systematic review and empirical evidence. Taking an iterative approach, data from activities and audio recordings were analysed following each workshop and findings used to inform subsequent workshops, to inform both the activities of the next workshop and ongoing intervention development.Findings: Co-production workshop participants (n = 43) included 17 staff, 14 stroke survivors, six caregivers, and six researchers. The target behaviour for stroke survivors is to increase standing and moving, and the target behaviour for caregivers and staff is to support and encourage stroke survivors to increase standing and moving. The developed intervention is primarily based on co-produced solutions to barriers to achieving the target behaviour. The developed intervention includes 34 behaviour change techniques. The intervention is to be delivered through stroke services, commencing in the inpatient setting and following through discharge into the community. Participants reported that taking part in intervention development was a positive experience. Conclusions: To our knowledge, this is the first study that has combined the use of co-production and the BCW to develop an intervention for use in stroke care. In-depth reporting of how a co-production approach was combined with the BCW framework, including the design of bespoke materials for workshop activities, should prove useful to other researchers and practitioners involved in intervention development in stroke.
Older persons are frailer after an emergency care visit to the out-of-hours General Practitioner Cooperative in the Netherlands: a cross-sectional descriptive TOPICS-MDS study
Authors: Bloemhoff Anneke , Schoon Yvonne , Smulders Kien , Akkermans Reinier , Vloet Lilian , Berg Karen van den , Berben Sivera
Published: July 2020

Background: In the Netherlands, community-dwelling older people with primary care emergency problems contact the General Practitioner Cooperative (GPC) after hours. However, frailty remains an often unobserved hazard with adverse health outcomes. The aim of this study was to provide insight into differences between older persons with or without GPC emergency care visits (reference group) regarding frailty and healthcare use.Methods: A cross-sectional descriptive study design was based on data from the public data repository of The Older Persons and Informal Caregivers Survey Minimum Dataset (TOPICS-MDS). Frailty in older persons (65+ years, n=32,149) was measured by comorbidity, functional and psychosocial aspects, quality of life and a frailty index. Furthermore, home care use and hospital admissions of older persons were identified. We performed multilevel logistic and linear regression analyses. A random intercept model was utilised to test differences between groups, and adjustment factors (confounders) were used in the multilevel analysis.Results: Compared to the reference group, older persons with GPC contact were frailer in the domain of comorbidity (mean difference 0.52; 95% CI 0.47-0.57, p <0.0001) and functional limitations (mean difference 0.53; 95% CI 0.46-0.60, p <0.0001), and they reported less emotional wellbeing (mean difference -4.10; 95% CI -4.59- -3.60, p <0.0001) and experienced a lower quality of life (mean difference -0.057; 95% CI -0.064- -0.050, p <0.0001). Moreover, older persons more often reported limited social function (OR = 1.50; 95% CI 1.39-1.62, p <0.0001) and limited perceived health (OR = 1.50, 95% CI 1.39-1.62, p <0.0001). Finally, older persons with GPC contact more often used home care (OR = 1.37; 95% CI 1.28-1.47, p <0.0001) or were more often admitted to the hospital (OR = 2.88; 95% CI 2.71-3.06, p <0.0001).Conclusions: Older persons with out-of-hours GPC contact for an emergency care visit were significantly frailer in all domains and more likely to use home care or to be admitted to the hospital compared to the reference group. Potentially frail older persons seemed to require adequate identification of frailty and support (e.g., advanced care planning) both before and after a contact with the out-of-hours GPC.
Spatial-temporal analysis of Tuberculosis in Chongqing, China 2011-2018
Authors: Yu Ya , Wu Bo , Wu Chengguo , Wang Qingya , Hu Daiyu , Chen Wei
Published: July 2020

Background: China is a country with a high burden of pulmonary tuberculosis (PTB). Chongqing is in the southwest of China, where the notification rate of PTB ranks tenth in China. This study analyzed the temporal and spatial distribution characteristics of PTB in Chongqing in order to improve TB control measures.Methods: A spatial-temporal analysis has been performed based on the data of PTB from 2011 to 2018, which was extracted from the National Surveillance System. The effect of TB control was measured by variation trend of pathogenic positive PTB notification rate and total TB notification rate. Time series, spatial autonomic correlation and spatial-temporal scanning methods were used to identify the temporal trends and spatial patterns at county level.Results: A total of 188,528 cases were included in this study. A downward trend was observed in PTB between 2011 and 2018 in Chongqing. The peak of PTB notification occurred in late winter and early spring annually. By calculating the value of Global Moran's I and Local Getis’s Gi*, we found that PTB was spatially clustered and some significant hot spots were detected in the southeast and northeast of Chongqing. One most likely cluster and three secondary clusters were identified by Kulldorff’s scan spatial-temporal Statistic.Conclusions: This study identified seasonal patterns and spatial-temporal clusters of PTB cases in Chongqing. Priorities should be given to southeast and northeast of Chongqing for better TB control.
3-Methylxanthine production through biodegradation of theobromine by Aspergillus sydowii PT-2
Authors: ZHOU bin-xing , Ma Cunqiang , Zheng Chengqin , Xia Tao , Ma Bingsong , Liu Xiaohui
Published: July 2020

Background: Methylxanthines, including caffeine, theobromine and theophylline, are natural and synthetic compounds in tea, which could be metabolized by certain kinds of bacteria and fungi. Previous studies confirmed that several microbial isolates from Pu-erh tea could degrade and convert caffeine and theophylline. We speculated that these candidate isolates also could degrade and convert theobromine through N-demethylation and oxidation. In this study, seven tea-derived fungal strains were inoculated into various theobromine agar medias and theobromine liquid mediums to assess their capacity in theobromine utilization. Related metabolites with theobromine degradation were detected by using HPLC in the liquid culture to investigate their potential application in the production of 3-methylxanthine. Results: Based on theobromine utilization capacity, Aspergillus niger PT-1, Aspergillus sydowii PT-2, Aspergillus ustus PT-6 and Aspergillus tamarii PT-7 have demonstrated the potential for theobromine biodegradation. Particularly, A. sydowii PT-2 and A. tamarii PT-7 could degrade theobromine significantly (p < 0.05) in all given liquid mediums. 3,7-Dimethyluric acid, 3-methylxanthine, 7-methylxanthine, 3-methyluric acid, xanthine, and uric acid were detected in A. sydowii PT-2 and A. tamarii PT-7 culture, respectively, which confirmed the existence of N-demethylation and oxidation in theobromine catabolism. 3-Methylxanthine was common and main demethylated metabolite of theobromine in the liquid culture. 3-Methylxanthine in A. sydowii PT-2 culture showed a linear relation with initial theobromine concentrations that 177.12 ± 14.06 mg/L 3-methylxanthine was accumulated in TLM-S with 300 mg/L theobromine. Additionally, pH at 5 and metal ion of Fe2+ promoted 3-methylxanthine production significantly (p < 0.05). Conclusions: This study is the first to confirm that A. sydowii PT-2 and A. tamarii PT-7 degrade theobromine through N-demethylation and oxidation, respectively. A. sydowii PT-2 showed the potential application in 3-methylxanthine production with theobromine as feedstock through the N-demethylation at N-7 position.
Health-related publications on people living in fragile states in the alert zone: a bibliometric analysis
Authors: Sweileh Waleed
Published: July 2020

Background: Fragile states pose a global challenge. Assessing health research activity on people living in these states can help identify neglected health domains in fragile settings. The objective of the current study was to assess and describe health research activity on people living in fragile states in the alert zone. Method: A bibliometric method was applied using SciVerse Scopus. Research articles published on people in fragile states in the alert zone were retrieved and analyzed. The Fragile State Index (FSI) score was used for selection of states in the alert zone. The analysis was limited to one year; 2018. Results: The search query found 2299 research articles giving an average of 2 research articles per one million population per year in the selected fragile states. The number of research articles per one million population was not significantly correlated (p=0.053; r= - 0.349) with FSI scores. However, it was significantly correlated with the extent of international research collaboration (P<0.01, r=065). Research on communicable diseases was the largest research domain (763 articles; 33.2%) followed by maternal/women’s health (430 articles; 18.7%), non-communicable diseases (291 articles; 12.7%), health system/policy (271 articles; 11.8%) and psychosocial and mental health (89; 3.9%). There were three research themes in the research domain of infectious diseases: HIV/AIDS; water-borne infectious diseases; and miscellaneous infectious diseases such as tuberculosis and malaria. The top ten cited articles were mainly on infectious diseases, particularly on malaria and Lassa fever. Of all the retrieved documents, 727 (31.6%) research articles appeared in national/regional journals while the remaining appeared in international journals. The World Health organization was the most active funding organization for research on fragile states. Top ten active institutions were mainly based in fragile states with the lowest FSI score, specifically Ethiopia, Uganda, Nigeria, and Pakistan. Conclusion: Research on fragile states was relatively low. Research on mental health and health system/policy should be encouraged. Collaboration and funding might help academic institutions in fragile states to make health problems in these countries more visible
Dynamic RMST Curves for Survival Analysis in Clinical Trials
Authors: Liao Jason , Liu G. Frank , Wu Wen-Chi
Published: July 2020

Background: The data from immuno-oncology (IO) therapy trials often show delayed effects, cure rate, crossing hazards, or some mixture of these phenomena. Thus, the proportional hazards (PH) assumption is often violated such that the commonly used log-rank test can be very underpowered. In these trials, the conventional hazard ratio for describing the treatment effect may not be a good estimand due to the lack of an easily understandable interpretation. To overcome this challenge, restricted mean survival time (RMST) has been strongly recommended for survival analysis in clinical literature due to its independence of the PH assumption as well as a more clinically meaningful interpretation. The RMST also aligns well with the estimand associated with the analysis from the recommendation in ICH E-9 (R1), and the test/estimation coherency. Currently, the Kaplan Meier (KM) curve is commonly applied to RMST related analyses. Due to some drawbacks of the KM approach such as the limitation in extrapolating to time points beyond the follow-up time, and the large variance at time points with small numbers of events, the RMST may be hindered. Methods: The dynamic RMST curve using a mixture model is proposed in this paper to fully enhance the RMST method for survival analysis in clinical trials. It is constructed that the RMST difference or ratio is computed over a range of values to the restriction time τ which traces out an evolving treatment effect profile over time.Results: This new dynamic RMST curve overcomes the drawbacks from the KM approach. The good performance of this proposal is illustrated through three real examples. Conclusions: The RMST provides a clinically meaningful and easily interpretable measure for survival clinical trials. The proposed dynamic RMST approach provides a useful tool for assessing treatment effect over different time frames for survival clinical trials. This dynamic RMST curve also allows ones for checking whether the follow-up time for a study is long enough to demonstrate a treatment difference. The prediction feature of the dynamic RMST analysis may be used for determining an appropriate time point for an interim analysis, and an evaluation tool for study recommendation from data monitoring committee (DMC).
Association between pelvic obliquity and scoliosis, hip displacement and asymmetric hip abduction in children with cerebral palsy. A cross-sectional registry study
Authors: Hägglund Gunnar
Published: July 2020

Background: Pelvic obliquity (PO) is common in individuals with cerebral palsy (CP). I analysed the prevalence of PO in a population of children with CP and its associations with scoliosis, hip displacement and asymmetric hip abduction. Methods: Over a 5-year period all pelvic radiographs from the Swedish surveillance programme for CP and the recorded data for scoliosis and hip abduction in children from southern Sweden at Gross Motor Function Classification System (GMFCS) levels II–V were analysed. PO and hip displacement calculated as migration percentage (MP) were measured on supine pelvic radiographs and compared with side difference in hip abduction. Statistical analyses comprised chi-squared testing and binominal confidence intervals. Results: In total, 337 children were analysed, of whom 79 had a PO of >5°. The proportion of children with PO increased from 16% in GMFCS level II to 34% in level V. Scoliosis combined with PO was reported in 38 children, of whom 34 (89%, 95% confidence interval [CI] 80–99%) had the convexity opposite the high side of the PO. Asymmetric abduction with PO was reported in 45 children, of whom 40 (89%, CI 79–99%) had reduced abduction on the high side of the PO. Asymmetric MP of >5% with PO was seen in 62 children, of whom 50 had higher MP on the high side of the PO (81%, CI 71–90%). Children in GMFCS levels II–IV more often had isolated infra-pelvic association with PO (47% versus 19% in GMFCS V, P=0.025), while combined supra- and infrapelvic association was more common in GMFCS level V (65% versus 30% in GMFCS II–IV, P=0.004). Isolated infrapelvic or no association was seen in 74% of children < 10 years of age while 76% of children >11 years old had suprapelvic or combined supra- and infrapelvic association with PO ( P=0.0001). Conclusions: There was a strong association between the high side of PO and the side of scoliosis, highest MP and lowest range of abduction when PO was measured in supine position. PO was more often associated with infrapelvic factors. PO was seen in young children indicating the need for early awareness of this complication.
Spatial Estimation of Soil Erosion Using RUSLE Modeling: A case study of Dolakha District, Nepal
Authors: Thapa Pawan
Published: July 2020

Background: Soil erosion causes topsoil loss, which decreases fertility in agricultural land. Spatial estimation of soil erosion essential for an agriculture-dependent country like Nepal for developing its control plans. This study evaluated impacts on Dolakha using the Revised Universal Soil Loss Equation (RUSLE) model; analyses the effect of Land Use and Land Cover (LULC) on soil erosion. Results: The soil erosion rate categorized into six classes based on the erosion severity, and 5.01% of the areas found under extreme severe erosion risk (> 80 Mg ha-1yr-1) addressed by decision-makers for reducing its rate and consequences. Followed by 10 % classified between high and severe range from 10 to 80 Mg ha-1yr-1. While 15% and 70% of areas remained in a moderate and low-risk zone, respectively. Result suggests the area of the north-eastern part suffers from a high soil erosion risk due to steep slope. Conclusions: The result produces a spatial distribution of soil erosion over Dolakha, which applied for conservation and management planning processes, at the policy level, by land-use planners and decision-makers.
Identification and validation of an immune-related prognostic signature for hepatocellular carcinoma
Authors: Xia Xinxin , Liu Hui , Li Yuejun
Published: July 2020

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality. The immune system plays vital roles in HCC initiation and progression. The present study aimed to construct an immune-gene related prognostic signature (IRPS) for predicting the prognosis of HCC patients. Methods: Gene expression data were retrieved from The Cancer Genome Atlas database. Univariate Cox regression analysis was carried out to identify differentially expressed genes that associated with overall survival. The IRPS was established via Lasso and multivariate Cox regression analysis. Both Cox regression analyses were conducted to determine the independent prognostic factors for HCC. Next, the association between the IRPS and clinical-related factors were evaluated. The prognostic values of the IRPS were further validated using the International Cancer Genome Consortium (ICGC) dataset. Gene set enrichment analyses (GSEA) were conducted to understand the biological mechanisms of the IRPS. Results: A total of 62 genes were identified to be candidate immune-related prognostic genes. Transcription factors-immunogenes network was generated to explore the interactions among these candidate genes. According to the results of Lasso and multivariate Cox regression analysis, we established an IRPS and confirmed its stability and reliability in ICGC dataset. The IRPS was significantly associated with advanced clinicopathological characteristics. Both Cox regression analyses revealed that the IRPS could be an independent risk factor influencing the prognosis of HCC patients. The relationships between the IRPS and infiltration immune cells demonstrated that the IRPS was associated with immune cell infiltration. GSEA identified significantly enriched pathways, which might assist in elucidating the biological mechanisms of the IRPS. Furthermore, a nomogram was constructed to estimate the survival probability of HCC patients. Conclusions: The IRPS was effective for predicting prognosis of HCC patients, which might serve as novel prognostic and therapeutic biomarkers for HCC.
Uterine Transcriptome Analysis Reveals Mechanism Underlying the Ultrastructure Differences of Eggshell in Young and Aged Laying Hens
Authors: Feng Jia , Zhang Hai-jun , Wu Shu-geng , Qi Guang-hai , Wang J.
Published: July 2020

Background: Lower eggshell quality in the late laying period leads to economic loss. It is a major threat to the quality and safety of egg products. Age-related variations in ultrastructure were thought to induce this deterioration. Eggshell mineralization is a highly complex process under precise regulation of genes and biological pathways in uterus of laying hens. Herein, we evaluated the physical, mechanical and ultrastructure properties of eggshell and conducted RNA sequencing to learn the transcriptomic differences in uterus between laying hens in the peak (young hens) and late phase (aged hens) of production.Results: The declined breaking strength and fracture toughness of eggshell were observed in aged hen group compared to those in young hen group, accompanied with ultrastructure variations including the increased thickness of mammillary layer and the decreased incidence of early fusion. During the initial stage of eggshell formation, a total of 183 differentially expressed genes (DEGs; 125 upregulated and 58 downregulated) were identified in uterus of laying hens in the late phase in relative to those at peak production. The DEGs annotated to Gene Ontology terms related to antigen processing and presentation were downregulated in aged hens compared to young hens. The contents of proinflammatory cytokine IL-1β in uterus were higher in aged hens relative to those in young hens. Besides, the genes of some matrix proteins potentially involved in eggshell mineralization, such as ovalbumin, versican and glypican 3, were also differentially expressed between two groups.Conclusions: Altered gene expression of matrix proteins along with the compromised immune function in uterus of laying hens in the late phase of production may conduce to age-related impairments of eggshell ultrastructure and mechanical properties. The current study enhances our understanding of the age-related deteriorations in eggshell ultrastructure and provides potential targets for improvement of eggshell quality in the late laying period.
Correction of immunosuppression in aged septic rats by human ghrelin and growth hormone through the vagus nerve-dependent inhibition of TGF-β production
Authors: Zhou Mian , Aziz Monowar , Ochani Mahander , Wang Ping
Published: July 2020

Background: Co-administration of human ghrelin and growth hormone (GH) reverse immunosuppression in septic aged animals, but the mechanism remains elusive. Here we hypothesize that ghrelin and GH co-treatment restores the immune response in aged septic rats by inhibiting the production of transforming growth factor-β (TGF-β), an immunoregulatory cytokine, through the vagus nerve. Methods: Male aged Fischer rats (22-23-month-old) were made septic by cecal ligation and puncture (CLP) with or without dissecting the vagus nerve (vagotomy). Human ghrelin and GH or vehicle (PBS) were administrated subcutaneously at 5 h post CLP. After 20 h of CLP, serum and spleens were harvested. Results: Serum TGF-β levels were increased in septic aged rats, while ghrelin and GH treatment significantly reduced its levels. Expression of TGF-β in the spleen was upregulated after sepsis, while ghrelin and GH treatment significantly inhibited its expression. TNF-α and IL-6 levels were significantly reduced after ex vivo LPS stimulation of splenocytes from rats that underwent CLP compared to sham rats; while these levels were significantly higher in splenocytes from ghrelin and GH-treated CLP rats compared to vehicle-treated CLP rats. Ghrelin and GH treatment reduced program death receptor-1 (PD-1) expression, increased human leukocyte antigen (HLA) expression, attenuated lymphopenia, and cleaved caspase-3 levels in splenocytes in septic aged rats. Vagotomy diminished the beneficial effects of ghrelin and GH treatment in septic rats. In vitro, the addition of ghrelin, GH, or ghrelin and GH together had no effect on restoring immune response in splenocytes from CLP rats following LPS stimulation, indicating the requirement of the vagus nerve for ghrelin and GH’s effect. Conclusions: Ghrelin and GH attenuate immunosuppression in aged septic rats through the vagus nerve-dependent inhibition of TGF-β production.
The impacts of fuel price policies on air pollution: A case study of Tehran
Authors: raeissi pouran , harati touraj , hadian mohammad , Ahmadian Sepehr , Farhadi Kobra
Published: July 2020

Background: This study aims to investigate the impacts of fuel price policies on the concentration of air pollutants emitted from the transport sector.Methods: Autoregressive distributed lag (ARDL) estimation models were used to investigate the impacts of gasoline and diesel prices along with the weather and economic variables on the following traffic-related pollutants: Carbon monoxide (CO), Nitrogen dioxide (NO2), and Particular matter 10 micrometers or less (PM10).Results: In the short term, one percent increase in gasoline prices leads to 0.02 and 0.012 percent decrease in the concentration of CO and PM10, respectively. In addition, in the short term, one percent increase in diesel prices leads to 0.008, 0.02, and 0.015 percent decrease in the concentration of CO, PM10, and NO2, respectively. Results demonstrate that one percent increase in gasoline prices leads to 0.011 and 0.02 percent increase in NO2 concentration in the short term and long term, respectively. Fuel prices had a greater impact on air pollutant concentration in the long term than in the short term. In the long term, one percent increase in diesel prices leads to 0.011, 0.024, and 0.029 percent decrease in the concentration of CO, NO2, and PM10, respectively.Conclusion: Although fuel price increases lead to a significant reduction in air pollution concentration, other factors related to weather conditions (wind speed, temperature, and rainfall) as well as economic activities have a greater impact on air pollution. Therefore, other policies such as improving fuel quality and technology along with other economic policies can be more effective.
Sudden Death in The Young Adult: An Autopsy-Based Series
Authors: Saadi Said , Jomaa Sami Ben , Hadj Mariem Bel , Oualha Dorra , Salem Nidhal Haj
Published: July 2020

Background: We aim to study the epidemiological and pathological characteristics of sudden death in young, to determine the etiology of death and to purpose recommendations for prevention. Methods: we performed a retrospective cohort study using autopsy data from the Department of Forensic Medicine of Monastir. A review of all autopsies performed during 28 years was done. In each case, clinical information and circumstances of death were obtained and a complete forensic autopsy and histological and toxicological investigations were performed. We have included all sudden death in persons aged between 18 years and 35 years.Results: we collected 137 cases of sudden death during studied period. The mean age of the studied population was 26.47 years. In 72.6% death was classified as cardiac death and was due to ischemic heart disease in 32.32%. Sudden death was attributed to a pleuropulmonary cause in 7.4%, an abdominal cause in 6% and from a neurological origin in 4.5%. The cause of sudden death in this group was not established in 9.5%.Conclusion: there are several potential causes of sudden unexplained death such as structural abnormalities, ion channels abnormalities. Unexplained deaths, presumed to result from sudden primary arrhythmogenic causes, occur in young adult with structurally normal hearts. That underlying disease-causing genetic defects may be involved has clinical implications for family members. Our findings suggest that prevention of sudden death among young adults under the age of 35 years should also focus on evaluation for causes not associated with structural heart disease.