bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian cancer cells direct monocyte differentiation through a non-canonical pathway
Authors: Fogg Kaitlin C. , Miller Andrew E. , Li Ying , Flanigan Will , Walker Alyssa , O’Shea Andrea , Kendziorski Christina , Kreeger Pamela K.
Published: October 2020

Background

Alternatively-activated macrophages (AAMs), an anti-inflammatory macrophage subpopulation, have been implicated in the progression of high grade serous ovarian carcinoma (HGSOC). Increased levels of AAMs are correlated with poor HGSOC survival rates, and AAMs increase the attachment and spread of HGSOC cells in vitro. However, the mechanism by which monocytes in the HGSOC tumor microenvironment are differentiated and polarized to AAMs remains unknown.

Methods

Using an in vitro co-culture device, we cultured naïve, primary human monocytes with a panel of five HGSOC cell lines over the course of 7 days. An empirical Bayesian statistical method, EBSeq, was used to couple RNA-seq with observed monocyte-derived cell phenotype to explore which HGSOC-derived soluble factors supported differentiation to CD68+ macrophages and subsequent polarization towards CD163+ AAMs. Pathways of interest were interrogated using small molecule inhibitors, neutralizing antibodies, and CRISPR knockout cell lines.

Results

HGSOC cell lines displayed a wide range of abilities to generate AAMs from naïve monocytes. Much of this variation appeared to result from differential ability to generate CD68+ macrophages, as most CD68+ cells were also CD163+. Differences in tumor cell potential to generate macrophages was not due to a MCSF-dependent mechanism, nor variance in established pro-AAM factors. TGFα was implicated as a potential signaling molecule produced by tumor cells that could induce macrophage differentiation, which was validated using a CRISPR knockout ofTGFAin the OVCAR5 cell line.

Conclusions

HGSOC production of TGFα drives monocytes to differentiate into macrophages, representing a central arm of the mechanism by which AAMs are generated in the tumor microenvironment.
Age and gender specific association between obesity and depressive symptoms: a large-scale cross-sectional study
Authors: Liao Wei , Luo Zhicheng , Hou Yitan , Cui Ningning , Liu Xiaotian , Huo Wenqian , Wang Fang , Wang Chongjian
Published: October 2020

Background

This is a cross-sectional study to explore the age and gender specific association between obesity and depression in Chinese rural adults.

Methods

A total of 29,900 eligible participants from the Henan Rural Cohort Study were included. Standard anthropometric measurements were undertaken to obtain data on body mass index (BMI) and waist circumference (WC). The Patient Health Questionnaire-2 (PHQ-2) was utilized to discover depressive symptoms. Logistic regression was performed to explore the association between obesity (independent variable) and depressive symptoms (dependent variable).

Results

There were 1777 subjects with depressive symptoms, accounting for 5.94%. After multivariable adjustment, compared with normal weight group, the odds ratios (ORs) [95% confidence interval (CI)] for depressive symptoms in underweight, overweight and general obese groups were 1.41 (1.08–1.84), 0.87 (0.78–0.97) and 0.86 (0.74–0.99), respectively. Similarly, the OR (95% CI) of abdominal obesity group was 0.84 (0.76–0.93). Besides, there was linear decreasing trend of WC with depressive symptoms, but not BMI. Moreover, the inverse association between obesity and depressive symptoms was stronger in men and the elderly than that in women and the young.

Conclusion

Underweight was associated with a higher prevalence of depressive symptoms, which indicated that health care should pay attention to underweight as well as obesity, especially for women and the young.

Clinical trial registration

The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-07-06.
Public awareness and knowledge of factors associated with dementia in China
Authors: Zheng Yong-Bo , Shi Le , Gong Yi-Miao , Wang Xiao-Xiao , Lu Qing-Dong , Que Jian-Yu , Khan Muhammad Zahid , Bao Yan-Ping , Lu Lin
Published: October 2020

Background

Dementia is a global public health priority. Many modifiable factors have been shown to influence the development of dementia, but these factors are not adequately known by the general public. This study aimed to assess public awareness of the factors that are associated with dementia in China.

Methods

A cross-sectional study was conducted from May to October 2019 using an Internet-based questionnaire. Data on basic sociodemographic characteristics were collected, and the knowledge of risk and protective factors for dementia was investigated. Logistic regression analysis was performed to compare levels of the knowledge of factors associated with dementia across populations with different demographic characteristics.

Results

Data from 3338 respondents were analyzed. The percentages of participants who accurately identified the risk factors of dementia were follows: 84.24% for negative affect, 65.07% for alcohol use, 56.68% for smoking, 48.74% for hypertension, and 42.66% for diabetes. The percentages of participants who accurately identified the protective factors for dementia were follows: 90.00% for exercise, 84.69% for social activity, 80.92% for intelligence games, 74.45% for reading, and 6.14% for antihypertensive or hypolipidemic drugs. The majority of Chinese people correctly recognized the role of lifestyle factors in the development of dementia but not medical factors. The levels of knowledge of the factors associated with dementia were significantly distinct across populations with different characteristics. The following sociodemographic characteristics were associated with more comprehensive knowledge of dementia risk and protective factors: women, young age, high education levels, nonmanual jobs, and contact with patients with dementia.

Conclusions

Public awareness and knowledge of risk and protective factors for dementia in China are still insufficient. More efforts are needed to publicize information to reduce the risk of dementia.
A new decellularized tendon scaffold for rotator cuff tears – evaluation in rabbits
Authors: de Lima Santos Alex , da Silva Camila Gonzaga , de Sá Barreto Leticia Siqueira , Leite Katia Ramos Moreira , Tamaoki Marcel Jun Sugawara , Ferreira Lydia Massako , de Almeida Fernando Gonçalves , Faloppa Flavio
Published: October 2020

Background

Scaffolds have considerably advanced in recent years. In orthopaedic surgery, scaffolds have been used as grafts in procedures involving tendon and ligament reconstruction. This paper aimed to produce and evaluate decellularized tendon scaffolds (DTSs) from biomechanical, microscopic, macroscopic and in vivo perspectives.

Methods

Bilateral gastrocnemius muscle tendons from 18 adult New Zealand rabbits were collected. Of these 36 tendons, 11 were used as controls (Group A - control), and 25 were used in the decellularization protocol (Group B - DTS). The groups were subjected to histological, biomechanical and macroscopic analyses, and Group B - DTS was subjected to an additional in vivo evaluation. In the decellularization protocol, we used a combination of aprotinin, ethylenediamine tetraacetic acid (EDTA), sodium dodecyl sulfate (SDS) and t-octyl-phenoxypolyethoxyethanol (Triton X-100) for six days. During this period, the scaffolds were kept at room temperature on an orbital shaker with constant motion.

Results

The DTSs showed an increased cross-sectional area and inter-fascicular distance and no change in parallelism or matrix organization. The nuclear material was not organized in the DTSs as it was in the control. In the biomechanical analysis, no significant differences were found between the groups after analysing the ultimate tensile load, stiffness, and elongation at the ultimate tensile load. During the in vivo evaluation, mononuclear cell infiltration was noted.

Conclusions

The evaluated decellularization protocol generated a tendon scaffold, maintained the most important biomechanical characteristics and permitted cell infiltration.
Epidemiology of Achilles tendon surgery in Italy: a nationwide registry study, from 2001 through 2015
Authors: Longo Umile Giuseppe , Salvatore Giuseppe , Risi Ambrogioni Laura , Cella Eleonora , Candela Vincenzo , Carnevale Arianna , Schena Emiliano , Ciccozzi Massimo , Maffulli Nicola , Denaro Vincenzo
Published: October 2020

Background

This study aims (1) to estimate the yearly number of Achilles tendon (AT) surgeries in Italy from 2001 to 2015 based on official hospitalization records; (2) to investigate the eventual presence of geographical variation in equity in access to AT surgery between three macroregions of Italy (North, Center and South); (3) to perform statistical projections of the number of AT procedure volumes and rates based on these data.

Methods

We analysed the National Hospital Discharge records (SDO) maintained at the Italian Ministry of Health for a 15-year period, from 2001 through 2015. These data are anonymous and include the patient’s age (evaluated in the class of age), sex, census region, the region of hospitalization, length of the hospitalization, public or private reimbursement and diagnosis.

Results

During the 15-year study period, 118,652 AT repair were performed in Italy, whose peak of incidence was in 2010. More than half of AT repairs was performed in the North of Italy (52.1%), while 27.2% was performed in the South of Italy and 20.6% Center of Italy. The projection model predicted a slight growth of 2.65% in 2025 in comparison with 2015.

Conclusion

The current study provides detailed information about the national population-weighted incidence of AT surgery, distribution and projection. The peak of average age was 35–45 year. The majority of AT procedures was performed in the North of Italy. The projection model predicts a slight growth of AT surgery by 2025. Furthermore, this 15-year nationwide registry study shows that the age of incidence of AT injuries shifted from 30 to 40 to 35–45 years compared to the available literature. The higher prevalence of AT surgery was found in men during the working age. Moreover, a low rate of procedures in pediatric and elder age classes was observed.
Gossypiboma with perforation of the umbilicus mimicking a complicated urachal cyst: a case report
Authors: Kabba Mustapha S. , Forde Martha Y. , Beckley Kevin S. , Johnny Bernadette , Jah-Kabba Ann-Marie B. M. , Seisay Samuel B. , Dawoh Alusine M. , Ogundiran Temidayo
Published: October 2020

Background

A retained surgical sponge, also known as a gossypiboma, is a rare cause of serious postoperative complications. Diverse retained surgical materials including instruments such as clamps and sutures have been reported, but surgical sponges are the most common material. We report an unusual case of a gossypiboma mimicking a complicated urachal cyst that led to perforation of the umbilicus.

Case presentation

A 38-year-old female patient presented in our facility with a palpable periumbilical mass and discharge of pus from the umbilicus for 7 months after an open appendectomy. Since the onset of symptoms, the patient had been treated conservatively in a peripheral hospital where she had been operated on. As no improvement was seen, an ultrasound scan was performed that suggested an intraperitoneal abscess adjacent to the umbilicus. Consequently, the patient was referred to our specialist outpatient department for surgical intervention. Suspecting a complicated urachal cyst, an exploratory laparotomy was performed but revealed a retained surgical sponge as the underlying cause. The gossypiboma was resected, and the postoperative period was unremarkable.

Conclusion

This case demonstrates that gossypibomas, even though rare, continue to occur. They may clinically and radiologically mimic other pathologies, especially abscesses and tumors. Preventive measures as well as the inclusion of gossypibomas in the differential diagnosis of intraabdominal masses or fistulation detected in patients with a history of surgery are of utmost importance to minimize morbidity, mortality, and potential medicolegal implications.
Association between early childhood oral health impact scale (ECOHIS) scores and pediatric dental surgery wait times
Authors: Lee Victor H. K. , Grant Cameron G. , Mittermuller Betty-Anne , Singh Sarbjeet , Weiss Brenda , Edwards Jeanette M. , Schroth Robert J.
Published: October 2020

Background

Severe Early Childhood Caries (S-ECC) is an aggressive form of tooth decay that often requires pediatric dental rehabilitative surgery. The Early Childhood Oral Health Impact Scale (ECOHIS) measures oral health-related quality of life (OHRQL). The purpose of this study was to determine whether there is an association between ECOHIS scores and surgery wait times for children undergoing dental treatment for S-ECC under general anesthesia (GA).

Methods

The hypothesis was that there is no present association between wait times and ECOHIS score. Children under 72 months of age with S-ECC were recruited on the day of their slated dental surgery under GA. Parents/caregivers completed a questionnaire that included the ECOHIS. Data were merged with other ECOHIS scores from a previous study. Wait times were acquired from the Patient Access Registry Tool (PART) database. Data analysis included descriptive statistics and bivariate analyses. A p-value of ≤0.05 was considered statistically significant; 95% confidence intervals (CIs) were reported for each correlation coefficient. This study was approved by the University of Manitoba’s Health Research Ethics Board.

Results

Overall, 200 children participated, the majority of whom were Indigenous (63%) and resided in Winnipeg (52.5%). The mean age was 47.6 ± 13.8 months and 50.5% were female. Analyses showed ECOHIS scores were not significantly correlated with children’s wait times. Observed correlations between ECOHIS and children’s wait times were low and not statistically significant, ranging from ρ = 0.11 for wait times and child impact section (CIS) scores (95% CI: − 0.04, 0.26; p = 0.14), ρ = − 0.08 for family impact section (FIS) scores (95% CI: − 0.23, 0.07; p = 0.28), and ρ = 0.04 for total ECOHIS scores (95% CI: − 0.11, 0.19; p = 0.56).

Conclusion

No significant associations were observed between ECOHIS scores and wait times. In fact, those with worse OHRQL appeared to wait longer for surgery. ECOHIS scores could, however, still be used to help prioritize children for dental surgery to ensure that they receive timely access to dental care under GA. This is essential given the challenges posed by COVID-19 on timely access to surgical care.
Network analysis of autistic disease comorbidities in Chinese children based on ICD-10 codes
Authors: Li Xiaojun , Liu Guangjian , Chen Wenxiong , Bi Zhisheng , Liang Huiying
Published: October 2020

Background

Autism is a lifelong disability associated with several comorbidities that confound diagnosis and treatment. A better understanding of these comorbidities would facilitate diagnosis and improve treatments. Our aim was to improve the detection of comorbid diseases associated with autism.

Methods

We used an FP-growth algorithm to retrospectively infer disease associations using 1488 patients with autism treated at the Guangzhou Women and Children’s Medical Center. The disease network was established using Cytoscape 3.7. The rules were internally validated by 10-fold cross-validation. All rules were further verified using the Columbia Open Health Data (COHD) and by literature search.

Results

We found 148 comorbid diseases including intellectual disability, developmental speech disorder, and epilepsy. The network comprised of 76 nodes and 178 directed links. 158 links were confirmed by literature search and 105 links were validated by COHD. Furthermore, we identified 14 links not previously reported.

Conclusion

We demonstrate that the FP-growth algorithm can detect comorbid disease patterns, including novel ones, in patients with autism.
Cell-specific toxicity of short-term JUUL aerosol exposure to human bronchial epithelial cells and murine macrophages exposed at the air–liquid interface
Authors: Pinkston Rakeysha , Zaman Hasan , Hossain Ekhtear , Penn Arthur L. , Noël Alexandra
Published: October 2020

Backgroud

JUUL, an electronic nicotine delivery system (ENDS), which first appeared on the US market in 2015, controled more than 75% of the US ENDS sales in 2018. JUUL-type devices are currently the most commonly used form of ENDS among youth in the US. In contrast to free-base nicotine contained in cigarettes and other ENDS, JUUL contains high levels of nicotine salt (35 or 59 mg/mL), whose cellular and molecular effects on lung cells are largely unknown. In the present study, we evaluated the in vitro toxicity of JUUL crème brûlée-flavored aerosols on 2 types of human bronchial epithelial cell lines (BEAS-2B, H292) and a murine macrophage cell line (RAW 264.7).

Methods

Human lung epithelial cells and murine macrophages were exposed to JUUL crème brûlée-flavored aerosols at the air–liquid interface (ALI) for 1-h followed by a 24-h recovery period. Membrane integrity, cytotoxicity, extracellular release of nitrogen species and reactive oxygen species, cellular morphology and gene expression were assessed.

Results

Crème brûlée-flavored aerosol contained elevated concentrations of benzoic acid (86.9 μg/puff), a well-established respiratory irritant. In BEAS-2B cells, crème brûlée-flavored aerosol decreased cell viability (≥ 50%) and increased nitric oxide (NO) production (≥ 30%), as well as iNOS gene expression. Crème brûlée-flavored aerosol did not affect the viability of either H292 cells or RAW macrophages, but increased the production of reactive oxygen species (ROS) by ≥ 20% in both cell types. While crème brûlée-flavored aerosol did not alter NO levels in H292 cells, RAW macrophages exposed to crème brûlée-flavored aerosol displayed decreased NO (≥ 50%) and down-regulation of the iNOS gene, possibly due to increased ROS. Additionally, crème brûlée-flavored aerosol dysregulated the expression of several genes related to biotransformation, inflammation and airway remodeling, including CYP1A1, IL-6, and MMP12 in all 3 cell lines.

Conclusion

Our results indicate that crème brûlée-flavored aerosol causes cell-specific toxicity to lung cells. This study contributes to providing scientific evidence towards regulation of nicotine salt-based products.
Improved thermostability of creatinase from Alcaligenes Faecalis through non-biased phylogenetic consensus-guided mutagenesis
Authors: Bai Xue , Li Daixi , Ma Fuqiang , Deng Xi , Luo Manjie , Feng Yan , Yang Guangyu
Published: October 2020

Background

Enzymatic quantification of creatinine has become an essential method for clinical evaluation of renal function. Although creatinase (CR) is frequently used for this purpose, its poor thermostability severely limits industrial applications. Herein, we report a novel creatinase from Alcaligenes faecalis (afCR) with higher catalytic activity and lower KM value, than currently used creatinases. Furthermore, we developed a non-biased phylogenetic consensus method to improve the thermostability of afCR.

Results

We applied a non-biased phylogenetic consensus method to identify 59 candidate consensus residues from 24 creatinase family homologs for screening afCR mutants with improved thermostability. Twenty-one amino acids of afCR were selected to mutagenesis and 11 of them exhibited improved thermostability compared to the parent enzyme (afCR-M0). Combination of single-site mutations in sequential screens resulted in a quadruple mutant D17V/T199S/L6P/T251C (M4-2) which showed ~ 1700-fold enhanced half-life at 57 °C and a 4.2 °C higher T5015 than that of afCR-M0. The mutant retained catalytic activity equivalent to afCR-M0, and thus showed strong promise for application in creatinine detection. Structural homology modeling revealed a wide range of potential molecular interactions associated with individual mutations that contributed to improving afCR thermostability.

Conclusions

Results of this study clearly demonstrated that the non-biased-phylogenetic consensus design for improvement of thermostability in afCR is effective and promising in improving the thermostability of more enzymes.
Enhancing the insecticidal activity of new Bacillus thuringiensis X023 by copper ions
Authors: Liu Zhuolin , Xie Junyan , Deng Ziru , Wang Mulan , Dang Dandan , Luo Sha , Wang Yunfeng , Sun Yunjun , Xia Liqiu , Ding Xuezhi
Published: October 2020

Background

A new Bacillus thuringiensis X023 (BtX023) with high insecticidal activity was isolated in Hunan Province, China. The addition of metals (Cu, Fe, Mg and Mn) to the medium could influence the formation of spores and/or insecticidal crystal proteins (ICPs). In previous studies, Cu ions considerably increased the synthesis of ICPs by enhancing the synthesis of poly-β-hydroxy butyrate. However, the present study could provide new insights into the function of Cu ions in ICPs.

Results

Bioassay results showed that wild strain BtX023 exhibited high insecticidal activity against Plutella xylostella. The addition of 1 × 10−5 M Cu2+ could considerably increase the expression of cry1Ac and vip3Aa, and the insecticidal activity was enhanced. Quantitative real-time polymerase chain reaction (qRT-PCR) and proteomic analyses revealed that the upregulated proteins included amino acid synthesis, the glyoxylate pathway, oxidative phosphorylation, and poly-β-hydroxy butyrate synthesis. The Cu ions enhanced energy metabolism and primary amino acid synthesis, will providing abundant raw material accumulation for ICP synthesis.

Conclusion

The new strain BtX023 exerted a strong insecticidal effect on P. xylostella by producing ICPs. The addition of 1 × 10−5 M Cu2+ in the medium could considerably enhance the expression of the cry1Ac and vip3Aa genes, thereby further increasing the toxicity of BtX023 to Helicoverpa armigera and P. xylostella by enhancing energy synthesis, the glyoxylate cycle, and branched-chain amino acids synthesis, but not poly-β-hydroxy butyrate synthesis.
Identification of PKP 2/3 as potential biomarkers of ovarian cancer based on bioinformatics and experiments
Authors: Gao Lingling , Li Xiao , Guo Qian , Nie Xin , Hao Yingying , Liu Qing , Liu Juanjuan , Zhu Liancheng , Yan Limei , Lin Bei
Published: October 2020

Background

Plakophilins (PKPs) are widely involved in gene transcription, translation, and signal transduction, playing a crucial role in tumorigenesis and progression. However, the function and potential mechanism of PKP1/2/3 in ovarian cancer (OC) remains unclear. It’s of great value to explore the expression and prognostic values of PKP1/2/3 and their potential mechanisms, immune infiltration in OC.

Methods

The expression levels, prognostic values and genetic variations of PKP1/2/3 in OC were explored by various bioinformatics tools and databases, and PKP2/3 were selected for further analyzing their regulation network and immune infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted. Finally, the expression and prognosis of PKP2 were validated by immunohistochemistry.

Results

The expression level and prognosis of PKP1 showed little significance in ovarian cancer, and the expression of PKP2/3 mRNA and protein were upregulated in OC, showing significant correlations with poor prognosis of OC. Functional enrichment analysis showed that PKP2/3 and their correlated genes were significantly enriched in adaptive immune response, cytokine receptor activity, organization of cell–cell junction and extracellular matrix; KEGG analysis showed that PKP2/3 and their significantly correlated genes were involved in signaling pathways including cytokine-mediated signaling pathway, receptor signaling pathway and pathways in cancer. Moreover, PKP2/3 were correlated with lymphocytes and immunomodulators. We confirmed that high expression of PKP2 was significantly associated with advanced stage, poor differentiation and poor prognosis of OC patients.

Conclusion

Members of plakophilins family showed various degrees of abnormal expressions and prognostic values in ovarian cancer. PKP2/3 played crucial roles in tumorigenesis, aggressiveness, malignant biological behavior and immune infiltration of OC, and can be regarded as potential biomarker for early diagnosis and prognosis evaluation in OC.
Evaluation of the malaria reporting system supported by the District Health Information System 2 in Solomon Islands
Authors: Wangdi Kinley , Sarma Haribondu , Leaburi John , McBryde Emma , Clements Archie C. A.
Published: October 2020

Background

District Health Information Systems 2 (DHIS2) is used for supporting health information management in 67 countries, including Solomon Islands. However, there have been few published evaluations of the performance of DHIS2-enhanced disease reporting systems, in particular for monitoring infectious diseases such as malaria. The aim of this study was to evaluate DHIS2 supported malaria reporting in Solomon Islands and to develop recommendations for improving the system.

Methods

The evaluation was conducted in three administrative areas of Solomon Islands: Honoria City Council, and Malaita and Guadalcanal Provinces. Records of nine malaria indicators including report submission date, total malaria cases,Plasmodium falciparumcase record,Plasmodium vivaxcase record, clinical malaria, malaria diagnosed with microscopy, malaria diagnosed with (rapid diagnostic test) (RDT), record of drug stocks and records of RDT stocks from 1st January to 31st December 2016 were extracted from the DHIS2 database. The indicators permitted assessment in four core areas: availability, completeness, timeliness and reliability. To explore perceptions and point of view of the stakeholders on the performance of the malaria case reporting system, focus group discussions were conducted with health centre nurses, whilst in-depth interviews were conducted with stakeholder representatives from government (province and national) staff and World Health Organization officials who were users of DHIS2.

Results

Data were extracted from nine health centres in Honoria City Council and 64 health centres in Malaita Province. The completeness and timeliness from the two provinces of all nine indicators were 28.2% and 5.1%, respectively. The most reliable indicator in DHIS2 was ‘clinical malaria’ (i.e. numbers of clinically diagnosed malaria cases) with 62.4% reliability. Challenges to completeness were a lack of supervision, limited feedback, high workload, and a lack of training and refresher courses. Health centres located in geographically remote areas, a lack of regular transport, high workload and too many variables in the reporting forms led to delays in timely reporting. Reliability of reports was impacted by a lack of technical professionals such as statisticians and unavailability of tally sheets and reporting forms.

Conclusion

The availability, completeness, timeliness and reliability of nine malaria indicators collected in DHIS2 were variable within the study area, but generally low. Continued onsite support, supervision, feedback and additional enhancements, such as electronic reporting will be required to further improve the malaria reporting system.
Multivariate Bayesian meta-analysis: joint modelling of multiple cancer types using summary statistics
Authors: Jahan Farzana , Duncan Earl W. , Cramb Susana M. , Baade Peter D. , Mengersen Kerrie L.
Published: October 2020

Background

Cancer atlases often provide estimates of cancer incidence, mortality or survival across small areas of a region or country. A recent example of a cancer atlas is the Australian cancer atlas (ACA), that provides interactive maps to visualise spatially smoothed estimates of cancer incidence and survival for 20 different cancer types over 2148 small areas across Australia.

Methods

The present study proposes a multivariate Bayesian meta-analysis model, which can model multiple cancers jointly using summary measures without requiring access to the unit record data. This new approach is illustrated by modelling the publicly available spatially smoothed standardised incidence ratios for multiple cancers in the ACA divided into three groups: common, rare/less common and smoking-related. The multivariate Bayesian meta-analysis models are fitted to each group in order to explore any possible association between the cancers in three remoteness regions: major cities, regional and remote areas across Australia. The correlation between the pairs of cancers included in each multivariate model for a group was examined by computing the posterior correlation matrix for each cancer group in each region. The posterior correlation matrices in different remoteness regions were compared using Jennrich’s test of equality of correlation matrices (Jennrich in J Am Stat Assoc. 1970;65(330):904–12.10.1080/01621459.1970.10481133).

Results

Substantive correlation was observed among some cancer types. There was evidence that the magnitude of this correlation varied according to remoteness of a region. For example, there has been significant negative correlation between prostate and lung cancer in major cities, but zero correlation found in regional and remote areas for the same pair of cancer types. High risk areas for specific combinations of cancer types were identified and visualised from the proposed model.

Conclusions

Publicly available spatially smoothed disease estimates can be used to explore additional research questions by modelling multiple cancer types jointly. These proposed multivariate meta-analysis models could be useful when unit record data are unavailable because of privacy and confidentiality requirements.
A non-invasive ultrasound imaging method to measure acute radiation-induced bladder wall thickening in rats
Authors: Spinelli Antonello E. , Bresolin Andrea , Zuppone Stefania , Perani Laura , Fallara Giuseppe , Di Muzio Nadia , Vago Riccardo , Fiorino Claudio , Cozzarini Cesare
Published: October 2020

Background

Methods for the non-invasive quantification of changes in bladder wall thickness as potential predictors of radiation cystitis in pre-clinical research would be desirable. The use of ultrasound for this aim seems promising, but is still relatively unexplored. A method using ultrasound for bladder wall thickness quantification in rats was developed and applied to measure early radiation-induced bladder wall thickness changes.

Methods

Two groups (n = 9 each) of female Fischer rats were treated with a single radiation dose of 25–30 and 35–40 Gy respectively, using an image-guided micro-irradiator; six untreated rats were monitored as a control group. Empty, half-filled and fully-filled bladder volumes were determined for four non-irradiated rats by measuring axes from ultrasound 3D-images and applying the ellipsoid formula. Mean bladder wall thickness was estimated for both ventral and dorsal bladder sides through the measurement of the bladder wall area along a segment of 4 mm in the central sagittal scan, in order to minimize operator-dependence on the measurement position. Ultrasound acquisitions of all fully-filled rat bladders were also acquired immediately before, and 4 and 28 days after irradiation. Mean bladder wall thickness normalized to the baseline value and corrected for filling were then used to evaluate acute bladder wall thickening and to quantify the dose–effect.

Results

The relationship between mean bladder wall thickness and volume in unirradiated rats showed that for a bladder volume > 1.5 mL the bladder wall thickness is almost constant and equal to 0.30 mm with variations within ± 15%. The average ratios between post and pre irradiation showed a dose–effect relationship. Bladder wall thickening was observed for the 25–30 Gy and 35–40 Gy groups in 2/9 (22%) and 5/9 (56%) cases at day 4 and in 4/9 (44%) and 8/9 (89%) cases at day 28, respectively. The two groups showed significantly different bladder wall thickness both relative to the control group (p < 0.0001) and between them (p = 0.022). The bladder wall thickness increment was on average 1.32 ± 0.41, and was 1.30 ± 0.21 after 25–30 Gy and 1.47 ± 0.29 and 1.90 ± 0.83 after 35–40 Gy at days 4 and 28 respectively.

Conclusions

The feasibility of using ultrasound on a preclinical rat model to detect bladder wall thickness changes after bladder irradiation was demonstrated, and a clear dose–effect relationship was quantified. Although preliminary, these results are promising in addressing the potential role of this non-invasive approach in quantifying radiation cystitis.
A case report of aortic root repair using a pericardial autograft for type A aortic dissection
Authors: Chang Yi , Guo Hongwei , Qian Xiangyang , Fang Fang
Published: October 2020

Background

Acute type A aortic dissection with a dissection flap extending into the sinus segment often involves the commissures and the coronary ostia. In most cases, the intimal flap must be retained in order to restore aortic valve competence and reconstruct the coronary ostia. Residual dissection flap has the potential risks of proximal bleeding and adverse effects on long-term durability. We established a novel technique to reconstruct the aortic root using a pericardial autograft and significantly reduce remnant dissection tissues.

Case presentation

A 50-year-old female was admitted to our center with acute anterior chest pain and backache lasting about 10 h. Computed tomographic (CT) scans showed type A aortic dissection, with both coronary ostia being involved. Doppler echocardiography showed moderate aortic insufficiency. The dissection intimal flap was removed to the normal aorta wall near the annulus at the noncoronary sinus, leaving a 5 mm rim of intimal flap near the commissures and coronary ostia. Using a pericardial patch as a new aortic wall to reconstruct the root while preserving the aortic adventitia to fix and strengthen the new pericardial aortic wall. Ascending aorta and total arch replacement combined with frozen elephant trunk procedure was performed at the same time. The patient got an uneventful postoperative course.

Conclusion

Aortic root repair with a pericardial autograft is a safe and effective technique to treat acute type A dissection involving the sinus. Using this technique, residual dissection tissues could be significantly reduced, which subsequently decreases the risk of proximal bleeding and hence increases long-term durability.
LINC01094/miR-577 axis regulates the progression of ovarian cancer
Authors: Xu Jing , Zhang Ping , Sun Huajun , Liu Yang
Published: October 2020

Background

Long intergenic non-coding RNA 01094 (LINC01094) is probably a novel regulator in cancer biology. This study aimed to probe into the function and mechanism of LINC01094 in ovarian cancer (OC).

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) assay was utilized to measure LINC01094 and miR-577 expressions in OC tissues and cell lines. Western blot was used to examine the expressions of epithelial-mesenchymal transition (EMT)-related proteins, β-catenin, c-Myc and cyclin D1. Cell counting kit-8 (CCK-8) and Transwell assays were used to detect the proliferation, migration and invasion of SKOV3 and 3AO cells, respectively. Eventually, dual-luciferase reporter gene assay was employed to detect the regulatory relationship between miR-577 and LINC01094.

Results

LINC01094 expression was elevated in OC tissues and cell lines. High LINC01094 expression was associated with higher FIGO stage, lymph node metastasis and the shorter overall survival rate in patients with OC. Meanwhile, LINC01094 knockdown inhibited OC cell proliferation, migration, invasion and EMT. In addition, miR-577 was demonstrated to be a direct downstream target of LINC01094 in OC and inhibition of miR-577 reversed the biological effects of LINC01094 knockdown on OC cells. Additionally, LINC01094 / miR-577 axis regulated the expressions of β-catenin, c-Myc and cyclin D1 in OC cells.

Conclusion

LINC01094 promotes the proliferation, migration, invasion and EMT of OC cells by adsorbing miR-577.
Species diversity and insecticide resistance within the Anopheles hyrcanus group in Ubon Ratchathani Province, Thailand
Authors: Sumarnrote Anchana , Overgaard Hans J. , Corbel Vincent , Thanispong Kanutcharee , Chareonviriyaphap Theeraphap , Manguin Sylvie
Published: October 2020

Background

Members of the Anopheles hyrcanus group have been incriminated as important malaria vectors. This study aims to identify the species and explore the insecticide susceptibility profile within the Anopheles hyrcanus group in Ubon Ratchathani Province, northeastern Thailand where increasing numbers of malaria cases were reported in 2014.

Methods

Between 2013 and 2015, five rounds of mosquito collections were conducted using human landing and cattle bait techniques during both the rainy and dry seasons. Anopheles mosquitoes were morphologically identified and their insecticide susceptibility status was investigated. Synergist bioassays were carried out with An. hyrcanus (s.l.) due to their resistance to all insecticides. An ITS2-PCR assay was conducted to identify to species the Hyrcanus group specimens.

Results

Out of 10,361 Anopheles females collected, representing 18 taxa in 2 subgenera, 71.8% were morphologically identified as belonging to the Hyrcanus Group (subgenus Anopheles), followed by An. barbirostris group (7.9%), An. nivipes (6.5%), An. philippinensis (5.9%) and the other 14 Anopheles species. Specimens of the Hyrcanus Group were more prevalent during the rainy season and were found to be highly zoophilic. Anopheles hyrcanus (s.l.) was active throughout the night, with an early peak of activity between 18:00 h and 21:00 h. ITS2-PCR assay conducted on 603 DNA samples from specimens within the Hyrcanus Group showed the presence of five sisters species. Anopheles peditaeniatus was the most abundant species (90.5%, n = 546), followed by An. nitidus (4.5%, n = 27), An. nigerrimus (4.3%, n = 26), An. argyropus (0.5%, n = 3), and An. sinensis (0.2%, n = 1). All An. hyrcanus (s.l.) specimens that were found resistant to insecticides (deltamethrin 0.05%, permethrin 0.75% and DDT 4% and synergist tests) belonged to An. peditaeniatus. The degree of resistance in An. peditaeniatus to each of these three insecticides was approximately 50%. Addition of PBO (Piperonyl butoxide), but not DEF (S.S.S-tributyl phosphotritioate), seemed to restore susceptibility, indicating a potential role of oxidases as a detoxifying enzyme resistance mechanism.

Conclusions

A better understanding of mosquito diversity related to host preference, biting activity and insecticide resistance status will facilitate the implementation of locally adapted vector control strategies.
Aß40 displays amyloidogenic properties in the non-transgenic mouse brain but does not exacerbate Aß42 toxicity in Drosophila
Authors: De Mena Lorena , Smith Michael A. , Martin Jason , Dunton Katie L. , Ceballos-Diaz Carolina , Jansen-West Karen R. , Cruz Pedro E. , Dillon Kristy D. , Rincon-Limas Diego E. , Golde Todd E. , Moore Brenda D. , Levites Yona
Published: October 2020

Background

Self-assembly of the amyloid-β (Aβ) peptide into aggregates, from small oligomers to amyloid fibrils, is fundamentally linked with Alzheimer’s disease (AD). However, it is clear that not all forms of Aβ are equally harmful and that linking a specific aggregate to toxicity also depends on the assays and model systems used (Haass et al., J Biol. Chem 269:17741–17748, 1994; Borchelt et al., Neuron 17:1005–1013, 1996). Though a central postulate of the amyloid cascade hypothesis, there remain many gaps in our understanding regarding the links between Aβ deposition and neurodegeneration.

Methods

In this study, we examined familial mutations of Aβ that increase aggregation and oligomerization, E22G and ΔE22, and induce cerebral amyloid angiopathy, E22Q and D23N. We also investigated synthetic mutations that stabilize dimerization, S26C, and a phospho-mimetic, S8E, and non-phospho-mimetic, S8A. To that end, we utilized BRI2-Aβ fusion technology and rAAV2/1-based somatic brain transgenesis in mice to selectively express individual mutant Aβ species in vivo. In parallel, we generated PhiC31-based transgenic Drosophila melanogaster expressing wild-type (WT) and Aβ40 and Aβ42 mutants, fused to the Argos signal peptide to assess the extent of Aβ42-induced toxicity as well as to interrogate the combined effect of different Aβ40 and Aβ42 species.

Results

When expressed in the mouse brain for 6 months, Aβ42 E22G, Aβ42 E22Q/D23N, and Aβ42WT formed amyloid aggregates consisting of some diffuse material as well as cored plaques, whereas other mutants formed predominantly diffuse amyloid deposits. Moreover, while Aβ40WT showed no distinctive phenotype, Aβ40 E22G and E22Q/D23N formed unique aggregates that accumulated in mouse brains. This is the first evidence that mutant Aβ40 overexpression leads to deposition under certain conditions. Interestingly, we found that mutant Aβ42 E22G, E22Q, and S26C, but not Aβ40, were toxic to the eye of Drosophila. In contrast, flies expressing a copy of Aβ40 (WT or mutants), in addition to Aβ42WT, showed improved phenotypes, suggesting possible protective qualities for Aβ40.

Conclusions

These studies suggest that while some Aβ40 mutants form unique amyloid aggregates in mouse brains, they do not exacerbate Aβ42 toxicity in Drosophila, which highlights the significance of using different systems for a better understanding of AD pathogenicity and more accurate screening for new potential therapies.
Object detection in real time based on improved single shot multi-box detector algorithm
Authors: Kumar Ashwani , Zhang Zuopeng Justin , Lyu Hongbo
Published: October 2020

In today’s scenario, the fastest algorithm which uses a single layer of convolutional network to detect the objects from the image is single shot multi-box detector (SSD) algorithm. This paper studies object detection techniques to detect objects in real time on any device running the proposed model in any environment. In this paper, we have increased the classification accuracy of detecting objects by improving the SSD algorithm while keeping the speed constant. These improvements have been done in their convolutional layers, by using depth-wise separable convolution along with spatial separable convolutions generally called multilayer convolutional neural networks. The proposed method uses these multilayer convolutional neural networks to develop a system model which consists of multilayers to classify the given objects into any of the defined classes. The schemes then use multiple images and detect the objects from these images, labeling them with their respective class label. To speed up the computational performance, the proposed algorithm is applied along with the multilayer convolutional neural network which uses a larger number of default boxes and results in more accurate detection. The accuracy in detecting the objects is checked by different parameters such as loss function, frames per second (FPS), mean average precision (mAP), and aspect ratio. Experimental results confirm that our proposed improved SSD algorithm has high accuracy.
Incidence, risk factors, and outcomes of early postoperative hyperglycemia in surgical patients: a protocol for a systematic review and meta-analysis
Authors: Ssentongo Paddy , Lewcun Joseph A. , Ssentongo Anna E. , Soybel David I.
Published: October 2020

Background

Early postoperative hyperglycemia (POHG) is common and associated with poor postoperative outcomes. Currently, there is no systematic review and meta-analysis that addresses the knowledge gap of the incidence of POHG in surgical patients and that explores the associated risk factors and complications. The objective of this study will be to estimate the pooled incidence, risk factors, and clinical outcomes of early postoperative hyperglycemia in men and women globally.

Methods

We designed and registered a study protocol for a systematic review and meta-analysis of studies reporting the incidence of postoperative hyperglycemia (POHG). We will search PubMed (MEDLINE), Scopus, Web of Science, EMBASE, Cochrane Library, OVID (HEALTH STAR), OVID (MEDLINE), and Joana Briggs Institute EBF Database (from inception onwards). Randomized controlled trials and observational cohort studies reporting the incidence of POHG and conducted in surgical patients will be included. No age, geographical location, study design, or language limits will be applied. The primary outcome will be the incidence of POHG. Secondary outcomes will be risk factors and clinical outcomes of POHG. Two reviewers will independently screen citations, full text articles, and abstract data, extract data, and evaluate the quality and bias of included studies. Discrepancies will be resolved through discussion or consultation with a third researcher. The risk of bias and study methodological quality of included studies will be evaluated by the appropriate Cochrane risk of bias tool for randomized trials and Newcastle-Ottawa Scale for cohort studies. If feasible, we will conduct random effects meta-analysis with a logit transformation of proportions. We will report the probability of postoperative hyperglycemia as a measure of incidence rate, relative risk ratios (RR), and 95% confidence intervals to report the effects of the risk factors and postoperative outcomes. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., age, gender, geographical location, publication year, comorbidities, type of surgical procedure). The Egger test and funnel plots will be used to assess small study effects (publication bias).

Discussion

This systematic review and meta-analysis will identify, evaluate, and integrate the evidence on the incidence, risk factors, and outcomes of early POHG in surgical patients. The results of this study can be used to identify populations which may be at particular risk for POHG. Future studies which use this information to better guide post-operative glycemic control in surgical patients could be considered.

Systematic review registration

PROSPERO registration number CRD42020167138
Dynamics of an HIV model with cytotoxic T-lymphocyte memory
Authors: Liu Chunhua , Kong Lei
Published: October 2020

We consider a four-dimensional HIV model that includes healthy cells, infected cells, primary cytotoxic T-lymphocyte response (CTLp), and secondary cytotoxic T-lymphocyte response (CTLe). The CTL memory generation depends on CD4+ T-cell help, and infection of CD4+ T cells results in impaired T-cell help. We show that the system has up to five equilibria. By the Routh–Hurwitz theorem and central manifold theorem we obtain some sufficient conditions for the local stability, globally stability of the equilibria, and the bifurcations. We still discover the bistability case where in the system there may coexist two stable equilibria or a stable equilibrium together with a stable limit cycle. Several numerical analyses are carried out to illustrate the validity of our theoretical results.