Aristolochic acid (AA), a natural product of Aristolochia plants found in herbal remedies and health supplements, is a group 1 carcinogen that can cause nephrotoxicity and upper urinary tract urothelial cell carcinoma (UTUC). Whole-genome and exome analysis of nine AA-associated UTUCs revealed a strikingly high somatic mutation rate (150 mutations/Mb), exceeding smoking-associated lung cancer (8 mutations/Mb) and ultraviolet radiation-associated melanoma (111 mutations/Mb). The AA-UTUC mutational signature was characterized by A:T to T:A transversions at the sequence motif A[C|T]AGG, located primarily on nontranscribed strands. AA-induced mutations were also significantly enriched at splice sites, suggesting a role for splice-site mutations in UTUC pathogenesis. RNA sequencing of AA-UTUC confirmed a general up-regulation of nonsense-mediated decay machinery components and aberrant splicing events associated with splice-site mutations. We observed a high frequency of somatic mutations in chromatin modifiers, particularly KDM6A, in AA-UTUC, demonstrated the sufficiency of AA to induce renal dysplasia in mice, and reproduced the AA mutational signature in experimentally treated human renal tubular cells. Finally, exploring other malignancies that were not known to be associated with AA, we screened 93 hepatocellular carcinoma genomes/exomes and identified AA-like mutational signatures in 11. Our study highlights an unusual genome-wide AA mutational signature and the potential use of mutation signatures as "molecular fingerprints" for interrogating high-throughput cancer genome data to infer previous carcinogen exposures.

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The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identifi ed Janus kinase 3 (JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3 mutations was determined by Sanger sequencing and high-resolution melt (HRM) analysis in an additional 61 cases. In total, 23 of 65 (35.4%) cases harbored JAK3 mutations. Functional characterization of the JAK3 mutations support its involvement in cytokine-independent JAK/ STAT constitutive activation leading to increased cell growth. Moreover, treatment of both JAK3-mutant and wild-type NKTCL cell lines with a novel pan-JAK inhibitor, CP-690550, resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis. Hence, targeting the deregulated JAK/STAT pathway could be a promising therapy for patients with NKTCLs. SIGNIFICANCE:Gene mutations causing NKTCL have not been fully identifi ed. Through exome sequencing, we identifi ed activating mutations of JAK3 that may play a signifi cant role in the pathogenesis of NKTCLs. Our fi ndings have important implications for the management of patients with NKTCLs.Cancer Discov; 2(7); 591-7.

Purpose -Based upon the E-VALUE model developed, this paper aims to investigate the impact of e-commerce usage on business performance in the tourism sector. Design/methodology/approach -A cross-sectional survey is carried out on 165 Malaysian firms involved in the tourism sector (hotels, resorts, and hospitals engaged in health tourism) through the use of a structured questionnaire. Findings -The structural equation modeling results indicate that technology competency, firm size, firm scope, web-technology investment, pressure intensity, and back-end usage have significant influence on e-commerce usage. Among these variables, back-end integration is found to function as a mediator. E-commerce experience (in years) is found to moderate the relationship between e-commerce usage and business performance.Research limitations/implications -The paper focuses on the tourism sector in Malaysia and concentrates only on the management perspective of e-commerce adoption. Practical implications -The results provide insights to the Malaysian tourism sector and other organizations of similar structures of how they could improve upon their e-commerce adoption and/or usage for improved business performance. Originality/value -This paper is perhaps one of the first to investigate e-commerce usage in the tourism sector using a comprehensive set of variables through an interactive, comprehensive and multi-dimensional theoretical model (the E-VALUE model) in investigating their influences on business performance.

Purpose -The purpose of this paper is to examine the gap between knowledge management (KM) practices and key strategic enablers in public universities. For this purpose, a 57-item survey on two dimensions -"use" and "importance" -was used as the instrument for this study. Design/methodology/approach -The questionnaire was administered to academics of four public universities which fall under the Malaysian Technical University Network. Findings -The results from 191 responses show that the academics of public universities find the KM practices and key strategic enablers to be important but are not used as much.Research limitations/implications -This research has overcome the gaps identified through the use of a set of KM practices and key strategic enablers. These variables could be replicated in different settings, across different economies, with the possibility of incorporating more constructs. The small sample size and the cross-sectional nature of the study suggest that a larger sample size through a longitudinal study is required in future research. Practical implications -The recommendations proposed will provide strategic directions for the management of public universities to deal more effectively with the KM practices and key strategic enablers. Originality/value -This study has extended knowledge in KM, specifically concerning the importance and use of key strategic enablers of KM. Moreover, it is amongst the first empirical works to examine the use and importance of KM practices and key strategic enablers in unison.

Purpose -Using the extended task-technology fit (TTF) model, the purpose of this paper is to examine the impact of intranet usage on middle managers' performance in the port industry. Design/methodology/approach -The study was conducted on 357 middle managers from various organisations in the Malaysian port industry. Findings -The structural equation modelling results indicate that TTF and usage significantly explains the variance on managers' performance. TTF is a predictor of perceived usefulness and usage but it does not predict user resistance. Perceived usefulness is a predictor of usage but it does not predict user resistance. User resistance does not predict managers' performance.Research limitations/implications -The study focuses only on the port industry in Malaysia and concentrates only on the management perspective of intranet usage. Practical implications -The results provide insights on how the Malaysian port industry and other organisations of a similar structure could improve on their intranet adoption. Originality/value -This study is perhaps one of the first to address the intranet adoption in the port industry using a comprehensive, extended TTF model (perceived usefulness, usage, user resistance) to investigate their influences on individual job performance.

PurposeIn view of the promising growth of e‐payment in Malaysia, this study aims to discover the factors influencing perception towards electronic payment (e‐payment) from the Malaysian consumers’ perspective.Design/methodology/approachLiterature indicates that factors such as benefits, trust, self‐efficacy, ease of use, and security influence consumers’ perception towards e‐payment. A self‐reporting questionnaire was developed and disseminated to 200 respondents, out of which 183 valid responses were considered for further statistical analysis.FindingsThe multiple linear regression results reveal that benefits, self‐efficacy, and ease of use exert significant influences on consumers’ perception towards e‐payment. However, the insignificant results obtained for trust and security warrant further investigation.Research limitations/implicationsThis study proposes five factors for measuring consumers’ perception towards e‐payment which is replicable across different economies. However, the small sample size raises the issue of generalizability which future studies should seek to address.Practical implicationsThe use of e‐payment by the majority of respondents confirms that there is a great potential for future expansion of such payment devices. The challenge is to ensure that it continues to meet consumers’ expectations which will subsequently lead to its increased adoption and use.Originality/valueThis study has advanced knowledge for it has provided information on the current state of e‐payment acceptance and use, particularly among Malaysians. The significant factors identified are beneficial to the policy maker, banking institutions, online transaction facilities providers, and software developers as they develop strategies directed at increasing e‐payment acceptance and use.

If you would like to write for this, or any other Emerald publication, then please use our Emerald for Authors service information about how to choose which publication to write for and submission guidelines are available for all. Please visit www.emeraldinsight.com/authors for more information. About Emerald www.emeraldinsight.comEmerald is a global publisher linking research and practice to the benefit of society. The company manages a portfolio of more than 290 journals and over 2,350 books and book series volumes, as well as providing an extensive range of online products and additional customer resources and services.Emerald is both COUNTER 4 and TRANSFER compliant. The organization is a partner of the Committee on Publication Ethics (COPE) and also works with Portico and the LOCKSS initiative for digital archive preservation. AbstractPurpose -The aim of this research is to attempt to reveal the difference between what fresh graduates expect and their actual experiences pertaining to the working environment. Design/methodology/approach -Using a set of self-administered questionnaires, data were collected from 128 graduates. They were asked to indicate their preferences on organizational culture, leadership, communication, decision making, team working, motivation, and development. Using the same dimensions, the respondents then reported their actual experiences, thus enabling gaps to be determined. Findings -The results from paired-sample t-tests suggest that significant expectation gaps exist in all the areas surveyed. While communication, decision making and motivation are found to be significantly related to job satisfaction, none of the seven variables is found to be significantly correlated to organizational commitment. Research limitations/implications -The study focuses only on a rather limited sample size of Malaysian graduates; therefore it cannot ensure generalization of results obtained. Practical implications -The resulting expectation gaps, and their influence on the graduates' job satisfaction and organizational commitment, have implications for the important roles played by employers, higher learning institutions, and graduate themselves. Originality/value -This study makes significant contributions in three key areas. First, it is perhaps one of the earliest studies to comprehensively address the issue of expectation gaps using a myriad factors. Second, it is also one of the few that examines the influence of the expectation gaps on job satisfaction and commitment. Third, instead of focusing on employees as a whole, which has been the practice of prior research, this study concentrates only on fresh graduates who have been in the workforce for less than two years.