bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking Drought Impacts to Drought Severity at the State Level
Authors: Noel Mary , Bathke Deborah , Fuchs Brian , Gutzmer Denise , Haigh Tonya , Hayes Michael , Poděbradská Markéta , Shield Claire , Smith Kelly , Svoboda Mark
Published: April 2020

The U.S. Drought Monitor (USDM), a weekly map depicting severity and spatial extent of drought, is used to communicate about drought in state and federal decision-making, and as a trigger in response policies, including the distribution of hundreds of millions of dollars for agricultural financial relief in the United States annually. An accompanying classification table helps interpret the map and includes a column of possible impacts associated with each level of drought severity. However, the column describing potential drought impacts is generalized for the entire United States. To provide more geographically specific interpretation of drought, state and regionally specific drought impact classification tables were developed by linking impacts chronicled in the Drought Impact Reporter (DIR) to USDM severity levels across the United States and Puerto Rico and identifying recurrent themes at each level. After creating state-level tables of impacts observed for each level of drought, a nationwide survey was administered to drought experts and decision-makers (n = 89), including the USDM authors, to understand whether the tables provided accurate descriptions of drought impacts in their state. Seventy-six percent of respondents indicated the state table was an acceptable or good characterization of drought impacts for their respective state. This classification scheme was created with a reproducible qualitative methodology that used past observations to identify themes in drought impacts across multiple sectors to concisely describe expected impacts at different levels of drought in each state.
Excessive ITCZ but Negative SST Biases in the Tropical Pacific Simulated by CMIP5/6 Models: The Role of the Meridional Pattern of SST Bias
Authors: Zhou Shijie , Huang Gang , Huang Ping
Published: April 2020

In phases 5 and 6 of the state-of-the-art Coupled Model Intercomparison Project (CMIP5 and CMIP6, respectively) models, there is an apparent excessive rainfall bias with a negative SST bias in the tropical Pacific intertropical convergence zone (ITCZ). The regime of the excessive ITCZ but negative SST bias is inconsistent with the common positive rainfall–SST correlation of climate anomalies over the tropics. Using a two-mode model, we decomposed the rainfall bias into two components and found that the surface convergence (SC) bias is the key factor forming the excessive ITCZ bias in the historical runs of 25 CMIP5 models and 23 CMIP6 models. A mixed layer model was further applied to connect the formation of the SC bias with the SST pattern bias. The results suggest that the meridional pattern of the SST bias plays a key role in forming the SC bias. In the CMIP5 and CMIP6 models, the overall negative SST bias has two apparent meridional troughs at around 10°S and 10°N, respectively. The two meridional troughs in the SST bias drive two convergence centers in the SC bias favoring the excessive ITCZ, even though the local SST bias is negative.
Efficacy of intravitreal injection of conbercept on non-proliferative diabetic retinopathy: a retrospective study
Authors: Wang Jing , Jiang Peng-Fei , Liu Min , Kou Ming-Rong , Lei Jia-Ying , Yu Xiao-Ting , Zhao Ying , Wang Hong , Zhang Lin-Na
Published: April 2020

Objective

This study assessed the efficacy of conbercept for patients with non-proliferative diabetic retinopathy (NPDR).

Methods

In this retrospective clinical study, 54 patients with NPDR (54 eyes) were treated with intravitreal injection of conbercept using a 3+ pro re nata regimen and followed up for 12 months. Best corrected visual acuity (BCVA), central foveal thickness (CFT), area of hard exudate (HE), and number of microaneurysms (MAs) were used as indicators of therapeutic effects. Systemic adverse reactions were recorded to assess safety.

Results

During the 12-month follow-up period, the mean number of injections was 6.12 ± 1.89 on demand. From baseline to the 12-month follow-up, the BCVA of patients with NPDR increased from 0.71 ± 0.20 logMAR to 0.43 ± 0.16 logMAR, CFT decreased from 424.26 ± 64.89 μm to 269.27 ± 44.79 μm, and the number of MAs declined from 79.53 ± 27.18 to 33.34 ± 16.53. Moreover, the area of HE was significantly reduced after 9 months of treatment. There were no serious systemic adverse events during the follow-up.

Conclusions

Intravitreal injection of conbercept has a stable and robust effect on patients with NPDR over a 12-month follow-up period. Thus, conbercept is an effective and feasible treatment for NPDR.
Budget impact analysis of breast cancer screening in Italy: The role of new technologies
Authors: Foglia Emanuela , Marinelli Sissi , Garagiola Elisabetta , Ferrario Lucrezia , Depretto Catherine , Cartia Francesco , Ferranti Claudio , Porazzi Emanuele , Scaperrotta Gianfranco
Published: April 2020

Although mammography screening significantly reduces breast cancer mortality, women could present different morphological characteristics that do not allow the correct vision of their breasts and the detection of cancer, resulting in a delay of diagnosis and an increase in the risk of mortality. The present study aims at analyzing potential areas of improvement of the current screening programs and then hypothesizing alternative technologies to use within the diagnostic phase, from an economic point of view. A Budget Impact Analysis approach was implemented, considering the Italian National Healthcare Service perspective, and representing the healthcare expenditure evolution, over three years. In the Budget Impact Analysis model, two distinct phases of the screening programs were considered: (1) the screening/diagnosis phase and (2) the phase related to cancer care and treatments of patients. The results provide clinicians and policy makers with a rational method to forecast economic resources in the screening programs in a general context of limited resources. In particular, results of the Budget Impact Analysis showed that, while the introduction of the ABUS InveniaTM technology into the screening programs would lead to an increase in the screening phase expenditure, it would generate an economic advantage related to the patients treatment and care.
Trump, Twitter, and news media responsiveness: A media systems approach
Authors: Wells Chris , Shah Dhavan , Lukito Josephine , Pelled Ayellet , Pevehouse Jon CW , Yang JungHwan
Published: April 2020

How populists engage with media of various types, and are treated by those media, are questions of international interest. In the United States, Donald Trump stands out for both his populism-inflected campaign style and his success at attracting media attention. This article examines how interactions between candidate communications, social media, partisan media, and news media combined to shape attention to Trump, Clinton, Cruz, and Sanders during the 2015–2016 American presidential primary elections. We identify six major components of the American media system and measure candidates’ efforts to gain attention from them. Our results demonstrate that social media activity, in the form of retweets of candidate posts, provided a significant boost to news media coverage of Trump, but no comparable boost for other candidates. Furthermore, Trump tweeted more at times when he had recently garnered less of a relative advantage in news attention, suggesting he strategically used Twitter to trigger coverage.
Child of the Elder Blood: A Semiotics of Folklorism in the Soundtrack of The Witcher 3: Wild Hunt
Authors: Stevens Joshua
Published: April 2020

This article considers how folklorism (i.e., artistic representations of folk culture) is aesthetically coded in the soundtrack of the commercially and critically successful The Witcher 3: Wild Hunt video game. Using the tripartite model developed by French musical semiotician Jean-Jacques Nattiez, I consider how the player encounters music and its attendant folklorism in the game (neutral level), how folklorism is embedded in the text through composer activities (poiesis), and how that folklorism can be interpreted by the game’s primarily Western Anglophone player-base (esthesis). The soundtrack’s folklorism as a stylistic musical phenomenon is also related to relevant ethnomusicological scholarship and considered within the larger cultural industry surrounding the game. In doing so, it is shown not only how The Witcher 3’s musical folklorism contributes to the game’s spatiotemporal aesthetics but also how creative musical intentions are transmitted, received, and mediated through the video game medium and its surrounding cultural discourses.
A recurrent reinforcement learning approach applicable to highly uncertain environments
Authors: Li Yang , Guo Shijie , Zhu Lishuang , Mukai Toshiharu , Gan Zhongxue
Published: April 2020

Reinforcement learning has been a promising approach in control and robotics since data-driven learning leads to non-necessity of engineering knowledge. However, it usually requires many interactions with environments to train a controller. This is a practical limitation in some real environments, for example, robots where interactions with environments are restricted and time inefficient. Thus, learning is generally conducted with a simulation environment, and after the learning, migration is performed to apply the learned policy to the real environment, but the differences between the simulation environment and the real environment, for example, friction coefficients at joints, changing loads, may cause undesired results on the migration. To solve this problem, most learning approaches concentrate on retraining, system or parameter identification, as well as adaptive policy training. In this article, we propose an approach where an adaptive policy is learned by extracting more information from the data. An environmental encoder, which indirectly reflects the parameters of an environment, is trained by explicitly incorporating model uncertainties into long-term planning and policy learning. This approach can identify the environment differences when migrating the learned policy to a real environment, thus increase the adaptability of the policy. Moreover, its applicability to autonomous learning in control tasks is also verified.
Patient-reported outcomes in survivors of childhood hematologic malignancies with hematopoietic stem cell transplant
Authors: Yen Hsiu-Ju , Eissa Hesham M. , Bhatt Neel S. , Huang Sujuan , Ehrhardt Matthew J. , Bhakta Nickhill , Ness Kirsten K. , Krull Kevin R. , Srivastava D. Kumar , Robison Leslie L. , Hudson Melissa M. , Huang I-Chan
Published: April 2020

Patient-reported outcomes among survivors of pediatric hematopoietic stem cell transplant (HSCT) are understudied. We compared symptom prevalence, health-related quality of life (HRQOL), and risk factors in adult survivors of childhood hematologic malignancies treated with HSCT to those treated with conventional therapy and noncancer controls. Survivors of childhood hematologic malignancies (HSCT N = 112 [70% allogeneic, 30% autologous]; conventionally treated N = 1106) and noncancer controls (N = 242) from the St. Jude Lifetime Cohort Study completed surveys assessing 10 symptom domains and SF-36 HRQOL summary scores. Chronic health conditions (CHCs) were validated by clinical assessment. Multivariable logistic regression reveals that compared with noncancer controls, HSCT survivors endorsed a significantly higher symptom prevalence in sensation (OR = 4.7, 95% confidence interval [CI], 2.6-8.4), motor/movement (OR = 4.3, 95% CI, 1.6-11.0), pulmonary (OR = 4.6, 95% CI, 1.8-11.8), and memory domains (OR = 4.8, 95% CI, 2.5-9.2), and poorer physical HRQOL (OR = 6.9, 95% CI, 2.8-17.0). HSCT and conventionally treated survivors had a similar prevalence of all symptom domains and HRQOL (all P > .05); however, HSCT survivors had a significantly higher cumulative prevalence for specific symptoms: double vision (P = .04), very dry eyes (P < .0001), and trouble seeing when wearing glasses (P < .0001). Occurrence of organ-specific CHCs, instead of transplant receipt, was significantly associated with a higher prevalence of all symptom domains (all P < .05) in adult survivors of childhood cancer, except for pain and anxiety domains. This study found that patient-reported outcomes were equally impaired between HSCT and conventionally treated survivors, but poorer in both groups compared with noncancer controls. Poor patient-reported outcomes in all survivors of childhood hematologic malignancies correlated with the presence of CHCs, whether treated with conventional therapy or HSCT.
A systematic review of indicators to assess the sustainability of road infrastructure projects
Authors: Suprayoga Gede B. , Bakker Martha , Witte Patrick , Spit Tejo
Published: April 2020

Background

This study aims to examine to what extent sustainability has been incorporated into assessments of road infrastructure projects. It identifies promising approaches that include indicators reflecting core sustainability criteria, determines criteria that were insufficiently covered as indicators, and develops an integrated indicator set covering all criteria.

Methods

A systematic review was performed to obtain all related papers/reports in two academic databases: Scopus and Web of Sciences. The indicators extracted from papers/reports were first coded, then evaluated by using quantitative and qualitative content analysis.

Results

The project appraisal methods for decision-making is found to be a promising approach, covering more extensive criteria than others. Two criteria – namely adaptation and precaution and intergenerational equity – were hardly ever adopted as indicators. Ten main groups of indicators were extracted to construct an integrated set incorporating all core criteria.

Conclusions

Some criteria appear to have become mainstream, while others deserve attention. The safest choice is to combine methods/tools or to adopt the integrated set developed for exhaustive criteria inclusion.
Visualizing metabolic network dynamics through time-series metabolomic data
Authors: Buchweitz Lea F. , Yurkovich James T. , Blessing Christoph , Kohler Veronika , Schwarzkopf Fabian , King Zachary A. , Yang Laurence , Jóhannsson Freyr , Sigurjónsson Ólafur E. , Rolfsson Óttar , Heinrich Julian , Dräger Andreas
Published: April 2020

Background

New technologies have given rise to an abundance of -omics data, particularly metabolomic data. The scale of these data introduces new challenges for the interpretation and extraction of knowledge, requiring the development of innovative computational visualization methodologies. Here, we present GEM-Vis, an original method for the visualization of time-course metabolomic data within the context of metabolic network maps. We demonstrate the utility of the GEM-Vis method by examining previously published data for two cellular systems—the human platelet and erythrocyte under cold storage for use in transfusion medicine.

Results

The results comprise two animated videos that allow for new insights into the metabolic state of both cell types. In the case study of the platelet metabolome during storage, the new visualization technique elucidates a nicotinamide accumulation that mirrors that of hypoxanthine and might, therefore, reflect similar pathway usage. This visual analysis provides a possible explanation for why the salvage reactions in purine metabolism exhibit lower activity during the first few days of the storage period. The second case study displays drastic changes in specific erythrocyte metabolite pools at different times during storage at different temperatures.

Conclusions

The new visualization technique GEM-Vis introduced in this article constitutes a well-suitable approach for large-scale network exploration and advances hypothesis generation. This method can be applied to any system with data and a metabolic map to promote visualization and understand physiology at the network level. More broadly, we hope that our approach will provide the blueprints for new visualizations of other longitudinal -omics data types. The supplement includes a comprehensive user’s guide and links to a series of tutorial videos that explain how to prepare model and data files, and how to use the software SBMLsimulator in combination with further tools to create similar animations as highlighted in the case studies.
OffsampleAI: artificial intelligence approach to recognize off-sample mass spectrometry images
Authors: Ovchinnikova Katja , Kovalev Vitaly , Stuart Lachlan , Alexandrov Theodore
Published: April 2020

Background

Imaging mass spectrometry (imaging MS) is an enabling technology for spatial metabolomics of tissue sections with rapidly growing areas of applications in biology and medicine. However, imaging MS data is polluted with off-sample ions caused by sample preparation, particularly by the MALDI (matrix-assisted laser desorption/ionization) matrix application. Off-sample ion images confound and hinder statistical analysis, metabolite identification and downstream analysis with no automated solutions available.

Results

We developed an artificial intelligence approach to recognize off-sample ion images. First, we created a high-quality gold standard of 23,238 expert-tagged ion images from 87 public datasets from the METASPACE knowledge base. Next, we developed several machine and deep learning methods for recognizing off-sample ion images. The following methods were able to reproduce expert judgements with a high agreement: residual deep learning (F1-score 0.97), semi-automated spatio-molecular biclustering (F1-score 0.96), and molecular co-localization (F1-score 0.90). In a test-case study, we investigated off-sample images corresponding to the most common MALDI matrix (2,5-dihydroxybenzoic acid, DHB) and characterized properties of matrix clusters.

Conclusions

Overall, our work illustrates how artificial intelligence approaches enabled by open-access data, web technologies, and machine and deep learning open novel avenues to address long-standing challenges in imaging MS.
MI-MAAP: marker informativeness for multi-ancestry admixed populations
Authors: Chen Siqi , Ghandikota Sudhir , Gautam Yadu , Mersha Tesfaye B.
Published: April 2020

Background

Admixed populations arise when two or more previously isolated populations interbreed. A powerful approach to addressing the genetic complexity in admixed populations is to infer ancestry. Ancestry inference including the proportion of an individual’s genome coming from each population and its ancestral origin along the chromosome of an admixed population requires the use of ancestry informative markers (AIMs) from reference ancestral populations. AIMs exhibit substantial differences in allele frequency between ancestral populations. Given the huge amount of human genetic variation data available from diverse populations, a computationally feasible and cost-effective approach is becoming increasingly important to extract or filter AIMs with the maximum information content for ancestry inference, admixture mapping, forensic applications, and detecting genomic regions that have been under recent selection.

Results

To address this gap, we present MI-MAAP, an easy-to-use web-based bioinformatics tool designed to prioritize informative markers for multi-ancestry admixed populations by utilizing feature selection methods and multiple genomics resources including 1000 Genomes Project and Human Genome Diversity Project. Specifically, this tool implements a novel allele frequency-based feature selection algorithm, Lancaster Estimator of Independence (LEI), as well as other genotype-based methods such as Principal Component Analysis (PCA), Support Vector Machine (SVM), and Random Forest (RF). We demonstrated that MI-MAAP is a useful tool in prioritizing informative markers and accurately classifying ancestral populations. LEI is an efficient feature selection strategy to retrieve ancestry informative variants with different allele frequency/selection pressure among (or between) ancestries without requiring computationally expensive individual-level genotype data.

Conclusions

MI-MAAP has a user-friendly interface which provides researchers an easy and fast way to filter and identify AIMs. MI-MAAP can be accessed at https://research.cchmc.org/mershalab/MI-MAAP/login/.
Fine mapping of a Phytophthora-resistance locus RpsGZ in soybean using genotyping-by-sequencing
Authors: Jiang Bingzhi , Cheng Yanbo , Cai Zhandong , Li Mu , Jiang Ze , Ma Ruirui , Yuan Yeshan , Xia Qiuju , Nian Hai
Published: April 2020

Background

Phytophthora root rot (PRR) caused by Phytophthora sojae (P. sojae) is one of the most serious limitations to soybean production worldwide. The identification of resistance gene(s) and their incorporation into elite varieties is an effective approach for breeding to prevent soybean from being harmed by this disease. A valuable mapping population of 228 F8:11 recombinant inbred lines (RILs) derived from a cross of the resistant cultivar Guizao1 and the susceptible cultivar BRSMG68 and a high-density genetic linkage map with an average distance of 0.81 centimorgans (cM) between adjacent bin markers in this population were used to map and explore candidate gene(s).

Results

PRR resistance in Guizao1 was found to be controlled by a single Mendelian locus and was finely mapped to a 367.371-kb genomic region on chromosome 3 harbouring 19 genes, including 7 disease resistance (R)-like genes, in the reference Willliams 82 genome. Quantitative real-time PCR assays of possible candidate genes revealed that Glyma.03 g05300 was likely involved in PRR resistance.

Conclusions

These findings from the fine mapping of a novel Rps locus will serve as a basis for the cloning and transfer of resistance genes in soybean and the breeding of P. sojae-resistant soybean cultivars through marker-assisted selection.
Entropy based analysis of vertebrate sperm protamines sequences: evidence of potential dityrosine and cysteine-tyrosine cross-linking in sperm protamines
Authors: Powell Christian D. , Kirchoff Daniel C. , DeRouchey Jason E. , Moseley Hunter N. B.
Published: April 2020

Background

Spermatogenesis is the process by which germ cells develop into spermatozoa in the testis. Sperm protamines are small, arginine-rich nuclear proteins which replace somatic histones during spermatogenesis, allowing a hypercondensed DNA state that leads to a smaller nucleus and facilitating sperm head formation. In eutherian mammals, the protamine-DNA complex is achieved through a combination of intra- and intermolecular cysteine cross-linking and possibly histidine-cysteine zinc ion binding. Most metatherian sperm protamines lack cysteine but perform the same function. This lack of dicysteine cross-linking has made the mechanism behind metatherian protamines folding unclear.

Results

Protamine sequences from UniProt’s databases were pulled down and sorted into homologous groups. Multiple sequence alignments were then generated and a gap weighted relative entropy score calculated for each position. For the eutherian alignments, the cysteine containing positions were the most highly conserved. For the metatherian alignment, the tyrosine containing positions were the most highly conserved and corresponded to the cysteine positions in the eutherian alignment.

Conclusions

High conservation indicates likely functionally/structurally important residues at these positions in the metatherian protamines and the correspondence with cysteine positions within the eutherian alignment implies a similarity in function. One possible explanation is that the metatherian protamine structure relies upon dityrosine cross-linking between these highly conserved tyrosines. Also, the human protamine P1 sequence has a tyrosine substitution in a position expecting eutherian dicysteine cross-linking. Similarly, some members of the metatherian Planigales genus contain cysteine substitutions in positions expecting plausible metatherian dityrosine cross-linking. Rare cysteine-tyrosine cross-linking could explain both observations.
Genome-wide analysis of wheat DNA-binding with one finger (Dof) transcription factor genes: evolutionary characteristics and diverse abiotic stress responses
Authors: Liu Yue , Liu Nannan , Deng Xiong , Liu Dongmiao , Li Mengfei , Cui Dada , Hu Yingkao , Yan Yueming
Published: April 2020

Background

DNA binding with one finger (Dof) transcription factors play important roles in plant growth and abiotic stress responses. Although genome-wide identification and analysis of the DOF transcription factor family has been reported in other species, no relevant studies have emerged in wheat. The aim of this study was to investigate the evolutionary and functional characteristics associated with plant growth and abiotic stress responses by genome-wide analysis of the wheat Dof transcription factor gene family.

Results

Using the recently released wheat genome database (IWGSC RefSeq v1.0), we identified 96 wheat Dof gene family members, which were phylogenetically clustered into five distinct subfamilies. Gene duplication analysis revealed a broad and heterogeneous distribution of TaDofs on the chromosome groups 1 to 7, and obvious tandem duplication genes were present on chromosomes 2 and 3.Members of the same gene subfamily had similar exon-intron structures, while members of different subfamilies had obvious differences. Functional divergence analysis indicated that type-II functional divergence played a major role in the differentiation of the TaDof gene family. Positive selection analysis revealed that the Dof gene family experienced different degrees of positive selection pressure during the process of evolution, and five significant positive selection sites (30A, 31 T, 33A, 102G and 104S) were identified. Additionally, nine groups of coevolving amino acid sites, which may play a key role in maintaining the structural and functional stability of Dof proteins, were identified. The results from the RNA-seq data and qRT-PCR analysis revealed that TaDof genes exhibited obvious expression preference or specificity in different organs and developmental stages, as well as in diverse abiotic stress responses. Most TaDof genes were significantly upregulated by heat, PEG and heavy metal stresses.

Conclusions

The genome-wide analysis and identification of wheat DOF transcription factor family and the discovery of important amino acid sites are expected to provide new insights into the structure, evolution and function of the plant Dof gene family.
Dysbiosis of saliva microbiome in patients with oral lichen planus
Authors: Yu Fei Yan , Wang Qian Qian , Li Miao , Cheng Ya-Hsin , Cheng Yi-Shing Lisa , Zhou Yu , Yang Xi , Zhang Fang , Ge Xuejun , Zhao Bin , Ren Xiu Yun
Published: April 2020

Background

Oral microbiota is not only important for maintaining oral health but also plays a role in various oral diseases. However, studies regarding microbiome changes in oral lichen planus (OLP) are very limited. To the best of our knowledge, there has been only two studies investigating salivary microbiome changes in OLP. Therefore, the purpose of this study was to identify the characteristic microbial profile in the saliva of OLP patients, with or without erosive lesions, and compare that with recurrent aphthous ulcer (RAU), a common oral immunological disorder that also shows multiple erosive/ulcerative lesions. Whole saliva samples were collected from 20 patients with OLP (erosive E, n = 10 and non-erosive NE, n = 10), 10 patients with RAU (U) and 10 healthy controls (C). DNA was extracted from the saliva samples, and the 16S rDNA gene V4 hypervariable region was analyzed using Illumina sequencing.

Results

We obtained 4949 operational taxonomic units (OTUs) from the V4 region in all saliva samples. Community composition analysis showed a clear decreased relative abundance of genera Streptococcus and Sphingomonas in saliva from RAU patients when compared to the other three groups. Relative abundance of Lautropia and Gemella were higher in E group, whereas relative abundance of Haemophilus and Neisseria were higher in NE group when compared to C group. Abiotrophia and Oribacterium were higher in OLP (combining E and NE groups), while Eikenella and Aggregatibacter were lower when compared to C group. There was statistically significance in α-diversity between E and RAU groups(p < 0.05). Significant differences in β-diversity were detected in bacteria between E and C; NE and C; as well as E and NE groups. The LDA effect size algorithm identified the g_Haemophilus might be the potential biomarker in NE group.

Conclusions

We found that salivary microbiome in erosive OLP was significantly different from that found in RAU; and these changes may be related to the underlying disease process rather than presence of ulcerative/erosive lesions clinically. In addition, our findings in bacterial relative abundance in OLP were significantly different from the previously reported findings, which points to the need for further research in salivary microbiome of OLP.
Flowering in Persian walnut: patterns of gene expression during flower development
Authors: Hassankhah Amin , Rahemi Majid , Ramshini Hossein , Sarikhani Saadat , Vahdati Kourosh
Published: April 2020

Background

Flower development and sufficient fruit set are important parameters with respect to walnut yield. Knowledge about flowering genes of fruit trees can help to conduct better molecular breeding programs. Therefore, this study was carried out to investigate the expression pattern of some flowering genes (FT,SOC1,CAL,LFYandTFL1) in Persian walnut (cv. Chandler) during the growing season and winter dormancy.

Results

The results showed that walnut flower induction and initiation in Shahmirzad, Iran occurred in early June and late September, respectively. After meeting chilling and heat requirement, flower differentiation and anthesis occurred in late-March and mid-April to early-May, respectively. Study of flowering gene expression showed that the expression of theFTgene increased in three stages including before breaking of bud dormancy, from late March to late April (coincided with flower differentiation and anthesis) and from late May to mid-June (coincided with flower induction). LikeFT, the expression ofSOC1gene increased during flower induction and initiation (mid-May to early-August) as well as flower anthesis (mid-April to early-May).LFYandCALgenes as floral meristem identity genes are activated byFTandSOC1genes. In contrast with flowering stimulus genes,TFL1showed overexpression during winter dormancy which prevented flowering.

Conclusion

The expression ofFTgene activated downstream floral meristem identity genes includingSOC1,CALandLFYwhich consequently led to release bud dormancy as well as flower anthesis and induction. Also,TFL1as a flowering inhibitor gene in walnut showed overexpression during the bud dormancy. Chilling accumulation reducedTFL1gene expression and increased the expression of flowering genes which ultimately led to overcome dormancy.
Correction to: 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: April 2020

Following publication of the original article [1], it was brought to our attention of an error in the article title.
Using estimated probability of pre-diagnosis behavior as a predictor of cancer survival time: an example in esophageal cancer
Authors: Fahey Paul P. , Page Andrew , Stone Glenn , Astell-Burt Thomas
Published: April 2020

Background

Information on the associations between pre-diagnosis health behavior and post-diagnosis survival time in esophageal cancer could assist in planning health services but can be difficult to obtain using established study designs. We postulated that, with a large data set, using estimated probability for a behavior as a predictor of survival times could provide useful insight as to the impact of actual behavior.

Methods

Data from a national health survey and logistic regression were used to calculate the probability of selected health behaviors from participant’s demographic characteristics for each esophageal cancer case within a large cancer registry data base. The associations between survival time and the probability of the health behaviors were investigated using Cox regression.

Results

Observed associations include: a 0.1 increase in the probability of smoking 1 year prior to diagnosis was detrimental to survival (Hazard Ratio (HR) 1.21, 95% CI 1.19,1.23); a 0.1 increase in the probability of hazardous alcohol consumption 10 years prior to diagnosis was associated with decreased survival in squamous cell cancer (HR 1.29, 95% CI 1.07, 1.56) but not adenocarcinoma (HR 1.08, 95% CI 0.94,1.25); a 0.1 increase in the probability of physical activity outside the workplace is protective (HR 0.83, 95% CI 0.81,0.84).

Conclusions

We conclude that probability for health behavior estimated from demographic characteristics can provide an initial assessment of the association between pre-diagnosis health behavior and post-diagnosis health outcomes, allowing some sharing of information across otherwise unrelated data collections.
The role of a multidisciplinary team in the management of portal hypertension
Authors: Tseng Yujen , Ma Lili , Lv Minzhi , Luo Tiancheng , Liu Chengfeng , Wei Yichao , Liu Chu , Zhou Ji , Yan Zhiping , Xu Pengju , Hu Guohua , Ding Hong , Ji Yuan , Chen Shiyao , Wang Jian
Published: April 2020

Background

Gastroesophageal variceal hemorrhage is the most severe complication of portal hypertension, with a high mortality rate. The current recommendations for gastroesophageal varices include pharmacological treatment, endoscopic treatment, transjugular intrahepatic portosystemic shunt (TIPS) placement, and splenectomy with devascularization surgery. Multidisciplinary team (MDT) comprises of a group of medical experts and specialists across a range of disciplines, providing personalized and targeted patient care tailored to each individual’s condition, circumstances, and expectations.

Methods

Patients referred to the MDT clinic since its establishment in September 2014 were prospectively enrolled and followed-up for at least 12 months. Patient baseline characteristics, treatment methods, outcome and survival were compared to non-MDT patients retrieved from a prospectively maintained database with propensity score matching.

Results

Propensity-score matching (PSM) was carried out to balance available covariates, resulting in 58 MDT patients vs. 111 non-MDT patients. Overall survival and variceal rebleed was compared between the two groups. The rate of variceal rebleed was significantly higher in the non-MDT group, while no difference in overall survival was observed.

Conclusions

This study is the first to investigate the role of a multidisciplinary team in the management of gastroesophageal varices secondary to portal hypertension. Patients treated based on MDT clinic recommendations had a significantly lower risk for variceal rebleed.
Q fever seroprevalence in parturient women: the EQRUN cross-sectional study on Reunion Island
Authors: Jaubert Julien , Atiana Laura , Larrieu Sophie , De Vos Philippe , Somon-Payet Claudine , Porcherat Sylvaine , Mboussou Yoan , Naze Florence , Picot Sandrine , Boukerrou Malik , Robillard Pierre-Yves , Gérardin Patrick
Published: April 2020

Background

Q fever (Coxiella burnetii infection) has been associated with adverse perinatal outcomes. After investigating the obstetrical importance of Q fever on Reunion island and demonstrating an association between incident Q fever and miscarriage, we conducted a cross-sectional serosurvey to assess the prevalence of Coxiella burnetii infection among parturient women.

Methods

Between January 9 and July 24, 2014, within the level-4 maternity of Saint Pierre hospital and the level-1 maternity of Le Tampon, we proposed to screen all parturient women for Coxiella burnetii serology. Seropositivity was defined using indirect immunofluorescence for a dilution of phase 2 IgG titre ≥1:64. Further dilutions were chosen to discriminate recent or active infections from past or prevalent infections (< 1:128) and classify these as either possible (1:128), or probable (≥1:256). Recurrent miscarriage, stillbirth, preterm birth, small-for-gestational as well as a composite outcome of these adverse pregnancy outcomes were compared according to seropositivity using bivariate analysis or propensity score matching of seropositive and seronegative women on confounding factors.

Results

Among 1112 parturient women screened for Q fever over this 7-month period, 203 (18.3%) were seropositive. Overall weighted seroprevalence was of 20.1% (95%CI, 17.7–22.5%). Weighted seroprevalence of probable infections was 4.7% (95%CI 3.4–5.9%), while > 90% of positive serologies corresponded to past infections or false positives. Seropositivity was associated with none of the abovementioned adverse perinatal outcomes, whether in unpaired or matched analyses on propensity score.

Conclusion

The magnitude and the pattern of seroprevalence suggest that Q fever is endemic on Reunion island. In this context, we found no significant contribution of prevalent Coxiella burnetii infection to adverse pregnancy outcomes. Although reassuring, these data put in our endemic context, with a previously demonstrated increased risk of incident Q fever associated miscarriage, encourage us to protect pregnant women against the risk of new infection, periconceptional or early in pregnancy.
Ombitasvir/paritaprevir/ritonavir & dasabuvir ± ribavirin following protease inhibitors failure - a prospective multi-centre trial
Authors: Deutsch Liat , Houri Inbal , Ben-Ari Ziv , Shlomai Amir , Veitsman Ella , Cohen-Ezra Oranit , Issachar Assaf , Mor Orna , Gozlan Yael , Bruck Rafael , Menachem Yoram , Zelber-Sagi Shira , Katchman Helena , Shibolet Oren
Published: April 2020

Background

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease and hepatocellular carcinoma. Treatment with first generation protease inhibitors (PI) + peg-interferon (pegIFN) and ribavirin (RBV) achieved sustained virologic response (SVR) rates of 65–75% but was associated with multiple side effects. The aim of this study was to evaluate safety and efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir (3D) ± RBV in HCV genotype 1 patients that failed previous treatment with first generation PIs.

Methods

An investigator-initiated, open-label, multi-centre clinical trial. HCV Genotype 1 patients who were previously null/partial responders or relapsers to telaprevir, boceprevir or simepravir+pegIFN/RBV and met eligibility criteria were included. 3D ± RBV were administrated for 12 or 24 weeks according to label. The primary outcome was antiviral response (SVR12); Secondary outcomes were patient reported outcomes, adverse events and resistance associated variants.

Results

Thirty-nine patients initiated treatment according to study protocol (59% men, age 54.0 ± 8.7 years, BMI 28.7 ± 4.5 kg/m2). Thirty-seven (94.9%) completed the study. Thirty-five patients had genotype 1b (9 cirrhotics) and 4 had genotype 1a (2 cirrhotics). Intention-to-treat SVR12 was 92.3% and per-protocol SVR12 was 97.3%. The rate of advanced fibrosis (FibroScan® score F3–4) declined from 46.2 to 25.7% (P = 0.045). Abnormal ALT levels declined from 84.6 to 8.6% (P < 0.001). Seven patients (17.9%) experienced serious adverse events (3 Psychiatric admissions, 1 pneumonia, 1 ankle fracture, 2 palpitations), and 12 patients (30.8%) experienced self-reported adverse events, mostly weakness.

Conclusion

3D ± RBV is safe and effective in achieving SVR among patients with HCV genotype 1 who failed previous first-generation PI treatment.

Trial registration

NCT02646111 (submitted to ClinicalTrials.gov, December 28, 2015).
Case report: adult onset diabetes with partial pancreatic agenesis and congenital heart disease due to a de novo GATA6 mutation
Authors: Sanchez-Lechuga Begona , Saqlain Muhammad , Ng Nicholas , Colclough Kevin , Woods Conor , Byrne Maria
Published: April 2020

Background

Mutations in GATA6 are the most frequent cause of pancreatic agenesis. Most cases present with neonatal diabetes mellitus.

Case presentation

The case was a female born after an uncomplicated pregnancy and delivery in a non-consanguineous family (3.59 kg, 70th percentile). Severe cardiac malformations were diagnosed at two and a half months old. No hyperglycaemic episodes were recorded in the neonatal period. Diabetes was diagnosed at 21 years due to the detection of incidental glycosuria. She had a low but detectable C-peptide level at diagnosis. Anti-GAD and Islet-cell antibodies were negative and she failed oral hypoglycaemic therapy and was started on insulin. Abdominal MRI revealed the absence of most of the neck, body, and tail of pancreas with normal pancreas elastase levels. Criteria for type 1 or type 2 diabetes were not fulfilled, therefore a next generation sequencing (NGS) panel was performed. A novel heterozygous pathogenic GATA6 mutation (p.Tyr235Ter) was identified. The GATA6 variant was not detected in her parents, implying that the mutation had arisen de novo in the proband.

Conclusion

Rarely GATA6 mutations can cause adult onset diabetes. This report highlights the importance of screening the GATA6 gene in patients with adult-onset diabetes, congenital cardiac defects and pancreatic agenesis with no first-degree family history of diabetes. It also emphasizes the importance of genetic counselling in these patients as future offspring will be at risk of inheriting the variant and developing GATA6 anomalies.
Synergistic enhancement of efficacy of platinum drugs with verteporfin in ovarian cancer cells
Authors: Dasari Venkata Ramesh , Carey David J. , Gogoi Radhika
Published: April 2020

Background

Epithelial ovarian cancers (EOCs) comprises the majority of malignant ovarian neoplasms. Combination treatment with chemotherapeutic agents seems to be a promising strategy in ovarian cancer (OVCA) patients in order to overcome drug resistance. In this in vitro study, we investigated the therapeutic efficacy of verteporfin (VP) alone and in combination with cisplatin (CDDP), carboplatin (CP) and paclitaxel (Taxol). The main objectives of this study are to determine the nature of interactions between VP and CDDP/CP/Taxol and to understand the mechanism of action of VP in OVCA cells.

Methods

The efficacy of VP on cell proliferation, cytotoxicity, invasion and clonogenic capacity was assayed in CDDP-sensitive (COV504, OV-90) and CDDP-resistant (A2780Cis) cell lines. The cytotoxic effects of drugs either alone or in combination were evaluated using MTT assay and Cell Viability Blue assay. The effects of drugs on the metabolic functions were studied using matrigel invasion assay and clonogenic assay. Immunoblot analysis was carried out to investigate changes in YAP and cell cycle genes. Changes in the cytokines due to drug treatments were analyzed using a cytokine array.

Results

Treatment with VP inhibited cell proliferation, invasion and increased cytotoxicity of OVCA cells. We observed that VP chemosensitized CDDP-resistant cells, even at lower doses. When added either in constant or non-constant ratios, VP produced synergistic effects in combination with CDDP/CP/Taxol. A cytokine array identified upregulation of cytokines in OVCA cells that were inhibited by VP treatment.

Conclusions

Either in cisplatin-resistant cell lines or cisplatin-sensitive cell lines, VP proves to be more efficient in inhibiting cell proliferation and inducing cytotoxicity. Our results suggest that novel combinations of VP with CDDP or CP or Taxol might be an attractive therapeutic strategy to enhance OVCA chemosensitivity. The fact that lower doses of VP are effective in chemosensitizing the CDDP-resistant cells, might ultimately lead to the development of an innovative combination therapy for the treatment of OVCA patients.
Clinical performance evaluation of the Idylla™ EGFR Mutation Test on formalin-fixed paraffin-embedded tissue of non-small cell lung cancer
Authors: Delgado-García Mercedes , Weynand Birgit , Gómez-Izquierdo Lourdes , Hernández María José , Blanco Ángela María , Varela Mar , Matias-Guiu Xavier , Nadal Ernest , Márquez-Lobo Bélgica , Alarcão Ana , de Álava Enrique , Biscuola Michele
Published: April 2020

Background

Detection of epidermal growth factor receptor (EGFR)mutations in exons 18–21 is recommended in all patients with advanced Non-small-cell lung carcinoma due to the demonstrated efficiency of the standard therapy with tyrosine kinase inhibitors inEGFR-mutated patients. Therefore, choosing a suitable technique to testEGFRmutational status is crucial to warrant a valid result in a short turnaround time using the lowest possible amount of tissue material.

The Idylla™EGFRMutation Test is a simple, fast and reliable method designed for the detection ofEGFRmutations from formalin-fixed paraffin-embedded samples.

The aim of this study was the Clinical Performace Evaluation of the Idylla™ EGFR Mutation Test on the Idylla™ System.

Methods

EGFRmutational status was determined on 132 archived formalin-fixed paraffin-embedded tissue sections with Idylla™ technology. Results were compared with the results previously obtained by routine method in the reference lab (Therascreen®EGFRRGQ PCR v2, Qiagen in Molecular Pathology lab, Hospital Universitario Virgen del Rocío de Sevilla).

Results

The overall agreement between results obtained with the Idylla™EGFRMutation Test and the Comparator test method was 95.38% (with 1-sided 95% lower limit of 91.7%) showing Positive Diagnostic Agreement of 93.22% and Negative Diagnostic Agreement of 97.18%, with a Limit Of Detection ≤5%.

Conclusions

The Idylla™EGFRMutation Test passed its clinical validity performance characteristics for accuracy.
Value of digital mammography in predicting lymphovascular invasion of breast cancer
Authors: Liu Zhuangsheng , Li Ruqiong , Liang Keming , Chen Junhao , Chen Xiangmeng , Li Xiaoping , Li Ronggang , Zhang Xin , Yi Lilei , Long Wansheng
Published: April 2020

Background

Lymphovascular invasion (LVI) has never been revealed by preoperative scans. It is necessary to use digital mammography in predicting LVI in patients with breast cancer preoperatively.

Methods

Overall 122 cases of invasive ductal carcinoma diagnosed between May 2017 and September 2018 were enrolled and assigned into the LVI positive group (n = 42) and the LVI negative group (n = 80). Independent t-test and χ2 test were performed.

Results

Difference in Ki-67 between the two groups was statistically significant (P = 0.012). Differences in interstitial edema (P = 0.013) and skin thickening (P = 0.000) were statistically significant between the two groups. Multiple factor analysis showed that there were three independent risk factors for LVI: interstitial edema (odds ratio [OR] = 12.610; 95% confidence interval [CI]: 1.061–149.922; P = 0.045), blurring of subcutaneous fat (OR = 0.081; 95% CI: 0.012–0.645; P = 0.017) and skin thickening (OR = 9.041; 95% CI: 2.553–32.022; P = 0.001).

Conclusions

Interstitial edema, blurring of subcutaneous fat, and skin thickening are independent risk factors for LVI. The specificity of LVI prediction is as high as 98.8% when the three are used together.