Aims
Young-onset T2D (YT2D) is associated with a more fulminant course and greater propensity for diabetic complications. The association of PAX4 R192H (rs2233580) variation with YT2D was inconsistent partly because of its Asian-specificity and under-representation of Asians in international consortiums. Interestingly, in our preliminary YT2D (mean?=?25?years old) cohort, the prevalence of PAX4 R192H variant was remarkably higher (21.4%) than the general population. Therefore, we sought to determine whether PAX4 R192H is associated with younger onset of T2D in our East Asian (Chinese) population.Methods
Genotyping of PAX4 R192H was carried out using Illumina OmniExpress BeadChips as part of a genome-wide association study. Data analysis was performed using SPSS Ver. 22.Results
PAX4 R192H genotype was associated with younger onset age (CC: 47.1, CT: 46.0, TT: 42.6) after adjusting for gender, F?=?5.402, p?=?0.005. Independently, onset of diabetes was younger among males by 2.52?years, 95% CI [?3.45, ?1.59], p?<?0.0001. HOMA-IR and HOMA-%B were not significantly different across genotypes for a subset (n?=?1045) of the cohort.Conclusions
Minor allele (T) of PAX4 R192H is associated with younger onset diabetes among Chinese in Singapore. Determining this genotype is important for identifying at-risk individuals for earlier onset diabetes and diabetic complications. 相似文献Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta?=????1.167, PAdj?=?2.75?×?10?4). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.
相似文献Aim
The intensity and duration of surveillance for rectal cancer after surgical resection remain contentious. We evaluated the pattern of recurrences in a rectal cancer cohort followed up beyond 10 years.Methods
An analysis was performed on a retrospective database of 326 patients with rectal cancer who underwent curative surgical resection from 1999 to 2007. The above study duration was chosen to ensure at least 10 years of follow-up. Data on patient demographics, peri-operative details, and follow-up outcomes were extracted from the database. The pattern of recurrences and investigative modality that detected recurrences was identified. Patients were followed up until either year 2016 or the day of their demise.Results
Two hundred seventeen patients (66.6%) were male and 109 patients (33.3%) female. Median age was 64 years old. Close to a third of the patients received adjuvant therapy (34%). Among the 326 patients studied, 29.8% of (97/326) patients developed recurrence. 7.7% (25/326) had loco-regional recurrence while 22.1% (72/326) had distant metastasis. Median time to recurrence was 16 months (4–83) and 18 months (3–81), respectively. Computed tomography scan was the best modality to detect both loco-regional and distant recurrences (48% in loco-regional and 41.7% in distant metastasis). The most common site of distant metastasis is the lung (34.7%). The salvage rate for loco-regional and distant recurrences was 52 and 12.5%, respectively.Conclusion
The predominant pattern of recurrence in rectal cancer is distant disease. Surveillance regimes may need to be altered to increase early detection of distant metastases.Substandard medicines are medicines that fail to meet their quality standards and/or specifications. Substandard medicines can lead to serious safety issues affecting public health. With the increasing number of pharmaceuticals and the complexity of the pharmaceutical manufacturing supply chain, monitoring for substandard medicines via manual environmental scanning can be laborious and time consuming.
MethodsA web crawler was developed to automatically detect and extract alerts on substandard medicines published on the Internet by regulatory agencies. The crawled data were labelled as related to substandard medicines or not. An expert-derived keyword-based classification algorithm was compared against machine learning algorithms to identify substandard medicine alerts on two validation datasets (n = 4920 and n = 2458) from a later time period than training data. Models were comparatively assessed for recall, precision and their F1 scores (harmonic mean of precision and recall).
ResultsThe web crawler routinely extracted alerts from the 46 web pages belonging to nine regulatory agencies. From October 2019 to May 2020, 12,156 unique alerts were crawled of which 7378 (60.7%) alerts were set aside for validation and contained 1160 substandard medicine alerts (15.7%). An ensemble approach of combining machine learning and keywords achieved the best recall (94% and 97%), precision (85% and 80%) and F1 scores (89% and 88%) on temporal validation.
ConclusionsCombining robust web crawler programmes with rigorously tested filtering algorithms based on machine learning and keyword models can automate and expand horizon scanning capabilities for issues relating to substandard medicines.
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