Health-related quality of life in pediatric patients with leukemia in Singapore: a cross-sectional pilot study

There has been a paradigm shift in health service delivery to a more holistic approach, which considers Quality of Life (QoL) and overall functioning. Health-Related Quality of Life (HRQoL) is a multidimensional construct that encompasses physical functioning as well as psychosocial aspects of emotional and social functioning. This study explored factors related to HRQoL in Asian pediatric patients with leukemia in Singapore. The available variables included: age, treatment duration, household income, gender, ethnicity, religion, diagnosis, and phase of treatment. It is hypothesized that the relationships will be significant. In the current study, there were 60 patients (60% males) with leukemia; their ages ranged from 1 to 21 years (Mean = 8.03, Standard Deviation = 4.55). The hypothesis was partially supported. Age had a significant positive relationship with physical functioning, r(60) = 0.28, p < 0.05, physical health, r(60) = 0.28, p < 0.05, and the total HRQoL score, r(60) = 0.29, p < 0.05. Treatment duration had a positive relationship with school functioning, r(60) = 0.28, p < 0.05. All other correlations were statistically non-significant. The effects of the available psychosocial variables of gender, ethnicity, and religion were examined on scores from the Pediatric Quality of Life Inventory (PedsQL). Ethnicity had a significant effect on social functioning, U = 292.00, p < 0.05, r = 0.3 (medium effect size). Specifically, Chinese (Median = 85.00, n = 33) had significantly higher scores on social functioning than others (Median = 70.00, n = 27). The remaining comparisons were statistically non-significant. The current findings added to QoL research, and provided an impetus for more research in the area of HRQoL for children with leukemia in Singapore

Functional Hand Proportion is Approximated by the Fibonacci Series

The debatable relationship of functional human hand proportion with the Fibonacci series has remained an obscure scientific enigma short of clinical interest. The main difficulty of proving such a relationship lies in defining what should constitute true "functional" proportion. In this study, we re-evaluate this unique relationship using hand flexion creases as anatomical surrogates for the functional axes of joint rotation. Standardized desktop photocopies of palmar views of both hands in full digital extension and abduction were obtained from 100 healthy male volunteers of Chinese ethnicity. The functional axes were represented by the distal digital crease (distal interphalangeal joint, DIPJ), proximal digital crease (proximal interphalangeal joint, PIPJ), as well as the midpoint between the palmar digital and transverse palmar creases (metacarpophalangeal joint, MCPJ). The ratio of DIPJ-Fingertip:PIPJ-DIPJ:MCPJ-PIPJ (p3:p2:p1) were measured by two independent observers and represented as standard deviation about the mean, and then compared to the theoretical ratio of 1:1:2. Our results showed that, for the 2nd to 5th digits, the p2:p3 ratios were 0.97±0.09, 1.10±0.10, 1.04±0.12 and 0.80±0.08 respectively; whilst the p1:p2 ratios were 1.91±0.17, 1.98±0.14, 1.89±0.16 and 2.09±0.24 respectively. When the data were analyzed for all digits, they showed a combined p3:p2:p1 ratio of 1:0.98:2.01. In conclusion, our results suggest that functional human hand proportion, as defined by flexion creases, is approximated by the Fibonacci series

Tailor-Made Zinc-Finger Transcription Factors Activate FLO11 Gene Expression with Phenotypic Consequences in the Yeast Saccharomyces cerevisiae

Cys2His2 zinc fingers are eukaryotic DNA-binding motifs, capable of distinguishing different DNA sequences, and are suitable for engineering artificial transcription factors. In this work, we used the budding yeast Saccharomyces cerevisiae to study the ability of tailor-made zinc finger proteins to activate the expression of the FLO11 gene, with phenotypic consequences. Two three-finger peptides were identified, recognizing sites from the 5′ UTR of the FLO11 gene with nanomolar DNA-binding affinity. The three-finger domains and their combined six-finger motif, recognizing an 18-bp site, were fused to the activation domain of VP16 or VP64. These transcription factor constructs retained their DNA-binding ability, with the six-finger ones being the highest in affinity. However, when expressed in haploid yeast cells, only one three-finger recombinant transcription factor was able to activate the expression of FLO11 efficiently. Unlike in the wild-type, cells with such transcriptional activation displayed invasive growth and biofilm formation, without any requirement for glucose depletion. The VP16 and VP64 domains appeared to act equally well in the activation of FLO11 expression, with comparable effects in phenotypic alteration. We conclude that the functional activity of tailor-made transcription factors in cells is not easily predicted by the in vitro DNA-binding activity

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate

Hepatitis C Virus Antigenic Convergence

Vaccine development against hepatitis C virus (HCV) is hindered by poor understanding of factors defining cross-immunoreactivity among heterogeneous epitopes. Using synthetic peptides and mouse immunization as a model, we conducted a quantitative analysis of cross-immunoreactivity among variants of the HCV hypervariable region 1 (HVR1). Analysis of 26,883 immunological reactions among pairs of peptides showed that the distribution of cross-immunoreactivity among HVR1 variants was skewed, with antibodies against a few variants reacting with all tested peptides. The HVR1 cross-immunoreactivity was accurately modeled based on amino acid sequence alone. The tested peptides were mapped in the HVR1 sequence space, which was visualized as a network of 11,319 sequences. The HVR1 variants with a greater network centrality showed a broader cross-immunoreactivity. The entire sequence space is explored by each HCV genotype and subtype. These findings indicate that HVR1 antigenic diversity is extensively convergent and effectively limited, suggesting significant implications for vaccine development

Drosophila orthologue of WWOX, the chromosomal fragile site FRA16D tumour suppressor gene, functions in aerobic metabolism and regulates reactive oxygen species

Common chromosomal fragile sites FRA3B and FRA16D are frequent sites of DNA instability in cancer, but their contribution to cancer cell biology is not yet understood. Genes that span these sites (FHIT and WWOX, respectively) are often perturbed (either increased or decreased) in cancer cells and both are able to suppress tumour growth. While WWOX has some tumour suppressor characteristics, its normal role and functional contribution to cancer has not been fully determined. We find that a significant proportion of Drosophila Wwox interactors identified by proteomics and microarray analyses have roles in aerobic metabolism. Functional relationships between Wwox and either CG6439/isocitrate dehydrogenase (Idh) or Cu–Zn superoxide dismutase (Sod) were confirmed by genetic interactions. In addition, altered levels of Wwox resulted in altered levels of endogenous reactive oxygen species. Wwox (like FHIT) contributes to pathways involving aerobic metabolism and oxidative stress, providing an explanation for the ‘non-classical tumour suppressor’ behaviour of WWOX. Fragile sites, and the genes that span them, are therefore part of a protective response mechanism to oxidative stress and likely contributors to the differences seen in aerobic glycolysis (Warburg effect) in cancer cells

Bioinformatics research in the Asia Pacific: a 2007 update

We provide a 2007 update on the bioinformatics research in the Asia-Pacific from the Asia Pacific Bioinformatics Network (APBioNet), Asia's oldest bioinformatics organisation set up in 1998. From 2002, APBioNet has organized the first International Conference on Bioinformatics (InCoB) bringing together scientists working in the field of bioinformatics in the region. This year, the InCoB2007 Conference was organized as the 6th annual conference of the Asia-Pacific Bioinformatics Network, on Aug. 27–30, 2007 at Hong Kong, following a series of successful events in Bangkok (Thailand), Penang (Malaysia), Auckland (New Zealand), Busan (South Korea) and New Delhi (India). Besides a scientific meeting at Hong Kong, satellite events organized are a pre-conference training workshop at Hanoi, Vietnam and a post-conference workshop at Nansha, China. This Introduction provides a brief overview of the peer-reviewed manuscripts accepted for publication in this Supplement. We have organized the papers into thematic areas, highlighting the growing contribution of research excellence from this region, to global bioinformatics endeavours

Efficient error correction for next-generation sequencing of viral amplicons

<p>Abstract</p> <p>Background</p> <p>Next-generation sequencing allows the analysis of an unprecedented number of viral sequence variants from infected patients, presenting a novel opportunity for understanding virus evolution, drug resistance and immune escape. However, sequencing in bulk is error prone. Thus, the generated data require error identification and correction. Most error-correction methods to date are not optimized for amplicon analysis and assume that the error rate is randomly distributed. Recent quality assessment of amplicon sequences obtained using 454-sequencing showed that the error rate is strongly linked to the presence and size of homopolymers, position in the sequence and length of the amplicon. All these parameters are strongly sequence specific and should be incorporated into the calibration of error-correction algorithms designed for amplicon sequencing.</p> <p>Results</p> <p>In this paper, we present two new efficient error correction algorithms optimized for viral amplicons: (i) k-mer-based error correction (KEC) and (ii) empirical frequency threshold (ET). Both were compared to a previously published clustering algorithm (SHORAH), in order to evaluate their relative performance on 24 experimental datasets obtained by 454-sequencing of amplicons with known sequences. All three algorithms show similar accuracy in finding true haplotypes. However, KEC and ET were significantly more efficient than SHORAH in removing false haplotypes and estimating the frequency of true ones.</p> <p>Conclusions</p> <p>Both algorithms, KEC and ET, are highly suitable for rapid recovery of error-free haplotypes obtained by 454-sequencing of amplicons from heterogeneous viruses.</p> <p>The implementations of the algorithms and data sets used for their testing are available at: <url>http://alan.cs.gsu.edu/NGS/?q=content/pyrosequencing-error-correction-algorithm</url></p

Hepatitis C Virus Infection in Phenotypically Distinct Huh7 Cell Lines

In 2005, the first robust hepatitis C virus (HCV) infectious cell culture system was developed based on the HCV genotype 2a JFH-1 molecular clone and the human-derived hepatoma cell line Huh7. Although much effort has been made to dissect and expand the repertoire of JFH-1-derived clones, less attention has been given to the host cell despite the intriguing facts that thus far only Huh7 cells have been found to be highly permissive for HCV infection and furthermore only a limited number of Huh7 cell lines/stocks appear to be fully permissive. As such, we compiled a panel of Huh7 lines from disparate sources and evaluated their permissiveness for HCV infection. We found that although Huh7 lines from different laboratories do vary in morphology and cell growth, the majority (8 out of 9) were highly permissive for infection, as demonstrated by robust HCV RNA and de novo infectious virion production following infection. While HCV RNA levels achieved in the 8 permissive cell lines were relatively equivalent, three Huh7 lines demonstrated higher infectious virion production suggesting these cell lines more efficiently support post-replication event(s) in the viral life cycle. Consistent with previous studies, the single Huh7 line found to be relatively resistant to infection demonstrated a block in HCV entry. These studies not only suggest that the majority of Huh7 cell lines in different laboratories are in fact highly permissive for HCV infection, but also identify phenotypically distinct Huh7 lines, which may facilitate studies investigating the cellular determinants of HCV infection