bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenocarcinoma with mixed subtypes is a rare but aggressive histologic subtype in colorectal cancer
Authors: Sheng Hui , Wei Xiaoli , Mao Minjie , He Jincan , Luo Tianqi , Lu Shilin , Zhou Liye , Huang Zhixin , Yang Anli
Published: November 2019

Background

Although numerous studies have investigated the clinicopathologic and prognostic relevance of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC) compared with classic adenocarcinoma (CA), little is known about the prognosis of adenocarcinoma with mixed subtypes (AM) and the differences among these four subtypes.

Methods

The statistics of colorectal cancer registered in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and analyzed. We also compared the clinicopathologic and prognostic relevance between CA, SRCC, MAC, and AM.

Results

The frequencies of these four subtypes were 69.9% (CA, n = 15,812), 25.1% (MAC, n = 5689), 3.6% (SRCC, n = 814) and 1.4% (AM, n = 321), respectively. All of MAC, SRCC, and AM were significantly related with aggressive features. Only SRCC and AM were identified as independent poor prognostic markers for overall survival by multivariate analysis. The aggressiveness of AM was between MAC and SRCC according to the clinicopathologic associations. The prognosis of AM was significantly worse than MAC but comparable with SRCC.

Conclusions

We confirmed the clinicopathologic relevance with aggressive features of MAC and SRCC, as well as poor prognostic relevance of SRCC by analyzing a large study population data set. Furthermore, we identified AM as a rare but aggressive histologic subtype in colorectal cancer, to which particular attention should be given in clinical practice.
The distribution of Preputial vessels in different severity of rat congenital hypospadias model: imaging study using micro-computerized tomography
Authors: Lin Defu , Liu Pei , Wang Guannan , Zhang Weiping , Sun Ning
Published: November 2019

Background

Micro-computerized tomography (micro-CT) is considered as an innovative non-invasive and high-resolution imaging technology. The current research aims to reconstruct the distribution of preputial vessels in different severity of rat congenital hypospadias model by micro-CT, and to provide an anatomic basis for the selection of preputial vessel pedicle flaps in surgery.

Methods

Pregnant rats were exposed to finasteride from gestational day 12 to 17. Depending on the position of the urethral meatus, the pups were divided into normal, mild hypospadias and severe hypospadias groups. Six months after birth, the preputial blood vessels were observed in vascular perfusion with Microfil (a silicone-based polymer) and scanned by micro-CT. CTvox and NRecon were utilized to reconstruct 3-dimentional (3D) images. A pathological analysis of the specimen was taken in order to determine the position of Microfil.

Results

The normal group and the mild hypospadias group had similar preputial image characteristics. At the junction of the inner and outer prepuce, the deep layer vessels of the superficial fascia were transversely distributed and formed a vascular ring-like structure. Among the severe hypospadias group, five had sufficient blood circulation while six had insufficient blood circulation. In sufficient blood circulation type, the ring-like vessels were found at the junction of the inner and outer prepuce similar to that of the normal and mild hypospadias group. However, only a small amount of capillary supply to this area in the insufficient type.

Conclusion

The junction of the inner and outer prepuce with abundant blood circulation was suitable to be a vascular pedicle flap. The tubularized preputial island flaps were consistent with the ring-like vessels area, and the original blood supply was retained to the greatest extent.
The application of virtual reality and augmented reality in Oral & Maxillofacial Surgery
Authors: Ayoub Ashraf , Pulijala Yeshwanth
Published: November 2019

Background

Virtual reality is the science of creating a virtual environment for the assessment of various anatomical regions of the body for the diagnosis, planning and surgical training. Augmented reality is the superimposition of a 3D real environment specific to individual patient onto the surgical filed using semi-transparent glasses to augment the virtual scene.. The aim of this study is to provide an over view of the literature on the application of virtual and augmented reality in oral & maxillofacial surgery.

Methods

We reviewed the literature and the existing database using Ovid MEDLINE search, Cochran Library and PubMed. All the studies in the English literature in the last 10 years, from 2009 to 2019 were included.

Results

We identified 101 articles related the broad application of virtual reality in oral & maxillofacial surgery. These included the following: Eight systematic reviews, 4 expert reviews, 9 case reports, 5 retrospective surveys, 2 historical perspectives, 13 manuscripts on virtual education and training, 5 on haptic technology, 4 on augmented reality, 10 on image fusion, 41 articles on the prediction planning for orthognathic surgery and maxillofacial reconstruction. Dental implantology and orthognathic surgery are the most frequent applications of virtual reality and augmented reality. Virtual planning improved the accuracy of inserting dental implants using either a statistic guidance or dynamic navigation. In orthognathic surgery, prediction planning and intraoperative navigation are the main applications of virtual reality. Virtual reality has been utilised to improve the delivery of education and the quality of training in oral & maxillofacial surgery by creating a virtual environment of the surgical procedure. Haptic feedback provided an additional immersive reality to improve manual dexterity and improve clinical training.

Conclusion

Virtual and augmented reality have contributed to the planning of maxillofacial procedures and surgery training. Few articles highlighted the importance of this technology in improving the quality of patients’ care. There are limited prospective randomized studies comparing the impact of virtual reality with the standard methods in delivering oral surgery education.
Total saponins of Bolbostemma paniculatum (maxim.) Franquet exert antitumor activity against MDA-MB-231 human breast cancer cells via inhibiting PI3K/Akt/mTOR pathway
Authors: Dou Jian-Wei , Shang Rong-Guo , Lei Xiao-Qin , Li Kang-Le , Guo Zhan-Zi , Ye Kai , Yang Xiao-Juan , Li Yu-Wei , Zhou Yun-Yun , Yao Jia , Huang Qian
Published: November 2019

Background

The aim of the present study was to examine the effects of theBolbostemma paniculatum(Maxim.) Franquet (BP) active compound, BP total saponins (BPTS), on MDA-MB-231 cells, and investigate the underlying mechanism regarding BPTS-mediated attenuation of the PI3K/Akt/mTOR pathway.

Methods

The effect of BPTS on cytotoxicity, induction of apoptosis and migration on MDA-MB-231 cells at three different concentrations was investigated. A CCK-8 assay, wound-healing assay and flow cytometry were used to demonstrate the effects of BPTS. Additionally, expression of the primary members of the PI3K/Akt/mTOR signaling pathway was assessed using western blotting. To verify the underlying mechanisms, a PI3K inhibitor and an mTOR inhibitor were used.

Results

BPTS inhibited proliferation of MDA-MB-231 cells with an IC50value of 10 μg/mL at 48 h. BPTS inhibited migration of MDA-MB-231 cells, and the western blot results demonstrated that BPTS reduced p-PI3K, p-Akt and p-mTOR protein expression levels in MDA-MB-231 cells. Additionally, the results were confirmed using a PI3K inhibitor and an mTOR inhibitor. BPTS decreased proliferation and migration of MDA-MB-231 cells possibly through inhibiting the PI3K/Akt/mTOR signaling pathway.

Conclusions

The results highlight the therapeutic potential of BPTS for treating patients with triple-negative breast cancer.
Lipid and metabolic profiles in female dogs with mammary carcinoma receiving dietary fish oil supplementation
Authors: Costa-Santos Keidylania , Damasceno Karine , Portela Ricardo Dias , Santos Ferlando Lima , Araújo Genira Carneiro , Martins-Filho Emanoel Ferreira , Silva Laís Pereira , Barral Thiago Doria , Santos Stefanie Alvarenga , Estrela-Lima Alessandra
Published: November 2019

Background

Dyslipidemias induce angiogenesis and accelerate the development and in vitro growth of breast tumors. The aim of this study was to assess the lipid and metabolic profile of female dogs with mammary carcinomas and their correlations with body condition score and degree of tumor malignancy, as well as to study the effect of dietary fish oil supplementation on these animals.

Results

Overweight or obese dogs had more aggressive carcinomas and higher triglyceride (p = 0.0363), VLDL (p = 0.0181), albumin (p = 0.0188), globulin (p = 0.0145) and lactate (p = 0.0255) concentrations. There was no change in the lipid profile after supplementation with fish oil at any concentration. However, in relation to the metabolic profile, glucose (p = 0.0067), total protein (p = 0.0002) and globulin (p = 0.0002) concentrations were increased when 90% omega-3 fish oil was used as a dietary supplement.

Conclusion

Obese dogs showed altered lipid and metabolic profiles and more aggressive tumors, suggesting an important relationship between dyslipidemia and tumor aggressiveness. Supplementation with fish oil, rich in omega-3 fatty acids, may alter metabolic parameters in cancer patients.
YY1 mediates TGF-β1-induced EMT and pro-fibrogenesis in alveolar epithelial cells
Authors: Zhang Chuyi , Zhu Xiaoping , Hua Yifei , Zhao Qian , Wang Kaijing , Zhen Lixiao , Wang Guangxue , Lü Jinhui , Luo An , Cho William C. , Lin Xin , Yu Zuoren
Published: November 2019

Pulmonary fibrosis is a chronic, progressive lung disease associated with lung damage and scarring. The pathological mechanism causing pulmonary fibrosis remains unknown. Emerging evidence suggests prominent roles of epithelial–mesenchymal transition (EMT) of alveolar epithelial cells (AECs) in myofibroblast formation and progressive pulmonary fibrosis. Our previous work has demonstrated the regulation of YY1 in idiopathic pulmonary fibrosis and pathogenesis of fibroid lung. However, the specific function of YY1 in AECs during the pathogenesis of pulmonary fibrosis is yet to be determined. Herein, we found the higher level of YY1 in primary fibroblasts than that in primary epithelial cells from the lung of mouse. A549 and BEAS-2B cells, serving as models for type II alveolar pulmonary epithelium in vitro, were used to determine the function of YY1 during EMT of AECs. TGF-β-induced activation of the pro-fibrotic program was applied to determine the role YY1 may play in pro-fibrogenesis of type II alveolar epithelial cells. Upregulation of YY1 was associated with EMT and pro-fibrotic phenotype induced by TGF-β treatment. Targeted knockdown of YY1 abrogated the EMT induction by TGF-β treatment. Enforced expression of YY1 can partly mimic the TGF-β-induced pro-fibrotic change in either A549 cell line or primary alveolar epithelial cells, indicating the induction of YY1 expression may mediate the TGF-β-induced EMT and pro-fibrosis. In addition, the translocation of NF-κB p65 from the cytoplasm to the nucleus was demonstrated in A549 cells after TGF-β treatment and/or YY1 overexpression, suggesting that NF-κB-YY1 signaling pathway regulates pulmonary fibrotic progression in lung epithelial cells. These findings will shed light on the better understanding of mechanisms regulating pro-fibrogenesis in AECs and pathogenesis of lung fibrosis.
Epitope‐based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: an immune-informatics study
Authors: Tahir ul Qamar Muhammad , Saleem Saman , Ashfaq Usman Ali , Bari Amna , Anwar Farooq , Alqahtani Safar
Published: November 2019

Background

Middle East Respiratory Syndrome Coronavirus (MERS-COV) is the main cause of lung and kidney infections in developing countries such as Saudi Arabia and South Korea. This infectious single-stranded, positive (+) sense RNA virus enters the host by binding to dipeptidyl-peptide receptors. Since no vaccine is yet available for MERS-COV, rapid case identification, isolation, and infection prevention strategies must be used to combat the spreading of MERS-COV infection. Additionally, there is a desperate need for vaccines and antiviral strategies.

Methods

The present study used immuno-informatics and computational approaches to identify conserved B- and T cell epitopes for the MERS-COV spike (S) protein that may perform a significant role in eliciting the resistance response to MERS-COV infection.

Results

Many conserved cytotoxic T-lymphocyte epitopes and discontinuous and linear B-cell epitopes were predicted for the MERS-COV S protein, and their antigenicity and interactions with the human leukocyte antigen (HLA) B7 allele were estimated. Among B-cell epitopes, QLQMGFGITVQYGT displayed the highest antigenicity-score, and was immensely immunogenic. Among T-cell epitopes, MHC class-I peptide YKLQPLTFL and MHC class-II peptide YCILEPRSG were identified as highly antigenic. Furthermore, docking analyses revealed that the predicted peptides engaged in strong bonding with the HLA-B7 allele.

Conclusion

The present study identified several MERS-COV S protein epitopes that are conserved among various isolates from different countries. The putative antigenic epitopes may prove effective as novel vaccines for eradication and combating of MERS-COV infection.
Subcutaneous fat mass is associated with genetic risk scores related to proinflammatory cytokine signaling and interact with physical activity in middle-aged obese adults
Authors: Daily James W. , Yang Hye Jeong , Liu Meiling , Kim Min Jung , Park Sunmin
Published: November 2019

Background and aims

Subcutaneous fat mass is negatively correlated with atherogenic risk factors, but its putative benefits remain controversial. We hypothesized that genetic variants that influence subcutaneous fat mass would modulate lipid and glucose metabolism and have interactions with lifestyles in Korean middle-aged adults with high visceral fat.

Materials and methods

Subcutaneous fat mass was categorized by dividing the average of subscapular skin-fold thickness by BMI and its cutoff point was 1.2. Waist circumferences were used for representing visceral fat mass with Asian cutoff points. GWAS of subjects aged 40–65 years with high visceral fat (n = 3303) were conducted and the best gene-gene interactions from the genetic variants related to subcutaneous fat were selected and explored using the generalized multifactor dimensionality reduction. Genetic risk scores (GRS) were calculated by weighted GRS that was divided into low, medium and high groups.

Results

Subjects with high subcutaneous fat did not have dyslipidemia compared with those with low subcutaneous fat, although both subject groups had similar amounts of total fat. The best model to influence subcutaneous fat included IL17A_rs4711998, ADCY2_rs326149, ESRRG_rs4846514, CYFIP2_rs733730, TCF7L2_rs7917983, ZNF766_rs41497444 and TGFBR3_rs7526590. The odds ratio (OR) for increasing subcutaneous fat was higher by 2.232 folds in the high-GRS group, after adjusting for covariates. However, total and LDL cholesterol, triglyceride and C-reactive protein concentrations in the circulation were not associated with GRS. Subjects with high-GRS had higher serum HDL cholesterol levels than those with low-GRS. Physical activity and GRS had an interaction with subcutaneous fat. In subjects with low physical activity, the odds ratio for high subcutaneous fat increased by 2.232, but subcutaneous fat deposition was not affected in the high-GRS group with high physical activity.

Conclusion

Obese adults with high-GRS had more subcutaneous fat, but they did not show more dyslipidemia and inflammation compared to low-GRS. High physical activity prevented subcutaneous fat deposition in subjects with high GRS for subcutaneous fat.
A better future for children with cancer in Africa: a dream transforming into reality Dr. D Cristina Stefan- AORTIC president
Authors: Stefan Daniela Cristina
Published: November 2019

The WHO Global Initiative for Childhood Cancer launched in 2018 will translate into an additional one million lives saved or a survival rate of at least 60% for children with cancer to be attained by 2030. This new target represents a doubling of the global cure rate for children with cancer. African children with cancer will be amongst the global group which will benefit from an improved cancer care and better outcome.
NF1 microdeletion syndrome: case report of two new patients
Authors: Serra Gregorio , Antona Vincenzo , Corsello Giovanni , Zara Federico , Piro Ettore , Falsaperla Raffaele
Published: November 2019

Background

17q11.2 microdeletions, which include the neurofibromatosis type 1 (NF1) gene region, are responsible for the NF1 microdeletion syndrome, observed in 4.2% of all NF1 patients. Large deletions of the NF1 gene and its flanking regions are associated with a more severe NF1 phenotype than the NF1 general population.

Case presentation

We hereby describe the clinical and molecular features of two girls (aged 2 and 4 years, respectively), with non-mosaic atypical deletions. Patient 1 showed fifteen café-au-lait spots and axillary freckling, as well as a Lisch nodule in the left eye, strabismus, high-arched palate, malocclusion, severe kyphoscoliosis, bilateral calcaneovalgus foot, mild generalized hypotonia, hyperactivity and deficits of speech-related abilities. NF1 genomic rearrangements through multiplex ligation-dependent probe amplification (MLPA) detected an heterozygous deletion of the whole NF1 gene. Array comparative genomic hybridization (a-CGH) analysis defined a 17q11.2 deletion of about 1 Mb (breakpoints at positions 29,124,299 and 30,151,654), which involved different genes (partially CRLF3, ATAD5, TEFM, ADAP2, RNF135, OMG, EVI2B, EVI2A, RAB11FIP4), including NF1. Patient 2 showed growth and developmental delay, supravalvular pulmonary stenosis, twenty-five café-au-lait spots, axillary freckling, craniofacial dysmorphic features, short neck with pterygium, limb abnormalities and foci of neural dysplasia on brain magnetic resonance imaging (MRI). MLPA detected an heterozygous deletion of NF1, which was detailed by a-CGH indicating the positions 29,124,299 and 30,326,958 as its breakpoints, and which included aside from the genes deleted in Patient 1 also COPRS, UTP6 and partially SUZ12. Fluorescent in situ hybridization (FISH) analysis of the parents documented a de novo origin of the deletions in both cases.

Conclusions

The present report will likely provide further insights and a better characterization of NF1 microdeletion syndrome.
Mining the biomass deconstructing capabilities of rice yellow stem borer symbionts
Authors: Singh Rahul , Bennett Joseph P. , Gupta Mayank , Sharma Medha , Eqbal Danish , Alessi Anna M. , Dowle Adam A. , McQueen-Mason Simon J. , Bruce Neil C. , Yazdani Syed Shams
Published: November 2019

Background

Efficient deconstruction of lignocellulosic biomass into simple sugars in an economically viable manner is a prerequisite for its global acceptance as a feedstock in bioethanol production. This is achieved in nature by suites of enzymes with the capability of efficiently depolymerizing all the components of lignocellulose. Here, we provide detailed insight into the repertoire of enzymes produced by microorganisms enriched from the gut of the crop pathogen rice yellow stem borer (Scirpophaga incertulas).

Results

A microbial community was enriched from the gut of the rice yellow stem borer for enhanced rice straw degradation by sub-culturing every 10 days, for 1 year, in minimal medium with rice straw as the main carbon source. The enriched culture demonstrated high cellulolytic and xylanolytic activity in the culture supernatant. Metatranscriptomic and metaexoproteomic analysis revealed a large array of enzymes potentially involved in rice straw deconstruction. The consortium was found to encode genes ascribed to all five classes of carbohydrate-active enzymes (GHs, GTs, CEs, PLs, and AAs), including carbohydrate-binding modules (CBMs), categorized in the carbohydrate-active enzymes (CAZy) database. The GHs were the most abundant class of CAZymes. Predicted enzymes from these CAZy classes have the potential to digest each cell-wall components of rice straw, i.e., cellulose, hemicellulose, pectin, callose, and lignin. Several identified CAZy proteins appeared novel, having an unknown or hypothetical catalytic counterpart with a known class of CBM. To validate the findings, one of the identified enzymes that belong to the GH10 family was functionally characterized. The enzyme expressed in E. coli efficiently hydrolyzed beechwood xylan, and pretreated and untreated rice straw.

Conclusions

This is the first report describing the enrichment of lignocellulose degrading bacteria from the gut of the rice yellow stem borer to deconstruct rice straw, identifying a plethora of enzymes secreted by the microbial community when growing on rice straw as a carbon source. These enzymes could be important candidates for biorefineries to overcome the current bottlenecks in biomass processing.
Comparative analysis of host resistance to Sarcoptes scabiei var. cuniculi in two different rabbit breeds
Authors: Wei Wenrui , Ren Yongjun , Shen Nengxing , Song Hongyu , Xu Jing , Hua Ruiqi , Zhang Haojie , Angel Christiana , Gu Xiaobin , Kuang Liangde , Xie Yue , Peng Xuerong , Xie Xiaohong , Yang Guangyou
Published: November 2019

Background

Scabies, caused by infestation of the miteSarcoptes scabiei, is one of the most severe ectoparasitic diseases in rabbits. Scabies seriously affects the commercial rabbit breeding, causing severe economic losses. Host resistance toS. scabieiis an important factor in further development of the rabbit industry. In the present study, we compared the host resistance toS. scabieivar.cuniculiof a new breed of domestic rabbit propagated by the Sichuan Animal Sciences Academy (QiXing rabbit, QX) compared with that of a traditional rabbit breed in the domestic rabbit industry (IRA rabbit, IRA).

Methods

Both QX and IRA rabbits were experimentally infested with liveS. scabieivar.cuniculimites for 48 h. Then, during the course of four-week experimental infestation period, the body weight of rabbits was recorded every two weeks for calculating body-weight variations in comparison to the non-infested control rabbits. Skin lesions in the foot area were assessed on weekly basis and serum samples were tested weekly for the estimation of changes in the total antibody levels (IgG, IgE and IgM). Moreover, DNA extracted from the blood samples was amplified for analysis of the genetic diversity in the major histocompatibility complex, class II, DQ Alpha (MHC-DQA) gene.

Results

Compared to the IRA rabbits, the QX rabbits showed a significantly higher (P < 0.05) relative body weight gain compared to the non-infested control rabbits and significantly lower (P < 0.05) scores for foot skin lesions and higher levels of IgG, IgE and IgM at weeks 1 to 4, week 2 and week 1 post-infestation, respectively. Furthermore, a polymorphism site at position 103 bp of exon two ofMHC-DQAgene and a different gene frequency were found between two rabbit breeds, suggesting the genetic basis for the differential host resistance to theS. scabieivar.cuniculibetween two rabbit breeds.

Conclusions

The QX rabbits showed higher host resistance toS. scabieivar.cuniculicompared to the IRA rabbits at the clinical, immunological and genetic levels. These results provide a reference for the breeding of rabbits with adequately improved and sustained host resistance to scabies in the domestic rabbit industry.
The role of the liver in the migration of parasites of global significance
Authors: Deslyper Gwendoline , Doherty Derek G. , Carolan James C. , Holland Celia V.
Published: November 2019

Many parasites migrate through different tissues during their life-cycle, possibly with the aim to enhance their fitness. This is true for species of three parasite genera of global importance, Ascaris, Schistosoma and Plasmodium, which cause significant global morbidity and mortality. Interestingly, these parasites all incorporate the liver in their life-cycle. The liver has a special immune status being able to preferentially induce tolerance over immunity. This function may be exploited by parasites to evade host immunity, with Plasmodium spp. in particular using this organ for its multiplication. However, hepatic larval attrition occurs in both ascariasis and schistosomiasis. A better understanding of the molecular mechanisms involved in hepatic infection could be useful in developing novel vaccines and therapies for these parasites.
Glucose 6 phosphate dehydrogenase deficiency and hemoglobinopathy in South Western Region Nepal: a boon or burden
Authors: Gautam Narayan , Gaire Bhagwati , Manandhar Trishna , Marasini Bishnu P. , Parajuli Niranjan , Lekhak Sunil P. , Nepal Monica
Published: November 2019

Objectives

The study was carried out to optimize the phenotypic method to characterize the sickle cell trait (SCT), sickle cell anemia (SCA), and β-thalassemia (β-TT) suspected sample from tharu community of South Western province-5, Nepal. SCT and SCA were further evaluated by genotypic method employing amplification refractory mutation system (ARMS PCR). Moreover, Glucose 6 phosphate dehydrogenase (G6PD) was estimated in those hemoglobinopathy to observe its prevalence. The accurate and reliable method can play an important role in reduction of morbidity and mortality rate.

Results

The 100 suspected cases were subjected to phenotypic method adopting cellulose acetate electrophoresis and genotypic method using ARMS PCR which portraits (5%) SCA positive test showing HBS/HBS, (38%) SCT positive trait HBA/HBS and (36%) cases normal HBA/HBA. β-TT (21%) cases were confirmed by electropherogram. G6PD deficiency was observed in (40%) of SCA, (18.4%) of SCT, (4.8%) of β-TT and (2.8%) in normal cases. Increased G6PD were developed only in SCT (5.3%) and β-TT (4.8%). The study highlighted sickle cell disorder (SCD) and β-TT as the most common hemoglobinopathy coexisting with G6PD deficiency. Though hemoglobinopathy sometime could be protective in malaria but G6PD deficiency can cause massive hemolysis which may exacerbate the condition.
Efficacy of three innovative bacterin vaccines against experimental infection with Mycoplasma hyopneumoniae
Authors: Matthijs Anneleen Marguerite Filip , Auray Gaël , Boyen Filip , Schoos Alexandra , Michiels Annelies , García-Nicolás Obdulio , Barut Güliz Tuba , Barnier-Quer Christophe , Jakob Virginie , Collin Nicolas , Devriendt Bert , Summerfield Artur , Haesebrouck Freddy , Maes Dominiek
Published: November 2019

New vaccine formulations that include novel strains of Mycoplasma hyopneumoniae and innovative adjuvants designed to induce cellular immunity could improve vaccine efficacy against this pathogen. The aim of this experimental study was to assess the efficacy of three experimental bacterin formulations based on M. hyopneumoniae field strain F7.2C which were able to induce cellular immunity. The formulations included a cationic liposome formulation with the Mincle receptor ligand trehalose 6,6-dibehenate (Lipo_DDA:TDB), a squalene-in-water emulsion with Toll-like receptor (TLR) ligands targeting TLR1/2, TLR7/8 and TLR9 (SWE_TLR), and a poly(lactic-co-glycolic acid) micro-particle formulation with the same TLR ligands (PLGA_TLR). Four groups of 12 M. hyopneumoniae-free piglets were primo- (day (D) 0; 39 days of age) and booster vaccinated (D14) intramuscularly with either one of the three experimental bacterin formulations or PBS. The pigs were endotracheally inoculated with a highly and low virulent M. hyopneumoniae strain on D28 and D29, respectively, and euthanized on D56. The main efficacy parameters were: respiratory disease score (RDS; daily), macroscopic lung lesion score (D56) and log copies M. hyopneumoniae DNA determined with qPCR on bronchoalveolar lavage (BAL) fluid (D42, D56). All formulations were able to reduce clinical symptoms, lung lesions and the M. hyopneumoniae DNA load in the lung, with formulation SWE_TLR being the most effective (RDSD28–D56 −61.90%, macroscopic lung lesions −88.38%, M. hyopneumoniae DNA load in BAL fluid (D42) −67.28%). Further experiments raised under field conditions are needed to confirm these results and to assess the effect of the vaccines on performance parameters.
An IoT-based task scheduling optimization scheme considering the deadline and cost-aware scientific workflow for cloud computing
Authors: Ma Xiaojin , Gao Honghao , Xu Huahu , Bian Minjie
Published: November 2019

Large-scale applications of Internet of things (IoT), which require considerable computing tasks and storage resources, are increasingly deployed in cloud environments. Compared with the traditional computing model, characteristics of the cloud such as pay-as-you-go, unlimited expansion, and dynamic acquisition represent different conveniences for these applications using the IoT architecture. One of the major challenges is to satisfy the quality of service requirements while assigning resources to tasks. In this paper, we propose a deadline and cost-aware scheduling algorithm that minimizes the execution cost of a workflow under deadline constraints in the infrastructure as a service (IaaS) model. Considering the virtual machine (VM) performance variation and acquisition delay, we first divide tasks into different levels according to the topological structure so that no dependency exists between tasks at the same level. Three strings are used to code the genes in the proposed algorithm to better reflect the heterogeneous and resilient characteristics of cloud environments. Then, HEFT is used to generate individuals with the minimum completion time and cost. Novel schemes are developed for crossover and mutation to increase the diversity of the solutions. Based on this process, a task scheduling method that considers cost and deadlines is proposed. Experiments on workflows that simulate the structured tasks of the IoT demonstrate that our algorithm achieves a high success rate and performs well compared to state-of-the-art algorithms.
Type 2 diabetes and pre-diabetes mellitus: a systematic review and meta-analysis of prevalence studies in women of childbearing age in the Middle East and North Africa, 2000–2018
Authors: Al-Rifai Rami H. , Majeed Maria , Qambar Maryam A. , Ibrahim Ayesha , AlYammahi Khawla M. , Aziz Faisal
Published: November 2019

Background

Investing in women’s health is an inevitable investment in our future. We systematically reviewed the available evidence and summarized the weighted prevalence of type 2 diabetes (T2DM) and pre-diabetes mellitus (pre-DM) in women of childbearing age (15–49 years) in the Middle East and North African (MENA) region.

Methods

We comprehensively searched six electronic databases to retrieve published literature and prevalence studies on T2DM and pre-DM in women of childbearing age in the MENA. Retrieved citations were screened and data were extracted by at least two independent reviewers. Weighted T2DM and pre-DM prevalence was estimated using the random-effects model.

Results

Of the 10,010 screened citations, 48 research reports were eligible. Respectively, 46 and 24 research reports on T2DM and pre-DM prevalence estimates, from 14 and 10 countries, were included. Overall, the weighted T2DM and pre-DM prevalence in 14 and 10 MENA countries, respectively, were 7.5% (95% confidence interval [CI], 6.1–9.0) and 7.6% (95% CI, 5.2–10.4). In women sampled from general populations, T2DM prevalence ranged from 0.0 to 35.2% (pooled, 7.7%; 95% CI, 6.1–9.4%) and pre-DM prevalence ranged from 0.0 to 40.0% (pooled, 7.9%; 95% CI, 5.3–11.0%). T2DM was more common in the Fertile Crescent countries (10.7%, 95% CI, 5.2–17.7%), followed by the Arab Peninsula countries (7.6%, 95% CI, 5.9–9.5%) and North African countries and Iran (6.5%, 95% CI, 4.3–9.1%). Pre-DM prevalence was highest in the Fertile Crescent countries (22.7%, 95% CI, 14.2–32.4%), followed by the Arab Peninsula countries (8.6%, 95% CI, 5.5–12.1%) and North Africa and Iran (3.3%, 95% CI, 1.0–6.7%).

Conclusions

T2DM and pre-DM are common in women of childbearing age in MENA countries. The high DM burden in this vital population group could lead to adverse pregnancy outcomes and acceleration of the intergenerational risk of DM. Our review presented data and highlighted gaps in the evidence of the DM burden in women of childbearing age, to inform policy-makers and researchers.

Systematic review registration

PROSPERO CRD42017069231
The association between depressive symptoms or depression and health outcomes in adults with low back pain with or without radiculopathy: protocol of a systematic review
Authors: Wong Jessica J. , Tricco Andrea C. , Côté Pierre , Rosella Laura C.
Published: November 2019

Background

A considerable proportion of adults with low back pain (LBP) suffer from depressive symptoms or depression. Those with depressive symptoms or depression may be at risk of poorer LBP recovery and require more health care. Understanding the role of prognostic factors for LBP is critically important to guide management and health services delivery. Our objective is to conduct a systematic review to assess the association between depressive symptoms or depression and health outcomes in adults with LBP with or without radiculopathy.

Methods

Electronic databases including MEDLINE, Embase, CINAHL, and PsycINFO will be searched from inception to April 2019 to identify relevant studies. Additional citations will be identified by searching reference lists of included studies and related systematic reviews. Cohort and case-control studies assessing the association between depressive symptoms/depression and health outcomes in adults aged 16 years and older with LBP with or without radiculopathy will be included. The following will be included: depressive symptoms as measured on standardized questionnaires (e.g., Center for Epidemiologic Studies Depression Scale, Beck Depression Index), and depression as standardized diagnoses (e.g., International Classification of Diseases codes) or self-reported depression diagnosis on standardized questionnaires. Outcomes of interest are standardized measures for pain, disability, overall health status, satisfaction with care, and health care utilization. These are informed by core outcome domains that international expert panels consider important for LBP research. Pairs of reviewers will screen articles retrieved from the search, extract data, and assess risk of bias using the Risk Of Bias In Non-randomized Studies-of Exposures (ROBINS-E) tool. Reviewers will use these criteria to inform their judgment on the internal validity of studies (e.g., low, moderate, or high risk of bias). If studies are deemed homogeneous, a random effects meta-analysis on the association between depressive symptoms and health outcomes will be performed. The results of the included studies will be descriptively outlined if studies are deemed heterogeneous.

Discussion

The impact of depressive symptoms and depression on health- and health care-related outcomes for LBP with or without radiculopathy will be assessed and quantified. Findings of this systematic review will advance our understanding of LBP prognosis, and guide decision-making and improve quality of care for adults with LBP.

Systematic review registration

PROSPEROCRD42019130047
Beyond crime rates and community surveys: a new approach to police accountability and performance measurement
Authors: Hodgkinson Tarah , Caputo Tullio , McIntyre Michael L.
Published: November 2019

In this conceptual piece, we argue that the current approach to police performance measurement typically based on the use of traditional police metrics has failed to achieve the desired results and that a different strategy is required. Traditional police metrics have a narrow focus on crime and the police response to it. They provide little information on how well police organizations are performing. Importantly, traditional police metrics do not incorporate input from police stakeholders in goal identification, nor do they use specifically designed indicators to assess progress towards achieving these goals. Following an analysis of the criticisms levelled at the use of traditional police metrics, and subsequent attempts to address these issues, we argue that a networked governance approach represents a more promising foundation for undertaking police organizational performance assessment. Such an approach would engage stakeholders more directly in goal identification and performance assessment, and potentially lead to more successful, responsive and accountable policing.
Osteoporosis recovery in severe anorexia nervosa: a case report
Authors: Anand Pratibha , Mehler Philip S.
Published: November 2019

Background

Osteoporosis represents a common and severe complication in patients with anorexia nervosa (AN) that normally persists despite weight restoration and the resumption of regular menses. The condition may result in significant pain, injury, and disability.

Case presentation

We report the only published case of a complete return to normal bone density following many years of severe osteoporosis in a severely malnourished patient with AN. We describe a patient with severe and enduring AN whose osteoporosis, with resultant fractures, was completely reversed. Available patient records, imaging, and laboratory data were evaluated.

Conclusions

This case represents a common yet often improperly treated complication of AN. It demonstrates the potential important clinical role that targeted medicines coupled with a multifaceted supplementation and lifestyle interventions, may have for some very malnourished patients with AN. Medications, in the treatment of osteoporosis in patients with severe AN, may decrease fracture risk, enhance overall bone density, and contribute to an improved quality of life.
The potential role of illness expectations in the progression of medical diseases
Authors: Pagnini Francesco
Published: November 2019

To what extent can one’s mind promote direct changes to the body? Can one’s beliefs about the body become a physical reality, without mediating effects from behaviors? Specifically, can medical symptoms and the course of a disease be directly affected by a person’s mindset about the illness?

There is a vast literature about placebo and nocebo effects, that promote physical changes by creating the expectation of a change through a primer (for example, a fake pill). Placebos, however, often imply deception, or at least ambiguity, to be effective. The concept of Illness Expectation describes the expectations, both implicit and explicit, that a person who has received a diagnosis makes about the course of the disease. It can be characterized by different degrees of rigidity, and it is argued here that these expectations can ultimately lead to changes in the disease progression. These changes may happen through behavior modifications, or through a non-behavioral pathway, which may deserve exploration efforts from the scientific literature.
Synergistic toxicity in an in vivo model of neurodegeneration through the co-expression of human TDP-43M337V and tauT175D protein
Authors: Moszczynski Alexander J. , Harvey Madeline , Fulcher Niveen , de Oliveira Cleusa , McCunn Patrick , Donison Neil , Bartha Robert , Schmid Susanne , Strong Michael J. , Volkening Kathryn
Published: November 2019

Although it has been suggested that the co-expression of multiple pathological proteins associated with neurodegeneration may act synergistically to induce more widespread neuropathology, experimental evidence of this is sparse. We have previously shown that the expression of Thr175Asp-tau (tauT175D) using somatic gene transfer with a stereotaxically-injected recombinant adeno-associated virus (rAAV9) vector induces tau pathology in rat hippocampus. In this study, we have examined whether the co-expression of human tauT175D with mutant human TDP-43 (TDP-43M337V) will act synergistically. Transgenic female Sprague-Dawley rats that inducibly express mutant human TDP-43M337V using the choline acetyltransferase (ChAT) tetracycline response element (TRE) driver with activity modulating tetracycline-controlled transactivator (tTA) were utilized in these studies. Adult rats were injected with GFP-tagged tau protein constructs in a rAAV9 vector through bilateral stereotaxic injection into the hippocampus. Injected tau constructs were: wild-type GFP-tagged 2N4R human tau (tauWT; n = 8), GFP-tagged tauT175D 2N4R human tau (tauT175D, pseudophosphorylated, toxic variant, n = 8), and GFP (control, n = 8). Six months post-injection, mutant TDP-43M337V expression was induced for 30 days. Behaviour testing identified motor deficits within 3 weeks after TDP-43 expression irrespective of tau expression, though social behaviour and sensorimotor gating remained unchanged. Increased tau pathology was observed in the hippocampus of both tauWT and tauT175D expressing rats and tauT175D pathology was increased in the presence of cholinergic neuronal expression of human TDP-43M337V. These data indicate that co-expression of pathological TDP-43 and tau protein exacerbate the pathology associated with either individual protein.
Chemokines modulate the tumour microenvironment in pituitary neuroendocrine tumours
Authors: Marques Pedro , Barry Sayka , Carlsen Eivind , Collier David , Ronaldson Amy , Awad Sherine , Dorward Neil , Grieve Joan , Mendoza Nigel , Muquit Samiul , Grossman Ashley B. , Balkwill Frances , Korbonits Márta
Published: November 2019

Non-tumoural cells within the tumour microenvironment (TME) influence tumour proliferation, invasiveness and angiogenesis. Little is known about TME in pituitary neuroendocrine tumours (PitNETs). We aimed to characterise the role of TME in the aggressive behaviour of PitNETs, focusing on immune cells and cytokines. The cytokine secretome of 16 clinically non-functioning PitNETs (NF-PitNETs) and 8 somatotropinomas was assessed in primary culture using an immunoassay panel with 42 cytokines. This was correlated with macrophage (CD68, HLA-DR, CD163), T-lymphocyte (CD8, CD4, FOXP3), B-lymphocyte (CD20), neutrophil (neutrophil elastase) and endothelial cells (CD31) content, compared to normal pituitaries (NPs, n = 5). In vitro tumour–macrophage interactions were assessed by conditioned medium (CM) of GH3 (pituitary tumour) and RAW264.7 (macrophage) cell lines on morphology, migration/invasion, epithelial-to-mesenchymal transition and cytokine secretion. IL-8, CCL2, CCL3, CCL4, CXCL10, CCL22 and CXCL1 are the main PitNET-derived cytokines. PitNETs with increased macrophage and neutrophil content had higher IL-8, CCL2, CCL3, CCL4 and CXCL1 levels. CD8+ T-lymphocytes were associated to higher CCL2, CCL4 and VEGF-A levels. PitNETs had more macrophages than NPs (p < 0.001), with a 3-fold increased CD163:HLA-DR macrophage ratio. PitNETs contained more CD4+ T-lymphocytes (p = 0.005), but fewer neutrophils (p = 0.047) with a 2-fold decreased CD8:CD4 ratio. NF-PitNETs secreted more cytokines and had 9 times more neutrophils than somatotropinomas (p = 0.002). PitNETs with higher Ki-67 had more FOXP3+ T cells, as well as lower CD68:FOXP3, CD8:CD4 and CD8:FOXP3 ratios. PitNETs with “deleterious immune phenotype” (CD68hiCD4hiFOXP3hiCD20hi) had a Ki-67 ≥ 3%. CD163:HLA-DR macrophage ratio was positively correlated with microvessel density (p = 0.015) and area (p < 0.001). GH3 cell-CM increased macrophage chemotaxis, while macrophage-CM changed morphology, invasion, epithelial-to-mesenchymal transition and secreted cytokines of GH3 cells. PitNETs are characterised by increased CD163:HLA-DR macrophage and reduced CD8:CD4 and CD8:FOXP3 T cell ratios. PitNET-derived chemokines facilitate macrophage, neutrophil and T cell recruitment into the tumours which can determine aggressive behaviour.
Multicentre quantitative 68Ga PET/CT performance harmonisation
Authors: Huizing Daphne M. V. , Koopman Daniëlle , van Dalen Jorn A. , Gotthardt Martin , Boellaard Ronald , Sera Terez , Sinaasappel Michiel , Stokkel Marcel P. M. , de Wit-van der Veen Berlinda J.
Published: November 2019

Purpose

Performance standards for quantitative 18F-FDG PET/CT studies are provided by the EANM Research Ltd. (EARL) to enable comparability of quantitative PET in multicentre studies. Yet, such specifications are not available for 68Ga. Therefore, our aim was to evaluate 68Ga-PET/CT quantification variability in a multicentre setting.

Methods

A survey across Dutch hospitals was performed to evaluate differences in clinical 68Ga PET/CT study protocols. 68Ga and 18F phantom acquisitions were performed by 8 centres with 13 different PET/CT systems according to EARL protocol. The cylindrical phantom and NEMA image quality (IQ) phantom were used to assess image noise and to identify recovery coefficients (RCs) for quantitative analysis. Both phantoms were used to evaluate cross-calibration between the PET/CT system and local dose calibrator.

Results

The survey across Dutch hospitals showed a large variation in clinical 68Ga PET/CT acquisition and reconstruction protocols. 68Ga PET/CT image noise was below 10%. Cross-calibration was within 10% deviation, except for one system to overestimate 18F and two systems to underestimate the 68Ga activity concentration. RC-curves for 18F and 68Ga were within and on the lower limit of current EARL standards, respectively. After correction for local 68Ga/18F cross-calibration, mean 68Ga performance was 5% below mean EARL performance specifications.

Conclusions

68Ga PET/CT quantification performs on the lower limits of the current EARL RC standards for 18F. Correction for local 68Ga/18F cross-calibration mismatch is advised, while maintaining the EARL reconstruction protocol thereby avoiding multiple EARL protocols.
Heterozygosity fitness correlations and generation interval of the Norway lobster in the Aegean Sea, eastern Mediterranean
Authors: Gkafas Georgios A. , Hatziioannou Marianthi , Malandrakis Emmanouil E. , Tsigenopoulos Costas S. , Karapanagiotidis Ioannis T. , Mente Elena , Vafidis Dimitrios , Exadactylos Athanasios
Published: November 2019

Background

Comprehensively detailed information on population dynamics for benthic species is crucial since potential admixture of individuals could shift the genetic subdivision and age structure during a full breeding period. The apparent genetic impact of the potential recruitment strategy of Norway lobsterNephrops norvegicusis still under research. For this reason the present study was focused on genetic variation of the species over a given continuous year period in a semi-enclosed gulf of the Aegean Sea.

Results

Analyses revealed that the relative smaller size class in females and the apparent faster growth of males may represent a key-role differential strategy for the two sexes, whereas females tend to mature slower. Heterozygosity fitness correlations (HFCs) showed substantially significant associations suggesting that inbreeding depression for females and outbreeding depression for males are the proximate fitness mechanisms, respectively.

Conclusions

Nephrops norvegicusuniformal genetic composition (background of high gene flow), could be attributed to potential population recolonization, due to a hypothesized passive larval movement from deeper waters, which may suggest that some offspring of local residents and potential male non-breeders from other regions admixture randomly.