bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing Paradigms in the Management of Acute Uncomplicated Diverticulitis
Authors: Chabok A. , Thorisson A , Nikberg M. , Schultz J. K. , Sallinen V
Published: May 2021

Left-sided colonic diverticulitis is a common condition with significant morbidity and health care costs in Western countries. Acute uncomplicated diverticulitis which is characterized by the absence of organ dysfunction, abscesses, fistula, or perforations accounts for around 80% of the cases. In the last decades, several traditional paradigms in the management of acute uncomplicated diverticulitis have been replaced by evidence-based routines. This review provides a comprehensive evidence-based and clinical-oriented overview of up-to-date diagnostics with computer tomography, non-antibiotic treatment, outpatient treatment, and surgical strategies as well as follow-up of patients with acute uncomplicated diverticulitis.
Facts into faults: The grammar of guilt in jury deliberations
Authors: Gibson David R , Fox Matthew P
Published: May 2021

Jurors customarily do their work with very little by way of instruction from the court, other than about the law. This suggests that they enter the jury room with the relevant cognitive and interactional tools at the ready, drawn from everyday life. This paper focuses on a specific conversational device jurors use to do their work: conditional-contrastive inculpations (CCIs), whereby the defendant’s actions are compared unfavorably to what a normal, innocent person would have done, with the implication that the discrepancy indicates guilt. We examine the logic, variants, sequential precursors, and immediate consequences of this phenomenon in two real-life American criminal juries deliberating the same charges. This study offers a rare glimpse into the operation of real (rather than mock) juries, and specifically the way in which they appropriate a practice from ordinary conversation in order to perform the unordinary work demanded of them by the legal system.
Let there be . . . visual optimal innovations: making visual meaning through Michelangelo’s The Creation of Adam
Authors: Schilperoord Joost , Cohn Neil
Published: May 2021

This article addresses visual optimal innovations such as memes, advertising images and editorial cartoons which take Michelangelo’s fresco The Creation of Adam as input, and rework it so that novel meaning is created that takes the meaning of the input as base. The authors focus on the cognitive and structural aspects of these kinds of visual stimulus. They argue that visual optimal innovations are aesthetically rewarding owing to how they invite meaning construction, and they further demonstrate that these aspects of visual communication are encoded in human memory to make up entries in a ‘visual lexicon’. The main questions addressed are: What graphic procedures are employed to create such stimuli, and how are they structured? How are existing and novel meanings evoked by visual optimal innovations, and how are they aligned? How are visual optimal innovations processed and interpreted? And, finally, how is all this knowledge – structural and conceptual – cognitively represented?
Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia
Authors: Li Qinzhi , Liu Yang , Wang Xiujuan , Sun Mingling , Wang Lei , Wang Xinyou , Liu Ying , Fan Wenxia , Zhang Kaile , Sui Xiao , Guo Xinhong
Published: May 2021

This study investigates the regulatory effect of plasmacytoid dendritic cells (pDC)/myeloid dendritic cells (mDC) imbalance on balance of Th1/Th2 and Th17/Treg in primary immune thrombocytopenia (ITP). A total of 30 untreated ITP patients and 20 healthy controls were recruited. Compared with healthy control, the pDC proportion of ITP patients was significantly reduced ( P = 0.004), while the mDC proportion was not significantly changed ( P = 0.681), resulting in a decrease in the pDC/mDC ratio ( P = 0.001). Additionally, compared with controls, serum levels of interleukin (IL)-6, IL-12, and IL-23 were increased in ITP patients ( P < 0.001), and mRNA levels of IL-12p40, IL-12p35, and IL-23p19 were also increased ( P =0.014, P = 0.043, P < 0.001). Compared with the healthy control, the proportion of Th1 and Th17 cells in ITP patients increased ( P = 0.001, P = 0.031). Serum levels of interferon gamma (IFN-γ) and IL-17 in ITP patients also increased ( P = 0.025, P = 0.005). Furthermore, T-bet and RORγt mRNA levels were increased in peripheral blood of ITP patients ( P = 0.018, P < 0.001). Correspondingly, the proportion of Th2 and Treg cells decreased ( P = 0.007, P < 0.001), along with a decrease in serum IL-4 and transforming growth factor beta (TGF-β) ( P = 0.028, P = 0.042), and an increase in GATA-3 mRNA ( P < 0.001). However, there was no significant difference in Foxp3 mRNA levels ( P = 0.587). Pearson correlation analysis showed that the proportion of total dendritic cells (DCs) was positively correlated with IL-12 ( r = 0.526, P = 0.003) and IL-23 ( r = 0.501, P = 0.005) in ITP patients. Th1/Th2 ratio, IFN-γ, and IL-12 levels were negatively correlated with platelet counts ( r = −0.494, P = 0.009; r = –0.415, P = 0.028; r = –0.492, P = 0.032). However, IL-23 was positively correlated with IL-17 ( r = 0.489, P = 0.006) and negatively correlated with platelet count ( r = –0.564, P = 0.001). The ratio of IL-6 and Th17 cells was negatively correlated with platelet count ( r = –0.443, P = 0.014; r = –0.471, P = 0.011). The imbalance of pDC/mDC and the increase of IL-6, IL-12, and IL-23 lead to the increased differentiation of CD4+ T cells into Th1 and Th17 cells, which might be the important mechanisms underlying the imbalance of Th1/Th2 and Th17/Treg in ITP patients.
Phase I trial compensation: How much do healthy volunteers actually earn from clinical trial enrollment?
Authors: Fisher Jill A , McManus Lisa , Kalbaugh Julianne M , Walker Rebecca L
Published: May 2021

Background/aims

Financial compensation for research participation is a major focus of ethical concern regarding human subject recruitment. Phase I trials are sometimes considered to be a lucrative source of income for healthy volunteers, encouraging some people to become “professional guinea pigs.” Yet, little is known about how much these clinical trials actually pay and how much healthy volunteers earn from them.

Methods

As part of a mixed-methods, longitudinal study of healthy volunteers, we required participants to complete clinical trial diaries, or surveys that captured detailed information about screening and enrollment in Phase I trials. Over a 3-year period, participants provided information online or via telephone about each clinical trial for which they screened (e.g. the clinic name, the study’s therapeutic area, the length of the trial, the number of nights spent in the clinic, and the study compensation), and whether they qualified for trial inclusion. Clinical trial diaries generated data about whether participants continued to screen for and enroll in clinical trials and how much money they earned from their participation.

Results

131 participants routinely completed clinical trial diaries or confirmed that they had not screened for any new clinical trials. Together, these participants screened for 1001 clinical trials at 73 research facilities during a 3-year period. Overall, the median clinical trial compensation was US$3070 (range = US$150–US$13,000). Participants seeking new healthy volunteer trials tended to screen for three studies per year, participate in one or two studies, and earn roughly US$4000 annually. Participants who were unemployed earned the most income from clinical trials compared to those with full-time or part-time jobs, and those individuals whom we label “occupational” participants because of their persistent pursuit of clinical trials earned more than people who screened occasionally. Notably, the median annual trial compensation was well below US$10,000 for all employment groups, and most occupational healthy volunteers also earned less than US$10,000 each year. The 10% of participants who earned the most had a median annual income of US$18,885 from clinical trials, and there was significant volatility in these individuals’ earnings from year to year.

Conclusion

Despite the perception that Phase I enrollment can generate significant earnings, it was exceedingly rare for anyone in this study to make more than US$20,000 in a single year, and unusual to earn even between US$10,000 and US$20,000. From an ethics perspective, individual trials might appear to unduly induce enrollment by offering significant sums of money, but given our findings, the larger problem for low-income participants may be the unrealistic perception that clinical trials alone could be a way of earning a living.
Can chemical cues from a predator change the nest-selection of birds?
Authors: Lee Jong Koo
Published: May 2021

The nest-selection process of many birds can be affected by traces of potential predators. However, it remains debatable if birds are capable of recognizing and responding to chemical cues of predators when selecting their nest sites. To investigate this, I installed a pair of nest boxes at 12 sites in 2013 and 2014 and 24 sites in 2015 and 2016, each with nest conditions that differed for two variables, that is, height (high or low), hole depth (deep or shallow). Under these experimental conditions, tree swallows displayed a strong preference for high nests over low ones and deep hole nests over shallow holes. In a consecutive experiment, we applied chemical cues (i.e. urine, feces) of domestic cats to the preferred nests to determine if this would alter the nests selected; the chemical cues led to a stepwise alteration in the nests selected. The birds changed their nest selection by chemical cues of a predator when one variable (nest height or hole depth) was applied. Interestingly, however, when provided with a choice between the most preferred nest combination (high and with a deep hole) and the least preferred nest combination (low and with a shallow hole), tree swallows selected the most preferred nest even in the presence of the chemical cues.
Effect of Patient Height and Sex on the Patellar Tendon and Anterior Cruciate Ligament
Authors: Campbell Abigail L. , Caldwell Jon-Michael E. , Yalamanchili Dheeraj , Sepanek Lia , Youssefzadeh Keon , Uquillas Carlos A. , Limpisvasti Orr
Published: May 2021

Background:

Graft-tunnel mismatch is an avoidable complication in anterior cruciate ligament (ACL) reconstruction. Patient height and sex may be predictors of patellar tendon length (PTL) and intra-articular ACL length (IAL). Understanding these relationships may assist in reducing graft-tunnel mismatch during ACL reconstruction with bone–patellar tendon–bone (BTB) autograft.

Purpose:

To determine the association of patient height and sex with PTL and IAL.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

Magnetic resonance imaging (MRI) studies were obtained on the healthy knees of 100 male and 100 female patients. Patients with prior surgery, open physes, significant degenerative changes, ACL rupture, or extensor mechanism injury were excluded. Three independent readers measured PTL, IAL, and Caton-Deschamps Index (CDI) on MRI. Bivariate and linear regression analysis was performed to detect the association of anthropometric data with anatomic parameters measured on MRI studies.

Results:

The mean age and body mass index were not significantly different between the male and female patients; however, male patients were significantly taller than female patients (1.75 vs 1.72 m, respectively; P < .001). There was a substantial agreement between the 3 readers for all parameters (κ > 0.75). Overall, female patients had significantly longer PTL (47.38 vs 43.92 mm), higher CDI (1.146 vs 1.071), and shorter IAL (33.05 vs 34.39 mm) ( P < .001 for all). Results of the linear regression analysis demonstrated that both height and female sex were predictive of longer PTL. Further, height was independently predictive of IAL but sex was not.

Conclusion:

PTL was correlated more with patient sex than height. IAL was also correlated with patient sex. Longer BTB grafts are expected to be harvested in female patients compared with male patients of the same height despite shorter IAL. These associations should be considered during BTB ACL reconstruction to minimize graft-tunnel mismatch.
Aspirin and antiplatelet treatments in cancer
Authors: Tao Derrick L. , Tassi Yunga Samuel , Williams Craig D. , McCarty Owen J. T.
Published: May 2021

Platelets have been hypothesized to promote certain neoplastic malignancies; however, antiplatelet drugs are still not part of routine pharmacological cancer prevention and treatment protocols. Paracrine interactions between platelets and cancer cells have been implicated in potentiating the dissemination, survival within the circulation, and extravasation of cancer cells at distant sites of metastasis. Signals from platelets have also been suggested to confer epigenetic alterations, including upregulating oncoproteins in circulating tumor cells, and secretion of potent growth factors may play roles in promoting mitogenesis, angiogenesis, and metastatic outgrowth. Thrombocytosis remains a marker of poor prognosis in patients with solid tumors. Experimental data suggest that lowering of platelet count may reduce tumor growth and metastasis. On the basis of the mechanisms by which platelets could contribute to cancer growth and metastasis, it is conceivable that drugs reducing platelet count or platelet activation might attenuate cancer progression and improve outcomes. We will review select pharmacological approaches that inhibit platelets and may affect cancer development and propagation. We begin by presenting an overview of clinical cancer prevention and outcome studies with low-dose aspirin. We then review current nonclinical development of drugs targeted to platelet binding, activation, and count as potential mitigating agents in cancer.
Introduction to a review series on platelets and cancer
Authors: López José A.
Published: May 2021

Platelets are critical for hemostasis and thrombosis, but recent research highlights their role in many other processes, including inflammation, wound healing, and lymphangiogenesis. Edited by José López, this series focuses on the emerging role of platelets in cancer, influencing tumor growth and metastasis, immune evasion, and tumor angiogenesis. The reviews present the current understanding of mutual cross talk between platelets and tumors, communication mediated by RNA transfer and extracellular vesicles, and the potential of antiplatelet agents for cancer treatment.
Molecular analysis of the erythroid phenotype of a patient with BCL11A haploinsufficiency
Authors: Wessels Marja W. , Cnossen Marjon H. , van Dijk Thamar B. , Gillemans Nynke , Schmidt K. L. Juliëtte , van Lom Kirsten , Vinjamur Divya S. , Coyne Steven , Kurita Ryo , Nakamura Yukio , de Man Stella A. , Pfundt Rolph , Azmani Zakia , Brouwer Rutger W. W. , Bauer Daniel E. , van den Hout Mirjam C. G. N. , van IJcken Wilfred F. J. , Philipsen Sjaak
Published: May 2021

The BCL11A gene encodes a transcriptional repressor with essential functions in multiple tissues during human development. Haploinsufficiency for BCL11A causes Dias-Logan syndrome (OMIM 617101), an intellectual developmental disorder with hereditary persistence of fetal hemoglobin (HPFH). Due to the severe phenotype, disease-causing variants in BCL11A occur de novo. We describe a patient with a de novo heterozygous variant, c.1453G>T, in the BCL11A gene, resulting in truncation of the BCL11A-XL protein (p.Glu485X). The truncated protein lacks the 3 C-terminal DNA-binding zinc fingers and the nuclear localization signal, rendering it inactive. The patient displayed high fetal hemoglobin (HbF) levels (12.1-18.7% of total hemoglobin), in contrast to the parents who had HbF levels of 0.3%. We used cultures of patient-derived erythroid progenitors to determine changes in gene expression and chromatin accessibility. In addition, we investigated DNA methylation of the promoters of the γ-globin genes HBG1 and HBG2. HUDEP1 and HUDEP2 cells were used as models for fetal and adult human erythropoiesis, respectively. Similar to HUDEP1 cells, the patient’s cells displayed Assay for Transposase-Accessible Chromatin (ATAC) peaks at the HBG1/2 promoters and significant expression of HBG1/2 genes. In contrast, HBG1/2 promoter methylation and genome-wide gene expression profiling were consistent with normal adult erythropoiesis. We conclude that HPFH is the major erythroid phenotype of constitutive BCL11A haploinsufficiency. Given the essential functions of BCL11A in other hematopoietic lineages and the neuronal system, erythroid-specific targeting of the BCL11A gene has been proposed for reactivation of γ-globin expression in β-hemoglobinopathy patients. Our data strongly support this approach.
Influence of moisture content on NO2 sorption ability of cedar wood
Authors: Nakagawa Miyuki , Kawai Shuichi , Kanayama Kozo , Umemura Kenji
Published: May 2021

This study examined the influence of moisture content (MC) on NO2 sorption ability of cedar (Cryptomeria japonica) wood using the specimens with different MCs. Four MC conditions were applied, namely 0%, 8.6%, 12.7% and 16.5%, based on the differences of bonding condition of water molecule in the wood substances. As a result, the NO2 sorption volume increased drastically due to the presence of water, and as the MC increased, the NO2 sorption volume increased slightly. The NO generation volume and nitric acid concentration in the specimens were evaluated after an aeration test, and it was strongly indicated that the NO2 reacted with water in the specimen, and that the NO generation volume increased as the content of multilayer adsorbed water increased. The nitric acid seemed to be formed by the reaction between NO2 and water, and it was then held in the specimen. Based on the NO2 sorption volume calculated using the NO generation volume, it was shown that the NO2 sorption after 12-h aeration was caused mainly by the reaction between NO2 and water. Furthermore, the presence of both water and extractives contributed to the NO2 sorption in the initial period, and the presence of water contributed greatly to the NO2 sorption over the long term.
Influence of slenderness ratio and sectional geometry on the axial compression behavior of original bamboo columns
Authors: Nie Yuhan , Wei Yang , Huang Linjie , Liu Ying , Dong Fenghui
Published: May 2021

Bamboo has been widely used as a load-bearing material in construction; however, there are limited studies on the stability of slender original bamboo columns. Based on the experimental investigation of thirty-nine original bamboo columns, parametric analyses were conducted to investigate the influence of the diameter–thickness ratio, cross-sectional area and slenderness ratio on the axial compression behavior of original bamboo columns. The test results indicate that the failure modes of the columns are substantially affected by the slenderness ratio and diameter–thickness ratio. For columns with the same diameter–thickness ratio, the ultimate bearing capacity was negatively correlated with the slenderness ratio, and the highest reduction rate for the load-bearing capacity caused by the slenderness ratio was 44.39%. Under the same slenderness ratio, when the diameter–thickness ratio increased by 18.75%, the ultimate bearing capacity increased by 82.65%. An excessive slenderness ratio may result in local buckling, leading to underutilization of the material strength when failure occurs and substantially reducing the load capacity of bamboo columns. Local buckling can be mitigated by decreasing the slenderness ratio and increasing the diameter–thickness ratio. According to the test results, the model predicting the compressive bearing capacity of the original bamboo column was proposed considering the slenderness ratio and diameter–thickness ratio, and it was indicated that the proposed model can provide satisfactory predictive results.
Studies on the electrostatic effects of stretched PVDF films and nanofibers
Authors: Lin Yixuan , Zhang Yuqiong , Zhang Fan , Zhang Meining , Li Dalong , Deng Gaofeng , Guan Li , Dong Mingdong
Published: May 2021

The electroactive β-phase in Poly (vinylidene fluoride, PVDF) is the most desirable conformation due to its highest pyro- and piezoelectric properties, which make it feasible to be used as flexible sensors, wearable electronics, and energy harvesters etc. In this study, we successfully developed a method to obtain high-content β-phase PVDF films and nanofiber meshes by mechanical stretching and electric spinning. The phase transition process and pyro- and piezoelectric effects of stretched films and nanofiber meshes were characterized by monitoring the polarized light microscopy (PLM) images, outputting currents and open-circuit voltages respectively, which were proved to be closely related to stretching ratio (λ) and concentrations. This study could expand a new route for the easy fabrication and wide application of PVDF films or fibers in wearable electronics, sensors, and energy harvesting devices.
Doping of Mg on ZnO Nanorods Demonstrated Improved Photocatalytic Degradation and Antimicrobial Potential with Molecular Docking Analysis
Authors: Ikram Muhammad , Aslam Sidra , Haider Ali , Naz Sadia , Ul-Hamid Anwar , Shahzadi Anum , Ikram Mujtaba , Haider Junaid , Ahmad Syed Ossama Ali , Butt Alvina Rafiq
Published: May 2021

Various concentrations of Mg-doped ZnO nanorods (NRs) were prepared using co-precipitation technique. The objective of this study was to improve the photocatalytic properties of ZnO. The effect of Mg doping on the structure, phase constitution, functional groups presence, optical properties, elemental composition, surface morphology and microstructure of ZnO was evaluated with XRD, FTIR, UV–Vis spectrophotometer, EDS, and HR-TEM, respectively. Optical absorption spectra obtained from the prepared samples showed evidence of blueshift upon doping. XRD results revealed hexagonal wurtzite phase of nanocomposite with a gradual decrease in crystallite size with Mg addition. PL spectroscopy showed trapping efficiency and migration of charge carriers with electron–hole recombination behavior, while HR-TEM estimated interlayer d-spacing. The presence of chemical bonding, vibration modes and functional groups at the interface of ZnO was revealed by FTIR and Raman spectra. In this study, photocatalytic, sonocatalytic and sonophotocatalytic performance of prepared NRs was systematically investigated by degrading a mixture of methylene blue and ciprofloxacin (MBCF). Experimental results suggested that improved degradation performance was shown by Mg-doped ZnO NRs. We believe that the product synthesized in this study will prove to be a beneficial and promising photocatalyst for wastewater treatment. Conclusively, Mg-doped ZnO exhibited substantial (p < 0.05) efficacy against gram-negative (G-ve) as compared to gram-positive (G+ve) bacteria. In silico molecular docking studies of Mg-doped ZnO NRs against DHFR (binding score: − 7.518 kcal/mol), DHPS (binding score: − 6.973 kcal/mol) and FabH (− 6.548 kcal/mol) of E. coli predicted inhibition of given enzymes as possible mechanism behind their bactericidal activity.
Effect of diurnal temperature range on emergency room visits for acute upper respiratory tract infections
Authors: Jang Jin Young , Chun Byung Chul
Published: May 2021

Background

An acute upper respiratory tract infection (URI) is the most common disease worldwide, irrespective of age or sex. This study aimed to evaluate the short-term effect of diurnal temperature range (DTR) on emergency room (ER) visits for URI in Seoul, Korea, between 2009 and 2013.

Methods

Daily ER visits for URI were selected from the National Emergency Department Information System, which is a nationwide daily reporting system for ER visits in Korea. URI cases were defined according to International Classification of Diseases, 10thRevision codes J00–J06. The search for DTR effects associated with URI was performed using a semi-parametric generalized additive model approach with log link.

Results

There were 529,527 ER visits for URI during the study period, with a daily mean of 290 visits (range, 74–1942 visits). The mean daily DTR was 8.05 °C (range, 1.1–17.6 °C). The cumulative day (lag 02) effect of DTR above 6.57 °C per 1 °C increment was associated with a 1.42% (95% confidence interval [CI] 0.04–2.82) increase in total URI. Children (≤ 5 years of age) were affected by DTR above 6.57 °C per 1 °C, with 1.45% (95% CI 0.32–2.60) at lag 02, adults (19–64 years) with 2.77% (95% CI 0.39–5.20) at lag 07. When the DTR (lag02) was 6.57 °C to 11.03 °C, the relative risk was significant at 6.01% (95% CI 2.45–9.69) for every 1 °C increase in youth subjects aged for 6 to 18 years.

Conclusions

DTR was associated with a higher risk for ER visits for URI. In addition, the results suggested that the lag effects and relative risks of DTR on URI were quite different according to age.
Ultrasensitive bioassaying of HER-2 protein for diagnosis of breast cancer using reduced graphene oxide/chitosan as nanobiocompatible platform
Authors: Nasrollahpour Hassan , Isildak Ibrahim , Rashidi Mohammad-Reza , Hashemi Esmat Alsadat , Naseri Abdolhosein , Khalilzadeh Balal
Published: May 2021

Background

In this label-free bioassay, an electrochemiluminescence (ECL) immunosensor was developed for the quantification of breast cancer using HER-2 protein as a metastatic biomarker.

Method

For this purpose, the ECL emitter, [Ru(bpy)3]2+, was embedded into biocompatible chitosan (CS) polymer. The prepared bio-composite offered high ECL reading due to the depletion of human epidermal growth factor receptor 2 (HER-2) protein. Reduced graphene oxide (rGO) was used as substrate to increase signal stability and achieve greater sensitivity. For this, rGO was initially placed electrochemically on the glassy carbon electrode (GCE) surface by cyclic voltammetry (CV) technique. Next, the prepared CS/[Ru(bpy)3]2+biopolymer solution was coated on a drop of the modified electrode such that the amine groups of CS and the carboxylic groups of rGO could covalently interact. Using EDC/NHS chemistry, monoclonal antibodies (Abs) of HER-2 were linked to CS/[Ru(bpy)3]2+/rGO/GCE via amide bonds between the carboxylic groups of Ab molecules and amine groups of CS. The electrochemical behavior of the electrode was studied using different electrochemical techniques such as electrochemical impedance spectroscopy (EIS), differential pulse voltammetry (DPV) and square wave voltammetry (SWV) and also ECL tests.

Results

After passing all optimization steps, the lower limit of detection (LLOQ) and linear dynamic range (LDR) of HER-2 protein were practically obtained as 1 fM and 1 fM to 1 nM, individually. Importantly, the within and between laboratory precisions were performed and the suitable relative standard deviations (RSDs) were recorded as 3.1 and 3.5%, respectively.

Conclusions

As a proof of concept, the designed immunosensor was desirably applied for the quantification of HER-2 protein in breast cancer suffering patients. As a result, the designed ECL-based immunosensor has the capability of being used as a conventional test method in biomedical laboratories for early detection of HER-2 protein in biological fluids.

Graphic Abstract
SPEAQeasy: a scalable pipeline for expression analysis and quantification for R/bioconductor-powered RNA-seq analyses
Authors: Eagles Nicholas J. , Burke Emily E. , Leonard Jacob , Barry Brianna K. , Stolz Joshua M. , Huuki Louise , Phan BaDoi N. , Serrato Violeta Larios , Gutiérrez-Millán Everardo , Aguilar-Ordoñez Israel , Jaffe Andrew E. , Collado-Torres Leonardo
Published: May 2021

Background

RNA sequencing (RNA-seq) is a common and widespread biological assay, and an increasing amount of data is generated with it. In practice, there are a large number of individual steps a researcher must perform before raw RNA-seq reads yield directly valuable information, such as differential gene expression data. Existing software tools are typically specialized, only performing one step–such as alignment of reads to a reference genome–of a larger workflow. The demand for a more comprehensive and reproducible workflow has led to the production of a number of publicly available RNA-seq pipelines. However, we have found that most require computational expertise to set up or share among several users, are not actively maintained, or lack features we have found to be important in our own analyses.

Results

In response to these concerns, we have developed a Scalable Pipeline for Expression Analysis and Quantification (SPEAQeasy), which is easy to install and share, and provides a bridge towards R/Bioconductor downstream analysis solutions. SPEAQeasy is portable across computational frameworks (SGE, SLURM, local, docker integration) and different configuration files are provided (http://research.libd.org/SPEAQeasy/).

Conclusions

SPEAQeasy is user-friendly and lowers the computational-domain entry barrier for biologists and clinicians to RNA-seq data processing as the main input file is a table with sample names and their corresponding FASTQ files. The goal is to provide a flexible pipeline that is immediately usable by researchers, regardless of their technical background or computing environment.
A fast wavelet-based functional association analysis replicates several susceptibility loci for birth weight in a Norwegian population
Authors: Denault William R. P. , Romanowska Julia , Helgeland Øyvind , Jacobsson Bo , Gjessing Håkon K. , Jugessur Astanand
Published: May 2021

Background

Birth weight (BW) is one of the most widely studied anthropometric traits in humans because of its role in various adult-onset diseases. The number of loci associated with BW has increased dramatically since the advent of whole-genome screening approaches such as genome-wide association studies (GWASes) and meta-analyses of GWASes (GWAMAs). To further contribute to elucidating the genetic architecture of BW, we analyzed a genotyped Norwegian dataset with information on child’s BW (N=9,063) using a slightly modified version of a wavelet-based method by Shim and Stephens (2015) called WaveQTL.

Results

WaveQTL uses wavelet regression for regional testing and offers a more flexible functional modeling framework compared to conventional GWAS methods. To further improve WaveQTL, we added a novel feature termed “zooming strategy” to enhance the detection of associations in typically small regions. The modified WaveQTL replicated five out of the 133 loci previously identified by the largest GWAMA of BW to date by Warrington et al. (2019), even though our sample size was 26 times smaller than that study and 18 times smaller than the second largest GWAMA of BW by Horikoshi et al. (2016). In addition, the modified WaveQTL performed better in regions of high LD between SNPs.

Conclusions

This study is the first adaptation of the original WaveQTL method to the analysis of genome-wide genotypic data. Our results highlight the utility of the modified WaveQTL as a complementary tool for identifying loci that might escape detection by conventional genome-wide screening methods due to power issues. An attractive application of the modified WaveQTL would be to select traits from various public GWAS repositories to investigate whether they might benefit from a second analysis.
Genome-wide analysis of ATP-binding cassette transporter provides insight to genes related to bioactive metabolite transportation in Salvia miltiorrhiza
Authors: Yan Li , Zhang Jianhong , Chen Hongyu , Luo Hongmei
Published: May 2021

Background

ATP-binding cassette (ABC) transporters have been found to play important roles in metabolic transport in plant cells, influencing subcellular compartmentalisation and tissue distribution of these metabolic compounds. Salvia miltiorrhiza Bunge, known as Danshen in traditional Chinese medicine, is a highly valued medicinal plant used to treat cardiovascular and cerebrovascular diseases. The dry roots and rhizomes of S. miltiorrhiza contain biologically active secondary metabolites of tanshinone and salvianolic acid. Given an assembled and annotated genome and a set of transcriptome data of S. miltiorrhiza, we analysed and identified the candidate genes that likely involved in the bioactive metabolite transportation of this medicinal plant, starting with the members of the ABC transporter family.

Results

A total of 114 genes encoding ABC transporters were identified in the genome of S. miltiorrhiza. All of these ABC genes were divided into eight subfamilies: 3ABCA, 31ABCB, 14ABCC, 2ABCD, 1ABCE, 7ABCF, 46ABCG, and 10 ABCI. Gene expression analysis revealed tissue-specific expression profiles of these ABC transporters. In particular, we found 18 highly expressed transporters in the roots of S. miltiorrhiza, which might be involved in transporting the bioactive compounds of this medicinal plant. We further investigated the co-expression profiling of these 18 genes with key enzyme genes involved in tanshinone and salvianolic acid biosynthetic pathways using quantitative reverse transcription polymerase chain reaction (RT-qPCR). From this RT-qPCR validation, we found that three ABC genes (SmABCG46, SmABCG40, and SmABCG4) and another gene (SmABCC1) co-expressed with the key biosynthetic enzymes of these two compounds, respectively, and thus might be involved in tanshinone and salvianolic acid transport in root cells. In addition, we predicted the biological functions of S. miltiorrhiza ABC transporters using phylogenetic relationships and analysis of the transcriptome to find biological functions.

Conclusions

Here, we present the first systematic analysis of ABC transporters in S. miltiorrhiza and predict candidate transporters involved in bioactive compound transportation in this important medicinal plant. Using genome-wide identification, transcriptome profile analysis, and phylogenetic relationships, this research provides a new perspective on the critical functions of ABC transporters in S. miltiorrhiza.
Basic leucine zipper (bZIP) transcription factor genes and their responses to drought stress in ginseng, Panax ginseng C.A. Meyer
Authors: Li Hongjie , Chen Jing , Zhao Qi , Han Yilai , Li Li , Sun Chunyu , Wang Kangyu , Wang Yanfang , Zhao Mingzhu , Chen Ping , Lei Jun , Wang Yi , Zhang Meiping
Published: May 2021

Background

Ginseng is an important medicinal herb in Asia and Northern America. The basic leucine zipper (bZIP) transcription factor genes play important roles in many biological processes and plant responses to abiotic and biotic stresses, such as drought stress. Nevertheless, the genes remain unknown in ginseng.

Results

Here, we report 91 bZIP genes identified from ginseng, designated PgbZIP genes. These PgbZIP genes were alternatively spliced into 273 transcripts. Phylogenetic analysis grouped the PgbZIP genes into ten groups, including A, B, C, D, E, F, G, H, I and S. Gene Ontology (GO) categorized the PgbZIP genes into five functional subcategories, suggesting that they have diversified in functionality, even though their putative proteins share a number of conserved motifs. These 273 PgbZIP transcripts expressed differentially across 14 tissues, the roots of different ages and the roots of different genotypes. However, the transcripts of the genes expressed coordinately and were more likely to form a co-expression network. Furthermore, we studied the responses of the PgbZIP genes to drought stress in ginseng using a random selection of five PgbZIP genes, including PgbZIP25, PgbZIP38, PgbZIP39, PgbZIP53 and PgbZIP54. The results showed that all five PgbZIP genes responded to drought stress in ginseng, indicating that the PgbZIP genes play important roles in ginseng responses to drought stress.

Conclusions

These results provide knowledge and gene resources for deeper functional analysis of the PgbZIP genes and molecular tools for enhanced drought tolerance breeding in ginseng.
Identification and characterization of HAK/KUP/KT potassium transporter gene family in barley and their expression under abiotic stress
Authors: Cai Kangfeng , Zeng Fanrong , Wang Junmei , Zhang Guoping
Published: May 2021

Background

HAK/KUP/KT (High-affinity K+ transporters/K+ uptake permeases/K+ transporters) is the largest potassium transporter family in plants, and plays pivotal roles in K+ uptake and transport, as well as biotic and abiotic stress responses. However, our understanding of the gene family in barley (Hordeum vulgare L.) is quite limited.

Results

In the present study, we identified 27 barley HAK/KUP/KT genes (hereafter called HvHAKs) through a genome-wide analysis. These HvHAKs were unevenly distributed on seven chromosomes, and could be phylogenetically classified into four clusters. All HvHAK protein sequences possessed the conserved motifs and domains. However, the substantial difference existed among HAK members in cis-acting elements and tissue expression patterns. Wheat had the most orthologous genes to barley HAKs, followed by Brachypodium distachyon, rice and maize. In addition, six barley HAK genes were selected to investigate their expression profiling in response to three abiotic stresses by qRT-PCR, and their expression levels were all up-regulated under salt, hyperosmotic and potassium deficiency treatments.

Conclusion

Twenty seven HAK genes (HvHAKs) were identified in barley, and they differ in tissue expression patterns and responses to salt stress, drought stress and potassium deficiency.
RNA sequencing-based analysis of the magnum tissues revealed the novel genes and biological pathways involved in the egg-white formation in the laying hen
Authors: Sah Nirvay , Kuehu Donna Lee , Khadka Vedbar Singh , Deng Youping , Jha Rajesh , Wasti Sanjeev , Mishra Birendra
Published: May 2021

Background

The mechanism of egg formation in the oviduct of laying hens is tightly controlled; each segment of the oviduct contributes a unique component of the egg. Several genes/proteins are involved in the synthesis of a completely healthy egg. This implies a time- and tissue-specific expression of genes and proteins in the different oviductal segments. We used hens at different physiological stages and time points to understand the transcriptional regulation of egg-white (albumen) synthesis and secretion onto the eggs in the magnum of laying hens. This study used Next-Generation Sequencing and quantitative real-time PCR (qPCR) to detect the novel genes and the cognate biological pathways that regulate the major events during the albumen formation.

Results

Magnum tissues collected from laying (n = 5 each at 3 h post-ovulation, p.o. and 15–20 h p.o.), non-laying (n = 4), and molting (n = 5) hens were used for differential gene expression analyses. A total of 540 genes (152 upregulated and 388 down-regulated) were differentially expressed at 3 h p.o. in the magnum of laying hens. Kyoto Encyclopedia of Genes and Genomes pathways analysis of the 152 upregulated genes revealed that glycine, serine, and threonine metabolism was the most-enriched biological pathway. Furthermore, the top two most enriched keywords for the upregulated genes were amino-acid biosynthesis and proteases. Nine candidate genes associated with albumen formation were validated with qPCR to have differential expression in laying, non-laying, and molting hens. Proteases such as TMPRSS9, CAPN2, MMP1, and MMP9 (protein maturation, ECM degradation, and angiogenesis); enzymes such as PSPH, PHGDH, and PSAT1 (amino-acid biosynthesis); RLN3, ACE, and REN (albumen synthesis, secretion and egg transport); and AVD, AvBD11, and GPX3 (antimicrobial and antioxidants) were recognized as essential molecules linked to albumen deposition in the magnum.

Conclusions

This study revealed some novel genes that participate in the signaling pathways for egg-white synthesis and secretion along with some well-known functional genes. These findings help to understand the mechanisms involved in albumen biosynthesis.
Prevalence and antibiotics susceptibility profiles of Streptococcus pyogenes among pediatric patients with acute pharyngitis at Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia
Authors: Kebede Destaw , Admas Alemale , Mekonnen Daniel
Published: May 2021

Background

Streptococcus pyogenes (S. pyogenes) is a Gram positive bacterium which is a leading cause of pharyngitis, skin and soft tissue infection and post streptococcal syndromes. Due to lack of β-lactamase enzyme production, it was considered universally susceptible to penicillin group and later generation of β-lactam antibiotics. As such, empirical treatment was common which might leads to development of antibiotics resistance. Therefore, the aims of this study were to determine the prevalence, antibiotics susceptibility profile; and associated factors of S. pyogenes among pediatric patients with acute pharyngitis in Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Northwest Ethiopia.

Methods

Hospital based cross-sectional study was carried out on 154 pediatric patients, whose age ranged from 0 to 18 years old using consecutive convenient sampling technique from 1st February to 19th June 2020 at FHCSH. S. pyogenes were identified by throat swab culture on 5% sheep blood agar with an overnight incubation at 37 °C in candle jar containing 5% CO2. Gram stain, catalase test and bacitracin test were used to identify S. pyogenes. Then,the data were entered into EpiData version 3.1 and analyzed by SPSS version 20 software. Finally, stepwise, bivariable and multivariable logistic regressions were carried out for identifyying factors having significant ssociation (p<0.05) with  acute pharyngitis. 

Results

From the total throat swabs, 14 (9.1%) with (95% CI; 4.5–14.3) were culture positive for S. pyogenes. From these, all isolates were sensitive to penicillin and ampicillin. On the otherhand, 4 (35.7%), 4 (35.5%), 3 (21.4%), 2 (14.3%), 1 (7.1%), 7 (50.0%) and 1 (7.1%) isolates were resistant for ceftriaxone, vancomycin, erythromycin, tetracycline, chloramphenicol, clindamycin and levofloxacin, respectively. The presence of any smoker in home showed significant association with S. pyogenes acute pharyngitis. Furthermore, having tender lymphadenopathy and recurrence were clinical predictors for S. pyogenes acute pharyngitis (P < 0.05).

Conclusion

The prevalence of S. pyogenes was guaged at 9.1% which is considered as low prevalence. All S. pyogenes isolats remain sensitive to penicillin. However, resistance was reported to clindamycin 7 (50.0%), ceftriaxone 5 (35.7%) and erythromycin 3 (21.4%). The current practice of giving erythromycin, clindamycin instead of penicillin and ampicillin is againest the microbiology result. Therefore, current empirical treatment of acute pharyngitis shall take in to account the current evidences. Continuous surveillance of antibiotics resistance pattern of S. pyogenes for acute pharyngitis must be strengthen to improve the use of antibiotics in hospitals.
Comparative genome analysis of multidrug-resistant Pseudomonas aeruginosa JNQH-PA57, a clinically isolated mucoid strain with comprehensive carbapenem resistance mechanisms
Authors: Hao Mingju , Ma Wanshan , Dong Xiutao , Li Xiaofeng , Cheng Fang , Wang Yujiao
Published: May 2021

Background

The prevalence of clinical multidrug-resistant (MDR) Pseudomonas aeruginosa has been increasing rapidly worldwide over the years and responsible for a wide range of acute and chronic infections with high mortalities. Although hundreds of complete genomes of clinical P. aeruginosa isolates have been sequenced, only a few complete genomes of mucoid strains are available, limiting a comprehensive understanding of this important group of opportunistic pathogens. Herein, the complete genome of a clinically isolated mucoid strain P. aeruginosa JNQH-PA57 was sequenced and assembled using Illumina and Oxford nanopore sequencing technologies. Genomic features, phylogenetic relationships, and comparative genomics of this pathogen were comprehensively analyzed using various bioinformatics tools. A series of phenotypic and molecular-genetic tests were conducted to investigate the mechanisms of carbapenem resistance in this strain.

Results

Several genomic features of MDR P. aeruginosa JNQH-PA57 were identified based on the whole-genome sequencing. We found that the accessory genome of JNQH-PA57 including several prophages, genomic islands, as well as a PAPI-1 family integrative and conjugative element (ICE), mainly contributed to the larger genome of this strain (6,747,067 bp) compared to other popular P. aeruginosa strains (with an average genome size of 6,445,223 bp) listed in Pseudomonas Genome Database. Colony morphology analysis and biofilm crystal staining assay respectively demonstrated an enhanced alginate production and a thicker biofilm formation capability of JNQH-PA57. A deleted mutation at nt 424 presented in mucA gene, resulted in the upregulated expression of a sigma-factor AlgU and a GDP mannose dehydrogenase AlgD, which might explain the mucoid phenotype of this strain. As for the carbapenem resistance mechanisms, our results revealed that the interplay between impaired OprD porin, chromosomal β-lactamase OXA-488 expression, MexAB-OprM and MexXY-OprM efflux pumps overexpression, synergistically with the alginates-overproducing protective biofilm, conferred the high carbapenem resistance to P. aeruginosa JNQH-PA57.

Conclusion

Based on the genome analysis, we could demonstrate that the upregulated expression of algU and algD, which due to the truncation variant of MucA, might account for the mucoid phenotype of JNQH-PA57. Moreover, the resistance to carbapenem in P. aeruginosa JNQH-PA57 is multifactorial. The dataset presented in this study provided an essential genetic basis for the comprehensive cognition of the physiology, pathogenicity, and carbapenem resistance mechanisms of this clinical mucoid strain.
Oxytocin ameliorates impaired social behavior in a Chd8 haploinsufficiency mouse model of autism
Authors: Cherepanov Stanislav M. , Gerasimenko Maria , Yuhi Teruko , Furuhara Kazumi , Tsuji Chiharu , Yokoyama Shigeru , Nakayama Keiichi I. , Nishiyama Masaaki , Higashida Haruhiro
Published: May 2021

Background

Autism spectrum disorder (ASD) is characterized by the core symptoms of impaired social interactions. Increasing evidence suggests that ASD has a strong genetic link with mutations in chromodomain helicase DNA binding protein 8 (CHD8), a gene encoding a chromatin remodeler. It has previously been shown that Chd8 haplodeficient male mice manifest ASD-like behavioral characteristics such as anxiety and altered social behavior. Along with that, oxytocin (OT) is one of the main neuropeptides involved in social behavior. Administration of OT has shown improvement of social behavior in genetic animal models of ASD. The present study was undertaken to further explore behavioral abnormalities of Chd8 haplodeficient mice of both sexes, their link with OT, and possible effects of OT administration. First, we performed a battery of behavioral tests on wild-type and Chd8+/∆SL female and male mice. Next, we measured plasma OT levels and finally studied the effects of intraperitoneal OT injection on observed behavioral deficits.

Results

We showed general anxiety phenotype in Chd8+/∆SL mice regardless of sex, the depressive phenotype in Chd8+/∆SL female mice only and bidirectional social deficit in female and male mice. We observed decreased level of OT in Chd+/∆SL mice, possibly driven by males. Mice injected by OT demonstrated recovery of social behavior, while reduced anxiety was observed only in male mice.

Conclusions

Here, we demonstrated that abnormal social behaviors were observed in both male and female Chd8+/∆SL mice. The ability of peripheral OT administration to affect such behaviors along with altered plasma OT levels indicated a possible link between Chd8 + /∆SL and OT in the pathogenesis of ASD as well as the possible usefulness of OT as a therapeutic tool for ASD patients with CHD8 mutations.