CircadiPy: An open-source toolkit for analyzing chronobiology time series.

BACKGROUND: Chronobiology is the scientific field focused on studying periodicity in biological processes. In mammals, most physiological variables exhibit circadian rhythmicity, such as metabolism, body temperature, locomotor activity, and sleep. The biological rhythmicity can be statistically evaluated by examining the time series and extracting parameters that correlate to the period of oscillation, its amplitude, phase displacement, and overall variability. NEW METHOD: We have developed a library called CircadiPy, which encapsulates methods for chronobiological analysis and data inspection, serving as an open-access toolkit for the analysis and interpretation of chronobiological data. The package was designed to be flexible, comprehensive and scalable in order to assist research dealing with processes affected or influenced by rhythmicity. RESULTS: The results demonstrate the toolkit's capability to guide users in analyzing chronobiological data collected from various recording sources, while also providing precise parameters related to the circadian rhythmicity. COMPARISON WITH EXISTING METHODS: The analysis methodology from this proposed library offers an opportunity to inspect and obtain chronobiological parameters in a straightforward and cost-free manner, in contrast to commercial tools. CONCLUSIONS: Moreover, being an open-source tool, it empowers the community with the opportunity to contribute with new functions, analysis methods, and graphical visualizations given the simplified computational method of time series data analysis using an easy and comprehensive pipeline within a single Python object.

Trastorno por Déficit de Atención con Hiperactividad: Ritmo Circanual en el Mes de Nacimiento / Attention Deficit Hyperactivity Disorder: Circannual Rhythm in the Month of Birth

Estudiamos la existencia de ritmo circanual en el mes de nacimiento en participantes con trastorno de déficit de atención e hiperactividad (TDAH)y analizamos la asociación entre meses de nacimiento y TDAH. La muestra incluye 10978 participantes (1778 TDAH / 9200 no TDAH), entre 3 y18 años, reclutados mediante muestreo consecutivo de primeras consultas atendidas en salud mental entre 1992 y 2021. Los participantes conTDAH presentan un ritmo circanual significativo en los meses de nacimiento, con una acrofase en octubre. Nacer en el último cuatrimestre del añoincrementa significativamente la probabilidad de ser diagnosticado TDAH, controlando el efecto de sexo y edad. Con el transcurso de los meses delaño, existe una tendencia lineal creciente significativa de ser diagnosticado de TDAH, no observada en población general, ni en casos sin TDAH.Es necesario tener precaución en el diagnóstico y tratamiento de los niños nacidos en los últimos meses del año, que, por su mayor inmadurez encomparación con los demás niños de la clase, pudieran ser diagnosticados y tratados erróneamente como TDAH. (AU)

We studied the existence of circanual rhythm in the month of birthin participants with attention deficit hyperactivity disorder (ADHD) and analyzed the association between months of birth and ADHD. We analyzed10,978 participants (1,778 ADHD/9,200 non-ADHD), aged 3 to 18 years. A consecutive sample of first visits to mental health between 1992 and2021 is used. Participants with ADHD exhibit a significant circannual rhythm in the months of birth, with an acrophase in October. Being born in thelast quarter of the year significantly increases the probability of being diagnosed with ADHD, controlling for the effect of sex and age. As the monthsof the year go by, there is a significant increasing linear trend of being diagnosed with ADHD, which is not observed neither in general populationnor in cases without ADHD. Caution is necessary in diagnosis and treatment of children born in the last months of year, who, due to their greaterimmaturity compared to the other children in class, could be misdiagnosed and treated as ADHD. (AU)

Content Validation of a Chrononutrition Questionnaire for the General and Shift Work Populations: A Delphi Study.

Unusual meal timing has been associated with a higher prevalence of chronic disease. Those at greater risk include shift workers and evening chronotypes. This study aimed to validate the content of a Chrononutrition Questionnaire for shift and non-shift workers to identify temporal patterns of eating in relation to chronotype. Content validity was determined using a Delphi study of three rounds. Experts rated the relevance of, and provided feedback on, 46 items across seven outcomes: meal regularity, times of first eating occasion, last eating occasion, largest meal, main meals/snacks, wake, and sleep, which were edited in response. Items with greater than 70% consensus of relevance were accepted. Rounds one, two, and three had 28, 26, and 24 experts, respectively. Across three rounds, no outcomes were irrelevant, but seven were merged into three for ease of usage, and two sections were added for experts to rate and comment on. In the final round, all but one of 29 items achieved greater than 70% consensus of relevance with no further changes. The Chrononutrition Questionnaire was deemed relevant to experts in circadian biology and chrononutrition, and could represent a convenient tool to assess temporal patterns of eating in relation to chronotype in future studies.

Moving geroscience from the bench to clinical care and health policy.

Geriatricians and others must embrace the emerging field of geroscience. Until recently geroscience research was pursued in laboratory animals, but now this field requires specialized expertise in the care of vulnerable older patients with multiple chronic diseases and geriatric syndromes, the population likely to benefit the most from emerging therapies. While chronological aging measures the inevitable passage of clock time that occurs equally for everyone, biological aging varies among individuals, and importantly, it is modifiable. Advances in our understanding of biological aging, the discovery of strategies for modifying its rate, and an appreciation of aging as a shared risk factor for chronic diseases have jointly led to the Geroscience Hypothesis. This hypothesis states that interventions modifying aging biology can slow its progression-resulting in the delay or prevention of the onset of multiple diseases and disorders. Here we wish to report on the Third Geroscience Summit held at National Institutes of Health on November 4-5, 2019, which highlighted the importance of engaging other disciplines including clinicians. Involvement by scientists with expertise in clinical trials, health outcomes research, behavioral and social sciences, health policy, and economics is urgently needed to translate geroscience discoveries from the bench to clinical care and health policy. Adding to the urgency of broadening this geroscience coalition is the emergence of biological aging as one the most important modifiable factors of COVID-19, combined with the inability of our society to once again recognize and confront aging as a priority and opportunity when facing these types of public health emergencies.

The 2020 Pittendrigh/Aschoff Lecture: My Circadian Journey.

The circadian field has come a long way since I started as a postdoctoral fellow ~30 years ago. At the time, the only known animal clock gene was period, so I had the privilege of witnessing, and participating in, the molecular revolution that took us from the discovery of the circadian clock mechanism to the identification of pathways that link clocks to behavior and physiology. This lecture highlights my role and perspective in these developments, and also demonstrates how the successful use of Drosophila for studies of circadian rhythms inspired us to develop a fly model for sleep. I also touch upon my experiences as a non-white immigrant woman navigating my way through the US science and education system, and hope my story will be of interest to some.

TimeTrial: An Interactive Application for Optimizing the Design and Analysis of Transcriptomic Time-Series Data in Circadian Biology Research.

The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues, coordinating physiological processes. The effect of this rhythm on health has generated increasing interest in discovering genes under circadian control by searching for periodic patterns in transcriptomic time-series experiments. While algorithms for detecting cycling transcripts have advanced, there remains little guidance quantifying the effect of experimental design and analysis choices on cycling detection accuracy. We present TimeTrial, a user-friendly benchmarking framework using both real and synthetic data to investigate cycle detection algorithms' performance and improve circadian experimental design. Results show that the optimal choice of analysis method depends on the sampling scheme, noise level, and shape of the waveform of interest and provides guidance on the impact of sampling frequency and duration on cycling detection accuracy. The TimeTrial software is freely available for download and may also be accessed through a web interface. By supplying a tool to vary and optimize experimental design considerations, TimeTrial will enhance circadian transcriptomics studies.

Chronotype assessment via a large scale socio-demographic survey favours yearlong Standard time over Daylight Saving Time in central Europe.

Abandoning daylight saving time in Europe raises the topical issue of proper setting of yearlong social time, which needs mapping of various socio-demographic factors, including chronotype, in specific geographic regions. This study represents the first detailed large scale chronotyping in the Czech Republic based on data collected in the complex panel socio-demographic survey in households (total 8760 respondents) and the socio-physiological survey, in which chronotyped participants also provided blood samples (n = 1107). Chronotype assessment based on sleep phase (MCTQ questions and/or time-use diary) correlated with a self-assessed interval of best alertness. The mean chronotype of the Czech population defined as mid sleep phase (MSFsc) was 3.13 ± 0.02 h. Chronotype exhibited significant east-to-westward, north-to-southward, and settlement size-dependent gradients and was associated with age, sex, partnership, and time spent outdoors as previously demonstrated. Moreover, for subjects younger than 40 years, childcare was highly associated with earlier chronotype, while dog care was associated with later chronotype. Body mass index correlated with later chronotype in women whose extreme chronotype was also associated with lower plasma levels of protective HDL cholesterol. Based on the chronotype prevalence the results favour yearlong Standard Time as the best choice for this geographic region.

Tipologia circadiana de estudantes de psicologia: diferenças entre a qualidade de sono, sonolência excessiva e hábitos diários / Circadian typology of psychology students: differences between sleep quality, excessive sleepiness and daily habits / Tipología circadiana de estudiantes de psicología: diferencias entre la calidad de sono, somnolencia excesiva y hábitos diarios

A tipologia circadiana é uma dimensão comportamental associada a preferências de hábitos diários. Contudo, este estudo objetivou avaliar a qualidade de sono e a sonolência excessiva de acadêmicos de Psicologia. Participaram deste estudo quase-experimental 56 estudantes com idade entre 17 e 34 anos. Utilizaram-se como instrumentos o Índice de Qualidade de Sono de Pittsburgh (PSQI), o Questionário de Matutinidade e Vespertinidade, a Escala de Sonolência de Karolinska e a Escala de Ritmo Social Breve. Após avaliar o PSQI, todos os participantes responderam os instrumentos por um período de 14 dias consecutivos. A MANOVA mostrou diferença significativa para sonolência diária durante os dias úteis [λ=0.81; F(4;47)=451,53; p<0,05], especificamente para o horário das 21h [F(2;5)=3,03; p<0,05]. Conclui-se que os estudantes possuem qualidade de sono ruim e, geralmente, tentam compensar as faltas de noites de sono durante a semana nos finais de semana.

The circadian typology is a behavioral dimension associated with preferences of daily habits. Thus, this study aimed to evaluate the quality of sleep and excessive sleepiness of undergraduates in psychology. Fifty-five students aged between 17 and 34 years participated in this quasi-experimental study. The Pittsburgh Sleep Quality Index, the Morningness-Eveningness Questionnaire, the Karolinska Sleepiness Scale, and the Brief Social Rhythm Scale were used as instruments. After assessing the PSQI, all participants answered the instruments for a period of 14 consecutive days. MANOVA showed significant difference for daily sleepiness during the working days [λλ=.81; F(4.47)=451.53; p<.05], specifically for business hours of 21h [F(2;5)=3.03; p<.05]. It is concluded that students have poor sleep quality and generally try to compensate for the lack of nights of sleep during the week on weekends.

La tipología circadiana es una dimensión comportamental asociada a preferencias de hábitos diarios. Sin embargo, este estudio tuvo como objetivo evaluar la calidad del sueño y la somnolencia excesiva de académicos de psicología. Participaron de este estúdio quase-experimental 56 estudiantes con edad entre 17 y 34 años. Se utilizaron como instrumentos o Índice de Calidad de Sono de Pittsburgh (PSQI), o Cuestionario de Matutinidad-Vespertinidad, la Escala de Somnolencia de Karolinska y Escala de Ritmo Social Breve. Aprobar la PSQI, todos los participantes respondan os instrumentos por un período de 14 días consecutivos. A MANOVA mostró una diferencia para somnolencia durante los días laborables [λ=0,81; F(4; 47)=451,53; p<0.05], específicamente para el horario de las 21h [F(2; 5)=3,03; p<0.05]. Las conclusiones de estos estudios tienen la cualidad de su ruina y de manera general como compensar las faltas de la noche durante la semana.

The case for a chronobiological approach to neonatal care.

Time of day is a critical factor for most biological functions, but concepts from the field of chronobiology have yet to be fully translated to clinical practice. Circadian rhythms, generated internally and synchronised to the external environment, promote function and support survival in almost every living species. Fetal circadian rhythms can be observed in utero from 30weeks gestation, coupled to the maternal rhythm, but synchronise to the external environment only after birth. Important cues for synchronisation include the light/dark cycle, the timing of feeding, and exposure to melatonin in breast milk. Disruption to these cues may occur during admission to the neonatal intensive care unit. This can impair the development of circadian rhythms, and influence survival and function in the neonatal period, with a potential to impact health and well-being throughout adult life. Here we outline the rationale and evidence to support a chronobiological approach to neonatal care.

Chronobiology --2017 Nobel Prize in Physiology or Medicine.

Chronobiology is a field of biology that examines the generation of biological rhythms in various creatures and in many parts of body, and their adaptive fitness to solar- and lunar-related periodic phenomena. The synchronization of internal circadian clocks with external timing signals confers accurate phase response and tissue homeostasis. Herein we state a series of studies on circadian rhythms and introduce the brief history of chronobiology. We also present a detailed timeline of the discoveries on molecular mechanisms controlling circadian rhythm in Drosophila, which was awarded the 2017 Nobel Prize in Physiology or Medicine. The latest findings and new perspectives are further summarized to indicate the significance of circadian research.

Introduction to Chronobiology.

A diverse range of species, from cyanobacteria to humans, evolved endogenous biological clocks that allow for the anticipation of daily variations in light and temperature. The ability to anticipate regular environmental rhythms promotes optimal performance and survival. Herein we present a brief historical timeline of how circadian concepts and terminology have emerged since the early observation of daily leaf movement in plants made by an astronomer in the 1700s.

Methods in field chronobiology.

Chronobiological research has seen a continuous development of novel approaches and techniques to measure rhythmicity at different levels of biological organization from locomotor activity (e.g. migratory restlessness) to physiology (e.g. temperature and hormone rhythms, and relatively recently also in genes, proteins and metabolites). However, the methodological advancements in this field have been mostly and sometimes exclusively used only in indoor laboratory settings. In parallel, there has been an unprecedented and rapid improvement in our ability to track animals and their behaviour in the wild. However, while the spatial analysis of tracking data is widespread, its temporal aspect is largely unexplored. Here, we review the tools that are available or have potential to record rhythms in the wild animals with emphasis on currently overlooked approaches and monitoring systems. We then demonstrate, in three question-driven case studies, how the integration of traditional and newer approaches can help answer novel chronobiological questions in free-living animals. Finally, we highlight unresolved issues in field chronobiology that may benefit from technological development in the future. As most of the studies in the field are descriptive, the future challenge lies in applying the diverse technologies to experimental set-ups in the wild.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'.

Sleep research goes wild: new methods and approaches to investigate the ecology, evolution and functions of sleep.

Despite being a prominent aspect of animal life, sleep and its functions remain poorly understood. As with any biological process, the functions of sleep can only be fully understood when examined in the ecological context in which they evolved. Owing to technological constraints, until recently, sleep has primarily been examined in the artificial laboratory environment. However, new tools are enabling researchers to study sleep behaviour and neurophysiology in the wild. Here, we summarize the various methods that have enabled sleep researchers to go wild, their strengths and weaknesses, and the discoveries resulting from these first steps outside the laboratory. The initial studies to 'go wild' have revealed a wealth of interindividual variation in sleep, and shown that sleep duration is not even fixed within an individual, but instead varies in response to an assortment of ecological demands. Determining the costs and benefits of this inter- and intraindividual variation in sleep may reveal clues to the functions of sleep. Perhaps the greatest surprise from these initial studies is that the reduction in neurobehavioural performance resulting from sleep loss demonstrated in the laboratory is not an obligatory outcome of reduced sleep in the wild.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'.