bluuebunny/crossref_metadata_2025 huggingface dataset:
Circ-ABCB10 knockdown inhibits the malignant progression of cervical cancer through microRNA-128-3p/ZEB1 axis
Authors: Feng Wei , Zhang Dongya , Zhang Ruitao
Published: September 2021

Aims

We focused on the detailed functions of circ-ABCB10 in cervical cancer (CC) development and its mechanisms.

Background

The increasing findings have proposed the central roles of circular RNAs (circRNAs) in the tumorigenesis of various human cancers. Circ-ABCB10 displays promising oncogenic effect in several tumors.

Methods

Circ-ABCB10 and miR-128-3p production levels in CC tissues and cells were tested through RT-qPCR. The association of circ-ABCB10 expression with clinicopathologic parameters of CC patients was statistically analyzed. Cell proliferation, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) were evaluated by MTT, transwell invasion assays, flow cytometry analyses, and western blot examination of EMT markers. The binding activity between miR-128-3p and circ-ABCB10 or zinc finger E-box binding homeobox 1 (ZEB1) was explored through pull-down assay or luciferase reporter assay. The influence of circ-ABCB10 on CC tumorigenesis was evaluated by in vivo xenograft experiments.

Results

The elevated circ-ABCB10 expression was determined in CC tissues and cells. Moreover, higher production level of circ-ABCB10 was close related to lymph-node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, and tumor size in CC patients. Loss of circ-ABCB10 weakened cell proliferative and invasive abilities, inhibited EMT, and induced apoptosis in CC. Loss of circ-ABCB10 inhibited ZEB1 expression by serving as a sponge of miR-128-3p in CC cells. Circ-ABCB10 sponged miR-128-3p to enhance cell proliferation, invasion, EMT and inhibit apoptosis in CC cells. Xenograft tumor assays confirmed that circ-ABCB10 knockdown inhibited CC tumor growth.

Conclusion

Our study suggests that circ-ABCB10 depletion inhibits proliferation, invasion and EMT and promotes apoptosis of cervical cancer cells through miR-128-3p/ZEB1 axis and represses CC tumor growth.
Comparative analysis of the complete mitochondrial genome sequences and anther development cytology between maintainer and Ogura-type cytoplasm male-sterile cabbage (B. oleracea Var. capitata)
Authors: Zhong Xionghui , Chen Denghui , Cui Jian , Li Hailong , Huang Yuxin , Kang Jungen
Published: September 2021

Background

Cytoplasmic male sterility (CMS) has been widely used for commercial F1 hybrid seeds production. CMS is primarily caused by chimeric genes in mitochondrial genomes. However, which specific stages of anther development in cabbage are affected by the chimeric genes remain unclear.

Results

In the present study, the complete mitochondrial genomes were sequenced and assembled for the maintainer and Ogura CMS cabbage lines. The genome size of the maintainer and Ogura CMS cabbage are 219,962 bp and 236,648 bp, respectively. There are 67 and 69 unknown function ORFs identified in the maintainer and Ogura CMS cabbage mitochondrial genomes, respectively. Four orfs, orf102a, orf122b, orf138a and orf154a were specifically identified in the Ogura CMS mitochondrial genome, which were likely generated by recombination with Ogura type radish during breeding process. Among them, ORF138a and ORF154a possessed a transmembrane structure, and orf138a was co-transcribed with the atp8 and trnfM genes. orf154a is partially homologous to the ATP synthase subunit 1 (atpA) gene. Both these genes were likely responsible for the CMS phenotype. In addition, cytological sections showed that the abnormal proliferation of tapetal cells might be the immediate cause of cytoplasmic male-sterility in Ogura CMS cabbage lines. RNA-seq results showed that orf138a and orf154a in Ogura CMS might influence transcript levels of genes in energy metabolic pathways.

Conclusions

The presence of orf138a and orf154a lead to increased of ATPase activity and ATP content by affecting the transcript levels of genes in energy metabolic pathways, which could provide more energy for the abnormal proliferation of tapetal cells. Our data provides new insights into cytoplasmic male-sterility from whole mitochondrial genomes, cytology of anther development and transcriptome data.
A tetraploidization event shaped the Aquilaria sinensis genome and contributed to the ability of sesquiterpenes synthesis
Authors: Meng Fanbo , Chu Tianzhe , Tang Qiang , Chen Wei
Published: September 2021

Background

Agarwood, generated from the Aquilaria sinensis, has high economic and medicinal value. Although its genome has been sequenced, the ploidy of A. sinensis paleopolyploid remains unclear. Moreover, the expression changes of genes associated with agarwood formation were not analyzed either.

Results

In the present work, we reanalyzed the genome of A. sinensis and found that it experienced a recent tetraploidization event ~ 63–71 million years ago (Mya). The results also demonstrated that the A. sinensis genome had suffered extensive gene deletion or relocation after the tetraploidization event, and exhibited accelerated evolutionary rates. At the same time, an alignment of homologous genes related to different events of polyploidization and speciation were generated as well, which provides an important comparative genomics resource for Thymelaeaceae and related families. Interestingly, the expression changes of genes related to sesquiterpene synthesis in wounded stems of A. sinensis were also observed. Further analysis demonstrated that polyploidization promotes the functional differentiation of the key genes in the sesquiterpene synthesis pathway.

Conclusions

By reanalyzing its genome, we found that the tetraploidization event shaped the A. sinensis genome and contributed to the ability of sesquiterpenes synthesis. We hope that these results will facilitate our understanding of the evolution of A. sinensis and the function of genes involved in agarwood formation.
Case report: Spinal anesthesia for cesarean section in a parturient with Potocki-Lupski syndrome
Authors: Li Junfeng , Bao Jie , Zhang Di , Zhou Shuzhen
Published: September 2021

Background

Potocki -Lupski syndrome is an uncommon disorder caused by a micro-duplication in chromosome 17p11.2. Variable clinical manifestations bring troubles to the general and neuraxial anesthesia, including mental retardation, facial dysmorphisms, structural cardiovascular anomalies, scoliosis, and malignant hyperthermia. Until now, the anesthesia management for cesarean section in these patients has not been reported yet.

Case presentation

Here we present a 23-year-old Chinese parturient with Potocki -Lupski syndrome who underwent elective cesarean section under spinal anesthesia. She was transferred to our hospital in her 40th week of gestation. She had a history of IgA nephropathy for more than three years and was diagnosed with Potocki -Lupski syndrome (17p12p11.2 segment 3.1 Mb repeat) in the 29th week of pregnancy. Amniocentesis showed the fetus had no abnormal autosomes. Preoperative multidisciplinary consultation suggested that she should terminate the pregnancy as soon as possible. She was ASA II. Her BMI was 26.43 kg/m2. Her airway evaluation was normal. Her spine could bend well and her spinal interspace could be touched clearly. We did the single spinal anesthesia at L2-3 interspace and gave 0.5% bupivacaine 1.7 ml. The absolute anesthesia level reached T8. The Apgar score for the newborn infant was 10 for 1st minute, 5th minute, and 10th minute. The vital signs were steady without using any vasoactive drugs. The patient had a good prognosis, and was subsequently discharged from hospital.

Conclusion

To date, the case may be the first reported spinal anesthesia for the parturient with Potocki -Lupski syndrome. Although its manifestations are variable, the spinal anesthesia is feasible under careful and comprehensive preoperative evaluation.
Small bowel hemorrhage from check point inhibitor enteritis: a case report
Authors: Young Kellie , Lin Emery , Chen Emerson , Brinkerhoff Brian , Scott Gregory , Yu Jessica
Published: September 2021

Background

There is rising utilization of immune checkpoint inhibitors (ICI) for a growing number of metastatic malignancies. While gastrointestinal side effects of ICI are common, isolated ICI-induced enteritis leading to small bowel hemorrhage is rare.

Case presentation

A 71-year-old man with a previously resected right colon adenocarcinoma on atezolizumab and recently treated Clostridioides difficile presented with acute on chronic abdominal pain and non-bloody diarrhea. A CT scan revealed enteritis of the duodenum and jejunum without colitis. Initial endoscopic work-up revealed many clean-based non-bleeding duodenal ulcers to the third portion of the duodenum and normal rectosigmoid mucosa. The patient initially improved on steroids but was readmitted on day after discharge with hematochezia and hemorrhagic shock. Repeat CT showed improvement in enteritis; however, repeat push enteroscopy revealed multiple duodenal and jejunal ulcers, two with visible vessels requiring endoscopic intervention. He continued to have significant hemorrhage requiring transfusions despite IV methylprednisolone. Conventional angiogram revealed multiple sites of active extravasation, and he underwent small bowel resection and subsequent IR embolization due to persistent bleeding. He was then started on infliximab 10 mg/kg with resolution of his small bowel hemorrhage and diarrhea.

Conclusions

Severe isolated ICI-enteritis is rare and can lead to clinically significant gastrointestinal hemorrhage. Patients with severe ICI-enteritis on endoscopy should be carefully monitored for steroid refractory disease for consideration of step-up therapy such as infliximab.
Association of elevated serum aminotransferase levels with chronic kidney disease measures: hispanic community health study/study of latinos
Authors: Missikpode Celestin , Kramer Holly , Cotler Scott J. , Durazo-Arvizu Ramon , Lash James P. , Kallwitz Eric , Cai Jianwen , Kuniholm Mark H. , Rosas Sylvia E. , Ricardo Ana C. , Talavera Gregory A. , Raij Leopoldo , Pirzada Amber , Daviglus Martha L.
Published: September 2021

Background

Previous studies have shown an association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), but it is unclear whether the association is independent of metabolic syndrome.

Methods

Data from 13,006 participants aged 18 to 74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) without viral hepatitis, excessive alcohol consumption, or high transferrin saturation levels were analyzed. Suspected NAFLD was defined as presence of sex-specific elevations in serum aminotransferase levels (aspartate aminotransferase (AST) > 37 U/L or alanine aminotransferase (ALT) > 40 U/L for men and AST or ALT > 31 U/L for women). Logistic regression was used to examine cross-sectional associations of elevated serum aminotransferase levels with low estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2 based on cystatin C), and with high urinary albumin-to-creatinine ratio (UACR) (> 17 mg/g in men and > 25 mg/ g in women) in separate models adjusting for demographic characteristics and metabolic syndrome.

Results

Mean (SD) age was 41 (0.27) years, and 45 % were male. Elevated serum aminotransferase levels were noted in 18.8 % of the population and were associated with greater odds of high UACR (OR = 1.31; 95 % CI = 1.10, 1.56) after adjusting for demographic characteristics; this association became non-significant after adjustment for metabolic syndrome (OR = 1.11, 95 % CI = 0.92, 1.33). In contrast, elevated serum aminotransferase levels were not associated with low eGFR (odds ratio (OR) = 0.73; 95 % confidence interval (CI) = 0.45, 1.18) after adjusting for covariates.

Conclusions

In this sample of diverse U.S. Hispanic Latino adults, elevated serum aminotransferase levels were not independently associated with measures of CKD.
Association between serum NLRP3 and malignant brain edema in patients with acute ischemic stroke
Authors: Wang Yanan , Huang Hexiao , He Weihong , Zhang Shihong , Liu Ming , Wu Simiao
Published: September 2021

Background

We aimed to explore the association of serum level of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and its related inflammatory biomarkers (hypoxia inducible factor-1α, cathepsin B, caspase-1 and matrix metalloproteinase-9) with malignant brain edema (MBE) in patients with acute ischemic stroke.

Methods

We prospectively enrolled patients with acute ischemic stroke admitted < 24 h from onset of symptoms. Brain CT was performed on admission and blood samples were collected. Repeated brain CT/MRI was performed < 7 days of admission to identify the presence of MBE, defined as neurological deterioration with imaging signs of midline shift or compressed basal cisterns. Logistic regression analysis was performed to assess the association between inflammatory biomarkers and MBE, adjusted for age and National Institutes of Health Stroke Scale (NIHSS).

Results

200 patients (69.3 ± 14.3 years; male 55 %) were included for analysis, of whom 26 patients developed MBE (median time from stroke onset to MBE 32.5 h). Compared with patients without MBE, those with MBE had higher level of serum concentration of NLRP3 (median time from onset to blood collection 3 h, 1.85 ng/ml vs. 1.11 ng/ml, P = 0.026). NLRP3 level was positively correlated with NIHSS on admission (Spearman ρ = 0.18, P = 0.01) and the association between NLRP3 and MBE was attenuated (OR 1.47, 95 % CI 0.88–2.46, P = 0.138) after adjusting for age and NIHSS. There was no significant difference in other biomarkers between MBE and non-MBE groups.

Conclusions

There was a trend of association between a higher level of serum concentration of NLRP3 and an increased risk of MBE after ischemic stroke, possibly confounded by the severity of stroke, which is worth further validation in large cohort studies.
Transcriptional analysis of the expression, prognostic value and immune infiltration activities of the COMMD protein family in hepatocellular carcinoma
Authors: Wang Xiaobo , He Shujiao , Zheng Xin , Huang Shanzhou , Chen Honghui , Chen Huadi , Luo Weixin , Guo Zhiyong , He Xiaoshun , Zhao Qiang
Published: September 2021

Background

The copper metabolism MURR1 domain (COMMD) protein family involved in tumor development and progression in several types of human cancer, but little is known about the function of COMMD proteins in hepatocellular carcinoma (HCC).

Methods

The ONCOMINE and the UALCAN databases were used to evaluate the expression of COMMD1–10 in HCC and the association of this family with individual cancer stage and tumor grade. Kaplan-Meier (K-M) Plotter and Cox analysis hint the prognostic value of COMMDs. A network comprising 50 most similar genes and COMMD1–10 was constructed with the STRING database. Gene set enrichment analysis (GSEA) was performed using LinkedOmics database. The correlations between COMMD expression and the presence of immune infiltrating cells were also analyzed by the tumor immune estimation resource (TIMER) database. GSE14520 dataset and 80 HCC patients were used to validated the expression and survival value of COMMD3. Human HCC cell lines were also used for validating the function of COMMD3.

Results

The expression of all COMMD family members showed higher expression in HCC tissues than that in normal tissues, and is associated with clinical cancer stage and pathological tumor grade. In HCC patients, the transcriptional levels of COMMD1/4 are positively correlated with overall survival (OS), while those of COMMD2/3/7/8/9 are negatively correlated with OS. Multivariate analysis indicated that a high level of COMMD3 mRNA is an independent prognostic factor for shorter OS in HCC patients. However, the subset of patients with grade 3 HCC, K-M survival curves revealed that high COMMD3/5/7/8/9 expression and low COMMD4/10 expression were associated with shorter OS. In addition, the expression of COMMD2/3/10 was associated with tumor-induced immune response activation and immune infiltration in HCC. The expression of COMMD3 from GSE14520 dataset and 80 patients are both higher in tumor than that in normal tissue, and a higher level of COMMD3 mRNA is associated with shorter OS. Knockdown of COMMD3 inhibits human HCC cell lines proliferation in vitro.

Conclusions

Our study indicates that COMMD3 is an independent prognostic biomarker for the survival of HCC patients. COMMD3 supports the proliferation of HCC cells and contributes to the poor OS in HCC patients.
Race disparities in mortality by breast cancer from 2000 to 2017 in São Paulo, Brazil: a population-based retrospective study
Authors: Marcelino Ana Cláudia , Gozzi Bruno , Cardoso-Filho Cássio , Machado Helymar , Zeferino Luiz Carlos , Vale Diama Bhadra
Published: September 2021

Background

In Brazil, inequalities in access may interfere with cancer care. This study aimed to evaluate the influence of race on breast cancer mortality in the state of São Paulo, from 2000 to 2017, contextualizing with other causes of death.

Methods

A population-based retrospective study using mortality rates, age and race as variables. Information on deaths was collected from the Ministry of Health Information System. Only white and black categories were used. Mortality rates were age-adjusted by the standard method. For statistical analysis, linear regression was carried out.

Results

There were 60,940 deaths registered as breast cancer deaths, 46,365 in white and 10,588 in black women. The mortality rates for 100,000 women in 2017 were 16.46 in white and 9.57 in black women, a trend to reduction in white (p = 0.002), and to increase in black women (p = 0.010). This effect was more significant for white women (p < 0.001). The trend to reduction was consistent in all age groups in white women, and the trend to increase was observed only in the 40–49 years group in black women. For ‘all-cancer causes’, the trend was to a reduction in white (p = 0.031) and to increase in black women (p < 0.001). For ‘ill-defined causes’ and ‘external causes’, the trend was to reduce both races (p < 0.001).

Conclusion

The declared race influenced mortality rates due to breast cancer in São Paulo. The divergences observed between white and black women also were evident in all cancer causes of death, which may indicate inequities in access to highly complex health care in our setting.
Saving babies’ lives (SBL) – a programme to reduce neonatal mortality in rural Cambodia: study protocol for a stepped-wedge cluster-randomised trial
Authors: Patel Kaajal , Say Sopheakneary , Leng Daly , Prak Manila , Lo Koung , Mukaka Mavuto , Riedel Arthur , Turner Claudia
Published: September 2021

Background

Neonatal mortality remains unacceptably high. Many studies successful at reducing neonatal mortality have failed to realise similar gains at scale. Effective implementation and scale-up of interventions designed to tackle neonatal mortality is a global health priority. Multifaceted programmes targeting the continuum of neonatal care, with sustainability and scalability built into the design, can provide practical insights to solve this challenge. Cambodia has amongst the highest neonatal mortality rates in South-East Asia, with rural areas particularly affected. The primary objective of this study is the design, implementation, and assessment of the Saving Babies’ Lives programme, a package of interventions designed to reduce neonatal mortality in rural Cambodia.

Methods

This study is a five-year stepped-wedge cluster-randomised trial conducted in a rural Cambodian province with an estimated annual delivery rate of 6615. The study is designed to implement and evaluate the Saving Babies’ Lives programme, which is the intervention. The Saving Babies’ Lives programme is an iterative package of neonatal interventions spanning the continuum of care and integrating into the existing health system. The Saving Babies’ Lives programme comprises two major components: participatory learning and action with community health workers, and capacity building of primary care facilities involving facility-based mentorship. Standard government service continues in control arms. Data collection covering the whole study area includes surveillance of all pregnancies, verbal and social autopsies, and quality of care surveys. Mixed methods data collection supports iteration of the complex intervention, and facilitates impact, outcome, process and economic evaluation.

Discussion

Our study uses a robust study design to evaluate and develop a holistic, innovative, contextually relevant and sustainable programme that can be scaled-up to reduce neonatal mortality.

Trial registration

ClinicalTrials.gov: NCT04663620. Registered on 11th December 2020, retrospectively registered.
Effects of the PRIMROSE prevention trial of childhood obesity on parental self-efficacy
Authors: Döring Nora , Ghaderi Ata , Enö Persson Johanna , Tynelius Per , Rasmussen Finn , Bohman Benjamin
Published: September 2021

Background

Parental self-efficacy (PSE) has been suggested as a key factor for enabling parents to support children in the development of healthy dietary and physical activity behaviors and to prevent childhood obesity. However, studies of intervention effects on PSE are lacking. The present study involved a secondary analysis of data on PSE collected in a previous primary prevention trial of childhood obesity called the PRIMROSE trial. The trial involved a family-based intervention using motivational interviewing and principles of cognitive-behavioral therapy within a social-cognitive theory framework.

Methods

In the PRIMROSE trial, parents and their children were randomly allocated to the intervention or usual care. In the present study, 928 mothers who responded to the Parental Self-Efficacy for Promoting Healthy Physical Activity and Dietary Behaviors in Children Scale (PSEPAD) at follow-up assessment were included. Data were analyzed using linear regression based on generalized estimating equations, with adjustment made for PSE at baseline.

Results

At follow-up assessment, there was a statistically significant difference of 1.4 units, 95% CI [0.4, 2.4], p = 0.009, between the intervention and control conditions on the subscale of the PSEPAD concerning PSE for promoting healthy dietary behaviors in children. However, this difference was deemed as without clinical importance. On the total scale or other subscales of the PSEPAD there were no statistically significant differences in PSE between conditions.

Conclusions

There was a statistically significant, but not clinically meaningful, intervention effect on PSE. However, because previous research repeatedly has shown positive associations of PSE with dietary and physical activity behaviors in children and that self-efficacy mediates behaviors, the construct may be important for influencing dietary and physical behaviors in children. Therefore, more research is warranted evaluating the effects of interventions on PSE in the context of childhood obesity prevention.

Trial registration

Retrospectively registered 9 October 2013 at ISRCTN (ISRCTN16991919).
Clinical profile of reading ability and reading and writing achievement of children with borderline full-scale intellectual quotient: a prospective study
Authors: Ueda Riyo , Kaga Yoshimi , Kita Yosuke , Nakagawa Eiji , Okada Takashi , Inagaki Masumi
Published: September 2021

Background

Poor reading ability is one of the common causes of low academic performance. In previous studies, children with dyslexia were found to demonstrate poor academic achievement due to poor reading ability. However, the relationship between academic achievement and reading ability in children with a borderline full-scale intellectual quotient (FSIQ) is unknown. This study aimed to clarify the clinical characteristics of children with borderline FSIQ and poor reading ability, and differentiate these characteristics from those of children with higher FSIQ and poor reading ability.

Methods

A total of 126 children (aged 6–15 years) identified as having low academic performance were enrolled. The reading ability of children was assessed through their performance on the hiragana (Japanese syllabary) reading task, while their reading and writing achievement was assessed through their reading and writing score on the Kaufman Assessment Battery for Children, Second Edition. Children were categorized into two groups based on their FSIQ score (FSIQ > 85 and 85 ≥ FSIQ ≥ 70). Reading ability in children was evaluated by referring to the linear relationship between FSIQ and the standard deviation value of reading tasks in typically developing children. A one-way analysis of variance (ANOVA) was performed to examine clinical characteristics between higher and lower FSIQ groups. Associations between reading and writing achievement, reading ability, and ages of children were assessed using Pearson’s product-moment correlation coefficients for the higher and lower FSIQ groups.

Results

Poorer reading and writing achievement was associated with poorer reading ability in the higher FSIQ group. Conversely, poorer reading and writing achievement and poor reading ability were associated with older age in the lower FSIQ group.

Conclusions

Poor reading and writing achievement were associated with older age, not with poor reading ability in the lower FSIQ group. Children with lower FSIQ need appropriate educational interventions based on independent assessments to further their academic achievement and reading ability. Moreover, they need more frequent evaluations of their academic achievement than do children with higher FSIQ and poor reading ability since they are more likely to be at a lower academic achievement level at an older age.
Aspects associated with waterpipe smoking in Iranian youths: a qualitative study
Authors: Jafaralilou Hamid , Latifi Arman , Khezeli Mehdi , Afshari Atefeh , Zare Farahnaz
Published: September 2021

Background

Waterpipe is one of the oldest methods of tobacco smoking, which has become the public health challenge, especially in the Eastern Mediterranean countries such as Iran. This study aimed to investigate the waterpipe smoking (WPS) in the young people of Kermanshah in 2020, using a qualitative method.

Methods

This was a qualitative study conducted with the approach of content analysis. Participants were young waterpipe user aged 17 to 25 years selected by purposeful sampling method in Kermanshah city, located in the west of Iran. Data were collected through semi-structured interviews in face-to-face and audio-recorded methods based on an interview guideline during June to August 2020. Then researchers transcribed verbatim and analyzed the content of the interviews thematically.

Results

In this study, 23 young people who were waterpipe users at the time of the study participated. The results showed that social aspects in three sub-categories were involved in WPS including “socio-cultural aspects”, “socio-environmental aspects”, and “social relations”. Individual aspects of waterpipe use as second category also consisted of two sub-categories including “motivational aspects” and “lack of psycho-protective aspects”.

Conclusions

It seems that the implementation of the policy of reducing access to waterpipe in public environments is effective in reducing waterpipe consumption. It is suggested that educational and interventions, based on targeted models and theories be implemented in order to increase young people’s belief and perception on dangers of WPS, and to improve their self-efficacy to smoking cessation.
Endovascular management of a large renal artery aneurysm: a case report and review of the literature
Authors: Zhu Alec , Connolly Peter , Hakimi A. Ari
Published: September 2021

Background

A renal artery aneurysm is a rare clinical presentation that can be found incidentally on imaging or during workup for refractory hypertension. Its presentation can be similar to that of a renal artery pseudoaneurysm, but the etiologies of the two vascular lesions differ. We present a patient who had an incidental finding of a large renal artery aneurysm that was managed with endovascular embolization. We also describe the literature surrounding the etiology, presentation and management of both renal artery aneurysms and renal artery pseudoaneurysms.

Case presentation

A 62-year-old man was referred to a urologic oncologist for workup of a newly found renal mass. Initial imaging with computed tomography showed a homogenous, well-circumscribed mass arising from the right kidney. Further evaluation with Doppler ultrasonography demonstrated pulsatile flow within the renal mass that was concerning for a renal artery pseudoaneurysm. The patient initially underwent a diagnostic angiogram by interventional radiology and was found to have a true renal artery aneurysm. Interventional radiology considered placement of a covered stent or angioembolization, but treatment was deferred due to concern for compromising the patient’s renal function. Patient was subsequently transferred to a neighboring hospital for management by vascular surgery. After considering both open surgical and endovascular approaches, the patient ultimately underwent angioembolization of the renal artery aneurysm. Short-term follow-up showed successful exclusion of the aneurysm with minimal adverse effects to the patient.

Conclusions

Our case report documents a unique case of an incidentally found large renal artery aneurysm that was successfully managed with endovascular embolization. Renal artery aneurysms and renal artery pseudoaneurysms, which can present similarly on imaging, are important diagnostic considerations in a patient presenting with a new renal mass. While open surgical approaches can be used to repair aneurysms, endovascular approaches using stenting or angioembolization are safe and effective options for treating renal aneurysms and renal pseudoaneurysms.
Intersectional social-economic inequalities in breast cancer screening in India: analysis of the National Family Health Survey
Authors: Negi Jyotsna , Nambiar Devaki
Published: September 2021

Background

Breast cancer incidence rates are increasing in developing countries including India. With 1.3 million new cases of cancer been diagnosed annually, breast cancer is the most common women’s cancer in India. India’s National Family Health Survey (NFHS-4) data 2015–2016 shows that only 9.8% of women between the ages of 15 and 49 had ever undergone breast examination (BE). Further, access to screening and treatment is unequally distributed, with inequalities by socio-economic status. It is unclear, however, if socio-economic inequalities in breast examination are similar across population subgroups.

Methods

We compared BE coverage in population sub-groups categorised by place of residence, religion, caste/tribal groups, education levels, age, marital status, and employment status in their intersection with economic status in India. We analysed data for 699,686 women aged 15–49 using the NFHS-4 data set conducted during 2015–2016. Descriptive (mean, standard errors, and confidence intervals) of women undergoing BE disaggregated by dimensions of inequality (education, caste/tribal groups, religion, place of residence) and their intersections with wealth were computed with national weights using STATA 12. Chi-square tests were performed to assess the association between socio-demographic factors and breast screening. Additionally, the World Health Organisation’s Health Equity Assessment Toolkit Plus was used to compute summary measures of inequality: Slope index for inequality (SII) and Relative Concentration Indices (RCI) for each intersecting dimension.

Results

BE coverage was concentrated among wealthier groups regardless of other intersecting population subgroups. Wealth-related inequalities in BE coverage were most pronounced among Christians (SII; 20.6, 95% CI: 18.5–22.7), married (SII; 14.1, 95% CI: 13.8–14.4), employed (SII: 14.6, 95%CI: 13.9, 15.3), and rural women (SII; 10.8, 95% CI: 10.5–11.1). Overall, relative summary measures (RCI) were consistent with our absolute summary measures (SII).

Conclusions

Breast examination coverage in India is concentrated among wealthier populations across population groups defined by place of residence, religion, age, employment, and marital status. Apart from this national analysis, subnational analyses may also help identify strategies for programme rollout and ensure equity in women’s cancer screening.
A novel delivery nanobiotechnology: engineered miR-181b exosomes improved osteointegration by regulating macrophage polarization
Authors: Liu Wei , Yu Muyu , Chen Feng , Wang Longqing , Ye Cheng , Chen Qing , Zhu Qi , Xie Dong , Shao Mingzhe , Yang Lili
Published: September 2021

Background

Many patients suffer from implant loosening after the implantation of titanium alloy caused by immune response to the foreign bodies and this could inhibit the following osteogenesis, which could possibly give rise to aseptic loosening and poor osteointegration while there is currently no appropriate solution in clinical practice. Exosome (Exo) carrying miRNA has been proven to be a suitable nanocarrier for solving this problem. In this study, we explored whether exosomes overexpressing miR-181b (Exo-181b) could exert beneficial effect on promoting M2 macrophage polarization, thus inhibiting inflammation as well as promoting osteogenesis and elaborated the underlying mechanism in vitro. Furthermore, we aimed to find whether Exo-181b could enhance osteointegration.

Results

In vitro, we firstly verified that Exo-181b significantly enhanced M2 polarization and inhibited inflammation by suppressing PRKCD and activating p-AKT. Then, in vivo, we verified that Exo-181b enhanced M2 polarization, reduced the inflammatory response and enhanced osteointegration. Also, we verified that the enhanced M2 polarization could indirectly promote the migration and osteogenic differentiation by secreting VEGF and BMP-2 in vitro.

Conclusions

Exo-181b could suppress inflammatory response by promoting M2 polarization via activating PRKCD/AKT signaling pathway, which further promoting osteogenesis in vitro and promote osteointegration in vivo.

Graphic abstract
MicroRNA-3935 promotes human trophoblast cell epithelial-mesenchymal transition through tumor necrosis factor receptor-associated factor 6/regulator of G protein signaling 2 axis
Authors: Jin Meiyuan , Xu Shouying , Li Jiayong , Yao Yingyu , Tang Chao
Published: September 2021

Background

Insufficient migration and invasion during trophoblast epithelial-mesenchymal transition (EMT) results in the occurrence and development of preeclampsia (PE), and our previous study has screened 52 miRNAs, whose expression levels are altered in the placental samples from PE patients, compared with the normal group. Among those, miR-3935 is one of the miRNAs being most significantly down-regulated, indicating its involvement in PE. However, the exact effect and molecular mechanisms remain unknown.

Methods

In the present study, we investigate the roles and underlying mechanisms of miR-3935 in trophoblast EMT by use of the human extra-villous trophoblast cell line HTR-8/SVneo as well as human placental tissues and maternal blood samples obtained from 15 women with normal pregnancies and 15 women with PE. Experimental methods include transfection, quantitative reverse transcription-PCR (qRT-PCR), western blot, immunofluorescence staining, dual-luciferase assays, in vitro invasion and migration assays, RNA-Seq analysis, bisulfite sequencing and immunohistochemistry staining.

Results

MiR-3935 expression is significantly decreased in both placentas and peripheral blood specimens of PE, and functionally, miR-3935 promotes EMT of trophoblast cells. Mechanistically, TRAF6 is identified to be a direct target of miR-3935 and TRAF6 exerts its negative effect on EMT of trophoblast cells by inhibition of RGS2, which down-regulates the methylation status of promoter ofCDH1gene that encodes E-Cadherin protein through induction of ALKBH1, resulting in increase of E-Cadherin and subsequently insufficient trophoblast EMT.

Conclusions

Together these results uncover a hitherto uncharacterized role of miR-3935/TRAF6/RGS2 axis in the function of human trophoblasts, which may pinpoint the molecular pathogenesis of PE and may be a prognostic biomarker and therapeutic target for such obstetrical diseases as PE.
Point-of-care detection and differentiation of anticoagulant therapy - development of thromboelastometry-guided decision-making support algorithms
Authors: Schäfer Simon T. , Otto Anne-Christine , Acevedo Alice-Christin , Görlinger Klaus , Massberg Steffen , Kammerer Tobias , Groene Philipp
Published: September 2021

Background

DOAC detection is challenging in emergency situations. Here, we demonstrated recently, that modified thromboelastometric tests can reliably detect and differentiate dabigatran and rivaroxaban. However, whether all DOACs can be detected and differentiated to other coagulopathies is unclear. Therefore, we now tested the hypothesis that a decision tree-based thromboelastometry algorithm enables detection and differentiation of all direct Xa-inhibitors (DXaIs), the direct thrombin inhibitor (DTI) dabigatran, as well as vitamin K antagonists (VKA) and dilutional coagulopathy (DIL) with high accuracy.

Methods

Following ethics committee approval (No 17–525-4), and registration by the German clinical trials database we conducted a prospective observational trial including 50 anticoagulated patients (n = 10 of either DOAC/VKA) and 20 healthy volunteers. Blood was drawn independent of last intake of coagulation inhibitor. Healthy volunteers served as controls and their blood was diluted to simulate a 50% dilution in vitro. Standard (extrinsic coagulation assay, fibrinogen assay, etc.) and modified thromboelastometric tests (ecarin assay and extrinsic coagulation assay with low tissue factor) were performed. Statistical analyzes included a decision tree analyzes, with depiction of accuracy, sensitivity and specificity, as well as receiver-operating-characteristics (ROC) curve analysis including optimal cut-off values (Youden-Index).

Results

First, standard thromboelastometric tests allow a good differentiation between DOACs and VKA, DIL and controls, however they fail to differentiate DXaIs, DTIs and VKAs reliably resulting in an overall accuracy of 78%. Second, adding modified thromboelastometric tests, 9/10 DTI and 28/30 DXaI patients were detected, resulting in an overall accuracy of 94%. Complex decision trees even increased overall accuracy to 98%. ROC curve analyses confirm the decision-tree-based results showing high sensitivity and specificity for detection and differentiation of DTI, DXaIs, VKA, DIL, and controls.

Conclusions

Decision tree-based machine-learning algorithms using standard and modified thromboelastometric tests allow reliable detection of DTI and DXaIs, and differentiation to VKA, DIL and controls.

Trial registration

Clinical trial number: German clinical trials database ID: DRKS00015704.
Sanziguben polysaccharides inhibit diabetic nephropathy through NF-κB-mediated anti-inflammation
Authors: Zhou Kang , Zhang Jianing , Liu Chang , Ou Lijuan , Wang Fan , Yu Yang , Wang Yumei , Bai Shasha
Published: September 2021

Background

Sanziguben polysaccharides (SZP) are large amounts of classical Chinese medicines from Sanziguben (SZGB). Moreover, SZGB is a widely applied compound prescription for diabetic nephropathy (DN) treatment, but the role is still unclear. This study initially explores the mechanism of SZP in the treatment of DN.

Methods

The high-fat diet plus streptozotocin injections were used to replicate the DN models in male C57BL/6 mice. DN mice were divided into five groups: DN mice, DN mice treated with SZP(1.01 or 2.02 g/kg), DN mice treated with SZGB decoction(4.7 g/kg), and DN mice treated with metformin (300 mg/kg). HG and LPS plus TNFα stimulated human tubule epithelial (HK-2) cells to establish an in vitro model and treated with SZP (100 or 200 μg/mL).

Results

SZP was found to comprise sugar, protein, and uronic acid. Furthermore, SZP alleviated the progression of inflammation in vivo and in vitro by inhibiting the expression of NF-κB.

Conclusions

NF-κB plays a critical role in the development of DN induced by STZ and HG. Furthermore, SZP can attenuate the NF-κB‐mediated progression of diabetic nephropathy, improve DN through anti-inflammation.
Comprehensive analysis of LASS6 expression and prognostic value in ovarian cancer
Authors: Xing Jinshan , Yi Jingyan
Published: September 2021

Background

Ceramide plays an important role in the occurrence and development of tumor. The synthesis of ceramide needs the participation of LASS. Current studies have shown that different LASS family members play different functions in tumors, especially LASS6, has been proved to play a key role in breast cancer, gastric cancer, melanoma and so on, but the research on ovarian cancer is very limited.

Methods

Bioinformatics web resources, including Oncomine, UALCAN, Kaplan–Meier Plotter and TIMER were used to analyze the expression profile, prognostic value and immune infiltration of LASS6. The related genes of LASS6 in ovarian cancer were mined by Regulome Explorer and LinkedOmics database, and cluster analysis was done by DAVID. The PPI network involving LASS6 was constructed by STRING database. Finally, the correlation between 10 genes and LASS6 was analyzed by GEPIA database, and their prognostic value in ovarian cancer was analyzed by Kaplan–Meier plotter.

Results

The expression of LASS6 was up-regulated in ovarian cancer, which was related to the progression and poor prognosis of ovarian cancer. Through GO/KEGG cluster analysis, we also found that LASS6 may affect calcium ion channel and its transport pathways. The analysis of regulatory network involved in LASS6 showed that the high mRNAs of 7 key genes were associated with poor prognosis of OS in patients with ovarian cancer, among which DEGS1 was the most significant.

Conclusions

LASS6 may play an important role in the regulation of calcium pathway and become a new therapeutic target and potential prognostic marker in ovarian cancer.
Gut microbiota regulation of P-glycoprotein in the intestinal epithelium in maintenance of homeostasis
Authors: Foley Sage E. , Tuohy Christine , Dunford Merran , Grey Michael J. , De Luca Heidi , Cawley Caitlin , Szabady Rose L. , Maldonado-Contreras Ana , Houghton Jean Marie , Ward Doyle V. , Mrsny Randall J. , McCormick Beth A.
Published: September 2021

Background

P-glycoprotein (P-gp) plays a critical role in protection of the intestinal epithelia by mediating efflux of drugs/xenobiotics from the intestinal mucosa into the gut lumen. Recent studies bring to light that P-gp also confers a critical link in communication between intestinal mucosal barrier function and the innate immune system. Yet, despite knowledge for over 10 years that P-gp plays a central role in gastrointestinal homeostasis, the precise molecular mechanism that controls its functional expression and regulation remains unclear. Here, we assessed how the intestinal microbiome drives P-gp expression and function.

Results

We have identified a “functional core” microbiome of the intestinal gut community, specifically genera within theClostridiaandBacilliclasses, that is necessary and sufficient for P-gp induction in the intestinal epithelium in mouse models. Metagenomic analysis of this core microbial community revealed that short-chain fatty acid and secondary bile acid production positively associate with P-gp expression. We have further shown these two classes of microbiota-derived metabolites synergistically upregulate P-gp expression and function in vitro and in vivo. Moreover, in patients suffering from ulcerative colitis (UC), we find diminished P-gp expression coupled to the reduction of epithelial-derived anti-inflammatory endocannabinoids and luminal content (e.g., microbes or their metabolites) with a reduced capability to induce P-gp expression.

Conclusion

Overall, by means of both in vitro and in vivo studies as well as human subject sample analysis, we identify a mechanistic link between cooperative functional outputs of the complex microbial community and modulation of P-gp, an epithelial component, that functions to suppress overactive inflammation to maintain intestinal homeostasis. Hence, our data support a new cross-talk paradigm in microbiome regulation of mucosal inflammation.
Testing angular velocity as a new metric for metabolic demands of slow-moving marine fauna: a case study with Giant spider conchs Lambis truncata
Authors: Hopkins Lloyd W. , Geraldi Nathan R. , Pope Edward C. , Holton Mark D. , Lurgi Miguel , Duarte Carlos M. , Wilson Rory P.
Published: September 2021

Background

Quantifying metabolic rate in free-living animals is invaluable in understanding the costs of behaviour and movement for individuals and communities. Dynamic body acceleration (DBA) metrics, such as vectoral DBA (VeDBA), are commonly used as proxies for the energy expenditure of movement but are of limited applicability for slow-moving species. It has recently been suggested that metrics based on angular velocity might be better suited to characterise their energetics. We investigated whether a novel metric—the ‘Rate of change of Rotational Movement (RocRM)’, calculated from the vectoral sum of change in the pitch, roll and yaw/heading axes over a given length of time, is a suitable proxy for energy expenditure.

Results

We found that RocRM can be used as an alternative energy expenditure proxy in a slow-moving benthic invertebrate. Eleven Giant spider conchs Lambis truncata (collected in the Red Sea) were instrumented with multiple channel (Daily Diary) tags and kept in sealed chambers for 5 h while their oxygen consumption, V̇O2, was measured. We found RocRM to be positively correlated with V̇O2, this relationship being affected by the time-step (i.e. the range of the calculated differential) of the RocRM. Time steps of 1, 5, 10 and 60 s yielded an explained variability of between 15 and 31%. The relationship between V̇O2 and VeDBA was not statistically significant, suggesting RocRM to provide more accurate estimations of metabolic rates in L. truncata.

Conclusions

RocRM proved to be a statistically significant predictor of V̇O2 where VeDBA did not, validating the approach of using angular-based metrics over dynamic movement-based ones for slower moving animals. Further work is required to validate the use of RocRM for other species, particularly in animals with minimally dynamic movement, to better understand energetic costs of whole ecosystems. Unexplained variability in the models might be a consequence of the methodology used, but also likely a result of conch activity that does not manifest in movement of the shell. Additionally, density plots of mean RocRM at each time-step suggest differences in movement scales, which may collectively be useful as a species fingerprint of movement going forward.
Differential roles of RIG-I like receptors in SARS-CoV-2 infection
Authors: Yang Duo-Meng , Geng Ting-Ting , Harrison Andrew G. , Wang Peng-Hua
Published: September 2021

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses. Herein we investigate their functions in human epithelial cells, the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A deficiency in MDA5, RIG-I or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication. The expression of the type I/III interferon (IFN) during infection was impaired in MDA5−/− and MAVS−/−, but not in RIG-I−/−, when compared to wild type (WT) cells. The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2), the cellular entry receptor for SARS-CoV-2, was ~ 2.5-fold higher in RIG-I−/− than WT cells. These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor, IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-I in epithelial cells.