Primary paediatric epidural sarcomas are extremely rare. Overall, there remains a paucity of knowledge in paediatric epidural sarcomas owing to the infrequent number of cases. The Archer FusionPlex ...Sarcoma Kit (ArcherDX, Inc) is a next-generation sequencing assay that has been reported to be a useful technique to detect recurrent fusion in sarcomas. We report the molecular exploration of 3 primary paediatric epidural sarcomas-one in the cranium (mesenchymal chondrosarcoma) and 2 in the spine (mesenchymal chondrosarcoma and Ewing sarcoma respectively).
This is a study approved by the hospital ethics board. Clinico-pathological information from 3 consenting patients with primary epidural sarcomas was collected. These selected tumours are interrogated via Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) for genomic aberrations. Results were validated with RT-PCR and Sanger sequencing. All findings are corroborated and discussed in concordance with current literature. Our findings show 2 variants of the HEY1-NCOA2 gene fusion: HEY1 (exon 4)-NCOA2 (exon 13) and HEY1 (exon 4)-NCOA2 (exon 14), in both mesenchymal chondrosarcoma patients. Next, the Ewing sarcoma tumour is found to have EWSR1 (exon 10)-FLI1 (exon 8) translocation based on NGS. This result is not detected via conventional fluorescence in situ testing.
This is a molecularly-centered study based on 3 unique primary paediatric epidural sarcomas. Our findings to add to the growing body of literature for these exceptionally rare and malignant neoplasms. The authors advocate global collaborative efforts and in-depth studies for targeted therapy to benefit affected children.
Lipid droplets (LDs) are phylogenetically conserved cytoplasmic organelles that store neutral lipids within a phospholipid monolayer. LDs compartmentalize lipids and may help to prevent cellular ...damage caused by their excess or bioactive forms. FIT2 is a ubiquitously expressed transmembrane endoplasmic reticulum (ER) membrane protein that has previously been implicated in LD formation in mammalian cells and tissue. Recent data indicate that FIT2 plays an essential role in fat storage in an in vivo constitutive adipose FIT2 knock-out mouse model, but the physiological effects of postnatal whole body FIT2 depletion have never been studied. Here, we show that tamoxifen-induced FIT2 deletion using a whole body ROSA26CreERT2-driven FIT2 knock-out (iF2KO) mouse model leads to lethal intestinal pathology, including villus blunting and death of intestinal crypts, and loss of lipid absorption. iF2KO mice lose weight and die within 2 weeks after the first tamoxifen dose. At the cellular level, LDs failed to form in iF2KO enterocytes after acute oil challenge and instead accumulated within the ER. Intestinal bile acid transporters were transcriptionally dysregulated in iF2KO mice, leading to the buildup of bile acids within enterocytes. These data support the conclusion that FIT2 plays an essential role in regulating intestinal health and survival postnatally.
Background: FIT2 is an ER protein implicated in regulating cytosolic LD formation in mammals.
Results: FIT2 deficiency in an inducible whole body knock-out mouse model leads to lethal enteropathy.
Conclusion: FIT2 is required for normal intestinal homeostasis and survival.
Significance: This study provides evidence that FIT2 is essential for murine intestinal health.
To validate EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires and to measure the health-related quality of life (HRQOL) of women with breast cancer in Singapore during their first 4 years of ...post-diagnosis and treatments.
A quantitative and cross-descriptive sectional study. All of 170 subjects were recruited in a Singapore tertiary cancer center. The European Organization for Research and Treatment-QOL questionnaire and breast cancer specific module (EORTC QLQ-C30 and QLQ-BR23) were used to measure the HRQOL among women with breast cancer. All statistical tests were performed using SPSS Version 18. The reliability of the EORTC QLQ-C30 and QLQ-BR23 questionnaires was examined using Cronbach’s alpha test. EORTC QLQ-C30 was validated against EuroQol Group’s 5-domain questionnaires (EQ5D) by examining its concurrent validity using Pearson Product Moment Correlation to calculate the total scores.
The Cronbach’s alpha coefficient results for EORTC QLQ-C30 and QLQ BR-23 were 0.846 and 0.873 respectively which suggested relatively good internal consistency. The correlation between EORTC QLQ-C30 and EQ5D QOL instruments demonstrated a modest linear relationship (r=0.597; P<0.001) that indicated a moderately strong correlation between the two measures. The study showed that Singaporean women with breast cancer had enjoyed high levels of HRQOL during their first 4 years of survivorship but they had significant concern over the financial impact of breast cancer. One of the key findings was younger women had experienced more physical and psychosocial concerns than older women.
The EORTC QLQ-C30 and QLQ-BR23 questionnaires are feasible and promising instruments to measure the levels of HRQOL in Singaporean women with breast cancer in future studies.
Ischemic heart disease, which is often associated with irreversibly damaged heart muscle, is a major global health burden. Here, we report the potential of stem cell-derived committed cardiac ...progenitors (CCPs) have in regenerative cardiology. Human pluripotent embryonic stem cells were differentiated to CCPs on a laminin 521 + 221 matrix, characterized with bulk and single-cell RNA sequencing, and transplanted into infarcted pig hearts. CCPs differentiated for eleven days expressed a set of genes showing higher expression than cells differentiated for seven days. Functional heart studies revealed significant improvement in left ventricular ejection fraction at four and twelve weeks following transplantation. We also observed significant improvements in ventricular wall thickness and a reduction in infarction size after CCP transplantation (p-value < 0.05). Immunohistology analyses revealed in vivo maturation of the CCPs into cardiomyocytes (CM). We observed temporary episodes of ventricular tachyarrhythmia (VT) in four pigs and persistent VT in one pig, but the remaining five pigs exhibited normal sinus rhythm. Importantly, all pigs survived without the formation of any tumors or VT-related abnormalities. We conclude that pluripotent stem cell-derived CCPs constitute a promising possibility for myocardial infarction treatment and that they may positively impact regenerative cardiology.
Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer in adults. In addition, these patients also suffered from a low grade inflammation that ...activates the immune system and thus increased shunting of energy to host defense mechanisms. To assess whether a H. pylori infection could affect growth in early life, we determined the expression levels of selected metabolic gut hormones in germ free (GF) and specific pathogen-free (SPF) mice with and without the presence of H. pylori. Despite H. pylori-infected (SPFH) mice display alteration in host metabolism (elevated levels of leptin, insulin and peptide YY) compared to non-infected SPF mice, their growth curves remained the same. SPFH mice also displayed increased level of eotaxin-1. Interestingly, GF mice infected with H. pylori (GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced weight gain and malnutrition. These preliminary findings show that exposure to H. pylori alters host metabolism early in life; but the commensal microbiota in SPF mice can attenuate the growth retarding effect from H. pylori observed in GF mice. Further investigations of possible additional side effects of H. pylori are highly warranted.
The multidimensional Positive Mental Health Instrument (PMHI) has 47 items and six subscales. This study aimed to develop and validate a short unidimensional version of the PMHI among Singapore's ...adult resident population.
Using pooled data from three earlier studies (n = 1050), PMHI items were reduced by Partial Credit Rasch Model (PCRM) runs in a random split-half sample, while psychometric properties of the resulting measure were tested through confirmatory factor analysis (CFA), item response theory-graded response model and internal consistency reliability in the other half. Its reliability, construct and concurrent validity, agreement with the original scale, floor and ceiling effect, and scale estimates were further investigated in an external representative general population sample (n = 1925).
The average age of the participants was around 41 years. Four PCRM re-runs for item selection resulted in a 6-item unidimensional Rapid PMHI (R-PMHI). CFA confirmed the unidimensional structure of the R-PMHI in the internal (RMSEA = 0.075, CFI = 0.985, TLI = 0.974) and external (RMSEA = 0.051, CFI = 0.992, TLI = 0.987) validation samples. In the external validation sample, the R-PMHI met concurrent validity criteria, showing high agreement with the 47-item version with intra-class correlation coefficient of 0.872 (95% CI: 0.861 to 0.882) and low floor and ceiling effects. Weight-adjusted mean (SE, 95% CI) R-PMHI score in the population was 4.86 (0.2, 4.82-4.90).
The unidimensional 6-item R-PMHI offers brevity over the original multidimensional measure while appropriately representing the positive mental health construct. Prospective studies are needed to assess its responsiveness and test-retest reliability.
Background Deletion of 1p is associated with poor prognosis in neuroblastoma, however selected 1p-intact patients still experience poor outcomes. Since mutations of 1p genes may mimic the deleterious ...effects of chromosomal loss, we studied the incidence, spectrum and effects of mutational variants in 1p-intact neuroblastoma. Methods We characterized the 1p status of 325 neuroblastoma patients, and correlated the mutational status of 1p tumor suppressors and neuroblastoma candidate genes with survival outcomes among 100 1p-intact cases, then performed functional validation of selected novel variants of 1p36 genes identified from our patient cohort. Results Among patients with adverse disease characteristics, those who additionally had 1p deletion had significantly worse overall survival. Among 100 tumor-normal pairs sequenced, somatic mutations of 1p tumor suppressors KIF1Bbeta and CHD5 were most frequent (2%) after ALK and ATRX (8%), and BARD1 (3%). Mutations of neuroblastoma candidate genes were associated with other synchronous mutations and concurrent 11q deletion (P = 0.045). In total, 24 of 38 variants identified were novel and predicted to be deleterious or pathogenic. Functional validation identified novel KIF1Bbeta I1355M variant as a gain-of-function mutation with increased expression and tumor suppressive activity, correlating with indolent clinical behavior; another novel variant CHD5 E43Q was a loss-of-function mutation with decreased expression and increased long-term cell viability, corresponding with aggressive disease characteristics. Conclusions Our study showed that chromosome 1 gene mutations occurred frequently in 1p-intact neuroblastoma, but may not consistently abrogate the function of bonafide 1p tumor suppressors. These findings may augment the evolving model of compounding contributions of 1p gene aberrations toward tumor suppressor inactivation in neuroblastoma. Keywords: Neuroblastoma, Chromosome 1, Tumor suppressor, Next-generation sequencing, Synchronous Mutations
We have developed a unique DNA-assembled gold nanoparticles (AuNPs) dimer for dynamic light scattering (DLS) sensing of transcription factors, exemplified by estrogen receptor (ER) that binds ...specifically to a double-stranded (ds) DNA sequence containing estrogen response element (ERE). Here, ERE sequence is incorporated into the DNA linkers to bridge the AuNPs dimer for ER binding. Coupled with DLS, this AuNP dimer-based DLS detection system gave distinct readout of a single 'complex peak' in the presence of the target molecule (i.e., ER). This unique signature marked the first time that such nanostructures can be used to study transcription factor-DNA interactions, which DLS alone cannot do. This was also unlike previously reported AuNP-DLS assays that gave random and broad distribution of particles size upon target binding. In addition, the ERE-containing AuNP dimers could also suppress the light-scattering signal from the unbound proteins and other interfering factors (e.g., buffer background), and has potential for sensitive detection of target proteins in complex biological samples such as cell lysates. In short, the as-developed AuNP dimer probe coupled with DLS is a simple (mix and test), rapid (readout in ~5 min) and sensitive (low nM levels of ER) platform to detect sequence-specific protein-DNA binding event.
Most agricultural activities generate a significant quantity of biomass waste that has not been fully utilized. This study utilized palm kernel shells as the primary material to produce sulfonated ...magnetic palm kernel shell biochar. The post-sulfonation magnetic palm kernel shell biochar had a greater particle size of around 137 nm compared to the pre-sulfonation biochar. This increase in size can be attributed to the presence of the − SO
3
H group. The biochar that underwent post-sulfonation was chosen for a techno-economic evaluation to ascertain its viability in terms of economics and energy efficiency. Soybean straw and coconut shell-derived biochar were chosen for the techno-economic assessment. The energy intake for soybean straws, coconut shells, and palm kernel shells derived from biochar is 48.85 MJ∙kg
−1
, 23.83 MJ∙kg
−1
, and 52.44 MJ∙kg
−1
, respectively. The energy output for soybean straws, coconut shells, and palm kernel shells derived biochar is determined to be 22.54 MJ∙kg
−1
, 23.68 MJ∙kg
−1
, and 31.55 MJ∙kg
−1
, respectively. The ultimate profit-to-cost ratios of soybean straws, coconut shells, and palm kernel shells derived biochar are 0.21, 4.92, and 1.11, respectively. The techno-economic assessment indicates that coconut shell-derived biochar production is favourable, primarily due to its attributes of low net energy balance, high porosity, and lower density. Both coconut shells and palm kernel shells derived biochar productions are economically viable and efficient due to their high profit-to-cost ratio. The microwave-assisted technology is proven efficient and demands less energy to generate an equivalent quantity of biochar compared to traditional furnaces.
Article Highlights
Pyrolysis of sulfonated magnetic waste palm kernel shell are studied by economic and energy analysis.
A comparison between coconut shell-derived biochar and soybean straw-derived biochar is made.
Coconut shell-derived biochar performs better in energy and economic analysis.
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