bluuebunny/crossref_metadata_2025 huggingface dataset:
Introducing NMMF WAMS, an open-source PAMGuard plug-in, and some pilot data for its use as a welfare acoustic monitoring system
Authors: Jones Brittany L , Oswald Michael , Tufano Samantha , Baird Mark , Ridgway Sam H.
Published: August 2020

BackgroundThe National Marine Mammal Foundation presents a new veterinary and animal welfare monitoring tool, WAMS (i.e., Welfare Acoustic Monitoring System) for open-source use in PAMGuard. While the use of passive acoustic monitoring systems has been invaluable in wild conservation efforts, vocal behavior is a vastly underutilized welfare biomarker for both terrestrial and aquatic species in zoos and aquaria. We describe one successful use for WAMS at the Navy Marine Mammal Program for monitoring a discrete population of dolphins’ acoustic behavior. By constantly recording both five minute and hourly counts of acoustic detections and providing an automated comparison to historical data, WAMS can alert us to rare instances of high vocal rates relative to their typical output. Having a validated acoustic indicator for events such as agnostic social interactions and/or an instance of distress in bottlenose dolphins provides a unique opportunity for acoustic monitoring to be used as a tool for the early identification and possible prevention of rare and unexpected instances of an illness or injury.ResultsWe identified a high success rate (82%) and low false positive rate (1%) for WAMS identification of whistle occurrence. Further, we identified time and money saving applications for use in conservation settings such as marine mammal mitigation surveys and long-term hydrophone deployments. When running in real-time, WAMS used in conjunction with other PAMGuard features saved almost 6.5 days in manual labor for every month processing data (almost 78.5 work days a year). ConclusionsWe propose that this tool could be considered for implementation at any facility that houses marine mammals and wishes to include acoustic monitoring into their preventative healthcare plans. Early identification of atypical social interactions and/or distress calls in both aquatic and terrestrial species can lead to early intervention, better management of social groupings, and better overall health and welfare for all animals.
Preparedness for practice: Is there a disparity between what undergraduate medical students are taught and what is felt to be essential knowledge in the postgraduate paediatric domain?
Authors: McCrossan Patrick , Nicholson Alf , O'Donoghue Dara , McCallion Naomi
Published: August 2020

BackgroundThis study aimed to evaluate how undergraduate students and junior paediatric doctors performed against an examination of knowledge set by non-academic consultants at a “must –know “ level for starting in paediatrics. We named this the Minimum Accepeted Competency (MAC) examination.MethodsExamination (comprised of 30 MCQ questions) was delivered to undergraduates also to new junior paediatric doctors. Results of this examination ascertained if participants had reached a clinician determined MAC, were compared with official university examination results and compared students to junior doctor performance.ResultsTotal of 478 participants. Mean MAC score was 45.9% for students and 64.2% for doctors (significantly higher [p < 0.01]). A significantly reduced number of students passed the MAC compared with their official university examinations 68% V 97%). A Spearman’s rank co-efficient showed a moderate but statistically significant positive correlation between students results in their official university examinations and their score in the MAC examination.ConclusionThis work demonstrates a disparity between student and junior doctor levels of knowledge with consultant expectations from an exam based on what front-line paediatricians determined to as “must-know” standards. This study demonstrates the importance of involvement of end-users and future supervisors in undergraduate teaching.
Validity and Reliability of Institutional Assessments in Predicting USMLE STEP 1 Scores: Lessons from a Traditional 2 x 2 Curricular Model
Authors: Puri Nitin , Graham-Smith Sydney , McCarthy Michael , Miller Bobby
Published: August 2020

Purpose: We have observed that students’ performance in our PreClerkship curriculum does not align well with their USMLE STEP1 scores. Students at-risk of failing or underperforming on STEP1 have often excelled in our institutional assessments. We sought to test the validity and reliability of our course-assessments in predicting STEP1 scores, and in the process generate and validate a more accurate prediction model for STEP1 performance.Methods: Student pre-matriculation and course assessment data of the Class of 2020 (n = 76) is used to generate a stepwise STEP1 prediction model, which is tested with the students of the Class of 2021 (n = 71). Predictions are generated for the end of each course in the programing language R. For the Class of 2021, predicted STEP1 score is correlated with their actual STEP1 scores and data-agreement is tested with means-difference plots. A similar model is generated and tested for the Class of 2022.Results: STEP1 predictions based pre-matriculation data are unreliable and fail to identify at-risk students (R2 = 0.02). STEP1 predictions for most year 1 courses (anatomy, biochemistry, physiology) correlate poorly with students’ actual STEP1 scores (R2 = 0.30). STEP1 predictions improve for year 2 courses (microbiology, pathology and pharmacology), but reliable predictions are based on truly integrated courses with customized NBMEs as comprehensive exams (0.66). Predictions based on these NBMEs and integrated courses are reproducible for the Class of 2022.Conclusion: MCAT and undergraduate GPA are poor predictors of students’ STEP1 scores. Partially integrated courses with biweekly assessments do not promote problem-solving skills and leave students’ at-risk of failing STEP1. Only truly integrated courses with comprehensive assessments are reliable indicators of students STEP1 preparation.
Non-associative phase separation in an evaporating droplet as a model for prebiotic compartmentalization
Authors: Guo Wei , Kinghorn Andrew , Zhang Yage , Li Qingchuan , Poonam Aditi , Tanner Julian , Shum Ho
Published: August 2020

Liquid-liquid phase separation (LLPS) is a mechanism by which membraneless organelles form inside cells, and has been hypothesized as a mechanism for prebiotic compartmentalization. Here we present a prebiotically plausible pathway for non-associative phase separation, which could drive biopolymer self-organization and compartmentalization to form the earliest membraneless compartments, within an evaporating all-aqueous sessile droplet. Through a quantitative understanding of the kinetic pathway of phase separation, we find that non-uniform evaporation rates across the droplet surface induce compositional gradients and surface tension differences, triggering LLPS and polymer self-organization inside the sessile droplet. With the ability to undergo LLPS, the drying droplets provide a robust mechanism for formation of prebiotic membraneless compartments. These self-organized membraneless compartments, with volumes comparable to subcellular structures, could represent a mechanism for the enrichment of information-carrying molecules and formation of RNA-containing organelles. We demonstrated compartmentalized localization and storage of nucleic acids, in vitro transcription, as well as a three-fold enhancement of ribozyme activity. This model system demonstrates a cell-like, aqueous, macromolecular crowded and thermodynamically non-equilibrium microenvironment. Such a mechanism for compartmentalization is feasible on wet organophilic silica-rich surfaces during early molecular evolution.
In-Silico Identification, Expressional Profile and Regulatory Network Analysis of Mitogen Activated Protein Kinase Kinase Kinase (MAPKKK) Gene Family in Tea (C. Sinensis)
Authors: Paul Abhirup , Srivas Anurag P. , Subrahmanya Shreya , Shen Guoxin , MISHRA NEELAM
Published: August 2020

Background: Mitogen activated protein kinase kinase kinase (MAPKKK) form the upstream component of MAPK cascade. It is well characterized in several plants such as Arabidopsis and rice however the knowledge about MAPKKKs in tea plant is largely unknown.Result: In the present study, MAPKKK genes of tea were obtained through a genome wide search using Arabidopsis thaliana as the reference genome. Among 59 candidate MAPKKK genes in tea, 17 genes were MEKK-like, 31 genes were Raf-like and 11 genes were ZIK- like. Additionally, phylogenetic relationships were established along with structural analysis which includes gene structure, its location as well as conserved motifs and functional domain signatures that were systematically examined and further, predictions were validated by the results. Also, on the basis of orthologous genes in Arabidopsis, functional interaction was carried out in C. sinensis. The expressional profiles indicated major involvement of MAPKKKK genes from tea in response to various abiotic stress factors.Conclusion: The present study provides the targets for additional inclusive identification, functional study, and also might provide comprehensive knowledge for a better understanding of the MAPKKK cascade regulatory network in C. sinensis.
Co-Expression Network Analyses of Anthocyanin Biosynthesis Genes in Ruellia (Wild Petunias; Acanthaceae)
Authors: Tripp Erin , Zhuang Yongbin
Published: August 2020

Background. Anthocyanins are major pigments contributing to flower coloration and as such knowledge of molecular architecture underlying the anthocyanin biosynthetic pathway (ABP) is key to understanding flower color diversification. To identify ABP structural genes and associated regulatory networks, we sequenced 16 transcriptomes generated from 10 species of Ruellia and then conducted co-expression analyses among resulting data. Results. Complete coding sequences for 12 candidate structural loci representing eight genes plus nine candidate regulatory loci were assembled. Analysis of non-synonymous/synonymous (dn/ds) mutation rates indicated all identified loci are under purifying selection, suggesting overall selection to prevent the accumulation of deleterious mutations. Additionally, upstream enzymes have lower rates of molecular evolution compared to downstream enzymes. However, site-specific tests of selection yielded evidence for positive selection at several sites, including four in F3'H2 and five in DFR3, and these sites are located in protein binding regions. A species-level phylogenetic tree constructed using a newly implemented hybrid transcriptome–RADseq approach implicates numerous flower color transitions among the 10 species. We found evidence of both regulatory and structural mutations to F3'5'H in helping to explain the evolution of red flowers from purple-flowered ancestors.Conclusions. Sequence comparisons and co-expression analyses of ABP loci revealed that mutations in regulatory loci are likely to play a greater role in flower color transitions in Ruellia compared to mutations in underlying structural genes.
A Modified Delphi to Define Drug Dosing Errors in Pediatric Critical Care
Authors: Roumeliotis Nadia , Pullenayegum Eleanor , Rochon Paula , Taddio Anna , Parshuram Chris
Published: August 2020

Background There is no globally accepted definition for dosing error in adult or pediatric practice. The definition of pediatric dosing error varies greatly in the literature. The objective of this study was to develop a framework, informed by a set of principles, for a clinician-based definition of drug dosing errors in critically ill children, and to identify the range that practitioners agree is a dosing error for different drug classes and clinical scenarios.MethodsWe conducted a nationwide three staged modified Delphi from May to December 2019. Expert clinicians included Canadian pediatric intensive care unit (PICU) physicians, pharmacists and nurses, with a least 5 years’ experience.Outcomes were dosing principles and error thresholds, as defined by proportion above and below reference range, for common PICU medications and clinical scenarios. ResultsForty-four participants met eligibility, and response rates were 95, 86 and 84% for all three rounds respectively. Consensus was achieved for 13 of 15 principles, and 23 of 30 error thresholds. An over-dosed drug that is intercepted, an under-dose of a possibly life-saving medication, dosing 50% above or below target range and not adjusting for a drug interaction were agreed principles of dosing error. Expert clinicians agreed, for most medication categories and clinical scenarios, that dosing over or below 10% of reference range was considered an error threshold.ConclusionExpert clinicians in the PICU agree that, for most intermittent medications and clinical scenarios, dosing over 10% below or above reference range is considered a dosing error.The threshold may be larger for non-toxic medications, and narrower for very toxic medications. This consensus driven definition will help guide routine clinical dosing practice, standardized reporting and drug quality improvement in pediatric critical care.
Outcome of infants born to pregnant women with syphilis: A nationwide study in Korea
Authors: Lim Joohee , Yoon So Jin , Shin Jeong Eun , Han Jungho , Lee Soon Min , Eun Ho Seon , Park Min soo , Park Kook In
Published: August 2020

BackgroundAlthough expansion of antenatal syphilis screening programs, congenital syphilis (CS) is still remaining issue. This study aimed to analyze the manifestation and progress of CS including treatment and follow-up based on nationwide study.MethodsFrom the Korean National Health Insurance Service database, a total of 548 infants were examined for CS during first year of life from 2013 to 2018. Neurosyphilis and complications were investigated using International Classification of Diseases-10 codes.ResultsThe birth rate from mother with syphilis was 2.8 per 10,000 live birth for 5 years, not showing tendency to decrease. One hundred forty-eight infants were proven or highly probable or possible for CS with treatment over 10 days. Sixty-six infants were possible or less likely CS with only 1-day treatment. Jaundice (56%) was most common and hearing impairment (14%), renal disease (8%), mental retardation (8%) followed. Total of 14 cases of neurosyphilis occurred. Patients who have complications such as mental retardation, eye involvement, hearing impairment and renal disease were significantly associated with neurosyphilis (OR 8.49, P < 0.0001). Among 250 patients with treatment, 92.8% was treated with 1 medication; Benzathine penicillin G was more used (72.4%) than aqueous crystalline penicillin G. Only 4 patients were retreated due to treatment failure. In addition to the treponemal test, fluorescent treponemal antibody-absorption was the most prescribed tool of diagnosis for follow up.ConclusionSharing a standardized guideline for evaluation and treatment regimens and follow up plan at a national level is needed for maternal neonatal care leading to eradication of CS.
Correlation between sarcopenia and arteriosclerosis in elderly community dwellers: A multicenter study
Authors: Sun Ting , Ma Zuchang , Gao Lisheng , Xie Hui
Published: August 2020

Background

Evidence suggests that arteriosclerosis and sarcopenia (decreased muscle mass) share some of their many causes. However, after controlling for confounding factors, it is unclear whether the presence of arteriosclerosis correlates with sarcopenia. The aim of this paper is to explore whether sarcopenia is associated with arteriosclerosis.
Methods

A total of 2511 elderly subjects from six Chinese community health service centers in Anhui province were surveyed through an e-health promotion system to collect basic data and measurements of brachial-ankle pulse wave (baPWV), body composition, and handgrip strength (HGS). Pearson's correlation and binary logistic regression analyses were performed to identify associations between sarcopenia and high baPWV.
Results

The prevalence rates of sarcopenia were 12.9% in men and 15.3% in women according to the 2019 standard of Asian Working Group for Sarcopenia. Among subjects with high baPWV, the proportion of sarcopenia was higher compared to those with normal baPWV (men: 17.7% vs 3.7%; women: 20.4% vs 4.9%, both P < 0.001). Binary logistic regression analysis revealed that sarcopenia was associated with high baPWV (P < 0.0001, odds ratio 1.619) after adjusting for confounding factors. HGS slightly and negatively correlated with baPWV (-0.19 in men and − 0.18 in women).
Conclusions

The intertwined pathophysiological mechanisms shared by arteriosclerosis and sarcopenia are potential targets for future interventions to reduce morbimortality in subjects with both disorders. Upcoming prospective studies and clinical trials are expected to advance these findings.
Folic Acid Conjugated PEG-PCL-PEG Triblock Copolymer Nanoparticles for Enhanced Delivery of 5-Fluorouracil to HT29 Colon Cancer Cells
Authors: Mirzaghavami Parvin Sadat , Khoei Samideh , Khoee Sepideh , Shirvalilou Sakine
Published: August 2020

Background: In the current study, folic acid conjugated magnetite PEG-PCL-PEG triblock copolymer were synthesized and loaded with 5-Fluorouracil (5-FU-SPION-PEG-PCL-PEG-FA) for targeted delivery of drug to HT29 colon cancer cells.Methods: The cytotoxic effect and cellular uptake of synthesized nanoparticles was assessed on HUVEC and HT29 cell lines. In addition, antitumor effects of nanoparticles were investigated based on gene expression of Bax and Bcl2, Annexin V/PI staining, ROS production and colony formation.Results: As compared to 5-FU, an improvement in therapeutic index was demonstrated for 5-FU-SPION-PEG-PCL-PEG-FA according to cytotoxicity induced in HUVEC and HT29 cells. In addition, 5-FU-SPION-PEG-PCL-PEG-FA was found to be more antitumor efficient in comparison to 5-FU based on Bax/Bcl2 ratio, percentage of cell death, ROS production and colony formation ability (P<0.05).Conclusion: The obtained results suggested that 5-FU-SPION-PEG-PCL-PEG-FA could be considered as promising targeted drug delivery system.
Anxiety and Depression Are Risk Factors for Recurrent Pregnancy Loss: A Nested Case-control Study
Authors: Wang Yanxia , Meng Zhaoyan , Pei Jianyin , Qian Liu , Mao Baohong , Li Yamei , Li Jing , Dai Zhirong , Cao Jianing , Zhang Chunhua , Chen Lina , Jin Yuxia , Yi Bin
Published: August 2020

Background: To evaluate the depression–anxiety interaction with the development of recurrent pregnancy loss (RPL). Methods: A nested case–control study involving 2,558 participants was conducted with data from the prospective Miscarriage Woman Cohort study between 2017 and 2019 in the province of Gansu, China. The questionnaire data, the Self-Rating Anxiety Scale and the Self-Rating Depression Scale were collected after each participant’s first miscarriage. Information on RPL outcomes was obtained from the medical records within the subsequent two years. The logistic regression and the addition and multiplication interaction effects between anxiety and depression to RPL were analysed.Results: The prevalence of anxiety (28.7% vs. 19.5%) and depression symptoms (48.6% vs. 41.3%) for the 1,132 RPL cases were higher than 1,426 non-RPL controls (P< 0.001). After adjustment for possible confounding variables, compared with the non-RPL participants without depression and anxiety symptoms, the odds ratio (OR) value, reflecting the multiplicative interaction, was 2.788 (95%CI: 1.511–5.144, P < 0.001) for cases with both anxiety and depression symptoms. Moreover, among these, the OR for cases with mild anxiety and severe depression was 5.369 (95%CI: 1.074–26.832, P < 0.001), and the OR for cases with severe anxiety and mild depression was 5.339 (95%CI: 1.033–27.590, P < 0.001). The relative excess risk of interaction value (RERI), reflecting the additive interaction between anxiety and depression to RPL was also 1.148 (95%CI: 0.316–4.212).Conclusions: Either depression or anxiety alone could increase risk of subsequent RPL. There also was a synergistic effect of anxiety and depression after the first miscarriage that increased the development of subsequent RPL disease.
Surgical Sites Infection After Gastrointestinal Surgeries in a Public Teaching Hospital in Sudan
Authors: Hassan Rawan Sharaf Eldein Elamein , Osman Sarah Osman Sayed , Aabdeen Mohamed Abdulmonem Salih , Mohamed Walid Elhaj Abdelrahim , Hassan Razan Sharaf Eldein Elamein , Mohamed Sagad Omer Obeid
Published: August 2020

Background: Surgical site infections (SSIs) are common healthcare-associated infections and associated with prolonged hospital stays, additional financial burden, and significantly hamper the potential benefits of surgical interventions. Causes of SSIs are multi-factorials and patients undergoing gastrointestinal tract (GIT) procedures carry a high risk of bacterial contamination. This study aimed to determine the prevalence, associated factors, and causing microorganisms of SSIs among patients undergoing GIT surgeries.Methods: A hospital based, cross-sectional study conducted at Soba University Hospital (SUH) in Khartoum, Sudan. We included all patients from all age groups attending the GIT surgical unit at SUH between September-December 2017. We collected data about the socio-demographic characteristics, risk factors of SSI, and isolated microorganisms from patients with SSIs. Data analysis was done using the SPSS software version 20 (SPSS Inc., Chicago, IL, USA). A Chi-square test was conducted to determine the relationship between the independent categorical variables and the occurrence of SSI. The significance level for all analyses was set at p < .05.Results: A total of 80 participants were included in the study. The mean age was 51 +/- 16 years and most of the patients (67.5%) did not have any chronic illness prior to the surgical operation. Most of them (46.3%) of them underwent large bowel surgery. Twenty-two patients (27.5%) developed SSI post operatively and superficial SSI was the most common type of SSIs (81.8%). Occurrence of SSI was found to be associated with long operation time (p > .001), malignant nature of the disease (p > .001), intra-operative blood loss (p > .001), and intra-operative hypotension (p =.013). The most prevalent microorganism isolated from SSI patients was E coli (47.8%), followed by Enterococcus fecalis (13.0%) and combined Pseudomonas aeruginosa + E coli infection (13.0%).Conclusion: The results showed a high prevalence of SSIs among patients attending the GIT unit in SUH and the most prevalent microorganism isolated from them was E coli. Measures should be taken to reduce the magnitude of SSI by mitigating the identified associated factors.
Protective Effects of Ginkgo Biloba Dropping Pills Against Liver Ischemia/reperfusion Injury in Mice
Authors: Wang Zheng , Zhang Ping , Wang Qingqing , Sheng Xueping , Zhang Jianbing , Lu Xiaoyan , Fan Xiaohui
Published: August 2020

Background: Liver ischemia-reperfusion (I/R) injury is an inevitable pathological phenomenon in various clinical conditions, such as liver transplantation, resection surgery, or shock, which is the major cause of morbidity and mortality after operation. Ginkgo Biloba Dropping Pill (GBDP) is a unique Chinese Ginkgo Biloba leaf extract preparation that exhibits a variety of beneficial biological activities. The aim of this study is to investigate the protective effects of GBDP on the liver I/R injury both in vitro and in vivo. Methods: Hypoxia/reoxygenation (H/R) experiments were performed in AML-12 cells and primary hepatocytes, which were pretreated with GBDP (60 or 120 μg/mL) followed by incubation in a hypoxia chamber. Cell viability and cell apoptosis were detected by MTT assay and annexin V staining respectively. C57BL/6 mice were used to establish liver I/R injury model, and were pretreated with GBDP (100 or 200 mg/kg/day, i.g.) for two weeks. Liver damage was detected by plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST). Liver necrosis and neutrophil infiltration were determined by H&E and myeloperoxidase immunohistochemistry staining. Finally, TUNEL staining and western blot analysis of apoptosis-related proteins were used to investigate the anti-apoptotic effect of GBDP. Results: In the in vitro study, GBDP pretreatment improved the cell viability of AML-12 cells in H/R injury model. Similarly, the same result was found in the primary hepatocytes isolated from C57BL/6 mice. Moreover, GBDP decreased the number of apoptotic cells induced by H/R. In the in vivo study, oral administration of GBDP ameliorated liver injury evidenced by a significant decline in the levels of ALT and AST. Furthermore, the result of H&E staining showed that GBDP reduced the size of necrosis area. In addition, the decreased infiltration of neutrophils indicated that GBDP may play an anti-inflammatory effect. More importantly, GBDP reduced TUNEL-positive cells and the expression of Bax and caspase-3 in liver indicating GBDP has anti-apoptotic effects.Conclusion: Our findings elucidated that GBDP has potential effects for protecting against liver I/R injury characterized by its anti-apoptotic, anti-necrotic, and anti-inflammatory properties, which would promisingly make a contribution to the exploration of therapeutic strategies in the liver I/R injury.
Development of an Autonomous Wheelchair for The Disabled and Performance Analysis Using ANFIS Model
Authors: Okwu Modestus O. , Tartibu Lagouge K. , Ayomoh Michael , Ighalo Daniel
Published: August 2020

Navigation for persons with physical disability very often poses a major challenge to both the victims and their dedicated navigation assistance-provider. This age-long problem has been a major concern in diverse research fields in the literature ranging from assistive medicine to applied intelligence amongst others. This research work is a build-up to the literature, hence, has presented an automated wheelchair system designed, fabricated and enhanced with joystick capability for obstacle detection and autonomous stoppage. A microcontroller unit known as Arduino uno was built into the system architecture to synchronise the entire set-up by driving the DC motor for directional and linear motion of the wheel chair. The developed system would greatly improve the community of people who have lost some means of independent mobility thereby leading to an improvement in their self-esteem enabling them pursue their vocational and educational goals. Conclusively, the developed system was tested using Adaptive Neuro-Fuzzy Inference System (ANFIS), the sensitivity rule viewer at the first trial gave a total intelligence of 63.8%, further improvement was made and a second trial gave a rating of 75% and the final gave a value of approximately 80%. This shows that the system is efficient, effective and of excellent performance.
Telomere Length De Novo Assembly of all 7 Chromosomes and Mitogenome Sequencing of the Model Entomopathogenic Fungus, Metarhizium Brunneum, by Means of a Novel Assembly Pipeline
Authors: Saud Zack , Kortsinoglou Alexandra M. , Kouvelis Vassili N. , Butt Tariq M.
Published: August 2020

More accurate and complete reference genomes have improved understanding of gene function, biology, and evolutionary mechanisms. Hybrid genome assembly approaches leverage benefits of both long, relatively error-prone reads from third-generation sequencing technologies and short, accurate reads from second-generation sequencing technologies, to produce more accurate and contiguous de novo genome assemblies in comparison to using either technology independently. In this study, we present a novel hybrid assembly pipeline that allowed for both mitogenome de novo assembly and telomere length de novo assembly of all 7 chromosomes of the model entomopathogenic fungus, Metarhizium brunneum. The improved assembly allowed for better ab initio gene prediction and a more BUSCO complete proteome set has been generated in comparison to the eight current NCBI reference Metarhizium spp. genomes. Remarkably, we note that including the mitogenome in ab initio gene prediction training improved overall gene prediction. The assembly was further validated by comparing contig assembly agreement across various assemblers, assessing the assembly performance of each tool. Genomic synteny and orthologous protein clusters were compared between Metarhizium brunneum and three other Hypocreales species with complete genomes, identifying core proteins, and listing orthologous protein clusters shared uniquely between the two entomopathogenic fungal species, so as to further facilitate the understanding of molecular mechanisms underpinning fungal-insect pathogenesis. The novel assembly pipeline may be used for other haploid fungal species, facilitating the need to produce high-quality reference fungal genomes, leading to better understanding of fungal genomic evolution, chromosome structuring and gene regulation.
The Effect of Daily Intake of Vitamin D-Fortified Yogurt Drink, With and Without Added Calcium, on Serum Adiponectin and Sirtuins 1 and 6 in Adult Subjects with Type 2 Diabetes
Authors: Nikooyeh Bahareh , Hollis Bruce W. , Neyestani Tirang R.
Published: August 2020

BackgroundThere is evidence suggesting an effect of vitamin D on glycemic status through mediators including adiponectin and sirtuins.ObjectiveTo evaluate the effects of daily intake of vitamin D-fortified yogurt drink, either with or without added calcium, on serum adiponectin, sirtuins (SIRT)1 and 6. DesignBriefly, 75 adults aged 30-60 yrs from both sexes with type 2 diabetes were randomly allocated to one of the three groups: (i) D-fortified-yogurt drink (DY; containing 1000 IU vitamin D and 300 mg calcium), (ii) Ca+D-fortified-yogurt drink (CDY; containing 1000 IU vitamin D and 500 mg calcium) and (iii) plain yogurt drink (PY; containing no detectable vitamin D and 300 mg calcium). All assessments were performed initially and after 12 weeks. ResultsA significant within-group increment in serum adiponectin concentrations was observed in both DY and CDY groups (+60.4± 8.6, +57.5± 6.4 µg/L, respectively; p<0.001 for both). The concentrations of SIRT1 and SIRT6 had a significant within-group increment only in the CDY group (p=0.003, p=0.001 respectively). Being in CDY group was more favorable predictor of improvement in SIRT6 concentrations. Changes of 25(OH)D was a significant predictor of changes of adiponectin. However, this association disappeared following adjustment for changes of SIRT1. In contrast, the association between changes of 25(OH)D and HbA1c remained significant even after adjustment for SIRT1. ConclusionDaily consumption of vitamin D-fortified yogurt drink for 12 weeks resulted in an increase in circulating concentrations of SIRT1 and SIRT6 in T2D subjects and D+Ca-fortified yogurt drink was more in favor of SIRT6 increment.
Understanding Stakeholders’ Perspectives on Implementing Deprescribing for Older People Living in Long-term Residential Care Homes: The STOPPING Study Protocol
Authors: Warmoth Krystal , Day Jo , Cockcroft Emma , Reed Donald Nigel , Pollock Lucy , Coxon George , Heneker Julia , Walton Bridget , Stein Ken
Published: August 2020

Background: Older people with multimorbidity often experience polypharmacy. Taking multiple medicines can be beneficial; however, some older adults are prescribed multiple medicines when they are unlikely to improve clinical outcomes and may lead to harm. Deprescribing means reducing or stopping prescription medicines which may no longer be providing benefit. While appropriate deprescribing may usually be safely undertaken, there is a lack of guidance about how to implement it in practice settings such as care homes. Implementing deprescribing in care homes is often challenging, due to differing concerns of residents, staff, clinicians, friends/family members and carers along with differences in care home structures. The STOPPING study will support the development of better deprescribing practice in care homes, considering different views and environments. This paper aims to introduce the research protocol. Methods: We will use qualitative approaches informed by the widely accepted Consolidated Framework for Implementation Research (CFIR) to aid analysis. To understand the barriers, facilitators and contextual factors influencing deprescribing in care homes, we will employ individual interviews with care home residents and family members, focus groups with care home staff and healthcare professionals, and observations from care homes. Then, we will examine acceptability, feasibility, and suitability of existing deprescribing approaches using cognitive interviews with care home staff and healthcare professionals. Lastly, we will use narrative synthesis to integrate findings and develop guidance for implementing a deprescribing approach for care homes.Discussion: This research will support the development of implementable approaches to deprescribing in care homes. The insights from this project will be shared with various stakeholders: care home residents, staff, pharmacists, general practitioners, nurses, and other health professionals, carers, researchers, and the public. This work will support deprescribing to be implemented effectively in care homes to benefit residents and the wider health economy.
The Next Challenge in Implementation Science: Transferring Implementation Strategy Knowledge and Skills
Authors: Kirchner JoAnn E , Dollar Katherine M. , Smith Jeffrey L. , Pitcock Jeffery A. , Curtis Nyssa D. , Morris Krissi K. , Fletcher Terri L. , Toper David R.
Published: August 2020

Background: Complex evidence-based clinical innovations are challenging to implement, with many settings requiring implementation assistance to increase likelihood of innovation uptake with fidelity. Implementation science researchers are identifying evidence-based implementation strategies that support the uptake of evidence-based practices and other clinical innovations. However, there is limited information regarding how to develop methods to educate implementation practitioners on the use of implementation strategies and how to sustain these competencies over time. We developed, initiated, and evaluated an implementation training program for both implementation researchers and practitioners.Methods: Participants who attended 7 trainings were asked to complete an electronic survey 2 weeks before training, immediately post-training, and 6 months post-training. We assessed participant knowledge and confidence in applying implementation facilitation skills using a 4-point Likert scale. Scores were compared at baseline to those provided post-training and at 6 months, as well as post-training to 6 months post-training (using nonparametric Wilcoxon Signed Rank tests).Results: One hundred and two participants (76 in-person, 26 virtually) completed the pre-and post-training evaluation. Participants reported a significant increase in perceived knowledge and confidence across all implementation facilitation domains from pre- to post-training and pre- to 6-month training follow up. There was no significant difference between virtual and in-person participants. When comparing post-training to 6-months, increases in perceptions of knowledge remained unchanged though half of the domains showed significantly lower perceived confidence to apply facilitation skills. Conclusions: Our findings indicate that we have developed and conducted an effective Implementation Facilitation Program with participants reporting significant increased knowledge and confidence applying implementation facilitation skills. These results were sustained among trainees at 6 months post-training, as participants reported perceived improvements in knowledge and confidence in applying implementation facilitation skills in all domains. Additionally, knowledge and confidence change scores did not differ based on in-person versus virtual attendance, suggesting that implementation training can successfully be provided to a remote site without loss of knowledge/skills transfer. The decrease in perceived confidence in applying skills from post-training to 6-months post training in some areas indicate a need for ongoing support of facilitation practitioners.
Tumor-Associated Macrophages Secret Exosomal miR-155 to Promote Metastasis of Non-Small-Cell Lung Cancer
Authors: Li Xiang , Chen Zhipeng , Ni Yaojun , Zhu Quan , Wu Weibing , He Zhicheng , Xia Yang , Chen Liang , Xie Xueying , Wang Jun
Published: August 2020

Background: Understanding the molecular basis underlying metastasis of non-small-cell lung cancer (NSCLC) may provide new therapeutic modality for the treatment of NSCLC. However, the mechanisms by which tumor-associated macrophages (TAMs) affect NSCLC metastasis still remain undefined.Methods: The role of macrophages in NSCLC was elucidated by gene set enrichment analysis via The Cancer Genome Atlas database (TCGA) database, and we further verified it through Quantitative real-time PCR and immunohistochemical staining. Exosomes from TAMs were extracted and co-cultured with A549 cells,the biological functions of miR-155 were evaluated through miRNAs sequencing, transwell assays,western blotting,fluorescence labeling,luciferase reporter assay, and animal experiments.Results: We found that M2 TAMs are abundant in metastatic tissues of NSCLC patients and exosomes secreted by M2 TAMs promote epithelial mesenchymal transition(EMT) and migration of A549 cells.Mechanistically,we demonstrated that miR-155 is the biomolecule in exosomes secreted by M2 TAMs and targets 3’-untranslated regions (UTRs) of RASSF4 to promote NSCLC metastasis.Conclusions: MiR-155 is the key functional molecule in M2 TAMs-released exosomes that promote EMT of NSCLC cells through targeting RASSF4. Our study suggests that miR-155 in TAMs and exosomes may serve as a novel therapeutic target in the treatment of lung cancer.
Zika Virus Public Health Crisis and the Perpetuation of Gender Inequality in Brazil
Authors: Coutinho Raquel Zanatta , Montalvo Aida Villanueva , Weitzman Abigail , Marteleto Letícia
Published: August 2020

Background: In 2015-2017, the Americas experienced a highly consequencial epidemics for pregnancy and childbearing. Mainly transmitted by the mosquito Aedes aegypti, but also through sexual intercourse, the Zika virus poses the risk of congenital Zika syndrome to fetus, which includes microcephaly and other child development complications. When a public health crisis taps directly into reproductive health, typically a feminine realm, gender systems may reproduce deeply-rooted gender norms, especially those linked to cultural beliefs and expectations. This paper investigated the role of gender in two relational contexts: public health messaging to prevent Zika infections and women’s Zika and pregnancy prevention negotiation with their sexual partners during the Zika outbreak. Methods: We conducted a systematic content analysis of 94 unique pieces, governmental agencies mass-produced public health communication campaigns promoting Zika awareness. Print and online materials were collected for one year (May 2016-May 2017), such as TV ads, Internet Pop-ups, and pamphlets. We also analyzed transcripts from 16 focus groups we conducted with reproductive-aged women (18-40) in Belo Horizonte and Recife, two large cities differently affected by the Zika outbreak. Women answered open-ended questions related to personal knowledge of and experiences with the Zika virus, the related experiences of their friends and acquaintances, their primary information sources, and their perceptions of public health efforts and women’s contraceptive use.Results: Campaign pieces handling pregnancy and microcephaly demonstrated robust gendering, drastically targeting women, placing on their shoulders the responsibility for protecting a potential fetus from the disease. Campaigns neglected male´s participation on Zika prevention and contraceptive management, and failed to address Brazil´s large proportion of unplanned pregnancies. Women were placed in a double bind by being expected to prevent pregnancy and Zika amidst a relationship power dynamic that included unprotected sexual intercourse and gender norms regarding division of labor. Conclusion: Government and individual responses to the epidemics reinforced gender roles, situating pregnant women as responsible for averting mosquito bites and microcephaly, emphasizing prevention of both disease and vector among women while excluding men. Since low-socioeconomic status women possessed fewer resources to preclude infection, we also find that beyond the gender divide, this subgroup faced more pronounced Zika prevention challenges.
Incidence and Predictors of Loss-to-follow-up Among Pregnant and Breastfeeding Women on Option B+ PMTCT Program in Northwest Ethiopia: a Retrospective Follow-up Study.
Authors: Azanaw Melkalem Mamuye , Baraki Adhanom Gebreegziabher , Yenit Melaku Kindie
Published: August 2020

Background: Although Ethiopia is implementing an option B+ program for the last seven years, lost to follow-up among HIV positive women remains the major problem for ART treatment. The study was conducted on lost to follow-up among human immunodeficiency virus infected pregnant and breastfeeding women after Option B+ modality since there was a scarcity of literatures in Northwest Ethiopia. The result is also expected to strengthen the effort to eliminate mother-to-child transmission of HIV to 5%. Methods: A retrospective follow-up study was conducted among 403 pregnant and breastfeeding women between June 2013 and December 2019 at the University of Gondar comprehensive specialized Hospital. Cox proportional hazards regression model was used for identifying predictors of lost-to-follow-up. Results were reported as hazard ratios with 95% confidence interval at a significance level of p=0.05. Results: The overall incidence rate of loss to follow-up was 9.4 per 1000 person-months of observation (95% confidence interval (CI): 7. 4‒11. 9). According to the multivariable Cox regression, rural residency (adjusted hazard ratio(AHR): 2.30; 95% CI:1.08‒4.88), being Muslim religion follower (AHR: 2.44; 95% CI:1.23‒4.81), having no baseline viral load measurement (AHR: 4.21; 95% CI:2.23–7.96, being on ART before enrolment (AHR: 0.30; 95% CI:0.15–0.62), having drug side effects (AHR: 1.82; 95% CI:1.01–3.33), same day ART initiation (AHR: 3.23; 95% CI:1.53–6.84) and having sub-optimal adherence level (AHR: 3.96; 95% CI:2.18–7.19) were significant predictors of lost to follow up.Conclusion: The incidence of lost to follow-up is lower as compared to evidence from most African countries but slightly higher than the WHO target. It is better to strength and expand viral load measurement for all women and giving attention to those women who are residing in a rural area and having fair/poor adherence level.
LncRNA CCAT1 Enhances Chemoresistance in Hepatocellular Carcinoma by Targeting QKI-5
Authors: Shi Jing , Guo Cao , Ma Junli
Published: August 2020

Background: A major reason for treatment failure of cancer is acquisition of drug resistance. The specific mechanisms underlying hepatocellular carcinoma (HCC) chemoresistance need to be fully elucidated. lncRNAs involve in drug resistance in some cancers, however, the exact functions of lncRNA colon cancer-associated transcript 1 (CCAT1) in oxaliplatin resistance in HCC need to be elucidated.Methods: Functional analysis of CCAT1 on oxaliplatin sensitivity was performed in HCC cell lines HCCLM3 and HepG2, and in a subcutaneous tumor model receiving OXA treatment. Furthermore, the downstream signaling targets of CCAT1 in HCC were explored. Results: CCAT1 promoted HCC proliferation and reduced the apoptosis induced by oxaliplatin. Knockout of CCAT1 could increased chemosensitivity in vitro and in vivo. Further study found that QKI-5 was an important mediator and blocking of QKI-5/p38 MAPK signaling pathway enhanced oxaliplatin sensitivity.Conclusions: CCAT1 promoted proliferation and oxaliplatin resistance by QKI-5/p38 MAPK signaling pathway in HCC. Targeting CCAT1 in combination with chemotherapeutics may be a promising alternative to reverse drug resistance in HCC treatment.
An 8-lncRNA Signature Predicts Survival of Triple-Negative Breast Cancer Patients Without Germline BRCA1/2 Mutation
Authors: Liu Minling , Dai Wei , Zhu Mengyuan , Li Xueying , Huang Shan , Wei Min , Li Lei , Fang Shuo
Published: August 2020

Background: Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and strong heterogeneity. TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment.Methods: 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas (TCGA) database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort (N = 59). Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The signature related mRNAs were identified using the Pearson correlation. Functional enrichment analysis of related mRNA was performed using the Metascape. The qPCR assay was performed to confirm the expressions and clinicopathological correlationsof two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm.Results:We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. In both the training and validation cohort, patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores(P=0.00018 and P =0.0068 respectively). 1, 5, 8-year AUC in the training cohort were 1.000, 1.000 and 0.908 respectively, in the validation cohort were 0.785, 0.790 and 0.892 respectively indicating that our signature has a good prognostic capacity. Signature related mRNA mainly enriched in terms include RNA metabolic process, DNA repair pathways, and so on. Two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed in TNBC without gBRCAm, and significantly associated with tumor grade and invasion.Conclusions: We constructed a novel 8-lncRNA signaturewhich significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targetswhich function needed further exploration.