bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Changes Underlie Allelic Divergence ofCUP2BetweenSaccharomycesSpecies
Authors: Li Xueying C , Fay Justin C 
Published: September 2019

AbstractUnder the model of micromutationism, phenotypic divergence between species is caused by accumulation of many small-effect changes. While mapping the causal changes to single nucleotide resolution could be difficult for diverged species, genetic dissection via chimeric constructs allows us to evaluate whether a large-effect gene is composed of many small-effect nucleotide changes. In a previously described non-complementation screen, we found an allele difference of CUP2, a copper-binding transcription factor, underlies divergence in copper resistance between Saccharomyces cerevisiae and S. uvarum. Here, we tested whether the allele effect of CUP2 was caused by multiple nucleotide changes. By analyzing chimeric constructs containing four separate regions in the CUP2 gene, including its distal promoter, proximal promoter, DNA binding domain and transcriptional activation domain, we found that all four regions of the S. cerevisiae allele conferred copper resistance, with the proximal promoter showing the largest effect, and that both additive and epistatic effects are likely involved. These findings support a model of multiple changes underlying evolution and suggest an important role of both protein coding and cis-regulatory changes in evolution.
De Novo Assembly and Annotation from Parental and F1 Puma Genomes of the Florida Panther Genetic Restoration Program
Authors: Ochoa Alexander , Onorato David P , Fitak Robert R , Roelke-Parker Melody E , Culver Melanie 
Published: September 2019

Abstract
In the mid-1990s, the population size of Florida panthers became so small that many individuals manifested traits associated with inbreeding depression (e.g., heart defects, cryptorchidism, high pathogen-parasite load). To mitigate these effects, pumas from Texas were introduced into South Florida to augment genetic variation in Florida panthers. In this study, we report a de novo puma genome assembly and annotation after resequencing 10 individual genomes from partial Florida-Texas-F1 trios. The final genome assembly consisted of ∼2.6 Gb and 20,561 functionally annotated protein-coding genes. Foremost, expanded gene families were associated with neuronal and embryological development, whereas contracted gene families were associated with olfactory receptors. Despite the latter, we characterized 17 positively selected genes related to the refinement of multiple sensory perceptions, most notably to visual capabilities. Furthermore, genes under positive selection were enriched for the targeting of proteins to the endoplasmic reticulum, degradation of mRNAs, and transcription of viral genomes. Nearly half (48.5%) of ∼6.2 million SNPs analyzed in the total sample set contained putative unique Texas alleles. Most of these alleles were likely inherited to subsequent F1 Florida panthers, as these individuals manifested a threefold increase in observed heterozygosity with respect to their immediate, canonical Florida panther predecessors. Demographic simulations were consistent with a recent colonization event in North America by a small number of founders from South America during the last glacial period. In conclusion, we provide an extensive set of genomic resources for pumas and elucidate the genomic effects of genetic rescue on this iconic conservation success story.
Activity-Dependent Regulation of the Proapoptotic BH3-Only Geneegl-1in a Living Neuron Pair inCaenorhabditis elegans
Authors: Cohn Jesse , Dwivedi Vivek , Valperga Giulio , Zarate Nicole , de Bono Mario , Horvitz H Robert , Pierce Jonathan T 
Published: September 2019

AbstractThe BH3-only family of proteins is key for initiating apoptosis in a variety of contexts, and may also contribute to non-apoptotic cellular processes. Historically, the nematode Caenorhabditis elegans has provided a powerful system for studying and identifying conserved regulators of BH3-only proteins. In C. elegans, the BH3-only protein egl-1 is expressed during development to cell-autonomously trigger most developmental cell deaths. Here we provide evidence that egl-1 is also transcribed after development in the sensory neuron pair URX without inducing apoptosis. We used genetic screening and epistasis analysis to determine that its transcription is regulated in URX by neuronal activity and/or in parallel by orthologs of Protein Kinase G and the Salt-Inducible Kinase family. Because several BH3-only family proteins are also expressed in the adult nervous system of mammals, we suggest that studying egl-1 expression in URX may shed light on mechanisms that regulate conserved family members in higher organisms.
Dapagliflozin : manfaat dan risiko pada diabetes melitus tipe 2
Authors: Kalumpiu Joice Viladelvia 
Published: September 2019

Dapagliflozin merupakan salah satu obat antidiabetes pemberian oral golongan penghambat sodium-glucose cotransporter-2 (SGLT2) yang digunakan pada penderita diabetes melitus tipe 2 (DMT2). Berbeda dengan antidiabetes oral lain yang bekerja menstimulasi sekresi insulin atau meningkatkan sensitivitas insulin, dapagliflozin bekerja di ginjal dengan cara menghambat secara kompetitif protein SGLT2 secara reversibel yang berperan dalam reabsorpsi glukosa di glomerulus sehingga menurunkan kadar gula dalam darah penderita DMT2. Beberapa studi telah dilakukan untuk melihat efek penghamabat SGLT2 dalam menurunkan kejadian kardiovaskular seperti Empagliflozin Cardiovascular Outcome Event Trial in Type-2 Diabetes Patients-Remove Excess Glucose, Canagliflozin Cardiovascular Assessment Study, dan studi multisenter yang mengevaluasi efek dapagliflozin pada insiden kejadian kardiovaskular yaitu Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) menunjukkan hasil yang kontradiksi. DECLARE-TIMI58 menunjukkan dapagliflozin tidak meningkatkan atau menurunkan risiko major adverse cardiovascular events (MACE) berbeda dengan obat golongan penghambat SGLT2 lainnya, namun studi ini menunjukkan dapagliflozin dapat menurunkan tingkat kematian dan rawat inap akibat penyakit gagal jantung.
The American College of Cardiology, the American Diabetes Association (ADA), dan The European Society of Cardiology guideline saat ini sudah merekomendasikan penggunaan penghambat SGLT2 (empagliflozin dan canagliflozin) sebagai obat tambahan pada pasien DMT2 dengan aterosklerosis. Hingga saat ini dapagliflozin belum direkomendasikan penggunaannya untuk penyakit kardiovaskular pencegahan aterosklerosis pada pasien DMT2 karena masih kurangnya studi-studi yang mendukung. Ketoasidosis merupakan risiko yang perlu dipantau pada penggunaan obat penghambat SGLT2. Baru-baru ini FDA mengeluarkan adanya peringatan kejadian Fournier’s gangrene. Selain itu, peningkatan risiko fraktur dilaporkan pada penggunaan dapagliflozin dan perlu dipantau bila dimanfaatkan pada penderita DMT2 dalam praktik klinik.
Developing innovation pedagogy
Authors: Konst Taru , Kairisto-Mertanen Liisa 
Published: September 2019

The purpose of this paper is to discuss the concept of a pedagogical strategy called innovation pedagogy and study how it has been and will be developed. The paper provides a discussion of the changes in innovation pedagogy and, more generally, in higher education, including the changes in educational goals and involving a sustainable future as the priority in all education. The research methodology is based on action research and participatory observation as well as on the experiences of the authors of the development process, which has taken place in a Finnish university of applied sciences during the past 12 years. The study helps to understand how education development takes place gradually and how it can simultaneously respond to the demands of a sustainable future. This paper strengthens the understanding of innovation pedagogy by providing a set of concrete steps to advise how to put innovation pedagogy in practice.
Keywords: Education development, higher education, innovation pedagogy, sustainable future
Team-based learning versus traditional didactic lectures in teaching clinical biochemistry; learning outcomes and student satisfaction: a case control study at King Abdul Aziz University
Authors: Alamoudi Aliaa A. , Alsawwa Lana Adey , Gad Hoda , Tekian Ara 
Published: September 2019

Abstract
Background: Team-Based Learning (TBL) which encourages students to become active rather than passive learners has gained world-wide popularity in medical education due to its proven positive effect on more than one aspect of the educational process. At King Abdulaziz University (KAU), clinical biochemistry is still taught in the form of didactic lectures, and while there is a need for introducing active learning, student learning response from TBL has not been explored. Methods: In our case-control study, we compared learning outcomes and student satisfaction in a clinical biochemistry course taught either via TBL to second year Clinical Nutrition students (n= 33) or via traditional lectures to same year Nursing students (n=70). The same summative post-course exam was given to both student groups to assess impact on learning. Focus group discussion and a self-administered questionnaire were used to gain insight into Clinical Nutrition students’ level of satisfaction with TBL. Results: In the post-course exam results of recall and reasoning questions, Nursing students scored an average of 38%±2.4 in the recall questions while Clinical Nutrition students scored higher with an average of 74.5%±4.3 (p<0.0001). In reasoning questions, Nursing students scored lower than Clinical Nutrition students, 23%±2.7 versus 40%±4.2 respectively (p<0.001). In comparing results of pre- and post-test recall questions within each group, there was no significant difference between pre- and post-results for Nursing students while Clinical Nutrition students showed a significant increase in post- versus pre-test results of 71% versus 41% (p<0.0001). In the final summative post-course exam, Nursing students scored an average of 60% ±2.4 while Clinical Nutrition students scored significantly higher with an average of 78%±2.4 (p<0.001). Qualitative studies revealed that accountability and team-work were positive aspects perceived by students regarding TBL and 84% of surveyed students enjoyed the experience while self-study was their main challenge. Conclusion: TBL proved to be a successful, learner-centered approach for Clinical Nutrition students at KAU in their clinical biochemistry course resulting in improved learning outcomes and higher student satisfaction when compared with traditional didactic methods of teaching.
Uses of Quick Response Codes in Healthcare Education: A Scoping Review
Authors: Karia Chiraag Thakrar , Hughes Andrew , Carr Sue 
Published: September 2019

Abstract
Background To review published literature on the use of quick response (QR) codes within healthcare education. In addition, the authors aimed to gain information on user perceptions and the challenges faced when implementing QR codes in an educational context.Methods Medline, EMBASE, CINAHL, HMIC and HBE were searched using specified search terms that included ‘quick response code’ and ‘education’. Title and abstract review of 217 publications was performed. Papers which discussed the application of QR codes relevant to healthcare education were included. A total of 24 articles were reviewed and thematic analysis conducted to generate themes.Results Use of QR codes in healthcare education could be broadly aligned to four common themes These included: to increase participant engagement, for simulation training, for just-in-time learning and to facilitate with administrative tasks in training. Perceptions towards the use of QR codes was generally positive. Challenges identified included: problems with technical infrastructure, unavailability of smartphones and resistance to use in certain environments.Conclusions The use of QR codes for healthcare education is increasing and whilst they offer some advantages there are also some important considerations including: provision of the necessary technological infrastructure, patient and staff safety, and governance and adherence to guidelines on safe and appropriate use of this technology in sensitive settings.
Incidence, clinical implications and impact on public health of infections with Shigella spp. and entero-invasive Escherichia coli (EIEC): results of a multicenter cross-sectional study in the Netherlands during 2016-2017
Authors: Beld Maaike van den , Warmelink Esther , Friedrich Alexander W. , Reubsaet Frans A.G. , Schipper Maarten , de Boer Richard F. , Notermans Daan W. , Petrignani Mariska W. F. , Zanten Evert van , Rossen John W.A. , Friesema Ingrid H.M. , Kooistra A.M.D. (Mirjam) 
Published: September 2019

Abstract
Background Shigella spp. and entero-invasive E. coli (EIEC) use the same invasive mechanism to cause diarrheal diseases. Public health regulations apply only to Shigella spp. infections, but are hampered by the lack of simple methods to distinguish them from EIEC. In the last decades, molecular methods for detecting Shigella spp. and EIEC were implemented in medical microbiological laboratories (MMLs). However, shigellosis cases identified with molecular techniques alone are not notifiable in most countries. Our study investigates the impact of EIEC versus Shigella spp. infections and molecular diagnosed shigellosis versus culture confirmed shigellosis for re-examination of the rationale for the current public health regulations. Methods In this multicenter cross-sectional study, fecal samples of patients suspected for gastro-enteritis, referred to fifteen MMLs in the Netherlands, were screened by PCR for Shigella spp. or EIEC. Samples were also cultured to discriminate between the two pathogens. We compared, risk factors, symptoms, severity of disease, secondary infections and socio-economic consequences for (i) culture-confirmed Shigella spp. versus culture-confirmed EIEC cases (ii) culture positive versus PCR positive only shigellosis cases. Results In 2016-2017, 777 PCR positive fecal samples with patient data were included, 254 of these were culture-confirmed shigellosis cases and 32 were culture-confirmed EIEC cases. EIEC cases were more likely to report ingestion of contaminated food or water and were less likely to be men who have sex with men (MSM). Both pathogens were shown to cause serious disease although differences in specific symptoms were observed. Additionally, culture-negative but PCR positive cases were more likely report travel or ingestion of contaminated food or water and were less likely to be MSM than culture-positive cases. Culture-negative cases were more likely to suffer from multiple symptoms. No differences in degree of secondary infections were observed between both Shigella spp. and EIEC, and culture-negative and culture-positive cases.Conclusions No convincing evidence was found to support the current guidelines. Therefore, culture and molecular detection methods for Shigella spp. and EIEC should be considered equivalent for case definition and public health regulations regarding shigellosis. Differences were found regarding risks factors, indicating that different prevention strategies may be required.
The CD4 cell count at which to initiate HIV-associated cryptococcal antigen (CrAg) screening and pre-emptive antifungal treatment among CrAg positive persons should be raised to 200 cells/μL: evidence based on a meta-analysis
Authors: Li Yao , Huang Xiaojie , Chen Hui , Qin Yuanyuan , Hou Jianhua , Li Aixin , Wu Hao , Yan Xiaofeng , Chen Yaokai 
Published: September 2019

Abstract
Background: Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV+ persons with CD4<100 cells/μL, followed by pre-emptive antifungal therapy among CrAg positive (CrAg+) persons, to prevent CM-related deaths. The strategy may also be considered for those persons with a CD4 count of < 200 cells/uL) according the WHO guidelines. However, there remains little evidence for doing so in those HIV+ persons with this CD4 cell count. Objective: We aimed to assess the necessity of CrAg screening and the efficacy of pre-emptive antifungal therapy in CrAg+ persons with CD4<200 cells/µL. Methods: We conducted a meta-analysis using data obtained from randomized controlled studies (RCTs) and cohort studies found in Pubmed, Web of Science, Cochrane Library and EMBASE/MEDLINE . Results: The pooled prevalence of CrAg positivity in HIV+ persons with CD4<200 cells/µL was 5% (95%CI: 3-6). The incidence of CM in CrAg+ persons was 7- fold (7%, 95%CI: 4-10) higher than that of CrAg negative (CrAg-) persons (1%, 95%CI: 0-1). All-cause mortality in CrAg+ persons was 15% (95%CI: 12-18), more than 1.67 times that of CrAg- persons (9%, 95%CI: 6-13). Among CrAg+ persons who did not receive any treatment or only received placebo, the incidence of CM was 9% (95%CI: 4-13), whereas the incidence of CM among those who received antifungal therapy was 2% (95%CI: 0-3), a highly statistically significant reduction of 78% (RR: 0.17, 95%CI: 0.08-0.36, p <0.00001). Conclusions: In our meta-analysis, the incidence of CM and all-cause mortality in CrAg+ persons were significantly higher than in CrAg(-) persons with CD4<200 cells/µL. Furthermore, the incidence of CM was significantly reduced by pre-emptive antifungal therapy in CrAg+ persons. Our results suggest that the CD4 level for initiating CrAg screening and pre-emptive therapy should now definitely be raised to 200 cells/µL in these HIV-infected individuals.
Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China
Authors: Sun Zesong , Ouyang Jinming , Zhao Bin , An Minghui , Wang Lin , Ding Haibo , Han XiaoXu , Shang Hong 
Published: September 2019

Abstract
Background The impacts of genetic polymorphisms on drug resistance mutations (DRMs) among various HIV-1 subtypes have long been debated. In this study, we aimed to analyze the natural polymorphisms and acquired DRM profile in HIV-1 CRF01_AE-infected patients in a large Tenofovir/Lamivudine/Efavirenz (TDF/3TC/EFV) first-line antiretroviral therapy (ART) cohort in northeastern China.Methods The natural polymorphisms of CRF01_AE were analyzed in 2034 patients from a long-term ART cohort in northeastern China. The polymorphisms in 105 treatment failure (TF) patients were compared with those in 1148 treatment success (TS) patients. The acquired DRM profile of 42 patients who experienced TF with TDF/3TC/EFV treatment was analyzed by comparing the mutations at TF to those at baseline. The Stanford HIVdb algorithm was used to interpret the DRMs. Binomial distribution, McNemar test, and CorMut package were used to analyze the mutation rates and co-variation. Deep sequencing was used to analyze the evolutionary dynamics of co-variation.Results Before ART, the natural polymorphisms of 31 sites on reverse transcriptase (RT) were significantly higher in CRF01_AE than subtype B HIV-1 (|Z value|≥3), including five known drug resistance-associated sites (238, 118, 179, 103, and 40). However, only the polymorphism at site 75 was associated with TF (|Z value|≥3). The mutation rate at 14 sites increased significantly at TF compared to baseline, with the most common DRMs comprising G190S/C, K65R, K101E/N/Q, M184V/I, and V179D/I/A/T/E, ranging from 66.7% to 45.2%. Moreover, two unknown mutations (V75L and L228R) increased by 19.0% and 11.9% respectively, and they were under positive selection (Ka/Ks>1, log odds ratio [LOD]>2) and were associated with several other DRMs (cKa/Ks>1, LOD>2). Deep sequencing of longitudinal plasma samples showed that L228R occurred simultaneously or followed the appearance of Y181C.Conclusion The high levels of polymorphisms in CRF01_AE had little impact on treatment outcomes. The findings regarding potential new CRF01_AE-specific minor DRMs indicate the need for more studies on the drug resistance phenotype of CRF01_AE.
OBSESTRIC AND PERINATAL OUTCOMES OF PRETERM LABOR IN WOMEN LIVING WITH HIV
Authors: Kravchenko E. N. , Yakovlevа O. A. , Kuklina L. V. 
Published: September 2019

The objective of the present study is to reveal characteristics of the course of gestation and perinatal outcomes of preterm, labor associated with human immunodeficiency viral infection. Materials and methods. Retrospective case control study with the participation of 76 pregnant HIV-positive women with preterm labor (main group) and their 76 newborns was held. Comparison group consisted of 198 pregnant women without HIV-infection and their 198 newborns. HIV-infection verification was conducted in accordance with the standard procedure regulated by the Order of the Ministry of Health of the Russian Federation. Results. Antenatal chemoprophylaxis with antiretroviral drugs was used in 92,1% of infected patients. In the vast majority of cases (89,4%) the therapy was conducted with the combination of drugs: Combivir (zidovudine 300 mg + lamivudine 150 mg) taken 1 tablet twice daily combined with Kaletra (lopinavir 200 mg + ritonavir 25 mg) taken 2 tablets twice daily. Initiation of ART vary depending on the HIV infection date: in the first trimester of pregnancy, 48,9% of pregnant were intended to treat, in the second trimester — 36,2%, in the third — 6,4%. 7,9 patients did not receive treatment. Intranatal chemoprophylaxis of prevention of mother-to-child transmission was held in 69 (90,8%) HIV-infected patients. HIV-infection was detected in 2 (2,6%) newborns from mothers who did not receive etiotropic treatment. Common complications of gestation under HIV-infection include anemia (61,8%) and intrauterine growth retardation (34,2%), during labor — meconium in the amniotic fluid (31,6%). Respiratory distress syndrome occurred in 6 (7,6%) newborns, cerebral ischemia was diagnosed in 86,8% of newborns, respiratory distress — in 7,9%. Respiratory distress prophylaxis was conducted in 46% cases only. Conclusion. The course of gestation in women living with HIV with preterm labor was complicated by iron-deficiency anemia, intrauterine growth retardation, meconium in the amniotic fluid; cerebral ischaemia and respiratory distress syndrome most commonly occurred in newborns.