bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of miR-29c promotes muscle wasting by modulating the activity of leukemia inhibitory factor in lung cancer cachexia
Authors: Xie Kairu , Xiong Hairong , Xiao Wen , Xiong Zhiyong , Hu Wenjun , Ye Jiaxin , Xu Ning , Shi Jian , Yuan Changfei , Chen Zhixian , Miao Daojia , Zhang Xiaoping , Yang Hongmei
Published: November 2021

Background

Cancer cachexia is a wasting disorder characterized by significant weight loss, and is attributed to skeletal muscle weakness. In the process of cancer development, microRNAs act as oncogenes or tumor suppressors. Moreover, they are implicated in muscle development and wasting. This study sought to explore the mechanisms and correlation between miR-29c and muscle wasting in lung cancer cachexia.

Methods

Data for expression analysis were retrieved from the Cancer Genome Atlas (TCGA) database. qRT-PCR analyses were performed to explore the expression levels of miR-29c and Leukemia Inhibitory Factor (LIF). Lewis lung carcinoma (LLC) cell line was used to establish a cachexia model to explore the functions of miR-29c and LIF in lung cancer cachexia. Furthermore, in vitro (in C2C12 myotubes) and in vivo (in LLC tumor-bearing mice) experiments were performed to explore the mechanisms of miR-29c and LIF in lung cachexia.

Results

Analysis of the lung cancer cachexia model showed that miR-29c was down-regulated, and its expression was negatively correlated with muscle catabolic activity. Overexpression of miR-29c mitigated the cachectic phenotype. Mechanistic studies showed that LIF was a direct target gene of miR-29c, and LIF was upregulated in vitro and in vivo. Analysis showed that LIF promoted muscle wasting through the JAK/STAT and MAP-kinase pathways.

Conclusions

The findings indicated that miR-29c was negatively correlated with the cachectic phenotype, and the miR-29c-LIF axis is a potential therapeutic target for cancer cachexia.
The circular RNA circSLC7A11 functions as a mir-330-3p sponge to accelerate hepatocellular carcinoma progression by regulating cyclin-dependent kinase 1 expression
Authors: Huang Yu , Ge Wenhao , Ding Yuan , Zhang Lufei , Zhou Jiarong , Kong Yang , Cui Bijun , Gao Bingqiang , Qian Xiaohui , Wang Weilin
Published: November 2021

Background

Circular RNAs (circRNAs), which are endogenous non-coding RNAs, are associated with various biological processes including development, homeostatic maintenance, and pathological responses. Accumulating evidence has implicated non-coding RNAs in cancer progression, and the role of circRNAs in particular has drawn wide attention. However, circRNA expression patterns and functions in hepatocellular carcinoma (HCC) remain poorly understood.

Methods

CircRNA sequencing was performed to screen differentially expressed circRNAs in HCC. Northern blotting, quantitative real-time polymerase chain reaction, nucleocytoplasmic fractionation, and fluorescence in situ hybridization analyses were conducted to evaluate the expression and localization of circSLC7A11 in HCC tissues and cells. CircSLC7A11 expression levels were modified in cultured HCC cell lines to explore the association between the expression of circSLC7A11 and the malignant behavior of these cells using several cell-based assays. The modified cells were implanted into immunocompetent nude mice to assess tumor growth and metastasis in vivo. We applied bioinformatics methods, RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays to explore the mechanisms of circSLC7A11 in HCC.

Results

CircSLC7A11 (hsa_circ_0070975) was conserved and dramatically overexpressed in HCC tissues and cells. HCC patients showing high circSLC7A11 expression had worse prognoses. Our in vitro and in vivo experiments showed that circSLC7A11 markedly accelerated HCC progression and metastasis through the circSLC7A11/miR-330-3p/CDK1 axis.

Conclusions

The acceleration of HCC progression and metastasis by circSLC7A11 through the circSLC7A11/miR-330-3p/CDK1 axis suggests that circSLC7A11 is a potential novel diagnostic and therapeutic target for HCC treatment.
Automated landmarking of bends in vascular structures: a comparative study with application to the internal carotid artery
Authors: Kjeldsberg Henrik A , Bergersen Aslak W , Valen-Sendstad Kristian
Published: November 2021

Automated tools for landmarking the internal carotid artery (ICA) bends have the potential for efficient and objective medical image-based morphometric analysis. The two existing algorithms rely on numerical approximations of curvature and torsion of the centerline. However, input parameters, original source code, comparability, and robustness of the algorithms remain unknown. To address the former two, we have re-implemented the algorithms, followed by sensitivity analyses. Of the input parameters, the centerline smoothing had the least impact resulting in 6–7 bends, which is anatomically realistic. In contrast, centerline resolution showed to completely over- and underestimated the number of bends varying from 3 to 33. Applying the algorithms to the same cohort revealed a variability that makes comparison of results between previous studies questionable. Assessment of robustness revealed how one algorithm is vulnerable to model smoothness and noise, but conceptually independent of application. In contrast, the other algorithm is robust and consistent, but with limited general applicability. In conclusion, both algorithms are equally valid albeit they produce vastly different results. We have provided a well-documented open-source implementation of the algorithms. Finally, we have successfully performed this study on the ICA, but application to other vascular regions should be performed with caution.
15-Lipoxygenase and its metabolites in the pathogenesis of breast cancer: A double-edged sword
Authors: Vaezi Mohammad Amin , Safizadeh Banafsheh , Eghtedari Amir Reza , Ghorbanhosseini Seyedeh Sara , Rastegar Mostafa , Salimi Vahid , Tavakoli-Yaraki Masoumeh
Published: November 2021

15-lipoxygenase is one of the key enzymes for the metabolism of unsaturated fatty acids that its manipulation has been proposed recently as a new molecular target for regulating cancer cell growth. Aberrant expression of 15-lipoxygenase enzyme seems to play an indicative role in the pathology of different cancer types, tumor progression, metastasis, or apoptosis. Based on the fact that breast cancer is one of the most common cancers that imposes a burden of mortality in women also, on the other hand, evidence in experimental models and human studies indicate the emerging role of the 15-lipoxygenase pathway in breast cancer pathogenesis, we present a review of recent findings related to the role of 15- lipoxygenase enzyme and metabolites in breast cancer growth, apoptosis, metastasis, and invasion as well as their local and circulating expression pattern in patients with breast cancer. Our review supports the emerging role of 15- lipoxygenase in molecular and cellular processes regulating breast tumor cell fate with both positive and negative effects.
Zinc oxide nanosphere for hydrogen sulfide scavenging and ferroptosis of colorectal cancer
Authors: Pan Xiang , Qi Yuchen , Du Zhen , He Jian , Yao Sheng , Lu Wei , Ding Kefeng , Zhou Min
Published: November 2021

Background

Colorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H2S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H2S and the regulation of the enzymes on the H2S pathways are of great significance for colorectal cancer therapy.

Methods

Here, we investigated the H2S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H2S in colorectal cancer. Accordingly, we developed an H2S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer.

Results

Owing to its excellent H2S scavenging ability, VZnO could effectively reduce H2S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H2S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H2S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H2S rich cancers, such as the 4T1 breast cancer model.

Conclusions

We anticipate that the H2S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise.

Graphic abstract
Bone morphogenetic protein 2 inhibits growth differentiation factor 8-induced cell signaling via upregulation of gremlin2 expression in human granulosa-lutein cells
Authors: Luo Xiaoyan , Chang Hsun-Ming , Yi Yuyin , Sun Yingpu , Leung Peter C. K.
Published: November 2021

Background

Bone morphogenetic protein 2 (BMP2), growth differentiation factor 8 (GDF8) and their functional receptors are expressed in human ovarian follicles, and these two intrafollicular factors play essential roles in regulating follicle development and luteal function. As BMP antagonists, gremlin1 (GREM1) and gremlin2 (GREM2) suppress BMP signaling through blockage of ligand-receptor binding. However, whether BMP2 regulates the expression of GREM1 and GREM2 in follicular development remains to be determined.

Methods

In the present study, we investigated the effect of BMP2 on the expression of GREM1 and GREM2 and the underlying mechanisms in human granulosa-lutein (hGL) cells. An established immortalized human granulosa cell line (SVOG) and primary hGL cells were used as study models. The expression of GREM1 and GREM2 were examined following cell incubation with BMP2 at different concentrations and time courses. The TGF-β type I inhibitors (dorsomorphin, DMH-1 and SB431542) and small interfering RNAs targeting ALK2, ALK3, SMAD2/3, SMAD1/5/8 and SMAD4 were used to investigate the involvement of the SMAD-dependent pathway.

Results

Our results showed that BMP2 significantly increased the expression of GREM2 (but not GREM1) in a dose- and time-dependent manner. Using a dual inhibition approach combining kinase inhibitors and siRNA-mediated knockdown, we found that the BMP2-induced upregulation of GREM2 expression was mediated by the ALK2/3-SMAD1/5-SMAD4 signaling pathway. Moreover, we demonstrated that BMP2 pretreatment significantly attenuated the GDF8-induced phosphorylation of SMAD2 and SMAD3, and this suppressive effect was reversed by knocking down GREM2 expression.

Conclusions

Our findings provide new insight into the molecular mechanisms by which BMP2 modulates the cellular activity induced by GDF8 through the upregulated expression of their antagonist (GREM2).
A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer
Authors: Naderi Elnaz , Crijns Anne Petra Gerarda , Steenbakkers Roel Johannes Henricus Marinus , van den Hoek Johanna Geertruida Maria , Boezen Hendrika Marike , Alizadeh Behrooz Ziad , Langendijk Johannes Albertus
Published: November 2021

Background

Most head and neck cancer (HNC) patients receive radiotherapy (RT) and develop toxicities. This genome-wide association study (GWAS) was designed to identify single nucleotide polymorphisms (SNPs) associated with common acute radiation-induced toxicities (RITs) in an HNC cohort.

Methods

A two-stage GWAS was performed in 1279 HNC patients treated with RT and prospectively scored for mucositis, xerostomia, sticky saliva, and dysphagia. The area under the curve (AUC) was used to estimate the average load of toxicity during RT. At the discovery study, multivariate linear regression was used in 957 patients, and the top-ranking SNPs were tested in 322 independent replication cohort. Next, the discovery and the replication studies were meta-analyzed.

Results

A region on 5q21.3 containing 16 SNPs showed genome-wide (GW) significance association at P-value < 5.0 × 10–8 with patient-rated acute xerostomia in the discovery study. The top signal was rs35542 with an adjusted effect size of 0.17*A (95% CI 0.12 to 0.23; P-value <  = 3.78 × 10–9). The genome wide significant SNPs were located within three genes (EFNA5, FBXL17, and FER). In-silico functional analysis showed these genes may be involved in DNA damage response and co-expressed in minor salivary glands. We found 428 suggestive SNPs (P-value < 1.0 × 10–5) for other toxicities, taken to the replication study. Eleven of them showed a nominal association (P-value < 0.05).

Conclusions

This GWAS suggested novel SNPs for patient-rated acute xerostomia in HNC patients. If validated, these SNPs and their related functional pathways could lead to a predictive assay to identify sensitive patients to radiation, which may eventually allow a more individualized RT treatment.
A large National Institute for Health Research (NIHR) Biomedical Research Centre facilitates impactful cross-disciplinary and collaborative translational research publications and research collaboration networks: a bibliometric evaluation study
Authors: Kiparoglou Vasiliki , Brown Laurence A. , McShane Helen , Channon Keith M. , Shah Syed Ghulam Sarwar
Published: November 2021

Background

The evaluation of translational health research is important for various reasons such as the research impact assessment, research funding allocation, accountability, and strategic research policy formulation. The purpose of this study was to evaluate the research productivity, strength and diversity of research collaboration networks and impact of research supported by a large biomedical research centre in the United Kingdom (UK).

Methods

Bibliometric analysis of research publications by translational researchers affiliated with the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) from April 2012 to March 2017.

Results

Analysis included 2377 translational research publications that were published during the second 5-year funding period of the NIHR Oxford BRC. Author details were available for 99.75% of the publications with DOIs (2359 of 2365 with DOIs), and the number of authors per publication was median 9 (mean  = 18.03, SD  = 3.63, maximum  = 2467 authors). Author lists also contained many consortia, groups, committees, and teams (n  = 165 in total), with 1238 additional contributors, where membership was reported. The BRC co-authorship i.e., research collaboration network for these publications involved 20,229 nodes (authors, of which 1606 nodes had Oxford affiliations), and approximately 4.3 million edges (authorship linkages). Articles with a valid DOIs (2365 of 2377, 99.5%) were collectively cited more than 155,000 times and the average Field Citation Ratio was median 6.75 (geometric mean  = 7.12) while the average Relative Citation Ratio was median 1.50 (geometric mean  = 1.83) for the analysed publications.

Conclusions

The NIHR Oxford BRC generated substantial translational research publications and facilitated a huge collaborative network of translational researchers working in complex structures and consortia, which shows success across the whole of this BRC funding period. Further research involving continued uptake of unique persistent identifiers and the tracking of other research outputs such as clinical innovations and patents would allow a more detailed understanding of large research enterprises such as NIHR BRCs in the UK.
Contraceptive counselling experiences in Spain in the process of creating a web-based contraceptive decision support tool: a qualitative study
Authors: Reyes-Martí Laura , Rubio-Rico Lourdes , Ortega-Sanz Laura , Raigal-Aran Laia , de la Flor-López Miriam , Roca-Biosca Alba , Valls-Fonayet Francesc , Moharra-Francés Montse , Escuriet-Peiro Ramon , de Molina-Fernández María Inmaculada
Published: November 2021

Background

The choice of contraceptive method is a complex decision, and professionals should offer counselling based on the preferences, values and personal situation of the user(s). Some users are unsatisfied with the counselling received, which may, among other consequences, adversely affect method use adherence. In view of this situation, we propose exploring the experiences and needs of users and professionals for contraceptive counselling, in the context of creating a web-based contraceptive decision support tool.

Methods/design

Qualitative research was conducted through focus group discussions (64 users split into eight groups, and 19 professionals in two groups, in Tarragona, Spain) to explore the subjects’ experiences and needs. The data were categorized and the categories were defined and classified based on the three-step protocol or framework for Quality on Contraceptive Counseling (QCC), created by experts, which reviews the quality of interactions between user and professional during the counselling process.

Results

In counselling, users demand more information about the different methods, in an environment of erroneous knowledge and misinformation, which lead to false beliefs and myths in the population that are not contrasted by the professional in counselling. They complain that the method is imposed on them and that their views regarding the decision are not considered. Professionals are concerned that their lack of training leads to counselling directed towards the methods they know best. They acknowledge that a paternalistic paradigm persists in the healthcare they provide, and decision support tools may help to improve the situation.

Conclusions

Users feel unsatisfied and/or demand more information and a warmer, more caring approach. Professionals are reluctant to assume a process of shared decision-making. The use of a contraception DST website may solve some shortcomings in counselling detected in our environment.
Human rhinovirus serotypes induces different immune responses
Authors: Kim Ji Heui , Jang Jung Yeon , Jang Yong Ju
Published: November 2021

Background

Different species of human rhinovirus (HRV) can induce varied antiviral and inflammatory responses in human blood macrophages and lower airway epithelium. Although human nasal epithelial cells (HNECs) are a primary infection route of HRV, differences between major and minor groups of HRV in the upper airway epithelium have not been studied in detail. In this study, we investigated viral replications and immune responses of major and minor groups of HRV in the HNECs.

Methods

Viral replication, immune responses of IFN-β, IFN-λ, proinflammatory cytokines, and viral receptors, and mRNA expression of transcription factors of HRV16 (major group) and HRV1B (minor group) in the HNECs were assessed.

Results

Compared with HRV16, HRV1B replicated more actively without excessive cell death and produced higher IFN-β, IFN-λ1/3, CXCL10, IL-6, IL-8, and IL-18 levels. Furthermore, low-density lipoprotein receptor (LDLR), TLR3, MDA5, NF-κB, STAT1, and STAT2 mRNA levels increased in HRV1B-infected HNECs.

Conclusion

HRV1B induces a stronger antiviral and inflammatory response from cell entry to downstream signaling compared with HRV16.
Problem-based learning for in-service training on breastfeeding in Friuli Venezia Giulia, Italy
Authors: Pessa Valente Emanuelle , Cattaneo Adriano , Sola Maria Vittoria , Travan Laura , Quintero Romero Sofia , Milinco Mariarosa , Decorti Cinzia , Giornelli Roberta , Braida Cinzia , Dalmin Patrizia , Giangreco Manuela , Ronfani Luca ,   for the FVG Working Group for Instructional Design on Breastfeeding Training, Bomben Julia , Calligaris Maria Chiara , Casetta Giada , Causin Enrica , Crevatin Franca , Demitri Francesca , Marocco Sara , Nassimbeni Graziella , Piasentin Isa , Sola Maria Vittoria , Pigat Marta , Pittini Carla , Travan Laura
Published: November 2021

Background

Problem-Based Learning (PBL) is extensively used in pre- and post-graduate teaching programmes. However, it has been seldom used for in-service training and continuing medical education. We aimed to develop a PBL curriculum for a short in-service training on breastfeeding for maternal and child health professionals, and to assess the effect of these courses on their knowledge and skills. Also, the project aimed at increasing exclusive breastfeeding rates and duration in an Italian region.

Methods

After initial training on PBL and an assessment of the learning needs of about 400 health professionals, a small working group developed learning objectives, designed a curriculum, produced manuals, and shaped assessment tools for a new PBL course on breastfeeding. The field test of the new course allowed selection of the tutors for the scaling up of the training to the whole region. During this extension phase, participants were asked to complete an evaluation questionnaire. In addition, the health professionals who attended the PBL courses in 2019 were asked to complete an online survey to assess knowledge, attitudes and practices (KAP) just before, soon after the course, and 4–6 months later.

Results

The new 29 − hour PBL course, to be delivered in four days over four consecutive weeks, gives priority to tutorial groups and practical activities (71% of the total time). Supervised clinical practices absorb 16% of time. Ethics, communication and woman-centred clinical management content run throughout the four days and all activities. The three manuals, for tutors, participants and practical activities, facilitate the tasks and performance of tutors and participants. After the field test, 32 regional tutors ran courses for 562 health professionals. The analysis of the evaluation showed a high level of satisfaction for perceived effectiveness, relevance to practice, and educational quality. The KAP questionnaires indicated a general improvement after the course and retention after 4–6 months.

Conclusions

Despite some predictable shortcomings, this new PBL approach for short in-service training courses on breastfeeding showed encouraging results as far as participants’ satisfaction and KAP are concerned. The possible effects on rates and duration of exclusive breastfeeding need further research.
Risk of developing second malignant neoplasms in patients with neuroblastoma: a population study of the US SEER database
Authors: Zhen Hongnan , Guan Hui , Ma Jiabin , Wang Wenhui , Jing Shen , Miao Zheng , Zhang Fuquan , Liu Zhikai
Published: November 2021

Background

Neuroblastoma is a common extracranial malignant tumor in children. Its main treatment modality is a combination of chemotherapy, radiotherapy, and surgery. Given the advances in chemotherapy regimens and the widespread use of bone marrow transplantation over the decades, there has been improvement in treatment efficacy, which has led to prolonged patient survival. Accordingly, long-term complications have become a growing concern among physicians and patients. This study aimed to analyze the survival rate of patients with neuroblastoma and the risk factors for developing second malignant neoplasms (SMNs).

Methods

The SEER 18 Regs (1973–2015) and SEER 9 Regs (1973–2015) data of the surveillance, epidemiology, and end results (SEER) database of the US National Cancer Institute were adopted for survival and SMN analysis.

Results

The 5-, 10-, and 20-year overall survival rates of patients with neuroblastoma were 67%, 65%, and 62%, respectively. Among 38 patients with neuroblastoma who presented with SMNs, those with abdomen as the primary site accounted for the majority (63.2%), followed by those with thorax (26.3%) and other sites (10.5%). SMNs occurred more commonly in non-specific neuroblastoma (incidence: 0.87%) than ganglioneuroblastoma (incidence: 0.3%). Compared with the general population, the risk of SMN is significantly higher (SIR = 4.36). The risk of developing SMNs was significantly higher in the digestive system (SIR = 7.29), bones and joints (SIR = 12.91), urinary system (SIR = 23.48), brain and other nervous systems (SIR = 5.70), and endocrine system (SIR = 5.84). Multivariate analysis revealed that the year of diagnosis (OR = 2.138, 95% CI = 1.634–2.797, p < 0.001) was the only independent risk factor for developing SMNs.

Conclusion

This study identifies the risk factor for developing SMNs in patients with neuroblastoma, which could facilitate individualized screening for high-risk patients, to allow early diagnosis and treatment of SMNs.
Development of a prognostic model for 1-year survival after fragile hip fracture in Chinese
Authors: Fu Hairui , Liang Bin , Qin Wei , Qiao Xiaoxiong , Liu Qiang
Published: November 2021

Background

No prognostic model for the survival of fragile hip fracture has been developed for Asians. The goal of this study was to develop a simple and practical prognostic model to predict survival within 1 year after fragile hip fracture in Asians.

Methods

A single-center retrospective cohort study was designed. Under a multivariable Cox proportional hazards regression model, we used the preoperative characteristics of patients to predict survival within 1 year after hip fracture. We built a full model and then used the least absolute shrinkage and selection operator (LASSO) method to further shrink the model coefficients and achieved variable screening. Finally, we obtained a LASSO model. The model performance was evaluated with Nagelkerke’s R2 and the concordance (c) statistic. We assessed the internal validity with a bootstrapping procedure of 1 000 repetitions.

Results

A total of 735 eligible patients were admitted to our department for hip fracture from January 2015 to December 2020, but 11 (1.5%) patients were lost to follow-up. Among the remaining patients, 68 (9.3%) died within 1 year after hip fracture. We identified 12 candidate predictors from the preoperative characteristics of the patients. The last model contained nine predictors: surgery, age, albumin, sex, serum creatinine, malignancy, hypertension, ability to live independently, and cardiovascular and cerebrovascular diseases. Among them, surgery, age, and albumin are effective predictors of survival. The discrimination c statistic of the model is 0.814 (95% confidence interval 0.762–0.865); the corrected value through internal validation is 0.795.

Conclusions

This prognostic model can accurately predict a 1-year survival rate for patients with fragile hip fractures. This information can help clinicians develop a reasonable and personalized treatment plan.
The diagnostic value of D-dimer in acute aortic dissection: a meta-analysis
Authors: Yao Jian , Bai Tao , Yang Bo , Sun Lizhong
Published: November 2021

Objective

This study aims to evaluate the diagnostic value of D-dimer for acute aortic dissection (AAD) by the method of meta-analysis.

Methods

PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases from the establishment of the databases to December 2020 were systematically searched, and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) system was used to evaluate the quality of the literature. STATA 15.0 software was applied to calculate the pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (+LR), negative likelihood ratio (−LR) to draw summary receiver operating characteristics (SROC) curve and calculate the area under the curve (AUC). Meta-regression and subgroup analyses were used to explore the source of heterogeneity.

Results

A total of 16 clinical studies were enrolled in this study, including 1135 patients. The results of the meta-analysis showed that the pooled sensitivity was 0.96 (95% CI 0.91–0.98), the pooled specificity was 0.70 (95% CI 0.57–0.81), and the pooled DOR was 56.57 (95% CI 25.11–127.44), the pooled +LR was 3.25 (95% CI 2.18–4.85), the pooled −LR was 0.06 (95% CI 0.03–0.12), and the AUC was 0.94 (95% CI 0.91–0.95). Meta-regression and subgroup analysis results showed that publication year, sample size and cutoff value might be sources of heterogeneity. When the concentration of D-dimer was less than or equal to 500 ng/ml, the sensitivity significantly increased.

Conclusion

D-dimer has an excellent diagnostic value for AAD. It is a useful tool for detecting suspected AAD because of the excellent pooled sensitivity. D-dimer ≤ 500 ng/ml increases the potential to identify the suspected patients with AAD.
Integrated DIA proteomics and lipidomics analysis on non-small cell lung cancer patients with TCM syndromes
Authors: Cang Song , Liu Ran , Jin Wei , Tang Qi , Li Wanjun , Mu Kunqian , Jin Pengfei , Bi Kaishun , Li Qing
Published: November 2021

Background

Lung cancer remains the leading cause of mortality from malignant tumors, non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, and individualized diagnosis and treatment is an effective trend. The individual characteristics of different traditional Chinese medicine (TCM) syndromes of NSCLC patients may be revealed by highly specific molecular profiles.

Methods

In this study, 10 NSCLC patients with Qi deficiency and Yin deficiency (QDYD) syndrome and 10 patients with Qi deficiency of lung-spleen (QDLS) syndrome in TNM stage III-IV as well as 10 healthy volunteers were enrolled. Aiming at the varied syndromes of NSCLC patients with “Yin deficiency” as the main difference, a proteomics research based on data-independent acquisition (DIA) was developed. Of the dysregulated proteins in NSCLC patients, lipid metabolism was significantly enriched. Thereafter, nontargeted lipidomics research based on UPLC-Q-TOF/MS was performed in 16 patients, with 8 individuals randomly selected from each syndrome group. Furthermore, the considerably different characteristics between the syndromes and pathological mechanisms of NSCLC were screened by statistical and biological integrations of proteomics and lipidomics and the differential metabolic pathways of the two similar syndromes were further explored. Besides, lipids biomarkers were verified by a clinically used anticancer Chinese medicine, and the level of key differential proteins in the two syndromes was also validated using ELISA.

Results

The results showed that glycerophospholipid metabolism, sphingolipid metabolism, glycolipid metabolism, and primary bile acid biosynthesis were altered in NSCLC patients and that glycerophospholipid metabolism was significantly changed between the two syndromes in lipidomics analysis. Among the proteins and lipids, ALDOC and lysophosphatidylcholine (LPCs) were revealed to have a strong relationship by statistical and biological integration analysis, and could effectively distinguish QDLS and QDYD syndromes. Notably, the patients with different syndromes had the most typical metabolic patterns in glycerophospholipid metabolism and glycolysis, reflecting the differences in the syndromes dominated by “Yin deficiency”.

Conclusions

ALDOC and LPCs could be employed for the differentiation of NSCLC patients with QDLS and QDYD syndromes, and “Yin deficiency” might be associated with glycerophospholipid metabolism and glycolysis pathway. The results provided a theoretical basis for “Syndrome differentiation” in TCM diagnosis. Moreover, the developed integrated strategy could also provide a reference for individualized diagnosis and treatment of other diseases.
Quality of life and mental health of children with rare congenital surgical diseases and their parents during the COVID-19 pandemic
Authors: Fuerboeter Mareike , Boettcher Johannes , Barkmann Claus , Zapf Holger , Nazarian Rojin , Wiegand-Grefe Silke , Reinshagen Konrad , Boettcher Michael
Published: November 2021

Background

COVID-19 has affected our society at large, particularly vulnerable groups, such as children suffering from rare diseases and their parents. However, the psychosocial influences of COVID-19 on these have yet to be investigated. As such, the study’s goal was to evaluate the health-related quality of life (HRQoL), quality of life (QoL), and mental health of children with rare congenital surgical diseases and their parents during the COVID-19 pandemic and lockdown measures.

Methods

A survey of n = 210 parents of children with rare congenital surgical diseases and a control group of n = 88 parents of children without rare diseases was conducted cross-sectionally between April 2020 to April 2021. Data on HRQoL, QoL, and mental health was collected using standardized psychometric questionnaires for children and parents presenting to the pediatric surgery department at a university hospital.

Results

Mothers of children with rare pediatric surgical diseases showed significantly lower QoL and significantly higher impairment in mental health than a control group and norm data. For fathers, this was solely the case for their QoL. Children’s parent-reported HRQoL and mental health were partially impaired. Social and disease-specific risk factors of the respective outcomes in affected families were identified through regression analysis models.

Conclusion

Parents of children with rare diseases report severe psychosocial impairment regarding themselves and their children during the COVID-19 pandemic. Therefore, affected families should receive attention and supportive care in the form of a family-center approach to alleviate the additional burden of the COVID-19 pandemic.
Impact of parental divorce versus separation due to migration on mental health and self-injury of Chinese children: a cross sectional survey
Authors: Wang Feng , Lu Jingjing , Lin Leesa , Cai Jingjing , Xu Jiayao , Zhou Xudong
Published: November 2021

Background

There has been an increasing prevalence of parental separation in China due to divorce or migration for work in recent decades. However, few studies have compared the impacts of these two types of separation on children’s mental health. This study aimed to investigate how parental divorce and parental migration impact children’s mental health and self-injurious thoughts and behaviors (SITB), while considering positive factors, including parent-adolescent communication and psychological resilience.

Methods

We randomly recruited participants in grades 5–8 from 18 schools in 2 counties in Anhui Province. A self-administered questionnaire was conducted to measure children’s mental health, SITB, parent-adolescent communication, psychological resilience, and socio-demographic characteristics.

Results

Data from 1026 children with both parents migrating (BLBC), 1322 children with one parent migrating (SLBC), 475 children living in a divorced family (DC) and 1160 children with non-migrating parents (NLBC) were included. Regression model results showed that, compared to the other three groups (BLBC, SLBC, NLBC), DC exhibited higher internalizing problems (p < 0.05), higher externalizing problems (p < 0.01), less prosocial behaviors (p < 0.05), and higher rates of suicidal ideation (SI) (p < 0.05) and non-suicidal self-injury (NSSI) behaviors (p < 0.05) when adjusting for social-demographic variables. However, when further adjusting for parent-adolescent communication and psychological resilience, DC no longer had higher levels of internalizing problems, externalizing problems, NSSI and SI than left-behind groups (BLBC, SLBC).

Conclusions

The experience of separation from divorced parents had stronger negative effects on the mental health of children than was observed in LBC. The Chinese government should design special policy frameworks that provide support to DC.
Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report
Authors: Futagawa Mashu , Yamamoto Hideki , Kochi Mariko , Urakawa Yusaku , Sogawa Reimi , Kato Fumino , Okazawa-Sakai Mika , Ennishi Daisuke , Shinozaki Katsunori , Inoue Hirofumi , Yanai Hiroyuki , Hirasawa Akira
Published: November 2021

Background

RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development.

Case presentation

A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3′-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma.

Conclusions

We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.
A multicenter randomized placebo-controlled trial of intravenous thyroxine for heart-eligible brain-dead organ donors
Authors: Dhar Rajat , Klinkenberg Dean , Marklin Gary
Published: November 2021

Background

Brain death frequently induces hemodynamic instability and cardiac stunning. Impairments in cardiac performance are major contributors to hearts from otherwise eligible organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid-stimulating hormone) may contribute to hemodynamic instability, and replacement of thyroid hormone has been proposed as a means of improving stability and increasing hearts available for transplantation. Intravenous thyroxine is commonly used in donor management. However, small controlled trials have not been able to demonstrate efficacy.

Methods

This multicenter study will involve organ procurement organizations (OPOs) across the country. A total of 800 heart-eligible brain-dead organ donors who require vasopressor support will be randomly assigned to intravenous thyroxine for at least 12 h or saline placebo. The primary study hypotheses are that thyroxine treatment will result in a higher proportion of hearts transplanted and that these hearts will have non-inferior function to hearts not treated with thyroxine. Additional outcome measures are the time to achieve hemodynamic stability (weaning off vasopressors) and improvement in cardiac ejection fraction on echocardiography.

Discussion

This will be the largest randomized controlled study to evaluate the efficacy of thyroid hormone treatment in organ donor management. By collaborating across multiple OPOs, it will be able to enroll an adequate number of donors and be powered to definitively answer the critical question of whether intravenous thyroxine treatment increases hearts transplanted and/or provides hemodynamic benefits for donor management.

Trial registration

ClinicalTrials.govNCT04415658. Registered on June 4, 2020
Metacognitive therapy and work-focused interventions for patients on sick leave due to anxiety and depression: study protocol for a randomised controlled wait-list trial
Authors: Sandin Kenneth , Gjengedal Ragne G. H. , Osnes Kåre , Hannisdal Marit , Berge Torkil , Leversen Jonas S. R. , Røv Lars G. , Reme Silje Endresen , Lagerveld Suzanne , Blonk Roland , Nordahl Hans M. , Shields Gemma , Wells Adrian , Hjemdal Odin
Published: November 2021

Background

Common mental disorders such as depression and anxiety are major contributors to the global burden of disease. Affected individuals suffer reduced quality of life, impaired functioning and reduced capacity to work. Maintaining employment is an important determinant for health and wellbeing, and the economic impact of depression and anxiety is a significant societal expense. Treatments providing effective symptom reduction and helping patients return to work (RTW) would thus have substantial public health benefits. The present study will explore the effectiveness of metacognitive therapy (MCT) and work-focused interventions on reducing symptoms and increasing RTW rates for patients on sick leave due to depression and anxiety.

Methods

The study is a randomised controlled wait-list trial (RCT; N = 240). The intervention group will receive protocol-based MCT and work-focused interventions immediately after inclusion. The control condition is a wait-list control group. All patients will receive up to 12 weekly sessions. The study context is a Norwegian outpatient clinic part of a national programme aimed at reducing sick leave. The co-primary outcomes are change in RTW and symptoms of depression and anxiety at the end of treatment. In addition to self-report, sick leave will also be collected from national registries from 2 years prior to intervention to 4 years after intervention. Symptoms of depression and anxiety will be collected by self-report at pre- and post-treatment and at 6 and 12 months follow-up after treatment. A cost-effectiveness analysis will use total cost and quality-adjusted life-years as the secondary outcomes.

Discussion

There is broad consensus on the importance of identifying treatment that effectively reduces depression and anxiety symptoms and aids RTW. This study is an important contribution to the field as it is the first RCT on MCT and work-focused interventions for patients on sick leave due to anxiety and depression.

Trial registration

ClinicalTrials.gov NCT03301922. Registered on October 4, 2017.
Phylogenetic analysis of the Neotropical Albitarsis Complex based on mitogenome data
Authors: Bourke Brian P. , Justi Silvia A. , Caicedo-Quiroga Laura , Pecor David B. , Wilkerson Richard C. , Linton Yvonne-Marie
Published: November 2021

Background

Some of the most important malaria vectors in South America belong to the Albitarsis Complex (Culicidae; Anophelinae; Anopheles). Understanding the origin, nature, and geographical distribution of species diversity in this important complex has important implications for vector incrimination, control, and management, and for modelling future responses to climate change, deforestation, and human population expansion. This study attempts to further explore species diversity and evolutionary history in the Albitarsis Complex by undertaking a characterization and phylogenetic analysis of the mitogenome of all 10 putative taxa in the Albitarsis Complex.

Methods

Mitogenome assembly and annotation allowed for feature comparison among Albitarsis Complex and Anopheles species. Selection analysis was conducted across all 13 protein-coding genes. Maximum likelihood and Bayesian inference methods were used to construct gene and species trees, respectively. Bayesian methods were also used to jointly estimate species delimitation and species trees.

Results

Gene composition and order were conserved across species within the complex. Unique signatures of positive selection were detected in two species—Anopheles janconnae and An. albitarsis G—which may have played a role in the recent and rapid diversification of the complex. The COI gene phylogeny does not fully recover the mitogenome phylogeny, and a multispecies coalescent-based phylogeny shows that considerable uncertainty exists through much of the mitogenome species tree. The origin of divergence in the complex dates to the Pliocene/Pleistocene boundary, and divergence within the distinct northern South American clade is estimated at approximately 1 million years ago. Neither the phylogenetic trees nor the delimitation approach rejected the 10-species hypothesis, although the analyses could not exclude the possibility that four putative species with scant a priori support (An. albitarsis G, An. albitarsis H, An. albitarsis I, and An. albitarsis J), represent population-level, rather than species-level, splits.

Conclusion

The lack of resolution in much of the species tree and the limitations of the delimitation analysis warrant future studies on the complex using genome-wide data and the inclusion of additional specimens, particularly from two putative species, An. albitarsis I and An. albitarsis J.

Graphical Abstract
The interrelationship and accumulation of cardiometabolic risk factors amongst young adults in the United Arab Emirates: The UAE Healthy Future Study
Authors: Mezhal Fatima , Oulhaj Abderrahim , Abdulle Abdishakur , AlJunaibi Abdulla , Alnaeemi Abdulla , Ahmad Amar , Leinberger-Jabari Andrea , Al Dhaheri Ayesha S. , Tuzcu E. Murat , AlZaabi Eiman , Al-Maskari Fatma , Alanouti Fatme , Alameri Fayza , Alsafar Habiba , Alblooshi Hamad , Alkaabi Juma , Wareth Laila Abdel , Aljaber Mai , Kazim Marina , Weitzman Micheal , Al-Houqani Mohammad , Ali Mohammad Hag , Oumeziane Naima , El-Shahawy Omar , Al-Rifai Rami H. , Scherman Scott , Shah Syed M. , Loney Tom , Almahmeed Wael , Idaghdour Youssef , Ahmed Luai A. , Ali Raghib
Published: November 2021

Introduction

Similar to other non-communicable diseases (NCDs), people who develop cardiovascular disease (CVD) typically have more than one risk factor. The clustering of cardiovascular risk factors begins in youth, early adulthood, and middle age. The presence of multiple risk factors simultaneously has been shown to increase the risk for atherosclerosis development in young and middle-aged adults and risk of CVD in middle age.

Objective

This study aimed to address the interrelationship of CVD risk factors and their accumulation in a large sample of young adults in the United Arab Emirates (UAE).

Methods

Baseline data was drawn from the UAE Healthy Future Study (UAEHFS), a volunteer-based multicenter study that recruits Emirati nationals. Data of participants aged 18 to 40 years was used for cross-sectional analysis. Demographic and health information was collected through self-reported questionnaires. Anthropometric data and blood pressure were measured, and blood samples were collected.

Results

A total of 5126 participants were included in the analysis. Comorbidity analyses showed that dyslipidemia and obesity co-existed with other cardiometabolic risk factors (CRFs) more than 70% and 50% of the time, respectively. Multivariate logistic regression analysis of the risk factors with age and gender showed that all risk factors were highly associated with each other. The strongest relationship was found with obesity; it was associated with four-fold increase in the odds of having central obesity [adjusted OR 4.70 (95% CI (4.04–5.46)], and almost three-fold increase odds of having abnormal glycemic status [AOR 2.98 (95% (CI 2.49–3.55))], hypertension (AOR 3.03 (95% CI (2.61–3.52))] and dyslipidemia [AOR 2.71 (95% CI (2.32–3.15)]. Forty percent of the population accumulated more than 2 risk factors, and the burden increased with age.

Conclusion

In this young population, cardiometabolic risk factors are highly prevalent and are associated with each other, therefore creating a heavy burden of risk factors. This forecasts an increase in the burden of CVD in the UAE. The robust longitudinal design of the UAEHFS will enable researchers to understand how risk factors cluster before disease develops. This knowledge will offer a novel approach to design group-specific preventive measures for CVD development.