bluuebunny/crossref_metadata_2025 huggingface dataset:
Is adherence to the 24-hour movement guidelines associated with a reduced risk of adiposity among children and adolescents?
Authors: Jakubec Lukáš , Gába Aleš , Dygrýn Jan , Rubín Lukáš , Šimůnek Adam , Sigmund Erik
Published: July 2020

Background

Little is known about the combined effect of physical activity (PA), recreational screen time (ST), and sleep in preventing childhood obesity. Hence, this study aimed to analyze the associations between meeting the PA, ST, and sleep recommendations within the 24-hour movement guidelines and adiposity indicators among children and adolescents.

Methods

A total of 679 children and adolescents aged 8–18 years were included. The time spent in moderate-to-vigorous PA and the sleep duration were estimated from raw data from a wrist-worn accelerometer. Recreational ST was reported by the child or parent. Body mass index (BMI) z-score, fat mass percentage (FM%), and visceral adipose tissue (VAT) were used as adiposity indicators. Participants with ≥ 60 min/day of moderate-to-vigorous PA, < 2 h/day of recreational ST, and uninterrupted sleep for 9–11 h/day (for children) or 8–10 h/day (for adolescents) were considered to meet the overall 24-hour movement guidelines.

Results

Meeting the ST only recommendation was associated with reduced odds of a high BMI z-score (odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.17–0.89), excess FM% (OR = 0.34, 95% CI: 0.13–0.93), and excess VAT (OR = 0.27, 95% CI: 0.10–0.74) in adolescents. Significantly reduced odds of a high BMI z-score was associated with meeting the combination of the ST and sleep recommendations (OR = 0.11, 95% CI: 0.01–0.89). Adolescents who met one recommendation (OR = 0.51, 95% CI: 0.27–0.96) or any two recommendations (OR = 0.33, 95% CI: 0.11–0.94) had reduced ORs of having a high BMI z-score. Adolescents had lower odds of having excess VAT if they met one recommendation (OR = 0.39, 95% CI: 0.19–0.81) or any two recommendations (OR = 0.25, 95% CI: 0.07–0.90). No significant associations were found in children.

Conclusions

The present study showed no associations between meeting all three recommendations within the 24-hour movement guidelines and adiposity indicators. However, meeting ST only recommendation and the combination of the ST and sleep recommendations was associated with a reduced risk of excess adiposity. This finding should be considered when designing effective strategies and interventions to prevent childhood obesity.
SFRP1 increases TMPRSS2-ERG expression promoting neoplastic features in prostate cancer in vitro and in vivo
Authors: Cruz-Hernández Carlos D. , Cruz-Burgos Marian , Cortés-Ramírez Sergio A. , Losada-García Alberto , Camacho-Arroyo Ignacio , García-López Patricia , Langley Elizabeth , González-Covarrubias Vanessa , Llaguno-Munive Monserrat , Albino-Sánchez Martha E. , Cruz-Colín José L. , Pérez-Plasencia Carlos , Beltrán-Anaya Fredy O. , Rodríguez-Dorantes Mauricio
Published: July 2020

Background

Prostate cancer (PCa) is the second cause of cancer related death in North American men. Androgens play an important role in its progression by regulating the expression of several genes including fusion ones that results from structural chromosome rearrangements. TMPRSS2-ERG is a fusion gene commonly observed in over 50% of PCa tumors, and its expression can be transcriptionally regulated by the androgen receptor (AR) given its androgen responsive elements. TMPRSS2-ERG could be involved in epithelial–mesenchymal transition (EMT) during tumor development. ERG has been reported as a key transcriptional factor in the AR-ERG-WNT network where five SFRP proteins, structurally similar to WNT ligands and considered to be WNT pathway antagonists, can regulate signaling in the extracellular space  by binding to WNT proteins or Frizzled receptors. It has been shown that over-expression of SFRP1 protein can regulate the transcriptional activity of AR and inhibits the formation of colonies in LNCaP cells. However, the effect of SFRP1 has been controversial since differential effects have been observed depending on its concentration and tissue location. In this study, we explored the role of exogenous SFRP1 protein in cells expressing the TMPRSS2-ERG fusion.

Methods

To evaluate the effect of exogenous SFRP1 protein on PCa cells expressing TMPRSS2-ERG, we performed in silico analysis from TCGA cohort, expression assays by RT-qPCR and Western blot, cell viability and cell cycle measurements by cytometry, migration and invasion assays by xCELLigance system and murine xenografts.

Results

We demonstrated that SFRP1 protein increased ERG expression by promoting cellular migration in vitro and increasing tumor growth in vivo in PCa cells with the TMPRSS2-ERG fusion.

Conclusions

These results suggest the possible role of exogenous SFRP1 protein as a modulator of AR-ERG-WNT signaling network in cells positive to TMPRSS2-ERG. Further, investigation is needed to determine if SFRP1 protein could be a target in against this type of PCa.
Expression and function of transmembrane 4 superfamily proteins in digestive system cancers
Authors: Qi Yaoyue , Li Hui , Lv Jing , Qi Weiwei , Shen Liwei , Liu Shihai , Ding Aiping , Wang Gongjun , Sun Libin , Qiu Wensheng
Published: July 2020

Background

Although the medical level is constantly improving, cancer is still a major disease that threatens human health, and very effective treatments have not been found. In recent years, studies have found that four-transmembrane superfamily proteins are involved in multiple stages of tumorigenesis and development, but their expression and function in tumors have not been systematically studied.

Methods

We used the Oncomine database to analyze the mRNA expression levels of TSPAN family in various cancers. Then differentially expressed genes were screened out and verified by liver cancer, colorectal cancer, and gastric cancer cells by q-PCR and Western blot analysis. CCK8 and EDU analysis are used to detect cell proliferation, Cell wound scrape assay and Cell invasion assay are used to analyze cell invasion and metastasis. Nude tumor formation test used to verify the tumor suppressive effect of TSPAN7 in vivo.

Results

Differential analysis of 33 TSPAN proteins revealed that a total of 11 proteins showed differential expression in 10% of independent analyses, namely TSPAN1, TSPAN3, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN13, TSPAN25, TSPAN26, TSPAN29, TSPAN30. TSPAN7 is the only four-transmembrane protein with reduced expression in three types of digestive tract tumors, so we chose TSPAN7 to be selected for cellular and molecular level verification. We found that compared with normal cells, the expression of TSPAN7 in liver cancer cells was significantly reduced, while the expression of gastric and colon cancer was not significantly different from that of normal cells. In addition, we also found that the high expression of Tspan7 not only inhibited the proliferation of HCC-LM3 cells, but also inhibited its invasion and metastasis.

Conclusions

Our study evaluated the expression and function of the TSPANs family in digestive cancers and explored TSPAN7 in hepatoma cells in detail. We found some members of the TSPAN family show significant expression differences between cancer and normal tissues, of which TSPAN7 may be a potential biomarker for liver cancer.
Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network
Authors: Kang Zhichen , Guo Lixin , Zhu Zhuo , Qu Rongfeng
Published: July 2020

Background

Accumulating amount of evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor pathogenesis. However, the roles of long non coding RNAs (lncRNAs) in the lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) still remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC.

Methods

The transcriptome sequencing data of lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from the SRA and TCGA databases. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct an lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the protein–protein interaction (PPI) network. The expression of the top 6 genes in the hub module was validated with mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The relationship between the hub gene-associated ceRNA network and the overall survival of patients with ICC was predicted by conducting a Kaplan–Meier survival analysis.

Results

Sixty co-expressed DEmRNAs were identified in the ceRNA network. The top 6 hub genes consisted of downregulated FOS, IGF2, FOXO1 and NTF3, upregulated IGF1R, and insignificantly downregulated HGF in ICC tissues, when compared to that of normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network consisting of 86 ceRNA modules. MME-AS1 and hsa-miR-182 were associated with overall survival in ICC patients. FOS, IGF1R, IGF2, FOXO1, and NTF3 might target “TGF-β signaling pathway”, “the hedgehog signaling pathway”, “retinol metabolism”, or “type II diabetes mellitus” pathways respectively.

Conclusion

These results indicate that FOS, IGF1R, IGF2, FOXO1, and NTF3 were useful prognostic factors in determining the prognosis of patients with ICC.
Patterns of pesticide usage in agriculture in rural Tanzania call for integrating agricultural and public health practices in managing insecticide-resistance in malaria vectors
Authors: Matowo Nancy S. , Tanner Marcel , Munhenga Givemore , Mapua Salum A. , Finda Marceline , Utzinger Jürg , Ngowi Vera , Okumu Fredros O.
Published: July 2020

Background

Unrestricted use of pesticides in agriculture is likely to increase insecticide resistance in mosquito vectors. Unfortunately, strategies for managing insecticide resistance in agriculture and public health sectors lack integration. This study explored the types and usage of agricultural pesticides, and awareness and management practices among retailers and farmers in Ulanga and Kilombero districts in south-eastern Tanzania, where Anopheles mosquitoes are resistant to pyrethroids.

Methods

An exploratory sequential mixed-methods approach was employed. First, a survey to characterize pesticide stocks was conducted in agricultural and veterinary (agrovet) retail stores. Interviews to assess general knowledge and practices regarding agricultural pesticides were performed with 17 retailers and 30 farmers, followed by a survey involving 427 farmers. Concurrently, field observations were done to validate the results.

Results

Lambda-cyhalothrin, cypermethrin (both pyrethroids) and imidacloprids (neonicotinoids) were the most common agricultural insecticides sold to farmers. The herbicide glyphosate (amino-phosphonates) (59.0%), and the fungicides dithiocarbamate and acylalanine (54.5%), and organochlorine (27.3%) were also readily available in the agrovet shops and widely used by farmers. Although both retailers and farmers had at least primary-level education and recognized pesticides by their trade names, they lacked knowledge on pest control or proper usage of these pesticides. Most of the farmers (54.4%, n = 316) relied on instructions from pesticides dealers. Overall, 93.7% (400) farmers practised pesticides mixing in their farms, often in close proximity to water sources. One-third of the farmers disposed of their pesticide leftovers (30.0%, n = 128) and most farmers discarded empty pesticide containers into rivers or nearby bushes (55.7%, n = 238).

Conclusion

Similarities of active ingredients used in agriculture and malaria vector control, poor pesticide management practices and low-levels of awareness among farmers and pesticides retailers might enhance the selection of insecticide resistance in malaria vectors. This study emphasizes the need for improving awareness among retailers and farmers on proper usage and management of pesticides. The study also highlights the need for an integrated approach, including coordinated education on pesticide use, to improve the overall management of insecticide resistance in both agricultural and public health sectors.
Health-related quality of life in women with polycystic ovary syndrome attending to a tertiary hospital in Southeastern Spain: a case-control study
Authors: Sánchez-Ferrer María L. , Adoamnei Evdochia , Prieto-Sánchez María T. , Mendiola Jaime , Corbalán-Biyang Shiana , Moñino-García Miriam , Palomar-Rodríguez Joaquín A. , Torres-Cantero Alberto M.
Published: July 2020

Background

Polycystic ovary syndrome (PCOS) is a chronic condition with symptoms affecting many women at reproductive age and evaluating their health-related quality of Life (HRQoL) is an important issue. Moreover, differences in the HRQoL between women with different PCOS phenotypes have never been analyzed. Therefore, the aim of our study was to compare the HRQoL between women with PCOS -and its phenotypes- and controls attending to a tertiary hospital.

Methods

A group of 117 women with PCOS and 153 controls were studied between 2014 and 2016. Controls were women without PCOS attending the gynecological outpatient clinic for routine examinations. Cases were women attending the same setting and diagnosed with PCOS. PCOS diagnose was performed following the Rotterdam Criteria and women were further classified by anovulatory or ovulatory phenotypic subtype. Women underwent physical and gynecological exams and completed health questionnaires including the Short Form-12v2. Eight scales and two component summary scores [Physical (PCS) and Mental (MCS), respectively] were calculated. Bivariate and multivariate analyses were performed to assess differences in HRQoL between women with PCOS and controls.

Results

All women with PCOS and anovulatory PCOS presented lower score in PCS compared to controls [mean (95%CI): 53.7 (52.5–54.9) and 52.9 (51.5–54.4) vs. 55.8 (54.8–56.8); p-values< 0.01], as well as lower scores for five out of the eight scales (p-values < 0.05) after adjusting by age, body mass index, infertility, educational level and current occupation. No significant differences were observed for the MCS between women with or without PCOS or its phenotypic subtypes.

Conclusions

HRQoL was significantly decreased in adult women with PCOS and its anovulatory phenotype compared to controls attending the outpatient clinic of a tertiary hospital. These results may have implications for the clinical practice and suggest the need for specific interventions in women with PCOS.
A comprehensive study on the oncogenic mutation and molecular pathology in Chinese lung adenocarcinoma patients
Authors: Zhang Xilin , Jiang Yan , Yu Huanming , Xia Hui , Wang Xiang
Published: July 2020

Background

Several genetic driver alterations have been identified in micropapillary lung adenocarcinoma (MPA). However, the frequency of co-alteration of ROS1, EGFR, and EML4-ALK is yet unclear. Herein, we investigated the relationship between clinicopathologic characteristics and well-identified driver mutations of MPA compared with non-micropapillary lung adenocarcinoma (LA).

Methods

Formalin-fixed paraffin-embedded (FFPE) sections derived from lung adenocarcinoma patients who never received adjuvant chemotherapy or radiation therapy prior to surgical resection were collected from October 2016 to June 2019. EGFR mutations, ROS1 rearrangements, and EML4-ALK fusion were identified in a set of 131 MPA and LA cases by using the amplification refractory mutation system (ARMS). The response rate and duration of response were assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

Results

EGFR mutations had occurred in 42 (76.4%) MPA patients and 42 (55.3%) LA patients. Interestingly, ROS1 rearrangements were highly enriched only in the MPA cases (6/55, 10.9%) but rarely in the LA cases (1/76, 1.3%). Furthermore, 7.3% (4/55) MPA samples had double gene mutations, while only 1.3% (1/76) LA cases had double gene alterations. Of 5 patients with harboring two driver oncogene mutations, four patients (80%) obtained partial response, and one patient (20%) suffered recurrence.

Conclusions

A higher prevalence of ROS1 rearrangement or combined mutations of ROS1, EGFR, and EML4-ALK may play a critical role in the tumorigenesis of MPA. These findings provide a novel therapeutic strategy for patients with malignant MPA through combining TKIs than one TKI.
The impact of physical activity on healthy ageing trajectories: evidence from eight cohort studies
Authors: Moreno-Agostino Darío , Daskalopoulou Christina , Wu Yu-Tzu , Koukounari Artemis , Haro Josep Maria , Tyrovolas Stefanos , Panagiotakos Demosthenes B. , Prince Martin , Prina A. Matthew
Published: July 2020

Background

Research has suggested the positive impact of physical activity on health and wellbeing in older age, yet few studies have investigated the associations between physical activity and heterogeneous trajectories of healthy ageing. We aimed to identify how physical activity can influence healthy ageing trajectories using a harmonised dataset of eight ageing cohorts across the world.

Methods

Based on a harmonised dataset of eight ageing cohorts in Australia, USA, Mexico, Japan, South Korea, and Europe, comprising 130,521 older adults (Mage = 62.81, SDage = 10.06) followed-up up to 10 years (Mfollow-up = 5.47, SDfollow-up = 3.22), we employed growth mixture modelling to identify latent classes of people with different trajectories of healthy ageing scores, which incorporated 41 items of health and functioning. Multinomial logistic regression modelling was used to investigate the associations between physical activity and different types of trajectories adjusting for sociodemographic characteristics and other lifestyle behaviours.

Results

Three latent classes of healthy ageing trajectories were identified: two with stable trajectories with high (71.4%) or low (25.2%) starting points and one with a high starting point but a fast decline over time (3.4%). Engagement in any level of physical activity was associated with decreased odds of being in the low stable (OR: 0.18; 95% CI: 0.17, 0.19) and fast decline trajectories groups (OR: 0.44; 95% CI: 0.39, 0.50) compared to the high stable trajectory group. These results were replicated with alternative physical activity operationalisations, as well as in sensitivity analyses using reduced samples.

Conclusions

Our findings suggest a positive impact of physical activity on healthy ageing, attenuating declines in health and functioning. Physical activity promotion should be a key focus of healthy ageing policies to prevent disability and fast deterioration in health.
Possible role of plasma Galectin-9 levels as a surrogate marker of viremia in HIV infected patients on antiretroviral therapy in resource-limited settings
Authors: Shete Ashwini , Dhayarkar Sampada , Dhamanage Ashwini , Kulkarni Smita , Ghate Manisha , Sangle Shashikala , Medhe Uttam , Verma Vinita , Rajan Shobini , Hattori Toshio , Gangakhedkar Raman
Published: July 2020

Background

Early detection of viremia in HIV infected patients on anti-retroviral therapy (ART) is important to prevent disease progression as well as accumulation of drug resistance mutations. This makes HIV viral load (VL) monitoring indispensable in HIV infected patients on ART. However VL, being an expensive test, results in heavy financial burden on health services. Hence, cheaper surrogate markers of viremia are desired to reduce overall cost of management of HIV infected patients.

Methods

We enrolled aviremic (n = 63, M:F = 31:32) and viremic (n = 43, M:F = 21:22) HIV infected patients at 1 year after ART initiation. Viremic individuals were identified as those having a plasma VL of more than 1000 copies/µl and aviremic individuals as less than 40 copies/µl. The study participants also included immuno-virologically discordant patients as they demonstrate differential degrees of immune-reconstitution and are likely to harbour concomitant infections influencing levels of immune-activation markers screened as the surrogate markers. Immune activation markers viz. plasma hs-CRP, soluble-CD14 and Galectin-9 levels were estimated by ELISA, IL-6 by luminex assay and percentages of CD38+ CD8+ cells were determined by flow cytometry. The levels were compared between viremic and aviremic patients and correlated with plasma viral load. Receiver operated curve (ROC) analysis was done for plasma Galectin-9 levels.

Results

Viremic patients had significantly higher levels of Galectin-9 and %CD38+ CD8+ cells (p values < 0.0001) than aviremic patients. Levels of the other activation markers did not differ between viremic and aviremic individuals. Galectin-9 levels (r = 0.76) and %CD38+ CD8+ cells (r = 0.39) correlated positively with VL. Area under curve for Galectin-9 levels for distinguishing between viremic and aviremic individuals was 0.98. Youden index, sensitivity, specificity, positive predictive value and negative predictive value for Galectin-9 levels were 0.87, 0.97, 0.90, 0.87 and 0.98, respectively, at the cut-off value of 5.79 ng/ml.

Conclusions

Plasma Galectin-9 levels could identify viremic individuals with sensitivity and specificity of more than 90%. Thus, they showed a potential to serve as a surrogate marker of viremia in HIV infected patients on ART and would have cost implications on HIV management especially in resource-limited settings. However, the findings need to be confirmed in the patients on ART for different durations of time.
Determinants of undisclosed HIV status to a community-based HIV program: findings from caregivers of orphans and vulnerable children in Tanzania
Authors: Charles John , Exavery Amon , Barankena Asheri , Kuhlik Erica , Mubyazi Godfrey M. , Abdul Ramadhani , Koler Alison , Kikoyo Levina , Jere Elizabeth
Published: July 2020

Background

HIV status disclosure facilitates receipt of HIV prevention and treatment services. Although disclosure to sexual partners, family members or friends has been extensively studied, disclosure to community-based HIV programs is missing. This study assesses the magnitude of, and factors associated with undisclosed HIV status to a community-based HIV prevention program among caregivers of orphans and vulnerable children (OVC) in Tanzania.

Methods

Data are from the USAID-funded Kizazi Kipya project that seeks to increase uptake of HIV, health, and social services by OVC and their caregivers in Tanzania. Data on OVC caregivers who were enrolled in the project during January–March 2017 in 18 regions of Tanzania were analyzed. Caregivers included were those who had complete information on their HIV status disclosure, household socioeconomic status, and sociodemographic characteristics. HIV status was self-reported, with undisclosed status representing all those who knew their HIV status but did not disclose it. Multilevel mixed-effects logistic regression, with caregivers’ HIV status disclosure being the outcome variable was conducted.

Results

The analysis was based on 59,683 OVC caregivers (mean age = 50.4 years), 71.2% of whom were female. Of these, 37.2% did not disclose their HIV status to the USAID Kizazi Kipya program at the time of enrollment. Multivariate analysis showed that the likelihood of HIV status non-disclosure was significantly higher among: male caregivers (odds ratio (OR) = 1.22, 95% confidence interval (CI) 1.16–1.28); unmarried (OR = 1.12, 95% CI 1.03–1.23); widowed (OR = 1.12, 95% CI 1.07–1.18); those without health insurance (OR = 1.36, 95% CI 1.28–1.45); age 61 + years (OR = 1.72, 95% CI 1.59–1.88); those with physical or mental disability (OR = 1.14, 95% CI 1.04–1.25); and rural residents (OR = 1.58, 95% CI 1.34–1.86). HIV status non-disclosure was less likely with higher education (p < 0.001); and with better economic status (p < 0.001).

Conclusion

While improved education, economic strengthening support and expanding health insurance coverage appear to improve HIV status disclosure, greater attention may be required for men, unmarried, widowed, rural residents, and the elderly populations for their higher likelihood to conceal HIV status. This is a clear missed opportunity for timely care and treatment services for those that may be HIV positive. Further support is needed to support disclosure in this population.
Genetic variability, phylogeny and functional implication of the long control region in human papillomavirus type 16, 18 and 58 in Chengdu, China
Authors: Fang Liyuan , Lin Xiaoli , Yang Yasi , Song Zhilin , Ding Xianping , Tan Liping , Gao Peng
Published: July 2020

Background

Long control region (LCR) of human papillomavirus (HPV) has shown multiple functions on regulating viral transcription. The variations of LCR related to different lineages/sub-lineages have been found to affect viral persistence and cervical cancer progression differently. In this study, we focused on gene polymorphism of HPV16/18/58 LCR to assess the effect variations caused on transcription factor binding sites (TFBS) and provided more data for further study of LCR in Southwest China.

Methods

LCR of HPV16/18/58 were amplified and sequenced to do polymorphic and phylogenetic anlysis. Sequences of each type were aligned with the reference sequence by MEGA 6.0 to identify SNPs. Neighbor-joining phylogenetic trees were constructed using MEGA 6.0. Transcription factor binding sites were predicted by JASPAR database.

Results

The prevalence of these three HPVs ranked as HPV16 (12.8%) > HPV58 (12.6%) > HPV18 (3.5%) in Chengdu, Southwest China. 59 SNPs were identified in HPV16-LCR, 18 of them were novel mutations. 30 SNP were found in HPV18-LCR, 8 of them were novel. 55 SNPs were detected in HPV58-LCR, 18 of them were novel. Also, an insertion (CTTGTCAGTTTC) was detected in HPV58-LCR between position 7279 and 7280. As shown in the neighbor-joining phylogenetic trees, most isolates of HPV16/18/58 were clustered into lineage A. In addition, one isolate of HPV16 was classified into lineage C and 3 isolates of HPV58 were classified as lineage B. JASPAR results suggested that TFBS were potentially influenced by 7/6 mutations on LCR of HPV16/18. The insertion and 5 mutations were shown effects in LCR of HPV58.

Conclusion

This study provides more data for understanding the relation among LCR mutations, lineages and carcinogenesis. It also helps performing further study to demonstrate biological function of LCR and find potential marker for diagnosis and therapy.
A response to the letter to the editor by Driscoll et al.
Authors: Saber Anne T. , Poulsen Sarah S. , Hadrup Niels , Jacobsen Nicklas R. , Vogel Ulla
Published: July 2020

In response to the Letter to the Editor by Kevin Driscoll et al., we certainly agree that particle clearance halftimes are increased with increasing lung burden in rats, hamsters and mice, whereas complete inhibition of particle clearance has only been observed in rats, and only at high particle concentrations (50 mg/m3). Where we disagree with Kevin Driscoll and colleagues, is on the implications of the increased clearance halftimes observed at higher lung burden. We argue that it does not hamper the extrapolations from relatively high dose levels to lower dose levels.

Furthermore, we highlight, again, the challenges of detecting particle-induced lung cancer in epidemiological studies where occupational, particle-induced lung cancer has to be detected on top of the background lung cancer incidence. Almost all available epidemiological studies on carbon black and titanium dioxide suffer from a number of limitations, including lack of control for smoking, the use of background population cancer rates as reference in the US studies, lack of information regarding particle size of the exposure, and incomplete follow-up for cause of death of the study population.
Comment on Saber et al. (2019), “Commentary: the chronic inhalation study in rats for assessing lung cancer risk may be better than its reputation”
Authors: Driscoll Kevin E. , Borm Paul A. , Chaudhuri Ishrat , Levy Len , Yong Mei , Warheit David , McCunney Robert , Oberdörster Günter
Published: July 2020

In their Commentary Saber et al. (Part Fibre Toxicol 16: 44, 2019) argue that chronic inhalation studies in rats can be used for assessing the lung cancer risk of insoluble nanomaterials. The authors make several significant errors in their interpretation and representation of the underlying science. In this Letter to the Editor we discuss these inaccuracies to correct the scientific record. When the science is recounted accurately it does not support Saber et al’s statements and conclusions.
Ovarian cancer: diagnostic accuracy and tumor types distribution in East Africa compared to North America
Authors: Rambau Peter F. , Köbel Martin , Tilley Derek , Mremi Alex , Lukande Robert , Muller William
Published: July 2020

Background

Ovarian cancer is a spectrum of several histologically distinct tumor types that differ in etiology, response to therapy, and prognosis. In resource-limited settings, the diagnosis of ovarian cancer can be challenging. This study describes the distribution of ovarian cancer tumor types in East Africa as well as assessing the diagnostic accuracy by using contemporary methods.

Methods

Data from 210 women identified from the records with a diagnosis of ovarian cancer in a period of 15 years were included. Two tissue microarrays were constructed and stained with 20 antibodies relevant to ovarian cancer subtyping. An integrated diagnosis was reached by the review of full Haematoxylin and Eosin stained sections, with consideration of immunohistochemical results. The integrated diagnoses were compared with the original diagnoses, and the degree of agreement was evaluated by percentage and Kappa statistics.

Results

Though limited by selection bias, the results suggest lower rates of ovarian cancer in East Africa compared to a North American population from Alberta, Canada. There was a higher proportion of sex cord stromal tumors and germ cell tumors in the East African population. Diagnostic accuracy for main ovarian tumor type categories was substantial (Kappa 0.70), but only fair for specific ovarian carcinoma histotypes (Kappa 0.34). Poor Haematoxylin and Eosin stain was the main factor hindering the correct diagnosis, which was not related to tissue processing.

Conclusions

In a resource-limited setting, where immunohistochemistry is not routinely carried out, diagnostic accuracy for the main categories of ovarian carcinoma is substantial and could be further improved by standardization of the basic Haematoxylin and Eosin stain.
A data workflow to support plant breeding decisions from a terrestrial field-based high-throughput plant phenotyping system
Authors: Thompson Alison L. , Thorp Kelly R. , Conley Matthew M. , Roybal Michael , Moller David , Long Jacob C.
Published: July 2020

Field-based high-throughput plant phenotyping (FB-HTPP) has been a primary focus for crop improvement to meet the demands of a growing population in a changing environment. Over the years, breeders, geneticists, physiologists, and agronomists have been able to improve the understanding between complex dynamic traits and plant response to changing environmental conditions using FB-HTPP. However, the volume, velocity, and variety of data captured by FB-HTPP can be problematic, requiring large data stores, databases, and computationally intensive data processing pipelines. To be fully effective, FB-HTTP data workflows including applications for database implementation, data processing, and data interpretation must be developed and optimized. At the US Arid Land Agricultural Center in Maricopa Arizona, USA a data workflow was developed for a terrestrial FB-HTPP platform that utilized a custom Python application and a PostgreSQL database. The workflow developed for the HTPP platform enables users to capture and organize data and verify data quality before statistical analysis. The data from this platform and workflow were used to identify plant lodging and heat tolerance, enhancing genetic gain by improving selection accuracy in an upland cotton breeding program. An advantage of this platform and workflow was the increased amount of data collected throughout the season, while a main limitation was the start-up cost.
D-dimer in the diagnosis of periprosthetic joint infection: a systematic review and meta-analysis
Authors: Lu Guangxu , Li Tong , Ye Haoqi , Liu Shujin , Zhang Peng , Wang Wenliang
Published: July 2020

Background

D-dimer, a coagulation-related indicator, has recently been used as a tool for the diagnosis of periprosthetic joint infection (PJI), but its reliability is uncertain. The purpose of this systematic review and meta-analysis was to explore the accuracy of D-dimer in the diagnosis of PJI after joint arthroplasty.

Methods

We systematically searched the MEDLINE, EMBASE, and Cochrane databases for relevant literature about D-dimer in the diagnosis of PJI. QUADAS-2 was used to assess the risk of bias and clinical applicability of each included study. We used the bivariate meta-analysis framework to pool the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the SROC curve (AUC). Univariate meta-regression and subgroup analyses were performed to explore the sources of heterogeneity.

Results

We included 8 eligible studies. The pooled diagnostic sensitivity and specificity were 0.82 (95% CI, 0.70–0.89) and 0.70 (95% CI, 0.55–0.82), respectively. The pooled PLR, NLR, and DOR were 2.7 (95% CI, 1.7–4.4), 0.26 (95% CI, 0.15–0.46), and 10 (95% CI, 4–25), respectively. The AUC was 0.83 (95% CI, 0.8–0.86). Serum D-dimer might have higher diagnostic accuracy than plasma D-dimer for PJI (pooled sensitivity: 0.88 vs 0.67; pooled specificity: 0.76 vs 0.61).

Conclusions

D-dimer has limited performance for the diagnosis of PJI.
Outcome of osteofibrous dysplasia-like versus classic adamantinoma of long bones: a single-institution experience
Authors: Deng Zhiping , Gong Lihua , Zhang Qing , Hao Lin , Ding Yi , Niu Xiaohui
Published: July 2020

Background

The clinical and molecular characteristics of osteofibrous dysplasia (OFD)-like adamantinoma (AD) differ from those of classic AD. Most reports about OFD-like AD are case reports or small case series. More cases from different centers are still warranted.

Methods

The orthopedic oncology database of our institution was searched to identify patients with AD. The cases of OFD-like and classic AD of the long bones were retrospectively analyzed. Between December 1999 and August 2016, 23 patients were treated for AD, comprising seven with OFD-like AD and 16 with classic AD. The outcomes were compared between AD subtypes.

Results

In the OFD-like AD group, four lesions were treated with extensive curettage, while three were treated with wide resection. The median follow-up duration in the OFD-like AD group was 66 months (range 43–131 months). At the end of follow-up, there was only one case of local recurrence (LR) in the OFD-like AD group, giving a LR rate of 14.3% (1/7). No distant metastasis or progression to classic AD was detected in the OFD-like AD group. In the classic AD group, the treatments were below-the-knee amputation in one patient with extensive tibial and fibular lesions, curettage with a bone graft in one patient who was diagnosed with OFD based on a core needle biopsy, hemi-cortical excision and reconstruction in two patients, and segmental resection and reconstruction in 12 patients. At the end of follow-up, there were three cases of LR in the classic AD group, giving a LR rate of 18.8% (3/16); two patients developed lung metastasis after LR and died of the disease at 88 and 126 months after the first surgery in our hospital, respectively. The classic AD group had a metastatic rate of 12.5% (2/16), a final limb salvage rate of 75%, and estimated 5- and 10-year survival rates of 88.9% and 77.1%, respectively.

Conclusions

OFD-like AD has a better outcome than classic AD. For OFD-like AD, extensive curettage is suggested if the tumor extent allows. For classic AD, aggressive resection with wide margins is essential to achieve local control. A long-term follow-up is necessary due to the possibility of late complications.
Crisis checklist (Code Red) for the management of cardiac arrest during minimally invasive thoracic surgery: case report
Authors: Rinieri Philippe , Selim Jean , Le Guillou Vincent , Baste Jean-Marc
Published: July 2020

Background

The management of cardiac arrest during video assisted thoracic surgery is challenging. Checklist use improve the management of operating-room crises.

Case presentation: Cardiac arrest (asystole) occurred during anatomical pulmonary resection by minimally invasive surgery. Conversion to thoracotomy was decided (thoracic surgeon and anesthesiologist conjointly) to check for absence of cardiac bleeding and to start cardiac massage (4 min no-flow). After few minutes, ventricular fibrillation occurred and persisted despite shocks. Extracorporeal life support with veno-arterial extracorporeal membrane oxygenation allowed a return of spontaneous circulation (45 min low-flow).

Conclusions

The patient survived without central neurologic deficit due to perfect team work process using a crisis check-list (strengthened by a comprehensive simulation program with crisis resource management).
Efficacy of interleukin-6 in combination with D-dimer in predicting early poor postoperative prognosis after acute stanford type a aortic dissection
Authors: Wu Qingsong , Li Jiahui , Chen Liangwan , Yan Liang Liang , Qiu Zhihuang , Shen Yue , Xie Xianbiao , Xie Linfeng
Published: July 2020

Background

We studied early poor postoperative prognosis in acute Stanford type A aortic dissection (ATAAD) patients and investigated the predictive effect of interleukin-6 (IL-6) combined with D-dimer in the early poor postoperative prognosis after ATAAD.

Methods

Data on 141 ATAAD patients, who underwent emergency surgery between January 2018 and December 2018 at our hospital, were studied. We analyzed early postoperative prognosis using two patient groups. Patients with good prognosis were included in group A and those with poor prognosis were in group B. Univariate logistic and multivariable logistic regression analysis were performed for poor early postoperative prognosis.

Results

Preoperative IL-6 level was lower (57.8 ± 39.0 vs 211.0 ± 153.7 pg/mL, p < 0.001) and the D-dimer was also lower (7.3 ± 6.1 vs. 16.7 ± 5.8 μg/mL, p < 0.001) in group A than in B. The cut-off points, determined by the ROC curve, were preoperative IL-6 > 108 pg/mL (area under the curve: AUC = 0.901) and D-dimer > 14.0 μg/mL (AUC = 0.817). Univariate logistic regression analysis showed that IL-6 > 108 pg/mL, D-dimer > 14.0 μg/mL, prothrombin time > 15 s, creatinine > 135 mmol/mL, and operation time > 306 min for ATAAD appeared to be early postoperative risk factors of poor prognosis. Multivariable logistic regression analysis showed that IL-6 > 108 pg/mL and D-dimer > 14.0 μg/mL were early postoperative risk factors for poor prognosis after ATAAD, and the odds ratios (ORs) of IL-6 > 108 pg/mL and D-dimer > 14.0 μg/mL were 24.937 (6.837, 90.931) and 18.757 (5.094, 69.075), respectively. When IL-6 was > 108 pg/mL (AUC = 0.901), the sensitivity and specificity of predicting early postoperative prognosis after ATAAD were 79.4 and 89.7%, respectively (95% confidence interval [CI] 0.839 to 0.963). When D-dimer was > 14.0 g/mL (AUC = 0.817), the sensitivity and specificity were 82.4 and 84.1%, respectively (95% CI 0.731 to 0.903). When combined with D-dimer (AUC = 0.936) (95% CI 0.793 to 0.979), the AUC values were more predictive than those for the individual marker.

Conclusion

IL-6 > 108 pg/mL and D-dimer > 14.0 μg/mL is of high predictive value for the assessment of early poor postoperative prognosis after ATAAD. And IL-6 > 108 pg/mL in combination with D-dimer > 14.0 μg/mL is of higher predictive value.
Integrated metabolomic and transcriptomic profiling reveals the tissue-specific flavonoid compositions and their biosynthesis pathways in Ziziphora bungeana
Authors: He Jiang , Yang Weijun , Cheng Bo , Ma Lina , Tursunjiang Dilinuer , Ding Zimian , Li Yong , Wang Zhaofeng , Ma Yimian , Li Guan
Published: July 2020

Background

Ziziphora bungeana Juz. is a folk medicine from the Xinjiang Uygur Autonomous Region. The herb or the aerial parts of it have been used to medicinally treat cardiovascular diseases. Flavonoids are the main pharmacologically active ingredients in Z. bungeana. Identification of the tissue-specific distribution of flavonoids in Z. bungeana is crucial for effective and sustainable medicinal use of the plant. Furthermore, understanding of the biosynthesis pathways of these flavonoids in Z. bungeana is of great biological significance.

Methods

The flavonoids from different tissues of Z. bungeana were identified using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The full-length transcriptome of Z. bungeana was determined using a strategy based on a combination of Illumina and PacBio sequencing techniques. The functions of differentially expressed unigenes were predicted using bioinformatics methods and further investigated by real-time quantitative PCR and phylogenetic relationship analysis.

Results

Among the 12 major flavonoid components identified from Z. bungeana extracts, linarin was the most abundant component. Nine flavonoids were identified as characteristic components of specific tissues. Transcriptome profiling and bioinformatic analysis revealed that 18 genes were putatively involved in flavonoid biosynthesis. The gene expression and phylogenetic analysis results indicated that ZbPALs, Zb4CL3, ZbCHS1, and ZbCHI1 may be involved in the biosynthesis of the main flavonoid intermediate. ZbFNSII, ZbANS, and ZbFLS may be involved in the biosynthesis of flavones, anthocyanins, and flavonols, respectively. A map of the biosynthesis pathways of the 12 major flavonoids in Z. bungeana is proposed.

Conclusions

The chemical constituent analysis revealed the compositions of 9 characteristic flavonoids in different tissues of Z. bungeana. Linarin can be hydrolysed into acacetin to exert a pharmaceutical role. Apigenin-7-O-rutinoside is hypothesised to be the precursor of linarin in Z. bungeana. There was greater content of linarin in the aerial parts of the plant than in the whole herb, which provides a theoretical basis for using the aerial parts of Z. bungeana for medicine. These results provide a valuable reference for further research on the flavonoid biosynthesis pathways of Z. bungeana and will be significant for the effective utilisation and ecological protection of Z. bungeana.
Role of CD47 in Hematological Malignancies
Authors: Eladl Entsar , Tremblay-LeMay Rosemarie , Rastgoo Nasrin , Musani Rumina , Chen Wenming , Liu Aijun , Chang Hong
Published: July 2020

CD47, or integrin-associated protein, is a cell surface ligand expressed in low levels by nearly all cells of the body. It plays an integral role in various immune responses as well as autoimmunity, by sending a potent “don’t eat me” signal to prevent phagocytosis. A growing body of evidence demonstrates that CD47 is overexpressed in various hematological malignancies and its interaction with SIRPα on the phagocytic cells prevents phagocytosis of cancer cells. Additionally, it is expressed by different cell types in the tumor microenvironment and is required for establishing tumor metastasis. Overexpression of CD47 is thus often associated with poor clinical outcomes. CD47 has emerged as a potential therapeutic target and is being investigated in various preclinical studies as well as clinical trials to prove its safety and efficacy in treating hematological neoplasms. This review focuses on different therapeutic mechanisms to target CD47, either alone or in combination with other cell surface markers, and its pivotal role in impairing tumor growth and metastatic spread of various types of hematological malignancies.
Modeling neoplastic disease with spheroids and organoids
Authors: Zanoni Michele , Cortesi Michela , Zamagni Alice , Arienti Chiara , Pignatta Sara , Tesei Anna
Published: July 2020

Cancer is a complex disease in which both genetic defects and microenvironmental components contribute to the development, progression, and metastasization of disease, representing major hurdles in the identification of more effective and safer treatment regimens for patients. Three-dimensional (3D) models are changing the paradigm of preclinical cancer research as they more closely resemble the complex tissue environment and architecture found in clinical tumors than in bidimensional (2D) cell cultures. Among 3D models, spheroids and organoids represent the most versatile and promising models in that they are capable of recapitulating the heterogeneity and pathophysiology of human cancers and of filling the gap between conventional 2D in vitro testing and animal models. Such 3D systems represent a powerful tool for studying cancer biology, enabling us to model the dynamic evolution of neoplastic disease from the early stages to metastatic dissemination and the interactions with the microenvironment. Spheroids and organoids have recently been used in the field of drug discovery and personalized medicine. The combined use of 3D models could potentially improve the robustness and reliability of preclinical research data, reducing the need for animal testing and favoring their transition to clinical practice. In this review, we summarize the recent advances in the use of these 3D systems for cancer modeling, focusing on their innovative translational applications, looking at future challenges, and comparing them with most widely used animal models.
Morphological characteristics of the Lisfranc ligament
Authors: Suzuki Y. , Edama M. , Kaneko F. , Ikezu M. , Matsuzawa K. , Hirabayashi R. , Kageyama I.
Published: July 2020

Background

This study aimed to clarify the morphological characteristics of the Lisfranc ligament and the cuneiform 1‐metatarsal 2&3 plantar ligament (CMPL).

Methods

Forty legs from 20 cadavers were examined. Classification proceeded according to the number of fiber bundles in the Lisfranc ligament and the CMPL. Morphological features measured were fiber bundle length, width, thickness, and angle.

Results

In Type I‐a, the Lisfranc ligament and the CMPL were a single fiber bundle; in Type I‐b, the Lisfranc ligament was a single fiber bundle, and the CMPL was two fiber bundles; in Type II‐a, the Lisfranc ligament was a two fiber bundle, and the CMPL was a single fiber bundle; in Type II‐b, the Lisfranc ligament and the CMPL were two fiber bundles; in Type III‐a, the Lisfranc ligament was three fiber bundles, and the CMPL was a single fiber bundle; in Type III‐b, the Lisfranc ligament was three fiber bundles, and the CMPL was two fiber bundles; in Type IV, the Lisfranc ligament and the CMPL could not be separated. Type I‐a was seen in 37.5%, Type I‐b in 10%, Type II‐a in 30%, Type II‐b in 7.5%, Type III‐a in 7.5%, Type III‐b in 2.5%, and Type IV in 5%. The Lisfranc ligament was significantly larger than the CMPL in total fiber bundle width, total fiber bundle thickness, and total fiber bundle angle.

Conclusion

The Lisfranc ligament had up to 3 fiber bundles and the CMPL had one or two fiber bundles; classifications were four types and two subgroups.