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Pacific Island Countries and Territories (PICTs) are experiencing a Diet-Related Non-Communicable Disease (DR-NCD) health crisis(1). Increasing rates of DR-NCDs such as Type 2 diabetes and cardiovascular disease have been linked to dietary transitions and increasing food insecurity in the region(2). Anthropogenic climate change has also been identified as a significant threat to food security in PICTs(3). Additionally, the impacts of the COVID-19 Pandemic have been identified as both a contributor to food insecurity in the region and as an opportunity to transform PICT food systems and reduce rates of DR-NCDs(4). Yet, the drivers of dietary change, food security and agricultural practices in peripheral PICT communities are not well documented or understood. To determine how these drivers may change in the future and the impacts this may have on Pacific peoples, a deeper understanding of the historical and contemporary drivers of change is necessary. The aim of this scoping review was to collate existing information to improve this understanding, by mapping key factors evident in the literature that underpin the links between DR-NCDs and food security with a focus on women in PICT peripheral communities, to better clarify the challenges, working definitions and conceptual boundaries in the research area. The review maps where research has been conducted geographically and how the links between DR-NCDs and food security in PICTs have been investigated over time and identifies projections and suggestions for the future. The scoping review was conducted in accordance with a pre-defined protocol available online(5). A total of 476 peer-reviewed sources and 126 grey literature sources were identified by the initial search criteria. Two independent researchers completed title/abstract and full text screening using Covidence, and data extraction using a data extraction tool. The resulting data was quantified in table format, with common themes and ideas presented qualitatively. Sources spanned all sectors of PICT food systems with a heavy focus on production from fisheries and agriculture. Most PICTs were represented in the findings. Many drivers of change within food systems were identified, some of which included the impacts of anthropogenic climate change, the COVID-19 pandemic, and urbanisation. The drivers impacted all four pillars of food security, and many were directly or indirectly related to dietary and lifestyle changes associated with DR-NCD risk factors. This data is accompanied by an interpretation of results and a narrative summary. These results provide a useful platform to further explore the drivers of dietary change, food security, agricultural practices and DR-NCD's in this region. [ABSTRACT FROM AUTHOR]

The rise of atmospheric CO2 concentration ([ CO2]) affects stomatal conductance and thus transpiration and leaf temperature. We evaluated the effect of elevated [ CO2] levels under different water supply on daily sap flow and canopy microclimate (air temperature (Tc) and vapour pressure deficit ( VPD)) of maize. The crop was cultivated in circular field plots under ambient ( AMB, 378 μmol mol−1) and elevated [ CO2] ( FACE, 550 μmol mol−1) using free-air CO2 enrichment with sufficient water in 2007, while in 2008 a DRY semicircle received only half as much water as compared to the WET semicircle from mid of July. In 2007, sap flow was measured in WET simultaneously under AMB and FACE conditions and was significantly decreased by elevated [ CO2]. In 2008, sap flow was measured in all four treatments but not simultaneously. Therefore, data were correlated with potential evaporation and the slopes were used to determine treatment effects. Drought reduced whole-plant transpiration by 50 % and 37 % as compared to WET conditions under AMB and FACE, respectively. Moreover, CO2 enrichment did not affect sap flow under drought but decreased it under WET by 20 % averaged over both years. The saving of water in the period before the drought treatment resulted in a displacement of dry soil conditions under FACE as compared to AMB. Under WET, CO2 enrichment always increased Tc and VPD during the day. Under DRY, FACE plots were warmer and drier most of the time in August, but cooler and damper short after the start of drought in July and from the end of August onwards. Thus, the CO2 effect on transpiration under drought was variable and detectable rather easy by measuring canopy microclimate. [ABSTRACT FROM AUTHOR]

Background: Nearly half of all preschoolers are not meeting physical activity (PA) guidelines. Currently, very few studies have examined the impact of PA programs incorporated into the preschool day, and none have implemented a PA program rooted in their academic curriculum. PA has been shown to improve on-task behavior, one component of classroom behavior, in preschoolers. Poor classroom behavior has been associated with sleep habits. However, current data provide conflicting evidence for PA and sleep relationships in children. The purpose of this secondary analysis was to examine associations between sedentary behavior, PA, sleep habits, and classroom behavior variables in preschool children. Methods: Baseline data from children (n=52, age=3.6±0.8 years, BMI percentile=50.1 ±27.1) in two preschools participating in the Preschool Activity, Diet, and Sleep (PADS) Pilot Study was utilized for this analysis. Both sedentary behavior and PA were measured with an Actigraph accelerometer for seven consecutive days. The Strengths and Difficulties Questionnaire behavioral screening tool was used to assess classroom behavior. This 25-item form was completed by teachers and includes subscales encompassing hyperactivity/inattention, emotional symptoms, conduct problems, peer problems, and prosocial behavior. Parents completed the Sleep Disturbance Scale to assess sleep habits. Pearson correlations were used to examine associations between physical activity, sleep, and classroom behavior variables. Results: Sedentary behavior (% time) was negatively associated with conduct problems (r=-0.46, p=0.005) and peer problems (r=-0.34, p=0.04). Light activity (% time) was positively associated with conduct problems (r=0.51, p=0.002), peer problems (r= 0.43, p=0.01), and total behavior difficulty score (r=0.42, p=0.01). Moderate-to-vigorous PA (% time) was positively associated with conduct problems (r=0.39, p=0.02). Sleep disturbance total score was negatively associated with BMI percentile (r=-0.36, p=0.03) and positively related to conduct problems (r=0.32, p=0.049). Emotional problems were positively associated with excessive somnolence (r=0.36, p=0.03). Discussion: Sedentary behavior and PA seem to be related to classroom behavior variables. It is possible that structured PA may reduce classroom behavior problems in preschoolers. The inverse relationships between sleep and classroom behavior problems suggests that improving sleep quality and duration may impact classroom behavior. [ABSTRACT FROM AUTHOR]

The adverse effects of tropospheric ozone (O3) on crop photosynthesis, growth and yield have been documented in numerous studies over the last decades, but little information from field experimentation exists on how modern European winter wheat cultivars respond to O3. Two winter wheat cultivars (Astron and Pegassos) differing in development characteristics were exposed to non-filtered ambient air or non-filtered air plus 30 ppb and non-filtered air plus 60 ppb O3 (8 h day−1) in open-top field chambers. At several dates during growth, green leaf area was determined by destructive harvests. Leaf gas exchange, pigment content and xanthophyll cycle activity, and photochemical efficiency by chlorophyll a fluorescence were measured. O3 exposure induced accelerated senescence with no difference between cultivars. Photosynthesis declined especially in Pegassos; however, stomatal conductance was hardly affected by O3. Pigment contents were reduced by O3 exposure, and de-epoxidation index increased. Photochemical efficiency ( Fv/ Fm) declined, whereas actual quantum yield (Φ PSII) did not respond to O3. O3 exposure reduced grain yield in both cultivars. However, yield of Pegassos was more affected by O3 exposure than yield of Astron, suggesting a higher O3 sensitivity of Pegassos. The data presented in this manuscript indicate a need to test whether high-yield varieties such as Pegassos are particularly sensitive to O3 exposure. [ABSTRACT FROM AUTHOR]

An arable crop rotation (winter barley-sugar beet-winter wheat) was exposed to elevated atmospheric CO concentrations ([CO]) using a FACE facility (Free-Air CO Enrichment) during two rotation periods. The atmospheric [CO] of the treatment plots was elevated to 550 ppm during daylight hours (T > 5 °C). Canopy transpiration (E) and conductance (G) were measured at selected intervals (>10% of total growing season) using a dynamic CO/HO chamber measuring system. Plant available soil water content (gravimetry and TDR probes) and canopy microclimate conditions were recorded in parallel. Averaged across both growing seasons, elevated [CO] reduced E by 9%, 18% and 12%, and G by 9%, 17% and 12% in barley, sugar beet and wheat, respectively. Both global radiation (Rg) and vapour pressure deficit (VPD) were the main driving forces of E, whereas G was mostly related to Rg. The responses of E and especially G to [CO] enrichment were insensitive to weather conditions and leaf area index. However, differences in LAI between plots counteracted the [CO] impact on E and thus, at least in part, explained the variability of seasonal [CO] responses between crops and years. As a consequence of lower transpirational canopy water loss, [CO] enrichment increased plant available soil water content in the course of the season by ca. 15 mm. This was true for all crops and years. Lower transpirational cooling due to a [CO]-induced reduction of E increased canopy surface and air temperature by up to 2 °C and 0.5 °C, respectively. This is the first study to address effects of FACE on both water fluxes at canopy scale and water status of a European crop rotation. [ABSTRACT FROM AUTHOR]

Sugar beet ( Beta vulgaris ssp . altissima Döll) was grown in the field under free-air CO2 enrichment (FACE, 550 ppm) and different nitrogen (N) supply (2001: 126 (N100) and 63 kg·ha−1 (N50); 2004: 156 (N100) and 75 kg·ha−1) during two crop rotations. Canopy CO2 exchange rates (CCER) were measured during the main growth phase (leaf area index ≥2) using a dynamic chamber system. Canopy CO2 exchange data were analysed with respect to treatment effects on seasonal means and light use efficiency and light response characteristics. CO2 enrichment enhanced CCER throughout the season. However, in both years, CCER declined after the second half of August independent of radiation and [CO2]. Elevated [CO2] strongly stimulated CCER on a seasonal basis, whereas the reduction of CCER caused by low N was below 10% and not significant. There were no effects of N on daily radiation use efficiency of carbon gain calculated from CCER data, but a strong enhancement by CO2 enrichment. CCER closely tracked diurnal variations in incident photosynthetic photon flux density (PPFD, μmol·m−2·s−1). The relationship between CCER and incident PPFD was curvilinear. In both seasons, initial slopes and maximum rates (CCERmax) were determined from two 6-day periods using these relationships. The first period was measured after canopy closure (first half of July) and the second in the second half of August. In the first period, elevated [CO2] increased the initial slopes. Low N supply affected neither the initial slopes nor their response to elevated [CO2] in either period. In contrast to initial slopes, N stress limited the [CO2] response of CCERmax in the first period. In the second period, however, this interaction of [CO2] and N on CCERmax was completely dominated by a general decline of CCERmax whereas no general decline of the initial slopes occurred in the second period. This response of light response parameters to [CO2] and N suggests that, in sugar beet, the decline of CCER in the late season may rely on limiting mechanisms such as photosynthetic acclimation responses to elevated [CO2] caused by sink limitations. [ABSTRACT FROM AUTHOR]

Primary objective : To understand the temporal evolution of brain reorganization during recovery from stroke. Research design : A patient who suffered left middle cerebral artery stroke 9 months earlier was studied on three occasions, ∼⃒1 month apart. Methods and procedures : Brain activation was studied using functional Magnetic Resonance Imaging (fMRI). During each session, the patient performed a finger-to-thumb opposition task, which involved one bimanual and two unimanual conditions. Each condition consisted of overt movement of fingers and imagery of the same task. Results : With recovery, greater recruitment was observed of the affected primary motor cortex (M1) and a decrease in activation of the unaffected M1 and supplementary motor area. In addition, the widespread activation of brain areas seen during the initial session changed to a more focused pattern of activation as the patient recovered. Imagery tasks resulted in similar brain activity as overt execution pointing to imagery as a potential tool for rehabilitation. [ABSTRACT FROM AUTHOR]

Summary • The predictive capacity of two simulation models with different degrees of complexity for the calculation of assimilate production, was tested at different time scales, using a data set of wheat grown in an open-top-chamber experiment at two CO2 concentrations. • Observed values of net canopy assimilation (Pn) were obtained from wheat plants grown at ambient (410 µmol mol-1 ) and elevated (680 µmol mol-1 ) CO2 mole fractions. Pn was simulated by using either simple multiple regression equations (AFRCWHEAT2) or by highly detailed calculations of leaf energy balances and the coupling of photosynthesis with stomatal conductance (LINTULCC2). • Irrespective of the developmental stage of the crop or variation in weather, the models accurately simulated canopy assimilation and growth. We conclude that the response of aboveground-biomass production to elevated CO2 concentrations was explained primarily by the effects of CO2 on radiation-use efficiency and assimilate production. • The models explained satisfactorily the daily course of Pn, its integrated daily totals, and the seasonally produced aboveground biomass, both at ambient and elevated CO2 concentrations. Specific problems in the simulations were identified and discussed. [ABSTRACT FROM AUTHOR]

Background: Among elementary-aged children (5-12yrs), summer vacation is associated with accelerated gains in Body Mass Index (BMI). A key behavioral driver of BMI gain is a lack of physical activity (PA). Previous studies indicate PA decreases during summer, compared to the school year but whether this difference is consistent among boys and girls, across age, and by income status remains unclear. This study examined differences in school and summer movement behaviors in a diverse cohort of children across three years., Methods: Children (N = 1,203, age range 5-14 years, 48% girls) wore wrist-placed accelerometers for a 14-day wear-period during school (April/May) and summer (July) in 2021 to 2023, for a total of 6 timepoints. Mixed-effects models examined changes in school vs. summer movement behaviors (moderate-to-vigorous physical activity [MVPA], sedentary) for boys and girls, separately, and by age and household income groups (low, middle, and upper based on income-to-poverty ratio)., Results: Children provided a total of 35,435 valid days of accelerometry. Overall, boys (+ 9.1 min/day, 95CI 8.1 to 10.2) and girls (+ 6.2 min/day, 95CI 5.4 to 7.0) accumulated more MVPA during school compared to summer. Boys accumulated less time sedentary (-9.9 min/day, 95CI -13.0 to -6.9) during school, while there was no difference in sedentary time (-2.7 min/day, 95CI -5.7 to 0.4) for girls. Different patterns emerged across ages and income groups. Accumulation of MVPA was consistently greater during school compared to summer across ages and income groups. Generally, the difference between school and summer widened with increasing age, except for girls from middle-income households. Accumulation of sedentary time was higher during school for younger children (5-9yrs), whereas for older children (10-14yrs), sedentary time was greater during summer for the middle- and upper-income groups. For boys from low-income households and girls from middle-income households, sedentary time was consistently greater during summer compared to school across ages., Conclusions: Children are less active and more sedentary during summer compared to school, which may contribute to accelerated BMI gain. However, this differs by biological sex, age, and income. These findings highlight the complex factors influencing movement behaviors between school and summer., (© 2024. The Author(s).)

Migration, from rural to urban settings is a common phenomenon in Latin America, due to social, economic, political, and other factors. Young people in search of economic and educational opportunities, financial, and social stability, have been migrating to larger urban centers, thus crafting important shifts in rural labor, generational transfer, and domestic economies. Through a systematic literature review of scientific literature, and documents from public institutions and international organizations, published between 2012 and 2022, this article addresses rural-urban migration of youth in Colombia and Guatemala's cattle sector, particularly identifying (i) driving factors, (ii) their impacts on cattle farming, and (iii) public policies implemented to counteract prejudicial effects. Results show that unemployment, lack of educational opportunities, and insecurity are the main reasons for youth migration to cities or abroad, with Mexico, the United States, and Spain being the most common destinations. Additionally, impacts on the cattle sector include shortage of labor and a perfectible generational transfer, hindering the modernization of the industry and investments in climate change adaptation and mitigation strategies. Despite various implemented public policies, the results are partial, and the issue of accelerated youth migration remains relevant. Consequently, without more effective measures adopted by national governments, the cattle sector will lag behind its regional and international competitors, deterring the achievement of the Sustainable Development Goals. As the main contribution of the study, the analysis of migration is highlighted based on its effects on a specific economic sector and not focused on its causes, as evidenced in a wide range of literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Díaz Baca, Moreno Lerma, Burkart and Triana Ángel.)

We examined the comparability of children's nocturnal sleep estimates using accelerometry data, processed with and without a sleep log. In a secondary analysis, we evaluated factors associated with disagreement between processing approaches. Children (n = 722, age 5-12 years) wore a wrist-based accelerometer for 14 days during Autumn 2020, Spring 2021, and/or Summer 2021. Outcomes included sleep period, duration, wake after sleep onset (WASO), and timing (onset, midpoint, waketime). Parents completed surveys including children's nightly bed/wake time. Data were processed with parent-reported bed/wake time (sleep log), the Heuristic algorithm looking at Distribution of Change in Z-Angle (HDCZA) algorithm (no log), and an 8 p.m.-8 a.m. window (generic log) using the R-package 'GGIR' (version 2.6-4). Mean/absolute bias and limits of agreement were calculated and visualised with Bland-Altman plots. Associations between child, home, and survey characteristics and disagreement were examined with tobit regression. Just over half of nights demonstrated no difference in sleep period between sleep log and no log approaches. Among all nights, the sleep log approach produced longer sleep periods (9.3 min; absolute mean bias [AMB] = 28.0 min), shorter duration (1.4 min; AMB = 14.0 min), greater WASO (11.0 min; AMB = 15.4 min), and earlier onset (13.4 min; AMB = 17.4 min), midpoint (8.8 min; AMB = 15.3 min), and waketime (3.9 min; AMB = 14.8 min) than no log. Factors associated with discrepancies included smartphone ownership, bedroom screens, nontraditional parent work schedule, and completion on weekend/summer nights (range = 0.4-10.2 min). The generic log resulted in greater AMB among sleep outcomes. Small mean differences were observed between nights with and without a sleep log. Discrepancies existed on weekends, in summer, and for children with smartphones and screens in the bedroom., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with tumor cells or other components of the tumor microenvironment (TME) remains elusive. We established an SC-related 43-gene set as a surrogate for peripheral nerves in the TME. Head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA) were classified into low, intermediate and high SC score groups based on the expression of this gene set. Perineural invasion (PNI) and TGF-β signaling were hallmarks of SC high tumors, whereas SC low tumors were enriched for HPV16-positive OPSCC and higher PI3K-MTOR activity. The latter activity was partially explained by a higher frequency of PTEN mutation and PIK3CA copy number gain. The inverse association between PI3K-MTOR activity and peripheral nerve abundance was context-dependent and influenced by the TP53 mutation status. An in silico drug screening approach highlighted the potential vulnerabilities of HNSCC with variable SC scores and predicted a higher sensitivity of SC low tumors to DNA topoisomerase inhibitors. In conclusion, we have established a tool for assessing peripheral nerve abundance in the TME and provided new clinical and biological insights into their regulation. This knowledge may pave the way for new therapeutic strategies and impart proof of concept in appropriate preclinical models.

Study Objectives: Evaluate wrist-placed accelerometry predicted heartrate compared to electrocardiogram (ECG) heartrate in children during sleep., Methods: Children (n=82, 61% male, 43.9% Black) wore a wrist-placed Apple Watch Series 7 (AWS7) and ActiGraph GT9X during a polysomnogram. 3-Axis accelerometry data was extracted from AWS7 and the GT9X. Accelerometry heartrate estimates were derived from jerk (the rate of acceleration change), computed using the peak magnitude frequency in short time Fourier Transforms of Hilbert transformed jerk computed from acceleration magnitude. Heartrates from ECG traces were estimated from R-R intervals using R-pulse detection. Lin's Concordance Correlation Coefficient (CCC), mean absolute error (MAE) and mean absolute percent error (MAPE) assessed agreement with ECG estimated heartrate. Secondary analyses explored agreement by polysomnography sleep stage and a signal quality metric., Results: The developed scripts are available on Github. For the GT9X, CCC was poor at -0.11 and MAE and MAPE were high at 16.8 (SD=14.2) beats/minute and 20.4% (SD=18.5%). For AWS7, CCC was moderate at 0.61 while MAE and MAPE were lower at 6.4 (SD=9.9) beats/minute and 7.3% (SD=10.3%). Accelerometry estimated heartrate for AWS7 was more closely related to ECG heartrate during N2, N3 and REM sleep than lights on, wake, and N1 and when signal quality was high. These patterns were not evident for the GT9X., Conclusions: Raw accelerometry data extracted from AWS7, but not the GT9X, can be used to estimate heartrate in children while they sleep. Future work is needed to explore the sources (i.e., hardware, software, etc.) of the GT9X's poor performance., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Preliminary studies play a prominent role in the development of large-scale behavioral interventions. Though recommendations exist to guide the execution and interpretation of preliminary studies, these assume optimal scenarios which may clash with realities faced by researchers. The purpose of this study was to explore how principal investigators (PIs) balance expectations when conducting preliminary studies. We surveyed PIs funded by the National Institutes of Health to conduct preliminary behavioral interventions between 2000 and 2020. Four hundred thirty-one PIs (19% response rate) completed the survey (November 2021 to January 2022, 72% female, mean 21 years post-terminal degree). Most PIs were aware of translational models and believed preliminary studies should precede larger trials but also believed a single preliminary study provided sufficient evidence to scale. When asked about the relative importance of preliminary efficacy (i.e. changes in outcomes) and feasibility (i.e. recruitment, acceptance/adherence) responses varied. Preliminary studies were perceived as necessary to successfully compete for research funding, but among PIs who had peer-reviewed federal-level grants applications (n = 343 [80%]), responses varied about what should be presented to secure funding. Confusion surrounding the definition of a successful, informative preliminary study poses a significant challenge when developing behavior interventions. This may be due to a mismatch between expectations surrounding preliminary studies and the realities of the research enterprise in which they are conducted. To improve the quality of preliminary studies and advance the field of behavioral interventions, additional funding opportunities, more transparent criteria in grant reviews, and additional training for grant reviewers are suggested., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

Background: In the behavioral sciences, conducting pilot and/or feasibility studies (PFS) is a key step that provides essential information used to inform the design, conduct, and implementation of a larger-scale trial. There are more than 160 published guidelines, reporting checklists, frameworks, and recommendations related to PFS. All of these publications offer some form of guidance on PFS, but many focus on one or a few topics. This makes it difficult for researchers wanting to gain a broader understanding of all the relevant and important aspects of PFS and requires them to seek out multiple sources of information, which increases the risk of missing key considerations to incorporate into their PFS. The purpose of this study was to develop a consolidated set of considerations for the design, conduct, implementation, and reporting of PFS for interventions conducted in the behavioral sciences., Methods: To develop this consolidation, we undertook a review of the published guidance on PFS in combination with expert consensus (via a Delphi study) from the authors who wrote such guidance to inform the identified considerations. A total of 161 PFS-related guidelines, checklists, frameworks, and recommendations were identified via a review of recently published behavioral intervention PFS and backward/forward citation tracking of a well-known PFS literature (e.g., CONSORT Ext. for PFS). Authors of all 161 PFS publications were invited to complete a three-round Delphi survey, which was used to guide the creation of a consolidated list of considerations to guide the design, conduct, and reporting of PFS conducted by researchers in the behavioral sciences., Results: A total of 496 authors were invited to take part in the three-round Delphi survey (round 1, N = 46; round 2, N = 24; round 3, N = 22). A set of twenty considerations, broadly categorized into six themes (intervention design, study design, conduct of trial, implementation of intervention, statistical analysis, and reporting) were generated from a review of the 161 PFS-related publications as well as a synthesis of feedback from the three-round Delphi process. These 20 considerations are presented alongside a supporting narrative for each consideration as well as a crosswalk of all 161 publications aligned with each consideration for further reading., Conclusion: We leveraged expert opinion from researchers who have published PFS-related guidelines, checklists, frameworks, and recommendations on a wide range of topics and distilled this knowledge into a valuable and universal resource for researchers conducting PFS. Researchers may use these considerations alongside the previously published literature to guide decisions about all aspects of PFS, with the hope of creating and disseminating interventions with broad public health impact., (© 2024. The Author(s).)

Background: Twenty-four hour movement behaviors (ie, physical activity [PA], screen time [ST], and sleep) are associated with children's health outcomes. Identifying day-level contextual factors, such as child care, that positively influence children's movement behaviors may help identify potential intervention targets, like improving access to child care programs. This study aimed to examine the between- and within-person effects of child care on preschoolers' 24-hour movement behaviors., Methods: Children (N = 74, 4.7 [0.9] y, 48.9% girls, 63.3% White) wore an Axivity AX3 accelerometer on their nondominant wrist 24 hours per day for 14 days to measure PA and sleep. Parents completed surveys each night about their child's ST and child care attendance that day. Linear mixed effects models predicted day-level 24-hour movement behaviors from hours spent in child care., Results: Children spent an average of 5.0 (2.9) hours per day in child care. For every additional hour of child care above their average, children had 0.3 hours (95% CI, -0.3 to -0.2) less ST that day. Between-person effects showed that compared with children who attended fewer overall hours of child care, children who attended more hours had less overall ST (B = -0.2 h; 95% CI, -0.4 to 0.0). Child care was not significantly associated with PA or sleep., Conclusions: Child care attendance was not associated with 24-hour PA or sleep; however, it was associated with less ST. More research utilizing objective measures of ST and more robust measures of daily schedules or structure is necessary to better understand how existing infrastructure may influence preschool-aged children's 24-hour movement behaviors. In addition, future research should consider how access to child care may influence child care attendance.

Objective: Families with low-income experience suboptimal sleep compared to families with higher-income. Unique drivers likely contribute to these disparities, along with factors that universally impede sleep patterns, despite income level. To inform intervention tailoring, this mixed-methods study gathered parent's perceptions about child sleep challenges to identify similarities/differences in families with lower-income and higher-income., Methods: Parents who experienced difficulties with their child (ages 2-4years) sleep were categorized as lower income (n = 15; $30,000 ± 17,845/year) or higher income (n = 15; $142,400 ± 61,373/year). Parents completed a survey and semistructured interview to explore barriers and facilitators for child sleep. Two coders independently evaluated transcripts for lower-income and higher-income groups using inductive analyses. Constant-comparison methods generated themes and characterized similarities/differences by income group., Results: Groups were similar in themes related to diverse bedtime routines, nighttime struggles with child sleep, parent strategies to reduce night wakings, parent effort to provide a sleep-promoting environment, and presence of electronic rules. Groups differed in themes related to factors influencing routine setting (eg, lower income: external factors influencing routines; higher income: personal attributes for structure), parent appraisal of child sleep (eg, higher income: ambivalence; lower income: mostly negative appraisal), nap timing and duration (eg, lower income: longer naps), and strategy utilization and pursuit of resources (eg, higher income: more parents tried various strategies and accessed online/print resources)., Conclusions: Parents experienced many similar barriers to child sleep, with a few distinct differences by income group. These findings can inform future intervention components for all families, as well as customized components to address the unique needs of families across income levels., Competing Interests: Declaration of conflicts of interest The authors declare no conflict of interest., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Drivers of summer body mass index (BMI) gain in children remain unclear. The Circadian and Circannual Rhythm Model (CCRM) posits summer BMI gain is biologically driven, while the Structured Days Hypothesis (SDH) proposes it is driven by reduced structure. Objectives: Identify the mechanisms driving children's seasonal BMI gain through the CCRM and SDH. Methods: Children's ( N  = 147, mean age = 8.2 years) height and weight were measured monthly during the school year, and once in summer (July-August). BMI z-score (zBMI) was calculated using CDC growth charts. Behaviors were measured once per season. Mixed methods regression estimated monthly percent change in children's height (%HΔ), weight (%WΔ), and monthly zBMI for school year vs. summer vacation, seasonally, and during school months with no breaks vs. school months with a break ≥1 week. Results: School year vs. summer vacation analyses showed accelerations in children's %WΔ (Δ = 0.9, Standard Error (SE) = 0.1 vs. Δ = 1.4, SE = 0.1) and zBMI (Δ = -0.01, SE = 0.01 vs. Δ = 0.04, SE = 0.3) during summer vacation, but %HΔ remained relatively constant during summer vacation compared with school (Δ = 0.3, SE = 0.0 vs. Δ = 0.4, SE = 0.1). Seasonal analyses showed summer had the greatest %WΔ (Δ = 1.8, SE = 0.4) and zBMI change (Δ = 0.05, SE = 0.03) while %HΔ was relatively constant across seasons. Compared with school months without a break, months with a break showed higher %WΔ (Δ = 0.7, SE = 0.1 vs. Δ = 1.6, SE = 0.2) and zBMI change (Δ = -0.03, SE = 0.01 vs. Δ = 0.04, SE = 0.01), but %HΔ was constant (Δ = 0.4, SE = 0.0 vs. Δ = 0.3, SE = 0.1). Fluctuations in sleep timing and screen time may explain these changes. Conclusions: Evidence for both the CCRM and SDH was identified but the SDH may more fully explain BMI gain. Interventions targeting consistent sleep and reduced screen time during breaks from school may be warranted no matter the season.

The purpose of this study was to evaluate the reliability and validity of the raw accelerometry output from research-grade and consumer wearable devices compared to accelerations produced by a mechanical shaker table. Raw accelerometry data from a total of 40 devices (i.e., n = 10 ActiGraph wGT3X-BT, n = 10 Apple Watch Series 7, n = 10 Garmin Vivoactive 4S, and n = 10 Fitbit Sense) were compared to reference accelerations produced by an orbital shaker table at speeds ranging from 0.6 Hz (4.4 milligravity-mg) to 3.2 Hz (124.7mg). Two-way random effects absolute intraclass correlation coefficients (ICC) tested inter-device reliability. Pearson product moment, Lin's concordance correlation coefficient (CCC), absolute error, mean bias, and equivalence testing were calculated to assess the validity between the raw estimates from the devices and the reference metric. Estimates from Apple, ActiGraph, Garmin, and Fitbit were reliable, with ICCs = 0.99, 0.97, 0.88, and 0.88, respectively. Estimates from ActiGraph, Apple, and Fitbit devices exhibited excellent concordance with the reference CCCs = 0.88, 0.83, and 0.85, respectively, while estimates from Garmin exhibited moderate concordance CCC = 0.59 based on the mean aggregation method. ActiGraph, Apple, and Fitbit produced similar absolute errors = 16.9mg, 21.6mg, and 22.0mg, respectively, while Garmin produced higher absolute error = 32.5mg compared to the reference. ActiGraph produced the lowest mean bias 0.0mg (95%CI = -40.0, 41.0). Equivalence testing revealed raw accelerometry data from all devices were not statistically significantly within the equivalence bounds of the shaker speed. Findings from this study provide evidence that raw accelerometry data from Apple, Garmin, and Fitbit devices can be used to reliably estimate movement; however, no estimates were statistically significantly equivalent to the reference. Future studies could explore device-agnostic and harmonization methods for estimating physical activity using the raw accelerometry signals from the consumer wearables studied herein., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Unrelated to this work Dr. Weaver and Dr. Armstrong report board membership and ownership shares in Trackster LLC. Unrelated to this work Dr. de Zambotti reports grants from Noctrix Health and Verily Life Science LLC (Alphabet Inc.), and is a co-founder and Chief Scientific Officer at Lisa Health Inc. and has ownership of shares in Lisa Health., (Copyright: © 2024 White et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: This study examined the potential of a device agnostic approach for predicting physical activity from consumer wearable accelerometry compared with a research-grade accelerometry., Methods: Seventy-five 5- to 12-year-olds (58% male, 63% White) participated in a 60-min protocol. Children wore wrist-placed consumer wearables (Apple Watch Series 7 and Garmin Vivoactive 4) and a research-grade device (ActiGraph GT9X) concurrently with an indirect calorimeter (COSMED K5). Activity intensities (i.e., inactive, light, moderate-to-vigorous physical activity) were estimated via indirect calorimetry (criterion), and the Hildebrand thresholds were applied to the raw accelerometer data from the consumer wearables and research-grade device. Epoch-by-epoch (e.g., weighted sensitivity, specificity) and discrepancy (e.g., mean bias, absolute error) analyses evaluated agreement between accelerometry-derived and criterion estimates. Equivalence testing evaluated the equivalence of estimates produced by the consumer wearables and ActiGraph., Results: Estimates produced by the raw accelerometry data from ActiGraph, Apple, and Garmin produced similar criterion agreement with weighted sensitivity = 68.2% (95% confidence interval (CI), 67.1%-69.3%), 73.0% (95% CI, 71.8%-74.3%), and 66.6% (95% CI, 65.7%-67.5%), respectively, and weighted specificity = 84.4% (95% CI, 83.6%-85.2%), 82.0% (95% CI, 80.6%-83.4%), and 75.3% (95% CI, 74.7%-75.9%), respectively. Apple Watch produced the lowest mean bias (inactive, -4.0 ± 4.5; light activity, 2.1 ± 4.0) and absolute error (inactive, 4.9 ± 3.4; light activity, 3.6 ± 2.7) for inactive and light physical activity minutes. For moderate-to-vigorous physical activity, ActiGraph produced the lowest mean bias (1.0 ± 2.9) and absolute error (2.8 ± 2.4). No ActiGraph and consumer wearable device estimates were statistically significantly equivalent., Conclusions: Raw accelerometry estimated inactive and light activity from wrist-placed consumer wearables performed similarly to, if not better than, a research-grade device, when compared with indirect calorimetry. This proof-of-concept study highlights the potential of device-agnostic methods for quantifying physical activity intensity via consumer wearables., (Copyright © 2023 by the American College of Sports Medicine.)

The purpose of this meta-analysis was to quantify the difference in physical activity and sleep estimates assessed via 1) movement, 2) heart rate (HR), or 3) the combination of movement and HR (MOVE+HR) compared to criterion indicators of the outcomes. Searches in four electronic databases were executed September 21-24 of 2021. Weighted mean was calculated from standardized group-level estimates of mean percent error (MPE) and mean absolute percent error (MAPE) of the proxy signal compared to the criterion measurement method for physical activity, HR, or sleep. Standardized mean difference (SMD) effect sizes between the proxy and criterion estimates were calculated for each study across all outcomes, and meta-regression analyses were conducted. Two-One-Sided-Tests method were conducted to metaanalytically evaluate the equivalence of the proxy and criterion. Thirty-nine studies (physical activity k = 29 and sleep k = 10) were identified for data extraction. Sample size weighted means for MPE were -38.0%, 7.8%, -1.4%, and -0.6% for physical activity movement only, HR only, MOVE+HR, and sleep MOVE+HR, respectively. Sample size weighted means for MAPE were 41.4%, 32.6%, 13.3%, and 10.8% for physical activity movement only, HR only, MOVE+HR, and sleep MOVE+HR, respectively. Few estimates were statistically equivalent at a SMD of 0.8. Estimates of physical activity from MOVE+HR were not statistically significantly different from estimates based on movement or HR only. For sleep, included studies based their estimates solely on the combination of MOVE+HR, so it was impossible to determine if the combination produced significantly different estimates than either method alone.

The cattle sector plays a pivotal role in the economies of numerous Latin American and Caribbean countries. However, it also exerts a significant impact on environmental degradation, including substantial contributions to greenhouse gas emissions (accounting for 23.5 % of global livestock emissions) and deforestation (70 % attributed to livestock in South America). This article aims to investigate the complex, long-term, and short-term relationships between population growth, pastureland expansion, deforestation, and the cattle sector in 15 countries across the region, focusing on their effects on greenhouse gas emissions as well as beef and dairy production. Utilizing data from FAOSTAT spanning the period from 1990 to 2019, a cointegrated panel model was developed using the Pooled Mean Group technique, resulting in the estimation of six models. The aggregate-level results for the region reveal the presence of relatively stable long-term relationships. This implies that over time, the influence of population growth, pastureland expansion, and deforestation on greenhouse gas emissions from cattle production tends to diminish in significance. This long-term behavior may be particularly pronounced in countries with more developed cattle sectors, where efforts to mitigate the environmental impacts of cattle production, such as promoting improved forage technologies, silvo-pastoral systems, grazing management practices, and the implementation of policies, regulatory frameworks, and incentives, have gained traction. These progressive countries can serve as regional benchmarks, and the lessons they have learned hold valuable insights for the sustainable intensification of cattle production in countries with less-developed cattle sectors., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Stefan Burkart reports financial support was provided by 10.13039/501100015815CGIAR Consortium. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Children from low-income households, and who are overweight or obese (OWOB), are at risk of accelerated weight gain during summer. Summer day camps (SDCs) have the potential to mitigate accelerated weight gain during summer as these settings can positively influence children's obesogenic behaviors ( i.e., increase physical activity); however, barriers exist to attending, most notably cost. Little is known on whether low-income caregivers of children with OWOB would be interested in having their child attend SDC for free. Caregivers ( n  = 109, 82% mother respondents, >75% Medicaid and Minority Household) with a child attending pediatric endocrinology clinics completed a one-page survey to explore demand. Approximately 66% of respondents expressed interest for their child to attend SDC for free. Providing free SDC for children with OWOB and from low-income households is a possible strategy to tackle childhood obesity during summer.

Background: RAB11B was described previously once with a severe form of intellectual disability. We aim at validation and delineation of the role of RAB11B in neurodevelopmental disorders., Methods: We present seven novel individuals with disease-associated variants in RAB11B when compared with the six cases described in the literature. We performed a cross-sectional analysis to identify the clinical spectrum and the core phenotype. Additionally, structural effects of the variants were assessed by molecular modeling., Results: Seven distinct de novo missense variants were identified, three of them recurrent (p.(Gly21Arg), p.(Val22Met), and p.(Ala68Thr)). Molecular modeling suggests that those variants either affect the nucleotide binding (at amino acid positions 21, 22, 33, 68) or the interaction with effector molecules (at positions 72 and 75). Our data confirmed the main manifestations as neurodevelopmental disorder with intellectual disability (85%), muscular hypotonia (83%), structural brain anomalies (77%), and visual impairment (70%). Combined analysis indicates a genotype-phenotype correlation; variants impacting the nucleotide binding cause a severe phenotype with intellectual disability, and variants outside the binding pocket lead to a milder phenotype with epilepsy., Conclusions: We confirm that disease-associated missense variants in RAB11B cause a neurodevelopmental disorder and suggest a genotype-phenotype correlation based on the impact on nucleotide binding functionality of RAB11B., Competing Interests: Declaration of competing interest T.B.P., R.E.S., and I.M.W. are employees of GeneDx, LLC. S.C.J. is supported by NIH/National Heart Lung and Blood Institute (NHLBI) Pathway to Independence award R00HL143036-02, the Clinical & Translational Research Funding Program award (CTSA1405), the Hydrocephalus Association Innovator Award, and the Cerebral Palsy Alliance Research Foundation Project Grant. The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: It is essential to quantify the accuracy and precision of bioelectrical impedance (BIA)-estimated percent body fat (%BF) to better interpret community-based research findings that utilize opportunistic measures. Methods: Study 1 measured the accuracy of a new dual-frequency foot-to-foot BIA device (Tanita DC-430U) compared with dual-energy X-ray absorptiometry (DXA) among healthy elementary school-aged children ( N  = 50). Study 2 examined the precision of BIA %BF estimates within and between days among children and adults ( N  = 38). Results: Regarding accuracy, Tanita DC-430U underestimated %BF by 8.0 percentage points compared with DXA (20.6% vs. 28.5%), but correctly ranked children in terms of %BF. Differences in %BF between BIA and DXA were driven by lower BIA-estimated fat mass (7.8 kg vs. 9.9 kg, p  < 0.05) and higher BIA-estimated fat-free mass (25.3 kg vs. 24.1 kg, p  < 0.05). The absolute agreement between BIA and DXA for estimated %BF was moderate (concordance correlation coefficients = 0.53). Regarding precision, measures taken at the same time, but on different days (root mean square standard deviation [RMSD] = 0.42-0.74) were more precise than the measures taken at different times within a single day (RMSD = 1.04-1.10). Conclusion: The Tanita DC-430U substantially underestimated %BF compared with DXA, highlighting the need to assess accuracy of new BIA devices when they are introduced to the market. Opportunistic measures of %BF estimates were most precise when taken at consistent times and in the morning, but may be utilized throughout the day with an understanding of within- and between-day variability.

Background: Guidelines, checklists, frameworks, and recommendations (GCFRs) related to preliminary studies serve as essential resources to assist behavioral intervention researchers in reporting findings from preliminary studies, but their impact on preliminary study reporting comprehensiveness is unknown. The purpose of this study was to conduct a scoping bibliometric review of recently published preliminary behavioral-focused intervention studies to (1) examine the prevalence of GCFR usage and (2) determine the associations between GCFR usage and reporting feasibility-related characteristics., Methods: A systematic search was conducted for preliminary studies of behavioral-focused interventions published between 2018 and 2020. Studies were limited to the top 25 journals publishing behavioral-focused interventions, text mined to identify usage of GCFRs, and categorized as either not citing GCFRs or citing ≥ 2 GCFRs (Citers). A random sample of non-Citers was text mined to identify studies which cited other preliminary studies that cited GCFRs (Indirect Citers) and those that did not (Never Citers). The presence/absence of feasibility-related characteristics was compared between Citers, Indirect Citers, and Never Citers via univariate logistic regression., Results: Studies (n = 4143) were identified, and 1316 were text mined to identify GCFR usage (n = 167 Citers). A random sample of 200 studies not citing a GCFR were selected and categorized into Indirect Citers (n = 71) and Never Citers (n = 129). Compared to Never Citers, Citers had higher odds of reporting retention, acceptability, adverse events, compliance, cost, data collection feasibility, and treatment fidelity (OR range = 2.62-14.15, p < 0.005). Citers also had higher odds of mentioning feasibility in purpose statements, providing progression criteria, framing feasibility as the primary outcome, and mentioning feasibility in conclusions (OR range = 6.31-17.04, p < 0.005) and lower odds of mentioning efficacy in purpose statements, testing for efficacy, mentioning efficacy in conclusions, and suggesting future testing (ORrange = 0.13-0.54, p < 0.05). Indirect Citers had higher odds of reporting acceptability and treatment fidelity (OR range = 2.12-2.39, p < 0.05) but lower odds of testing for efficacy (OR = 0.36, p < 0.05) compared to Never Citers., Conclusion: The citation of GCFRs is associated with greater reporting of feasibility-related characteristics in preliminary studies of behavioral-focused interventions. Researchers are encouraged to use and cite literature that provides guidance on design, implementation, analysis, and reporting to improve the comprehensiveness of reporting for preliminary studies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Goal and Aims: Evaluate the performance of a sleep scoring algorithm applied to raw accelerometry data collected from research-grade and consumer wearable actigraphy devices against polysomnography., Focus Method/technology: Automatic sleep/wake classification using the Sadeh algorithm applied to raw accelerometry data from ActiGraph GT9X Link, Apple Watch Series 7, and Garmin Vivoactive 4., Reference Method/technology: Standard manual PSG sleep scoring., Sample: Fifty children with disrupted sleep (M = 8.5 years, range = 5-12 years, 42% Black, 64% male)., Design: Participants underwent to single night lab polysomnography while wearing ActiGraph, Apple, and Garmin devices., Core Analytics: Discrepancy and epoch-by-epoch analyses for sleep/wake classification (devices vs. polysomnography)., Additional Analytics and Exploratory Analyses: Equivalence testing for sleep/wake classification (research-grade actigraphy vs. commercial devices)., Core Outcomes: Compared to polysomnography, accuracy, sensitivity, and specificity were 85.5, 87.4, and 76.8, respectively, for Actigraph; 83.7, 85.2, and 75.8, respectively, for Garmin; and 84.6, 86.2, and 77.2, respectively, for Apple. The magnitude and trend of bias for total sleep time, sleep efficiency, sleep onset latency, and wake after sleep were similar between the research and consumer wearable devices., Important Additional Outcomes: Equivalence testing indicated that total sleep time and sleep efficiency estimates from the research and consumer wearable devices were statistically significantly equivalent., Core Conclusion: This study demonstrates that raw acceleration data from consumer wearable devices has the potential to be harnessed to predict sleep in children. While further work is needed, this strategy could overcome current limitations related to proprietary algorithms for predicting sleep in consumer wearable devices., (Copyright © 2023 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Policy, systems, and environmental (PSE) approaches can facilitate physical activity in priority populations (e.g., racial and ethnic minority, low wealth groups) within early childhood education (ECE) settings. The purpose of this review was to 1) characterize the inclusion of priority populations within ECE physical activity interventions containing PSE approaches and 2) identify and describe interventions within these populations. Seven databases were systematically searched (January 2000-Febrary 2022) for ECE-based interventions focusing on children (0-6 years) that utilized at least one PSE approach. Eligible studies included a child physical activity or physical activity environment outcome and child or center-level population characteristics. Forty-four studies, representing 42 interventions were identified. For Aim 1, half of interventions included one PSE approach (21/42), with only 11/42 including three or more approaches. Physical environment changes [e.g., adding play equipment, modifying space (25/42)] were the most used PSE approaches followed by system [e.g., integrating activity into routines, (21/42)] and policy [e.g., outdoor time (20/42)] approaches. Nearly half of interventions were conducted in predominantly priority populations (18/42). Studies were primarily rated as good (51%) or fair (38%) methodological quality using the Downs and Black checklist. In Aim 2, of the 12 interventions assessing child physical activity in priority populations, 9/12 reported at least one physical activity outcome in the expected direction. Of the 11 interventions assessing the physical activity environment, 9/11 reported an effect in the expected direction. Findings indicate clear opportunities exist to target priority populations by incorporating PSE approaches in ECE physical activity interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The number of preliminary studies conducted and published has increased in recent years. However, there are likely many preliminary studies that go unpublished because preliminary studies are typically small and may not be perceived as methodologically rigorous. The extent of publication bias within preliminary studies is unknown but can prove useful to determine whether preliminary studies appearing in peer-reviewed journals are fundamentally different than those that are unpublished. The purpose of this study was to identify characteristics associated with publication in a sample of abstracts of preliminary studies of behavioral interventions presented at conferences., Methods: Abstract supplements from two primary outlets for behavioral intervention research (Society of Behavioral Medicine and International Society of Behavioral Nutrition and Physical Activity) were searched to identify all abstracts reporting findings of behavioral interventions from preliminary studies. Study characteristics were extracted from the abstracts including year presented, sample size, design, and statistical significance. To determine if abstracts had a matching peer-reviewed publication, a search of authors' curriculum vitae and research databases was conducted. Iterative logistic regression models were used to estimate odds of abstract publication. Authors with unpublished preliminary studies were surveyed to identify reasons for nonpublication., Results: Across conferences, a total of 18,961 abstracts were presented. Of these, 791 were preliminary behavioral interventions, of which 49% (388) were published in a peer-reviewed journal. For models with main effects only, preliminary studies with sample sizes greater than n = 24 were more likely to be published (range of odds ratios, 1.82 to 2.01). For models including interactions among study characteristics, no significant associations were found. Authors of unpublished preliminary studies indicated small sample sizes and being underpowered to detect effects as barriers to attempting publication., Conclusions: Half of preliminary studies presented at conferences go unpublished, but published preliminary studies appearing in peer-reviewed literature are not systematically different from those that remain unpublished. Without publication, it is difficult to assess the quality of information regarding the early-stage development of interventions. This inaccessibility inhibits our ability to learn from the progression of preliminary studies., (© 2023. The Author(s).)

Objectives: Preliminary studies play a key role in developing large-scale interventions but may be held to higher or lower scientific standards during the peer review process because of their preliminary study status., Study Design and Setting: Abstracts from 5 published obesity prevention preliminary studies were systematically modified to generate 16 variations of each abstract. Variations differed by 4 factors: sample size (n = 20 vs. n = 150), statistical significance (P < 0.05 vs. P > 0.05), study design (single group vs. randomized 2 groups), and preliminary study status (presence/absence of pilot language). Using an online survey, behavioral scientists were provided with a randomly selected variation of each of the 5 abstracts and blinded to the existence of other variations. Respondents rated each abstract on aspects of study quality., Results: Behavioral scientists (n = 271, 79.7% female, median age 34 years) completed 1,355 abstract ratings. Preliminary study status was not associated with perceived study quality. Statistically significant effects were rated as more scientifically significant, rigorous, innovative, clearly written, warranted further testing, and had more meaningful results. Randomized designs were rated as more rigorous, innovative, and meaningful., Conclusion: Findings suggest reviewers place a greater value on statistically significant findings and randomized control design and may overlook other important study characteristics., Competing Interests: Declaration of Competing Interest The authors have no competing interests or conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Perineural invasion is a prevalent pathological finding in head and neck squamous cell carcinoma and a risk factor for unfavorable survival. An adequate diagnosis of perineural invasion by pathologic examination is limited due to the availability of tumor samples from surgical resection, which can arise in cases of definitive nonsurgical treatment. To address this medical need, we established a random forest prediction model for the risk assessment of perineural invasion, including occult perineural invasion, and characterized distinct cellular and molecular features based on our new and extended classification. RNA sequencing data of head and neck squamous cell carcinoma from The Cancer Genome Atlas were used as a training cohort to identify differentially expressed genes that are associated with perineural invasion. A random forest classification model was established based on these differentially expressed genes and was validated by inspection of H&E-stained whole image slides. Differences in epigenetic regulation and the mutational landscape were detected by an integrative analysis of multiomics data and single-cell RNA-sequencing data were analyzed. We identified a 44-gene expression signature related to perineural invasion and enriched for genes mainly expressed in cancer cells according to single-cell RNA-sequencing data. A machine learning model was trained based on the expression pattern of the 44-gene set with the unique feature to predict occult perineural invasion. This extended classification model enabled a more accurate analysis of alterations in the mutational landscape and epigenetic regulation by DNA methylation as well as quantitative and qualitative differences in the cellular composition in the tumor microenvironment between head and neck squamous cell carcinoma with or without perineural invasion. In conclusion, the newly established model could not only complement histopathologic examination as an additional diagnostic tool but also guide the identification of new drug targets for therapeutic intervention in future clinical trials with head and neck squamous cell carcinoma patients at a higher risk for treatment failure due to perineural invasion.