bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying disincentives to ethics consultation requests among physicians, advance practice providers, and nurses: a quality improvement all staff survey at a tertiary academic medical center
Authors: Cederquist Lynette , LaBuzetta Jamie Nicole , Cachay Edward , Friedman Lawrence , Yi Cassia , Dibsie Laura , Zhang Yiran
Published: April 2021

Background

Ethics consult services are well established, but often remain underutilized. Our aim was to identify the barriers and perceptions of the Ethics consult service for physicians, advance practice providers (APPs), and nurses at our urban academic medical center which might contribute to underutilization.

Methods

This was a cross-sectional single-health system, anonymous written online survey, which was developed by the UCSD Health Clinical Ethics Committee and distributed by Survey Monkey. We compare responses between physicians, APPs, and nurses using standard parametric and non-parametric statistical methods. Satisfaction with ethics consult and likelihood of calling Ethics service again were assessed using a 0–100 scale using a 5-likert response structured (0 being “not helpful at all” to 100 being “extremely helpful”) and results presented using box plots and interquartile ranges (IQR).

Results

From January to July 2019, approximately 3800 surveys were sent toallphysicians, APPs and nurses with a return rate of 5.5—10%. Although the majority of respondents had encountered an ethical dilemma (85–92.1%) only approximately half had ever requested an Ethics consult. The primary reason for physicians never having requested a consult was that they never felt the need for help (41%). For APPs the primary reasons were not knowing an Ethics consult service was available (33.3%) or not knowing how to contact Ethics (27.8%). For nurses, it was not knowing how to contact the Ethics consult service (30.8%) or not feeling the need for help (26.2%). The median satisfaction score (IQR) for Ethics consult services rated on a 0–100 scale, from physicians was 76 (29), for AAPs 89 (49), and nurses 70 (40) (p = 0.62). The median (IQR) of likelihood of consulting Ethics in the future also on a 0–100 scale was 71 (47) for physicians, 69 (45) for APPs, and 61 (45) for nurses (p = 0.79). APP’s and nurses were significantly more likely than physicians to believe that the team did not act on the Ethics consult’s recommendations.

Conclusions

Based on the results presented, we were able to identify actionable steps to better engage healthcare providers—and in particular APPs and nurses—and scale up institutional educational efforts to increase awareness of the role of the Ethics consult service at our institution. Actionable steps included implementing a system of ongoing feedback that is critical for the sustainability of the Ethics service role. We hope this project can serve as a blueprint for other hospital-based Ethics consult services to improve the quality of their programs.
Implementing dedicated education units in 6 European undergraduate nursing and midwifery students clinical placements
Authors: Pedregosa Sara , Fabrellas Núria , Risco Ester , Pereira Mariana , Stefaniak Małgorzata , Şenuzun Fisun , Martin Sandra , Zabalegui Adelaida
Published: April 2021

Background

Undergraduate students’ clinical experience, working directly with patients and the healthcare team is essential to ensure students acquire the necessary competence for practice. There are differences in the quality of clinical environments and in students’ clinical placement experiences and not all clinical sites are optimal learning environments. The Dedicated Education Unit clinical education model allows students to develop the practical knowledge, skills and professionalism they will need as nurses/midwives.

Methods

We employed the Consolidated Framework for Implementation Research to identify and compare barriers and facilitators in the implementation of the Dedicated Education Unit in 6 European undergraduate nursing/midwifery student clinical placement settings and to describe the experience of nurses/midwives involved in the Dedicated Education Unit model implementation and evaluation. A pre-post implementation interpretive assessment was based on participants’ responses to the Consolidated Framework for Implementation Research construct questions.

Results

Although Dedicated Education Unit model implementation in our project was heterogeneous, no main implementation barriers were perceived. Qualitative data showed that educational-service collaboration, including a focus on mutual goals, organizational communication and networking, satisfaction of educational and healthcare professionals, and the establishment of a safe space for professional discussion and feedback, were considered facilitators.

Conclusions

This study describes the key elements guiding educational and healthcare stakeholders in Dedicated Education Unit implementation, engaging participants in the entire process, and offering other organizations the opportunity to consider the benefits of this clinical education model.
The association between varying levels of palliative care involvement on costs during terminal hospitalizations in Canada from 2012 to 2015
Authors: Isenberg Sarina R. , Meaney Christopher , May Peter , Tanuseputro Peter , Quinn Kieran , Qureshi Danial , Saunders Stephanie , Webber Colleen , Seow Hsien , Downar James , Smith Thomas J. , Husain Amna , Lawlor Peter G. , Fowler Rob , Lachance Julie , McGrail Kimberlyn , Hsu Amy T.
Published: April 2021

Background

Inpatient palliative care is associated with lower inpatient costs; however, this has yet to be studied using a more nuanced, multi-tiered measure of inpatient palliative care and a national population-representative dataset. Using a population-based cohort of Canadians who died in hospital, our objectives were to: describe patients’ receipt of palliative care and active interventions in their terminal hospitalization; and examine the relationship between inpatient palliative care and hospitalization costs.

Methods

Retrospective cohort study using data from the Discharge Abstract Database in Canada between fiscal years 2012 and 2015. The cohort were Canadian adults (age ≥ 18 years) who died in hospital between April 1st, 2012 and March 31st, 2015 (N = 250,640). The exposure was level of palliative care involvement defined as: medium-high, low, or no palliative care. The main measure was acute care costs calculated using resource intensity weights multiplied by the cost of standard hospital stay, represented in 2014 Canadian dollars (CAD). Descriptive statistics were represented as median (IQR), and n(%). We modelled cost as a function of palliative care using a gamma generalized estimating equation (GEE) model, accounting for clustering by hospital.

Results

There were 250,640 adults who died in hospital. Mean age was 76 (SD 14), 47% were female. The most common comorbidities were: metastatic cancer (21%), heart failure (21%), and chronic obstructive pulmonary disease (16%). Of the decedents, 95,450 (38%) had no palliative care involvement, 98,849 (38%) received low involvement, and 60,341 (24%) received medium to high involvement. Controlling for age, sex, province and predicted hospital mortality risk at admission, the cost per day of a terminal hospitalization was: $1359 (95% CI 1323: 1397) (no involvement), $1175 (95% CI 1146: 1206) (low involvement), and $744 (95% CI 728: 760) (medium-high involvement).

Conclusions

Increased involvement of palliative care was associated with lower costs. Future research should explore whether this relationship holds for non-terminal hospitalizations, and whether palliative care in other settings impacts inpatient costs.
Physiotherapists’ awareness of risk of bone demineralisation and falls in people living with HIV: a qualitative study
Authors: Charumbira Maria Y. , Berner Karina , Louw Quinette
Published: April 2021

Background

Recent research has indicated a seemingly increased propensity for both falls and accelerated bone loss in people living with HIV (PLWH). Physiotherapists play a crucial role in optimising function and quality of life of PLWH through prevention of falls and reducing the harm that results.

Aim

This study aimed to explore physiotherapists’ awareness of falls risk and accelerated bone demineralisation in PLWH and their perceptions of current falls prevention strategies in the care of PLWH in selected regions of sub-Saharan Africa.

Method

An exploratory descriptive qualitative research method was employed to explore physiotherapists’ perceptions and experiences regarding bone health and falls in PLWH. In-depth semi-structured telephonic interviews were used to collect data from 21 physiotherapists working in primary HIV care. Transcribed interview data were coded in Atlas.ti.8® and analysed using inductive thematic analysis.

Results

The primary study revealed a lack of awareness by physiotherapists of falls risk and bone demineralisation in PLWH. As such, physiotherapists did not link falls or fractures to HIV or antiretroviral therapy (ART) when they did observe such events during their general patient assessments. However, in retrospect, some physiotherapists were able to recognise risk factors linked to falls in those with HIV. Current services for falls prevention, as perceived by the physiotherapists, were sub-optimal.

Conclusion

Physiotherapists may need to be more aware of the potential risk of falls and bone demineralisation in PLWH and routinely assess for these phenomena in both older and younger PLWH.
Budget impact analysis of surfactant therapy for bronchiolitis in critically ill infants: the Colombian National Health System perspective
Authors: Buendía Jefferson Antonio , Patiño Diana Guerrero
Published: April 2021

Background

Severe bronchiolitis requiring mechanical ventilation was associated with an absence of surfactant activity and phosphatidylglycerol, causing airway obstruction in acute bronchiolitis. Exogen surfactant in mechanically ventilated infants decreased duration of stay in the intensive care unit and had favorable effects on oxygenation and carbon dioxide removal. This study aimed to evaluate the budget impact of surfactant therapy for bronchiolitis in critically ill infants in Colombia.

Methods

Budget impact analysis was performed to estimate the economic impact of surfactant therapy (ST) for the treatment of infants with a diagnosis of bronchiolitis, requiring mechanical ventilation. The analysis considered a 4-year time horizon and Colombian National Health System perspective. The model estimated drug costs associated with current scenario using humidified oxygen or adrenaline nebulization, and new scenario adding exogen surfactant. The size of the target population was calculated using epidemiological national data. Univariate one-way sensitivity analyses and scenario analyses were performed.

Results

In the base-case analysis the 4-year costs associated to ST and no-ST were estimated to be US$ 55,188,132 and US$ 55,972,082 respectively, indicating savings for Colombian National Health equal to US$ 783,950 if ST is adopted for the routine management of patients with bronchiolitis requiring mechanical ventilation. In the one-way sensitivity analysis, only increases in the cost of the surfactant drug and cost or length of stay in the pediatric intensive unit reduce the potential savings of ST.

Conclusion

ST was cost-saving in emergency settings for treating infants with severe bronchiolitis requiring mechanical ventilation. This shift in treatment approach proved to be economically favorable in the Colombian context.
Comparison of 15 dinoflagellate genomes reveals extensive sequence and structural divergence in family Symbiodiniaceae and genus Symbiodinium
Authors: González-Pech Raúl A. , Stephens Timothy G. , Chen Yibi , Mohamed Amin R. , Cheng Yuanyuan , Shah Sarah , Dougan Katherine E. , Fortuin Michael D. A. , Lagorce Rémi , Burt David W. , Bhattacharya Debashish , Ragan Mark A. , Chan Cheong Xin
Published: April 2021

Background

Dinoflagellates in the family Symbiodiniaceae are important photosynthetic symbionts in cnidarians (such as corals) and other coral reef organisms. Breakdown of the coral-dinoflagellate symbiosis due to environmental stress (i.e. coral bleaching) can lead to coral death and the potential collapse of reef ecosystems. However, evolution of Symbiodiniaceae genomes, and its implications for the coral, is little understood. Genome sequences of Symbiodiniaceae remain scarce due in part to their large genome sizes (1–5 Gbp) and idiosyncratic genome features.

Results

Here, we present de novo genome assemblies of seven members of the genusSymbiodinium, of which two are free-living, one is an opportunistic symbiont, and the remainder are mutualistic symbionts. Integrating other available data, we compare 15 dinoflagellate genomes revealing high sequence and structural divergence. Divergence among someSymbiodiniumisolates is comparable to that among distinct genera of Symbiodiniaceae. We also recovered hundreds of gene families specific to each lineage, many of which encode unknown functions. An in-depth comparison between the genomes of the symbioticSymbiodinium tridacnidorum(isolated from a coral) and the free-livingSymbiodinium natansreveals a greater prevalence of transposable elements, genetic duplication, structural rearrangements, and pseudogenisation in the symbiotic species.

Conclusions

Our results underscore the potential impact of lifestyle on lineage-specific gene-function innovation, genome divergence, and the diversification ofSymbiodiniumand Symbiodiniaceae. The divergent features we report, and their putative causes, may also apply to other microbial eukaryotes that have undergone symbiotic phases in their evolutionary history.
Rac1 activation can generate untemplated, lamellar membrane ruffles
Authors: Leyden F. , Uthishtran S. , Moorthi U. K. , York H. M. , Patil A. , Gandhi H. , Petrov E. P. , Bornschlögl T. , Arumugam S.
Published: April 2021

Background

Membrane protrusions that occur on the dorsal surface of a cell are an excellent experimental system to study actin machinery at work in a living cell. Small GTPase Rac1 controls the membrane protrusions that form and encapsulate extracellular volumes to perform pinocytic or phagocytic functions.

Results

Here, capitalizing on rapid volumetric imaging capabilities of lattice light-sheet microscopy (LLSM), we describe optogenetic approaches using photoactivable Rac1 (PA-Rac1) for controlled ruffle generation. We demonstrate that PA-Rac1 activation needs to be continuous, suggesting a threshold local concentration for sustained actin polymerization leading to ruffling. We show that Rac1 activation leads to actin assembly at the dorsal surface of the cell membrane that result in sheet-like protrusion formation without any requirement of a template. Further, this approach can be used to study the complex morpho-dynamics of the protrusions or to investigate specific proteins that may be enriched in the ruffles. Deactivating PA-Rac1 leads to complex contractile processes resulting in formation of macropinosomes. Using multicolour imaging in combination with these approaches, we find that Myo1e specifically is enriched in the ruffles.

Conclusions

Combining LLSM and optogenetics enables superior spatial and temporal control for studying such dynamic mechanisms. Demonstrated here, the techniques implemented provide insight into the complex nature of the molecular interplay involved in dynamic actin machinery, revealing that Rac1 activation can generate untemplated, lamellar protrusions.
Dietary Arthrospira platensis improves systemic antioxidant potential and changes plasma lipids without affecting related hepatic metabolic pathways in post-weaned piglets
Authors: dos Santos Madeira Marta Sofia Morgado , Lopes Paula Alexandra Antunes Brás , Martins Cátia Falcão , Assunção José Miguel Pestana , Alfaia Cristina Maria Riscado Pereira Mate , Pinto Rui Manuel Amaro , Prates José António Mestre
Published: April 2021

Background

The ability of a high level of dietaryArthrospira platensis, individually or in combination with two exogenous carbohydrate-degrading enzymes (lysozyme and Rovabio®), to improve systemic antioxidant potential and hepatic lipid metabolism was tested in piglets. Forty malepost-weaned piglets, sons of Large White × Landrace sows crossed with Pietrain boars, were allocated into 4 groups (n = 10) and fed during 28 days one of the following diets: 1) a control basal diet (cereal and soybean meal); 2) a basal diet with 10% ofA. platensis(AP); 3) the AP diet supplemented with 0.005% of Rovabio®(AP + R); 4) the AP diet supplemented with 0.01% of lysozyme (AP + L).

Results

Arthrospira platensisdecreased BW gain of piglets, regardless the addition of feed enzymes. The majority of plasma metabolites were affected by diets.A. platensisincreased total lipids, total cholesterol and LDL-cholesterol, without changing hepatic fatty acid content or modulating, in an expressive manner, the transcriptional profile of lipid sensitive mediators. The antioxidant potential in general, and total carotenoids in particular, were improved by the microalga, regardless lysozyme or Rovabio®.

Conclusions

Summing up,A. platensis, individually and combined with feed enzymes, impacts negatively on piglets’ growth but improves the systemic antioxidant potential and changes plasma lipids with a minor modulation on related hepatic metabolic pathways.
Characterizing sensitivity and coverage of clinical WGS as a diagnostic test for genetic disorders
Authors: Sun Yan , Liu Fengxia , Fan Chunna , Wang Yaoshen , Song Lijie , Fang Zhonghai , Han Rui , Wang Zhonghua , Wang Xiaodan , Yang Ziying , Xu Zhenpeng , Peng Jiguang , Shi Chaonan , Zhang Hongyun , Dong Wei , Huang Hui , Li Yun , Le Yanqun , Sun Jun , Peng Zhiyu
Published: April 2021

Background

Due to its reduced cost and incomparable advantages, WGS is likely to lead to changes in clinical diagnosis of rare and undiagnosed diseases. However, the sensitivity and breadth of coverage of clinical WGS as a diagnostic test for genetic disorders has not been fully evaluated.

Methods

Here, the performance of WGS in NA12878, the YH cell line, and the Chinese trios were measured by assessing their sensitivity, PPV, depth and breadth of coverage using MGISEQ-2000. We also compared the performance of WES and WGS using NA12878. The sensitivity and PPV were tested using the family-based trio design for the Chinese trios. We further developed a systematic WGS pipeline for the analysis of 8 clinical cases.

Results

In general, the sensitivity and PPV for SNV/indel detection increased with mean depth and reached a plateau at an ~ 40X mean depth using down-sampling samples of NA12878. With a mean depth of 40X, the sensitivity of homozygous and heterozygous SNPs of NA12878 was > 99.25% and > 99.50%, respectively, and the PPV was 99.97% and 98.96%. Homozygous and heterozygous indels showed lower sensitivity and PPV. The sensitivity and PPV were still not 100% even with a mean depth of ~ 150X. We also observed a substantial variation in the sensitivity of CNV detection across different tools, especially in CNVs with a size less than 1 kb. In general, the breadth of coverage for disease-associated genes and CNVs increased with mean depth. The sensitivity and coverage of WGS (~ 40X) was better than WES (~ 120X). Among the Chinese trios with an ~ 40X mean depth, the sensitivity among offspring was > 99.48% and > 96.36% for SNP and indel detection, and the PPVs were 99.86% and 97.93%. All 12 previously validated variants in the 8 clinical cases were successfully detected using our WGS pipeline.

Conclusions

The current standard of a mean depth of 40X may be sufficient for SNV/indel detection and identification of most CNVs. It would be advisable for clinical scientists to determine the range of sensitivity and PPV for different classes of variants for a particular WGS pipeline, which would be useful when interpreting and delivering clinical reports.
Gene variants associated with acne vulgaris presentation and severity: a systematic review and meta-analysis
Authors: Heng Anna Hwee Sing , Say Yee-How , Sio Yang Yie , Ng Yu Ting , Chew Fook Tim
Published: April 2021

Background

Multiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the major factors.

Methods

We performed a systematic review on the genes and their variants that have been investigated for association with acne presentation and severity. A random-effect meta-analysis using the allele model (minor allele vs. major allele) was also conducted to provide an overall estimation of risk effects of frequently reported gene variants. This included a subset data of 982 acne cases and 846 controls extracted from our existing GWAS database on various allergic and skin diseases among Singapore Chinese.

Results

Systematic review of 51 articles covering Asians and Caucasians found 60 genes/loci and their 100 variants implicated in acne; majority of them were in the intron, coding region/missense, and promoter regions. The commonly studied candidate genes/gene families include tumor necrosis factor (TNF), and the interleukin (IL) and cytochrome P450 (CYP) gene families. Our meta-analysis showed that most of the analyzed gene variants exhibited insignificant pooled odds ratio (pOR) and significant heterogeneity between studies. Nevertheless, we found thatTNFrs1800629 A allele carriers andCYP17A1rs743572 T allele carriers had significantly reduced mild acne risk [pOR: 0.60; 95% Confidence Interval (CI): 0.33–0.86] and severe acne risk (pOR: 0.59; 95% CI: 0.40–0.79), respectively, across populations. Overall,FST(follistatin) rs629725 A allele poses a significantly modest increased risk for acne presentation (pOR: 1.19, 95% CI: 1.14, 1.23), but neitherTIMP2(TIMP metallopeptidase inhibitor 2) rs8179090 norCYP1A1rs4646903 (pOR: 0.96, 95% CI: 0.80–1.12; pOR: 0.95, 95% CI: 0.83, 1.08), respectively. We discovered 15 novel SNPs in the 3′ UTR region of the Toll-like Receptor 4 gene (TLR4) associated with acne presentation.

Conclusions

This systematic review and meta-analysis suggest that genes influencing inflammatory responses, specificallyTNF, and genes influencing the function and activity of sebaceous glands, specificallyCYP17A1andFST, have potential risk variants for acne presentation and severity across populations. Understanding the genetic susceptibility factors and biological pathways involved in the pathogenesis of acne will help us to gain insights into developing effective acne treatments.
Identification of genes and pathways involved in malignant pleural mesothelioma using bioinformatics methods
Authors: Liu Xingsheng , Qian Kun , Lu Gaojun , Chen Peng , Zhang Yi
Published: April 2021

Background

Malignant pleural mesothelioma (MPM) is a rare tumor in the pleura. This study was carried out to identify key genes and pathways that may be involved in MPM.

Methods

Microarray datasets GSE51024 and GSE2549 were analyzed for differentially expressed genes (DEGs) between normal and MPM tissues. The identified DEGs were subjected to functional analyses using bioinformatics tools.

Results

A total of 276 DEGs were identified, consisting of 187 downregulated and 79 upregulated genes. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis indicated that the DEGs were enriched in extracellular structure organization, extracellular matrix, and ECM−receptor interaction. Due to high degree of connectivity among 24 hub genes, EZH2 and HMMR are likely to play roles in the carcinogenesis and progression of MPM. The two genes were found over-expressed in MPM tissues. Patients with elevated EZH2 and HMMR expressions had poor overall survival.

Conclusions

EZH2 and HMMR are identified to be the hub genes for MPM and they may be further characterized to better understand the molecular mechanisms underlying the carcinogenesis of MPM.
High CFP score indicates poor prognosis and chemoradiotherapy response in LARC patients
Authors: Lu Siyi , Liu Zhenzhen , Wang Bingyan , Li Fei , Meng Yan , Wang Junwei , Wang Yuxia , Wang Hao , Zhou Xin , Fu Wei
Published: April 2021

Background

Preoperative tumor markers, inflammation, and nutritional status are considered important predictors of prognosis and tumor response in locally advanced rectal cancer (LARC) patients. This study aims to explore the prognostic and predictive role of carcinoembryonic antigen (CEA), the Fibrinogen-Albumin Ratio Index (FARI), the Prognostic Nutritional Index (PNI) in LARC patients and compared them with a novel combined CEA-FARI-PNI (CFP) scoring system.

Methods

A total of 138 LARC patients undergoing radical surgery following neoadjuvant chemoradiotherapy (NCRT) between January 2012 and March 2019 were enrolled. The X-tile program was used to determine the optimal cut-off values of CEA, FARI, and PNI, and CFP scoring system was constructed accordingly. The prognostic ability of these factors was assessed by the time-dependent receiver operating characteristic (ROC) curve, Kaplan–Meier, Cox regression, and logistic regression. Nomogram was established to evaluate the predictive role of these factors in tumor response.

Results

The optimal cut-off values of CEA, FARI, and PNI were 5.15 ng/l, 10.56%, and 42.25 g/L, respectively. The time-dependent ROC curve showed that compared to CEA, FARI, and PNI, CFP showed stable predictive efficacy for overall survival (OS) and disease-free survival (DFS). In multivariate analysis, CFP was the only factor that could independently predict OS (HR = 8.117, p = 0.001) and DFS (HR = 4.994, p < 0.001). Moreover, high CFP (OR = 3.693, p = 0.002) was also an independent risk factor of poor response. The area under the ROC curve (AUC) of the nomograms for predicting tumor response was better including CFP (0.717) than without CFP (0.656) (p < 0.05).

Conclusions

The CFP score was a more reliable marker for predicting OS, DFS, and NCRT efficacy in LARC patients, and the score could apparently improve predicted efficacy of the nomogram.
Influence of icariin on inflammation, apoptosis, invasion, and tumor immunity in cervical cancer by reducing the TLR4/MyD88/NF-κB and Wnt/β-catenin pathways
Authors: Li Chunyang , Yang Shuangqing , Ma Huaqing , Ruan Mengjia , Fang Luyan , Cheng Jing
Published: April 2021

Background

Cervical cancer is a type of the most common gynecology tumor in women of the whole world. Accumulating data have shown that icariin (ICA), a natural compound, has anti-cancer activity in different cancers, including cervical cancer. The study aimed to reveal the antitumor effects and the possible underlying mechanism of ICA in U14 tumor-bearing mice and SiHa cells.

Methods

The antitumor effects of ICA were investigated in vivo and in vitro. The expression of TLR4/MyD88/NF-κB and Wnt/β-catenin signaling pathways were evaluated.

Results

We found that ICA significantly suppressed tumor tissue growth and SiHa cells viability in a dose-dependent manner. Also, ICA enhanced the anti-tumor humoral immunity in vivo. Moreover, ICA significantly improved the composition of the microbiota in mice models. Additionally, the results clarified that ICA significantly inhibited the migration, invasion capacity, and expression levels of TGF-β1, TNF-α, IL-6, IL-17A, IL-10 in SiHa cells. Meanwhile, ICA was revealed to promote the apoptosis of cervical cancer cells by down-regulating Ki67, survivin, Bcl-2, c-Myc, and up-regulating P16, P53, Bax levels in vivo and in vitro. For the part of mechanism exploration, we showed that ICA inhibits the inflammation, proliferation, migration, and invasion, as well as promotes apoptosis and immunity in cervical cancer through impairment of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways.

Conclusions

Taken together, ICA could be a potential supplementary agent for cervical cancer treatment.
Critical signaling pathways governing hepatocellular carcinoma behavior; small molecule-based approaches
Authors: Farzaneh Zahra , Vosough Massoud , Agarwal Tarun , Farzaneh Maryam
Published: April 2021

Hepatocellular carcinoma (HCC) is the second leading cause of death due to cancer. Although there are different treatment options, these strategies are not efficient in terms of restricting the tumor cell’s proliferation and metastasis. The liver tumor microenvironment contains the non-parenchymal cells with supportive or inhibitory effects on the cancerous phenotype of HCC. Several signaling pathways are dis-regulated in HCC and cause uncontrolled cell propagation, metastasis, and recurrence of liver carcinoma cells. Recent studies have established new approaches for the prevention and treatment of HCC using small molecules. Small molecules are compounds with a low molecular weight that usually inhibit the specific targets in signal transduction pathways. These components can induce cell cycle arrest, apoptosis, block metastasis, and tumor growth. Devising strategies for simultaneously targeting HCC and the non-parenchymal population of the tumor could lead to more relevant research outcomes. These strategies may open new avenues for the treatment of HCC with minimal cytotoxic effects on healthy cells. This study provides the latest findings on critical signaling pathways governing HCC behavior and using small molecules in the control of HCC both in vitro and in vivo models.
DNA methylation in the adipose tissue and whole blood of Agent Orange-exposed Operation Ranch Hand veterans: a pilot study
Authors: Rytel Matthew R. , Butler Rondi , Eliot Melissa , Braun Joseph M. , Houseman E. Andres , Kelsey Karl T.
Published: April 2021

Background

Between 1962 and 1971, the US Air Force sprayed Agent Orange across Vietnam, exposing many soldiers to this dioxin-containing herbicide. Several negative health outcomes have been linked to Agent Orange exposure, but data is lacking on the effects this chemical has on the genome. Therefore, we sought to characterize the impact of Agent Orange exposure on DNA methylation in the whole blood and adipose tissue of veterans enrolled in the Air Force Health Study (AFHS).

Methods

We received adipose tissue (n = 37) and whole blood (n = 42) from veterans in the AFHS. Study participants were grouped as having low, moderate, or high TCDD body burden based on their previously measured serum levels of dioxin. DNA methylation was assessed using the Illumina 450 K platform.

Results

Epigenome-wide analysis indicated that there were no FDR-significantly methylated CpGs in either tissue with TCDD burden. However, 3 CpGs in the adipose tissue (contained within SLC9A3, LYNX1, and TNRC18) were marginally significantly (q < 0.1) hypomethylated, and 1 CpG in whole blood (contained within PTPRN2) was marginally significantly (q < 0.1) hypermethylated with high TCDD burden. Analysis for differentially methylated DNA regions yielded SLC9A3, among other regions in adipose tissue, to be significantly differentially methylated with higher TCDD burden. Comparing whole blood data to a study of dioxin exposed adults from Alabama identified a CpG within the gene SMO that was hypomethylated with dioxin exposure in both studies.

Conclusion

We found limited evidence of dioxin associated DNA methylation in adipose tissue and whole blood in this pilot study of Vietnam War veterans. Nevertheless, loci in the genes of SLC9A3 in adipose tissue, and PTPRN2 and SMO in whole blood, should be included in future exposure analyses.
Comprehensive analyses of m6A regulators and interactive coding and non-coding RNAs across 32 cancer types
Authors: Shen Sipeng , Zhang Ruyang , Jiang Yue , Li Yi , Lin Lijuan , Liu Zhonghua , Zhao Yang , Shen Hongbing , Hu Zhibin , Wei Yongyue , Chen Feng
Published: April 2021

N6-Methyladenosine (m6A) is an RNA modification that interacts with numerous coding and non-coding RNAs and plays important roles in the development of cancers. Nonetheless, the clinical impacts of m6A interactive genes on these cancers largely remain unclear since most studies focus only on a single cancer type. We comprehensively evaluated m6A modification patterns, including 23 m6A regulators and 83 interactive coding and non-coding RNAs among 9,804 pan-cancer samples. We used clustering analysis to identify m6A subtypes and constructed the m6A signature based on an unsupervised approach. We used the signatures to identify potential m6A modification targets across the genome. The prognostic value of one target was further validated in 3,444 samples from six external datasets. We developed three distinct m6A modification subtypes with different tumor microenvironment cell infiltration degrees: immunological, intermediate, and tumor proliferative. They were significantly associated with overall survival in 24 of 27 cancer types. Our constructed individual-level m6A signature was associated with survival, tumor mutation burden, and classical pathways. With the signature, we identified 114 novel genes as potential m6A targets. The gene shared most commonly between cancer types, BCL9L, is an oncogene and interacts with m6A patterns in the Wnt signaling pathway. In conclusion, m6A regulators and their interactive genes impact the outcome of various cancers. Evaluating the m6A subtype and the signature of individual tumors may inform the design of adjuvant treatments.
Mutual influence of selenium nanoparticles and FGF2-STAB® on biocompatible properties of collagen/chitosan 3D scaffolds: in vitro and ex ovo evaluation
Authors: Muchová Johana , Hearnden Vanessa , Michlovská Lenka , Vištejnová Lucie , Zavaďáková Anna , Šmerková Kristýna , Kočiová Silvia , Adam Vojtěch , Kopel Pavel , Vojtová Lucy
Published: April 2021

In a biological system, nanoparticles (NPs) may interact with biomolecules. Specifically, the adsorption of proteins on the nanoparticle surface may influence both the nanoparticles' and proteins' overall bio-reactivity. Nevertheless, our knowledge of the biocompatibility and risk of exposure to nanomaterials is limited. Here, in vitro and ex ovo biocompatibility of naturally based crosslinked freeze-dried 3D porous collagen/chitosan scaffolds, modified with thermostable fibroblast growth factor 2 (FGF2-STAB®), to enhance healing and selenium nanoparticles (SeNPs) to provide antibacterial activity, were evaluated. Biocompatibility and cytotoxicity were tested in vitro using normal human dermal fibroblasts (NHDF) with scaffolds and SeNPs and FGF2-STAB® solutions. Metabolic activity assays indicated an antagonistic effect of SeNPs and FGF2-STAB® at high concentrations of SeNPs. The half-maximal inhibitory concentration (IC50) of SeNPs for NHDF was 18.9 µg/ml and IC80 was 5.6 µg/ml. The angiogenic properties of the scaffolds were monitored ex ovo using a chick chorioallantoic membrane (CAM) assay and the cytotoxicity of SeNPs over IC80 value was confirmed. Furthermore, the positive effect of FGF2-STAB® at very low concentrations (0.01 µg/ml) on NHDF metabolic activity was observed. Based on detailed in vitro testing, the optimal concentrations of additives in the scaffolds were determined, specifically 1 µg/ml of FGF2-STAB® and 1 µg/ml of SeNPs. The scaffolds were further subjected to antimicrobial tests, where an increase in selenium concentration in the collagen/chitosan scaffolds increased the antibacterial activity. This work highlights the antimicrobial ability and biocompatibility of newly developed crosslinked collagen/chitosan scaffolds involving FGF2-STAB® and SeNPs. Moreover, we suggest that these sponges could be used as scaffolds for growing cells in systems with low mechanical loading in tissue engineering, especially in dermis replacement, where neovascularization is a crucial parameter for successful skin regeneration. Due to their antimicrobial properties, these scaffolds are also highly promising for tissue replacement requiring the prevention of infection.
Association of health literacy and medication adherence with health-related quality of life (HRQoL) in patients with ischemic heart disease
Authors: Suhail Muzna , Saeed Hamid , Saleem Zikria , Younas Saman , Hashmi Furqan Khurshid , Rasool Fawad , Islam Muhammad , Imran Imran
Published: April 2021

Background

Medication Adherence (MA) and Health Related Quality of Life (HRQoL) are two inter-connected concepts, co-influenced by Health Literacy (HL), with significant impact on patient management and care. Thus, we aimed to estimate the association of HL and MA with HRQoL in IHD patients.

Methods

Cross-sectional study of 251 IHD patients recruited from Lahore over 6 months period. HL, MA and HRQoL was assessed using validated questionnaires; 16-items of HL, Morisky Green Levine Scale (MGLS) and SF-12, respectively. Chi-square for significance, logistic-regression for association and linear regression for predictions were used.

Results

IHD patients; males (p = 0.0001), having secondary—higher education (p = 0.0001), middle/upper class (p = 0.0001) and employed (p = 0.005) had adequate HL, and were more likely to be adherent (OR; 4.3, p = 0.014). Both physical (PCS-12) and mental (MCS-12) component scores of HRQoL for age, gender, education, area of residence, employment and MA were significantly higher in patients with adequate HL. In multinomial regression, improved PCS-12 scores tend to be higher in subjects having secondary—higher education (OR; 3.5, p = 0.067), employed (OR; 6.1, p = 0.002) and adherent (OR; 2.95, p = 0.218), while MCS-12 scores tend to be higher in patients < 65 years (OR; 2.2, p = 0.032), employed (OR; 3, p = 0.002) and adherent (OR; 4, p = 0.004). In adjusted model, HL (β;0.383, p = 0.0001) and MA (β; − 0.133, p = 0.018) were significantly associated with PCS-12, and MCS-12 with MA (β; − 0.161, p = 0.009) only.

Conclusion

Data suggested that adequate HL was significantly associated with adherence and both physical and mental dimensions of HRQoL were higher in IHD patients with adequate HL. Besides, HL and MA are independent predictors of HRQoL in IHD patients.
Validation of an 8-item Recovery Assessment Scale (RAS-8) for people with schizophrenia in China
Authors: He Si-jia , Fang Yan-wen , Huang Zi-xin , Yu Yu
Published: April 2021

Background

The 24-item Recovery Assessment Scale (RAS) is the most widely-used and well-validated tool for measuring recovery for people with mental illness. The current study aims to assess the reliability and validity of an 8-item short form of RAS (RAS-8) among a Chinese sample of people living with schizophrenia.

Methods

A sample of 400 people living with schizophrenia were recruited for scale validation. Internal consistency was tested by calculating Cronbach's α. Test–retest reliability was calculated using the intraclass correlation coefficient (ICC) for the total score and weighted kappa for each item. Factor structure was tested with confirmatory factor analysis, and concurrent validity was examined by investigating the correlation of the RAS-8 with patient symptoms, disability, depression, anxiety, patient functioning, quality of life and general health.

Results

The RAS-8 full scale and subscales showed good internal consistency with Cronbach’s alpha ranging from 0.87 to 0.92. ICC of 0.99 and weighted kappa ranged from 0.62 to 0.88, which generally indicates good test–retest reliability. The findings supported an a priori two-factor structure, χ2/df = 2.93, CFI = 0.98, TLI = 0.98, RMSEA = 0.07, SRMR = 0.035. Concurrent validity of the RAS-8 was further supported by its significant negative correlations with patient symptoms (r =  −0.24, p < 0.01), disability (r =  −0.30, p < 0.01), depression (r =  −0.16, p < 0.05), and anxiety (r =  −0.14, p < 0.05), and its significant positive relationships with patient functioning (r = 0.26, p < 0.01), quality of life (r = 0.39, p < 0.01) and general health (r = 0.34, p < 0.01).

Conclusions

This study confirmed the reliability and validity of an 8-item short-form RAS for people living with schizophrenia in Chinese communities. The validation of the RAS-8 allows for its use as an alternative for the full RAS as a rapid assessment tool in clinical and research settings. The findings are discussed for their implications for application and validation with other populations and in other countries.
Loco-regional recurrence trend and prognosis in young women with breast cancer according to molecular subtypes: analysis of 1099 cases
Authors: Li Yang , Lu Su , Zhang Yuhan , Wang Shuaibing , Liu Hong
Published: April 2021

Background

The number of young patients diagnosed with breast cancer is on the rise. We studied the rate trend of local recurrence (LR) and regional recurrence (RR) in young breast cancer (YBC) patients and outcomes among these patients based on molecular subtypes.

Methods

A retrospective cohort study was conducted based on data from Tianjin Medical University Cancer Institute and Hospital for patients ≤ 35 years of age with pathologically confirmed primary invasive breast cancer surgically treated between 2006 and 2014. Patients were categorized according to molecular subtypes on the basis of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The 5-year rates for LR, RR, and distant metastases (DM) were estimated by Kaplan-Meir statistics. Nelson-Aalen cumulative-hazard plots were used to describe local recurrence- and distant metastasis-free intervals.

Results

We identified 25,284 patients with a median follow-up of 82 months, of whom 1099 (4.3%) were YBC patients ≤ 35 years of age. The overall 5-year LR, RR, and DM rates in YBC patients were 6.7%, 5.1%, and 16.6%, respectively. The LR and RR rates demonstrated a decreasing trend over time (P = 0.028 and P = 0.015, respectively). We found that early-stage breast cancer and less lymph node metastases increased over time (P = 0.004 and P = 0.007, respectively). Patients with HR−/HER2+ status had a significantly higher LR (HR 20.4; 95% CI, 11.8–35.4) and DM (HR 37.2; 95% CI, 24.6–56.3) at 10 years. Breast-conserving surgery (BCS) or mastectomy did not influence rates of LR and RR. In the overall population, the 5-year survival of YBC patients exceeded 90%.

Conclusions

The rates of LR and RR with YBC patients demonstrated a downward trend and the proportion of early-stage breast cancer increased between 2006 and 2014. We report the highest LR rates in this young population were associated with HR−/HER2+ tumors.
MicroRNA-490-3p inhibits migration and chemoresistance of colorectal cancer cells via targeting TNKS2
Authors: Li Jing , Mo Rubing , Zheng Linmei
Published: April 2021

Objective

Colorectal cancer is one of the most common malignancy in the world. The oncogenesis of colorectal cancer is still not fully elucidated. It was reported that microRNA-490-3p (miR-490-3p) was closely related to the regulation of cancers. However, if miR-490-3p could also affect colorectal cancer and the specific mechanism remains unclear.

Methods

qRT-PCR was conducted to examine the expression of miR-490-3p. DIANA, miRDB, and TargetScan databases were used to identify target genes. LOVO and SW480 cells were transfected by miR-490-3p mimics and inhibitors. Transwell assay was used to measure cell invasion and migration. Cisplatin and fluorouracil were administered to investigate chemotherapy resistance. Western blot was used to measure TNKS2 protein expression. Binding sites were verified using the double luciferase assay.

Results

miR-490-3p expression was low in the colorectal cancer cells. The level of miR-490-3p was negatively correlated with cell migration and invasion of cancer cells. miR-490-3p could bind to TNKS2 mRNA 3′UTR directly. miR-490-3p can suppress cell viability and resistance to chemotherapy in colorectal cancer cells through targeting TNKS2.

Conclusions

miR-490-3p could affect colorectal cancer by targeting TNKS2. This study may provide a potential therapeutic target for colorectal cancer.
Eight-hour time-restricted feeding improves endocrine and metabolic profiles in women with anovulatory polycystic ovary syndrome
Authors: Li Chunzhu , Xing Chuan , Zhang Jiaqi , Zhao Han , Shi Wenjing , He Bing
Published: April 2021

Background

Time-restricted feeding (TRF) is a form of intermittent fasting, which is beneficial for weight loss and cardiometabolic health. Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine and metabolic diseases affecting women of childbearing age. It is associated with an increased prevalence of metabolic syndrome, cardiovascular diseases and type 2 diabetes. The effects of TRF on PCOS patients remains undefined, here we investigated the impact of TRF on women with anovulatory PCOS.

Methods

Eighteen PCOS women aged between 18 and 31 with anovulation participated in a 6-week trial which were divided into two consecutive periods: (1) 1-week baseline weight stabilization period and (2) 5-week TRF period. Fifteen participants completed the study. Changes in body weight, body mass index (BMI), Waist-to-Hip Ratio, skeletal muscle mass, body fat mass (BFM), body fat percentage (BF%), visceral fat area (VFA), luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH, total testosterone (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting glucose, fasting insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), area under the curve (AUC) for insulin (AUCIns), area under the curve (AUC) for glucose (AUCGlu), AUCIns/AUCGlu Ratio, lipids, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase, high-sensitivity C-reactive protein (hsCRP), insulin-like growth factor (IGF-1), menstrual cycle and eating behaviors were evaluated.

Results

Significant changes in body weight, BMI, BFM, BF%, VFA, TT, SHBG, FAI, FINS, HOMA-IR, AUCIns, AUCIns/AUCGlu Ratio, ALT, hsCRP and IGF-1 were found after the TRF period. An improvement in menstrual cycle irregularity was detected in 73.3% (11/15) patients.

Conclusion

The diet of TRF may be beneficial to anovulatory PCOS on weight loss especially reducing body fat, improving menstruation, hyperandrogenemia, insulin resistance and chronic inflammation.

Trial registration Clinicaltrial.gov, NCT04580433, registered October 8, 2020, https://clinicaltrials.gov/ct2/show/NCT04580433.