This paper demonstrates that a shift from a purely technical to a more socio-technical perspective has significant implications for the conceptualization, design, and implementation of smart city ...technologies. Such implications are discussed and illustrated through the case of an emerging urban analytics tool, the City-scale Digital Twin. Based on interdisciplinary insights and a participatory knowledge co-production and tool co-development process, including both researchers and prospective users, we conclude that in order to move beyond a mere "hype technology," City-Scale Digital Twins must reflect the specifics of the urban and socio-political context.
PIWI-interacting RNAs (piRNAs) are emerging players in cancer genomics. Originally described in the germline, there are over 20,000 piRNA genes in the human genome. In contrast to microRNAs, piRNAs ...interact with PIWI proteins, another member of the Argonaute family, and function primarily in the nucleus. There, they are involved in the epigenetic silencing of transposable elements in addition to the transcriptional regulation of genes. It has recently been demonstrated that piRNAs are also expressed across a variety of human somatic tissue types in a tissue-specific manner. An increasing number of studies have shown that aberrant piRNA expression is a signature feature across multiple tumour types; however, their specific tumorigenic functions remain unclear. In this article, we discuss the emerging functional roles of piRNAs in a variety of cancers, and highlight their potential clinical utilities.
Summary Background Clinical prognostic groupings for localised prostate cancers are imprecise, with 30–50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to ...test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. Methods We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy. We validated these indices in two independent cohorts of 154 (Memorial Sloan Kettering Cancer Center cohort MSKCC cohort) and 117 (Cambridge cohort) radical prostatectomy specimens from low-risk to high-risk patients. We applied unsupervised and supervised machine learning techniques to the copy-number profiles of 126 pre-image-guided radiotherapy diagnostic biopsies to develop prognostic signatures. Our primary endpoint was the development of a set of prognostic measures capable of stratifying patients for risk of biochemical relapse 5 years after primary treatment. Findings Biochemical relapse was associated with indices of tumour hypoxia, genomic instability, and genomic subtypes based on multivariate analyses. We identified four genomic subtypes for prostate cancer, which had different 5-year biochemical relapse-free survival. Genomic instability is prognostic for relapse in both image-guided radiotherapy (multivariate analysis hazard ratio HR 4·5 95% CI 2·1–9·8; p=0·00013; area under the receiver operator curve AUC 0·70 95% CI 0·65–0·76) and radical prostatectomy (4·0 1·6–9·7; p=0·0024; AUC 0·57 0·52–0·61) patients with prostate cancer, and its effect is magnified by intratumoral hypoxia (3·8 1·2–12; p=0·019; AUC 0·67 0·61–0·73). A novel 100-loci DNA signature accurately classified treatment outcome in the MSKCC low-risk to intermediate-risk cohort (multivariate analysis HR 6·1 95% CI 2·0–19; p=0·0015; AUC 0·74 95% CI 0·65–0·83). In the independent MSKCC and Cambridge cohorts, this signature identified low-risk to high-risk patients who were most likely to fail treatment within 18 months (combined cohorts multivariate analysis HR 2·9 95% CI 1·4–6·0; p=0·0039; AUC 0·68 95% CI 0·63–0·73), and was better at predicting biochemical relapse than 23 previously published RNA signatures. Interpretation This is the first study of cancer outcome to integrate DNA-based and microenvironment-based failure indices to predict patient outcome. Patients exhibiting these aggressive features after biopsy should be entered into treatment intensification trials. Funding Movember Foundation, Prostate Cancer Canada, Ontario Institute for Cancer Research, Canadian Institute for Health Research, NIHR Cambridge Biomedical Research Centre, The University of Cambridge, Cancer Research UK, Cambridge Cancer Charity, Prostate Cancer UK, Hutchison Whampoa Limited, Terry Fox Research Institute, Princess Margaret Cancer Centre Foundation, PMH-Radiation Medicine Program Academic Enrichment Fund, Motorcycle Ride for Dad (Durham), Canadian Cancer Society.
Once thought to be a part of the 'dark matter' of the genome, long non-coding RNAs (lncRNAs) are emerging as an integral functional component of the mammalian transcriptome. LncRNAs are a novel class ...of mRNA-like transcripts which, despite no known protein-coding potential, demonstrate a wide range of structural and functional roles in cellular biology. However, the magnitude of the contribution of lncRNA expression to normal human tissues and cancers has not been investigated in a comprehensive manner. In this study, we compiled 272 human serial analysis of gene expression (SAGE) libraries to delineate lncRNA transcription patterns across a broad spectrum of normal human tissues and cancers. Using a novel lncRNA discovery pipeline we parsed over 24 million SAGE tags and report lncRNA expression profiles across a panel of 26 different normal human tissues and 19 human cancers. Our findings show extensive, tissue-specific lncRNA expression in normal tissues and highly aberrant lncRNA expression in human cancers. Here, we present a first generation atlas for lncRNA profiling in cancer.
Unlike the studies of freshmen entrants, the learning experiences of community college transfer (CCT) students in the receiving university is a topic that has only started to gain attention in recent ...decades. Little is known about the differences between CCT and freshmen entrants with regard to their study workload stress and its relationship with their perceptions of the teaching and learning environment, approaches to learning, self-efficacy and generic skills. The purpose of our study was to address this gap. This was a cross-sectional survey study conducted from April 2018 to November 2018 in a university in Hong Kong. The HowULearn questionnaire was adapted to local usage and validated for data collection. In total, 841 CCT students and 978 freshmen entrants completed the survey. The respondents were aged between 19 and 52 years (mean = 21.6, SD = 1.92), and 66.0% were women. The HowULearn questionnaire was determined by factor analyses to have eight factors. The reliabilities of the eight factors were found to be acceptable (Cronbach alphas = 0.709-0.918). The CCT students scored significantly higher than the freshmen entrants for perceived study workload stress and surface approaches to learning, but lower on teaching for understanding & encouraging learning, peer support, and self-efficacy beliefs. The surface approach to learning, deep & organized studying, alignment & constructive feedback, and generic skills were found to be predictors of study workload stress in both groups of students, and in the overall student data. This study has shown that CCT students and freshmen entrants differed with regard to their study workload stress and learning experiences. Our findings provide a message, both for educators in higher education and policy makers in the government-there is not a one-size-fits-all approach to different student populations when it comes to enhancing their learning experiences.
Small cell lung cancer (SCLC) is a highly aggressive lung neoplasm with extremely poor clinical outcomes and no approved targeted treatments. To elucidate the mechanisms responsible for driving the ...SCLC phenotype in hopes of revealing novel therapeutic targets, we studied copy number and methylation profiles of SCLC. We found disruption of the E2F/Rb pathway was a prominent feature deregulated in 96% of the SCLC samples investigated and was strongly associated with increased expression of EZH2, an oncogene and core member of the polycomb repressive complex 2 (PRC2). Through its catalytic role in the PRC2 complex, EZH2 normally functions to epigenetically silence genes during development, however, it aberrantly silences genes in human cancers. We provide evidence to support that EZH2 is functionally active in SCLC tumours, exerts pro-tumourigenic functions in vitro, and is associated with aberrant methylation profiles of PRC2 target genes indicative of a "stem-cell like" hypermethylator profile in SCLC tumours. Furthermore, lentiviral-mediated knockdown of EZH2 demonstrated a significant reduction in the growth of SCLC cell lines, suggesting EZH2 has a key role in driving SCLC biology. In conclusion, our data confirm the role of EZH2 as a critical oncogene in SCLC, and lend support to the prioritization of EZH2 as a potential therapeutic target in clinical disease.
Inorganic arsenic is a well-established human carcinogen, able to induce genetic and epigenetic alterations. More than 200 million people worldwide are exposed to arsenic concentrations in drinking ...water exceeding the recommended WHO threshold (10μg/l). Additionally, chronic exposure to levels below this threshold is known to result in long-term health effects in humans. The arsenic-related health effects in humans are associated with its biotransformation process, whereby the resulting metabolites can induce molecular damage that accumulates over time. The effects derived from these alterations include genomic instability associated with oxidative damage, alteration of gene expression (including coding and non-coding RNAs), global and localized epigenetic reprogramming, and histone posttranslational modifications. These alterations directly affect molecular pathways involved in the onset and progression of many conditions that can arise even decades after the exposure occurs. Importantly, arsenic metabolites generated during its biotransformation can also pass through the placental barrier, resulting in fetal exposure to this carcinogen at similar levels to those of the mother. As such, more immediate effects of the arsenic-induced molecular damage can be observed as detrimental effects on fetal development, pregnancy, and birth outcomes. In this review, we focus on the genetic and epigenetic damage associated with exposure to low levels of arsenic, particularly those affecting early developmental stages. We also present how these alterations occurring during early life can impact the development of certain diseases in adult life.
Change detection using multi-sensor remote sensing images, such as synthetic aperture radar (SAR) and optical images, is poorly researched and thus remains a challenging task. In this study, we ...address this problem by proposing a novel automatic change detection method. Different sensors have completely different physical principles. Thus, the resulting multi-sensor images have completely different radiometric values. First, we introduce a sorted histogram concept that sorts the bins in descending order, noticing that multi-sensor images with absence of change have the same combination of objects, and each object in different images has the same proportions and a unique range of grey values. The sorted histogram discards the visual property correspondence between images and is capable of capturing the local internal image layout. Then, various histogram-based distances are employed to estimate the distance between each sorted histogram pair. After the whole image has been analysed, we obtain a divergence index map. The sorted histogram not only has the theoretical advantage of robustness in the intensity variations in multi-sensor images but also the practical advantage of low computational complexity compared with existing methods. Experiments on SAR and optical datasets with different resolutions show promising results in terms of detection capability and run time.
We explored whether parents of children with hematopathy had more psychosocial problems than parents of healthy children during the COVID-19 outbreak.
An online survey was performed, and a total of ...1,116 parents participated. The mental health variables were assessed via the Simplified Coping Style Questionnaire (SCSQ) and the Symptom Checklist-Revised (SCL-90-R).
Compared with parents of healthy children, parents of children with hematopathy have a higher possibility of negative coping style (70.9% vs. 33.2%, p=0.01) and are more concerned with media reports related to the pandemic (37.8% vs. 17.6%, p=0.02). In SCL-90-R somatization, obsessive-compulsive, and anxiety scale, the parents of children with hematopathy have higher scores than parents of healthy children (12.50±1.69 vs. 12.23±1.37, p<0.01; 13.42±6.69 vs. 10.47±2.25, p<0.01; 15.21±5.53 vs. 10.52±2.34, p<0.01, respectively). History of visiting Wuhan, and history of epidemics occurring in the community are independent risk factors of parental obsessive-compulsive and anxiety symptoms (p<0.01).
Parents of children with hematopathy had evident severe symptoms of obsessive-compulsive and anxiety during the outbreak of COVID-19. Providing psychological interventions and beneficial approaches to parents of children with hematopathy urgently needs to be realized.
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