Systolic (S) and diastolic (D) blood pressures (BP) [SBP and DBP] are circadian rhythmic with period (τ) in healthy persons assumed to be maintained at 24.0h. We tested this assumption in a sample of 30 healthy career (mean >12 yrs) 30-to-46 yr-old male Caucasian French firefighters (FFs) categorized into three groups according to work schedule and duties: Group A - 12 FFs working 12h day, 12h night, and occasionally 24h shifts and whose primary duties are firefighting plus paramedical and road rescue services; Group B - 9 FFs working mostly 12h day and 12h night shifts and whose duties are answering incoming emergency calls and coordinating service vehicle dispatch from fire stations with Group A personnel; Group C - 9 day shift (09:00-17:00h) FFs charged with administrative tasks. SBP and DBP, both in winter and in summer studies of the same FFs, were sampled by ambulatory BP monitoring every 1h between 06:00-23:00h and every 2h between 23:01-05:59h, respectively, their approximate off-duty wake and sleep spans, for 7 consecutive days. Activity (wrist actigraphy) was also sampled at 1-min intervals. Prominent τ of each variable was derived by a power spectrum program written for unequal-interval time series data, and between-group differences in incidence of τ≠24h of FFs were assessed by chi square test. Circadian rhythm disruption (τ≠24h) of either the SBP or DBP rhythm occurred almost exclusively in night and 24h shift FFs of Group A and B, but almost never in day shift FFs of Group C, and it was not associated with altered τ from 24.0h of the circadian activity rhythm. In summer, occurrence of τ≠24 for FFs of Group A and B differed from that for FFs of Group C in SBP (p=0.042) and DBP (p=0.015); no such differences were found in winter (p>0.10). Overall, manifestation of prominent τ≠24h of SBP or DBP time series was greater in summer than winter, 27.6% versus 16.7%, when workload of Group B FFs, i.e. number of incoming emergency telephone calls, and of Group A FFs, i.e. number of dispatches for provision of emergency services, was, respectively, two and fourfold greater and number of 12h night shifts worked by Group B FFs and number of 24h shifts worked by Group A FFs was, respectively, 92% and 25% greater. FFs of the three groups exhibited no winter-summer difference in τ≠24h of SBP or SDP; however, τ≠24h of DBP in Group B FFs was more frequent in summer than winter (p=0.046). Sleep/wake cycle disruption, sleep deprivation, emotional and physical stress, artificial light-at-night, and altered nutrient timings are hypothesized causes of τ≠24h for BP rhythms of affected Groups A and B FFs, but with unknown future health effects.
Motivation: Acute Myeloid Leukemia is a highly heterogeneous disease. Although current classifications are well-known and widely adopted, many patients experience drug resistance and disease relapse. New biomarkers are needed to make classifications more reliable and propose personalized treatment. Results: We performed tests on a large scale in 3 AML cohorts, 1112 RNAseq samples. The accuracy to distinguish NPM1 mutant and non-mutant patients using machine learning models achieved more than 95% in three different scenarios. Using our approach, we found already described genes associated with NPM1 mutations and new genes to be investigated. Furthermore, we provide a new view to search for signatures/biomarkers and explore diagnosis/prognosis, at the k-mer level. Availability: Code available at https://github.com/railorena/npm1aml and https://osf.io/4s9tc/. The cohorts used in this article were authorized for use.
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