HRM and KM as catalysts of environmental performance: A conceptual framework

The purpose of this paper is to develop a theoretical framework to investigate the relationships among human resource management (HRM), knowledge management (KM) and environmental performance (EP).Environmental friendly business activities demand high level of human resource competency in terms of knowledge, skills and capabilities in order to better firm performance. This paper serves to establish the link among HRM, KM, and EP to fill the gap in the current literature.The research model is proposed based on reviews of the literature on HR and KM perspectives on environmental management and performance.Both theoretical and practical implications are discussed in this paper.With new knowledge gained on the associations among HRM, KM and EP, manufacturing firm managers can focus their effort and resources on HRM and KM to deliver better environmental management effectiveness.It is anticipated that this paper will contribute towards sustainability development for a better living environment

Acrometastasis from an epidermal-growth-factor-receptor (EGFR) mutation-positive lung adenocarcinoma

AbstractWe report the first case of epidermal-growth-factor-receptor (EGFR) mutation-positive lung adenocarcinoma with acrometastasis in a 51-year-old woman who presented with a swelling on her right hand. Magnetic resonance imaging revealed an expansile lesion at the base of the 5th metacarpal bone of her right hand with cortical erosion and patchy enhancement suggestive of a malignant transformation of a giant-cell tumor. A core needle biopsy of this lesion showed a metastatic adenocarcinoma on histopathological examination which was immunoreactive to cytokeratin (CK) 7 and thyroid transcription factor (TTF)-1 but not to CK20 suggesting a lung primary. A chest radiograph and computed tomography (CT) scan revealed a right upper lobe lung mass. Fluoro-deoxyglucose hypermetabolism was noted in the lung mass and the right 5th metacarpal bone lesion but not elsewhere on positron-emission-tomography/CT scan. Needle biopsy of the lung mass showed adenocarcinoma with histopathological and immunohistochemical features similar to that of the right 5th metacarpal bone lesion. Both the primary lung adenocarcinoma and the acrometastatic lesion were tested positive for EGFR mutation in exon 21 (L858R substitution). She underwent R0 resection of her right upper and middle lobes with systematic mediastinal lymph nodes resection and wide excision of the metacarpal metastasis followed by cytotoxic chemotherapy. A curative approach with complete resection of the primary tumor and oligometastastic site in Stage IV non-small cell lung carcinoma (NSCLC) followed by additive cytotoxic chemotherapy has not been reported to date and as such there is still no data on disease-free survival with this approach

Quality Of Life Of Patients With Chronic Obstructive Pulmonary Disease Based On Clinical Phenotypes

Background and Aims: Spanish chronic obstructive pulmonary disease (COPD) guideline classifies COPD into 4 clinical phenotypes: nonexacerbator (A), asthma-COPD overlap (B), exacerbator with emphysema(C) and exacerbator with bronchitis (D). Methods: A cross-sectional study of quality of life (QOL) based on COPD phenotypes utilizing St George’s Respiratory Questionnaire (SGRQ-c) conducted in University Malaya Medical Center from 1 June 2017 – 31 May 2018. Results: Of 220 patients, 189 patients with post bronchodilator force expiratory volume in 1 second (FEV1)/force vital capacity (FVC) of <0.70 were recruited. Their demographic, clinical characteristics and SGRQ-c score are as shown in Table 1. Patients with phenotype C and D had poorer modified medical research center (MMRC) performance status and global initiative for COPD (GOLD) class based on FEV1. Nevertheless, only patients with phenotype D had significant higher total SGRQ-c score than others. They also scored significant higher in sub-components of COPD symptoms, activities and impacts. Patients with phenotypes B had numerically higher SGRQ-c total and symptoms score than those with phenotype A and C. The total and sub-components SGRQ-c score of patients with phenotype A and C were almost similar. Conclusion: Patients with phenotype D had poorest QOL, followed by phenotype B. These groups of patients need additional medical attention, in terms of pharmacology treatment, physiotherapy and rehabilitation

Structural Modeling and Biochemical Characterization of Recombinant KPN_02809, a Zinc-Dependent Metalloprotease from Klebsiella pneumoniae MGH 78578

Klebsiella pneumoniae is a Gram-negative, cylindrical rod shaped opportunistic pathogen that is found in the environment as well as existing as a normal flora in mammalian mucosal surfaces such as the mouth, skin, and intestines. Clinically it is the most important member of the family of Enterobacteriaceae that causes neonatal sepsis and nosocomial infections. In this work, a combination of protein sequence analysis, structural modeling and molecular docking simulation approaches were employed to provide an understanding of the possible functions and characteristics of a hypothetical protein (KPN_02809) from K. pneumoniae MGH 78578. The computational analyses showed that this protein was a metalloprotease with zinc binding motif, HEXXH. To verify this result, a ypfJ gene which encodes for this hypothetical protein was cloned from K. pneumoniae MGH 78578 and the protein was overexpressed in Escherichia coli BL21 (DE3). The purified protein was about 32 kDa and showed maximum protease activity at 30 °C and pH 8.0. The enzyme activity was inhibited by metalloprotease inhibitors such as EDTA, 1,10-phenanthroline and reducing agent, 1,4-dithiothreitol (DTT). Each molecule of KPN_02809 protein was also shown to bind one zinc ion. Hence, for the first time, we experimentally confirmed that KPN_02809 is an active enzyme with zinc metalloprotease activity

Comparison of pattern of disease progression and prevalence of acquired T790M mutation in Malaysia patients with EGFR mutant lung adenocarcinoma upon failure of first-line afatinib, gefitinib and erlotinib

Abstract Background Patients receiving first-line afatinib, gefitinib or erlotinib for epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer develop progression of disease (PD) after an average of 9-13 months. Methods A retrospective analysis of PD pattern and prevalence of acquired T790M mutation among patients failing first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. Results Of 87 patients who developed PD while on first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, 19 (21.8%) were on afatinib, 49 (56.3%) were on gefitinib, and 19 (21.8%) were on erlotinib. The median progression-free survival (mPFS) of these patients is as shown in the table. Of 20 patients (23.0%) who developed new symptomatic brain metastases, one (5.0%) had new leptomeningeal metastases, three (15.0%) had both new leptomeningeal metastases and solid brain metastases, and the remaining 16 (80.0%) had new solid brain metastases only. New leptomeningeal metastases occurred in one patient treated with afatinib and three patients treated with gefitinib. Forty-nine patients (56.3%) were investigated for acquired T790M mutation either by plasma biopsy or tissue biopsy or both. The prevalence of acquired T790M mutation was 61.2%. There was no difference in the pattern of PD or prevalence of acquired T790M mutation among patients treated with afatinib, gefitinib or erlotinib. Conclusions New leptomeningeal metastases were uncommon in patients receiving first-line EGFR-TKI. The choice of first-line first- or second generation EGFR-TKI did not influence the pattern of PD and prevalence of acquired T790M mutation. However, patients receiving afatinib appeared to have longer mPFS than those on gefitinib or erlotinib

Large-scale evolutionary surveillance of the 2009 H1N1 influenza A virus using resequencing arrays

In April 2009, a new influenza A (H1N1 2009) virus emerged that rapidly spread around the world. While current variants of this virus have caused widespread disease, particularly in vulnerable groups, there remains the possibility that future variants may cause increased virulence, drug resistance or vaccine escape. Early detection of these virus variants may offer the chance for increased containment and potentially prevention of the virus spread. We have developed and field-tested a resequencing kit that is capable of interrogating all eight segments of the 2009 influenza A(H1N1) virus genome and its variants, with added focus on critical regions such as drug-binding sites, structural components and mutation hotspots. The accompanying base-calling software (EvolSTAR) introduces novel methods that utilize neighbourhood hybridization intensity profiles and substitution bias of probes on the microarray for mutation confirmation and recovery of ambiguous base queries. Our results demonstrate that EvolSTAR is highly accurate and has a much improved call rate. The high throughput and short turn-around time from sample to sequence and analysis results (30 h for 24 samples) makes this kit an efficient large-scale evolutionary biosurveillance tool

Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1)

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization

Lung adenocarcinoma promotion by air pollutants

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden