bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping genomic regions affecting milk traits in Sarda sheep by using the OvineSNP50 Beadchip and principal components to perform combined linkage and linkage disequilibrium analysis
Authors: Usai Mario Graziano , Casu Sara , Sechi Tiziana , Salaris Sotero L. , Miari Sabrina , Sechi Stefania , Carta Patrizia , Carta Antonello
Published: November 2019

Background

The detection of regions that affect quantitative traits (QTL), to implement selection assisted by molecular information, remains of particular interest in dairy sheep for which genetic gain is constrained by the high costs of large-scale phenotype and pedigree recording. QTL detection based on the combination of linkage disequilibrium and linkage analysis (LDLA) is the most suitable approach in family-structured populations. The main issue in performing LDLA mapping is the handling of the identity-by-descent (IBD) probability matrix. Here, we propose the use of principal component analysis (PCA) to perform LDLA mapping for milk traits in Sarda dairy sheep.

Methods

A resource population of 3731 ewes belonging to 161 sire families and genotyped with the OvineSNP50 Beadchip was used to map genomic regions that affect five milk traits. The paternally and maternally inherited gametes of genotyped individuals were reconstructed and IBD probabilities between them were defined both at each SNP position and at the genome level. A QTL detection model fitting fixed effects of principal components that summarize IBD probabilities was tested at each SNP position. Genome-wide (GW) significance thresholds were determined by within-trait permutations.

Results

PCA resulted in substantial dimensionality reduction, in fact 137 and 32 (on average) principal components were able to capture 99% of the IBD variation at the locus and genome levels, respectively. Overall, 2563 positions exceeded the 0.05 GW significance threshold for at least one trait, which clustered into 75 QTL regions most of which affected more than one trait. The strongest signal was obtained for protein content onOvis aries(OAR) chromosome 6 and overlapped with the region that harbours the casein gene cluster. Additional interesting positions were identified on OAR4 for fat content and on OAR11 for the three yield traits.

Conclusions

PCA is a good strategy to summarize IBD probabilities. A large number of regions associated to milk traits were identified. The outputs provided by the proposed method are useful for the selection of candidate genes, which need to be further investigated to identify causative mutations or markers in strong LD with them for application in selection programs assisted by molecular information.
Twelve complete chloroplast genomes of wild peanuts: great genetic resources and a better understanding of Arachis phylogeny
Authors: Wang Juan , Li Yuan , Li Chunjuan , Yan Caixia , Zhao Xiaobo , Yuan Cuiling , Sun Quanxi , Shi Chengren , Shan Shihua
Published: November 2019

Background

The cultivated peanut (Arachis hypogaea) is one of the most important oilseed crops worldwide, however, its improvement is restricted by its narrow genetic base. The highly variable wild peanut species, especially within Sect.Arachis, may serve as a rich genetic source of favorable alleles to peanut improvement; Sect.Arachisis the biggest taxonomic section within genusArachisand its members also include the cultivated peanut. In order to make good use of these wild resources, the genetic bases and the relationships of theArachisspecies need first to be better understood.

Results

Here, in this study, we have sequenced and/or assembled twelveArachiscomplete chloroplast (cp) genomes (eleven from Sect.Arachis). These cp genome sequences enriched the publishedArachiscp genome data. From the twelve acquired cp genomes, substantial genetic variation (1368 SNDs, 311 indels) has been identified, which, together with 69 SSR loci that have been identified from the same data set, will provide powerful tools for future explorations. Phylogenetic analyses in our study have grouped the Sect.Arachisspecies into two major lineages (I & II), this result together with reports from many earlier studies show that lineage II is dominated by AA genome species that are mostly perennial, while lineage I includes species that have more diverse genome types and are mostly annual/biennial. Moreover, the cultivated peanuts andA.monticolathat are the only tetraploid (AABB) species withinArachisare nested within the AA genome species-dominated lineage, this result together with the maternal inheritance of chloroplast indicate a maternal origin of the two tetraploid species from an AA genome species.

Conclusion

In summary, we have acquired sequences of twelve completeArachiscp genomes, which have not only helped us better understand how the cultivated peanut and its close wild relatives are related, but also provided us with rich genetic resources that may hold great potentials for future peanut breeding.
Accuracy in detecting inadequate research reporting by early career peer reviewers using an online CONSORT-based peer-review tool (COBPeer) versus the usual peer-review process: a cross-sectional diagnostic study
Authors: Chauvin Anthony , Ravaud Philippe , Moher David , Schriger David , Hopewell Sally , Shanahan Daniel , Alam Sabina , Baron Gabriel , Regnaux Jean-Philippe , Crequit Perrine , Martinez Valeria , Riveros Carolina , Le Cleach Laurence , Recchioni Alessandro , Altman Douglas G. , Boutron Isabelle
Published: November 2019

Background

The peer review process has been questioned as it may fail to allow the publication of high-quality articles. This study aimed to evaluate the accuracy in identifying inadequate reporting in RCT reports by early career researchers (ECRs) using an online CONSORT-based peer-review tool (COBPeer) versus the usual peer-review process.

Methods

We performed a cross-sectional diagnostic study of 119 manuscripts, from BMC series medical journals, BMJ, BMJ Open, and Annals of Emergency Medicine reporting the results of two-arm parallel-group RCTs. One hundred and nineteen ECRs who had never reviewed an RCT manuscript were recruited from December 2017 to January 2018. Each ECR assessed one manuscript. To assess accuracy in identifying inadequate reporting, we used two tests: (1) ECRs assessing a manuscript using the COBPeer tool (after completing an online training module) and (2) the usual peer-review process. The reference standard was the assessment of the manuscript by two systematic reviewers. Inadequate reporting was defined as incomplete reporting or a switch in primary outcome and considered nine domains: the eight most important CONSORT domains and a switch in primary outcome(s). The primary outcome was the mean number of domains accurately classified (scale from 0 to 9).

Results

The mean (SD) number of domains (0 to 9) accurately classified per manuscript was 6.39 (1.49) for ECRs using COBPeer versus 5.03 (1.84) for the journal’s usual peer-review process, with a mean difference [95% CI] of 1.36 [0.88–1.84] (p < 0.001). Concerning secondary outcomes, the sensitivity of ECRs using COBPeer versus the usual peer-review process in detecting incompletely reported CONSORT items was 86% [95% CI 82–89] versus 20% [16–24] and in identifying a switch in primary outcome 61% [44–77] versus 11% [3–26]. The specificity of ECRs using COBPeer versus the usual process to detect incompletely reported CONSORT domains was 61% [57–65] versus 77% [74–81] and to identify a switch in primary outcome 77% [67–86] versus 98% [92–100].

Conclusions

Trained ECRs using the COBPeer tool were more likely to detect inadequate reporting in RCTs than the usual peer review processes used by journals. Implementing a two-step peer-review process could help improve the quality of reporting.

Trial registration

Clinical.Trials.govNCT03119376 (Registered April, 18, 2017).
Comparison of Apolipoprotein B/A1 ratio, Framingham risk score and TC/HDL-c for predicting clinical outcomes in patients undergoing percutaneous coronary intervention
Authors: Tian Min , Li Rui , Shan Zhilei , Wang Dao Wen , Jiang Jiangang , Cui Guanglin
Published: November 2019

Background

Apolipoproteins (Apo) are known atherogenic factors that play important roles in many mechanisms related to coronary heart disease (CHD). However, it is unclear whether the apoB/apoA1 ratio is an equal or a better predictor than the Framingham Risk Score or TC/HDL-c for predicting clinical outcomes in patients undergoing percutaneous coronary intervention.

Methods

We investigated the association between Apolipoprotein B/A1 ratio and cardiovascular risk factors as well as the severity of CHD in 2256 Han Chinese patients. The potential of Apolipoprotein B/A1 ratio, Framingham Risk Score and TC/HDL-c were assessed as a marker to predict cardiovascular adverse events in a prospective subgroup of 1639 CHD patients during a 5-year follow-up.

Results

In the multivariate model, adjusted odds ratios (ORs) were significant for 3-VD vs. 1-VD (OR = 2.36; 95% CI: 1.65–3.38, for the fourth vs. first quartile; Ptrend < 0.001). The subgroup analysis showed that patients with a higher ApoB/ApoA1 ratio had an increased risk of developing multi-branch lesions and potentially suffer more cardiovascular adverse events (anginas, myocardial infarctions, heart failures, strokes, and cardiac deaths) in the future (adjusted HR =1.92; 95% CI: 1.10–3.13, for the fourth vs. first quartile). In the ROC analysis, the AUC for ApoB/A1 ratio was larger than that of Framingham Risk Score (0.604 vs. 0.543, p = 0.01) and TC/HDL-c (0.604 vs. 0.525, p < 0.01).

Conclusion

Our results suggest a significant association between ApoB/ApoA1 ratio and CHD severity and cardiovascular outcomes among patients with existing CHD and ApoB/A1 ratio demonstrated a better predictive accuracy for clinical outcomes compared with Framingham Risk Score and TC/HDL-c.
Incidence and risk factors of portomesenteric venous thrombosis after colorectal surgery for cancer in the elderly population
Authors: Manigrasso Michele , Milone Marco , Velotti Nunzio , Vertaldi Sara , Schettino Pietro , Musella Mario , Aprea Giovanni , Gennarelli Nicola , Maione Francesco , Sarnelli Giovanni , Venetucci Pietro , De Palma Giovanni Domenico , Milone Francesco
Published: November 2019

Background

Although it is known that portomesenteric venous thrombosis (PMVT) is associated with total colectomy and proctocolectomy in young patients with inflammatory bowel disease, little is known about incidence and risk factors of PMVT among the elderly population undergoing colorectal surgery for cancer.

Methods

Data of elderly patients (> 70 years) undergoing surgery for colorectal cancer were retrospectively registered. The occurrence of PMVT was correlated with the patients’ characteristics and operative variables. Data collected included age, sex, obesity, ASA score, tumor degree, type of surgical resection, surgical approach (laparoscopic or open), and duration of surgery (from skin incision to the application of dressings).

Results

A total of 137 patients > 70 years who underwent surgery for colorectal cancer and developed an acute intraabdominal process with suggestive symptoms, needing a CT scan, were included. Three of these patients (2.1%) had portomesenteric venous thrombosis during the study period, which was proved with CT scan. There were no significant patients’ characteristics or operative variables between patients with or without the occurrence of PMVT after surgery. Of interest, only operative time was significantly higher in patients with PMVT after surgery (256 ± 40 vs 140 ± 41, p < 0.001).

Conclusions

PMVT as a cause of abdominal pain after colorectal surgery for cancer in the elderly population is uncommon. An index of suspicion for PMVT in an elderly postoperative colorectal cancer patient with sudden onset of abdominal pain must be maintained.
TPP-related mitochondrial targeting copper (II) complex induces p53-dependent apoptosis in hepatoma cells through ROS-mediated activation of Drp1
Authors: Shao Jiangjuan , Li Mengmeng , Guo Zijian , Jin Chun , Zhang Feng , Ou Chunyan , Xie Yaochen , Tan Shanzhong , Wang Zhenyi , Zheng Shizhong , Wang Xiaoyong
Published: November 2019

Background

In recent years, copper complexes have gradually become the focus of potential anticancer drugs due to their available redox properties and low toxicity. In this study, a novel mitochondrion-targeting copper (II) complex, [Cu (ttpy-tpp)Br2] Br (simplified as CTB), is first synthesized by our group. CTB with tri-phenyl-phosphine (TPP), a targeting and lipophilic group, can cross the cytoplasmic and mitochondrial membranes of tumor cells. The present study aims to investigate how CTB affects mitochondrial functions and exerts its anti-tumor activity in hepatoma cells.

Methods

Multiple molecular experiments including Flow cytometry, Western blot, Immunofluorescence, Tracker staining, Transmission Electron Microscopy and Molecular docking simulation were used to elucidate the underlying mechanisms. Human hepatoma cells were subcutaneously injected into right armpit of male nude mice for evaluating the effects of CTB in vivo.

Results

CTB induced apoptosis via collapse of mitochondrial membrane potential (MMP), ROS production, Bax mitochondrial aggregation as well as cytochrome c release, indicating that CTB-induced apoptosis was associated with mitochondrial pathway in human hepatoma cells. Mechanistic study revealed that ROS-related mitochondrial translocation of p53 was involved in CTB-mediated apoptosis. Simultaneously, elevated mitochondrial Drp1 levels were also observed, and interruption of Drp1 activation played critical role in p53-dependent apoptosis. CTB also strongly suppressed the growth of liver cancer xenografts in vivo.

Conclusion

In human hepatoma cells, CTB primarily induces mitochondrial dysfunction and promotes accumulation of ROS, leading to activation of Drp1. These stimulation signals accelerate mitochondrial accumulation of p53 and lead to the eventual apoptosis. Our research shows that CTB merits further evaluation as a chemotherapeutic agent for the treatment of Hepatocellular carcinoma (HCC).
Correction to: Inhibition of the key metabolic pathways, glycolysis and lipogenesis, of oral cancer by bitter melon extract
Authors: Sur Subhayan , Nakanishi Hiroshi , Flaveny Colin , Ippolito Joseph E. , McHowat Jane , Ford David A. , Ray Ratna B.
Published: November 2019

Following publication of the original article [1], it was reported that Fig. 1c was not entirely readable due to overlapping Fig. 1d. The publishers apologise for this error.
Optimising the use of caesarean section: a generic formative research protocol for implementation preparation
Authors: Bohren Meghan A. , Opiyo Newton , Kingdon Carol , Downe Soo , Betrán Ana Pilar
Published: November 2019

Background

Caesarean section rates are rising across all geographical regions. Very high rates for some groups of women co-occur with very low rates for others. Both extremes are associated with short and longer term harms. This is a major public health concern. Making the most effective use of caesarean section is a critical component of good quality, sustainable maternity care. In 2018, the World Health Organization published evidence-based recommendations on non-clinical interventions to reduce unnecessary caesarean section. The guideline identified critical research gaps and called for formative research to be conducted ahead of any interventional research to define locally relevant determinants of caesarean birth and factors that may affect implementation of multifaceted optimisation strategies. This generic formative research protocol is designed as a guide for contextual assessment and understanding for anyone planning to take action to optimise the use of caesarean section.

Methods

This formative protocol has three main components: (1) document review; (2) readiness assessment; and (3) primary qualitative research with women, healthcare providers and administrators. The document review and readiness assessment include tools for local mapping of policies, protocols, practices and organisation of care to describe and assess the service context ahead of implementation. The qualitative research is organized according to twelve identified interventions that may optimise use of caesarean section. Each intervention is designed as a “module” and includes a description of the intervention, supporting evidence, theory of change, and in-depth interview/focus group discussion guides. All study instruments are included in this protocol.

Discussion

This generic protocol is designed to underpin the formative stage of implementation research relating to optimal use of caesarean section. We encourage researchers, policy-makers and ministries of health to adapt and adopt this design to their context, and share their findings as a catalyst for rapid uptake of what works.
JNER at 15 years: analysis of the state of neuroengineering and rehabilitation
Authors: Reinkensmeyer David J.
Published: November 2019

On JNER’s 15th anniversary, this editorial analyzes the state of the field of neuroengineering and rehabilitation. I first discuss some ways that the nature of neurorehabilitation research has evolved in the past 15 years based on my perspective as editor-in-chief of JNER and a researcher in the field. I highlight increasing reliance on advanced technologies, improved rigor and openness of research, and three, related, new paradigms – wearable devices, the Cybathlon competition, and human augmentation studies – indicators that neurorehabilitation is squarely in the age of wearability. Then, I briefly speculate on how the field might make progress going forward, highlighting the need for new models of training and learning driven by big data, better personalization and targeting, and an increase in the quantity and quality of usability and uptake studies to improve translation.
Potential risk factors and triggers for back pain in children and young adults. A scoping review, part II: unclear or mixed types of back pain
Authors: Beynon Amber M , Hebert Jeffrey J , Lebouef-Yde Charlotte , Walker Bruce F
Published: November 2019

Background

Back pain is a global problem in terms of disability and financially, with a large burden both to the individual and to society. Back pain was previously believed to be uncommon in children. However, there is a growing body of evidence that this is not the case.

Objective

Part I of this scoping review studied risk factors of incident and episodic back pain. In this part II we aimed to identify all risk factors and triggers with unclear or mixed type back pain in young people and to identify any gaps in the literature.

Methods

A scoping review design was selected to summarise the evidence, as there are many studies on “risk factors” for back pain. The scoping review followed the PRISMSA-ScR guidelines. We considered all studies that tested potential risk factors and triggers for thoracic and/or lumbar spine pain, in children, adolescents, and young adults (≤ 24 years). PubMed and Cochrane databases were searched from inception to September 2018, to identify relevant English language articles. The results regarding potential risk factors were separated into temporal precursors and bidirectional risk factors and the studies were classified by study design.

Results

Our comprehensive search strategy identified 7356 articles, of which 83 articles were considered eligible for this review (part II). There were 53 cross-sectional studies and 30 cohort studies. Potential risk factors for back pain were: female sex, older age, later pubertal status, positive family history of back pain, increased growth, and a history of back pain, most of which are temporal precursor variables. There was limited research for the illness factors, spinal posture, and muscle endurance in the development of back pain.

Conclusion

Many of the included studies approached risk factors in similar ways and found factors that were associated with back pain but were not obvious risk factors as causality was uncertain. Future research should be more rigorous and innovative in the way that risk factors are considered. This could be through statistical approaches including cumulative exposures, or longitudinal approaches including multi-trajectory methods. Additionally, data on proposed risk factors should be collected before the onset of back pain.
Genetic dynamics in untreated CLL patients with either stable or progressive disease: a longitudinal study
Authors: Ramassone Alice , D’Argenio Andrea , Veronese Angelo , Basti Alessio , Soliman Shimaa Hassan AbdelAziz , Volinia Stefano , Bassi Cristian , Pagotto Sara , Ferracin Manuela , Lupini Laura , Saccenti Elena , Balatti Veronica , Pepe Felice , Rassenti Laura Z. , Innocenti Idanna , Autore Francesco , Marzetti Laura , Mariani-Costantini Renato , Kipps Thomas J. , Negrini Massimo , Laurenti Luca , Visone Rosa
Published: November 2019

Clonal evolution of chronic lymphocytic leukemia (CLL) often follows chemotherapy and is associated with adverse outcome, but also occurs in untreated patients, in which case its predictive role is debated. We investigated whether the selection and expansion of CLL clone(s) precede an aggressive disease shift. We found that clonal evolution occurs in all CLL patients, irrespective of the clinical outcome, but is faster during disease progression. In particular, changes in the frequency of nucleotide variants (NVs) in specific CLL-related genes may represent an indicator of poor clinical outcome.
Artificial intelligence in clinical and genomic diagnostics
Authors: Dias Raquel , Torkamani Ali
Published: November 2019

Artificial intelligence (AI) is the development of computer systems that are able to perform tasks that normally require human intelligence. Advances in AI software and hardware, especially deep learning algorithms and the graphics processing units (GPUs) that power their training, have led to a recent and rapidly increasing interest in medical AI applications. In clinical diagnostics, AI-based computer vision approaches are poised to revolutionize image-based diagnostics, while other AI subtypes have begun to show similar promise in various diagnostic modalities. In some areas, such as clinical genomics, a specific type of AI algorithm known as deep learning is used to process large and complex genomic datasets. In this review, we first summarize the main classes of problems that AI systems are well suited to solve and describe the clinical diagnostic tasks that benefit from these solutions. Next, we focus on emerging methods for specific tasks in clinical genomics, including variant calling, genome annotation and variant classification, and phenotype-to-genotype correspondence. Finally, we end with a discussion on the future potential of AI in individualized medicine applications, especially for risk prediction in common complex diseases, and the challenges, limitations, and biases that must be carefully addressed for the successful deployment of AI in medical applications, particularly those utilizing human genetics and genomics data.
Nutritional deficiency and associated factors among new pulmonary tuberculosis patients of Bale Zone Hospitals, southeast Ethiopia
Authors: Hussien Bedru , Hussen Mohammedaman Mama , Seid Abdulwahab , Hussen Abduljewad
Published: November 2019

Objective

Tuberculosis remains deadliest communicable diseases accountable for health problem among various individuals annually and is related to malnutrition. Addressing nutritional deficiency in Tuberculosis patients is a crucial side of tuberculosis management programme. Therefore, the aim was to assess the magnitude of nutritional deficiency and associated factors among new pulmonary tuberculosis patients of Bale Zone Hospitals, south-east Ethiopia, 2018. Cross-sectional study design was utilized. Data collection was carried out using structured questionnaires and anthropometric measurements. Body mass index was calculated to see nutritional deficiency. Crude and adjusted odds ratios in conjunction with their corresponding 95% confidence intervals were computed. p-value < 0.05 was thought of to declare a result as statistically associated.

Results

Prevalence of nutritional deficiency was 63.2%. The mean Body mass index for all listed participants was 17.86 kg/m2. Employment status of the patients, p-value 0.012 (AOR = 1.82; 95% CI 1.14, 2.89) and Khat chewing, p-value 0.02 (AOR = 0.43; 95% CI 0.23, 0.85) were factors independently associated with nutritional deficiency. Prevalence of nutritional deficiency was found to be high. Nutritional support for the impoverished, regular nutritional assessment and dietary counseling are necessary for better treatment outcome and effective Tuberculosis management programme.
Determinants of underweight among 6–59 months old children in Berahle, Afar, North East Ethiopia: a case control study 2016
Authors: Hintsa Solomon , Gereziher Kiros
Published: November 2019

Objective

The objective of this study was to identify determinants of underweight among 6–59 months old children in Berahle Woreda, Afar, North East Ethiopia, in 2016.

Result

The median age (IQR) of cases and controls were 24 (34) and 18 (23) months respectively and 51.6% of the children were not exclusively breast-fed but 64.8% controls were exclusively breastfed. Age group of 48–59 months (AOR = 11.93; 95% CI 3.88–36.67), illiterate mothers (AOR = 2.32; 95% CI 1.19–4.55), low dietary diversity (AOR = 4.57; 95% CI 2.40–8.69), diarrhea in the past of 2 weeks (AOR = 2.93; 95% CI 1.46–5.85), birth interval (AOR = 5.17; 95% CI 2.37–11.26) and unprotected source of water (AOR = 2.62; 95% CI 1.42–4.85) were determinant factors of underweight.
Human mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayers
Authors: Islam Md Nahidul , Griffin Tomás P. , Sander Elizabeth , Rocks Stephanie , Qazi Junaid , Cabral Joana , McCaul Jasmin , McMorrow Tara , Griffin Matthew D.
Published: November 2019

Background

Renal proximal tubular epithelial cells (RPTEC) are dysfunctional in diabetic kidney disease (DKD). Mesenchymal stromal cells (MSC) may modulate DKD pathogenesis through anti-inflammatory mediators. This study aimed to investigate the pro-inflammatory effect of extended exposure to high glucose (HG) concentration on stable RPTEC monolayers and the influence of MSC on this response.

Methods

Morphologically stable human RPTEC/TERT1 cell monolayers were exposed to 5 mM and 30 mM (HG)D-glucoseor to 5 mMD-glucose + 25 mMD-mannitol(MAN) for 5 days with sequential immunoassays of supernatants and end-point transcriptomic analysis by RNA sequencing. Under the same conditions, MSC-conditioned media (MSC-CM) or MSC-containing transwells were added for days 4–5. Effects of CM from HG- and MAN-exposed RPTEC/MSC co-cultures on cytokine secretion by monocyte-derived macrophages were determined.

Results

After 72–80 h, HG resulted in increased RPTEC/TERT1 release of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL). The HG pro-inflammatory effect was attenuated by concentrated (10×) MSC-CM and, to a greater extent, by MSC transwell co-culture. Bioinformatics analysis of RNA sequencing data confirmed a predominant effect of HG on inflammation-related mediators and biological processes/KEGG pathways in RPTEC/TERT1 stable monolayers as well as the non-contact-dependent anti-inflammatory effect of MSC. Finally, CM from HG-exposed RPTEC/MSC transwell co-cultures was associated with attenuated secretion of inflammatory mediators by macrophages compared to CM from HG-stimulated RPTEC alone.

Conclusions

Stable RPTEC monolayers demonstrate delayed pro-inflammatory response to HG that is attenuated by close proximity to human MSC. In DKD, this MSC effect has potential to modulate hyperglycemia-associated RPTEC/macrophage cross-talk.
ETV2/ER71 regulates the generation of FLK1+ cells from mouse embryonic stem cells through miR-126-MAPK signaling
Authors: Kim Ju Young , Lee Dong Hun , Kim Joo Kyung , Choi Hong Seo , Dwivedi Bhakti , Rupji Manali , Kowalski Jeanne , Green Stefan J. , Song Heesang , Park Won Jong , Chang Ji Young , Kim Tae Min , Park Changwon
Published: November 2019

Previous studies including ours have demonstrated a critical function of the transcription factor ETV2 (ets variant 2; also known as ER71) in determining the fate of cardiovascular lineage development. However, the underlying mechanisms of ETV2 function remain largely unknown. In this study, we demonstrated the novel function of the miR (micro RNA)-126-MAPK (mitogen-activated protein kinase) pathway in ETV2-mediated FLK1 (fetal liver kinase 1; also known as VEGFR2)+cell generation from the mouse embryonic stem cells (mESCs). By performing a series of experiments including miRNA sequencing and ChIP (chromatin immunoprecipitation)-PCR, we found that miR-126 is directly induced by ETV2. Further, we identified that miR-126 can positively regulate the generation of FLK1+cells by activating the MAPK pathway through targeting SPRED1 (sprouty-related EVH1 domain containing 1). Further, we showed evidence that JUN/FOS activate the enhancer region of FLK1 through AP1 (activator protein 1) binding sequences. Our findings provide insight into the novel molecular mechanisms of ETV2 function in regulating cardiovascular lineage development from mESCs.
Knowledge and perception of small holding farmers on supplementation and feeding sweet potato vines to goats
Authors: Luthuli Cynthia Fikile , Fon Fabian Nde , Gunya Busisiwe
Published: November 2019

Goats in rural communities are often raised in conditions which do not allow them to achieve their maximum performance nor express their genetic potentials. For goats to perform to their full potential, they require high nutritious feed especially in the winter season when there is food shortage or during high milk-producing periods. However, supplementation can be done using fresh green feeds, protein blocks or vitamins which are often expensive, hence the need to source for indigenous crop residues. This study assessed the knowledge and perceptions of farmers on feeding sweet potato vines to their goats. The data were gathered by administering a total of 105 structured questionnaires using face-to-face interviews. The results showed that the majority of farmers (71.4%) were aware and practise some sort of supplementary feeding. Most farmers (72.4%) cultivated sweet potatoes, and they used them for different purposes such as income generation (53.3%), consumption (27.5%) or both (8%). Sweet potato vines were being discarded as waste or burnt (32.4%), left on the field as manure (25.7%), conserved as propagation material (8.6%) or randomly fed to livestock (7.6%). Nevertheless, most of the farmers (78.1%) rejected the use of sweet potato vines as feed to livestock. In conclusion, more intervention measures are required for developing farmers’ knowledge and perception on feeding sweet potatoe vines to livestock. Farmers may be assisted through training and workshops on the use of sweet potato vines and other indigenous forage supplementation as feed.
Transcriptome analysis reveals an important candidate gene involved in both nodal metastasis and prognosis in lung adenocarcinoma
Authors: Zhu Xiao , Luo Hui , Xu Ying
Published: November 2019

Lymph node metastasis of lung cancer is a serious problem. Therefore, there is a need for a detailed transcriptome study of metastatic lung adenocarcinoma. The lung adenocarcinoma RNA-seq data and the corresponding clinical information available from TCGA were analyzed. Differential expression, gradient changes, and biological pathways were carried out. Potential gene(s) associated with tumor metastasis and survival were validated by Cox regression. A total of 406 and 439 differentially expressed genes were identified for lymph node metastasis and TNM stages, respectively. Of the 296 intersection genes, 112 were associated with nodal metastasis and/or staging. Only 25 of these 112 genes with gradient changes were involved in nodal metastasis, and 13 were involved in staging. Only one gene, RN7SL494P, might be involved in lung adenocarcinoma development and poor outcome. Finally, Cox regression results verified that age, pathology classification, radiotherapy and chemotherapy are all the independent prognostic factors. In particular, RN7SL494P was further verified to be an independent factor affecting lymph node metastasis and patient survival. Furthermore, we verified the RN7SL494P function using simulation data generated by mixing cell lines of the Cancer Cell Line Encyclopedia (CCLE) and obtained consistent results. Our findings suggest a potential clinical application of the RN7SL494P as a promising marker in the evaluation of patients with primary lung adenocarcinoma, not only for predicting nodal metastasis, but also for the prognosis of the outcome.
Periodic pulse control of Hopf bifurcation in a fractional-order delay predator–prey model incorporating a prey refuge
Authors: Liu Xiuduo , Fang Hui
Published: November 2019

This paper is concerned with periodic pulse control of Hopf bifurcation for a fractional-order delay predator–prey model incorporating a prey refuge. The existence and uniqueness of a solution for such system is studied. Taking the time delay as the bifurcation parameter, critical values of the time delay for the emergence of Hopf bifurcation are determined. A novel periodic pulse delay feedback controller is introduced into the first equation of an uncontrolled system to successfully control the delay-deduced Hopf bifurcation of such a system. Since the stability theory is not well-developed for nonlinear fractional-order non-autonomous systems with delays, we investigate the periodic pulse control problem of the original system by a semi-analytical and semi-numerical method. Specifically, the stability of the linearized averaging system of the controlled system is first investigated, and then it is shown by numerical simulations that the controlled system has the same stability characteristics as its linearized averaging system. The proposed periodic pulse delay feedback controller has more flexibility than a classical linear delay feedback controller guaranteeing the control effect, due to the fact that the pulse width in each control period can be flexibly selected.
Clinical significance of stromal ER and PR expression in periampullary adenocarcinoma
Authors: Andersson Gustav , Lundgren Sebastian , Heby Margareta , Nodin Björn , Elebro Jacob , Jirström Karin
Published: November 2019

Background

Tamoxifen treatment has previously been reported to confer life-prolonging effects in patients with advanced pancreatic cancer, and most evidently so in women. None of these trials did however include biomarkers, and the relevance of female hormone signaling in pancreatic or other periampullary adenocarcinoma remains largely unexplored. The aim of this study was to examine the extent and potential clinical significance of estrogen receptor-α (ER) and progesterone receptor (PR) expression in pancreatic and other periampullary cancers.

Methods

ER and PR expression was examined using immunohistochemistry on tissue microarrays with primary tumors from a retrospective consecutive cohort of 175 patients with resected periampullary adenocarcinoma, with long-term clinical follow-up. Non-parametric and Chi square tests were applied to examine the associations of stromal ER and PR expression with patient and tumor characteristics. Kaplan-Meier analysis and log rank test were applied to illustrate survival differences in relation to ER and PR expression. Cox regression proportional hazards models were applied to examine the associations between investigative factors and risk of death and recurrence, and to test for interactions between KRAS mutation status and hormone receptor expression in relation to survival.

Results

Expression of both ER and PR was more frequent in the tumor-associated stroma than in the epithelium. A significant prognostic interaction, independent of tumor morphology, was found between stromal PR expression and KRAS mutation status in relation to both overall and recurrence-free survival (pinteraction = 0.026 and pinteraction = 0.005), in particular in women (pinteraction = 0.002 and pinteraction = 0.005). Specifically, stromal PR expression was associated with a prolonged survival in patients with KRAS-mutated tumors, whereas the opposite was seen for KRAS wild-type tumors. The prognostic value of ER positivity was limited to the subgroup of women with tumors of pancreatic origin.

Conclusions

These results demonstrate that stromal PR rather than ER expression, together with KRAS mutation status, provides long-term prognostic information in patients with periampullary adenocarcinoma. Further study into the mechanistic basis for these observations may unveil important clues to the pathogenesis of these cancers and open up for the discovery of novel treatment options.
Exosome release and neuropathology induced by α-synuclein: new insights into protective mechanisms of Drp1 inhibition
Authors: Fan Rebecca Z. , Guo Min , Luo Shouqing , Cui Mei , Tieu Kim
Published: November 2019

Targeting alpha-synuclein (α-syn) as a therapeutic strategy for Parkinson’s disease (PD) has been intensively pursued largely due to its well-recognized pathogenic role. Since its discovery as the first familial link to PD over two decades ago, this protein has been associated with multiple neurotoxic mechanisms, such as mitochondrial dysfunction and impaired autophagic flux. We report here that blocking dynamin-related protein 1 (Drp1) improved both mitochondrial function and autophagic flux in experimental models of α-syn. Using rat dopaminergic neuronal cells with inducible wild-type human α-syn, we observed excessive mitochondrial fragmentation and increased Drp1 levels 48 h after gene induction. Functionally, these cells exhibited lower mitochondrial membrane potential, reduced ATP production rate and mitochondrial spare respiratory capacity, as well as increased levels of mitochondrial reactive oxygen species. To evaluate the protective role of Drp1 inhibition, we used three complementary approaches: gene silencing mediated by siRNA, overexpression of Drp1-dominant negative and the small molecule mitochondrial division inhibitor-1 (mdivi-1). Both morphological and functional defects induced by α-syn were attenuated by these strategies. Importantly, Drp1 inhibition reduced proteinase K-resistant α-syn aggregates. Based on that observation, we investigated the involvement of autophagy. Through a combination of stable autophagy reporter cells and immunoreactivity for LC3 and p62 in neuronal cells with either α-syn overexpression or treatment of human α-syn preformed fibrils (PFF), we observed that Drp1 inhibition abolished autophagic impairment induced by α-syn. Consistent with its role in improving autophagy function, Drp1 inhibition reduced exosome release and spread of α-syn pathology from neurons to neurons and from microglia to neurons. In summary, this study highlights new insights that Drp1 inhibition confers neuroprotection through both mitochondrial and autophagy-lysosomal pathways, further strengthening the therapeutic potential of targeting Drp1.
Bioactivity of Citrus essential oils (CEOs) against microorganisms associated with spoilage of some fruits
Authors: Ajayi-Moses Oluwatayo Benjamin , Ogidi Clement Olusola , Akinyele Bamidele Juliet
Published: November 2019

Background

This study evaluated the antimicrobial potentials of Citrus essential oils (CEOs) against spoilage microorganisms isolated from selected fruits. The fruits were randomly purchased from different markets in Akure, Nigeria.

Methods

The microorganisms were isolated and identified using molecular tools. In vitro antimicrobial efficacies of CEOs and their synergistic potentials were tested against spoilage microorganisms using agar well diffusion. The bioactive compounds in CEOs were identified using gas chromatography–mass spectrometry (GC–MS).

Results

The highest bacterial count (5.84 × 105 cfu/g) was recorded in tomatoes, while African star apple had the highest fungal count of 3.04 × 105 sfu/g. Microorganisms isolated from fruits were Bacillus spp., Micrococcus luteus, Serratia marcescens, Aspergillus spp., Mucor piriformis, Fusarium oxysporum, Penicillium spp., Rhizopus spp., Alternaria alternata and others. Phytochemicals in the CEOs were anthraquinones, cardiac glycosides, tannins, alkaloids, terpenoids, saponins, steroids, flavonoids and phenol. The diameter zones of inhibition displayed by CEOs against tested microorganisms at 100 mg/ml ranged from 3.3 mm to 26.8 mm with B. muralis being the most susceptible bacteria. The minimum inhibitory concentration (MIC) against all the tested isolates ranged from 12.5 to 100 mg/ml, while the minimum bactericidal and fungicidal concentrations ranged from 25 to ≥ 100 mg/ml. The synergism between lime and lemon at ratio 1:1 had better antimicrobial activity than each essential oil when used singly. GC–MS revealed the presence of limonene, beta-pinene, alpha-phellandrene, terpinen-4-ol, alpha-terpineol and geraniol in EOs of lime and lemon.

Conclusion

The inhibitory potential of CEOs could be attributed to their bioactive compounds, which can be exploited and used as preservatives by food industries.
Neoplastic cells parasitized by Mycobacterium leprae: report of two cases of melanocytic nevus and one of basal cell carcinoma
Authors: Teixeira Cleverson Soares , Montalvão Patricia Pinheiro , de Oliveira Isabella Tostes , Wachholz Patrick Alexander
Published: November 2019

Background

Leprosy is a major public health concern in many developing countries. Mycobacterium leprae (M. leprae), the causative agent of leprosy, has the ability to parasitize different types of human cells and tissues. In this article, the uncommon parasitism of nevus and neoplastic and epithelial cells byM. lepraeare described using histological sections doubly stained by Fite-Faraco (FF) and immunohistochemistry (IHC), respectively.

Case presentation

Three patients with borderline-lepromatous and lepromatous leprosy underwent excision of melanocytic nevi (cases 1–2) and basal cell carcinoma (case 3). Histological sections confirmed the clinical diagnosis of melanocytic nevus and basal cell carcinoma, but leprosy lesions were evident in adjacent tissues. FF staining and IHC (CD68, Melan A, and 34βE12) demonstrated the presence of bacilli within the nevus cells and also in the epithelial cells of the basal cell carcinoma.

Conclusions

M. lepraehas the ability to parasitize different types of cells, including neoplastic cells. Pathologists working in settings where leprosy is endemic should be aware that some cutaneous biopsy specimens may also present with leprosy findings.
Tenophages: a novel macrophage-like tendon cell population expressing CX3CL1 and CX3CR1
Authors: Lehner Christine , Spitzer Gabriel , Gehwolf Renate , Wagner Andrea , Weissenbacher Nadja , Deininger Christian , Emmanuel Katja , Wichlas Florian , Tempfer Herbert , Traweger Andreas
Published: November 2019

Tendon disorders frequently occur and recent evidence has clearly implicated the presence of immune cells and inflammatory events during early tendinopathy. However, the origin and properties of these cells remain poorly defined. Therefore, the aim of this study was to determine the presence of cells in healthy rodent and human tendon tissue fulfilling macrophage-like functions. Using various transgenic reporter mouse models, we demonstrate the presence of tendon resident cells in the dense matrix of the tendon core expressing the fractalkine (Fkn) receptor CX3CR1 and its cognate ligand CX3CL1/Fkn. Pro-inflammatory stimulation of 3D tendon-like constructs in vitro resulted in a significant increase in the expression of IL-1ß, IL-6, Mmp3, Mmp9, Cx3cl1, and epiregulin which has been reported to contribute to inflammation, wound healing, and tissue repair. Furthermore, we demonstrate that inhibition of the fractalkine receptor blocked tendon cell migration in vitro and show the presence of CX3CR1/CX3CL1/EREG expressing cells in healthy human tendons. Taken together, we demonstrate the presence of CX3CL1+/CX3CR1+ “tenophages” within the healthy tendon proper potentially fulfilling surveillance functions in tendons.
Tuberculous meningitis: new tools and new approaches required
Authors: Seddon James A , Thwaites Guy E ,   International Tuberculous Meningitis Research Consortium
Published: November 2019

Tuberculous meningitis is the most severe form of tuberculosis and causes widespread mortality and morbidity. Understanding of the epidemiology and pathogenesis is incomplete, and the optimal diagnosis and treatment are poorly defined. To generate research collaboration and coordination, as well as to promote sharing of ideas and advocacy efforts, the International Tuberculous Meningitis Research Consortium was formed in 2009. During the most recent meeting of this group in Lucknow, India, in March 2019, the Consortium decided to bring together key articles on tuberculous meningitis in one supplement. The supplement covers recent scientific updates, expert perspectives on specific clinical challenges, consensus statements on how to conduct research, and a set of priorities for future investigation.
“Owning one's story is as important as the ownership of physical space”: An Interview with Susan Abulhawa
Authors: Qabaha Ahmad
Published: November 2019

In this interview, American-Palestinian writer, political commentator and human rights activist Susan Abulhawa, author of Mornings in Jenin (2006), My Voice Sought the Wind (2013) and The Blue Between Sky and Water (2015), discusses why it is important for Palestinians to reciprocate solidarity with other social justice struggles and the ways in which she engages with the notions of strangeness and exile in her fiction. Abulhawa also comments on the human, cultural and communal aspects of her work, as well as the relationship between literature, especially the novel, history and politics.
The comparative study of geographically and demographically of the of animal protein consumption from livestock source
Authors: Novra Ardi , Fatati Fatati , Mulawarman Mulawarman
Published: November 2019

Livestock is one of the important sources for  protein in Jambi Province. However, the information on the consumption behavior of animal protein by local people was not available . Hence, the study aimed to analyze the behavior of consumption of protein sources from livestock between geographically and demographically separate regions.The researchsurveyconductedfor sixmonthsusingcross-section datawith the unitof analysisis the household. The multistage cluster random sampling(CRS) technique was used to selectthreetypes sub-districts(urban, migrantandnativerural) inthreedistrictsrepresentingthe western,central and eastern. The selected numbers of 150 householdswhere are allocatedequally with50electedforeach district. Simultaneous equationsmodel ofAIDS(Almost Ideal Demand System) was usedtoanalyze the difference inthe proportion ofconsumer spendingforfood material sources ofanimal protein from livestock. The AIDS model estimated bySeeminglyUnrelatedEquation (SUR) technique usingthe SAS/ETS9.12. The result showed that geographically,  the household expenditure for eggs significantdifferencesamong the others and the highestoccur ineastern regions; while demographically, the household expenditure formeatin rural areas was significantly higher thanin the urban, but fordairysignificantly higher than in urban areas. The household expenditure for eggs more responsive to the other prices, but the meat more responsive to own and dairy prices. The same non-price factor was significantly influenced to all commodities for livestock products, and the relationship between eggandmeatcommodities weresubstituted, but with dairywascomplementary. It is concluded that demographic factors are more influential than geographic factors on the behavior of animal protein consumption from livestockKeywords: Geographically, Demographically, Livestock, Protein, AIDS