bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED ARTICLE: Downregulation of miR-483-5p decreases hypoxia-induced injury in human cardiomyocytes by targeting MAPK3
Authors: Hao Yan , Yuan Haitao , Yu Houzhi
Published: March 2020

Background

MiR-483-5p was recently identified as a risk factor in the early stages of acute myocardial infarction (AMI) patients. Here, we further investigated how miR-483-5p affects cardiomyocyte apoptosis and oxidative stress under hypoxic conditions.

Methods

Plasma samples were collected from AMI patients and healthy volunteers. The expression of miR-483-5p was determined using quantitative real-time PCR. An in vitro hypoxic model was constructed to mimic AMI in AC16 cells. Cell viability, apoptosis and oxidative stress biomarker levels (MDA, SOD and CAT) were respectively determined using CCK-8, flow cytometry and commercial assay kits.

Results

The expression levels of miR-483-5p were significantly higher in AMI patients than in control subjects. Circulating levels of miR-483-5p positively correlated with creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) levels. The in vitro experiments showed that the expression levels of miR-483-5p were also upregulated in hypoxia-induced AC16 cell injury. MiR-483-5p overexpression significantly increased hypoxia-induced cardiomyocyte apoptosis and oxidative stress, while knockdown attenuated these effects. Mechanistically, miR-483-5p directly targets MAPK3 in AC16 cells. Furthermore, the protective effects of miR-483-5p knockdown against hypoxia-induced cardiomyocyte injury are partially dependent on MAPK3.

Conclusions

MiR-483-5p, which targets MAPK3, might be a potential therapeutic target for the diagnosis and prevention of hypoxia-induced myocardial injury.
Factors influencing termination of resuscitation in children: a qualitative analysis
Authors: Campwala Rashida T. , Schmidt Anita R. , Chang Todd P. , Nager Alan L.
Published: March 2020

Background

Pediatric Advanced Life Support provides guidelines for resuscitating children in cardiopulmonary arrest. However, the role physicians’ attitudes and beliefs play in decision-making when terminating resuscitation has not been fully investigated. This study aims to identify and explore the vital “non-medical” considerations surrounding the decision to terminate efforts by U.S.-based Pediatric Emergency Medicine (PEM) physicians.

Methods

A phenomenological qualitative study was conducted using PEM physician experiences in terminating resuscitation within a large freestanding children’s hospital. Semi-structured interviews were conducted with 17 physicians, sampled purposively for their relevant content experience, and continued until the point of content saturation. Resulting data were coded using conventional content analysis by 2 coders; intercoder reliability was calculated as κ of 0.91. Coding disagreements were resolved through consultation with other authors.

Results

Coding yielded 5 broad categories of “non-medical” factors that influenced physicians’ decision to terminate resuscitation: legal and financial, parent-related, patient-related, physician-related, and resuscitation. When relevant, each factor was assigned a directionality tag indicating whether the factor influenced physicians to terminate a resuscitation, prolong a resuscitation, or not consider resuscitation. Seventy-eight unique factors were identified, 49 of which were defined by the research team as notable due to the frequency of their mention or novelty of concept.

Conclusion

Physicians consider numerous “non-medical” factors when terminating pediatric resuscitative efforts. Factors are tied largely to individual beliefs, attitudes, and values, and likely contribute to variability in practice. An increased understanding of the uncertainty that exists around termination of resuscitation may help physicians in objective clinical decision-making in similar situations.
Distribution of variants in multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP24A1, VDR, RXRα and RXRγ) vary between European, East-Asian and Sub-Saharan African-ancestry populations
Authors: Jones Patrice , Lucock Mark , Chaplin George , Jablonski Nina G. , Veysey Martin , Scarlett Christopher , Beckett Emma
Published: March 2020

Background

The frequency of vitamin D-associated gene variants appear to reflect changes in long-term ultraviolet B radiation (UVB) environment, indicating interactions exist between the primary determinant of vitamin D status, UVB exposure and genetic disposition. Such interactions could have health implications, where UVB could modulate the impact of vitamin D genetic variants identified as disease risk factors. However, the current understanding of how vitamin D variants differ between populations from disparate UVB environments is limited, with previous work examining a small pool of variants and restricted populations only.

Methods

Genotypic data for 46 variants within multiple vitamin D-related loci (DHCR7/NADSYN1,GC,CYP2R1,CYP11A1,CYP27A1,CYP24A1,VDR,RXRαandRXRγ) was collated from 60 sample sets (2633 subjects) with European, East Asian and Sub-Saharan African origin via the NCBI 1000 Genomes Browser and ALFRED (Allele Frequency Database), with the aim to examine for patterns in the distribution of vitamin D-associated variants across these geographic areas.

Results

The frequency of all examined genetic variants differed between populations of European, East Asian and Sub-Saharan African ancestry. Changes in the distribution of variants inCYP2R1,CYP11A1,CYP24A1,RXRαandRXRγgenes between these populations are novel findings which have not been previously reported. The distribution of several variants reflected changes in the UVB environment of the population’s ancestry. However, multiple variants displayed population-specific patterns in frequency that appears not to relate to UVB changes.

Conclusions

The reported population differences in vitamin D-related variants provides insight into the extent by which activity of the vitamin D system can differ between cohorts due to genetic variance, with potential consequences for future dietary recommendations and disease outcomes.
Understanding vestibular-related physiological functions could provide clues on adapting to a new gravitational environment
Authors: Morita Hironobu , Kaji Hiroshi , Ueta Yoichi , Abe Chikara
Published: March 2020

The peripheral vestibular organs are sensors for linear acceleration (gravity and head tilt) and rotation. Further, they regulate various body functions, including body stability, ocular movement, autonomic nerve activity, arterial pressure, body temperature, and muscle and bone metabolism. The gravitational environment influences these functions given the highly plastic responsiveness of the vestibular system. This review demonstrates that hypergravity or microgravity induces changes in vestibular-related physiological functions, including arterial pressure, muscle and bone metabolism, feeding behavior, and body temperature. Hopefully, this review contributes to understanding how human beings can adapt to a new gravitational environment, including the moon and Mars, in future.
Machine learning prediction of oncology drug targets based on protein and network properties
Authors: Dezső Zoltán , Ceccarelli Michele
Published: March 2020

Background

The selection and prioritization of drug targets is a central problem in drug discovery. Computational approaches can leverage the growing number of large-scale human genomics and proteomics data to make in-silico target identification, reducing the cost and the time needed.

Results

We developed a machine learning approach to score proteins to generate a druggability score of novel targets. In our model we incorporated 70 protein features which included properties derived from the sequence, features characterizing protein functions as well as network properties derived from the protein-protein interaction network. The advantage of this approach is that it is unbiased and even less studied proteins with limited information about their function can score well as most of the features are independent of the accumulated literature. We build models on a training set which consist of targets with approved drugs and a negative set of non-drug targets. The machine learning techniques help to identify the most important combination of features differentiating validated targets from non-targets. We validated our predictions on an independent set of clinical trial drug targets, achieving a high accuracy characterized by an Area Under the Curve (AUC) of 0.89. Our most predictive features included biological function of proteins, network centrality measures, protein essentiality, tissue specificity, localization and solvent accessibility. Our predictions, based on a small set of 102 validated oncology targets, recovered the majority of known drug targets and identifies a novel set of proteins as drug target candidates.

Conclusions

We developed a machine learning approach to prioritize proteins according to their similarity to approved drug targets. We have shown that the method proposed is highly predictive on a validation dataset consisting of 277 targets of clinical trial drug confirming that our computational approach is an efficient and cost-effective tool for drug target discovery and prioritization. Our predictions were based on oncology targets and cancer relevant biological functions, resulting in significantly higher scores for targets of oncology clinical trial drugs compared to the scores of targets of trial drugs for other indications. Our approach can be used to make indication specific drug-target prediction by combining generic druggability features with indication specific biological functions.
Joining Illumina paired-end reads for classifying phylogenetic marker sequences
Authors: Liu Tsunglin , Chen Chen-Yu , Chen-Deng An , Chen Yi-Lin , Wang Jiu-Yao , Hou Yung-I , Lin Min-Ching
Published: March 2020

Background

Illumina sequencing of a marker gene is popular in metagenomic studies. However, Illumina paired-end (PE) reads sometimes cannot be merged into single reads for subsequent analysis. When mergeable PE reads are limited, one can simply use only first reads for taxonomy annotation, but that wastes information in the second reads. Presumably, including second reads should improve taxonomy annotation. However, a rigorous investigation of how best to do this and how much can be gained has not been reported.

Results

We evaluated two methods of joining as opposed to merging PE reads into single reads for taxonomy annotation using simulated data with sequencing errors. Our rigorous evaluation involved several top classifiers (RDP classifier, SINTAX, and two alignment-based methods) and realistic benchmark datasets. For most classifiers, read joining ameliorated the impact of sequencing errors and improved the accuracy of taxonomy predictions. For alignment-based top-hit classifiers, rearranging the reference sequences is recommended to avoid improper alignments of joined reads. For word-counting classifiers, joined reads could be compared to the original reference for classification. We also applied read joining to our own real MiSeq PE data of nasal microbiota of asthmatic children. Before joining, trimming low quality bases was necessary for optimizing taxonomy annotation and sequence clustering. We then showed that read joining increased the amount of effective data for taxonomy annotation. Using these joined trimmed reads, we were able to identify two promising bacterial genera that might be associated with asthma exacerbation.

Conclusions

When mergeable PE reads are limited, joining them into single reads for taxonomy annotation is always recommended. Reference sequences may need to be rearranged accordingly depending on the classifier. Read joining also relaxes the constraint on primer selection, and thus may unleash the full capacity of Illumina PE data for taxonomy annotation. Our work provides guidance for fully utilizing PE data of a marker gene when mergeable reads are limited.
The genetic control of leaf allometry in the common bean, Phaseolus vulgaris
Authors: Zhang Miaomiao , Zhang Shilong , Ye Meixia , Jiang Libo , Vallejos C. Eduardo , Wu Rongling
Published: March 2020

Background

To maximize photosynthetic efficiency, plants have evolved a capacity by which leaf area scales allometrically with leaf mass through interactions with the environment. However, our understanding of genetic control of this allometric relationship remains limited.

Results

We integrated allometric scaling laws expressed at static and ontogenetic levels into genetic mapping to identify the quantitative trait loci (QTLs) that mediate how leaf area scales with leaf mass and how such leaf allometry, under the control of these QTLs, varies as a response to environment change. A major QTL detected by the static model constantly affects the allometric growth of leaf area vs. leaf mass for the common bean (Phaseolus vulgaris) in two different environments. The ontogenetic model identified this QTL plus a few other QTLs that determine developmental trajectories of leaf allometry, whose expression is contingent heavily upon the environment.

Conclusions

Our results gain new insight into the genetic mechanisms of how plants program their leaf morphogenesis to adapt to environmental perturbations.
miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4
Authors: Wang Wenwen , Li Xiuxiu , Ding Ning , Teng Jun , Zhang Shen , Zhang Qin , Tang Hui
Published: March 2020

Background

Intramuscular fat (IMF) content is an important factor in porcine meat quality. Previously, we showed that miR-34a was less abundant in liver tissue from pigs with higher backfat thickness, compared to pigs with lower backfat thickness. The purpose of this present study was to explore the role of miR-34a in adipogenesis.

Result

Bioinformatics analysis identified Acyl-CoA synthetase long chain family member 4 (ACSL4) as a putative target of miR-34a. Using a luciferase reporter assay, we verified that miR-34a binds theACSL4mRNA at the 3’UTR. To examine the role of the miR-34a-ACSL4interaction in IMF deposition in the pig, mRNA and protein expression of theACSL4gene was measured in primary intramuscular preadipocytes transfected with miR-34a mimic and inhibitor. Our results showed thatACSL4is expressed throughout the entire differentiation process in pig preadipocytes, similar to the lipogenesis-associated genesPPARγandaP2.Transfection with miR-34a mimic reduced lipid droplet formation during adipogenesis, while miR-34a inhibitor increased lipid droplet accumulation. Transfection with miR-34a mimic also reduced the mRNA and protein expression ofACSL4and lipogenesis genes, includingPPARγ, aP2,andSREBP-1C, but increased the expression of steatolysis genes such asATGLandSirt1. In contrast, the miR-34a inhibitor had the opposite effect on gene expression. Further, knockdown ofACSL4decreased lipid droplet accumulation.

Conclusions

Our results support the hypothesis that miR-34a regulates intramuscular fat deposition in porcine adipocytes by targetingACSL4.
Multiple association analysis of loci and candidate genes that regulate body size at three growth stages in Simmental beef cattle
Authors: An Bingxing , Xu Lei , Xia Jiangwei , Wang Xiaoqiao , Miao Jian , Chang Tianpeng , Song Meihua , Ni Junqing , Xu Lingyang , Zhang Lupei , Li Junya , Gao Huijiang
Published: March 2020

Background

Body size traits as one of the main breeding selection criteria was widely used to monitor cattle growth and to evaluate the selection response. In this study, body size was defined as body height (BH), body length (BL), hip height (HH), heart size (HS), abdominal size (AS), and cannon bone size (CS). We performed genome-wide association studies (GWAS) of these traits over the course of three growth stages (6, 12 and 18 months after birth) using three statistical models, single-trait GWAS, multi-trait GWAS and LONG-GWAS. The Illumina Bovine HD 770 K BeadChip was used to identify genomic single nucleotide polymorphisms (SNPs) in 1217 individuals.

Results

In total, 19, 29, and 10 significant SNPs were identified by the three models, respectively. Among these, 21 genes were promising candidate genes, includingSOX2, SNRPD1, RASGEF1B, EFNA5, PTBP1, SNX9, SV2C, PKDCC, SYNDIG1, AKR1E2,andPRIM2identified by single-trait analysis;SLC37A1, LAP3, PCDH7, MANEA,andLHCGRidentified by multi-trait analysis; andP2RY1, MPZL1, LINGO2, CMIP,andWSCD1identified by LONG-GWAS.

Conclusions

Multiple association analysis was performed for six growth traits at each growth stage. These findings offer valuable insights for the further investigation of potential genetic mechanism of growth traits in Simmental beef cattle.
Genome-wide identification and expression analysis of WRKY transcription factors in pearl millet (Pennisetum glaucum) under dehydration and salinity stress
Authors: Chanwala Jeky , Satpati Suresh , Dixit Anshuman , Parida Ajay , Giri Mrunmay Kumar , Dey Nrisingha
Published: March 2020

Background

Plants have developed various sophisticated mechanisms to cope up with climate extremes and different stress conditions, especially by involving specific transcription factors (TFs). The members of the WRKY TF family are well known for their role in plant development, phytohormone signaling and developing resistance against biotic or abiotic stresses. In this study, we performed a genome-wide screening to identify and analyze the WRKY TFs in pearl millet (Pennisetum glaucum; PgWRKY), which is one of the most widely grown cereal crops in the semi-arid regions.

Results

A total number of 97 putative PgWRKY proteins were identified and classified into three major Groups (I-III) based on the presence of WRKY DNA binding domain and zinc-finger motif structures. Members of Group II have been further subdivided into five subgroups (IIa-IIe) based on the phylogenetic analysis. In-silico analysis of PgWRKYs revealed the presence of various cis-regulatory elements in their promoter region like ABRE, DRE, ERE, EIRE, Dof, AUXRR, G-box, etc., suggesting their probable involvement in growth, development and stress responses of pearl millet. Chromosomal mapping evidenced uneven distribution of identified 97 PgWRKY genes across all the seven chromosomes of pearl millet. Synteny analysis of PgWRKYs established their orthologous and paralogous relationship among the WRKY gene family of Arabidopsis thaliana, Oryza sativa and Setaria italica. Gene ontology (GO) annotation functionally categorized these PgWRKYs under cellular components, molecular functions and biological processes. Further, the differential expression pattern of PgWRKYs was noticed in different tissues (leaf, stem, root) and under both drought and salt stress conditions. The expression pattern of PgWRKY33, PgWRKY62 and PgWRKY65 indicates their probable involvement in both dehydration and salinity stress responses in pearl millet.

Conclusion

Functional characterization of identified PgWRKYs can be useful in delineating their role behind the natural stress tolerance of pearl millet against harsh environmental conditions. Further, these PgWRKYs can be employed in genome editing for millet crop improvement.
Tracy: basecalling, alignment, assembly and deconvolution of sanger chromatogram trace files
Authors: Rausch Tobias , Fritz Markus Hsi-Yang , Untergasser Andreas , Benes Vladimir
Published: March 2020

Background

DNA sequencing is at the core of many molecular biology laboratories. Despite its long history, there is a lack of user-friendly Sanger sequencing data analysis tools that can be run interactively as a web application or at large-scale in batch from the command-line.

Results

We present Tracy, an efficient and versatile command-line application that enables basecalling, alignment, assembly and deconvolution of sequencing chromatogram files. Its companion web applications make all functionality of Tracy easily accessible using standard web browser technologies and interactive graphical user interfaces. Tracy can be easily integrated in large-scale pipelines and high-throughput settings, and it uses state-of-the-art file formats such as JSON and BCF for reporting chromatogram sequencing results and variant calls. The software is open-source and freely available at https://github.com/gear-genomics/tracy, the companion web applications are hosted at https://www.gear-genomics.com.

Conclusions

Tracy can be routinely applied in large-scale validation efforts conducted in clinical genomics studies as well as for high-throughput genome editing techniques that require a fast and rapid method to confirm discovered variants or engineered mutations. Molecular biologists benefit from the companion web applications that enable installation-free Sanger chromatogram analyses using intuitive, graphical user interfaces.
Temporal responses of conserved miRNAs to drought and their associations with drought tolerance and productivity in rice
Authors: Xia Hui , Yu Shunwu , Kong Deyan , Xiong Jie , Ma Xiaosong , Chen Liang , Luo Lijun
Published: March 2020

Background

Plant miRNAs play crucial roles in responses to drought and developmental processes. It is essential to understand the association of miRNAs with drought-tolerance (DT), as well as their impacts on growth, development, and reproduction (GDP). This will facilitate our utilization of rice miRNAs in breeding.

Results

In this study, we investigated the time course of miRNA responses to a long-term drought among six rice genotypes by high-throughput sequencing. In total, 354 conserved miRNAs were drought responsive, representing obvious genotype- and stage-dependent patterns. The drought-responsive miRNAs (DRMs) formed complex regulatory network via their coexpression and direct/indirect impacts on the rice transcriptome. Based on correlation analyses, 211 DRMs were predicted to be associated with DT and/or GDP. Noticeably, 14.2% DRMs were inversely correlated with DT and GDP. In addition, 9 pairs of mature miRNAs, each derived from the same pre-miRNAs, were predicted to have opposite roles in regulating DT and GDP. This suggests a potential yield penalty if an inappropriate miRNA/pre-miRNA is utilized. miRNAs have profound impacts on the rice transcriptome reflected by great number of correlated drought-responsive genes. By regulating these genes, a miRNA could activate diverse biological processes and metabolic pathways to adapt to drought and have an influence on its GDP.

Conclusion

Based on the temporal pattern of miRNAs in response to drought, we have described the complex network between DRMs. Potential associations of DRMs with DT and/or GDP were disclosed. This knowledge provides valuable information for a better understanding in the roles of miRNAs play in rice DT and/or GDP, which can facilitate our utilization of miRNA in breeding.
Modified high-throughput Nile red fluorescence assay for the rapid screening of oleaginous yeasts using acetic acid as carbon source
Authors: Miranda Catarina , Bettencourt Sara , Pozdniakova Tatiana , Pereira Joana , Sampaio Paula , Franco-Duarte Ricardo , Pais Célia
Published: March 2020

Background

Over the last years oleaginous yeasts have been studied for several energetic, oleochemical, medical and pharmaceutical purposes. However, only a small number of yeasts are known and have been deeply exploited. The search for new isolates with high oleaginous capacity becomes imperative, as well as the use of alternative and ecological carbon sources for yeast growth.

Results

In the present study a high-throughput screening comprising 366 distinct yeast isolates was performed by applying an optimised protocol based on two approaches: (I) yeast cultivation on solid medium using acetic acid as carbon source, (II) neutral lipid estimation by fluorimetry using the lipophilic dye Nile red.

Conclusions

Results showed that, with the proposed methodology, the oleaginous potential of yeasts with broad taxonomic diversity and variety of growth characteristics was discriminated. Furthermore, this work clearly demonstrated the association of the oleaginous yeast character to the strain level, contrarily to the species-level linkage, as usually stated.
Methylation in HT22 cells and primary hippocampal neurons with and without isoflurane exposure
Authors: Klenke Stefanie , Specking Christian , Stegen Maike , Engler Andrea , Peters Jürgen
Published: March 2020

Background

Epigenetic modulation may play a role in anesthesia related phenotypes, such as cognitive impairment or memory loss, especially with exposure to anesthetics in the vulnerable phase of brain development. While isoflurane anesthesia can evoke neuroinflammation and neuroapoptosis in young animals, we investigated in a permanent hippocampal cell line (HT22) and in primary hippocampal neurons in an a priori in vitro analysis, whether isoflurane exposure 1) evokes DNA methylation changes in genes involved in apoptosis and inflammation, and 2) results observed in a permanent hippocampal cell line are comparable to primary hippocampal neurons. In case of methylation changes in specific genes, (3) mRNA analysis was performed to assess possible effects on gene expression.

Methods

HT22 cells and primary mouse hippocampal neurons were exposed to 3% isoflurane for 4 h and DNA (each 6 single experiments) and RNA (3 single independent experiments) were extracted. Methylation analysis (EpiTect Methyl II PCR Array Systems, Qiagen) included the methylation status of 66 genes involved in apoptosis, cytokine production, inflammatory response, and autoimmunity. Quantitative Real-Time PCR was performed using the Quantitect SYBR Green Kit on a Step One Plus.

Results

Methylation status was markedly different between immortalized HT22 cells and cultured primary hippocampal neurons without isoflurane exposure. Of 66 genes investigated, 29 were methylated to a significantly greater degree in HT22 cells compared to primary hippocampal neurons. In cultured primary hippocampal neurons, in contrast, there was a greater methylation in several genes involved in inflammation, accompanied with significant downregulation of C-X-C motif chemokine 12 with isoflurane exposure (p = 0.023).

Conclusions

We demonstrate marked differences in gene methylation between HT22 cells and cultured primary hippocampal neurons without isoflurane exposure, with a greater methylation of several genes involved in inflammation upon isoflurane exposure and significant downregulation of Cxcl12 mRNA expression in primary hippocampal neurons. Accordingly, further investigations of anesthesia related DNA methylation should be performed with special consideration being given to the choice of cells targeted for such investigations.
Refractoriness to subcutaneous implantable cardioverter defibrillator after frequent therapies for ventricular fibrillation storms in a Brugada syndrome case
Authors: Nakao Yasuhisa , Suenari Kazuyoshi , Yamashiro Kohei , Nakagawa Hiroshi , Shiode Nobuo
Published: March 2020

Background

The subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to the transvenous implantable cardioverter defibrillator for the prevention of sudden cardiac death. Here, we report a rare case of refractoriness to an S-ICD after frequent therapies for ventricular fibrillation (VF) storms.

Case presentation

A 24-year-old man underwent a bout of syncope with vomiting and incontinence at home. He was brought to the emergency room and was witnessed to spontaneously go into VF successfully converted by external defibrillation. Previously, he was diagnosed with a type I Brugada electrocardiogram pattern by a pilsicainide administration test in another hospital. Although he had a family history of sudden cardiac death in 3 relatives, including his brother, he was followed closely without any therapies because he had never had an episode of syncope. He was implanted with an S-ICD without any trouble. Seven months later, frequent S-ICD shocks for VF storms occurred. His VF was controlled by using intravenous amiodarone, which was converted to an oral preparation. However, his VF recurred after another 2 months. The analysis of his S-ICD data revealed that 4 consecutive shock deliveries could not terminate his VF and the final shock delivered could fortunately terminate it because of a high defibrillation threshold test (DFT) due to an increasing shock impedance (64 to 90 Ω). First, we performed an epicardial Brugada syndrome ablation and subsequently replaced and repositioned the S-ICD lead from a left to a right parasternal site. After the re-implantation of the S-ICD, the DFT test improved to within normal range. According to the pathological analysis, infiltration of inflammatory cells and extensive fibrosis were confirmed in the subcutaneous tissue around the shock lead and S-ICD body.

Conclusion

Frequent S-ICD shocks for VF storms might cause various pathological changes around the device and lead to a high DFT.
Giant coronary artery fistula complicated with coronary artery aneurysm and acute myocardial infarction: a case report
Authors: Yang Zhuoxuan , Zhang Liang , Gao Jin , Cui Jingang , Yuan Jiansong , Liu Shengwen , Zhou Yue , Qiao Shubin
Published: March 2020

Background

Coronary artery fistula (CAF) is an abnormal connection between a coronary artery and either a cardiac chamber or the great vessels. Although most patients are asymptomatic, potential complications such as heart failure, angina pectoris or acute myocardial infarction can be fatal.

Case presentation

We present here a 62-year-old man diagnosed with giant coronary artery fistula complicated with gross coronary artery aneurysm and acute myocardial infarction. He underwent intravenous thrombolysis treatment at a local hospital, coronary angiography at a regional hospital and complex surgery at a national centre for cardiovascular disease. The patient had no major adverse cardiac events during the 3-year follow-up.

Conclusion

Early diagnosis of CAF patients and an appropriate treatment plan are the key factors for avoiding serious complications. Because of the rare incidence of this disease, it is necessary to discover and discuss management strategies, including medical management, percutaneous interventions or surgical treatment, for a successful outcome.
Analytical methods used in estimating the prevalence of HIV/AIDS from demographic and cross-sectional surveys with missing data: a systematic review
Authors: Mosha Neema R. , Aluko Omololu S. , Todd Jim , Machekano Rhoderick , Young Taryn
Published: March 2020

Background

Sero- prevalence studies often have a problem of missing data. Few studies report the proportion of missing data and even fewer describe the methods used to adjust the results for missing data. The objective of this review was to determine the analytical methods used for analysis in HIV surveys with missing data.

Methods

We searched for population, demographic and cross-sectional surveys of HIV published from January 2000 to April 2018 in Pub Med/Medline, Web of Science core collection, Latin American and Caribbean Sciences Literature, Africa-Wide Information and Scopus, and by reviewing references of included articles. All potential abstracts were imported into Covidence and abstracts screened by two independent reviewers using pre-specified criteria. Disagreements were resolved through discussion. A piloted data extraction tool was used to extract data and assess the risk of bias of the eligible studies. Data were analysed through a quantitative approach; variables were presented and summarised using figures and tables.

Results

A total of 3426 citations where identified, 194 duplicates removed, 3232 screened and 69 full articles were obtained. Twenty-four studies were included. The response rate for an HIV test of the included studies ranged from 32 to 96% with the major reason for the missing data being refusal to consent for an HIV test. Complete case analysis was the primary method of analysis used, multiple imputations 11(46%) was the most advanced method used, followed by the Heckman’s selection model 9(38%). Single Imputation and Instrumental variables method were used in only two studies each, with 13(54%) other different methods used in several studies. Forty-two percent of the studies applied more than two methods in the analysis, with a maximum of 4 methods per study. Only 6(25%) studies conducted a sensitivity analysis, while 11(46%) studies had a significant change of estimates after adjusting for missing data.

Conclusion

Missing data in survey studies is still a problem in disease estimation. Our review outlined a number of methods that can be used to adjust for missing data on HIV studies; however, more information and awareness are needed to allow informed choices on which method to be applied for the estimates to be more reliable and representative.
Incorporating sampling weights into robust estimation of Cox proportional hazards regression model, with illustration in the Multi-Ethnic Study of Atherosclerosis
Authors: Sitlani Colleen M. , Lumley Thomas , McKnight Barbara , Rice Kenneth M. , Olson Nels C. , Doyle Margaret F. , Huber Sally A. , Tracy Russell P. , Psaty Bruce M. , Delaney Joseph A. C.
Published: March 2020

Background

Cox proportional hazards regression models are used to evaluate associations between exposures of interest and time-to-event outcomes in observational data. When exposures are measured on only a sample of participants, as they are in a case-cohort design, the sampling weights must be incorporated into the regression model to obtain unbiased estimating equations.

Methods

Robust Cox methods have been developed to better estimate associations when there are influential outliers in the exposure of interest, but these robust methods do not incorporate sampling weights. In this paper, we extend these robust methods, which already incorporate influence weights, so that they also accommodate sampling weights.

Results

Simulations illustrate that in the presence of influential outliers, the association estimate from the weighted robust method is closer to the true value than the estimate from traditional weighted Cox regression. As expected, in the absence of outliers, the use of robust methods yields a small loss of efficiency. Using data from a case-cohort study that is nested within the Multi-Ethnic Study of Atherosclerosis (MESA) longitudinal cohort study, we illustrate differences between traditional and robust weighted Cox association estimates for the relationships between immune cell traits and risk of stroke.

Conclusions

Robust weighted Cox regression methods are a new tool to analyze time-to-event data with sampling, e.g. case-cohort data, when exposures of interest contain outliers.
Incidence and epidemiology of acute kidney injury in a pediatric Malawian trauma cohort: a prospective observational study
Authors: Bjornstad Erica C. , Muronya William , Smith Zachary H. , Gibson Keisha , Mottl Amy K. , Charles Anthony , Marshall Stephen W. , Golightly Yvonne M. , Munthali Charles K. , Gower Emily W.
Published: March 2020

Background

Acute kidney injury (AKI) is highly associated with mortality risk in children worldwide. Trauma can lead to AKI and is a leading cause of pediatric death in Africa. However, there is no information regarding the epidemiology of pediatric, trauma-associated AKI in Africa.

Methods

Prospective cohort study of pediatric trauma patients admitted to a tertiary referral hospital in Malawi. Participants enrolled at admission were followed prospectively throughout their hospitalization. AKI was defined by creatinine-only Kidney Disease Improving Global Outcomes criteria. We calculated descriptive statistics and univariate relative risks (RR) for hypothesis-generation of potential risk factors associated with AKI.

Results

We analyzed data from 114 participants. Depending on baseline creatinine definition, AKI incidence ranged from 4 to 10%. The new Schwartz equation estimated baseline creatinine values best and yielded an AKI incidence of 9.7%. Almost one in ten children died during hospitalization, but those with AKI (n = 4) were at significantly higher risk of death compared to those without AKI (40.0% vs 6.2%; RR 6.5, 95% CI 2.2–19.1). Burn injuries were most commonly associated with AKI (63.6%). Other potential AKI risk factors included multiple injuries, trunk or facial injuries, and recent consumption of herbal remedies.

Conclusions

AKI occurs in up to 10% of admitted pediatric trauma patients in Malawi and increases the risk of death 7-fold compared to those without AKI. This large unrecognized burden in trauma requires further investment by researchers, clinicians and policymakers to develop evidenced-based triage, recognition, and management approaches to prevent the associated sequelae and potential mortality from AKI.
Design of a non-interventional post-marketing study to assess the long-term safety and effectiveness of ocrelizumab in German real world multiple sclerosis cohorts – the CONFIDENCE study protocol
Authors: Dirks Petra , Zingler Vera , Leemhuis Jost , Berthold Heike , Hieke-Schulz Stefanie , Wormser David , Ziemssen Tjalf
Published: March 2020

Background

Multiple sclerosis (MS) is a chronic disease that requires lifelong treatment. A highly effective drug not only for relapsing but also for progressive forms of MS with a favorable safety profile is needed to further improve overall patient outcomes. Ocrelizumab, a recombinant humanized monoclonal antibody that selectively targets CD20-expressing B-cells, is the first drug indicated for the treatment of adult patients with relapsing forms of MS (RMS) and primary progressive MS (PPMS). Its safety and effectiveness profile has yet to be studied in a large, real-world setting. CONFIDENCE aims to further characterize the safety profile of ocrelizumab in routine clinical practice. In addition, real-world effectiveness data will be collected to complement the efficacy data documented in the pivotal clinical trials.

Methods

CONFIDENCE is a non-interventional, prospective, multicenter, long-term study collecting primary data from 3000 RMS and PPMS patients newly treated with ocrelizumab and 1500 patients newly treated with other selected MS disease-modifying therapies (DMTs). Treatment must be in accordance with the local label and follow routine practice. Data will be collected at approximately 250 neurological centers and practices across Germany. The recruitment period of 30 months started in April 2018. The observation period per patient is planned 7.5 to 10 years, depending on the date of inclusion, regardless of whether patients discontinue treatment. Visits follow routine practice and will be documented approximately every 6 months. The primary endpoint is the incidence and type of uncommon adverse events and death. Statistical analyses will be mainly descriptive and exploratory.

Discussion

CONFIDENCE is a large, non-interventional, post-authorization safety study that assesses long-term safety and effectiveness of ocrelizumab and other DMTs in a real-world setting. Data collected in CONFIDENCE will also be integrated into studies that have been developed to fulfil international regulatory requirements.
Pregnancy and perinatal outcomes in pregnancies resulting from time interval between a freeze-all cycle and a subsequent frozen-thawed single blastocyst transfer
Authors: Hu Shiqiao , Xu Bei , Long Rui , Jin Lei
Published: March 2020

Background

Adverse obstetric outcomes are correlated with altered circulating hormone levels at the time implantation by the trophectoderm. What’ more, embryo freezing process may also have adverse effect on perinatal outcomes. This study aims to evaluate whether increasing interval time between a freeze-all cycle and a subsequent frozen-thawed single blastocyst transfer could have any effect on pregnancy and perinatal outcomes.

Methods

This was a retrospective cohort study included the first single blastocyst transfer in artificially cycles of all patients who underwent a freeze-all cycle between January 1st, 2016 and September 30th, 2018. All patients were divided into two groups according to the time interval between oocyte retrieval and the day of first frozen-thawed embryo transferred (FET): Group 1 (immediate FET cycles) and Group 2 (delayed FET cycles).

Results

No significant differences were reported between the two groups regarding the rates of clinical pregnancy, live birth, biochemical pregnancy and pregnancy loss even after adjusting for measured confounding. When accounting for perinatal outcomes, gestational age, birth weight, delivery mode, fetus gender, preterm birth, gestational hypertension, GDM, placenta previa, fetal malformation and low birthweight also did not vary significantly between the two groups. Only the incidence of macrosomia was more frequently in the Group 2 compared with the Group 1 (AOR 3.886, 95%CI 1.153–13.103, P = 0.029) after adjusting with a multiple logistic regression model.

Conclusions

We found delayed FET cycles for blastocyst transfer following freeze-all cycles may not improve the pregnancy outcomes. On the contrary, postponement of FET cycles may increase the risk of macrosomia. Therefore, FET cycles for blastocyst transfer should be done immediately to avoid adverse effects of delayed time on perinatal outcomes.
Polyclonal BRCA2 mutations following carboplatin treatment confer resistance to the PARP inhibitor rucaparib in a patient with mCRPC: a case report
Authors: Simmons Andrew D. , Nguyen Minh , Pintus Elias
Published: March 2020

Background

Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for the treatment of breast cancer susceptibility genes 1 and 2 (BRCA1/2) mutant ovarian and breast cancers, and are now being evaluated in metastatic castration-resistant prostate cancer (mCRPC). Reversion mutations that restoreBRCA1/2function have been shown to be responsible for resistance to platinum-based chemotherapy and PARP inhibitors, however there is no information on the sequential use of these agents in prostate cancer.

Case presentation

A patient with mCRPC associated with a germlineBRCA2mutation was sequentially treated with carboplatin and the PARP inhibitor rucaparib. Genomic profiling of the available baseline tumor and progression blood samples using next-generation sequencing panel tests identified polyclonalBRCA2reversion mutations post carboplatin treatment but prior to rucaparib treatment. A total of 12 somatic reversion mutations were detected and ranged from small indels to larger deletions of up to 387 amino acids. These alterations are all predicted to restore theBRCA2open reading frame and potentially protein function. The patient received limited benefit while on rucaparib, likely due to these reversion mutations observed prior to treatment.

Conclusions

Here we report a case of a patient with prostate cancer who received a platinum agent and PARP inhibitor sequentially and in whom polyclonalBRCA2reversion mutations were identified as the likely mechanism of acquired resistance to carboplatin and primary resistance to PARP inhibition. These findings suggest caution is warranted in sequencing these agents.
Prognostic significance of stem cell/ epithelial-mesenchymal transition markers in periampullary/pancreatic cancers: FGFR1 is a promising prognostic marker
Authors: Chong Yosep , Thakur Nishant , Paik Kwang Yeol , Lee Eun Jung , Kang Chang Suk
Published: March 2020

Background

Periampullary cancers (PAC) including pancreatic, ampulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with a lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to assess the expression and prognostic significance of stem cell/EMT markers in PACs.

Methods

Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed.

Results

A total of 126 PAC cases were evaluated. The average age was 63 years, with 76 male and 50 female patient samples. Age less than 74 years, AOV cancers, lower T & N stage, lower tumor size, no lymphatic, vascular, perineural invasion and histologic well differentiation, intestinal type, no fibrosis, severe inflammation were significantly associated with the better overall survival High expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to better overall survival, while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival.

Conclusions

In addition to other clinicopathologic parameters, severe fibrosis was related to frequent tumor recurrence, and high FGFR1 expression was associated with better overall survival. Histologic changes such as extensive fibrosis need to be investigated further in relation to EMT of PACs.
Evaluation of NID2 promoter methylation for screening of Oral squamous cell carcinoma
Authors: Srisuttee Ratakorn , Arayataweegool Areeya , Mahattanasakul Patnarin , Tangjaturonrasme Napadon , Kerekhanjanarong Virachai , Keelawat Somboon , Mutirangura Apiwat , Kitkumthorn Nakarin
Published: March 2020

Background

Oral squamous cell carcinoma (OSCC) is an aggressive human malignancy. Because of late diagnosis and recurrence of OSCC, the treatment of patients with OSCC is often ineffective. Thus, finding novel biomarkers of OSCC are essential. Here we derived a methylation marker by utilizing methylation microarray data and testing its capacity in cross-sectional study designed for OSCC detection and screening.

Methods

According to bioinformatics analysis of total of 27,578 cg sites, cg22881914 of Nidogen 2 (NID2) methylation was selected for evaluation. Next, we confirmed the methylation status by bisulfite sequencing from the microdissected OSCC cells in comparison with the microdissected oral epithelia. Subsequently, we developed a simple technique using real-time PCR with the specific probe to examine the ability for the detection of OSCC in the oral epithelial samples, which included 103 oral rinse and 82 oral swab samples.

Results

Based on the comparison of microdissected tissue, cg22881914 ofNID2was proved to be methylated in most OSCC cells but unmethylated in the normal oral epithelia. Furthermore, the methylatedNID2-relied quantitative PCR approach has demonstrated that this marker assists in distinguishing among patients with OSCC from normal oral epithelia, smokers, and patients with oral lichen planus using the non-invasive oral rinse and swab samples.

Conclusions

Specific methylation at cg22881914 ofNID2of OSCC could be used as an important potential marker for detecting OSCC. Thus, to certify the utility of this marker, further studies with a larger sample size are needed.