bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNF115 promotes lung adenocarcinoma through Wnt/β-catenin pathway activation by mediating APC ubiquitination
Authors: Wu Xiao-Ting , Wang Yu-Han , Cai Xiao-Yue , Dong Yun , Cui Qing , Zhou Ya-Ning , Yang Xi-Wen , Lu Wen-Feng , Zhang Ming 
Published: January 2021

Abstract
Background
Patients with lung adenocarcinoma (LUAD) have high mortality rate and poor prognosis. The LUAD cells display increased aerobic glycolysis, which generates energy required for their survival and proliferation. Deregulation of Wnt/β-catenin signaling pathway induces the metabolism switching and oncogenesis in tumor cells. RING finger protein 115 (RNF115) is an E3 ligase for ubiquitin-mediated degradation. Although the oncogenic functions of RNF115 have been revealed in breast tumor cells, the effect of RNF115 on lung cancer is still not clear.

Methods
RNF115 expression and its correlation with the features of LUAD patients were analyzed by using public database and our own cohort. The functions of RNF115 in proliferation and energy metabolism in LUAD cells were explored by downregulating or upregulating RNF115 expression.

Results
We demonstrated that RNF115 was overexpressed in LUAD tissues and its expression was positively correlated with the poor overall survival of LUAD patients. Moreover, RNF115 overexpression inhibited LUAD cell apoptosis and promoted cellular proliferation and metabolism in LUAD cells. On the contrary, RNF115 knockdown displayed reverse effects. Furthermore, the underlying mechanism of the biological function of RNF115 in LUAD was through regulating Wnt/β-catenin pathway via ubiquitination of adenomatous polyposis coli (APC).

Conclusion
The current study reveals a close association between RNF115 expression and prognostic conditions in LUAD patients and the oncogenic roles of RNF115 in LUAD at the first time. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for lung cancer in future.
Genetic risk factors for autoimmune hepatitis: implications for phenotypic heterogeneity and biomarkers for drug response
Authors: Higuchi Takashi , Oka Shomi , Furukawa Hiroshi , Tohma Shigeto , Yatsuhashi Hiroshi , Migita Kiyoshi 
Published: January 2021

AbstractAutoimmune hepatitis (AIH) is a rare chronic progressive liver disease with autoimmune features. It mainly affects middle-aged women. AIH is occasionally complicated with liver cirrhosis that worsens the prognosis. Genetic and environmental factors are involved in the pathogenesis of AIH. Genetic studies of other diseases have been revealing of pathogenesis and drug efficacy. In this review, we summarize the genetic risk factors for AIH, including human leukocyte antigen (HLA) and non-HLA genes. A genome-wide association study (GWAS) on European AIH revealed the strongest associations to be with single nucleotide variants (SNVs) in HLA. Predisposing alleles for AIH were DRB1*03:01 and DRB1*04:01 in Europeans; DRB1*04:04, DRB1*04:05, and DRB1*13:01 in Latin Americans; and DRB1*04:01 and DRB1*04:05 in Japanese. Other risk SNVs in non-HLA genes for AIH were found by a candidate gene approach, but several SNVs were confirmed in replication studies. Some genetic factors of AIH overlapped with those of other autoimmune diseases. Larger-scale GWASs of other ethnic groups are required. The results of genetic studies might provide an explanation for the phenotypic heterogeneity of AIH and biomarkers for drug responses.
Epigenetic immunomodulatory effect of eugenol and astaxanthin on doxorubicin cytotoxicity in hormonal positive breast Cancer cells
Authors: Fouad Mariam A. , Sayed-Ahmed Mohamed M. , Huwait Etimad A. , Hafez Hafez F. , Osman Abdel-Moneim M. 
Published: January 2021

Abstract
Background
Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to investigate the molecular mechanism (s) whereby EUG and AST could enhance DOX cytotoxicity in MCF7 cells.

Methods
Cytotoxic activity of DOX alone and combined with either 1 mM EUG or 40 μM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins.

Results
DOX alone resulted in concentration-dependent cytotoxicity with IC50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1 mM EUG or 40 μM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 μM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions.

Conclusion
EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic approaches in MCF7 cells.
Safety of natural anthraquinone emodin: an assessment in mice
Authors: Sougiannis Alexander T. , Enos Reilly T. , VanderVeen Brandon N. , Velazquez Kandy T. , Kelly Brittany , McDonald Sierra , Cotham William , Chatzistamou Ioulia , Nagarkatti Mitzi , Fan Daping , Murphy E. Angela 
Published: January 2021

Abstract
Background
Emodin, a natural anthraquinone, has shown potential as an effective therapeutic agent in the treatment of many diseases including cancer. However, its clinical development is hindered by uncertainties surrounding its potential toxicity. The primary purpose of this study was to uncover any potential toxic properties of emodin in mice at doses that have been shown to have efficacy in our cancer studies. In addition, we sought to assess the time course of emodin clearance when administered both intraperitoneally (I.P.) and orally (P.O.) in order to begin to establish effective dosing intervals.

Methods
We performed a subchronic (12 week) toxicity study using 3 different doses of emodin (~ 20 mg/kg, 40 mg/kg, and 80 mg/kg) infused into the AIN-76A diet of male and female C57BL/6 mice (n = 5/group/sex). Body weight and composition were assessed following the 12-week feeding regime. Tissues were harvested and assessed for gross pathological changes and blood was collected for a complete blood count and evaluation of alanine transaminase (ALT), aspartate transaminase (AST) and creatinine. For the pharmacokinetic study, emodin was delivered intraperitoneally I.P. or P.O. at 20 mg/kg or 40 mg/kg doses to male and female mice (n = 4/group/sex/time-point) and circulating levels of emodin were determined at 1, 4 and 12 h following administration via liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis.

Results
We found that 12 weeks of low (20 mg/kg), medium (40 mg/kg), or high (80 mg/kg) emodin feeding did not cause pathophysiological perturbations in major organs. We also found that glucuronidated emodin peaks at 1 h for both I.P. and P.O. administered emodin and is eliminated by 12 h. Interestingly, female mice appear to metabolize emodin at a faster rate than male mice as evidenced by greater levels of glucuronidated emodin at the 1 h time-point (40 mg/kg for both I.P. and P.O. and 20 mg/kg I.P.) and the 4-h time-point (20 mg/kg I.P.).

Conclusions
In summary, our studies establish that 1) emodin is safe for use in both male and female mice when given at 20, 40, and 80 mg/kg doses for 12 weeks and 2) sex differences should be considered when establishing dosing intervals for emodin treatment.
Post treatment of anaerobically treated brewery effluent using pilot scale horizontal subsurface flow constructed wetland system
Authors: Alayu Ermias , Leta Seyoum 
Published: January 2021

AbstractThe anaerobic process is considered to be a sustainable technology for the treatment of wastewaters rich in organic matter mainly due to its lower energy consumption and production of value-added products such as biogas and organic fertilizer. However, it cannot be seen as providing ‘complete’ environmental solution as its treated effluents would typically not meet the desired discharge limits in terms of residual carbon, nutrients and other pollutants. This has given impetus to subsequent post treatment in order to meet the environmental standards and protect the receiving water bodies and environment. The aim of this study was to evaluate the post-treatment potential of a pilot scale two-stage horizontal subsurface flow constructed wetland (HSSFCW) system planted with Cyperus alternifolius and Typha latifolia, respectively, for enhanced removal of residual carbon and nutrient from an up-flow anaerobic sludge blanket (UASB) reactor treated brewery effluent. A pilot scale two-stage HSSFCW was integrated with the UASB reactor, and its performance efficiency was assessed for the removal of total suspended solids (TSS), chemical oxygen demand (COD), total nitrogen (TN), ammonium–nitrogen (NH4–N), total phosphorous (TP), and orthophosphate (PO43−). Macrophytes aboveground biomass and nutrient accumulation potential were also determined following standard methods. The results from this study showed that Cyperus alternifolius planted CW cell removed 68.5% TSS, 74.2% COD, 55.7% TN, 68.6% NH4–N, 41.1% TP and 48.1% PO43−. Moreover, further polishing with Typha latifolia planted CW cell enhanced the removal efficiencies to 89% TSS, 92% COD, 83.6% TN, 92.9% NH4–N, 74.4% TP, and 79.5% PO43−. Strong linearity and Pearson correlation was found between macrophyte biomass and nutrient accumulation in each CW cell (Cyperus alternifolius: R2 = 0.91, r = 0.97 for TN; R2 = 0.92, r = 0.96 for TP; and Typha latifolia: R2 = 0.96, r = 0.98 for TN and TP), and showed substantial nutrient reduction with cumulative nutrient accumulation of 1290 gTNm−2 and 708.7 gTPm−2 in the complete system. The performance of the pilot CW system as a tertiary treatment for brewery wastewater showed that the effluent meets the permissible discharge standards throughout the year excluding phosphorous.
Species diversity and molecular analysis of opportunistic Mycobacterium, Nocardia and Rhodococcus isolated from the hospital environment in a developing country, a potential resources for nosocomial infection
Authors: Siavashifar Marzieh , Rezaei Fatemeh , Motallebirad Tahereh , Azadi Davood , Absalan Abdorrahim , Naserramezani Zahra , Golshani Mohadeseh , Jafarinia Morteza , Ghaffari Kazem 
Published: January 2021

Abstract
Background
Hospital environmental resources have a significant role in cross-transmission of opportunistic pathogens such as actinomycetes species to the patients. Actinomycetes have a remarkable capability to survive in adverse and harsh conditions of hospital environments; therefore, they are a threat to the health of patients. Due to this issue, we aimed to determine the frequency and diversity of actinomycetes species in hospital soil, water and dust by using a combination of conventional and molecular methods including the phenotypic and biochemical tests for preliminary identification and the PCR amplification of the specific region of the 16S rRNA, hsp65 gene and sequence analyses of 16S rRNA for the genus and species identification.

Results
A total of 50 (35.2%) actinomycetes isolates from 7 genera were isolated from 142 hospital environmental samples. The three most prevalent species were M. setense 10%, R. erythropolis and M. fortuitum 8% followed by N.cyriacigeorgica and M. gordonae 6%, M. chelonae, M. abscessus, M. lentiflavum, M. mucogenicum, N. asteroides, N. farcinica, R. equi and L. shinushuensis 4% and the single isolates of M. conceptionense, M. septicum, N. rhamnosophilia, N. bravicatena, M. flavescens, M. arupense, M. doricum, M. frederiksbergense, S. heliomycini, S. albus, S. albogriseolus, R. facians, D. maris, G. terae and A. globiformis.

Conclusions
In conclusion we showed that the hospital environment is a potential reservoir for a broad range of actinomycetes species, due to the remarkable survival capability of these microorganisms in adverse hospital environment, carrying a threat to the health of patients.
Highlight selection of radiochemistry and radiopharmacy developments by editorial board (January–June 2020)
Authors: Al-Qahtani Mohammed , Behe Martin , Bormans Guy , Carlucci Giuseppe , Dasilva Jean , Decristoforo Clemens , Elsinga Philip H. , Kopka Klaus , Li Xiang-Guo , Mach Robert , Middel Oskar , Passchier Jan , Patt Marianne , Penuelas Ivan , Rey Ana , Scott Peter J. H. , Todde Sergio , Toyohara Jun , Vugts Danielle 
Published: January 2021

Abstract
Background
The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field.

Results
This commentary of highlights has resulted in 19 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals.

Conclusion
Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.
Image-Guided Biopsy for Relapsed Neuroblastoma: Focus on Safety, Adequacy for Genetic Sequencing, and Correlation of Tumor Cell Percent With Quantitative Lesion MIBG Uptake
Authors: Samoyedny Andrew , Srinivasan Abhay , States Lisa , Mosse Yael P. , Alai Emma , Pawel Bruce , Pogoriler Jennifer , Shellikeri Sphoorti , Vatsky Seth , Acord Michael , Escobar Fernando , Edgar J. Christopher , Maris John M. , Cahill Anne Marie 
Published: January 2021

PURPOSE Many novel therapies for relapsed and refractory neuroblastoma require tumor tissue for genomic sequencing. We analyze our experience with image-guided biopsy in these patients, focusing on safety, yield, adequacy for next-generation sequencing (NGS), and correlation of tumor cell percent (TC%) with quantitative uptake on 123I-meta-iodobenzylguanidine (MIBG) single-photon emission computed tomography with computed tomography (SPECT/CT). MATERIALS AND METHODS An 11-year retrospective review of image-guided biopsy on 66 patients (30 female), with a median age of 8.7 years (range, 0.9-49 years), who underwent 95 biopsies (55 bone and 40 soft tissue) of relapsed or refractory neuroblastoma lesions was performed. RESULTS There were seven minor complications (7%) and one major complication (1%). Neuroblastoma was detected in 88% of MIBG- or fluorodeoxyglucose-avid foci. The overall NGS adequacy was 69% (64% in bone and 74% in soft tissue, P = .37). NGS adequacy within neuroblastoma-positive biopsies was 88% (82% bone and 96% soft tissue, P = .11). NGS-adequate biopsies had a greater mean TC% than inadequates (51% v 18%, P = .03). NGS-adequate biopsies had a higher mean number of needle passes (7.5 v 3.4, P = .0002). The mean tissue volume from NGS-adequate soft-tissue lesions was 0.16 cm3 ± 0.12. Lesion:liver and lesion:psoas MIBG uptake ratios correlated with TC% (r = 0.74, r = 0.72, and n = 14). Mean TC% in NGS-adequate samples was 51%, corresponding to a lesion:liver ratio of 2.9 and a lesion:psoas ratio of 9.0. Thirty percent of biopsies showed an actionable ALK mutation or other therapeutically relevant variant. CONCLUSION Image-guided biopsy for relapsed or refractory neuroblastoma was safe and likely to provide NGS data to guide therapy decisions. A lesion:liver MIBG uptake ratio of ≥ 3 or a lesion:psoas ratio of > 9 was associated with a TC% sufficient to deliver NGS results.
Sex differences in postprandial blood glucose and body surface temperature are contingent on flight in the fruit bat, Cynopterus sphinx
Authors: Nagarajan-Radha Venkatesh , Devaraj Paramanantha Swami Doss 
Published: January 2021

ABSTRACT
The postprandial blood glucose level is very high for the body size in frugivorous bats. Like other homeotherms, bats release heat during digestion of dietary macronutrients. Despite males and females of the same species exhibiting different foraging behaviour, empirical support for sex differences in blood glucose and body surface temperature in fruit bats is poor. Moreover, while flight affects postprandial metabolism, whether such effects are different in each sex of fruit bats is unclear. Here, we studied these questions in the fruit bat, Cynopterus sphinx. We first assessed whether there are sex differences in the postprandial level of blood glucose and body surface temperature over time in rested bats. We then assessed whether flight affects outcomes of sex differences in both traits. We found that the estimated marginal means of both traits were generally higher in females than males, in rested bats. Notably, the sex difference in both traits was only significant at specific sampling time of the assay. Further, the trait means significantly differed between the sexes only in the rested, but not active, bats, meaning that signals of sex difference in metabolic traits eroded when bats were active. Taken together, our findings suggest that in C. sphinx, the sex specificity in the expression of metabolic traits is significantly dependent on physical activity.
AI-aided detection of malignant lesions in mammography screening – evaluation of a program in clinical practice
Authors: Johansson Greta , Olsson Caroline , Smith Frida , Edegran Maria , Björk-Eriksson Thomas 
Published: January 2021

Objectives: Evaluation of the degree of concordance between an artificial intelligence (AI) program and radiologists in assessing malignant lesions in screening mammograms. Methods: The study population consisted of all consecutive cases of screening-detected histopathologically confirmed breast cancer in females who had undergone mammography at the NU Hospital Group (Region Västra Götaland, Sweden) in 2018 to 2019. Data were retrospectively collected from the AI program (lesion risk score in percent and overall malignancy risk score ranging from 1 to 10) and from medical records (independent assessments by two radiologists). Ethical approval was obtained. Results: Altogether, 120 females with screening-detected histopathologically confirmed breast cancer were included in this study. The AI program assigned the highest overall malignancy risk score 10 to 86% of the mammograms. Five cases (4%) were assigned an overall malignancy risk score ≤5. Lack of consensus between the two radiologists involved in the initial assessment was associated with lower overall malignancy risk scores (p = 0,002). Conclusion: The AI program detected a majority of the cancerous lesions in the mammograms. The investigated version of the program has, however, limited use as an aid for radiologists, due to the pre-calibrated risk distribution and its tendency to miss the same lesions as the radiologists. A potential future use for the program, aimed at reducing radiologists’ workload, might be to preselect and exclude low-risk mammograms. Although, depending on cut-off score, a small percentage of the malignant lesions can be missed using this procedure, which thus requires a thorough risk–benefit analysis. Advances in knowledge: This study conducts an independent evaluation of an AI program’s detection capacity under screening-like conditions which has not previously been done for this program.
Applying an ecological framework to examine the multiple levels of influence affecting the utilisation of private sector adult asthma services in Khartoum, Sudan: a mixed methods study
Authors: Thomson Rachael , Noor Magde , Elsony Asma 
Published: January 2021

Background: Asthma is the third most common cause of hospital visits in Sudan. Sudan has a pluralistic health care system, with a strong and varied private sector. While research examining public sector asthma services exists, very little is known about which asthma services are available in the private sector. Methods: An explanatory sequential mixed-method social ecological approach was used to examine influencing factors of asthma service utilisation in the private sector, considering five levels: policy, organisational, community, familial, individual environment. Quantitative research involved surveying private healthcare facilities to describe asthma services. Qualitative research involved in-depth interviews with asthma patients to explore facility decision-making. Nine private chest clinics, 44 pharmacies, and 21 private hospitals offering asthma services in Khartoum were studied - 46 female and 28 male health providers were surveyed; 7 male and 7 female asthma patients were interviewed. Results: At the health policy level, there is no current asthma management policy for the private sector. At the organisational and health systems level, the survey found low rates of diagnostic equipment available, little asthma-specific training, and little use of asthma treatment cards, guidelines, and registers. At the community level, high levels of stigma from the community were felt by most of the patients interviewed. At the familial level, asthma was often viewed as a hereditary condition, and, as a long-term condition, there were worries about marriage potential and impact on jobs/future activities. At the individual level, patients sought frequent, short-term care at private facilities for acute attacks. The severity of the disease and the major impact it had, particularly on younger adults’, was striking. Conclusions: Applying an ecological framework to examine asthma care management enables review of all levels of service provision: inclusive health policy, government commitment, high quality service delivery, uninterrupted affordable drug supply, community involvement, and patient empowerment.