bluuebunny/crossref_metadata_2025 huggingface dataset:
Is bronchiectasis really a disease?
Authors: Shteinberg Michal , Flume Patrick A. , Chalmers James D.
Published: January 2020

The definition of a disease requires that distinguishing signs and symptoms are present that are common, and that the constellation of signs and symptoms differentiate the condition from other causes. In bronchiectasis, anatomical changes, airways inflammation and airway infection are the distinguishing features that are common to this disease. However, bronchiectasis is a heterogenous disease: signs and symptoms are shared with other airway diseases, there are multiple aetiologies and certain phenotypes of bronchiectasis have distinct clinical and laboratory features that are not common to all people with bronchiectasis. Furthermore, response to therapeutic interventions in clinical trials is not uniform. The concept of bronchiectasis as a treatable trait has been suggested, but this may be too restrictive in view of the heterogeneity of bronchiectasis. It is our opinion that bronchiectasis should be defined as a disease in its own right, but one that shares several pathophysiological features and “treatable traits” with other airway diseases. These traits define the large heterogeneity in the pathogenesis and clinical features and suggest a more targeted approach to therapy.
Facile Synthesis of Eggshell Membrane-Templated Au/CeO2 3D Nanocomposite Networks for Nonenzymatic Electrochemical Dopamine Sensor
Authors: Liu Qingquan , Chen Xiaoyu , Kang Ze-Wen , Zheng Chaohui , Yang Da-Peng
Published: January 2020

Dopamine acts as a neurotransmitter to regulate a variety of physiological functions of the central nervous system. Thus, the fabrication of electrochemical active nanomaterials for sensitive dopamine detection is extremely important for human health. Herein, we constructed a highly efficient dopamine nonenzymatic biosensor using eggshell membrane (ESM) as a 3D network-like carrier-loaded Au and CeO2 nanocomposites. This approach has led to the uniform distribution of CeO2 and Au nanoparticles on the surface of ESM. The structure and properties of the as-prepared ESM templated Au/CeO2 (ESM-AC) nanocomposites were characterized. The electrochemical properties of non-enzymatic oxidation of dopamine by ESM-AC electrode were studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The detection limit of the ESM-AC modified electrode for dopamine is 0.26 μM with a linear range from 0.1 to 10 mM. The ESM-AC-modified electrode performs a higher catalytic activity for dopamine electrocatalytic oxidation than that ESM-templated CeO2 (ESM-C) electrode, which is mainly due to the unique structure of ESM and more active sites provided from Au. Collectively, this biological waste-ESM provides a cheap and unique template for the preparation of 3D network-like nanostructures and expands the application in electrochemical dopamine detection.

Graphical abstract

ESM-AC nanocomposites prepared from biological waste was successfully modified on the surface of glassy carbon electrode and a dopamine-based electrochemical biosensor was constructed.
pSpatiocyte: a high-performance simulator for intracellular reaction-diffusion systems
Authors: Arjunan Satya N.V. , Miyauchi Atsushi , Iwamoto Kazunari , Takahashi Koichi
Published: January 2020

Background

Studies using quantitative experimental methods have shown that intracellular spatial distribution of molecules plays a central role in many cellular systems. Spatially resolved computer simulations can integrate quantitative data from these experiments to construct physically accurate models of the systems. Although computationally expensive, microscopic resolution reaction-diffusion simulators, such as Spatiocyte can directly capture intracellular effects comprising diffusion-limited reactions and volume exclusion from crowded molecules by explicitly representing individual diffusing molecules in space. To alleviate the steep computational cost typically associated with the simulation of large or crowded intracellular compartments, we present a parallelized Spatiocyte method called pSpatiocyte.

Results

The new high-performance method employs unique parallelization schemes on hexagonal close-packed (HCP) lattice to efficiently exploit the resources of common workstations and large distributed memory parallel computers. We introduce a coordinate system for fast accesses to HCP lattice voxels, a parallelized event scheduler, a parallelized Gillespie’s direct-method for unimolecular reactions, and a parallelized event for diffusion and bimolecular reaction processes. We verified the correctness of pSpatiocyte reaction and diffusion processes by comparison to theory. To evaluate the performance of pSpatiocyte, we performed a series of parallelized diffusion runs on the RIKEN K computer. In the case of fine lattice discretization with low voxel occupancy, pSpatiocyte exhibited 74% parallel efficiency and achieved a speedup of 7686 times with 663552 cores compared to the runtime with 64 cores. In the weak scaling performance, pSpatiocyte obtained efficiencies of at least 60% with up to 663552 cores. When executing the Michaelis-Menten benchmark model on an eight-core workstation, pSpatiocyte required 45- and 55-fold shorter runtimes than Smoldyn and the parallel version of ReaDDy, respectively. As a high-performance application example, we study the dual phosphorylation-dephosphorylation cycle of the MAPK system, a typical reaction network motif in cell signaling pathways.

Conclusions

pSpatiocyte demonstrates good accuracies, fast runtimes and a significant performance advantage over well-known microscopic particle methods in large-scale simulations of intracellular reaction-diffusion systems. The source code of pSpatiocyte is available at https://spatiocyte.org.
Unsupervised inference of implicit biomedical events using context triggers
Authors: Chung Jin-Woo , Yang Wonsuk , Park Jong C.
Published: January 2020

Background

Event extraction from the biomedical literature is one of the most actively researched areas in biomedical text mining and natural language processing. However, most approaches have focused on events within single sentence boundaries, and have thus paid much less attention to events spanning multiple sentences. The Bacteria-Biotope event (BB-event) subtask presented in BioNLP Shared Task 2016 is one such example; a significant amount of relations between bacteria and biotope span more than one sentence, but existing systems have treated them as false negatives because labeled data is not sufficiently large enough to model a complex reasoning process using supervised learning frameworks.

Results

We present an unsupervised method for inferring cross-sentence events by propagating intra-sentence information to adjacent sentences using context trigger expressions that strongly signal the implicit presence of entities of interest. Such expressions can be collected from a large amount of unlabeled plain text based on simple syntactic constraints, helping to overcome the limitation of relying only on a small number of training examples available. The experimental results demonstrate that our unsupervised system extracts cross-sentence events quite well and outperforms all the state-of-the-art supervised systems when combined with existing methods for intra-sentence event extraction. Moreover, our system is also found effective at detecting long-distance intra-sentence events, compared favorably with existing high-dimensional models such as deep neural networks, without any supervised learning techniques.

Conclusions

Our linguistically motivated inference model is shown to be effective at detecting implicit events that have not been covered by previous work, without relying on training data or curated knowledge bases. Moreover, it also helps to boost the performance of existing systems by allowing them to detect additional cross-sentence events. We believe that the proposed model offers an effective way to infer implicit information beyond sentence boundaries, especially when human-annotated data is not sufficient enough to train a robust supervised system.
TopoFilter: a MATLAB package for mechanistic model identification in systems biology
Authors: Rybiński Mikołaj , Möller Simon , Sunnåker Mikael , Lormeau Claude , Stelling Jörg
Published: January 2020

Background

To develop mechanistic dynamic models in systems biology, one often needs to identify all (or minimal) representations of the biological processes that are consistent with experimental data, out of a potentially large set of hypothetical mechanisms. However, a simple enumeration of all alternatives becomes quickly intractable when the number of model parameters grows. Selecting appropriate dynamic models out of a large ensemble of models, taking the uncertainty in our biological knowledge and in the experimental data into account, is therefore a key current problem in systems biology.

Results

The TopoFilter package addresses this problem in a heuristic and automated fashion by implementing the previously described topological filtering method for Bayesian model selection. It includes a core heuristic for searching the space of submodels of a parametrized model, coupled with a sampling-based exploration of the parameter space. Recent developments of the method allow to balance exhaustiveness and speed of the model space search, to efficiently re-sample parameters, to parallelize the search, and to use custom scoring functions. We use a theoretical example to motivate these features and then demonstrate TopoFilter’s applicability for a yeast signaling network with more than 250’000 possible model structures.

Conclusions

TopoFilter is a flexible software framework that makes Bayesian model selection and reduction efficient and scalable to network models of a complexity that represents contemporary problems in, for example, cell signaling. TopoFilter is open-source, available under the GPL-3.0 license at https://gitlab.com/csb.ethz/TopoFilter. It includes installation instructions, a quickstart guide, a description of all package options, and multiple examples.
Correction to: Identifying miRNA synergism using multiple-intervention causal inference
Authors: Zhang Junpeng , Pham Vu Viet Hoang , Liu Lin , Xu Taosheng , Truong Buu , Li Jiuyong , Rao Nini , Le Thuc Duy
Published: January 2020

After publication of this supplement article [1], it was brought to our attention that the Fig. 3 was incorrect. The correct Fig. 3 is as below:
Absence of reproduction-immunity trade-off in male Drosophila melanogaster evolving under differential sexual selection
Authors: Syed Zeeshan Ali , Gupta Vanika , Arun Manas Geeta , Dhiman Aatashi , Nandy Bodhisatta , Prasad Nagaraj Guru
Published: January 2020

Background

The theory of trade-off suggests that limited resources should lead to trade-off in resource intensive traits such as, immunity related and sexually selected traits in males. Alternatively, sexual exaggerations can also act as an honest indicator of underlying immunocompetence, leading to positive correlations between these traits. Evidences in support of either hypothesis in invertebrates are equivocal. Whereas several studies have addressed this question, few have used naturally occurring pathogens and realized post infection realized immunity (e.g., survivorship) to assay the fitness correlations between these two sets of traits.

Results

Adopting an experimental evolution approach, we evolved replicate populations of Drosophila melanogaster under high and low sexual selection regimes for over a hundred generations and found the following in virgin and mated males in three separate assays:

Post infection survivorship against two natural pathogens - Pseudomonas entomophila (Pe) and Staphylococcus succinus (Ss): Mated males survived better against Pe, but were no different than virgins against Ss.

Bacterial clearance ability against a third natural pathogen Providencia rettgeri (Pr): Mated males had significantly lower CFUs than virgins.

However, sexual selection history had no effect on realized immunity of either virgin or mated males.

Conclusion

We show that while mating can affect realized immunity in a pathogen specific way, sexual selection did not affect the same. The results highlight that complex polygenic traits such as immunity and reproductive traits not necessarily evolve following a binary trade-off model. We also stress the importance natural pathogens while studying sexual selection-immunity correlations.
New insights on intercontinental origins of paternal lineages in Northeast Brazil
Authors: Schaan Ana Paula , Gusmão Leonor , Jannuzzi Juliana , Modesto Antonio , Amador Marcos , Marques Diego , Rabenhorst Silvia Helena , Montenegro Raquel , Lopes Thayson , Yoshioka France Keiko , Pinto Giovanny , Santos Sidney , Costa Lorenna , Silbiger Vivian , Ribeiro-dos-Santos Ândrea
Published: January 2020

Background

The current Brazilian population is the product of centuries of admixture between intercontinental founding groups. Although previous results have revealed a heterogeneous distribution of mitochondrial lineages in the Northeast region, the most targeted by foreign settlers during the sixteenth century, little is known about the paternal ancestry of this particular population. Considering historical records have documented a series of territorial invasions in the Northeast by various European populations, we aimed to characterize the male lineages found in Brazilian individuals in order to discover to what extent these migrations have influenced the present-day gene pool. Our approach consisted of employing four hierarchical multiplex assays for the investigation of 45 unique event polymorphisms in the non-recombining portion of the Y-chromosome of 280 unrelated men from several Northeast Brazilian states.

Results

Primary multiplex results allowed the identification of six major haplogroups, four of which were screened for downstream SNPs and enabled the observation of 19 additional lineages. Results reveal a majority of Western European haplogroups, among which R1b-S116* was the most common (63.9%), corroborating historical records of colonizations by Iberian populations. Nonetheless, FST genetic distances show similarities between Northeast Brazil and several other European populations, indicating multiple origins of settlers. Regarding Native American ancestry, our findings confirm a strong sexual bias against such haplogroups, which represented only 2.5% of individuals, highly contrasting previous results for maternal lineages. Furthermore, we document the presence of several Middle Eastern and African haplogroups, supporting a complex historical formation of this population and highlighting its uniqueness among other Brazilian regions.

Conclusions

We performed a comprehensive analysis of the major Y-chromosome lineages that form the most dynamic migratory region from the Brazilian colonial period. This evidence suggests that the ongoing entry of European, Middle Eastern, and African males in the Brazilian Northeast, since at least 500 years, was significantly responsible for the present-day genetic architecture of this population.
The evolutionary arms race between transposable elements and piRNAs in Drosophila melanogaster
Authors: Luo Shiqi , Zhang Hong , Duan Yuange , Yao Xinmin , Clark Andrew G. , Lu Jian
Published: January 2020

Background

Thepiwi-interacting RNAs (piRNAs) are small non-coding RNAs that specifically repress transposable elements (TEs) in the germline ofDrosophila. Despite our expanding understanding of TE:piRNA interaction, whether there is an evolutionary arms race between TEs and piRNAs was unclear.

Results

Here, we studied the population genomics of TEs and piRNAs in the worldwide strains ofD. melanogaster. By conducting a correlation analysis between TE contents and the abundance of piRNAs from ovaries of representative strains ofD. melanogaster, we find positive correlations between TEs and piRNAs in six TE families. Our simulations further highlight that TE activities and the strength of purifying selection against TEs are important factors shaping the interactions between TEs and piRNAs. Our studies also suggest that the de novo generation of piRNAs is an important mechanism to repress the newly invaded TEs.

Conclusions

Our results revealed the existence of an evolutionary arms race between the copy numbers of TEs and the abundance of antisense piRNAs at the population level. Although the interactions between TEs and piRNAs are complex and many factors should be considered to impact their interaction dynamics, our results suggest the emergence, repression specificity and strength of piRNAs on TEs should be considered in studying the landscapes of TE insertions inDrosophila. These results deepen our understanding of the interactions between piRNAs and TEs, and also provide novel insights into the nature of genomic conflicts of other forms.
Evaluation of genetic diversity, agronomic traits, and anthracnose resistance in the NPGS Sudan Sorghum Core collection
Authors: Cuevas Hugo E. , Prom Louis K.
Published: January 2020

Background

The United States Department of Agriculture (USDA) National Plant Germplasm System (NPGS) sorghum core collection contains 3011 accessions randomly selected from 77 countries. Genomic and phenotypic characterization of this core collection is necessary to encourage and facilitate its utilization in breeding programs and to improve conservation efforts. In this study, we examined the genome sequences of 318 accessions belonging to the NPGS Sudan sorghum core set, and characterized their agronomic traits and anthracnose resistance response.

Results

We identified 183,144 single nucleotide polymorphisms (SNPs) located within or in proximity of 25,124 annotated genes using the genotyping-by-sequencing (GBS) approach. The core collection was genetically highly diverse, with an average pairwise genetic distance of 0.76 among accessions. Population structure and cluster analysis revealed five ancestral populations within the Sudan core set, with moderate to high level of genetic differentiation. In total, 171 accessions (54%) were assigned to one of these populations, which covered 96% of the total genomic variation. Genome scan based on Tajima’s D values revealed two populations under balancing selection. Phenotypic analysis showed differences in agronomic traits among the populations, suggesting that these populations belong to different ecogeographical regions. A total of 55 accessions were resistant to anthracnose; these accessions could represent multiple resistance sources. Genome-wide association study based on fixed and random model Circulating Probability (farmCPU) identified genomic regions associated with plant height, flowering time, panicle length and diameter, and anthracnose resistance response. Integrated analysis of the Sudan core set and sorghum association panel indicated that a large portion of the genetic variation in the Sudan core set might be present in breeding programs but remains unexploited within some clusters of accessions.

Conclusions

The NPGS Sudan core collection comprises genetically and phenotypically diverse germplasm with multiple anthracnose resistance sources. Population genomic analysis could be used to improve screening efforts and identify the most valuable germplasm for breeding programs. The new GBS data set generated in this study represents a novel genomic resource for plant breeders interested in mining the genetic diversity of the NPGS sorghum collection.
Comprehensive analysis of the Gossypium hirsutum L. respiratory burst oxidase homolog (Ghrboh) gene family
Authors: Wang Wei , Chen Dongdong , Liu Dan , Cheng Yingying , Zhang Xiaopei , Song Lirong , Hu Mengjiao , Dong Jie , Shen Fafu
Published: January 2020

Background

Plant NADPH oxidase (NOX), also known as respiratory burst oxidase homolog (rboh), encoded by the rboh gene, is a key enzyme in the reactive oxygen species (ROS) metabolic network. It catalyzes the formation of the superoxide anion (O2•−), a type of ROS. In recent years, various studies had shown that members of the plant rboh gene family were involved in plant growth and developmental processes as well as in biotic and abiotic stress responses, but little is known about its functional role in upland cotton.

Results

In the present study, 26 putative Ghrboh genes were identified and characterized. They were phylogenetically classified into six subfamilies and distributed at different densities across 18 of the 26 chromosomes or scaffolds. Their exon-intron structures, conserved domains, synteny and collinearity, gene family evolution, regulation mediated by cis-acting elements and microRNAs (miRNAs) were predicted and analyzed. Additionally, expression profiles of Ghrboh gene family were analyzed in different tissues/organs and at different developmental stages and under different abiotic stresses, using RNA-Seq data and real-time PCR. These profiling studies indicated that the Ghrboh genes exhibited temporal and spatial specificity with respect to expression, and might play important roles in cotton development and in stress tolerance through modulating NOX-dependent ROS induction and other signaling pathways.

Conclusions

This comprehensive analysis of the characteristics of the Ghrboh gene family determined features such as sequence, synteny and collinearity, phylogenetic and evolutionary relationship, expression patterns, and cis-element- and miRNA-mediated regulation of gene expression. Our results will provide valuable information to help with further gene cloning, evolutionary analysis, and biological function analysis of cotton rbohs.
Tuberomics: a molecular profiling for the adaption of edible fungi (Tuber magnatum Pico) to different natural environments
Authors: Vita Federico , Giuntoli Beatrice , Bertolini Edoardo , Taiti Cosimo , Marone Elettra , D’Ambrosio Chiara , Trovato Emanuela , Sciarrone Danilo , Zoccali Mariosimone , Balestrini Raffaella , Scaloni Andrea , Mondello Luigi , Mancuso Stefano , Alessio Massimo , Alpi Amedeo
Published: January 2020

Background

Truffles are symbiotic fungi that develop underground in association with plant roots, forming ectomycorrhizae. They are primarily known for the organoleptic qualities of their hypogeous fruiting bodies. Primarily,Tuber magnatumPico is a greatly appreciated truffle species mainly distributed in Italy and Balkans. Its price and features are mostly depending on its geographical origin. However, the genetic variation withinT. magnatumhas been only partially investigated as well as its adaptation to several environments.

Results

Here, we applied an integrated omic strategy toT. magnatumfruiting bodies collected during several seasons from three different areas located in the North, Center and South of Italy, with the aim to distinguish them according to molecular and biochemical traits and to verify the impact of several environments on these properties. With the proteomic approach based on two-dimensional electrophoresis (2-DE) followed by mass spectrometry, we were able to identify proteins specifically linked to the sample origin. We further associated the proteomic results to an RNA-seq profiling, which confirmed the possibility to differentiate samples according to their source and provided a basis for the detailed analysis of genes involved in sulfur metabolism. Finally, geographical specificities were associated with the set of volatile compounds produced by the fruiting bodies, as quantitatively and qualitatively determined through proton transfer reaction-mass spectrometry (PTR-MS) and gas-chromatography-mass spectrometry (GC-MS). In particular, a partial least squares-discriminant analysis (PLS-DA) model built from the latter data was able to return high confidence predictions of sample source.

Conclusions

Results provide a characterization of white fruiting bodies by a wide range of different molecules, suggesting the role for specific compounds in the responses and adaptation to distinct environments.
The effect of brief pre-anesthetic exercise therapy of jaw and neck joints on mouth opening, neck extension, and intubation conditions during induction of general anesthesia: a randomized controlled trial
Authors: Lee Sue Young , Bae Sung Il , Do Sang-Hwan , Sohn Ju-Tae , Park Jin-Woo
Published: January 2020

Background

The effort to improve tracheal intubation process is clinically valuable. We hypothesized that a preoperative brief exercise therapy would increase mouth opening and neck extension, enhancing intubation conditions during general anesthesia.

Methods

Patients undergoing general anesthesia were randomized into two groups. The exercise group performed the exercise regimen including masseter muscle massage and stretching of jaw and neck joints before anesthetic induction, while the control did not. Before (baseline) and after the intervention, we evaluated Mallampati score, mouth aperture size, and sternomental distance. After tracheal intubation, intubation difficulty scale with direct laryngoscope and oropharyngeal soft tissue injury were also evaluated.

Results

A total of 138 patients completed the analysis (control = 68, exercise = 70). Baseline characteristics did not differ between groups. At anesthetic induction, there was a significant difference in Mallampati score between the two groups (P = 0.039) and the incidence of Mallampati scores of 1 was higher in the exercise group (odds ratio [95% CI]: 2.1 [1.0–4.3], P = 0.043). Mouth opening after the intervention was greater in the exercise group than in the control group (estimated difference [95% CI]: − 2.4 [− 4.8 – -0.1], P = 0.042) and sternomental distance was similar between the two groups (estimated difference [95% CI]: − 3.7 [− 9.0–1.7, P = 0.175). The exercise group showed less soft tissue injuries (odds ratio [95% CI]: 0.2 [0.1–0.8], P = 0.009), however, intubation difficulty scale did not differ between the study groups (P = 0.112).

Conclusions

The brief pre-anesthetic exercise improved intubation conditions and enabled faster tracheal intubation with less injury to oropharyngeal soft tissue.

Trial registration

Clinical Research Information Service (registration number: KCT0002618), registered at December 28, 2017.
Evaluation of an ambulatory geriatric rehabilitation program - results of a matched cohort study based on claims data
Authors: Kiel Simone , Zimak Carolin , Chenot Jean-François , Schmidt Carsten Oliver
Published: January 2020

Background

Ambulatory geriatric rehabilitation (AGR) is a multidisciplinary outpatient prevention program designed to decrease hospitalisation and dependence on nursing care in multimorbid patients ≥70 years of age. We evaluated the effectiveness of AGR compared to usual care on progression of nursing care levels, nursing home admissions, hospital admissions, incident fractures, mortality rate and total cost of care during a one-year follow-up period.

Methods

Analyses were based on claims data from the health insurance company AOK Nordost. Propensity Score matching was used to match 4 controls to each person receiving the AGR intervention.

Results

A total of 632 AGR participants and 2528 matched controls were included. The standardized mean difference of matching variables between cases and controls was small (mean: + 1.4%; range: − 4.4/3.9%). In AGR patients, the progression of nursing care levels (+ 2.2%, 95%CI: − 0.9 /5.3), nursing home admissions (+ 1.7%, 95%CI: − 0.1/3.5), hospital admissions (+ 1.1%, 95%CI: − 3.2/5.4), incident fractures (+ 11.1%, 95%CI: 7.3/15) and mortality rate (+ 1.2%, p = 0.20) showed a less favourable course compared to controls. The average total cost per AGR participant was lower than in the control group (− 353€, 95%CI: − 989€/282€), not including costs for AGR.

Conclusions

Analysis based on claims data showed no clinical benefit from AGR intervention regarding the investigated outcomes. The slightly worse outcomes may reflect limitations in matching based on claims data, which may have insufficiently reflected morbidity and psychosocial factors. It is possible that the intervention group had poorer health status at baseline compared to the control group.

Trial registration

German Clinical Trials Register DRKS00008926, registered 29.07.2015.
Bioinformatics analysis on multiple Gene Expression Omnibus datasets of the hepatitis B virus infection and its response to the interferon-alpha therapy
Authors: Zhu Zebin , Huang Shanzhou , Zhang Yixi , Sun Chengjun , Tang Yunhua , Zhao Qiang , Zhou Qi , Ju Weiqiang , He Xiaoshun
Published: January 2020

Background

Hepatitis B virus (HBV) infection is a global health problem and interferon-alpha (IFN-α) is one of the effective therapies. However, little is known about the genetic background of the HBV infection or the genetic determinants of the IFN-α treatment response. Thus, we aim to explore the possible molecular mechanisms of HBV infection and its response to the IFN-α therapy with a comprehensive bioinformatics analysis.

Methods

The Gene Expression Omnibus datasets (GSE83148, GSE84044 and GSE66698) were collected and the differentially expressed genes (DEGs), key biological processes and intersecting pathways were analyzed. The expression of the co-expressed DEGs in the clinical samples was verified by quantitative real time polymerase chain reaction (qRT-PCR).

Results

Analysis of all the 3 datasets revealed that there were eight up-regulated and one down-regulated co-expressed DEGs following the HBV infection and after IFN-α treatment. In clinical samples, the mRNA level of HKDC1, EPCAM, GSN, ZWINT and PLD3 were significantly increased, while, the mRNA level of PLEKHA2 was significantly decreased in HBV infected liver tissues compared to normal liver tissues. PI3K-Akt signaling pathway, focal adhesion, HTLV-I infection, cytokine-cytokine receptor interaction, metabolic pathways, NF-κB signaling pathway were important pathways associated with the HBV infection and the response of IFN-α treatment.

Conclusions

The co-expressed genes, common biological processes and intersecting pathways identified in the study might play an important role in HBV infection and response of IFN-α treatment. The dysregulated genes may act as novel biomarkers and therapeutic targets for HBV.
Relationship between vascular endothelial growth factor -2578C > a gene polymorphism and lung cancer risk: a meta-analysis
Authors: Zhao Hui-liu , Yu Jia-hua , Huang Ling-sha , Li Pei-zhang , Lao Ming , Zhu Bo , Ou Chao
Published: January 2020

Background

Several reports were published on the relationship between the vascular endothelial growth factor (VEGF) -2578C > A gene polymorphism and lung cancer risk; however, the results are debatable. This meta-analysis was conducted to assess the relationship between VEGF -2578C > A gene polymorphism and lung cancer risk.

Methods

The associated literatures were identified on the 1st of September 2018 from CBM-disc (China Biological Medicine Database) and PubMed.

Result

A total of 14 reports were recruited into our meta-analysis to assess the association between VEGF -2578C > A gene polymorphism and lung cancer susceptibility. There was a marked association between VEGF -2578C > A A allele / CC genotype and lung cancer risk in overall and Asian populations (overall populations: A allele: OR = 1.26, 95% CI: 1.08–1.46, P = 0.003; CC genotype: OR = 0.72, 95% CI: 0.54–0.95, P = 0.02; Asians: A allele: OR = 1.33, 95% CI: 1.15–1.55, P = 0.0002; CC genotype: OR = 0.68, 95% CI: 0.50–0.93, P = 0.01). However, VEGF -2578C > A gene polymorphism was not associated with the risk of lung cancer in Caucasians.

Conclusion

VEGF -2578C > A A allele / CC genotype is associated with the lung cancer susceptibility in Asians and in overall populations.
Linking disease registries and nationwide healthcare administrative databases: the French renal epidemiology and information network (REIN) insight
Authors: Raffray Maxime , Bayat Sahar , Lassalle Mathilde , Couchoud Cécile
Published: January 2020

Background

Record linkage is increasingly used in health research worldwide. Combining the patient information available in healthcare, administrative and clinical databases broadens the research perspectives, particularly for chronic diseases. Recent guidelines highlight the need for transparency on the used record linkage processes and the extracted data to be used by researchers.

Methods

Therefore, the aim of this study was to describe the deterministic iterative approach used to link the French Epidemiology and Information Network (REIN), a French national End-Stage Renal Disease registry, with the Système National des Données de Santé (SNDS), a French nationwide medico-administrative healthcare database.

Results

Among the 22,073 patients included in the REIN registry who started renal replacement therapy between 2014 and 2015 in France, 19,223 (87.1%) were matched with patients in the SNDS database. Comparison of matched and unmatched patients confirmed the absence of any major selection bias. Then, the record linkage was evaluated using the comorbidity status (diabetes).

Conclusions

This fast and efficient method of record linkage with pseudonymized data and without unique and direct identifier might inspire other research teams. It also opens the path for new research on chronic kidney disease.
Characteristic electron-microscopic features of cryofibrinogen-associated glomerulonephritis: a case report
Authors: Ibuki Emi , Shiraishi Aiko , Sofue Tadashi , Kushida Yoshio , Kadota Kyuichi , Honda Kazuho , Kang Dedong , Joh Kensuke , Minamino Tetsuo , Haba Reiji
Published: January 2020

Background

Cryofibrinogenemia is a rare disorder that mainly affects the skin and occasionally the kidney. However, there are few published reports of cryofibrinogenemia-associated renal pathology. We therefore report a patient with cryofibrinogen-associated glomerulonephritis. Samples from this patient were examined by electron microscopy, laser microdissection, and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Case presentation

A 78-year-old Japanese man presented with declining renal function, proteinuria, and gross hematuria. Kidney biopsy showed a membranoproliferative pattern with crescent formation and dominant C3c deposition in which subendothelial deposits with uniquely organized electron-microscopic features were observed. Additional ultrastructural analysis of cryoprecipitates extracted from plasma revealed similar structures of the glomerular subendothelial deposits. LC-MS/MS identified an increase in fibrinogen α, β, and γ chains, fibronectin, filamin-A, and C3. The glomerular lesions were diagnosed as cryofibrinogen-associated glomerulonephritis on the basis of these findings.

Conclusions

Although there are few reports of cryofibrinogen-associated glomerulonephritis, we believe that accurate diagnosis can be achieved by performing LC-MS/MS and ultrastructural analysis.
Access to CKD Care in Rural Communities of India: a qualitative study exploring the barriers and potential facilitators
Authors: Jafar Tazeen Hasan , Ramakrishnan Chandrika , John Oommen , Tewari Abha , Cobb Benjamin , Legido-Quigley Helena , Sungwon Yoon , Jha Vivekanand
Published: January 2020

Background

Despite the high and rising burden of chronic kidney disease (CKD) in South Asia, factors that influence access to CKD care at the community level have not been studied previously, especially in the rural areas. We conducted a mixed methods study and interviewed key stakeholders to explore the views and experiences of key stakeholders, and identify barriers and potential facilitators that influence access to CKD care at the primary care level in rural India.

Methods

A total of 21 stakeholders participated in the study. We conducted 15 in-depth interviews on a purposive sample of stakeholders (CKD patients, healthcare providers and health planners) and one focus group discussion with 6 community health workers. The interviews were audio-recorded and transcribed verbatim. We employed the Lévesque’s framework for access to care to base interview guides and structure the initial codes. By inductive and deductive approaches, thematic analysis was undertaken using QSR NVivo version 11.

Results

The major patient-level barriers to CKD care as reported by the most patients and healthcare providers was poor knowledge and awareness of CKD. Health system-level barriers included shortages of skilled healthcare professionals and medicines, fragmented referrals pathways to the specialists at the hospitals with inadequate follow up care. Many patients and healthcare providers, when asked about areas for improving access to CKD care, reported educational initiatives to increase awareness of CKD among healthcare providers and patients, provision of CKD related supplies, and a systems-level approach to care coordination including task shifting by engaging community health workers in CKD care, as potential facilitators.

Conclusions

We identified several barriers to access CKD care at the primary care level in rural India that need urgent attention. Targeted CKD screening programs and CKD specific educational initiatives may improve awareness of CKD. Additionally, primary care infrastructure needs to be strengthened for CKD care, ensuring trained staff, availability of essential diagnostics and medications, and creating efficient referral pathways for quality CKD care.
Effect of repetitive transcranial magnetic stimulation on the ascending reticular activating system in a patient with disorder of consciousness: a case report
Authors: Jang Sung Ho , Kwon Young Hyeon
Published: January 2020

Background

We report on a stroke patient with disorder of consciousness (DOC) who underwent repetitive transcranial magnetic stimulation (rTMS) and showed recovery of an injured upper ascending reticular activating system (ARAS) injury, which was demonstrated by using serial diffusion tensor tractography (DTT).

Case presentation

A 45-year-old male patient was diagnosed as subarachnoid and intracerebral hemorrhages in the left fronto-parieto-temporal lobes. At 5 months after onset, the patient exhibited a persistent vegetative state, with a Coma Recovery Scale-Revised (CRS-R) score of 4. He underwent comprehensive rehabilitative therapy that included drugs for recovery of impaired consciousness and rTMS of the right dorsolateral prefrontal lobe. He recovered to a minimally conscious state (CRS-R: 13) at 7 months after onset and was transferred to a local rehabilitation hospital where he underwent similar rehabilitation but without rTMS. At 9 months after onset, his CRS-R score remained at 13. He was then readmitted to our hospital and underwent rehabilitation with rTMS until 10 months after onset. His CRS-R remained at 13, but his higher cognition had improved. The tract volume (TV) of the neural tract in the right prefrontal lobe in the upper ARAS on the 7-month DTT was higher than that on the 5-month DTT. However, compared to the 7-month DTT, the right prefrontal lobe TV was lower on the 9-month DTT. On the 10-month DTT, the TV of that neural tract had again increased.

Conclusions

Increases in neural TV in the right prefrontal lobe of the upper ARAS that were associated with the periods of rTMS application were demonstrated in a stroke patient with DOC.
Childhood maltreatment as a risk factor for cancer: findings from a population-based survey of Canadian adults
Authors: Hovdestad Wendy E. , Shields Margot , Shaw Amanda , Tonmyr Lil
Published: January 2020

Background

Childhood maltreatment (CM) is an established risk factor for various mental and substance use disorders. This study adds to existing evidence that CM may also be a risk factor for cancer.

Methods

Based on data from a sample of 9783 men and 12,132 women from the 2012 Canadian Community Health Survey - Mental Health (CCHS-MH), this analysis explores mediated associations between cancer in adulthood and different levels of exposure to three types of CM—childhood physical abuse (CPA), childhood sexual abuse (CSA), and childhood exposure to intimate partner violence (CEIPV). “Cancer” was defined as an affirmative response to either of these questions: “Do you have cancer?” or “Have you ever been diagnosed with cancer?” The potential mediators were: smoking, depression, alcohol abuse/dependence, life stress, obesity, and physical activity.

Results

For women, but not men, having experienced CM was significantly associated with a cancer diagnosis in adulthood, even when effects due to age and socio-demographic characteristics were controlled. Smoking, life stress, depression, and alcohol abuse/dependence reduced the strength of the association between CM and cancer in women. However, most associations remained statistically significant when controlling for effects due to these behavioural and other mediators. Evidence indicated a “dose-response” relationship, in that the likelihood of reporting cancer increased with the number of abuse types (CPA, CSA, CEIPV) reported, and with the severity of CPA.

Conclusions

The analyses suggest an association between CM and cancer in women, even when the effects of known risk factors were taken into account. The association was graded, becoming stronger as CM exposure increased. Implications for the provision of cancer screening and other health care services to women with histories of CM to reduce health disparities are discussed.
Real-world use of chemotherapy for Kaposi’s sarcoma in a large community-based HIV primary care system in Kenya
Authors: Freeman Esther E. , Busakhala Naftali , Regan Susan , Asirwa Fredrick Chite , Wenger Megan , Seth Divya , Moon Khatiya Chelidze , Semeere Aggrey , Maurer Toby , Wools-Kaloustian Kara , Bassett Ingrid , Martin Jeffrey
Published: January 2020

Background

Kaposi’s sarcoma (KS) is one of the most common HIV-associated malignancies in sub-Saharan Africa. Worldwide, the availability of antiretroviral therapy (ART) has improved KS survival. In resource-rich settings, survival has also benefited from chemotherapy, which is widely available. Little is known, however, about the epidemiology of chemotherapy use for HIV-associated KS in resource-limited regions such as sub-Saharan Africa.

Methods

We identified all patients newly diagnosed with HIV-related KS from 2009 to 2012 in the 26-clinic AMPATH network, a large community-based care network in Kenya. We ascertained disease severity at diagnosis, frequency of initiation of chemotherapy, and distribution of chemotherapeutic regimens used. Indications for chemotherapy included AIDS Clinical Trial Group T1 stage and/or “severe” disease defined by WHO KS treatment guidelines.

Results

Of 674 patients diagnosed with KS, charts were available for 588; 61% were men, median age was 35 years, and median CD4 at KS diagnosis was 185 cells/μl. At time of diagnosis, 58% had at least one chemotherapy indication, and 22% had more than one indication. For patients with a chemotherapy indication, cumulative incidence of chemotherapy initiation (with death as a competing event) was 37% by 1 month and 56% by 1 year. Median time from diagnosis to chemotherapy initiation was 25 days (IQR 1–50 days). In multivariable regression, patients with > 3 chemotherapy indications at time of diagnosis had a 2.30 (95% CI 1.46–3.60) increased risk of rapid chemotherapy initiation (within 30 days of diagnosis) compared to those with only one chemotherapy indication (p < 0.001). Initial regimens were bleomycin-vincristine (78%), adriamycin-bleomycin-vincristine (11%), etoposide (7%), and gemcitabine (4%).

Conclusions

A substantial fraction of patients with KS in East Africa are diagnosed at advanced disease stage. For patients with chemotherapy indications, nearly half did not receive chemotherapy by one year. Liposomal anthracyclines, often used in resource-rich settings, were not first line. These findings emphasize challenges in East Africa cancer care, and highlight the need for further advocacy for improved access to higher quality chemotherapy in this setting.
Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV
Authors: Yamamoto Keiko , Ohnishi Shunsuke , Mizushima Takeshi , Kodaira Junichi , Ono Masayoshi , Hatanaka Yutaka , Hatanaka Kanako C. , Kuriki Yugo , Kamiya Mako , Ehira Nobuyuki , Shinada Keisuke , Takahashi Hiroaki , Shimizu Yuichi , Urano Yasuteru , Sakamoto Naoya
Published: January 2020

Background

It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD).

Methods

Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV.

Results

Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV.

Conclusions

Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.
Ovarian hyperstimulation closely associated with resumption of follicular growth after chemotherapy during tamoxifen treatment in premenopausal women with breast cancer: a multicenter retrospective cohort study
Authors: Yamazaki Rena , Inokuchi Masafumi , Ishikawa Satoko , Ayabe Takuya , Jinno Hiromitsu , Iizuka Takashi , Ono Masanori , Myojo Subaru , Uchida Soko , Matsuzaki Toshiya , Tangoku Akira , Kita Masato , Sugie Tomoharu , Fujiwara Hiroshi
Published: January 2020

Background

We previously reported that tamoxifen (TAM)-induced ovarian hyperstimulation (OHS) is associated with high serum concentrations of estradiol in premenopausal women with breast cancer. To investigate risk factors for TAM-induced OHS, we performed a retrospective multicenter study.

Methods

Premenopausal patients who received surgical therapy for endocrine-dependent breast cancer (n = 235) were recruited in this study and classified into 4 groups: group A, treated with TAM alone; group B, TAM treatment after 2-year-combined therapy with a gonadotropin-releasing hormone (Gn-RH) agonist; group C, TAM treatment after chemotherapy; group D, 5-year-combined therapy with TAM and a Gn-RH agonist. A serum estradiol value of more than 300 pg/mL or mean follicular diameter of more than 30 mm was defined as OHS.

Results

The incidence of OHS in group A (n = 13/26, 50.0%) was significantly higher than those in group B (n = 17/63, 27.0%), group C (n = 20/110, 18.2%), and group D (n = 0/36, 0%). The incidence of OHS was significantly correlated with aging, and the median serum concentration of estradiol in the presence of OHS was 823.0 pg/mL. The incidence of OHS (less than 47 years old) was 62.5% in group A, 48.6% in group B, and 28.2% in group C, respectively. Notably, the incidence rate of OHS following amenorrhea in group C (n = 13/20, 65.0%) was significantly higher than that in group B (n = 1/17, 5.9%).

Conclusions

These findings indicate that the onset of OHS following amenorrhea was common in the post-chemotherapeutic group, while its ratio was low in the group after Gn-RH analog treatment, suggesting that combined treatment-based management involving TAM therapy is necessary for premenopausal patients with breast cancer.