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1.
R Soc Open Sci ; 11(3): 231386, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38545613

ABSTRACT

The presence of intra-specific acoustic communication in diurnal butterflies is not well established. Here, we examined the function of the tympanal ear (Vogel's organ, VO) in the seasonally polyphenic butterfly Bicyclus anynana in the context of sexual signalling. We investigated how the VO and the flanking enlarged veins, which are suggested sound resonance chambers, scale with wing size across sexes and seasonal forms, and how disruptions to the VO alter courtship behaviour and mating outcomes. We found that males have VOs similar in size to females despite having smaller wings, and dry season (DS) male cubital and anal veins do not scale with the wing size. This suggests that the VO plays an important role in males and that cubital and anal veins in DS males may be tuned to amplify specific sound frequencies. Behavioural assays performed with deafened and hearing males of different seasonal forms, in pair and triad settings, showed that deafened DS males, but not wet season males, experienced lower mating success relative to their hearing counterparts. Our study documents a novel function for the wing tympanal membrane in mediating courtship and mating outcomes in diurnal butterflies.

2.
Vaccine ; 41(47): 6910-6913, 2023 11 13.
Article in English | MEDLINE | ID: mdl-37880070

ABSTRACT

BBIBP-CorV inactivated vaccine is one of the most prevalent vaccines globally, but immune responses are far less studied than novel COVID-19 vaccine platforms. Longitudinal studies on BBIBP-CorV with homologous and heterologous booster doses are limited. This study follows a subset of participants from a national study comparing the immunogenicity of COVID-19 vaccines and levels of SARS-CoV-2 neutralising antibody (NAb). Homologous and heterologous booster dose significantly increased NAb levels in BBIBP-CorV-vaccinated individuals. Similar NAb levels were observed 1 month following BNT162b2 or mRNA-1273 booster. Interestingly, NAb persisted following mRNA-1273 booster (n = 95), but waned significantly at 6 and 9 months following BNT162b2 booster (n = 50; P > 0.001). The persistence of NAb was also observed following breakthrough infection. This study provides evidence that not all mRNA vaccines are equal in the longer term and should provide valuable information for policy makers planning booster programmes for BBIBP-CorV vaccinated populations.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , COVID-19 Vaccines , Humans , BNT162 Vaccine , Antibodies, Viral , Antibodies, Neutralizing
3.
Asian Pac J Cancer Prev ; 24(7): 2389-2396, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37505771

ABSTRACT

BACKGROUND: Cancer has been the most common cause of deaths in Brunei Darussalam including lung cancer as one of the top killers. This study presents the survival analysis of primary lung cancer patients in Brunei Darussalam. METHODS: This is a retrospective cohort study of a 15-year period (2002-2016) involving 797 primary lung cancer cases. De-identified data extracted from Brunei Darussalam Cancer Registry was analyzed using Kaplan-Meier method and log-rank test. Bonferroni corrections were performed. RESULTS: 6 months, 1-year, 3-year, 5-year survival rates of lung cancer patients were 62.2%, 51.0%, 38.0% and 34.7% respectively. The median survival time was 12.4 months (95% Cl: 9.2, 15.7). Patients diagnosed 2002-2006 had significant longer survival than patients diagnosed 2007-2011 (p=0.039) and those diagnosed 2011-2016 (p<0.001). Survival time of patients diagnosed 2007-2011 was significantly longer than patients diagnosed 2012-2016 (p=0.049). Patients with localised disease had significantly longer survival time than patients with regional involvement (p<0.001) and distal site involvement (p<0.001). Patients with distal disease had significantly poorer survival rate than patients with regional involvement (p<0.001). Patients aged 50 or above had significantly shorter survival time than patients diagnosed at age 40-49 (p=0.003). There was no significant difference between survival time of other demographic characteristics. CONCLUSIONS: The median survival time for lung cancer patients in this study was 12.4 months. Early diagnosis, early stage of cancer, and younger age were associated with longer survival time among lung cancer patients in Brunei Darussalam.


Subject(s)
Lung Neoplasms , Humans , Adult , Middle Aged , Retrospective Studies , Brunei/epidemiology , Survival Analysis
4.
BMC Cancer ; 23(1): 466, 2023 May 22.
Article in English | MEDLINE | ID: mdl-37217954

ABSTRACT

This study presents the trends of age-standardised incidence and mortality rates of common cancers in Brunei Darussalam from 2011 to 2020. All cancer cases diagnosed among Brunei Darussalam citizens and permanent residents in the period 2011 to 2020 were included in the study. De-identified data were provided by the CanReg5 based BDCR, Ministry of Health Brunei Darussalam. The annual age-standardised incidence and mortality rates per 100,000 persons were standardised by the direct method using the World Health Organization (WHO) world standard population distribution. Joinpoint regression analyses were used to study the incidence and mortality trends of cancer in Brunei Darussalam over the 2011-2020 period. Trends were expressed as average annual percent change (AAPC) over 2011 to 2020, or annual percent change (APC) for a given time period. There were a total of 6,495 new cancer cases diagnosed and 3,359 death cases recorded from 2011 to 2020, in Brunei Darussalam. The five common cancers for males were colorectal, lung and bronchus, prostate, liver, and non-Hodgkin lymphoma. Among females, the five most common cancers were breast, colorectal, lung and bronchus, corpus uteri and cervix uteri. The five leading cancer deaths for males were lung and bronchus, colorectal, liver, prostate, and stomach, while for females, the five leading cancer deaths were breast, lung and bronchus, colorectal, ovary, and cervix uteri. There was a significant increase in the incidence trend of corpus uteri (AAPC[Formula: see text]) and a significant decline in the incidence trend for cervical cancer (AAPC[Formula: see text]) from 2011 to 2020. There was a significant increase in the mortality trend of female breast cancer from 2011 to 2015 (APC[Formula: see text]), but the trend significantly declined from 2015 to 2020 (APC[Formula: see text]). We also found a significant decrease in mortality trends for stomach cancer (AAPC[Formula: see text]) from 2011 to 2020 for both genders combined. The burden of common cancers is expected to continue to grow with ageing population, effective public health interventions targeting high burden cancers and high-risk groups, and control of modifiable risk factors will continue to be the essential approaches in reducing cancer burden.


Subject(s)
Colorectal Neoplasms , Stomach Neoplasms , Uterine Cervical Neoplasms , Humans , Female , Male , Incidence , Brunei/epidemiology , Mortality
5.
Heliyon ; 9(5): e16080, 2023 May.
Article in English | MEDLINE | ID: mdl-37215873

ABSTRACT

Objective: Cervical cancer is the fourth leading cause of cancer deaths among Bruneian women. This study aims to investigate the survival rate of cervical cancer patients in Brunei Darussalam between 2002 and 2017, to compare survival of cervical cancer patients between two periods: 2002-2009 and 2010-2017 and to identify prognostic factors of cervical cancer. Methods: A retrospective cohort study on cervical cancer patients registered in Brunei Darussalam Cancer Registry between 2002 and 2017. De-identified data from the registry was extracted and survival analysis was performed using Kaplan-Meier estimator, log-rank test and multiple Cox regression analysis. Results: The 1-, 3- and 5-year survival rates of cervical cancer patients in Brunei Darussalam were 87.3%, 77.4% and 72.5% respectively from 2002 to 2017. The 5-year survival rate for 2002-2009 and 2010-2017 were 77.3% and 69.1% respectively. The risk of mortality was significantly higher in 2010-2017 compared to 2002-2009 after adjusting for variables (Adjusted HR = 1.59; 95% CI: 1.08, 2.40; p = 0.019). Patients with distant cancer (Adjusted HR = 11.21; 95% CI: 6.18, 20.30; p < 0.001) had the highest risk of mortality. Conclusion: The 5-year survival rate of cervical cancer patients in Brunei Darussalam was 72.5%, which ranks relatively high globally. However, increased mortality among elderly patients, and patients diagnosed with cervical cancers at the later stages, calls for public health efforts to raise awareness, early detection, and disease management.

6.
Hum Vaccin Immunother ; 19(1): 2167438, 2023 12 31.
Article in English | MEDLINE | ID: mdl-36705277

ABSTRACT

The effectiveness of the vero cell inactivated vaccine (CoronaVac®) against severe acute respiratory infection ( SARI) caused by SARS-CoV-2 in the real world was assessed. A matched test-negative case-control design was employed using the web-based national information system, as well as the hospitalization dataset in Sibu Hospital. Vaccine effectiveness was measured by conditional logistic regression with adjustment for gender, underlying comorbidity, smoking status, and education level. Between 15 March and 30 September 2021, 838 eligible SARI patients were identified from the hospitalization records. Vaccine effectiveness was 42.4% (95% confidence interval [CI]: -28.3 to 74.1) for partial vaccination (after receiving the first dose to 14 days after receiving the second dose), and 76.5% (95% CI: 45.6 to 89.8) for complete vaccination (at 15 days or more after receiving the second dose). This analysis indicated that two doses of CoronaVac® vaccine provided efficacious protection against SARI caused by SARS-CoV-2 in the short term. However, the duration of protection, and performance against new variants need to be studied continuously.


Subject(s)
COVID-19 , Pneumonia , Vaccines , Chlorocebus aethiops , Animals , Humans , Malaysia/epidemiology , Vero Cells , Retrospective Studies , COVID-19/prevention & control , SARS-CoV-2
7.
Neural Comput Appl ; 35(18): 13037-13046, 2023.
Article in English | MEDLINE | ID: mdl-33424133

ABSTRACT

To predict the mortality of patients with coronavirus disease 2019 (COVID-19). We collected clinical data of COVID-19 patients between January 18 and March 29 2020 in Wuhan, China . Gradient boosting decision tree (GBDT), logistic regression (LR) model, and simplified LR were built to predict the mortality of COVID-19. We also evaluated different models by computing area under curve (AUC), accuracy, positive predictive value (PPV), and negative predictive value (NPV) under fivefold cross-validation. A total of 2924 patients were included in our evaluation, with 257 (8.8%) died and 2667 (91.2%) survived during hospitalization. Upon admission, there were 21 (0.7%) mild cases, 2051 (70.1%) moderate case, 779 (26.6%) severe cases, and 73 (2.5%) critically severe cases. The GBDT model exhibited the highest fivefold AUC, which was 0.941, followed by LR (0.928) and LR-5 (0.913). The diagnostic accuracies of GBDT, LR, and LR-5 were 0.889, 0.868, and 0.887, respectively. In particular, the GBDT model demonstrated the highest sensitivity (0.899) and specificity (0.889). The NPV of all three models exceeded 97%, while their PPV values were relatively low, resulting in 0.381 for LR, 0.402 for LR-5, and 0.432 for GBDT. Regarding severe and critically severe cases, the GBDT model also performed the best with a fivefold AUC of 0.918. In the external validation test of the LR-5 model using 72 cases of COVID-19 from Brunei, leukomonocyte (%) turned to show the highest fivefold AUC (0.917), followed by urea (0.867), age (0.826), and SPO2 (0.704). The findings confirm that the mortality prediction performance of the GBDT is better than the LR models in confirmed cases of COVID-19. The performance comparison seems independent of disease severity. Supplementary Information: The online version contains supplementary material available at(10.1007/s00521-020-05592-1).

8.
Br J Cancer ; 128(3): 459-460, 2023 02.
Article in English | MEDLINE | ID: mdl-36216884

ABSTRACT

Recent technological advances uncovered intricate biological processes underlying intratumor heterogeneity with clinical implications. These insights led to novel biomarkers for immunotherapies, justified serial tumour biopsies for therapeutic target profiling, inspired new treatment strategies, and ultimately might yield novel therapeutics that target clonal interdependence.


Subject(s)
Neoplasms , Humans , Neoplasms/therapy , Neoplasms/drug therapy , Genetic Heterogeneity
9.
BMJ Open ; 12(12): e067020, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36456015

ABSTRACT

INTRODUCTION: Neutralising antibodies (NAbs) have been shown to be correlative of immune protection against SARS-CoV-2. We report the protocol for a national longitudinal study to assess and compare the level of NAbs generated in response to COVID-19 vaccines in Brunei Darussalam in adults 2-6 weeks post primary series (BBIBP-CorV, AZD1222, or mRNA-1273 vaccines) and their subsequent follow-up after administration of a third (booster-1) dose (BBIBP-CorV, mRNA-1273, or BNT162b2). METHODS AND ANALYSIS: Participant data will be extracted and processed from the national electronic health record system (Bru-HIMS) and the national mobile health application (BruHealth) into a research data platform. Eligible adults who have received their primary or booster vaccine will be invited using a stratified random sampling strategy based on age, gender and vaccine type (baseline target population, n=3000; 2-6 weeks post last dose). Blood serum will be isolated, and NAb levels assessed using the cPass surrogate virus neutralisation test. Baseline participants will then be screened for eligibility for subsequent longitudinal analysis. Those who have received a third dose will be followed up at 1, 3, 6, 9 and up to 12 months. NAb levels will be evaluated across the participant population according to vaccine platform/booster type, time since the last dose and correlated with demographic data. The study period is from December 2021 to January 2023 and aims to evaluate how NAb levels wane following a third vaccine dose across different vaccine platforms and determine the impact and rate of breakthrough infections. ETHICS AND DISSEMINATION: This study has been approved by the Medical and Ethical Research Committee of Ministry of Health, Brunei Darussalam. Individual NAb test results will be shared with each participant by text message. The findings from this study will help policy-makers in Brunei develop future vaccination strategies and establish regulations across multiple agencies.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Adult , Longitudinal Studies , SARS-CoV-2 , Brunei , BNT162 Vaccine , ChAdOx1 nCoV-19 , COVID-19/epidemiology , COVID-19/prevention & control , Antibodies, Neutralizing
10.
NPJ Breast Cancer ; 8(1): 119, 2022 Nov 07.
Article in English | MEDLINE | ID: mdl-36344517

ABSTRACT

The RxPONDER and TAILORx trials demonstrated benefit from adjuvant chemotherapy in patients age ≤ 50 with node-positive breast cancer and Recurrence Score (RS) 0-26, and in node-negative disease with RS 16-25, respectively, but no benefit in older women with the same clinical features. We analyzed transcriptomic and genomic data of ER+/HER2- breast cancers with in silico RS < 26 from TCGA (n = 530), two microarray cohorts (A: n = 865; B: n = 609), the METABRIC (n = 867), and the SCAN-B (n = 1636) datasets. There was no difference in proliferation-related gene expression between age groups. Older patients had higher mutation burden and more frequent ESR1 copy number gain, but lower frequency of GATA3 mutations. Younger patients had higher rate of ESR1 copy number loss. In all datasets, younger patients had significantly lower mRNA expression of ESR1 and ER-associated genes, and higher expression of immune-related genes. The ER- and immune-related gene signatures showed negative correlation and defined three subpopulations in younger women: immune-high/ER-low, immune-intermediate/ER-intermediate, and immune-low/ER-intermediate. We hypothesize that in immune-high cancers, the cytotoxic effect of chemotherapy may drive the benefit, whereas in immune-low/ER-intermediate cancers chemotherapy induced ovarian suppression may play important role.

11.
Front Public Health ; 10: 983571, 2022.
Article in English | MEDLINE | ID: mdl-36172211

ABSTRACT

A national study was conducted in Brunei to assess and compare the immunogenicity of the various brands of COVID-19 vaccines administered to the population as part of the National COVID-19 Vaccination Programme. Most of the population have had received at least 2 doses of BBIBP-CorV, AZD1222 or MRNA-1273 vaccines. Neutralising antibodies against SARS-CoV-2 induced by these vaccines will be analysed to infer population-level immune protection against COVID-19. During the 5-week recruitment period, 24,260 eligible individuals were invited to the study via SMS, out of which 2,712 participants were enrolled into the study. This paper describes the novel adaptive strategy used to recruit the study participants. Digital technology was leveraged to perform targeted online recruitment to circumvent the limitations of traditional recruitment methods. Technology also enabled stratified random selection of these eligible individuals who were stratified based on age, gender and vaccine brand. Data was extracted from the electronic health records, the national mobile health application and a third-party survey platform and integrated into a dedicated research platform called EVYDResearch. The instant availability and access to up-to-date data on EVYDResearch enabled the study team to meet weekly and adopt an adaptive recruitment strategy informed by behavioural science, where interventions could be quickly implemented to improve response rates. Some examples of these include incorporating nudge messaging into SMS invitations, involving the Minister of Health to make press announcements on this study, media coverage, setting up an enquiries hotline and reaching out to foreign language speaking expatriates of a local multinational company to participate in this study. Data integration from various data sources, real time information sharing and a strong teamwork led to good outcomes adaptable to the progress of recruitment, compared to the more time-consuming and static traditional recruitment methods.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Brunei , COVID-19/prevention & control , ChAdOx1 nCoV-19 , Humans , Immunogenicity, Vaccine , SARS-CoV-2 , Technology
12.
BMC Public Health ; 22(1): 1742, 2022 09 14.
Article in English | MEDLINE | ID: mdl-36104666

ABSTRACT

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality globally. This review aimed to summarise evidence on the key features, usability and benefits of CVD risk calculators using digital platforms for CVDs prevention and management in populations. METHODS: We used search engines and thematic analyses to conduct a scoping review. As the reporting guideline for this review, we used Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). RESULTS: A total of 17 studies meeting eligibility criteria were included in the analysis, from which about 70% of the studies have prognostic level I (n = 8) and level II (n = 4) evidence. The review found that various guidelines are recommending different algorithms for CVD risk prediction. The QRISK® was the most accurate CVD risk calculator for several study populations, whereas World Health Organization/International Society of Hypertension (WHO/ISH) risk scores were the least accurate. The key features of CVD risk calculators are variables, predictive accuracy, discrimination index, applicability, understandability, and cost-effectiveness. CONCLUSION: For the selected risk prediction tool, development and validation research must be done, which considers a mix of stroke-specific risk and CVD risk to establish its usability in the local community and advantages to the particular health-care environment. To get healthcare professionals more involved in preventing and treating CVDs, each healthcare setting should use an online CVD risk assessment tool that is more useful, accurate, and easy to use, based on the population and health system.


Subject(s)
Cardiovascular Diseases , Hypertension , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/prevention & control , Delivery of Health Care , Humans , Risk Assessment , Risk Factors
13.
BMC Med Res Methodol ; 22(1): 209, 2022 07 30.
Article in English | MEDLINE | ID: mdl-35907796

ABSTRACT

BACKGROUND: Although books and articles guiding the methods of sample size calculation for prevalence studies are available, we aim to guide, assist and report sample size calculation using the present calculators. RESULTS: We present and discuss four parameters (namely level of confidence, precision, variability of the data, and anticipated loss) required for sample size calculation for prevalence studies. Choosing correct parameters with proper understanding, and reporting issues are mainly discussed. We demonstrate the use of a purposely-designed calculators that assist users to make proper informed-decision and prepare appropriate report. CONCLUSION: Two calculators can be used with free software (Spreadsheet and RStudio) that benefit researchers with limited resources. It will, hopefully, minimize the errors in parameter selection, calculation, and reporting. The calculators are available at: ( https://sites.google.com/view/sr-ln/ssc ).


Subject(s)
Software , Cross-Sectional Studies , Humans , Sample Size
14.
J Nurs Manag ; 30(7): 3553-3567, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35666587

ABSTRACT

AIMS: This study investigated stress levels and coping strategies among working and nonworking women in the United Arab Emirates. BACKGROUND: Stress levels in working and nonworking women have previously been studied, but few studies used cortisol to measure stress or examined how coping strategies affect stress levels. METHODS: We employed a cross-sectional design with a convenience sample of women aged 20-65 years. Information on women's sociodemographic characteristics, perceived stress (using the Perceived Stress Scale) and coping strategies (using the Brief-COPE) was collected. Participants' morning (07:00-08:00) and evening (19:00-20:00) cortisol levels were measured using unstimulated saliva samples. RESULTS: In total, 417 working and 403 nonworking women participated in this study. More nonworking women reported high stress levels than working women (14.1% vs. 4.1%, p = .001). Working women reported more use of informational support and venting to cope with stress compared with nonworking women (94.0% vs. 88.1%, p = .001). More nonworking women had impaired morning (<0.094 mg/dl) and evening (>0.359 mg/dl) cortisol compared with working women (58.1% vs. 28.5% and 41.7% vs. 18.0%, respectively). Compared with working women, nonworking women had 3.25 (95%CI: 2.38, 4.47) and 3.78 (95%CI: 2.65, 5.43) times the odds of impaired morning and evening cortisol, respectively. CONCLUSION: Nonworking women exhibited higher levels of stress than working women. There is an urgent need to support nonworking women to manage stress through appropriate awareness campaigns and public health policies. IMPLICATIONS FOR MANAGEMENT: Policymakers and community leaders should consider the mental health of nonworking women as a priority in planning public health policies and programmes. Nurse managers must have a voice in reforming public health policy to support early assessment and management of stress among nonworking women.


Subject(s)
Adaptation, Psychological , Hydrocortisone , Female , Humans , Cross-Sectional Studies , Mental Health , Stress, Psychological/complications
15.
Asian Pac J Cancer Prev ; 23(4): 1415-1423, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35485704

ABSTRACT

BACKGROUND: This study provides population-based study of cancer incidence, mortality and survival rates for women diagnosed with epithelial ovarian cancer (EOC), and evaluate the prognostic factors of EOC patients survival in Brunei Darussalam. METHODS: This is a retrospective  study of patients diagnosed with EOC between 1st January 2007 and 31st December 2017 in Brunei Darussalam. Crude, age-specific, age-standardized incidence and mortality rates per 100,000 women were calculated. Kaplan-Meier method was used to determine the overall 5-years survival rate. Log-rank test was used to examine the differences in survival between groups. The multivariable Cox Proportional Hazard regression models were used to estimate the hazard ratio for overall survival and to identify the prognostic factors. RESULTS: A total of 207 patients were included in the study. The crude incidence and mortality rates were 9.7 and 3.6 per 100,000 respectively while the age-standardized incidence and mortality rates were 11.3 (95% CI: 9.7,12.9) and 4.5 (95% CI: 3.4,5.6) per 100,000 respectively in the period 2007-2017. The overall mean age at diagnosis was 48.4 (standard deviation=15.3) years. The overall survival rates at 1, 3, and 5 years for EOC patients were 79.7%, 69.7%, and 61.4% respectively. Age at diagnosis, cancer stage, and histology were significant prognostic factors for patients' survival. Older age at diagnosis (≥70 years vs <40 years), regional or advanced stage (vs localized stage) and having undifferentiated or other epithelial ovarian (vs serous carcinoma) were associated with having higher hazard of death. CONCLUSION: Early detection of disease should be emphasized through public education and  raising awareness to improve survival rates of patients with EOC.


Subject(s)
Ovarian Neoplasms , Brunei/epidemiology , Carcinoma, Ovarian Epithelial/pathology , Female , Humans , Incidence , Male , Ovarian Neoplasms/diagnosis , Proportional Hazards Models , Retrospective Studies
16.
Cancer Res ; 82(9): 1698-1711, 2022 05 03.
Article in English | MEDLINE | ID: mdl-35247885

ABSTRACT

Metabolic reprogramming is a hallmark of malignant transformation, and loss of isozyme diversity (LID) contributes to this process. Isozymes are distinct proteins that catalyze the same enzymatic reaction but can have different kinetic characteristics, subcellular localization, and tissue specificity. Cancer-dominant isozymes that catalyze rate-limiting reactions in critical metabolic processes represent potential therapeutic targets. Here, we examined the isozyme expression patterns of 1,319 enzymatic reactions in 14 cancer types and their matching normal tissues using The Cancer Genome Atlas mRNA expression data to identify isozymes that become cancer-dominant. Of the reactions analyzed, 357 demonstrated LID in at least one cancer type. Assessment of the expression patterns in over 600 cell lines in the Cancer Cell Line Encyclopedia showed that these reactions reflect cellular changes instead of differences in tissue composition; 50% of the LID-affected isozymes showed cancer-dominant expression in the corresponding cell lines. The functional importance of the cancer-dominant isozymes was assessed in genome-wide CRISPR and RNAi loss-of-function screens: 17% were critical for cell proliferation, indicating their potential as therapeutic targets. Lists of prioritized novel metabolic targets were developed for 14 cancer types; the most broadly shared and functionally validated target was acetyl-CoA carboxylase 1 (ACC1). Small molecule inhibition of ACC reduced breast cancer viability in vitro and suppressed tumor growth in cell line- and patient-derived xenografts in vivo. Evaluation of the effects of drug treatment revealed significant metabolic and transcriptional perturbations. Overall, this systematic analysis of isozyme expression patterns elucidates an important aspect of cancer metabolic plasticity and reveals putative metabolic vulnerabilities. SIGNIFICANCE: This study exploits the loss of metabolic isozyme diversity common in cancer and reveals a rich pool of potential therapeutic targets that will allow the repurposing of existing inhibitors for anticancer therapy. See related commentary by Kehinde and Parker, p. 1695.


Subject(s)
Breast Neoplasms , Isoenzymes , Breast Neoplasms/genetics , Cell Line, Tumor , Female , Humans , Isoenzymes/genetics , Isoenzymes/metabolism , Kinetics
17.
BMC Geriatr ; 22(1): 179, 2022 03 03.
Article in English | MEDLINE | ID: mdl-35236280

ABSTRACT

BACKGROUND: The older person is at greater risk of falls due to multiple intrinsic and extrinsic factors. This is compounded when the elderly is admitted to hospitals, as they are acutely ill and placed in an unfamiliar environment. Delirium and polypharmacy further complicate these problems. As falls reflect quality of care with potential for grave outcomes, this study aimed to identify the extent and risk of falls in public hospitals. METHODS: We conducted a nested case control study in 12 public hospitals in Malaysia. In the cohort section, we screened all inpatients 60 years of age and above daily until discharge, or the end of the study period. Daily, we identified those who fell, inclusive of near falls, in the preceding 24 h. Our enumerators interviewed patients on experience of fall, and supplemented data from the nurses and caregivers. For each case, ten controls were chosen. RESULTS: The incidence of falls/near falls was 1.0 per 1000 patient days (95% CI: 0.9, 1.1). Intrinsic risk factors found to be significant included patients who were not from a nursing home or not cared for by a domestic helper prior to admission, had prior history of indoor fall either in home or hospital, had four or more clinical diagnoses or exited from the bed on the weak side. Significant extrinsic factors were the absence of transfer bar in toilet, call bells, light switches or walking aids that were not within reach, as well as not having a walking aid. Non-sturdy chair was associated with lesser falls than when sturdy chairs with armrests were present. CONCLUSION: Querying patients for falls produced better results than incident reporting. Several intrinsic factors such as history of indoor or in-hospital fall, having four or more clinical diagnoses or exiting from weaker side and residence history may help to identify those at higher risk. Addressing significant extrinsic factors such as transfer bars and the identification of switches may help in reducing falls risk in hospitals. TRIAL REGISTRATION: This study was registered in National Medical Research Register of Malaysia ( NMRR-07-772-1044 ; date 26/05/2008) with Ethics Approval from Medical Research and Ethics Committee (MREC: MRG-07-LOI-HSR-1).


Subject(s)
Inpatients , Aged , Case-Control Studies , Humans , Incidence , Malaysia/epidemiology , Risk Factors
18.
J Gastrointest Cancer ; 53(1): 130-143, 2022 Mar.
Article in English | MEDLINE | ID: mdl-33392958

ABSTRACT

INTRODUCTION: Oesophagogastric cancer is one of the leading causes of cancer death worldwide due to its aggressive nature. Despite the high mortality rate, there is limited information regarding this cancer in Brunei. AIM: To estimate the incidence and survival duration of oesophagogastric cancer patients, to identify prognostic factors of oesophagogastric cancer and associated factors for late-stage oesophagogastric cancer detection. METHODS: A retrospective study on all oesophagogastric cancer patients registered in the population-based national cancer registry in Brunei from January 2010 to December 2018. Kaplan-Meier and Cox proportional hazard regression survival analyses and multiple logistic regression were applied. RESULTS: Sixty-eight oesophagogastric cancer patients' data were retrieved from the registry. The incidence was 2.75 cases per 100,000 adults per year. Median survival time was 1.18 years (95% CI: 0.77, 1.80) and the 3-year survival rate was 26.3%. Age (61-70 years) (adjusted HR = 0.38; 95% CI: 0.17, 0.89; p = 0.025) and those who have undergone chemotherapy (adj. HR = 0.40; 95% CI: 0.18, 0.90; p = 0.026) have a significantly lower mortality risk. Obesity (adj. HR = 11.94; 95% CI: 1.94, 73.36; p = 0.007), and stage 4 (advanced stage) cancer (adj. HR=4.11; 95% CI: 1.97, 8.58; p< 0.001) have a significantly higher mortality risk. Females have 3-time odds (adj. OR = 3.05; 95% CI: 1.09, 9.02; p = 0.038) of presenting with stage 4 cancer. Smokers have 13-time odds (Adj. OR=12.99; 95% CI: 1.92, 262.0; p = 0.025) of presenting with stage 4 cancer. CONCLUSION: Prognosis of oesophagogastric cancer remains poor. Addressing late detection and improve endoscopic surveillance and awareness of symptoms may help improve prognosis and mortality.


Subject(s)
Neoplasms , Adult , Aged , Female , Humans , Incidence , Kaplan-Meier Estimate , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
19.
Int Nurs Rev ; 69(3): 285-293, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34878183

ABSTRACT

AIMS: To assess the extent of posttraumatic stress disorder (PTSD) symptoms and severity, factors motivating work continuation, and factors influencing PTSD development among frontline nurses caring for patients with COVID-19. BACKGROUND: The COVID-19 pandemic has an emotional toll on nurses. Exposure to traumatic events associated with the pandemic places frontline nurses at risk for developing PTSD. DESIGN: Cross-sectional study. METHODS: Frontline nurses (n = 370) who cared for COVID-19 patients in three governmental hospitals in the United Arab Emirates were recruited from November 2020 to January 2021. The self-reported Posttraumatic Diagnostic Scale (PDS) was used to assess PTSD. The motivational factors for work continuation explored were: work-related factors (e.g., availability of personal protective equipment and management recognition), family support, and obligation to care. We used correlation and multiple regression analyses to investigate factors that influenced PDS score, including sociodemographic characteristics (e.g., gender, age, exercising status, and general health status), work factors (e.g., hospital type [COVID vs non-COVID], prior work experience, and encountering deaths), and factors motivating work continuation. The reporting of this study was consistent with STROBE guidelines. RESULTS: In total, 36.2% participants had a probable PTSD diagnosis (PDS score ≥28) with most reporting unwanted memories. Family support (95.9%) and management recognition (90.8%) were the most frequently reported motivating factors. Factors significantly associated with higher PDS score were smoking, lack of management recognition, not exercising, and encountering COVID-19 deaths; the correlation and regression coefficients (b) were significant (p < 0.05). CONCLUSIONS AND IMPLICATIONS FOR NURSING/HEALTH POLICY: Policy makers must expand healthcare policies to address frontline nurses' mental health as a priority during the pandemic. Nurse leaders must be involved in health policy development to protect nurses in anticipation of and during global health emergencies.


Subject(s)
COVID-19 , Nurses , Stress Disorders, Post-Traumatic , COVID-19/epidemiology , Cross-Sectional Studies , Humans , Nurses/psychology , Pandemics , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , Surveys and Questionnaires
20.
BMC Med Educ ; 21(1): 542, 2021 Oct 27.
Article in English | MEDLINE | ID: mdl-34702230

ABSTRACT

BACKGROUND: In keeping with nation-wide efforts to contain the spread of COVID-19, Universiti Brunei Darussalam (UBD) transformed fully its pedagogical delivery to online mode, where we investigated teaching and learning experiences, physical and mental health of undergraduate students and lecturers during the COVID-19 pandemic. METHODS: We conducted a cross-sectional study on undergraduate students and lecturers in a health science faculty using a self-developed pretested questionnaire through anonymous online data collection method. RESULTS: Fifty-six lecturers (100% response rate) and 279 students (93.3% response rate) participated. The positive experiences reported by students include becoming independent (72.8%) and adapting to online learning (67.4%), while lecturers learned new teaching techniques (50.0%) and became more innovative (50.0%) by learning new tools (48.2%). However, studying at home caused students to feel more distracted (72.0%) with a feeling of uncertainty towards examinations (66.7%), while lecturers felt that students' laboratory skills were compromised (44.6%). Even though online delivery of assessments enabled lecturers to explore all options (50.0%), they found it difficult to maintain appropriate questions (41.1%) and fair assessments (37.5%). Majority of students missed eating out (68.8%) and felt a lack of participation in extracurricular activities (64.9%), while lecturers reported more time for exercise (51.8%), despite having more screen time (50.0%) and computer-related physical stress (44.6%). In terms of mental health, increased stress in students was reported (64.9%), though they had more time for self-reflection (54.8%). Although lecturers reported a closer relationship with family (44.6%), they also felt more stressed due to deadlines, unexpected disruptions and higher workloads (44.6%) as well as concerns related to work, family and self (39.3%). CONCLUSION: In this abrupt shift to online teaching, students and lecturers in our study identified both positive and negative experiences including the impact on their physical and mental health. Our findings are important to provide the evidence for online pedagogical benefits and can serve to promote the enhancement and adaptation of digital technology in education. Our findings also aim to promote the importance of addressing physical and mental health issues of the university community's well-being through provision of emotional and mental health support and appropriate programs.


Subject(s)
COVID-19 , Pandemics , Cross-Sectional Studies , Delivery of Health Care , Humans , Mental Health , SARS-CoV-2 , Students
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