Data_Sheet_1_Telemonitored Human Circadian Temperature Dynamics During Daily Routine.docx

BackgroundCircadian rhythms in body temperature coordinate peripheral molecular clocks, hence they could potentially predict optimal treatment timing (chronotherapy) in individual patients. Circadian parameters in chest surface body temperature (Chesttemp) were recorded remotely and in real time through the use of wearable sensors.MethodsThe dynamics of circadian oscillations in Chesttemp and core body temperature (Coretemp) and their moderation by sex and age were analysed in 38 men and 50 women, aged 21–78 years. In two studies (ST1 and ST2), Chesttemp was measured every minute and teletransmitted using a BLE-connected sensor for 3.6–28.3 days. Additionally, in ST2, Coretemp was recorded per minute in 33 age- and sex-stratified subjects using electronic ingestible pills with radio-frequency transmissions. Circadian parameters were computed using spectral analysis and cosinor modelling. The temporal relations between Chesttemp and Coretemp cosinor parameters were summarised with principal component (PC) analysis. The effect of sex and age was analysed through multivariate regression.ResultsUsing spectral analysis, a dominant period of 24- or 12-h was identified in 93.2% of the Chesttemp and in 100% of the Coretemp time series. The circadian parameters varied largely between-subjects both for Chesttemp (ranges: mesors, 33.2–36.6°C; amplitudes, 0.2–2.5°C; acrophases, 14:05–7:40), and Coretemp (mesors, 36.6–37.5°C; amplitudes, 0.2–0.7°C; bathyphases, 23:50–6:50). Higher PC loadings mainly corresponded to (i) large Chesttemp amplitudes, and phase advance of both temperature rhythms for the first PC (PC1, 27.2% of variance var.), (ii) high mesors in both temperature rhythms for PC2 (22.4% var.), and (iii) large Coretemp amplitudes for PC3 (12.9% var.). Chesttemp and Coretemp mesors and PC2 loadings decreased in females, while remaining quite stable in males as a function of age. In contrast, Coretemp amplitude and PC3 loadings increased with age in females, but decreased in males. Finally, older subjects, both female and male, displayed a reduction in ultradian variabilities, and an increase in both Chesttemp circadian amplitude and PC1 loadings.InterpretationThe dynamics relations between Chesttemp and Coretemp rhythms were largely moderated by age and sex, with results suggesting that treatment timing could be most critical for therapeutic index in women and in order people.

背景：人体体温的昼夜节律与外周分子时钟相协调，因此它们有可能预测个体患者最佳治疗时机（时辰治疗）。通过佩戴式传感器，远程且实时地记录了胸部表面体温（Chesttemp）的昼夜参数。方法：在38名男性和50名女性（年龄介于21至78岁之间）中，分析了Chesttemp与核心体温（Coretemp）的昼夜振荡动态及其性别和年龄的调节作用。在两项研究（ST1和ST2）中，Chesttemp每分钟测量一次，并通过蓝牙连接的传感器进行3.6至28.3天的远程传输。此外，在ST2中，33名按年龄和性别分层的主试使用带有射频传输的电子可吞咽药片每分钟记录Coretemp。昼夜参数通过光谱分析和余弦模型计算得出。Chesttemp与Coretemp余弦参数的时间关系通过主成分分析（PCA）进行总结。通过多元回归分析研究了性别和年龄的影响。结果：使用光谱分析，在93.2%的Chesttemp时间序列和100%的Coretemp时间序列中确定了24小时或12小时的占主导地位的周期。昼夜参数在个体之间存在较大差异，对于Chesttemp（范围：平均值，33.2–36.6°C；振幅，0.2–2.5°C；峰值，14:05–7:40），以及Coretemp（平均值，36.6–37.5°C；振幅，0.2–0.7°C；谷值，23:50–6:50）。较高的PC负荷主要对应于（i）较大的Chesttemp振幅，以及第一个温度节律的相位提前对于主成分1（PC1，方差变异的27.2%），（ii）两个温度节律中的高平均值对于PC2（方差变异的22.4%），以及（iii）对于PC3（方差变异的12.9%）的大Coretemp振幅。Chesttemp和Coretemp的平均值以及PC2负荷在女性中随年龄而降低，而在男性中则相对稳定。相反，Coretemp振幅和PC3负荷在女性中随着年龄的增长而增加，但在男性中则减少。最后，无论是女性还是男性，年龄较大的受试者都表现出超昼夜变异性减少，以及Chesttemp昼夜振幅和PC1负荷的增加。解释：Chesttemp与Coretemp节律之间的动态关系在很大程度上受到年龄和性别的调节，研究结果提示治疗时机对女性及有规律的人群的治疗效果可能最为关键。