AREAS COVERED: The steps involved in preparing the mRNA-based cancer vaccines are isolation of the mRNA cancer from the target protein using the nucleic acid RNA-based vaccine, sequence construction to prepare the DNA template, in vitro transcription for protein translation from DNA into mRNA strand, 5' cap addition and poly(A) tailing to stabilize and protect the mRNA from degradation and purification process to remove contaminants produced during preparation.
EXPERT OPINION: Lipid nanoparticles, lipid/protamine/mRNA nanoparticles, and cell-penetrating peptides have been used to formulate mRNA vaccine and to ensure vaccine stability and delivery to the target site. Delivery of the vaccine to the target site will trigger adaptive and innate immune responses. Two predominant factors of the development of mRNA-based cancer vaccines are intrinsic influence and external influence. In addition, research relating to the dosage, route of administration, and cancer antigen types have been observed to positively impact the development of mRNA vaccine.
DESIGN: Prospective cohort study.
SETTING: Community-dwelling older adults interviewed at baseline (2013-2016) and follow-up (2020-2022) as a part of the Malaysian Elders Longitudinal Research study were included.
PARTICIPANTS: Participants who attended face-to-face follow-up visits.
PRIMARY AND SECONDARY OUTCOME MEASURES: Fall occurrence over 12 months preceding the follow-up visit was determined. Anthropometric, bioimpedance analysis and physical performance measurements were obtained at both time points. Participants were categorised into three groups according to changes in weight and body composition using≥5% increase or decrease in weight to determine loss or gain.
RESULTS: Of the 225 participants, aged 71.8±6.8 years, 128 (56.9%) were women. Weight gain was associated with increased fall risk at follow-up compared with stable weight (adjusted rate ratio, aRR (95% confidence interval, CI)=2.86 (1.02-8.02)) following adjustments for age and body mass index (BMI), but this relationship was attenuated by low baseline percentage lean body mass (%LBM) in women. The association was strenghtened after adjusting for age, BMI, and low muscle strength (aRR (95% CI)=2.89 (1.01-8.28)). Weight change did not influence falls risk in men. No difference was observed with changes in percentage body fat and %LBM over time with fall occurrence for both genders.
CONCLUSION: Lower baseline lean body mass influenced the relationship between weight gain and falls longitudinally. Interventions addressing low lean body mass should be considered in the prevention of weight-gain-related falls in older women.
METHODS: Twenty children including 10 with ASD and 10 normally developing children aged 6-12 years were recruited for this study. One accessible ear was exposed to transient-evoked OAE, whereas the other was exposed to suppressor tones. Contralateral suppressors included white noise, Quranic recitations, environmental noise, and natural sound. The magnitude of OAE suppression was determined from the difference between the OAE amplitude with and without the masker (in dB sound pressure levels) for all sound types. The sound with the highest suppression effect was determined using effect size calculation and repeated-measures analysis of variance at a 95% confidence level. A high suppression effect may suggest a high sensory gating performance, whereas low suppression may indicate low sensory gating performance.
RESULTS: Based on the analysis, the sound with the highest suppression effect was that of the waterfall. The suppression results were supported by descriptive analysis findings and effect-size calculations.
CONCLUSIONS: This study provides a better understanding of the alternative sound stimuli, besides the standard white noise tone, for the assessment of sensory gating deficits among children with ASD. Sounds with a high suppression effect have the potential to be used as sound therapy interventions for children with ASD as part of rehabilitation and therapy.
RESEARCH QUESTION: We aim to determine if clusters of Chinese patients with COPD exist and their association with clinical outcomes and inflammation.
STUDY DESIGN AND METHODS: Chinese patients with stable COPD were prospectively recruited into two cohorts (derivation and validation) from six hospitals across three Southeast Asian countries (Singapore, Malaysia, and Hong Kong; n = 1,480). Each patient was followed more than 2 years. Clinical data (including co-morbidities) were employed in unsupervised hierarchical clustering (followed by validation) to determine the existence of patient clusters and their prognostic outcome. Accompanying systemic cytokine assessments were performed in a subset (n = 336) of patients with COPD to determine if inflammatory patterns and associated networks characterized the derived clusters.
RESULTS: Five patient clusters were identified including: (1) ex-TB, (2) diabetic, (3) low comorbidity: low-risk, (4) low comorbidity: high-risk, and (5) cardiovascular. The cardiovascular and ex-TB clusters demonstrate highest mortality (independent of Global Initiative for Chronic Obstructive Lung Disease assessment) and illustrate diverse cytokine patterns with complex inflammatory networks.
INTERPRETATION: We describe clusters of Chinese patients with COPD, two of which represent high-risk clusters. The cardiovascular and ex-TB patient clusters exhibit high mortality, significant inflammation, and complex cytokine networks. Clinical and inflammatory risk stratification of Chinese patients with COPD should be considered for targeted intervention to improve disease outcomes.
METHODS: This phase 3, randomised, double-blind, placebo-controlled trial was conducted at 66 centres across 11 countries and territories (ten in Asia-Pacific; one in the Middle East). The trial included patients aged 18 years and older with Dukes' C or high-risk Dukes' B colon cancer or Dukes' B or C rectal cancer who had undergone resection and had completed standard adjuvant therapy (at least 3 months of chemotherapy). Patients with contraindications to aspirin, familial syndromes of colorectal cancer, recent other cancers, and clinically significant history of cardiovascular disease or stroke were excluded. Patients were randomly assigned (1:1) to aspirin 200 mg daily or placebo for 3 years, and were followed up for 5 years. Randomisation was stratified by study centre, tumour site and stage, and inclusion of oxaliplatin in adjuvant chemotherapy. The patients, study team, and sponsor were masked to treatment assignment. The primary endpoint was disease-free survival. The primary analysis used a stratified Cox model in those commencing study treatment (modified intention-to-treat population), analysing all events to March 31, 2023. Safety was analysed in the same population. This trial is registered at ClinicalTrials.gov (NCT00565708). The primary analysis has been completed, but translational studies of putative aspirin sensitivity biomarkers are ongoing.
FINDINGS: Between Feb 25, 2009, and June 30, 2021, 1587 patients underwent randomisation, of whom 1550 were included in the modified intention-to-treat analysis: 791 (51%) in the aspirin group and 759 (49%) in the placebo group. Of these patients, the median age was 57 years (IQR 48-65); 897 (58%) were male and 653 (42%) female; 271 (17%) had Dukes' B colon cancer, 770 (50%) Dukes' C colon cancer, and 509 (33%) rectal cancer. Median follow-up at data cutoff was 59·2 months (IQR 36·7-60·0). 5-year disease-free survival was 77·0% (95% CI 73·6-80·0) in the aspirin group and 74·8% (71·3-77·9) in the placebo group (hazard ratio of 0·91 [95% CI 0·73-1·13]; p=0·38). Any-grade adverse events were reported in 390 (49%) of 791 patients in the aspirin group versus 386 (51%) of 759 in the placebo group. Serious adverse events were reported in 95 (12%) patients in the aspirin group versus 107 (14%) in the placebo group. There were no treatment-related deaths in either group. Among adverse events of special interest, there were no cases of acute myocardial infarction in the aspirin group versus two in the placebo group; no ischaemic cerebrovascular events in the aspirin group versus two in the placebo group; and three major gastrointestinal bleeds in the aspirin group versus one in the placebo group.
INTERPRETATION: In patients with colorectal cancer, aspirin 200 mg daily for 3 years after completion of standard adjuvant therapy was well tolerated but did not significantly improve disease-free survival.
FUNDING: SingHealth Foundation, National Medical Research Council Singapore, National Cancer Centre Research Fund, Rising Tide Foundation, Lee Foundation, Lee Kim Tah Foundation, Duke-NUS Khoo Bridge Funding Award, Terry-Fox Run, Silent Foundation, Cancer Australia, Bowel Cancer Australia, and Cancer Council NSW.
METHODS: Nineteen units participated with intention of including 100 patients per site as close to a consecutive series as possible in order to minimize selection bias.
RESULTS: There were 2136 patients with a median total number of PCI items selected of 5 (2-10). "Fear of the cancer returning" (39%) and "dry mouth" (37%) were most common. Twenty-five percent (524) reported less than good QOL.
CONCLUSION: There was considerable variation between units in the number of items selected and in overall QOL, even after allowing for case-mix variables. There was a strong progressive association between the number of PCI items and QOL.