Nasopharyngeal carcinoma (NPC) is an Epstein‐Barr virus (EBV)‐associated epithelial malignancy. The high expression of BART‐miRNAs (miR‐BARTs) during latent EBV infection in NPC strongly supports ...their pathological importance in cancer progression. Recently, we found that several BART‐miRNAs work co‐operatively to modulate the DNA damage response (DDR) by reducing Ataxia‐telangiectasia‐mutated (ATM) activity. In this study, we further investigated the role of miR‐BARTs on DDR. The immunohistochemical study showed that the DNA repair gene, BRCA1, is consistently down‐regulated in primary NPCs. Using computer prediction programs and a series of reporter assays, we subsequently identified the negative regulatory role of BART2‐3p, BART12, BART17‐5p and BART19‐3p in BRCA1 expression. The ectopic expression of these four miR‐BARTs suppressed endogenous BRCA1 expression in EBV‐negative epithelial cell lines, whereas BRCA1 expression was enhanced by repressing endogenous miR‐BARTs activities in C666‐1 cells. More importantly, suppressing BRCA1 expression in nasopharyngeal epithelial cell lines using miR‐BART17‐5p and miR‐BART19‐3p mimics reduced the DNA repair capability and increased the cell sensitivity to the DNA‐damaging chemotherapeutic drugs, cisplatin and doxorubicin. Our findings suggest that miR‐BARTs play a novel role in DDR and may facilitate the development of effective NPC therapies.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
青少年學生面對升學就業選擇時，往往尋求家人和朋友幫助。但對於缺乏文化及 社會資本的基層家庭學生來說，其識見及可得到的資訊有限，他們參與校內或校外的 升學就業活動更為重要。在這些活動中，透過「商界－學校」協作推出的活動，能為 弱勢學生提供更實際的升學就業資訊及職場體驗。本研究於2013 年收集了3,800 多 位曾參與香港一項「商界－學校」協作計劃的中學生的問卷數據，並以多元迴歸模型 ...分析方法，探討弱勢學生參與升學就業活動與他們掌握升學就業技能的關係。結果 顯示，若把學生的個人及家庭背景因素（性別、出生地、家庭結構及社經地位）納入 分析，弱勢學生透過參與由商界機構提供的升學就業活動，對他們掌握升學及就業 技能方面具有顯著的正面影響, In most cases, adolescents seek help from their parents and peers when facing the postsecondary decision: continuing education or going for immediate employment. However to those from underprivileged families lacking cultural and social capitals, the exposure and information accessible are limited in preparing them for future development. In such case, participation in activities inside and outside of school is important to them. In particular, activities initiated in the model of “business–school” partnership are seen as good sources of practical information and relevant experiences. The present study collected survey data from a large-scale “business– school” partnership project in Hong Kong, in
Overexpression of high mobility group AT-hook 1 (HMGA1) is common in human cancers. Little is known about the mechanisms underlying its deregulation and downstream targets, and information about its ...clinical and biological significance in medulloblastoma (MB) is lacking. Here, we demonstrated frequent genomic gain at 6p21.33–6p21.31 with copy number increase leading to overexpression of HMGA1 in MB. The overexpression correlated with a high proliferation index and poor prognosis. Moreover, we found that hsa-miR-124a targeted 3′UTR of HMGA1 and negatively modulated the expression in MB cells, indicating that loss/downregulation of hsa-miR-124a reported in our previous study could contribute to the overexpression. Regarding the biological significance of HMGA1, siRNA knockdown and ectopic expression studies revealed the crucial roles of HMGA1 in controlling MB cell growth and migration/invasion through modulation of apoptosis and formation of filopodia and stress fibers, respectively. Furthermore, we identified cdc25A as a target of HMGA1 and showed that physical interaction between HMGA1 and the cdc25A promoter is required for transcriptional upregulation. In clinical samples, HMGA1 and cdc25A were concordantly overexpressed. Functionally, cdc25A is involved in the HMGA1-mediated control of MB cell growth. Finally, netropsin, which competes with HMGA1 in DNA binding, reduced the expression of cdc25A by suppression of its promoter activity and inhibited in vitro and in vivo intracranial MB cell growth. In conclusion, our results delineate the mechanisms underlying the deregulation and reveal the functional significance of HMGA1 in controlling MB cell growth and migration/invasion. Importantly, the results highlight the therapeutic potential of targeting HMGA1 in MB patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
An increasing and aging patient population poses a growing burden on healthcare professionals. Automation of medical imaging diagnostics holds promise for enhancing patient care and reducing manpower ...required to accommodate an increasing patient-population. Deep learning, a subset of machine learning, has the potential to facilitate automated diagnostics, but commonly requires large-scaled labeled datasets. In medical domains, data is often abundant but labeling is a laborious and costly task. Active learning provides a method to optimize the selection of unlabeled samples that are most suitable for improvement of the model and incorporate them into the model training process. This approach proves beneficial when only a small number of labeled samples are available. Various selection methods currently exist, but most of them employ fixed querying schedules. There is limited research on how the timing of a query can impact performance in relation to the number of queried samples. This paper proposes a novel approach called dynamic querying, which aims to optimize the timing of queries to enhance model development while utilizing as few labeled images as possible. The performance of the proposed model is compared to a model trained utilizing a fully-supervised training method, and its effectiveness is assessed based on dataset size requirements and loss rates. Dynamic querying demonstrates a considerably faster learning curve in relation to the number of labeled samples used, achieving an accuracy of 70% using only 24 samples, compared to 82% for a fully-supervised model trained on the complete training dataset of 1017 images.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Denture plaque, a biofilm that develops on denture surfaces, could contribute to many oral and systemic afflictions. Hence, a quantitative assessment of denture plaque is important to evaluate the ...denture hygiene of denture wearers, particularly to prevent plaque biofilm-associated diseases. The aim of this systematic review, therefore, was to review and summarize the visual denture hygiene assessment methods using denture plaque indices and with planimetries published in the literature. English language studies published up to March 2022 in four electronic databases, PubMed, Medline, Embase, and Cochrane Library, were searched, followed by a manual search of Google Scholar by two assessors. The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) whenever possible. Details of the visual assessment methods, including the types of denture assessed, its materials and its surfaces, as well as the use of a disclosing agent, were the main outcomes. Of 492 screened studies, 74 were included per the inclusion and exclusion criteria. Of these, 60 studies utilized various denture plaque indices while 18 used planimetries. 43 out of 60 studies with indices and 17 out of 18 studies with planimetries used disclosing agents for visual evaluation of plaque. A total of 21 indices were described in the included studies, of which seven graded a divided denture surface, while the remainder graded entire denture surface. Of the 18 planimetric assessments, one study quantified squares of the disclosed plaques on denture images, 16 studies quantified such pixels with computer programs, and a single study quantified points, pixels, and contour of plaque areas. In summary, denture plaque indices appear to be popular in denture plaque assessment due to their simplicity. Computerized planimetric assessment, though more time-consuming, provides a more accurate assessment of plaque load as it is less prone to subjectivity and assessor errors.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Digital workflows for digital complete denture fabrication have a variety of clinical and laboratory procedures, but their outcomes and associated complications are currently unknown.
The purpose of ...this systematic review was to evaluate the clinical and laboratory procedures for digital complete dentures, their outcomes, and associated complications.
Electronic literature searches were conducted on PubMed/Medline, Embase, and Web of Science for studies published from January 2000 to September 2022 and screened by 2 independent reviewers. Information on digital complete denture procedures, materials, their outcomes, and associated complications was extracted.
Of 266 screened studies, 39 studies were included. While 26 assessed definitive complete dentures, 7 studies assessed denture bases, 2 assessed trial dentures, and 4 assessed the digital images only. Twenty-four studies used border molded impression technique, 3 studies used a facebow record, and 7 studies used gothic arch tracing. Only 13 studies performed trial denture placement. Twenty-one studies used milling, and 17 studies used 3D printing for denture fabrication. One study reported that the retention of maxillary denture bases fabricated from a border-molded impression (14.5 to 16.1 N) was statistically higher than the retention of those fabricated from intraoral scanning (6.2 to 6.6 N). The maximum occlusal force of digital complete denture wearers was similar across different fabrication procedures. When compared with the conventional workflow, digital complete dentures required statistically shorter clinical time with 205 to 233 minutes saved. Up to 37.5% of participants reported loss of retention and up to 31.3% required a denture remake. In general, ≥1 extra visit and 1 to 4 unscheduled follow-up visits were needed. The outcomes for patient satisfaction and oral health-related quality of life were similar between conventional, milled, and 3D-printed complete dentures.
Making a border-molded impression is still preferred for better retention, and trial denture placement is still recommended to optimize the fabrication of definitive digital complete dentures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Alterations in the anatomic and biomechanical properties of the ascending aorta (AAo) can give rise to various vascular pathologies. The aim of the current study is to gain additional insights in the ...biology of the AAo size and function.
We developed an AI based analysis pipeline for the segmentation of the AAo, and the extraction of AAO parameters. We then performed genome-wide association studies of AAo maximum area, AAo minimum area and AAo distensibility in up to 37,910 individuals from the UK Biobank. Variants that were significantly associated with AAo phenotypes were used as instrumental variables in Mendelian randomization analyses to investigate potential causal relationships with coronary artery disease, myocardial infarction, stroke and aneurysms.
Genome-wide association studies revealed a total of 107 SNPs in 78 loci. We annotated 101 candidate genes involved in various biological processes, including connective tissue development (THSD4 and COL6A3). Mendelian randomization analyses showed a causal association with aneurysm development, but not with other vascular diseases.
We identified 78 loci that provide insights into mechanisms underlying AAo size and function in the general population and provide genetic evidence for their role in aortic aneurysm development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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