Competitive speedcubing - the timed solving of Rubik's Cube puzzles under standardised World Cube Association (WCA) rules - uniquely couples rapid visuospatial processing and working memory with high-speed bimanual fine motor execution, making it a tractable paradigm for investigating time-of-day associations in real-world expert cognitive-motor performance. We analysed 6,600 record-setting performances across four puzzle categories (3 × 3 × 3, 4 × 4 × 4, 5 × 5 × 5, 6 × 6 × 6) from WCA competitions held between 2003 and 2025 using an exposure-adjusted framework in which record probability is expressed as records per attempt within 15-minute local-time bins, evaluated against a within-competition permutation null that preserves schedule structure. Raw record counts exhibit a bimodal distribution with morning and evening peaks; however, exposure adjustment demonstrates that this pattern is substantially attributable to the non-uniform scheduling of competition rounds across the day. After schedule correction, the 4 × 4 × 4 event shows a statistically significant suppression of record probability during the 12:30-15:00 window (outside-to-inside ratio: 1.14×; one-tailed permutation p = 0.020), consistent in timing with the post-prandial alertness dip. This effect is not statistically significant for the 3 × 3 × 3, 5 × 5 × 5, or 6 × 6 × 6 events. Sensitivity analyses confirm that the 4 × 4 × 4 finding is broadly distributed across regions and competitive eras and persists within early rounds alone. The late-evening elevation in raw counts is explained by final-round competitor selection. These results demonstrate the methodological importance of exposure adjustment in ecological performance analyses and identify a residual midday suppression in 4 × 4 × 4 record probability that warrants further investigation.
Introduction:Sleep plays a vital role in maintaining overall health, supporting processes like restoration, memory consolidation, emotional regulation, and metabolism. However, many people remain unaware of their sleep needs, leading to poor sleep quality and patterns that can negatively impact health, workplace performance, and daily life. Sleep behaviors are shaped by various factors, including cultural practices, urbanization, and lifestyle changes. This study focuses on adults in Karachi, Pakistan, where religious routines and modern living create unique sleep challenges. By exploring these patterns, we aim to identify ways to enhance sleep quality and promote better well-being in this population. Methodology:This cross-sectional study was conducted in Karachi, Pakistan, over one year, with 400 adults aged 18-64 were recruited. Exclusion criteria included conditions affecting sleep, chronic illnesses, and use of sleep aids. Data collection employed a Google Forms-based structured questionnaire covering demographics, religious practices, and sleep habits. Sleep quality and daytime sleepiness were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), respectively. Data analysis, performed in SPSS, included descriptive statistics and hypothesis testing using Chi-squared, Mann-Whitney, and Kruskal-Wallis tests. Sleep patterns were categorized as monophasic, biphasic, or polyphasic using conditional formulas in Excel. Results:The mean age of participants (n = 384) was 29 ± 0.1 years, with 66.4% women. The most common sleep pattern was monophasic (40.4%), followed by biphasic-siesta (21.6%), biphasic-dawn (20.8%), and polyphasic (17.2%). Women favored segmented sleep patterns (p = 0.019). Biphasic-dawn sleepers reported the least daytime sleepiness (ESS = 7.18 ± 3.85, p = 0.024), while biphasic-siesta sleepers had the poorest sleep quality (PSQI = 6.94 ± 3.01, p = 0.013). Men had better sleep quality (PSQI = 5.22 ± 2.70) and lower daytime sleepiness (ESS = 6.89 ± 3.65) than women (p < 0.001). Weekend sleep disruptions were significant (p < 0.001). Conclusions:Monophasic sleep dominates, though gender differences suggest women prefer segmented patterns. Biphasic-dawn sleep aligns with better quality and less daytime sleepiness, while biphasic-siesta sleepers experience the poorest outcomes. Men and employed individuals generally report better sleep metrics. Morning prayers improve sleep quality slightly. Students exhibit higher daytime sleepiness and worse sleep quality compared to others.
The hypothalamic suprachiasmatic nucleus (SCN), the circadian pacemaker of the mammalian brain, integrates both environmental and endogenous information to modulate various physiological and behavioral processes. Both light and physical activity entrain SCN circadian rhythmicity, but the underlying molecular mechanisms for physical activity remain elusive. Repetitive neuronal stimulation results in accumulation of the stable transcription factor ΔFOSB, that has been implicated in long-term brain plasticity, altered neuronal excitability, and changes in behavior. In rodents, voluntary wheel running (VWR) mimics aspects of exercise training and increases ΔFOSB in several brain regions. Whether VWR also alters ΔFOSB in the SCN is unexplored. Here, young-adult male and female Wistar rats were housed sedentary or allowed to run for four weeks followed by quantification of ΔFOSB in the SCN. VWR lowered SCN ΔFOSB-positive cell numbers in males and females compared to sedentary housing. Total running distance did not correlate with ΔFOSB suppression. Analysis taking estrous cycle into account revealed that ΔFOSB-positive cell numbers were cyclic in sedentary females, being lowest during proestrus and highest during diestrus. Remarkably, this cyclicity was absent in runners, where ΔFOSB-positive cell numbers remained comparable to those observed during proestrus in sedentary controls. Finally, estradiol replacement following ovariectomy in sedentary females lowered SCN ΔFOSB-positive cell numbers. Thus, VWR and estrous cycle, via, at least in part, estradiol, modulate SCN ΔFOSB. Given its role in long-term plasticity and behavioral adaptations, ΔFOSB may provide a molecular link between VWR and/or estrous cycle and the output of the SCN and its related behavioral adaptations.
Introduction:Circadian processes may be causal in the development and maintenance of binge eating. We used a rodent model of binge-like eating and a circadian disruption protocol to test whether circadian disruption causes increased consumption during 24h access to a high energy diet (HED). Method:Eight male mice underwent a two-week baseline with ad-lib standard chow and maintained a 12h light-dark schedule. Mice then completed two binge cycles. After, mice received a circadian disruption manipulation or remained on typical light schedule (i.e., were non-circadian disrupted). All mice received two binge cycles after manipulation. Chow and HED were measured every 12h and 24h. Independent samples t-tests compared consumption between the disrupted and non-disrupted groups. Results:Binge-like eating occurred in both experimental groups across all phases of the study. Circadian disrupted mice consumed more during HED access than non-disrupted mice, indicating that circadian disruptions may exacerbate binge-like eating. Circadian disruption also altered consumption timing; disrupted mice consumed more during typical rest hours (7:00-19:00) than non-disrupted mice but did not alter consumption during typical active hours (19:00-7:00). Conclusions:These results provide justification for research examining circadian processes implicated in binge eating. Future research may inform on the utility of circadian regulating adjunctive treatment (e.g., bright light therapy or exercise).
Morningness is associated with several positive health outcomes and personality traits such as conscientiousness. In the current report, meta-analysis demonstrated a significant association between morningness and conscientiousness, data that are consistent with previous meta-analyses. Further, survey report and resting-state functional Magnetic Resonance Imaging (rs-fMRI, N = 43) indicated that the relationship between morningness and conscientiousness was moderated by functional connectivity with the Default Mode Network (DMN). DMN connectivity has been implicated in a number of cognitive functions and higher connectivity in this network is associated with higher conscientiousness.
The anterior region of the hypothalamus accommodates a bilateral structure called the suprachiasmatic nucleus (SCN), which controls, modulates, and perpetuates the homeostasis of circadian rhythm and sleep hormone release. These SCN have a predominance over multitudinous peripheral tissues like the uterus, liver, intestine, pancreas, endocrine system, immune system, reproductive system, and cardiovascular system. This peripheral clock acts as a pacemaker for circadian rhythm timing, which regulates crucial metabolic pathways and organizes numerous activities in the female reproductive network of mammals. The circadian CLOCK genes are expressed in various reproductive organs. The CLOCK, BMAL1, CRY, and PER genes harmonize the balance and manifestation of nuclear receptors (NRs) expression, and the other way round, NRs regulate these circadian genes. Several NRs, in particular estrogen, progesterone, androgen, and PPARs, nurture the ovary and uterus. Bidirectional coordination between SCN and NRs maintains the circadian rhythm of the hypothalamic-pituitary-gonadal (HPG) axis of the female reproductive organs.
The influence of morningness-eveningness preference and dietary components on the circadian variation in peak expiratory flow (PEF), an established criterion for pulmonary function, is not fully understood. This study aimed to investigate (a) how the chronotype influences the 24-h variation in PEF and (b) whether the bronchodilator theobromine affects this variation differently in different chronotypes. Ninety-seven healthy non-smoking females (54 early chronotypes, ET; 43 late chronotypes, LT; 18-35 years) recorded their PEF over 24 hours at 4-h intervals (08:00/12:00/16:00/20:00/24:00/04:00/08:00 h). In a subgroup (26 ET, 18 LT), the effect of 48 mg theobromine (40 g dark chocolate) on PEF was compared on three consecutive 24-h days with no administration, morning administration and evening administration of theobromine. Repeated measures ANOVA tested for 24-h variation in PEF. Both chronotypes displayed significant 24-h variation in PEF (P < 0.0001) explaining 36% (ET) and 31% (LT) of variance of PEF. The time of maximum PEF was three hours earlier in ET than in LT (P = 0.003) and correlated negatively with chronotype scores (P = 0.001) and positively with bedtimes (awakening time: P < 0.001; sleep-onset time: P = 0.012). The chronotypes showed no differences in 24-h mean and amplitude % mean for PEF. Administration of theobromine strengthened the morning increase (P = 0.004) and weakened the evening decrease (P = 0.063) of PEF in LT, but had no effect in ET. The differences found between chronotypes in timing of maximum PEF and responsiveness to the bronchodilator theobromine might have clinical relevance. Therapy for respiratory diseases should consider the chronotype of patients for drug timing and dosage.
Sleep disturbance is common following acute coronary syndrome (ACS) and may contribute to a worse prognosis. We describe the rationale, design, and findings of a pilot and feasibility randomized clinical trial (RCT) of an intervention to improve post-ACS sleep. Fifteen post-ACS patients with insomnia and/or short sleep were randomized (2:1 allocation) to combined chronotherapy (CC) plus sleep hygiene education (SHE) or SHE control. CC was bright light therapy (BLT) delivered by a wearable light visor for 30 minutes after awakening and short-wavelength light avoidance using blue-light blocking (BLB) glasses in the evening from 8:00pm to bedtime daily for 4 weeks. Primary outcomes were feasibility, acceptability, appropriateness, usability, and adherence. Secondary outcomes were insomnia symptoms, sleep quality, and sleep duration. Two patients in the CC intervention group dropped before initiating study procedures. Completion of study procedures in remaining patients was high in the CC and control groups (88% and 100%, respectively). Self-reported adherence to CC (i.e., using BLT and BLB on ≥50% of days) was high (88% and 100%, respectively). The proportion of CC patients who perceived the intervention as feasible (71%) and usable (100%) was high, though fewer CC patients rated the intervention as acceptable (57%) and appropriate to improve sleep (29%). Improvements in insomnia symptoms and self-reported sleep quality and duration were seen in response to the CC intervention (71%). Post-ACS patients with sleep disturbance had high adherence to this chronotherapeutic intervention, and most viewed it as feasible and usable. This intervention should be tested in a larger RCT to determine efficacy to improve sleep. Trial Registration:ClinicalTrials.gov number NCT05299723. Date of registration:March 29, 2022. URL of trial registry record:https://classic.clinicaltrials.gov/ct2/show/NCT05299723.
8-hydroxy-2’deoxyguanosine (8-OHdG) is an oxidative product removed from DNA following radical oxygen species-induced damage. As a water-soluble molecule, it can be measured non-invasively in urine and is commonly used as a marker for ‘whole-body’ oxidative stress. However, its validity and reliability in assessing oxidative stress across various chronic diseases and in early carcinogenesis screening in clinical diagnosis and research remain subjects of debate. To determine optimal measurement timing and duration, it is essential to establish the circadian profile of 8-OHdG under everyday life conditions. Here, applying the integrative single-case design, we show the presence of day-night differences for 8-OHdG in continuous time series of two breast cancer survivors while considering different correction approaches. The participants sampled their urine in 12-h-pooled collections over one month. In both subjects, 8-OHdG levels were significantly higher during the day than at night regardless of whether they were corrected by creatinine or urine volume (creatinine corrected: t = –6.43, p < 0.01 [subject 1], t = –2.69, p = 0.01 [subject 2]; volume corrected: t = –7.30, p < 0.01 [subject 1], t = –3.69, p < 0.01 [subject 2]). Notably, urinary 8-OHdG levels show higher variability in night samples compared to day samples. These findings underscore the importance of considering daily fluctuations in 8-OHdG levels in both clinical and research studies, as well as the need to account for the dynamic characteristics of stress markers to minimize the risk of inconsistent or misleading results in clinical diagnostics.
The developmental origins of health and disease theory suggests that environmental exposures during early life, particularly during prenatal life, can greatly influence health status later in life. Irregular light-dark cycles, such as those experienced during shift work, result in the repeated disruption of circadian rhythms, which negatively impacts physiological and behavioral cycles. The purpose of our study was to assess parameters in the developing mouse embryo and fetus using high frequency ultrasound when exposed to circadian disruption. Pregnant female mice were subjected to a seven-hour advanced circadian disrupted protocol or remained on a normal 12/12 light-dark cycle throughout pregnancy. Significant differences were observed in placental length (p = 0.00016), placental thickness (p = 0.0332), and stomach diameter (p = 0.0186) at E14.5-18.5. These findings suggest that circadian disruption in pregnant dams, mimicking shift work, alters embryonic and fetal development in specific organs in utero.
Background: Stroke patients often present circadian disruption due to multiple causes e.g., primary disease, comorbidities, medication, immobilization, reduced daylight entrainment and sleep disturbances. Objective: To investigate the circadian rhythm of temperature in forehead skin in patients with moderate to severe stroke admitted for rehabilitation. Methods: A physiologic study in form of a secondary analysis of a former randomized study. In total 27 patients with moderate to severe stroke were included between May 1st 2014, and June 1st 2015. Circadian temperature was collected approx. seven days after admission at the acute stroke unit by a skin surface temperature probe as part of a Polysomnography (PSG) measurement. Results: Temperature variations show no circadian rhythm (Type 3 tests of fixed effects by SAS, p = 0.1610). The median temperature variance did fluctuate, but not significantly, and the small changes in circadian temperature variance did not follow the normal temperature variance. Conclusion: Patients with moderate to severe stroke show an abrogated circadian rhythm of temperature. There is an unmet need to understand the mechanisms for this, significance for stroke outcome and treatment.
Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.
Circadian Biology intersects with diverse scientific domains, intricately woven into the fabric of organismal physiology and behavior. The rhythmic orchestration of life by the circadian clock serves as a focal point for researchers across disciplines. This retrospective examination delves into several of the scientific milestones that have fundamentally shaped our contemporary understanding of circadian rhythms. From deciphering the complexities of clock genes at a cellular level to exploring the nuances of coupled oscillators in whole organism responses to stimuli. The field has undergone significant evolution lately guided by genetics approaches. Our exploration here considers key moments in the circadian-research landscape, elucidating the trajectory of this discipline with a keen eye on scientific advancements and paradigm shifts.
The human circadian timing system depends on the light/dark cycle as its main cue to synchronize with the environment, and thus with solar time. However, human activities depend also on social time, i.e. the set of time conventions and restrictions dictated by society, including Daylight Saving Time (DST), which adds an hour to any degree of desynchrony between social and solar time. Here, we used Google Trends as a data source to analyze diurnal variation, if any, and the daily peak in the relative search volume of 26 Google search queries in relation to the transitions to/from DST in Italy from 2015 to 2020. Our search queries of interest fell into three categories: sleep/health-related, medication and random non sleep/health-related. After initial rhythm and phase analysis, 11 words were selected to compare the average phase of the 15 days before and after the transition to/from DST. We observed an average phase advance after the transition to DST, and a phase delay after the transition to civil time, ranging from 25 to 60 minutes. Advances or delays shorter than 60 minutes, which were primarily observed in the sleep/health-related category, may suggest that search timing for these queries is at least partially driven by the endogenous circadian rhythm. Finally, a significant trend in phase anticipation over the years was observed for virtually all words. This is most likely related to an increase in age, and thus in earlier chronotypes, amongst Google users.
We aimed to examine the difference in rest-activity rhythm (RAR) and light exposure rhythm (LER) between patients with mild cognitive impairment (MCI) and normal controls (NC), and to verify their relationships with cognitive functions. The neuropsychological battery was administered to participants above 50 years old. The MCI diagnosis was made according to Petersen's criteria. Ten patients with MCI (77.90 ± 6.95 years) and eight NC (74.75 ± 5.06 years) were studied. Actigraphy (Actiwatch 2; Philips Respironics) was recorded at home for 5 days. RAR and LER variables, including interdaily stability (IS), intradaily variability (IV) and relative amplitude, were calculated using nonparametric analyses. The associations between cognitive performance and RAR and LER variables were explored using generalized linear models. There were no significant differences in RAR or LER variables between MCI and NC. There was a significant main effect of RAR-IS on the Stroop Color and Word Test (SCWT), indicating a positive relationship between RAR stability and SCWT performance. There was a significant group by RAR-IS interaction on Trail Making Test-A, indicating a negative relationship in MCI compared to NC. There was a significant group by LER-IV interaction on the Boston Naming Test, indicating a positive relationship in MCI compared to NC. There was no disruption in RAR and LER in patients with MCI. Our study showed that circadian rhythm abnormality was associated with a decline in executive function. However, circadian rhythm abnormality was not associated with declines in processing speed and language function in patients with MCI, implying an altered pathophysiology compared to NC.
The circadian clock is adjusted by light inputs via the retinohypothalamic tract. Because environmental light is controllable for modern humans at the individual’s preference although under social schedules, individual differences in time-related psychology and behavior may be associated with morningness-eveningness preference (M-E preference). To examine this hypothesis, we used the Time Management Scale and Time Anxiety Scale to quantify time-related psychology and behavior. These scales aim to evaluate “awareness of effective time management and utilization” and “anxiety about uncontrollable time schedule and unexpected time-related outcome”, respectively. According to our correlation analysis using mid-sleep time as a marker for M-E preference, we obtained results supporting our hypothesis in the correlation between the M-E preference values and the Time Management Scale scores, with larger “time estimation” and “taking each moment as it comes” scores associated with more morningness and eveningness, respectively. Considering that modern humans likely become night owls under artificial light conditions, it appears plausible that lower awareness of time management leads to more eveningness.
The circadian clock regulates the "push-pull" of the molecular signaling mechanisms that arrange the rhythmic organization of the physiology to maintain cellular homeostasis. In mammals, molecular clock genes tightly arrange cellular rhythmicity. It has been shown that this circadian clock optimizes various biological processes, including the cell cycle and autophagy. Hence, we explored the dynamic crosstalks between the circadian rhythm and endoplasmic reticulum (ER)-quality control (ERQC) mechanisms. ER-associated degradation (ERAD) is one of the most important parts of the ERQC system and is an elaborate surveillance system that eliminates misfolded proteins. It regulates the steady-state levels of several physiologically crucial proteins, such as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and the metastasis suppressor KAI1/CD82. However, the circadian oscillation of ERQC members and their roles in cellular rhythmicity requires further investigation. In the present study, we provided a thorough investigation of the circadian rhythmicity of the fifteen crucial ERQC members, including gp78, Hrd1, p97/VCP, SVIP, Derlin1, Ufd1, Npl4, EDEM1, OS9, XTP3B, Sel1L, Ufd2, YOD1, VCIP135 and FAM8A1 in HEK293 cells. We found that mRNA and protein accumulation of the ubiquitin conjugation, binding and processing factors, retrotranslocation-dislocation, substrate recognition and targeting components of ERQC exhibit oscillation under the control of the circadian clock. Moreover, we found that Hrd1 and gp78 have a possible regulatory function on Bmal1 turnover. The findings of the current study indicated that the expression level of ERQC components is fine-tuned by the circadian clock and major ERAD E3 ligases, Hrd1 and gp78, may influence the regulation of circadian oscillation by modulation of Bmal1 stability.
Many critical life processes are regulated by input from 24-hour external light/dark cycles, such as metabolism, cellular homeostasis, and detoxification. The circadian clock, which helps coordinate the response to these diurnal light/dark cycles, remains rhythmic across lifespan; however, rhythmic transcript expression is altered during normal aging. To better understand how aging impacts diurnal expression, we present an improved Fourier-based method for detecting and visualizing rhythmicity that is based on the relative power of the 24-hour period compared to other periods (RP24). We apply RP24 to transcript-level expression profiles from the heads of young (5-day) and old (55-day) Drosophila melanogaster, and reveal novel age-dependent rhythmicity changes that may be masked at the gene level. We show that core clock transcripts phase advance during aging, while most rhythmic transcripts phase delay. Transcripts rhythmic only in young flies tend to peak before lights on, while transcripts only rhythmic in old peak after lights on. We show that several pathways including glutathione metabolism, gain or lose coordinated rhythmic expression with age providing insight into possible mechanisms of age-onset neurodegeneration. Remarkably, we find that many pathways show very robust coordinated rhythms across lifespan, highlighting their putative roles in promoting neural health. We investigate statistically enriched transcription factor binding site motifs that may be involved in these rhythmicity changes.
The purpose of this study was to analyze the light-dark variations in the concentrations of several neurotransmitters in the lumbar spinal cord of rats. Six groups of male Wistar rats were exposed to a 12 h light-12 h dark cycle for 70 days. At different time points of the experimental day (8, 12, 16, 20, 24 and 4 h), one of the groups of rats was randomly selected to be sacrificed, and the spinal cords were removed. The gamma-aminobutyric acid (GABA), glutamate (GLU), dopamine, serotonin, epinephrine (E), and norepinephrine (NE) levels in each extracted spinal cord were measured with high-pressure liquid chromatography (HPLC)-EQ and HPLC-fluorescence systems. Our results indicate that the spinal concentrations of GABA and GLU showed sinusoidal variation in a 24 h cycle, with the highest peak in the dark period (~20 h). Dopamine and serotonin also fluctuated in concentration but peaked in the light period (between 8 and 12 h), while E and NE concentrations showed no significant fluctuations. The possible relationship between neurotransmitter spinal concentration and sensitivity to pain and locomotor activity is discussed. It was concluded that most of the neurotransmitter levels in the lumbar spinal cord showed circadian fluctuations coupled to a light-dark cycle.
Background: To address a critical gap for application of cancer chronotherapy of when would be the best time(s) for treating an individual cancer patient, we conducted a pilot study to characterize diurnal variations of gene expression in oral mucosal tissue, which is vulnerable to damage from cancer therapies. Methods: We conducted RNA-seq assay on individual oral mucosal samples collected from 11 healthy volunteers every 4 hours (6 time points). Using a cosine-based method, we estimated the individual and average values of peak-time and amplitude for each gene. Correlations between gene expression peak-times and age was examined, adjusting for individual’s sleep timing. Results: Among candidate gene pathways that are relevant to treatment response, 7 of 16 genes ('PER3, CIART, TEF, PER1, PER2, CRY2, ARNTL') involved in circadian regulation and 1 of 118 genes ('WEE1') involved in cell cycle regulation achieved p-value ≤ 0.1 and relative amplitude>0.1. The average peak times were approximately 10:15 for PER3, CIART and TEF, 10:45 for PER1, 13:00 for WEE1, PER2 and CRY2, and 19:30 for ARNTL. Ranges in peak times across individuals differed by gene (e.g., 8 hours for PER1; 16.7 hours for WEE1). Older people had later peak times for PER1 (r = 0.77, p = 0.03) and PER3 (r = 0.69, p-value = 0.06). Conclusion: In oral mucosa, expression of some genes relevant to treatment response displayed diurnal variation. These genes may be candidates for development of biomarkers for optimizing individual timing of cancer therapy using non-invasively collected oral mucosa.
