bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of multiple cytokines in aqueous humor of patients with idiopathic macular hole
Authors: Wang Heping , Li Yuqi , Han Song , Niu Tongtong
Published: January 2021

Background

Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. Thus far, there has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. To provide clarity regarding the treatment and prognosis of idiopathic macular holes, specifically regarding the levels of cytokines in affected patients, this study examined and analyzed multiple cytokine levels in aqueous humor from patients with idiopathic macular holes.

Methods

This comparative cross-sectional study included 38 patients in two groups: a cataract control group (n = 17) and an idiopathic macular hole group (n = 21). The levels of 48 cytokines in aqueous humor were detected by multiplex analysis with antibody-coupled magnetic beads. The Kolmogorov–Smirnov test was used to check whether the data were normally distributed; Student’s t-test and the Mann–Whitney U test were used to assess differences in cytokine levels between the two groups. Spearman correlation analysis was used to assess relationships among cytokine levels in the experimental group. Signaling pathways containing cytokines with significantly different expression in the experimental group were identified.

Results

There were significant differences in aqueous humor cytokine levels between patients with idiopathic macular holes and patients in the cataract control group. Notably, hepatocyte growth factor (p = 0.0001), GM-CSF (p = 0.0111), and IFN-γ (p = 0.0120) were significantly upregulated in the experimental group, while TNF-α (p = 0.0032), GRO-α (p < 0.0001), and MIF (p < 0.0001) were significantly downregulated in the experimental group. Furthermore, the GM-CSF level showed significant positive correlations with levels of IL-1 (r = 0.67904, p < 0.001), IL-4 (r = 0.76017, p < 0.001), and IFN-γ (r = 0.59922, p = 0.004097) in the experimental group. Moreover, the levels of nerve growth factor and hepatocyte growth factor showed a significant positive correlation (r = 0.64951, p = 0.001441) in the experimental group.

Conclusions

Patients with idiopathic macular holes showed significant variation in aqueous humor immune response after the onset of hole formation, including the recruitment of immune cells and regulation of cytokine expression. Our findings also suggest that it is not appropriate to use patients with macular holes as the control group in studies of aqueous humor cytokine levels in ophthalmic diseases.
Effectiveness of the Close Collaboration with Parents intervention on parent-infant closeness in NICU
Authors: He Felix B. , Axelin Anna , Ahlqvist-Björkroth Sari , Raiskila Simo , Löyttyniemi Eliisa , Lehtonen Liisa
Published: January 2021

Background

Parent-infant closeness during hospital care of newborns has many benefits for both infants and parents. We developed an educational intervention for neonatal staff, Close Collaboration with Parents, to increase parent-infant closeness during hospital care. The aim of this study was to evaluate the effectiveness of the intervention on parent-infant closeness in nine hospitals in Finland.

Methods

Parents of hospitalized infants were recruited in the hospitals during 3-month periods before and after the Close Collaboration with Parents intervention. The data were collected using daily Closeness diaries. Mothers and fathers separately filled in the time they spent in the hospital and the time of skin-to-skin contact with their infant during each hospital care day until discharge. Statistical analyses were done using a linear model with covariates.

Results

Diaries were kept before and after the intervention by a total of 170 and 129 mothers and 126 and 84 fathers, respectively. Either parent was present on average 453 min per day before the intervention and 620 min after the intervention in the neonatal unit. In the adjusted model, the increase was 99 min per day (p = 0.0007). The infants were in skin-to-skin contact on average 76 min per day before the intervention and 114 min after the intervention. In the adjusted model, skin-to-skin contact increased by 24 min per day (p = 0.0405).

Conclusion

The Close Collaboration with Parents intervention increased parents’ presence and skin-to-skin contact in nine hospitals. This study suggests that parent-infant closeness may be one mediating factor explaining benefits of parenting interventions.

Trial registration

ClinicalTrials.govNCT04635150. Retrospectively registered.
Initial engagement and persistence of health risk behaviors through adolescence: longitudinal findings from urban South Africa
Authors: Kowalski Alysse J. , Addo O. Yaw , Kramer Michael R. , Martorell Reynaldo , Norris Shane A. , Waford Rachel N. , Richter Linda M. , Stein Aryeh D.
Published: January 2021

Background

Little is known about longitudinal patterns of adolescent health risk behavior initial engagement and persistence in low- and middle-income countries.

Methods

Birth to Twenty Plus is a longitudinal birth cohort in Soweto-Johannesburg, South Africa. We used reports from Black African participants on cigarette smoking, alcohol, cannabis, illicit drug, and sexual activity initial engagement and adolescent pregnancy collected over 7 study visits between ages 11 and 18 y. We fit Kaplan-Meier curves to estimate behavior engagement or adolescent pregnancy, examined current behavior at age 18 y by age of first engagement, and performed a clustering analysis to identify patterns of initial engagement and their sociodemographic predictors.

Results

By age 13 y, cumulative incidence of smoking and alcohol engagement were each > 21%, while the cumulative incidence of other behaviors and adolescent pregnancy were < 5%. By age 18 y (15 y for cannabis), smoking, alcohol, and sexual activity engagement estimates were each > 65%, cannabis and illicit drug engagement were each > 16%; adolescent pregnancy was 31%. Rates of engagement were higher among males. Current risk behavior activity at age 18 y was generally unrelated to age of initial engagement. We identified three clusters reflecting low, moderate, and high-risk patterns of initial risk behavior engagement. One-third of males and 17% of females were assigned to the high-risk cluster. Sociodemographic factors were not associated with cluster membership.

Conclusions

Among urban dwelling Black South Africans, risk behavior engagement across adolescence was common and clustered into distinct patterns of initial engagement which were unrelated to the sociodemographic factors assessed. Patterns of initial risk behavior engagement may inform the timing of primary and secondary public health interventions and support integrated prevention efforts that consider multiple behaviors simultaneously.
Efficacy and safety of the syrup “KalobaTUSS®” as a treatment for cough in children: a randomized, double blind, placebo-controlled clinical trial
Authors: Carnevali Ilaria , La Paglia Rita , Pauletto Lara , Raso Floriana , Testa Marco , Mannucci Carmen , Sorbara Emanuela Elisa , Calapai Gioacchino
Published: January 2021

Background

Acute cough in children often causes discomfort to children and parents, reducing their quality of life. Despite the extensive utilization of over-the-counter remedies for cough, the efficacy of most of these treatments in children has not been confirmed.

Methods

We conducted a randomized, double blind, placebo-controlled clinical trial of 106 children with acute cough to evaluate the efficacy and safety of KalobaTUSS®, a paediatric cough syrup based on acacia honey and on Malva sylvestris extract, Inula helenium extract, Plantago major extract, and Helichrysum stoechas extract by using a validated 6 points Likert scale.

Results

Children were orally treated with KalobaTUSS® or placebo for 8 days. Children receiving KalobaTUSS® showed an early and significant reduction in night-time and day-time cough scores measured using a specific scale and a shorter duration of cough than children treated with the placebo.

Conclusions

KalobaTUSS® is well tolerated and produces positive effects by reducing the severity and shortening the duration of cough in children.

Trial registration

Clinicaltrials.gov no. NCT04073251. Retrospectively registered.
Self-reported interpersonal and educational/vocational difficulties in young adults with a history of transient psychotic experiences: findings from a population-based study
Authors: Coughlan Helen , Walton-Ball Erin , Carey Eleanor , Healy Colm , O’Regan-Murphy Grace , Uidhir Aoife Nic , Clarke Mary C. , Cannon Mary
Published: January 2021

Background

Psychotic experiences (PEs) are not uncommon in young people and are associated with both psychopathology and compromised global functioning. Although psychotic experiences are transient (short-lived, self-resolving and non-recurring) for most people who report them, few studies have examined the association between early transient PEs and later functioning in population samples. Additionally, studies using self-report measures of interpersonal and educational/ vocational difficulties are lacking. The aim of this study was to examine the relationship between transient psychotic experiences and self-reported interpersonal and educational/vocational difficulties in adolescence and young adulthood.

Methods

Participants were 103 young people from a longitudinal population-based study cohort of mental health in Ireland. They attended for baseline clinical interviews in childhood (age 11–13) and were followed up in young adulthood (age 19–25). Participants who reported psychotic experiences at baseline but not at follow-up were classified as having transient psychotic experiences. Data from both time-points were used to examine the association between transient psychotic experiences and self-reported interpersonal and educational/ vocational difficulties in young adulthood using poisson regression modelling.

Results

Young people with a history of transient psychotic experiences reported significantly higher interpersonal (adj IRR: 1.83, 95%ileCI: 1.10–3.02, p = .02) and educational/vocational (adj IRR: 2.28, 95%ileCI: 1.43–3.64, p = .001) difficulties during adolescence. However, no significant differences in interpersonal (adj IRR: 0.49, 95%ileCI: 0.10–2.30, p = .37) or educational/vocational (adj IRR: 0.88, 95%ileCI: 0.37–2.08, p = .77) difficulties were found in young adulthood. Self-reported interpersonal and educational/vocational difficulties in young people both with and without a history of transient psychotic experiences decreased between adolescence and young adulthood.

Conclusions

Young people with transient psychotic experiences have increased interpersonal and educational/vocational difficulties in adolescence but these may not persist into the young adult years. This finding indicates that early psychotic experiences may not confer high risk for long-term interpersonal or educational/vocational deficits among young people who experience these phenomena transiently.
Suicidality among gender minorities in Karnataka, South India
Authors: Halli Shiva S. , Isac Shajy , Bhattacharjee Parinita , Dutta Sumit , Ramesh B. M. , Lorway Robert , Blanchard James
Published: January 2021

Background

It is argued that Indian gender minorities displayed differential mental health problems and suicide attempts. Hence, the study was intended to understand the prevalence of anxiety, depression and suicidality among this group, specifically those living in a metropolitan city in South India.

Methods

The data was generated from a cross-sectional study that employed a structured questionnaire to collect information about experiences of anxiety, depression and suicidal behavior among gender-diverse individuals in Bangalore, the capital city of Karnataka state. The study used stratified simple random sampling of eligible individuals who were 18 years of age and older and who were enrolled in an HIV prevention program implemented for gender-diverse individuals run by the Karnataka Health Promotion Trust and the University of Manitoba at the time of the study (2012). Bivariate and multivariate analyses were used to assess the relative contribution of various factors that affect suicide ideation or actual attempts among the gender diverse participants.

Results

Results showed that 62% whose main source of income was Basti (socially sanctioned practice of begging), 52% of Hijras, 56% who lived with their Gurus, 58% who were not happy with their physical appearance, 55% who consumed alcohol daily, and 63% who experienced high depression had ever thought of or attempted suicide in the month prior to the survey. However, multivariate analysis showed that respondents who were not happy with their physical appearance and thought of changing it had significantly higher odds (AOR = 2.861; CI 1.468,5.576; p = 0.002) of either having thoughts that it was better being dead or wished they died. Similarly, those who experienced high depression, their odds of either having had thoughts of or having attempted suicide increased by three times (AOR = 3.997; CI 1.976, 8.071; p < 0.000).

Conclusions

It is observed that a high percentage of gender minorities had attempted suicide or thought of suicide during the month preceding the data collection. The findings bring new insights on the proximate determinant of physical appearance on the suicidality of gender minorities assigned male at birth and appropriate to account for this while addressing the mental health issues.
A randomized control trial to test a peer support group approach for reducing social isolation and depression among female Mexican immigrants
Authors: Page-Reeves Janet , Murray-Krezan Cristina , Regino Lidia , Perez Jackie , Bleecker Molly , Perez Daniel , Wagner Bill , Tigert Susan , Bearer Elaine L. , Willging Cathleen E.
Published: January 2021

Background

Female Mexican Immigrants (FMIs) experience high rates of depression compared with other populations. For this population, depression is often exacerbated by social isolation associated with the experience of immigration.

Aim 1. To measure whether a culturally situated peer group intervention will reduce depression and stress associated with the experience of immigration.

Aim 2. To test whether an intervention using a “women’s funds of knowledge” approach results in improved resilience, knowledge and empowerment.

Aim 3. To investigate whether a culturally situated peer group intervention using a women’s funds of knowledge approach can give participants a sense and experience of social and physical connection (“emplacement”) that is lost in the process of immigration.

Methods

This mixed-methods study will implement “Tertulias” (“conversational gatherings” in Spanish), a peer support group intervention designed to improve health outcomes for FMI participants in Albuquerque, New Mexico. We will document results of the intervention on our primary hypotheses of a decrease in depression, and increases in resilience and social support, as well as on our secondary hypotheses of decreased stress (including testing of hair cortisol as a biomarker for chronic stress), and an increase in social connectedness and positive assessment of knowledge and empowerment.

Discussion

This project will address mental health disparities in an underserved population that experiences high rates of social isolation. Successful completion of this project will demonstrate that health challenges that may appear too complex and too hard to address can be using a multi-level, holistic approach. Our use of hair samples to test for the 3-month average levels of systemic cortisol will contribute to the literature on an emerging biomarker for analyzing chronic stress.

Trial registration

This study was registered with ClinicalTrials.gov on 2/3/20, Identifier #NCT04254198.
Assessment of the design and implementation challenges of the National Health Insurance Scheme in Nigeria: a qualitative study among sub-national level actors, healthcare and insurance providers
Authors: Alawode Gbadegesin O. , Adewole David A.
Published: January 2021

Background

Health insurance is an important mechanism to prevent financial hardship in the process of accessing health care. Since the launch of Nigeria’s National Health Insurance Scheme (NHIS) in 2005, only 5% of Nigerians have health insurance and 70% still finance their healthcare through Out-Of-Pocket (OOP) expenditure. Understanding the contextualized perspectives of stakeholders involved in NHIS is critical to advancing and implementing necessary reforms for expanding health insurance coverage at national and sub-national levels in Nigeria. This study explored the perspectives of sub-national level actors/stakeholders on the design and implementation challenges of Nigeria’s NHIS.

Methods

A descriptive case study design was used in this research. Data were collected in Ibadan, Oyo State in 2016 from health insurance regulators, healthcare providers, and policymakers. Key informant interviews (KII) were conducted among purposively selected stakeholders to examine their perspectives on the design and implementation challenges of Nigeria’s National Health Insurance Scheme. Data were analysed using inductive and deductive thematic approaches with the aid of NVIVO software package version 11.

Results

Implementation challenges identified include abject poverty, low level of awareness, low interest (in the scheme), superstitious beliefs, inefficient mode of payment, drug stock-out, weak administrative and supervisory capacity. The scheme is believed to have provided more coverage for the formal sector, its voluntary nature and lack of legal framework at the subnational levels were seen as the overarching policy challenge. Only NHIS staff currently make required financial co-contribution into the scheme, as all other federal employees are been paid for by the (federal) government.

Conclusions

Sub-national governments should create legal frameworks establishing compulsory health insurance schemes at the subnational levels. Effective and efficient platforms to get the informal sector enrolled in the scheme is desirable. CBHI schemes and the currently approved state supported health insurance programmes may provide a more acceptable platform than NHIS especially among the rural informal sector. These other two should be promoted. Awareness and education should also be raised to enlighten citizens. Stakeholders need to address these gaps as well as poverty.
Antitumor effect and molecular mechanism of fucoidan in NSCLC
Authors: Chen Xiaohan , Sun Li , Wei Xiaojuan , Lu Haijun , Tan Ye , Sun Zhanyi , Jiang Jinju
Published: January 2021

Background

Fucoidan, a water-soluble polysaccharide, exerts anticoagulant and antiviral functions. It was recently reported that fucoidan also exerts an antitumor function. Lung cancer is one of the most common cancers in the world. The aim of this study was to investigate anti-tumor,apoptosis and anti-metastasis effects of fucoidan in both cell-based assays and mouse xenograft model, as well as to clarify possible role of m-TOR pathway in the protection.

Methods

In vitro: Different concentrations of fucoidan were given to act on non-small cell lung cancer (NSCLC) cell lines A549 and H1650. The effects of fucoidan on cell proliferation were observed by detecting cyclin expression levels, CCK8 and EDU experiments and cloning experiments. The apoptotic level was detected by flow cytometry and the apoptotic protein level was detected by Westernblot. By detecting the expression of adhesion molecules, the expression of matrix metalloproteinase (MMP) family, and Transwell cell invasion and migration experiment, the effect of fucoidan on cell adhesion, invasion and migration was observed. Meanwhile the effect of fucoidan on angiogenesis was observed by detecting the expression of vascular endothelial growth factor (VEGF).

In vivo experiment: An animal model of NSCLC cell mouse subcutaneous xenograft tumor was established to analyze the correlation between the consumption of fucoidan and the size and volume of xenograft tumor through gross observation. Through immunohistochemical staining and immunofluorescence double staining, ki67 and cell adhesion molecules (E-cadherin, N-cadherin and CD31) and VEGF-A in the tumor were detected, and the correlation between the amount of fucoidan and the above indexes was analyzed.

Results

Fucoidan inhibited the proliferation and angiogenesis of NSCLC cells via the mTOR pathway and promoted their apoptosis by increasing the Bax/Bcl-2 ratio. Not only that, fucoidan inhibited NSCLC cell invasion via epithelial–mesenchymal transformation (EMT). The mice fed fucoidan exhibited significant reductions in tumor volumes and weights. These indicators (Ki67, VEGF-A,N-cadherin) were decreased and E-cadherin expression was up-regulated in A549 mice that treated with fucoidan. The results showed that fucoidan inhibited tumor proliferation in vivo by affecting the expression of related proteins.

Conclusion

Fucoidan conveys antitumor effects and our results represent an ideal therapeutic agent for NSCLC.
Lactate as a metabolite from probiotic Lactobacilli mitigates ethanol-induced gastric mucosal injury: an in vivo study
Authors: Huang Yingpeng , Zhang Jiali , Dong Renjie , Ji Xiawei , Jiang Yusha , Cen Jianke , Bai Zhihuai , Hong Kairui , Li Huihui , Chen Jiajing , Zhou Jinhui , Qian Fanyu , Wang Fangyan , Qu Yue , Zhou Yan
Published: January 2021

Background

Pre-administration of probioticLactobacilliattenuates ethanol-induced gastric mucosal injury (GMI). The underpinning mechanisms remain to be elucidated. We speculated that lactate, the main metabolite ofLactobacillusthat can be safely used as a common food additive, mediated the gastroprotective effect. This study aimed to gain experimental evidence to support our hypothesis and to shed lights on its underlying mechanisms.

Methods

Lactate was orally administrated to mice at different doses 30 min prior to the induction of GMI. Gastric tissue samples were collected and underwent histopathological and immunohistochemical assessments, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction (qPCR) and western blot analyses.

Results

Pretreatment with lactate at 1–3 g/kg significantly curtailed the severity of ethanol-induced GMI, as shown by morphological and histopathological examinations of gastric tissue samples. Significantly lower level of cytokines indicative of local inflammation were found in mice receiving lactate treatment prior to ethanol administration. Western-blot, immunohistochemical analysis and qPCR suggested that gastroprotective properties of lactate were mediated by its modulatory effects on the expression of the apoptosis regulator geneBax, the apoptotic executive protein geneCasp3, and genes critical for gastric mucosal integrity, including those encoding tight junction proteins Occludin, Claudin-1, Claudin-5, and that for lactate receptor GPR81.

Conclusion

Lactate mitigates ethanol-induced GMI by curtailing local gastric inflammatory response, down-regulating the expression of the apoptosis regulator and executor genesBaxandCasp3, and up-regulating the expression of genes encoding tight junction proteins Occludin, Claudin-1, and Claudin-5 and the lactate receptor GPR81.
As a biomarker for gastric cancer, circPTPN22 regulates the progression of gastric cancer through the EMT pathway
Authors: Ma Shuo , Kong Shan , Gu Xinliang , Xu Yanhua , Tao Mei , Shen Lei , Shen Xianjuan , Ju Shaoqing
Published: January 2021

Background

Gastric cancer (GC) is one of the most common cancers in the world. Due to the lack of specific symptoms, more than 80% of patients are diagnosed as the advanced stage with a high mortality rate, so the early diagnosis of GC is incredibly essential. Circular RNAs (CircRNAs) are a kind of endogenous non-coding RNA with stable structure, the long half-life, and tumor specificity. It can be used as a diagnostic marker for tumors.

Method

Using circRNA sequencing technology screened three pairs of GC and adjacent tissues, and circRNAs with significant expression differences were screened out. The circular structure and characteristics of circPTPN22 were determined by RT-qPCR, agarose gel electrophoresis, Sanger sequencing, RNase R, and actinomycin D assays. Cell Counting Kit‐8, colony formation, Transwell, Wound healing, tumor formation in mice and western blotting assays were used to detect the effects of circPTPN22 on the proliferation, invasion, migration, tumor growth of GC cells in vitro and protein expression.

Result

CircPTPN22 is up-regulated and positively correlated with metastasis in GC tissues, cells, and plasma. RT-qPCR results showed that circPTPN22 had good diagnostic efficacy and could be used to predict the prognosis of GC patients. In vitro and vivo experiments showed that the downregulation of circPTPN22 could inhibit cell proliferation, migration, and invasion through the epithelial-mesenchymal transformation (EMT) pathway. CircPTPN22 may regulate GC progression through the competitive binding of miRNAs.

Conclusion

CircPTPN22 can be used as a potential diagnostic and prognostic marker for GC and can inhibit cell proliferation and metastasis through the competitive binding of miRNA to inhibit the EMT pathway.
Neural progenitor cell-derived nanovesicles promote hair follicle growth via miR-100
Authors: Cao Lei , Tian Tian , Huang Yuanbo , Tao Shiqin , Zhu Xiaohong , Yang Mifang , Gu Jing , Feng Guangdong , Ma Yinni , Xia Rushan , Xu Wenrong , Wang Lei
Published: January 2021

Background

Accumulating evidence shows that mesenchymal stem cell-derived extracellular vesicles (EVs) hold great promise to promote hair growth. However, large-scale production of EVs is still a challenge. Recently, exosome-mimetic nanovesicles (NV) prepared by extruding cells have emerged as an alternative strategy for clinical-scale production. Here, ReNcell VM (ReN) cells, a neural progenitor cell line was serially extruded to produce NV.

Results

ReN-NV were found to promote dermal papilla cell (DPC) proliferation. In addition, in a mouse model of depilation-induced hair regeneration, ReN-NV were injected subcutaneously, resulting in an acceleration of hair follicle (HF) cycling transition at the site. The underlying mechanism was indicated to be the activation of Wnt/β-catenin signaling pathway. Furthermore, miR-100 was revealed to be abundant in ReN-NV and significantly up-regulated in DPCs receiving ReN-NV treatment. miR-100 inhibition verified its important role in ReN-NV-induced β-catenin signaling activation.

Conclusion

These results provide an alternative agent to EVs and suggest a strategy for hair growth therapy.
High miR-324-5p expression predicts unfavorable prognosis of gastric cancer and facilitates tumor progression in tumor cells
Authors: Zheng Zhong , Li Jun , An Junyan , Feng Yikuan , Wang Lirong
Published: January 2021

Background

Gastric cancer (GCa) is one of the six major malignancies in the world with low survival rate. Although there are advances in therapeutic approaches, the prognosis of patients with GCa remains not optimistic. Therefore, this study aimed to evaluate the prognostic value of miR-324-5p, as well as its functional role in GCa progression.

Methods

The expression of miR-324-5p in tumor tissues and cell lines was examined using real-time quantitative PCR. The prognostic value of miR-324-5p in patients with GCa was evaluated by Kaplan-Meier survival curve and Cox regression analysis. Gain- and loss-of-function experiments were performed to evaluate the biological function of miR-324-5p during the progression of GCa, and a target gene of miR-324-5p was proposed.

Results

The expression of miR-324-5p was up-regulated in GCa tissues and cell lines. Patients with high expression of miR-324-5p had more cases with positive lymph node metastasis, advanced TNM stage, and worse overall survival compared with patients with low expression. The elevated miR-324-5p was an independent prognostic indicator of GCa. In addition, the inhibition of miR-324-5p could suppress GCa cell proliferation, migration and invasion and promote cell apoptosis, and PTEN was demonstrated to serve as a direct target of miR-324-5p in GCa progression.

Conclusion

The present study indicates that miR-324-5p overexpression predicts poor prognosis in GCa patients, and the reduction of miR-324-5p can inhibit GCa biological processes. PTEN is a target gene of GCa, which may mediate the biological function of miR-324-5p in GCa progression.
Microarray expression profile of mRNAs and long noncoding RNAs and the potential role of PFK-1 in infantile hemangioma
Authors: Yang Kaiying , Zhang Xuepeng , Chen Linwen , Chen Siyuan , Ji Yi
Published: January 2021

Background

Infantile hemangioma (IH) is the most common benign tumor in children. Long noncoding RNAs (lncRNAs) play a critical role in tumorigenesis. However, the expression levels and biological functions of lncRNAs in IH have not been well-studied. This study aimed to analyze the expression profile of lncRNAs and mRNAs in proliferating and involuting IHs.

Methods

The expression profiles of lncRNAs and mRNAs in proliferating and involuting IHs were identified by microarray analysis. Subsequently, detailed bioinformatics analyses were performed. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) analyses were conducted to validate the microarray results.

Results

In total, 146 differentially expressed (DE) lncRNAs and 374 DE mRNAs were identified. The DE mRNAs were enriched mostly in angiogenesis-related biological processes (BPs) and pathways by bioinformatics analysis. In addition, metabolism-related BPs (e.g., “glycogen biosynthetic process” and “metabolic process”) and pathways (e.g., “oxidative phosphorylation”) were identified. A lncRNA-mRNA co-expression network was constructed from 42 DE lncRNAs and 217 DE mRNAs. Twelve lncRNAs were predicted to have cis-regulated target genes. The microarray analysis results were validated by qRT-PCR using 5 randomly selected lncRNAs and 13 mRNAs. The IHC results revealed that both LOXL2 and FPK-1 exhibited higher protein expression levels in proliferating IH than in involuting IH. Moreover, inhibition of PFK-1 could suppress hemangioma-derived endothelial cell proliferation and migration, induce cell arrest, and reduce glucose uptake and lactate and ATP production.

Conclusions

The findings suggest that the identified DE lncRNAs and mRNAs may be associated with the pathogenesis of IH. The data presented herein can improve our understanding of IH development and provide direction for further studies investigating the mechanism underlying IH.
The reporting checklist for public versions of guidelines: RIGHT-PVG
Authors:   The RIGHT working group, Wang Xiaoqin , Chen Yaolong , Akl Elie A. , Tokalić Ružica , Marušić Ana , Qaseem Amir , Falck-Ytter Yngve , Lee Myeong Soo , Siedler Madelin , Barber Sarah L. , Zhang Mingming , Chan Edwin S. Y. , Estill Janne , Kwong Joey S. W. , Okumura Akiko , Zhou Qi , Yang Kehu , Norris Susan L.
Published: January 2021

Background

Public or patient versions of guidelines (PVGs) are derivative documents that “translate” recommendations and their rationale from clinical guidelines for health professionals into a more easily understandable and usable format for patients and the public. PVGs from different groups and organizations vary considerably in terms of quality of their reporting. In order to address this issue, we aimed to develop a reporting checklist for developers of PVGs and other potential users.

Methods

First, we collected a list of potential items through reviewing a sample of PVGs, existing guidance for developing and reporting PVGs or other similar evidence-based patient tools, as well as qualitative studies on original studies of patients’ needs about the content and/or reporting of information in PVGs or similar evidence-based patient tools. Second, we conducted a two-round Delphi consultation to determine the level of consensus on the items to be included in the final reporting checklist. Third, we invited two external reviewers to provide comments on the checklist.

Results

We generated the initial list of 45 reporting items based on a review of a sample of 30 PVGs, four PVG guidance documents, and 46 relevant studies. After the two-round Delphi consultation, we formed a checklist of 17 items grouped under 12 topics for reporting PVGs.

Conclusion

The RIGHT-PVG reporting checklist provides an international consensus on the important criteria for reporting PVGs.
Establishment and assessment of a nomogram for predicting blood transfusion risk in posterior lumbar spinal fusion
Authors: Wang Haosheng , Wang Kai , Lv Bin , Xu Haotian , Jiang Weibo , Zhao Jianwu , Kang Mingyang , Dong Rongpeng , Qu Yang
Published: January 2021

Background

The aim of this study was to determine the risk factors and develop a nomogram for blood transfusions after posterior lumbar spinal fusion (PSL).

Methods

We conducted a retrospective, single-center study based on 885 patients receiving PSL, and data was obtained from May 2015 to September 2019. Univariable and multivariable logistics regression analysis were conducted to identify risk factors for blood transfusion, and a nomogram was constructed to individually evaluate the risk of blood transfusion. Discrimination, calibration, and clinical usefulness were validated by the receiver operating characteristics (ROC), C-index, calibration plot, and decision curve analysis, respectively. Bootstrapping validation was performed to assess the performance of the model.

Results

Of 885 patients, 885 were enrolled in the final study population, and 289 received blood transfusion. Statistical analyses showed that low preoperative hemoglobin (Hb), longer time to surgery, operative time, levels of fusion > 1, longer surgery duration, and higher total intraoperative blood loss (IBL) were the risk factors for transfusion. The C-index was 0.898 (95% CI 0.847–0.949) in this dataset and 0.895 in bootstrapping validation, respectively. Calibration curve showed satisfied discrimination and calibration of the nomogram. Decision curve analysis (DCA) shown that the nomogram was clinical utility.

Conclusions

In summary, we investigated the relationship between the blood transfusion requirement and predictors: levels of fusion, operative time, time to surgery, total intraoperative EBL, and preoperative Hb level. Our nomogram with a robust performance in the assessment of risk of transfusion can contribute to clinicians in making clinical decision. However, external validation is still needed in the further.
miR-107 affects cartilage matrix degradation in the pathogenesis of knee osteoarthritis by regulating caspase-1
Authors: Qian Jiatian , Fu Peiliang , Li Shiao , Li Xiang , Chen Yancheng , Lin Zhenen
Published: January 2021

Background

Knee osteoarthritis (KOA) seriously affects the quality of life of KOA patients. This study aimed to investigate whether miR-107 could regulate KOA through pyroptosis to affect collagen protein secreted by chondrocytes through IL-1β.

Methods

The proliferation of chondrocytes was detected by CCK-8 assay. RT-qPCR analysis was used to identify miR-107 expression and transfection effects. The expression of Col II, IL-1β, IL-18, and MMP13 in supernatant of chondrocytes or chondrocytes was detected by ELISA assay and western blot analysis. The pyroptosis of chondrocytes was analyzed by TUNEL assay and the expression of pyroptosis-related proteins was analyzed by western blot. Luciferase reporter assay confirmed the relation of miR-107 to caspase-1.

Results

The proliferation of chondrocytes was decreased after LPS induction and further decreased by treatment of ATP. Single LPS treatment for chondrocytes downregulated the Col II expression while upregulated the expression of IL-1β, IL-18, and MMP-13, which was further changed by ATP treatment. miR-107 expression was decreased in chondrocytes induced by LPS and further decreased in chondrocytes induced by LPS and ATP. In addition, miR-107 overexpression increased the proliferation and decreased the pyroptosis of chondrocytes induced by LPS and ATP. miR-107 overexpression upregulated the Col II expression while down-regulated the expression of IL-1β, IL-18, and MMP-13 in supernatant of chondrocytes or chondrocytes induced by LPS and ATP. miR-107 overexpression down-regulated the expression of caspase-1, c-caspase-1, GSDMD-N, and TLR4 in chondrocytes induced by LPS and ATP. Furthermore, miR-107 directly targeted caspase-1.

Conclusions

miR-107 can protect against KOA by downregulating caspase-1 to decrease pyroptosis, thereby promoting collagen protein secreted by chondrocytes by down-regulating IL-1β.
A biomechanics study on ligamentous injury in anterior-posterior compression type II pelvic injury
Authors: Kong Jianzhong , Chu Yupeng , Zhou Chengwei , Sun Shuaibo , Bao Guodong , Xu Yu , Guo Xiaoshan , Shui Xiaolong
Published: January 2021

Background

Anterior-posterior compression (APC) type II pelvis fracture is caused by the destruction of pelvic ligaments. This study aims to explore ligaments injury in APC type II pelvic injury.

Method

Fourteen human cadaveric pelvis samples with sacrospinous ligament (SPL), sacrotuberous ligament (SBL), anterior sacroiliac ligament (ASL), and partial bone retaining unilaterally were acquired for this study. They were randomly divided into hemipelvis restricted and unrestricted groups. We recorded the separation distance of the pubic symphysis and anterior sacroiliac joint, external rotation angle, and force when ASL ruptured. We observed the external rotation damage to the pelvic bone and ligaments.

Result

When ASL failed, there was no significant difference in pubic symphysis separation (28.6 ± 8.4 mm to 23.6 ± 8.2 mm, P = 0.11) and anterior sacroiliac joint separation (11.4 ± 3.8 mm to 9.7 ± 3.9 mm, P = 0.30) between restricted and unrestricted groups. The external rotation angle (33.9 ± 5.5° to 48.9 ± 5.2°, P < 0.01) and force (553.9 ± 82.6 N to 756.6 ± 41.4 N, P < 0.01) were significantly different. Pubic symphysis separation between two groups ranged from 14 to 40 mm. In the restricted group, both SBL and SPL were injured. SPL ruptured first, and then SBL and the interosseous sacroiliac ligament were damaged while the posterior ligament remained unharmed. In the unrestricted group, interosseous sacroiliac ligament and posterior sacroiliac ligaments were damaged, while SBL and SPL were not. When the ASL, SBL, and SPL all failed, pubic symphysis and anterior sacroiliac joint separation between two groups increased significantly (from 28.6 ± 8.4 to 42.0 ± 7.6 mm, 11.4 ± 3.8 to 16.7 ± 4.2 mm respectively, all P < 0.05).

Conclusion

Pelvic external rotation injury is either hemipelvic restricted or unrestricted, which can result in different outcomes. When the ASL ruptures, the unrestricted group needs greater external rotation angle and force, without SBL or SPL injury, while both SBL and SPL were injured in another group. When ASL fails in two groups, pubic symphysis separation fluctuates considerably. Finally, when the ASL ruptures, SBL and SPL may be undamaged.
The patient journey toward a diagnosis of hereditary transthyretin (ATTRv) amyloidosis
Authors: Vera-Llonch Montserrat , Reddy Sheila R. , Chang Eunice , Tarbox Marian H. , Pollock Michael
Published: January 2021

Background

Despite emerging treatments for hereditary transthyretin (ATTRv) amyloidosis, the disease is often misdiagnosed, with reported diagnostic delays of up to several years. Knowledge of the patient journey leading up to diagnosis may help to promote earlier intervention. The study’s objective was to examine patient clinical characteristics and healthcare utilization prior to ATTRv amyloidosis diagnosis.

Methods

Patients ≥ 18 years and newly diagnosed with ATTRv amyloidosis identified in IBM® MarketScan® Commercial and Medicare Supplemental data using a claims-based algorithm as follows: diagnosis required ≥ 1 medical claim with relevant amyloidosis diagnosis code (ICD-10-CM: E85.0-.4, E85.89, E85.9; excludes light chain and wild type) during identification (ID) period (1/1/2016–12/31/2017), and ≥ 1 occurrence of qualifying criteria during 2011–2017: ≥ 15 days diflunisal use without > 30-day gap, liver transplant, or claim with specific codes E85.1 or E85.2. The index date was defined as the date of first claim with amyloidosis diagnosis code in ID period. Patients had continuous enrollment ≥ 5 years pre-index date (look-back period). Occurrence of selected comorbid conditions and symptoms and healthcare utilization (testing, emergency department visits and hospitalization) measured during the look-back period; demographics, physician specialty, and Charlson comorbidity index (CCI) measured 1 year pre-index. Patients with an ICD-9/10 amyloidosis code during the look-back period were excluded. An ATTRv-free reference cohort was created from a random sample of enrollees who lacked any diagnosis of amyloidosis and matched 3:1 to ATTRv patients on age, gender, and region to provide reference values; same index and enrollment requirement as match.

Results

For the 141 qualifying patients with ATTRv and 423 matched controls, mean (standard deviation) age was 62.5 (14.2) years and 53.9% were female. Mean CCI for ATTRv cohort was 2.7 (3.0) versus 1.1 (1.9) among controls. Selected comorbidities, testing, visits, and hospitalization were common among patients with ATTRv during the look-back period with higher rates versus controls.

Conclusions

Patients with ATTRv amyloidosis experience multiple neurological, cardiovascular, and other clinical manifestations, testing, and hospitalization prior to diagnosis. Occurrence of potential markers of illness is most common in the year before diagnosis.
Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients
Authors: Sklar Michael Chaim , Madotto Fabiana , Jonkman Annemijn , Rauseo Michela , Soliman Ibrahim , Damiani L. Felipe , Telias Irene , Dubo Sebastian , Chen Lu , Rittayamai Nuttapol , Chen Guang-Qiang , Goligher Ewan C. , Dres Martin , Coudroy Remi , Pham Tai , Artigas Ricard M. , Friedrich Jan O. , Sinderby Christer , Heunks Leo , Brochard Laurent
Published: January 2021

Background

In patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity.

Methods

Prospective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering.

Results

Seventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0–50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering.

Conclusion

Low levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity.

Trial RegistrationClinicalTrials.gov (NCT02434016). Registered on April 27, 2015. First patients enrolled June 2015.
Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences
Authors: Ross Caroline Jane , Rom Aviv , Spinrad Amit , Gelbard-Solodkin Dikla , Degani Neta , Ulitsky Igor
Published: January 2021

Background

Animal genomes contain thousands of long noncoding RNA (lncRNA) genes, a growing subset of which are thought to be functionally important. This functionality is often mediated by short sequence elements scattered throughout the RNA sequence that correspond to binding sites for small RNAs and RNA binding proteins. Throughout vertebrate evolution, the sequences of lncRNA genes changed extensively, so that it is often impossible to obtain significant alignments between sequences of lncRNAs from evolutionary distant species, even when synteny is evident. This often prohibits identifying conserved lncRNAs that are likely to be functional or prioritizing constrained regions for experimental interrogation.

Results

We introduce here LncLOOM, a novel algorithmic framework for the discovery and evaluation of syntenic combinations of short motifs. LncLOOM is based on a graph representation of the input sequences and uses integer linear programming to efficiently compare dozens of sequences that have thousands of bases each and to evaluate the significance of the recovered motifs. We show that LncLOOM is capable of identifying specific, biologically relevant motifs which are conserved throughout vertebrates and beyond in lncRNAs and 3′UTRs, including novel functional RNA elements in the CHASERR lncRNA that are required for regulation of CHD2 expression.

Conclusions

We expect that LncLOOM will become a broadly used approach for the discovery of functionally relevant elements in the noncoding genome.