Upregulation of the Wnt Co-Receptor LRP6 Promotes Hepatocarcinogenesis and Enhances Cell Invasion

Background: Activation of the Wnt/b-catenin signaling pathway plays a crucial role in hepatocellular carcinoma (HCC). Lowdensity lipoprotein (LDL) receptor-related protein-6 (LRP6) is one of the co-receptors of the Wnt/b-catenin pathway and forms a signaling complex with Wnt ligand and Frizzled receptor to activate downstream signaling. However, the role of LRP6 in hepatocarcinogenesis is unclear. In this study, we examined its expression and roles in human HCC. Methodology/Principal Findings: Using real-time quantitative RT-PCR, we found that LRP6 was frequently (45%) overexpressed in human HCCs (P = 0.003). In vitro studies showed that ectopic expression of LRP6 increased the protein level of b-catenin. Moreover, overexpression of the full-length and constitutively active LRP6, respectively, activated the WNT/b-catenin signaling pathway, as shown by the TCF/b-catenin reporter assay. With regard to the effects of LRP6 overexpression in HCC cells, stable overexpression of the constitutively active LRP6 in BEL-7402 HCC cells enhanced cell proliferation, cell migration, and invasion in vitro as well as tumorigenicity in nude mice. Conclusions/Significance: Our findings indicate that overexpression of LRP6 contributes to the hyperactivation of the Wnt

COVID-19 In Children Across Three Asian Cosmopolitan Regions

As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p < 0.001, respectively) and had more imported cases (87.5% vs. 16.5% vs. 0%, p < 0.001, respectively). The imported cases were also older (13.4 vs. 7.6 years, p < 0.001). More cases in HKSAR were asymptomatic compared to Korea and Wuhan (45.5% vs. 22.0% vs. 20.9%, p < 0.001, respectively), and significantly more patients from Wuhan developed fever (40.6% vs. 29.7% vs. 21.6%, p=0.003, respectively). There were significantly less imported cases than domestic cases developing fever after adjusting for age and region of origin (p = 0.046). 5.4% to 10.8% of patients reported anosmia and ageusia. None developed pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS). In general, adolescents were more likely to be asymptomatic and less likely to develop fever, but required longer hospital stays. In conclusion, majority patients in this pediatric Asian cohort had a mild disease. None developed PIMS-TS. Their clinical characteristics were influenced by travel history and age

A Nation-Wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in china

<p>Abstract</p> <p>Background</p> <p>According to the very limited cancer registry, incidence and mortality rates for female breast cancer in China are regarded to be increasing especially in the metropolitan areas. Representative data on the breast cancer profile of Chinese women and its time trend over years are relatively rare. The aims of the current study are to illustrate the breast cancer profile of Chinese women in time span and to explore the current treatment approaches to female breast cancer.</p> <p>Methods</p> <p>This was a hospital-based nation-wide and multi-center retrospective study of female primary breast cancer cases. China was divided into 7 regions according to the geographic distribution; from each region, one tertiary hospital was selected. With the exception of January and February, one month was randomly selected to represent each year from year 1999 to 2008 at every hospital. All inpatient cases within the selected month were reviewed and related information was collected based on the designed case report form (CRF). The Cancer Hospital/Institute, Chinese Academy of Medical Sciences (CICAMS) was the leading hospital in this study.</p> <p>Results</p> <p>Four-thousand two-hundred and eleven cases were randomly selected from the total pool of 45,200 patients and were included in the analysis. The mean age at diagnosis was 48.7 years (s.d. = 10.5 yrs) and breast cancer peaked in age group 40-49 yrs (38.6%). The most common subtype was infiltrating ductal carcinoma (86.5%). Clinical stage I & II accounted for 60.6% of 4,211 patients. Three-thousand five-hundred and thirty-four cases had estrogen receptor (ER) and progestin receptor (PR) tests, among them, 47.9% were positive for both. Two-thousand eight-hundred and forty-nine cases had human epidermal growth factor receptor 2(HER-2) tests, 25.8% of them were HER-2 positive. Among all treatment options, surgery (96.9% (4,078/4,211)) was predominant, followed by chemotherapy (81.4% (3,428/4,211). Much less patients underwent radiotherapy (22.6% (952/4,211)) and endocrine therapy (38.0% (1,599/4,211)).</p> <p>Conclusions</p> <p>The younger age of breast cancer onset among Chinese women and more advanced tumor stages pose a great challenge. Adjuvant therapy, especially radiotherapy and endocrine therapy are of great unmet needs.</p

Stem Cell Therapy: Pieces of the Puzzle

Acute ischemic injury and chronic cardiomyopathies can cause irreversible loss of cardiac tissue leading to heart failure. Cellular therapy offers a new paradigm for treatment of heart disease. Stem cell therapies in animal models show that transplantation of various cell preparations improves ventricular function after injury. The first clinical trials in patients produced some encouraging results, despite limited evidence for the long-term survival of transplanted cells. Ongoing research at the bench and the bedside aims to compare sources of donor cells, test methods of cell delivery, improve myocardial homing, bolster cell survival, and promote cardiomyocyte differentiation. This article reviews progress toward these goals

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Performance of the ATLAS muon trigger in pp collisions at [Formula: see text] TeV

The performance of the ATLAS muon trigger system is evaluated with proton-proton collision data collected in 2012 at the Large Hadron Collider at a centre-of-mass energy of 8 TeV. It is primarily evaluated using events containing a pair of muons from the decay of [Formula: see text] bosons. The efficiency of the single-muon trigger is measured for muons with transverse momentum [Formula: see text] GeV, with a statistical uncertainty of less than 0.01 % and a systematic uncertainty of 0.6 %. The [Formula: see text] range for efficiency determination is extended by using muons from decays of [Formula: see text] mesons, [Formula: see text] bosons, and top quarks. The muon trigger shows highly uniform and stable performance. The performance is compared to the prediction of a detailed simulation

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Student perspectives on plagiarism in computing

Prevention and detection of plagiarism have formed the basis for many research projects, but student perceptions on plagiarism are arguably not well understood, and this is particularly true in the computing disciplines. This paper considers two aspects of the student experience, (i) the types of plagiaristic activity that students engage in, and (ii) the specific understanding of what plagiarism means for students who write computer programs. In a recent study we classified types of plagiarism in computing, collecting data from two sources: published material (books, published papers, web sites), and on-line formative quizzes and questionnaires used by universities to test student knowledge of what constitutes plagiarism. Facet analysis was used to categorise the data into four initial categories (sources, actions, material, extrinsic). Further analysis suggested a refinement to six categories and 23 sub-categories which directly relate to the computing disciplines. In a further study we analysed data collected from 18 UK institutions via an online questionnaire, in which over 700 computing students were invited to scrutinise fifteen scenarios which may (or may not) contain plagiarism, and to identify which they thought did contain plagiarism. The results of this study suggest that there are certain types of plagiaristic activity which are poorly understood, and demographic factors which correlate with student understanding. This paper summarises and compares the results of these two studies and reflects on the implications for educating computing students about how they should avoid plagiarism