bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docosahexaenoic acid inhibits zymogen activation by suppressing vacuolar ATPase activation in cerulein-stimulated pancreatic acinar cells
Authors: Park Yeeun , Ku Leeyeon , Lim Joo Weon , Kim Hyeyoung 
Published: March 2020

AbstractBackgroundThe premature activation of digestive enzyme zymogens within pancreatic acinar cells is an important early feature of acute pancreatitis. Supraphysiological concentrations of cholecystokinin (CCK) cause intrapancreatic zymogen activation and acute pancreatitis. Stimulation of vacuolar ATPase (vATPase) activity is required for zymogen activation in pancreatic acinar cells. Parkin, a multiprotein E3 ubiquitin ligase complex, promotes vATPase ubiquitination and degradation, which inhibits vATPase activity. Docosahexaenoic acid (DHA), an omega-3 fatty acid, exerts anti-inflammatory effects. It is reported to bind to G-protein coupled receptor 120 (GPR120) and GPR40. DHA induces the degradation of certain proteins by activating ubiquitin-proteasome system in various cells. This study aimed to investigate whether DHA induces Parkin and inhibits vATPase activity, resulting in zymogen inactivation in pancreatic acinar AR42J cells stimulated with cerulein, a CCK analog.ResultsCerulein induced the translocation of the cytosolic V1 domain (E subunit) of vATPase to the membrane, which indicated vATPase activation, and zymogen activation in AR42J cells. DHA suppressed the association of the vATPase with membranes, and zymogen activation (increased trypsin activity and amylase release) induced by cerulein. Pretreatment with a GPR120 antagonist AH-7614, a GPR40 antagonist DC260126, or an ubiquitination inhibitor PYR-41 reduced the effect of DHA on cerulein-induced zymogen activation. Treatment with PYR-41 reversed the DHA-induced decrease in vATPase activation in cerulein-treated cells. Furthermore, DHA increased the level of Parkin in membranes of cerulein-treated cells.ConclusionsDHA upregulates Parkin which inhibits vATPase-mediated zymogen activation, via GPR120 and GPR40, in cerulein-stimulated pancreatic acinar cells.
Molecular effects of dADD1 misexpression in chromatin organization and transcription
Authors: Meyer-Nava Silvia , Torres Amada , Zurita Mario , Valadez-Graham Viviana 
Published: March 2020

AbstractBackgrounddADD1 and dXNP proteins are the orthologs inDrosophila melanogasterof the ADD and SNF2 domains, respectively, of the ATRX vertebrate’s chromatin remodeler, they suppress position effect variegation phenotypes and participate in heterochromatin maintenance.ResultsWe performed a search in human cancer databases and found that ATRX protein levels were elevated in more than 4.4% of the samples analyzed. Using theDrosophilamodel, we addressed the effects of over and under-expression of dADD1 proteins in polytene cells. Elevated levels of dADD1 in fly tissues caused different phenotypes, such as chromocenter disruption and loss of banding pattern at the chromosome arms. Analyses of the heterochromatin maintenance protein HP1a, the dXNP ATPase and the histone post-translational modification H3K9me3 revealed changes in their chromatin localization accompanied by mild transcriptional defects of genes embedded in heterochromatic regions. Furthermore, the expression of heterochromatin embedded genes in nulldadd1organisms is lower than in the wild-type conditions.ConclusionThese data indicate that dADD1 overexpression induces chromatin changes, probably affecting the stoichiometry of HP1a containing complexes that lead to transcriptional and architectural changes. Our results place dADD1 proteins as important players in the maintenance of chromatin architecture and heterochromatic gene expression.
Association between depression and healthcare expenditures among elderly cancer patients
Authors: Gu Dian , Morgan Robert O. , Li Ruosha , Weber Ellerie S. , Shen Chan 
Published: March 2020

Abstract
Background
Both depression and cancer are economically burdensome. However, how depression affects the healthcare expenditures of elderly cancer patients from payers’ and patients’ perspectives is largely unknown. This study investigated whether depression resulted in higher healthcare expenditures among these patients from both payers’ and patients’ perspectives and identified health service use categories associated with increased expenditures.

Methods
From the Medicare Current Beneficiary Survey (MCBS)-Medicare database, we identified breast, lung and prostate cancer patients aged 65 years and over who were newly diagnosed between 2007 and 2012. Presence of depression was based on self-reports from the surveys. We used generalized linear models (GLM) and two-part models to examine the impact of depression on healthcare expenditures during the first two years of cancer diagnosis controlling for a vast array of covariates. We stratified the analyses of total healthcare expenditures by healthcare services and payers.

Results
Out of the 710 elderly breast, lung and prostate cancer patients in our study cohort, 128 (17.7%) reported depression. Individuals with depression had $11,454 higher total healthcare expenditures, $8213 higher medical provider expenditures and $405 higher other services expenditures compared to their counterparts without depression. Also, they were significantly more likely to have inpatient services. For payers, they incurred $8280 and $1270 higher expenditures from Medicare’s and patients’ perspectives, respectively.

Conclusions
Elderly cancer patients with depression have significantly higher healthcare expenditures from both payers’ and patients’ perspectives and over different expenditure types. More research is needed in depression screening, diagnosis and treatment for this population.
Standalone oblique lateral interbody fusion vs. combined with percutaneous pedicle screw in spondylolisthesis
Authors: He Wei , He Da , Sun Yuqing , Xing Yonggang , Wen Jiankun , Wang Weiheng , Xi Yanhai , Liu Mingming , Tian Wei , Ye Xiaojian 
Published: March 2020

Abstract
Background
To compare standalone oblique lateral interbody fusion (OLIF) vs. OLIF combined with posterior bilateral percutaneous pedicle screw fixation (OLIF combined) for the treatment of lumbar spondylolisthesis.

Methods
This was a retrospective study of patients who underwent standalone OLIF or combined OLIF between 07/2014 and 08/2017 at two hospitals in China. Direct decompressions were not performed. Visual analog scale (VAS), Oswestry Disability Index (ODI), satisfaction rate, anterior/posterior disc heights (DH), foraminal height (FH), foraminal width (FW), cage subsidence, cage retropulsion, fusion rate, and complications were analyzed. All imaging examinations were read independently by two physicians and the mean measurements were used for analysis.

Results
A total of 73 patients were included: 32 with standalone OLIF and 41 with combined OLIF. The total complication rate was 25.0% with standalone OLIF and 26.8% with combined OLIF. There were no differences in VAS and ODI scores by 2 years of follow-up, but the scores were better with standalone OLIF at 1 week and 3 months (P < 0.05). PDH and FW was smaller in the combined OLIF group compared with the standalone OLIF group before and after surgery (all P < 0.05). There were significant differences in FH before surgery and at 1 week and 3 months between the two groups (all P < 0.05), but the difference disappeared by 2 years (P = 0.111). Cage subsidence occurred in 7.3% (3/41) and 7.3% (3/41) of the patients at 3 and 24 months, respectively, in the combined OLIF group, compared with 6.3% (2/32) and 15.6% (5/32), respectively, in the standalone OLIF group at the same time points (P = 0.287). There was no cage retropulsion in both groups at 2 years. The fusion rate was 85.4%(35/41) in the combined OLIF group and 84.4% (27/32) in the standalone OLIF group at 3 months(P = 0.669). At 24 months, the fusion rate was 100.0% in the combined OLIF group and 93.8% (30/32) in the standalone OLIF group (P = 0.066).

Conclusion
Standalone OLIF may achieve equivalent clinical and radiological outcomes than OLIF combined with fixation for spondylolisthesis. The rate of complications was similar between the two groups. Patients who are osteoporotic might be better undergoing combined rather than standalone OLIF. The possibilty of proof lies within a future prospective study, preferably an RCT.
Statistical validity and reliability of the Persian version of the Western Ontario Meniscal Evaluation Tool (WOMET) according to the COSMIN checklist
Authors: Ebrahimi Naghmeh , Naghdi Soofia , Ansari Noureddin Nakhostin , Jalaie Shohreh , Salsabili Nasser 
Published: March 2020

Abstract
Background
The Western Ontario Meniscal Evaluation Tool (WOMET) is the only questionnaire available to assess quality of life in patients with isolated meniscal injuries. The aims of this study were to prepare the Persian version of the WOMET (PWOMET) and validate it in Iranian patients with isolated meniscal tears.

Methods
In the first stage, the English version of WOMET was translated into Persian. Content validity, and qualitative and quantitative (impact score) face validity were tested by specialists and in a sample of 30 patients. In the second stage, PWOMET was assessed for the evaluation of psychometric properties in 100 patients with isolated meniscal injury and 50 healthy people based on the COSMIN checklist. Construct validity was tested based on structural validity (factor analysis) and hypothesis testing. Correlation with the total scores on the SF-36, IKDC and KOOS were used for concurrent criterion validity. Test-retest reliability and internal consistency were calculated using intraclass correlation coefficient (ICC) and Cronbach’s alpha, respectively. In addition the standard error of measurement (SEM) and smallest detectable change were calculated. Interpretability was investigated as the ceiling and floor effects and minimal important difference.

Results
The PWOMET had acceptable qualitative face validity and content validity. The impact score (quantitative face validity) was more than 1.5 for all items. For construct validity, structural validity (factor analysis) and hypothesis testing ability were confirmed. Correlations between the PWOMET total score and IKDC, SF-36, KOOS scores were 0.61, 0.54 and 0.63, respectively (p < 0.001), thus confirming concurrent criterion validity. The intraclass correlation coefficient, Cronbach’s alpha, SEM and smallest detectable change for the PWOMET were 0.73, 0.89, 9.43 and 26.13, respectively. The PWOMET had no ceiling or floor effects, and minimal important difference was 9.07.

Conclusion
The PWOMET provides valid and reliable scores for assessment of the quality of life in patients with isolated meniscal injury.
Antiviral activity of silymarin in comparison with baicalein against EV-A71
Authors: Lalani Salima S. , Anasir Mohd Ishtiaq , Poh Chit Laa 
Published: March 2020

Abstract
Background
The hand, foot and mouth disease (HFMD) is a febrile and exanthematous childhood disease mainly caused by Enterovirus 71 (EV-A71). In severe HFMD, virulent EV-A71 strains can cause acute flaccid paralysis and cardiopulmonary edema leading to death. Currently, no FDA approved antiviral treatment or vaccine is available for EV-A71. Flavonoids such as silymarin and baicalein are known to possess in vitro antiviral properties against viruses. In this study, the cytotoxicity and antiviral activity of silymarin, baicalein and baicalin were investigated.

Methods
The cytotoxic effects of three flavonoids towards rhabdomyosarcoma (RD) cells were first examined using cell proliferation MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. Compounds found to be non-cytotoxic in RD cells were evaluated for their in vitro antiviral properties against the EV-A71 subgenotype B4 strain 41 (5865/SIN/000009) using antiviral assays. Viral infectivity was determined by reduction of the formation of plaques in RD cells. For the measurement of RNA copy number, the real time quantitative reverse transcription PCR (qRT-PCR) was used. The most potent compound was further evaluated to determine the mode of action of inhibition by time course, virus attachment and entry assays in Vero cells.

Results
Silymarin was shown to exert direct extracellular virucidal effects against EV-A71 at 50% inhibitory concentration (IC50) of 15.2 ± 3.53 μg/mL with SI of 10.53. Similarly, baicalein exhibited direct extracellular virucidal effects against EV-A71 at a higher IC50 value of 30.88 ± 5.50 μg/mL with SI of 13.64. Besides virucidal activity, silymarin was shown to block both viral attachment and entry of EV-A71 to inhibit infection in Vero cells.

Conclusions
Silymarin has a stronger inhibition activity against EV-A71 in comparison to baicalein. It could serve as a promising antiviral drug to treat EV-A71 infections.
Exploring hospital certification processes from the certification body’s perspective - a qualitative study
Authors: Johannesen Dag Tomas Sagen , Wiig Siri 
Published: March 2020

AbstractBackgroundHospital certification is an external assessment mechanism to assure quality and safety systems. Auditors representing the certification body play a key role in certification processes, as they perform the assessment activities and interact with the involved healthcare organizations. There is limited knowledge about the approaches and methods that auditors use, such as role repertoire, conduct, and assessment practice. The purpose of this study was to explore auditors’ practice in hospital certification processes, guided by the following research questions: What styles do auditors apply in hospital certification processes, and how do auditors perceive their role in hospital certification processes?MethodsThe study was performed in two stages. In the first stage, non-participant observations (59 h) were conducted, to explore the professional practice of three lead auditors in certification processes of Norwegian hospitals. In the second stage, semi-structured interviews were conducted with these three observed lead auditors. The role repertoires and conducts identified were analyzed by using a deductive approach according to a surveyor (equivalent with auditor) styles typology framework.ResultsTwo distinct auditor styles (“explorer” and “discusser”) were identified among the three studied auditors. Both styles were characterized by their preference for an opportunistic and less structured type of interview practice during certification audits. All three auditors embedded a guiding approach (reflections about findings, stimulate improvements, experience transfer from other industries) to their perception and practice of certification audits, interacting with the auditees. The use of group interviews instead of individual interviews during certification audits, was the rule of their professional practice.ConclusionThe auditors’ perceptions and styles demonstrated a multifaceted certification reality, in contrast to what is often presumed as consistent, stringent and independent practices. These findings may have implications for reliability judgements when developing hospital certification programs, and for the refinement of the current framework used here to study the different auditing practices.
Identifying potential causal effects of age at menarche: a Mendelian randomization phenome-wide association study
Authors: Magnus Maria C. , Guyatt Anna L. , Lawn Rebecca B. , Wyss Annah B. , Trajanoska Katerina , Küpers Leanne K. , Rivadeneira Fernando , Tobin Martin D. , London Stephanie J. , Lawlor Debbie A. , Millard Louise A. C. , Fraser Abigail 
Published: March 2020

Abstract
Background
Age at menarche has been associated with various health outcomes. We aimed to identify potential causal effects of age at menarche on health-related traits in a hypothesis-free manner.

Methods
We conducted a Mendelian randomization phenome-wide association study (MR-pheWAS) of age at menarche with 17,893 health-related traits in UK Biobank (n = 181,318) using PHESANT. The exposure of interest was the genetic risk score for age at menarche. We conducted a second MR-pheWAS after excluding SNPs associated with BMI from the genetic risk score, to examine whether results might be due to the genetic overlap between age at menarche and BMI. We followed up a subset of health-related traits to investigate MR assumptions and seek replication in independent study populations.

Results
Of the 17,893 tests performed in our MR-pheWAS, we identified 619 associations with the genetic risk score for age at menarche at a 5% false discovery rate threshold, of which 295 were below a Bonferroni-corrected P value threshold. These included potential effects of younger age at menarche on lower lung function, higher heel bone-mineral density, greater burden of psychosocial/mental health problems, younger age at first birth, higher risk of childhood sexual abuse, poorer cardiometabolic health, and lower physical activity. After exclusion of variants associated with BMI, the genetic risk score for age at menarche was related to 37 traits at a 5% false discovery rate, of which 29 were below a Bonferroni-corrected P value threshold. We attempted to replicate findings for bone-mineral density, lung function, neuroticism, and childhood sexual abuse using 5 independent cohorts/consortia. While estimates for lung function, higher bone-mineral density, neuroticism, and childhood sexual abuse in replication cohorts were consistent with UK Biobank estimates, confidence intervals were wide and often included the null.

Conclusions
The genetic risk score for age at menarche was related to a broad range of health-related traits. Follow-up analyses indicated imprecise evidence of an effect of younger age at menarche on greater bone-mineral density, lower lung function, higher neuroticism score, and greater risk of childhood sexual abuse in the smaller replication samples available; hence, these findings need further exploration when larger independent samples become available.
Molecular epidemiology and genetic variation analyses of porcine circovirus type 2 isolated from Yunnan Province in China from 2016-2019
Authors: Lv Nianci , Zhu Li , Li Wengui , Li Zhilan , Qian Qisheng , Zhang Tianyu , Liu Lu , Hong Jinmei , Zheng Xiaolin , Wang Yuan , Zhang Yifang , Chai Jun 
Published: March 2020

Abstract
Background
Porcine circovirus type 2 (PCV2) is the causative agent of porcine circovirus-associated disease (PCVAD). Its prevalence in swine herds was first reported in China in 2000. PCV2 infection causes immunosuppression that leads to multiple diseases, causing serious economic problems for the swine industry in China. Since information on the genetic variation of PCV2 in Yunnan province is limited, this study aims to investigate the molecular epidemiological and evolutionary characteristics of PCV2 from 2016 to 2019.

Methods
A total of 279 clinical samples were collected from different regions of Yunnan between 2016 to 2019, and PCV2 was detected by PCR. We then amplified full genomes from the positive samples, and the sequences were analysed for homology and genetic evolution.

Results
Overall, 60.93% (170/279) of the screened swine herd samples were positive for PCV2. We sequenced 15 Yunnan province PCV2 strains from positive samples. Analyses of the complete genomes and Cap genes led to the classification of the 15 Yunnan PCV2 strains into PCV2a (2 of 15), PCV2b (1of 15) and PCV2d (12 of 15). All strains shared 94.3–99.9% of their identities with the nucleotide sequences of complete genomes in this study and shared 94.2–99.9% identity with the reference sequences. All strains share 89.4–100% and 86.8–100% of their identities with the nucleotide and amino acid (aa) sequences of Cap, respectively.

Conclusions
The results of this study provide evidence that PCV2a, PCV2b and PCV2d genotypes coexisted in Yunnan Province from 2016 to 2019, and the priority prevalence genotype was PCV2d. The data provide evidence for the increased genetic diversity and insights into the molecular epidemiology of PCV2. This study also provides basic data for the Yunnan province PCV2 molecular epidemiological survey and accumulates effective materials for the development of PCV2 vaccines.
Dietary alterations modulate the microRNA 29/30 and IGF-1/AKT signaling axis in breast Cancer liver metastasis
Authors: Shastri Anuradha A. , Saleh Anthony , Savage Jason E. , DeAngelis Tiziana , Camphausen Kevin , Simone Nicole L. 
Published: March 2020

Abstract
Background
Metastatic cancer is incurable and understanding the molecular underpinnings is crucial to improving survival for our patients. The IGF-1/Akt signaling pathway is often impaired in cancer leading to its progression and metastases. Diet modification is known to alter the IGF-1/Akt pathway and affect the expression of microRNA involved in tumor initiation, growth and metastases. Liver metastases are one of the most common type of metastases in breast and colon cancer. In the present study, we looked at the effect of diet modification on the expression of microRNA in normal liver and liver with breast cancer metastases using in vivo model.

Methodology
6-month-old C57BL/6 J mice were put on either an ad libitum (AL) diet, or 40% calorie restricted (CR) diet or were fasted for 24 h (FA) before sacrifice. MicroRNA array analysis, western blot and qRT-PCR were performed using liver tissue to compare the treatment groups. A breast cancer model was also used to study the changes in microRNA expression in liver of a group of BALB/c mice orthotopically injected with 4 T1 cells in the mammary fat pad, put on either an AL or 30% CR diet. Liver and primary tumor tissues were used to perform qRT-PCR to compare the treatment groups.

Results
MicroRNA array analysis showed significant changes in miRNA expression in both CR and FA conditions in normal liver. Expression of miR-29 and miR-30 family members was increased in both CR and FA. Western blot analysis of the normal liver tissue showed that CR and FA downregulated the IGF-1/Akt pathway and qRT-PCR showed that the expression of miR-29b, miR-29c, miR-30a and miR-30b were increased with CR and FA. Liver tissue collected from mice in the breast cancer model showed an increase in expression of miR-29b, miR-29c and miR-30b while tumor tissue showed increased expression of miR-29c, miR-30a and miR-30b.

Discussion
Members of the miR-29 family are known to target and suppress IGF-1, while members of the miR-30 family are known to target and suppress both IGF-1 and IGF-1R. In the present study, we observe that calorie restriction increased the expression of miR-29 and miR-30 in both the normal liver as well as the liver with breast cancer metastases. These findings suggest that dietary alterations may play a role in the treatment of liver metastasis, which should be evaluated further.