bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival prediction in acute myeloid leukemia using gene expression profiling
Authors: Lai Binbin , Lai Yanli , Zhang Yanli , Zhou Miao , OuYang Guifang 
Published: March 2022

Abstract
Background
Acute myeloid leukemia (AML) is a genetically heterogeneous blood disorder. AML patients are associated with a relatively poor overall survival. The objective of this study was to establish a machine learning model to accurately perform the prognosis prediction in AML patients.

Methods
We first screened for prognosis-related genes using Kaplan–Meier survival analysis in The Cancer Genome Atlas dataset and validated the results in the Oregon Health & Science University dataset. With a random forest model, we built a prognostic risk score using patient’s age, TP53 mutation, ELN classification and normalized 197 gene expression as predictor variable. Gene set enrichment analysis was implemented to determine the dysregulated gene sets between the high-risk and low-risk groups. Similarity Network Fusion (SNF)-based integrative clustering was performed to identify subgroups of AML patients with different clinical features.

Results
The random forest model was deemed the best model (area under curve value, 0.75). The random forest-derived risk score exhibited significant association with shorter overall survival in AML patients. The gene sets of pantothenate and coa biosynthesis, glycerolipid metabolism, biosynthesis of unsaturated fatty acids were significantly enriched in phenotype high risk score. SNF-based integrative clustering indicated three distinct subsets of AML patients in the TCGA cohort. The cluster3 AML patients were characterized by older age, higher risk score, more frequent TP53 mutations, higher cytogenetics risk, shorter overall survival.

Conclusions
The random forest-based risk score offers an effective method to perform prognosis prediction for AML patients.
Socio-cultural barriers to the delivery and utilisation of child healthcare services in rural Ghana: a qualitative study
Authors: Nyande Felix Kwasi , Ricks Esmeralda , Williams Margaret , Jardien-Baboo Sihaam 
Published: March 2022

Abstract
Background
Over half of global deaths among children under five years of age occur in sub-Saharan Africa. Prompt and consistent access to and utilisation of child healthcare services improves child health outcomes. However, socio-cultural barriers impede the utilisation of child healthcare services among rural dwellers in Ghana. There is a paucity of studies that explore the experiences of nurses and caregivers regarding the socio-cultural barriers to the delivery and utilisation of child healthcare services in rural areas in Ghana such as the Nkwanta South Municipality.

Purpose
The purpose of this study was to explore the experiences of nurses and caregivers regarding the socio-cultural barriers that impede the delivery and utilisation of child healthcare services by caregivers for their children in the Nkwanta South Municipality, Ghana.

Methods
Data were collected through semi-structured interviews conducted with a purposive sample of ten nurses and nine caregivers of children under five years of age who utilised the available child healthcare services in a rural setting. The consent of all participants was sought and given before interviews were conducted. Data analysis entailed coding and the generation of themes the codes.

Results
The exploration of experiences of nurses and caregivers of children under-five years of age revealed that certain socio-cultural beliefs and practices, language barriers and reliance of caregivers on self-medication were the main socio-cultural barriers that impeded the delivery and utilisation of child healthcare services in the Nkwanta South Municipality.

Conclusion
Nurses and caregivers experienced several socio-cultural barriers which either delayed care seeking by caregivers for their sick children or interfered with the smooth and prompt delivery of needed child healthcare services by nurses. Some of the barriers negatively affected the interaction between nurses and caregivers with the tendency to affect subsequent child healthcare service utilisation. It is recommended that healthcare managers and nurses should foster close collaboration with caregivers and community leaders to address these socio-cultural barriers and facilitate prompt and consistent utilisation of child healthcare service in rural areas.
Expanding the phenotype associated with SMARCC2 variants: a fetus with tetralogy of Fallot
Authors: Sun Hairui , Zhang Siyao , Wang Jingyi , Zhou Xiaoxue , Zhang Hongjia , Yang Huixia , He Yihua 
Published: March 2022

Abstract
Background
Coffin-Siris syndrome-8 (CSS8) is a rare autosomal dominant disorder caused by variants in SMARCC2, a core subunit of the chromatin-remodeling complex BRG1-associated factor (BAF). The clinical characteristics of this disorder have not been entirely determined because of the rarity of clinical reports. The BAF complex plays a crucial role in embryogenesis and cardiac development, and pathogenic variants in genes encoding the components of the BAF complex have been associated with congenital heart disease (CHD). However, variants in SMARCC2 have not been reported in patients with CHD.

Case presentation
A 28-year-old primigravida was referred at 24 weeks gestation for prenatal echocardiography. The echocardiographic findings were consistent with a prenatal ultrasound diagnosis of tetralogy of Fallot (TOF). After detailed counseling, the couple decided to terminate the pregnancy and undergo genetic testing. A trio (fetus and the parents) whole-exome sequencing (WES) and copy number variation sequencing (CNV-seq) were performed. CNV-seq identified no chromosomal abnormalities. WES analysis revealed a pathogenic, de novo heterozygous frameshift variant in SMARCC2 (NM_003075.5: c.3561del, p.Leu1188fs). The genetic diagnosis of CSS8 was considered given the identification of the SMARCC2 pathogenic variant.

Conclusions
We report the first prenatal case with the SMARCC2 variant. The presence of CHD further broadens the phenotypic spectrum of SMARCC2-related disease.
A microenvironment-responsive FePt probes for imaging-guided Fenton-enhanced radiotherapy of hepatocellular carcinoma
Authors: Zhao Xingyang , Sun Xiang , Huang Wenchao , Chen Ronghe , Chen Kang , Nie Liming , Fang Chihua 
Published: March 2022

AbstractHepatocellular carcinoma (HCC) continues to be one of the most fatal malignancies with increasing morbidity, and potent therapeutics are urgently required given its insensitivity to traditional treatments. Here, we have developed a microenvironment-responsive FePt probes for the highly efficient Fenton-enhanced radiotherapy (FERT) of HCC. The selective release of Fe2+ in the acidic tumor microenvironment, but not in normal tissue, together with enhanced levels of hydrogen peroxide produced through the Pt radiosensitization effect, facilitates the generation of an enormous amount of hydroxyl radicals through the Fenton reaction, thereby extending the radiotherapeutic cascade and realizing a powerful therapeutic efficacy for HCC. Moreover, the “burst” release of Fe2+ contributes to the T2-to-T1 magnetic resonance imaging (MRI) switching effect, which informs the release of Fe2+, making imaging-guided cancer therapy feasible. This work not only breaks the bottleneck of traditional radiotherapy for HCC while minimally affecting normal tissues, but also provides a new strategy for FERT imaging guidance.
Graphical Abstract
Integrated analysis of ceRNA network reveals potential prognostic Hint1-related lncRNAs involved in hepatocellular carcinoma progression
Authors: Zhang Cheng , Bao Tianhao , Ke Yang , Liu Xin , Wang Xinghong , Liao Weiran , He Yutao , Wang Lin 
Published: March 2022

Abstract
Background
Hint1 is a novel tumor suppressor gene, and inactivation of its expression is closely associated with the carcinogenesis of a variety of malignancies. The effects of Hint1 deficiency on the competing endogenous RNA (ceRNA) regulatory network in the context of HCC remains to be fully characterized. This study aims to explore Hint1-related hub lncRNAs in HCC and to establish a reliable prognostic model for HCC patients based on these hub lncRNAs.

Methods
lncRNA + mRNA microarray was used to identify differentially expressed (DE) lncRNAs and mRNAs in Huh7 cells before and after Hint1 knockdown. A Hint1-related ceRNA network was mapped by bioinformation technology. The DEmRNAs in the network were analyzed via GO and KEGG enrichment analyses. Hub DElncRNAs associated with HCC patient prognosis were then detected through univariate and multivariate Cox regression analyses and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, and nomograms. We also utilized Kaplan-Meier curves to validate the relationship between hub lncRNAs and the overall survival (OS) of HCC patients. Finally, A Hint1-related core ceRNA network based on the hub DElncRNAs and DEmRNAs was mapped.

Results
We identified 417 differentially expressed DElncRNAs and 2096 DEmRNAs in Huh7 cells before and after Hint1 knockdown. Three hub DElncRNAs (LINC00324, SNHG3, and DIO3OS) in the Hint1-associated ceRNA network were screened out using univariate and multivariate Cox regression analyses. A hepatocellular carcinoma (HCC) prognostic risk-scoring model and nomogram were constructed using these three hub lncRNAs, and it was confirmed that the risk score of the model could be used as an independent predictor of HCC prognosis. A Hint1-related core ceRNA network based on the hub DElncRNAs and DEmRNAs was also mapped.

Conclusion
We constructed a reliable prognostic model for HCC patients based on three Hint1-related hub lncRNAs, and we believe these three hub lncRNAs may play critical roles in hepatocarcinogenesis, and progression.
Global analysis of miRNA-mRNA regulation pair in bladder cancer
Authors: Fan Xingchen , Zou Xuan , Liu Cheng , Peng Shuang , Zhang Shiyu , Zhou Xin , Wang Tongshan , Zhu Wei 
Published: March 2022

Abstract
Purpose
MicroRNA (miRNA) is a class of short non-coding RNA molecules that functions in RNA silencing and post-transcriptional regulation of gene expression. This study aims to identify critical miRNA-mRNA regulation pairs contributing to bladder cancer (BLCA) pathogenesis.

Patients and methods
MiRNA and mRNA microarray and RNA-sequencing datasets were downloaded from gene expression omnibus (GEO) and the cancer genome atlas (TCGA) databases. The tool of GEO2R and R packages were used to screen differential miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) and DAVID, DIANA, and Hiplot tools were used to perform gene enrichment analysis. The miRNA-mRNA regulation pair were screened from the experimentally validated miRNA-target interactions databases (miRTarbase and TarBase). Twenty-eight pairs of BLCA tissues were used to further verify the screened DE-miRNAs and DE-mRNAs by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). The diagnostic value of the miRNA-mRNA regulation pairs was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). The correlation analysis between the selected miRNA-mRNAs regulation pair and clinical, survival and tumor-related phenotypes was performed in this study.

Results
After miRTarBase, the analysis of 2 miRNA datasets, 6 mRNA datasets, and TCGA-BLCA dataset, a total of 13 miRNAs (5 downregulated and 8 upregulated in BLCA tissues) and 181 mRNAs (72 upregulated and 109 downregulated in BLCA tissues) were screened out. The pairs of miR-17-5p (upregulated in BLCA tissues) and TGFBR2 (downregulated in BLCA tissues) were verified in the external validation cohort (28 BLCA vs. 28 NC) using qRT-PCR. Areas under the ROC curve of the miRNA-mRNA regulation pair panel were 0.929 (95% CI: 0.885–0.972, p < 0.0001) in TCGA-BLCA and 0.767 (95% CI: 0.643–0.891, p = 0.001) in the external validation. The DCA also showed that the miRNA-mRNA regulation pairs had an excellent diagnostic performance distinguishing BLCA from normal controls. Correlation analysis showed that miR-17-5p and TGFBR2 correlated with tumor immunity.

Conclusions
The research identified potential miRNA-mRNA regulation pairs, providing a new idea for exploring the genesis and development of BLCA.
Adjusted D-dimer cutoff levels to rule out pulmonary embolism in patients hospitalized for COPD exacerbation: results from the SLICE trial
Authors: Rodríguez Carmen , Jara-Palomares Luis , Tabernero Eva , Tenes Andrés , González Sara , Briceño Winnifer , Lobo José Luis , Morillo Raquel , Bikdeli Behnood , Jiménez David 
Published: March 2022

Abstract
Background
For patients with suspected pulmonary embolism (PE), age- or clinically-adjusted D-dimer threshold level can be used to define a negative test that safely excludes PE and reduces the use of imaging. However, the utility of this approach in patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbation is undefined.

Methods
We ran an analysis of the patients hospitalized for COPD exacerbation and randomized to the intervention in the SLICE trial. Using the conventional strategy as the reference, we compared the proportion of patients with a negative D-dimer result, and the negative predictive value and sensitivity of three D-dimer threshold strategies for initial PE or subsequent diagnosis of venous thromboembolism (VTE): the age-adjusted strategy, the Wells-adjusted strategy, and the YEARS-adjusted strategy.

Results
We included 368 patients. Using a conventional threshold, 182 (49.5%) patients had negative D-dimer values, of whom 1 (0.6%) had PE (sensitivity, 94.1%). The use of an age-adjusted threshold increased the number of patients in whom PE could be excluded from 182 to 233 patients (63.3%), and the proportion of false-negative findings increased from 0.5% to 1.7% (sensitivity, 76.5%). With the use of the Wells or YEARS strategies, 64.4% and 71.5% had negative values, and the proportion of false-negative findings was 2.5% (sensitivity, 64.7%) and 2.7% (sensitivity, 58.8%), respectively.

Conclusions
In patients hospitalized for COPD exacerbation, compared with the conventional strategy, age- or clinically-adjusted strategies of D-dimer interpretation were associated with a larger proportion of patients in whom PE was ruled out with a higher failure rate.

Trial Registration
ClinicalTrials.gov number: NCT02238639.
Sec23a inhibits the self-renewal of melanoma cancer stem cells via inactivation of ER-phagy
Authors: Sun Zhiwei , Liu Doudou , Zeng Bin , Zhao Qiting , Li Xiaoshuang , Chen Hao , Wang Jianyu , Rosie Xing H. 
Published: March 2022

Abstract
Background
The genesis and developments of solid tumors, analogous to the renewal of healthy tissues, are driven by a subpopulation of dedicated stem cells, known as cancer stem cells (CSCs), that exhibit long-term clonal repopulation and self-renewal capacity. CSCs may regulate tumor initiation, growth, dormancy, metastasis, recurrence and chemoresistance. While autophagy has been proposed as a regulator of the stemness of CSCs, the underlying mechanisms requires further elucidation.

Methods
The CSC component in human melanoma cell lines M14 and A375 was isolated and purified by repetitive enrichments for cells that consistently display anchorage-independent spheroid growth. The stemness properties of the CSCs were confirmed in vitro by the expressions of stemness marker genes, the single-cell cloning assay and the serial spheroid formation assay. Subcutaneous tumor transplantation assay in BALB/c nude mice was performed to test the stemness properties of the CSCs in vivo. The autophagic activity was confirmed by the protein level of LC3 and P62, mRFP-LC3B punta and cytoplasmic accumulation of autolysosomes. The morphology of ER was detected with transmission electron microscopy.

Results
In the present study, by employing stable CSC cell lines derived from human melanoma cell lines M14 and A375, we show for the first time that Sec23a inhibits the self-renewal of melanoma CSCs via inactivation of ER-phagy. Mechanistically, inhibition of Sec23a reduces ER stress and consequently FAM134B-induced ER-phagy. Furthermore, TCGA data mining and analysis show that Sec23a is a favorable diagnostic and prognostic marker for human skin cutaneous melanoma.

Conclusion
This study has elucidated a new mechanism underlying the regulation of autophagy on stemness, i.e. CSCs can exploit the SEC23A/ER-stress/FAM134B/ER-phagy axis for the self-renewal. These observations provide new ideas for exploration of the regulatory network of CSC self-renewal to develop CSCs-based therapy strategies for malignant tumors.
Association between dietary saturated fat with cardiovascular disease risk markers and body composition in healthy adults: findings from the cross-sectional BODYCON study
Authors: Ozen Ezgi , Mihaylova Rada , Weech Michelle , Kinsella Sam , Lovegrove Julie A. , Jackson Kim G. 
Published: March 2022

Abstract
Background
Diets high in saturated fatty acids (SFAs) and greater abdominal obesity are both associated with raised low-density lipoprotein cholesterol (LDL-C) concentrations, an independent cardiovascular disease (CVD) risk marker. Although reducing SFA intake is a public health strategy for CVD prevention, the role of body fat distribution on the relationship between SFA and LDL-C is unclear. Therefore, our objective was to investigate whether the association between dietary SFAs and LDL-C concentrations is related to body composition.

Methods
In the BODYCON (impact of physiological and lifestyle factors on body composition) study, 409 adults [mean age 42 ± 16 years and median BMI of 23.5 (21.5–25.9) kg/m2] underwent a measure of body composition by dual energy x-ray absorptiometry, assessment of habitual dietary intake using a 4-day weighed food diary and physical activity level using a tri-axial accelerometer. Blood pressure was measured, and a fasting blood sample was collected to determine cardiometabolic disease risk markers. Correlations between body composition, circulating risk markers and dietary macronutrients were assessed prior to multivariate regression analysis. The effect of increasing intakes of dietary SFA on outcome measures was assessed using ANCOVA after adjusting for covariates.

Results
Abdominal visceral adipose tissue (VAT) mass was moderately positively correlated with total cholesterol (TC), LDL-C, systolic blood pressure (SBP), diastolic blood pressure and HOMA-IR (rs = 0.25–0.44, p < 0.01). In multiple regression analysis, 18.3% of the variability in LDL-C was explained by SFA intake [% total energy (TE)], abdominal VAT mass, carbohydrate%TE and fat%TE intakes. When data were stratified according to increasing SFA%TE intakes, fasting TC, LDL-C and non-high-density lipoprotein-cholesterol were higher in Q4 compared with Q2 (p ≤ 0.03). SBP was higher in Q4 versus Q3 (p = 0.01). Android lean mass was also higher in Q3 versus Q1 (p = 0.02). Other anthropometric and CVD risk markers were not different across quartile groups.

Conclusions
Although dietary SFA was found to explain 9% of the variability in LDL-C, stratification of data according to quartiles of SFA intake did not reveal a dose-dependent relationship with LDL-C concentration. Furthermore, this association appeared to be independent of abdominal obesity in this cohort.
Clinical Trail registration: Trial registration: clinicaltrials.gov as NCT02658539. Registered 20 January 2016, https://clinicaltrials.gov/ct2/show/NCT02658539.
COVID 19—impact on substance use treatment utilization and provision in South Africa
Authors: Harker Nadine , Johnson Kim , Erasmus Jodilee , Myers Bronwyn 
Published: March 2022

Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic has impacted people with substance use disorders (SUDs) worldwide. The aim of this study was to explore, changes in the number of SUD treatment episodes provided during the height of the pandemic and, SUD treatment providers’ perceptions of the impact of COVID-19-related restrictions on people with SUDs and the delivery of SUD treatment services in South Africa.

Methods
We used administrative data collected as part of the South African Community Epidemiology Network on Drug Use (SACENDU) project to assess whether the number of treatment episodes changed during the height of COVID-19 restrictions. We used data from an online survey of SUD treatment providers to assess providers’ perceptions of the impact of COVID-19 on SUD treatment delivery. Eight seven SUD facilities were recruited to participate in the online survey.

Results
Sixty-three organisations (out of a total of 86) participated in the survey, yielding a 73.2% response rate. About half (n = 30; 47.6%) of the sample thought the need for SUD treatment had remained the same or had increased during the COVID-19 lockdown. Half the sample (n = 32; 50.7%) reported decreased availability of SUD services during COVID-19 lockdowns. Participants believed that the lack of services during COVID-19 lockdown impacted negatively on patients that were enrolled in their programmes and on individuals who wished to access the service. Furthermore, changes in service provision seemed to increase patients’ anxiety, exacerbate pre-existing mental health problems and in some cases were thought to precipitate relapse. In addition, patient disengagement and attrition from treatment were thought to have increased during this period. Whilst 47.6% (n = 30) of providers agreed with the value of the alcohol ban, 23.8% (n = 15) of providers thought it had unintended negative consequences.

Conclusion
Based on the findings it is evident that SUD treatment services in South Africa have been significantly affected during the COVID-19 pandemic and more severely during the onset of the pandemic. Together with service providers, more effective ways should be sought on how to feasibly expand access to SUD treatment for all South Africans and enhance the country’s preparedness for future health emergencies.
A novel open synovectomy technique using an arthroscopy shaver blade in revision surgery to treat infected total knee arthroplasty: a technical note
Authors: Shon Oog-Jin , Lee In Jun , Kim Gi Beom 
Published: March 2022

Abstract
Background
This article introduces a novel open synovectomy technique using an arthroscopy shaver blade to effectively remove intra-articular synovitis during revision surgery for infected primary total knee arthroplasty.

Methods (techniques)
Open synovectomy is performed using a 4.2-mm arthroscopy shaver blade, and the handpiece is connected to suction drainage. Suction is supplied through the central cylinder of the shaver blade to bring the debrided fragments of soft tissue into the window. Grossly inflamed, reddened, diseased synovium is debrided to reveal yellowish, healthy synovium. The inflamed tissues of the knee joint (suprapatellar pouch, medial and lateral gutters, and peripatellar area) are debrided. Then, with maintaining full flexion of the knee joint, a shaver equipped with a longer bar can be used to easily access the medial and lateral posterior compartments, which are generally difficult to access.

Results
During a mean of 13.5-month follow-up, there was no recurrent infection in either group; however, patients who underwent the novel technique improved significantly faster in terms of acute serological markers during the first period.

Conclusions
This technique yielded favorable outcomes compared with the conventional technique. In particular, it may facilitate the approach to the posterior joint space, which is difficult to access.